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A L Gibson

Publications and source records attributed to A L Gibson.

14 recordsLinked to original sources
PubMed2005

Molecular analysis of isoniazid-resistant Mycobacterium tuberculosis isolates from England and Wales reveals the phylogenetic significance of the ahpC -46A polymorphism.

The present study investigated the prevalence and diagnostic potential of the most commonly reported mutations associated with isoniazid resistance, katG 315Thr, katG 315Asn, inhA -15T, inhA -8A, and the oxyR-ahpC intergenic region, in a population sample of 202 isoniazid-resistant Mycobacterium tuberculosis isolates and 176 randomly selected fully sensitive isolates from England and Wales identified by using a directed oligonucleotide array and limited DNA sequencing. The strains were recovered from patients originating from 29 countries; 41 isolates were multidrug resistant. Mutations affecting katG 315, the inhA promoter, and the oxyR-ahpC intergenic region were found in 62.7, 21.9, and 30% of 169 genotypically distinct isoniazid-resistant isolates, respectively, whereas they were found in 0, 0, and 8% of susceptible strains, respectively. The frequency of mutation at each locus was unrelated to the resistance profile or previous antituberculous drug therapy. The commonest mutation in the oxyR-ahpC intergenic region, ahpC -46A, was present in 23.7% of isoniazid-resistant isolates and 7.5% of susceptible isolates. This proved to be a phylogenetic marker for a subgroup of M. tuberculosis strains originating on the Indian subcontinent, which shared IS6110-based restriction fragment length polymorphism and spoligotype features with the Delhi strain and Central Asian strain CAS1; and this marker is strongly associated with isoniazid resistance and the katG 315Thr mutation. In total, 82.8% of unrelated isoniazid-resistant isolates could be identified by analysis of just two loci: katG 315 and the inhA promoter. Analysis of the oxyR-ahpC intergenic region, although phylogenetically interesting, does not contribute significantly to further identification of isoniazid-resistant isolates.

Antitubercular Agents↗
PubMed2000

Validation of air displacement plethysmography for assessing body composition.

PURPOSE: The purpose of this study was to verify the validity of an air displacement plethysmography device (Bod Pod) for estimating body density (Db). METHODS: The Db from the Bod Pod (DbBP) was compared with the Db from hydrostatic weighing (DbHW) at residual lung volume in a heterogeneous sample of 30 black men who varied in age (32.0 +/- 7.7 yr), height (180.3 +/- 7.5 cm), body mass (84.2 +/- 15.0 kg), body fatness (16.1 +/- 7.5%), and self-reported physical activity level and socioeconomic status. The Db for each method was converted to relative body fat (%BF) using race-specific conversion formulas and subsequently compared with %BF obtained from dual-energy x-ray absorptiometry (%BFDXA). RESULTS: Linear regression, using DbHW as the dependent variable and DbBP as the predictor, produced an R2 = 0.84 and SEE = 0.00721 g x cc(-1). However, the mean difference between the two methods (0.00450 +/- 0.00718 g x cc(-1) was significant (P < 0.01). The Bod Pod underestimated the Db of 73% of the sample. The %BF estimates from the Bod Pod, HW, and DXA differed significantly (P < 0.01). The average %BFBP (17.7 +/- 7.4%) was significantly greater than %BFHW (15.8 +/- 7.5%) and %BFDXA (16.1 +/- 7.5%); however, there was no significant difference between %BFHW and %BFDXA. CONCLUSION: The Bod Pod significantly and systematically underestimated Db, resulting in an overestimation of %BF. More cross-validation research is needed before recommending the Bod Pod as a reference method.

Absorptiometry, Photon↗
PubMed1991

A bacterial system for investigating transport effects of cystic fibrosis--associated mutations.

