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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 541 records · Page 30Linked to original sources
PubMed1982

Reduced umbilical artery prostacyclin formation in complicated pregnancies.

Prostacyclin synthesis is severely depressed in the umbilical arteries of neonates of mothers with gestational diabetes mellitus, juvenile-onset diabetes mellitus, or preeclamptic symptoms, and of mothers who smoke during pregnancy and diabetic mothers who smoke. The reduced production of prostacyclin might be responsible for an increased abortion rate and a higher rate of intrauterine fetal death because of a decrease in placental perfusion and umbilical blood flow.

Adult↗
PubMed1982

[On the growth of cultured bovine aortic endothelial cells. Preliminary observations on ultrastructural morphology by freeze-etching and quantitation of growth rate by phase contrast microscopy: effect of glycosaminoglycans].

Bovine aortic endothelial cells (BAEC), detached from thoracic aorta by collagenase treatment, have been studied after adding a mixture of glycosaminoglycans (GAGs) (the composition of which has been studied by Casu et al. -6), at different concentrations. GAGs at the concentration of 90 mg/100 ml of medium (Dulbecco's modification of Eagle's MEM with 10% foetal calf serum) produced an increase in the growth speed. We have quantitized these data both by counting the number of cells 24 h after trypsinization in phase-contrast-microscopy, and by measuring the time necessary to reach a certain number of influences. Ultrastructural observation at transmission electron microscope after freeze-etching preparation, didn't show any relevant modification either in the organization of cell membrane or in the cytoplasmatic structures. In some observations a conspicuous increase of "vesicular openings" ("pits") on the plasmatic membrane was evident. Statistical evaluation of this phenomenon is under consideration.

Animals↗
PubMed1982

[Effects of high density lipoproteins (HDL) and low density lipoproteins (LDL) on cultured bovine aorta endothelial cells. Preliminary observations on ultrastructural morphology of the plasma membrane by freeze-fracturing].

Bovine aortic endothelial cells (BAEC), detached with collagenase, have been studied morphologically after administration, in vitro, of human lipoprotein fractions (200 micrograms/ml of LDL, 200 micrograms/ml of HDL), 24 h before the confluence. One day after the treated cells and the control one were detached with trypsine and prepared for freeze-etching examination. The plasma-membrane has revealed, in the lipoprotein treated cells (HDL or LDL) an increased average value of the number of "pits" present upon a surface unit (P less than 0,05). Moreover, in the HDL-treated cells, the "pits", sometimes, have appeared with a different morphological evidence, similar to the aspects of exocytosis as seen e.g. in platelets or in Langerhans isle cells.

Animals↗
PubMed1982

Fluorescence depolarization and rotational modes of tyrosine in bovine pancreatic trypsin inhibitor.

The fluorescence of bovine pancreatic trypsin inhibitor (BPTI) is due to one or more of its four tyrosine residues. Observations of the stationary polarization of the fluorescence over a large range of temperatures and viscosities permit the demonstration of at least three modes of tyrosine rotation, and perhaps an ultrafast fourth one. The slowest mode is one of motion of the whole molecule; the second, a much faster motion limited to an amplitude of 11 degrees, is not changed by quenching of the fluorescence through addition of citrate and is therefore ascribed to the motion of internal tyrosines of BPTI. The third mode of motion is faster still; it has an amplitude similar to that of the second and, being sensitive to citrate quenching, is attributed to the rotation of the external tyrosine residue. A residual depolarization corresponding to a rotational amplitude of 22 degrees is deduced by comparison of the polarizations of BPTI and tyrosine dissolved in 80% glycerol-water at -40 degrees C. It is in accord in amplitude with the picosecond tyrosine rotations predicted by Karplus and collaborators from molecular dynamics computer simulations, but it could also originate, in whole or in part, from electronic energy transfer among the tyrosines.

Aprotinin↗
PubMed1982

Biochemical pharmacology of acivicin in rat hepatoma cells.

