Search PubMed⌕ Search

Biomedical subjects

R Braun

Publications and source records attributed to R Braun.

At least 145 records · Page 8Linked to original sources
PubMed1985

Human cytomegalovirus infection: recent developments in diagnosis and epidemiology.

Cytomegalic inclusion disease (CID) is caused by a horizontally or vertically transmitted human herpes virus infection and may persist for life without obvious clinical symptoms. A serious course of horizontal primary and recurrent infections, however, is often observed in immunocompromised persons such as recipients of organ transplants and patients receiving fresh blood transfusions. Vertical infection may cause fetopathies. The human cytomegalovirus (HCMV) is thought to inherit an oncogenic potential as lately discussed for AIDS and M. Kaposi. Laboratory diagnosis of HCMV infection is performed by light microscopy (inclusion bodies), electron microscopy, virus isolation in cell culture, demonstration of viral DNA and antigen in clinical specimens, by histochemical methods (e.g. immunoperoxidase technique) and by DNA and peptide analysis for identification of different isolates and viral finger prints. Evaluation of cell-mediated immunity in HCMV infection is performed quantitatively (assessment of Thelper/Tsuppressor ratios) or qualitatively (specific lymphocyte stimulation by the antigen). In most cases laboratory diagnosis is achieved by serological methods, i.e. demonstration and quantitation of HCMV-specific antibodies. In this context, a number of liquid- and solid-phase immunoassays have been developed, of which immunofluorescence and ELISA are most commonly used, besides complement fixation and passive haemagglutination. These procedures on the one hand allow the use of different antigen preparations as early and late viral proteins, and on the other hand permit a specific determination of different Ig classes and subclasses. A variety of assays has been established especially for determination of virus-specific IgM antibodies, which are predominantly found in active infection. These, however, at least in part may show non-specific results caused by interference of rheumatoid factor or IgG competition. Such problems have now been dealt with and are avoided by IgG precipitation or IgM immunosorption ("mu-capture" technique). These recent methods allow an exact epidemiological identification of risk groups for CMV infection. Results from our laboratory revealed 13% HCMV-IgM positive patients among pregnant women, 16% IgM positive patients among renal transplant recipients, 4% IgM positive cases in patients after cardiosurgery and 1.7% IgM positives among prostitutes. The prevalence of HCMV infection as indicated by specific IgG antibodies was 56%, 90%, 83%, and 90%, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1985

In vitro mutagenicity of valepotriates.

Valepotriates are epoxide-bearing triesters of the monoterpene alcohol 4,7-dimethylcyclopenta-(c)-pyrane isolated from the roots of several Valerianacae species. They are regarded as the main tranquilizing constituents of these drugs. Although the valepotriates valtrate/isovaltrate (VAL) and dihydrovaltrate (DH-VAL) showed a strong alkylating activity against the nucleophilic agent 4-(p-nitrobenzyl)-pyridine (NBP), they were not clearly mutagenic for the strains TA98, TA100, TA1535, and TA1537 of Salmonella typhimurium or for the strains WP2 and WP2 uvrA- of Escherichia coli in the absence of a metabolic activation system (S9-mix). However, the valepotriates were mutagenic for TA100, WP2 and WP2 uvrA- at concentrations up to about 1.0 mumole/plate when S9-mix was added to the test system. With more than 1 mumole/plate the valepotriates were toxic in the presence of a metabolic activation system for all strains tested. The mutagenicity of the valepotriates was inversely related to the protein content of the S9-mix used. The mutagenicity and toxicity of the valepotriates could be inhibited when the S9-mix was preincubated with the esterase inhibitor paraoxon (1 mM) for 5 min before the test compounds and bacteria were added. Therefore, bioactivation of the valepotriates by an enzymatic hydrolysis of their ester groups is considered. This could be proven by activating the valepotriates with purified esterase.

Animals↗
PubMed1985

In vitro and in vivo investigations for the development of cytostatic methylhydrazones.

In in vitro short-term (3 h) assays, the beta-chloroethyl-methyl-hydrazones B 1 and B 2 inhibit the uptake of 3H-thymidine by EAC and L 1210 leukemia cells, B 2 being 5 to 10 times more effective than B 1. The growth inhibitory effect of both compounds was also confirmed in long-term (7 days) clonal assays using agar-containing glass capillaries, B 2 again being more effective than B 1. In contrast to these differences in vitro, in vivo both substances showed remission to the same degree in EAC- and complete resistance in L 1210-bearing mice. The diverging in vitro/in vivo sensitivities were thought to result from differences in the affinity of the methylhydrazones to the tumor cells: using short exposure periods (3 h) B 1 was more inhibitory than B 2 on both EAC and L 1210 colony growth; i.e., the more hydrophilic B 2 could more easily be washed off. To further test the idea of different cell membrane affinities, the methylhydrazones ZB 1 and P 1 with increasing lipophilic properties were synthesized. In vitro, after both pulse and continuous exposure ZB 1 and P 1 showed enforced inhibitory effects on colony growth. In vivo, ZB 1 and P 1 reduced the tumor weight of EAC mice, while only P 1 increased the survival time of L 1210 mice. The results suggest that from the combination of in vitro/in vivo assays mechanistic conclusions can be derived that are valuable for further development of these cystostatics.

