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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heart disease is an entity frequently seen in the fetal alcohol syndrome. This paper describes the effect of in utero ethanol exposure on the postnatal ultrastructural development of rat cardiac muscle. To determine this time-pregnant Sprague-Dawley rats were fed either a nutritionally balanced protein- and vitamin-enriched liquid ethanol diet (with 36% of the calories derived from ethanol) or a liquid diet with maltose-dextrins isocalorically substituted for ethanol. The latter group was designated the pairfed control group. At birth, pups of both the groups were surrogate-fostered by normal dams. Body weights and crown-rump lengths were significantly less in the rat pups exposed to ethanol in utero at 21 days postnatal. Ultrastructural analysis of the cardiac muscle was performed at 7, 14, and 21 days postnatal in ethanol and pairfed groups. Several morphological features of myocyte damage were observed in ethanol-exposed pups, predominantly at 7 days postnatal, with nearly total absence of myocyte damage by 21 days postnatal. The most outstanding changes were observed in the myofibrils, which showed dysplastic changes at 7 days postnatal, a delay in M-band structural development at 14 days postnatal, and a significantly smaller myofibril volume density per tissue volume at 21 days postnatal in the ethanol rat pups compared to the pairfed controls.
Exp Mol Pathol 1994 Jun
PMID:Fetal alcohol effects on the postnatal development of the rat myocardium: an ultrastructural and morphometric analysis. 795 76

Abnormal myocardial long-chain fatty acid uptake is suspected of being involved in certain types of heart disease, but the mechanism by which the heart takes up long-chain fatty acids remains unclear. The sulfo-N-succinimidyl derivatives of long-chain fatty acids have been reported to undergo covalent binding to a membrane protein and to irreversibly inhibit the transport of long-chain fatty acids by rat adipocytes (Harmon et al., 1991). It has been suggested that the membrane protein bound by these derivatives is a candidate transporter for long-chain fatty acids in adipocytes. However, myocardial membrane long-chain fatty acid-binding proteins have not yet been fully investigated. Rat hearts were isolated and perfused with a sulfo-N-succinimidyl derivative of tritium-labeled palmitate ([3H]SSP). Then the [3H]SSP-binding protein was characterized by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) autoradiography and histological autoradiography. Myocardial palmitic acid uptake was examined after pretreatment of isolated perfused rat hearts with SSP. The SSP-binding protein was isolated from bovine hearts by successive chromatography, and the amino acid sequences of lysylendopeptidase-digested peptide fragments were determined. SDS-PAGE autoradiography revealed that [3H]SSP bound to an 85-90 kDa protein derived from the myocardial microsomal fraction, and histological autoradiography demonstrated that [3H]SSP radioactivity was localized to the myocardial cell membrane. Pre-incubation with SSP inhibited palmitic acid uptake by isolated perfused rat hearts. A [3H]SSP-binding protein was also found in canine and bovine hearts, and was isolated from the bovine cardiac membrane fraction. Amino acid sequencing revealed that four peptide fragments showed strong sequence homology with rat adipocyte membrane protein, which is implicated in the binding or transport of long-chain fatty acids (Abumrad et al., 1993). We conclude that the SSP-binding protein is localized to the myocardial cell membrane and might be involved in the uptake or transport of long-chain fatty acids.
J Mol Cell Cardiol 1995 Aug
PMID:Isolation of myocardial membrane long-chain fatty acid-binding protein: homology with a rat membrane protein implicated in the binding or transport of long-chain fatty acids. 852 24

Immunocytochemistry of muscarinic receptors on human heart biopsies from patients with heart disease was studied using rabbit antibodies against a synthetic peptide corresponding to amino acids 168-192 of the second extracellular loop of the human M2 muscarinic receptor. By using both light and electron microscopic immunocytochemistry techniques, muscarinic receptors were visualized on sarcolemma of human myocytes from patients with different heart diseases such as coronary heart disease and dilated cardiomyopathy in adults and congenital heart disease in children. The patchy distribution of immunoreactivity suggests a muscarinergic activity in vivo. These reactivities were abolished by preincubation of antibodies with antigenic peptide and were not shown in the absence of antibodies. Moreover, these antibodies were able to interfere with muscarinic ligand binding in myocardium from human dilated cardiomyopathy as shown by decreases in binding sites and antagonist affinity. These results demonstrate that the antibodies against the second extracellular loop of the human M2 muscarinic receptor can specifically recognize muscarinic receptors in human tissue and display pharmacological activity in human diseased myocardium, confirming their usefulness for the study of localization and function of muscarinergic activity in the human heart.
J Mol Cell Cardiol 1995 Aug
PMID:Localization of muscarinic receptors in human heart biopsies using rabbit anti-peptide antibodies. 852 36