The antiglutamine agent acivicin, L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, inhibited the growth of hepatoma 3924A cells in culture. After 7 days of incubation with the drug, an LC50 of 1.4 microM was observed by determination of colony forming ability. A combination of cytidine (1 mM), deoxycytidine (10 microM) and guanosine (10 microM) completely protected the hepatoma cells against the cytotoxic action of acivicin, but each nucleoside by itself had no effect. Acivicin (0.1 mM) inhibited the incorporation of uridine and thymidine into macromolecules, but not that of leucine. Acivicin depressed the pools of CTP, GTP, dCTP, dGTP and dTTP to 46, 62, 40, 64 and 53%, respectively, but it increased UTP level to 152% of the values of untreated cancer cells. The activity of a highly purified CTP synthetase (EC 6.3.4.2) from rat liver and hepatoma 3924A was inhibited by acivicin. The inhibition was competitive with respect to L-glutamine, and the Ki values with liver and hepatoma enzymes, determined by Dixon and reciprocal plots, were 1.1 and 3.6 microM respectively. The hydroxy analog of acivicin was also a competitive inhibitor, but it was less effective than acivicin, with a Ki value of 1.8 mM for the hepatoma enzyme. Our observations on the impact of acivicin on the behavior of pools of ribonucleotides and deoxyribonucleotides and the competitive inhibition of purified CTP synthetase from hepatoma cells suggest that a major mechanism of action for this drug is the inhibition of CTP synthetase and GMP synthetase (EC 6.3.5.2).

Animals↗
PubMed1982

[Measures to be taken in burns and scaldings at the site of the accident and in the clinic].

The treatment of severe burns must be individual because age, extent and degree of burned body surface, type of accident, previous and additional damages are variable factors in burn disease. Thus there will be given only guidelines to the treatment at the place of accident and in the clinic. There are recommendations to fluid-, electrolyte- and protein replacement, medication and local treatment depending on the extent and degree of burned area. Monitoring is necessary, it includes controls of vital parameters and laboratory results.

Analgesics↗
PubMed1982

Rapid in vivo inactivation by acivicin of CTP synthetase, carbamoyl-phosphate synthetase II, and amidophosphoribosyltransferase in hepatoma.

A single injection of the anti-glutamine drug, acivicin (NSC 163501), in tumor-bearing rats in 30 min decreased the activities of amidophosphoribosyltransferase, carbamoyl-phosphate synthetase II and CTP synthetase to 56, 50, and 7% of those of the controls. By 1 hr the activities were down to 32, 13 and 3% and they remained low for 12 hr, after which they slowly returned towards normal range in 72 hr. The decline of the activity of CTP synthetase (a loss of 80% in 10 min) was the most rapid, and the activity only returned to 60% of the controls by 3 days after the acivicin injection. In the hepatoma the concentrations of ATP and UTP changed little, but those of GTP and CTP rapidly decreased, reaching at the lowest point 32 and 2%, respectively, of control values 2 hr after acivicin; concentrations started to rise at 12 hr, reaching normal levels by 48 hr. The drop in enzyme activities preceded the decline in the pools of GTP and CTP. The behavior of enzyme activities and nucleotide concentrations in the host liver had a pattern similar to that in the hepatoma; however, the changes were less extensive than those in the tumor. The differential response between tumor and liver is attributed, in part at least, to the tissue L-glutamine concentration which in the hepatoma (0.5 mM) was 9 times lower than in the liver (4.5mM). The selectivity of acivicin action in inhibiting glutamine-utilizing enzymes is also demonstrated by the lack of effect on aspartate carbamoyltransferase, an enzymic activity which resides in the same complex as that of carbamoyl-phosphate synthetase II. The rapid decline in the activities of glutamine-utilizing enzymes is attributed to an inactivation of the enzymes by acivicin which functions as an active sitedirected affinity analog of L-glutamine. The rapid modulation of the enzymic phenotype and ribonucleotide concentrations by acivicin provides a useful tool for elucidating the role of enzymic and nucleotide imbalance in the commitment of cancer cells to replication and in the targeting of anticancer chemotherapy.

Amidophosphoribosyltransferase↗
PubMed1982

In vivo inactivation by acivicin of carbamoyl-phosphate synthetase II in rat hepatoma.

