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 pathologic substrate for sudden death in the middle-aged or elderly adult is usually ischemic heart disease. In contrast, few data are available regarding the pathology of sudden death in teenagers. This report describes three teenagers without clinically suspected heart disease dying suddenly. Patient 1 (age 15, male) was known to have right ventricular premature ventricular beats. Postmortem examination revealed marked premature aging, sclerosis of the cardiac skeleton extending to the right side of the summit with fibrosis of the left and right bundle branches. Patient 2 (age 17, male) was a trained athlete who died during football scrimmage. Autopsy revealed moderate mitral valve prolapse and marked premature aging, sclerosis of the left side of the cardiac skeleton, which extended to the right ventricular side, and secondary involvement of the trifascicular conduction system with mononuclear cell infiltration. Patient 3 (age 19, female) died suddenly at home. Autopsy revealed mitral valve prolapse, thrombosis of the sinoatrial (SA) node artery, and premature aging, sclerosis of the left side of the cardiac skeleton, with involvement of the ventricular septum more on the right ventricular side and involvement of the atrioventricular bundle and trifascicular conduction system. In conclusion, unexpected deaths in three teenagers occurred with demonstrable pathologic findings in the heart. Two of the three patients had mitral valve prolapse, one of whom also had thrombosis or embolism of the sinoatrial node artery. All three had sclerosis of not only the left side but also the right side of the ventricular septum with involvement of the conduction system. The anatomic substrate demonstrated in these three patients could relate to lethal bradyarrhythmia or tachyarrhythmia, or both.
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PMID:Sudden death in three teenagers: conduction system studies. 682 76

Data was compiled from a wide variety sources in order to construct a demographic profile of elderly women in Latin America. Data was organized into a cross-classification matrix based on three age groups (midlife, young old, and old old) and three country types (highly rural, mixed, and highly urban). The macro-level overview takes into account such factors as education, family structure, and employment. Smaller reports and research project reports of micro conditions are used to help explain the macro trends. Women older than 40 represented 9-20% of the population of the region (of 21 Latin American and Caribbean countries). 6-14% of midlife women were widowed, with the highest concentrations in urban countries. Widows and single women comprised about 20-35% of midlife women and 50-65% of older women. Female household headship increased with age from 9-23% in midlife to 24-41% among women 60 years and older. In all countries with the exception of Uruguay, women had less primary schooling than men. Women's salaried employment in the formal sector decreased rapidly with increasing age. For example, in highly urban countries the range of employment was from 34% of women in midlife to only 4% among women 65 years and older. Women were working, but often in the informal sector or as prostitutes or beggars. Women's health conditions included 12-37% with chronic anemia and many with signs of premature aging (early onset of diabetes, hypertension, and osteoarthritic joint changes). Depression among older women may have been as high as 40%. The strain of maintaining a double work load of child care and housekeeping and employment is unmeasured. Regardless of the level of development, older women suffered primarily from heart disease. Breast cancer was more common in urban countries. Highly rural or mixed countries had greater incidence of cervical cancer. Chronic liver disease was appearing in some countries. In highly rural countries infectious diseases and malnutrition still contributed significantly to causes of death. Most women did not have social security coverage. Evidence points to women's remarkable responses (creativity, initiative, and persistence) to fulfilling survival needs.
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PMID:Older women in Latin America: the health and socioeconomic situation of this important subgroup. 857 13

The human Cu/Zn superoxide dismutase (hSOD-1) gene, catalyses the dismutation of O2 to H2O2 and O2. It is located on chromosome 21 in q22.1 and is overexpressed in Down's syndrome (DS) patients. These patients present various abnormalities including mental retardation, congenital heart disease, immunological deficits and premature aging. In order to explore the potential role of SOD-1 overexpression in DS, we have generated two lineages of transgenic mice for the hSOD-1 gene and studied, at the ultrastructural level, the effect of hSOD-1 overexpression on the thymic microenvironment. Modification of the cellular architecture and morphology associated with a lipidic invasion, signs of a premature involution of the thymus, were observed in both lineages. A rupture of the filamentous network in the extracellular and probably also in the intracellular matrix was first observed. These results correlate the thymic alterations visualized in light microscopy, on the thymus from DS patients, and raise the question of the relationship between the SOD-1 overexpression and the different morphological alterations associated with the premature thymic involution observed in SOD-1 transgenic mice. They suggest that thymic and immunological impairments present in DS patients may be related to the SOD-1 gene dosage effect.
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PMID:Premature thymic involution, observed at the ultrastructural level, in two lineages of human-SOD-1 transgenic mice. 922 11

