Search PubMed⌕ Search

Biomedical subjects

G Thomas

Publications and source records attributed to G Thomas.

At least 649 records · Page 36Linked to original sources
PubMed1989

Effects of a pure antiandrogen on gonadotropin secretion in normal women and in polycystic ovarian disease.

To assess the role of androgens in gonadotropin regulation in women, we studied the effects of a pure nonsteroidal antiandrogen, Anandron (Cassenne, Paris, France). Nine normally cycling women (group 1) with acne and/or seborrhoea and nine patients with polycystic ovarian disease (PCOD) (group 2) received Anandron (100 mg twice a day) and a placebo. Both treatments were administered orally, in a cross-over randomized design, for two consecutive cycles (group 1) or months (group 2) separated by one cycle or 1 month. Luteinizing hormone (LH) pulse frequency and amplitude (cluster analysis), basal and gonadotropin-releasing hormone (GnRH)-stimulated plasma LH/follicle-stimulating hormone (FSH) levels were determined on day 5 of each treatment or placebo cycle. On days 5, 10, 20, and 24 of each cycle or month, plasma estradiol (E2), estrone (E1), testosterone (T), dihydrotestosterone (DHT), androstenedione (A), dehydroepiandrosterone sulfate (DHAS), sex hormone-binding globulin (SHBG) levels, and urinary androstanediol glucuronide (3 alpha-diol G) were measured. Plasma progesterone (P) levels were determined on days 20 and 24 of each cycle (group 1) and on days 5, 10, 20, and 24 (group 2). In both groups, seborrhea and acne decreased markedly within the first month and practically disappeared after 2 months of Anandron treatment. No adverse side effects were reported. None of the normal patients had any disturbance of menstrual cycles as assessed by basal body temperature shift, ultrasonography, and plasma P levels. In PCOD patients, cycles remained anovulatory.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Human mesangial cells secrete a GBM-degrading neutral proteinase and a specific inhibitor.

The factors operative during normal and disease states which govern the degradation of the glomerular extracellular matrix (ECM, glomerular basement membrane and mesangial matrix) remain poorly understood. These structures consist primarily of types IV and V collagen, which are highly resistant to the action of classical interstitial collagenases. Here we report that an intrinsic glomerular cell type, the human mesangial cell, secretes: 1) a neutral proteinase with specific activity against type IV basement membrane collagen and, 2) an inhibitory protein with the characteristics of the tissue inhibitor of metalloproteinases (TIMP). The purified enzyme has a neutral pH optimum, consists of a basic (pI 8.4) protein doublet with molecular weight of 66 and 68 kilodaltons, and is inhibited by calcium and zinc chelators. The enzyme degrades both soluble and basement membrane type IV collagen, but does not specifically degrade types I or V collagen or casein. Immunohistochemistry of cultured cells demonstrated homogeneous staining for the neutral proteinase antigen, while the TIMP antigen was detected in fewer than one-third of cultured cells. These findings suggest that the synthesis of these proteins may be independently regulated. The secretion of these factors may play an important role in the turnover of the glomerular ECM under basal or pathologic conditions.

Basement Membrane↗
PubMed1989

Expression of Drosophila Shaker potassium channels in mammalian cells infected with recombinant vaccinia virus.

A recombinant vaccinia virus containing a Drosophila potassium channel (Shaker H4) cDNA was constructed by homologous recombination between wild-type vaccinia virus DNA and a transfer plasmid. The new virus was used to infect four types of mammalian cells in culture. Electrophysiological recording 24-72 hr after infection revealed the expression of voltage-gated transient potassium channels in all four cell types. The properties of the induced currents were identical to those previously observed following injection of the Shaker H4 transcript into oocytes. Vaccinia promises to be an effective vehicle for the heterologous expression of transmembrane ion channels in a variety of cell types.

4-Aminopyridine↗
PubMed1989

Model-independent pharmacokinetics of colchicine after oral administration to healthy volunteers.

