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Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 289 records · Page 16Linked to original sources
PubMed1987

Bioavailability and disposition of metoclopramide after single- and multiple-dose administration in diabetic patients with gastroparesis.

The disposition of metoclopramide after acute and chronic administration was determined in four diabetic patients with gastroparesis who had a creatinine clearance of 70.8 +/- 10.7 mL/min (mean +/- SD). Single, 10-mg oral and intravenous doses were administered on days 1 and 2, respectively, followed by 10 mg orally every six hours for three weeks. A second, 10-mg intravenous bolus dose was administered on the last morning of chronic therapy. Metoclopramide concentrations were determined by high performance liquid chromatography. The elimination half-life, steady-state volume of distribution, and total body clearance after the initial intravenous dose were 3.9 +/- 1.2 hr, 2.7 +/- 0.3 L/kg, and 0.57 +/- 0.14 L/hr/kg, respectively. The initial bioavailability was 67.7 +/- 12.6%. After three weeks of chronic therapy, no significant differences in total body clearance (0.72 +/- 0.42 L/hr/kg) or bioavailability (77.5 +/- 16.8%) were observed. Thus the pharmacokinetics and bioavailability of metoclopramide were not altered during chronic therapy in these diabetic patients.

Adult↗
PubMed1987

Acute chondrolysis complicating Legg-Calvé-Perthes disease.

Of 270 children with Legg-Calvé-Perthes (LCP) disease, roentgenographic evidence of chondrolysis was noted in 12 (4.5%) within one year after diagnosis and appropriate management. Only in six hips of these 12 patients did the retrospective clinical, histological, and orthopedic findings fulfill the diagnostic requirements for chondrolysis. Sequential roentgenographic findings included initial periarticular osteoporosis and subchondral cortical irregularities, subsequent narrowing of the joint space, premature fusion of the growth plate, and eventual development of degenerative arthritis. The early roentgenographic recognition of chondrolysis is emphasized because it has an untoward effect on the prognosis of LCP and should therefore prompt a different orthopedic approach.

Acute Disease↗
PubMed1987

Congener derivatives and conjugates of histamine: synthesis and tissue and receptor selectivity of the derivatives.

A series of 19 congener derivatives and conjugates of histamine was synthesized and tested to determine whether the ligands would alter the conventional histamine activity in various tissues. The derivatives, which contained either branched or unbranched aliphatic groups, aromatic amide groups, or dipeptides, exhibited affinities for histamine type 1 and/or type 2 receptors that were widely different from the progenitor. The p-trifluoromethyl derivative of histamine with an intermediate chain length of four methylenes (compound 13) was the most potent lymphocytes H2 receptor agonist but was inactive on guinea pig myocardium H2 receptors. The deletion of a single methylene chain (compound 12) from this compound resulted in total loss of its H2 activity on lymphocytes and its H1 activity on aorta. Compound 12 became an exclusive H1 agonist on lymphocytes H1 receptors. The dipeptide conjugate (compound 17) and the aliphatic congener derivative (compound 18), both with four methylenes, retained some of the activity on guinea pig myocardium H2 receptors, but lost their activity on lymphocytes H2 receptors. Therefore, histamine can be modified at sites that are at a distance from the imidazole moiety, resulting in tissue selective histamine receptor agonists.

Animals↗
PubMed1987

Possible origin of a calmodulin gene that lacks intervening sequences.

The divergent, muscle-specific allele of the chicken calmodulin gene contains no intervening sequences and apparently was produced by a reverse transcriptase-mediated event. The nucleotide and deduced amino acid sequences of this gene were compared with nucleotide and amino acid sequence data of other known calmodulin genes in order to investigate its evolutionary history. These comparisons, as well as the CpG dinucleotide content, support the conclusion that this highly divergent chicken calmodulin gene did not exist for any significant period of times as a pseudogene and suggest plausible alternative genetic histories. The most parsimonious history involves the viral import of a very old foreign gene of high CpG content.

Amino Acid Sequence↗
PubMed1987

Conjugates of catecholamines. VII. Synthesis and beta-adrenergic activity of peptide catecholamine conjugates.

A series of novel catecholamine derivatives has been prepared in which one of the N-methyl substituents of isoproterenol has been extended by a spacer consisting of a chain of four methylenes which terminates with an amide linkage to a peptide, the point of attachment being via the aromatic amino group of p-aminophenylalanine. In one of the derivatives, two catecholamines are attached to the same peptide in this manner. The peptides, which range in size from three to eight amino acid residues and contain phenylalanine, glycine, and L-alpha-amino-delta-hydroxyvaleric acid, were synthesized via stepwise and fragment condensation techniques. The beta-adrenergic agonist activities of the derivatives were evaluated in vitro by measuring the intracellular accumulation of cyclic AMP in S49 mouse lymphoma cells.

Adrenergic beta-Agonists↗
PubMed1987

Specific cross-gender behaviour in boyhood and later homosexual orientation.

