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Biomedical subjects

M Schweizer

Publications and source records attributed to M Schweizer.

At least 91 records · Page 5Linked to original sources
PubMed1996

MxA protein in infants and children with respiratory tract infection.

MxA protein--a stable product of cells stimulated by type I interferons--was examined prospectively for its ability to discriminate between viral and bacterial respiratory tract infections (RTIs) in 182 infants and children. The nasopharyngeal secretions (NPSs) of all of them were tested for MxA using enzyme-linked immunosorbent assay (ELISA), and the whole blood of 92. Seventy-three children undergoing elective surgery served as controls. These apparently healthy children had higher levels of serum MxA than adult controls. Using antigen detection and serology, a viral aetiology was diagnosed in 81/182 cases. The sensitivity and specificity of MxA ELISA were assessed at 92 and 76% for the blood test and at 40 and 91% for the NPS, respectively. The positive predictive value for a viral RTI was superior to a leucocyte count or C-reactive protein when determined only once.

Adult↗
PubMed1996

[Calcium antagonists in treatment of ventricular tachycardia].

Of the traditional antiarrhythmic agents administered in the treatment of ventricular tachycardias, those belonging to Class III are most commonly used. However, some ventricular tachycardias displaying special clinical, electrocardiographic and/or electrophysiologic characteristics have been successfully treated with calcium antagonists. Otherwise, Class IV antiarrhythmic agents are primarily used in the treatment of supraventricular tachyarrhythmias. It is reasonable to suspect that calcium-dependent phenomena underlie ventricular tachyarrhythmias in a number of patients. Verapamil-sensitive sustained left ventricular tachycardias represent a typical example. Sufficient response to calcium antagonists has also been demonstrated for exercise-induced ventricular tachycardias and repetitive monomorphic ventricular tachycardias. Characteristically, these arrhythmias occur in young patients with no structural heart disease. The long-term prognosis of these patients is in fact very good, but because of intrusive symptoms, pharmacological or nonpharmacological (radiofrequency ablation) treatment is often indicated. Through correct diagnosis and implementation of a short- and long-term therapy with calcium antagonists, and excellent alternative to the potentially harmful therapy with Class I and Class III antiarrhythmic agents can be offered.

Anti-Arrhythmia Agents↗
PubMed1995

Oxidants in mitochondria: from physiology to diseases.

Reactive oxygen species (ROS: superoxide radical, O2.-; hydrogen peroxide, H2O2; hydroxyl radical, OH.), which arise from the univalent reduction of dioxygen are formed in mitochondria. We summarize here results which indicate that ROS, and also the radical nitrogen monoxide ('nitric oxide', NO), act as physiological modulators of some mitochondrial functions, but may also damage mitochondria. Hydrogen peroxide, which originates in mitochondria predominantly from the dismutation of superoxide, causes oxidation of mitochondrial pyridine nucleotides and thereby stimulates a specific Ca2+ release from intact mitochondria. This release is prevented by cyclosporin A (CSA). Hydrogen peroxide thus contributes to the maintenance of cellular Ca2+ homeostasis. A stimulation of mitochondrial ROS production followed by an enhanced Ca2+ release and re uptake (Ca2+ 'cycling') by mitochondria causes apoptosis and necrosis, and contributes to hypoxia/reperfusion injury. These kinds of cell injury can be attenuated at the mitochondrial level by CSA. When ROS are produced in excessive amounts in mitochondria nucleic acids, proteins, and lipids are extensively modified by oxidation. Physiological (sub-micromolar) concentrations of NO potently and reversibly deenergize mitochondria at oxygen tensions that prevail in cells by transiently binding to cytochrome oxidase. This is paralleled by mitochondrial Ca2+ release and uptake. Higher NO concentrations or prolonged exposure of cells to NO causes their death. It is concluded that ROS and NO are important physiological reactants in mitochondria and become toxic only when present in excessive amounts.

Animals↗
PubMed1995

Phylogenetic analysis of primate foamy viruses by comparison of pol sequences.

