Metabolism of ethanol and carcinogens by glutathione transferases.

Nonoxidative alcohol metabolism to form fatty acid ethyl esters contributes to alcohol-related end-organ damage, and these products are formed by two synthase enzymes. We recently purified the major (pI 4.9) synthase from human myocardium.

Mapping of recombinants near the Huntington disease locus by using G8 (D4S10) and newly isolated markers in the D4S10 region.

Genetic linkage between the marker G8 (D4S10) and Huntington disease (HD) was studied in six Dutch pedigrees. The informativeness of the D4S10 locus was increased by isolation of a cosmid, C5.5, with a G8 subclone used as probe.

Cyclosporin neurotoxicity in cardiac transplant recipients.

Cyclosporin toxicity may produce a wide range of neurological disorders. We report three patients whose neurological problems developed while taking cyclosporin following cardiac transplantation, but resolved rapidly when the drug was discontinued. In two cases, MRI revealed abnormalities which disappeared with clinical recovery.

Receptor-like function of heparin in the binding and uptake of neutral lipids.

Molecular mechanisms regulating the binding, amphipathic stabilization, and metabolism of the major neutral lipids (e.g., cholesteryl esters, triglycerides, and fatty acids) are well studied, but the details of their movement from a binding compartment to a metabolic compartment deserve further attention.

Chemical modification of acyl-CoA:cholesterol O-acyltransferase. 2. Identification of a coenzyme A regulatory site by p-mercuribenzoate modification.

Acyl-CoA:cholesterol O-acyltransferase (EC 2.3.1.

Chemical modification of acyl-CoA:cholesterol O-acyltransferase. 1. Identification of acyl-CoA:cholesterol O-acyltransferase subtypes by differential diethyl pyrocarbonate sensitivity.

Acyl-CoA:cholesterol O-acyltransferase (EC 2.3.1.

Comparison of myoelectric and conventional prostheses for adolescent amputees.

We questioned whether myoelectric prostheses were a reasonable alternative to conventional prostheses for adolescents with unilateral, congenital, below-elbow amputations in respect to fit, function, cosmesis, and cost. Ten patients were studied. Each received a physical, functional, and psychosocial evaluation prior to prosthetic fitting.

Immune cytokine inhibition of beta-adrenergic agonist stimulated cyclic AMP generation in cardiac myocytes.

We hypothesize that reversible depression of cardiac function in cardiac allograft rejection and lymphocytic myocarditis reflects down modulation of the beta-adrenergic receptor system by a soluble product of activated immune cells. Thus, exposure of cultured cardiac myocytes to mixed lymphocyte culture or activated splenocyte supernatants produces 70% inhibition of isoproterenol-stimulated cAMP concentrations (Ki = 5% supernatant) in the absence of gross cellular injury or control media effects. This cAMP suppressive factor is not dialyzable and is ammonium sulfate precipitable.

[Methodologic preferences and content of psychiatric research in an international comparison].

Empirical publications from six psychiatric journals and five countries have been investigated for differences in methodical approaches and concerning the subjects of the articles. The differences between the branches of psychiatry and neurology within the journals are more discernible both with research subjects and with methodical aspects than the differences between the journals from different countries. Some differences between psychiatric journals from different countries, relating to the subjects of research, were found in the independent variables, the dependent variables and the kinds of subjects in the samples.

Antibodies against the paramyxovirus SV5 in the cerebrospinal fluids of some multiple sclerosis patients.

Multiple sclerosis is a demyelinating disease of the central nervous system and although there is little doubt that an infectious agent (or agents) is involved it has not been possible to demonstrate this unequivocally by any direct relationship to a given agent. Here we show that a significant proportion of patients with multiple sclerosis have antibodies against the paramyxovirus SV5 (simian virus 5) in their cerebrospinal fluid and in some of these such antibodies form a major proportion of the total immunoglobulin content. Further, we have been able to demonstrate that the oligoclonal bands displayed on electrophoresis of the cerebrospinal fluid of these patients can be removed by prior absorption with SV5 virus antigen.

Metabolism of ethanol by human brain to fatty acid ethyl esters.

Although the most prominent acute and chronic effect of alcohol ingestion in man is alteration of brain function, metabolism of ethanol by human brain has not been documented. This study was designed to detect and localize a new family of nonoxidative ethanol metabolites, fatty acid ethyl esters, in human brain and characterize their synthetic pathways. Fatty acid ethyl ester synthase activity was present in 10 different locations in human brain, with gray matter containing more activity than white matter (0.

Regulation of adult and fetal myocardial phosphofructokinase. Relief of cooperativity and competition between fructose 2,6-bisphosphate, ATP, and citrate.

