Marshall Protocol Knowledge Base - home:publications

Poster - Web 2.0 offers new opportunities for patient care and research

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

06.14.2010		current
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-	====== Abstract - Web 2.0 offers new opportunities for patient care and research ======	+	====== Poster - Web 2.0 offers new opportunities for patient care and research ======


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	Location: Ljubljana, Slovenia\\		Location: Ljubljana, Slovenia\\
	Date: May 2010\\		Date: May 2010\\
		+	Additional Content: [[https://mpkb.org/_media/home/publications/ica2010_albert.pdf\|PDF of poster]]



	===== Abstract =====		===== Abstract =====
-

	One of the most obvious means for bridging the gap between bench and bedside is the social Internet, also known as Web 2.0. As web services devoted to medical therapies figure more prominently in patients' lives, the ways in which we deliver patient care is in the process of being altered in fundamental ways. Web 2.0 medical sites improve patient care in several key respects: facilitating doctor-doctor interaction, keeping a record of patient progress, and bringing to light the need for urgent care between routine doctors' visits. New and easy-to-use patient-centric informational resources also now offer basic medical information on demand as well as advanced medical information for those capable of assimilating it.		One of the most obvious means for bridging the gap between bench and bedside is the social Internet, also known as Web 2.0. As web services devoted to medical therapies figure more prominently in patients' lives, the ways in which we deliver patient care is in the process of being altered in fundamental ways. Web 2.0 medical sites improve patient care in several key respects: facilitating doctor-doctor interaction, keeping a record of patient progress, and bringing to light the need for urgent care between routine doctors' visits. New and easy-to-use patient-centric informational resources also now offer basic medical information on demand as well as advanced medical information for those capable of assimilating it.
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-	{{tag>abstracts Paul_Albert 2010}}	+	{{tag>posters Paul_Albert 2010}}

-	===== Notes and comments =====
-	<html><form>
-	<a href="http://AutoimmunityResearch.org/transcripts/2010AI_Marshall.pdf"><input type="image" name="Submit" value="Download as PDF" src="http://mpkb.org/_media/home/downloadpdf.gif"; class="buttoncalc hide" /></a>
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Paper - Vitamin D: the alternative hypothesis

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

09.10.2010		current
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	Authors: Paul J. Albert, Amy D. Proal, Trevor G. Marshall, PhD\\		Authors: Paul J. Albert, Amy D. Proal, Trevor G. Marshall, PhD\\
	Publication: //Autoimmunity Reviews//\\		Publication: //Autoimmunity Reviews//\\
-	Citation: {{pubmed>long:19393200}}\\	+	Citation: {{pmid>long:19393200}}\\
-	See also: [[http://autoimmunityresearch.org/transcripts/AR-Albert-VitD.pdf\|Pre-print]]	+
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		+	<a href="https://autoimmunityresearch.org/transcripts/AR-Albert-VitD.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
		+	</html>

	===== Abstract =====		===== Abstract =====

Poster - Multiple reports of symptom exacerbation on immunostimulatory treatment for autoimmune ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

09.03.2010		current
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	Location: Washington University, St. Louis\\		Location: Washington University, St. Louis\\
	Date: August 31 - September 1, 2010\\		Date: August 31 - September 1, 2010\\
-	Additional Content: [[http://mpkb.org/_media/home/publications/2010-Albert-HMRC.pdf\|PDF of poster]]	+	Additional Content: [[https://mpkb.org/_media/home/publications/albert_hmrc2010.pdf\|PDF of poster]]

Applications to the FDA for orphan drug status for Marshall Protocol medications

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

03.06.2011		current
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-	====== Applications to the FDA for orphan drug status for Marshall Protocol medications ======	+	~~NOTOC~~
		+
		+	====== Applications to the FDA for orphan drug status for Marshall Protocol medications ======

	Autoimmunity Research Foundation has submitted multiple applications to the Office of Orphan Products Development, a division of the FDA. The goal of submitting these applications would be to make it easier for doctors to prescribe and harder for insurance companies to deny coverage of MP medications.		Autoimmunity Research Foundation has submitted multiple applications to the Office of Orphan Products Development, a division of the FDA. The goal of submitting these applications would be to make it easier for doctors to prescribe and harder for insurance companies to deny coverage of MP medications.
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-	* submitted by ARF (September 2005) - [[http://autoimmunityresearch.org/orphan-app-mino.pdf\|Application for Orphan Drug Status]] for minocycline in sarcoidosis	+	* submitted by ARF (September 2005) - [[https://autoimmunityresearch.org/orphan-app-mino.pdf\|Application for Orphan Drug Status]] for minocycline in sarcoidosis
-	* FDA approval (March 2006) - [[http://www.fda.gov/orphan/designat/alldes.rtf\|minocycline]] as an orphan drug for sarcoidosis	+	* FDA approval (March 2006) - [[https://www.fda.gov/orphan/designat/alldes.rtf\|minocycline]] as an orphan drug for sarcoidosis

	===== Clindamycin =====		===== Clindamycin =====


-	* submitted by ARF (September 2005) - [[http://autoimmunityresearch.org/orphan-clindamycin-25jul06.pdf\|Application for Orphan Drug Status]] for clindamycin in treatment of sarcoidosis and Post-Treatment Lyme Disease Syndrome	+	* submitted by ARF (September 2005) - [[https://autoimmunityresearch.org/orphan-clindamycin-25jul06.pdf\|Application for Orphan Drug Status]] for clindamycin in treatment of sarcoidosis and Post-Treatment Lyme Disease Syndrome
-	* FDA approval (August 2006) - [[http://www.fda.gov/orphan/designat/alldes.rtf\|clindamycin]] as an orphan drug for sarcoidosis	+	* FDA approval (August 2006) - [[https://www.fda.gov/orphan/designat/alldes.rtf\|clindamycin]] as an orphan drug for sarcoidosis

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	===== Olmesartan =====		===== Olmesartan =====

-	* submitted by ARF (July 2006) - [[http://autoimmunityresearch.org/orphan-app-benicar.pdf\|Application for Orphan Drug Status]] for olmesartan in treatment of Post-Treatment Lyme Disease Syndrome	+	* submitted by ARF (July 2006) - [[https://autoimmunityresearch.org/orphan-app-benicar.pdf\|Application for Orphan Drug Status]] for olmesartan in treatment of Post-Treatment Lyme Disease Syndrome
	* //application pending//		* //application pending//

Poster - Bipolar disorders and autoimmune disease share a similar etiology

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

06.14.2010		current
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-	====== Abstract - Bipolar disorders and autoimmune disease share a similar etiology======	+	====== Poster - Bipolar disorders and autoimmune disease share a similar etiology======


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	Location: Ljubljana, Slovenia\\		Location: Ljubljana, Slovenia\\
	Date: May 2010\\		Date: May 2010\\
		+	Additional Content: [[https://mpkb.org/_media/home/publications/ica2010_benediktsson.pdf\|PDF of poster]]
		+
		+
		+
		+

	===== Abstract =====		===== Abstract =====
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	We have been conducting an observational study since 2002 of a VDR agonist along with pulsed low dose antibiotics for treatment of chronic inflammatory diseases. Intriguingly, many of the study subjects had initially reported comorbid symptoms of cognitive impairment, including brain fog and major depression, consistent with advanced chronic disease. Four patients, who had noted prior diagnoses of bipolar disorder 1 and II, reported significant improvement in bipolar symptoms after therapy. The improvement in mental function was concurrent with improvements in the symptoms of the comorbid autoimmune disease. This is consistent with a shared etiology and strongly suggestive of the involvement of bacterial pathogens.		We have been conducting an observational study since 2002 of a VDR agonist along with pulsed low dose antibiotics for treatment of chronic inflammatory diseases. Intriguingly, many of the study subjects had initially reported comorbid symptoms of cognitive impairment, including brain fog and major depression, consistent with advanced chronic disease. Four patients, who had noted prior diagnoses of bipolar disorder 1 and II, reported significant improvement in bipolar symptoms after therapy. The improvement in mental function was concurrent with improvements in the symptoms of the comorbid autoimmune disease. This is consistent with a shared etiology and strongly suggestive of the involvement of bacterial pathogens.
		+
		+
		+
		+
		+
		+	{{tag>posters Chris_Benediktsson Janet_Raty Trevor_Marshall_PhD 2010}}
		+

Paper - Vitamin D metabolites as clinical markers in autoimmune and chronic disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 06:37:14 +0000

09.10.2010		current
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-
	====== Paper - Vitamin D metabolites as clinical markers in autoimmune and chronic disease ======		====== Paper - Vitamin D metabolites as clinical markers in autoimmune and chronic disease ======

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	Authors: Greg Blaney, MD, Paul J. Albert, Amy D. Proal\\		Authors: Greg Blaney, MD, Paul J. Albert, Amy D. Proal\\
	Publication: //Annals of the New York Academy of Sciences//\\		Publication: //Annals of the New York Academy of Sciences//\\
-	Citation: {{pubmed>long:19758177}}\\	+	Citation: {{pmid>long:19758177}}\\
-	See also: [[http://autoimmunityResearch.org/preprints/BlaneyAnnals2009Preprint.pdf\|Pre-print]]	+
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		+	<a href="https://autoimmunityResearch.org/preprints/BlaneyAnnals2009Preprint.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
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	===== Abstract =====		===== Abstract =====
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	{{tag>papers Greg_Blaney_MD Paul_Albert Amy_Proal 2009}}		{{tag>papers Greg_Blaney_MD Paul_Albert Amy_Proal 2009}}
-

Presentation - Olmesartan medoxomil & treatment of autoimmune disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

01.03.2012		current
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	{{ youtube>X0y0PcVJ5Ss}}		{{ youtube>X0y0PcVJ5Ss}}

-	<note>Dear MPKB Reader: You have arrived at an article that has not yet been completed. Thanks for your patience.</note>

	Type: Conference presentation\\		Type: Conference presentation\\
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	{{tag>presentations videos Greg_Blaney_MD 2010}}		{{tag>presentations videos Greg_Blaney_MD 2010}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

	Add this to heading after the PDF is completed:		Add this to heading after the PDF is completed:
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-	<a href="http://AutoimmunityResearch.org/transcripts/2010AI_Blaney.pdf"><img src="http://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>	+	<a href="https://AutoimmunityResearch.org/transcripts/2010AI_Blaney.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>

	</html>		</html>


-	===== References =====	+	===== References =====</nodisp>

Presentation - Vitamin D metabolites as clinical markers in autoimmune and chronic illness

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

06.14.2010		current
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	Type: Conference presentation\\		Type: Conference presentation\\
	Presenter: Greg Blaney, MD\\		Presenter: Greg Blaney, MD\\
-	Conference: [[http://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]]\\	+	Conference: [[https://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]]\\
	Location: Porto, Portugal\\		Location: Porto, Portugal\\
	Date: September 11, 2008\\		Date: September 11, 2008\\
-	Additional content: [[http://bacteriality.com/2008/09/22/coa/\|Notes from the 2008 International Congress on Autoimmunity]] by Amy Proal; [[http://mpkb.org/_media/pdf/ica2008_transcript_gregblaney.pdf\|PDF of transcript alongside slides]]	+	Additional content: [[https://bacteriality.com/2008/09/22/coa/\|Notes from the 2008 International Congress on Autoimmunity]] by Amy Proal; [[https://AutoimmunityResearch.org/transcripts/ICA2008_Transcript_GregBlaney.pdf\|PDF of transcript alongside slides]]

Presentation - Psychiatric and neurologic comorbidities as systemic dysfunctions

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

01.03.2012		current
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	Date: November 17-19, 2011\\		Date: November 17-19, 2011\\

		+	[[https://autoimmunityresearch.org/transcripts/Singapore_ACA2011_Goetze-Pelka.pdf\|transcript]]

	{{tag>presentations videos Roswitha_Goetze-Pelka 2011}}		{{tag>presentations videos Roswitha_Goetze-Pelka 2011}}

Poster - Immunostimulation: a treatment innovation in chronic inflammatory and autoimmune disorders

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

04.30.2016		current
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	Location: Leipzig, Germany\\		Location: Leipzig, Germany\\
	Date: April 6-10, 2016\\		Date: April 6-10, 2016\\
-	Additional Content: [[http://mpkb.org/_media/home/publications/ica2016_heil.pdf\|PDF of poster]]	+	Additional Content: [[https://mpkb.org/_media/home/publications/ica2016_heil.pdf\|PDF of poster]]


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-	Due to the increasingly complex and comorbid nature of chronic inflammatory and auto-immune disorders, treatment of these conditions calls for a new approach, as many patients do not respond to current treatment modalities. Seven years ago, we began exploring a novel immuno-modulating monotherapy to volunteer patients using a retargeted drug, olmesartan medoxomil, which, when dosed more frequently than usual, stimulates the innate immune system by acting as a VDR nuclear receptor agonist. Patients who had previously failed to respond to long term “standard of care,” “feel better” palliative, immune suppressive therapy associated with significant relapse rates were no longer interested in defensively managing their conditions with unscientifically based expectations of recovery. Instead, these patients engaged in long-term novel offensive positioning and effective treatment which involved “feeling worse at first” accompanied by synergistic immune stimulation, having a full scientifically-based intent and expectation of cure. Sixty-two (62) volunteer patients from a nurse practitioner practice in Arizona were admitted as participants in this observational cohort between 2008 and 2012. Conventional clinical symptoms were monitored using a consistent 10-point self-reporting scale at each encounter. Self-reported symptoms monitored include: insomnia, depression, incontinence, fatigue, irritability, pain, and loss of focus. Objective laboratory data was collected to measure various health parameters. Emotional support was offered to assist in subject retention, utilizing both collaboration on an Internet discussion site and in person local support meetings. Many symptoms and diagnoses responded well to this novel immunostimulation. Case-series data will be presented with case details available upon request.	+	Due to the increasingly complex and comorbid nature of chronic inflammatory and auto-immune disorders, treatment of these conditions calls for a new approach, as many patients do not respond to current treatment modalities. Seven years ago, we began exploring a novel immuno-modulating monotherapy to volunteer patients using a retargeted drug, olmesartan medoxomil, which, when dosed more frequently than usual, stimulates the innate immune system by acting as a VDR nuclear receptor agonist. Patients who had previously failed to respond to long term “standard of care,” “feel better” palliative, immune suppressive therapy associated with significant relapse rates were no longer interested in defensively managing their conditions with unscientifically based expectations of recovery. Instead, these patients engaged in long-term novel offensive positioning and effective treatment which involved “feeling worse at first” accompanied by synergistic immune stimulation, having a full scientifically-based intent and expectation of cure.
		+
		+	Sixty-two (62) volunteer patients from a nurse practitioner practice in Arizona were admitted as participants in this observational cohort between 2008 and 2012. Conventional clinical symptoms were monitored using a consistent 10-point self-reporting scale at each encounter. Self-reported symptoms monitored include: insomnia, depression, incontinence, fatigue, irritability, pain, and loss of focus. Objective laboratory data was collected to measure various health parameters. Emotional support was offered to assist in subject retention, utilizing both collaboration on an Internet discussion site and in person local support meetings. Many symptoms and diagnoses responded well to this novel immunostimulation. Case-series data will be presented with case details available upon request.

	{{tag>posters Trudy_Heil 2016}}		{{tag>posters Trudy_Heil 2016}}

Paper - Electrosmog and autoimmune disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

07.18.2016		current
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	Authors: Trevor G Marshall PhD and T.J.R.Heil \\		Authors: Trevor G Marshall PhD and T.J.R.Heil \\
	Publication: //Immunologic Research//\\		Publication: //Immunologic Research//\\
-	Citation: {{pubmed>long:27412293}}\\	+	Citation: {{pmid>long:27412293}}\\
-	See: [[http://link.springer.com/article/10.1007%2Fs12026-016-8825-7\|Full text]]\\	+	See: [[https://link.springer.com/article/10.1007%2Fs12026-016-8825-7\|Full text]]\\

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-	<a href="http://link.springer.com/content/pdf/10.1007%2Fs12026-016-8825-7.pdf"><img src="http://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>	+	<a href="https://link.springer.com/content/pdf/10.1007%2Fs12026-016-8825-7.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>


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	{{tag>papers Trevor_Marshall_PhD Heil_TJR}}		{{tag>papers Trevor_Marshall_PhD Heil_TJR}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====
	--- //Sallie Q 07.17.2016// new page adapted from another MPKB publication page		--- //Sallie Q 07.17.2016// new page adapted from another MPKB publication page
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	I have not yet worked out how to do non-pubmed references.		I have not yet worked out how to do non-pubmed references.

-	removed from copy-and-paste	+	--- //Joyful 07.18.2016// nice work Sallie Q. reference and PDF link set up now. :)</nodisp>
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Poster - Clinical observation of immunostimulation in chronic nervous and immune disorders: ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

08.01.2015		current
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-	====== Poster - Clinical Observation of Immunostimulation In Chronic Nervous and Immune Disorders: Retargeted Olmesartan Medoxomil in 62 Patients ======	+	====== Poster - Clinical observation of immunostimulation in chronic nervous and immune disorders: retargeted olmesartan medoxomil in 62 patients ======


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	Location: Institute of Experimental Medicine, St. Petersburg, Russia\\		Location: Institute of Experimental Medicine, St. Petersburg, Russia\\
	Date: June 23-26, 2015\\		Date: June 23-26, 2015\\
-	Additional Content: [[http://mpkb.org/_media/home/publications/heil_nim_2015.pdf\|PDF of poster]]	+	Additional Content: [[https://mpkb.org/_media/home/publications/heil_nim_2015.pdf\|PDF of poster]]

Presentation - Treatment of chronic fatigue syndrome as an immune disorder

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

05.20.2012		current
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-	{{ youtube>g6sH7NTXkjw}}	+	{{ youtube>2IMdAV6SIMU}}



	Type: Conference presentation\\		Type: Conference presentation\\
-	Presenter: Trevor Marshall, PhD\\	+	Presenter: Inge Lindseth\\
	Conference: 8th International Congress on Autoimmunity \\		Conference: 8th International Congress on Autoimmunity \\
	Location: Grenada, Spain\\		Location: Grenada, Spain\\
	Date: May 9-13, 2012\\		Date: May 9-13, 2012\\
-	Additional content: [[http://autoimmunityresearch.org/transcripts/Auto2012_IngeLindseth.pdf\|PDF transcript]]	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Auto2012_IngeLindseth.pdf\|PDF transcript]]


-	{{tag>presentations videos Trevor_Marshall_PhD 2012}}	+	{{tag>presentations videos Inge_Lindseth 2012}}

Paper - Immunostimulation in the treatment for chronic fatigue syndrome/myalgic encephalomyelitis

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

04.13.2013		current
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-	====== Paper - The human microbiome and autoimmunity ======	+	====== Paper - Immunostimulation in the treatment for chronic fatigue syndrome/myalgic encephalomyelitis ======


	Type: Paper\\		Type: Paper\\
-	Authors: Amy D. Proal PhD, Paul J. Albert, Trevor G Marshall PhD, Greg P. Blaney, Inge A. Lindset\\	+	Authors: Amy D. Proal PhD, Paul J. Albert, Trevor G Marshall PhD, Greg P. Blaney, Inge A. Lindseth\\
	Publication: //Immunologic research//\\		Publication: //Immunologic research//\\
-	Citation: {{pubmed>long:23576059}}\\	+	Citation: {{pmid>long:23576059}}\\
-	See also: [[http://AutoimmunityResearch.org/preprints/2013-Lindseth-ImmunologicResearch.pdf\|Full text]]\\	+	See also: [[https://AutoimmunityResearch.org/preprints/2013-Lindseth-ImmunologicResearch.pdf\|Full text]]\\

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-	<a href="http://AutoimmunityResearch.org/preprints/2013-Lindseth-ImmunologicResearch.pdf"><img src="http://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>	+	<a href="https://AutoimmunityResearch.org/preprints/2013-Lindseth-ImmunologicResearch.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>


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-	{{tag>papers Trevor_Marshall_PhD Paul_Albert Amy_Proal }}	+	{{tag>papers Trevor_Marshall_PhD Paul_Albert Amy_Proal Inge_Lindseth Greg_Blaney }}

Poster - Monitoring cognitively-impaired subjects in an interactive Internet-based clinical ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

04.21.2009	current
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	+	====== Poster - Monitoring cognitively-impaired subjects in an interactive Internet-based clinical trial of a multi-factorial treatment based on a molecular model of chronic disease ======

	+	{{ vimeo>952759}}
	+
	+	Type: Abstract presentation\\
	+	Presented by: Meg Mangin RN\\
	+	Conference: [[https://www.massgeneral.org/cvrc/meetings_molecular_agenda.html\|Days of Molecular Medicine 2008]]\\
	+	Location: Karolinska Institue, Sweden\\
	+	Date: April 17 -19, 2008\\
	+	Related content: [[https://autoimmunityresearch.org/dmm2008/DMM2008_Meg_Poster.pdf\|poster]]; [[https://bacteriality.com/2008/04/25/dmm/\|Notes from the Conference]] by Amy Proal\\
	+	Notes: Meg Mangin's presentation begins at 16:50.
	+
	+
	+
	+
	+
	+	===== Abstract =====
	+
	+	Based on this author’s experience on an NIH monitoring board, we devised and conducted a phase II clinical study of a VDR-agonist, antibacterial therapy which demonstrated proof of concept of a novel biological description of the autoimmune disease process(({{pmid>long:18200565}})). We collected evidence that restoring innate immune system competence will reverse the disease progression((Marshall TG et al. //The Journal of the Interregional Clinical-Diagnostic Center//, Kazan. ISSN:1726-6149)). This multi-factorial therapy activates the Vitamin D Nuclear-Receptor, enabling the innate immune system to attack the intracellular microbiota which dysregulates Vitamin D metabolism. Additionally, it reduces elevated 1,25-dihydroxyvitamin-D and reduces co-morbid cognitive impairment((Mangin M. Abstract presentation Days of Molecular Medicine April 2008)). Nurses who monitor the subject’s progress are well-grounded in molecular science to help them accurately assess the effects of the recovery process. Instruction of subjects and their participating physicians occurs online. All communication is done in writing using a standard report form to facilitate accurate assessment and collect objective data. Ongoing, regular reports and rapid feedback by Nurses, ensures early detection of unexpected treatment effects. We describe the observational skills needed, the assessment techniques used and the limits/advantages of monitoring subjects using this format. As a result of the therapy subjects experienced diminishing relapse and remission of inflammatory symptoms(({{pmid>long:15246025}})). Over 3-5 years this resulted in recovery from the disease process.
	+
	+	{{tag>posters videos Meg_Mangin_RN DMM 2008}}
	+
	+
	+	===== References =====

Presentation - Autoimmune Disease succumbs to a VDR Nuclear Receptor Agonist

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.21.2018		current
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-	{{tag>presentations videos Trevor_Marshall_PhD 2015}}	+	{{tag>presentations videos Trevor_Marshall_PhD 2009}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: [[http://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT AVAILABLE	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT AVAILABLE
		+	</nodisp>

Presentation - How borrelia evades the immune system, and how we help the immune system kill ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

04.21.2009	current
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	+
	+	====== Presentation - How borrelia evades the immune system, and how we help the immune system kill this Th1 bacterium ======
	+
	+
	+
	+	Type: Conference presentation\\
	+	Presenter: Trevor Marshall, PhD\\
	+	Conference: 30th Anniversary of Lyme Disease\\
	+	Location: Farmington, CT\\
	+	Date: May 7, 2005\\
	+	Related content: [[https://autoimmunityresearch.org/trevor-30th.ram\|Video of presentation (.ram file)]]
	+
	+
	+	===== Transcript =====
	+
	+	{{tag>presentations videos Trevor_Marshall_PhD 2005}}
	+
	+

Presentation - Autoantibodies - are they the cause of disease, or the result of disease?

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.19.2018		current
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-	====== Presentation - Environmental Radiation modulates symptoms in Human Immune Disease ======	+	====== Presentation - Autoantibodies - are they the cause of disease, or the result of disease? ======


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	{{tag>presentations videos Trevor_Marshall_PhD 2013}}		{{tag>presentations videos Trevor_Marshall_PhD 2013}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: [[http://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE
		+	</nodisp>

Presentation - The VDR nuclear receptor is key to understanding ‘diseases of the aging’

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

04.21.2009	current
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	+	====== Presentation - The VDR nuclear receptor is key to understanding ‘diseases of the aging’ ======
	+
	+	{{ vimeo>1268542}}
	+
	+	Type: Conference presentation\\
	+	Presenter: Trevor Marshall, PhD\\
	+	Conference: [[https://www.methuselahfoundation.org/UABBA/index.html\|Aging 2008]]\\
	+	Location: UCLA\\
	+	Date: April 17-19, 2008\\
	+	Additional content: [[https://bacteriality.com/2008/07/09/aging08/\|Reflections from the Aging Conference]] by Amy Proal; [[https://vimeo.com/1293451\|additional video footage]] from the Conference
	+
	+
	+
	+
	+
	+
	+	===== Abstract =====
	+
	+
	+	In 2006 we reported routinely inducing recovery from chronic inflammatory disease, including 'autoimmune' syndromes. In 2008 we additionally reported inducing recovery from chromic neurological disease, including neuropathies, cognitive and memory deficiencies, depression, Bipolar and Obsessive Compulsive Disorders. These chronic diseases are all caused by an intraphagocytic biofilm-like metagenomic microbiota which has apparently been part of the human experience since Neolithic times, but which, due to changes in lifestyle and medicine during the 20th century, has expanded into epidemic prominence over the last three decades. Located in the phagocyte cytoplasm, this microbiota has direct access to both the transcription and translation machinery of Homo sapiens. We have demonstrated that the intraphagocytic pathogens have evolved a survival mechanism whereby VDR transcription is inhibited. Transcription of a minimum 913 genes is thus directly affected by the pathogens, notably including MTSS1. Life Extension research can derive much from our observations on this cohort, as they transition to recovery.
	+
	+	Firstly, we now have objective data showing that chronic organ damage, including fibrotic tissue deposition, can be reversed, even in patients who are beyond middle-age. Further, we have shown that neurological damage can be reversed, and that neurological recovery appears complete. After recovery, patients are left re-invigorated, and report levels of cognition and memory often described as "feeling 20 years younger". Recovery is induced by activation of the VDR Nuclear Receptor with Olmesartan, an agonist, and long-term (3-6 years) administration of low-dose sub-inhibitory antibiotics which target protein synthesis by the bacterial 70S ribosome.
	+
	+	Aging-related diagnoses already shown to be reversible include: osteoporosis, periodontal disease, uveitis, arthritis, hypertension and cardiovascular disease. It should be noted that as the pathogens are killed, the infected cells often undergo apoptosis. This immunopathology manifests itself as an exacerbation of symptoms, and can make the patient quite ill. It is therefore important to start therapy early. A small German pilot study in Dementia had to be terminated, even though the subjects were responding to therapy as expected, because subjects were too ill to rationalize what they were experiencing. We propose that further studies of individuals recovering from chronic illness will quickly yield insight into not only the diseases of the aging, but also into the processes of aging.
	+
	+	{{tag>presentations videos Trevor_Marshall_PhD aging 2008}}

Presentation - A new approach to treating intraphagocytic CWD bacterial pathogens in ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

