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)

Recent findings have demonstrated that terminally differentiated adult ventricular myocytes are capable of repairing DNA that has been damaged by exposure to oxygen free radicals. Despite the potential importance of DNA repair in cells that may survive many decades after injury, little is known about the mechanisms or regulation of repair. Since tobacco use has a well-defined role in the epidemiology and pathophysiology of heart disease, we tested the effects of nicotine on repair of free radical damaged plasmids by whole-cell protein extracts from adult myocytes. Exposure to a concentration of 25 microM nicotine increased incorporation of (32P)dCTP into damaged plasmids by 16%, and 50 or 100 microM nicotine increased incorporation by 32%. Nicotine did not alter the rate or amount of poly (ADP-ribose) on the major protein acceptor of molecular weight 113-116 kDa. Inhibition of DNA polymerase activity with pyridoxal 5'-phosphate revealed greater plasmid degradation in the presence of nicotine. We conclude that nicotine enhances DNA degradation and the increased repair is a consequence of this greater degradation.
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PMID:The effect of nicotine on DNA repair in adult myocytes. 973 35

The 'antioxidant hypothesis' proposes that vitamin C, vitamin E, carotenoids, and other antioxidants occurring in fruit and vegetables afford protection against heart disease and cancer by preventing oxidative damage to lipids and to DNA, respectively. To test elements of this hypothesis, we have measured blood levels of dietary antioxidants, and 8-oxodeoxyguanosine (8-oxo-dG) concentrations in lymphocyte DNA, in healthy men and women from five European countries: France, Ireland, The Netherlands, Spain, and the U.K. Volunteers, aged 25 45, all nonsmokers, gave blood samples before and after a 12-wk carotenoid supplementation regime. Vitamin C was measured in plasma and vitamin E and carotenoids were measured in serum by high-performance liquid chromatography (HPLC). 8-oxo-dG was assayed by HPLC (with coulometric detection) in DNA isolated from lymphocytes from the same blood samples. Mean values were calculated for groups of volunteers at each sampling time according to country, sex, and supplementation (between 9 and 24 individual samples contributing to each mean). We found that 8-oxo-dG levels in lymphocyte DNA vary significantly according to sex and country. A low mean 8-oxo-dG concentration is seen in DNA of women from all five countries, and of men from France and Spain. 8-oxo-dG is significantly higher (up to about threefold) in lymphocyte DNA from men in Ireland and the U.K. Oxidative DNA damage is not significantly affected by carotenoid supplementation; nor is there any association with mean baseline levels of antioxidants, which are generally similar in the five countries. The five countries sampled lie on an axis from northern to southern Europe with a steep gradient in terms of premature heart disease. There is a strong association between premature coronary heart disease mortality in men and the mean levels of 8-oxo-dG for the five countries (r = 0.95, P < 0.01). Women have low coronary heart disease mortality rates, which do not correlate with 8-oxo-dG. In terms of cancer deaths, only colorectal cancer in men shows a significant positive correlation (r = 0.91, P < 0.05), and stomach cancer in women is negatively correlated with DNA oxidation (r = -0.92, P = 0.01).
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PMID:Oxidative DNA damage measured in human lymphocytes: large differences between sexes and between countries, and correlations with heart disease mortality rates. 976 83

This article addresses social and ethical priorities on the agenda for women's health research in the next century. Specifically, the relevance of genetic discoveries for healthcare reform and why both topics ought to be among these priorities are discussed. If the present gap between diagnosis and treatment of genetic diseases could be bridged, especially in such common diseases as cancer and heart disease, arguments for universal access to healthcare would be vastly strengthened. Important scientific and ethical problems are involved in bridging the gap, including volatile issues of research with human embryos and fetuses. Other issues deserve high priority on the women's health research agenda: adequate funding for biomedical research, maintaining an equitable number of women in clinical trials, and creating a knowledge base in gender-based biology. Progress in genetic research is clearly relevant to women's health for understanding and treating common diseases, as well as for reproductive decisions. Until recently, genetic services have been aimed exclusively at reproductive choices, including counseling, prenatal diagnosis, and carrier screening. However, the meaning of the term needs to be vastly broadened to include the uses of genetic information in mainstream medicine. Through genetic testing and DNA technology, it will be increasingly possible for physicians to have access to family history and a reliable profile of each patient's genetic health risks. Drugs will be designed that will be responsive to individual genetic variability and risks for disease. If scientific and ethical obstacles are overcome, there may also be effective human gene therapy to correct mutations and prevent lifelong harm. In my view, linking the agenda for women's health research with the unfinished social task of ensuring access to adequate primary and preventive care, which foreseeably will include genetic services and human gene therapy, strengthens the agenda and promotes solidarity with the needs of the majority of Americans. This link will help to prevent political and moral isolation of women's health research.
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PMID:The long view: how genetic discoveries will aid healthcare reform. 978 7

