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Biomedical subjects

M D Bregman

Publications and source records attributed to M D Bregman.

31 records · Page 2Linked to original sources
PubMed1983

Dexamethasone, prostaglandin A, and retinoic acid modulation of murine and human melanoma cells grown in soft agar.

The cloning efficiencies of a murine melanoma cell line (S91 CCL 53.1) and a human melanoma cell strain (C8146c) were inhibited by dexamethasone (DEX), prostaglandin A1 (PGA1), and beta-all-trans-retinoic acid (RA) in a dose-dependent manner. Murine melanoma tumor colony-forming units (MTCFU) were inhibited more than 99% by DEX (1 X 10(-7) M) and RA (1 X 10(-7) M) with a concentration needed to produce a 50% reduction in colony formation for both hormones of 5 X 10(-9) M. Combinations of DEX and RA effected a synergistic inhibition on colony formation, which was reflected by a 11/2 log reduction in the hormone concentration needed to produce a greater than 99% inhibition of colony formation. When PGA1 was added to DEX and RA, a greater than additive reduction in colony formation was observed. Human MTCFU from cell strain C8146c were inhibited more than 85% at an RA concentration of 1 X 10(-7) M, but they were reduced only to 40% of control at a DEX concentration of 1 X 10(-6) M. DEX-RA produced an additive inhibition of colony formation. Addition of submaximal amounts of PGA1 to DEX-RA combinations or to either hormone alone resulted in synergistic reduction of human MTCFU. These results demonstrated that the proliferative potential of human and murine melanomas can be simultaneously regulated by DEX, PGA1, and RA.

Agar↗
PubMed1982

Hyperglycemia of diabetic rats decreased by a glucagon receptor antagonist.

The glucagon analog [l-N alpha-trinitrophenylhistidine, 12-homoarginine]-glucagon (THG) was examined for its ability to lower blood glucose concentrations in rats made diabetic with streptozotocin. In vitro, THG is a potent antagonist of glucagon activation of the hepatic adenylate cyclase assay system. Intravenous bolus injections of THG caused rapid decreases (20 to 35 percent) of short duration in blood glucose. Continuous infusion of low concentrations of the inhibitor led to larger sustained decreases in blood glucose (30 to 65 percent). These studies demonstrate that a glucagon receptor antagonist can substantially reduce blood glucose levels in diabetic animals without addition of exogenous insulin.

Animals↗
PubMed1981

Glucagon structure-function relationships using isolated rat hepatocytes.

The ability of glucagon and several of its semi-synthetic analogues to stimulate glucose production in isolated rat hepatocytes was measured and compared for relative potencies. The order of decreasing biological activities of glucagon in this assay was as follows: glucagon greater than [HArg12]-glucagon greater than [des-Asn28, Thr29][homoserinehydrazide27]-glucagon approx. equal to [des-His1]-glucagon greater than [des-Asn28, Thr29][homoserinelactone27]-glucagon greater than [des-Asn28, Thr29]-[n-butylhomoserineamide27]-glucagon greater than glucagon1-21. Qualitatively, these results are similar to those obtained previously in the hepatic plasma membrane adenylate cyclase assay. Minor exceptions were noted for the hydrazide derivative and the partial agonist [des-His1]-glucagon, both of which were slightly more potent relative to glucagon in the glycogenolytic assay than in the adenylate cyclase assay. The assay provides important insight into glucagon structure-function relationships.

Amino Acid Sequence↗
PubMed1980

Glucagon amino groups. Evaluation of modifications leading to antagonism and agonism.