To clarify the physiological role of fructose 2,6-bisphosphate in the perinatal switching of myocardial fuels from carbohydrate to fatty acids, the kinetic effects of fructose 2,6-bisphosphate on phosphofructokinase purified from fetal and adult rat hearts were compared. For both enzymes at physiological pH and ATP concentrations, 1 microM fructose 2,6-bisphosphate induced a greater than 10-fold reduction in S0.5 for fructose 6-phosphate and it completely eliminated subunit cooperativity.

Nonoxidative ethanol metabolism in human leukocytes: detection of fatty acid ethyl ester synthase activity.

Oxidative pathways of alcohol metabolism such as alcohol dehydrogenase usually are not present in human blood and therefore clinical studies correlating ethanol metabolism with alcohol abuse syndromes have not been performed. To assess the activity of nonoxidative ethanol metabolism in blood, we assayed for the activity of fatty acid ethyl ester synthase, a pathway recently described as abundant in the human organs most commonly damaged by alcohol. Indeed, peripheral human leukocytes contain detectable fatty acid ethyl ester synthase activity: 1.

DNA probe analysis for carrier detection and prenatal diagnosis of Duchenne muscular dystrophy: a standard diagnostic procedure.

Thirteen marker loci localised on the short arm of the X chromosome are available for use in genetic studies for Duchenne muscular dystrophy (DMD). This large number of probes detecting about 20 RFLPs encouraged us to set up a standard procedure using a sequence of selected probes and restriction enzymes for the diagnosis of DMD families. The application of DNA probe analysis for carrier detection and prenatal diagnosis, involving 61 pedigrees of both familial and isolated cases, has yielded the following results.

Right-heart echocontrast in the anesthetized dog after i.v. administration of a new standardized sonographic contrast agent. 2nd communication: dependence of the intensity of contrast on the interval between preparation of the suspension and its injection.

The right-ventricular echocontrast provided by 5 different concentrations of the new standardized sonographic contrast agent SH U 454 (100, 150, 200, 300 and 400 mg microparticles/ml), which consists of pure galactose microparticles, was examined in 3 anesthetized female beagle dogs (8.6-9.3 kg) in order to assess the influence of the period of time which elapsed between preparation of the suspension and its injection.

Right-heart echocontrast in the anesthetized dog after i.v. administration of a new standardized sonographic contrast agent. 1st communication: dose-response relationship.

The newly developed standardized sonographic contrast agent SH U 454, which consists of pure galactose microparticles, was examined for opacification of the right heart by 2 D echocardiography in 10 anesthetized female beagle dogs (6.8-12.7 kg) following i.

Right-heart echocontrast in the anesthetized dog after i.v. administration of a new standardized sonographic contrast agent. 3rd communication: comparison of various contrast agents employed in contrast echocardiography.

Right-ventricular contrast provided by the new standardized sonographic contrast agent SH U 454, which consists of pure galactose microparticles, with 300 mg microparticles/ml and by 5 other currently employed ultrasonic contrast media was examined by 2 D echocardiography in 10 anesthetized female beagle dogs (6.8-12.7 kg) following i.

Cardiac dysfunction during acute lung injury induced by oleic acid in dogs.

Circulatory abnormalities are common during the adult respiratory distress syndrome and contribute importantly to the high mortality seen with this illness, but what causes them is not well characterized. Oleic acid-induced acute lung injury is an experimental model of the human syndrome in which hemodynamic changes are also common. To characterize a possible link between lung injury and cardiac dysfunction in this model, we evaluated cardiac function in mongrel dogs after oleic acid administration.

Metabolism of very low density lipoproteins after cessation of cholesterol feeding in rabbits. A factor potentially contributing to the slow regression of atheromatous plaques.

Aortic atheromatous plaques regress slowly in cholesterol-fed rabbits that have been returned to normal laboratory diet. To delineate metabolic factors potentially responsible for persistence of atherosclerosis under these conditions, the physical, chemical, and metabolic characteristics were determined for lipoproteins of d less than 1.006 g/ml; such lipoproteins are thought to be the major determinant of progression of atherosclerotic lesions in cholesterol-fed rabbits.

Presence of nonoxidative ethanol metabolism in human organs commonly damaged by ethanol abuse.

Acetaldehyde, the end product of oxidative ethanol metabolism, contributes to alcohol-induced disease in the liver, but cannot account for damage in organs such as the pancreas, heart, or brain, where oxidative metabolism is minimal or absent; nor can it account for the varied patterns of organ damage found in chronic alcoholics. Thus other biochemical mediators may be important in the pathogenesis of alcohol-induced organ damage. Many human organs were found to metabolize ethanol through a recently described nonoxidative pathway to form fatty acid ethyl esters.