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Biomedical subjects

R Böhme

Publications and source records attributed to R Böhme.

16 recordsLinked to original sources

[Hypoxyradiotherapy: changes in the oxygen partial pressure distribution in the tumor and in the healthy tissue under acute respiratory hypoxia].

PURPOSE: Based on the oxygen effect a new therapeutic modality has been developed to protect healthy tissues while breathing hypoxic gas mixture during irradiation. MATERIAL AND METHODS: The effect of breathing hypoxic gas mixture (8.1% O2) on pO2 in Yoshida sarcoma and muscle was studied using rats of Wistar strain. Different fractionation schedules were used: 10 x 3 Gy, 6 x 5 Gy and 3 x 10 Gy. Tissue oxygenation was assessed with a polarographic electrode system. RESULTS: The median pO2 in Yoshida sarcoma was 10 mm Hg. 21% of pO2-values were lower than 5 mm Hg. During breathing of hypoxic gas mixture no significant changes in median tumor pO2 or radiobiologic hypoxic values (< or = 5 mm Hg) were recorded. The median pO2 in muscle was 30 mm Hg. During breathing of gas hypoxic mixture a significant decrease of the median to the value 12 mm Hg and an increase of the radiobiologic hypoxic values (p < 0.00001) were observed. The changes of pO2-values were constant independent from fractionation. CONCLUSIONS: Between tumor and healthy tissue exists a significant difference regarding changes in the radiobiologic fraction during breathing of hypoxic gas mixture. This fact explains the experimental and clinical experience, that the breathing hypoxic gas mixture protects the healthy tissue without changes in the radiosensibility of chronic hypoxic tumor tissue.

Acute Disease

[The methods and results of simultaneous radiochemotherapy with carboplatin in advanced cervical carcinomas].

PURPOSE: The frequency and the poor therapeutic results in advanced cervical cancer establish the demand for effectiveness of treatment. Recent clinical data have shown that simultaneous radiochemotherapy may yield high remission rates in squamous cell carcinomas of other organs. PATIENTS AND METHODS: In our Department of Radiotherapy and Radiooncology of the University of Leipzig we treated since 1.6.1991 17 patients with advanced cancer of the uterine cervix with a simultaneous radiochemotherapy with carboplatin. RESULTS: The rate of complete remission was 76%. Follow-up is available from six to 24 months. Severe or toxic side effects of the treatment we didn't observe. Eight (47%) patients live relapse-free. CONCLUSIONS: In our opinion randomized studies are required to determine: What is better? Simultaneous radiochemotherapy or radiotherapy?

Adolescent

A high-affinity plasma membrane Ca2+-ATPase in Dictyostelium discoideum: its relation to cAMP-induced Ca2+ fluxes.

Chemotactic stimulation of Dictyostelium discoideum induces an uptake of Ca2+ by the cells followed by a release of Ca2+. In this study we investigated the mechanism of Ca2+ release and found that it was inhibited by La3+, Cd2+ and azide. Ca2+ release occurred in the absence of external Na+, indicating that an Na+/Ca2+ exchange was not involved. Plasma membranes contained high- and low-affinity ATPase activities. Apparent K0.5 values were 8 microM for the major Mg2+-ATPase and 1.1 microM for the high-affinity Ca2+-ATPase, respectively. The Mg2+-ATPase activity was inhibited by elevated concentrations of Ca2+, whereas both Ca2+-ATPases were active in the absence of added Mg2+. The activities of the Ca2+-ATPases were not modified by calmodulin. The high-affinity Ca2+-ATPase was competitively inhibited by La3+ and Cd2+; we suggest that this high-affinity enzyme mediates the release of Ca2+ from D. discoideum cells.

Azides

Histophotometrical measurements concerning the distribution of myofibrillar ATPase activity within the tissue block after aldehyde fixation.

The inhibition of myofibrillar ATPase activity by aldehyde fixation in tissue pieces of myocardium of the rat was measured by scanning histophotometry. The relative amount of the final reaction product of the histochemical method for ATPase (Padykula and Herman 1955) was taken as a measure for the enzyme activity. Along scanning lines in slides from the surface to the centre of tissue block, a higher activity was found in the centre in contrast to the marginal zone. Compared with the centre of the block (approximately equal to 100%), in the marginal region a loss of about 40% (in paraformaldehyde PFA) and of 75% (in glutaraldehyde GA) was found, the latter with a sharp decline between the marginal zone and the central part. For quantitative enzyme histochemistry by histophotometry unfixed material is recommended.

Adenosine Triphosphatases

[In vitro studies on the adsorption of various resins of the Wofatit type for drugs].

The capacities of the resins Wofatit Y 29, Y 55 and Y 56 (VEB Chemiekombinat Bitterfeld) to adsorb various medicaments were compared with that of the resin XAD-4. Methaquelone, diazepam, krotylbarbital, promazine phosphate and ethyloxamine were used as test substances. The resin Y 56 proved to have an adsorption capacity similar to that of XAD-4 (e.g. maximum saturation for methaquelone 98%, half-maximum saturation at 7 minutes). In further tests on various batches of this resin the best results were given by the resin Y 56/7. Adsorption was quite clearly shown to be dependent on concentration. At a blood-flow of 100 ml/min clearance values of 34.5 ml/min for krotylbarbitol and 22.1 ml/min for methaquelone were calculated. According to these findings the resin Y 56/7 is suitable for further testing in a haemoperfusion system with a view to clinical use.

Barbiturates

Regulation of phosphorylation of myosin heavy chain during the chemotactic response of Dictyostelium cells.

