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Biomedical subjects

B Schumann

Publications and source records attributed to B Schumann.

At least 19 recordsLinked to original sources

Pharmacodynamics of FTY720, the first member of a new class of immune-modulating therapeutics in transplantation medicine.

FTY is a novel immunomodulator currently undergoing clinical investigation and has the potential of improving immunosuppressive therapy after organ transplantation. Previous experimental studies in animals have shown that FTY has a unique mechanism of action. We have studied the pharmacodynamic effects of FTY in stable renal allograft recipients taking part in a phase I clinical trial. As in various animal models including non-human primates, a single oral dose of FTY (0.25 - 3.5 mg) significantly reduced peripheral lymphocyte count by 30 - 70%. The peripheral lymphocyte count returned to baseline within 24 hours. Only in those patients treated with the highest dose of FTY (3.5 mg), did peripheral lymphopenia persist for more than 96 hours. FTY reduced all lymphocyte subsets, T cells more than B cells and CD4+ cells more than CD8+ cells. The reduction in CD3+CD62L+ cell counts was more pronounced, whereas CD3+CCR5+ cell counts were less affected in comparison to the total number of CD3+ lymphocytes. We found only slightly increased apoptosis rates (< 5%) in peripheral lymphocytes, and this change does not explain the marked reduction in lymphocyte count. In cultured human lymphocytes only suprapharmacological doses of 10 microM FTY induced apoptosis (20.6 +/- 2.8%) after a 4-h incubation. More important, clinically relevant doses of 0.1 microM FTY increased lymphocyte mobility 2-fold. No effect of FTY on anti-CD3mAb-stimulated lymphocyte proliferation was detected and there was no change in phagocytosis rates in whole-blood cultures incubated with FTY. Further studies are necessary to investigate the mechanism of action of FTY in detail.

Apoptosis↗

[Determination of serum S-100 protein and 5-S-cysteinyl-DOPA levels in melanoma patients].

This was the first time that authors detected se-S-100 and 5-SCD values with patients with malignant melanoma in Hungary. They examined the change of serum S-100 and 5-SCD value parallel. Sera were obtained with 184 melanoma patients 326 times. Patients were ranked into groups on the basis of clinical symptoms: free of symptoms and suffering from it (primary tumour, regional lymph node metastasis, soliter or multiplex distant metastasis). On the basis of the initial results the following have been found: S-100 protein and 5-SCD serum levels had no prognostic value in patients with primary melanoma. Patients without symptoms showed values around the normal level. There was significant difference in both markers between patients with or without symptoms. Significant differences were found between clinical stage I and II, as well as in clinical stage II and III. In the case of S-100 protein there was significant difference between the values of patients with soliter and multiplex distant metastasis.

Dihydroxyphenylalanine↗

Shifts of intracellular pH distribution as a part of the signal mechanism leading to the elicitation of benzophenanthridine alkaloids . Phytoalexin biosynthesis in cultured cells of eschscholtzia californica

Cultured cells of Eschscholtzia californica (Californian poppy) respond to a yeast elicitor preparation or Penicillium cyclopium spores with the production of benzophenanthridine alkaloids, which are potent phytoalexins. Confocal pH mapping with the probe carboxy-seminaphthorhodafluor-1-acetoxymethylester revealed characteristic shifts of the pH distribution in challenged cells: within a few minutes after elicitor contact a transient acidification of cytoplasmic and nuclear areas occurred in parallel with an increase of the vacuolar pH. The change of proton concentration in the vacuole and in the extravacuolar area showed a nearly constant relation, indicating an efflux of vacuolar protons into the cytosol. A 10-min treatment with 2 mM butyric or pivalic acid caused a transient acidification of the cytoplasm comparable to that observed after elicitor contact and also induced alkaloid biosynthesis. Experimental depletion of the vacuolar proton pool reversibly prevented both the elicitor-triggered pH shifts and the induction of alkaloid biosynthesis. pH shifts and induction of alkaloid biosynthesis showed a similar dependence on the elicitor concentration. Net efflux of K+, alkalinization of the outer medium, and browning of the cells were evoked only at higher elicitor concentrations. We suggest that transient acidification of the cytoplasm via efflux of vacuolar protons is both a necessary and sufficient step in the signal path toward biosynthesis of benzophenanthridine alkaloids in Californian poppy cells.

Journal Article↗

Biotransformation of benzo[a]pyrene and other polycyclic aromatic hydrocarbons and heterocyclic analogs by several green algae and other algal species under gold and white light.

