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Biomedical subjects

D H Williams

Publications and source records attributed to D H Williams.

At least 145 records · Page 8Linked to original sources
PubMed1986

The epidemiology of mental illness in Afro-Americans.

The epidemiologic study of mental illness among Afro-Americans has progressed since the antebellum period when the rate of mental illness among free Afro-Americans living in the North was inflated to justify continued slavery. Community-wide surveys conducted after World War II demonstrated that when socioeconomic variables were controlled, the rate of mental illness among Afro-Americans was no higher than that of other groups. The rates of mental illness and substance abuse of Afro-Americans vary according to socioeconomic class and are also related to differential family structure, early performance in school, and antisocial behavior of fathers. Despite progress, undersampling of middle-class Afro-Americans and poor, unemployed, young, urban Afro-American males are consistent deficiencies of surveys that even the ambitious NIMH Epidemiologic Catchment Area Program seems to share.

Adolescent↗
PubMed1985

Conformations of two duplex forms of d(TCGA) in slow-exchange equilibrium characterized by NMR.

Two conformations adopted by the tetranucleoside triphosphate d(TCGA) in aqueous solution are in slow-exchange equilibrium on the NMR time scale. 1H and 31P NMR spectra obtained at temperatures below 25 degrees C contain two sets of signals that vary in relative proportions with changing temperature. High-field NMR techniques allow the conformations of these species to be examined. Both forms are right-handed double-helical structures, and their interconversion does not involve a single-stranded species since transfer of saturation is observed between corresponding imino protons held in the base pairs of each duplex. The form that predominates at higher temperatures resembles B-DNA, but the other, while of similar conformation at the ends of the molecule, is distorted at the C-G step. Shearing at the center of the duplex results in interstrand stacking of the two cytosines in a way that is reminiscent of Z-DNA. Distances between nonexchangeable protons in this model are consistent with nuclear Overhauser effects observed for resonances of the low-temperature form, while the 1H NMR spectrum shows cytidine H-2' resonances at unusually high field. The relative stabilities of the two forms are discussed in terms of base stacking and hydration, but the origin of the high activation energy for interconversion implicit in the slow-exchange rate is unclear. The conformation of the low-temperature form may represent a sequence-dependent structural feature important in natural DNA, although somewhat fortuitously exemplified by this tetramer. The suggested involvement in correct nucleosome phasing of the pentamer d(TTCGA), present in some eukaryotic genes, is noted.

Kinetics↗
PubMed1985

A mass spectrometric assay for novel peptides: application to Xenopus laevis skin secretions.

The peptides secreted by the South African frog Xenopus laevis were screened systematically using a strategy based on fast atom bombardment mass spectrometry (FAB-MS). High performance liquid chromatography (HPLC) of crude and Sephadex G-10 chromatographed secretions showed that many more peptides were present in these secretions than those previously identified, i.e., xenopsin, caerulein, TRH and PGLa. Fractions from the HPLC were analyzed directly by FAB-MS to determine the molecular weights of these novel peptides. Subsequent analyses, using a combination of FAB-MS, manual Edman degradation, enzymatic digestions and amino acid analyses, identified the partial and sometimes complete sequences of these peptides which had molecular weights ranging from 700-2,700. Many peptides with structural features that are often indicative of biological activity, e.g., C-terminal amides and pyroglutamic acid, were readily identified by FAB-MS. In some cases, molecular weight data combined with partial sequence data was sufficient to identify peptides as originating from PGLa and the spacer regions in the precursors to xenopsin and caerulein.

Amides↗
PubMed1985

Incorporation of fluorotryptophan into triostin antibiotics by Streptomyces triostinicus.

