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Biomedical subjects

L Müller

Publications and source records attributed to L Müller.

At least 127 records · Page 7Linked to original sources
PubMed1989

Radiosynthesis of [14C]acarbose.

Acarbose (O-4,6-dideoxy-4-[[(1S, 4R, 5S, 6S)-4,5,6-trihydroxy-3- (hydroxymethyl)-2-cyclohexen-1-yl]amino]-a-D-glucopyranosyl-(1---- 4)-O-a-D- glucopyranosyl-(1----4)-4-glucopyranose, Bay g 5421), an a-glucosidase inhibitor from Actinoplanes, has been developed for the treatment of diabetes mellitus. To investigate the pharmacokinetics and the biotransformation, 14C-labelled acarbose ([14C]Bay g 5421) was required. About 37 GBq (1 Ci) D-[U-14C]glucose was used as a precursor to obtain [14C]acarbose with a radiochemical yield of between 1.58 and 2.56%. For fermentation purposes resting cells of the Actinoplanes mutant SN 1667/47 were used under cometabolism conditions with a 10-fold excess of maltose. The specific radioactivities achieved in individual preparations were 7.77 MBq/mg (210 microCi/mg), 8.03 MBq/mg (217 microCi/mg), and 9.14 MBq/mg (247 microCi/mg), with a radiochemical purity of greater than 98% in each case. By hydrolysis and subsequent investigation of the hydrolysis products it was shown that [14C]carbon atoms originating from the radioactive glucose are present only in the core and not in the maltose unit of [14C]acarbose.

Acarbose↗
PubMed1989

[An unusual complication after the partial resection of the ascending duodenum of a cow].

In a heifer portions of the ascending duodenum, which had been perforated by an obstructing phytobezoar, were resected. This resulted in an unexpected complication. The shortened ligamentum duodenocolicum exerted steady traction on the descending colon. This traction caused a kink and finally resulted in a total obstruction of the colon. The pathogenesis of this complication is illustrated. Surgical--possibly preventive--procedures are discussed.

Animals↗
PubMed1988

Stage-related induction of chromosomal aberrations and SCE in mouse embryos treated transplacentally during organogenesis with MMC and DMBA.

During organogenesis, mouse embryos were treated transplacentally with MMC and DMBA. The clastogenic and SCE-inducing effects of MMC and the clastogenic effects of DMBA were analyzed in metaphases from whole embryo suspensions. Positive effects were observed on all the days of pregnancy on which the embryos were analyzed, i.e., on days 10, 11, 12, and 13. Whereas the MMC-induced SCE-frequencies did not change significantly during the tested period, the clastogenic effects of MMC and DMBA varied drastically. Extremely high aberration rates were observed in embryos on day 11; on the other days the aberration rates were much lower. Factors that might have given rise to these stage-related effects are discussed.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Micronucleus induction in mouse and rat fetuses treated transplacentally during histogenesis with mitomycin C and 7,12-dimethylbenz(a)anthracene.

During histogenesis, mouse and rat fetuses were treated transplacentally with mitomycin C (MMC) and 7,12-dimethylbenz(a)anthracene (DMBA). The micronucleus (MN)-inducing effects of MMC were analysed in mouse fetal blood and liver; the effects of DMBA were analysed in mouse fetal and rat fetal blood and in maternal bone marrow of both species. Both test substances were clearly clastogenic during the period of development in which the embryos were analysed--i.e., MMC from gestational day 14 until day 18 in mice and DMBA on days 14 and 17 in mice and days 16 and 19 in rats. In mouse fetal liver and blood the MMC-induced MN frequencies did not vary significantly during the whole period. MMC was more effective in fetal blood than in fetal liver. DMBA-induced MN frequencies in maternal bone marrow were slightly higher in rats than in mice. Compared to maternal bone marrow, fetal MN frequencies were about four to five times higher in rats but less than two times higher in mice. Thus, rat fetuses were far more susceptible to the clastogenic action of DMBA than mouse fetuses. These results are discussed with respect to fetal development and maternal/fetal metabolism.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1988

Steroid hormone receptors and prognosis in breast cancer.