The antitumor drug acivicin, L-(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, in vivo irreversibly inactivated carbamoyl-phosphate synthetase II(glutamine-dependent)(EC 6.3.5.5), the first and rate-limiting enzyme of de novo pyrimidine nucleotide biosynthesis, in transplantable rat hepatoma and host liver. With two injections of 0.5 mg acivicin per 100 g body weight to one group and two injections of 5 mg to another group, enzyme activity decreased to 20 and 1% in hepatoma and to 99 and 31% in liver respectively. Aspartate carbamoyltransferase (EC 2.1.3.2) activity was not affected. Acivicin in vitro selectively inactivated glutamine-dependent activity of the synthetase II from the hepatoma and liver, with an inactivation constant (Kinact) of 90 microM and a minimum inactivation half-time (T) of 0.7 min. The inactivation velocity with 10 microM acivicin was 5.0-fold stimulated by 2 mM MgATP and 18.4-fold by 2 mM MgATP plus 16.7 mM bicarbonate. MgATP at 0.5 mM caused half-maximum stimulation of the inactivation velocity. Under in vitro conditions, L-glutamine (1 mM) protected the enzyme from inactivation by 10 microM acivicin. The synthetase activity was protected in vitro by 6 mM concentrations for glycine (84%), L-glutamate (59%) and L-aspartate (51%) and by 0.5 mM UTP (35%) from inactivation by 20 microM acivicin. The results are compatible with the suggestion that acivicin is an active site-directed affinity analog of L-glutamine.

Adenosine Triphosphate↗
PubMed1982

Regulatory properties and behavior of activity of carbamoyl phosphate synthetase II (glutamine-hydrolyzing) in normal and proliferating tissues.

In rat livers and hepatomas, carbamoyl phosphate synthetase (glutamine-hydrolyzing) (EC 6.3.5.5) (synthetase II), the rate-limiting enzyme of de novo pyrimidine nucleotide biosynthesis, was separated from carbamoyl phosphate synthetase (ammonia) (EC 6.3.4.16) (synthetase I) ammonium sulfate and hydroxylapatite fractionations and gel filtration on Sephadex G-25. Both liver and hepatoma 3924A synthetase II activities were subject to feedback inhibition by UTP and to stimulation by 5-phosphoribosyl 1-pyrophosphate. UTP (0.5 mM) enhanced the apparent Km for MgATP from 2.3 to 7.6 mM, whereas 0.1 mM 5-phosphoribosyl 1-pyrophosphate reduced it to 0.5 mM. At 2 mM MgATP, 3 or 7 microM 5-phosphoribosyl 1-pyrophosphate yielded half-maximal activation (Ka) in the absence or presence of 0.5 mM UTP; UTP altered the stimulation kinetics from hyperbolic to sigmoidal. In the rat, synthetase II activities were highest in thymus, testis and spleen. In differentiating and regenerating rat livers, activities were 2.2- and 1.5-fold higher than in adult livers. In 17 hepatomas of different growth rates, synthetase II activity increased 1.3- to 9.5-fold over liver values; the rise correlated positively with tumor growth rates. Synthetase II activities also increased in a kidney tumor (5.0-fold) and in a sarcoma (18.1-fold) in the rat and in a human colon tumor (3.3-fold).

Animals↗
PubMed1982

Treatment of psoriasis with somatostatin.

In 22 of 26 patients suffering from psoriasis the drip infusion therapy with Somatostatin, an inhibitor of the human growth hormone (HGH), leads to complete or partial remission of skin lesions. Fast reduction of joint pains in arthropathic psoriasis could be observed in four of four patients. The repeated measurement of HGH blood level showed a decrease of HGH in five cases following the Somatostatin therapy combined with the clinical remission.

Adult↗
PubMed1982

Psychological identification of breast cancer patients before biopsy.

