Search PubMed⌕ Search

Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 235 records · Page 13Linked to original sources
PubMed1995

Genetic predisposition to adverse consequences of anti-cholinesterases in 'atypical' BCHE carriers.

Normal butyrylcholinesterase (BuChE), but not several of its common genetic variants, serves as a scavenger for certain anti-cholinesterases (anti-ChEs). Consideration of this phenomenon becomes urgent in view of the large-scale prophylactic use of the anti-ChE, pyridostigmine, during the 1991 Persian Gulf War, in anticipation of nerve gas attack and of the anti-ChE, tacrine, for improving residual cholinergic neurotransmission in Alzheimer's disease patients. Adverse symptoms were reported for subjects in both groups, but have not been attributed to specific causes. Here, we report on an Israeli soldier, homozygous for 'atypical' BuChE, who suffered severe symptoms following pyridostigmine prophylaxis during the Persian Gulf War. His serum BuChE and recombinant 'atypical' BuChE were far less sensitive than normal BuChE to inhibition by pyridostigmine and several other carbamate anti-ChEs. Moreover, atypical BuChE demonstrated 1/200th the affinity for tacrine of normal BuChE or the related enzyme acetylcholinesterase (AChE). Genetic differences among BuChE variants may thus explain at least some of the adverse responses to anti-ChE therapies.

Acetylcholinesterase↗
PubMed1995

Inhibition of apoptosis during 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated tumour promotion in rat liver.

The effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on cell division and cell death (apoptosis) in glutathione S-transferase (GST-P)-positive liver foci were analyzed in diethylnitrosamine-initiated female Wistar rats that were treated with TCDD, either acutely for 3 days or chronically for 115 days. Apoptotic bodies were quantitated in liver sections simultaneously stained for GST-P expression and H&E using a novel fluorescence microscopic detection method which greatly facilitates recognition of apoptotic bodies due to their high level of eosin fluorescence. While TCDD treatment only marginally affected cell division in GST-P-positive liver foci, as estimated by 5-bromo-2'-deoxyuridine-labelling, apoptotic indices were decreased to approximately 60% and approximately 10% of control values after acute and chronic TCDD treatment, respectively. In normal liver tissue, apoptotic indices were only slightly reduced by TCDD treatment, suggesting selective inhibition of apoptosis in the enzyme-altered cell population by the dioxin. Since inhibition of apoptosis in GST-P-positive liver foci was by far more pronounced than changes in cell division, our data suggest that the promoting activity of TCDD is preferentially mediated by a decrease of apoptosis in enzyme-altered liver foci.

Animals↗
PubMed1995

Pulmonary alveolar epithelial inducible NO synthase gene expression: regulation by inflammatory mediators.

Nitric oxide (.NO) is a short-lived mediator that can be induced by different cytokines and lipopolysaccharide (LPS) in a variety of cell types and produces many physiological and metabolic changes in target cells. In the current study, we show that a combination of cytokines, LPS, and zymosan-activated serum (ZAS; called for convenience cytomix Z) induces production of high concentrations of the NO oxidation products nitrite (NO2-) and nitrate (NO3-) by cultured rat fetal lung epithelial type II cells in a time-dependent fashion. Interferon-gamma and tumor necrosis factor-alpha alone did not significantly affect .NO synthesis, whereas ZAS, LPS, and interleukin-1 beta caused only a modest increase in formation of .NO oxidation products. Production of NO2- and NO3- was inhibited by NG-monomethyl-L-arginine and cyclohexmide. After exposure of these cells to a combination of the above cytokines, Escherichia coli LPS, and ZAS (cytomix Z), enhanced inducible nitric oxide synthase (iNOS) expression was indicated by an elevation in steady-state mRNA specific for iNOS (via Northern blot analysis) and increased immunofluorescence for iNOS after cell permeabilization, incubation with anti-iNOS antibody, and treatment with Cy3.18-conjugated rabbit-specific antibody. The extent of inflammatory mediator-induced.NO production by alveolar epithelium, which exceeds that of other lung cell types, reveals new insight into mechanisms of pulmonary host defense and pathways of free radical-mediated lung injury.

Amino Acid Oxidoreductases↗
PubMed1995

High-level IL-10 production by monoclonal antibody-stimulated human T cells.

