Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alcohol is a major cause of liver cirrhosis in the Western world and accounts for the majority of cases of liver cirrhosis seen in district general hospitals in the UK. The three most widely recognised forms of alcoholic liver disease are alcoholic fatty liver (steatosis), acute alcoholic hepatitis, and alcoholic cirrhosis. The exact pathogenesis of alcoholic liver injury is still not clear but immune mediated and free radical hepatic injury are thought to be important. There is increasing interest in genetic factors predisposing to hepatic injury in susceptible individuals. Diagnosis is based on accurate history, raised serum markers such as gamma-glutamyltransferase, mean corpuscular volume, and IgA and liver histology when obtainable. Abstinence is the most important aspect of treatment. Newer drugs such as acamprosate and naltrexone are used to reduce alcohol craving. Vitamin supplements and nutrition are vital while corticosteroids have a role in acute alcoholic hepatitis where there is no evidence of gastrointestinal haemorrhage or sepsis. Liver transplantation has excellent results in abstinent patients with end stage liver disease but there are concerns about recidivism after transplant.
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PMID:Alcoholic liver disease. 1077 80

A 13-year-old patient developed severe shock due to administration of a Yersinia enterocolitica-contaminated red blood cell concentrate. Y. enterocolitica (serotype O:9, biotype II) was cultivated from the residual blood in the blood bag and from a stool sample of the blood donor. In the donor's plasma immunoglobulin M (IgM), IgA, and IgG antibodies against Yersinia outer proteins (YopM, -H, -D, and -E) were found. Since the donor remembered a short-lasting, mild diarrhea 14 days prior to blood donation, a transient attack of Yersinia enteritis may be associated with a longer than expected period of asymptomatic bacteremia that causes contamination of donor blood. Serological screening for IgM antibodies against Yersinia outer proteins might offer a way to reduce the risk of transfusion-associated Y. enterocolitica sepsis.
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PMID:Bacteriological and serological findings in a further case of transfusion-mediated Yersinia enterocolitica sepsis. 1087 90

The immaturity of the infant's immune system and the rapid evolution of pathogens has created a demand for the mother to provide ready made specific defence factors to her offspring. This is achieved during the fetal period by transplacental transport of IgG antibodies, and after birth via IgA antibodies in the breast milk. The breast milk also contains a variety of nonspecific defence factors contributing to its antimicrobial effect. Breast feeding has been shown to decrease morbidity in gastroenteritis, septicemia, otitis media, urinary tract infection, encephalitis, pneumonia, and necrotizing enterocolitis. The antibody content in the mother's milk probably contributes not only to the immediate but also to the long term protection of the infant including both resistance to infection and development of immunological tolerance to harmless environmental antigens.
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PMID:Antibodies in milk. 1088 98

Mucosal immunity was established in the rat prostate by stimulating the common mucosal system through serosal exposure of formalin-killed Escherichia coli. Immunized but not sham-immunized rats developed bacterial specific IgG and IgA in prostatic fluid, and IgA in urine. Immunized (n = 21) and sham-immunized control rats (n = 30) were challenged by transurethral injection of E. coli into the prostate ducts. Mortality, gross and microscopic pathology, tissue bacterial counts, bacterial associated immunoglobulins, and antibody titers in serum and urine were assessed at 7 days following the challenge. Increased E. coli specific immunoglobulin titers were seen in immunized rats, and E. coli, but not Proteus, found in the prostates of immunized animals were coated with IgG and IgA. Immunization protected against toxaemia and septicemia, seen as a rare complication of acute prostatitis, but did not protect against acute prostatitis, nor alter the degree of tissue damage seen in the rat model.
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PMID:Specific mucosal immunity in the pathophysiology of bacterial prostatitis in a rat model. 1090 22