The pharmacokinetics of colchicine were studied after oral administration of three doses (0.5, 1.0 and 1.5 mg) to nine healthy male volunteers according to randomized cross-over design. Plasma and urine samples were collected during 48 h after ingestion, and assayed for colchicine levels by a specific and highly sensitive radio-immunoassay. Pharmacokinetic parameters t1/2 beta, AUC, MRT, CIT/F, CIR, Vd area/F) were calculated by model-independent methods and compared across doses by multiway analysis of variance. Terminal half-life (15.5-19.2 h), mean residence time (15.7-20.3 h), oral systemic (32.2-40.3 l/h) and renal (3.9-4.7 l/h) clearances, and oral volume of distribution (11.4-14.9 l/kg) did not differ significantly between doses, whereas the area under the concentration-time curve was proportional to dose. Our results show that: 1. within the dose range studied (0.5-1.5 mg), the pharmacokinetics of colchicine are linear; 2. monitoring colchicine levels up to 48 hours yields much larger estimates of terminal half-life and volume of distribution than previously reported from considerably shorter studies.

Administration, Oral↗
PubMed1989

Clobazam increases pulsatile luteinizing hormone secretion in normal men.

To investigate the effects of the 1,5-benzodiazepine, clobazam, on LH secretion in normal men, LH pulsatile secretion was defined after oral administration of 40 mg of clobazam or a placebo to 6 healthy male volunteers, according to a randomized cross-over design. LH pulse frequency increased significantly from a mean of 3.8 (range 3-5) pulses/8 h after placebo, to a mean of 5 (range 4-7) pulses/8 h (P less than 0.05), after clobazam. Mean LH concentrations and peak amplitudes did not change significantly. These results suggest that clobazam mediates its effects on LH secretion at the hypothalamic level by increasing the frequency of episodic GnRH release.

Adult↗
PubMed1989

[2-stage reconstruction in large loss of substance of the thigh using a fasciocutaneous flap and later on massive bone allograft].

The authors are reporting an observation in a 60 years old patient, of a serious gaping after a traumatism of the thigh with a massive loss of skin and muscles on the lateral aspect and a comminuted fracture the femoral diaphysis over 14 cm. There was no major vascular nervous lesion and after some time of paring and monitoring a fascio-cutaneous fore-inner flap of the thigh was realized. In the second stage, after the closing-up, a frozen-kept femoral allo-transplant was fitted and kept in by means of a bolted nailing. 36 months after the traumatism the transplant was assimilated and the patient was able to walk without any stick. The lack of any serious nervous vascular lesion in this particular case led to realize a rarely employed flap which enabled to solve the problem of the loss of the skin and muscles quickly and to realize the reconstruction by means of a massive bone allo-transplant, the only alternative to obtain a functional member.

Bone Transplantation↗
PubMed1989

Interdisciplinary aspects of iodine prophylaxis in German Democratic Republic.

Endemic goiter still occurs in several European countries. Alimentary iodine deficiency could be proved as the main cause of endemic prevalence. Extensive epidemiologic surveys showed the great medical and economical impact of this matter for the GDR. Over 200 million Marks might be spent for diagnosis and treatment of thyroid patients per year. Also in the field of veterinary medicine and animal production iodine deficiency plays an important role. Under the conditions of iodine deficiency the fodder containing nitrate and glucosinolates (e.g. bruised rape extraction) results in additional goitrogenic effects (so-called indirect or relative iodine deficiency). Due to iodine deficiency disorders considerable losses of yields in cattle, pigs and sheep occurred. The content of iodine in animal products used for human nutrition was subsequently low. Considering the ecological implication of these problems an Interdisciplinary Iodine Commission within the Society for Endocrinology and Diseases of Metabolism of the GDR was established. Together with the governement authorities it worked out corresponding recommendations for the prophylaxis and control of its efficiency. In 1986 the iodination of most of the packed salt (32 mg KIO3/kg = = 19 mg I/kg) and the administration of iodinated mineral mixtures for the animal production were started for pigs in the whole territory of GDR and for cattle in the southern counties of the GDR only. These activities have been accompanied by information of TV as well as in the newspapers and medical journals. Thus, an improved supply of iodine to the population through iodinated table salt and animal products can be taken into account. The efficiency of these prophylactic measures is controlled interdisciplinarily.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Husbandry↗
PubMed1988

Selective channelling of arachidonic and linoleic acids into glycerolipids of rat hepatocytes in primary culture.

