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home:protocol:immunopathology [10.25.2018] – [Related publications and presentations] sallieqhome:protocol:immunopathology [09.14.2022] (current) – external edit 127.0.0.1
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-Many MP patients who have experienced prolonged periods of immunopathology have reached stages of significant improvement or remission. This supports the conclusion that immunopathology is a necessary result of chronic bacterial death, and a precursor to disease reversal. The MP is not unique in this regard. A number of other diseases and/or therapies generate immunopathological or immunopathological-like reactions.(({{pubmed>long:11997718}})) (({{pubmed>long:18600241}})) (({{pubmed>long:12604286}}))+Many MP patients who have experienced prolonged periods of immunopathology have reached stages of significant improvement or remission. This supports the conclusion that immunopathology is a necessary result of chronic bacterial death, and a precursor to disease reversal. The MP is not unique in this regard. A number of other diseases and/or therapies generate immunopathological or immunopathological-like reactions.(({{pmid>long:11997718}})) (({{pmid>long:18600241}})) (({{pmid>long:12604286}}))
  
 Lab work and patient reports can be used to [[home:mp:immunopathology#assessing_immunopathology|track clinical signs of immunopathology]]. Lab work and patient reports can be used to [[home:mp:immunopathology#assessing_immunopathology|track clinical signs of immunopathology]].
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 ===== Competing models for immunopathology ===== ===== Competing models for immunopathology =====
  
-According to a 2010 review by evolutionary biologist Paul Ewald, PhD, there are essentially three categories of explanations for immunopathology in chronic disease:(({{pubmed>long:20415848}}))+According to a 2010 review by evolutionary biologist Paul Ewald, PhD, there are essentially three categories of explanations for immunopathology in chronic disease:(({{pmid>long:20415848}}))
  - The immune system is exposed to environmental conditions to which the individual is not well adapted. One hypothesis within this category, often referred to as the hygiene hypothesis, proposes that new more hygienic environmental conditions have generated compositions of symbionts that differ from those to which humans have been adapted.   - The immune system is exposed to environmental conditions to which the individual is not well adapted. One hypothesis within this category, often referred to as the hygiene hypothesis, proposes that new more hygienic environmental conditions have generated compositions of symbionts that differ from those to which humans have been adapted. 
  - Infectious agents act as triggers of immunopathology by shifting the immune system into a self-destructive state.   - Infectious agents act as triggers of immunopathology by shifting the immune system into a self-destructive state. 
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 ===== Symptoms of infection are caused by the body's response to microbes ===== ===== Symptoms of infection are caused by the body's response to microbes =====
  
-A 2011 study, using a novel mouse model, showed that mice that were engineered to have a reduced innate immune response to the common cold actually showed less – not more – airway inflammation and bronchoconstriction (airway spasm) following infection.(({{pubmed>long:21637773}})) According to the study's lead author:+A 2011 study, using a novel mouse model, showed that mice that were engineered to have a reduced innate immune response to the common cold actually showed less – not more – airway inflammation and bronchoconstriction (airway spasm) following infection.(({{pmid>long:21637773}})) According to the study's lead author:
  
 <blockquote>In our study, we offer the first direct evidence that limiting the immune response reduces the manifestations of rhinovirus infection. In our model, cold-induced asthma flare-ups were caused by the body's immune response to the virus, not the virus itself. Chemicals produced by the immune system inflame cells and tissues, causing asthma symptoms such as cough and wheeze. <blockquote>In our study, we offer the first direct evidence that limiting the immune response reduces the manifestations of rhinovirus infection. In our model, cold-induced asthma flare-ups were caused by the body's immune response to the virus, not the virus itself. Chemicals produced by the immune system inflame cells and tissues, causing asthma symptoms such as cough and wheeze.
  
