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Biomedical subjects

G Weber

Publications and source records attributed to G Weber.

At least 973 records · Page 54Linked to original sources
PubMedDate not supplied

Regulation of signal transduction activity in normal and cancer cells.

UNLABELLED: The purpose of this investigation is to clarify critical aspects of the behavior and regulation of signal transduction activity in normal and cancer cells. MATERIALS AND METHODS: Signal transduction activity was determined by measuring the steady-state activity of the three synthetic enzymes involved in the conversion of 1-phosphatidylinositol to IP3, PI 4-kinase, PI 4-phosphate 5-kinase and phospholipase C. These enzymic activities were opposed by the activities of the degradative enzymes, 4-phosphatase and 5-phosphatase. RESULTS: We observed in hepatocellular carcinomas the operation of an integrated imbalance in signal transduction which was manifested in the up-regulation of the steady-state activities of the three synthetic enzymes and in the reduction of the activities of the two catabolic phosphatases. As a consequence of this enzyme imbalance there was an increase in the concentration of IP3 in hepatomas. Increased IP3 levels were also observed in numerous human carcinomas in clinical samples and in tissue culture cells. The signal transduction activity was subject to nutritional regulation and to drug action. The elevated signal transduction activity, as measured by the IP3 concentration, was down-regulated in a time- and dose-dependent fashion by the anticancer drug, tiazofurin, by the flavonoids, quercetin and genistein, and by the anti-estrogen receptor, tamoxifen. CONCLUSIONS: Our studies show that signal transduction activity is stringently linked with transformation and progression in rat and human carcinomas. Down-regulation of signal transduction activity by various drugs led to a marked reduction of IP3 concentration and then to apoptosis and induced differentiation.

Animals↗
PubMedDate not supplied

Amplified increase in signal transduction activity in cancer cells.

AIM: To elucidate the behavior of 1 phosphatidylinositol 4,5 bisphosphate (PIP2) 5 phosphatase (PIP2 5-Pase, EC 3.1.3.36) and 1 phosphatidylinositol 4 phosphate (PIP) 4-phosphatase (PIP 4-Pase) in cancer cells, the steady state activities of PIP2 5-Pase and PIP 4-Pase were determined in the particulate fractions of rat liver and in a spectrum of rat hepatomas of different growth rates and malignancy. METHODS: A standard method was developed using exogenous PIP2 or PIP as substrates. RESULTS AND DISCUSSION: One half of the maximum activities was reached at about 0.3 mM of the substrates and at 0.1 to 0.2 mM magnesium chloride. The optimum concentrations of Triton X-100 and cetyltrimethyl ammonium bromide were 0.25% (w/v) and 1 mM, respectively. PIP2 5-Pase and PIP 4-Pase activities were linear with time for 20 min and proportional with protein concentrations up to 22 micrograms per 50 microliters reaction mixture. In rat liver the steady state activities of PIP2 5-Pase and PIP 4-Pase were 1849 to 1881 and 1394 to 1670 nmol/h/mg protein. In three rat hepatomas the enzyme activities decreased to 50-51% and 33-42%, respectively. These results and our earlier data showing increased 1 phosphatidylinositol 4 kinase (EC 2.7.1.67), PIP 5-kinase (EC 2.7.1.68) and phospholipase C, PIP2 phosphodiesterase (EC 3.1.4.11) activities provide evidence of a transformation linked amplified increased capacity in signal transduction activity in cancer cells. The discovery and documentation of this integrated imbalance in regulation in phosphoinositide metabolism in cancer cells are in line with our observations in cancer cells for enzymes of purine and pyrimidine metabolism. The amplified increase in signal transduction capacity in cancer cells provides novel targets for the development of anticancer drugs.

Animals↗
PubMedDate not supplied

Differences in thermostability of thymidine kinase isoenzymes in normal ovary and ovarian carcinoma.

UNLABELLED: Thymidine kinase 1 (TK 1 EC. 2.7.1.21) the most specific and cell-cycle regulated salvage enzyme for pyrimidine nucleoside supply of DNA synthesis is a promising target to rationally designed chemo- and other therapies. The present study was undertaken to compare the heat stability of TK isoenzymes of both normal ovarian and epithelial ovarian cancer cells. Tissue extracts of epithelial ovarian carcinomas (N = 7) and normal ovaries (N = 9) were analyzed for thymidine kinase activity using the polyethyleneimine-cellulose disc radioassay. The TK activity in extracts of ovarian carcinomas was 12-fold higher than in extracts of normal ovaries. The TK activity of ovarian carcinomas decreased significantly even after 30 minutes incubation at 37 degrees C while, the enzyme activity of normal ovarian extracts was more stable and decreased to the same extent after 120 minutes. The half-life time of the enzyme activity was 82 min in the normal but only 36 minutes in the cancer tissue extract at 37 degrees C. CONCLUSION: The TK activity of malignant ovarian cells was much higher but more unstable (t1/2 = 36 minutes) than the enzyme isolated from healthy ovaries (t1/2 = 82 minutes). This profound difference in thermostability might provide the molecular background for hyperthermia combined with chemotherapy as a promising treatment for ovarian malignancies.

