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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 415 records · Page 23Linked to original sources
PubMed1988

Ultrastructural computerized morphometry of platelets in chronic myelogenous leukemia making use of ultra-thin sections and freeze-fracture procedure. A preliminary approach.

Biochemical and morphological data have shown that the circulating platelets are deeply altered in patients with chronic myelogenous leukemia. In this report we describe the results of ultrastructural morphometry performed by means of a computerized device of the platelet shape (ultra-thin sectioned platelets) and of the platelet plasma-membrane (freeze-fractured platelets). Platelets appeared deeply modified: reduced mean platelet area and perimeter, increased surface density of the openings of the surface connected canalicular system, abnormal features of the platelet cytoplasm and some aspects of platelets joined together even if with heterogeneity in these findings did appear from patient to patient.

Adult↗
PubMed1988

Investigation of metal-species (Ca, Mg, Zn, Fe, Cu, Pb, Cd, Sn) in urine by HPLC-AAS.

Urine is separated by reversed-phase HPLC and metal-species are detected on-line by flame-AAS (Ca, Mg, Zn, Cu and Fe) or by ETAAS in fractions (Pb, Cd, Sn). With the exception of lead, which is present in urine in two forms (bound to chloride and to sulfate), all the metals are present as chlorides or chloro-complexes. The same results are found for two control urines. It is shown that addition of some drugs to urine (Ca-EDTA, tetracycline and barbiturate) alters the distribution of metal-species by formation of coordination compounds.

Barbiturates↗
PubMed1988

Insulin regulatory effects on purine- and pyrimidine metabolism in alloxan diabetic rat liver.

Aim of this study was to elucidate insulin regulatory effects on purine and pyrimidine metabolism. Livers of alloxan diabetic and insulin treated rats were freeze clamped and nucleotide pools measured using HPLC techniques. Activities of key enzymes of de novo and salvage pathways were analyzed with radioassays. In diabetic liver nucleotide triphosphate pools were reduced between 46 and 75% of controls, nucleotide monophosphate concentrations increased. Activities of de novo biosynthetic enzymes amidophosphoribosyltransferase, FGAM synthase, IMP dehydrogenase, GMP synthase, carbamoylphosphate synthase II were curtailed by 16-61%, those of salvage enzymes hypoxanthine-guanine-phosphoribosyltransferase, adenine-phosphoribosyltransferase, thymidine kinase also decreased to 31-58%. Insulin treatment for 2 and 7 days normalized nucleotide pools, activities of key enzymes of de novo and salvage pathways were increased between 2.4 and 4.1 fold compared to diabetic untreated. Activation of nucleic acid metabolism by insulin can be explained by the requirement for high energy phosphates of certain anabolic key enzymes in carbohydrate and lipid metabolism. Impaired synthesis in insulin deficiency of end products of guanylate and pyrimidine pathway required as substrates for a variety of enzymes synthesising membrane structures throw new light on the pathogenesis of some late complications of diabetic disease.

Animals↗
PubMed1988

Atherosclerosis and aging. A morphometric study on arterial lesions of elderly and very elderly necropsy subjects.

A histomorphometric study was performed on arterial wall lesions of different arterial regions (arch, thoracic, abdominal parts of the aorta; right and left common and internal carotid arteries; coronary arteries; and basilar and middle cerebral arteries), collected from 108 elderly and very elderly (greater than 90 years of age) subjects who underwent necropsy. Lumen stenosis percentage, mean intimal thickening, and mean thickness of the media were measured by means of a computerized system using a manual input and graphic printout; statistical tests were performed using variance and regression analysis. Results showed that the arterial wall lesions in patients over 60 years of age tend to be stabilized in all regions studied except for the cerebral region, where the lesions tend to have a continuous progression related to age, even in a group of subjects over 90 years of age.

Aged↗
PubMed1988

Increased thymidylate synthase (EC 2.1.1.45) activity in normal and neoplastic proliferation.

Thymidylate (dTMP) synthase (EC 2.1.1.45) activity was measured in 100,000 x g supernatant fluid with a sensitive, rapid radio assay. The activity in normal rat liver was low (0.098-0.204 nmol/hr/mg protein). dTMP synthase specific activities in rat thymus, spleen, bone marrow, testis, lung, heart, brain, kidney, and small intestine were 6297, 1842, 1500, 788, 215, 76, 61, 39 and 24%, respectively, of that of the liver. The activity in 5-day-old rat liver was 16-fold higher than in adult. dTMP synthase activity increased in rat hepatomas to 7- to 125-fold of that of normal rat liver. There was a significant correlation between the increase in synthase activity and the proliferation rates of the hepatomas. In 8 human colon carcinomas, dTMP synthase activity increased to 2.9- to 8-fold of that of normal human colon mucosa. In leukemic leukocytes from 3 leukemia patients, activity was 8- to 10-fold higher than in normal leukocytes.