04.21.2009	current
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	+
	+	====== Presentation - A new approach to treating intraphagocytic CWD bacterial pathogens in sarcoidosis, CFS, Lyme and other inflammatory diseases ======
	+
	+	{{ youtube>-FzYARFQ9ZE}}
	+
	+
	+	Type: Conference presentation\\
	+	Presenter: Trevor Marshall PhD\\
	+	Conference: 41st Annual Meeting of AAEM\\
	+	Location: Hilton Head, SC \\
	+	Date: Oct. 26-29, 2006\\
	+	Additional content: [[https://autoimmunityresearch.org/transcripts/marshall_aaem_2006.pdf\|Transcript and slides]]
	+
	+
	+
	+
	+	===== Transcript =====
	+
	+
	+	Thank you John, and thank you to the academy for inviting me to
	+	come.
	+
	+	Well the first two slides are just links to some of the papers that
	+	we've published on these topics. They are there for your references.
	+
	+	Our FDA coordinator also told me to make sure that I point out
	+	that there are FDA applications current for both Sarcoidosis,
	+	designations in the drugs in Sarcoidosis, and also in PTLDS or Post
	+	Treatment Lyme Disease Syndrome(what most of you would know
	+	as chronic Lyme) active; and the numbers are all at the bottom
	+	and you can find a copies of all of those applications on the
	+	Internet if you want to look in more detail at the regulatory issues.
	+
	+
	+	The disclaimers. Many of the disease states that I am going to
	+	cover in this presentation, including neurological states are not
	+	generally accepted as being caused by pathogens. Much of this
	+	presentation is based on leading edge science and not on weight
	+	of evidence. The Phase 2 clinical trial is ongoing.
	+	Even when shown the science and the microscopy, some experts
	+	still disagree to the existence of persistent pathogens.
	+
	+	The FDA has now designated trials for long term use of
	+	Minocycline and Clindamycin in the treatment of Sarcoidosis but
	+	not in the other indications I am going to discuss. We are going to
	+	Phase 3 trials over the next year or two.
	+
	+	Now in addition to our previous papers, the list of which I've just
	+	gone through, many of the slides have Pub Med ID numbers on
	+	them. Those are citations to support the science in any specific
	+	slide. So if there is something on a specific slide that you feel I'm
	+	reaching a bit with, make sure you look at the Pub Med ID
	+	citations first.
	+
	+	And there are also a few new slides resulting from recently
	+	published peer review papers which are not in the syllabus and
	+	which have not been reviewed by AAEM. These have that little red
	+	logo at the bottom saying "NOT IN SYLLABUS."
	+
	+
	+	So here is the first one, "Not in Syllabus." Well, actually, the top
	+	part is in the syllabus but I changed the text on the bottom, as you
	+	will see on the next slide.
	+
	+	The quotation at the top, from a gentleman called John Arbuthnot,
	+	from Sixteen Hundred and Ninety two. Believe it or not, this
	+	quotation really forms the basis of evidence-based medicine. This
	+	is the gentleman that wrote the first book on statistics of the laws
	+	of chance in 1692 and as you would all know, without statistics and
	+	without the concepts of statistics, we wouldn't have the clinical
	+	evidence-base that we have at the moment.
	+
	+	What John said ... [read quote from slide].
	+
	+	The primary difference between mathematical science, which is
	+	primarily what I'm going to deal with in this presentation, and
	+	evidence-based medicine is that one is definitive and one is
	+	interpretive. Mathematical science tries to define relationships
	+	between metabolites. Tries to define what's going on. Evidence-
	+	based medicine tries to interpret the results of observations in a
	+	reliable manner.
	+
	+	As we enter the 21st century, the tools to reduce some important
	+	medical dilemma to mathematical precision are now available in
	+	Molecular Genomics. Now one thing I want to point out is that
	+	true science has no concept of weight of evidence. It doesn't
	+	matter how many times you add up the balance in your checking
	+	account, you can start at the bottom of the page and work up, you
	+	can start at the top of the page and work down, the numbers you
	+	are going to get are exactly the same and any body who has done
	+	high school arithmetic can sit down and check your calculations
	+	for you. So therefore, there is no need for weight of evidence.
	+
	+	As a hypothesis is advanced, it can be tested and it stands until it is
	+	rejected or improved. E=MC2 has been improved many times
	+	over the years, but the basic E=MC2 is still there, still in place.
	+	If the problem is deterministic, then there is a solution.
	+
	+	This is a new slide, and as an example of how molecular and
	+	evidence-based knowledge are symbiotic and the need for both
	+	fields to work in closer cooperation, last week The Lancet
	+	published my answer to a question which had been posed in July
	+
	+
	+	(2006) by Dr DS Grimes. Dr Grimes posed the hypothesis, "Are
	+	statins analogues of Vitamin D?"
	+
	+
	+	Now that's my paraphrase and I'm being a little bit cruel but I
	+	wanted to give you a quick encapsulation of what the hypothesis is
	+	about. This is a hypothesis which cannot be solved by evidence-
	+	based medicine. It cannot be solved because the variables that are
	+	involved, the number of variables that are involved is too high and
	+	they are not appreciated by the investigator.
	+
	+	When you have too many degrees of freedom, your statistical
	+	analyses of the epidemiology just break down. However, the
	+	evidence-based dilemma is easily solved by Molecular Biology and
	+	I'll show you this later in the presentation. I'm going to be talking
	+	about statins. That was actually in the syllabus.
	+
	+
	+	But I wanted to point out that biochemists are also failing. [Read
	+	slide to 'Vitamins D']. The VDR stands for Vitamin D Receptor.
	+	[Continue reading slide to knowledge] Yet the insights that are
	+	resulting from science that the biochemists are producing [continue
	+	slide].
	+
	+	First I need to say little bit about Th1 inflammatory disease. [Read
	+	slide first Paragraph]
	+	Unfortunately, interferon-gamma is a paracrine cytokine. It exists
	+	only in the tissues and it's not an endocrine hormone. It doesn't
	+	circulate through the bloodstream. [Read 2nd Paragraph to tissue]
	+	if you want to do a biopsy [finish 2nd Paragraph].
	+
	+	Consequently, a number of other paracrine cytokine have
	+	historically been measured in order to try and infer whether a
	+	patient is presenting with a type Th1 inflammation, or a type Th2
	+	inflammation. A type Th1 inflammation is typically those which
	+	result from infection, such as Tuberculosis, Leprosy, Syphilis. All
	+	those are Th1 or they cause Th1 immune responses. Th2 is more
	+	typically those which result from what we call allergies. However,
	+	none of these other cytokine are specific and this has led to
	+	considerable confusion. People think in terms of Th1 and Th2, but
	+	basically all of the autoimmune diseases are Th1.
	+
	+	Louis Pasteur once noted that in science, chance favors the
	+	prepared mind. There are 2 factors: Chance, it's all based on luck
	+	(chuckle), being in the right place at the right time. But the
	+	prepared mind is important. You have to be able to observe what
	+	you see, when you are there. We were lucky, we were able to
	+	break that particular nexus and realized that all of these diseases
	+	we were dealing with were in fact, Th1 diseases.
	+
	+	... Suicidal idealation, this is not something I've heard anybody
	+	speak about, so far at the conference. It's a big problem with us.
	+	As the immunopathology takes over, the cytokine storm hits.
	+	Suicidal idealationoccurs in a significant number of these people
	+	and it's treatable. As a matter of fact, it's avoidable.
	+
	+	Now those of you that know about the Marshall Protocol and have
	+	been following what we have been doing over the last five or six
	+	years would know that we've conducted this on the Internet as an
	+	open study. Any physician such as yourselves can register and get
	+	full access to the database of all the reporting from the patients in
	+	the study going right back to day one, right back to about 2001.
	+	A year ago, this was heresy. Everybody said you can't do an open
	+	study. You can't do an adaptive study. You can't change the
	+	conditions as you are going along. You can't do anything on the
	+	Internet.
	+
	+	Well, things change. The drug pipeline is now nearly empty and
	+	the FDA is getting quite concerned that not only is the drug
	+	pipeline nearly empty, but the drugs that are there don't work
	+	properly anyway.
	+
	+	And so I put a quote in there now which is given by the FDA
	+	Deputy Commissioner for Medical and Scientific Affairs, who is
	+	actually in charge of clinical trial evaluation at the FDA, Dr Scott
	+	Gottlieb, from an actual conference that was held earlier this year
	+	on adaptive trial design. And basically, I'll save time by saying that
	+	he says [paraphrase] "we've got to figure out better ways of doing
	+	these things, guys." And whenever I read the stuff he writes, it
	+	makes me think of the things we are doing.
	+
	+	Now we published our initial results in 2004 in the Th1 syndrome
	+	called Sarcoidosis. Sarcoidosis is a rare disease and it's a disease
	+	that we chose to investigate first. We were lucky to choose this
	+	one, it happens to be a prototypical case for all of the Th1
	+	diseases. And there are a number of things in Sarcoidosis which
	+	makes the analysis of the disease state very much easier than it is
	+	in some of the more complex conditions.
	+	And in particular, by the time the inflammation has advanced to
	+	the stage where it forms self-perpetuating granuloma, there are
	+	very few antibodies being formed. So there is no longer the red
	+	herring of the antibody formation and perhaps the antibodies
	+	making people sick. We knew the antibodies weren't making
	+	people sick because there weren't any. We knew there was
	+	something else that was making people sick, probably a cytokine
	+	storm. Where was it coming from?
	+
	+	That was the other Pasteur piece of luck. We happened to be
	+	studying the correct disease that turned out to be the prototype for
	+	many, many other Th1 diseases.
	+
	+	So at Karolinska institutet in Stokholm, at DMM 2006, I gave the
	+	following figures for the recovery rate in several key autoimmune
	+	diagnoses. These were extracted from the Phase 2 and 3 reports.
	+	These are people that have mainly been on the protocol for twelve
	+	months or so on average.
	+
	+	As you can see, Rheumatoid Arthritis has very good success. Eight
	+	have a primary diagnosis of Rheumatoid Arthritis, seven of them
	+	are reporting improvement in their condition.
	+
	+	With Hashimoto's Thyroiditis it is a lot easier. Either they need the
	+	supplements or they don't. There the ratio is twenty out of twenty-
	+	five are improving.
	+
	+	Osteo Arthritis is an interesting one. I was surprised how many
	+	people with Osteo Arthritis we had in the cohort.
	+	And then the ones that we are known for: CFS/CFIDS/Myalgia
	+	Encephalmyelitis. Let me stick with Chronic Fatigue Syndrome.
	+	Seventy-seven with about forty reporting ongoing resolution.
	+	Cardiac Arrhythmia is an interesting one. This came up in a case
	+	study yesterday. And I would like to have an opportunity to join this
	+	group again in about five years time when we have more data and
	+	a lot more history under our belts. And talking again about
	+	cardiac arrhythmia, this is a very classic symptom of late stage Th1
	+	disease.
	+
	+	Sarcoidosis of course, ninety-two with fifty seven recovering.
	+
	+	Diabetes, five and three.
	+
	+	Uveitis, eighteen and twelve.
	+
	+	34/20 in Fibromyalgia and 10/8 in Irritable bowel syndrome.
	+	It is an open study, we don't put any preselection conditions on the
	+	patients that want to join, and that's why we have accumulated
	+	such a wide range of diagnoses. There are about 500 patients at
	+	the moment that are regularly reporting and about ten times that
	+	number that we are aware of... of course, that don't report.
	+
	+	There are a few more diagnoses on this slide. It is in your syllabus
	+	so I won't go over them in too much detail. Point out Psoriatic
	+	Arthritis is a new one, also Multiple Sclerosis. We have quite a few
	+	Multiple Sclerosis patients now, at least it is getting up to statistical
	+	significance. Most of those are being looked after by Dr Greg
	+	Blaney in Canada.
	+
	+	Tinnitus resolves. Usually acute Tinnitus resolves quite quickly and
	+	then takes quite a lot longer to resolve fully, several years to
	+	resolve fully. Like peripheral neuropathy, Tinnitus is one of the slow
	+	symptoms to resolve.
	+
	+	Juvenile ADHD, I've got two out of two and I've already chatted
	+	with the autism, the people that are interested in autism. That was
	+	quite a surprise to us. Both of those patients had primary diagnosis
	+	in other areas. One had a Lyme disease diagnosis, the other had
	+	Sarcoidosis and Uveitis diagnosis. The uveitis being key there. The
	+	patient was going blind. All of the problems have resolved. As the
	+	primary inflammatory diagnosis resolved, the attention and other
	+	problems, psychological problems, resolved as well. Resolved
	+	spectacularly. Both are back at school and doing very well.
	+
	+	Well, five steps basically. [Read to end of step 2]
	+	Olmesartan is licensed for sale throughout the world as an
	+	angiotensin-receptor blocker. But it has significant activity in other
	+	receptors. One of the receptors it is very active in is the VDR. It
	+	activates the VDR.
	+
	+	[Read step 3, to "25"] And when the patients start with 25mg every
	+	48 hours it is usually all they can handle. And then increasing to
	+	100mg over about three months.
	+
	+	[Read step 4] The choice is made based on suicidal ideation.
	+	Clindamycin tends to exacerbate any suicidal ideation or
	+	depression that is present and we avoid it in the early stages of the
	+	protocol with people who have that tendency.
	+
	+	[Read step 5 to 3 antibiotic combo] "Low dose?", well
	+	Azythromycin, some of them can handle 1/8 of a tablet every ten
	+	days when they start. They eventually work up to about half of an
	+	Azythromycin tablet as ultimately the bacterial load is totally
	+	removed, and then they can just guzzle the antibiotic like candy,
	+	like a healthy person can.
	+
	+	But initially, when the immune system is working, those antibiotics
	+	do an incredible job of killing the bacteria.
	+
	+
	+	So, this was a warning that my FDA liaison — contact — said
	+	"please put in."
	+
	+	[Read warning to apoptosis] programmed cell death [continue
	+	warning].
	+
	+	Immunopathology. That is the word that is being used instead of
	+	"Jarisch-Herxheimer." Jarisch-Herxheimer typically refers to the
	+	cytokine storm that occurs in acute episodes. "Immunopathology," I
	+	first heard Rolf Zinkernagle use it at Karolinska and it is becoming
	+	more and more commonly used. It is basically what happens to
	+	the body when the immune system is doing its job. It includes
	+	apoptosis, cytokene storm, all of the other effects on the body from
	+	the immune system doing its job. Immunopathology.
	+	[Read Steps needed].
	+
	+	The moment pathogens start being recognized and start being
	+	killed, your white and red blood cell counts are going to go all
	+	over the place.
	+
	+	[Read Step 1 to receptors], which is rather handy to reduces
	+	fibriotic tissue deposition.
	+
	+	Now we use special antibiotics. You might not think they are
	+	special, but they are special in their interaction. The antibiotics
	+	have a direct action on a part of the bacterial genome which is
	+	called the ribosome. The ribosome, if you cast your mind back to
	+	molecular biology, is where the messenger RNA from gene
	+	transcription, are turned into protein.
	+
	+	In bacteria, they only have one ribosome. The human body has
	+	two ribosomes. Bacteria only have one, called the 70S ribosome,
	+	and the antibiotics that we use block the action of the 70S
	+	ribosome. They block the ability of the bacteria to produce protein.
	+	Particularly to use the protein that they use to evade the immune
	+	system. Because clearly, the bacteria wouldn't be capable of living
	+	within the phagocytes unless they had a mechanism evolved
	+	probably over centuries that allows them to evade phagocytosis.
	+	So the rate of bacterial death is controlled by inhibiting the protein
	+	synthesis, using only intermittent low doses of bacteriostatic
	+	antibiotics.
	+
	+	The other advantage of going after the ribosome is a small
	+	amount of antibiotics kills a small number of bacteria. In fact, one
	+	molecule binds into one ribosome. So it is not quite linear, but it is
	+	a proportional response.
	+
	+	So why? Why does this intervention work when all the previous
	+	antibiotic therapies used for these diseases didn't induce recovery?
	+
	+	[Read 1]
	+	In other words, there is a model. We can fit the disease that we
	+	observe to a model. So when I say that five MS patients is a good
	+	sized sample, its because they are behaving exactly as the model
	+	predicts. So we have the extra statistical guidance from the model
	+	as well as from the data.
	+
	+	It works because [Read 2].
	+	[Read 3] The VDR, which was long thought to be 'just' associated
	+	with 'vitamin D', is now known to be at the heart of innate
	+	immunity. And I'll talk a LOT more about this as we go forward.
	+	[emphasis repeat] Vitamin D is at the heart of innate immunity.
	+	[Read 4]. That is part of the model. We have to know how the
	+	people get sick, and how the sickness progresses over the years.
	+	[Reference 5]. For example, sequencing the bacterial genomes
	+	have shown that many of the common bacteria, even Staph
	+	aurious, has got plasmids. Plasmids are little self-replicating loops
	+	or sticks of DNA that can exist and replicate on their own without
	+	the main chromosome. And many bacteria have these plasmids.
	+	The plasmids can persist and if they are not destroyed by the
	+	immune system, they can interact with other species of bacteria.
	+	Toward the end, I will show you exactly how that happens with a
	+	bacterium species called antrhax.
	+
	+	So the plasmids are persistent and prolific. So when you have a
	+	chronic disease which is accumulating over a lifetime, certainly
	+	over many years, you're not going to have just one species that is
	+	active. You are going to have a number of species that are active.
	+	You are going to have a number of plasmids that are active. You
	+	are going to have a number of viruses that are active.
	+	The ubiquitous EBV. I think I can find a paper for just about any
	+	disease you like name which blames EBV as the cause of that
	+	disease. No. But EBV is very hard to kill off. Its plasmids is just two
	+	genomes long; something like a 160,000 base pairs long; it's very,
	+	very small; very, very hard for the immune system to recognize and
	+	kill; and it persists. And it interacts with any other species of
	+	pathogens in exactly the same way as it interacts with the human
	+	genome. And it will cause mutations. The bacteria cause
	+	mutations.
	+
	+	And the last reason the intervention works is [reference 6] because
	+	the MODEL recognizes that neo-natal pathogens persist in the
	+	brain. [Repeat intended] Neo-natal pathogens persist in the brain.
	+
	+	Well, now we get into some pretty pictures.
	+	These are pictures of a receptor, it is a G-Protein Coupled
	+	Receptor that goes through a membrane. And each of the little
	+	colored balls are atoms. Each of the similarly colored atoms form
	+	part of an amino acid, which together make the protein which is
	+	folded into the receptor.
	+
	+	Well it's not very easy analyzing that sort of diagram, so
	+	biochemists tend to draw everything in terms of spirals and loops.
	+	Each one of these spirals is a cascade of amino acids. It is shown
	+	diagramatically as a spiral so that we can see more easily what it
	+	is actually doing.
	+
	+	We also have a more precise 2-dimensional representation that
	+	you will find in some of my papers. And here we have the actual
	+	amino acid of the protein (see lower right "Leu 293" highlighted in
	+	video) and it shows which are the atoms or ligand of the chemical.
	+	In this case it is olmesartan but it could be any of the vitamins D.
	+	It shows which of the atoms interact with the ammino acid residues
	+	(see lower right O1 red atom highlighted in video), and it also
	+	shows the hydrogen bonds when they exist as well. Making it very
	+	easy to try and figure out whether we are dealing with an agonist,
	+	or an ANtagonist. Much harder to do that in 3-dimensions.
	+
	+
	+	I want to talk about the nuclear receptor type one family because it
	+	turns out that this family is most closely related to the operation of
	+	the immune system — both the innate immune system, and the
	+	adaptive immune system.
	+
	+	The key receptors for which we have known structure models. In
	+	other words, we not only know that the bacterial genome looks like
	+	this but we also know in 3-dimensional space that x-ray
	+	spectroscopy has told us exactly where each atom is in the
	+	molecule. In this case, we're talking about the human genome. But
	+	it's the same theory, we've got the VDR (Vitamin D Receptor), the
	+	Progesterone Receptor, PPAR-alpha (which is one of the lipid and
	+	immune system mediators), PPAR-gamma (which is also lipid and
	+	immune system), Androgen Receptor, the Estrogen Receptor,
	+	glucocorticoid receptor, Thyroid-alpha-1, Thyroid-beta-1, and the
	+	mineralcorticoid receptor.
	+
	+	Now surprisingly, if you look at the pictures of each of these drawn
	+	as spirals (I guess maybe I should have done a slide of it for you),
	+	but they are all very, very similar. And that is why they are the type
	+	1 nuclear receptors.
	+
	+	And you know molecules that will go into the VDR usually only go
	+	into PPAR-gamma and some of the other type 1 receptors as well.
	+	They affect more than one function of the body.
	+
	+
	+	So nuclear receptors are responsible for the transcription of the
	+	DNA genes to strands of RNA, which are then translated into
	+	proteins in the ribosomes. And they are very important.
	+	I've put a link there to a simplified set of flash animations for those
	+	of you that want a crash course on how this all works. It is a very
	+	simple crash course. I really recommend you have a look at it.
	+	(https://www.johnkyrk.com/)
	+
	+
	+	Now we're going to look at some simplified 3-D animations of the
	+	transcription molecules, just to give us an overview.
	+
	+	What we have here, we have a strand or double strand of DNA
	+	(highlight blue/grey/red/pink balls base right of diagram). These
	+	are the base pairs that run across (highlight on video shows
	+	vertical ball lines at bottom center of diagram) the two backbones
	+	of the DNA. Across the center you have the hydrogen bonds that
	+	hold the DNA together (highlight moves L-R across center of
	+	vertical ball lines). Hydrogen bonds that are peeled apart is when
	+	the RNA is produced. The RNA is basically ½ of the DNA double
	+	spiral.
	+
	+	So when the nuclear receptors do their job and transcribe a gene,
	+	what they are actually doing is breaking the hydrogen bonds and
	+	producing the RNA in a very complex and clever fashion which
	+	doesn't occur very fast because it requires a lot of things, the
	+	statistically drift around and come together in exactly the right way.
	+	Nuclear receptors typically take days to effect their action.
	+	Key to nuclear receptors are the zinc fingers here (video highlights
	+	upper left center large yellow/green balls). The green atoms are
	+	zinc, the yellow, sulpher-disulfides. Actually cystines to be honest.
	+	And they are a key part to positioning the helixes which go through
	+	the (video highlights lower left solid light grey spiral) DNA and find
	+	the exact chain that needs to be translated based on the exact
	+	mapping of attractive and repulsive forces and then do the DNA
	+	transcription.
	+
	+	It is an amazing system. I've shown here that there two receptors
	+	because usually one nuclear receptor doesn't do it by itself. It can
	+	form a homodimer but it usually forms a Heterodimer. So you have
	+	a VDR coupled with a retinoid-X receptor and then the two of them
	+	transcribe genes. There is also a cofacter that gets involved as
	+	well. Quite complex and we really don't know a lot about it yet.
	+	I mean we now have the genes to transcribe, but we don't know
	+	exactly which co-factors go with which receptors.
	+
	+
	+	The biggest surprise we got when we started doing this modeling,
	+	was the high affinity of the ARBs and Statins for VDR and PPAR-
	+	gamma, Nuclear Receptors which are both key to the immune
	+	system.
	+
	+	Now these are very flexible, highly polar ligands. And we thought
	+	they might have an affinity for other G-protein coupled receptor
	+	membrane receptors, in other words receptors that go through a
	+	membrane rather than exist in the nucleus of the atom.
	+
	+	But their affinity for the Nuclear receptors was a real surprise.
	+
	+
	+	Here's a big table which represents months of computing.
	+	But what we have done here is used special software that
	+	computes the interaction between thousands of atoms and figures
	+	out for each of the (video highlights drug names in the sartan
	+	group) ARBs and each of the Statins (video highlights drug names
	+	in the statin group), which receptors they are going to have an
	+	affinity for — if any — and which receptors they are going to
	+	switch on or switch off.
	+
	+	And if we just look at the statins first, thinking back to the question
	+	posed by Grimes in The Lancet: "Are statins analogues of vitamin
	+	D?" Well the first thing that pops out is that the VDR here (video
	+
	+	highlights VDR column head), there is a huge difference between
	+	the statins.
	+
	+	Simvastatin (video highlights 4 at base of the VDR column) hs got
	+	quite a low number which means quite a high affinity, but
	+	Rosuvastatin, fluvastatin, and particularly Atorvastatin (Lipitor) don't
	+	have any affinity for the VDR at all. Pravastatin that is effectively no
	+	affinity. Lovastatin would have a little affinity if a low dose is used
	+	in vivo.
	+
	+	So there is a huge difference between the statins. Just thinking of
	+
	+	the statins as a group is a concept that is dangerous clinically, let
	+	alone to try and extrapolate that to talking about the statins
	+	functioning as a hormone would.
	+
	+	But you can also see if you take Simvastatin, not only does it have
	+	a high affinity for the VDR, it's got 10x higher affinity for the PPAR-
	+	gamma, same for PPAR-alpha as the VDR. The Gluco-corticoid
	+	receptor -the home for cortisole- it has a high affinity for, also the
	+	MCR. The Progesterone receptor, the Alpha-Thyroid and the Beta-
	+	Thyroid. Simvastatin is a very, very active statin.
	+
	+	Whereas Atorvastatin for example, primarily hits PPAR-gamma and
	+	alpha and incidently hits the Gluco-cortisole axis for the GCR.
	+	However, some of the ARBs are a little bit better behaved than that.
	+	Telmisartan is very poorly behaved. It totally shuts off the VDR the
	+	moment you give it to somebody. This is NOT good.
	+
	+	Olmesartan, here (video highlights 10 in the VDR column) has got
	+	a moderately low affinity for the VDR, and that is one of the
	+	reasons why we have to use a higher dose when we are using it to
	+	modify the VDR than when we are modifying the Angiotensen-
	+	receptor where it has a much higher affinity. But it is nicely
	+	controlled in the PPAR-gamma and -alpha (video highlight across
	+	Olmesartan Estimated Ki row) and GCR. It hits the progestrone
	+	receptor but it doesn't really hit Alpha-Thyroid.
	+
	+	Beta-Thyroid it hits but we're not really sure what Beta-Thyroiod
	+	does yet. What we know about Beta Thyroid is that if you breed
	+	mice that don't have the beta thyroid receptor, then they are born
	+	deaf. Otherwise they seem to be fine. (Audience chuckles) So we're
	+	still trying to figure out what the Beta Thyroid does.
	+
	+	The ability to breed mice with gene knock-outs without these
	+	receptors is a PRIMARY new tool that has become available to the
	+	biochemist. It is invaluable. Unfortunately with the GCR, if you
	+	knock out the GCR the mice never survive past gestation. So we
	+	don't know a heck of a lot about the GCR either except it is at the
	+	root of the Cortisole axis of the adrenal.
	+
	+	But anyway, it is a big table and I have it printed on a sheet of
	+	paper and I have to refer to it all the time, so I'm not going to
	+	expect any of you to commit that to memory.
	+
	+	Now I'm going to look at a very simple hormonal system. The
	+	adrenal axis. And up here (video highlights top word
	+	"GlucoCortocoid Receptor"), I'm just looking at part of it and I'm
	+	looking at the GlucoCortocoid Receptor, the nuclear receptor, with
	+	a promotor which is "c" AMP (cAMP). Promotor binds to the
	+	receptors, and then the promotor and the receptor together bind
	+	to the DNA and transcribe the gene.
	+
	+	The GlucoCortocoid Receptor is responsible for producing
	+	Corticotrophin Releasing Hormone (CRH highlighted), and that in
	+	turn produces the Pro-Opeo-Milleno Cortin and when that is
	+	metabolized, you get Beta-endorphin and also an ACTH
	+	produced. ACTH of course you know, that catalyzes the conversion
	+	of Cholesterol into Cortisol. Then Cortisol goes up and docs into
	+	the GlucoCortocoid Receptor (highlight shows arrow line path left
	+	and up to GCR) and you have a feedback loop, which keeps the
	+	Cortisol levels of the body at roughly constant levels.
	+	That is a very simple, straight forward hormone loop.
	+
	+
	+	Unfortunately, with 'vitamin' D, it is a little bit more complex. As you
	+	would expect for something that is at the heart of the immune
	+	system. It has adapted over many, many millennia.
	+	The "not in Syllabus" flag indicates some of the enzymes here have
	+	shifted from what is printed in your syllabus. Also, since that
	+	syllabus was published, there has been new studies showing that
	+	the Androgens (video highlights lower left corner word
	+	"Androgens"), particularly testosterone, reduce the breakdown of
	+	1,25-D by the enzyme CYP24.
	+
	+	But basically, the body starts off with 7-dehydro-Cholesterol, which
	+	is part of the sterol subsystem. It is a cholesterol derivative (video
	+	highlights upper left 7-dehydro-Cholesterol), and that is converted
	+	to pre-Vitamin D by energy. Conventionally thought to be UVB, but
	+	the biochemists will easily tell you it doesn't have to be UVB and it
	+	can even be an enzyme. Enzyme at this point, we have no idea
	+	what that enzyme would be if it is an enzyme. But it certainly
	+	doesn't have to be UVB to convert to Pre-Vitamin D (Pre-Vitamin D
	+	highlighted). All you need is a contra-rotatory electrocyclic reaction
	+	which occurs in other substances and which is pretty well
	+	characterized.
	+
	+	(Vitamin D highlighted) Then, Pre-Vitamin D is formed into Vitamin
	+	D by a Sigmatrophic shift. A very small shift of the electrons (????).
	+	Vitamin D is converted by the enzyme CYP27A1 -or- CYP2R1 and
	+	both of these are P450 digestive system enzymes into 25-
	+	hydroxyvitamin-D (highlight drops to 25-hydroxyvitamin-D) and this
	+	is the one that most of you are measuring when you measure
	+	somebody's 'vitamin' D levels, you are almost certainly measuring
	+	the 25-hydroxyvitamin-D.
	+
	+	(Highlight drops to 1,25-dihydroxyvitamin-D) That then is
	+	converted to 1,25-dihydroxyvitamin-D, hydroxillation by enzyme
	+	either CYP27A1 or CYP27B1, both of them will hydroxyllate. And
	+	that 1,25-dihydroxillate with activate (highlight moves to
	+	activate) the VDR and allow the VDR to do the gene transcription
	+	that is at the heart of innate immunity.
	+
	+
	+	And then finally, the 1,25-D is inactivated (highlight opens on
	+	lower left "Inactive 24,25 & 25,26") by the VDR up regulating this
	+	CYP24 enzyme so that you don't end up with too much of it in the
	+	body.
	+
	+	And that is what goes wrong in Th1 disease. You end up with too
	+	much 1,25-D in the body because the VDR inactivation path —
	+	something goes wrong with it.
	+
	+
	+	Well, OK. Here we have some pretty pictures. We have atoms and
	+	bonds. The grey atoms (highlight upper left picture, left grey atom
	+	selected highlight in video) are carbons, the red ones are oxygen,
	+	that green is a fluorine, That's a hydroxy OH there (highlight
	+	moving from green to lower center red/grey center bottom), the
	+	light blue is the H of the hydroxy. And this molecule is
	+	Dexamethasone in exactly the configuration where it binds into the
	+	Gluco-Corticoid Receptor (GCR binding pocket), you know the
	+	adrenal axis, the Gluco-corticoid receptor.
	+
	+	And here (video highlights lower right figure center), we see 1,25-
	+	Dihydroxyvitamin D competing with Dexamethasone for the
	+	binding pocket of the GlucoCortocoid receptor.
	+
	+	1,25-D has a very high affinity for the adrenal axis. This is new, it
	+	is not in the syllabus, it's taken from a paper which was accepted
	+	for the nuclear receptors conference next week, actually.
	+
	+
	+	So what does that mean? If we go back to our nice simple adrenal
	+	axis, what does that mean?
	+
	+	Well it means that (highlight focuses on top black box 25-D and
	+	1,25-D) 25-D and 1,25-D can both bind into the GlucoCortocoid
	+	Receptor and displace Cortisol from doing that.
	+
	+	When it does that, the amount of CRH and particularly ACTH is
	+	down regulated, and you end up with Adrenal Insufficiency
	+	(highlight on lower black box "Adrenal Insufficiency").
	+
	+
	+	OK, the vitamins D also compete for the Thyroid binding pocket.
	+	I'm talking about the alpha thyroid here, the important one.
	+	There we have T3 as it docs into the alpha thyroid to activate the
	+	alpha thyroid (highlight shows green end molecules on the top left
	+	illustration). These are the iodine molecules, three of them of
	+	course.
	+
	+	Here we have 1,25-D competing (highlight center of lower R
	+	figure) with T3 for the alpha thyroid Binding Pocket. It wants to
	+	dock in exactly the same binding pockets as the T3 would. And by
	+	doing that in high enough concentration, it will stop the T3 from
	+
	+	binding. It will stop the alpha thyroid from working properly.
	+	We end up with, among other things, hypothyroidism.
	+
	+	So I've done a summary slide here of the operation of the VDR. It
	+	is key to both the endocrine and immune systems.
	+	The VDR is responsible for decreasing parathyroid Hormone
	+	Transcription. [Reference slide to TLR4], and therefore the
	+	bacterial response.
	+
	+	Toll-like Receptor 4 is responsible for sensing
	+	lipopolysaccarhride. Toll-like Receptor 2 is responsible for
	+	sensing the presence of other bacteria protein. When the VDR is
	+	not working, because you have administered vitamin D and are
	+	experiencing the immuno suppressive action of the vitamin D,
	+	when the VDR is not working, you do not have a functioning TLR2
	+	and TLR4 system.
	+
	+	But you also lose the antimicrobial peptides. It transcribes the
	+	cathelicidin antimicrobial peptide (cAMP) and it's also responsible
	+	for beta defensins. The beta defensins are absolutely key to the
	+	proper operation of small intestine. The small intestine, in fact,
	+	the whole GI tract is critically dependent on the defensins and
	+	especially the beta defensins and the cathelicidins to work
	+	properly. When you knock out the VDR with immunosupression
	+	— either a steroid or 'vitamin' D — you lose that ability.
	+	And finally, the VDR is responsible for binding the interluken 2
	+	(IL2) promoter. Now you all probably know that you measure
	+	interluken 2 when you want to measure a Th1 reaction. Well, that
	+	is why, because the VDR actually produces the interluken 2, even
	+	if you can't measure it.
	+
	+	I've got some other functions there, I guess the main one there is
	+	it regulates the TACO gene, which is responsible for
	+	mycobacterium tuberculosis intraphagocytic survival, and it
	+	promotes transcription of Insulin Receptors.
	+
	+	Let's skip the rest because we're running a little late bit short in
	+	time.
	+
	+
	+	The current status of the VDR is that the VDR is responsible for
	+	TLR2 and TLR4 expression, as well as cAMP... hey, I just said that
	+	on the previous slide! Sorry.
	+
	+	What we've got here is two pictures and we have all the vitamin
	+	D's (video highlights left image) superimposed. We've got 1,25-
	+	Dihydroxyvitamin-D, that's the one that has the activating hydroxyl
	+	(highlight arrow and red atom in lower right of left image) here,
	+	the only one that can activate the VDR. Various other atoms can
	+	activate the GCR or de-activate the GCR and the thyroid, but the
	+	only one that will activate the VDR is this one (highlight again on
	+	arrow and red atom) on the 1,25-Dihydroxy. But you can see that
	+	all the vitamins D fit into the receptor in almost identical
	+	positions. Whether it is 24,25-D, 25,26-D or 1,25-D. Even
	+	vitamin D itself fits in there as well and they are all competitive.
	+	If you're giving people 40mg, if you're giving people vitamin D
	+	such as such as to get the blood concentration at 25-D to 40
	+	nanograms per ml, then you're sitting with 25-D in most of your
	+	VDRs and they are NOT activated, it is immuno-suppressive. The
	+	patient will feel better short term because the inflammation is
	+	suppressed. Long term, with the bacterial pathogens running right,
	+	it's a different situation.
	+
	+	The picture on the right hand side just shows olmesartan binding
	+	into the VDR pocket and you can see if you look at it carefully, you
	+	can see that the olmesartan hydroxyl here (video highlights upper
	+	right atoms O1 and O2 in lower right of right image) are actual
	+	capable of activating the VDR in the same way as 1,25-D does.
	+
	+
	+	So, we've got some little pictures here. We have 2 molecules.
	+	What we have here is the steroid rings (video highlights right
	+	image, upper right rings of molecule) of prednisone. This is
	+	actually prednisone.
	+
	+	We have the steroid rings of prednisone, and over here (video
	+	highlights middle two rings on left figure) we have the steroid rings
	+	of "vitamin" D. What I wanted to show you was that you've got the
	+	steroid rings.... I want to show you the only difference between the
	+	secosteroid and the steroid is one bond. It's this carbon to carbon
	+	bond across here (highlight shows critical top left ring closure of
	+	right image, in 2nd ring from left). And it is missing across here
	+	(highlight now shows open ring in left image in the 2nd ring from
	+	left) in the seco-steroid. And that is why it is a secosteroid rather
	+	than a steroid.
	+
	+	It is a very subtle change, it actually gives the [vitamin D] [not VDR]
	+	more flexibility to move in a socket and that is one of the reasons
	+	why it binds into so many of the nuclear receptors. The structural
	+	similarity (video highlights cortisone bond again) between
	+	prednisone and vitamin D basically come down to that one carbon
	+	bond. And that is why it is a secosteroid and not a corticosteroid.
	+
	+	So I have a slide here on Vitamin D in Bone Remodeling because I
	+	know all of you are going to say "well, If I withdraw vitamin D from
	+	my patients, their bones are going to get weaker." This gives you
	+	some up to date citations you can go away and look at, which
	+	show that actually "vitamin" D is not really responsible for calcium
	+	at all. It's the Calcium Sensing Receptor and the Parathyroid
	+	hormone that are responsible for Calcium homeostasis. And
	+	secondly, even the cannabinoid receptors play a key role in bone
	+	remodeling and bone mass. That paper is only a few weeks old.
	+	The sex hormones are also players in bone density, I think you
	+	know that one.
	+
	+	And that elevated levels of 1,25-dihydroxyvitamin-D, such as we
	+	have found to be associated with Th1 immune disease, actually
	+	encourage osteoclastic actions and breakdown of bone and
	+	deposition of bone into soft tissue. The last thing you want in these
	+	patients is high levels of 1,25-Dihydroxyvitamin-D.
	+
	+	So this has got a "not in syllabus" picture because the text that I
	+	had in the syllabus was a lot more caustic. This is diluted.
	+
	+	Public-Health Consequences of Regarding 'vitamin D' as a
	+	'Vitamin.' Sometime during the 20th century, we began to view
	+	"Cholecarciferol' as a 'Vitamin' rather than recognizing its steroidal
	+	and hormonal activity. And we put the seco-steroid
	+	'Cholecarciferol' into the food chain, in a futile attempt to eliminate
	+	the rare disease, Rickets. And as physicians, you would know the
	+	side effects from administration of steroids.
	+
	+	So the CDC now says we are heading towards half of all US
	+	seniors being Diabetic by the year 2050.
	+
	+	And, Oh, steroids often induce obesity. I'll leave you to connect the
	+	dots.
	+
	+	I haven't said anything about bacteria yet. When I was trying to
	+	figure out how Sarcoidosis patients could be made sick in the
	+	absence of antibodies, this paper was published back in late 2001
	+	on the Internet, and what it showed was Rickettsia Helvetica inside
	+	Phagocytes (video highlights upper right image E at two arrows).
	+	Persistent inside phagocytes, not broken down by phagocytosis but
	+	actually living in the phagocytes of Sarcoidosis patients.
	+	That was the Eureka moment for me. I should have known it, there
	+	is plenty of other literature talking about mycobacterium being
	+	intraphagocytic, but that was the actual paper.
	+
	+
	+	And then the real studies that you all will want to see if you are
	+	interested in the actual pathogens, were the Wirostko Studies from
	+	Columbia University in the late 80's. There are bout 30 or 40
	+	electron transmisional microscopy photographs showing stained
	+	bacteria. Tiny, tiny colonies (video highlight shows lower left arrow
	+	circle of bacteria, then moves to second to left arrow colony, to
	+	middle arrow pointing to colony and then to upper right arrow) of
	+	stained bacteria in the phagocytes. This is a quarter of a
	+	macrophage.
	+
	+	And they were very thorough, they did macrophages, monocytes,
	+	lymphocytes and neutrophils. And they found that in the
	+	Sarcoidosis patient, they found the intraphagocytic bacteria
	+	persistent in all of them.
	+
	+	And in fact, the nucleus here (video highlights heavy bolded arrow
	+	left of center pointing to nucleus) is breaking away a little bit near
	+	this larger colony of bacteria (video highlights second lower left
	+	small arrow). That's why it has the big arrow on it.
	+
	+	Fascinating photographs. Very important if you want to understand
	+	the actual bacterial pathogens, the L-forms that cause these
	+	diseases (cell wall deficient bacteria called L-forms for the Lister
	+	institute where they were first identified). They are tiny pathogens.
	+	They are so small. They are hundredths the diameter of the
	+	macrophage. I've got 200 nanometers here (video highlights lower
	+	right slide legend). We're talking about cocciodes, tiny little dots
	+	that are about 10-15 nanometers in diameter.
	+
	+
	+	These are pictures that show the diagrammatically show the
	+	survival of bacteria in the phagocyte. I've covered these in my 30th
	+	anniversary of Lyme meeting and with your permission, I'll skip over
	+	this. You can find it in any book. (because we're running late on
	+	time).
	+
	+	Bacterial protein synthesis, and remember I talked about the 70S
	+	Ribosome, the bacterial Ribosome. Here we actually have the
	+	structure of the bacterial Ribosome, it is primarily made up of RNA,
	+	unlike the human ribosomes which are primarily protein based.
	+	But the 16S RNA (video highlights the lower left 16S rRNA on
	+	figure), which you would all recognize as being the PCR, the
	+	substance which is used as the target for most PCR tests. 16S rRNA
	+	forms the 30S side of the ribosome (video highlights upper left 30S
	+	figure subhead). The top of this 30S we have a heliacal structure
	+	(video highlights top left ribbons) which is responsible for translate
	+	but actually for ... translating the mRNA into a protein.
	+	The actual translation is done on the 50S side, you can see a
	+	protein (video highlights lower right quadrant) coming out the
	+	bottom here and it's in yellow. The protein transferase center
	+	(video highlights middle, slightly right) is right in the center which
	+	you see, and there we have tRNA (video highlights blue grape
	+	cluster mid top) which is donating the amino acid into the growing
	+	protein.
	+
	+
	+	And this is an Xray structure, which was produced from the Max
	+	Planck group in Germany, and this x-ray structure shows a
	+	number of antibiotic molecules found in, you can look at them in
	+	your syllabus', but the one's we're interested in primarily are the
	+	tetracycline. And in fact, the tetracycline binds right at the top
	+	(video highlights top of 30S Sub-unit, see Orange color), and
	+	inhibits RNA translation.
	+
	+
	+	On the 50S side, you can see how the protein is assembled and
	+	exits the exit tube a little more easily. And in particular, the
	+	important thing is here, you will notice that Clindamycin (video
	+	highlights center formation), just the light orange one, sits right at
	+	the PTC. And the Azythromycin sits a little bit below it, so they are
	+	actually symbiotic antibiotics.
	+
	+	All three antibiotics that we use are symbiotic. That means that
	+	each of them progressively reduces the function of the [bacterial]
	+	ribosome. That means that when you give them together, they are
	+	not competing with each other, they're complementary. It is
	+	symbiotic. Very important. Something that the genome, the
	+	bacterial genome, has told us quite clearly.
	+
	+
	+	So now we talk about the species.
	+
	+	Which species of bugs is it?
	+
	+	Well, it is not a single species. We're dealing with a polymicrobial
	+	disease. If you look at the various diseases, and the bacteria that
	+	have been reported with them all, the common ones like Staph-
	+	aureus and Propionibacterium-acnes, Propionibacterium-
	+	granulosum, seem to be the ones that crop up most of all, with the
	+	nasty bugs, micobactera cropping up far less frequently. And
	+	certainly less than 100%.
	+
	+	So we're almost certainly dealing with a polymicrobial disease.
	+	And depending on the exact mix of pathogens, determines which
	+	of the Th1 diseases, which of the Th1 symptom syndromes the
	+	patient will progress to. Whether it turns into Rheumatoid Arthritis,
	+	Multiple Sclerosis, or Anorexia Nervosa.
	+
	+	It's become obvious that most bacteria species are not
	+	homogenous. They've got not only the chromosome, but also the
	+	self-replicating plasmids which carry DNA and genes. Borrelia
	+	burgdorferi has got a large number of plasmids, in fact, nearly half
	+	of its genome exists on 21 self-replicating plasmids sub-units.
	+	Now I'm not saying that makes it any more strong of a pathogen,
	+	but it certainly adds quite a lot to the "Pea Soup" which I like to
	+	think of as mix of DNA which accumulates in the chronic diseases.
	+	Yet even Staph. epidermidis gives rise to plasmids. It's got about
	+	10% of its DNA spread over six self-replicating plasmids.
	+
	+	These can be shared between species. But the plasmids are not
	+	targeted by antibiotics. Antibiotics don't target plasmids. Only the
	+	innate immune system can go after the plasmids. So unless the
	+	plasmids are destroyed by the immune system, they will persist in
	+	chronic intra-cellular infections.
	+
	+	And I think of it as a "DNA Pea-Soup."
	+
	+
	+	Plasmids do transmit DNA horizontally. Notice the citation here, it
	+	was published in the Proceedings of the National Academy of
	+
	+	Sciences in 2004. And what you had was, you had a patient that
	+	got very, very ill with a species of Bacillus cereus. Now, Bacillus
	+	cereus, we all know is a [relatively] harmless bacteria. It's a
	+	Bacillus that doesn't cause the body [much] trouble, it clears it
	+	(video highlights B.cereus yellow circle on figure, upper right of
	+	center).
	+
	+	Whereas just a little bit further around on the phylogeny here, we
	+	have Bacillus-anthracus (video highlights red spike circle far upper
	+	right). And what distinguishes Bacillus-anthracus is 2 plasmids.
	+	One plasmids contains the ability to evade the immune system, the
	+	proteins that give it the ability to evade the immune system, the
	+	other plasmids carries the ability to produce a cytokine storm and
	+	kill the host.
	+
	+	Now what happened in this case was the two plasmids from
	+	anthracus were transferred into cereus and formed an extremely
	+	toxic combination.
	+
	+
	+	And you can see that the mice that were just challenged with
	+	cereus, they all survived (video highlights upper center double red
	+	circles on figure 4).
	+
	+	Those that were challenged with anthrax (video moves down to
	+	yellow circle dropping line) -which color is anthrax? yellow- most
	+	of them died.
	+
	+	BUT they died a lot quicker if they were the hybrid (video highlights
	+	green circle line) of the anthrax plasmids and the cereus genome.
	+	This is a big, big problem!
	+
	+	Why is it a problem?
	+
	+	Well, (video returns to first horizontally slide) if you look further
	+	around on this phylogeny (video highlights B thuringiensis
	+	israeliensis, mid far left green triangle), you'll find here Bacillus
	+	thuringiensis Israelensis. That one is sprayed onto agricultural
	+	crops as a herbicide. Sorry, it is an insecticide.
	+
	+	Anyway, you might have noticed, for example, Garth Nicholson
	+	found a higher incidence of autism in the agricultural areas. This
	+	fellow (video highlights B thuringiensis israeliensis) is sprayed in the
	+	agricultural areas.
	+
	+	If the chronic infection allows the plasmids to spread, these people
	+	will get very ill.
	+
	+	The final thing that I want to show is that the pathogens actually
	+	persist in the brain.
	+
	+	This [slide] is taken from a paper by Rolf Zinkernagle, whom I was
	+	lucky to meet at Karolinska, the home of Team Nobel. Rolf gave
	+	the keynote speech there back in May [2006]. And what they
	+	found they've done, is they injected the brains of mice at a very
	+	young age (video highlights A - neonate mice figure upper right
	+	figure), neonatal in fact, with a virus. And this is injected before the
	+	mice have an adaptive immune system.
	+
	+	As you all know, the adaptive immune system in humans and mice
	+	takes some time to kick in (video highlights top time line center,
	+	showing Time after rLCMV/INDG). I think these are helper cells
	+	coming up to indicate the adaptive immune system has kicked in
	+	after about 7 days.
	+
	+	But when the mice are born, the only thing they have to protect
	+	themselves is the innate immune system. You know, the thing we're
	+	knocking out with 'vitamin' D.
	+
	+	Anyway, what Rolf did was, he showed that if they injected this virus
	+	during this period, it remained dormant in the mouse. And later,
	+	when a similar virus was used to challenge the mouse, It killed
	+	them (video highlights upper right dead mouse figure).
	+
	+	Whereas mice that were challenged in adulthood by the same
	+	virus (video highlights lower left time line, far left), injected by the
	+	same pathway were not killed when they were re-challenged, in
	+	fact, they survived primarily.
	+
	+	This is a fascinating paper, it is quite detailed with citations there at
	+	the bottom [of the slide]. And Rolf is working on dispelling a myth
	+	of autoimmunity — or response to self — by showing occult
	+	viruses can, in fact, can exist and they can indeed persist in the
	+	brain. Very important when we are trying to understand the
	+	symptoms of our patients.
	+
	+	And here is the slide from Professor Bach, Jean-Francois Bach,
	+	which was presented in Budapest in 2004. Jean-Francois Bach
	+	was the person who proposed the hygiene synthesis.
	+	But what he found was that bacteria, the particular strain of mice
	+	called non-obese diabetic mice (NOD), where typically 60% of
	+	them died (video highlights upper right dark dot line) from
	+	diabetes — type 1 diabetes during their lifetime — that if he
	+	injected them early enough with a mix of common bacterial
	+	proteins, that they survived (video highlights cyan and yellow end
	+	point line).
	+
	+	And the ones that survived best were the ones that got the
	+	bacterial proteins earlier in life than later in life (video highlights
	+	magenta square dotted line lower right).
	+	Again, another fascinating insight into exactly how these diseases
	+	persist and why some people get ill, and other people carry the
	+	bacteria and don't get ill.
	+
	+	Because it is no secret that the NIH/NHLBI did a study in 2001
	+	where they tested with PCR, they tested the blood of controls. No,
	+	they didn't use PCR, they cultured the L-form using Wayne State
	+	Lyda Mattman's technology. And they found 60% of their controls
	+	were carrying L-forms in the blood. Supposedly a sterile
	+	compartment.
	+
	+	This has since been confirmed by the Relman Lab, Dave Relman
	+	up at Stanford published a paper in the last year, where he too has
	+	noted that 60-80% of the population are carrying around bacterial
	+	RNA in their blood. It should not be there. Many of them, most of
	+	them in fact, are not ill or certainly not diagnosably ill. Some
	+	however, regress to really serious illness. It all depends on the DNA
	+	mix and how the mutations progress in life.
	+
	+
	+	So just a few quick final thoughts that my colleagues at FDA felt I
	+	had to put in because I am talking to clinicians here, [are] just the
	+	simple stuff again.
	+
	+	Final thoughts, if you are thinking if your patient might in fact be
	+	suffering from Th1 diseases, then the therapeutic probe is really
	+	the gold standard. That's because it is greater than 95% response
	+	rate. Most of the patients will immediately feel immunopathology.
	+	They'll immediately feel more ill when they start taking the
	+	antibiotics. At that point you know that you are killing bugs. You
	+	know that these people are responding.
	+
	+	The only thing I would say is 25-D levels above about 20ng/ml
	+	you will be getting immuno-suppression there and it will be
	+	suppressing the therapeutic probe. So you need to be somewhat
	+	careful about the 25-D level before initiating a therapeutic probe.
	+	Hypotension is not a concern, even though we are using an
	+	angiotensin-receptor blocker. These are the graphs from the FDA
	+	describing insert, the package insert [see slide figure]. As you can
	+	see, the maximum drop is about 12 millimeters of mercury [12mm
	+	Hg], and that value is independent of dose. You can see the dose
	+	along the bottom here the response tops at 40mg. It is not a very
	+	good hypotensive. Benicar is not a very good hypotensive. Luckily,
	+	it does other things as well like protect the kidneys, and protect the
	+	eyes and all the other things that you are reading about in the
	+	clinical literature right now.
	+
	+	Hypotension is not a concern.
	+
	+	Dizziness. When the patients get dizziness, especially in the first
	+	month, it's usually a sign of the disease process. It is not
	+	hypotension. It's actually better to increase the Benicar to give
	+	them a better blockade than to back off the Benicar.
	+	There is no way you can start with a low dose and work up. You've
	+	got to have those receptors being blocked, all the receptors being
	+	blocked, or it doesn't work properly. You will increase the
	+	immunopathology with only a low dose. That means the patient
	+	will get, "Herxheimer" if you wish, they will get ill from only a low
	+	dose of Benicar, but they won't get the palliative effects, they won't
	+	get the renal-protective effects, until the dose goes up.
	+	So it is very important to give them the correct dose so they are
	+	actually going to make it through the therapy and kill those bugs
	+	off.
	+
	+	The only thing I didn't mention was how long it would take: three
	+	to five years for the seriously-ill patients to totally get their lives
	+	back. Most of them are happy with some form of recovery. They
	+	see the light at the end of the tunnel after about six months. Very
	+	few have not seen the light by twelve months but actually, they are
	+	symptom free or say they are symptom free at about two years. But
	+	all that means is they are getting along from day to day very nicely
	+	and much better than they were before. There is still a lot of
	+	disease present, they are still getting a lot of reaction to the
	+	antibiotics.
	+
	+	It takes about another two years to where they can just guzzle the
	+	antibiotics like candy. At that point, the bacterial load is low
	+	enough for them to pronounce recovery.
	+
	+	Thank you.
	+
	+	{{tag>presentations videos Trevor_Marshall_PhD AAEM 2006}}