The relationship between primate foamy viruses was determined by comparing a 425-bp DNA segment obtained by PCR using primers homologous to highly conserved portions of the pol gene. The phylogenetic tree of 14 foamy viruses investigated reflects the relationship between their host species: A cluster of Asian Old World monkey foamy viruses including simian foamy virus (SFV) prototypes 1 and 2 (isolated from Macaca cyclopsis) is separated from African Old World foamy viruses including prototype SFV-3 and SFV-3 strain LK-3 (isolated from African green monkeys, Cercopithecus aethiops). These two clusters of Old World monkey foamy viruses are more distantly related to a cluster of ape and human foamy viruses including prototypes SFV-6, SFV-7, SFV cpz (all isolated from chimpanzees), and human foamy virus (HFV). The New World prototype SFV-8 (isolated from a spider monkey, Ateles sp.) is distinct from the Old World cluster. Our own foamy virus isolates from a rhesus monkey (Macaca mulatta) and an African green monkey were grouped to the Asian or the African Old World monkey foamy virus cluster, respectively. The foamy virus sequences obtained from lymphocytes of two humans, one exposed to African green monkeys and the other to cultured HFV, were compared. The first sequence was closely related to the African Old World monkey foamy virus cluster, whereas the second was identical to HFV, except for a single mismatch. We conclude that limited sequencing of amplified DNA is a powerful tool for classification as well as molecular epidemiology of foamy viruses.

Animals↗
PubMed1995

A 29.425 kb segment on the left arm of yeast chromosome XV contains more than twice as many unknown as known open reading frames.

The nucleotide sequence of a 29.425 kb fragment localized on the left arm of chromosome XV from Saccharomyces cerevisiae has been determined. The sequence contains 13 open reading frames (ORFs) of which four encode the known genes ADH1, COQ3, MSH2 and RCF4. Predictions are made concerning the functions of the unknown ORFs. Some of the ORFs contain sequences similar to expressed sequence tags (EST) found in the database made available by TIGR. In particular, the highly expressed ADH1 gene is represented in this database by no less than 20 EST sequences. Two ARS sequences and a putative functional GCN4 motif have also been detected. One ORF (O0953) containing nine putative transmembrane segments is similar to a hypothetical membrane protein of Arabidopsis thaliana. Characteristic features of the other ORFs include ATP/GTP binding sites, a fungal Zn(2)-Cys(6) binuclear centre, an endoplasmic reticulum targeting sequence, a beta-transducin repeat signature and in two instances, good similarity to the prokaryotic lipoprotein signal peptide motif.

Amino Acid Sequence↗
PubMed1995

Determination of the molecular weight of DNA-binding proteins using UV-crosslinking and SDS-PAGE.

We describe the use of UV-crosslinking in combination with SDS-PAGE to determine the approximate molecular weight of DNA-binding proteins. A 5-bromo-2'-deoxyuridine (5-BrdU)-substituted, radioactively labeled double-stranded oligonucleotide representing the protein binding site is incubated with a crude nuclear extract containing the protein of interest. Following irradiation with a UV light source, the DNA/protein complex is subjected to SDS-PAGE and its molecular weight determined by comparison with appropriate protein standards.

Animals↗
PubMed1995

TIPS: a new therapy for esophageal variceal bleeding caused by EHBA.

Clinical and procedural experience using transjugylar intrahepatic portosystemic shunt (TIPS) on 7 children with recurrent hemorrhage of esophageal varices is reported. Recurrent hemorrhage from esophageal varices following repeated paravasal sclerosing of the varices as well as severe-grade hypersplenism are proposed as the indication for its use. The technical details of TIPS, observed and possible early and late complications, the demand for a decrease in the portosystemic pressure gradient to less than 15 mmHg and the influence of TIPS on improvement of the varices, hypersplenism and the frequently observed malabsorption are described.

Adolescent↗
PubMed1995

Markers of foamy virus infections in monkeys, apes, and accidentally infected humans: appropriate testing fails to confirm suspected foamy virus prevalence in humans.

