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Biomedical subjects

G F Weber

Publications and source records attributed to G F Weber.

9 recordsLinked to original sources
PubMed1992

Platinum anticancer drugs modulate P-450 mRNA levels and differentially alter hepatic drug and steroid hormone metabolism in male and female rats.

Treatment of male rats with the anticancer drug cisplatin leads to feminization of the profile of cytochrome P-450 and other microsomal enzymes involved in steroid hormone and drug metabolism (G.A. LeBlanc, and D.J. Waxman, J. Biol. Chem., 263: 15732-15739, 1988). The present study uses the rat model to evaluate the differential effects of cisplatin treatment on liver microsomal enzymes between genders, and also examines whether the modulation of enzyme activities by cisplatin and its analogues involves changes in P-450 gene expression. While cisplatin treatment of male rats caused a severalfold increase in female-predominant hepatic enzymes, including testosterone 5 alpha-reductase and testosterone 7 alpha-hydroxylase (P-450 form 2A1), it partially decreased the expression of these enzymes in females. The reduced expression of these estrogen-dependent enzymes in females may derive from the loss of circulating estradiol that was shown to occur in response to cisplatin treatment. Analysis of mRNA levels of individual P-450 forms revealed that the effects of cisplatin on P-450-catalyzed steroid hydroxylase activities in both male and female rats are primarily operative through the drug's effects on P-450 mRNA expression. P-450-dependent cyclophosphamide activation was significantly compromised in male rats after cisplatin administration; however, this activity was not altered in cisplatin-treated females. This sex-dependent effect of cisplatin was due to its suppression of P-450 form 2C11, a male-specific P-450 that is a major contributor to microsomal cyclophosphamide bioactivation in male rat liver. The clinically active cisplatin analogue iproplatin elicited effects very similar to those of cisplatin, while carboplatin and transplatin did not have significant effects on hepatic P-450 expression. Together, these findings demonstrate that the response of rat liver to cisplatin-induced changes in hepatic P-450 enzyme profiles and cyclophosphamide bioactivation capacity differs between the sexes, and in addition, these effects can be minimized by use of carboplatin in place of cisplatin.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1992

Inhibition of the neutrophil NADPH oxidase by folic acid and antagonists of the folic acid metabolism.

The influence of folic acid and several antagonists of the folic acid metabolism on neutrophil superoxide generation was investigated with the cytochrome c reduction assay. The compounds were found to be partial competitive inhibitors of the NADPH oxidase, their activity apparently increasing with larger substituents at the 10 position. There is evidence that compounds with a 4-oxo substituent are taken up more slowly by neutrophils than those with a 4-amino functionality. Scavenging properties could be excluded from control measurements with the xanthine/xanthine oxidase assay.

Adult↗
PubMed1992

Current methods in histopathology.

The past decade has presented many new methods to histopathology. However, there are important reasons for establishing these methods in every institute for pathology. It is not enough just to exchange old equipment into new systems. It takes a careful judgement what will be the benefits from a new system for the institute, the hospital and the patient. Important factors like institute management, quality assurance, quality control, speed, competitiveness, profitability and environmental safety aspects are high ranking tasks in the modern institute of pathology, next to the specialization in new diagnostic areas like immunohistochemistry, bone-pathology (bone-morphometry/undecalcifield iliac crest biopsy histology), flow cytometry, image analyzing or PCR-techniques etc. The main target of each institute of pathology, weather of private nature or a governmental/state institution, is the establishment of a high quality, safe and reliable diagnosis in the fastest time and for a price based on a standardized, accepted and economical system. Institutions will be more controlled by certain economical departments which have to watch the cost-/profit situation of the hospital and it's individual institutions in comparison to the average country standard and the average European standard. The introduced methods are mostly standard in "Western" institutes. However, it is of utmost importance that the institutes in "Eastern Europe" establish these standards as soon as possible in order to be competitive and to be able to join research-projects with "Western" universities - a necessary source of income.

Europe, Eastern↗
PubMed1991

Glutathione peroxidase deficiency and childhood seizures.

