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Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 19 recordsLinked to original sources

Reexamination of the African hominoid trichotomy with additional sequences from the primate beta-globin gene cluster.

Additional DNA sequence information from a range of primates, including 13.7 kb from pygmy chimpanzee (Pan paniscus), was added to data sets of beta-globin gene cluster sequence alignments that span the gamma 1, gamma 2, and psi eta loci and their flanking and intergenic regions. This enlarged body of data was used to address the issue of whether the ancestral separations of gorilla, chimpanzee, and human lineages resulted from only one trichotomous branching or from two dichotomous branching events. The degree of divergence, corrected for superimposed substitutions, seen in the beta-globin gene cluster between human alleles is about a third to a half that observed between two species of chimpanzee and about a fourth that between human and chimpanzee. The divergence either between chimpanzee and gorilla or between human and gorilla is slightly greater than that between human and chimpanzee, suggesting that the ancestral separations resulted from two closely spaced dichotomous branchings. Maximum parsimony analysis further strengthened the evidence that humans and chimpanzees share the longest common ancestry. Support for this human-chimpanzee clade is statistically significant at P = 0.002 over a human-gorilla clade or a chimpanzee-gorilla clade. An analysis of expected and observed homoplasy revealed that the number of sequence changes uniquely shared by human and chimpanzee lineages is too large to be attributed to homoplasy. Molecular clock calculations that accommodated lineage variations in rates of molecular evolution yielded hominoid branching times that ranged from 17-19 million years ago (MYA) for the separation of gibbon from the other hominoids to 5-7 MYA for the separation of chimpanzees from humans. Based on the relatively late dates and mounting corroborative evidence from unlinked nuclear genes and mitochondrial DNA for the close sister grouping of humans and chimpanzees, a cladistic classification would place all apes and humans in the same family. Within this family, gibbons would be placed in one subfamily and all other extant hominoids in another subfamily. The later subfamily would be divided into a tribe for orangutans and another tribe for gorillas, chimpanzees, and humans. Finally, gorillas would be placed in one subtribe with chimpanzees and humans in another, although this last division is not as strongly supported as the other divisions.

Africa

A molecular perspective on mammalian evolution from the gene encoding interphotoreceptor retinoid binding protein, with convincing evidence for bat monophyly.

The evolutionary relationships of the various orders of placental mammals remain an issue of uncertainty and controversy. Molecular studies of mammalian phylogeny at the DNA level that include more than just a few orders are still relatively meager. Here we report results on mammalian phylogeny deduced from the coding sequence of the single-copy nuclear gene for the interphotoreceptor retinoid binding protein (IRBP). Analysis of 13 species representing eight eutherian orders and one marsupial yielded results that falsify the hypothesis that megachiropteran bats are "flying primates," only convergently resembling microchiropteran bats. Instead, in agreement with more traditional views, as well as those from other recent molecular studies, the results strongly support a monophyletic Chiroptera (micro- and megabats grouped together). The IRBP results also offer some rare molecular support for the Glires concept, in which rodents and lagomorphs form a superordinal grouping. Also in congruence with other recent molecular evidence, IRBP sequences do not support the view of a superorder Archonta that includes Chiroptera along with Dermoptera (flying lemur), Scandentia (tree shrew), and Primates. IRBP was not however, without its shortcomings as a molecular phylogenetic system: high levels of homoplasy, evident in the marsupial outgroup, did not allow us to properly root the tree, and several of the higher level eutherian clades were only weakly supported (e.g., a Carnivora/Chiroptera clade and an Artiodactyla/Carnivora/Chiroptera clade). We suggest that these shortcomings may be diminished as the phylogenetic density of the data set is increased.

Amino Acid Sequence

Partially modified retro-inverso-enkephalinamides: topochemical long-acting analogs in vitro and in vivo.

The synthesis of four enkephalinamide analogs is described in which the peptide bond between residues 4 and 5 is reversed with or without simultaneous reversal of the carboxyl-terminal amide bond. These so-called partially modified retro-inverso-isomers are new, potent, topochemical analogs of the enkephalins. Tests, both in vitro and in vivo, have shown that these analogs are considerably longer acting than any previously studied enkephalins. Thus, partial reversal of the peptide bonds of the backbone can result in peptides with enhanced activity compared to a parent compound, provide that the structural complementarity of both the side chains and end groups are conserved.