Recent studies from our laboratory demonstrated that mucosal lymphoid tissue such as Peyer's patch cells and lamina propria (LP) B lymphocytes from mice shows evidence of increased apoptosis after sepsis that is associated with localized inflammation/activation. The mechanism for this is poorly understood. Endotoxin as well as Fas/Fas ligand (FasL) have been shown to augment lymphocyte apoptosis; however, their contribution to the increase of apoptosis in LP B-cells during sepsis is not known. To study this, sepsis was induced by cecal ligation and puncture (CLP) in endotoxin-tolerant C3H/HeJ or FasL-deficient C3H/HeJ-FasL(gld) (FasL(-)) mice and LP lymphocytes were isolated 24 h later. Phenotypic, apoptotic, and functional indexes were assessed. The number of LP B cells decreased markedly in C3H/HeJ mice but not in FasL-deficient animals at 24 h after CLP. This was associated with comparable alteration in apoptosis and Fas antigen expression in the B cells of these mice. Septic LP lymphocytes also showed increased IgA production, which was absent in the FasL-deficient CLP mice. Furthermore, Fas ligand deficiency appeared to improve survival of septic challenge. These data suggest that the increase in B cell apoptosis in septic animals is partially due to a Fas/FasL-mediated process but not endotoxin.
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PMID:Increased apoptosis in lamina propria B cells during polymicrobial sepsis is FasL but not endotoxin mediated. 1129 88

Neisseria meningitidis serogroup B infections are among the major causes of fulminant septicemia and meningitis, especially severe in young children, and no broad vaccine is available yet. Because of poor immunogenicity of the serogroup B capsule, many efforts are now devoted to the identification of protective protein antigens. Among those are PorA and, more recently, transferrin-binding protein B (TbpB). In this study, TbpB of N. meningitidis was genetically fused to the N-terminal domain of the Bordetella pertussis filamentous hemagglutinin (FHA), and the fha-tbpB hybrid gene was expressed in B. pertussis either as a plasmid-borne gene or as a single copy inserted into the chromosome. The hybrid protein was efficiently secreted by the recombinant strains, despite its large size, and was recognized by both anti-FHA and anti-TbpB antibodies. A single intranasal administration of recombinant virulent or pertussis-toxin-deficient, attenuated B. pertussis to mice resulted in the production of antigen-specific systemic immunoglobulin G (IgG), as well as local IgG and IgA. The anti-TbpB serum antibodies were of the IgG1, IgG2a, and IgG2b isotypes and were found to express complement-mediated bactericidal activity against N. meningitidis. These observations indicate that recombinant B. pertussis may be a promising vector for the development of a mucosal vaccine against serogroup B meningococci.
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PMID:Production of Neisseria meningitidis transferrin-binding protein B by recombinant Bordetella pertussis. 1150 Apr 15

The C protein alpha- and beta-antigens are immunodominant components of the surface of Streptococcus agalactiae, the most frequent cause of neonatal sepsis. Both proteins are thought to contribute significantly to virulence of S. agalactiae. They are mainly expressed by serotypes Ia, Ib, and II. The C protein beta-antigen (Cbeta-protein) binds to the Fc portion of human IgA and seems to be of importance in bacterial resistance to mucosal immune defense mechanisms. In this study, PCR analysis of S. agalactiae isolates obtained from 189 neonates and 112 pregnant women revealed the presence of the Cbeta-protein gene in 19% and 22% of the isolates, respectively. Size polymorphisms of the PCR products within the gene region encoding the cell wall-spanning domain indicated a high degree of genetic variability. Thirteen different variants of the amplified region were differentiated among the 60 Cbeta-protein-positive isolates by sequence analysis. In all variants, the polymorphisms were caused by insertions and deletions of repetitive DNA elements that did not alter the open reading frame. Comparison of the Cbeta-protein gene polymorphisms showed a significantly higher rate of isolates carrying deletions >50 bp in serotype Ib than in serotype II isolates (p = 0.001); this was also true for neonatal isolates analyzed separately (p = 0.01). Neonatal isolates carried a higher rate of large deletions when compared with maternal isolates; this difference, however, did not reach statistical significance (p = 0.08). We hypothesize that polymorphisms in the cell wall-spanning domain of the Cbeta-protein are of functional relevance with regard to maternofetal transmission of the pathogen.
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PMID:Polymorphisms in the cell wall-spanning domain of the C protein beta-antigen in clinical Streptococcus agalactiae isolates are caused by genetic instability of repeating DNA sequences. 1175 48