4 children with intractable seizures, repeated infections, and intolerance to anticonvulsants had evidence of glutathione peroxidase deficiency. 2 had low intracellular enzyme activity but normal blood selenium and high plasma glutathione peroxidase concentrations. The other 2 had low intracellular glutathione peroxidase activity with low circulating glutathione peroxidase and selenium concentrations. The clinical state of the children improved after discontinuation of anticonvulsant medication and selenium substitution.

Anticonvulsants↗
PubMed1991

The antifolate 10-deazaaminopterin inhibits neutrophil chemotaxis and superoxide generation.

The effect of the dihydrofolate reductase inhibitor 10-deazaaminopterin on several neutrophil functions was tested in vitro. At 100 uM it inhibited chemotaxis by 50% and reduced the generation of superoxide by 30%. It had no influence on phagocytosis and did not significantly change the secretion of beta-D-glucuronidase, a marker enzyme of degranulation. After preincubation of white cells with various concentrations of 10-deazaaminopterin, followed by resuspension in drug-free medium, no inhibition of chemotaxis or superoxide generation was seen. Therefore, the effects on chemotaxis and NADPH oxidase appear to be reversible and not due to metabolic transformation of the dihydrofolate reductase inhibitor.

Adult↗
PubMed1990

The measurement of oxygen-derived free radicals and related substances in medicine.

Due to the high reactivity of the chemical species and the presence of multiple potentially interfering substances, the measurement of oxygen-derived free radicals in biological material requires highly developed techniques. The currently employed methods are reviewed according to the reactions upon which they are based, the assays, possible interferences and their use in medical research. Detection of the emission of light is a very popular method. Although it is in principle unspecific, there are modifications to measure individual radical species. The only direct way to detect radicals is electron spin resonance spectroscopy. Among the specific assays for O2- the reductions of nitroblue tetrazolium or cytochrome c are predominant. For the detection of H2O2 different techniques are employed for either intracellular or extracellular determination. An array of substances has been used for the measurement of OH. Which of them is the most useful depends on the question to be answered. There are also indirect methods that determine free radicals based on chemical modifications caused by them; the most important assays of this kind quantify lipid peroxides. In addition, assays for thiobarbituric acid-reactive substances and DNA strand breaks and interstrand crosslinks are used.

Animals↗
PubMed1979

Nature of human serum blood group T antibodies.

Antibodies against blood group substance T in normal human sera consist of two types, depending upon whether or not the molecules remain immunochemically active at 37 degrees C. The two agglutinins were isolated by means of T antigen-coupled Sepharose 48 affinity chromatography. Temperature-sensitive agglutinin was eluted from the affinity column at 37 degrees C, while temperature-independent agglutinin remained bound to the antigen. Subsequently, the latter was dissociated from the column in the presence of 2.5 M MgCl2. Examination of six normal sera revealed that the levels of temperature-independent agglutinin was about twice that of temperature-sensitive agglutinin. More than 90% of anti-T agglutinins in normal sera were of the IgM class, in 8 of 11 samples studied. No direct relationship appeared to exist between anti-T titers and blood type. Thermal effects on hemagglutination, at least for anti-T agglutinin interacting with T antigen bearing red cells, is primarily due to the molecular characteristics of the agglutinin and not to the conformational change of the red cell membranes.

Adsorption↗
PubMed1979

Extraction of human plasma or sera by heat treatment for a solid-phase radioimmunoassay of carcinoembryonic antigen.

Heat treatment and a solid-phase radioimmunoassay are combined to give a relatively simple and rapid procedure for assay of carcinoembryonic antigen in plasma or serum. The new way we describe to extract this antigen is an alternative to the conventional method of extraction with perchloric acid. Heating plasma or serum samples in acetate buffer (0.16 mol/L, pH 5.0) at 70 degrees C for 15 min precipitates out most of the heat-labile, nonspecific plasma proteins, but leaves most of the antigen in solution, with its immunochemical properties apparently unaffected. Comparison between the heat treatment and the perchloric acid extraction yielded comparable values when tested either by solid-phase radioimmunoassay or by the zirconyl phosphate precipitation method. An added advantage of our method is that it gives the same assay values for both plasma and serum. Results for a group of pathological plasma samples, assayed by both our method and the perchloric acid-zirconyl phosphate precipitation method, gave a correlation coefficient of 0.90.

Carcinoembryonic Antigen↗