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Biomedical subjects

M Goodman

Publications and source records attributed to M Goodman.

At least 559 records · Page 31Linked to original sources
PubMedDate not supplied

Synthesis and conformation of sequential polypeptides of L-alanine and beta-aminobutyric acid.

Sequential polypeptides with the repeating units L-alanyl-(S)-beta-aminobutyric acid, L-alanyl-(R)-beta-aminobutyric acid, and L-alanyl-(R,S)-beta-aminobutyric acid have been synthesized by polycondensation of the N-hydroxysuccinimide ester hydrochloride salts of the corresponding dipeptides. Circular dichroism and infrared spectroscopy studies of films of the polypeptides and circular dichroism study of their solutions in hexafluoro-2-propanol and hexafluoropropane-2,2-diol show the tendency of the polypeptides to adopt the beta conformation in the solid state. In pure hexafluoro-2-propanol or hexafluoroacetone, the three polymers adopt what we interpret as random coil conformations. In mixtures of hexafluoro-2-propanol-water or hexafluoropropane-2,2-diol-water, the polypeptide containing the S isomer shows a definite tendency to form beta structure. This tendency is not established for the R and the R,S isomers.

Alanine↗
PubMedDate not supplied

Polydepsipeptides. 5. Experimental conformational analysis of poly(L-alanyl-L-lactic acid) and related model compounds.

In this paper we report an experimental conformational analysis of the depsipeptide model compounds acetyl-L-alanine methyl ester, acetyl-L-lactic acid N-methylamide, and acetyl-L-alanyl-L-lactic acid N-methylamide and of the sequential polydepsipeptide poly(L-alanyl-L-lactic acid). The model depsipeptides were examined in dilute organic solutions by infrared and nuclear magnetic resonance spectroscopy. Neither acetyl-L-alanine methyl ester nor acetyl-L-lactic acid N-methylamide assumes an intramolecularly hydrogen-bonded conformation. Acetyl-L-alanyl-L-lactic acid N-methylamide, on the other hand, in dilute chloroform or dilute carbon tetrachloride solutions, strongly favors a conformation with an intramolecular hydrogen bond between the N-H hydrogen atom of its N-methylamide group and the carbonyl oxygen atom of its acetyl group. Comparison of theoretical and experimental circular dichroism suggests that poly(L-alanyl-L-lactic acid) is partially ordered in chloroform solution with approximately 50% of its repeat units in the R10 helix, an ordered conformation found by our previous theoretical analysis to have a low intramolecular conformational energy.

Alanine↗
PubMedDate not supplied

Evidence on human origins from haemoglobins of African apes.

Molecular data have influenced views concerning human origins, first, by supporting the genealogical classification of Pan (chimpanzee) and Gorilla with Homo rather than with Pongo (orangutan) and, second, by suggesting that only a few million years separate humans and chimpanzees from their last common ancestor. Indeed, the cladistic distances in phylogenetic trees constructed from amino acid sequence data, on detecting many superimposed mutations, yielded a 'molecular-clock' divergence date between Homo and Pan of only 1-1.5 Myr BP. This date, which is even more recent than (4.2-5.3 Myr BP) calculated using phenetic distances from immunological and DNA-hybridization comparisons (Table 1), is too near the present considering the existence of 3-4 Myr-old fossils of bipedal human ancestors (and a 5.5 Myr-old jaw fragment assigned to Australopithecus). Perhaps decelerated sequence evolution occurred; alternatively, hominoid distances could have been underestimated, because chimpanzee and gorilla were represented mostly by sequences inferred from peptide amino acid compositions, as was the case for their haemoglobins. To help rectify this situation we report here the rigorously determined alpha- and beta-haemoglobin amino acid sequences not only of chimpanzee (Pan troglodytes) and Gorilla gorilla but also pygmy chimpanzee (Pan paniscus). Our findings favour the explanation of decelerated evolution and point to selection preserving perfected haemoglobin molecules.