Foamy viruses (FVs) persist in healthy individuals of various mammalian species, including nonhuman primates. Laboratory markers of FV infection are (1) virus in throat epithelium or peripheral blood lymphocytes (PBLs), (2) proviral DNA sequences in PBLs and various solid organs, and (3) antibodies reactive to viral antigens on Western blots, in radioimmunoprecipitation tests, and in immunofluorescence assays. Using PCR and serological tests, we readily detected FV markers in naturally infected African green monkeys, rhesus monkeys, and chimpanzees, as well as in accidentally infected humans. Transmission of simian foamy viruses to humans (by bite or inadvertent laboratory infection) leads to viral markers, without affecting the recipient. Reports on FV-associated clinical disorders (e.g., thyroid or neurological) have remained controversial. In this study we failed to detect, by PCR, viral sequences in the samples from 223 patients, including 16 HIV-infected Africans, 46 Graves' disease patients, and 28 patients with the de Quervain's thyroiditis. Evaluation of 2688 sera from suspected high-risk areas (e.g., Central and East Africa, or high-risk groups such as HIV-infected individuals and patients with AIDS, thyroid, and neurological disorders) did not reveal FV-specific antibodies in a single case. Previously reported FV seroprevalence in various populations has never been verified by appropriate confirmatory tests. The strain of "human foamy virus" has remained a unique isolate. In conclusion, FVs are unlikely--at present--to circulate in human populations.

Africa↗
PubMed1994

Nitric oxide kills hepatocytes by mobilizing mitochondrial calcium.

We have recently shown (Schweizer, M., and Richter, C. (1994) Biochem. Biophys. Res. Commun. 204, 169-175) that nitric oxide (nitrogen monoxide, NO) at low concentrations potently and reversibly deenergizes isolated liver and brain mitochondria at oxygen concentrations that prevail in cells and tissues. We now report that also in freshly prepared hepatocytes NO deenergizes mitochondria. Deenergization is reversible at low, but longer-lasting at higher NO concentrations. The drop and the recovery of the mitochondrial membrane potential are accompanied by a rise and fall of cytosolic Ca2+ levels. At higher concentrations NO kills hepatocytes. Killing is reduced when the cytosolic Ca2+ is chelated, or when the cyclic uptake and release of Ca2+ ("Ca2+ cycling") by mitochondria is prevented. We conclude that NO can kill cells by deenergizing mitochondria and thereby flooding the cytosol with Ca2+.

Animals↗
PubMed1994

Gliotoxin stimulates Ca2+ release from intact rat liver mitochondria.

Gliotoxin is an epidithiodioxopiperazine compound which can both react with sulfhydryl groups and form hydrogen peroxide. Rat liver mitochondria contain a prooxidant-regulated specific Ca2+ release pathway. Here we report that gliotoxin at low concentrations stimulates Ca2+ release via this pathway in isolated mitochondria. Ca2+ release is not promoted by gliotoxin exposed to disulfide-reducing reagents prior to addition to mitochondria or when its disulfide moiety is dimethylated. Gliotoxin is equally effective in glutathione-depleted and glutathione-adequate mitochondria. This and the unchanged mitochondrial oxygen consumption in the presence of gliotoxin suggest that the compound stimulates Ca2+ release by reacting with critical mitochondrial thiol compounds and not by increasing hydrogen peroxide formation in mitochondria. The gliotoxin-induced Ca2+ release is paralleled by hydrolysis of mitochondrial pyridine nucleotides, and both pyridine nucleotide hydrolysis and Ca2+ release are inhibited by cyclosporin A. These findings provide further insight into the regulation of Ca2+ release from intact mitochondria.

Animals↗
PubMed1994

Nitric oxide potently and reversibly deenergizes mitochondria at low oxygen tension.

Nitric oxide (nitrogen monoxide, NO) at low concentrations can potently deenergize isolated liver and brain mitochondria at oxygen concentrations that prevail in cells and tissues. Deenergization is observed when mitochondria utilize respiratory substrates such as pyruvate plus malate, succinate, or ascorbate plus tetramethylphenylenediamine, but not when mitochondria are energized with ATP. The extent and duration of deenergization is determined by the concentration of NO and oxygen, and the kind of respiratory substrate. The NO-induced changes of the mitochondrial energy state are transient and are paralleled by release and reuptake of mitochondrial calcium. These findings reveal a direct action of NO on the mitochondrial respiratory chain and suggest that NO exerts some of its physiological and pathological effects by deenergizing mitochondria.

