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Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 325 records · Page 18Linked to original sources
PubMed1985

Isolation and characterization of deoxyribonucleic acid from tissue of the woolly mammoth, Mammuthus primigenius.

DNA was isolated from tissue samples of several mammoth specimens, radiocarbon dated between 10,000 and 53,000 years old. The DNA was purified by chromatography on hydroxyapatite at 60 degrees C and was characterized as a heterogeneous population of fragments ranging in size from 3000 to 200 base pairs. Thermal denaturation analysis demonstrated that approximately 25% of the DNA had a base composition similar to Asian elephant DNA calculated as 36% G + C. Preliminary analysis by nucleic acid hybridization indicated that only a small fraction of DNA isolated from mammoth tissue (2-5%) was homologous to DNA of Asian elephant, a close living relative of the mammoth. Our results provide the first definitive isolation and characterization of DNA from ancient tissue and suggest a purification strategy that will lead to preparations of DNA from mammoth tissue significantly enriched in elephant-related DNA sequences.

Animals↗
PubMed1985

Blunt chest trauma and suspected aortic rupture: reliability of chest radiograph findings.

The chest radiographs of 86 patients with suspected aortic rupture from blunt chest trauma were reviewed. Seventy-three patients had no evidence of aortic rupture on aortography or surgical exploration, and 13 patients had surgically confirmed rupture. Sixteen radiographic findings were analyzed for sensitivity and specificity in detecting aortic rupture. The following findings were not statistically significant: hemothorax on either side; rib fractures on either side; pneumothorax on either side; lung contusion; widened left paravertebral stripe; and widening of the mediastinum, along with an increased ratio of mediastinal width to chest width. The most helpful findings leading to suspicion of aortic rupture included nasogastric tube or tracheal deviation to the right at the T4 level; depression of the left mainstem bronchus; and loss of the aortic contour or knob and left apical cap. False positives and false negatives occurred with each radiographic sign, indicating that there is no single finding that is absolutely reliable in predicting or excluding significant injury in every patient with suspected aortic rupture. Analysis of combinations of findings found that when the aortic contour and knob are normal and the nasogastric tube and trachea are not deviated, there was no case of aortic rupture in four consecutive years of experience. These four signs can be used to exclude aortic rupture.

Aortic Rupture↗
PubMed1985

Peptide sweeteners. 8. Synthesis and structure-taste relationship studies of L-aspartyl-D-alanyl tripeptides.

Several L-aspartyl-D-alanyl tripeptides have been synthesized to investigate the structural requirements of the C-terminal amino acid needed to elicit a taste response. Following our suggestion that a rigid, hydrophobic residue is required, both alpha, alpha-dialkane and cycloalkane alpha-amino acid methyl esters were incorporated into the tripeptide. The L-aspartyl-D-alanine-based tripeptide derivatives of alpha-aminoisobutyric acid methyl ester, alpha, alpha-diethylglycine methyl ester, and alpha-aminocycloalkanecarboxylic acid methyl esters from three- to six-membered rings are sweet. The higher analogues of the cycloalkane series containing alpha-aminocycloheptanecarboxylic acid methyl ester and alpha-aminocyclooctanecarboxylic acid methyl ester are bitter. It is important to note that this series of tripeptides (analogous to the previously reported dipeptides) goes from sweet to bitter to tasteless as the ring size of the C-terminal amino acid increases. The relationships between effective volume of the C-terminal residue, size requirements of the sweet receptor, and taste are discussed.

Motion↗
PubMed1985

Conjugates of catecholamines. 5. Synthesis and beta-adrenergic activity of N-(aminoalkyl)norepinephrine derivatives.