Amino Acid Sequence↗
PubMedDate not supplied

Primate eta-globin DNA sequences and man's place among the great apes.

Molecular studies indicate that chimpanzee and gorilla are the closest relatives of man (refs 1-7 and refs therein). The small molecular distances found point to late ancestral separations, with the most recent being between chimpanzee and man, as judged by DNA hybridization. Kluge and Schwartz contest these conclusions: morphological characters group a chimpanzee-gorilla clade with the Asian ape orang-utan in Kluge's cladistic study and with an orang-utan-human clade in Schwartz's study. Clearly, extensive sequencing of nuclear DNA is needed to resolve by cladistic analysis the branching order within Hominoidea. Towards this goal, we are sequencing orthologues of the primate psi eta-globin locus. Here, we compare the newly completed sequences of orang-utan and rhesus monkey with human, chimpanzee, gorilla, owl monkey, lemur and goat orthologues. Our findings substantially increase the evidence indicative of a human-chimpanzee-gorilla clade with ancestral separations around 8 to 6 Myr ago. We also verify that neutral hominoid DNA evolved at markedly retarded rates.

Animals↗
PubMedDate not supplied

MR imaging of a lymphangioma involving the masseter muscle.

Lymphangiomas and cystic hygromas are tumors of lymphatic origin that are relatively common in the head and neck area. However, based on our literature review of this subject, the masseter muscle has never been implicated as a primary tumor site. It is our purpose to report such a case and to emphasize the value of magnetic resonance imaging for diagnosing a mass located in the masseteric region.

Adult↗
PubMedDate not supplied

Evaluation of the limulus amebocyte lysate assay for presumptive diagnosis of gonorrhea in men at a clinic for sexually transmitted diseases.

Specimens of urethral exudate from 200 men with uncomplicated urethritis were tested for Neisseria gonorrhoeae by the limulus amebocyte lysate assay, culture on modified Thayer-Martin medium, and gram-stained smear. As compared with cultures, the sensitivity and specificity of the limulus assay were 94.8% and 89.3%, respectively, while the sensitivity and specificity of the gram stain were 98.8% and 100.0%, respectively. The accuracy of prediction of the presence of N. gonorrhoeae was significantly better by gram-stained smear than by the limulus assay. Unless the limulus assay is modified, as it was in this study, it does not appear to have a role in the presumptive diagnosis of the gonorrhea in men at a clinic for sexually transmitted diseases.

Adolescent↗
PubMedDate not supplied

Comparative study of methods to couple hindered peptides.

A comparative study of modern coupling reactions involving Boc-protected amino acid derivatives and dipeptides with N-terminal alpha,alpha-dialkylation and N-methylation was carried out. The coupling reactions were run using either equimolar amounts of the amino and activated carboxyl components or an excess of the activated carboxyl component. Yields of the target tripeptide Boc-Phe-Xaa-Phe-OBzl (Xaa = (NMe)Ala, (NMe)Aib, or (NMe) alpha Ac5c) were compared. Less than 10% of the product was obtained from methods utilizing pivaloyl mixed anhydride, pentafluorophenyl ester or acyl fluoride activation when Xaa = (NMe)Aib and (NMe) alpha Ac5c. At room temperature, significant yields of these two products were obtained from reactions which utilized an excess of the HBTU reagent (O-benzotriazol-1-yl-N,N,N',N'-tetramethyluronium hexafluorophosphate), the PyBroP reagent (bromo-tris-pyrrolidino-phosphonium hexafluorophosphate) or Boc-Phe-NCA (Boc-protected phenylalanine N-carboxyanhydride). Moreover, the Boc-Phe-NCA method was superior when used over a prolonged reaction time or at elevated temperature.

Amino Acid Sequence↗
PubMedDate not supplied

Synthesis, crystal structure and conformation in solution of four stereoisomeric cyclo-lanthionine derivatives.