Rat hepatocytes in primary culture were incubated with a mixture of linoleic and arachidonic acid at various total fatty acid/serum albumin molar ratios. Mixed fatty acids were taken up at the same rate and distributed with the same pattern as fatty acids added separately. The rates of total uptake, incorporation into hepatocyte and secreted triacylglycerols and beta-oxidation were linearly related to the fatty acid/albumin ratios, whereas the rate of incorporation into phospholipids was saturable. Neither the uptake rate nor the distribution of both fatty acids considered together varied with the arachidonic acid/linoleic acid molar ratio. Changes in this ratio and in the uptake rate led to significant variations in the respective fate of the fatty acids. The preferential channelling of arachidonic acid versus linoleic acid into beta-oxidation and phosphatidylinositol was greatest at a low uptake rate and then decreased as the uptake rose. Conversely, the preferential channelling of arachidonic acid versus linoleic acid into phosphatidylcholine, but not phosphatidylethanolamine, increased with the uptake rate. Moreover, both arachidonic acid and linoleic acid were preferentially incorporated into the 1-palmitoyl molecular species of phosphatidylcholine and phosphatidylethanolamine at a low uptake rate, and of phosphatidylcholine at a high uptake rate. This could be related to the synthesis of biliary phosphatidylcholine, of which 1-palmitoyl-2-linoleoyl and 1-palmitoyl-2-arachidonoyl are the main molecular species. Linoleic and arachidonic acid were selectively distributed into distinct metabolic pools of triacylglycerol, the intrahepatocyte pool which preferentially incorporated linoleic acid at a low uptake rate and the secreted pool in which the relative enrichment of arachidonic acid increased with the uptake rate. This strengthens the central role of hepatic secretion in the supply of arachidonic acid to peripheral tissues.

Animals↗
PubMed1988

Concerted nonsyntenic allelic loss in human colorectal carcinoma.

Familial polyposis coli (FPC) is caused by an autosomal dominant gene on chromosome 5, and it has been proposed that colorectal cancer in the general population arises from loss or inactivation of the FPC gene, analogous to recessive tumor genes in retinoblastoma and Wilms' tumor. Since allelic loss can be erroneously scored in nonhomogeneous samples, tumor cell populations were first microdissected from 24 colorectal carcinomas, an additional nine cancers were engrafted in nude mice, and nuclei were flow-sorted from an additional two. Of 31 cancers informative for chromosome 5 markers, only 6 (19%) showed loss of heterozygosity of chromosome 5 alleles, compared to 19 of 34 (56%) on chromosome 17, and 17 of 33 (52%) on chromosome 18. Therefore, it appears that (i) FPC is a true dominant for adenomatosis but not a common recessive gene for colon cancer; and (ii) simple Mendelian models involving loss of alleles at a single locus may be inappropriate for understanding common human solid tumors.

Adenocarcinoma↗
PubMed1988

Identification of the 40 S ribosomal protein S6 phosphorylation sites induced by cycloheximide.

Injection of cycloheximide into rats induced the incorporation of up to 5 mol of phosphate/mol of liver 40 S ribosomal protein S6. Treatment of the protein with cyanogen bromide generated three phosphopeptides of Mr approximately 31,000, approximately 27,000, and approximately 4,000. Increasing the concentration of cyanogen bromide or redigestion of the larger peptides with additional cyanogen bromide converted almost all the phosphate-containing peptides into the Mr approximately 4,000 peptide. This peptide was isolated by reverse phase high pressure liquid chromatography, and the phosphoserines were identified by amino acid sequence analysis after being converted to S-ethyl-cysteine. The results show that the phosphate is incorporated into 5 of 7 serines clustered in a small 13-amino acid segment of the protein. By aligning the sequence of the Mr approximately 4,000 peptide with the recently published mouse cDNA sequence of S6, it is shown that this peptide resides at the carboxyl terminus of the protein. The relevance of the cycloheximide-induced sites of S6 phosphorylation to those stimulated by a variety of mitogens and oncogenes is discussed.

Animals↗
PubMed1988

Vasodilatory properties of mono-L-arginine-containing compounds.

