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Biomedical subjects

R Herrmann

Publications and source records attributed to R Herrmann.

At least 91 records · Page 5Linked to original sources

Calcium-requirement for activation of skinned vascular smooth muscle from spontaneously hypertensive (SHRSP) and normotensive control rats.

The aim of this study was to clarify whether the increased vascular tone in spontaneous hypertension of rats is due to a change of the calcium-sensitivity of the contractile proteins themselves. In skinned rat tail artery rings from SHRSP and WKY rats the calcium-requirement for half maximal activation (3.6 X 10(-6)M Ca++ for both rat strains) as well as relaxation half times (1.45 +/- 0.43 min, SHRSP and 1.63 +/- 0.48 min, WKY) were found to be identical. The extent of myosin phosphorylation in the contracted and in the relaxed state did not differ between SHRSP and WKY. It is concluded that changes at the level of the contractile proteins are not involved in the increased vascular tone of SHRSP essential hypertension.

Animals

Bacterial mutagenicity and chemical analysis of polycyclic aromatic hydrocarbons and some nitro derivatives in environmental samples collected in West Germany.

Snow and air particulate samples collected in Upper Frankonia, Federal Republic of Germany, have been analyzed for nitro-polycyclic aromatic hydrocarbons (PAH) and PAH content. A novel clean-up technique has been developed enabling interfering organochlorine environmental contaminants to be removed prior to analysis of the hydrocarbons by GC-MS. Mass fragmentation patterns are presented for 1-nitropyrene, 6-nitrobenzo(a)pyrene, 6-nitrochrysene, and 3-nitrofluoranthene. The level of these compounds found in air samples was in the range of 0.2-2.0 ng.m-3 with the exception of 6-nitrobenzo(a)pyrene, which was not detected. This compares with PAH values of between 1 and 6 ng.m-3. The freshly fallen snow sample collected at the side of a motorway had no detectable PAHs or nitro-PAHs. Parallel studies on the bacterial mutagenicity of the collected air samples using Salmonella typhimurium TA98 and TA100 in the presence and absence of aroclor-induced rat liver "S9" revealed both "direct" and "indirect" activity. Larger numbers of mutants were induced in the presence of S9 than in its absence. The snow sample was devoid of mutagenic activity. These studies show the utility of the biological approach to screen environmental samples prior to expensive and time-consuming chemical analysis.

Air Pollutants

Organization of the ribosomal RNA genes in Mycoplasma hyopneumoniae: the 5S rRNA gene is separated from the 16S and 23S rRNA genes.

In order to study the organization of the ribosomal RNA genes of Mycoplasma hyopneumoniae the rRNA genes were cloned in phage vectors lambda EMBL3 and lambda EMBL4. By subcloning the restriction fragments into various plasmids and analysing the resulting clones by Southern and Northern blot hybridization, a restriction map of the rRNA genes was generated and the organization of the rRNA genes was determined. The results show that the genes for the 16S and 23S rRNAs are closely spaced and occur only once in the genome, whereas the 5S rRNA gene is separated from the other two genes by more than 4 kb.

Base Sequence

Analysis of transcription and processing signals of the 16S-23S rRNA operon of Mycoplasma hyopneumoniae.

The 16S and 23S rRNA genes of Mycoplasma hyopneumoniae are closely spaced in one operon. The two genes are separated by a spacer region of 500 bp which shows no sequence homology to bacterial tRNA genes. Within this operon seven 5' and five 3' ends of various rRNA species were mapped and the corresponding DNA was sequenced. The results are consistent with the following model for synthesis of rRNAs: Transcription of the operon is initiated from either of two tandemly arranged promoters leading to a large precursor RNA consisting of both 16S and 23S rRNAs. This primary transcript is first cleaved within stem structures surrounding the two rRNAs to yield premature 16S and 23S rRNAs. By further processing events the mature 5' and 3' ends are generated. The promoter sequences of this operon differ from those of other eubacterial promoters in lacking the typical -35 region. The putative termination site at the 3' end of the operon is reminiscent of rho-independent terminators in Escherichia coli.

Base Sequence

Urinary polyamine excretion by tumor-bearing and tumor-free mice exposed to cyclophosphamide, 5-fluorouracil and 6-mercaptopurine.

