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Biomedical subjects

G Snyder

Publications and source records attributed to G Snyder.

At least 37 records · Page 2Linked to original sources
PubMed1985

Ab initio studies of the antiviral drug 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl) thymine.

The antiviral drug 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl) thymine (FMAU) exhibits a high therapeutic index against a number of herpesviruses. As with other drugs which are nucleoside analogs, such as 1-(2-fluoro-2-deoxy-beta-D-arabinofuranosyl)-5-iodocytosine and others, the activity seems to be strongly related to the presence of a fluorine atom in the sugar moiety, in the arabino position. Theoretical calculations, using quantum-chemical methods, are used to elucidate the role of the fluorine in the arabino position and to provide information about the sugar puckering. The results seem to indicate that the fluorine atom prevents the rotation of the base around the sugar-base bond, locking it into an anti structure (Fig. 2,A3) which might be related to its exposure to enzymatic attack. The sugar study confirms the endo position (above the plane) of the C'2 carbon as opposed to the endo position of the C'3 carbon.

Antiviral Agents↗
PubMed1984

Self-consistent-field comparative studies of some nitrosoureas and nitrosamides.

Ab initio (self-consistent-field) calculations are performed in order to obtain information about the most stable conformers of methylnitrosourea, chloroethyl nitrosourea, and their corresponding amides (methylnitrosamide and chloroethylnitrosamide). While nitrosoureas are found to exhibit a Z-conformation, nitrosamides are found to exhibit an E-conformation, a difference which could account for their different stabilities toward in vivo decomposition and which could, as such, influence their carcinostatic activity.

Chemical Phenomena↗
PubMed1981

Action of thyrotropin-releasing hormone on mammotrophs and thyrotrophs.

Anterior pituitary cells from 15-day female rats were separated by unit gravity sedimentation into four populations (designated regions I-IV) based on the profile of cell distribution and the resulting content of radioimmunoassayable (RIA) hormones. The cells in regions II and IV released thyrotropin (TSH) in response to thyrotropin-releasing hormone (TRH, 5 ng/ml); however, those in region IV released only approximately 5% of their RIA content, whereas those in region II released approximately 26% in response to the same stimulus. Concomitant elevation of cAMP and of cGMP occurred in region II cells but only cGMP was elevated in region IV cells. Mammotrophs were localized in region III. They responded to TRH by releasing prolactin (PRL) and exhibiting increased cAMP content. These data provide support for the existence of two functionally distinct populations of thyrotrophs in 15-day-old female rats. The data also imply that cAMP is involved in TRH induced PRL release, whereas cGMP is involved in TRH-induced TSH release.

Animals↗
PubMed1981

A self-consistent field molecular orbital study of hydroxyguanidine.

Theoretical self-consistent field molecular orbital calculations indicate that the hydroxyguanidinium ion can dissociate in alkaline or neutral medium by the loss of the hydroxyl proton, leading to the formation of a strong nucleophilic agent which can attack a positive receptor in enzymes, acting in this way as an antitumor and an antiviral agent. Geometry optimization, total energies, and net atomic charges are calculated using a Gaussian basis set for the hydroxyguanidinium ion and its conjugate bases.

Antineoplastic Agents↗
PubMed1980

In vitro stimulation of prolactin release by vasoactive intestinal peptide.

The effect of vasoactive intestinal peptide (VIP) on anterior pituitary hormone release was examined in a variety of in vitro preparations. Synthetic VIP was capable of stimulating increased prolactin (PRL) release from male rat hemipituitaries in doses as low as 10-9M only when the enzyme inhibitor bacitracin was present in the incubation medium. Natural porcine VIP was similarly capable of stimulating PRL release, but only at higher doses (10-6M). Additionally, synthetic VIP was capable of stimulating PRL release from dispersed anterior pituitary cells harvested from adult male and lactating female rats and from an enriched population of lactotrophs obtained by unit gravity sedimentation of similar dispersed cells from infantile female rats. No effect of VIP on luteinizing hormone, growth hormone or thyroid stimulating hormone release was seen. These findings taken in concert with the presence of VIP in the hypothalamus, pituitary and hypophyseal portal plasma of the rat suggest a physiological role for VIP in the control of PRL secretion.

Animals↗
PubMed1980

Chromatographic and biologic analysis of ME and OVLT LHRH.

The luteinizing hormone (LH)-releasing activities a pooled rat organum vasculosum lamina terminalis (OVLT) and median eminence (ME) tissues were evaluated for chromatographic and biologic similarity and compared to those of synthetic decapeptide LH-releasing hormone (LHRH). The LHRH detected in these extracts appeared similar chromatographically (Sephadex G-25) to synthetic LHRH. These extracts, as well as synthetic LHRH, were also capable of stimulating dose dependent gonadotropin release form cultures rat gonadotrophs. These findings suggest a physiological role of the LHRH present in the rat OVLT in the control of gonadotropin secretion.

Animals↗
PubMed1980

Gonadotropin release and cyclic nucleotides: evidence for luteinizing hormone-releasing hormone-induced elevation of guanosine 3',5'-monophosphate levels in gonadotrophs.