A novel series of N-aminoalkyl congeners and model derivatives of norepinephrine has been synthesized. Compounds that were structurally related to epinephrine were prepared from fully protected intermediates. Alternatively, isoproterenol-related compounds were synthesized via reductive amination of preformed methyl ketone derivatives with norepinephrine. The beta-adrenergic activities of these new compounds were assessed through measurement of intracellular cyclic AMP accumulation in S49 mouse lymphoma cells and displacement of iodocyanopindolol (ICYP) from membrane preparations. Congeners that contained an underivatized primary amine function exhibited virtually no activity in these assays. However, when this amine function was acylated (e.g., to an amide, carbamate, urea, sulfonamide, etc.), the products exhibited generally increased beta-adrenergic activity, which was, however, strongly dependent on the nature of the acylating group and also the length of the spacer. In particular, a benzyl carbamate derivative containing a branched, seven-carbon spacer group was 40 times more potent than isoproterenol in the in vitro S49 assay.

Adrenergic beta-Agonists↗
PubMed1985

Conjugates of catecholamines. 6. Synthesis and beta-adrenergic activity of N-(hydroxyalkyl)catecholamine derivatives.

A new series of catecholamines has been prepared in which the N-alkyl substituent of dl-epinephrine or dl-isoproterenol has been extended by a methylene chain terminated by a hydroxyl group or derived functionality (e.g., carbamate or ester). These functionalized catecholamines (congeners) and model compounds were prepared with the goal of eventual attachment to polymeric carrier molecules. The beta-adrenergic agonist activity of the derivatives was evaluated in vitro by measuring the intracellular accumulation of cyclic AMP in S49 mouse lymphoma cells and by the displacement of iodocyanopindolol (ICYP). A n-butylcarbamate derivative (compound 15) was the most active compound in this series with a potency 190 times greater than dl-isoproterenol in the S49 assay. The biological results indicate that minor modifications in structure in the N-alkyl substituent of the catecholamine can influence the pharmacologic activity.

Adrenergic beta-Agonists↗
PubMed1985

Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution.

The fetal globin genes G gamma and A gamma from one chromosome of a chimpanzee (Pan troglodytes) were sequenced and found to be closely similar to the corresponding genes of man and the gorilla. These genes contain identical promoter and termination signals and have exons 1 and 2 separated by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G gamma and A gamma, respectively). Each intron 2 has a stretch of simple sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The two chimpanzee genes encode polypeptide chains that differ only at position 136 (glycine in G gamma and alanine in A gamma) and that are identical to the corresponding human chains, which have aspartic acid at position 73 and lysine at 104 in contrast to glycine and arginine at these respective positions of the gorilla A gamma chain. Phylogenetic analysis by the parsimony method revealed four silent (synonymous) base substitutions in evolutionary descent of the chimpanzee G gamma and A gamma codons and none in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla) coding sequences evolved at one-tenth the average mammalian rate for nonsynonymous and one-fourth that for synonymous substitutions. Three sequence regions that were affected by gene conversions between chimpanzee G gamma and A gamma loci were identified: one extended 3' of the hot spot with G gamma replaced by the A gamma sequence, another extended 5' of the hot spot with A gamma replaced by G gamma, and the third conversion extended from the 5' flanking to the 5' end of intron 2, with G gamma replaced here by the A gamma sequence. A conversion similar to this third one has occurred independently in the descent of the gorilla genes. The four previously identified conversions, labeled C1-C4 (Scott et al. 1984), were substantiated with the addition of the chimpanzee genes to our analysis (C1 being shared by all three hominines and C2, C3, and C4 being found only in humans). Thus, the fetal genes from all three of these hominine species have been active in gene conversions during the descent of each species.

Animals↗
PubMed1985

Codon usage in the vertebrate hemoglobins and its implications.

A study of codon usage in vertebrate hemoglobins revealed an evolutionary trend toward elevated numbers of CpG codon boundary pairs in mammalian hemoglobin alpha genes. Selection for CpG codon boundaries countering the generally observed CpG suppression is strongly suggested by these data. These observations parallel recently published experimental results that indicate that constitutive expression of the human alpha-globin gene appears to be determined by regulatory information encoded within the structural gene. The possibility is raised that, in the absence of selection, CpG decay can be used to date the evolutionary origin of a mammalian alpha pseudogene from its active alpha gene.