-//**Marc B. Hershenson, M.D.,**  [[http://www.sciencedaily.com/releases/2011/06/110616081719.htm|ScienceDaily]]// June 17, 2011</blockquote> +//**Marc B. Hershenson, M.D.,**  [[https://www.sciencedaily.com/releases/2011/06/110616081719.htm|ScienceDaily]]// June 17, 2011</blockquote> 
  
 Even though it was conducted in a murine model, this work is relevant as it strongly suggests that symptoms of infection are due not so much to the infection but the body's response to it. Even though it was conducted in a murine model, this work is relevant as it strongly suggests that symptoms of infection are due not so much to the infection but the body's response to it.
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 During immunopathology, cytokines, are elevated. Cytokines are released by the inflammatory process. During immunopathology, cytokines, are elevated. Cytokines are released by the inflammatory process.
  
-The release of cytokines appears to be essential for recovery after an infection. One study found that the cytokine TNF-alpha was essential for the proper expression of acquired specific resistance following infection with //Mycobacterium tuberculosis//.(({{pubmed>long:18544042}})) (({{pubmed>long:12852719}})) (({{pubmed>long:15216471}})) For this reason among others, [[home:othertreatments:antitnf|TNF-alpha inhibitors]], drugs which suppress the cytokine, are contraindicated for MP patients.+The release of cytokines appears to be essential for recovery after an infection. One study found that the cytokine TNF-alpha was essential for the proper expression of acquired specific resistance following infection with //Mycobacterium tuberculosis//.(({{pmid>long:18544042}})) (({{pmid>long:12852719}})) (({{pmid>long:15216471}})) For this reason among others, [[home:othertreatments:antitnf|TNF-alpha inhibitors]], drugs which suppress the cytokine, are contraindicated for MP patients.
 ==== Endotoxins ==== ==== Endotoxins ====
  
 Endotoxins, sometimes referred to as lipopolysaccharides, are proteins associated with bacteria and bacterial communities (microbiota). When these bacteria are destroyed by the innate immune system, as will happen during the MP, endotoxins are released causing a spike in symptoms known as an immunopathological reaction. Endotoxins, sometimes referred to as lipopolysaccharides, are proteins associated with bacteria and bacterial communities (microbiota). When these bacteria are destroyed by the innate immune system, as will happen during the MP, endotoxins are released causing a spike in symptoms known as an immunopathological reaction.
  
-The body responds to the presence of endotoxins by producing cholesterol(({{pubmed>long:20377753}})) and C-reactive protein,(({{pubmed>long:15198851}})) among other defense mechanisms.+The body responds to the presence of endotoxins by producing cholesterol(({{pmid>long:20377753}})) and C-reactive protein,(({{pmid>long:15198851}})) among other defense mechanisms.
  
-In immunology, the term "LPS challenge" refers to the process of exposing a subject to a lipopolysaccharide that may act as a toxin. Injecting mice with LPS has been used as models for preterm labor,(({{pubmed>long:19995880}})) hyperactivity,(({{pubmed>long:18814846}})) lung injury,(({{pubmed>long:16273282}})) and periodontitis,(({{pubmed>long:15218043}})) to cite just a few examples.+In immunology, the term "LPS challenge" refers to the process of exposing a subject to a lipopolysaccharide that may act as a toxin. Injecting mice with LPS has been used as models for preterm labor,(({{pmid>long:19995880}})) hyperactivity,(({{pmid>long:18814846}})) lung injury,(({{pmid>long:16273282}})) and periodontitis,(({{pmid>long:15218043}})) to cite just a few examples.
  
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 Occasionally, patients may notice new symptoms occurring in organs not known to be infected. The MP cannot create new infection, such symptoms are due to exacerbation of previous sub-clinical microbiota. Occasionally, patients may notice new symptoms occurring in organs not known to be infected. The MP cannot create new infection, such symptoms are due to exacerbation of previous sub-clinical microbiota.
  
-The strength of an immunopathological or herx reaction is associated with the severity of disease.(({{pubmed>long:15896248}})) (({{pubmed>long:6017505}}))+The strength of an immunopathological or herx reaction is associated with the severity of disease.(({{pmid>long:15896248}})) (({{pmid>long:6017505}}))
  
 ===== Other examples of immunopathology ===== ===== Other examples of immunopathology =====
  