Presentation - Olmesartan overcomes antibiotic resistance, inducing recovery from advanced ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

05.02.2011		current
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-	<note>Dear MPKB Reader: You have arrived at an article that has not yet been completed. Thanks for your patience.</note>

	Type: Conference presentation\\		Type: Conference presentation\\
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	<blockquote>		<blockquote>
-	Vitamin D affects the immune system at many levels and by a number of mechanisms .. Vitamin D has multiple immunosuppressant properties .. On the whole, vitamin D confers an immunosuppressive effect.(({{pubmed>long:17557889}}))	+	Vitamin D affects the immune system at many levels and by a number of mechanisms .. Vitamin D has multiple immunosuppressant properties .. On the whole, vitamin D confers an immunosuppressive effect.(({{pmid>long:17557889}}))

-	The possible involvement of vitamin D //deficiency// in the development of autoimmune diseases has recently gained interest .. the impact of the vitamin D pathway on immune function .. its influence on both autoimmune diseases and cancer should be further elucidated. (([[http://www.ima.org.il/imaj/ar10mar-11.pdf\|The Role of Vitamin D in Regulating Immune Responses]]))	+	The possible involvement of vitamin D //deficiency// in the development of autoimmune diseases has recently gained interest .. the impact of the vitamin D pathway on immune function .. its influence on both autoimmune diseases and cancer should be further elucidated. (([[https://www.ima.org.il/imaj/ar10mar-11.pdf\|The Role of Vitamin D in Regulating Immune Responses]]))
	</blockquote>		</blockquote>

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	{{:home:publications:marshall_autoimmunity_2010:2010ai_marshall_slide3.jpg?630 \|click to to view slide}}		{{:home:publications:marshall_autoimmunity_2010:2010ai_marshall_slide3.jpg?630 \|click to to view slide}}

-	Vitamin D is important because it's associated with a nuclear receptor called the VDR. The VDR is a nuclear receptor which is diagrammatically shown here as just one element inside a cell. You have a macrophage. Here a nucleus cytoplasm. All of the things going on in the cytoplasm. If you want more details you can look on Wikipedia, or you can look in Nature Clinical Practice at this citation here.(({{pubmed>long:18212810}}))	+	Vitamin D is important because it's associated with a nuclear receptor called the VDR. The VDR is a nuclear receptor which is diagrammatically shown here as just one element inside a cell. You have a macrophage. Here a nucleus cytoplasm. All of the things going on in the cytoplasm. If you want more details you can look on Wikipedia, or you can look in Nature Clinical Practice at this citation here.(({{pmid>long:18212810}}))

	The VDR is important both for adaptive immunity, the T and B lymphocyte function outside the macrophage. And it's particularly important for innate immunity. It transcribes cathelicidin, TLR2, and the defensins inside the macrophages. The main defenses that our phagocytes have against pathogens getting inside the immune system.		The VDR is important both for adaptive immunity, the T and B lymphocyte function outside the macrophage. And it's particularly important for innate immunity. It transcribes cathelicidin, TLR2, and the defensins inside the macrophages. The main defenses that our phagocytes have against pathogens getting inside the immune system.
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	{{tag>presentations videos Trevor_Marshall_PhD 2010}}		{{tag>presentations videos Trevor_Marshall_PhD 2010}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

	Add this to heading after the PDF is completed:		Add this to heading after the PDF is completed:
	<html><form>		<html><form>
-	<a href="http://AutoimmunityResearch.org/transcripts/2010AI_Marshall.pdf"><input type="image" name="Submit" value="Download as PDF" src="http://mpkb.org/_media/home/downloadpdf.gif"; class="buttoncalc hide" /></a>	+	<a href="https://AutoimmunityResearch.org/transcripts/2010AI_Marshall.pdf"><input type="image" name="Submit" value="Download as PDF" src="https://mpkb.org/_media/home/downloadpdf.gif"; class="buttoncalc hide" /></a>
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-	===== References =====	+	===== References =====</nodisp>

Paper - Sarcoidosis succumbs to antibiotics: implications for autoimmune disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

09.10.2010		current
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	Authors: Trevor Marshall PhD, Frances E. Marshall\\		Authors: Trevor Marshall PhD, Frances E. Marshall\\
	Publication: //Autoimmunity reviews//\\		Publication: //Autoimmunity reviews//\\
-	Citation: {{pubmed>long:15246025}}\\	+	Citation: {{pmid>long:15246025}}\\
-	See also: [[http://yarcrip.com/sarcoidosissuccumbs-preprint.htm\|Preprint]] (full text)\\	+	Notes: Paper based on presentation ([[https://www.kenes.com/autoim2004/program/ViewAbstract.asp?SerialKey=308065\|abstract]]) given at [[https://www.kenes.com/autoim2004/\|4th International Conference on Autoimmunity]], Budapest, Hungary Nov 2004
-	Notes: Paper based on presentation ([[http://www.kenes.com/autoim2004/program/ViewAbstract.asp?SerialKey=308065\|abstract]]) given at [[http://www.kenes.com/autoim2004/\|4th International Conference on Autoimmunity]], Budapest, Hungary Nov 2004	+
		+
		+
		+	<html>
		+	<a href="https://yarcrip.com/sarcoidosissuccumbs-preprint.htm"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
		+	</html>
		+
		+

Presentation - Molecular mechanisms driving the current epidemic of chronic disease

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

01.03.2012		current
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	Location: University of Melbourne\\		Location: University of Melbourne\\
	Date: May 22-24, 2006\\		Date: May 22-24, 2006\\
-	Additional content: [[http://autoimmunityresearch.org/transcripts/marshall_bio21_2006.pdf\|transcript and slides]]; [[http://autoimmunityresearch.org/bio21a.ram\|streaming video (.ram file)]]	+	Additional content: [[https://autoimmunityresearch.org/transcripts/marshall_bio21_2006.pdf\|transcript and slides]]; [[https://autoimmunityresearch.org/bio21a.ram\|streaming video (.ram file)]]

	===== Transcript =====		===== Transcript =====

	This presentation is available on the DVD "The Science —		This presentation is available on the DVD "The Science —
-	Marshall Protocol" available upon request from the [[http://www.AutoimuunityResearch.org\|Autoimmunity	+	Marshall Protocol" available upon request from the [[https://www.AutoimuunityResearch.org\|Autoimmunity
	Research Foundation]].		Research Foundation]].
-	A lower quality real-time streaming version may be found at [[http://autoimmunityresearch.org/bio21a.ram\|this URL]].	+	A lower quality real-time streaming version may be found at [[https://autoimmunityresearch.org/bio21a.ram\|this URL]].


