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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 523 records · Page 29Linked to original sources
PubMed1984

Wedge-shaped epiphyses of the knees in two siblings: a new recessive rare dysplasia?

A peculiar form of metaphyseal dysplasia, mainly of the lower limbs, occurred in two male siblings born to healthy, unrelated parents. The clinical and radiological features were short stature, psychomotor retardation, accelerated bone maturation, the limbs and especially the knees showing cup-shaped widening of the ends of the metaphyses and wedge-shaped widening of the epiphyses. This condition does not fit the description of any syndrome reported so far and may therefore be classified as a new recessive dysplasia.

Bone Diseases, Developmental↗
PubMed1984

Proliferation-linked increase in phosphoribosylformylglycinamidine synthetase activity (EC 6.3.5.3).

The behavior of phosphoribosylformylglycinamidine ( FGAM ) synthetase (EC 6.3.5.3) activity was elucidated in normal and proliferating tissues and in murine and human neoplasms. Enzymic activity was measured in the 100,000 X g crude supernatant fluid prepared from tissue homogenates. The assay was based on coupling FGAM produced to diazotizable aminoimidazole ribonucleotide. In the crude extracts of normal rat liver and hepatoma 3924A, the apparent KmS of FGAM synthetase for formylglycinamide ribonucleotide, adenosine triphosphate and L-glutamine were 0.06, 1.5, and 0.03 mM, respectively. The liver and hepatoma 3924A FGAM synthetases were saturated at formylglycinamide ribonucleotide, adenosine triphosphate, and L-glutamine concentrations of 0.1, 7.0, and 0.5 mM, respectively; both enzymes had a pH optimum of 7.4. In the liver of normal adult rats, the FGAM synthetase activity was 7.2 to 10.7 nmol/hr/mg protein. The synthetase specific activity in hepatomas of slow and medium growth rates increased 1.2- to 2.2-fold, and in rapidly growing hepatomas it was elevated 3.2- to 5-fold over the values of the respective control normal livers. There was a positive correlation between the increase in synthetase activity and hepatoma proliferation rate. In rat tissues of high cell renewal activity, thymus, spleen, and testis, synthetase specific activity was 7.0-, 3.9-, and 3.3-fold higher than that of normal liver. In the 24- and 48-hr regenerating liver, FGAM synthetase specific activity was increased by 1.2- and 1.5-fold, respectively. In 5-day-old differentiating liver, specific activity was 202% of the adult value; when data were expressed per average cell, the activity was 55% of that of the adult liver. The markedly increased activity in the rapidly proliferating hepatomas appears to be more characteristic of neoplastic growth than of normal liver proliferation. FGAM synthetase activity was also increased in human renal cell carcinoma and hepatocellular and colon carcinomas to 1.4-, 2.7-, and 3.8-fold of the activity of the respective homologous normal and host tissues. The synthetase activity in the rapidly proliferating murine Lewis lung carcinoma was 9.6-fold that of the normal lung. The increased activity of FGAM synthetase should confer selective advantages to the cancer cells and marks this glutamine-utilizing enzyme as a potentially important target in the design of chemotherapy.

Animals↗
PubMed1983

Action of insulin on liver carbamoyl-phosphate synthetase II (glutamine-hydrolyzing) activity.

Carbamoyl-phosphate synthetase II (glutamine-hydrolyzing) (EC 6.3.5.5) (synthetase II), is the first and rate-limiting enzyme in the de novo UMP biosynthetic pathway. The present investigation showed that insulin has a regulatory action on hepatic synthetase II activity. When diabetes was induced with injection of different doses of alloxan the plasma insulin concentrations decreased in a dose-dependent fashion to 72, 38, 31 and 28% and concurrently the liver synthetase II activity decreased to 75, 43, 29 and 22% of the normal values. In diabetic rats dose response studies showed that with insulin injections of 4, 6, 8 or 10 U/day for 48 h the hepatic synthetase II activity increased to 81, 95, 99 and 103% of the control liver values. In the diabetic rats the insulin-induced rise in liver synthetase II activity was prevented by treatment of the rats with actinomycin.