The first case of Q fever endocarditis that has been diagnosed in Mexico is presented. A 10-year-old girl with discrete subaortic stenosis (SAS) and patent ductus arteriosus (PDA) was seen in December of 1996 with fever, hepatomegaly and splenomegaly. She presented also anemia, leukopenia, hypergammaglobulinemia, positive rheumatoid factor, cryoglobulinemia, antinuclear and anticytoplasmic antibodies (anti-RNA-proteins and anti-DNA). An aortic valve vegetation was seen by echocardiogram. Blood-cultures were negative. Antibody test for Coxiella burnetii was positive. Treatment with doxicyclin was initiated as soon the diagnosis was done. PDA was closed, SAS was liberated and two aortic vegetations were resected. Endocarditis in Q fever occurs when there is predisposing heart disease and/or immunodeficiency. Effective therapy has not yet been established. The diagnosis of Q fever endocarditis is difficult; it should be considered, in case of clinical suspicion of endocarditis with negative blood-cultures.
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PMID:[Coxiella burnetii endocarditis. A report of the first case diagnosed in Mexico]. 981 Mar 69

In view of the scarce references concerning the histological data in congenital parvovirus human B19 infection, we intend to provide a description of the pathological features observed in six autopsies. The virus was detected by DNA hybridization (ISH-DBH), PCR and electronmicroscopy (EM) in paraffin-embedded feto-placentary tissues. These cases constitute a subset from 86 Non Immunologic Hydrops Fetalis (NIHF) cases, in which a systemic complex of inflammatory/degenerative lesions of unknown etiology was visualized by optical microscopy. In one case a syphilitic process was detected, typefying a double infection. All fetuses showed a similar pathology--hydrops, hepato-splenomegaly, lung hypoplasia and erythroblastemia, the specific histological feature being the presence of intranuclear inclusions in the erythroid progenitors, in the erythropoietic visceral tissue and in blood marrow. Complex cardiopathy allied to abnormal lung lobulation and polisplenia were observed once; in 2 cases endocardial fibroelastosis was diagnosed. The pulmonary lesions were represented by dysmaturity allied to interstitial mononuclear infiltration. The hepatic consisted of cholestasis, portal fibrosis, canalicular proliferation, hemossiderosis, focal necroses and giant cell transformation. The central nervous system lesions were predominantly anoxic although the autolysis impaired a correct diagnosis.
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PMID:Feto-placentary pathology in human parvovirus B19 infection. 983 Jul 27

1. Transforming growth factor-beta1 is a cytokine with a very wide spectrum of biological activities. Previous studies have shown that it is involved in a number of physiological and pathological processes including heart disease. In our study we aimed to scan the transforming growth factor-beta1 locus for polymorphisms and to identify haplotypes significantly associated with a predisposition to coronary atherosclerosis.2. Two patient groups comprising 244 angiographically normal individuals and 655 patients with coronary artery disease were recruited from London and Sheffield. DNA samples from these subjects were screened for mutations in the transforming growth factor-beta1 locus and all subjects were genotyped by a coupled polymerase chain reaction-restriction enzyme digestion method.3. Five polymorphisms have been identified in the transforming growth factor-beta1 gene at positions G-800A, C-509T in the promoter region, Leu10-->Pro, Arg25-->Pro in exon 1 and Thr263-->Ile in exon 5. No significant difference in frequencies for any of the five polymorphisms was found between controls and patients with coronary artery disease. Similarly, there was no correlation between these polymorphisms and hypertension.4. The genotypes of all the individuals participating in the study were assigned to seven main haplotypes of the transforming growth factor-beta1 locus. Based on species comparison data we propose that GCCGC is the ancestral haplotype in humans.5. Our data suggest that these transforming growth factor-beta1 polymorphisms are not associated with coronary artery disease and therefore their presence alone would not be a genetic risk factor for predisposition to coronary artery disease.
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PMID:Transforming growth factor-beta1 gene polymorphisms and coronary artery disease. 983