LIV-I, a high-affinity system that transports neutral, branched-chain amino acids into Escherichia coli, has two components, LivG and LivF, that are homologous to the cystic fibrosis (CF) transmembrane conductance regulator (CFTR). CF-associated mutations of human CFTR were introduced into corresponding regions of LivG, and their effects on leucine transport could be grouped into three classes. Mutations were found that (i) abolished LIV-I--directed transport, (ii) retained about a quarter of wild-type activity at the Michaelis-Menten constant (KM), and (iii) had minimal activity at the KM. A mutation equivalent to a benign polymorphism had no effect on transport. The correlation of these mutational phenotypes in LivG and CFTR suggests that the LIV-I prokaryotic transporter is functionally similar to the CF protein and that this similarity can be exploited to clarify the properties of the nucleotide-binding fold in this superfamily of proteins.

ATP-Binding Cassette Transporters↗
PubMed1990

Nucleotide sequence and genetic characterization reveal six essential genes for the LIV-I and LS transport systems of Escherichia coli.

The nucleotide sequence of the genes encoding the high affinity, branched-chain amino acid transport systems LIV-I and LS has been determined. Seven genes are present on a 7568-base pair DNA fragment, six of which participate directly in branched-chain amino acid transport. Two periplasmic amino acid-binding proteins are encoded by the livJ (LIV-BP) and livK (LS-BP) genes. These two proteins confer specificity on the LIV-I and LS transport systems. livK is the first gene in a polycistronic message that includes four genes encoding membrane components, livHMGF. The protein products of the livHMGF genes are shared by the two systems. An analysis of the livH and livM DNA sequences suggests that they encode hydrophobic proteins capable of spanning the membrane several times. The LivG and LivF proteins are less hydrophobic, but are also tightly associated with the membrane. Both LivG and LivF contain the consensus sequence for adenine nucleotide binding observed in many other transport proteins. A deletion strain that does not express any of the liv genes was constructed. This strain was used to show that each of the membrane component genes is required for high affinity leucine transport, including two genes, livM and livF, for which no previous genetic evidence had been obtained.

Amino Acid Sequence↗
PubMed1988

Differences in crystal properties and ligand affinities of an antifluorescyl Fab (4-4-20) in two solvent systems.

An antigen-binding fragment (Fab) from a murine monoclonal antibody (4-4-20) with high affinity for fluorescein was cocrystallized with ligand in polyethylene glycol (PEG) and 2-methyl-2,4-pentanediol (MPD) in forms suitable for X-ray analyses. In MPD the affinity of the intact antibody for fluorescein was 300 times lower than the value (3.4 x 10(10) M-1) obtained in aqueous buffers. This decreased affinity was manifested by the partial release of bound fluorescein when MPD was added to solutions of liganded Fab during crystallization trials. In PEG, the ligand remained firmly bound to the protein. The liganded Fab crystallized in the monoclinic space group P2(1) in PEG, with a = 58.6, b = 97.2, c = 44.5 A and beta = 95.2 degrees. In MPD the space group was triclinic P1, with a = 58.3, b = 43.4, c = 42.3 A, alpha = 83.9 degrees, beta = 87.6 degrees, and gamma = 84.5 degrees. X-ray diffraction data were collected for both forms to 2.5-A resolution. Surprisingly, the triclinic form of the liganed antifluorescyl Fab had the same space group, closely similar cell dimensions, and practically the same orientation in the unit cell as an unliganded Fab (BV04-01) with activity against single-stranded DNA.

Animals↗
PubMed1977

Doxorubicin cardiotoxicity: possible role of digoxin in its prevention.

Twenty-nine patients with gynaecological cancers who received over 400 mg of doxorubicin were monitored electrocardiographically to determine whether cardiac glycosides countered the adverse effects of high total doses of doxorubicin. Minor electrocardiographical changes were noted in five out of six patients who were not receiving a cardiac glycoside and four out of six who were receiving ouabain, and none of the 16 who were receiving digoxin. One other patient on digoxin stopped taking it and developed cardiomyopathy. One patient on ouabain also developed cardiomyopathy. So far nine patients on digoxin have received between 550 and 1000 mg/m2 of doxorubicin without ill effect. Cardiac glycosides are thought to prevent doxorubicin cardiomyopathy by competitively inhibiting doxorubicin at its receptor sites, but ouabain has a much shorter half life than doxorubicin and its metabolites and so is less effective than digoxin.

Digoxin↗