Benzoyl derivatives of L-arginine, unlike arginine, elicited relaxation of pre-contracted rat aortic rings in a concentration dependent manner. The most potent relaxing agent was N-alpha-benzoyl-L-arginine ethyl ester. The relaxation was abolished by methylene blue, but not by indomethacin. When incubated with rat aortic rings, the benzoyl derivatives exhibited colorimetric reactions characteristic of citrulline and nitrite ion. This indicates the presence of a peptidyl arginine deiminase like activity in rat aorta. Citrulline had no vasodilatory property. The other product of the iminase reaction is ammonia which through oxygenase pathway may generate nitric oxide, the proposed endothelium derived relaxing factor(EDRF). Our results suggest that an as yet unidentified arginine derivative from the endothelium may be the biological precursor of EDRF.

Animals↗
PubMed1988

Yeast KEX2 endopeptidase correctly cleaves a neuroendocrine prohormone in mammalian cells.

Mammalian cell lines (BSC-40, NG108-15, and GH4C1) that cannot process the murine neuroendocrine peptide precursor prepro-opiomelanocortin (mPOMC) when its synthesis is directed by a vaccinia virus vector were coinfected with a second recombinant vaccinia virus carrying the yeast KEX2 gene, which encodes an endopeptidase that cleaves at pairs of basic amino acid residues. mPOMC was cleaved intracellularly to a set of product peptides normally found in vivo, including mature gamma-lipotropin and beta-endorphin1-31. In GH4C1 cells (a rat pituitary line), product peptides were incorporated into stored secretory granules. These results suggest that the inability of any particular cell line to process a prohormone precursor is due to the absence of a suitable endogenous processing enzyme.

Cell Line↗
PubMed1988

Loss of alleles on chromosome 18 and on the short arm of chromosome 17 in polyploid colorectal carcinomas.

The zygosity of 19 colorectal carcinomas (either near-diploid or polyploid) from patients known to be heterozygous for RFLPs located on chromosome 18 or on the short arm of chromosome 17 has been examined. In most cases, at least one allele was significantly under-represented. The reason for the absence of complete loss of heterozygosity was investigated for 5 polyploid tumors. It was shown that the diploid component which, in these tumors, is essentially composed of non-neoplastic cells, remains heterozygous as the polyploid component invariably loses heterozygosity. The results strongly suggest that many colorectal carcinomas originate from a single cell which had lost at least part of either chromosome 18 or of one short arm of chromosome 17, or both.

Adult↗
PubMed1988

Protein phosphatase 2A inactivates the mitogen-stimulated S6 kinase from Swiss mouse 3T3 cells.

Treatment of quiescent 3T3 cells with sodium orthovanadate induces a 10-fold stimulation of a kinase that phosphorylates ribosomal protein S6. The kinase in crude extracts is extremely labile and rapidly loses activity when incubated at 37 degrees C. This reaction is blocked by phosphatase inhibitors such as p-nitrophenyl phosphate and beta-glycerophosphate, suggesting that dephosphorylation of the kinase leads to its inactivation (Novak-Hofer, I., and Thomas, G. (1985) J. Biol. Chem. 260, 10314-10319). After three steps of purification the kinase can be separated from greater than 99% of the cellular phosphorylase a phosphatases. At this stage the kinase preparation is almost completely stable but can be inactivated by readdition of specific column fractions that contain both phosphorylase phosphatase and protease activity. However, employing a number of specific inhibitors it is shown that the inactivating agent in these fractions is a protein phosphatase. Furthermore, the physical and enzymatic properties of the kinase inactivator argue that it can be classified as a type 2A phosphatase. These results are consistent with the finding that the purified catalytic subunits of phosphatase type 1 and type 2A also inactivate the kinase. At equivalent phosphorylase a phosphatase activities, the type 2A catalytic subunit is 3 times more potent than the type 1 enzyme in carrying out this reaction. These data indicate that the major S6 kinase inactivator in 3T3 cell extracts is a type 2A phosphatase, supporting the hypothesis that the orthovanadate-stimulated S6 kinase is regulated in vivo by a phosphorylation-dephosphorylation mechanism.

Animals↗