The quinoxaline chromophores of the antibiotics produced by Streptomyces triostinicus are derived from tryptophan. Protoplasts of this organism made novel products when they were incubated with DL-5-fluorotryptophan or DL-6-fluorotryptophan. When added to batch cultures of the organism, DL-5-fluorotryptophan, at concentrations as low as 10 microM, inhibited both mycelial growth and triostin production, but gave rise to novel products. These have been characterized, using fast atom bombardment mass spectrometry, as novel triostins in which one or both of the quinoxaline rings contain an atom of fluorine. The chromatographic properties of the triostins arising from the incorporation of DL-5-fluorotryptophan are very similar to those of triostins containing chlorine or bromine at position 6 of the quinoxaline ring; they are clearly different from those having a chlorine atom at position 7. Accordingly, it is suggested that the carbon atom at position 5 of the indole ring of tryptophan ends up at position 6 of the quinoxaline ring system in triostins A and C.

Anti-Bacterial Agents↗
PubMed1984

A 15N nuclear magnetic resonance study of the biosynthesis of quinoxaline antibiotics.

Uniformly 15N-labelled triostin A and echinomycin have been prepared by growing the producing organisms on enriched media and their 15N nuclear magnetic resonance spectra partially assigned by a combination of nuclear Overhauser effect and scalar coupling constant measurements. Selective feeding experiments using unlabelled L-tryptophan-supplemented media have shown that N-1 and N-4 of the quinoxaline rings have their origins in the indole and amino groups of tryptophan, respectively.

Echinomycin↗
PubMed1984

Hydrophobic interactions affect hydrogen bond strengths in complexes between peptides and vancomycin or ristocetin.

A study on complexes of the glycopeptide antibiotics vancomycin and ristocetin with various dipeptides and tripeptides shows that the intermolecular hydrogen bond strengths of the complexes are reasonably well correlated with their free energy of formation. Such correlation is not anticipated on the basis of a purely hydrophobic interaction of the peptide side-chains with the antibiotics. It is also shown that the free energy changes observed are very different from those expected as a result of hydrophobic forces. These facts suggest that addition of a hydrophobic group not only allows hydrophobic bonding but also strengthens existing hydrogen bonds. The increased hydrogen bond strength can be an important factor in determining the overall binding energy.

Binding Sites↗
PubMed1984

The structure and mode of action of glycopeptide antibiotics of the vancomycin group.

It has been shown that after more than two decades of work on the structure and mode of action of the vancomycin group of antibiotics we have quite a detailed picture of aspects of their binding in vitro. Our introduction has indicated that these antibiotics are of continuing practical importance, whether in clinical use or animal husbandry. It is clear, however, that if one desires to modify these compounds to produce more effective antibiotic agents, more work is required--particularly to understand better the role of the sugar moieties. Nevertheless, with our present knowledge of the structure and mode of action of the antibiotics we can be fairly confident that they represent a group of compounds specifically evolved to aid the survival of the producing organisms by killing or inactivating competing gram-positive bacteria.

Anti-Bacterial Agents↗
PubMed1983

Use of inter-proton nuclear Overhauser effects to assign the nuclear magnetic resonance spectra of oligodeoxynucleotide and hybrid duplexes in aqueous solution.

Inter-proton nuclear Overhauser enhancements (NOEs) have been used to assign the aromatic, anomeric and 2' resonances in the 1H nuclear magnetic resonance spectrum of the duplex formed between d(T-C-A-C-A-T) and d(A-T-G-T-G-A). The same techniques have been applied to assignments in the hybrid duplex formed by d(T-C-A-C-A-T) with r(A-U-G-U-G-A). Comparison of intra-residue with inter-residue NOEs yields structural information which suggests that the conformations of both duplexes are similar. The NOEs are consistent with inter-proton distances measured from models of B-form DNA. Circular dichroic results confirm these deductions.

Chemical Phenomena↗
PubMed1983

Amino acid sequence around the active serine in the acyl transferase domain of rabbit mammary fatty acid synthase.

