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Biomedical subjects

A Wolf

Publications and source records attributed to A Wolf.

At least 145 records · Page 8Linked to original sources
PubMed1997

Adhesiveness of mononuclear cells in hypercholesterolemic humans is normalized by dietary L-arginine.

Hypercholesterolemia reduces vascular nitric oxide (NO) activity. This dysfunction may promote endothelial monocyte interaction, as NO is a potent inhibitor of cell adhesion. We have previously shown that in hypercholesterolemic (HC) rabbits, chronic oral supplementation of L-arginine (Arg) restores NO activity and inhibits monocyte-endothelial cell interaction, in association with a reduction in atherogenesis. We hypothesized that enhancement of endothelial NO activity in HC humans would reduce monocyte adhesiveness. We used a functional binding assay to assess the adhesiveness of human mononuclear cells (MNCs) ex vivo to determine the effects of hypercholesterolemia and L-arginine administration. MNCs from HC subjects adhered in greater numbers (50% more cells per high-power field; P < .0001) than cells derived from normocholesterolemic (NC) subjects. To determine whether enhancement of endogenous NO activity could inhibit mononuclear cell adhesiveness, in a double-blinded placebo-controlled study, oral arginine HCl (8.4 g/d) was administered to HC subjects. Over a course of 2 weeks, this treatment abolished the increased adhesiveness of HC MNCs (160 +/- 11% versus 104 +/- 5%; before and after 2 weeks of Arg treatment; results expressed as a percentage of the binding values obtained using cells derived from paired NC individuals). By contrast, MNC adhesion remained significantly elevated in placebo-treated HC subjects. To examine whether endothelium-derived NO could act as a paracrine modulator of monocyte behavior, monocytes were exposed to NO donors or cocultered in the presence of endothelial cells exposed to antagonists of NO synthase in the presence or absence of L-arginine. NO donors inhibited monocyte adhesiveness. Furthermore, the adhesiveness of monocytes cocultured with endothelial cells was increased by antagonists of NO synthase; this effect was reversed by L-arginine. This study shows that the adhesiveness of human MNCs is increased by hypercholesterolemia. The increase in adhesiveness was reversed in vivo by administration of the NO precursor L-arginine. NO donors or endothelium-derived NO inhibits the adhesiveness of monocytes in vitro, supporting the hypothesis that the effects of L-arginine are mediated by NO.

Adult↗
PubMed1997

Cyclosporine A-induced oxidative stress in rat hepatocytes.

In man the immunosuppressive drug Cyclosporine A (CsA) has been used successfully in organ transplantation and in the treatment of autoimmune disorders. The drug, however, causes side effects which occur mainly in the kidney but also in the liver. The mechanisms leading to the hepatic side effects are not yet fully understood. Because reactive oxygen production is a common mechanism of drug toxicity, the goal of this study was to evaluate whether CsA induces oxidative stress in rat liver cells. In primary rat hepatocyte 20-h cultures, CsA caused a concentration-dependent increase of free reactive oxygen species, thiobarbituric acid reactive substances, loss of protein thiols and decrease of molar ratios of glutathione and glutathione disulfide in the range of 0 to 50 microM CsA. The weakening or enforcement of the cellular glutathione state by the glutathione synthesis inhibitor buthionine sulfoximine or the glutathione disulfide -reducing agent dithiothreitol either increased or inhibited the CsA cytotoxicity, as determined by lactate dehydrogenase release. CsA also decreased the level of endogenous antioxidant ascorbic acid and increased its oxidation product dehydroascorbic acid. Supplementation of the cell cultures with ascorbic acid significantly reduced the CsA toxicity. The antioxidant DL-alpha-tocopherol-polyethylene-glycol-1000-succinate partly decreased CsA-mediated reactive oxygen species formation, totally decreased thiobarbituric acid reactive substances formation, prevented the loss of protein-bound sulfhydryl groups and in addition totally inhibited the CsA cytotoxicity. The present data provide good evidence that oxidative stress is part of the mechanism by which CsA causes toxicity in rat liver cells.

Animals↗
PubMed1996

Ligand-dependent conformational plasticity of the periplasmic histidine-binding protein HisJ. Involvement in transport specificity.

The periplasmic histidine permease of Salmonella typhimurium is composed of a membrane-bound complex and a soluble histidine-binding protein (the periplasmic receptor), HisJ. Liganded receptor interacts with the membrane-bound complex, inducing ATP hydrolysis and substrate translocation. Preliminary evidence had shown a lack of direct correlation between the affinity of HisJ for a ligand and translocation efficiency, suggesting that the precise form of the receptor is important in determining its interaction with the membrane-bound complex. We have investigated the nature of the conformations assumed by HisJ upon binding a variety of ligands by tryptophan fluorescence enhancement, reaction with a closed form-specific monoclonal antibody, and changes in UV absorption spectra. It is demonstrated that although HisJ binds all the ligands and undergoes a conformational change, it assumes measurably different conformations. We also show that the interaction between HisJ and the membrane-bound complex depends on the nature of the ligand. Transport specificity appears to be defined, at least in part, by the conformation of the bound receptor, manifested either by the effect of a given ligand on the closed structure per se, or by the effect of ligand association on the equilibrium constant relating the open and the closed liganded forms.

Antibodies, Monoclonal↗
PubMed1996

Effects of mianserin and ketanserin on lordosis behavior after systemic treatment or infusion into the ventromedial nucleus of the hypothalamus.