To investigate the participation of cyclic nucleotides in LHRH-mediated gonadotropin release, cells from the anterior pituitaries of 15-day-old female rats were fractionated on an albumin gradient by sedimentation at unit gravity. gonadotrophs and somatotrophs were detected in the fractions by histology and RIA of hormone content, then the cells were pooled into three subpopulations and cultured overnight. The effect of LHRH on hormone release and cyclic nucleotide content was examined by incubation in the presence or absence of the releasing hormone. After 60 min, LHRH (5 nM) had induced a 5- to 6-fold increase in LH release only from the cells in the subpopulation which was enriched in gonadotrophs. At no time did LHRH influence cAMP levels in any of the cells; however, the cGMP content of the cells in the gonadotroph-containing pool rose to twice that in the controls after only 15 min in the presence of LHRH. The increase in cGMP concentration in the cells was at or near maximum by the time of the initial sampling; however, LH continued to accumulate in the medium over the entire test period. These observations support the view that cGMP is involved in the action of LHRH.

Animals↗
PubMed1978

A possible role for cyclic GMP in mediating the effect of luteinizing hormone releasing hormone on gonadotropin release in dispersed pituitary cells of the female rat.

In continuing studies on cyclic nucleotide involvement in the regulation of gonadotropin release, we have measured the cyclic nucleotide content and rate of LH and FSH release during stimulation by LHRH of dispersed overnight cultured cells from the pituitaries of adult female rats. The minimal effective concentration of LHRH was 0.1 nM and half maximal stimulation of gonadotropin release was observed in the presence of 1.0 nM LHRH. Significant release of both LH and FSH was detectable after only 10 min in the presence of 5 nM LHRH. The presence of fetal calf serum (FCS) in the overnight culture medium increased basal cGMP levels significantly, whereas horse serum (HS) had no effect, therefore all experiments were conducted on cells cultured in the presence of HS. Treatment of the cultured cells with the phosphodiesterase inhibitors theophylline (TH) or isobutyl-methyl-xanthine (MIX) revealed a preferential stimulatory effect of TH on basal cAMP levels and of MIX on cGMP levels. Throughout these experiments, LHRH had no effect on cAMP levels. In the presence of MIX, concentrations of the releasing hormone as low as 1 nM induced a significant rise in the level of cGMP whereas in its absence, cGMP levels appeared to be unchanged by LHRH. The increase was detectable after 10 min of incubation. MIX alone slightly increased LH and FSH release and significantly potentiated the response of the cells to increasing doses of LHRH up to, but not beyond, 10 nM. The data support the possibility that cGMP may be involved in the mechanism of action of LHRH.

1-Methyl-3-isobutylxanthine↗
PubMed1977

Functional heterogeneity in somatotrophs isolated from the rat anterior pituitary.

Somatotrophs in suspensions of anterior pituitary cells from adult male rats can be separated into 2 fractions by density gradient centrifugation. In addition to their different densities, somatotrophs in these 2 fractions can be distinguished morphologically by their staining characteristics and ultrastructure. Somatotrophs of lesser density (type I; approximately 1.068 g/cm3) have fewer secretory granules and a more extensive Golgi apparatus than the somatotrophs of greater density (type II; approximately 1.073 g/cm3). Responsiveness of type I and type II cells to secretory agents (i.e., dibutyryl cyclic adenosine monophosphate, somatostatin, thyroxine, and hydrocortisone) was evaluated by GH radioimmunoassay. Type I cells were consistently more responsive (% GH release) than type II cells. During 7 days in culture, type I cells produced more (approximately 200%) GH than they initially contained, whereas type II cells did not show evidence of increased GH production. Hydrocortisone significantly stimulated GH production in type I, but not type II cells. These results support the hypothesis that at least 2 functionally distinct populations of somatotrophs are present in the anterior pituitary gland of the adult male rat.

Animals↗
PubMed1977

Experimental and clinical therapy of diabetes by transplantation.

Prevention, delay, or reversal of the microvascular complications of diabetes is the ultimate goal of pancreatic islet cell transplantation. Advances in surgical techniques and in islet isolation procedures have made the achievement of this goal a practical possibility. Microvascular lesions have indeed been prevented and even reversed in successful islet cell transplantation experiments in rats. Successful application of pancreatic islet cell transplantation in the human now awaits the development of effective suppression of rejection.

Animals↗
PubMed1975

A short method for the isolation of somatotrophs from the rat pituitary gland.

Application of a density gradient centrifugation procedure for the isolation of somatotrophs from dispersed rat anterior pituitary cells is described. Two sequential discontinuous gradients of bovine serum albumin are used to enrich the somatotroph population from a frequency of 38% in the initial cell suspension to a final purity of 85%. The isolated somatotrophs retain both histochemical and ultrastructural integrity throughout the isolation procedure. The isolated somatotrophs also release immunoassayable growth hormone when incubated with 6 mM dibutyryl 3',5'-cyclic AMP. The method offers the advantages of being both simple and short.

Animals↗