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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 469 records · Page 26Linked to original sources
PubMed1986

Decreased concentration of xanthine dehydrogenase (EC 1.1.1.204) in rat hepatomas.

Xanthine dehydrogenase (EC 1.1.1.204), the rate-limiting enzyme of purine degradation, was purified 642-fold to homogeneity from liver of male Wistar rats. Antibody was generated to the purified enzyme in white rabbits and was partially purified. For the immunotitration a radioassay of high sensitivity was developed to determine low enzyme activities. Titration curves with the antibody showed that the xanthine dehydrogenase enzyme protein amounts in slowly growing hepatoma 20 and rapidly growing hepatoma 3924A were 34 and 4% of those of normal liver, which was in good agreement with the decrease in the activity of the enzyme to 33 and 2%, respectively. The contents of flavin adenine dinucleotide, the essential cofactor of the enzyme, in the immunoprecipitates in hepatomas 20 and 3924A were 27 and 4% of that of the normal liver. This is the first report to provide immunological evidence that a decreased enzyme activity in rat hepatomas, that of xanthine dehydrogenase, was due to a decrease in the enzyme protein amount. The markedly decreased xanthine dehydrogenase activity and amount have far-reaching biochemical and pharmacological implications for the tumors.

Animals↗
PubMed1986

Increased synthesis of carbamoyl-phosphate synthase II (EC 6.3.5.5) in hepatoma 3924A.

Carbamoyl-phosphate synthase II (glutamine-hydrolyzing) (EC 6.3.5.5) (synthase II) is the first and rate-limiting enzyme in the de novo UTP biosynthetic pathway. Leucine pulse-labeling in the rat demonstrated that in the rapidly proliferating hepatoma 3924A the ratio of radioactivity of synthase II to that of total cytosolic protein was 168.2 +/- 11.0 (SE) X 10(-3). This synthetic rate for the tumor enzyme was 9.7-fold higher than that for the liver synthase II, 17.4 +/- 4.0 X 10(-3). Since the degradation rate for hepatoma 3924A enzyme (t1/2 = 65.5 h) was similar to the rate for liver synthase II (t1/2 = 69.3 h), the increase in tumor synthase II activity and amount was due primarily to an elevation in enzyme synthesis in the presence of an unaltered catabolic rate. The results indicate that the reprogramming of gene expression in the hepatoma entails an increased production rate of the rate-limiting enzyme of UTP synthesis. This increase in the activity, concentration, and synthesis of tumor synthase II should provide a heightened capacity for the de novo pyrimidine biosynthetic pathway, thus conferring a selective advantage to the cancer cells.

Animals↗
PubMed1986

[Hyperplasia of growth hormone-producing cells in the hypophysis in psoriasis. Study of 10 patients].

In previous investigations we observed an increase of growth hormone (HGH) in the blood serum of patients suffering from various clinical forms of psoriasis. The skin lesions disappeared in about 70% when treated systemically with somatostatin and/or bromocriptine, which are inhibitors of HGH secretion. These findings suggested a post mortem investigation of the pituitary glands of 10 patients who had suffered from psoriasis or psoriatic arthritis. Using histochemical and immunochemical methods, we investigated the distribution of cells producing HGH, PRL, LH or FSH. In all 10 pituitary glands we found hyperplasia of the HGH cells, whereas cells producing LH, TSH, FSH and PRL had a normal distribution. The pituitary glands of controls showed no accumulation or hyperplasia of HGH cells.

Growth Hormone↗
PubMed1986

Ultrastructural aspects of cynomolgus atherosclerotic carotid artery lesions on cholestyramine 'regression' treatment.

The carotid artery lesions of atherosclerotic cynomolgus monkeys treated with cholestyramine and studied with scanning electron microscopy appeared to be less bulging and largely covered by endothelial cells. With transmission electron microscopy these lesions showed an evident disappearance of cells and of extra- and intracellular lipid; a marked relative increase of fibrous material in the intercellular matrix, chiefly collagen and elastin fibers, was noted.

Animals↗
PubMed1986

Delayed development of intimal lesions in cerebral arteries of spontaneously hypertensive rats subjected to a short-term atherogenic diet (TEM observations).

In adult spontaneously hypertensive rats, subjected to an atherogenic diet (2% cholic acid in a 5% hypercholesterolic diet) for 19 weeks both aortic and carotid artery lesions were already detectable on TEM examination while the cerebral arteries did not show any lesions. Similar findings have been previously obtained in rabbits and in monkeys on atherogenic diets.

Animals↗
PubMed1986

Platelet plasma membrane changes in human type IIa hypercholesterolemia.

We have examined platelets collected from hypercholesterolemic (HC) young patients (n = 12) and from normocholesterolemic young volunteers (n = 9) by means of freeze fracture. The mean value of the surface density per square micrometer of the openings of the surface-connected canalicular system was significantly higher (p less than 0.03) in the HC patients (2.4 +/- 0.6) compared with the controls (1.8 +/- 0.5). It was also positively correlated with the low-density lipoprotein cholesterolemia/total cholesterol ratio (p less than 0.005) and inversely correlated with the high-density lipoprotein cholesterolemia/total cholesterol ratio (p less than 0.01). These data indicate that the circulating platelets of HC type IIa patients appear changed at ultrastructural level and that their modification may be somehow related to the atherogenetic processes.

