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D W Cox

Publications and source records attributed to D W Cox.

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

Duplication of the human immunoglobulin heavy chain gamma 2 gene.

The five C gamma genes in the human immunoglobulin heavy chain region show nonrandom association and segregation as haplotypes. From the study of genetic variation in C gamma genes of 58 healthy Caucasian volunteers, we have identified a haplotype that involves a duplication of C gamma 2. This haplotype contains both the 13.5-kilobase (kb) and 25-kb BamHI fragment alleles of C gamma 2. In addition, the patterns and relative intensity of BamHI fragments containing C gamma genes were those expected for genomic DNA containing three copies of C gamma 2 for every two copies of the four other C gamma genes. A new EcoRI polymorphism in C gamma 4 was useful in defining the haplotype containing the duplication. Alleles of the C gamma genes in the duplication haplotype, including Gm markers of C gamma 1 and C gamma 3 and DNA polymorphisms of C psi gamma, C gamma 2, and C gamma 4, were consistent with its origin from an unequal crossover between the two common C gamma haplotypes, H1 and H2. This recombinant haplotype, which has been designated H2;1(gamma 2 dup) to reflect its origin, occurred with a frequency of .043 in a random sample of 116 chromosomes.

Alleles↗
PubMed1986

Genetic polymorphism of alpha 2HS-glycoprotein.

A genetic polymorphism of the human serum glycoprotein, alpha 2HS-glycoprotein, can be recognized using isoelectric focusing in polyacrylamide, followed by silver-stain immunofixation. In a North American Caucasian population, two common alleles and one rare allele have been recognized, with frequencies as follows: AHSG*1: .6419, AHSG*2: .3535, and AHSG*3: .0046; polymorphism information content (PIC): .36. A black population from various islands of the Caribbean has the two most common alleles, plus a variant (B) not found in the white population. Allele frequencies in the blacks were: AHSG*1: .6901, AHSG*2: .2606, AHSG*B: .0493; PIC: .396. Family studies confirmed the allele designations. Alleles in both populations were in Hardy-Weinberg equilibrium. This polymorphism will be useful as a marker on chromosome 3q and for forensic studies. The serum concentration associated with AHSG*1 may be somewhat greater than that associated with AHSG*2. Differences between the allele products remained after removal of sialic acid from the glycoprotein with neuraminidase. The silver-stain immunofixation technique used for this polymorphism has wide application for the study of polymorphisms where the protein is present in low concentration or where only low titer antiserum is available.

Black People↗
PubMed1985

31P-saturation-transfer nuclear-magnetic-resonance measurements of phosphocreatine turnover in guinea-pig brain slices.

The technique of 31P saturation-transfer n.m.r. was used to determine the forward and the reverse rate constants of creatine phosphotransferase in superfused guinea-pig cerebral tissues in vitro. The calculated forward rate constant of 0.22 +/- 0.03s-1 compared well with a previously reported value for rat brain in vivo [Shoubridge, Briggs & Radda (1982) FEBS Lett. 140, 288-292]. The reverse rate constant was found to be 0.55 +/- 0.10s-1. 3. By using concentrations of ATP and phosphocreatine estimated previously for this superfused preparation [Cox, Morris, Feeney & Bachelard (1983) Biochem. J. 212, 365-370], forward and reverse flux rates were calculated to be 0.68 and 0.72 mumol X s-1 X g-1 respectively. The concordance of forward and reverse fluxes contrasts with the situation observed in vitro in other tissues, and suggests that the creatine phosphotransferase reaction is at equilibrium under the conditions used here. 4. Lowering the concentration of glucose in the superfusing medium from 10mM to 0.5mM had no significant effect on phosphocreatine concentration or on the forward (ATP-generating) flux through creatine phosphotransferase. The results indicate that a normal phosphocreatine content in the presence of lowered glucose availability is reflected by an unchanged turnover rate.

Animals↗
PubMed1985

X;14 translocation:an exception to the critical region hypothesis on the human X-chromosome.

We report on a family in which an X;14 translocation has been identified. A phenotypically normal female, carrier of an apparently balanced X-autosome translocation t(X;14)(q22;q24.3) in all her cells and a small interstitial deletion of band 15q112 in some of her cells had 2 offspring. She represents a fifth case of balanced X-autosome translocation with the break point inside the postulated critical region of Xq(q13 q26) associated with fertility. The break point in this case is located in Xq22, the same band as in four previously published exceptional cases. In most of her cells, the normal X was inactivated. Her daughter, the proposita, has an unbalanced karyotype 46,X,der(X), t(X;14)(q22;q24.3)mat, del(15)(q11.1q11.3)mat. She is mildly retarded and has some Prader-Willi syndrome manifestations. She has two normal 14 chromosomes, der(X), and deletion 15q11.2. Her clinical abnormalities probably could be attributed to the deletions 15q and Xq rather than 14q duplication. In most of cells, der(X) was inactivated. We assume that spreading of inactivation was extended to the 14q segment on the derivative X. Late replication and gene dose studies support this view. Another daughter, who inherited the balanced X;14 translocation and not deletion 15 chromosome, is phenotypically normal.

