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Biomedical subjects

C S Brown

Publications and source records attributed to C S Brown.

At least 127 records · Page 7Linked to original sources
PubMed1985

Genetic linkage relationships of seven DNA probes with Duchenne and Becker muscular dystrophy.

The inheritance of seven restriction fragment length polymorphisms detected by DNA probes has been studied in families with Duchenne and Becker muscular dystrophies (DMD and BMD). The probes used have all been mapped to the short arm of the X-chromosome, four being distal and three proximal to the disease loci located within the Xp21 region. Linkage analysis of the DNA polymorphisms in relation to the two disorders showed similar genetic distances. Data obtained from DMD and BMD families have been combined to give more precise values for the different recombination fractions. Combined use of these polymorphic DNA markers will be of practical value in the genetic counselling of women at risk for Duchenne and Becker muscular dystrophy.

Alleles↗
PubMed1985

Linkage analysis of a DNA polymorphism proximal to the Duchenne and Becker muscular dystrophy loci on the short arm of the X chromosome.

The inheritance of a restriction fragment length polymorphism (RFLP) detected by a cloned DNA sequence (p754) from the short arm of the X chromosome has been studied in 14 Duchenne muscular dystrophy kindreds and six Becker muscular dystrophy kindreds. The linkage data obtained suggest that both the DMD and BMD loci are located in the same region (p21) on the short arm of the X chromosome at a distance of about 15 to 20 cM from the 754 locus. Data from families informative for both the p754 and L1.28 polymorphisms suggest that p754 is closer to the disease loci than is L1.28.

Chromosome Mapping↗
PubMed1982

Preferential rheumatoid factor reactivity with disulphide bond altered IgG in radioimmunoassay.

Rheumatoid factor (RF) antibody populations were purified by immunoabsorption from rheumatoid arthritis patients' sera and from rabbit hyperimmune anti-streptococcal sera. On the basis of the particular affinity matrix from which the RF were eluted, the antibody populations were classified as being preferentially reactive with either mildly reduced and alkylated (MRA) or native, intact, homologous (with regard to species) IgG. Immune complexes formed between these RF preparations and IgG were characterized by their susceptibility to polyethylene glycol (PEG) precipitation. The two RF specificity populations were incubated in the presence of 125I-labelled MRA and intact homologous IgG preparations. The resultant complexes were subsequently precipitated in the presence of 0-20% (w/v) PEG. From the data generated by incubation of a constant amount of RF in the presence of either intact or MRA IgG, the amount of complex precipitated over the range of PEG concentrations examined was greatest when the form of IgG used for immunoadsorption was also used as the radiolabelled antigen. When a constant concentration of PEG was used and the concentration of the IgG antigen and RF were separately varied, precipitable complexes were formed at lower concentrations of each variable when radiolabelled antigen homology, with respect to the affinity matrix, was maintained. Therefore, although cross-reactive, the two RF specificities were clearly selective with regard to their affinity for a given form of IgG.

Antibody Specificity↗
PubMed1981

Word-retrieval difficulty and disfluent speech in adult anomic speakers.

The relationships existing between measures of disfluency and measures of word-retrieval ability in adult anomic aphasic and adult non-brain-damaged subjects were investigated. Subjects produced single-word naming responses for pictured stimuli consisting of objects, colors, and actions. The obtained number of correct naming responses and word-retrieval latency measurements were related to the number and types of disfluencies present in the subjects' connected speech samples. The major findings of the investigation include the following: (a) the anomic subject group presented significantly more disfluencies than did the nonaphasic group; (b) the number of disfluencies increased as word-retrieval difficulty increased for the anomic subjects; (c) when word-retrieval difficulty was measured by the number of correct responses those anomic subjects who tended to be most disfluent and to have the greatest word-retrieval difficulty also tended to have the highest proportions of those disfluencies most likely to be considered "stutterings" (part-word repetitions, vocal segregate repetitions, and prolongations) and the lowest proportions of hesitations; and (d) the proportion of stutterings increased as the total number of disfluencies increased for anomic and for nonaphasic subjects. Implications of results for testing of aphasic patients are discussed.

Adult↗
PubMed1981

Preferential reactivity of certain human and rabbit IgM and IgG rheumatoid factors with mildly reduced and amidomethylated IgG.

Two broadly defined populations were identified in affinity column-enriched rabbit and human rheumatoid factor (RF) preparations: one population reacted preferentially with mildly reduced and alkylated (MRA) homologous (with regard to species) IgG, and the other reacted preferentially with native, intact IgG. Each of these reactivities was identified by preferential association of RF with either intact or MRA IgG-Sepharose 4B conjugates and existed in both the IgM and IgG immunoglobulin classes. Use of soluble IgG inhibitor preparations in RF- dependent hemolytic and hemagglutination inhibition in RF-dependent hemolytic and hemagglutination inhibition assays showed that the preferred form of IgG inhibitor paralleled the preference of a particular RF preparation for a particular IgG affinity matrix. In addition, preferential reactivity was observed toward either intact or MRA Fc gamma inhibitors. On a molar basis RF reactivity with Fc gamma was significantly less than that observed in the presence of whole IgG. In contrast, neither IgG Fab nor F(ab')2 fragments were reactive with either of the 2 specificity populations of RF. The distribution of immunoglobulin class relative to specificity suggested that preferential reactivity with MRA IgG was usually associated with IgM RF, and reactivity with intact IgG was usually associated with IgG RF. These data suggest that in vivo perturbation of IgG structure may lead to an RF response identifiable by reactivity with an altered monomeric form of IgG.