This laboratory has shown that the metabolism of benzo[a]pyrene (BaP), a carcinogenic polycyclic aromatic hydrocarbon (PAH), by a freshwater green alga, Selenastrum capricornutum, under gold light proceeds through a dioxygenase pathway with subsequent conjugation and excretion. This study was undertaken to determine: (1) the effects of different light sources on the enzymatic or photochemical processes involved in the biotransformation of BaP over a dose range of 5-1200 mg/l; (2) the phototoxicity of carcinogenic PAHs and mutagenic quinones to a green alga; (3) the ability of other algal systems to metabolize BaP. Cultures were exposed to different doses of BaP for 2 days at 23 degrees C under gold, white or UV-A fluorescent light on a diurnal cycle of 16 h light, 8 h dark. Under gold light, metabolites of BaP produced by Selenastrum capricornutum were the dihydrodiols of which the 11,12-dihydrodiol was the major metabolite. Under white light, at low doses, the major metabolite was the 9,10-dihydrodiol. With increasing dose, the ratio of dihydrodiols to quinones decreased to less than two. With increasing light energy output, from gold to white to UV-A in the PAH absorbing region, BaP quinone production increased. Of other carcinogenic PAHs studied, only 7H-dibenz[c,g]carbazole was as phototoxic as BaP while 7,12-dimethylbenz[a]anthracene, dibenz[a,j]acridine and non-carcinogenic PAHs, anthracene and pyrene, were not phototoxic. The 3,6-quinone of BaP was found to be highly phototoxic while quinones that included menadione, danthron, phenanthrene-quinone and hydroquinone were not. The data suggest that the phototoxicity of BaP is due to photochemical production of quinones; the 3,6-quinone of BaP is phototoxic and is probably the result of the production of short lived cyclic reactive intermediates by the interaction of light with the quinone. Lastly, only the green algae, Selenastrum capricornutum, Scenedesmus acutus and Ankistrodesmus braunii almost completely metabolized BaP to dihydrodiols. The green alga Chlamydomonas reinhardtii, the yellow alga Ochromonas malhamensis, the blue green algae Anabaena flosaquae and euglenoid Euglena gracilis did not metabolize BaP to any extent. The data indicate that algae are important in their ability to degrade PAHs but the degradation is dependent on the dose of light energy emitted and absorbed, the dose of PAHs to which the algae are exposed, the phototoxicity of PAHs and their metabolite(s) and the species and strain of algae involved. All of these factors will be important in assessing the degradation and detoxification pathways of recalcitrant PAHs by algae.

Anabaena↗

Assessment of the efficiency of endovesical laser treatment of urinary bladder tumors on the basis of polyamine content measured in the eluent.

Authors describe a new analytical method for monitoring the treatment of vesicular tumors. Chromatographic analysis of the polyamine content of the eluent allows differential diagnostic judgement of the malignity of the laser treated tumorous tissue. The practical applicability of the method is demonstrated and evaluated on the basis of the analysis of 88 clinical cases.

Aged↗

Acute and custodial care among impaired aged.

The authors surveyed a community-based population of 628 persons who were 65 and over and who lived either in a rural Maryland county or in Baltimore. For each subject, the number of different medical problems, the subject's capacity to perform physical tasks, and the ability to function were assessed. The number and type of medical problems tended to be the best predictors of whether or not hospital or physician's office care were used, and of the volume of physician's office visits for subjects who sought outpatient care. The subject's ability to function was the best predictor of whether or not the subject used a paid home aide and the volume of family caregiving. Implications for research on association between need and use of long-term care are discussed.

Activities of Daily Living↗

Treating cocaine abusing methadone maintenance patients with desipramine.

Intravenous cocaine use in methadone patients has become a major problem because of both the complications of cocaine use and the potential spread of AIDS. During an eight week open trial we found that desipramine reduced cocaine craving and use in eight cocaine abusing methadone maintenance patients compared to eight patients getting no medication execept methadone.

Acquired Immunodeficiency Syndrome↗

The significance of neopterin determination as a tumour marker in ovarian cancer.

The neopterin level of 164 urine samples of ovarian cancer patients was determined by high pressure liquid chromatography. Parallelly, the serum levels of CA 125, CEA and of lipid bound sialic acid were also determined. A good correlation was found both with CA 125 and with lipid-bound sialic acid. There was a closer correlation with the latter both in the patients showing remission and in the active tumour carriers. In patients with negative tumour markers (TM) in the sera examined, a tumour-free state was confirmed in 87.5% by neopterin determinations. Accordingly, authors recommend neopterin determination in patients who face a critical decision.

Antigens, Tumor-Associated, Carbohydrate↗

The importance of polyamine determination in monitoring malignant gynaecological tumours.

By thin-layer chromatography, the serum polyamine levels together with those of CA 125, CEA, lipid-bound sialic acid and urinary neopterine were determined in 56 ovarian cancer patients. A correlation was found in the group of clinically active tumour carriers between the clinical finding and the results of polyamine determination only where other tumour markers were suggestive of complete remission.

Antigens, Tumor-Associated, Carbohydrate↗

Experience with the Pelorus stereotactic system.

The Pelorus stereotactic system, by its unique approach, alleviates the need for the traditional head frame and computer-generated coordinates which are common to most other systems. Despite its simplicity, it sacrifices nothing in terms of the range of problems for which it can be used to diagnose and treat. In fact, its unencumbered design may make it more appropriate for advanced procedures than conventional systems.