Animals↗
PubMed1994

Insulin-responsive regions of the rat fatty acid synthase gene promoter.

Here we show that insulin may play a role in the diet-induced regulation of the rat fatty acid synthase (FAS; EC 2.3.1.85). Transient transfection of human and rat hepatoma cell lines with successively deleted FAS/CAT promoter fusion plasmids was used to determine the effect of insulin on FAS promoter activity. Our results indicate the existence of cis-acting insulin-responsive elements in the FAS promoter; the position of one of these is coincident with the position of a previously determined diet-induced DNAse I hypersensitive site (HSi-1) at approximately -500 bp relative to the transcription start site of FAS mRNA.

Animals↗
PubMed1994

Phenylarsine oxide stimulates pyridine nucleotide-linked Ca2+ release from rat liver mitochondria.

Rat liver mitochondria contain a specific Ca2+ release pathway which operates when oxidized mitochondrial pyridine nucleotides are hydrolysed to ADPribose and nicotinamide. Here we report that the hydrophobic bifunctional thiol reagent phenylarsine oxide (PhAsO) at low concentrations stimulates this pathway by promoting a Ca(2+)-dependent hydrolysis of oxidized mitochondrial pyridine nucleotides. Ca2+ release is inhibited by cyclosporine A or m-iodobenzylguanidine, compounds known to prevent intramitochondrial pyridine nucleotide hydrolysis or protein mono(ADPribosyl)ation, respectively. At higher concentrations, PhAsO causes non-specific leakiness of mitochondria.

3-Iodobenzylguanidine↗
PubMed1994

The tripartite DNA element responsible for diet-induced rat fatty acid synthase (FAS) regulation.

We investigated which region of the 5'-flanking sequence of the rat fatty acid synthase (FAS)-encoding gene could be responsible for its nutritionally regulated expression. Diet-induced differences in chromatin structure were determined by DNase I treatment of intact nuclei from hepatic tissue. A low-fat diet results in a different pattern of DNase I-hypersensitive sites (HS) in the chromatin of the FAS promoter (pFAS) from that seen when the nuclear extract was prepared from the livers of normally fed rats. The protein-binding properties of the region defined by DNase I hypersensitivity were tested by gel retardation. A putative cis-acting element with a tripartite structure, 5'-GCCT, 6-bp spacer and a 3'-palindrome, could be localized between bp -518 to -495 in pFAS. Competition experiments with oligodeoxyribonucleotides (oligos) representing subfragments of this cis-element showed that the requirement for structure is stricter than that for sequence. This element could be one of the termini of the insulin-induced signal cascade.

Animals↗
PubMed1994

Phosphoribosylpyrophosphate synthetase (PRS): a new gene family in Saccharomyces cerevisiae.

Saccharomyces cerevisiae contains at least four PRS genes, all of which have been cloned and sequenced. Each of the four derived amino acid sequences have more than 60% similarity to the corresponding polypeptides of man, rat, Escherichia coli and Salmonella typhimurium. The PRS1 gene maps on chromosome XI, PRS2 on chromosome V, PRS3 on chromosome VIII and PRS4 on chromosome II. One member of this gene family, PRS1, contains a region of non-homology (NHR) shown by cDNA cloning and sequencing not to be an intron. The results presented here suggest that the presence of this NHR is not detrimental to the function of the gene. To date the possibility of protein splicing can be neither proven nor disputed.

Amino Acid Sequence↗
PubMed1994

Sequence of a 10.27 kb segment on the left arm of chromosome XV from Saccharomyces cerevisiae includes part of the IRA2 gene and a putative new gene.

A 10,270 bp fragment from the left arm of chromosome XV of Saccharomyces cerevisiae was sequenced and analysed. The sequence reveals the presence of two open reading frames (ORFs), one of them is the larger part of the previously sequenced gene IRA2 (YOL0951). The other ORF, YOL0950, has a length of 1245 nucleotides and exhibits no significant homology with any known gene, although there is some similarity of its upstream region to the corresponding region of the Schizosaccharomyces pombe cdr1/nim1 gene which is involved in the control of mitotic cell size.

Amino Acid Sequence↗