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Biomedical subjects

E Schweizer

Publications and source records attributed to E Schweizer.

At least 145 records · Page 8Linked to original sources
PubMed1987

A nuclear mutation affecting mitochondrial transcription in Saccharomyces cerevisiae.

Mitochondrial transcription was studied in a nuclear temperature-sensitive pet mutant of Saccharomyces cerevisiae. The mitochondrial RNA levels in vivo and the in vitro transcriptional activities of isolated mitochondria were analysed. In comparison to the wild-type an overall reduction of mitochondrial gene expression together with a changed expression pattern was observed for the mutant, indicating a defect in mitochondrial RNA synthesis. These findings were supported by studies with a purified DNA-protein complex from yeast mitochondria. This complex was able to synthesize ribosomal and messenger RNAs in an in vitro system. Proteins from wild-type and mutant transcription complexes were tested for their DNA-binding abilities; one of the proteins identified in the wild type had either lost this ability or was absent in the mutant.

Cell Nucleus↗
PubMed1987

Multiple hormonal responses to insulin-induced hypoglycemia in depressed patients and normal volunteers.

Studies have shown that some depressed patients may demonstrate multiple hormonal response abnormalities after a neuroendocrine challenge test; this finding has suggested the strategy of measuring several hormones after an insulin tolerance test. The authors gave insulin tolerance tests to 72 depressed patients and 51 age- and sex-matched healthy volunteer control subjects and measured glucose, cortisol, prolactin, and human growth hormone (GH) responses. Although there were no differences between patients and control subjects in the mean decrease in glucose levels after the insulin tolerance test, depressed men demonstrated significantly lower prolactin and GH levels after the test.

Adult↗
PubMed1987

Gepirone in anxiety: a pilot study.

Ten patients suffering from generalized anxiety disorder were treated, after a single-blind placebo washout week, with the nonbenzodiazepine anxiolytic gepirone in a 6-week open label trial. Mean Hamilton Anxiety scores improved from 24.8 to 7.1 (p less than 0.01). Other physician- and patient-rated scales showed comparable improvement on a mean maximal dose of 41 mg of gepirone. The medication appeared to be nonsedating and well tolerated. The anxiolytic effect of the medication was very marked in several cases, and gepirone appears to have promise as an anxiolytic agent.

Adult↗
PubMed1987

Treatment of MAOI hypertensive crisis with sublingual nifedipine.

Two cases are reported of hypertensive crisis, occurring during monoamine oxidase inhibitor treatment, that successfully responded to sublingual nifedipine. The authors discuss the use of sublingual calcium channel blockers as a possible alternative to phentolamine treatment of hypertensive crisis.

Acute Disease↗
PubMed1986

Isolation of a nuclear yeast gene involved in the mitochondrial import of cytoplasmically synthesized precursor proteins.

Several nuclear mutants of the yeast, Saccharomyces cerevisiae, have been characterized which synthesize only the higher-molecular weight precursor but not the mature subunit VI of the mitochondrial ubiquinol cytochrome c oxidoreductase. The mutants belong to different complementation groups and vary in the extent of their being simultaneously deficient in other components of the mitochondrial inner membrane. From a yeast genomic DNA library the plasmid pTS2326 was isolated which complements the defect in one of these mutants, ts2326. The cloned DNA fragment, 2.3 kilobases in length, was sequenced. It contains two open reading frames, ORF1 and ORF2, consisting of 723 and 417 base pairs, respectively. By selective deletion of either reading frame it was shown that only ORF1 containes the information necessary to complement the ts2326 mutation. The ORF1 coding sequence is not the structural gene of subunit VI. The postulated gene product of ORF1 has a molecular weight of 27.114 daltons. It exhibits several sequence characteristics typical of proteins which are internalized by the mitochondrial membrane systems. It is proposed that ORF1 is involved in the import and processing of cytoplasmically synthesized mitochondrial precursors.

Amino Acid Sequence↗
PubMed1986

The pentafunctional FAS1 gene of yeast: its nucleotide sequence and order of the catalytic domains.