We investigated interleukin-10 (IL-10) production in freshly isolated mononuclear cells and purified T cells in response to stimulation with monoclonal antibodies (mAb) recognizing CD3, CD2 and CD28, or with the bacterial products Staphylococcus aureus cells (SAC), staphylococcal enterotoxin (SEA) and lipopolysaccharide (LPS). IL-10 production was compared with that of IL-2, IL-4 and interferon-gamma (IFN-gamma). Similar to the other cytokines, in peripheral blood mononuclear cells (PBMC) from adult donors the highest IL-10 levels were produced in response to CD2 plus CD28 stimulation, within 72-96 hr of stimulation. Levels of IL-10 in response to CD2 plus CD28 stimulation (1.9 +/- 1 ng/ml) exceeded those in response to SEA (0.25 +/- 0.16 ng/ml), SAC (0.43 +/- 0.42 ng/ml), or LPS (0.19 +/- 0.14 ng/ml) stimulation. With adult purified T cells, high levels of IL-10 and IL-4 were measured following CD3 plus CD28 stimulation, and the amounts of both T-helper type-2 (Th2) cytokines decreased following the addition of phorbol myristate acetate (PMA), whereas the synthesis of the Th1 cytokines IL-2 and IFN-gamma was enhanced. When PBMC were stimulated with a CD3 mAb and different other cytokines were added, strong enhancement of IL-10 production was seen upon the addition of IL-2, IL-4, IL-7, IL-12 and IFN-gamma, whereas inhibition was found with transforming growth factor-beta 1 (TGF-beta 1). These data illustrate that in freshly isolated PBMC large amounts of IL-10 can be induced rapidly by appropriate mAb stimulation, and that even in freshly isolated cells IL-4 and IL-10 show signs of parallel regulation.

Antibodies, Monoclonal↗
PubMed1995

Adolescent suicide attempts: a general practice perspective.

General practitioners have a vital role in recognising, assessing and managing the suicidal adolescent. The GP's knowledge of the local community and services allows them to intervene effectively to prevent future suicidal behaviour. This may also involve the care and follow-up of survivors of youth suicide.

Adolescent↗
PubMed1994

Immunohistochemical evidence for flupirtine acting as an antagonist on the N-methyl-D-aspartate and homocysteic acid-induced release of GABA in the rabbit retina.

When rabbit retinas are exposed in vitro to specific excitatory amino acid receptor agonists certain GABAergic amacrine cells are activated to cause a release of GABA. The GABA that is not released can be detected by immunohistochemistry. Exposure of tissues to kainate or NMDA each caused a characteristic change in the GABA immunoreactivity. CNQX antagonised the kainate effect specifically while MK-801 counteracted the influence of NMDA. The effect produced by kainate was mimicked by domoic acid while the influence of homocysteic acid was identical with NMDA. Flupirtine alone did not influence the nature of the GABA immunoreactivity and so did not act as a kainate or NMDA agonist. However, flupirtine counteracted the influence produced by NMDA and homocysteic acid but had no effect on the kainate and domoic acid responses. Thus in this system flupirtine acts as an NMDA antagonist.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1994

Flupirtine protects against ischaemic retinal dysfunction in rats.

The present study investigated whether flupirtine attenuates the depression and enhances the recovery of the b-wave of the electroretinogram (ERG) in response to retinal ischaemia. The ERG was recorded from pentobarbital-anaesthetized rats before, during and after transient (24 min) occlusion of both common carotid arteries. Flupirtine administered 20 min before ischaemia reduced the depression of the b-wave during occlusion and accelerated recovery during reperfusion. When given at the onset of ischaemia flupirtine led to attenuation of the reduction of the b-wave during occlusion and to enhancement of the recovery during reperfusion. The present results suggest that flupirtine provides protection against ischaemic retinal dysfunction.

Aminopyridines↗
PubMed1994

Expression of human heat-shock protein 70 antigens and gamma/delta T-cell receptor antigens in human central nervous tissue.

