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Biomedical subjects

D Webb

Publications and source records attributed to D Webb.

At least 109 records · Page 6Linked to original sources
PubMed1990

Analysis of T lymphocytes cloned from the synovial fluid and blood of a patient with Lyme arthritis.

Cloned T lymphocytes reactive with Borrelia burgdorferi proteins were isolated from a patient with chronic Lyme arthritis. All of the T cell clones which proliferated in response to Borrelia proteins were CD3 + CD4 + CD8 - TCR alpha beta + and HLA-DR restricted. One T cell clone (GN30) exhibited HLA-DR-restricted cytotoxic activity against antigen-presenting cells pulsed with Borrelia antigen. In response to Borrelia antigen, the T cell clones produced TNF-alpha, INF-gamma, and GM-CSF. There are at least three distinct spirochetal proteins recognized by the four T cell clones analyzed. Purified Borrelia proteins triggered the HLA-DR-restricted proliferative and cytotoxic responses, as well as lymphokine secretion by two of the T cell clones. The spirochetal protein which triggered the HLA-DR-restricted proliferative and cytotoxic activities of the T cell clone (GN30) isolated from synovial fluid is the 41 kd flagellar protein.

Antigens, Bacterial↗
PubMed1989

Glomerulonephritis caused by chronic hepatitis B virus infection: treatment with recombinant human alpha-interferon.

STUDY OBJECTIVES: To assess the efficacy of alpha-interferon therapy in patients with hepatitis B virus (HBV)-related glomerulonephritis. DESIGN: Prospective, nonrandomized study. PATIENTS: Five patients with persistence of hepatitis B surface antigen, hepatitis B e antigen (HBeAg) and HBV DNA in serum for at least 6 months and histologic changes of chronic hepatitis on liver biopsy as well as persistent proteinuria of greater than 2 g/d and histologic changes of glomerulonephritis on renal biopsy. INTERVENTIONS: Patients received a 4-month course of recombinant human alpha-interferon (alfa-2b) beginning at a dose of 5 million units administered subcutaneously each day. RESULTS: Serum levels of HBV DNA decreased in all patients and fell to undetectable levels during treatment in four of five patients. In the four responding patients, serum HBeAg disappeared, aminotransferases fell into the normal range, and a follow-up liver biopsy showed an improvement in the hepatocyte necrosis and inflammation. Urine protein excretion also decreased during treatment. In the four responding patients, urine protein excretion gradually fell to less than 1 g/d and serum albumin levels rose into the normal range. Resolution of the biochemical and serologic evidence of chronic hepatitis and glomerulonephritis was accompanied by disappearance of signs and symptoms of liver and kidney disease. CONCLUSIONS: A high proportion of patients with HBV-related glomerulonephritis will respond to a 4-month course of alpha-interferon with a clinical, biochemical, and serologic remission.

Adult↗
PubMed1989

Specific amino acid residues in both the PstB and PstC proteins are required for phosphate transport by the Escherichia coli Pst system.

Three mutant alleles of the pstC gene and one mutant allele of the pstB gene were produced by site-directed mutagenesis. The pstC gene encodes an integral membrane protein of the phosphate-specific transport (Pst) system of Escherichia coli. The amino acid substitutions resulting from the pstC gene mutations, Arg-237----Gln, Glu-240----Gln, or a combination of both, caused the loss of phosphate transport through the Pst system, but the alkaline phosphatase activity remained repressed. The pstB gene encodes a peripheral membrane protein of the Pst system which carries a putative nucleotide-binding site. The amino acid substitutions Gly-48----Ile and Lys-49----Gln, resulting from the pstB mutations, caused the loss of phosphate transport through the Pst system and the derepression of alkaline phosphatase activity. The residues Gly-48 and Lys-49 are key residues in the putative nucleotide-binding site.

Alkaline Phosphatase↗
PubMed1989

Legionnaires' disease in a patient with rheumatoid arthritis treated with cyclosporine.