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	And we'll see if there are any questions.		And we'll see if there are any questions.

-	{{tag>presentations Trevor_Marshall_PhD 2007}}	+	{{tag>presentations Trevor_Marshall_PhD 2006}}

Paper - Vitamin D discovery outpaces FDA decision making

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

09.10.2010		current
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	Author: Trevor Marshall, PhD\\		Author: Trevor Marshall, PhD\\
	Publication: //Bioessays//\\		Publication: //Bioessays//\\
-	Citation: {{pubmed>long:18200565}}\\	+	Citation: {{pmid>long:18200565}}\\
-	See also: [[http://trevormarshall.com/BioEssays-Feb08-Marshall-Preprint.pdf\|Preprint of article]] (full text); [[http://autoimmunityresearch.org/Bioessays_reply_may08_preprint.pdf\|Preprint of author's full text reply to correspondence from Drs. Grant, Garland, and Boucher]]	+	See also: [[https://autoimmunityresearch.org/Bioessays_reply_may08_preprint.pdf\|Preprint of author's full text reply to correspondence from Drs. Grant, Garland, and Boucher]]


		+
		+	<html>
		+	<a href="https://trevormarshall.com/BioEssays-Feb08-Marshall-Preprint.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
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	{{tag>papers Trevor_Marshall_PhD 2008 vitamin_d}}		{{tag>papers Trevor_Marshall_PhD 2008 vitamin_d}}
-

Presentation - The VDR nuclear receptor is a novel proxy for MTSS1 and MTUS1 in breast, bladder ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

08.17.2009	current
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	+
	+
	+	~~NOTOC~~
	+	====== Presentation - The VDR nuclear receptor is a novel proxy for MTSS1 and MTUS1 in breast, bladder and colorectal cancers ======
	+
	+	{{ vimeo>6110400}}
	+
	+	Type: Conference presentation\\
	+	Presenter: Prof. Trevor Marshall\\
	+	Conference: 4th China Medicinal Biotech Forum\\
	+	Location: Dailan, China\\
	+	Date: August 7, 2009\\
	+	See also: [[https://autoimmunityresearch.org/transcripts/CMBF_2009_Dalian_Transcript.pdf\|Transcript with slides]]
	+
	+
	+	===== Abstract =====
	+
	+	Metastasis Suppressor 1 (MTSS1) is a gene encoding the protein Missing In Metastasis (MIM). MIM is
	+	large (circa 750 residues, 82kDa), with an actin-binding motif near its C-terminus. MTSS1 has been
	+	implicated in breast, ovarian and fallopian tube carcinomas, as well as gastric, colon, bladder and lung
	+	cancers. MIM acts on the actin cytoskeleton, although the mechanism is not completely understood.
	+	There is no drug available which directly targets MTSS1. However, recent studies have shown that
	+	MTSS1 is principally expressed by the activated VDR Nuclear Receptor.
	+
	+
	+	We have been investigating the VDR-agonist Olmesartan in a clinical trial focused on subjects with
	+	autoimmune and chronic inflammatory diseases, and our clinical data raises the possibility that a
	+	VDR-agonist may well have a profound direct effect on the incidence of metastatic cancers. During
	+	seven years of data collection in a cohort of over 700, many of whom have been totally disabled by
	+	their inflammatory disease, no cases of metastatic carcinoma, and only two confirmed carcinomas,
	+	have been reported. One breast ductal carcinoma in-situ (1.1cm in size) was reported, with all lymph
	+	nodes negative for metastatic carcinoma. The subject refused chemotherapy, continuing with the
	+	VDR-agonist study regime. Following resection 31 months ago, no recurrence has been observed.
	+	A high grade non-invasive papillary transitional-cell bladder carcinoma was found in another subject,
	+	who also refused chemotherapy in favor of the VDR-agonist. Following a transurethral resection, there
	+	has been no recurrence in the subsequent 30 months. Both of these carcinomas were judged to have
	+	most probably been present before the subjects were enrolled in the VDR-agonist trial.
	+
	+
	+	It must be noted that expression of the Mitochondrial Tumor Suppressor 1 (MTUS1) is down-regulated
	+	by the VDR. However, this may be offset by Olmesartan's direct action on the Angiotensin signaling
	+	pathways, which seem to be a primary target of MTUS1.
	+
	+
	+	Our initial clinical data shows that the VDR-agonist Olmesartan may be useful in the prevention of
	+	metastatic carcinomas, probably via up-regulation of MTSS1 expression, and more study is warranted.
	+
	+
	+	===== Transcript =====
	+
	+	The VDR and Metastasizing Cancers\\
	+	By Trevor Marshall\\
	+	China Medicinal Biotech Forum,\\
	+	Dalian, China, on August 7, 2009\\
	+
	+	<sub>00:00:00</sub> \\
	+	Greeting
	+
	+	Thank you Mr Chairman and thank you all for coming here today.
	+
	+
	+	<sub>00:00:30</sub> \\
	+	**The VDR Nuclear Receptor is a Novel Proxy for MTSS1 \\
	+	and MTUS1 in Breast, Bladder and Colorectal Cancers**
	+
	+	I'm going to talk about Translational medicine, actual clinical data, and how that clinical data sits in the molecular regions.
	+
	+	What I am going to talk about is the VDR nuclear receptor and why it should be pointing us towards MTSS1, particularly, in some of the more common cancers.
	+
	+
	+	<sub>00:00:43</sub> \\
	+	Pragma: "Everybody Knows Inflammation Induces Cancer"
	+
	+	So I'm going to start off with a Pragma:
	+	"Everybody knows inflammation induces cancer." This was the way that Francesco Marincola of NIH started off his presentation about four years ago at UCSD. It took me totally by surprise and, I think, the rest of the audience. It is a very good way to start.
	+
	+	Everybody knows inflammation induces cancer.
	+
	+	Now what I am going to go on and talk about, though, is question number one: "How?" and question number two: "Can this knowledge, or can this pragma, help us find drug targets?"
	+
	+
	+	<sub>00:01:23</sub> \\
	+	Co-morbidities Among Inflammatory Diagnoses
	+
	+	Well, what is inflammation? There are a lot of inflammatory diseases.
	+
	+	Here is a list of most of the autoimmune inflammatory diseases. There are some other diseases, for example, depression here, which was mentioned in some of the keynotes this morning as being a key problem now in China. And ... and all the standard allergies, Sjogren's, Thyroiditis, periodontal disease, inflammatory bowel disease; all of the autoimmune diseases.
	+
	+	Now what is interesting is this chart took a number of studies out of PubMed and it showed the co-morbitidies within the cohorts of people that had, for example, allergies, also typically had thyroiditis; typically had asthma. It shows the co-morbidities.
	+
	+	In other words, inflammation is not unique. It is so easy for us to think that because somebody has got a diagnosis of rheumatoid arthritis, that that is the only inflammatory disease they are suffering from. It is very unusual that it is a unique inflammatory disease.
	+
	+	In fact, in our own study, we did a lot more co-morbidity studies. You can see that the co-morbidity trajectories are even wider than they were in the PubMed search.
	+
	+	Why? Why could this be?
	+
	+
	+	<sub>00:02:49</sub> \\
	+	The NIH Human Microbiome Project
	+
	+	Well, the NIH started up, a year or two ago, the Human Microbiome Project to try and identify whether the human body really is a sterile compartment as clinical medicine has assumed for so many years.
	+
	+	Initially, what is studied is the external cavities, obviously nasal, all the external cavaties. Ultimately, the entire body will be studied and the expectation is that there will be about a million bacterial genes found active compared with about 25,000 human genes.
	+
	+
	+	<sub>00:03:24</sub> \\
	+	Salivary Microbiome
	+
	+	Some of the microbe biomes are starting to come out now. This is some salivary microbiome, and you can see the normal bacteria you had expected to find in saliva in the mouth: Streptococcus, perhaps Haemophilus, Porphyromonas, of course. But look, Neisseria is there in large concentration, and in smaller concentrations, you have got Yersinia and some of the other (Klebsiella) really nasty pathogens. Over a hundred species can be isolated using DNA techniques from the saliva of healthy human subjects.
	+
	+	<sub>00:04:11</sub> \\
	+	Hip Joint Microbiome
	+
	+	You go deeper inside the body and go into the hip joint and look at the composition of the hip joint, you find a different makeup; a different mix of the bacteria being involved. You have got Lysobacter, which is a gliding bacteria you would expect to find that in biofilms, and that is predominant.
	+
	+	But look, down here you have got Hydrothermal vent eubacterium. That is a eubacterium that is previously identified in hydrothermal vents under the ocean, and here it is showing up in the joints during revision arthroplasty.
	+
	+	Many people say that it is contamination; all these pathogens that are found in the body by researchers are contamination. Well, I'm not quite sure where you will get Hydrothermal vent eubacterium in a carefully controlled surgial environment.
	+
	+
	+	<sub>00:05:11</sub> \\
	+	Wirostko TEM study (1989) -- JRA Lymphocyte
	+
	+	But there are other microbiomes as well. Wirostko E. et al., at Columbia University, back in the 1980's, isolated colonies of bacteria, or certainly, entities that stained as bacteria inside the cytoplasm of phagosites. This is Juvenile Rheumatoid Arthritis, inflammatory eye disease, Ocular Leukocytes -- what I think is a Leukocyte -- yes. Molicute-like organisms, biofilm-like organisms. There are some long ones and a round one.
	+
	+
	+	<sub>00:05:48</sub> \\
	+	Video -- Blood With Infected Cytoplasms
	+
	+	We have been able to image the cytoplasms of some of these infected cells exploding, in patients that are very seriously ill, when the blood is allowed to age a little bit -- aged about 6 hours. You can see the whole cytoplasm of this monocyte has disintegrated, and throwing out long extruded polymers here, into the blood stream.
	+
	+
	+	<sub>00:06:15</sub> \\
	+	The VDR Nuclear Receptor
	+
	+	Well, what do we know about what is happening?
	+
	+	What could possibly be allowing persistent pathogens to remain in what we thought was the sterile compartment in the body?
	+
	+	Well, in //Homo sapiens//, and only in //Homo sapiens//, not even in the higher primates, only in //Homo sapiens//, there is one Nuclear Receptor called the VDR Type 1 Nuclear Receptor, which transcribes genes for TLR2, as well as the Cathelecidin, antimicrobial peptides, which are the primary body's intraphagocytic protection mechanism, and also beta-Defensin anti-microbial peptides.
	+
	+	These are essential to the intra-cellular innate immune devenses, so if we knocked out the VDR, then pathogens would be more readily able to persist.
	+
	+	However, when we knock out the VDR, we also cause human chronic disease.
	+
	+
	+	<sub>00:07:16</sub> \\
	+	//Mycobacterium tuberculosis//
	+
	+	If we look at some of the nasty pathogens that have been pretty well studied, //Mycobacterium tuberculosis//, a study here done, published in the Chinese medical journal in 2003, showed that the VDR receptor was down-regulated in monocytic cell line by an MTB infection by 3.3 times.
	+
	+
	+	<sub>00:07:41</sub> \\
	+	//Borrelia burgdorferi//
	+
	+	//Borrelia burgdorferi//, a pathogen that is getting increased attention these days, using a bead (BeadChip) assay which is more sensitive, found a 50 fold down-regulation of the VDR by live Bb, and 8 fold by lysed //Borrelia//.
	+
	+
	+	<sub>00:08:02</sub> \\
	+	EBV -- Epstein Barr Virus
	+
	+	EBV, which is one of these persistent pathogens that you will find in all of the inflammatory diseases. If you think of an inflammatory disease, search for PubMed/the disease name/EBV, and there will be somebody saying that that disease is caused by EBV because it is an omni-present pathogen.
	+
	+	It [EBV] is a very persistent pathogen and when the innate immune system gets weak, it is hard for the innate immune system to clear it.
	+
	+	What is particularly interesting, is you can see VDR (you can see there are a number of Nuclear Receptors quoted here), but VDR is downregulated, particularly in the Lympho-blastoid cell lines, the persistent, long-lasting, immature cell lines, after two months and after one and a half years the VDR is downregulated about 15 times. Very, very strong effect on VDR.
	+
	+	There is also a strong effect on Estrogen Receptor-beta, and that is not unreasonable because Estrogen Receptor-beta is believed to transcribe VDR -- at this point in time -- or express VDR.
	+
	+
	+	<sub>00:09:10</sub> \\
	+	HIV
	+
	+	And then of course, the big-daddy of them all, HIV.
	+
	+	HIV totally takes the VDR, it binds, the 'tat' protein binds, to human VDR and it then steals the VDR so that it can transcribe its own genome, so its long terminal repeats can be recognized and express the HIV RNA from the reverse DNA. So it is actually part of the survival mechanism of HIV to a much greater extent even than of the bacteria that we were talking about earlier.
	+
	+	Now what I want to talk about here is a simple HIV genome transcribes for about seventeen proteins. They are cleaved in to a number of other little proteins, but let us say that about seventeen proteins come from the HIV genome. But yet these seventeen proteins are documented to have over 3000 interactions with the human metabolome.
	+
	+	These seventeen proteins from HIV are documented to have over 3000 interactions within the human body.
	+
	+
	+	<sub>00:10:25</sub> \\
	+	Why the Complexity of Interactions?
	+
	+	Why does this occur [interactions within the human body]?
	+
	+	Well, if we take a human CBP / P300, which has some disordered 'loops' in it, you can see you have got these colored balls [I am indebted to Prof Peter Wright of the Scripps Institute for this image], we have got the colored balls which are structured areas of CBP and then you have got the disordered loops. And depending on what those disordered loops bind to, that will determine where the transcription factors are actually working along the DNA strand.
	+
	+	So what happens in the viruses, particularly, is that most of their proteins are disordered. They can really go after many, and go into many, many different conformations [or conformal shapes], depending on what proteins they are binding to.
	+
	+
	+	<sub>00:11:17</sub> \\
	+	If We Take the Salivary Metagenome....
	+
	+	So if we just look back at that salivary genome of about 100 species, and let us say each specie has about 500 proteins in its genome, and you realize that we are starting off then with 50,000 proteins rather than the seventeen of HIV, you can see we end up with an imponderable complexity of potential interactions between the human metabolome and any pathogen which is capable of persisting inside the cytoplasm of nucleated cells, particularly, inside the cytoplasm of the phagocytes.
	+
	+	Many, many human metabolites are affected by the metagenome, and the sum total of all these interactions gives rise to the totality of symptoms which are suffered during chronic disease; and also, the commonality of many of the symptoms, as well.
	+
	+	The genomes accumulate gradually during life, incrementally shutting down the innate immune system. Genes from the accumulated metagenome determine the clinical disease symptomology.
	+
	+	<sub>00:12:24</sub> \\
	+	The Catastrophic Failure...
	+
	+	The catastrophic flailure of the human metabolism, which we see in chronic inflammatory disease, which at first glance appears to be so diverse, is actually due to a common underlying mechanism -- an apparent ubiquitous microbiota which has evolved to persist in the cytoplasm of nucleated cells by knocking out the VDR nuclear receptor.
	+
	+	<sub>00:12:47</sub> \\
	+	Olmesartan Medoxomil is VDR Agonist
	+
	+	So what will you do? Well, of course you get a VDR agonist. Turn the VDR back on again.
	+
	+	It turns out that Olmesartan Medoxomil is quite an adequate VDR agonist. It forms hydrogen bonds with key amino acids, fits nicely there in the binding pocket, and reactivates the VDR.
	+
	+
	+	<sub>00:13:08</sub> \\
	+	Number of Patients Reporting Symptom Improvement by Diagnosis
	+
	+	When you do that, you suddenly find that you can reverse autoimmune disease. Well, actually, you do not SUDDENLY find you can reverse autoimmune disease, because the reversal recovery process is just about as chronic and as slow as the actual disease process, typically taking three to six years.
	+
	+	We have been running a study now for seven years, a Phase 2 study, in a variety of autoimmune diagnoses.
	+
	+	This [chart] was dated, we presented at the 6th International Congress on Autoimmunity last year [2008] in Porto, Portugal. And you can see a variety of diagnoses: Rheumatoid Arthritis, Hashimotos Thyroiditis, Uveitis, Psoraisis, Psoriatic Arthritis, etc., down to Diabetes Insipidus. The different colors reflect patients who improved in first year, second year, improved beyond second year, etc. (I will give you a copy of these slides afterward if you want more details.)
	+
	+	But the main thing is that eighty-one percent of the cohort experience reduced disease and symptoms between eighteen and fifty-three months, and a significant portion had total disease reversal.
	+
	+
	+	<sub>00:14:24</sub> \\
	+	Carcinomas in Our Cohort
	+
	+	But the thing that I am here to talk about, is carcinomas. Because in 750 subjects, our current reporting cohort, observed over a period of three to seven years, all with disabling, advanced, chronic inflammatory disease, we only had only two documented cases of carcinoma, and neither were metastatic.
	+
	+	There was a breast ductal carcinoma in-situ. All lymph nodes negative for metastatic carcinoma. The subject refused chemo, continuing with the VDR-agonist study-regime. Following resection thirty-one months ago, no recurrence has been observed.
	+
	+	And in another subject, a high grade non-invasive papillary transitional-cell bladder carcinoma was found. That subject also refused chemo in favor of continuing the VDR-agonist therapy. Following a resection, there has been no recurrence in the subsequent thirty months.
	+
	+	Thirty months is just getting to the stage where we can start to say, "Hey, this looks interesting." That is why I am here.
	+
	+	Both of these carcinomas, incidentally, were judged to have most probably been present before the subjects were enrolled in our VDR-agonist trial.
	+
	+
	+	<sub>00:15:44</sub> \\
	+	"Everybody Knows Inflammation Induces Cancer"
	+
	+	So, everybody knows inflammation induces cancer. So why does our study cohort not succumb to cancer? Can it just be a reduction in inflammation which leads to a reduction in carcinomas?
	+
	+	No. I am proposing a more direct relationship between chronic inflammation and cancers.
	+
	+	Chronic inflammation is a result of a diverse intraphagocytic metagenomic metagenomic microbiota. And when this metagenome reduces expression of the host VDR, in order to protect the microbiota against the endogenous antimicrobials, it also knocks out transcription of a key gene -- MTSS1.
	+
	+	If you do an expression map for the VDR, and it was done by Wang, et al., in about 2003. Of the 913 genes whose expression is affected when the VDR is liganded, of the 913 -- confirmed with array -- genes, the number one is CYP24 and the number two is MTSS1, in terms of the degree of expression changed when the receptor is liganded.
	+
	+	This is very important. MTSS1, the Metastasis Suppressor, has been identified as a drug target in carcinomas but it is devilishly hard to make a drug to deal with.
	+
	+
	+	<sub>00:17:10</sub> \\
	+	MIM, 750 aa, 85kDa
	+
	+	It is a large molecule, the exact mode of action is uncertain but it is something to do with actin polymerization and phagocytosis or maybe cytoskeletal reorganization. There is a paper here (where?) which goes into things with a bit more detail. But MIM is the protein which is transcribed from the Metastasis Suppressor Number 1 gene. MIM is "Missing In Metastasis," so obviously, when the VDR is knocked out, MIM is indeed missing. MIM is implicated in breast, ovarian and falopian tube carcinomas, as well as gastric, colon, bladder, and lung cancers. And implicated closely.
	+
	+
	+	<sub>00:17:54</sub> \\
	+	VDR as a Proxy target for MIM, MTSS1
	+
	+	So, what I want to propose here today, is that the VDR is a proxy target for MIM and MTSS1. It has not been reported up until now. Most people ignore the VDR as a Nuclear Receptor.
	+
	+	But MIM is a large molecule, it is a very difficult drug target on its own. A small molecule antagonist will not do and, obviously antibodies are very difficult to design.
	+
	+	I propose that VDR expression and activation is an entirely more suitable topic, a proxy target, and there is both human and murine data to indicate the liklihood of success (I had a murine citation on the previous slide).
	+
	+	Meanwhile, we are collaborating with West China Hospital in Chengdu to institute large-scale Phase 3 trials of the olmesartan VDR agaonist in Autoimmune inflammatory diagnoses.
	+
	+	These trials should also confirm that metastasis and inflammation can indeed be addressed with a singular therapy.
	+
	+	So West China Hospital is moving forward with us to do large Phase 3 trials in inflammatory diagnoses. The first inflammatory diagnoses we are collaborating on is Ankolizing Spondolitis. Over the next few years, it will be very interesting to see how things evolve.
	+
	+	Thank you very much.
	+
	+
	+	----
	+
	+	Questions
	+
	+	__Moderator__: Professor Marshall - any questions?
	+
	+	__Question__: Is there some example of a functional foundation for MIM, for example if a cell is missing MIM does it make more metastatic enzymes? For example, some cells which have MIM, and in those cells that MIM is knocked-down with [antisense] RNA, to see how the metacells will be inhibited or downgraded, is there such an example?
	+
	+	__Marshall__: No, there has been no... well, actually, there has been work on MIM in //those// cancers, which I think include knock-out mouse models. But I haven't been paying a lot of attention to the mouse, the murine, work because as I said in my first slide, the VDR Nuclear Receptor is unique to //Homo sapiens//. In fact, in the murine model, neither Cathelecidin or TLR2 or beta-Defensins are transcribed by the VDR. The murine VDR does not express those. So I guess that is why it has been so hard to get decent animal models for many of the inflammatory diseases.
	+
	+	__Moderator__: Thank you for your presentation.
	+
	+
	+
	+
	+
	+	{{tag>presentations videos Trevor_Marshall_PhD 2009}}

Presentation - The Marshall Protocol in a Clinical Environment - Observations from the Initial ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

01.03.2012		current
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	====== Presentation - The Marshall Protocol in a Clinical Environment - Observations from the Initial Cohort ======		====== Presentation - The Marshall Protocol in a Clinical Environment - Observations from the Initial Cohort ======

-	{{ vimeo>4293599}}	+

	Type: Conference presentation\\		Type: Conference presentation\\
Line 11:		Line 11:
	Location: Prague, Czech Republic\\		Location: Prague, Czech Republic\\
	Date: April 18, 2009\\		Date: April 18, 2009\\
-	See also: [[http://AutoimmunityResearch.org/prague_2009/MP.pdf\|Transcript with slides]]	+	See also: [[https://AutoimmunityResearch.org/prague_2009/MP.pdf\|Transcript with slides]] (video [[https://vimeo.com/4293599\|not available]] )
	===== Transcript =====		===== Transcript =====

Presentation - It is time to bury Koch - Infectious disease transitions to an understanding of ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 06:37:14 +0000

Presentation - Understanding human disease requires study of a metagenome, not just the human genome

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

Presentation - VDR receptor competence induces recovery from chronic autoimmune disease

