Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The long-term success of heart transplantation for end-stage heart disease has been hindered by the problems associated with acute and chronic graft rejection, opportunistic infections and potentially fatal complications of intensive immunosuppression. A more complete understanding of the biology of transplant rejection should provide the basis for the development of improved methods for controlling and monitoring rejection. Cytokines, the soluble factors which regulate the immune response, are central to the rejection process. The objective of this study was to analyse cytokine mRNA transcripts in 99 biopsy samples and 89 blood samples from 65 and 35 Stanford Medical Center cardiac transplant recipients, respectively, gathered between January 1990 and January 1992. Following RNA extraction and conversion to cDNA, samples were amplified with cytokine-specific primers for interleukins (IL) 1 to 8, TNF-beta (tumour necrosis factor-beta) and IFN-gamma (interferon-gamma) and were analysed by gel electrophoresis and Southern blot hybridization. Our results demonstrate that despite chronic immunosuppressive therapy, the peripheral blood of transplant recipients expressed a higher combined percentage of different cytokine transcripts than did peripheral blood obtained from normal volunteers. In transplant patients, detection of cytokine transcripts for IL-1 alpha, IL-1 beta and IL-2 increased with time after transplantation. Intragraft IL-7 gene expression was significantly increased in biopsies diagnosed with mild (grade 1) rejection when compared to those with no evidence of rejection or with moderate to severe rejection. Implications of these results in light of possible mechanisms of rejection and of new approaches to immunotherapy are discussed.
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PMID:Cytokine gene expression in human cardiac allograft recipients. 800 Aug 48

Genetic association studies have related the tumour necrosis factor-alpha gene (TNFA) guanine to adenine substitution of nucleotide -308 (-308G>A) polymorphism to increased risk of asthma, but results are inconsistent. The aim of the present study was to test whether two single-nucleotide polymorphisms, of TNFA and of the lymphotoxin-alpha gene (LTA), are associated with asthma, bronchial hyperresponsiveness and atopy in adults, by combining the results of two large population-based multicentric studies and conducting a meta-analysis of previously published studies. The European Community Respiratory Health Survey (ECRHS) and Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) used comparable protocols, including questionnaires for respiratory symptoms and measures of lung function and atopy. DNA samples from 11,136 participants were genotyped at TNFA -308 and LTA 252. Logistic regression employing fixed and random effects models and nonparametric techniques were used. The prevalence of asthma was 6%. The TNFA -308G>A polymorphism was associated with increased asthma prevalence and with bronchial hyperresponsiveness. No consistent association was found for atopy. The LTA 252A>G polymorphism was not associated with any of the outcomes. A meta-analysis of 17 studies showed an increased asthma risk for the TNFA -308 adenine allele. The tumour necrosis factor-alpha gene nucleotide -308 polymorphism is associated with a moderately increased risk of asthma and bronchial hyperresponsiveness, but not with atopy. These results are supported by a meta-analysis of previously published studies.
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PMID:TNFA -308G>A in two international population-based cohorts and risk of asthma. 1838 69

Obesity is a risk factor for asthma. Adipose tissue expresses pro-inflammatory molecules including tumour necrosis factor (TNF), and levels of TNF are also related to polymorphisms in the TNF-alpha (TNFA) gene. The current authors examined the joint effect of obesity and TNFA variability on asthma in adults by combining two population-based studies. The European Community Respiratory Health Survey and the Swiss Cohort Study on Air Pollution and Lung and Heart Disease in Adults used comparable protocols, questionnaires and measures of lung function and atopy. DNA samples from 9,167 participants were genotyped for TNFA -308 and lymphotoxin-alpha (LTA) +252 gene variants. Obesity and TNFA were associated with asthma when mutually adjusting for their independent effects (odds ratio (OR) for obesity 2.4, 95% confidence interval (CI) 1.7-3.2; OR for TNFA -308 polymorphism 1.3, 95% CI 1.1-1.6). The association of obesity with asthma was stronger for subjects carrying the G/A and A/A TNFA -308 genotypes compared with the more common G/G genotype, particularly among nonatopics (OR for G/A and A/A genotypes 6.1, 95% CI 2.5-14.4; OR for G/G genotype 1.7, 95% CI 0.8-3.3). The present findings provide, for the first time, evidence for a complex pattern of interaction between obesity, a pro-inflammatory genetic factor and asthma.
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PMID:Joint effect of obesity and TNFA variability on asthma: two international cohort studies. 1919 17