The importance of steroid receptors for the prognosis of mammary carcinoma has been evaluated by investigating the course of disease in 163 patients for a median follow up time of 66 months after mastectomy. Multivariate analysis including estrogen receptor (ER), progesterone receptor (PgR), the presence of 8S and 4S ER together or 4S ER only, and the lymph node status revealed only the latter to have significant (p less than 0.001) predictive potency. Lymph node positive (N-pos) patients had a 3.3 (1.7-6.2) fold risk of death and 2.8 (1.7-4.7) fold risk of recurrence relative to node negative (N-neg) patients. When we compared overall survival (OAS) and disease-free survival (DFS) in the various receptor-positive groups with the groups that displayed neither ER nor PgR, significant differences in prognosis were only seen in N-neg patients. PgR did not turn out to be a better prognostic factor than ER, nor was the 8S ER a sign of increased OAS and DFS compared to total ER. However, the number of patients in this group was too small to allow a definite statement.

Breast Neoplasms↗
PubMed1988

Subcellular toxicity of low level cadmium in rats: effect on cytochrome c oxidase.

The in vivo effect of cadmium (Cd) with or without prior administration of L-cysteine (Cys) or diethylmaleate (DEM) on hepatic and renal cytochrome c oxidase (Cyt-c-Ox), essential metals and mitochondrial thiols was investigated. Male Sprague-Dawley rats were given 25 micrograms Cd/kg (as Cd acetate) orally 5 times a week for 6 weeks. Different groups of animals additionally received either Cys (500 mg/kg per day, p.o.) or DEM (0.85 mg/kg, i.p.) by multiple administration. Parameters were determined 1 day after the last gavage. Cadmium decreased the activity of Cyt-c-Ox in mitochondria of livers but not in those of kidneys. Copper in both tissue and mitochondria were unaffected whereas hepatic tissue iron decreased by 50% upon Cd gavage. Cysteine pretreatment increased hepatic and especially renal mitochondrial Cd, but diminished the Cd effect on Cyt-c-Ox and increased hepatic tissue iron. Both DEM and DEM/Cd treatment decreased Cyt-c-Ox by 50% in liver but not in kidneys. Metallothionein was not significantly altered by either treatment. Considering data from all the experimental groups Cyt-c-Ox activity seems to be related rather to the amount of protein thiols than to either copper or iron in hepatic mitochondria. The data demonstrate the high susceptibility of hepatic vs. renal mitochondria and suggest the involvement of thiols in Cyt-c-Ox activity.

Animals↗
PubMed1988

[Not Available].

Explore the source record for details and available documents.

Germany↗
PubMed1987

[24-year survival in chronic myeloid leukemia].

A 55-year-old woman was diagnosed as having chronic myeloid leukemia in 1961. After 9 years with stable white blood cells, progression of the disease was noted (white cells up to 180 X 10(9)/l; splenomegaly to the umbilicus). Busulfan was given over 4 weeks resulting in a remission of 13 years duration. Progression was observed again in 1983, 22 years after the initial diagnosis of chronic myeloid leukemia. Therapy with hydroxyurea resulted in another remission of shorter duration. Two chromosome studies showed the Philadelphia chromosome in 100% of metaphases without additional aberrations. In 1985 blast crisis developed. The cause of death as determined at autopsy was an undiagnosed miliary tuberculosis. The presented case is of special interest since (1) it is a report of the longest surviving patient with chronic myeloid leukemia, and (2) in contrast to other cases with long survival, this patient did not show chromosomal mosaicism or any additional chromosomal aberrations.

Aged↗
PubMed1987

Metallothionein-determination in biological materials: interlaboratory comparison of 5 current methods.

Five current methods of metallothionein (MT)-estimation in biological materials (Hg/TCA-, Cd/heme-, SH-assay, G 75-method and RIA) were compared. Uniform calibration was ensured by measuring the nitrogen-content of the standard-apoprotein after "Kjeldahl-digestion". Known amounts of rabbit standard Cd-MT I were recovered from identical rat S9-samples. In an overall rating, RIA and Cd/heme-assay performed best, whereas the other methods either underestimated (SH-, G 75) or overestimated (Hg/TCA) the 100%-expectation.