We report the case of an 18-month-old girl who died of overwhelming pneumococcal sepsis. Autopsy revealed a small spleen with unusual architecture. There was a marked rarefaction of the white pulp with only very few but florid germinal centers. Immunohistochemical staining showed a low number of T and B lymphocytes in the spleen, whereas normal numbers and distribution of lymphocytes were found in all other primary and secondary lymphatic organs. Whereas levels of IgM were normal, IgA and IgG levels were significantly lower than in age-matched controls. Consistent with serological data, B cells mainly expressed IgM and IgD, whereas IgG expression was lower than expected. Additionally, intestinal immunoglobulin distribution in B-cell areas of lymphofollicular hyperplasia showed normal expression of IgM, but almost no expression of IgA. A review of the literature failed to disclose a similar case of dysgammaglobulinemia associated with isolated structural spleen anomalies. We propose that the patient suffered from a defect of the B-cell differentiation pathway.
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PMID:Lethal pneumococcal infection in an 18-month-old girl with splenic hypoplasia and dysgammaglobulinemia. 1175 27

The newborn has an immune system, very limited in size at birth and its postnatal expansion and maturation takes time. In the meantime the transplacental IgG antibodies from the mother play an important role for the protection of the infant. However, these antibodies act in tissues and induce inflammation and are energy-consuming. In contrast, the milk secretory IgA antibodies stop microbes already on the mucosa preventing infection, tissue engagement and energy loss. In addition, the milk contains many protective factors such as lactoferrin and oligosacharides functioning as analogues for microbial receptors preventing mucosal attachment, the initial step of most infections. As a result, breast-feeding significantly reduces the risk of neonatal septicemia, respiratory tract infections, otitis media, diarrhea, urinary tract infections, infection-induced wheezing and necrotizing enterocolitis. Via several mechanisms it seems that human milk can actively stimulate the immune system of the breast-fed infant. This reduces the risk of infections like otitis media, respiratory tract infections, diarrhea and infection-induced wheezing for several years after the termination of breast-feeding. Furthermore, it seems that breast-feeding decreases the risk of attracting celiac disease and allergic diseases. The latter has been much debated, but a recent critical review of published reports gives good support for long-term protection of allergic diseases, especially in high-risk children.
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PMID:Breast-feeding, a complex support system for the offspring. 1213 55

Studies indicate that critically ill patients who succumb to sequela of sepsis/multiorgan failure, as well as septic animals, exhibit an apparently pathological increase in apoptosis (Ao) in the immune system. However, the mechanisms regulating these changes are unclear. Studies also indicate that, dependent on the cell population and the nature and/or duration of the stimuli, activation of the nuclear factor (NF)-kappaB can either suppress or enhance Ao. Thus, the aim of this study was to determine the contribution of NF-kappaB activation to the onset of Ao seen in divergent immune cell populations during sepsis, as produced by cecal ligation and puncture (CLP). To assess this, C3H/HeN mice were pretreated (for 1 h) subcutaneously with either 100 mg/kg body weight of pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor, or with saline vehicle, prior to subjecting them to CLP or Sham-CLP (Sham). Thymocytes, phagocytes, and Peyers Patch cells were harvested 24 h later, and the extent of Ao was determined by flow cytometry. The results indicate that PDTC pretreatment had no marked effect on the increase in thymocyte or phagocyte Ao seen following CLP, but there was a significant decline in the extent of Ao observed in septic mouse Peyer's patch B cells. To the extent that this was a result of NF-kappaB inhibition, we demonstrate by Western analysis, electrophoretic mobility shift assay (EMSA) and transfactor assay that the translocation of c-Rel to septic mouse Peyer's patch B cell nuclei is attenuated by PDTC. PDTC pretreatment also markedly reduced the number of Peyer's patch B cells that were producing IgA as well as attenuated the increase of proinflammatory cytokines in the blood. Interestingly, PDTC pretreatment did not restore peritoneal macrophage function or improve animal survival. Taken together, the inability of PDTC pretreatment to alter the Ao response of thymocytes or phagocytes, while inhibiting the increase in Peyer's patch B cell Ao in septic mice, implies not only that the activation of NF-kappaB has highly tissue/cell-specific effects that must be discerned when trying to clarify the pathophysiological role of NF-kappaB in sepsis, but that the activation of NF-kappaB may contribute to the early adaptive responses required by the host to fend off septic challenge.
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PMID:NF-kappaB activation has tissue-specific effects on immune cell apoptosis during polymicrobial sepsis. 1239 84


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