Animals

The radioisotope spleen scan in the assessment of patients with suspected spleen trauma.

The radioisotope spleen scan was reviewed in 29 patients with suspected trauma of the spleen who had been admitted for observation to a surgical ward. At the time of the study, all patients had stable pulse rates and blood pressures. The scans of six patients showed space defects and, of these, splenic injury was subsequently proven operatively in five patients. As a detector of splenic trauma, the radionuclide scan proved to be reliable. Although the findings of radioisotope scanning are not specific for trauma, the interpretation of the scan in conjunction with other observations increases the accuracy of diagnosis.

Adolescent

In situ carcinoma of the vocal cords.

Eighty-one patients with preinvasive carcinoma of the vocal cord, seen over a thirteen year period, were reviewed histologically and analyzed for response to treatment. Sixty-seven cases were clinically T1 and fourteen cases T2 (by virtue of extension of disease beyond the vocal cord). All patients had mobile cords. Histological criteria for in situ carcinoma and the spectrum of microscopic patterns are presented. Sixty-nine patients were treated by external beam radiotherapy--the remainder by a variety of surgical procedures. Five and ten year actuarial, recurrence-free rates 83% and 75%, respectively for the group treated by irradiation. No difference in local control was observed when analyzed for: 1) dose response, 2) initial extent of disease, 3) treatment plan, or 4) histologic diagnosis. Analysis of failures reveals that 15/17 patients with local failure were salvaged, eleven of these patients requiring laryngectomy. Time to appearance of recurrence ranged from seven to one hundred and seven months.

Aged

Evolutionary diversification of structure and function in the family of intracellular calcium-binding proteins.

The maximum parsimony method was used to reconstruct the genealogical history of the family of intracellular calcium-binding proteins represented by six major present-day lineages, three of which--calcium dependent modulator protein, heart and skeletal muscle troponin Cs, and alkali light chains of myosin--were found to share a closer kinship with one another than with the other lineages. Similarly, parvalbumins and regulatory light chains of myosin were depicted as more closely related, whereas the branch of intestinal calcium-binding protein proved to have the most distant separation. The computer-generated amino acid sequence for the common ancestor of these six lineages described a four domain protein in which each domain of approximately 40 amino acid residues had a mid-region. 12 residue segment that bound calcium and had properties most resembling those of the calcium dependent modulator protein. It could then be deduced that parvalbumins evolved by deletion of domain I, inactivation of calcium-binding properties in domain II, and acquisition of increased affinity for Ca++ and Mg++ in domains III and IV. Regulatory light chains of myosin lost the cation binding property from three domains, retaining it in I, whereas alkali light chains of myosin lost this ability from each of the four domains. In skeletal muscle troponin C all domains retained their calcium-binding activity; however, like parvalbumins, domains III and IV acquired high affinity properties. Cardiac troponin C lost its binding activity from domain I but otherwise resembled the skeletal muscle form. Finally, intestinal calcium-binding protein evolved by deletion of domains III and IV. Positive selection could be implicated in these evolutionary changes in that the rate of fixation of mutations substantially increased in the mid portions of those domains which were loosing calcium-binding activity. Likewise, when the cation binding sites were changing from low to high affinity, an accelerated rate of fixed mutations was observed. Once this new functional parameter was selected these regions showed a remarkable conservatism, as did those binding sites which were maintaining the lower affinity. Moreover even in sequence regions not directly involved in cation binding, the lineage of troponin C because very conservative over the past 300 million years, perhaps becuase of the necessity for maintaining specific interfaces in order for the molecule to interact with troponin I and T in a functional thin myofilament. A similar phenomenon was observed in domain II of the regulatory light chains of the myosin lineage suggesting a possible binding site with the heavy chain of myosin.

Amino Acid Sequence

The use of amino acid sequence analysis in assessing evolution.

The thirteen year history of assessing evolution by amino acid sequence analysis has made apparent the limitations imposed upon this system by the finite nature of the characters. This finiteness exists on several levels and ultimately expresses itself as parallelism, back mutation and the retention of primitive characters in the sequences of proteins from present day species and the putative ancestral protein chains. Sequence analysis shares these problems with other molecular approaches, but because it is concerned both with the nucleotide substitutions in the genome and with the functional roles of proteins, it has unique advantages. For example, the large fluctuation in the rate of fixation of mutations in a protein's evolution can be detected and used to point out the unreliability of any molecular clock for estimating divergence dates. Moreover, when consideration is given to studies which assign functional significance to specific amino acid sites in a protein, changes in function during the descent of a protein can be appreciated and their significance correlated with organismal evolution.