Humans↗

[Nitrogen and amino acid absorption in the small intestine of growing pigs. 2. Apparent and true crude protein digestibility and amino acid absorption to the end of the small intestine].

Studies of the apparent and true ileal digestibility of crude protein and the apparent and true amino acid (AA) absorption were carried out with 7 female pigs in the live weight range between 22 and 34 kg after ileorectostomy. Protein sources of varied quality with regard to the method of treatment (toasted) and untoasted soybean oilmeal) and to the AA composition (vital gluten or vital gluten + L-lysine X HCl) were used. Distinct differences regarding the apparent ileal digestibility of crude protein and the apparent absorption of amino acids were discovered between the protein sources, the cause of which is to be seen in the different amounts of endogenous N. The true ileal digestibility of crude protein and amino acid absorption were partly distinctly higher than the values of the apparent ileal digestibility of crude protein and AA absorption. On the whole one can say that the results of the investigation gained by means of ileorectostomy can be compared to the values gained from cannulated animals. Thus the experimental method used is suitable for studying the absorption process to the end of the small intestine of pigs.

Amino Acids↗

[Nitrogen and amino acid resorption in the small intestine of growing swine. 1. Animal study method, nitrogen content and amino acid composition of the small intestine chyme by administration of various proteins].

The amount of endogenous N in the chyme at the end of the small intestine and the amino acid composition of the ileum chyme were ascertained with growing pigs with ileorectostomy after feeding qualitatively differentiated protein sources. In dependence on the protein used, distinct differences turned out for some amino acids with regard to their content in the ileum chyme. Bacteriologic and histologic investigations subsequent to the dissection of the test animals showed that - in comparison to the control animals-the functions of the small intestine remained the same during the time of the experiment. The experiment method described appears to be suitable for absorption investigations up to the end of the small intestine of growing pigs.

Amino Acids↗

[Exocrine pancreas secretion in swine after feeding soybean extract meal].

Exogenous N-secretion of the pancreas was investigated with growing pigs with fistulae in the pancreas. For this purpose the two protein sources toasted and untoasted soybean oilmeal were used. After the feeding of untoasted soybean oilmeal a significant increase of the secretion volume and of protein outpour could be observed in contrast to toasted soybean oilmeal within 24 h. The heat-labile soybean trypsin inhibitor also caused an activity increase of the pancreatic enzymes.

Amino Acids↗

[High-dosage oral gestagen therapy as a failure-regime in metastatic breast cancer].

High-dosage medroxyprogesterone (Farlutal, 1 g/d orally) was administered to 42 female patients with progressive disseminated carcinomas of the breast after conventional cytostatic and hormonal treatment had failed. Besides evaluation of success of treatment the pharmacokinetics of medroxyprogesterone were investigated. A remission rate of 37% (total and partial remissions) indicated that high-dosage oral treatment with gestagens can be used as "failure-regime" in patients at the end of conventional treatment. The plasma level of the gestagen approached values corresponding to high-dosage intramuscular application.

Administration, Oral↗

[Effect of metalaxyl on the synthesis of RNA, DNA and protein in Phytophthora nicotianae].

Metalaxyl is used to control diseases caused by fungi of the order of the Perenosporales. We investigated the action of this fungicid eon nucleic acid and protein synthesis in liquid cultures of Phytophthora nicotianae. The uptake of 32P, 3H-uridine, 3H-thymidine and 14C-leucine as precursors of nuclei acid and protein synthesis by the mycelium was not inhibited by metalaxyl. RNA synthesis as indicated by 3H-uridine incorporation was strongly inhibited (about 80%) by 0.5 micrograms/ml of metalaxyl. The inhibition was visible already few minutes after addition of the toxicant. Since the inhibition of incorporation of 3H-thymidine into DNA and of 14C-leucine into protein became significant 2-3 hours later, we conclude that metalaxyl primarily interfers with RNA synthesis. Synthesis of ribosomal RNA is more affected (more than 90%) than that of tRNA (about 55%) and poly(A)-containing RNA. Since in the presence of actinomycin, in contrast to metalaxyl, protein synthesis is inhibited immediately as a consequence of complete inhibition of RNA synthesis and of the short life-time of mRNA, it is also evident that mRNA synthesis is less strongly inhibited, at least during the early period of metalaxyl action. The molecular mechanism of metalaxyl inhibition of the transcription process remains open. The fungicide did not inhibit the activity of a partially purified RNA polymerase isolated from the fungus. On the other hand, the RNA synthesis (14C-UTP-incorporation) by a cell homogenate and by isolated nuclear fractions was inhibited significantly. Possibilities of the molecular action of metalaxyl are discussed. The RNA synthesis of some plant systems (cell cultures of Lycopersicon peruvianum, isolated nuclei from the same cell cultures, purified RNA polymerase from Spinacia oleracea chloroplasts) was not inhibited by metalaxyl, not even at high concentrations.

Alanine↗