Heart disease remains the most frequent cause of death in the general population and is intimately related to aging. Either extreme premature aging or marked longevity may be monogenic, but in most humans aging is a complex polygenic phenomenon. Hypercholesterolemia and hypertension are important factors. Cardiac amyloidosis and vascular elastin degradation may be separate factors. Humans with the greatest longevity are relatively refractory to atherosclerosis. Frequencies of heart deaths among relatives of a heart-death proband without dyslipoproteinemia conform to expectations of a polygenic trait. Careful, attentive medical management of major environmental factors and of heart senescence can result in more successful aging.
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PMID:Genetics, aging, and the heart. 977 Sep 46

Werner syndrome is a rare autosomal recessive disease characterized by a premature aging phenotype, genomic instability, and a dramatically increased incidence of cancer and heart disease. Mutations in a single gene encoding a 1432-amino acid helicase/exonuclease (hWRN) have been shown to be responsible for the development of this disease. We have cloned, overexpressed, and purified a minimal, 171-amino acid fragment of hWRN that functions as an exonuclease. This fragment, encompassing residues 70-240 of hWRN (hWRN-N(70-240)), exhibits the same level of 3'-5' exonuclease activity as the previously described exonuclease fragment encompassing residues 1-333 of the full-length protein. The fragment also contains a 5'-protruding DNA strand endonuclease activity at a single-strand-double-strand DNA junction and within single-stranded DNA, as well as a 3'-5' exonuclease activity on single-stranded DNA. We find hWRN-N(70-240) is in a trimer-hexamer equilibrium in the absence of DNA when examined by gel filtration chromatography and atomic force microscopy. Upon addition of DNA substrate, hWRN-N(70-240) forms a hexamer and interacts with the recessed 3'-end of the DNA. Moreover, we find that the interaction of hWRN-N(70-240) with the replication protein PCNA also causes this minimal, 171-amino acid exonuclease region to form a hexamer. Thus, the active form of this minimal exonuclease fragment of human WRN appears to be a hexamer. The implications these results have on our understanding of hWRN's roles in DNA replication and repair are discussed.
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PMID:A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'- 5' exonuclease and 5'-protruding strand endonuclease activities. 1186 28

Werner's syndrome is an autosomal recessive disorder resulting in premature aging. Most patients die in their fifth decade from malignancies or heart disease. The gene for Werner's syndrome (WRN) encodes a recQ helicase. Cells from patients with Werner's syndrome have increased sensitivity to DNA-damaging drugs in vitro. Here we present a patient with Werner's syndrome who developed severe chemotherapy-induced toxicity during treatment for acute myelogenous leukemia. We propose that lack of WRN resulted in increased sensitivity of the patient's cells to the toxicity of chemotherapy.
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PMID:Severe toxicity following induction chemotherapy for acute myelogenous leukemia in a patient with Werner's syndrome. 1601 64

Down syndrome (DS) is characterized by increased mortality rates, both during early and later stages of life, and age-specific mortality risk remains higher in adults with DS compared with the overall population of people with mental retardation and with typically developing populations. Causes of increased mortality rates early in life are primarily due to the increased incidence of congenital heart disease and leukemia, while causes of higher mortality rates later in life may be due to a number of factors, two of which are an increased risk for Alzheimer's disease (AD) and an apparent tendency toward premature aging. In this article, we describe the increase in lifespan for people with DS that has occurred over the past 100 years, as well as advances in the understanding of the occurrence of AD in adults with DS. Aspects of the neurobiology of AD, including the role of amyloid, oxidative stress, Cu/ZN dismutase (SOD-1), as well as advances in neuroimaging are presented. The function of risk factors in the observed heterogeneity in the expression of AD dementia in adults with DS, as well as the need for sensitive and specific biomarkers of the clinical and pathological progressing of AD in adults with DS is considered.
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PMID:Alzheimer's disease in Down syndrome: neurobiology and risk. 1791 85