Adolescent↗
PubMed1986

Morphometric analysis of the human corpus callosum fails to reveal sex-related differences.

No observations of sex differences in the splenium of the human corpus callosum are made. In the data there is no support for the concept that sex related functional hemispherical discrepancies are due to differences in area and width of the splenium of corpus callosum. However variability within a sex is often larger than the variability between the two sexes. The results are discussed with regard to a neurobiological theory of schizophrenia.

Aged↗
PubMed1985

Platelets in the platelet-vessel wall interaction.

Ultrastructural and biochemical aspects of reversible and non-reversible platelet-vessel wall interaction are presented. Special attention is directed towards the role of release products of platelets, the plasmatic coagulation factors and the prostaglandin system. An up-to-date view of the role of platelet-vessel wall interaction in atherogenesis is discussed.

Animals↗
PubMed1985

In vivo inactivation of formylglycinamidine ribonucleotide synthetase in rat hepatoma.

The antitumor drug acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, irreversibly inactivated in vivo formylglycinamidine ribonucleotide synthetase (FGAM synthetase, EC 6.3.5.3) in transplantable rat hepatoma 3924A while the activity in host liver remained unchanged. At acivicin doses of 1.0 and 5.0 mg/kg body weight, enzyme activity in the hepatoma decreased to 26 and 5%, respectively, after 2 hr. The activity of the in vivo inactivated hepatoma 3924A enzyme could not be restored by gel filtration or 40 hr of dialysis. In the absence of L-glutamine, acivicin in vitro inactivated both liver and hepatoma FGAM synthetase in a time-dependent fashion, with an inactivation constant Kinact = 66 microM and a minimum inactivation half-time T = 1.0 min. In the presence of L-glutamine, competitive inhibition was observed with a Ki = 5 microM. Protection against in vitro inactivation was observed in the presence of 1 mM L-glutamine, suggesting that L-glutamine concentrations are important in the selective toxicity of acivicin on hepatoma cells in vivo. Irreversible inhibition of FGAM synthetase by acivicin is consistent with the view that this antibiotic is an active site-directed affinity analog of L-glutamine and indicates that this enzyme is a sensitive target of acivicin action.

Animals↗
PubMed1985

Inactivation by acivicin of carbamoyl-phosphate synthetase II of human colon carcinoma.

The effect of the anti-tumor, anti-glutamine drug acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, was determined on the activity of the rate-limiting enzyme of de novo pyrimidine biosynthesis, carbamoyl-phosphate synthetase II (glutamine-hydrolyzing) (EC 6.3.5.5), in human colon carcinoma. The synthetase II activity in human colon carcinoma was elevated 2- to 3-fold over values of the normal colon mucosa, and the substrate kinetic constants were similar for the enzyme in normal and neoplastic colon. The Km for glutamine was 17 microM (colon carcinoma) and 23 microM (normal mucosa), whereas the Km for ATP was 2.1 and 1.7 mM in tumor and mucosa respectively. The synthetase II activity in colon carcinoma was inhibited to a similar extent by UMP, UDP and UTP (36-41%). The three uracil nucleotides were also equally effective in inhibiting the enzyme from normal mucosa (39-46%). Both enzymes were activated by PRPP (63 and 57%) in mucosa and carcinoma respectively. Acivicin in vitro selectively inactivated the glutamine-dependent synthetase II from human colon carcinoma, and it did not affect the ammonia-dependent activity. The acivicin inactivation constant (Kinact) was 100 microM, and the minimum inactivation half-time (T) was 0.7 min. Acivicin most likely exerts its effect against human colon synthetase II by acting as an active site directed affinity analogue of L-glutamine.

Antibiotics, Antineoplastic↗
PubMed1985

Mapping and expression of a regulatory nitrogen fixation gene (fixD) of Rhizobium meliloti.

A 3.5-kb HindIII fragment from the main nif/fix (nitrogen fixation) gene cluster of Rhizobium meliloti was characterized by studying its expression in Escherichia coli minicells. A coding region for two polypeptides of 68 K and 66 K was mapped using Tn5 insertions and hybrid fusion polypeptides. DNA sequence analysis of this region revealed the presence of an open reading frame capable of coding for a polypeptide of 59.9 K mol. wt. This coding region was designated fixD. Plasmids, constitutively expressing this fixD gene from vector promoters, activated a nifHD-lacZ fusion in E. coli at a low level. Higher levels of activation were obtained following an enhanced expression of the fixD gene in plasmid pRmW541 which was achieved by inducing deletions between the vector promoter and the fixD gene. Sequencing of these deletion mutants showed that, in most cases, fusion polypeptides of the fixD gene product and the aphI (aminoglycoside-3'-phosphotransferase) gene product were sufficient for activation. In E. coli the activation is strictly dependent upon a functional glnF (ntrA) gene.

Journal Article↗