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Biomedical subjects

G Müller

Publications and source records attributed to G Müller.

At least 415 records · Page 23Linked to original sources
PubMed1989

Learning and retention of active avoidance are differently impaired after dorsal and ventral lesions of the nucleus reticularis pontis caudalis of rats.

Four groups of 8 adult male hooded rats of the Long-Evans strain were investigated before and after bilateral symmetric lesions of the nucleus reticularis pontis caudalis (RPC) in a Y-maze and in a jump test box. After dorsal (d) RPC lesions the retention of preoperatively learnt simple tasks in the Y-maze or in the jump test was not impaired whereas brightness discrimination in the Y-maze was neither retained nor relearned. Postoperative acquisition without preoperative experience was impossible for dRPC rats in any of the tests. After ventral (v) RPC lesions there was no retention of active avoidance response in the Y-maze but rather normal retention of the jump test performance. The retention of brightness discrimination, however, was not impaired in the Y-maze after vRPC lesions. The relearning of the impaired active avoidance in the Y-maze was impossible for vRPC rats; though these rats showed intrasessional improvement, there was no retention between sessions. After retention of the simple jump test task the vRPC rats were not able to learn a go/no-go task in the jump test box. Acute extinction to the non-reinforced 2.5 KHz tone was prolonged. Intertrial responses in the jump test were reduced to zero after dRPC lesions, but significantly enhanced after vRPC lesions. The results indicate that CAR response initiation was reduced after dRPC lesions, but in vRPC rats the suppression of incorrect responses was reduced in the jump test. The lesions differently impair the control of learnt motor programs.

Animals↗
PubMed1989

[The mutagenicity of organic microcontamination in the environment. III. The mutagenicity of selected herbicides and insecticides in the SOS chromotest].

To determine the mutagenicity of selected herbicides and insecticides we examined 26 pure pesticide substances (polychlorinated alicyclic hydrocarbons, phenoxy fatty acids, triazines) with the help of SOS-Chromotest. We used Escherichia coli strain PQ37 in these tests without and with metabolic activation with Aroclor 1254 induced rat liver microsome fraction. None of the substances showed a provable induction of the E. coli-SOS-system, because a great number of the pesticides showed toxic effects against bacteria in high concentrations.

Animals↗
PubMed1989

[The mutagenicity of organic microcontaminants in the environment. IV. The mutagenicity of volatile organic halogens in the SOS-chromotest].

To determine the sensitivity and responsibility of microbial shortterm-tests for detection of the mutagenic potency of volatile halogenated hydrocarbons (OHC) 18 pure substances from the groups of halomethanes, -ethanes and ethylenes were examined with the SOS-Chromotest. The strain Escherichia coli PQ37 was used in the standard procedure (macro procedure) with and without metabolic activation by Aroclor 1254 induced rat-liver microsomes. Although the selected OHC were tested to high doses, none of the tested compounds showed mutagenic effects in Escherichia coli PQ37. Also those OHC's, which showed positive results in the Ames test or being suspected of carcinogenicity, showed no positive results in the SOS-Chromotest. Therefore, the standard procedure of SOS-Chromotest is not suitable to detect the mutagenicity of volatile organic and halogenated compounds. Supplementary investigations with modified methods are necessary to check the results, because there is a good correlation between Ames test and SOS-Chromotest by testing other groups of compounds.

Animals↗
PubMed1989

[Determination of mercapturic acid in urine samples for the monitoring of occupational exposure to xenobiotics].

The determination of mercapturic acids in urine samples of employees exposed to carcinogenic substances requires highly sensitive and specific methods such as GC/MS or HPLC/Fluorimetry. We applied GC/MS to the analysis of thiodiglycolic acid, which is an indicator metabolite of vinyl chloride exposure and of S-phenylmercapturic acid which can be used to control benzene exposure. S-cyanoethylmercapturic acid appears as a degradation product during acrylonitrile metabolism. This metabolite can be determined by HPLC combined with a sulfur specific fluorimetric detector. This procedure which is of general use offers the possibility to improve the biological monitoring in case of exposures to carcinogenic substances.

Acetylcysteine↗
PubMed1988

Isolation and sequence analysis of the fatty acid synthetase FAS2 gene from Penicillium patulum.

The fatty acid synthetase complex of Penicillium patulum was isolated and shown to be structurally similar to other known fungal fatty acid synthetases. It is composed of two subunit, alpha and beta, each with a molecular mass of about 200 kDa. P. patulum genomic and cDNA libraries were constructed in lambda gt11 and EMBL3 vectors. From these libraries, the P. patulum FAS2 gene together with its flanking DNA was isolated. The cloned genomic DNA was sequenced over a length of 6357 base pairs. The coding sequence of fatty acid synthetase subunit alpha, being 5571 nucleotides long, was identified within this DNA segment. The FAS2 gene is a mosaic of three exons (514, 4949 and 108 base pairs) and two introns, each of 54 base pairs in length. Both introns were absent in the corresponding cDNA sequences. Like other fungal introns both contain an internal CTAAC sequence, located 10 base pairs upstream of their 3'-exon/intron boundaries. In addition, they have, at their ends, the GTCAAGT and TAG consensus sequences characteristic of all eucaryotic introns. Furthermore, two pairs of direct repeats, of as yet unknown significance, were found in the two P. patulum introns. The P. patulum FAS2 gene encodes a protein of 1857 amino acids and 204.5 kDa molecular mass. It is 90 nucleotides shorter than the corresponding S. cerevisiae gene. In both organisms, the FAS2 genes and their products exhibit a high degree of overall sequence similarity at both the DNA (63%) and protein (68%) levels. Therefore, the fatty acid synthetase alpha subunits of P. patulum and S. cerevisiae obviously contain the same catalytic domains in an identical sequential order.