The effects of the 5-HT2A/2C antagonists, mianserin and ketanserin, were investigated in proestrous rats and in ovariectomized rats hormonally primed with estradiol benzoate and progesterone. Drugs were administered systemically or by infusion into the vicinity of the ventromedial nucleus of the hypothalamus (VMN). By both routes of administration, inhibition of lordosis behavior was seen following treatment with the 5-HT2A/2C antagonists, but the magnitude of the decline was smaller in proestrous than in hormone-primed, ovariectomized rats. The results of these studies are discussed in terms of the dual role of serotonin in the control of female sexual behavior.

Animals↗
PubMed1996

Influence of the N-methyl-D-aspartate receptor antagonist DL-2-amino-5-phosphonovaleric acid on auditory filial imprinting in the domestic chick.

Newly hatched domestic chicks were injected uni- or bilaterally into the imprinting relevant forebrain region mediostral neostriatum/ hyperstriatum ventrale (MNH) with different concentrations (1, 3, 12.5, 50 nmol) of the competitive NMDA antagonist DL-5-amino-5- phosphonovaleric acid (APV) prior to exposure to the imprinting stimulus (400-Hz tone pulses). In both APV-injected experimental groups there was a dose-dependent decrease of imprinting rates compared to that seen in controls, suggesting an APV-induced blockade of the learning process. In order to find out how the injected APV interferes with the stimulus-evoked enhanced metabolic activity in imprinting-relevant brain regions and to gain information about the spatial extent of its physiological effect, 2-fluorodeoxyglucose (2-FDG) experiments were performed. Chronically APV-treated chicks which failed in the imprinting tests showed similarly low 2-FDG uptake in imprinting relevant areas as naive untreated controls, further suggesting that no learning process has occurred in these animals. In imprinted chicks acute APV injections into the MNH led to a suppression of the stimulus-evoked 2-FDG uptake in this region. This pharmacologically induced reduction extended beyond the MNH region to adjacent regions. Furthermore, unilateral injections into the MNH always resulted in a bilateral reduction of 2-FDG uptake in this area. The results suggest that NMDA-mediated mechanisms in restricted telecephalic areas such as the MNH play a crucial role in the process of auditory filial imprinting.

2-Amino-5-phosphonovalerate↗
PubMed1996

Pattern of basic life support ambulance use in an urban pediatric population.

To evaluate the pattern of use of basic life support (BLS) ambulances in a pediatric population, emergency medical service (EMS) and pediatric emergency department (PED) records from an urban hospital PED for all children transported to PED by ambulance during a 1-month study period were retrospectively reviewed. Excluded were: (1) advanced life support transport, (2) transport from other medical facility, (3) patients with chronic medical disability without acute decompensation, and (4) patients in police custody. BLS transport was considered inappropriate if: (1) no intervention by BLS technicians, (2) minimal to no intervention in the PED, and (3) discharge without prescription medication. Of 376 ambulance transports evaluated, 238 (63%) met entry criteria, and 105 (44%) transports met criteria for being inappropriate. The mean charge for appropriate transport was $240.68, and for inappropriate, $237.12 (P = .2). The total charge for inappropriate transports was $26,523.20. Patients on federal assistance had a significantly higher rate of inappropriate transport (51%) compared with patients who had commercial insurance (30%) and those who self paid (42%). Trauma was the most common cause for transport, 48% of which was inappropriate. It was concluded that inappropriate BLS transport of pediatric patients is common. This use is costly and may disrupt the delivery of EMS care to the remainder of the community. Efforts aimed at public education and providing alternative means of transport may significantly reduce charges and improve the delivery of EMS care.

Ambulances↗
PubMed1996

Screening for mutations of the human thyroid peroxidase gene in patients with congenital hypothyroidism.

While congenital hypothyroidism in 80-90% of the affected individuals is caused by thyroid dysgenesis (athyrosis, ectopy or hypoplasia), hypothyroidism in patients with a thyroid gland of normal position and size can be due to regulatory or enzymatic defects of thyroid hormone biosynthesis. Beside defects of thyroglobulinsynthesis, defects of the sodium-iodide-transporter or the TSH-receptor, a defect of the thyroidperoxidase, the key-enzyme of thyroid hormone biosynthesis, can cause a total iodide organification defect and thereby congenital hypothyroidism. We screened 14 of 103 patients (13.6%) with non familial congenital hypothyroidism and a normally developed thyroid gland detected by the newborn screening program with the PCR-SSCP (single-stranded-conformational-polymorphism) technique for mutations in the exons 2, 8, 9, 10 and 14 of the human thyroperoxidase gene, and in which mutations had been described previously in Dutch and Brazilian families with total organification defects. Most of the previously reported mutations were found in exons 8, 9 and 10 which code for the caralytic part of the enzyme. In two patients a GGCC-duplication in exon 8 was detected leading to a premature stop codon in exon 9. While one patient without neonatal goiter was homozygous for this mutation, the second patient was only heterozygous thus demanding another mutation on the second TPO-allel to explain the phenotype. Since the GGCC duplication is easily demonstrable by a NaeI digestion, because it creates a restriction site for this enzyme, screening for this mutation is indicated since it is easy to perform. In contrast to the perchlorate discharge test molecular genetic studies are less invasive, but as useful in making a definitive diagnosis in the individual patient. Furthermore it is the first feasible step to study the etiology and epidemiology of the so far only putative defects of thyroid hormone biosynthesis leading to congenital hypothyroidism.

Congenital Hypothyroidism↗