Animals↗
PubMed1983

Increased concentration of thymidine kinase in rat hepatomas.

Thymidine kinase was purified to near homogeneity by affinity chromatography from cytosol fraction of rat hepatoma 3924A. The enzyme had a Mr of 81,000 and was composed of two subunits of Mr = 44,000. Antiserum made against it neutralized the activities of thymidine kinase from both rat livers and hepatomas. Neutralization studies with the antiserum revealed that hepatic transformation resulted in 4-, 15- and 25-fold increase in the amount of cytosol thymidine kinase in hepatomas 16, 7787 and 3924A of slow, medium and fast growth rate, respectively.

Animals↗
PubMed1983

A differential polarized phase fluorometric study of the effects of high hydrostatic pressure upon the fluidity of cellular membranes.

The effects of high hydrostatic pressure (up to 2 kbar) upon the fluidity and order of the synaptic and myelin membrane fractions of goldfish brain have been studied by using steady-state and differential polarized phase fluorometry. Probe motion provided a measure of membrane order (r infinity) and probe rotational rate (R). Membrane order became progressively greater as pressure was increased up to approximately 2 kbar. This effect was similar over the temperature range 5.6-34.3 degrees C. An increase in pressure of 1 kbar had an effect on membrane order that was equivalent to a 13-19 degrees C reduction in temperature. Membrane order was essentially identical during pressurization and depressurization. At 5.6 degrees C, pressurization caused a large increase in R, and similar, though less dramatic, anomalies occurred at higher temperatures. It is suggested that this is due to the segregation of probe molecules in highly ordered membranes, which leads either to excitation transfer between 1,6-diphenyl-1,3,5-hexatriene (DPH) molecules or to changes in the rotational motion of DPH from "sticking" to "slipping".

Animals↗
PubMed1983

Salvage capacity of hepatoma 3924A and action of dipyridamole.

The role and behavior of the salvage enzymes in the biosynthesis of purines (adenine and hypoxanthine-guanine phosphoribosyltransferases) and pyrimidines (uridine-cytidine, deoxycytidine and thymidine kinases) were elucidated. In liver purine metabolism the transferase activities were orders of magnitude higher than the activities of the enzymes of de novo biosynthesis. In both purine and pyrimidine biosynthesis the activities of the enzymes of the de novo pathways were low (23 pmol to 70 nmol/hr/mg protein), whereas those of salvage synthetic pathways ranged from 0.8 to 1,470 nmol/hr/mg protein. In purine metabolism the salvage enzymes had markedly higher affinity to the shared substrate PRPP (4 to 40 microM) than the rate-limiting enzyme of de novo synthesis, amidophosphoribosyltransferase (900 microM). In rapidly growing hepatoma 3924A the activities of the enzymes of de novo purine biosynthesis increased, whereas those of the salvage pathway changed little. However, the activities of the enzymes of the salvage pathways remained much higher than those of the enzymes of de novo purine production. In pyrimidine production in the hepatomas the activities of both de novo and salvage enzymes markedly increased. However, the activities of the salvage enzymes far outstripped those of the enzymes of the de novo pathways. To inhibit the operation of the salvage pathways, the action of the transport inhibitor, dipyridamole, was examined. In tissue culture, dipyridamole inhibited the transport of purine and pyrimidine nucleosides with an IC50 of 10(-6) or 10(-7) M. As measured by colony-forming assay, dipyridamole killed hepatoma cells with an IC50 of 20 microM. Dipyridamole markedly depressed the pools of ATP, GTP, CTP and UTP; in combination chemotherapy with acivicin, an anti-glutamine agent, synergistic action was observed on the pools of nucleotides in hepatoma 3924A in vivo. These investigations emphasize the importance of the capacity to utilize precursors by the salvage enzymes and may explain, in part at least, the failure of inhibitors of the de novo pathways to yield lasting chemotherapeutic results. Combination chemotherapy of inhibitors of the de novo pathways with an inhibitor of the salvage pathways (dipyridamole) should impact on our understanding of the contribution of salvage pathways and provide a rational basis for successful combination chemotherapy of neoplastic diseases.