Amino Acid Sequence↗
PubMed1988

[Hemolytic anemia caused by echinocytosis in liver cirrhosis].

Severe haemolytic anaemia developed in a 34-year-old patient with histologically proven alcoholic liver cirrhosis. While in the blood smear there were only a few acanthocytes, under light-microscopy of EDTA-blood 70% of erythrocytes in the counting chamber were acanthocytes or echinocytes, a finding confirmed under the electromicroscope. It is likely that the echinocytosis and acanthocytosis were the cause of the haemolytic anaemia. Biochemical investigation of the lipid composition of the erythrocyte membrane and of plasma and of the apolipoproteins in plasma revealed a series of changes whose role in haemolysis is discussed.

Acanthocytes↗
PubMed1988

Characterization of two allelic forms of Neurospora crassa laccase. Amino- and carboxyl-terminal processing of a precursor.

The complete structures of the laccase genes isolated from two different Neurospora crassa wild-type strains are described. The genes were cloned by screening partial genomic DNA libraries with a nick-translated laccase-specified 1.36-kilobase SalI fragment (Germann, U. A., and Lerch, K. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 8854-8858) as a hybridization probe. Nucleotide sequence analysis revealed the presence of two different allelic forms. They conform to the same structural organization, but show an overall divergence of 5.3% which is mainly the result of point mutations in the nontranslated regions. The coding parts are interrupted by a short intron. The encoded proteins differ in 12 out of 619 amino acid residues. A comparison of the primary structure deduced from the nucleotide sequence of the gene with a protein chemical analysis of the two terminal cyanogen bromide fragments of extracellular N. crassa laccase revealed that the enzyme is synthesized as a precursor. The precursor protein exceeds the mature protein by 49 amino acids at its amino terminus and by 13 amino acids at its carboxyl terminus, thus indicating a complex maturation pathway. The possible involvement of amino-terminal processing in secretion and of carboxyl-terminal processing in activation of the enzyme is discussed.

Alleles↗
PubMed1988

Import of honeybee prepromelittin into the endoplasmic reticulum: energy requirements for membrane insertion.

The import of small precursor proteins, derived from the honeybee secretory protein prepromelittin, into dog pancreas microsomes is independent of signal recognition particle (SRP) and docking protein, but requires that charged amino acids at the amino terminus of the mature part are counterbalanced by amino acids with the opposite charge at the carboxy terminus. The import pathway of such precursor proteins was resolved into two sequential steps: (i) binding of precursors to microsomes, and (ii) insertion of precursors into the membrane. Formation of an intramolecular disulfide bridge within the mature part of these precursor proteins allowed association of the oxidized precursors with the microsomal membrane but reversibly inhibited their membrane insertion. Furthermore, membrane insertion was inhibited by ATP depletion. Different prepromelittin derivatives were found to depend on ATP to varying degrees. We conclude that insertion of prepromelittin-derived precursor proteins into microsomal membranes involves a competent conformation of the precursor proteins and that, in general, this is accomplished with the help of both a cytoplasmic component and ATP.

Adenosine Triphosphate↗
PubMed1988

Multiple transcripts of the mouse tyrosinase gene are generated by alternative splicing.

We report the cloning and isolation of the mouse tyrosinase cDNA by screening mouse B16 melanoma cDNA libraries. Independent cDNA clones have been characterized by restriction enzyme analysis, hybridizations with individual subprobes and by partial sequencing analysis. Based on these criteria we have identified multiple transcripts, which in comparison to the major transcript, display deletions of internal sequences and have different 3' termini. The most abundant transcript encodes a functional tyrosinase. The structural gene which encodes five exons separated by large introns and spans a chromosomal region of approximately 70 kb has been isolated. Comparison of the cDNAs with the cloned genomic DNAs and sequencing of the exon/intron boundaries reveal that the multiple transcripts are generated by alternative splicing and putatively by alternate polyadenylation site usage. The alternative splicing mechanisms involve exon skipping as well as internal donor splice site usage. Primer extension analysis shows that the transcripts are produced from two different promoters. Southern blot analysis of DNAs derived from mice carrying the lethal albino deletion mutations demonstrates that the structural gene maps near or at the albino locus. The viable albino mouse BALB/c carries an apparently intact structural gene indicating that the albino phenotype is a consequence of a failure to express the tyrosinase gene or the inability to produce a tyrosinase enzyme.