Animals↗
PubMed1987

Effects of cadmium in rat hepatocytes: interaction with aluminum.

The influence of aluminium (Al) chloride on toxic responses to cadmium (Cd) chloride of hepatocytes isolated from fed rats were investigated. Hepatocytes exposed to 50-200 microM Al took up the Al-ion more efficiently when the cells were simultaneously incubated with 50 microM Cd for 60 min. Aluminium (50-200 microM) could not prevent the release of about 50% of lactate dehydrogenase (LDH) from cells due to 50 microM Cd. Aluminium itself increased LDH leakage only to a moderate extent, indicating the low toxicity of Al to hepatocytes. Cadmium diminished the total hepatocellular thiols (protein + non-protein) and, even more pronounced, the acid soluble thiols after 60 min of incubation. However, this response to Cd was inhibited by simultaneous exposure to 50-200 microM Al in an Al concentration-dependent manner. Concomitantly, the Cd-dependent lipid peroxidation (LPO; measured as thiobarbituric acid reactants) at 60 min was decreased by Al, which itself did not enhance basal LPO in hepatocytes. These data show that Al partly protects hepatocytes from Cd-induced depletion of acid soluble thiols (i.e. reduced glutathione) and from stimulation of LPO. However, Al did not prevent the Cd-induced damage of the cell membrane.

Aluminum↗
PubMed1987

Uptake and distribution of aluminium in rat hepatocytes and its effect on enzyme leakage and lactate formation.

Aluminium (Al) chloride (10-200 microM) increased the Al content in hepatocytes isolated from fed male rats in a time- and concentration-dependent manner. After 60 min of incubation with 100 microM Al about 45% of cellular Al was found each in the mitochondrial and the postmitochondrial fraction of hepatocytes, whereas about 5% of Al sedimented with nuclei and cell debris. Concomitantly, the leakage of lactate dehydrogenase (LDH), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) increased in the presence of Al time- and concentration-dependently, but only to a moderate extent. Aluminium (10-200 microM) also accelerated the formation of lactate by hepatocytes. No significant differences were found in Al uptake and distribution and its effect on LDH leakage and lactate formation when the metal ion was given as AlCl3, Al(NO3)3 or Al(lactate)3. Al concentrations (AlCl3) exceeding 250 microM severely disturbed the determination of LDH, AST and lactate in a cell free system. The data suggest only a moderate toxicity of Al compounds to isolated hepatocytes, when given in amounts approximating (patho)physiological conditions.

Alanine Transaminase↗
PubMed1987

Regional differences in protein and glycoprotein synthesis and their processing in the mouse brain as revealed by the incorporation of [3H]proline, N-6-[3H]acetyl-D-glucosamine and [3H]fucose.

The incorporation rate of [3H]fucose, N-6-[3H]acetyl-D-glucosamine and [3H]proline has been compared in five regions of the mouse brain on postnatal day 6. The olfactory bulbs and the cerebellum showed a prevalence of incorporation of [3H]fucose over other brain regions. Less expressed, but still well evident regional differences were observed in [3H]proline incorporation while the incorporation of N-6-[3H]acetyl-D-glucosamine was almost equal in all brain regions. The regional differences were also apparent after considering an actual pool of free isotopes in the individual regions. Gel electrophoresis of [3H]fucose-labelled membrane fraction showed that the higher incorporation of [3H]fucose in the olfactory bulbs is partly due to higher synthesis of low molecular weight glycoproteins, especially in the molecular range of 30,000. The data showed that the protein synthesis and fucosylation, and/or a fast transport of the corresponding molecules, varies more within the brain than the incorporation of N-6-[3H]acetyl-D-glucosamine and possibly also than the "core" part of glycan molecule synthesis.