Aging↗
PubMed1988

Reduction of pinocytotic vesicle surface density in cultured bovine aortic endothelial cells. A quantitative ultrastructural freeze-etching study.

The development of culture techniques for endothelium of the large vessels has stimulated many studies to understand endothelial functions in normal and pathological conditions. In this report we describe that in primary cultures the mean surface density of pinocytotic vesicles, evaluated by computerized morphometric analysis of endothelial cell plasma-membrane, dramatically decreases with respect to that of the cells immediately detached from the arterial wall (6.7 +/- 1.1 microns2 against 19.5 +/- 2.2 microns2, p less than 0.001). The results are unchanged if the cells are enzymatically or mechanically detached from the vessel wall or from the culture flask. After the first passage, the mean surface density of pinocytotic vesicles decreases further (2.5 +/- 1.3 microns2 p less than 0.01). After the 2nd and the 3rd passages, the morphometrical values of endothelial cell plasma-membrane remain low (1.5 +/- 0.2 microns2; 2.5 +/- 0.2 microns2). When endothelial cultures are employed to study pathological aspects of disease, not only the aging process but also the possible occurrence of early changes have to be taken into consideration.

Animals↗
PubMed1988

[Effect of various weather parameters on the incidence of inpatient treated children with stenosing laryngotracheitis (pseudocroup)].

A total of 1470 hospitalized children with croup in the cities of Bochum and Herne were examined over a period of 19 years, with the aim of checking whether there was any relationship between croup incidence and changes in different weather parameters such as temperature, air pressure, absolute and relative air humidity, and wind speed. The incidence of croup was seasonal, being higher in the months of January, February, and March and from September to December. Statistical evaluation by discriminant analysis, t-test and chi 2-test showed a significant correlation (alpha greater than or equal to 0.95) between croup incidence and individual weather parameters in some months. The results seem to indicate a higher frequency of croup after decreases in temperature and influx of dry air masses (decreases in absolute humidity). In some months an increased incidence of hospitalized children with croup was observed after decreases in air pressure and during weather with extremely high (w greater than 4.5) or low (w less than 1.5) wind speed. In summary, no clear and consistent relationship between incidence of croup and particular weather parameters could be found.

Adolescent↗
PubMed1987

Amphotericin B: a biological response modifier in targeting against the salvage pathways.

Dipyridamole, a nucleoside transport inhibitor which blocks the rescue effect of exogenous nucleosides, is a compound of interest for use in combination with antimetabolites of de novo purine and pyrimidine biosynthesis. This study has provided evidence that the dipyridamole inhibitory effect on nucleoside incorporation varied markedly during the course of cell growth in culture. Human colon cancer HT-29 cells in lag and log phases were highly sensitive to the blocking action of dipyridamole on thymidine incorporation with IC50 values of 0.06 and 0.07 microM respectively. In contrast, stationary phase cells were comparatively insensitive to dipyridamole with an IC50 of 46 microM. Amphotericin B restored the sensitivity of stationary phase cells to dipyridamole, lowering the IC50 value for thymidine incorporation to 0.03 microM. A similar pattern was observed for cytidine incorporation. Amphotericin B also enhanced the growth inhibitory action of dipyridamole in stationary phase cells. The combination of amphotericin B and dipyridamole should be potentially useful in cancer chemotherapy.

Amphotericin B↗
PubMed1987

Observations of serum trace elements in chronic lymphocytic leukemia.

Serum trace elements (STE) were measured in 50 patients with chronic lymphocytic leukemia (CLL) and 100 normal subjects. Copper was higher in patients than in controls (1.50 +/- 0.06 versus 1.10 +/- 0.02 micrograms/ml, P less than 0.001), increased steadily from Stage 0 to Stage 4 (P = 0.002), and correlated with the lymphocyte count and serum lactate dehydrogenase (P less than 0.01) but not with acute phase reactants. Zinc was lower in patients than in controls (0.94 +/- 0.03 versus 1.10 +/- 0.02 micrograms/ml, P less than 0.001). Zinc (NS), selenium (P = 0.039), and calcium (P = 0.033), were decreased in Stages 3-4 as compared to Stages 0-2. The copper-to-zinc ratio (CZR) increased continuously from Stage 0 to Stage 4 (P less than 0.001). Discriminant analysis between two groups, Stage 0-2 and Stage 3-4, based on serum copper, zinc, calcium, and protein levels, allowed for a correct classification of 94% of the patients. Moreover, the clinical staging of the remaining 6% was modified retrospectively according to the results of discriminant analysis. It was concluded that (1) serum copper and CZR are useful indices of the extent of disease, (2) they are independent of a nonspecific acute phase reaction, (3) STE determination could be helpful in the staging of a limited number of CLL patients, and (4) zinc deficiency could contribute to immune dysfunction in CLL.