Animals↗
PubMed1988

Functional analysis of alternatively spliced tyrosinase gene transcripts.

Three different cDNA clones (pmcTyr1, pmcTyr2 and pmcTyr3) representing mRNAs originating by alternative splicing of the primary transcript of mouse tyrosinase gene, were identified and characterized by sequence analysis and by a functional assay. These cDNAs were subcloned into the newly constructed expression vector pHD. After electroporation of these hybrid clones into tyrosinase negative cells, protein extracts were prepared and tested for tyrosinase enzyme activity. Only the cDNA insert of pmcTyr1 was able to confer tyrosinase enzyme activity. This cDNA encodes a protein 533 amino acid residues in length containing a putative leader peptide of 18 amino acids and six putative glycosylation sites. Comparisons of the deduced amino acid sequence of the cDNA clone pmcTyr1 with the protein sequence of tyrosinases from man, Streptomyces, Neurospora and with haemocyanin subunits from a spider showed two regions of sequence conservation. One of these regions is known to be involved in copper binding. Since this gene with the coding capacity for tyrosinase is absent in all studied c-locus lethal deletion mutant mice, we have evidence that albinism in mice is caused by mutations of the tyrosinase gene.

Amino Acid Sequence↗
PubMed1988

Biomonitoring of benzene exposure by trace analyses of phenylguanine.

From preliminary experiments it was known that radiolabelled benzene and some of its metabolites during its metabolic activation process produce different in vitro DNA-phenyladducts in mitoplasts. As we reported previously at least one of these adducts, N-7-phenylguanine, is excreted in the urine of rats in measurable amounts, probably through an excision-repair mechanism after an inhalation experiment. Now we found, after i.p. application of benzene in the urine of rats, a compound separated by cation-exchange chromatography that behaves like a synthesized N-7-phenylguanine reference substance with respect to its retention index and the UV-absorption. This finding could be confirmed by HPLC-measurements with reversed-phase carrier materials. Silylation and gas chromatographic/mass spectrometric (GC/MS) separation of the fraction, which contains the phenylguanine, revealed that these fractions contain further phenyl adducts. Furthermore we studied the time-dependent excretion of the DNA-base adduct. Surprisingly the excretion dropped to zero on the fourth day and showed a new increase thereafter.

Animals↗
PubMed1988

Investigations on metabolism and carcinogenicity of 1,1,2-trichloroethane.

Two groups of male and female Sprague-Dawley rats (50 animals/group per sex) were treated with either 15.37 or 46.77 mumole of 1,1,2-TCE in DMSO/rat for 2 years. The animals were treated once a week by s.c. injection of test compound in the skin of neck. Two groups of controls received either DMSO or no treatment at all. The incidence of benign mesenchymal and epithelial tumors was not significant when compared with either DMSO-treated or untreated controls. The animals treated with 46.77 mumole 1,1,2-TCE significantly developed sarcomas when compared with the untreated controls. In a further experiment, either 40 mumole or 160 mumole 1,1,2-TCE was injected into male Wistar rats and the metabolites, TdGA and HEMA, were determined in 24-h urine samples. Comparative studies were carried out giving equimolar amounts of chloroethanol and 2-chloroacetaldehyde diethyl acetal. Analysis of the metabolites showed that no detectable HEMA was excreted in urine after treatment of rats with 1,1,2-TCE or chloroethanol. TdGA was excreted in urine much more among chloroacetaldehyde-treated animals than among 1,1,2-TCE- or chloroethanol-treated rats.

Acetaldehyde↗
PubMed1988

A double-blind comparative study of doxazosin and nitrendipine in patients with mild-to-moderate essential hypertension.

The antihypertensive efficacy and safety of doxazosin, a selective alpha 1-inhibitor, were compared with nitrendipine. Seventy-two hypertensive patients were entered into the 18-week, double-blind parallel group study, which involved three phases: a 4-week baseline period, a 10-week period in which patients received 1 to 8 mg of doxazosin or 10 and 20 mg of nitrendipine once daily, and a 4-week maintenance period. For all patients, the mean final daily doses were 2.5 mg for doxazosin and 13.9 mg for nitrendipine. In efficacy evaluable patients the percentages of therapy successes (standing diastolic blood pressure less than or equal to 90 mm Hg with greater than or equal to 5 mm Hg reduction or greater than or equal to 10 mm Hg decrease) were comparable for doxazosin (94%) and nitrendipine (91%), as was the proportion in whom blood pressure was "normalized" (standing diastolic blood pressure less than or equal to 90 mm Hg), 91% and 85, respectively. Blood pressures (diastolic and systolic in supine and standing positions) were significantly reduced (p less than 0.05) at all visits in both treatment groups. Ten patients (28%) in each treatment group experienced at least one adverse event. No clinically significant laboratory changes were apparent in either the doxazosin or nitrendipine groups, and no trends were observed with regard to organ systems or correlations with dose or duration of treatments. The investigators' global assessment of efficacy was rated excellent or good for all doxazosin-treated patients and excellent or good for 32 and fair for four in the nitrendipine group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Antagonists↗