Amino Acid Sequence

Amino acid sequences of the alpha and beta chains of adult hemoglobin of the European hedgehog, Erinaceus europaeus.

Globin prepared from hemoglobin of the European hedgehog (Erinaceus europaeus) was separated into alpha and beta polypeptide chains by chromatography on a CM 52 column. The S-aminoethylated alpha and beta chains were each digested with trypsin and the resulting peptides were isolated. The sequences of all the tryptic peptides were established. The ordering of these peptides in the alpha and beta chains was deduced from their homology with the primary structures of alpha and beta chains of human adult hemoglobin. Comparing the primary structures of the alpha and beta chains of adult hemoglobin of the European hedgehog thus obtained with those of adult hemoglobin of the tupai (Tupaia glis), 35 amino acids substitutions in the alpha chains and 30 in the beta chains were recognized.

Amino Acid Sequence

Bone stress: a radionuclide imaging perspective.

Thirty-five college athletes with lower leg pain underwent radiography and radionuclide studies to rule out a stress fracture. Their asymptomatic extremities and 13 pain-free athletes served as controls. Four main patterns were observed: (a) sharply marginated scintigraphic abnormalities and positive radiographs; (b) sharply marginated scintigraphic abnormalities and negative radiographs; (c) ill-defined scintigraphic abnormalities and negative radiographs; and (d) negative radionuclide images and negative radiographs. Since the patients with the first two patterns were otherwise identical medically, the authors feel that this scintigraphic appearance is characteristic of bone stress in the appropriate clinical setting, regardless of the radiographic findings. A schema is proposed to explain the occurrence of positive radionuclide images and negative radiographs in the same patient, using a broad conceptual approach to the problem of bone stress.

Adolescent

Immunodiffusion systematics of the primates. Part V. The Platyrrhini.

Evolutionary relationships between New World monkeys and marmoset genera and the place of the Ceboidea within the primates are considered in terms of the immunological specificity of ceboid proteins. Antigenic distances between the New World primates are measured using antisera produced in rabbits to nine ceboid genera: Alouatta, Aotes, Ateles, Callicebus, Cebus, Chiropotes, Lagothrix, Saimiri and Saguinus. A cladogram constructed on the basis of increasing degrees of antigenic distance between branches depicts Ceboidea as a monophyletic assemblage within which Alouatta is grouped with the Atelinae genera, Lagothrix and Ateles, Chiropotes joins Cacajao and Cebus joins Saimiri. The joining of the cebid genera Aotes and Callicebus with callithricid genera Callimico and Saguinus into a single complex lineage suggests that Cebidae is a paraphyletic or polyphyletic taxon. A phylogenetic taxonomy for Platyrrhini is proposed.

Animals

Amino acid sequences of the alpha and beta chains of adult hemoglobin of the brown lemur, Lemur fulvus fulvus.

Globin prepared from hemoglobin of the brown lemur (Lemur fulvus fulvus) was separated into alpha and beta chains by chromatography on a CM 52 column. The S-aminoethylated alpha and beta chains were each digested with trypsin and resulting peptides were isolated. The amino acid sequences of the tryptic peptides were established. The ordering of these peptides in the alpha and beta chains was deduced from the homology of their amino acid sequences with that of human adult hemoglobin. The primary structure of brown lemur hemoglobin thus obtained differs from that of human hemoglobin in 15 amino acids in the alpha chain and 26 in the beta chain.

Amino Acid Sequence

Simultaneous scabies and gonococcal infection.

A case is presented of an unusual complication arising in a man with scabies and gonococcal urethritis: the secondary infection of excoriated genital lesions by Neisseria gonorrhoeae. This occurred after he had occluded his genitals with a plastic wrap.

Adult

Xanthogranulomatous pyelonephritis (XGP): a local disease with systemic manifestations. Report of 23 patients and review of the literature.