Using native glucagon and [12-homoarginine]glucagon (analogue A), prepared in high yield and purity by new procedures, we have synthesized the following glucagon analogues by semisynthetic methods: [1-deshistidine][12-homoarginine]glucagon (analogue B); N alpha-carbamoylglucagon (analogue C); N alpha, N epsilon-dicarbamoylglucagon (analogue D); [1-N alpha-carbamoylhistidine, 12-N epsilon-trinitrophenyllsyine]glucagon (analogue II); [1-deshistidine] [2-N alpha-trinitrophenylserine, 12-homoarginine]glucagon (analogue III); and [1-N alpha-trinitrophenylhistidine, 12-homoarginine]glucagon (analogue IV). The introduction of hydrophylic groups at the alpha- and epsilon-amino positions of glucagon results in a reduction in potency. The alpha-position is also involved in biological activity. Carbamylation of the alpha-position results in a partial agonist (analogues C and D). The introduction of hydrophobic groups and the neutralization of the positive charge at the alpha- and epsilon-amino positions result in glucagon antagonists (analogues II, III, and IV). [1-N alpha-Trinitrophenylhistidine, 12-homoarginine]glucagon (analogue IV) is the most potent inhibitor tested. Based on its competitive inhibitory action, this analogue appears to have about one-third the affinity of glucagon for the receptor site. These modifications at the epsilon-amino position cause an increase in the secondary structure of the peptide (as shown by circular dichroism studies) which may be related to their biological activities.

Adenylyl Cyclases↗
PubMed1980

Synthesis and structure-function studies of melanocyte stimulating hormone analogues modified in the 2 and 4(7) positions: comparison of activities on frog skin melanophores and melanoma adenylate cyclase.

The synthesis and purification of several analogues of the melanotropins with amino acid substitutions at the tyrosine-2 and methionine-4(7) positions are reported. The compounds synthesized included [4-norleucine]-alpha-MSH, [7-norleucine]-beta p-MSH, [2-3',5'-diiodotyrosine]-alpha-MSH, [2-D-tyrosine]-alpha-MSH, and [2-phenylalanine,4-norleucine]-alpha-MSH. The biological activities of these derivatives were measured and compared on normal melanocytes (frog skins) and on transformed melanocytes (mouse melanoma adenylate cyclase), over the entire dose-response range. All compounds tested were full agonists in both assay systems but varied considerably in potency. The relative potencies in the frog skin assay (alpha-MSH = 1.0) were as follows: [Nle7]-beta p-MSH (5.2) > [Nle4]-alpha-MSH (2.3) > alpha-MSH (1.0) > [Phe2,Nle4]-alpha-MSH (0.80) > beta p-MSH (0.55) > [I2-Tyr2]-alpha-MSH (0.12) > [D-Tyr2]-alpha-MSH (0.04). The relative potencies in the melanoma adenylate cyclase system were [Nle7]-beta p-MSH (4.2) > beta p-MSH (2.2) > [Nle4]-alpha-MSH (2.0) > alpha-MSH (1.0) approximately equal to [Phe2,Nle4]-alpha-MSH (0.9) > [I2-Tyr2]-alpha-MSH (0.40) > [D-Tyr2]-alpha-MSH (0.20). There appears to be some differences in structural specificity at the melanotropin receptors of the two cell systems.

Adenylyl Cyclases↗
PubMed1978

Synthesis and properties of a photoaffinity probe for the glucagon receptor in hepatocyte plasma membranes.

The reaction of glucagon with 4-fluoro-3-nitrophenylazide has been shown to afford the photosensitive derivative, Nepsilon-4-azido-2-nitrophenyl-glucagon. The structure and properties of this derivative were established by amino acid analysis, absorption and fluorescence spectroscopy, deamination, Edman degradation and photolysis. This photoaffinity derivative of glucagon has been used to label specifically glucagon binding sites on hepatocyte plasma membranes.

Amino Acids↗
PubMedDate not supplied

Effect of single dose ionizing radiation on the cellular proliferation and apparent radiosensitivity of melanoma.

An important variable in determining in vitro cell survival is the time interval between treatment and assay. One manifestation of radiation damage is the introduction of a division delay in which the post-radiation division rate is less than the pre-radiation division rate. We have examined the influence of length of incubation on radiosensitivity of murine and human melanoma cells in a soft-agar assay. In general, the longer the incubation period the larger was the median colony diameter within control or experimental groups. Hence apparent radiosensitivity decreased with increased length of incubation.

Animals↗