Animals↗
PubMed1984

Regions in the ribosomal minichromosome of Physarum polycephalum are protected from restriction nucleases; protection is insensitive to high salt in the G phase and sensitive in the M phase of the cell cycle.

In the central spacer region of the extrachromosomal ribosomal DNA of the slime mold Physarum polycephalum, four small regions of related sequence are completely inaccessible to restriction endonucleases (HinfI and MboI). In addition, some sequences neighboring the inaccessible ones, are partially inaccessible to restriction enzymes and micrococcal nuclease. Taking advantage of the natural synchrony of Physarum plasmodia, we found that this protection is present throughout the cell cycle. Treatment with high salt (2.5 M-NaCl) of nuclei from the G2 phase of the cell cycle left the protection essentially unchanged. When nuclei from the M phase were treated with salt, the protection was abolished. The inaccessible sites are located close to the origins of replication of the rDNA.

Base Sequence↗
PubMed1984

Isolation and purification of transcriptionally active ribosomal chromatin from the slime mould, Physarum polycephalum.

In the acellular slime mold Physarum polycephalum the ribosomal genes are all located on linear, extrachromosomal DNA molecules which are clustered in the nucleolus. This report describes the isolation and purification of these ribosomal genes as functionally active chromatin particles. Nucleolar lysates are fractionated by gel filtration to remove ribosomal precursors and other soluble material. The ribosomal chromatin is subsequently separated from contaminating nuclear chromatin by a sucrose gradient centrifugation step. This procedure allows the isolation of the ribosomal genes as intact nucleoprotein particles, which are now amenable to a biochemical analysis of their structural and functional properties.

Cell Fractionation↗
PubMed1984

Transplacental genetic and cytogenetic effects of alkylating agents in the mouse. I: Induction of somatic coat color mutations.

Induction of somatic coat color mutations by the alkylating agents ENU, MNU, EMS, MMS, DES, DMS, and trenimon and by the tuberculostatic drug INH was investigated in the mammalian spot test. Positive results were obtained with EMS (100 mg/kg), ENU (20-60 mg/kg), and INH (100 mg/kg), while trenimon (100 micrograms/kg), DES (225 mg/kg), and MNU (2 mg/kg) yielded inconclusive data. No mutagenic activity was found for MMS (125 mg/kg) and DMS (50 mg/kg). The mutagenic potency of monofunctional alkylating agents at subtoxic doses decreases as follows ENU greater than EMS greater than DES greater than MMS = DMS. The hypothesis that somatic coat color mutations in the mouse are predominantly due to intragenic changes is discussed. Differences in the RS frequency between offspring of the crosses NMRI X DBA and C57 X T are due to differences in loci available for mutation induction. Mutations that uncover the recessive allele p contribute to a significant extent to the total RS frequency observed in the mammalian spot test.

Alkylating Agents↗
PubMed1984

N-methyl-N-formylhydrazine: a toxic and mutagenic inhibitor of the intestinal diamine oxidase.

N-methyl-N-formylhydrazine is the first active intermediate of the poison gyromitrin of the mushroom: false morel. This compound is a non-competitive inhibitor of human intestinal diamine oxidase (ID50 = 1.6 X 10(-5) mol/l). This concentration corresponds to less than 5 g of wet weight of mushroom/l. The diamine oxidases from 5 other sources are inhibited in a similar manner. Semicarbazide and aminoguanidine are 10-respectively 1000-fold more potent inhibitors of the human intestinal diamine oxidase. An involvement of the diamine oxidase inhibitory property of N-methyl-N-formylhydrazine in toxic and mutagenic effects of the substance is considered.

Amine Oxidase (Copper-Containing)↗
PubMed1984

la-positive T lymphocytes are the producer cells of interferon gamma.

The production of gamma-interferon (IFN gamma) in human peripheral blood T lymphocytes was induced by stimulation with PHA. For identification of the producer cell of IFN gamma, double fluorescence studies were undertaken and titers of interferon were determined in preparatively separated T-cell subpopulations reactive with one of the monoclonal antibodies OKT3, OKT4, OKT8, and OKIal . Production of IFN gamma was found in OKT3+, OKT4+, and OKT8+ cells. However, IFN gamma production occurred only in T cells also reactive with the monoclonal antibody OKIal . Addition of macrophages had no substantial effect on interferon titers in these subpopulations. It is suggested that the T cell subset producing IFN gamma is characterized by its reactivity with the monoclonal antibodies OKT3, OKT4 or OKT8, and OKIal .