The human gamma delta T cell receptor is normally expressed on lymphoid tissue. Because expression of different molecules of the T-cell system has been described on human brain cells, we examined the expression of T-cell receptor gamma delta antigens with a panel of various anti-gamma/delta TCR mAbs using immunohistochemistry on different regions of frozen human postmortem tissue of five different brains. We found expression of gamma/delta TCR antigens on brain tissue in different regions of the brain, probably on neurons. Using mAbs against the 70-kd human heat-shock-protein (hsp 70), immunohistochemistry showed staining of microglia. A polymerase chain reaction analysis using a highly sensitive primer sequence against the constant region delta sequence supports the notion that the gamma/delta TCR is expressed in human brain; however, the sequence cannot be assigned to a specific tissue with this method. Both heat shock proteins and the gamma/delta TCR seem to be involved in autoimmune processes, and their expression on colocalizing structures in human CNS may play a role in triggering neuropsychiatric autoimmune disorders.

Base Sequence↗
PubMed1994

Ion channel properties of the reconstituted chloroplast triose phosphate/phosphate translocator.

The chloroplast triose phosphate/phosphate translocator (cTPT) was isolated from envelope membranes or from transformed yeast cells and reconstituted into artificial membranes. Ionic currents mediated by the cTPT across these membranes were investigated by flux measurements and by the patch-clamp technique. The results of the flux measurements indicate that inorganic phosphate (Pi) at saturating concentrations on both sides of the membrane and chloride (Cl-) at all applied concentrations are transported by the cTPT at rates about 20-fold higher than those measured in intact chloroplasts. After reconstitution of the protein into giant liposomes, single channel currents mediated by the cTPT were resolved with the patch-clamp technique. The protein was shown to be a voltage-dependent anion channel with complex gating revealing sublevels with conductances of 12, 54, 96, and 138 pS for Cl- and 6 pS and 18 pS for Pi, respectively. Recordings from patches compromising multiple channels show a synchronously appearing non-linear current voltage (I/V) relationship in symmetrical buffers, and a different gating at positive and negative membrane potentials. This suggests that the cTPT is incorporated into the membrane in a unidirectional orientation. 3-Phosphoglycerate, a high affinity substrate of the transporter protein, induced a reversible flickering of open channel, and the channel open probability was decreased 60%. It is concluded that, besides its normal counter-exchange mode, the cTPT can also work as a voltage-dependent anion selective channel.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1994

Expression of GFAP in the striatum and its projection areas in response to striatal quinolinic acid lesion in rats.

Injection of quinolinic acid (QA) into the rat striatum is known to produce neuropathological and neurochemical features of Huntington's disease (HD). In the present study the astrocytic response two weeks following intrastriatal injection of either QA (240 nmol) or solvent (1 microliter) was examined using immunohistochemistry for GFAP. Striatal QA lesion resulted in a marked GFAP expression within the whole striatum which is due to neuronal degeneration. Furthermore, the reticular part of substantia nigra, globus pallidus and ventromedial thalamic nucleus revealed increases in GFAP expression without neuronal damage. As this remote astrocytic response is located only in striatal projection areas it seems to reflect transsynaptic changes in response to the lesion.

Animals↗
PubMed1994

N-methyl-D-aspartate (NMDA)-mediated muscle relaxant action of flupirtine in rats.

The present study examined in urethane-chloralose anaesthetized rats whether N-methyl-D-aspartate (NMDA) is involved in the depressant effect of flupirtine on the monosynaptic Hoffmann (H)-reflex recorded from plantar foot muscles and on polysynaptic flexor reflexes recorded from tibialis muscle. Intrathecal administration of both the specific NMDA antagonist (-)-2-amino-7-phosphonoheptanoate and of flupirtine depressed the polysynaptic flexor reflex without affecting the monosynaptic H-reflex. In contrast, the non-NMDA antagonist 6,7-dinitroquinoxaline-2,3-dione depressed the H-reflex without affecting the flexor reflex. The depressant effect of flupirtine on the flexor reflex was prevented by co-administration of NMDA, but not by co-administration of the non-NMDA agonist alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazolepropionic acid. These observations suggest that NMDA might be involved in the action of flupirtine.

Aminopyridines↗
PubMed1994

Preneoplastic foci of altered hepatocytes induced in rats by irradiation with alpha-particles of Thorotrast and neutrons.