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

04.21.2009	current
Line 1:	Line 1:
	+	====== Presentation - VDR receptor competence induces recovery from chronic autoimmune disease ======
	+
	+	{{ vimeo>1787405}}
	+
	+	Type: Conference presentation\\
	+	Presenter: Trevor Marshall, PhD\\
	+	Conference: [[https://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]]\\
	+	Location: Porto, Portugal\\
	+	Date: September 11, 2008\\
	+	See also: [[https://autoimmunityResearch.org/transcripts/ICA2008_Transcript_TrevorMarshall.pdf\|Transcript and slides]]; [[https://bacteriality.com/2008/09/22/coa/\|Notes from the 2008 International Congress on Autoimmunity]] by Amy Proal
	+
	+
	+
	+	===== Transcript =====
	+
	+	Thank you. I am going to talk about the VDR receptor. It’s one of the family of nuclear receptors, which includes the glucocorticoid receptor, the thyroid receptors and a number of other very important receptors.
	+
	+	I just want to point out this statement from FDA commissioner Von Eschenbach to congress two years ago, pointing out that “New scientific discoveries are generating an emergent science of safety, where the new science combines an understanding of disease and its origins at the molecular level”. That is what I am going to talk about in this presentation: understanding Autoimmune Disease Pathogenesis at the molecular level.
	+
	+	There are three types of biology in common use today, in-vivo in-vitro and the newer in-silico. The first time I came across in-silico biology was back in 1981. This is a photograph of myself and my colleagues at the Hospital for Sick Kids back in 1981, which was when IBM showed us the in-silico techniques that they had used for the synthesis of the first human insulin. The Humulin, the first human insulin. That was the first time I came across in-silico and realized the power of being able to emulate the operation of the human body at the level of individual atoms.
	+
	+	Since then the in-silico work I think that everybody is most familiar with is the decoding of the human genome and probably more important now, but less well known, is the decoding of around 740 microbial genomes that have been fully decoded to this point in time.
	+
	+	And in fact, NIH has just started a big Human Micobiome Project, with the idea that they wanted to characterize all the DNA that’s available from human sources, all the DNA in the human body. The normal infectious areas that we are aware of: the nasal, oral, skin, GI and urogenital cavities, but also within the cells of the body itself. Because NIH has estimated that around 10 percent of the total cells in the human body are human cells and as many as 90 percent of the cells could be bacterial cells. You will be hearing a lot about the Microbiome project over the next decade.
	+
	+	Why is that important? Well it’s important because the bacterial cells, in many cases, perform functions that are very similar to those of the Homo sapiens itself, of the host. And what I have got here is a slide showing the E.coli Glucose Metabolism. And I know very few of you are going to follow every subtlety of it. Don’t worry; I just wanted to show you that this chart exists. I got this one from Vijay at the Bielefeld University in Germany. But it shows the way that the bacteria E.coli gets from Gluco-6-P substrate down to Pyruvate and produce the Serine Cystein Glycine amino acids, the Purine Nucleotides Adenine, the Tyrosine Phenylalanine, Tryptophan. All of these are produced by bacterial genes. Actually by proteins that are transcribed from bacterial genes – but the bacterium itself, the organism itself is capable of working on exactly the same metabolites as used in the human body for the production of energy and it produces very similar intermediates. You have got Fructose-6-Phosphate here; you’ve got Glycenaldehyde, Glycerade. Many of these intermediate metabolites are very common, very familiar to people who study the human genome. So, if you have got the bacterial genomes working in the same environment within the same cells, in fact infected cells as the human genome and the human body you can imagine the amount of interference between the operation of the two of them.
	+
	+	And that’s exactly what we have found. We have characterized that there is an intra-phagocytic metagenomic microbiota. Metagenomic: many genomes. Microbiota: community of pathogens. Intra-phagocytic: it does its most of its harm inside the phagocytes, the lymphocytes, the macrophages, monocytes of the immune system. And we have shown it to be the cause of most chronic disease. The genomes accumulate gradually during life, incrementally shutting down the innate immune system. They shut down the innate immune system incrementally during life. Genes from the accumulated metagenome determine the clinical disease symptomology depending on what genes accumulated in the metagenome that determines which effects they are going to have on the body, which of the metabolites of the human body are going to be affected by the pathogenic genomes. The microbiota is located in the cytoplasm of the nucleated cells, where it has access to both the DNA gene transcription and the protein translation machinery of Homo sapiens. In addition the host DNA repair mechanisms are susceptible to modification by junk from the metagenome. That’s very, very important. That, because it’s located in the cytoplasm the microbiota can upset the host DNA repair mechanisms.
	+
	+	At the congress in 2004 in Budapest, I reported that sarcoidosis had succumbed to an antibacterial therapy that we had developed. And over the last six years our cohort of over 500 human subjects has demonstrated reversibility of many auto-immune diagnosis. Reversibility, including Lupus, MS, RA, Type 2 Diabetes and Uveitis. My colleagues will give details of this later in this session.
	+
	+	But surprisingly, as the chronic inflammation receded, CFS (Chronic Fatigue Syndrome), osteoporosis, periodontal disease, cardiovascular disease, cognitive deficiencies, obsessive compulsive disorder, bipolar, memory loss, all of these also disappeared, as the chronic inflammatory condition disappeared.
	+
	+	Well, what do these microbiota look like? Here is a monocyte, an infected monocyte and the cytoplasm has effectively exploded from pressure of the pathogens and it is throwing out these tiny biofilm tubules. I’m not quite sure what, it’s not showing up perfectly but you can see here is probably a dozen tiny biofilm tubules. They are very long and they’re also extremely small. You can compare them with the size of the cell, the standard cell diameter there of 4 - 5 microns or so. And extremely tiny little biofilm parlemor tubules are thrown out as the cell disintegrates. This is untreated blood, this is human blood put between cover slips and allowed to age for six to thirty-six hours. Look at the length of these; this is about 26 cell diameters long. This one is about ten diameters long. It’s amazing and you can see them very easily under light microscopy if you are looking for them.
	+
	+	Under the electron microscope, they look a little bit different of course. Because you can actually look at them in the cells before they become heavily parasitized. This is an image from the Emile Wirostko TEM study in 1989 at Columbia University. This is a Juvenile Rheumatoid Arthritis lymphocyte. And what we have: we have the nucleus area of the lymphocyte. And then the cytoplasmic region outside, the nucleus and in the cytoplasmic region there is a staining artifact which is basically nucleic material, DNA material, inside some form of transparent biofilm type of protection and then a very thin exoskeleton to contain the whole lot. But what’s even more interesting are these tiny little elongated structures – which don’t come up all that well on the projection here, but when you look up the original paper -which was JRA Inflammatory Eye Disease, Parasitization of Ocular Leukocytes by Mollicute-like Organisms from 1989- when you look at the original photographs you can see the incredible detail of these transparent colonies that are living inside these lymphocytes. Of course, the lymphocyte should never allow this to happen. But it does allow it to happen because these microbiota have figured out how to overcome innate immunity. They have overcome the last line of defense.
	+
	+	Well, how does it do that? In Homo sapiens the VDR nuclear receptor transcribes genes for the Cathelicidin, beta-Defensin and anti-microbial peptides. It’s also involved in the expression of alpha-defensins as well. And these are key to the intra-phagocytic innate immune defenses. When these anti-microbial peptides and anti-microbial proteins get knocked out, then the phagocytes can no longer protect themselves from attack by the pathogenic microbiota. The microbiota evades the immune system by blocking DNA-transcription by the VDR. It blocks the VDR which consequently blocks expression of these endogenous anti-microbials. The body cannot produce the anti-microbials because the DNA-transcription, the receptor that would do that –express those anti-microbials- is blocked by the pathogens.
	+
	+	The microbiota changes the expressions of greater than 913 genes. And those are genes which do everything from create a parathyroid hormone precursor, right through to create the Missing in Metastasis protein. MTSS1 is the gene; Metastasis Suppressor number one.
	+
	+	All of these genes, the 913 that have already been confirmed, are transcribed by the VDR. The VDR nuclear receptor is a very key nuclear receptor in Homo sapiens. But homeostasis of the other type 1 nuclear receptors isn’t directly upset by these pathogens. The VDR of course but the PXR, the Pregnane Xenobiotic Receptor, the Glucocorticoid Receptor, Thyroid-alpha-1 and Thyroid-beta-1 are all profoundly affected by the elevated levels of the seco-steroid that are caused by the VDR being knocked out. And obviously, note especially a loss of Glucocorticoid and Thyroid homeostasis leads to the diagnosis of hypothyroidism and adrenal insufficiency. We have demonstrated that both of these are reversible.
	+
	+	So why haven’t we seen this microbiota before? There has been so much study of pathogens in mankind. Well there are a few reasons. The first one is that the VDR homology, the shape, the amino acids that go together to make up the VDR, is a little bit different in Homo sapiens to what it is in all of the other mammals and all of the other fish etc. as well which have VDR. And it transcribes different genes from the VDR of the mammals. And you know how much of our work we have been doing in animal models. Well, a very key-function of the bacteria that have evaded the human immune system do not appear in mammals because the VDR homology is so unique to Homo sapiens. The VDR from the murine and canine genomes for example doesn’t transcribe Cathelicidin or the Defensins, at all. So a human metagenomic microbiota won’t survive if it was transfected into, for example, a mouse. Because different species and different mutations would be necessary if the microbiota was to knock out the different gene pathways needed for survival in a mouse.
	+
	+	Further, the microbiota is only stable in-vivo. It defies extraction using standard techniques. You saw how that cell had disintegrated in about six hours of aging. You can imagine what it does under centrifuge. Further, most of these species in the biofilm microbiota defy attempts in-vitro (culture). This is a study from Dempsey et al, which was a study of biofilm from prosthetic hip-joints, which were removed during revision arthroplasties. And they did gene sequencing and tried to match up the 740 known genomes that we have for bacteria against what they found, the DNA that they found in the biofilm. And this is what they found. Lysobacter. Lysobacter was about 44 percent of the clones that were sequenced. Proteobacterium, Methylobacterium, Staphylococcus. Well Staph, Staphorus, you would actually expect to find that in a human biofilm, that’s not unusual. But its size is small, only about 4.2 percent. That is unusual. Unidentified clones… But look at this: Hydrothermal venteubacterium. This was a eubacterium that was first located in hydrothermal vents under the ocean and here it is, its DNA is popping up in man. And, at high concentration: 5.1 percent of the clones that were sequenced which is higher than Staphococcus genus. There are some other genus here, you can look up the paper and go into more detail. This is what the Human Microbiome project is aimed at setting out. Exactly what species, what genes exist in Man.
	+
	+	Until the genome was cracked, we only had the postulates of Koch as a guide. They caused us to search for Koch’s singular pathogenic species. We kept looking for one pathogenic species. As a result you can find a paper that will blame poor old EBV for just about every disease known to man. And CMV and HHV as well. Because Koch’s singular pathogenic species in this age of the genome really means very little. It sidetracks science from understanding horizontal transfer of DNA within the microbiota. Sharing of genes between the organisms, which we now know occurs very, very much faster than we ever could have dreamed to be the case. Science became fixated on the co-infections, those things we could see, like the EBV and missed the primary disease mechanism: the ability of the pathogens to knock out the innate immune system.
	+
	+	Another reason is that Vitamin D is the primary ligand that activates the VDR receptor. And at some stage during the twentieth century mankind decided that Vitamin D was nutrient. Well, Vitamin D is not a nutrient. It is a seco-steroid transcriptional activator. And its concentrations are very closely controlled by a very complex control system which involves not only the VDR but also the Pregnane X Receptor, the Pregnane Antibiotics Receptor, the P300/CBP PKA pathways and feedback via a number of enzymes. CYP24, 27, A1, 27B1. There is transrepression from VDR activation, feedback path, there is transrepression or actually antagonism, receptor antagonism from the metabolites. And there is also feed-forward pathways. Quite a complex mechanism… If Vitamin D was a nutrient we would see a simple first order mass action metabolism. We do not see that. We see the complex control system of a hormone. Of a seco-steroid transcriptional activator which is what it is. When we concentrate on the concentration of this intermediate substrate, 25-hydroxy-vitamin-D, that’s the one that Medicine has been measuring as an indication of Vitamin D status. That is down-regulated in disease. When the VDR is knocked out, the production of the CYP27A1 is down-regulated and the production of 25-hydroxy-vitamin-D in the body is down-regulated. Down-regulation is not ‘deficiency’. It is the body regulating the concentration of the metabolite. What is happening is, because the VDR is knocked out, no longer can these genes degrade the 1,25-D and the 1,25-D is becoming very high in concentration, affecting the other receptors and so it tries to block the metabolism of this pathway and in so-doing down-regulates the level of the thing that we’re measuring, thinking that it is a meaningful measure of Vitamin D homeostasis. It’s not. It’s down-regulated in disease. My paper “Vitamin D discovery outpaces FDA decision making” in Bio-essays last February has contained the diagram and all the associated description.
	+
	+	But, there is another problem too. Only 1,25-dihydroxy-vitamin-D, the doubly hydroxylated version can activate VDR transcription, can actually activate/transcribe the genes. Well, Vitamin D that we ingest and 25-hydroxy-vitamin-D that is hydroxylated from that, both inhibit transcription. Here we have in-silico data showing how each of these Vitamin D metabolites fit into the VDR receptor. And you can see that only one of them has the 1-alpha-hydroxylation which is necessary to actually activate the receptor so it transcribes genes. And yet all of them occupy similar space inside the VDR and they all have very similar values of Kd as well. So if you are getting a lot of Vitamin D supplementation, it is actually tending to displace, on a concentration dependant basis, the active metabolite from the VDR.
	+
	+	Well, luckily there is an agonist that works in-vivo. It’s a drug called Olmesartan. Here we have a molecular dynamics emulation of the human VDR with Olmesartan sitting in the binding pocket in an activated position. As you know, all proteins are in motion, at all times.
	+
	+	And, here we have the same thing in rat (Rattus Novegicus). It’s a very, very similar VDR and a very, very similar ligand, positioned, but they are not quite the same. And when we put them side by side you can really see the difference. In particular: look at this Tetrasol. The tetrasol-ring is a totally different orientation because it’s binding to totally different amino acids in the VDR of the rat and the VDR of the human being.
	+
	+	It’s only by getting down to the level of the molecules that we can really understand the difference between our animal models and Homo sapiens.
	+
	+	Then, once the innate immune system has been activated again, we can use very low-dose bacteriostatic antibiotics to block protein synthesis. Here I’ve got Azithromycin blocking the 70S-ribosome which translates RNA into proteins in the bacterial organisms. They are being blocked by Azithromycin.
	+
	+	The rate of bacterial death when you are using bacteriostatic antibiotics is controlled by inhibiting the protein synthesis and we can use sub-inhibitory, low doses of bacteriostatic antibiotics. Later on Dr. Blaney will talk a little bit about the dosing issues.
	+
	+	But just remember that one bacterium is weakened if just one antibiotic molecule is bound into one ribosome (because these antibiotics actually block the functioning of protein generation). So intermit low doses can proportionally control the rate of bacterial death. And that’s very fortunate. Because recovery isn’t easy. There’s a huge bacterial cellular load, whether it’s ninety percent of the body or not I would not know but it is a huge load. As the intra-cellular bacteria are killed, some of the infected cells undergo apoptosis, some even disintegrate.
	+
	+	The loss of cells -both white and red cells- and the cytokine storm which is concomitant with that, has to be controlled so it doesn’t become life-threatening. The damage is called immunopathology. And people who are seriously ill carrying a heavy bacterial load (which isn’t about every individual with an autoimmune diagnosis), they need to spread the therapy over many years if the immunopathology is to be kept at a tolerable level.
	+
	+	You can’t just give the patient the anti-biotics, kill the bacteria and send the patient home feeling well. The problem is, there are just too many bacteria to kill, the load is too high, and just like you have with for example Anthrax, the patient dies from the cytokine storm. You have got to be very, very careful.
	+
	+	Finally, I want to point out that what we have done is evolutionary. It’s not revolutionary. We have built on the work of people like Wirostko, Yahooda from back over the last couple of decades… Many of you, I’m sure, too in the audience… Our model, the molecular in-silico model of the disease fits your data! Please seek out my colleagues over the next couple of days. Talk with us about your data, your studies, especially if you think that our model does not stand up to scrutiny. We would love to discuss it with you. It does fit your data!
	+
	+	And, finally, we’ll end this presentation contemplating Newton. Thank you.
	+
	+	{{tag>presentations videos Trevor_Marshall_PhD Congress_on_Autoimmunity 2008 vitamin_d}}

Poster - VDR Nuclear Receptor competence is the key to recovery from chronic inflammatory and ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

09.05.2010		current
Line 1:		Line 1:
	~~NOTOC~~		~~NOTOC~~

-	====== Poster - VDR Nuclear Receptor Competence is the Key to Recovery from Chronic Inflammatory and Autoimmune Disease ======	+	====== Poster - VDR Nuclear Receptor competence is the key to recovery from chronic inflammatory and autoimmune disease ======


	Type: Abstract presentation\\		Type: Abstract presentation\\
	Presented by: Trevor Marshall, PhD\\		Presented by: Trevor Marshall, PhD\\
-	Conference: [[http://www.nature.com/nm/meetings/dmm/index.html\|Days of Molecular Medicine 2006]]\\	+	Conference: [[https://www.nature.com/nm/meetings/dmm/index.html\|Days of Molecular Medicine 2006]]\\
	Location: Karolinska Institute\\		Location: Karolinska Institute\\
	Date: 2006\\		Date: 2006\\
-	Additional content: [[http://autoimmunityresearch.org/karolinska-handout.pdf\|PDF of Poster]]	+	Additional content: [[https://autoimmunityresearch.org/karolinska-handout.pdf\|PDF of Poster]]


Line 21:		Line 21:

	{{tag>posters Trevor_Marshall_PhD 2006}}		{{tag>posters Trevor_Marshall_PhD 2006}}
-
-	===== References =====
-

Poster - Molecular static and dynamic analyses reveal flaw in murine model used by US FDA to ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 06:37:14 +0000

Poster - VDR nuclear receptor is key to recovery from cognitive dysfunction

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

04.21.2009	current
Line 1:	Line 1:
	+
	+	~~NOTOC~~
	+	====== Poster - VDR nuclear receptor is key to recovery from cognitive dysfunction ======
	+
	+	{{ vimeo>952759}}
	+
	+	Type: Poster presentation\\
	+	Presented by: Trevor Marshall, PhD\\
	+	Conference: [[https://www.massgeneral.org/cvrc/meetings_molecular_agenda.html\|Days of Molecular Medicine 2008]]\\
	+	Location: Karolinska Institue, Sweden\\
	+	Date: April 17-19, 2008\\
	+	Additional content: [[https://autoimmunityresearch.org/dmm2008/DMM2008_Trevor_Poster.pdf\|Dr. Marshall's poster]]; [[https://bacteriality.com/2008/04/25/dmm/\|Notes from the Conference]] by Amy Proal\\
	+	Notes: Dr. Marshall's presentation begins at 1:31.\\
	+
	+
	+
	+
	+	===== Abstract =====
	+
	+
	+	During DMM 2006 we reported that chronic inflammatory disease, including much 'autoimmune' disease, was caused by an intraphagocytic biofilm-like microbiota. Recovery followed activation of the VDR with Olmesartan, and long-term administration of subinhibitory antibiotics. Surprisingly, as the inflammatory disease disappeared from the subjects in that cohort, manifestations of comorbid neurological disease also receded. Memory and cognition returned as the inflammation waned, while suicidal ideation, depression, bipolar disorder, peripheral neuropathies and even obsessive compulsive disorder, receded. Additionally, we found that the neurological symptoms fluctuated with the level of Immunopathology during the healing process, presenting special problems with cohort management. The VDR is at the heart of the innate immune system, responsible for expression of a majority of the body's antimicrobial peptides(({{pmid>long:18200565}})). Changes in lifestyle and medicine during the 20th century have created an environment favorable to the proliferation of pathogens which evade the immune system by suppressing activation of the VDR((Marshall TG: Bacterial Capnine Blocks Transcription of Human Antimicrobial Peptides. Abstract presentation, Metagenomics 2007, San Diego, July 11-13, 2007. DOI 10.1038/npre.2007.164.1 Available from URL https://autoimmunityresearch.org/transcripts/metagenomics2007.pdf)). Kandel identified that short term memory involves activation of PKA((Eric R Kandel: The Molecular Biology of Memory Storage: A Dialog between Genes and Synapses. Nobel Lecture, Dec 8, 2000.)). We have determined that activation of PKA is regulated by the process of VDR homeostasis in chronic immune disease, pointing towards a putative mechanism whereby immune dysfunction can directly suppress short-term memory. However the above subjects not only reported the return of short term memory, but also of mid-term and long-term memory. The molecular mechanisms linking immune dysfunction and cognitive dysfunction are clearly profound. We propose that studies of linked dysfunction will provide more insight than studies of neurological manifestations alone.
	+	{{tag>posters videos Trevor_Marshall_PhD DMM 2008}}
	+
	+	===== References =====

Presentation - What more is there to discover about Vitamin D?

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.12.2017		current
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	===== Description =====		===== Description =====

-	A conference: " the 10th International Congress on Autoimmunity" was held in Leipzig, Germany, on 7 April 2016. Professor Trevor Marshall was invited to speak on the topic: "What more is there to discover about Vitamin D."	+	On April 7, 2016, Prof Trevor Marshall was invited to speak on the topic "What more is there to discover about Vitamin D" at the 10th International Congress on Autoimmunity in Leipzig, Germany ( #autoimmunity2016 ). At the 14:15 mark, Prof Marshall describes the mechanism by which electromagnetic waves affect the stability of hydrogen bonding in the human VDR. The Foundation has a number of the 'sleeping caps' left over from our study. We are making them available to groups and individuals who want to replicate our work. Please contact foundation@autoimmunityresearch.org

	{{tag>presentations videos Trevor_Marshall_PhD 2016}}		{{tag>presentations videos Trevor_Marshall_PhD 2016}}
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		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: Transcript not found --- //Sallie Q //	+	Additional content: Transcript not found --- //Sallie Q //</nodisp>

Presentation - The human microbiome lies at the heart of autoimmune disease

anonymous@undisclosed.example.com (Anonymous) — Tue, 03 Jan 2012 04:23:06 +0000

06.22.2011		current
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	This slide was presented by Claire Fraser-Liggett, University of Maryland, at the Human Microbiome Conference just last month. And it results from a study of Amish families that she did, a very concentrated, isolated community in America. And she was looking at lean, overweight, obese benign, and obese with metabolic syndrome. And when you look at it in terms of family, whether it's Rhuminococcaceae, Bacteroidaceae or whatever the family is, you can see that there is more variation from person to person – each vertical bar here is an individual person within the cohort – there is more variation from person to person than there is from phenotype to phenotype or disease to disease state. And, it doesn't matter, you can look at it by phylum and you see exactly the same result. No statistically determinant characteristics like we found in the mouse, or like Washington U. found in the mouse. Which is unfortunate.		This slide was presented by Claire Fraser-Liggett, University of Maryland, at the Human Microbiome Conference just last month. And it results from a study of Amish families that she did, a very concentrated, isolated community in America. And she was looking at lean, overweight, obese benign, and obese with metabolic syndrome. And when you look at it in terms of family, whether it's Rhuminococcaceae, Bacteroidaceae or whatever the family is, you can see that there is more variation from person to person – each vertical bar here is an individual person within the cohort – there is more variation from person to person than there is from phenotype to phenotype or disease to disease state. And, it doesn't matter, you can look at it by phylum and you see exactly the same result. No statistically determinant characteristics like we found in the mouse, or like Washington U. found in the mouse. Which is unfortunate.

-	Now EMBL in Europe has, is just in the middle of a big study, and they've gone even further. They have some Japanese human samples, some American human samples. This was published by Arumugam in Bioinformatics and you can see that if you look at the various phyla across here – the Japanese samples firstly are different from each other in the propensities, but also they are very different from the American samples. So there is intra-individual variation, which is quite high; and there is intra-regional variation, which is quite high. And it's at the level of the species, at the level of identifying the microbes that are present, really, at this point, human metagenomics has hit a brick wall. At this point the human microbiome project knows what's there. Pretty well they know what's there, certainly on all the externally facing tissues. The next phase is to figure out what is it doing. And clearly they can't figure out what is this doing based just on the species. We have to figure out other ways of analysis.	+	Now EMBL in Europe has, is just in the middle of a big study, and they've gone even further. They have some Japanese human samples, some American human samples. This was published by Arumugam in Bioinformatics and you can see that if you look at the various phyla across here – the Japanese samples firstly are different from each other in the propensities, but also they are very different from the American samples. So there is intra-individual variation, which is quite high; and there is intra-regional variation, which is quite high. And it's at the level of the species, at the level of identifying the microbes that are present, really, at this point, human metagenomics has hit a brick wall. At this point the Human Microbiome Project knows what's there. Pretty well they know what's there, certainly on all the externally facing tissues. The next phase is to figure out what is it doing. And clearly they can't figure out what is this doing based just on the species. We have to figure out other ways of analysis.

	Now this is also from Claire Fraser-Liggett's group at University of Maryland. This is a Manhattan Plot of the homology between the Fusobacter genome and the Human genome. And for more information on what we're talking about here, just read our chapter in the Metagenomics of the Human Body book because we point out the homology between genes in the microbiota and human genes is actually quite high. You can see some of the points in the Manhattan Plot here go well above the seven and a half line that Claire chose as being quite deterministic. You've got your chromosomes across the bottom obviously and log p up the left.		Now this is also from Claire Fraser-Liggett's group at University of Maryland. This is a Manhattan Plot of the homology between the Fusobacter genome and the Human genome. And for more information on what we're talking about here, just read our chapter in the Metagenomics of the Human Body book because we point out the homology between genes in the microbiota and human genes is actually quite high. You can see some of the points in the Manhattan Plot here go well above the seven and a half line that Claire chose as being quite deterministic. You've got your chromosomes across the bottom obviously and log p up the left.
Line 48:		Line 48:
	Q: What is the mass of the microbiome in a typical human being?		Q: What is the mass of the microbiome in a typical human being?

-	A: Well that too was discussed in Vancouver. And the original NIH estimate was 90% of human cells are likely bacterial cells. The current estimate is 99%. So even that is a moving target at this point as discovery continues forward. There's more money that the human microbiome project is basically looking at all the external cavities and documenting exactly what's there, multiple centers, but at this point it's far more than anybody ever imagined.	+	A: Well that too was discussed in Vancouver. And the original NIH estimate was 90% of human cells are likely bacterial cells. The current estimate is 99%. So even that is a moving target at this point as discovery continues forward. There's more money that the Human Microbiome Project is basically looking at all the external cavities and documenting exactly what's there, multiple centers, but at this point it's far more than anybody ever imagined.

	Q: How much of it gets into the blood, I mean do these peptides, proteins that you mentioned....		Q: How much of it gets into the blood, I mean do these peptides, proteins that you mentioned....

Presentation - Electrosmog Radiation - Its effects on the human VDR (and beyond)

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Presentation - Molecular genomics offers new insight into the exact mechanism of action of ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

Presentation - Is there a role for a Tin-Foil hat in PPPM?

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.12.2017		current
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	A conference: "EPMA World Congress on PPPM (Predictive, Preventative, Personalized and Participatory Medicine) " was held in Bonn, Germany, on 3-5 September 2015. The presentation of Professor Trevor Marshall: "Is there a role for a Tin-Foil hat in PPPM?."		A conference: "EPMA World Congress on PPPM (Predictive, Preventative, Personalized and Participatory Medicine) " was held in Bonn, Germany, on 3-5 September 2015. The presentation of Professor Trevor Marshall: "Is there a role for a Tin-Foil hat in PPPM?."

		+	==== ====
		+
		+	[[https://autoimmunityresearch.org/abstracts/RAMS_2015_abstract.pdf\|abstract]]

	{{tag>presentations videos Trevor_Marshall_PhD 2015}}		{{tag>presentations videos Trevor_Marshall_PhD 2015}}
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		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: Transcript not found --- //Sallie Q //	+	Additional content: full Transcript not found --- //Sallie Q //</nodisp>

Presentation - The microbiome, which feeds a myriad of autoimmune diseases

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

05.20.2012		current
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	Type: Conference presentation\\		Type: Conference presentation\\
	Presenter: Trevor Marshall, PhD\\		Presenter: Trevor Marshall, PhD\\
-	Conference: Autoimmunity Congress Asia\\	+	Conference: 8th International Congress on Autoimmunity \\
	Location: Grenada, Spain\\		Location: Grenada, Spain\\
	Date: May 9-13, 2012\\		Date: May 9-13, 2012\\
-	Additional content: [[http://autoimmunityresearch.org/transcripts/Auto2012_Marshall_plenary.pdf\|PDF Transcript]]	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Auto2012_Marshall_plenary.pdf\|PDF Transcript]]

	{{tag>presentations videos Trevor_Marshall_PhD 2012}}		{{tag>presentations videos Trevor_Marshall_PhD 2012}}
-

Presentation - What can microbial genomes tell us about human health?