The clinical, pathological and radiographic findings of 135 cases of xanthogranulomatous pyelonephritis have been reviewed. It is a form of renal suppuration and obstruction most commonly seen in middle aged women although all ages and both sexes may be affected. There is no race predilection. Gram-negative organisms are usually present and bilateral involvement has not been reported. The most common offending organism is Proteus mirabilis. Hepatic dysfunction is seen and appears to normalize with removal of the XGP process. Preoperative angiography may increase the accuracy of differentiating this disorder from hypernephroma and may aid the surgeon in planning his approach to kidney resection depending upon the staging of XGP. Chronic renal failure is not usually a feature of XGP and nephrectomy is curative without any incidence of recurrence.

Female

Intra-aortic balloon pumping: two-year experience.

Experience with 29 patients who underwent intra-aortic counterpulsation between January, 1975, and December, 1977, was reviewed to determine (1) if the results of this method of treatment were similar at the community hospital and university hospital levels and (2) if earlier institution of counterpulsation made possible by easy availability of equipment resulted in improved survival. The balloon was successfully inserted in 27 patients. Arterial blood pressure was below 80 mm. Hg in all patients prior to institution of either pharmacologic or balloon therapy. Pulmonary capillary wedge pressure was greater than 12 mm. Hg in the 22 patients in whom it was measured. In 15 patients counterpulsation was instituted less than 12 hours after infarction (Group A), and in the 14 elapsed time was greater than 12 hours (Group B). There was no difference in precounterpulsation hemodynamic measurements between Group A and Group B. Ten patients in Group A were weaned and survived hospitalization. Seven (54 percent) are long-term survivors (6 months to 2 years). Four are in New York Heart Association Class I, two are in Class II, and one is in Class III. Ten patients in Group B were weaned, seven survived hospitalization, and five are long-term survivors (35 percent). Two are in N.Y.H.A. Class I, two are in Class II, and one is in Class III. These results indicate that counterpulsation is possible at the local hospital level and that early institution of the intra-aortic balloon pumping may improve long-term results.

Assisted Circulation

The preferred conformations of protected homodito homoheptamethionine peptides. A1 H n.m.r. study in deuterochloroform medium.

Detailed analyses of the conformations of the homo-oligopeptide series, Boc-(L-Met)n-OME n = 2--7, in deuterochloroform have been carried out with proton n.m.r. and IR spectroscopy. Well-resolved high field n.m.r. spectra with assignments for the NH and alpha-CH resonances of these homo-methionine peptides are presented. Extensive n.m.r. concentration-dependent chemical shift studies are combined with IR results to delineate the involvement of the various methionine NH protons in intra- and/or intermolecular hydrogen bonding. N.m.r. chemical shift dependencies with temperature and solvent, DMSO-d6, are used to explore the strength of the hydrogen bonds for the various oligopeptides. At low concentrations, where peptide aggregation is absent, the dipeptide is found to be disordered. The tetra- to heptapeptides possess intramolecular hydrogen bonded seven-membered rings at internal residues. The number of internal rings and the oligopeptide self-association increase with increasing peptide chainlength. At intermediate concentrations associations of peptide molecules with folded structures occur with initial association at the C-terminal region. At high concentrations, "in-register" associated extended beta structures are formed.

Amino Acid Sequence

On investigating the statistical properties of the populous path algorithm by computer simulation. Counterconclusions to those of Tateno and Nei.

Goodman et al.'s (1974) populous path algorithm for estimating hidden mutational change in protein evolution is designed to be used as an adjunct to the maximum parsimony method. When the algorithm is so used, the augmented maximum parsimony distances, far from being overestimates, are underestimates of the actual number of nucleotide substitutions which occur in Tateno and Nei's (1978) computer simulation by the Poisson process model, even when the simulation is carried out at two and a half times the sequence density. Although underestimates, our evidence shows that they are nevertheless more accurate than estimates obtained by a Poisson correction. In the maximum parsimony reconstruction, there is a bias towards overrepresenting the number of shared nucleotide identities between adjacent ancestral and descendant nodal sequences with the bias being stronger in those portions of the evolutionary tree sparser in sequence data. Because of this particular property of maximum parsimony reconstructed sequences, the conclusions of Tateno and Nei concerning the statistical properties of the populous path algorithm are invalid. We conclude that estimates of protein evolutionary rates by the maximum parsimony--populous path approach will become more accurate rather than less as larger numbers of closely related species are included in the analysis.

Biological Evolution