Prestages of hepatocellular neoplasms induced in rats by continuous internal alpha-radiation of Thorotrast or by fractionated external radiation with neutrons were studied by cytomorphological, cytochemical and morphometric methods. Irradiation with both Thorotrast and neutrons resulted in a significant increase in the number and volume fraction of foci of altered hepatocytes (FAH), the occurrence of which at 14 months correlated well with the previously reported increased incidence of hepatocellular neoplasms appearing after long lag periods. The morphological and biochemical phenotypes of radiation-induced FAH were similar to those of preneoplastic lesions described earlier in hepatocarcinogenesis elicited by chemicals or viruses.

Alpha Particles↗
PubMed1994

Gamma-irradiation-induced micronuclei from mouse hepatoma cells accumulate high levels of the tumor suppressor protein p53.

The p53 tumor suppressor protein plays an important role in the G1 arrest of cells treated with DNA-damaging agents. Mouse hepatoma cells with wild-type or mutated p53 genotype were gamma-irradiated and the time course of p53 expression was determined by immunocytochemical staining. In p53 wild-type cells, gamma-irradiation led to a transient accumulation of the protein in the nuclei, whereas no such accumulation occurred in p53-mutated cells. Micronuclei were induced by gamma-irradiation in both wild-type and mutated cells in a dose- and time-dependent manner, but only micronuclei from p53 wild-type cells demonstrated a strongly positive staining reaction for p53 protein. This accumulation of p53 protein in micronuclei was not associated with a block in DNA synthesis as evidenced by bromodeoxyuridine labeling experiments.

Animals↗
PubMed1994

The depressant effect of GYKI 52466 on spinal reflex transmission in rats is mediated via non-NMDA and benzodiazepine receptors.

The present study examined the mechanisms by which GYKI 52466 (1-(amino-phenyl)-4-methyl-7,8-methyldioxy-5H-2,3-benzodiazepine) exerts its muscle relaxant effects. Intrathecal injection of the specific N-methyl-D-aspartate (NMDA) receptor antagonist (-)-2-amino-7-phosphonoheptanoate (AP7, 50-500 nmol) and systemic application of the benzodiazepine diazepam (0.2-5 mg/kg) dose dependently reduced the integrated area of the polysynaptic flexor reflex without affecting the monoxynaptic H-reflex. In contrast, intrathecal administration of the non-NMDA receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX, 0.1-10 nmol) depressed the H-reflex in a dose-dependent manner without affecting the flexor reflex. The depressant effect of GYKI 52466 on the flexor reflex was reduced by coadministration with flumazenil (5 mg/kg i.p.), an antagonist at the benzodiazepine receptor, whereas coadministration of the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-tertbutyl-4-isoxazole-propionic acid (ATPA, 0.1 pmol) with GYKI 52466 attenuated the reduction of the H-reflex induced by GYKI 52466. The chosen doses of flumazenil and ATPA did not affect spinal reflex transmission when given alone. These data suggest that GYKI 52466 depresses spinal reflex transmission via an action on non-NMDA receptors and on benzodiazepine receptors.

2-Amino-5-phosphonovalerate↗
PubMed1994

Cardiocirculatory and metabolic strain during rowing ergometry in coronary patients.

To investigate the suitability of rowing for cardiac rehabilitation, the cardiocirculatory and metabolic reactions during rowing (RE) and cycle (CE) ergometry were compared. Ten male normotensive subjects of an outpatient heart group (age 56 +/- 7 years, maximum performance on CE 2.0 +/- 0.4 W.kg-1) carried out a stepwise increasing test on an isokinetic rowing ergometer and a CE (increasing by 25 W every 3 min). In a 1-min break after each step, heart rate and blood pressure, blood concentrations of lactate, and the free catecholamines adrenaline and noradrenaline were measured. Four patients showed signs of myocardial ischemia occurring almost one step earlier on RE than on CE. In RE, the endurance and maximum performance were about 20 W lower than on CE. At similar workloads, heart rate, blood pressure, and concentrations of lactate and catecholamines measured significantly higher on RE than on CE. At workloads above the individual anaerobic threshold, the increase in adrenaline and noradrenaline was significantly higher on RE than on CE. The results can be explained by the lower work efficiency, the higher isometric demands with increased cardiac pressure load, and the higher mental stress in RE. Rowing is only suitable in cardiac rehabilitation when well-defined prerequisites have been considered.

Analysis of Variance↗