Adolescent↗
PubMed1985

Effects of metabolic inhibitors on evoked activity and the energy state of hippocampal slices superfused in vitro.

The effects of the metabolic inhibitors, arsenate (1,10 mM), iodoacetate (1 mM), alpha-cyano-4-hydroxycinnamate (alpha C4HC: 0.05, 0.15, 0.5 mM), malonate (10 mM) and 2,4-dinitrophenol (10 microM) on granule cell evoked activity and levels of energy metabolites of superfused hippocampal slices were investigated. Every inhibitor tested decreased the amplitudes of the population spikes, and also to a lesser extent, the rates of rise of EPSP. The effects were essentially reversible except in the case of iodoacetate. Concentrations of inhibitors, sufficient to depress evoked activity by at least 75%, did not significantly decrease tissue levels of phosphocreatine, ATP or total K+, with the exception of 1 mM iodoacetate. In slices superfused with 10 mM arsenate, 0.5 mM alpha C4HC, 10 mM malonate or 10 micron 2,4-dinitrophenol, the threshold EPSP for population spike generation was significantly higher than in inhibitor-free medium. These results are discussed in relation to the potential importance of non-oxidative glucose metabolism in maintaining evoked activity, and the possibility that during metabolic insults, tissue ATP utilisation is decreased to match reduced cytoplasmic ATP supply.

2,4-Dinitrophenol↗
PubMed1985

Direct assignment of orosomucoid to human chromosome 9 and alpha 2HS-glycoprotein to chromosome 3 using human fetal liver x rat hepatoma hybrids.

The production of plasma proteins has been monitored in somatic cell hybrids between a rat hepatoma cell line (7777) and human fetal liver cells. Production of 14 plasma proteins was assayed in concentrated serum-free culture supernatants by electroimmunoassay. Alpha 2HS-glycoprotein (AHSG) was produced by 10 of 19 hybrids; concordancy for presence or absence of protein production was 100% for human chromosome 3. Orosomucoid (ORM) was produced in 8 of 19 hybrids, with a concordancy for presence or absence of protein of 94.7% with human chromosome 9. The chromosome location for genes for these two proteins, previously assigned by linkage studies, is confirmed by direct assignment. These studies have also suggested possible chromosomal assignments for loci for alpha 1-antichymotrypsin and C1 esterase inhibitor. Other genes for proteins which could not be assigned to specific chromosomes using these hybrids were: complement C3, ceruloplasmin, hemopexin, inter-alpha-trypsin inhibitor, prealbumin, retinol-binding protein, transferrin and apolipoproteins CII, B, and sinking-pre-beta [Lp(a)].

Aconitate Hydratase↗
PubMed1985

An autosomal dominant syndrome with 'acromegaloid' features and thickened oral mucosa.

A previously undescribed autosomal dominant syndrome has been observed in a large kindred with affected relatives spanning at least five generations. The phenotype is highly variable and appears to show complete penetrance. Affected persons have a progressively coarse, acromegaloid-like facial appearance and thickening of the lips and intraoral mucosa. The differences are discussed between this syndrome and three rather similar syndromes, pachydermoperiostosis, the Ascher syndrome, and multiple neuroma syndrome.

Acromegaly↗
PubMed1985

A multigene deletion within the immunoglobulin heavy-chain region.

The immunoglobulin heavy-chain genes are located in a cluster on chromosome 14. The simultaneous absence of the human IgG1, IgG2, IgG4, and IgA1 subclasses was previously reported in a healthy Tunisian Berber and was later shown to be due to a multigene deletion. We now describe a serological and molecular study of a different deletion observed in a healthy Tunisian. Blot hybridization analysis of the proband's DNA using gamma, epsilon, alpha, and mu switch probes showed that the deletion involves a large region of the immunoglobulin heavy-chain gene cluster: C psi epsilon, C alpha 1, C psi gamma, C gamma 2, and C gamma 4. Incidentally, we showed that the restriction enzyme EcoRI alone can be used with the alpha probe to differentiate A2m types. The deletion described, present in a person homozygous for GM-Am haplotypes (Gm1,17;..;5,14,11,13,10 A2m2), is consistent with previous location, by association analysis, of C psi gamma between C alpha 1 and C gamma 2. There is evidence to suggest that deletions may be more common in the Mediterranean region than in North American Caucasians.

Base Sequence↗
PubMed1985

Effect of creatine on granule cell evoked activity in the presence of normal and decreased levels of glucose.