Fifty-six women admitted consecutively for a breast biopsy were interviewed on the day prior to the operation. Interviewer ratings and blind ratings (audiotapes) allowed a [statistically significant (alpha = 5%)] differentiation of women in whom the biopsy revealed a cancer from those whose tumor was benign. The ratings took into account characteristics assumed to be typical of the women with cancer: (1) being inaccessible or overwhelmed when interviewed; (2) emotional suppression with sudden outbursts; (3) rationalization; (4) little or no anxiety before the operation; (5) demonstration of optimism; (6) superautonomous self-sufficiency; (7) altruistic behaviour; (8) harmonization and avoidance of conflicts. On the basis of the interviews the interviewer and a blind rater predicted the correct diagnosis in 83% and 94% of all cancer patients and in 71% and 68% of all benign cases. This result is also significant (alpha = 5%). The identified psychological syndrome was found in all breast cancer patients but also in a quarter to a third of the patients with benign nodes. We interpret it as a long-standing defensive pattern adopted in the face of extreme emotional stress. A possible etiological significance for the cancerous disease cannot be derived from this study.

Adult↗
PubMed1982

Multi-enzyme-targeted chemotherapy by acivicin and actinomycin.

On the basis of our observation of the increased specific activities of glutamine-utilizing enzymes in purine and pyrimidine metabolism in hepatoma 3924A, and because the concentration of glutamine is ten times lower in the hepatomas than in the liver, the biochemical pharmacology of the anti-glutamine agent, acivicin, was examined. (1) Acivicin competitively inhibited the activities of amidophosphoribosyl-transferase, CTP synthetase and carbamoyl-phosphate synthetase II from extracts of liver and hepatoma 3924A. (2) In addition to the competitive inhibition exerted by acivicin, evidence was obtained that this drug also irreversibly inactivated in vitro the glutamine-utilizing enzymes. It is particularly relevant for the selectivity of acivicin that the activity of aspartate carbamoyltransferase, an enzyme present in the same complex as carbamoyl-phosphate synthetase II, was not affected by the anti-glutamine agent. (3) Acivicin in vivo brought down the activities of glutamine-utilizing enzymes in a period of 10 min to 1 hr after injection. CTP synthetase activity declined to less than 10% of that observed in the uninjected rats. The decreases were not reversible by various in vitro methods, but in vivo the activities returned to normal range in 72 hr. (4) The activity of aspartate carbamoyltransferase, which exists as a multi-enzyme complex with synthetase II, was not altered by acivicin injection. Similar results were observed in transplantable sarcoma in the rat. (5) The acivicin-induced decrease in enzymic activities could not be restored by purification of the enzymes. (6) In vitro studies indicated that addition of acivicin to liver or hepatoma extracts or purified enzymes rapidly decreased enzymic activities; the activities could not be restored. These results are consistent with an interpretation that acivicin acts either as a tight-binding inhibitor or as an inactivator through alkylation of the enzymes of glutamine utilization. (7) Acivicin in combination with actinomycin provided a synergistic kill of hepatoma cells in tissue culture and also inhibited the growth of transplantable solid hepatoma 3924A in the rat. (8) The synergistic biological results of combination chemotherapy with acivicin and actinomycin can be accounted for by the action of acivicin in inhibiting GMP and CTP synthetases, resulting in a decrease in GTP and CTP content, and by the actinomycin-caused inhibition of RNA polymerase in selectively blocking the utilization of GTP and CTP.

Animals↗
PubMed1982

Dynamics and time-averaged chemical potential of proteins: importance in oligomer association.

The chemical potential of a protein is a time-averaged quantity whose value depends upon the fractions of time spent in the different conformations and therefore upon the protein dynamics. If the monomer involved in an association equilibrium undergoes unfolding limited by its lifetime, its chemical potential as well as that of the associated form will not be constant and the free energy of association will be a diminishing function of the degree of dissociation. For a unique free energy of association, the logarithm of the protein concentration must change by 2.86 units to increase the degree of dissociation from 0.1 to 0.9. The dissociation of enolase appears to take place over a significantly smaller range (1.7 units), and dansyl conjugates of enolase show an even narrower range (0.9 unit). A simple descriptive theory is developed, and this shows that the values observed are explained by a difference in free energy of 1-3 kcal/mol (1 cal = 4.18 J) between the conformations present at negligible and almost complete dissociation.

Macromolecular Substances↗