Animals↗
PubMed1985

alpha-Crystallin A sequences of Alligator mississippiensis and the lizard Tupinambis teguixin: molecular evolution and reptilian phylogeny.

The amino acid sequences of the eye lens protein alpha-crystallin A from many mammalian and avian species, two frog species, and a dogfish have provided detailed information about the molecular evolution of this protein and allowed some useful inferences about phylogenetic relationships among these species. We now have isolated and sequenced the alpha-crystallins of the American alligator and the common tegu lizard. The reptilian alpha A chains appear to have evolved as slowly as those of other vertebrates, i.e., at two to three amino acid replacements per 100 residues in 100 Myr. The lack of charged replacements and the general types and distribution of replacements also are similar to those in other vertebrate alpha A chains. Maximum-parsimony analyses of the total data set of 67 vertebrate alpha A sequences support the monophyletic origin of alligator, tegu, and birds and favor the grouping of crocodilians and birds as surviving sister groups in the subclass Archosauria.

Alligators and Crocodiles↗
PubMed1985

Synthesis and biological activity of linear and cyclic enkephalins modified at the Gly3-Phe4 amide bond.

As part of our continuing effort to define structure-activity relationships for enkephalin and design enzymatically resistant analogs, we report the synthesis and biological activities of linear and cyclic enkephalin analogs modified at the Gly3-Phe4 amide bond. The partial retro-inverso enkephalin analog Tyr-D-Ala-gGly-(R,S)-mPhe-Leu-NH2 and its cyclic counterpart, Tyr-cyclo[D-A2 bu-gGly-(R,S)-mPhe-Leu-], were synthesized as diastereomeric mixtures using solution methodology. The racemic benzylmalonate allowed the linear analog to be synthesized by fragment coupling at the reversed bond. Cyclization of the second analog was carried out at high concentration, eliminating formation of polymer by the use of an insoluble base. All gem-diaminoalkyl residues were prepared by conversion of peptidyl amides with benzene iodonium bis(trifluoroacetate). Diastereomers of both compounds were separable by reverse phase HPLC but those of the linear compound racemized rapidly under conditions of testing and were therefore tested together. All analogs tested had activities ranging from 6 to 14% of the activity of Leu enkephalin, indicating that the Gly3-Phe4 amide bond is important, though not crucial, for receptor binding.

Animals↗
PubMed1985

Control of secretion vesicle margination and lysis by glucose, IBMX, and glyburide.

We have attempted to define the effect of glucose, glyburide, and isobutylmethylxanthine (IBMX) upon secretion vesicle margination to the plasma membrane and granule lysis. Margination of secretion vesicles during exocytosis was assessed by measuring the recruitment of somatostatin (SRIF) receptors. Secretion vesicle lysis was studied by measuring insulin release into the incubation media. Our observations suggest that glucose directly affects both secretion vesicle margination and lysis. Both events are rapidly influenced by this secretagogue (within 10 min of incubation). Trifluoperazine (TFP) and removal of Ca2+ from the incubation media significantly reduced glucose-induced margination of secretion vesicles and their lysis (P less than 0.001). IBMX primarily influences the lysis of secretion vesicles and not their margination. IBMX caused a rapid increase in insulin secretion within 10 min without recruitment of SRIF receptors. Neither TFP nor the absence of extracellular Ca2+ affected IBMX-induced insulin release. Late enhancement in margination of secretion vesicles (30 min of incubation with IBMX) is probably related to the initial event of secretion vesicle lysis and is independent of extracellular calcium. Glyburide exerts its action in a manner similar to glucose, affecting both the lysis of secretion vesicles and their margination. However, the action of glyburide is independent of extracellular calcium and partially dependent upon calmodulin.

