Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A six year old female presented with a recent history of pyoderma gangrenosum involving her legs and arms associated with an episode of Mycoplasma-like pneumonia. This was followed by Aspergillus osteomyelitis involving her left ulna and right femur. Both the skin lesions and the osteomyelitis responded to prolonged treatment with antifungal and antibiotic agents. Investigation of this patient revealed (1) an elevated serum IgE (4,800 units/ml), (2) defect in neutrophil chemotaxis that appeared to be due to immune complexes, (3) an abnormal nitroblue tetrazolium (NBT) result (0 percent stimulated and unstimulated), and (4) depressed mitogen responses to concanavalin A, phytohemagglutinin, and pokeweed mitogen, negative results of intradermal skin tests, and negative dinitrochlorobenzene (DNCB) sensitization. The patient's clinically unaffected sibling had similar findings except for a positive DNCB response. In both children, intracellular bacterial killing of catalase-positive and negative organisms was normal. Kindred studies revealed widespread T-cell abnormalities consistent with autosomal dominant inheritance. Tissue typing studies showed that affected siblings shared the A1, B8, DR3 haplotype. This kindred is unique in that both the proband and the sibling have abnormalities of both the hyper-IgE syndrome and chronic granulomatous disease.
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PMID:Combined neutrophil and T-cell deficiency: initial report of a kindred with features of the hyper-IgE syndrome and chronic granulomatous disease. 697 28

In order to explore the allelic polymorphism of HLA-DR and TNF B loci and susceptibility to systemic lupus erythematosus (SLE) in the Han nationality of northern China with the aid of methods of polymerase chain reaction/sequence specific primers (PCR/SSP) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) respectively. The findings from a case-control study on 151 blood samples (45 from the cases and 106 from the controls) indicated that there were significantly higher frequency of DR2 (P < 0.05, RR = 1.56) and DR3 (P < 0.01, RR = 2.69), which represent candidate susceptible genes or useful markers for SLE. The DR5 allele in the samples (P < 0.05, RR = 0.43) might be an antagonistic or protective allele, or a marker for such allele. The frequency of TNF B * 1 and TNF B * 2 alleles was investigated in 45 SLE patients and 80 healthy controls and it was found that the frequency of TNF B * 2 allele was significantly higher in the patient group (P < 0.05, RR = 1.84). It might also be a suspicious susceptible allele or a marker for such allele. The frequency of HLA polymorphisms in various clinical/immunological subsets of our patient population was also determined. Clinical findings used include plasma SC5b-9 level, SSA, SSB, Sm, RNP, ANA antibodies, and SLE complications (SLE nephritis, pneumonia & encephalopathy). It turned out that there was a positive association between HLA-DR2 allele and SLE nephritis (P < 0.05, RR = 1.32).
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PMID:[Study on some susceptible genes of systemic lupus erythematosus in Han nationality of China]. 927 40

With the aid of methods of polymerase chain reaction/sequence specific primers (PCR/SSP) and polymerase chain reaction-restriction fragment length polymorphism (PCR/RFLP), the allelic polymorphism of HLA-DR and TNFB loci and susceptibility to systemic lupus erythematosus (SLE) in northern Chinese Han nationality were studied. The genetic analysis of 51 patients with SLE and 106 healthy controls indicated that frequencies of DR2 and DR3 alleles were significantly increased in SLE patients (P < 0.05 and < 0.005, relative risks of 1.77 and 4.01 respectively), which represent candidate susceptible genes or useful marker for SLE. The frequency of DR5 was found to decrease in SLE patients compared with control population (P < 0.025, relative risk = 0.38). It might be an antagonistic or protective allele or a marker for such allele. Analysis of 51 patients with SLE and 80 healthy control also revealed that the frequency of TNFB*2 allele was significantly increased (P < 0.05, RR = 1.70). Therefore TNFB*2 gene may also be a susceptibility gene or a marker gene for SLE in northern Chinese Han nationality. It was also investigated the association between HLA-DR, TNF B alleles and Patient plasmic SC5b-9 levels, auto-antibodies (anti-SSA, SSB, Sm, RNP, ds DNA and ANA) and SLE complications (SLE nephritis, SLE pneumonitis and SLE encephalopathy), no relationship was found.
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PMID:The polymorphisms of HLA-DR and TNF B loci in northern Chinese Han nationality and susceptibility to systemic lupus erythematosus. 1132 94