FAS1, the structural gene of the pentafunctional fatty acid synthetase subunit beta in Saccharomyces cerevisiae has been sequenced. Its reading frame represents an intron-free nucleotide sequence of 5,535 base pairs, corresponding to a protein of 1,845 amino acids with a molecular weight of 205,130 daltons. In addition to the coding sequence, 1,468 base pairs of its 5'-flanking region were determined. S1 nuclease mapping revealed two transcriptional initiation sites; 5 and 36 base pairs upstream of the translational start codon. Within the flanking sequences two TATATAAA boxes, several A-rich and T-rich blocks and a TAG...TATGTT...TATGTT...TTT sequence were found and are discussed as transcriptional initiation and termination signals, respectively. The order of catalytic domains in the cluster gene was established by complementation of defined fas1 mutants with overlapping FAS1 subclones. Acetyl transferase (amino acids 1-468) is located proximal to the N-terminus of subunit beta, followed by the enoyl reductase (amino acids 480-858), the dehydratase (amino acids 1,134-1,615) and the malonyl/palmityl transferase (amino acids 1,616-1,845) domains. One major inter-domain region of about 276 amino acids with so far unknown function was found between the enoyl reductase and dehydratase domains. The substrate-binding serine residues of acetyl, malonyl and palmityl transferases were identified within the corresponding domains. Significant sequence homologies exist between the acyl transferase active sites of yeast and animal fatty acid synthetases. Similarly, a putative sequence of the enoyl reductase active site was identified.

Amino Acid Sequence↗
PubMed1986

Failure of buspirone to manage benzodiazepine withdrawal.

Fifteen patients with 146 cumulative years of tranquilizer use were withdrawn from their benzodiazepine (nine gradually and six abruptly), and buspirone, a new nonbenzodiazepine anxiolytic, was substituted. The addition of buspirone did not appear to lessen the intensity of the withdrawal state. This finding supports preclinical studies indicating that buspirone has no clinically significant benzodiazepine receptor activity.

Anti-Anxiety Agents↗
PubMed1986

Insulin-induced hypoglycemia and panic attacks.

To investigate whether hypoglycemia might trigger panic attacks, the authors administered intravenous insulin to 10 patients with panic disorder. All subjects developed hypoglycemia but no panic anxiety. They reported symptoms of adrenergic hyperactivity but differentiated them from spontaneous panic attacks.

Adult↗
PubMed1985

Therapeutic activities of nitrothiazole derivatives in experimental infections with Salmonella typhimurium and Bacteroides fragilis.

The antibacterial activities of niridazole (AmbilharR) and 12 other newly synthesized nitrothiazole derivatives were examined. Most of these compounds were active in vitro against Salmonella typhimurium (MICs 1-4 mg/l) and Bacteroides fragilis (MICs 0.015-0.03 mg/l). A therapeutic effect as determined by a reduction of bacterial counts per spleen of mice infected with Salm. typhimurium could only be achieved with those agents which displayed a similar side chain as niridazole, i.e. an imidazolidinone ring. Other nitrothiazole derivatives with a cleaved imidazolidinone ring as the side chain, although active in vitro, could not exert a reduction of bacterial counts in vivo. Similar results were obtained in mice infected with Bact. fragilis. Whereas niridazole and another nitrothiazole derivative with an imidazolidinone ring in the side chain were able to reduce the bacterial counts in a subcutaneous abscess, the derivative with a laminar side chain was inactive in vivo, although highly active in vitro.

Abscess↗
PubMed1984

Molecular cloning of the yeast fatty acid synthetase genes, FAS1 and FAS2: illustrating the structure of the FAS1 cluster gene by transcript mapping and transformation studies.

From a Saccharomyces cerevisiae gene bank contained in the novel yeast cosmid shuttle vector pMS201 the fatty acid synthetase (FAS) genes FAS1 and FAS2 were isolated. FAS clones were identified by in situ colony hybridization using two yeast DNA probes apparently capable of producing avian FAS cross-reacting material (J. Carbon, personal communication). Classification as FAS1 or FAS2 clones was achieved by their specific transformation of fas1 and fas2 yeast mutants. By transcription mapping FAS1 was assigned to about 5.3 kb within 14.8 kb of chromosomal DNA covered by two genomically adjacent BamHI fragments. The FAS2 gene was localized on a single BamHI fragment of 25 kb. One of the FAS clones ( FAS2 ) produces immunologically cross-reacting material in Escherichia coli. High frequency transformation of fas1 mutants was only observed with one subclone, pMS3021 , containing the intact FAS1 locus. Other DNA segments cloned in the same self-replicating vector but representing only part of FAS1 exhibited drastically lower transformation rates. As evident from this and from FAS1 /TRP1-cotransformation rates only the intact FAS1 gene in pMS3021 is capable of fas1 -mutant complementation. With partial FAS1 genes, even when coding for an intact equivalent of the mutated domain, their chromosomal integration is necessary for the expression of FAS. In integrative transformants the coexistence of integrated and autonomously replicating plasmid DNA was demonstrated. Both, the extrachromosomal and chromosomally integrated FAS DNA was mitotically unstable. Transformation studies using subcloned FAS1 DNA segments revealed the relative locations of the enoyl reductase and dehydratase domains within this pentafunctional cluster gene.