Data from a group of males aged 13 to 23, who as children exhibited extensive cross-gender behaviour, was analysed. In boyhood they frequently played with dress-up dolls, role-played as females, dressed in girls' clothes, stated the wish to be girls, primarily had girls as friends, and avoided rough-and-tumble play. The majority of the group evolved a bisexual or homosexual orientation; two types of behaviour, boyhood doll play and female role-playing, were found to be associated with later homosexual orientation. The findings suggest developmental associations between specific types of boyhood cross-gender behaviour and the objects of later sexual arousal.

Child Behavior↗
PubMed1986

Computer simulations of cyclic enkephalin analogues.

Molecular dynamics simulations and energy minimization studies of cyclic enkephalin analogues incorporating retro-inverso modifications have been carried out. The dynamic trajectories are analyzed in terms of the relative mobility of the 14-membered rings, conformational transitions among equilibrium states, and hydrogen-bonding patterns. The cyclization of the molecules reduces the motion of the ring structures substantially. Time-correlated conformational transitions resulting in the reorientation of peptide units are observed. Hydrogen bonds form principally C7 structures. Because of the incorporation of retro-inverso residues, C6 and C8 structures are also formed. Starting conformations for energy minimizations were obtained from the molecular dynamics simulations and from a systematic search of the conformational space available to the molecules. Several minimum energy backbone and side-chain conformations were found for each analogue. The effect of retro-inverso residues on hydrogen-bonding patterns and backbone conformations is discussed.

Amino Acid Sequence↗
PubMed1986

Conformational analysis of cyclic partially modified retro-inverso enkephalin analogues by proton NMR.

The conformations of five cyclic retro-inverso enkephalin analogues have been probed by proton NMR. After assignment of peaks, intramolecularly hydrogen-bonded amide protons were detected by temperature perturbation. Carbonyl hydrogen-bond acceptors were surmised from the computer simulations of minimum energy conformations of Hassan and Goodman [Hassan, M., & Goodman, M. (1986) Biochemistry (preceding paper in this issue)]. Hydrogen bonds were identified in dimethyl-d6 sulfoxide solutions and monitored as H2O was added. One hydrogen bond was observed in each of the retro-inverso-modified enkephalin analogues although in the parent analogue H-Tyr-c-(D-A2bu-Gly-Phe-Leu) two were detected. The change in solvent altered the conformations of two of the analogues.

Amino Acid Sequence↗
PubMed1986

High potency congeners of isoproterenol. Binding to beta-adrenergic receptors, activation of adenylate cyclase and stimulation of intracellular cyclic AMP synthesis.

The potency of a p-toluide derivative and a p-trifluoromethyl derivative of isoproterenol on the beta1 receptor of turkey erythrocytes and on the beta2 receptor of S49 lymphoma cells was measured in comparison with isoproterenol. Binding assays showed that the p-trifluoromethyl derivative possessed an affinity for the receptor, which was two hundred times higher than that of isoproterenol, in the case of turkey erythrocytes, and sixty times higher in the case of the S49 cells. By measuring the Kact of adenylate cyclase, the activity of the p-trifluoromethyl derivative was thirty to forty times higher than that of isoproterenol for the turkey erythrocyte membrane as well as for the S49 lysed cells. In stimulation of intracellular cyclic AMP accumulation, the Kact showed that the p-trifluoromethyl derivative was forty and twenty times more active than isoproterenol in turkey erythrocytes and in S49 cells, respectively. The p-toluide derivative gave similar results. The superior affinity of the above isoproterenol congeners for both beta 1 and beta 2 adrenergic receptors makes these compounds excellent candidates for use as labeled agonist ligands in studies of beta receptors. The possibility is discussed that the relatively large substituent on the amino group of the catecholamine congeners might perhaps bind to lipids associated with the receptor.

Adenylyl Cyclases↗
PubMed1986

The effects of derivatives of histamine on natural suppressor cells.

Histamine is an impressive modulator of immune functions at least via its effects on lymphoid cells. Its in vivo effects will not be used practically as long as they produce the profound cardiovascular and pulmonary effects for which the drug is known. A series of 13 congener derivatives and conjugates of histamine was constructed and was tested to investigate whether chemical alterations would result in pharmacologic actions on leukocytes that were more potent and effect specific than histamine. The new compounds, which contained spacer groups of varying lengths between ligand and carrier and with various aromatic modifying groups, showed potencies widely different from histamine when tested in natural suppressor cells. Some compounds showed selective effects on natural suppressor cells in that they were inactive on myocardial tissue, whereas other compounds were selectively active on the myocardium. Some compounds augmented the suppressive capacity of natural suppressor cells in mixed leukocyte reactions via H1 receptors. Our scheme might be more widely extrapolated to other low m.w. immune modulators in an attempt to make them lymphocyte specific. The data also encourage the in vivo testing of selected histamine analogues as selective modulators of immunity. Some of these modulators might be experimentally useful in vivo because they may lack actions in other tissues.

Adenylyl Cyclases↗