Long QT syndrome (LQT) is an inherited cardiac disorder that causes syncope, seizures and sudden death from ventricular tachyarrhythmias. We used single-strand conformation polymorphism (SSCP) and DNA sequence analyses to identify mutations in the cardiac sodium channel gene, SCN5A, in affected members of four LQT families. These mutations include two identical intragenic deletions and two missense mutations. These data suggest that SCN5A mutations cause LQT. The location and character of these mutations suggest that this form of LQT results from a delay in cardiac sodium channel fast inactivation or altered voltage-dependence of inactivation.
Hum Mol Genet 1995 Sep
PMID:Cardiac sodium channel mutations in patients with long QT syndrome, an inherited cardiac arrhythmia. 854 46

Cultured human myocardial fibroblasts of pediatric origin seem to be a useful species-specific model for studying various heart diseases which involve the myocardial interstitium, for example enterovirus heart disease. Cells were propagated from small samples of human ventricular tissues (0.2 g) obtained from standard surgical procedure for the correction of Fallot-tetralogy. Cultured cells exhibited typical fibroblastoid morphology over a period of 4 months and were uniformly immunoreactive with a monoclonal antibody directed against prolyl-4-hydroxylase, a marker enzyme of fibroblasts. Infection of cell cultures with coxsackievirus B3, a cardiotropic enterovirus, resulted in a typical carrier-state type of virus persistence. Average virus titers of 2.3 x 10(5) plaque-forming units/ml (SD = 9.9 x 10(4)) were maintained over a period of up to 10 weeks by productive infection of about 8-10% of the cell population. Coxsackievirus B3 carrier cultures of human myocardial fibroblasts were used to evaluate in vitro the long-term antiviral effects of recombinant interferon alpha-2a and natural human interferon-alpha. Recombinant interferon-alpha reduced virus yields by 90% with a concentration of 423 IU/ml, whereas with natural interferon-alpha a 90% reduction of virus yields was achieved with concentrations as low as 21 IU/ml. Antiviral effects of both recombinant and natural interferon-alpha were highly specific and not related to inhibition of cell-proliferation (< 50% with interferon-alpha concentrations as high as 6250 IU/ml). Since effective concentrations of interferon-alpha can be easily attained in vivo with subcutaneous application, interferon-alpha (in particular: natural interferon-alpha) may become useful in the treatment of patients with enterovirus myocarditis and enterovirus induced dilated cardiomyopathy.
J Mol Cell Cardiol 1995 Oct
PMID:Cultured human myocardial fibroblasts of pediatric origin: natural human interferon-alpha is more effective than recombinant interferon-alpha 2a in carrier-state coxsackievirus B3 replication. 857 36

Cigarette smoking alters the pattern of endogenous steroid levels. We examined this phenomenon in two separate male groups. Group A consisted of 189 dyslipidemic men participating in the Helsinki Heart Study and group B of 100 men including patients with heart disease and healthy controls. The subjects in the latter group underwent ACTH-testing. In group A, smokers had significantly higher basal androstenedione and dehydroepiandrosterone sulfate (DHEAS) levels and androstenedione/cortisol ratios than nonsmokers. Mean concentrations of cortisol, dehydroepiandrosterone (DHEA), androstanediol glucuronide, testosterone, and sex-hormone binding globulin (SHBG) did not differ between smokers and nonsmokers. In group B, smokers had lower high density lipoprotein (HDL)-cholesterol and apolipoprotein AI and higher triglyceride levels than nonsmokers. Basal androstenedione and ACTH stimulated androstenedione and DHEA concentrations were higher in smokers. No significant differences were found in basal insulin, SHBG, estrone, estradiol, testosterone, free testosterone, and dihydrotestosterone concentrations between smokers and nonsmokers. These results suggest that smoking decreases the activity of either 21- or 11 beta-hydroxylase in the adrenal cortex, which results in increased secretion of adrenal androgens.
J Steroid Biochem Mol Biol 1993 Aug
PMID:Cigarette smoking is associated with elevated adrenal androgen response to adrenocorticotropin. 866 73