Animals↗
PubMed1983

Enzymes of purine metabolism in cancer.

In cancer cells, a marked imbalance in the enzymic pattern of purine metabolism is linked with transformation and/or progression. In chemically-induced, transplantable hepatomas in rat, the specific activities of the anabolic enzymes, IMP dehydrogenase, GMP synthetase, adenylosuccinate synthetase, adenylosuccinase, AMP deaminase and amidophosphoribosyltransferase, increased to 13.5-, 3.7-, 3.1-, 1.8-, 5.5- and 2.8-fold, respectively, of those in normal liver. Activities of the catabolic enzymes, inosine phosphorylase, xanthine oxidase and uricase, decreased to 19, 10 and 4%, respectively. This enzymic imbalance was specific to hepatic neoplasia, since no similar pattern was observed in differentiating or regenerating liver. Most enzymic alterations were present also in chemically- and virus-induced animal tumors, in human kidney, liver and colon carcinomas, and in human colon carcinoma xenografts. The molecular correlation concept applies to purine biochemistry and an important segment of neoplastic gene expression was identified in the behavior of key purine-metabolizing enzymes.

Animals↗
PubMed1983

An ultrastructural comparison of diet-induced atherosclerosis of arteries supplying the central nervous system in cynomolgus and rhesus monkeys.

The carotid lesions of cynomolgus and rhesus monkeys fed an 8- to 12-months atherogenic diet are very severe. However, the basilar, vertebral and middle cerebral arteries of the same atherosclerotic monkeys look instead, at SEM examination, similar to the control ones. At TEM examination, these arteries of the atherosclerotic monkeys show only minimal lesions in the subendothelial space ('edema' and presence of fragments of basilar membrane) and sometimes necrobiosis of endothelial cells. The smooth muscle cells, which are also present in the controls in these arteries in the subendothelial space, are sometimes surrounded by a nest of basement membrane beads and do not contain lipid droplets.

Animals↗
PubMed1983

Effects of acivicin and dipyridamole on hepatoma 3924A cells.

Dipyridamole inhibited the incorporation of cytidine, thymidine, uridine, and guanosine in rat hepatoma 3924A cells with 50% inhibitory concentrations of 0.2 to 0.5 microM. For deoxycytidine, the 50% inhibitory concentration was about 100 times higher (23.8 microM). Addition of a combination of cytidine, deoxycytidine, and guanosine, at an optimal concentration of 80 microM each, protected the hepatoma cells from the growth-inhibitory action of the antiglutamine drug, acivicin. The protection provided by the nucleosides was blocked by dipyridamole (6 microM), but not by nitrobenzylthionosine (30 microM). The effect on cell survival of graded concentrations of 0.25 to 1.75 microM acivicin plus dipyridamole (5 microM) and 80 microM concentrations each of cytidine, deoxycytidine, and guanosine was investigated. At an acivicin concentration of 1.75 microM, survivals in the different groups were: (a) acivicin alone, 1%; (b) acivicin plus dipyridamole, 1%; (c) acivicin plus nucleosides, 78%; and (d) acivicin plus nucleosides plus dipyridamole, 3%. Acivicin and dipyridamole were cytotoxic for hepatoma 3924A cells with 50% inhibitory concentrations of 0.5 and 20.3 microM, respectively, as measured by clonogenic assay.

Animals↗
PubMed1983

[Tumor-like organ manifestations of actinomycosis].

This report describes a 36-year-old male suffering from a disease which began with subcutaneous nodules and tumors that opened to form fistulae for past 5 years. These lesions, localized in various areas, were combined with tumorlike symptoms of brain, lungs and liver. The histologic examination of one subcutaneous nodule led to the diagnosis of actinomycosis. The differential diagnosis of various forms of actinomycosis are discussed.

Actinomycosis↗