 The Jarisch-Herxheimer reaction is similar if not identical to immunopathology. These reactions have been accepted as an indication of progress and, according to the literature, have been observed in at least ten different diseases and conditions: The Jarisch-Herxheimer reaction is similar if not identical to immunopathology. These reactions have been accepted as an indication of progress and, according to the literature, have been observed in at least ten different diseases and conditions:
-  * syphillis including neurosyphillis(({{pubmed>long:12604286}})) and syphillitic alopecia(({{pubmed>long:606336}}))  +  * syphillis including neurosyphillis(({{pmid>long:12604286}})) and syphillitic alopecia(({{pmid>long:606336}}))  
-  * Lyme disease(({{pubmed>long:9610974}})) +  * Lyme disease(({{pmid>long:9610974}})) 
-  * //Borrelia// infection(({{pubmed>long:9846580}})) +  * //Borrelia// infection(({{pmid>long:9846580}})) 
-  * multiple sclerosis(({{pubmed>long:15617845}})) (({{pubmed>long:11516219}})) +  * multiple sclerosis(({{pmid>long:15617845}})) (({{pmid>long:11516219}})) 
-  * tuberculosis(({{pubmed>long:18600241}})) +  * tuberculosis(({{pmid>long:18600241}})) 
-  * leptospirosis(({{pubmed>long:12827534}})) +  * leptospirosis(({{pmid>long:12827534}})) 
-  * Whipple disease(({{pubmed>long:11721494}})) +  * Whipple disease(({{pmid>long:11721494}})) 
-  * sarcoidosis(({{pubmed>long:15246025}})) +  * sarcoidosis(({{pmid>long:15246025}})) 
-  * relapsing fever(({{pubmed>long:12380884}})) +  * relapsing fever(({{pmid>long:12380884}})) 
-  * kidney disease(({{pubmed>long:20428100}}))+  * kidney disease(({{pmid>long:20428100}}))
  
 Recovery from other infections and diseases also entails an immunopathological-like response:  Recovery from other infections and diseases also entails an immunopathological-like response: 
  
-  * **fever** – Fever, a natural increase in one's body temperature, has been conserved during evolution through millennia, because of its advantage for host defense.(({{pubmed>long:16613288}})) Important immunological reactions are sped up by temperature, and some pathogens with strict temperature preferences are hindered.(({{pubmed>long:9289813}})) +  * **fever** – Fever, a natural increase in one's body temperature, has been conserved during evolution through millennia, because of its advantage for host defense.(({{pmid>long:16613288}})) Important immunological reactions are sped up by temperature, and some pathogens with strict temperature preferences are hindered.(({{pmid>long:9289813}})) 
-    * **immune recovery uveitis** –  An intraocular inflammatory disorder originally described in individuals with human immunodeficiency virus (HIV) and inactive cytomegalovirus retinitis following highly active antiretroviral therapy (HAART). IRU can occur when immunosuppressed patients immune systems' become reinvigorated in HIV-positive or negative individuals.(({{pubmed>long:17362465}})) +    * **immune recovery uveitis** –  An intraocular inflammatory disorder originally described in individuals with human immunodeficiency virus (HIV) and inactive cytomegalovirus retinitis following highly active antiretroviral therapy (HAART). IRU can occur when immunosuppressed patients immune systems' become reinvigorated in HIV-positive or negative individuals.(({{pmid>long:17362465}})) 
-    * **Graves disease** – Rasul reported four cases of Graves' disease emerging in HIV patients on HAART.(({{pubmed>long:21804938}})) +    * **Graves disease** – Rasul reported four cases of Graves' disease emerging in HIV patients on HAART.(({{pmid>long:21804938}})) 
-  * **common cold (rhinovirus)** – Another example of immunopathology can be observed in the body's response to the rhinovirus. The symptoms of the common cold, which is caused by the rhinovirus, are an indication that the human host is in the midst of an activated immune response. Researchers have shown that during the common cold, the expression of many genes associated with the immune response, including chemokines and antivirals, are altered.(({{pubmed>long:18658112}})) It's important to note that the rhinovirus doesn't exactly cause the immune response so much as trigger it.  Similarly, olmesartan and MP antibiotics do not cause the immunopathological reaction so much as trigger it.+  * **common cold (rhinovirus)** – Another example of immunopathology can be observed in the body's response to the rhinovirus. The symptoms of the common cold, which is caused by the rhinovirus, are an indication that the human host is in the midst of an activated immune response. Researchers have shown that during the common cold, the expression of many genes associated with the immune response, including chemokines and antivirals, are altered.(({{pmid>long:18658112}})) It's important to note that the rhinovirus doesn't exactly cause the immune response so much as trigger it.  Similarly, olmesartan and MP antibiotics do not cause the immunopathological reaction so much as trigger it.
  