The human genome is contained within the nucleus and is separated from the cytoplasm by the nuclear envelope. Mutations in the nuclear envelope proteins emerin and lamin A cause a number of diseases including premature aging syndromes, muscular dystrophy, and cardiomyopathy. Emerin and lamin A are implicated in regulating muscle- and heart-specific gene expression and nuclear architecture. For example, lamin A regulates the expression and localization of gap junction and intercalated disc components. Additionally, emerin and lamin A are also required to maintain nuclear envelope integrity. Demonstrating the importance of maintaining nuclear integrity in heart disease, atrioventricular node cells lacking lamin A exhibit increased nuclear deformation and apoptosis. This review highlights the present understanding of lamin A and emerin function in regulating nuclear architecture, gene expression, and cell signaling and discusses putative mechanisms for how specific mutations in lamin A and emerin cause cardiac- or muscle-specific disease.
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PMID:Emerin and the nuclear lamina in muscle and cardiac disease. 1859 64

Age is a major risk factor for heart disease, and cardiac aging is characterized by elevated mitochondrial reactive oxygen species (ROS) with compromised mitochondrial and nuclear DNA integrity. To assess links between increased ROS levels and mutations, we examined in situ levels of ROS and cII mutation frequency, pattern and spectrum in the heart of harlequin (hq)/Big Blue mice. The hq mouse is a model of premature aging with mitochondrial dysfunction and increased risk of oxidative stress-induced heart disease with the means for in vivo mutation detection. The hq mutation produces a significant downregulation in the X-linked apoptosis-inducing factor gene (Aif) impairing both the antioxidant and oxidative phosphorylation functions of AIF. Brain and skin of hq disease mice have elevated frequencies of point mutations in nuclear DNA and histopathology characterized by cell loss. Reports of associated elevations in ROS in brain and skin have mixed results. Herein, heart in situ ROS levels were elevated in hq disease compared to AIF-proficient mice (p<0.0001) yet, mutation frequency and pattern were similar in hq disease, hq carrier and AIF-proficient mice. Heart cII mutations were also assessed 15 days following an acute exposure to an exogenous ROS inducer (10 mg paraquat/kg). Acute paraquat exposure with a short mutant manifestation period was insufficient to elevate mutation frequency or alter mutation pattern in the post-mitotic heart tissue of AIF-proficient mice. Paraquat induction of ROS requires mitochondrial complex I and thus is likely compromised in hq mice. Results of this preliminary survey and the context of recent literature suggest that determining causal links between AIF deficiency and the premature aging phenotypes of specific tissues is better addressed with assay of mitochondrial ROS and large-scale changes in mitochondrial DNA in specific cell types.
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PMID:Heart tissue of harlequin (hq)/Big Blue mice has elevated reactive oxygen species without significant impact on the frequency and nature of point mutations in nuclear DNA. 2054 63

Age is undoubtedly a major risk factor for heart disease. However, the reason for this is not entirely clear. In the course of our investigation into the mechanism of radiation-induced cardiovascular disease, we made several unexpected findings that inform us on this question. We observed that human coronary endothelial cells, while being able to initiate repair of radiation-induced DNA damage, often fail to complete the repair and become senescent. Such radiation-induced cellular aging occurs through a mutation-independent route. Endothelial cells that aged naturally through replication or as a result of radiation exhibited indistinguishable characteristics. The promoter regions of the CD44 gene in aging endothelial cells become demethylated, and the proteins are highly expressed on the cell surface, making the cells adhesive for monocytes. Adhesion is a cardinal feature that recruits monocytes to the endothelium, allowing them to infiltrate the vessel wall and initiate atherosclerosis. The epigenetic activation of CD44 expression is particularly significant as it causes persistent elevated CD44 protein expression, making senescent endothelial cells chronically adhesive. In addition to understanding why cardiovascular disease increases with age, these observations provide insights into the puzzling association between radiation and cardiovascular disease and highlight the need to consider premature aging as an additional risk of radiation to human health.
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PMID:Premature aging induced by radiation exhibits pro-atherosclerotic effects mediated by epigenetic activation of CD44 expression. 2505 16


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