Aged↗
PubMed1987

Hematological and biochemical action of tiazofurin (NSC 286193) in a case of refractory acute myeloid leukemia.

A patient with refractory acute myeloid leukemia was treated with tiazofurin, an agent that causes inhibition of tumor cell proliferation by depressing GTP concentrations in the malignant cells. The initial dose of 1100 mg/m2 was ineffective clinically and biochemically. Dose escalations to 1650, 2200, and finally 3300 mg/m2 resulted in a marked decrease in the absolute number of blasts without causing bone marrow hypoplasia or marked neutropenia. The decrease in the peripheral blast cell count was observed subsequent to a decline in GTP concentrations in the leukemic cells to less than 30% of the pretreatment value. Consecutive bone marrow examinations showed a remarkable shift from myeloblasts to more mature myeloid elements, suggesting an in vivo differentiative action of tiazofurin. Although a total dose of 23,650 mg/m2 was administered over a 13-day period, only very mild side effects were noted. The absence of complications reported by others in Phase I trials with tiazofurin may be related to our slow administration of the drug by pump over a 1-h period in this trial. Tiazofurin appears to be a promising agent in the treatment of leukemia because of its selective action on leukemic cells and the availability of a rapid in vitro method capable of predicting sensitivity of leukemic cells to the agent and monitoring its activity during treatment by measuring thiazole-4-carboxamide adenine dinucleotide and GTP concentrations. These observations are being tested in a larger group of leukemic patients.

Antineoplastic Agents↗
PubMed1987

Increased messenger RNA concentration for carbamoyl-phosphate synthase II in hepatoma 3924A.

Previous investigations demonstrated that carbamoyl-phosphate synthase II (synthase II) (EC 6.3.5.5) activity, amount, and in vivo synthetic rate increased approximately 9-fold in the rapidly proliferating rat hepatoma 3924A compared to normal liver. This study provides evidence by Northern and RNA dot blot hybridizations of a 13-fold increase in the amount of hepatoma 3924A synthase II mRNA compared to levels in normal liver. Southern and DNA dot blots indicated amplification of CAD hepatoma 3924A synthase II gene product.

Animals↗
PubMed1987

The modulation of serine metabolism in hepatoma 3924A during different phases of cellular proliferation in culture.

The activities of 3-phosphoglycerate dehydrogenase and serine hydroxymethyltransferase increased markedly during the transition of hepatoma cells from a resting non-proliferating culture into the proliferating growth phase. Activities declined as cells reached confluency and entered the plateau growth phase. This pattern was paralleled by changes in [14C]serine incorporation into nucleic acids. The experiments support the hypothesis that the biosynthesis of serine is metabolically coupled to its utilization for nucleotide precursor formation in cancer cells.

Animals↗
PubMed1987

Effect of ischemia on nucleosides and bases in rat liver and hepatoma 3924A.

A high-pressure liquid chromatographic method was developed which achieved a separation and quantitation of 20 biologically important nucleosides and bases. The concentrations of pyrimidine nucleosides and bases, namely deoxycytidine, cytosine, cytidine, uracil, and uridine (22.6, 10.1, 5.2, 2.9, and 2.4 nmol/ml, respectively) were high in plasma, whereas purine nucleosides and bases were present in concentrations less than 2.5 nmol/ml. In erythrocytes, the pools of xanthine, hypoxanthine, and xanthosine were 32-, 27-, and 22-fold larger, respectively, whereas cytidine, uridine, and deoxycytidine were only 21, 12, and 5% of plasma concentrations. The results suggest a compartmental system for transport of some of the purine and pyrimidine nucleosides and bases in the whole blood. Studies on the effect of ischemia on nucleoside and base pools in rat liver indicated marked increases within 30 s in the concentrations of adenine, adenosine, inosine, hypoxanthine, uridine, and xanthine, whereas in hepatoma the effects were less pronounced. By 2 and 5 min ischemia these perturbations were most marked in both liver and hepatoma. These results indicate a need for rapid freeze-clamp preparation of tissue samples to obtain precise and repeatable results in the determination of tissue nucleoside and nucleobase concentrations.

Animals↗
PubMed1987

Purification of IMP dehydrogenase from rat hepatoma 3924A.

IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme of de novo GTP biosynthesis and a promising target for cancer chemotherapy, was purified 4860-fold to homogeneity from rat hepatoma 3924A by a method including affinity chromatography in which IMP is bound to epoxy-activated Sepharose 6B. This affinity gel provided a specific elution of the enzyme with 0.5 mM IMP. The final enzyme preparation gave a single band with a molecular weight of 60,000 +/- 1000 on sodium dodecyl sulfate polyacrylamide gel electrophoresis.

Animals↗