Amides↗
PubMed1980

Mechanism of the magnesium ion activation of the catalytic activity of horse liver aldehyde dehydrogenase.

The activity of the pI 5 isozyme of horse liver aldehyde dehydrogenase is markedly enhanced by some divalent metal ions (Ca, Mn, Mg), inhibited by others (Fe, Cu, Cd), totally inhibited by Hg, and not significantly affected by still others (Zn, Ni, Co). Steady-state kinetics show that with 0.5 mM Mg or Mn a 2-fold activation of the velocity measured at pH 7.5 occurs when propionaldehyde is the substrate. In the pre-steady state, the magnitude burst of NADH formulation is increased from 2 moles formed per mole of tetrameric enzyme to 4 moles formed in the presence of Mg. The stoichiometry of coenzyme (NADH, NAD, epsilon-NAD) binding is also increased from essentially 2 moles binding to 4 moles binding per mole enzyme in the presence of Mg. It appears that the enzyme exhibits half of the site reactivity in the absence of metal but has a full complement of catalytic sites in the presence.

Aldehyde Oxidoreductases↗
PubMed1980

Metabolite gene regulation of the L-arabinose operon in Escherichia coli with indoleacetic acid and other indole derivatives.

The ability of indole derivatives to facilitate RNA polymerase transcription of the L-arabinose operon in Escherichia coli was shown to require the catabolite activator protein (CAP) as well as the araC gene product. Adenosine 3',5'-monophosphate (cAMP) was not obligatory for araBAD transcription when the cells were grown in the presence of 1 mM indole-3-acetic acid or in the presence of indole-3-acetamide, indole-3-propionic acid, indole-3-butyric acid, or 5-hydroxyindole-3-acetic acid. However, these indole derivatives were unable to circumvent the cAMP requirement for the induction of the lactose and the maltose operons. Catabolic repression occurred when glucose was added to cells grown in the presence of L-arabinose and 1 mM indoleacetic acid or 1 mM cAMP. This effect was reversed at higher concentrations of indoleacetic acid or cAMP. The induction and the catabolite repression phenomena were quantitated by measuring the differential rate of synthesis of L-arabinose isomerase (the araA gene product). These results indicated that indole metabolites from various living systems may regulate gene expression and may be involved in "metabolite gene regulation."

Arabinose↗
PubMed1980

Metabolite gene regulation: imidazole and imidazole derivatives which circumvent cyclic adenosine 3',5'-monophosphate in induction of the Escherichia coli L-arabinose operon.

Imidazole, histidine, histamine, histidinol phosphate, urocanic acid, or imidazolepropionic acid were shown to induce the L-arabinose operon in the absence of cyclic adenosine 3',5'-monophosphate. Induction was quantitated by measuring the increased differential rate of synthesis of L-arabinose isomerase in Escherichia coli strains which carried a deletion of the adenyl cyclase gene. The crp gene product (cyclic adenosine 3',5'-monophosphate receptor protein) and the araC gene product (P2) were essential for induction of the L-arabinose operon by imidazole and its derivatives. These compounds were unable to circumvent the cyclic adenosine 3',5'-monophosphate in the induction of the lactose or the maltose operons. The L-arabinose regulon was catabolite repressed upon the addition of glucose to a strain carrying an adenyl cyclase deletion growing in the presence of L-arabinose with imidazole. These results demonstrated that several imidazole derivatives may be involved in metabolite gene regulation (23).

Aldose-Ketose Isomerases↗
PubMed1978

A new locus (leuK) affecting the regulation of branched-chain amino acid, histidine, and tryptophan biosynthetic enzymes.

A locus (leuK) affecting regulation of the leucine operon was selected by isolating a spontaneous Ara+ derivative of an Escherichia coli B/r strain carrying an ara-leu fusion in which the arabinose operon is under leucine control. Genetic analyses by P1 transduction demonstrated that the lesion is located to the right of the galactose operon. Regulation of the biosynthetic enzymes for leucine, isoleucine-valine, histidine, and tryptophan was altered in a strain carrying leuK16. High-level gene expression in the heterozygous merodiploid strain F' leuK+/leuK16) demonstrated the dominance of the mutant allele to the wild-type allele. No apparent effect was observed in the mutant on N-acetylornithinase, a biosynthetic enzyme in the arginine pathway, nor on any of the 18 aminoacyl-tRNA synthetases examined. However, compared with that of the parent strain, the extent of the charging of leucyl-, isoleucyl-, valyl-, histidyl-, and arginyl-tRNA was decreased in the mutant.

Chromosome Mapping↗