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

04.29.2026	current
Line 1:	Line 1:
	+
	+
	+
	+	====== Presentation - What can microbial genomes tell us about human health? ======
	+
	+
	+	{{ youtube>_rFmAMDdbjs}}
	+
	+
	+
	+	Type: Conference presentation\\
	+	Presenter: Trevor Marshall, PhD\\
	+	Conference: Molecular Basis of Clinical Medicine \\
	+	Location: Saint Petersburg, Russia\\
	+	Date: June, 2012\\
	+	Additional content: [[https://autoimmunityresearch.org/transcripts/StPetersburg_2012_Marshall.pdf\|PDF Transcript]]
	+
	+	{{tag>presentations videos Trevor_Marshall_PhD 2012}}
	+
	+
	+

Poster - Bacterial capnine blocks transcription of human antimicrobial peptides

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 06:37:14 +0000

04.21.2009	current
Line 1:	Line 1:
	+
	+	~~NOTOC~~
	+	====== Poster - Bacterial capnine blocks transcription of human antimicrobial peptides ======

	+
	+	Type: Poster presentation\\
	+	Presented by: Trevor Marshall, PhD\\
	+	Conference: [[https://metagenomics.calit2.net/2007/index.php\|Third International Conference on Metagenomics]]\\
	+	Location: University of California, San Diego\\
	+	Date: July 11-13, 2007\\
	+	Additional content: [[https://autoimmunityresearch.org/transcripts/metagenomics2007.pdf\|poster]] (includes a number of Wirostko photographs); [[https://precedings.nature.com/documents/164/version/1\|post at Nature Precedings]]\\
	+
	+
	+
	+	===== Abstract =====
	+
	+	The US CDC believes that 65% of all infections in
	+	developed countries may be caused by pathogens in
	+	biofilms. Electron Microscopy has shown that these
	+	bacterial communities can evade phagocytosis, and persist
	+	in the cytoplasm of monocytes, macrophages, lymphocytes
	+	and neutrophils. Three decades ago, Wirostko, et al, found
	+	such intraphagocytic communities in Crohn’s disease,
	+	Juvenile Rheumatoid Arthritis and Sarcoidosis(({{pmid>long:8140710}})).
	+	However, the mechanism(s) by which such persistent
	+	bacteria could evade the immune system have remained
	+	elusive. Recently, 16S RNA from species of gliding bacteria
	+	never thought to be able to survive in-vivo, have been
	+	found in surgically removed biofilms.(({{pmid>long:17501992}})) This study set
	+	out to identify whether the genomes of these gliding
	+	bacteria might yield insight into mechanisms by which
	+	such persistent pathogens could evade phagocytosis.
	+
	+
	+	==== Methods ====
	+
	+
	+	A single Type 1 Nuclear Receptor, the VDR
	+	(commonly known as the ‘Vitamin D Receptor’), is
	+	responsible for transcription of LL-37, the human
	+	Cathelicidin antimicrobial peptide, as well as the beta
	+	Defensin anti-microbial peptides defB2/defB4(({{pmid>long:16002434}})). Disabling
	+	transcription by the VDR would allow a pathogen to persist
	+	inside phagocytes without threat from these anti-microbial
	+	peptides. Static molecular modeling (primarily using
	+	AutoDock) was used to screen a number of proteins and
	+	peptides known to be produced by the genomes of the
	+	gliding bacteria.
	+
	+	==== Results ====
	+
	+	A candidate bacterial sulfonolipid, Capnine, was
	+	identified to have a nanomolar Ki for the ligand binding
	+	pocket (LBP) of the VDR. Molecular Dynamics simulation of
	+	the human VDR in complex with Capnine confirmed that
	+	this substance is indeed stable in the VDR LBP, and that its
	+	action is that of a strong transcriptional antagonist.
	+
	+	==== Conclusion ====
	+
	+	Medical Metagenomics has demonstrated the
	+	ability to deliver important results in silico, potentially
	+	underpinning an infectious pathogenesis for idiopathicnic
	+	illness.((Waterhouse JC, Marshall TG, Fenter B, Mangin M, Blaney G:
	+	High levels of active 1,25-dihydroxyvitamin D despite low
	+	levels of the 25-hydroxyvitamin D precursor - Implications of
	+	dysregulated vitamin D for diagnosis and treatment of Chronic
	+	Disease. In Vitamin D: New Research. Volume 1. Edited by:
	+	Stoltz VD. New York: Nova Science Publishers; 2006.
	+	ISBN: 1-60021-000-7))((Marshall TG: VDR Nuclear Receptor Competence is the Key
	+	to Recovery from Chronic Inflammatory and Autoimmune
	+	Disease. Abstract presentation, DMM2006, Karolinska
	+	Institute, May 2006. Copy available from URL
	+	https://autoimmunityresearch.org/karolinska-handout.pdf))
	+
	+	{{tag>posters Trevor_Marshall_PhD Metagenomics capnine antimicrobial_peptides 2007}}
	+
	+	===== References =====

Presentation - Environmental Radiation modulates symptoms in Human Immune Disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.18.2018		current
Line 14:		Line 14:
	This is a presentation given in conjunction with the Max Planck Institute for Neurobiology.		This is a presentation given in conjunction with the Max Planck Institute for Neurobiology.

-	Prof Marshall discusses

		+	A PDF copy of the written abstract is here: [[https://autoimmunityresearch.org/abstracts/RAMS_2015_abstract.pdf\|Environmental Radiation Modulates Symptoms in Human
		+	Immune Disease ]]
		+
		+	A PDF of a recent paper (cited on slide 3) describing the Foundation's earlier research, "Inflammatory Disease and the Human Microbiome" is available from: [[https://autoimmunityresearch.org/preprints/Proal_2014_DiscoveryMedicine-Preprint.pdf\|Discovery Medicine]]
		+	Category
		+	Education

	{{tag>presentations videos Trevor_Marshall_PhD 2015}}		{{tag>presentations videos Trevor_Marshall_PhD 2015}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: [[http://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE
		+	</nodisp>

Presentation - The human microbiome is the mechanism fueling neurodegenerative disorders

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

01.03.2012		current
Line 12:		Line 12:
	Date: May 25, 2011\\		Date: May 25, 2011\\

		+
		+	As background, BBC Radio 4 has a broadcast describing the fundamentals of the Human Microbiome at [[https://www.bbc.co.uk/programmes/b011jv8r\|BBC radio]]
	===== Transcript =====		===== Transcript =====

Presentation - Chronic Disease, the Human Microbiome, and Personalized Medicine

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.19.2018		current
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-	====== Presentation - ======	+	====== Presentation - Chronic Disease, the Human Microbiome, and Personalized Medicine ======


Line 17:		Line 17:
	{{tag>presentations videos Trevor_Marshall_PhD 2013}}		{{tag>presentations videos Trevor_Marshall_PhD 2013}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: [[http://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE
		+	</nodisp>

Presentation - The Endomicrobiome as a strategic tool of PPPM

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.19.2018		current
Line 14:		Line 14:
	A conference on "Strategy of Personalized Medicine and Its Impact in Phtiziopulmonology" was held at the Central House of Scientists, Russian Academy of Sciences, on 19 December 2013. Prof Trevor Marshall gave a plenary address on "The Endomicrobiome as a strategic tool of PPPM		A conference on "Strategy of Personalized Medicine and Its Impact in Phtiziopulmonology" was held at the Central House of Scientists, Russian Academy of Sciences, on 19 December 2013. Prof Trevor Marshall gave a plenary address on "The Endomicrobiome as a strategic tool of PPPM

		+	A version of this video in Russian is available: [[https://www.youtube.com/watch?v=XFJGg3wZrxY\|Russian Audio translation]]

	{{tag>presentations videos Trevor_Marshall_PhD 2014}}		{{tag>presentations videos Trevor_Marshall_PhD 2014}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: [[http://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE
		+	</nodisp>

Presentation - The importance of the microbiome in chronic disease prevention

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.12.2017		current
Line 19:		Line 19:


		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: [[http://autoimmunityresearch.org/transcripts/Moscow_2015_Marshall.pdf\|PDF Transcript]]	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Moscow_2015_Marshall.pdf\|PDF Transcript]] not available</nodisp>

Presentation - Immune Disease and the Microbiome: PPPM Healthcare in response to New Knowledge

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.21.2018		current
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		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: [[http://autoimmunityresearch.org/transcripts/Moscow_2016_Marshall.pdf\|PDF Transcript]] NOT YET AVAILABLE	+	</nodisp>

Presentation - Can Waves Cause or Cure Disease?

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.24.2018		current
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	====== Presentation - Can Waves Cause or Cure Disease? ======		====== Presentation - Can Waves Cause or Cure Disease? ======

-
-	https://youtu.be/sMWkde5FlK8
-

		+	{{ youtube>sMWkde5FlK8}}

	Type: Conference presentation\\		Type: Conference presentation\\
Line 34:		Line 32:


		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	Additional content: [[http://autoimmunityresearch.org/transcripts/Moscow_2015_Marshall.pdf\|PDF Transcript]] not available	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Moscow_2015_Marshall.pdf\|PDF Transcript]] not available</nodisp>

Paper - Common angiotensin receptor blockers may directly modulate the immune system via VDR, ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

03.08.2019		current
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	Citation: Marshall, T.G., Lee, R.E. & Marshall, F.E. Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. //Theoretical biology & medical modelling// 3, 1(2006).		Citation: Marshall, T.G., Lee, R.E. & Marshall, F.E. Common angiotensin receptor blockers may directly modulate the immune system via VDR, PPAR and CCR2b. //Theoretical biology & medical modelling// 3, 1(2006).
	\\		\\
-	See also: [[http://www.tbiomed.com/content/3/1/1\|full text]]; [[http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1360063\|PubMed Central record]]	+	See also: [[https://www.tbiomed.com/content/3/1/1\|full text]]; [[https://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1360063\|PubMed Central record]]
		+
		+	//And see// Editor's note //below//

Presentation - The Marshall Protocol in a clinical environment – observations from the ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

04.24.2009	current
Line 1:	Line 1:
	+
	+	~~NOTOC~~
	+
	+	====== Presentation - The Marshall Protocol in a clinical environment – observations from the initial cohort ======
	+
	+	{{ vimeo>2599416}}
	+
	+	Type: Conference presentation\\
	+	Presenter: Trevor Marshall, PhD\\
	+	Conference: [[https://www.bitlifesciences.com/wcg2008/event_report.htm\|2008 World Gene Congress]]\\
	+	Location: West China Hospital, West China Medical School, Sichuan University\\
	+	Date: December 5-7, 2008\\
	+	See Also: [[https://curemyth1.org/flash/WCH.html\|A short promotional video describing West China Hospital]]
	+
	+
	+
	+
	+
	+	===== Transcript =====
	+
	+	==== Need to understand disease process ====
	+
	+
	+	This is a quotation from the commissioner of the U.S. FDA when he was speaking to congress back in 2006. He said, “New scientific discoveries are generating an emerging science of safety … This new science combines an understanding of disease and its origins at the molecular level (including adverse events) with new methods of signal detection, data mining, and analysis....”
	+
	+	The FDA Commissioner recognizes that we can do so much more in medicine if we understand the underlying disease processes, because then we can predict adverse effects; we can figure out what signals we should be detecting.
	+	That’s really what we have done. We started with an understanding of the disease process to try and produce a therapy that works.
	+
	+	==== Review ====
	+
	+
	+	Just reviewing quickly, this is what we’re dealing with. We’re dealing with the inclusions in the cytoplasm of nucleated phagocytic cells. This is a lymphocyte. This is a big inclusion but there are all sorts of different shapes, bacterial colonies as well.
	+
	+	Now we can use low-dose antibiotics to block the protein synthesis by blocking the 70S bacterial ribosome. One bacterium is weakened if just one abx molecule is bound into just one ribosome, because then the ribosome can’t function. You only need one antibiotic molecule to bind into one ribosome and you’ve blocked that bacterium from producing – out of that ribosome, at least. Intermittent, low doses can proportionally control the rate of bacterial death.
	+
	+	==== Antibiotics not enough====
	+
	+	But antibiotics on their own do not [always] work, because two things are disabling the innate immune system by blocking VDR transcription.
	+
	+	The first is bacterial products such as capnine. Capnine is just a bacterial product which comes out of gliding bacteria, such as the lysobacter type of bacteria, and it is very common in a biofilm. It’s sort of like a slug moving along the ground and leaving a trail behind it. It’s a similar sort of thing. When these bacteria move through biofilm, they leave a trail of capnine behind them. And capnine happens to block the VDR. We have shown that in silico. I’m sure there are lots of other substances that different species produce; that is just one of them.
	+	Secondly, exogenous (dietary) vitamin D will block the human innate immune system from doing its job properly. And as patients become more sick, they become more sensitive to dietary vitamin D.
	+
	+	==== Dietary Vitamin D ====
	+
	+
	+	Now, dietary vitamin D is not a problem here in China. You don’t have your milk supplemented – as far as I can read (I can’t read the box very well), but in America, everything is supplemented with vitamin D, because in America, people think that vitamin D is good for them, and the more they get, the better it is. So they have vitamin D in their milk, it’s put into the cheese, it’s put into some butters, it’s put into orange juice. Orange juice is fortified with vitamin D now. So in America it’s very hard to avoid vitamin D at this point.
	+
	+	Vitamin D makes people feel good, because it is an immune suppressant. It suppresses the immune system’s response to the microbiota. It makes people feel good because it suppresses the symptoms. In much the same way, you give people a corticosteroid to suppress the immune system, and they feel good. Well – generally they feel good, except for the neurological side effects. And, as we said in the previous presentation, the VDR activation is controlled by a number of nuclear receptors: the PXR, the P300/CBP which is actually a transcription factor, and the VDR.
	+	Vitamin D is not a nutrient.
	+
	+	==== Olmesartan medoxomil ====
	+
	+
	+	Now, what we have found is that olmesartan medoxomil is a VDR agonist. Olmesartan was produced as an angiotensin 2 receptor antagonist, the receptor blocker, which it does a very good job of, and at quite low concentrations. It has been extensively safety-tested by the FDA, and it’s one of the safest drugs uniformly. As far as the FDA is concerned, they have seen no data indicating any unsafe level for ingestion of olmesartan. It’s a very new drug; it was passed through the U.S. FDA in 2002. And I know there is a manufacturer here in China that is capable of manufacturing olmesartan – presumably for your local market.
	+
	+	This is the VDR, and this is a different type of in silico image. What we have here is a static image. It’s still three-dimensional, we’ve got some depth – the darker helices are supposed to be farther in the background than these lighter ones – but it’s not moving. It’s very quick to do these analyses. It’s very slow to do the analysis of a moving molecule, because you’ve got to do so many simulations. You’ve got to simulate each one of those little movements of the molecule.
	+
	+	But what I’ve shown here is olmesartan. This is the drug, with the two oxygens up here. But it exactly mimics the position of the active oxygens in the 1,25D molecule. And then you have the nitrogens involved, in the imidazole and the tetrazole loops down here, that do the rest of the agonistic functions that allow this molecule to “turn on” the VDR.
	+
	+	When this molecule is docked in the VDR, there is an average of seven hydrogen bonds that are active at any one point in time. It is very, very strongly bound into the molecule, and it binds in such a way that the receptor is activated. And for those of you who are technically inclined I’ve listed the hydrogen bonds, the residues that they’re formed with, and you’ll find that they’re exactly the same residues that 1,25 dioxyvitamin D binds to.
	+
	+	==== So what is olmesartan? ====
	+
	+
	+	Well, it’s a mild hypertensive agent. It’s given for high blood pressure. And as the head of the FDA Cardiovascular Disease Division told me, “It’s not a very good one, either. It doesn’t depress the blood pressure very much at all.” As you can see there’s a maximum effect of somewhere around 12 millimeters of mercury here, maximum – in systolic and diastolic, of course.
	+
	+	The interesting thing is you’ve got down here the dose of medication – 0, 20, 40, 60, through 160 mg, and up here you’ve got the reduction in blood pressure. Nearly all of the reduction in blood pressure occurs at quite low doses, down here. By the time you get to 20 mg a day, nearly all of the reduction in blood pressure has occurred. That’s because this drug is a very good angiotensin 2 receptor antagonist. It’s very good at blocking the angiotensin 2 receptors.
	+
	+	But the other task it does, the VDR agonism, it does at slightly higher concentrations – up in the region of this part of the curve, between 120 and 160 mg a day of olmesartan. And up there, it not only blocks the angiotensin 2 receptor, but it also activates the VDR.
	+
	+	==== Olmesartan alone ====
	+
	+
	+	Olmesartan on its own can be effective. It’s just giving the patient olmesartan, at the correct dose. Not the anti-hypertensive dose of 20 mg a day. That usually just makes them feel worse rather than better, because their system is pulsing on and off, every day, which is not much fun. So you have to give Olmesartan continuously, every six hours. We typically say, 40 mg every 6 hours is a base dose.
	+
	+	When you give that dose, quite often, right at the commencement of the blockade – within the first couple of weeks – you’ll find that fibromyalgia pain, typically, is reduced. Migraines also can disappear, but not in every individual. There was a study of ARBs in migraines, and I think they found about 60% efficacy with a different ARB (candesartan). But that’s about what we have seen.
	+
	+
	+	Of course, for those people whose migraines disappear, this is a godsend, because it’s such a difficult thing to treat.
	+
	+	Olmesartan alone can do that. Also, when you start olmesartan, we have found that about ten per cent – the most seriously ill patients – experience bad immunopathology, just from the VDR activation. When you turn on the immune system, the most seriously ill patients – the ones that have had the most therapy – typically, about ten per cent can experience quite a lot of immunopathology and be very uncomfortable.
	+
	+	Most of the patients, about seventy per cent, experience no real benefit or degradation. Sometimes they feel a little better. They usually feel a little better.
	+
	+	And about thirty per cent experience significant improvement, particularly in pain, in migraine, or just in general – “Hey, I feel better,” type of thing.
	+
	+	I’ve got a very important proviso down at the bottom. If the patient is on thyroid hormone supplementation, you must measure it regularly. When you start the Benicar (olmesartan), within just the first week, the requirement of the dose of T3 or T4 that you’re giving them may drop very rapidly as the hormones adjust in the body. So when you start olmesartan, you’ve got to be very careful to measure the thyroid hormones and adjust their supplementation those first few weeks. And certainly, within the first six months, you will find that most of the thyroid supplementation is no longer needed.
	+
	+	==== Dealing with immunopathology ====
	+
	+
	+	This is a repeat of the slide from the previous presentation. Recovery isn’t easy, because as the bacteria within the cells are killed, some of the cells will die as well. It’s a very important concept. There is no way of killing these bacteria within the cells without killing some cells as well. The secret of being able to do it is to understand that, and also to do it slowly. Slowly and surely.
	+
	+	This is the graph that was entered at the Portugal Autoimmunity Conference by Captain Tom Perez. This is a graph of immunopathology. It was drawn by one of the patients who have recovered, and it was her idea of what she felt immunopathology was like. It’s the symptom level in response over time.
	+
	+	She has 100% up here. That was the symptom level before she started the therapy. When she started the minocycline, 25 mg every two day dose – very low dose – 25 mg every 48 hours is what they start at. Then over a period of time they can build up the amount of minocycline they are taking as they work down their bacterial load. And you can see the jumps here in the immunopathology. When the IP drops down to a level that the patient is very comfortable with, then they say, Okay, let’s increase the dose again.
	+
	+	They begin the therapy at this 90% level, meaning a little less suffering than they had before they started the therapy. Then by the time they get to 100 mg of minocycline every 48 hours [and their symptoms become tolerable], at that point they are put onto the addition of a second antibiotic – either azithromycin or clyndomycin. This graph shows azithromycin.
	+
	+	Now, this is one-tenth of a tablet. When they add one-tenth of a tablet of azithromycin every ten days, many patients cannot handle the extra amount of immunopathology. It is just amazing to see how much the sensitivity to the antibiotics is increased by the activation of the VDR with the olmesartan.
	+	So they start at a tenth, they go to an eighth of a tablet, a fifth of a tablet, a third of a tablet, and finally end up with a half of a tablet (250 mg). And you’ll notice that you’ve got this ten day pulsation here in the symptom levels over time.
	+
	+	==== Rate of recovery ====
	+
	+
	+
	+	But you notice that she’s drawn that the symptom levels are gradually decreasing over time. If we have got days (she has 251 days here) by the time she’d got up to about nine months (251 days), she thought her symptoms were around forty to fifty per cent.
	+
	+	By the time they’ve got up to about two years, the blood work is essentially cleaned up. By the time they get to three years, their lipids, their cholesterol, their LDL and HDL level will be back in range; their glycerides will be back in range. You’ll see the blood work confirming the recovery of the body at about that point, between the two and three year mark. You’ll also see it earlier, but it’s less marked. When they get to about two years, that’s really the beginning of the recovery period. Up until that stage, it’s pretty tough going for the average patient.
	+
	+	==== Phase One ====
	+
	+
	+	How long do they stay on phase 1?
	+
	+	Phase 1 is the period where they are just getting minocycline. They’re building up the minocycline dose they can tolerate, from 25 mg every 48 hours to 100 mg every 48 hours. Phase 1 typically lasts three months. This is the diagram, the histogram that was produced from that same data that we saw on the other graph of all the ordinary conditions that have resolved – rheumatoid arthritis, Hashimoto’s, etc. – and you can see that the most common period is typically around 70 days. If you draw the curve through it, it comes somewhere around 120 days or 4 months. But we say typically 3 months. After 3 months, we try to transition people to two abx, because we’re very concerned about getting an even killing – killing the bacteria in an even manner, not just getting rid of one species or another species. And that’s best done with multiple attacks on the protein synthesis.
	+
	+	==== Phase Two ====
	+
	+
	+	So typically they stay about 90 days in Phase 1, and then in the two antibiotic stage, they typically stay about nine months. You can see down here the number of days, and somewhere around 270 days is the average amount of time. The most common is around 150 days, or about 5 months. But they are in the two abx phase for that long, and by the time they get out here, their immunopathology has dropped to a level where we can increment the antibiotic, increment the killing a little bit further.
	+
	+	We do that by adding a third antibiotic, either clyndomycin or azithromycin – depending on what we started phase 2 with.
	+
	+	==== Problems ====
	+
	+
	+	Now, here are some of the problems that we get. The VDR transcribes 913 genes. It affects just about every function of the body – which is one of the reasons that the body goes haywire when the bacteria blocks the VDR.
	+	This is from Porsti et al, in Kidney International, December 2008. This came out just a few days before I left the U.S. This paper shows that when the VDR is activated, it downregulates renin production; it downregulates the renin/prorenin receptor; it downregulates angiotensinogen, angiotensin II, and the angiotensin1 receptor. It also affects the angiotensin-converting enzyme – that ACE that we saw back there on the disease map – and also a new angiotensin-converting enzyme that’s still being identified. It affects the angiotensin2 receptor, oncogenes, and a number of other genes as well. These are subsets of the 913 genes affected by the VDR.
	+
	+	The Vitamin D receptor activation profoundly affects the renin/angiotensin system. As the kidneys heal, all of these metabolites will be changing around. But notice that renin, a nasty one, is being downregulated.
	+
	+	==== Renoprotection, despite surging metabolites ====
	+
	+
	+	However, that’s not what you see when you measure the kidney function. This is one patient, whose nurse practitioner reported the data to me. This particular patient was very sick. She presented with a Glomerular filtration rate, a GFR, as low as 23. The typical range is 60, and 15 is typically where you initiate dialysis. Hers was 23; and she was fine. Until the blood work results came back, and Doc said, “Wait a minute!”
	+	Creatinine went to 2.2 on a normal range of 0.5 to 1.2. I don’t know how that compares with the units you use here in China. These are U.S. units. That’s why I put the range on, as well as the value that she went to. She went to almost twice the maximum creatinine range.
	+
	+	This is really big, “hit the panic button” type of data coming back. And yet the patient was fine, because the VDR activation was protecting the kidneys. And as the kidneys were rebalancing their function, as they were healing, this is what you see in the blood work.
	+
	+	The blood urea nitrogen (BUN) went as high as 38 (normal 7-25). All of this occurred without any adverse events.
	+	The values typically return back to normal over a period of between one and six months, depending on the patient. That’s the time taken for the kidneys to heal.
	+
	+	==== Mitigation measures ====
	+
	+
	+	The only thing that a physician needs to do is increase fluid intake, and increase the olmesartan to 40 mg every four hours, to make sure the VDR is doing its job perfectly.
	+
	+	To treat a patient in this way is totally counter-intuitive. The thing that the average physician in the west does - he sees the creatinine high and says, “It’s got to be the angiotensin receptor blocker. I’ll stop the olmesartan.” The moment they do that, the patient loses the protection of the ARB, and the kidneys can degrade.
	+
	+	We had one patient that happened to, who went into hospital. The physician panicked, and the patient was on dialysis within two weeks. That’s the only patient out of our cohort of eleven hundred who had kidney problems, and that was after the drug was withdrawn instead of being left on to do its job.
	+
	+	==== Problem for structuring a clinical trial ====
	+
	+
	+	But this is totally the opposite response to what a physician would have. This presents a real problem when you’re trying to structure a clinical trial. How do you persuade a review board that this is the way you want to treat the patient? Anybody on the review board would say in advance, “Well, that’s ridiculous.”
	+
	+	Now, when you’re faced with a patient, and the patient is fine, and everything else is fine, it’s easier to make a clinical decision – “Well, let’s just stick with it and see what happens.” Which is, essentially, what we do.
	+	But when you try to plan a study, ahead, with a review board, this type of thing is a real problem.
	+
	+	==== Emergency situations ====
	+
	+
	+	There are emergency room situations, as well, when you’re preparing the emergency room instructions, which have to be very carefully monitored. For example, the average antibiotic used in the emergency room could create very high levels of immunopathology. Intravenous clyndomycin, for example, may well be fatal, because the immunopathology would just soar sky high. So you have to be careful what antibiotics you use. Luckily the fluoroquinolines are very effective against acute infections and have virtually no effect on this microbiota. A couple of the cephalosporins can be used. So there are antibiotics available for acute infection events, but it has to be written into the therapy plan.
	+
	+	We have emergency room instructions written in English that I can let you look at, and I think we’ve got most of the main issues covered in those.
	+
	+	==== Cardioprotection ====
	+
	+
	+	Now what about the heart? How does the heart change as we are getting rid of this systemic disease from the body? How does cardiac function change?
	+
	+	Well, this is what we typically see in patients when they start the protocol. We typically see tachycardia. We’ve seen tachycardia as high as 250 sometimes. Not very often, but sometimes. And of course it doesn’t do the patient any harm. The panic causes harm more than the tachycardia.
	+
	+	We see either hypertension or hypotension. That’s fairly common. But the thing to notice is that people can do a working job, a normal working job, with blood pressures of 65 over 35. We’ve had a number of subjects at that level. Because when they are on the angiotensin receptor blocker what you’re measuring as their blood pressure does not relate 100% to what a healthy person with that blood pressure would be feeling like.
	+
	+	There is fainting. Fainting, however, is due to a disease process. It’s not due to the blood pressure. The fainting and the feeling faint, dizziness, is not a side effect of the drug. It’s a side effect of the disease process.
	+	And very, very common is orthostatic hypotension. That means if somebody crouches down on their haunches and then stands up again, there will be a rush of blood away from their head, and they’ll feel momentarily dizzy. Virtually everybody experiences that – anybody who’s ill. People who are not so ill - okay. They won’t get it. But anybody who is seriously ill, like the people I was looking at in the wards today, will experience orthostatic hypotension.
	+
	+	Now, beyond three months into therapy, we haven’t seen any significant cardiac events, even in patients who had multiple by-pass surgeries, or who had implanted defibrillators.
	+
	+	We had several subjects in the cohort who had implanted defibrillators. What typically happens is that the defibrillators no longer have to work after about 6 to 12 months into the therapy. There are no longer any abnormal beats, and the defibrillator just sits there, and whenever it’s interrogated to see whether it’s fired, it usually hasn’t fired. However, I’ll point out, we have a limited sample size. We’ve just got two or three subjects with implanted defibrillators.
	+
	+	==== Careful antibiotic dosing necessary ====
	+
	+
	+	This is an example of what happens when you don’t follow the antibiotic dosing carefully. We had one case of bradycardia – 10 beats per minute (bpm) – observed on somebody who took a full tablet of azithromycin instead of 1/10 of a tablet at the start of phase 2. That resolved with just olmesartan 40 mg every 4 hours (and an extremely nervous cardiologist).
	+
	+	But the immunopathology is a real problem. Trying to figure out how to manage that in a clinical environment is key to being successful in treating these diseases.
	+
	+	==== Types of immunopathology ====
	+
	+
	+	So we’ve seen brachycardia, we’ve seen periodontitis, skin eruptions, shortness of breath, suicidal ideation, bipolar exacerbations, OCD exacerbations, and even one or two grand mal seizures caused by immunopathology.
	+
	+	Once again, the grand mal was caused by a Canadian who took a full tablet of azithromycin at the start of phase 2, instead of 1/10 of a tablet.
	+
	+	All these diseases are related. They’re all related to the microbiota, they’re all related to immunopathology.
	+	The chronic pathogens are very nasty indeed. We have to respect these bacteria. This microbiota has done a wonderful job of integrating itself with //Homo sapiens//. They’re very nasty pathogens, but at the same time, we must respect them. We must kill them slowly and steadily, and the therapy must be guided by an understanding of the disease model, just as the FDA commissioner was saying. When we understand the disease model, it is so much safer to move forward.
	+
	+	Okay. That is my last formal slide. So – are there any questions?
	+
	+	==== Question 1 ====
	+
	+
	+	Question: That was an excellent lecture. I got a new idea from you, that when we use an antibiotic to kill bacteria in the cell, we also kill the cell, and that produces a cytokine storm, and that can produce severe symptoms in the body. So you want to slow down the killing. I think that’s a good idea. The symptoms are not caused by the bacteria themselves, but by what happens when the bacteria are killed. I think you’re right.
	+
	+	So you use olmesartan to get the VDR working. But sometimes antibiotics will work alone. So what makes the VDR stop working? And also, how do these bacteria cause cardiovascular disease? And also, how many diseases does this microbiota cause?
	+
	+	Answer: Let me answer the first question. Firstly, the VDR doesn’t suddenly stop working. People get incrementally ill as they age. Mostly they get to middle age before the VDR is totally not working. So in the earlier stages of the disease process, you don’t need the olmesartan as much as you need the right antibiotics and a lowered intake of vitamin D. So you need to control the vitamin D, you need to control the antibiotics, and antibiotics alone will work with early stage disease. But as the disease gets worse and worse, more and more of the VDR function is blocked off. More and more of the genes cease to function properly.
	+
	+	Now, in terms of cardiovascular disease, coming from this microbiota, all I can tell you is what we have observed. If you think about it, cardiovascular disease – and I’m not talking about arrhythmia, I’m talking about straight out plaque and stroke and that sort of thing – is caused by an accumulation of dead cells in the mechanically quiet region of veins and arteries. There’s an accumulation of dead cells. You can find streptococcus in those cells. There’s a study within the last six months that found strep in plaque.
	+
	+	We don’t really know what forms the plaque, and we don’t have enough experience yet with using the MP – we’ve only been using it five or six years – we don’t have enough experience yet to know whether or not the plaque forms when the immune system is working properly. But everything we see points to the plaque being formed by the immune system not working properly. In other words, cardiovascular disease is related to this microbiota, because the microbiota turn off the innate immune system, and cause all these other things to go wrong, all the way from the neurological conditions to the cardiac conditions.
	+
	+	Now, as time goes by we’ll get more and more data, and also people like yourselves will get the data as well; and we’ll have to compare notes and get a better feeling for this. But we’ve had 1100 patients through our cohort at this point, we’ve got 550 still fully reporting, and most of them are at three plus years on the protocol, and some of them are at five, six years now.
	+
	+	We’ve had no strokes. We’ve had no fatal cardiac events. And we’ve had no [active] cancers in that cohort, and these are very, very sick patients. You can read their stories on the Internet. The study is open. Everybody can look at the data.
	+
	+	Well, not quite. We hide off the day to day reporting from the general public. But any physician can write me and get a password, and you see the entire site.
	+
	+	By physician I mean health professional. That includes nurses and other health professionals. Any health professional can get a password to see the private Professionals’ Discussion Area, where we discuss the science and specific patient cases. And also access to the entire message base. There are something like 150,000 messages at the moment that have been left by all the patients during this study. That can all be searched. So you can go and look at the data for yourself if you’ve got a question.
	+
	+	It’s a very different way of doing a study, but it was really the only way we could figure out to do it, given that when we started, we didn’t have this knowledge. We had a little bit of knowledge about immunopathology. We had very little knowledge about the kidney changes; we had very little knowledge about the cardiac changes. This bradycardia event was very early - that was 2003. And then we started to be very, very insistent on the dosing of azythromycin. So that was just the way we did it.
	+
	+	Now, as time goes by we’ll be able to get better data. We do have the data from the patients who were on defibrillators, which shows that demand for the defibrillator drops as they recover. So whatever was causing the arrhythmia that was firing the defibrillator goes away as the microbiota goes away. There’s another data point.
	+	At this point, it’s not a hundred per cent proven, but then, I don’t think anything much with regard to cardiovascular disease is a hundred per cent proven at this point. So it’s another possibility there that we can look at as we move forward.
	+
	+	Yes, there are a lot of genes transcribed by the VDR, and when these get knocked out, these are specific diseases, not just the autoimmune diseases. Obviously when the metastasis suppressor gets knocked out, you’d expect it to be easier for the cells to metastasize. The protein it generates is MIM - Missing In Metastasis. What effect does this have on cancers? We can’t tell you. All we can tell you is that the cohort has no active metastasis. The entire group, of fairly high risk individuals. So I think as time goes forward, the full impact of what this microbiota does to the body will be opened up by the NIH study by finding out what the organisms are, and what their genes are, and what the similarities are between those genes and the human genes, and what the interferences are between the bacterial genes and the human genes.
	+
	+	It will also be opened up as we collect more and more data on more and more individuals, which have slightly different microbiota accumulated over time. Different individuals are exposed to different foods. Many of the bacteria come down in the foods, from meat for example, different water supplies – you name it. And as we get more experience with the whole spectrum of diseases that the microbiota can cause, I think that the number of diseases is going to expand, rather than contract.
	+
	+	Does that answer your question? Do you want to ask the next question now?
	+
	+	==== Question 2 ====
	+
	+
	+	Question: Yes. I am just looking for confirmation. I’m not sure I understand you clearly. You mentioned VDR activation by PTH, by P300/CBP, and then you use olmesartan to regulate this.
	+
	+	Answer: What olmesartan does, it comes in directly here and turns on the transcription, regardless of what’s happening out here. So this can stay out of bounds, with the exception that, if the patient takes in a lot of vitamin D from their diet, some of it is converted to 1,25 dioxyvitamin-D, and that high level affects other receptors, not just the VDR. It affects the glucocorticoid and the thyroid, particularly. Therefore the dietary vitamin D has to be kept below 15 nanomolars, or there won’t be any immunopathology. There won’t be any bug-killing. So that’s the issue in relation to vitamin D.
	+
	+	Question: So it activates the vitamin D receptor, and that affects the genes for some of the peptides that are essential for antibacterial function?
	+
	+	Answer: Yes. In particular the cathelicidin, the beta defensin, and toll-like receptor 2, and to a lesser extent, toll-like receptor 4 are very dependent on VDR activation.
	+
	+	==== Question 3 ====
	+
	+
	+	By activating the Vitamin D receptor, according to your chart, it will affect many genes. Some it activates and some it represses. So some can treat patients with some disease, but some will have side-effects.
	+
	+	Answer: That’s an interesting thing. You’re saying there are negative effects of activating the VDR, as well as positive effects.
	+
	+	What we’re dealing with is a hormonal control system in man, where, if the VDR is working and the glucocorticoid receptor is working and the progesterone receptor is working and the estrogen receptor is working and the thyroid receptors are working, then the whole system works. What we’re doing is restoring the ability of that whole system to work by switching the VDR on again.
	+
	+	Now, what we are not doing is allowing the estrogen beta to downregulate the VDR, because VDR is transcribed by estrogen beta. So we’re not allowing the downregulation because that drug is forcing it hard-on.
	+	At some point, though, the patients stop taking the olmesartan, because they no longer need it. For example, we were talking about 4-hour dosing - 40 mg every four hours when the patients are ill. They desperately need it when they’re ill, because the effect of the drug has died off in four hours. But as they get better, they will go to six, eight, and even twelve hour spacing between the doses, because the symptoms disappear. At that point the body has the ability to start going in and down-regulating the VDR if that’s what’s necessary.
	+
	+	So by allowing the patient to adjust the olmesartan dosage within the range that we’ve specified, and with the guidelines that we print, and by allowing them to adjust their own antibiotic dosing, depending on what they can tolerate, we’ve really taken away a lot of the potential damage to be done by forcing the VDR on, or by creating too many cytokines.
	+
	+	But it’s a very different paradigm. What we’ve done is totally alien to normal, conventional medicine. And as we go forward from here we’ve got to sit down and collaborate and think about ways that we can move from what we have done – the proof of concept, if you like – into conventional medicine.
	+
	+	Last night I spoke about Dr. Greg Blaney in Canada. He’s done that with his patient base. He’s operating independently of us. He has about 200 seriously ill patients. At the Autoimmunity Congress he reported on a few of them, and also gave overall data on most of them.
	+
	+	Here’s another resource that we can use as we try and plan. What can we do with this knowledge? That’s really what we need to know from here on. We have this knowledge. The knowledge has been confirmed by Dr. Blaney and literally hundreds of doctors all around the world whose patients have managed to replicate our success, and who are part of our success, in fact. So the question now is, based on this knowledge, how can we use that to the benefit of the entire population? Certainly, the entire population who are ill and need help at this point.
	+
	+	Ultimately it’ll be the entire population, because once we understand the human microbiome, we’ll want to make sure we can control that human microbiome. I know, because that’s what human beings do. They try to control their environment.
	+
	+	==== Question 4 ====
	+
	+
	+	Question: I want to ask about vaccinations. Some vaccinations, I understand, can aggravate disease. What exactly is your position on vaccinations?
	+
	+	Answer: Well, there are a number of members of our cohort who have had vaccinations for everything from tetanus through to the normal influenza vaccination (routine every year, at least in America) without any obvious adverse events. However, we do discourage them from having the yearly influenza vaccination, because we feel it’s just adding a level of risk that they don’t need. Once they’re on the protocol, we don’t have any acute inflammatory events. We have periodontitis; we have lots of skin eruptions and things, but nothing that can be tracked back to an acute infection. That’s the first thing I would say.
	+
	+	Now in terms of vaccines themselves, vaccines do a very important job. Vaccines have wiped out smallpox, and they’ve wiped out polio, essentially. Those are very good, positive things.
	+
	+	We still have to fully investigate exactly what vaccines do, because we have used the postulates of Koch to decide that if we inject a live organism like BCG for example, in order to beat tuberculosis, that it beats tuberculosis. But we also know that BCG is associated with a very high incidence of sarcoidosis, many years after the vaccination. So the question is – what happens when we add vaccination to this microbiota? That is not very well defined. It’s something we just have to study as we move forward.
	+
	+	My feeling at this point would be to say, if you need the vaccination, you have to have the vaccination. The acute disease is worse than any increase in your microbiota, and we know how to work down that microbiota anyway, with the VDR agonist and antibiotic over time. So it’s better to have the vaccination.
	+
	+	But there’s no doubt - especially with vaccines that are produced in other animals – there’s no doubt that we’re introducing bacteria along with the known organism in those vaccines, because we can’t filter out these L-forms. (The NIH said that we’re dealing with approximately 10% human cells, and 90% bacterial cells.)
	+
	+	The reason is that these bacteria can form cells, in a biofilm environment, that are absolutely tiny; and those cells cannot be filtered through the manufacturing process. So, depending on the vaccine – whether it’s a live vaccine or a killed vaccine will determine whether there’s a chance that other bacteria, incidental to the manufacturing process (due perhaps to contamination or perhaps to something wrong with the animal) will be transferred through to the human being.
	+
	+	There’s no doubt some of that occurs, but we know the vaccine also does good. And now that we understand this microbiota and how it accumulates, and how to deal with it, I’m even more convinced that we need to use vaccinations for those diseases where the vaccinations are effective and needed. But we don’t typically advise the American subjects in our cohort to have their yearly vaccination against the 'flu.' And we haven’t had any problems from avoiding that.
	+
	+	So you know what I’m talking about: routine [as opposed to] important vaccinations.
	+
	+	What I would say, however, is that I’m very concerned about the practice in the west of giving vaccinations for hepatitis to children that are newborns, before they even leave the hospital after birth, because their immune systems are not working properly at this point. Their adaptive immune system doesn’t come in for a month or two, and when their innate immune systems are compromised by the large amount of vitamin D that children are given these days, that mothers are given in the west and that children are given when they’re born, their innate immune system isn’t capable of reacting correctly to that hepatitis vaccine that they’re given just after birth (in the west). I don’t know if you do that in China yet. That I am concerned about. But other vaccines are fine.
	+	{{tag>presentations videos Trevor_Marshall_PhD 2008}}
	+
	+	<nodisp>
	+	===== Notes and comments =====
	+
	+	* Some of this speech really needs the slides to go with it. The ones that contain only sentences don't matter because Marshall reads them anyway. But a) the in silico images and b) the graphs are needed to make the explanations comprehensible.
	+	* The graph that somebody made to show her impression of the symptoms of immunopathology is very interesting, but poorly explained, it seems to me. I think it would be great to stick in a note somewhere with a link to Amy's and/or Joyce's overview of the MP, for those who want a more detailed explanation.
	+
	+	</nodisp>