  
 ===== Immune reconstitution inflammatory syndrome (IRIS)==== ===== Immune reconstitution inflammatory syndrome (IRIS)====
  
-During IRIS, HIV/AIDS patients experience the worsening or onset of systemic inflammatory clinical signs and symptoms following treatment with highly active antiretroviral therapy (HAART). This syndrome results when HAART allows for partial recovery of the immune response. This causes renewed and exuberant host immunological responses towards opportunistic infectious agents, agents that the host accumulated during prior periods of immunosuppression.(({{pubmed>long:20507930}}))+During IRIS, HIV/AIDS patients experience the worsening or onset of systemic inflammatory clinical signs and symptoms following treatment with highly active antiretroviral therapy (HAART). This syndrome results when HAART allows for partial recovery of the immune response. This causes renewed and exuberant host immunological responses towards opportunistic infectious agents, agents that the host accumulated during prior periods of immunosuppression.(({{pmid>long:20507930}}))
  
-A number of well-known readily cultured pathogens have been conclusively linked to IRIS: the herpes viruses, cytomegalovirus, hepatitis B and C, //M. tuberculosis//, //Mycobacterium avium// complex and //Cryptococcus neoformans//.(({{pubmed>long:17488505}})) However, many more microbes likely contribute to the reaction since AIDS clinicians do not yet have access to the metagenomic tools. Certainly, the existence of IRIS in culture-negative HAART patients suggests that more microbes may be present than the few that have already been isolated.(({{pubmed>long:19365271}}))+A number of well-known readily cultured pathogens have been conclusively linked to IRIS: the herpes viruses, cytomegalovirus, hepatitis B and C, //M. tuberculosis//, //Mycobacterium avium// complex and //Cryptococcus neoformans//.(({{pmid>long:17488505}})) However, many more microbes likely contribute to the reaction since AIDS clinicians do not yet have access to the metagenomic tools. Certainly, the existence of IRIS in culture-negative HAART patients suggests that more microbes may be present than the few that have already been isolated.(({{pmid>long:19365271}}))
  
-Interestingly, patients experiencing IRIS often "develop" autoimmune conditions as a manifestation of immune restoration. These include sarcoidosis and other granulomatous reactions,(({{pubmed>long:10351953}})) (({{pubmed>long:10426909}})) diabetes mellitus, rheumatoid arthritis,(({{pubmed>long:12194745}})) systemic lupus erythematosus,(({{pubmed>long:9546531}})) Guillain–Barre syndrome,(({{pubmed>long:12715328}})) Graves disease(({{pubmed>long:11192862}})) and autoimmune thyroid disease.(({{pubmed>long:17488505}})) (({{pubmed>long:16325657}})) This suggests that these patients accumulated microbes that are directly involved in the pathogenesis of these disease states.+Interestingly, patients experiencing IRIS often "develop" autoimmune conditions as a manifestation of immune restoration. These include sarcoidosis and other granulomatous reactions,(({{pmid>long:10351953}})) (({{pmid>long:10426909}})) diabetes mellitus, rheumatoid arthritis,(({{pmid>long:12194745}})) systemic lupus erythematosus,(({{pmid>long:9546531}})) Guillain–Barre syndrome,(({{pmid>long:12715328}})) Graves disease(({{pmid>long:11192862}})) and autoimmune thyroid disease.(({{pmid>long:17488505}})) (({{pmid>long:16325657}})) This suggests that these patients accumulated microbes that are directly involved in the pathogenesis of these disease states.
  