Rabbit mammary fatty acid synthase was labelled in the acyl transferase domain(s) by the formation of the O-ester intermediates after incubation with [14C]acetyl- or malonyl-CoA. Elastase peptides containing the labelled acyl groups were isolated using high performance liquid chromatography and sequenced by fast atom bombardment mass spectrometry. An identical peptide (acyl-Ser-Leu-Gly-Glu-Val-Ala) was obtained after labelling with acetyl- or malonyl-CoA. This confirms the hypothesis that, unlike Escherichia coli or yeast, a single transferase catalyses the transfer of both acetyl- and malonyl-groups in the mammalian complex. The sequence at this site is compared with that around the active serine in other acyl transferases and hydrolases.

Acyltransferases↗
PubMed1983

A 1H nOe and CD study of the salt-concentration dependence of the structure of d(G-C).

Intra- and internucleotide 1H nuclear Overhauser effects (nOes) have been observed in the synthetic decancleoside nonaphosphate d(G-C)5 at low and high salt concentrations, and in conditions under which duplex formation is complete. Comparison of the nOes with interproton distances derived from model and X-ray structures suggest that the duplex is right-handed up to a sodium chloride concentration of 4M, in contrast to the behaviour of poly [d(G-C)]. C.D. spectra are consistent with this suggestion.

Circular Dichroism↗
PubMed1983

Proton nuclear Overhauser effect study of the structure of a deoxyoligonucleotide duplex in aqueous solution.

Nuclear Overhauser enhancements (NOEs) have been observed between some of the nonexchangeable protons of the self-complementary octanucleoside heptaphosphate d(G-G-T-A-T-A-C-C) in conditions under which duplex formation takes place. Comparison of inter- and intraresidue NOEs has made possible the assignment of all the aromatic and 1'- and 2'-ribosyl signals. In particular, and with the exception of the 5' terminal, NOEs of comparable magnitude are observed between H-8 of purines or H-6 of pyrimidines and pairs of anomeric protons. There are the H-1's of the nucleotide containing the relevant aromatic proton and those of the adjacent residue in the 5' direction. Differentially evolving NOEs are also generated between aromatic protons and the C-2' methylene protons on both the same residue and on the neighboring 5' residue. The relative magnitudes of these NOEs are discussed in terms of overall helical geometry and are consistent with a generally accepted B-type DNA model (R. Chandrasekaran and S. Arnott, personal communications).

Base Sequence↗
PubMed1983

Proton nuclear overhauser effect study of the structure of an actinomycin D complex with a self-complementary tetranucleoside triphosphate.

Saturation transfer and nuclear Overhauser effect (NOE) techniques have been used to assign some resonances of nonexchangeable protons in the NMR spectrum of the complex formed between actinomycin D and the self-complementary tetranucleoside triphosphate d(A-G-C-T). Intermolecular NOEs suggest that the drug chromophore intercalates between the two G-C base pairs of the nucleotide double helix, while the pentapeptide lactone rings fill the minor groove. Binding-induced distortions of helix geometry are discussed.

Binding Sites↗
PubMed1983

Studies related to the metabolism of anabolic steroids in the horse: the metabolism of 1-dehydrotestosterone and the use of fast atom bombardment mass spectrometry in the identification of steroid conjugates.

The metabolism and urinary excretion of 1,2(n)-3H-1-dehydrotestosterone were studied in cross-bred gelded horses. Approximately 40% of the dose was excreted in 24 h. The steroid metabolites were extracted by Amberlite XAD-2 resin and fractionated into glucuronides and sulphoconjugates. Unchanged 1-dehydrotestosterone was the only component identified by gas chromatography mass spectrometry after solvolysis of the sulphoconjugates. Positive and negative ion fast atom bombardment mass spectra were obtained on the purified 1-dehydrotestosterone sulphoconjugate isolated from horse urine and on the alkali metal salts of three standard steroid conjugates. Spectra obtained in the different modes were of comparable intensity. Positive ion spectra were generally more complex due to the formation of alkali metal adduct ions containing several sodium cations. The most abundant ion in the negative ion spectra corresponded to the loss of the alkali metal cation to give [M]-. Thus, the structure of a conjugate can be defined from the combination of mass spectrometric techniques.

Anabolic Agents↗