IsK, a slowly activating delayed rectifier K+ current through channels formed by the assembly of two channel proteins KvLQT1 and MinK, modulates the repolarization of cardiac action potentials. Mutations that map to the KvLQT1 and minK genes account for more than 50% of an inherited cardiac disorder, the Long QT syndrome (Splawski, I., Tristani-Firouzi, M., Lehmann, M. H., Sanguinetti, M. C., and Keating, M. T. (1997) Nat. Genet. 17, 338-340). Despite the importance of these channels to human cardiac function, the molecular basis of their uniquely slow gating properties as well as the stoichiometry and interaction sites of these two subunits are still unclear. We have constructed several fusion channel proteins to begin investigating the stoichiometry of these two subunits and the role of voltage-dependent subunit assembly in channel gating. Functional properties of these constructs were measured using whole cell patch clamp recordings of transiently transfected Chinese hamster ovary cells. The constructs we tested are as follows: MK24 (C terminus of MinK linked to N terminus of KvLQT1); KK40 (a tandem homodimer of KvLQT1); and MKK44 (C terminus of MinK linked to N terminus of KK40). In control experiments (no DNA, control DNA, or only MinK), no time-dependent K+ current was observed. Expression of KvLQT1 or KK40 produced currents that activate and inactivate in a voltage-dependent manner as reported by others for KvLQT1. In contrast, expression of MK24 and MKK44 elicited current with activation kinetics and voltage dependence very similar to native IsK and identical to currents expressed by cells co-transfected with independent MinK and KvLQT1 cDNA. Expression of MK24 plus additional MinK significantly slows current kinetics. Our data raise the possibility 1) of multiple MinK/KvLQT1 stoichiometries and 2) indicate that uniquely slow kinetics of IsK channels is due to voltage-dependent conformational changes of the channel protein and not to assembly of channel subunits.
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PMID:MinK-KvLQT1 fusion proteins, evidence for multiple stoichiometries of the assembled IsK channel. 985 64

Preparation of a pure autoantigen by way of recombinant DNA technology has an important value in an accurate diagnosis or prognosis of an autoimmune disease. BCOADC-E2 subunit, a mitochondrial protein, has been known to be the autoantigen of primary biliary cirrhosis (PBC), a chronic autoimmune liver disease, as well as idiopathic dilated cardiomypathy (IDCM), a chronic autoimmune heart disease. Recombinant form of this molecule had been expressed in E. coli but with low yield and severe degradation. Furthermore, sera from IDCM patients failed to recognized BCOADC-E2 molecule produced in prokaryotic expression system. In this study, a recombinant bovine BCOADC-E2 fusion protein has been expressed in insect cells using baculovirus expression system and analyzed anti-BCOADC-E2 reactivity in sera from patients with PBC or with IDCM. Optimal production of the recombinant fusion protein has been achieved at 20 multiplicity of infection (MOI), and the protein was affinity-purified using metal-binding resins. The affinity-purified BCOADC-E2 protein was successfully recognized by sera from PBC patients, but not by sera from IDCM patients suggesting that the different auto-immune response against BCOADC-E2 is needed to be elucidated in terms of epitope recognition.
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PMID:Expression of a recombinant branched chain alpha-oxo acid dehydrogenase complex E2 (BCOADC-E2) in insect cells and its immunoreactivity to autoimmune sera. 987 25

In the first phase of the Human Genome Project, new and ingenious tools have made it possible to map all the individual nucleotides that make up the 23 human chromosomes. During the next 5 years, the 3 billion DNA bases and the 50,000 to 100,000 genes will be sequenced. This knowledge will have widespread applications in biology, medicine and industry. The genetic research community currently has access to abundant DNA markers, detailed chromosome maps, extensive online databases as well as rapid DNA analysis technologies, all of which can be used to identify disease-causing genetic mutations. In the next 15 to 20 years, the Human Genome Project is expected to identify defective genes causing thousands of hereditary diseases, including common diseases such as heart disease, diabetes, asthma and cancer. The hope is that these discoveries will lead to better understanding of the causes of these diseases, and to better approaches to diagnosis, prevention and treatment of human genetic disorders.
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PMID:Joe Doupe Young Investigators Award. The Human Genome Project: tools for the identification of disease genes. 988 61

Diabetic patients have reduced antioxidant defenses and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. Epidemiological evidence has suggested that antioxidant dietary flavonoids may protect against heart disease, but a biological effect has yet to be demonstrated directly in humans. In this study, 10 stable type 2 diabetic patients were treated for 2 weeks on a low-flavonol diet and for 2 weeks on the same diet supplemented with 76-110 mg of flavonols (mostly quercetin) provided by 400 g of onions (and tomato sauce) and six cups of tea daily. Freshly collected lymphocytes were subjected to standard oxidative challenge with hydrogen peroxide, and DNA damage was measured by single-cell gel electrophoresis. Fasting plasma flavonol concentrations (measured by high-performance liquid chromatography) were 5.6 +/- 2.9 ng/ml on the low-flavonol diet and increased 12-fold to 72.1 +/- 15.8 ng/ml on the high-flavonol diet (P < 0.001). Oxidative damage to lymphocyte DNA was 220 +/- 12 on an arbitrary scale of 0-400 U on the low-flavonol diet and 192 +/- 14 on the high-flavonol diet (P = 0.037). This decrease was not accounted for by any change in the measurements of diabetic control (fasting plasma glucose or fructosamine) or by any change in the plasma levels of known antioxidants, including vitamin C, carotenoids, alpha-tocopherol, urate, albumin, and bilirubin. In conclusion, we have shown a biological effect of potential medical importance that appears to be associated with the absorption of dietary flavonols.
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PMID:Dietary flavonols protect diabetic human lymphocytes against oxidative damage to DNA. 989 40


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