Chemotactic stimulation of the cellular slime mould Dictyostelium discoideum by cyclic AMP increases the incorporation of 32P into a 210-kDa polypeptide. This was determined in lysates prepared from stimulated and nonstimulated cells. Earlier results suggesting that the 210-kDa polypeptide corresponds to myosin heavy chains [7] have now been confirmed. We have investigated the sequence of events following chemotactic stimulation that lead to the change of myosin heavy-chain phosphorylation. 1. Chemotactic stimulation did not activate myosin heavy chain kinase, but seemed to elicit the transient accumulation of dephosphorylated myosin heavy chains. Thus, the inefficient incorporation of 32P into myosin heavy chains in lysates of control cells seems to be due to the lack of dephosphorylated myosin heavy chains. 2. Using membranes of aggregation-competent cells, we found that incorporation of 32P into myosin heavy chains was inhibited by 0.1-1 mM Ca2+. The effect of calcium seems to be mediated by endogeneous calmodulin and was due to the inhibition of myosin kinase activity rather than to the activation of myosin phosphatase. 3. By the addition of calmodulin, the inhibition of myosin heavy-chain phosphorylation was further enhanced. 4. Folic acid, an attractant of undifferentiated cells, also caused enhanced incorporation of 32P into myosin heavy chains, as determined in cell lysates. 5. The amount of 32P incorporated in response to cyclic AMP into myosin heavy chains increased during differentiation to the aggregation-competent stage. Only a small fraction of the cell surface receptors had to be activated in order to elicit a maximal reaction. Our results suggest that a phosphorylated form of myosin heavy chains prevails at the onset of the chemotactic response and that dephosphorylation begins within 5-10 s at 23 degrees C.

Actomyosin

[Growth development of children suffering from chronic insufficiency of digestion under dietary therapy for several years (author's transl)].

83 children suffering from malabsorption and disorders of metabolism were investigated with regard to body growth and weight gain. Though at first the increase of weight in comparison to body height was more rapid, the norm was obtained by the time the children were starting school. The period of retardation depended on the severity of disease and the diet being strictly kept to. It is most important that the circumference of the head was normal, though the other proportions of the body were too small for the age. These findings are parallel with normal intellectual development.

Adolescent

Binding of phosphorylated histone H1 to DNA.

A chromatin associated protein kinase was used to add 3 moles of phosphate to seryl side chains of 1 mole of histone H1. The DNA binding properties of this in vitro phosphorylated H1 were compared with those of unmodified H1. Considerably more radioactive superhelical DNA was retained on nitrocellulose filters at 20mM-40mM NaCl by phosphorylated H1 than by unmodified H1. However, zone velocity sedimentation analysis of histone-DNA complexes indicated that similar amounts of phosphorylated and unmodified H1 are bound to DNA. It is therefore concluded that phosphorylated H1 binds distributively to many or all DNA molecules available (depending on the histone/DNA ratio) while unmodified H1 binds cooperatively to a fraction of the DNA molecules in the reaction mixture.

Animals

Some evidence for replication-transcription coupling in Physarum polycephalum.

Hydroxyurea, at concentrations of 40-60 mM, selectively and effectively blocked incorporation of thymidine into DNA. Inhibition occurred within 5-10 min of application of the agent when DNA synthesis was in progress, while the onset of replication at the beginning of S-phase and DNA synthesis in G2 phase were not affected. Uridine incorporation into TCA-precipitable material, in the presence of hydroxyurea, was significantly (up to 70%) inhibited in early S-phase of the cell cycle. Selective inhibition of RNA synthesis was confirmed for RNA separated into rRNA-rich and poly(A)-rich RNA fractions and analysed by the 2 kinds of DNA-RNA hybridization reactions. Uridine incorporation into poly (A) RNA was also inhibited under conditions where cycloheximide prevented maturation of nascent DNA molecules in early S-phase. We assume that chromatin which is replicating early DNA sequences may be a more competent template for transcription.

Chromatin

Alpha-isopropylmalate synthase from yeast: purification, kinetic studies, and effect of ligands on stability.

alpha-Isopropylmalate synthase, the first specific enzyme in leucine biosynthesis, was purified approximately 100-fold from extracts of Saccharomyces sp. (strain 60615), the most effective step being specific elution with the feedback inhibitor leucine from a hydroxyapatite column. In the early steps of purification, special care was taken to protect the synthase against proteolytic activities. The apparent molecular weight of the enzyme as determined from gel filtration on a calibrated column was 137,000 in the absence and 121,000 in the presence of leucine. Inhibition by leucine was specific and strongly pH-dependent, with the leucine concentration necessary for half-maximal inhibition increasing about 10-fold as the pH increased from 7.5 to 8.5. Within this pH range, catalytic activity remained almost unchanged. The apparent K(m) values for the two substrates were found to be 16 mum for alpha-ketoisovalerate and 9 mum for acetyl-coenzyme A. K(+) was required for full activity, the apparent K(a) value being 2 mm. Leucine inhibition was of the mixed type, resulting in decreased V(max) and increased apparent K(m) values forboth substrates. Whereas no cooperative effects were observed with either substrate, positive cooperativity was seen with leucine in the presence of saturating substrate concentrations. Leucine and, to a lesser extent, alpha-ketoisovalerate stabilized the purified enzyme against heat-inactivation. The presence of acetyl-coenzyme A, on the other hand, accelerated the inactivation. In subsequent experiments, coenzyme A was recognized as the actual inactivating ligand, being effective even at lower temperatures and in concentrations which were estimated to be in the range of the enzyme concentration.

Acyltransferases