-In a 2009 study, Sun and Singh reviewed the existence of IRIS in non-HIV immunocompromised patients including  solid organ transplant recipients, women during the postpartum period, neutropenic patients, and tumor necrosis factor antagonist recipients.(({{pubmed>long:19483618}}))+In a 2009 study, Sun and Singh reviewed the existence of IRIS in non-HIV immunocompromised patients including  solid organ transplant recipients, women during the postpartum period, neutropenic patients, and tumor necrosis factor antagonist recipients.(({{pmid>long:19483618}}))
  
  
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 Given its pervasiveness across diseases, immunopathology belies the common assumption that [[home:patients:assessing_literature:palliative|feeling well]] is the same as being healthy. Given its pervasiveness across diseases, immunopathology belies the common assumption that [[home:patients:assessing_literature:palliative|feeling well]] is the same as being healthy.
  
-In observing a set of worsening symptoms, patients and clinicians may be tempted to assume that the disease itself is worsening. Even a small number of researchers are mistakenly convinced that antibiotics cause or exacerbate chronic disease. The best example of this may be so-called "minocycline-induced lupus."(({{pubmed>long:17366961}})) In fact, there is no reasonable mechanism, proven or theoretical, which explains how minocycline, the primary action of which is to block the 30s ribosome of bacteria, can cause lupus – or any other disease.(({{pubmed>long:17511865}})) Nor is there a mechanism by which olmesartan can cause porphyria cutanea tarda (a blood disorder) as was reported in a 2010 //Journal of the European Academy of Dermatology and Venereology// paper.(({{pubmed>long:20015057}}))+In observing a set of worsening symptoms, patients and clinicians may be tempted to assume that the disease itself is worsening. Even a small number of researchers are mistakenly convinced that antibiotics cause or exacerbate chronic disease. The best example of this may be so-called "minocycline-induced lupus."(({{pmid>long:17366961}})) In fact, there is no reasonable mechanism, proven or theoretical, which explains how minocycline, the primary action of which is to block the 30s ribosome of bacteria, can cause lupus – or any other disease.(({{pmid>long:17511865}})) Nor is there a mechanism by which olmesartan can cause porphyria cutanea tarda (a blood disorder) as was reported in a 2010 //Journal of the European Academy of Dermatology and Venereology// paper.(({{pmid>long:20015057}}))
  
-Edward L. Krawitt, M.D. has it right when he suggests the possibility that minocycline, "unmasks" autoimmune hepatitis.(({{pubmed>long:16394302}})) +Edward L. Krawitt, M.D. has it right when he suggests the possibility that minocycline, "unmasks" autoimmune hepatitis.(({{pmid>long:16394302}})) 
  
 In the same vein, an “allergic” reaction to minocycline or any of the other antibiotics formerly used with Olmesartan was invariably due to the immunopathological response generated by taking olmesartan (Benicar) and antibiotics.  In the same vein, an “allergic” reaction to minocycline or any of the other antibiotics formerly used with Olmesartan was invariably due to the immunopathological response generated by taking olmesartan (Benicar) and antibiotics. 
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 //**Phil,** Bacteriality.com//</blockquote> //**Phil,** Bacteriality.com//</blockquote>
  
-Even olmesartan alone may reveal infection as a 2012 study by Mayo clinic researchers suggests.(({{pubmed>long:22728033}})) A study of 22 patients with diarrhea and taking standard doses of olmesartan showed that those symptoms improved upon discontinuation of the drug.+Even olmesartan alone may reveal infection as a 2012 study by Mayo clinic researchers suggests.(({{pmid>long:22728033}})) A study of 22 patients with diarrhea and taking standard doses of olmesartan showed that those symptoms improved upon discontinuation of the drug.
  
 ===== Immunopathology can be suppressed ===== ===== Immunopathology can be suppressed =====
  
-One of the common instincts among researchers who study immunopathological type reactions is to suppress this reaction.(({{pubmed>long:21637773}})) Indeed, two German papers have noted that the Jarisch-Herxheimer reaction can be suppressed with the administration of different kinds of prednisolone, a powerful corticosteroid.(({{pubmed>long:6862066}})) (({{pubmed>long:1226935}}))+One of the common instincts among researchers who study immunopathological type reactions is to suppress this reaction.(({{pmid>long:21637773}})) Indeed, two German papers have noted that the Jarisch-Herxheimer reaction can be suppressed with the administration of different kinds of prednisolone, a powerful corticosteroid.(({{pmid>long:6862066}})) (({{pmid>long:1226935}}))
  