Presentation - Why does Vitamin-D 'Work' So Well

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

06.20.2018		current
Line 37:		Line 37:
	We will revisit how the vitamins-D affect the human body, and discuss some of the options available to help mitigate chronic symptom surges		We will revisit how the vitamins-D affect the human body, and discuss some of the options available to help mitigate chronic symptom surges

		+	==== Poster ====

		+	{{.:home:publications:ica2016_heil.pdf}}
		+
		+	[[https://mpkb.org/_media/home/publications/ica2016_heil.pdf\|click to view]]
		+
		+
		+
		+
		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====


		+	</nodisp>

Survey of Marshall Protocol patients with autoimmune diagnoses (2008)

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

08.31.2019		current
Line 2:		Line 2:

	<relatedarticles> [[home:patients:cohort_statistics\|Cohort statistics]],		<relatedarticles> [[home:patients:cohort_statistics\|Cohort statistics]],
-	[[home:pathogenesis:innate_immunity\|Innate immunity]] , [[home:food:aim_health:aging\|Research into protective effect of Olmesartan on various organs]] ,	+	[[home:pathogenesis:innate_immunity\|Innate immunity]], [[home:food:aim_health:aging\|Research into protective effect of Olmesartan on various organs]]
-	[[home:starting:physician:reluctant#Specific_research\|List which contains the PMIDs in printable form]]	+
	</article>		</article>

Line 100:		Line 99:
	{{tag> }}		{{tag> }}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

Line 106:		Line 106:
	* I love this chart. When I first saw it in the presentation on the link from the legacy site, it gave me a sense of the relative number of cohort members with various conditions, and gave me some documented evidence I could quote to friends with MP-treatable conditions. The resolution of this chart on this site is much better than what I was originally able to see (from a photo showing the powerpoint in the background). Even being able to read only the RA results clearly at that earlier time, it was helpful. Shown clearly, I love it even more. My one suggestion is that the link to this study, in Recovery Rate in the main Statistics article, is described only as methodology. I was hoping to see the results, and seeing no link to results, I hit the methodology link just in case. I'd like to see the link described as results AND methodology not just methodology, to make the info easier to find. -//Dody 2009/03/08//		* I love this chart. When I first saw it in the presentation on the link from the legacy site, it gave me a sense of the relative number of cohort members with various conditions, and gave me some documented evidence I could quote to friends with MP-treatable conditions. The resolution of this chart on this site is much better than what I was originally able to see (from a photo showing the powerpoint in the background). Even being able to read only the RA results clearly at that earlier time, it was helpful. Shown clearly, I love it even more. My one suggestion is that the link to this study, in Recovery Rate in the main Statistics article, is described only as methodology. I was hoping to see the results, and seeing no link to results, I hit the methodology link just in case. I'd like to see the link described as results AND methodology not just methodology, to make the info easier to find. -//Dody 2009/03/08//
	* It doesn't say how the patients were selected		* It doesn't say how the patients were selected
-	* New sentence added to explain selection process. --- //Joyful 05.27.2011//	+	* New sentence added to explain selection process. --- //Joyful 05.27.2011//</nodisp>

Presentation - Bacteria induced vitamin D receptor dysfunction in autoimmune disease: ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

04.02.2010		current
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	====== Presentation - Bacteria induced vitamin D receptor dysfunction in autoimmune disease: theoretical and practical implications for interpretation of serum vitamin D metabolite levels ======		====== Presentation - Bacteria induced vitamin D receptor dysfunction in autoimmune disease: theoretical and practical implications for interpretation of serum vitamin D metabolite levels ======

-	{{ vimeo>1789735}}	+	{{ youtube>qyoCRdX7-Yk}}

	Presenter: Capt. Tom Perez MPH\\		Presenter: Capt. Tom Perez MPH\\
-	Conference: [[http://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]]\\	+	Conference: [[https://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]]\\
	Location: Porto, Portugal\\		Location: Porto, Portugal\\
	Date: September 11, 2008\\		Date: September 11, 2008\\
	See also:		See also:
-	[[http://autoimmunityresearch.org/transcripts/ICA2008_Transcript_TomPerez.pdf\|Transcript and slides]]; [[http://bacteriality.com/2008/09/22/coa/\|Notes from the 2008 International Congress on Autoimmunity]] by Amy Proal; [[mp2008_survey\|More study results]]	+	[[https://autoimmunityresearch.org/transcripts/ICA2008_Transcript_TomPerez.pdf\|Transcript and slides]]; [[https://bacteriality.com/2008/09/22/coa/\|Notes from the 2008 International Congress on Autoimmunity]] by Amy Proal; [[mp2008_survey\|More study results]]

Paper - Dysregulation of the Vitamin D Nuclear Receptor may contribute to the higher prevalence ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

09.10.2010		current
Line 5:		Line 5:
	Authors: Amy D. Proal, Paul J. Albert, Trevor Marshall PhD\\		Authors: Amy D. Proal, Paul J. Albert, Trevor Marshall PhD\\
	Publication: //Annals of the New York Academy of Sciences//\\		Publication: //Annals of the New York Academy of Sciences//\\
-	Citation: {{pubmed>long:19758159}}\\	+	Citation: {{pmid>long:19758159}}\\
-	See also: [[http://autoimmunityResearch.org/preprints/ProalAnnals2009Preprint.pdf\|Pre-print]]	+

		+	<html>
		+	<a href="https://autoimmunityResearch.org/preprints/ProalAnnals2009Preprint.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
		+
		+
		+	</html>

	===== Abstract =====		===== Abstract =====
Line 14:		Line 18:

	{{tag>papers Trevor_Marshall_PhD Paul_Albert Amy_Proal Cognitive_Dysfunction pregnancy 2009}}		{{tag>papers Trevor_Marshall_PhD Paul_Albert Amy_Proal Cognitive_Dysfunction pregnancy 2009}}
-
-

Presentation - Metagenomic symbiosis between bacterial and viral pathogens in autoimmune disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

Paper - Autoimmune disease in the era of the metagenome

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

06.03.2010		current
Line 5:		Line 5:
	Authors: Amy D. Proal, Paul J. Albert, Trevor Marshall PhD\\		Authors: Amy D. Proal, Paul J. Albert, Trevor Marshall PhD\\
	Publication: //Autoimmunity reviews//\\		Publication: //Autoimmunity reviews//\\
-	Citation: {{pubmed>long:19393196}}\\	+	Citation: {{pmid>long:19393196}}\\
-	See also: [[http://AutoimmunityResearch.org/transcripts/AR-Proal-Metagenome.pdf\|Preprint]] (full text)\\	+	See also: [[https://AutoimmunityResearch.org/transcripts/AR-Proal-Metagenome.pdf\|Preprint]] (full text)\\
-	Notes: Paper based on [[home:publications:proal_congress_on_autoimmunity_2008\|presentation]] given at [[http://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]], Porto, Portugal, September 2008	+	Notes: Paper based on [[home:publications:proal_congress_on_autoimmunity_2008\|presentation]] given at [[https://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]], Porto, Portugal, September 2008

-	<html><form>	+	<html>
-	<a href="http://AutoimmunityResearch.org/transcripts/AR-Proal-Metagenome.pdf"><input type="image" name="Submit" value="Download as PDF" src="http://mpkb.org/_media/home/downloadpdf.gif"; class="buttoncalc hide" /></a>	+	<a href="https://AutoimmunityResearch.org/transcripts/AR-Proal-Metagenome.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
-	</form>	+	</html>

-
-
-	<style type="text/css">
-	input.buttoncalc {background: #d2d2d2 !important; color: #000 !important; padding:2px !important; text-align: left !important; display: inline !important;}
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-	</html>

	===== Abstract =====		===== Abstract =====
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	=====Appraisal by Faculty of 1000 Medicine=====		=====Appraisal by Faculty of 1000 Medicine=====

-	Dr. Steven Witkin writing in the prestigious literary awareness tool, [[http://www.f1000medicine.com/browse/\|Faculty of 1000]] rated the Proal //et al.// paper a "must read," saying in part:	+	Dr. Steven Witkin writing in the prestigious literary awareness tool, [[https://www.f1000medicine.com/browse/\|Faculty of 1000]] rated the Proal //et al.// paper a "must read," saying in part:

Presentation - Vitamin D induced dysregulation of nuclear receptors may account for higher ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

04.24.2009	current
Line 1:	Line 1:
	+
	+	====== Presentation - Vitamin D induced dysregulation of nuclear receptors may account for higher prevalence of some autoimmune diseases in women ======

	+
	+
	+	Type: Conference presentation\\
	+	Presenter: Amy Proal\\
	+	Conference: [[https://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]]\\
	+	Location: Porto, Portugal\\
	+	Date: September 11, 2008\\
	+	See also: [[https://bacteriality.com/2008/09/22/coa/\|Notes from the 2008 International Congress on Autoimmunity]] by Amy Proal
	+
	+
	+	{{ vimeo>1788640}}
	+
	+
	+	===== Transcript =====
	+
	+	I'm going to examine why autoimmune diseases such as Hashimoto's Thyroditis are much more likely to occur in women than in men, especially during the childbearing years. For example, in the study described by Prof. Marshall in which both sexes are allowed to participate equally, out of 104 subjects surveyed, 24 have Hashimoto's, and only 3 of them are men.
	+
	+	What might be going on? Well, one obvious difference between the sexes is that they express hormones at different levels.
	+
	+	As Professor Marshall and other researchers have shown, the VDR controls important components of innate immunity, particularly the transcription of the cathelecidin and beta Defensin antimicrobial peptides.(({{pmid>long:18200565}}))
	+
	+	Vigano's recent work has confirmed a 1978 study showing that the active vitamin D metabolite 1,25-D is expressed in the human cycling endometrium.(({{pmid>long:16720713}})) He also showed, using Western blot analysis (see slide) and immunohistochemistry (see slide) that both cycling and early pregnant endometrial cells express the VDR, which is activated by 1,25-D. Finally, he noted 40% increase in 1,25-D production in the early pregnant decidua.
	+
	+	The endometrium may have evolved to express the VDR and produce 1,25-D in an effort to offset the drop in cell mediated immunity that occurs during the weeks before menstruation, or possibly to stimulate the infant innate immune system during gestation - a time when the adaptive immune system is not yet competent.
	+
	+	But increasing evidence indicates that at some point in the history of man, a microbiota composed largely of intraphagocytic and biofilm bacteria evolved a way to take advantage of the innate immune response by creating ligands that dysregulate VDR activity. For example Prof. Marshall has identified that the sulfonolipid capnine, which is produced by gliding biofilm bacteria, is a strong VDR antagonist. I should add that we refer to this microbiota as the Th1 pathogens as their presence is associated with elevated interferon gamma. Since the Th1 pathogens are able to dysregulate the VDR, they have perverted what the body intended to be a protective environment during pregnancy and menstruation into one that allows them to flourish. When the ligands they create disable the VDR, expression of betaDefensin and cathelecidin is curtailed rather than activated.
	+
	+	And unfortunately, VDR dysregulation may instigate a series of other events that would allow the Th1 pathogens to further proliferate. You can see from this figure that when active, the VDR transcribes CYP24, an enzyme that breaks 1,25-D down into the inactive vitamin D metabolites. But what happens if the VDR is dysregulated by the Th1 pathogens? Under such conditions CYP24 is no longer transcribed and 1,25-D levels are able to rise without a feedback system to keep them in check.
	+
	+	Marshall's in silico modeling indicates that 1,25-D also has a strong affinity for the body's other nuclear receptors, suggesting that at high levels it can interfere with their activity. Since I'm discussing Thyroiditis lets take a look at the effects of elevated 1,25-D on thyroid alpha.
	+
	+	Here is the emulation of the alpha thyroid nuclear receptor (ThRa). Marshall has shown that 1,25-D has a very high affinity for ThRa - a kD value of 8.41. Normally levels of T3 (which has a kD 7.20 for ThRa) keep 1,25-D out of the binding pocket, but as 1,25-D rises due to VDR dysregulation it starts to proportionately displace T3 and block transcription by thyroid alpha. The same thing should happen with thyroid beta since Marshall has shown that 1,25-D has a Kd of 8.44 for the receptor.
	+
	+	So, when 1,25-D displaces T3, the genes with alpha thyroid promoters can no longer be transcribed. T3 gets displaced, therefore the thyroid can't function properly resulting in the phenomenon known as thyroid hormone resistance. This explains why increasing levels of thyroid hormone may be necessary to keep 1,25-D out of ThRa as the disease progresses, a measure that is palliative but not curative. And since all the type 1 nuclear receptors work as a group, when transcription by ThRa is dysregulated, system wide gene transcription is also affected.
	+
	+	And as I mentioned before, this same pattern is be repeated when it comes to several of the body's other nuclear receptors. For example, Marshall has shown that 1,25-D has a kD of 8.05 for the Androgen receptor, and a kD of 8.12 for the Glucocorticoid receptor. So elevated 1,25-D can displace cortisol and testosterone from their target receptors as well, leading to an array of other hormonal imbalances.
	+
	+	An additional effect is also of importance. By disabling the nuclear receptors, 1,25-D also has detrimental effects on system-wide AMP production. Just as the VDR expresses cathelecidin and betaDefensin, other nuclear receptors also express AMPs. Take a look at this table which presents data taken from a recent analysis of AMP expression by Brahmachary. You can see that the Glucocorticoid receptor, the Androgen receptor, and the Vitamin D Receptor, seem to be in control of 20, 17 and 16 families respectively, out of 22 analyzed.
	+
	+	So disabling the VDR with flow on effects to glucocorticoid, thyroid, androgen, and other nuclear receptors delivers a knockout blow to the body's antimicrobial peptide production. Disabling the VDR and subsequently the AMPs is a very logical thing for pathogens to have done, so much so that if such a survival mechanism were possible, it seems very likely it would have evolved.
	+
	+	It comes as little surprise then that hormonal dysregulation is so intricately connected to autoimmune disease. For example, you can see here that most of the patients with Hashimoto's analyzed by our study have also been diagnosed with other inflammatory or autoimmune diseases. In fact, only 8% of subjects with Hashimoto's have Hashimoto's alone.
	+
	+	We now have a pathway in the molecular biology showing how these apparently diverse physiological conditions can interact. Essentially, VDR dysregulation and the system-wide drop in AMP expression that it instigates allow the Th1 pathogens that Marshall describes in autoimmune disease to proliferate with greater ease. Since patients are immunocompromised, they also pick up new pathogens including viral co-infections. And what's more, since women have an extra site of VDR gene transcripton - the endometrium - they express more VDRs than men. So the over-expersison of VDR in women means that, as they age, they are disproportionately affected by the drop in AMP expression associated with VDR dysfunction. So they accumulate heavier bacterial loads exhibit greater morbidity than their male counterparts.
	+
	+	This model may also explain why women with autoimmune disease often find their symptoms escalate after pregnancy. Since 1,25-D production rises by 40% in the pregnant decidua, its ability to dysregulate the nuclear receptors and the AMPs they express is particularly prevalent during this time. So at least during the early periods of gestation, bacterial load can likely increase with exceptional ease.
	+
	+	I should also add that Marshall has shown that 25-D, which is derived from supplemental vitamin D is able to displace exogenous ligands from the nuclear receptors just as easily as 1,25-D - marking yet another way in which it is able to suppress the innate immune response.
	+
	+	So it may indeed be possible that VDR dysregulation plays a significant role in the higher incidence of autoimmune disease observed among women, and that vitamin D supplementation could further account for the skew in incidence. More research is needed.
	+
	+	Finally, I would like to add one more thing. When it comes to correlating disease incidence with low levels of vitamin D, it's also incredibly important to consider the alternate hypothesis, which is that the low levels of vitamin D may not be causing the disease but may simply be a result of the disease process. So, a low level of vitamin D correlated with an illness may simply be an indicator that the disease process has taken an effect in that patient.
	+
	+	Thank you, and I appreciate your time.
	+
	+	{{tag>presentations videos Amy_Proal cognitive_dysfunction pregnancy women Congress_on_Autoimmunity 2008 vitamin_d}}
	+
	+	===== References =====
	+