Identification of the genetic basis for congenital heart defects has been a topic of inquiry for pediatric cardiologists for many years. Any genetic model proposed must account for three often puzzling features of congenital heart diseases, namely the high population incidence, the less than Mendelian recurrence risk, and low concordance rates of heart lesions within individual families. A multifactorial or polygenic inheritance model has been used to explain these observations. Although this model has been serviceable, it does not adequately explain the phenotypic variability within families. Further, the emphasis on teratogenic influences has not led to the elucidation of pathogenetic mechanisms. The multifactorial model should be modified to include the role of chance as originally proposed by Kurnit. Once the role of chance is acknowledged, the phenotypic variability of congenital heart diseases becomes less problematic, and the multifactorial model gives way to a model in which single genes are capable of producing congenital heart disease. Through recent work in animal models and humans, it is now clear that single congenital heart disease genes can be identified that produce phenotypic variability in families that is similar to that seen in the population as a whole. Examples demonstrating recent progress in the search for major congenital heart disease genes are discussed.
Cell Mol Biol Res 1995
PMID:The search for genetic mechanisms of congenital heart disease. 877 87

X-linked dilated cardiomyopathy (XLDC) is a familial heart disease presenting in young males as a rapidly progressive congestive heart failure, without clinical signs of skeletal myopathy. This condition has recently been linked to the dystrophin gene in some families and deletions encompassing the genomic region coding for the first muscle exon have been detected. In order to identify the defect responsible for this disease at the molecular level and to understand the reasons for the selective heart involvement, a family with a severe form of XLDC was studied. In the affected members, no deletions of the dystrophin gene were observed. Analysis of the muscle promoter, first exon and intron regions revealed the presence of a single point mutation at the first exon-intron boundary, inactivating the universally conserved 5' splice site consensus sequence of the first intron. This mutation introduced a new restriction site for MseI, which cosegregates with the disease in the analyzed family. Expression of the major dystrophin mRNA isoforms (from the muscle-, brain- and Purkinje cell-promoters) was completely abolished in the myocardium, while the brain- and Purkinje cell- (but not the muscle-) isoforms were detectable in the skeletal muscle. Immunocytochemical studies with anti-dystrophin antibodies showed that the protein was reduced in quantity but normally distributed in the skeletal muscle, while it was undetectable in the cardiac muscle. These findings indicate that expression of the muscle dystrophin isoform is critical for myocardial function and suggest that selective heart involvement in dystrophin-linked dilated cardiomyopathy is related to the absence, in the heart, of a compensatory expression of dystrophin from alternative promoters.
Hum Mol Genet 1996 Jan
PMID:A point mutation in the 5' splice site of the dystrophin gene first intron responsible for X-linked dilated cardiomyopathy. 878 42

In 1996, we are half-way through the Decade of the Brain, yet we still have few effective treatments for major disorders of the central nervous system. These include affective disorders, epilepsy, neurodegenerative disorders, brain tumours, infections and HIV encephalopathy; sufferers far outnumber the morbidity of cancer or heart disease. Increased understanding of the pharmacology of the brain and its blood supply, and methods for rational drug design, are leading to potential new drug therapies based on highly specific actions on particular target sites, such as neurotransmitter receptors and uptake systems. These methods are capable of reducing the side effects that are common with more general treatments. However, all these treatments and potential treatments meet a formidable obstacle--the blood-brain barrier. In this article, we review the properties of this barrier that complicate drug delivery to the brain, and some of the most hopeful strategies for overcoming or bypassing the barrier in humans.
Mol Med Today 1996 Mar
PMID:Transporting therapeutics across the blood-brain barrier. 879 67

Recent studies of heart disease suggest that immunologically mediated processes often accompany cardiac injury and can contribute to pathogenesis. Murine models of myocarditis have provided insight into the mechanisms by which autoimmune responses to cardiac antigens arise and cause tissue pathology. It is now evident that T cells, cytokines and antibodies can all contribute to cardiac injury. Furthermore, murine models have demonstrated that both the propensity to develop autoreactivity following cardiac injury and the vulnerability of the heart to these responses are under genetic control. Continued studies will help to identify susceptibility genes and might aid in the development of strategies to protect individuals at risk from immunologically mediated damage following cardiac injury.
Mol Med Today 1996 Aug
PMID:Autoimmunity in heart disease: mechanisms and genetic susceptibility. 879 19


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