 However, one of the factors that may play a large role in the [[home:pathogenesis:epidemiology|incidence and prevalence of chronic disease]] is that the immunopathological reaction is being systematically inhibited on a population-wide basis. There are a broad range of substances including prescription drugs, supplements, and foods that inactivate the innate immune response. These include, among many others: However, one of the factors that may play a large role in the [[home:pathogenesis:epidemiology|incidence and prevalence of chronic disease]] is that the immunopathological reaction is being systematically inhibited on a population-wide basis. There are a broad range of substances including prescription drugs, supplements, and foods that inactivate the innate immune response. These include, among many others:
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 ===== Read more ===== ===== Read more =====
  
-  * [[http://autoimmunityresearch.org/VDR-Time-Benicar.pdf|Depiction of the six stages of disease and recovery]] – prepared by Janet Raty+  * [[https://autoimmunityresearch.org/VDR-Time-Benicar.pdf|Depiction of the six stages of disease and recovery]] – prepared by Janet Raty
  
  
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 {{tag>Science IP Microbes_in_the_human_body}} {{tag>Science IP Microbes_in_the_human_body}}
 +<nodisp>
 ===== Notes and comments ===== ===== Notes and comments =====
  
  
 Lots of explanations about molecular nature of IP: Lots of explanations about molecular nature of IP:
-http://www.ncbi.nlm.nih.gov/pmc/articles/PMC118062+https://www.ncbi.nlm.nih.gov/pmc/articles/PMC118062
  
  
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 <blockquote>J Eur Acad Dermatol Venereol. 2010 Aug;24(8):977-8. Epub 2009 Dec 15. <blockquote>J Eur Acad Dermatol Venereol. 2010 Aug;24(8):977-8. Epub 2009 Dec 15.
-Porphyria cutanea tarda induced by olmesartan.(({{pubmed>long:20015057}}))+Porphyria cutanea tarda induced by olmesartan.(({{pmid>long:20015057}}))
  
 Mas-Vidal A, Coto-Segura P, García-Varona A, Santos-Juanes J. Mas-Vidal A, Coto-Segura P, García-Varona A, Santos-Juanes J.
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   * Antibiotic-induced release of endotoxin. A therapeutic paradox.   * Antibiotic-induced release of endotoxin. A therapeutic paradox.
   * Therapeutic paradox in CNS tuberculosis - The development of tuberculomas in cases of tuberculous meningitis whilst on anti-tubercular therapy, and in spite of satisfactory compliance is designated as paradoxical response or therapeutic paradox.   * Therapeutic paradox in CNS tuberculosis - The development of tuberculomas in cases of tuberculous meningitis whilst on anti-tubercular therapy, and in spite of satisfactory compliance is designated as paradoxical response or therapeutic paradox.
-http://www.pediatricneurosciences.com/text.asp?2009/4/2/133/57331+https://www.pediatricneurosciences.com/text.asp?2009/4/2/133/57331
  
  
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 ScienceDaily (May 19, 2011) — In the computer displays of medical equipment in hospitals and clinics, liquid crystal technologies have already found a major role. But a discovery reported from the University of Wisconsin-Madison suggests that micrometer-sized droplets of liquid crystal, which have been found to change their ordering and optical appearance in response to the presence of very low concentrations of a particular bacterial lipid, might find new uses in a range of biological contexts. ScienceDaily (May 19, 2011) — In the computer displays of medical equipment in hospitals and clinics, liquid crystal technologies have already found a major role. But a discovery reported from the University of Wisconsin-Madison suggests that micrometer-sized droplets of liquid crystal, which have been found to change their ordering and optical appearance in response to the presence of very low concentrations of a particular bacterial lipid, might find new uses in a range of biological contexts.
  
-http://www.sciencedaily.com/releases/2011/05/110519141615.htm+https://www.sciencedaily.com/releases/2011/05/110519141615.htm
 </blockquote> </blockquote>
-===== References =====+===== References =====</nodisp> 
home/protocol/immunopathology.1540507907.txt.gz · Last modified: 10.25.2018 by sallieq
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