The synthesis of the four stereoisomeric cyclo-lanthionine derivatives: [formula: see text] (where AlaL denotes one end of the lanthionine unit) was carried out on a Kaiser-oxime resin starting from orthogonally protected lanthionine units. The peptide ring was prepared in 79-85% yield via amide bond formation by utilizing the method of peptide cyclization on an oxime resin (PCOR). The crystal and molecular structures of the protected cyclic dipeptides have been determined by X-ray diffraction techniques. The two cyclic lanthionine derivatives with chiralities of [R,S] and [S,R] crystallized in the orthorhombic space group P2(1)2(1)2(1) and the [R,R]- and [S,S]-cyclo-lanthionine derivatives in the monoclinic space group C2. The structures were solved by direct methods and refined to an R factor of 0.0368-0.0573. The ring amide bonds in all four compounds are cis, while the urethane group is trans and extended. The NMR spectra of the four stereoisomers in DMSO-d6 were used to determine their conformation in solution. The analysis of the NMR data with constrained distance geometry search showed the same conformational features in solution as in the crystalline state.

Alanine↗
PubMedDate not supplied

Computer generated discharge summaries and their use as a case mix sensitive audit engine. A tale of two cities.

BACKGROUND: An 'audit engine' allows critical appraisal of clinical practice without necessitating cumbersome data input, editing or analysis. This is achieved by capturing data from an otherwise necessary task, in this case writing discharge summaries, and using standardised analyses to illustrate the effects of operational changes. DESIGN AND SETTING: Retrospective analysis of clinical outcome of 1,829 sequential discharges from one consultant's team in two geriatric medicine departments. MAIN OUTCOME MEASURES: Mortality, discharge destination and functional performance. RESULTS: Median length of stay in the two departments differed significantly (8 vs 13 days; p < 0.0001), but patients in the latter department were more disabled, with almost twice as many needing domiciliary services after discharge and suffering impaired mobility or incontinence. Despite this disparity, a similar proportion of survivors was placed in institutional care (31/300 (10%) vs 94/1,100 (8%); NS). CONCLUSIONS: This audit engine demonstrated that apparently worse performance indicators were explained by adverse case mix in one department, and the similar institutionalisation rates suggest superior care there.

Aged↗
PubMedDate not supplied

Topochemical design of bioactive peptides and peptidomimetics.

For the studies of bioactive peptides, our laboratories have been employed an integrated approach including synthesis, bioassays, and conformational analysis. To obtain highly potent, selective and metabolically stable analogs, peptidomimetics such as peptide backbone modifications (retro-inverso structures), constrained amino acids, and cyclic structures have been incorporated into many bioactive peptide sequences. The conformational studies of the resulting analogs have led to topochemical models for the bioactivities of those peptides. This lecture will be focused on the results of such studies on opioids and somatostatin. We have synthesized numerous opioid analogs with various peptidomimetics based on three classes: enkephalins, dermorphin-deltorphins, and morphiceptins. Many of these analogs exhibit high potency, selectivity, and metabolic stability. Conformational studies of these analogs have enabled us to define the structural characteristics necessary for bioactivities of morphiceptins, dermorphins, enkephalins, and deltorphins. From these results, we can propose conformational models responsible for bioactivities at the mu- and delta-receptors. Our studies of cyclic somatostatin analogs are based on the highly active Merck analog c(-Pro6-Phe7-D-Trp8-Lys9-Thr10-Phe11-) (where the superscripts denote position in native somatostatin). To investigate the topochemical preference of backbone and side chains, unusual amino acids, including beta-methylphenylalanine7 or 11, beta-methyltryptophan8, as well as backbone modifications such as retro-inverso structures have been incorporated. The bioactivity profiles of these peptidomimetic molecules provide much information on the effects of backbone and side chain constraints on bioactivity.

Amino Acid Sequence↗