Cloning, Molecular↗
PubMed1984

Antibacterial activities of nitrothiazole derivatives.

A new group of chemical agents with pronounced antibacterial activities is presented. Different nitrothiazole derivatives, but not all, exhibit antibacterial activities similar to that of niridazole (AmbilharR), a nitrothiazolyl-imidazolidinone. Certain aerobic bacteria are moderately susceptible to these agents. The efficacy of these agents is almost comparable to that of ampicillin and tetracyline. It is much better than the efficacy of nitrofuran derivatives, the nitroimidazole derivatives being inactive. The mode of action of the nitrothiazole derivatives is bactericidal. Against anaerobic bacteria the nitrothiazole derivatives are unique, since the extremely low MIC's are not approached by any other of the nitro-compounds nor by any other of the common antibiotics tested, such as clindamycin, ampicillin and tetracycline. It is suggested that the nitrogroup of the nitrothiazole ring moiety represents the chemical structure responsible for their excellent antibacterial activities.

Anti-Bacterial Agents↗
PubMed1983

Response to dexamethasone in psychotic depression.

The utility of the dexamethasone suppression test (DST) in the diagnosis of psychotic depression was examined by comparing the responses of 11 psychotic and 18 nonpsychotic depressed inpatients. Nine of 11 psychotic patients (81.8%) and 10 of 18 nonpsychotic patients (55.6%) showed nonsuppression (nonsignificant). Using the 0800h cortisol level alone, we found that significantly more psychotic patients (7 of 11; 63.6%) than nonpsychotic patients (3 of 18; 16.7%) showed nonsuppression. Nonsuppression at 0800h postdexamethasone may be a useful biologic marker for patients with psychotic depression. Implications of these data for the nosologic status of psychotic depression are discussed.

Adult↗
PubMed1982

Glycoprotein topology on intact human red blood cells reevaluated by cross-linking following amino group supplementation.

Protein-protein interactions were studied at 0-4 degrees C with amino group specific cross-linkers on intact human erythrocytes after introducing free alkylamino groups into glycoproteins to overcome the scarcity of accessible amino groups. Amino group supplementation is based on the formation of aldehydes by either enzymatic or chemical oxidation. Subsequently, an imine is formed between aldehyde groups and 2-(4-aminophenyl) [1-14C]ethylamine (arylalkyldiamine) in the presence of sodium cyanoborohydride (NaCNBH3). The arylamino group of arylalkyldiamine forms imines at least 280 times more rapidly than the alkylamino group. This property leaves the majority of alkylamino groups free for subsequent cross-linking with bifunctional reagents. Amino group supplementation enhances the cross-linking probability of glycophorins in glycophorin-containing vesicles. When applied to intact human erythrocytes of any age, in conjunction with the cross-linker disuccinimidyl 3,3'-dithiobis(propionate), the glycoproteins, band 3 and glycophorins, did not undergo substantial cross-linking (less than 2% of the total label cross-linked). However, substantial cross-linking (20% of the total label cross-linked) of either glycoprotein was detected on spectrin-free vesicles [Lutz, H. U., Liu, S. C., & Palek, J. (1977) J. Cell Biol. 73, 548-560] that are devoid of cytoskeletal restraints. The inability to cross-link these proteins on intact cells is not due to a lack of accessible amino groups on the surface of these glycoproteins, because amino group supplementation enhanced their ability to form cross-links on intact cells and on spectrin-free vesicles by the same factor (2-3-fold). This and various controls suggest a monomeric arrangement of the exoplasmic portions of band 3 on intact erythrocytes.

Anion Exchange Protein 1, Erythrocyte↗