Polymorphisms in the central major histocompatibility complex (MHC) (particularly TNF and adjacent genes) associate with several immunopathological diseases and with susceptibility to pneumonia. The MHC is characterised by strong linkage disequilibrium (LD), so identification of loci affecting disease must be based on haplotypes. We have defined 31 tumour necrosis factor (TNF) block haplotypes (denoted FV1-31) in Caucasians, Asians and Australian Aboriginals. This study correlates the carriage of TNF block haplotypes with TNF and lymphotoxin alpha (LTA) protein production by peripheral blood mononuclear cells from 205 healthy Caucasian subjects, following in vitro stimulation with Streptococcus pneumoniae (S. pneumoniae; gram-positive bacteria), Escherichia coli (E. coli; gram-negative bacteria) or TNF over 4, 8 and 24 h. Fifteen haplotypes were present at >1%, accounting for 94.5% of the cohort. The haplotypes were grouped into five families based on common alleles. Following stimulation, cells from carriers of the FV10 haplotype (family 2) produced less LTA compared with non-FV10 carriers. Carriers of the FV18 haplotype (family 4) produced more LTA than other donors. Induction of TNF by S. pneumoniae following 24 h stimulation was also greater in donors with FV18. The FV18 haplotype associated with the 44.1 MHC ancestral haplotype (HLA-A2, -C5, -B44, -DRB1*0401 and -DQB1*0301) that has few disease associations. FV16 occurred in the 8.1 MHC haplotype (HLA-A2, B8, DR3) that is associated with multiple immunopathological diseases. FV16 did not affect TNF or LTA levels. The findings suggest that many genetic variations critical in vivo are not effectively modelled by short-term cultures.
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PMID:Characterisation of TNF block haplotypes affecting the production of TNF and LTA. 2121 21

Staphylococcal superantigens (SAg) are a family of potent exotoxins produced by Staphylococcus aureus. They play an important role in the pathogenesis of staphylococcal shock and pneumonia by causing a robust activation of the immune system and eliciting a strong surge in systemic cytokine and chemokine levels. Given the biological functions of SAg, we evaluated the efficacy of tacrolimus, a potent immunosuppressive agent, in the prophylaxis and therapy of staphylococcal TSS and pneumonia using human leukocyte antigen (HLA)-DR3 transgenic mice. Tacrolimus significantly inhibited staphylococcal SAg induced T cell activation in vitro. In vivo, tacrolimus significantly suppressed the SAg-induced elevation in serum cytokine and chemokine levels when given prophylactically, when administered immediately or even 2 h following systemic SAg challenge. Paradoxically, neither the prophylactic nor post-exposure treatment with tacrolimus protected mice from lethal SAg-induced TSS. A closer examination revealed that tacrolimus failed to suppress SAg-induced T cell proliferation and systemic pathology, including gut dysfunction. Tacrolimus also failed to protect from lethal pneumonia induced by a SAg-producing S. aureus strain. Thus, our study showed that even though T cell activation by SAg plays a major role in the immunopathogenesis of TSS and pneumonia, tacrolimus alone has no beneficial effect.
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PMID:The impact of tacrolimus on the immunopathogenesis of staphylococcal enterotoxin-induced systemic inflammatory response syndrome and pneumonia. 2227 32

Superantigens (SAg), the potent activators of the immune system, are important determinants of Staphylococcus aureus virulence and pathogenicity. Superior response to SAg in human leukocyte antigen (HLA)-DR3 transgenic mice rendered them more susceptible than C57BL/6 mice to pneumonia caused by SAg-producing strains of S. aureus. Linezolid, a bacterial protein synthesis inhibitor, was superior to vancomycin in inhibiting SAg production by S. aureus in vitro and conferred greater protection from pneumonia caused by SAg-producing staphylococci.
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PMID:Linezolid is superior to vancomycin in experimental pneumonia caused by Superantigen-Producing staphylococcus aureus in HLA class II transgenic mice. 2285 May 9