The effects of cytostatic treatment on urinary polyamine excretion have been investigated in tumor-bearing (either Ehrlich carcinoma of S 180 sarcoma) and in tumor-free mice. The animals were exposed to single or multiple treatment with various doses of cyclophosphamide, 5-fluorouracil, or 6-mercaptopurine. Treatment invariably enhanced polyamine excretion dependent on dose and effectiveness of the cytostatic drug. The most pronounced increases were observed in the excretion of spermine and putrescine, with peak excretion usually occurring after 1-2 and 3-4 days, respectively. The urinary excretion of spermidine was relatively modest in untreated mice, but the increases observed following drug treatment were high in proportion. Significant differences in urinary polyamine excretion were observed between tumor-free and tumor-bearing animals following treatment with all cytostatic agents. Peak values were invariably higher in tumor-bearing mice even in those with small, barely detectable tumors. After discontinuation of treatment polyamine excretion returned to normal values and stabilized in groups in which regression predominated, whereas in those groups of animals which showed little or no tumor regression urinary polyamine levels gradually increased again during a 2-week observation period.

Animals

Phase III study of 5-FU and carmustine versus 5-FU, carmustine, and doxorubicin in advanced gastric cancer.

Seventy-seven patients with advanced gastric carcinoma were prospectively randomized to receive 5-FU and carmustine (FB) with or without doxorubicin (FAB). Thirty-five patients were evaluable for response. Neither the response rates (partial remission, 11% for FB and 24% for FAB) nor survival times (median, 4.0 months for FB and 5.5 months for FAB) were statistically different. The median survival of patients with partial remission (7.8 months) and those with no change (7.4 months) was significantly prolonged compared to patients with progressive disease (4.5 months). The side effects of both regimens after the first treatment cycle (except alopecia in FAB) were low. After the second cycle more pronounced myelosuppression in the FAB arm was observed.

Antineoplastic Combined Chemotherapy Protocols

gamma-Aminobutyric acid-mediated inhibition at cholinergic synapses formed by cultured retinal neurons.

The purpose of this study was to investigate the effect of gamma-aminobutyric acid (GABA) on the function of synapses formed by cholinergic neurons derived from the chick retina. We used an experimental culture system in which striated muscle cells served as postsynaptic targets for cholinergic neurons of the retina. This cell culture system permitted the physiological monitoring of acetylcholine release at synapses formed by retinal neurons. By plating a low density of dissociated retinal cells with myotubes, it was possible to study relatively isolated, presynaptic cholinergic neurons. We found that GABA and its agonists, muscimol and isoguvacine, inhibited spontaneous transmission at retina-muscle synapses. These inhibitory effects were reversibly blocked by bicuculline, a GABA receptor antagonist. The benzodiazepine, flurazepam, potentiated GABA-mediated inhibition. Overall, our findings suggest a direct inhibitory action of GABA on the cholinergic retinal neurons studied in our cell culture system.

Animals

Sequential methotrexate (MTX) and 5-fluorouracil (FU) in human tumor xenografts.

Human and animal tumor-lines heterotransplanted in nude mice were treated with MTX and FU sequentially. In order to investigate the relationship between tumor response and drug toxicity sequence, time and dose of both MTX and FU were varied. Pretreatment with MTX followed by FU with intervals of 3 or 24 h produced superior therapeutic results when compared to single administration of MTX or FU, simultaneous treatment, or the reverse sequence. In the MTX followed by FU regimen, dose reduction of either MTX or FU tended to decrease the anti-tumor effect. To investigate the toxic effects of different regimens, tumor-free nude mice were treated with MTX and FU the same way as the tumor-bearing animals. In this case, toxicity (weight loss, leukopenia) was more pronounced in those schedules with the best therapeutic results. However, toxicity appears to be more clearly related to the applied FU-dose.

Animals

Aclarubicin (aclacinomycin A) in the treatment of relapsing acute leukaemias.

Forty patients with relapsing acute leukaemias were treated with aclacinomycin A (aclarubicin, ACM), 25 mg/m2 i.v. daily for 7 days. Twenty-nine patients with acute myeloid (AML) and five with acute lymphoblastic (ALL) leukaemia were evaluable. The overall response rate was 29.5%. Eight complete (CR) and one partial (PR) remissions were achieved in AML (31%). A high CR rate was induced in patients treated at first relapse without prior reinduction (6/12 patients). A small proportion of leukaemias resistant to daunorubicin or doxorubicin responded to ACM (3/17 patients). Median remission duration was 5.5 months (range: 2-9 months). The most common toxic effects were nausea, vomiting, stomatitis and diarrhoea. Acute cardiotoxic effects were documented in three patients. Congestive cardiomyopathy was not observed despite prior treatment with anthracyclines. We conclude that the present dose scheduling of ACM is effective in the treatment of relapsing AML and that it should be introduced in combined chemotherapy in phase III trials to compare its activity to that of daunorubicin or doxorubicin.

Aclarubicin