1-Methyl-3-isobutylxanthine↗
PubMed1985

Mole rat hemoglobin: primary structure and evolutionary aspects in a second karyotype of Spalax ehrenbergi, Rodentia, (2n = 52).

The hemoglobins of the four karyotypes of Spalax ehrenbergi (2n = 52, 54, 58, 60) did not show any differences in their electrophoretic pattern and in high performance liquid chromatography. The complete amino-acid sequence of mole rat hemoglobin (Spalax ehrenbergi), chromosome species 2n = 52, is presented. It was elucidated by automatic Edman degradation of the chains, the tryptic peptides, and the C-terminal peptide obtained by acid hydrolysis of the Asp-Pro bond in beta-chains. The alpha- and beta-chains are identical with those of the chromosome species 2n = 60. A comparison of the hemoglobins of mole rat, mouse, and other rodents shows homology but no indication of adaptation to subterranean life. In all probability alpha 11(A9)Arg and alpha 120(H3)Gly, unique in mole rat among all mammalian hemoglobins, are not involved in high oxygen affinity. The construction of a phylogenetic tree by the maximum parsimony method, based on hemoglobin sequences, made it possible to show that Rodentia originated as a monophyletic clade, and to find the phylogenetic relationship of Spalacidae to other Rodentia (Mus, Rattus, Ondatra, Mesocricetus, Citellus, and Cavia). Among all rodents the slowest rate of nucleotide replacements occurred in the lineage to Spalax (20%) and the fastest in the lineage to Cavia (59%).

Amino Acid Sequence↗
PubMed1984

The eta-globin gene. Its long evolutionary history in the beta-globin gene family of mammals.

In phylogenetic reconstructions by the parsimony method, utilizing 62 sequenced globin genes and pseudogenes (including 34 of the beta-globin gene family from eutherian orders Primates, Lagomorpha, Artiodactyla and Rodentia), the branch of primate psi beta pseudogenes and the goat embryonically expressed epsilon II gene group monophyletically together as orthologues of a common ancestral gene (labelled eta) distinct from orthologues of epsilon, gamma, delta and beta. This primate psi eta-goat eta branch is cladistically closer to epsilon and gamma than to delta and beta branches. In each eutherian order gene conversions replaced portions of delta by beta sequences, whereas in descent of Primates epsilon, gamma and eta mostly retained their separate ancient identities predating the radiation of Eutheria in all their exons and non-coding regions. The loci of the ancestral beta-globin gene cluster in basal eutherians and proto-primates, as deduced from beta-clusters representing the four eutherian orders, were linked 5'-epsilon-gamma-eta-delta-beta-3' with epsilon, gamma and eta being embryonically expressed genes, and delta and beta ontogenetically later expressed genes. Through deletions gamma was lost in artiodactyl evolution, eta in lagomorph and rodent evolution, and all DNA between exon 2 3' boundaries of eta and delta in prosimian lemuriform evolution (lemur having the hybrid pseudogene psi eta delta). Simian primates retained intact the five loci of the ancestral cluster. Not only did eta, after it became a pseudogene in the basal primates, persist intact in descent to present-day simians but in the line to hominoids it evolved during the last 40 million years at the decelerated rate of 1 X 10(-9) substitutions/site per year which is one-fifth the expected neutral rate. The possibility is suggested that the psi eta locus situated between fetal and adult chromosomal domains of the simian beta-globin gene cluster might play some role in a mechanism for ontogenetic switches of globin gene expression. However, not enough sequence data on genes and intergenic regions in DNA of species of primates and other mammals as yet exist to know if the slow rate of 1 X 10(-9) reflects the rate of a conserved functional gene or primarily reflects a decelerated neutral rate of hominoid DNA evolution, conceivably from enhanced DNA repair and longer generation times in hominoids. The further possibility is raised that gene correction (repair of damaged DNA that prevents emergence of new alleles) and gene conversion both more often involve strand copying of conserved than of rapidly evolving DNA.

Animals↗