Antibodies, Monoclonal↗
PubMed1983

Localization and DNA sequence around the initiation site of ribosomal RNA transcription in Physarum polycephalum.

We have used S1 nuclease to map the initiation site of ribosomal RNA transcription in the acellular slime mold Physarum polycephalum, and we have determined the sequence of 1011 nucleotides surrounding the start site. Consistent with others' observations, there is little homology with the comparable region of other species. As predicted by previous restriction mapping, direct repeats roughly 30 base pairs in length are present upstream of the initiation site and a 148 base pair duplication occurs in the external transcribed spacer. The results also suggest the presence of a processing site within the external transcribed spacer of the ribosomal transcription unit.

Base Composition↗
PubMed1983

Activity of organophosphorus insecticides in bacterial tests for mutagenicity and DNA repair--direct alkylation versus metabolic activation and breakdown. II. O,O-dimethyl-O-(1,2-dibromo-2,2-dichloroethyl)-phosphate and two O-ether derivatives of trichlorfon.

The following organophosphates were tested for their ability to induce DNA damage in a rec-type repair test with Proteus mirabilis strains PG713 (rec- hcr-) and PG273 (wild-type) and point mutations in the his- strain TA100 of Salmonella typhimurium: O,O-dimethyl-O-(1,2-dibromo-2,2-dichloroethyl)-phosphate (NALED); trichlorfon-O-methyl ether (TCP-O-ME), O,O-dimethyl-(1-methoxy-2,2,2-trichlorethyl)-phosphonate; trichlorfon-O-methyl ether vinyl derivative (TCP-O-MEVD), O,O-dimethyl-(1-methoxy-2,2-dichlorovinyl)-phosphonate. All compounds were negative in the repair test but induced base pair substitutions in S. typhimurium. The mutagenicity of NALED is due to the direct alkylating ability of the parental molecule and to mutagenic metabolites generated by enzymatic splitting of the side chain. Glutathion-dependent enzymes in the S9-mix eliminate the mutagenic activity of NALED completely. Mutation induction by TCP-O-ME and TCP-O-MEVD is predominantly caused by the reactive O-methyl ether configuration of the side chain and is resistant to metabolic inactivation by NADPH- or glutathion-dependent enzymatic pathways in the S9-mix of mice.

Animals↗
PubMed1983

On the mutagenicity of metabolites derived from the mushroom poison gyromitrin.

The hepatotoxic and carcinogenic hydrazine N-methyl-N-formyl hydrazine (MFH), which is formed from the mushroom poison gyromitrin by hydrolytic cleavage in vivo and in vitro during food processing is much more mutagenic for the strain TA 100 of Salmonella typhimurium in the presence of a metabolic activation system than in its absence. On the other hand, acetylated MFH (Ac-MFH) was not mutagenic for TA 100 in both test conditions. For the strain TA 98 neither MFH nor Ac-MFH were mutagenic both with and without metabolic activation. Therefore, a metabolic conversion of the free NH2-moiety of MFH into a genotoxic metabolite of MFH is postulated.

Acetaldehyde↗
PubMed1983

Investigations on the mutagenic activity of STS 557.

The progestin STS 557 was tested for mutagenic activity in the rec-type repair test with Proteus mirabilis, the Ames-test and the host-mediated assay with Salmonella typhimurium, the cytogenetic assays with ascites tumour and bone-marrow cells of mice and the dominant lethal test with male and female mice. All results obtained indicate the absence of a genotoxic activity of STS 557.

Animals↗
PubMed1983

Tubulin genes of Trypanosoma brucei: a tightly clustered family of alternating genes.

African trypanosomes are the causative agents of many medically and economically important diseases of man and domestic animals. The cell body of these blood-dwelling protozoa is enveloped with a dense layer of pellicular microtubules, which confer both motility and mechanical stability on these cells; microtubules are also important components of the flagellum. The major structural components of the microtubuli are two related proteins, alpha- and beta-tubulin. We have analyzed the genomic organization of alpha- and beta-tubulin genes in Trypanosoma brucei. In this organism, the majority of these genes are arranged in a single, tightly packed cluster of alternating alpha- and beta-tubulin genes with a basic repeat length together of 3.6 kilobase pairs. A genomic library of T. brucei was constructed by using the phage vector A 1059, and recombinant phages carrying tubulin genes were isolated by screening the library with heterologous chicken tubulin cDNA probes. The results of restriction endonuclease and hybridization analysis of DNA isolated from recombinant phages, and subcloned fragments thereof, were compatible with the restriction maps derived from digestion and Southern blot hybridization of genomic DNA.

Animals↗