Adult↗
PubMedDate not supplied

[Aneurysm of the superior mesenteric vein: imaging findings].

The authors report two uncommon cases of incidental superior mesenteric vein aneurysm in two asymptomatic women. Patients underwent ultrasonography, CT and MR angiography. The etiology, clinical features and treatment are discussed along with a review of to the literature.

Aged↗
PubMedDate not supplied

Down syndrome: MR quantification of brain structures and comparison with normal control subjects.

For quantification of brain structures from MR scans, a novel, powerful stereologic tool known as Cavalieri's principle was applied. This tool enables an objective estimation of volume. The method was applied to detect differences in various brain structures between persons with Down syndrome and control subjects. On the basis of absolute values, smaller volumes for the whole brain, cerebral cortex, white matter, and cerebellum were seen in persons with Down syndrome. Similar results were observed when a normalization procedure, based on the volume of cranial cavity, was used. Stereologic determinations of the volumes of brain structures from MR images can reliably identify volume differences between persons with Down syndrome and control subjects.

Adult↗
PubMedDate not supplied

[Measuring the mineral content of the distal radius in the age of growth].

A study was carried out to characterize in the growing skeleton the absorptiometric measurement of the ultradistal radial epiphysis where the trabecular bone is higher than at proximal scanning planes. The study showed that a radius scan, 1 to 1.4 cm proximal to the ulnar tip, and consequently 4 to 6 mm proximal to the growing plate, gives reproducible informations in infants aged 6 years or more when the BMC, and not the BMC/BW, is considered, as the measurement error is 3.5% and 5.7%, respectively.

Adolescent↗
PubMedDate not supplied

Nephrocalcinosis in children and adolescents: sonographic evaluation during long-term treatment with 1,25-dihydroxycholecalciferol.

In order to study the presence of possible renal damage, 12 patients who had been chronically treated with 1,25-dihydroxycholecalciferol therapy, 1,25(OH)2D3, for hypoparathyroidism, pseudohypoparathyroidism, and hypophosphatemic rickets were examined by renal ultrasound. Two patients had normal values while 10 subjects showed nephrocalcinosis (NC) of mild, medium, or severe degree. The echographic results have been related to some calcium-phosphorus metabolism and therapeutic parameters. In those subjects with medium to severe NC, the age at the beginning of therapy was significantly younger and the dose of 1,25(OH)2D3 was significantly higher, than in the other patients. Laboratory data were not predictive of NC. Renal ultrasound is, therefore, a useful means of screening to detect even early stages of NC; its use in the follow-up is also recommended.

Adolescent↗
PubMedDate not supplied

Ultramicroscopic observations on the pseudointimal coating in implanted dacron vascular grafts.

The common use of Dacron arterial prostheses produced enormous improvement in vascular surgery, yet some serious complications such as thrombosis or infection persist, which are connected to the utilization of this material. Light and electron microscopic studies may allow a better understanding of such complications. Scanning electron microscopy and semithick sections were used to examine dacron arterial prostheses removed for failure after long-term implantation. Semithick sections showed periprosthetic inflammatory reaction and the neointimal surface never exhibited a regular endothelial layer (at S.E.M.).

Blood Vessel Prosthesis↗
PubMedDate not supplied

Some pathogenetic aspects of atherosclerotic lesions. Platelets and atherogenesis. Differences in atherogenesis in different body districts. Regression of arterial lesions in animal models.

The first part of the paper is devoted to the role of platelets in atherogenesis because the new ultrastructural techniques have revealed the morphological basis of platelet "activation". In the second part, the delayed involvement of intracranial vs extracranial cerebral arteries, afferent to the brain is examined on the basis of recent work both in man and in experimental animal models. Regression of arterial lesions is considered in the third part chiefly on the basis of contributions in experimental animals, while more data on regression in humans are expected in the near future.

Animals↗
PubMedDate not supplied

[Non-endocrine growth retardation. Diagnostic and therapeutic indications].

We analyze the most frequent conditions of non endocrine short stature divided into two groups by phenotypic criterion (dysmorphic or not). Furthermore we consider the different causes of short stature in relation to the appearance of stunted growth. The most recent etiopathogenetic advances in knowledge and the main auxologic features of each kind are reported. In the end we evaluate the current therapeutical measures and we analyse the usefulness of non specific treatments.

Alcohol Drinking↗
PubMedDate not supplied

Why some patients prefer to become manic-depressive rather than schizophrenic.

This paper reports the authors' observations on fifteen families in which a young adult member had been diagnosed as manic-depressive. All families were seen in systemic family therapy, with intervals of four to six weeks between sessions. The circular questioning method developed by Selvini-Palazzoli [1] and her team was widely employed. All families could be described as extremely rigid and bound-up systems characterized by a "restrictive parental complementarity," typical dynamics of reciprocal delegation, and certain cognitive features and shared assumptions. These "manic-depressive" families show similarities as well as differences when compared with families with schizophrenic members (i.e., "schizo-present" families). Finally, some therapeutic implications of this view and approach are developed.

Bipolar Disorder↗