Acetylglucosamine↗
PubMed1986

Determination of Cd-thionein in biological materials: comparative standard recovery by five current methods using protein nitrogen for standard calibration.

Five methods of metallothionein (MT) estimation in biological materials (Hg-saturation assay, Cd-saturation assay, thiolate group determination, Sephadex G-75 gel chromatography with subsequent Cd determination by Zeeman-AAS, and a radioimmunoassay (RIA) were compared for their ability to recover standard MT(rabbit Cd-MTI) from liver or kidney S9. Uniform molar calibration of all assays was achieved using the known amino acid composition of standard MT and the nitrogen content of the standard MT stock solution as measured after complete Kjeldahl digestion. Known molar amounts of standard MT were added exogenously to rat liver- or kidney-S9 samples and recoveries measured using the methods indicated. In an overall rating, RIA and Cd-saturation assay performed best with recoveries of 97 +/- 12.0 and 105 +/- 9.7%, respectively. On the other hand, the remaining methods either underestimated (thiolate group determination, G-75/Cd-AAS) or overestimated (Hg-saturation assay) the theoretical expectation by up to 44%.

Animals↗
PubMed1986

Consequences of cadmium toxicity in rat hepatocytes: mitochondrial dysfunction and lipid peroxidation.

Cadmium (Cd) (10-100 microM) decreased the ATP/ADP ratio and enhanced lipid peroxidation (LPO) (measured as thiobarbituric acid reactants) in incubated rat hepatocytes. Analysis of the subcellular distribution of Cd indicated its preferential attachment to the inner membranes of mitochondria. Incubation of isolated mitochondria with 0.005-0.05 microM Cd resulted in increased formation of formazans from nitroblue tetrazolium salts, indicating enhanced membrane permeability to succinate. These Cd-concentrations also diminished mitochondrial ATP. LPO in mitochondria strongly increased only after Cd-exposures above 1 microM Cd. Similarly, in Cd-treated hepatocytes decreases in ATP/ADP ratios corresponded to increases in LPO stimulation only at 30 and 60 min but not at 15 min of incubation when ATP/ADP ratios were already affected. Moreover, neither hepatocellular ATP/ADP decrease nor mitochondrial formazan formation due to Cd were prevented by (+)-cyanidanol-3, an effective inhibitor of Cd-induced LPO. These data suggest that even low Cd-concentrations in the hepatocyte disturb the integrity of its mitochondrial membranes concomitantly impairing the hepatocellular energy supply. LPO, only observed at higher Cd-concentrations, is not responsible for these adverse Cd-effects.

Adenosine Diphosphate↗
PubMed1986

Absorption and distribution of cadmium (Cd), copper and zinc following oral subchronic low level administration to rats of different binding forms of cadmium (Cd-acetate, Cd-metallothionein, Cd-glutathione).

Male Wistar rats received by gavage saline or about 25 micrograms cadmium (Cd)/kg/day as Cd-acetate (Cd-Ac), Cd-metallothionein (Cd-MT) or Cd-glutathione (Cd-GSH) 5 times per week for 28 times. At all treatments 0.2-0.3% of the totally administered Cd dose was found in liver, kidneys, small intestine and pancreas, whereas none of the Cd forms applied resulted in a Cd accumulation in testes. Cd in small intestine was not increased by Cd-MT. However, it was raised by Cd-Ac and even more by Cd-GSH. A smaller increase in hepatic and renal Cd resulted from Cd-GSH than from Cd-Ac or Cd-MT. Cd in pancreas increased after Cd-GSH but not after Cd-Ac or Cd-MT. Copper (Cu) rose in small intestine and testes but decreased in kidneys independent of either Cd treatment. Concomitantly, zinc (Zn) was decreased in small intestine and testes. The tissue concentration of metallothionein (MT) was only marginally increased by all treatments. The highest value (80%) above controls) was found in small intestine after Cd-GSH. Intestinal Cd as well as testicular Cu were related to the tissue MT. Therefore, the distribution of Cd between various organs depends on the Cd form applied. There is some relationship to the distribution of Cu and Zn.

Acetates↗