Paper - The human microbiome and autoimmunity

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 06:37:14 +0000

02.07.2013		current
Line 5:		Line 5:
	Authors: Amy D. Proal PhD, Paul J. Albert, and Trevor G Marshall PhD\\		Authors: Amy D. Proal PhD, Paul J. Albert, and Trevor G Marshall PhD\\
	Publication: //Current opinion in rheumatology //\\		Publication: //Current opinion in rheumatology //\\
-	Citation: {{pubmed>long:23370376}}\\	+	Citation: {{pmid>long:23370376}}\\
-	See also: [[http://journals.lww.com/co-rheumatology/Fulltext/2013/03000/The_human_microbiome_and_autoimmunity.14.aspx\|Full text]]\\	+	See also: [[https://autoimmunityresearch.org/preprints/Proal_2013_CurrentOpinion-Preprint.pdf\|Full text]]\\

	<html>		<html>


-	<a href="http://journals.lww.com/co-rheumatology/Fulltext/2013/03000/The_human_microbiome_and_autoimmunity.14.aspx"><img src="http://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>	+	<a href="https://autoimmunityresearch.org/preprints/Proal_2013_CurrentOpinion-Preprint.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>

Poster - Cognitive dysfunction in women with chronic fatigue syndrome: examining the role of ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 06:37:14 +0000

10.24.2009		current
Line 1:		Line 1:

-	====== Abstract - Cognitive dysfunction in women with chronic fatigue syndrome: examining the role of the endometrium, the nuclear receptors, and the antimicrobial peptides ======	+	====== Poster - Cognitive dysfunction in women with chronic fatigue syndrome: examining the role of the endometrium, the nuclear receptors, and the antimicrobial peptides ======

-	{{ vimeo>952759}}

	Type: Abstract presentation\\		Type: Abstract presentation\\
	Presented by: Amy Proal\\		Presented by: Amy Proal\\
-	Conference: [[http://www.massgeneral.org/cvrc/meetings_molecular_agenda.html\|Days of Molecular Medicine 2008]]\\	+	Conference: [[https://www.massgeneral.org/cvrc/meetings_molecular_agenda.html\|Days of Molecular Medicine 2008]]\\
	Location: Karolinska Institue, Sweden\\		Location: Karolinska Institue, Sweden\\
	Date: April 17-19, 2008\\		Date: April 17-19, 2008\\
-	Additional content: [[http://autoimmunityresearch.org/dmm2008/DMM2008_Amy_Poster.pdf\|poster]]; [[http://bacteriality.com/2008/04/25/dmm/\|Notes from the Conference]] by Amy Proal\\	+	Additional content: [[https://autoimmunityresearch.org/dmm2008/DMM2008_Amy_Poster.pdf\|poster]]; [[https://bacteriality.com/2008/04/25/dmm/\|Notes from the Conference]] by Amy Proal\\
	Notes: presentation begins at 28:13;		Notes: presentation begins at 28:13;

		+	{{ vimeo>952759}}


Line 18:		Line 18:


-	Chronic fatigue syndrome (CFS/ME) has recently been recognized by the CDC as a physiological disease that leaves patients substantially debilitated. Increasing evidence, including data from twin studies(({{pubmed>long:17605583}})), points to the fact that patients with the illness also suffer from a significant degree of cognitive dysfunction - impairing their ability to process information, and recall verbal and visual information(({{pubmed>long:8442710}})). We present data from a large cohort of CFS/ME patients in a study of a VDR nuclear receptor agonist, which suggest that women with CFS/ME tend to suffer from a greater decline in cognitive function then their male counterparts, and that cognitive function is at least partly restored by the agonist. The cognitive function of five women is examined in greater detail. For example, after falling ill with CFS/ME, one 45-year-old female went from being a corporate executive to reading at a 4th grade level. She became too confused to drive, lost her short-term memory, and forgot words, grammar, and basic math. Another patient was a corporate attorney who, after falling ill with CFS/ME, found that her reading skills fell to an 8th grade level. She lost the ability to problem solve and could not get beyond the first set of questions on an IQ test. In view of the recent report that the VDR nuclear receptor is over-expressed in the endometrium(({{pubmed>long:16720713}})), it is possible that the severity of cognitive dysfunction among women may not be due to serendipity and that there is need for future research of gene expression in the endometrium.	+	Chronic fatigue syndrome (CFS/ME) has recently been recognized by the CDC as a physiological disease that leaves patients substantially debilitated. Increasing evidence, including data from twin studies(({{pmid>long:17605583}})), points to the fact that patients with the illness also suffer from a significant degree of cognitive dysfunction - impairing their ability to process information, and recall verbal and visual information(({{pmid>long:8442710}})). We present data from a large cohort of CFS/ME patients in a study of a VDR nuclear receptor agonist, which suggest that women with CFS/ME tend to suffer from a greater decline in cognitive function then their male counterparts, and that cognitive function is at least partly restored by the agonist. The cognitive function of five women is examined in greater detail. For example, after falling ill with CFS/ME, one 45-year-old female went from being a corporate executive to reading at a 4th grade level. She became too confused to drive, lost her short-term memory, and forgot words, grammar, and basic math. Another patient was a corporate attorney who, after falling ill with CFS/ME, found that her reading skills fell to an 8th grade level. She lost the ability to problem solve and could not get beyond the first set of questions on an IQ test. In view of the recent report that the VDR nuclear receptor is over-expressed in the endometrium(({{pmid>long:16720713}})), it is possible that the severity of cognitive dysfunction among women may not be due to serendipity and that there is need for future research of gene expression in the endometrium.
-	{{tag>abstracts videos Amy_Proal DMM cognitive_dysfunction women 2008}}	+	{{tag>posters videos Amy_Proal DMM cognitive_dysfunction women 2008}}

	===== References =====		===== References =====

Paper - Inflammatory disease and the human microbiome

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 06:37:14 +0000

06.13.2014		current
Line 2:		Line 2:

	Type: Paper\\		Type: Paper\\
-	Authors: Amy D. Proal PhD, Paul J. Albert, and Trevor G Marshall PhD\\	+	Authors: Amy D. Proal PhD, Paul J. Albert, and Trevor G Marshall PhD\\
-	Publication: //Discovery Medicine//\\	+	Publication: //Discovery Medicine//\\
-	Citation: {{pubmed>long:24882717}}\\	+	Citation: {{pmid>long:24882717}}\\
-	See also: [[http://autoimmunityresearch.org/preprints/Proal_2014_DiscoveryMedicine-Preprint.pdf\|Full text]]\\	+	See also: [[https://autoimmunityresearch.org/preprints/Proal_2014_DiscoveryMedicine-Preprint.pdf\|Full text]]\\

	<html>		<html>


-	<a href="http://autoimmunityresearch.org/preprints/Proal_2014_DiscoveryMedicine-Preprint.pdf"><img src="http://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>	+	<a href="https://autoimmunityresearch.org/preprints/Proal_2014_DiscoveryMedicine-Preprint.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>

Paper - Microbe-microbe and host-microbe interactions drive microbiome dysbiosis and ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

03.29.2017		current
Line 1:		Line 1:
-	====== Paper - Microbe interactions drive microbiome dysbiosis and inflammatory processes. ======	+	====== Paper - Microbe-microbe and host-microbe interactions drive microbiome dysbiosis and inflammatory processes. ======

	Type: Paper\\		Type: Paper\\
	Authors: Amy D. Proal PhD, Inge A. Lindseth, and Trevor G Marshall PhD\\		Authors: Amy D. Proal PhD, Inge A. Lindseth, and Trevor G Marshall PhD\\
	Publication: //Discovery Medicine//\\		Publication: //Discovery Medicine//\\
-	Citation: {{pubmed>long:28245427}}\\	+	Citation: {{pmid>long:28245427}}\\
-	Full text see : [[http://www.discoverymedicine.com/Amy-D-Proal/2017/01/microbe-microbe-and-host-microbe-interactions-drive-microbiome-dysbiosis-and-inflammatory-processes/\|Microbe interactions]]\\	+	Full text see : [[https://www.discoverymedicine.com/Amy-D-Proal/2017/01/microbe-microbe-and-host-microbe-interactions-drive-microbiome-dysbiosis-and-inflammatory-processes/\|Microbe interactions]]\\

	<html>		<html>
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	{{tag>papers Trevor_Marshall_PhD Inge_Lindseth Amy_Proal}}		{{tag>papers Trevor_Marshall_PhD Inge_Lindseth Amy_Proal}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

	--- //Sallie Q 03.29.2017// found no pdf like the earlier paper		--- //Sallie Q 03.29.2017// found no pdf like the earlier paper
-	<a href="http://autoimmunityresearch.org/preprints/Proal_2014_DiscoveryMedicine-Preprint.pdf"><img src="http://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>	+	<a href="https://autoimmunityresearch.org/preprints/Proal_2014_DiscoveryMedicine-Preprint.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
		+	</nodisp>

Paper - Re-framing the Theory of Autoimmunity in the Era of the microbiome: Persistent ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

10.09.2018		current
Line 1:		Line 1:
-	====== Re-framing the Theory of Autoimmunity in the Era of the microbiome: Persistent Pathogens, Autoantibodies, and Molecular Mimicry ======	+	====== Paper - Re-framing the Theory of Autoimmunity in the Era of the microbiome: Persistent Pathogens, Autoantibodies, and Molecular Mimicry ======

	Type: Paper\\		Type: Paper\\
	Authors: Amy D. Proal PhD, Trevor G Marshall PhD\\		Authors: Amy D. Proal PhD, Trevor G Marshall PhD\\
	Publication: //Discovery Medicine//\\		Publication: //Discovery Medicine//\\
-	Citation: {{pubmed>long:30021103}}	+	Citation: {{pmid>long:30021103}}


-	Full text see : [[ http://www.discoverymedicine.com/Amy-D-Proal/2018/06/autoimmunity-in-era-of-microbiome-persistent-pathogens-autoantibodies-molecular-mimicry/\|Re-framing the Theory of Autoimmunity]]\\	+	Full text see : [[ https://www.discoverymedicine.com/Amy-D-Proal/2018/06/autoimmunity-in-era-of-microbiome-persistent-pathogens-autoantibodies-molecular-mimicry/\|Re-framing the Theory of Autoimmunity]]\\

	<html>		<html>
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	{{tag>papers Trevor_Marshall_PhD Amy_Proal}}		{{tag>papers Trevor_Marshall_PhD Amy_Proal}}

		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====

-	http://www.discoverymedicine.com/Amy-D-Proal/2018/06/autoimmunity-in-era-of-microbiome-persistent-pathogens-autoantibodies-molecular-mimicry/	+	https://www.discoverymedicine.com/Amy-D-Proal/2018/06/autoimmunity-in-era-of-microbiome-persistent-pathogens-autoantibodies-molecular-mimicry/

	<note important>add citation</note>		<note important>add citation</note>
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	Published on June 26, 2018		Published on June 26, 2018

-	{{pubmed>long:30021103}}	+	{{pmid>long:30021103}}

	Proal AD, Marshall TG.		Proal AD, Marshall TG.

	Discov Med. 2018 Jun;25(140):299-308.		Discov Med. 2018 Jun;25(140):299-308.
		+	</nodisp>

Paper - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: ...

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 20:53:47 +0000

02.10.2019		current
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-	====== Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity. ======	+	====== Paper - Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in the Era of the Human Microbiome: Persistent Pathogens Drive Chronic Symptoms by Interfering With Host Metabolism, Gene Expression, and Immunity. ======

	Type: Paper\\		Type: Paper\\
	Authors: Amy D. Proal PhD and Trevor G Marshall PhD\\		Authors: Amy D. Proal PhD and Trevor G Marshall PhD\\
	Publication: //Frontiers in Pediatrics//\\		Publication: //Frontiers in Pediatrics//\\
-	Citation: {{pubmed>long:30564562}}	+	Citation: {{pmid>long:30564562}}

	**Full text		**Full text
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-	===== Notes and comments =====	+	<nodisp>
		+	===== Notes and comments =====</nodisp>

Poster - Successive infection: a model for how metagenomic communities shift to become more ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

09.03.2010		current
Line 8:		Line 8:
	Location: Washington University, St. Louis, Missouri\\		Location: Washington University, St. Louis, Missouri\\
	Date: August 31 – September 1, 2010\\		Date: August 31 – September 1, 2010\\
-	Additional Content: [[http://mpkb.org/_media/home/publications/ProalHMRC.pdf\|PDF of poster]]	+	Additional Content: [[https://mpkb.org/_media/home/publications/proal_hmrc2010.pdf\|PDF of poster]]

Presentation - Antibodies and infection in the era of metagenome

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

06.21.2018		current
Line 4:		Line 4:
	Type: Conference presentation\\		Type: Conference presentation\\
	Presenter: Amy Proal\\		Presenter: Amy Proal\\
-	Conference: [[http://www.bitlifesciences.com/ica2009/\|1st International Congress of Antibodies]]\\	+	Conference: [[https://www.bitlifesciences.com/ica2009/\|1st International Congress of Antibodies]]\\
	Location: Beijing, China\\		Location: Beijing, China\\
	Date: May 22-24, 2009\\		Date: May 22-24, 2009\\
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	==== see also ====		==== see also ====
		+
		+	See also: [[https://bacteriality.com/2009/06/11/ica/ \|Notes from the 2009 International Congress of Antibodies]] by Amy Proal

	{{tag>presentations videos Trevor_Marshall_PhD 2009}}		{{tag>presentations videos Trevor_Marshall_PhD 2009}}

Book chapter - Autoimmune disease and the human metagenome

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

03.06.2011		current
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	Type: Book chapter\\		Type: Book chapter\\
	Authors: Amy Proal, Paul Albert, Trevor Marshall PhD\\		Authors: Amy Proal, Paul Albert, Trevor Marshall PhD\\
-	Publication: //Vitamin D: New Research//\\	+	Publication: //Metagenomics of the human body //\\
	Citation: Proal AD //et al//. Autoimmune disease and the human metagenome. //Metagenomics of the human body// 231-75(2010).\\		Citation: Proal AD //et al//. Autoimmune disease and the human metagenome. //Metagenomics of the human body// 231-75(2010).\\
-	See also: [[http://Autoimmunityresearch.org/preprints/Proal_MHB_Chapter_preprint.pdf\|Pre-print]]	+	See also: [[https://Autoimmunityresearch.org/preprints/Proal_MHB_Chapter_preprint.pdf\|Pre-print]]

Paper - Immunostimulation in the era of the metagenome

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

07.27.2011		current
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	Authors: Amy D. Proal, Paul J. Albert, Greg P. Blaney M.D., Inge A. Lindseth, Chris Benediktsson and Trevor G Marshall PhD\\		Authors: Amy D. Proal, Paul J. Albert, Greg P. Blaney M.D., Inge A. Lindseth, Chris Benediktsson and Trevor G Marshall PhD\\
	Publication: //Cellular & molecular immunology //\\		Publication: //Cellular & molecular immunology //\\
-	Citation: {{pubmed>long:21278764}}\\	+	Citation: {{pmid>long:21278764}}\\
-	See also: [[http://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf\|Preprint]] (full text)\\	+	See also: [[https://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf\|Preprint]] (full text)\\

	<html>		<html>
	<!--<form>		<!--<form>
-	<a href="http://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf"><input type="image" name="Submit" value="Download as PDF" src="http://mpkb.org/_media/home/downloadpdf.gif"; class="buttoncalc hide" /></a>	+	<a href="https://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf"><input type="image" name="Submit" value="Download as PDF" src="https://mpkb.org/_media/home/downloadpdf.gif"; class="buttoncalc hide" /></a>
	</form>-->		</form>-->

-	<form>	+
-	<a href="http://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf"><input type="image" name="Submit" value="Download as PDF" src="http://mpkb.org/_media/home/downloadpdf.gif"; class="buttoncalc hide" /></a>	+	<a href="https://autoimmunityresearch.org/preprints/Proal2010CellularMolecularImmunologyPreprint.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
-	</form>	+

	</html>		</html>

Paper - Reversing bacteria-induced Vitamin D Receptor dysfunction is key to autoimmune disease

anonymous@undisclosed.example.com (Anonymous) — Wed, 14 Sep 2022 05:14:49 +0000

09.10.2010		current
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	Authors: Joyce C. Waterhouse PhD, Thomas H. Perez, Paul J. Albert\\		Authors: Joyce C. Waterhouse PhD, Thomas H. Perez, Paul J. Albert\\
	Publication: //Annals of the New York Academy of Sciences//\\		Publication: //Annals of the New York Academy of Sciences//\\
-	Citation: {{pubmed>long:19758226}}\\	+	Citation: {{pmid>long:19758226}}\\
-	See also: [[http://autoimmunityResearch.org/preprints/WaterhouseAnnals2009Preprint.pdf\|Pre-print]]	+
		+
		+	<html>
		+	<a href="https://autoimmunityResearch.org/preprints/WaterhouseAnnals2009Preprint.pdf"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
		+	</html>

	===== Abstract =====		===== Abstract =====
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	{{tag>papers Paul_Albert Joyce_Waterhouse_PhD Thomas_Perez 2009}}		{{tag>papers Paul_Albert Joyce_Waterhouse_PhD Thomas_Perez 2009}}
-

Article - The Marshall Protocol for Lyme Disease and other chronic inflammatory conditions

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

04.21.2009	current
Line 1:	Line 1:
	+	====== Article - The Marshall Protocol for Lyme Disease and other chronic inflammatory conditions ======
	+
	+
	+	Type: Article\\
	+	Author: Joyce Waterhouse PhD\\
	+	Publication: //Townsend letter//\\
	+	Citation: Waterhouse, J. The Marshall Protocol for Lyme Disease and other chronic inflammatory conditions. //Townsend Letter// (2007).\\
	+	Related content: [[https://winmlm.neostrada.pl/mp/townsend/Townsend_Apr07.PartOne.pdf\|full text of Part One]]; [[https://winmlm.neostrada.pl/mp/townsend/Townsend_Letter_May2007.Part2.pdf\|full text of Part Two]]
	+
	+
	+
	+	===== Abstract =====
	+
	+	A new approach called the Marshall Protocol (MP), is now achieving success in treating chronic Lyme disease. This protocol was originally developed for sarcoidosis by Trevor Marshall PhD, of the Autoimmunity Research Foundation. The MP's main targets are the treatment-resistanct cell wall deficient (CWD, L-form or cyst) forms of //Borrelia burgdorferi// (Bb) and a variety of other bacterial species - though it also kills spirochetal/classical bacterial forms.
	+	{{tag>Joyce_Waterhouse_PhD 2007 Lyme_Disease}}

Book chapter - High levels of active 1,25-dihydroxyvitamin D despite low levels of the ...

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

12.02.2009		current
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	Publication: //Vitamin D: New Research//\\		Publication: //Vitamin D: New Research//\\
	Citation: Waterhouse, J. et al. High levels of active 1,25-dihydroxyvitamin D despite low levels of the 25-hydroxyvitamin D precursor — implications of dysregulated vitamin D for diagnosis and treatment of chronic disease. //Vitamin D: New Research// 1-23(2006).\\		Citation: Waterhouse, J. et al. High levels of active 1,25-dihydroxyvitamin D despite low levels of the 25-hydroxyvitamin D precursor — implications of dysregulated vitamin D for diagnosis and treatment of chronic disease. //Vitamin D: New Research// 1-23(2006).\\
-	See also: [[https://www.novapublishers.com/catalog/product_info.php?products_id=5380\|full text available for purchase from Nova Publishers]]; most/all of chapter available as scanned document at [[http://books.google.com/books?id=oSl8VY33634C&pg=PA1#v=onepage&q=&f=false\|Google Books]]	+	See also: [[https://www.novapublishers.com/catalog/product_info.php?products_id=5380\|full text available for purchase from Nova Publishers]]; [[https://books.google.com/books?id=oSl8VY33634C&pg=PA1#v=onepage&q=&f=false\|most/all of chapter available as scanned document at Google Books]]

Presentation - Vitamins D in chronic disease

anonymous@undisclosed.example.com (Anonymous) — Mon, 04 Jul 2022 12:06:16 +0000

01.29.2010		current
Line 7:		Line 7:
	Location: Los Angeles, CA\\		Location: Los Angeles, CA\\
	Date: June 17-18, 2006\\		Date: June 17-18, 2006\\
-	Related content: [[http://autoimmunityresearch.org/transcripts/waterhouse_lax2006.pdf\|slides and transcript]]\\	+	Related content: [[https://autoimmunityresearch.org/transcripts/waterhouse_lax2006.pdf\|slides and transcript]]\\


Line 100:		Line 100:
	is this little red oxygen. It’s actually an OH and this is added and it		is this little red oxygen. It’s actually an OH and this is added and it
	makes all the difference. And here we have a nice picture of a		makes all the difference. And here we have a nice picture of a
-	kidney. O.K. So we have the molecule is transformed by adding	+	kidney. O.K. So we have the molecule transformed by adding
	the hydroxyl group so it can now activate the vitamin D receptor.		the hydroxyl group so it can now activate the vitamin D receptor.
	Most doctors rely on the 25D precursor to decide how much		Most doctors rely on the 25D precursor to decide how much

09.03.2010		current
Line 8:		Line 8:
	Location: Washington University, St. Louis\\		Location: Washington University, St. Louis\\
	Date: August 31 - September 1, 2010\\		Date: August 31 - September 1, 2010\\
-	Additional Content: [[http://mpkb.org/_media/home/publications/2010-Albert-HMRC.pdf\|PDF of poster]]	+	Additional Content: [[https://mpkb.org/_media/home/publications/albert_hmrc2010.pdf\|PDF of poster]]

06.14.2010		current
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	Type: Conference presentation\\		Type: Conference presentation\\
	Presenter: Greg Blaney, MD\\		Presenter: Greg Blaney, MD\\
-	Conference: [[http://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]]\\	+	Conference: [[https://www.kenes.com/autoimmunity/\|6th International Congress on Autoimmunity]]\\
	Location: Porto, Portugal\\		Location: Porto, Portugal\\
	Date: September 11, 2008\\		Date: September 11, 2008\\
-	Additional content: [[http://bacteriality.com/2008/09/22/coa/\|Notes from the 2008 International Congress on Autoimmunity]] by Amy Proal; [[http://mpkb.org/_media/pdf/ica2008_transcript_gregblaney.pdf\|PDF of transcript alongside slides]]	+	Additional content: [[https://bacteriality.com/2008/09/22/coa/\|Notes from the 2008 International Congress on Autoimmunity]] by Amy Proal; [[https://AutoimmunityResearch.org/transcripts/ICA2008_Transcript_GregBlaney.pdf\|PDF of transcript alongside slides]]

05.20.2012		current
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-	{{ youtube>g6sH7NTXkjw}}	+	{{ youtube>2IMdAV6SIMU}}



	Type: Conference presentation\\		Type: Conference presentation\\
-	Presenter: Trevor Marshall, PhD\\	+	Presenter: Inge Lindseth\\
	Conference: 8th International Congress on Autoimmunity \\		Conference: 8th International Congress on Autoimmunity \\
	Location: Grenada, Spain\\		Location: Grenada, Spain\\
	Date: May 9-13, 2012\\		Date: May 9-13, 2012\\
-	Additional content: [[http://autoimmunityresearch.org/transcripts/Auto2012_IngeLindseth.pdf\|PDF transcript]]	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Auto2012_IngeLindseth.pdf\|PDF transcript]]


-	{{tag>presentations videos Trevor_Marshall_PhD 2012}}	+	{{tag>presentations videos Inge_Lindseth 2012}}

09.10.2010		current
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	Authors: Trevor Marshall PhD, Frances E. Marshall\\		Authors: Trevor Marshall PhD, Frances E. Marshall\\
	Publication: //Autoimmunity reviews//\\		Publication: //Autoimmunity reviews//\\
-	Citation: {{pubmed>long:15246025}}\\	+	Citation: {{pmid>long:15246025}}\\
-	See also: [[http://yarcrip.com/sarcoidosissuccumbs-preprint.htm\|Preprint]] (full text)\\	+	Notes: Paper based on presentation ([[https://www.kenes.com/autoim2004/program/ViewAbstract.asp?SerialKey=308065\|abstract]]) given at [[https://www.kenes.com/autoim2004/\|4th International Conference on Autoimmunity]], Budapest, Hungary Nov 2004
-	Notes: Paper based on presentation ([[http://www.kenes.com/autoim2004/program/ViewAbstract.asp?SerialKey=308065\|abstract]]) given at [[http://www.kenes.com/autoim2004/\|4th International Conference on Autoimmunity]], Budapest, Hungary Nov 2004	+
		+
		+
		+	<html>
		+	<a href="https://yarcrip.com/sarcoidosissuccumbs-preprint.htm"><img src="https://mpkb.org/_media/home/downloadpdf.gif" class="pdfbutton" /></a>
		+	</html>
		+
		+

05.20.2012		current
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	Type: Conference presentation\\		Type: Conference presentation\\
	Presenter: Trevor Marshall, PhD\\		Presenter: Trevor Marshall, PhD\\
-	Conference: Autoimmunity Congress Asia\\	+	Conference: 8th International Congress on Autoimmunity \\
	Location: Grenada, Spain\\		Location: Grenada, Spain\\
	Date: May 9-13, 2012\\		Date: May 9-13, 2012\\
-	Additional content: [[http://autoimmunityresearch.org/transcripts/Auto2012_Marshall_plenary.pdf\|PDF Transcript]]	+	Additional content: [[https://autoimmunityresearch.org/transcripts/Auto2012_Marshall_plenary.pdf\|PDF Transcript]]

	{{tag>presentations videos Trevor_Marshall_PhD 2012}}		{{tag>presentations videos Trevor_Marshall_PhD 2012}}
-

06.21.2018		current
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	Prof Marshall discusses how EM radiation especially affects people with chronic disease, and why a Physician needs to be alert to this factor when a patient is struggling.		Prof Marshall discusses how EM radiation especially affects people with chronic disease, and why a Physician needs to be alert to this factor when a patient is struggling.

-	The ABSTRACT for this presentation can be viewed on the Conference website at https://bit.ly/2LT9Bow	+	The ABSTRACT for this presentation can be viewed on the Conference website at [[https://bit.ly/2LT9Bow\|ENVIRONMENT, NUTRITION AND AUTOIMMUNITY]]

	Here are links to some cited resources:		Here are links to some cited resources:
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	1. Full 1 hr NASA video on Electromagnetics: [[https://science.nasa.gov/ems/01_intro\|Tour of the Electromagnetic Spectrum]]		1. Full 1 hr NASA video on Electromagnetics: [[https://science.nasa.gov/ems/01_intro\|Tour of the Electromagnetic Spectrum]]

-	2. Dr Amy Proal's Blog: [[http://MicrobeMinded.com\|Microbe Minded]]	+	2. Dr Amy Proal's Blog: [[https://MicrobeMinded.com\|Microbe Minded]]

	3. "Electrosmog and Autoimmune Disease" [[https://link.springer.com/article/10.1007%2Fs12026-016-8825-7\|Electrosmog and autoimmune disease]]		3. "Electrosmog and Autoimmune Disease" [[https://link.springer.com/article/10.1007%2Fs12026-016-8825-7\|Electrosmog and autoimmune disease]]

-	4. BioInitiative-2012 Consensus: [[http://www.bioinitiative.org/conclusions/\|Conclusions]]	+	4. BioInitiative-2012 Consensus: [[https://www.bioinitiative.org/conclusions/\|Conclusions]]

-	5. Sacco & Tomilin paper: [[http://www.vixra.org/pdf/1210.0158v1.pdf\|The study of electromagnetic processes in the experiments of Tesla]]	+	5. Sacco & Tomilin paper: [[https://www.vixra.org/pdf/1210.0158v1.pdf\|The study of electromagnetic processes in the experiments of Tesla]]

	{{tag>presentations videos Trevor_Marshall_PhD 2018}}		{{tag>presentations videos Trevor_Marshall_PhD 2018}}
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		+	<nodisp>
	===== Notes and comments =====		===== Notes and comments =====


		+	</nodisp>