This paper describes experiments to discover if hypoglycaemia-induced attenuation of evoked activity can be delayed by creatine-enrichment of superfusion medium. Dentate granule cell field potentials were evoked by stimulation of the perforant path in slices of guinea pig hippocampal formation superfused with medium containing 10 mM glucose. Addition of 25 mM creatine to the superfusate caused a rapid attenuation of field potentials which was followed by a gradual recovery of some components of the evoked activity over a period of about 2 h. During this period an increase in granule cell excitability became evident. In contrast, when the creatine was removed, the evoked activity was enhanced and then declined. Decreasing the superfusate concentration of glucose from 10 mM to 0.5 mM, in the absence of creatine, attenuated the conditioned response population spike by 25% in 32 +/- 10 min (mean +/- S.D., n = 4). After at least 2 h superfusion in medium containing 10 mM glucose and 25 mM creatine, lowering the glucose to 0.5 mM caused the conditioned population spike to decline by 25% in a significantly shorter period (18 +/- 6 min, significant at p less than 0.05). Differences between the observations described here and those reported earlier are discussed in terms of the superfusate K+ concentration and the contrasting effects of hypoxia and hypoglycaemia on levels of phosphagens and tissue pH.

Animals↗
PubMed1984

Occurrence of alpha-1-antitrypsin deficiency in 155 patients with alcoholic liver disease.

Liver biopsies from 155 patients with alcoholic liver disease were examined for periodic-acid-Schiff-positive, diastase-resistant (PAS-DR) intracytoplasmic globules in hepatocytes. Seven patients had these PAS-DR globules: each was a heterozygote for a deficiency allele of alpha-1-antitrypsin (AAT), or alpha-1-protease inhibitor, with the PAS-DR globules distributed in a pattern characteristic of this deficiency. One further patient with normal AAT had a few intracytoplasmic PAS-DR globules in occasional hepatocytes. The prevalence of AAT heterozygotes in this series did not differ from that in the reference population. The seven heterozygotes included five of PI (protease inhibitor) type MZ, one of PI type SZ, and one heterozygous for a rare deficiency allele, PI type MMmalton. The M and Mmalton alleles may be difficult to distinguish because they have similar mobilities with isoelectric focusing technics. Therefore, if PAS-DR inclusions are found in the liver of a patient with an apparently normal phenotype, the presence of a defective M variant allele, such as Mmalton, should be considered.

Adult↗
PubMed1984

Immunoglobulin (Gm) markers and alpha 1-antitrypsin (PI) types in rheumatoid arthritis and early onset chronic active hepatitis.

No Gm allotype, haplotype or phenotype was increased or decreased in frequency in two autoimmune diseases, rheumatoid arthritis (RA) or chronic active hepatitis (CAH) in comparison with control frequencies. The frequencies of the Gm haplotypes among 206 controls were 0.70, 0.19 and 0.11 for fb, ag and axg , respectively. Neither Gm heterozygosity nor homozygosity was associated with either disease. There was no interaction between alpha 1-antitrypsin (PI) and Gm type in the two diseases.

Adolescent↗
PubMed1984

Sensitivity of guinea-pig hippocampal granule cell field potentials to hexoses in vitro: an effect on cell excitability?

Evoked granule cell field potentials, and levels of tissue metabolites, in superfused guinea-pig hippocampal slices have been studied in the presence of low glucose and an alternative glycolytic substrate (D-fructose). The effects of glucose analogues (5-thio-D-glucose, 2-deoxy-D-glucose or 3-O-methyl-D-glucose) in the presence of glucose were also tested. Concentrations of glucose or fructose in excess of 2 mM and 10 mM respectively were required to maintain normal evoked activity. 5-Thioglucose (15 mM) in the presence of 5 mM-glucose decreased the amplitude of the population spike by 60% with little effect on population excitatory post-synaptic potential (e.p.s.p.). Tissue levels of phosphocreatine and ATP were essentially unchanged under all conditions tested, with the exception of 10 mM-fructose. The decrease in rates of lactate efflux from superfused tissue during and after superfusion with 3-O-methylglucose, 2-deoxyglucose or 5-thioglucose was found to be positively correlated with the extent of attenuation of field potentials. Analysis of the relationship between population spike amplitude and rates of rise of e.p.s.p., under conditions where field potentials were attenuated, showed that the population spike was always more sensitive to metabolic perturbation than was the e.p.s.p., thus indicating an effect on cell excitability. It is suggested that some aspect of non-oxidative glucose metabolism is important in maintaining this granule cell excitability.

Action Potentials↗
PubMed1984

Oxidation of plasma alpha 1-antitrypsin in smokers and nonsmokers and by an oxidizing agent.

The inhibitor activity of the protease inhibitor alpha 1-antitrypsin (alpha 1-protease inhibitor) is decreased by oxidizing agents such as those found in cigarette smoke. We have compared specific elastase and specific trypsin inhibitor activity, under defined conditions, in 26 smokers and 26 nonsmokers. Contrary to some previous reports, we have not found a difference between them. The oxidizing agent chloramine T was used to provide an additional oxidant stress for the comparison of plasma from nonsmokers and smokers. Although there was considerable variation between individual subjects in the extent of inactivation of inhibitor activity of alpha 1-antitrypsin, there was no significant difference between nonsmokers and smokers. Apparently there was sufficient antioxidant activity in the plasma of the smokers we tested to prevent the detection of oxidized inactivated alpha 1-antitrypsin.

Adult↗