We report a patient with long-standing rheumatoid arthritis (RA) treated with cyclosporine A; she developed a flare of her arthritis and evidence of vasculitis, cavitary pulmonary disease, nephritis and hepatitis, and was found to have Legionella pneumophila serotype I infection. Cyclosporine is a relatively new and investigational therapy in RA. Thus, it is important that any unusual complications in patients with RA treated with cyclosporine should be documented.

Arthritis, Rheumatoid↗
PubMed1988

Arg-220 of the PstA protein is required for phosphate transport through the phosphate-specific transport system in Escherichia coli but not for alkaline phosphatase repression.

The pstA gene encodes an integral membrane protein of the phosphate-specific transport system of Escherichia coli. The nucleotide change in the previously described pstA2 allele was found to be a G----A substitution at position 276 of the nucleotide sequence, resulting in the premature termination of translation. Three mutations in the pstA gene were produced by site-directed mutagenesis. The amino acid substitutions resulting from the three site-directed mutations were Arg-170----Gln, Glu-173----Gln, and Arg-220----Gln. These amino acid residues were selected because a previous PstA protein structure prediction placed them within the membrane. The Arg-220----Gln mutation resulted in the loss of phosphate transport through the phosphate-specific transport system, but the alkaline phosphatase activity remained repressed. Neither the Arg-170----Gln nor the Glu-173----Gln mutation affected phosphate transport. The results are discussed in relation to a proposed structure of the PstA protein.

Alkaline Phosphatase↗
PubMed1987

Evolutionary divergence of promoters and spacers in the rDNA family of four Drosophila species. Implications for molecular coevolution in multigene families.

The organization and sequence of the rDNA multigene family of four Drosophila species (melanogaster, orena, virilis and hydei) have been compared in order to understand the quality and quantity of the differences which are involved with interspecific divergence of promoters and the polymerase I complexes (molecular coevolution). Each species has an intergenic spacer (IGS) made up of subrepeats which contain duplications of the promoter. Major structural and point-mutational differences exist, most of which have been spread by unequal crossingover through the family and species. Structural differences involve the types, lengths and copy-number of the IGS subrepeats, and the lengths and position of "unique" regions between blocks of repeats. The 240 base-pair repeat array shared by D. melanogaster and D. orena has been replaced by a 220 base-pair repeat, and the 95 and 330 base-pair arrays are absent altogether in D. virilis and D. hydei. The length of the "unique" region between the 240/220 base-pair arrays and the start of transcription varies, with the unusual situation of the last of the 220 repeats ending at the external transcribed spacer (ETS) boundary in D. virilis. Other structural differences involve regions of high cryptic simplicity arising from slippage in D. virilis and D. hydei IGSs. Sequence analysis of IGS and the ETSs indicates that the rDNA is not uniformly divergent throughout its length. Apart from the genes, there are regions of relatively high conservation covering the promoter regions and at some but not all potential RNA processing sites. The conserved promoter regions are more extensive within each pair of species D. melanogaster versus D. orena and D. virilis versus D. hydei, in keeping with their phylogenetic distances. Slippage-like mechanisms are involved with large numbers of deletions/insertions that make up the ETS differences between the species. Patterns of shared mutations between IGS subrepeats indicate stages of transition during rDNA differentiation by continual homogenization. The simultaneous operation of different turnover mechanisms, at different periodicities and rates, generates a complex picture of reorganization, some of which would influence the process of molecular coevolution in the family.

Animals↗
PubMed1987

Amino acid substitutions in the epsilon-subunit of the F1F0-ATPase of Escherichia coli.

A mutant strain of Escherichia coli was isolated in which Gly-48 of the mature epsilon-subunit of the energy-transducing adenosine triphosphatase was replaced by Asp. This amino acid substitution caused inhibition of ATPase activity (about 70%), loss of ATP-dependent proton translocation and lowered oxidative phosphorylation, but did not affect proton translocation through the F0. Purified F1-ATPase from the mutant strain bound to stripped membranes with the same affinity as the normal F1-ATPase. Partial revertant strains were isolated in which Pro-47 of the epsilon-subunit was replaced by Ser or Thr. Pro-47 and Gly-48 are predicted to be residues 2 and 3 in a Type II beta-turn and the Gly-48 to Asp substitution is predicted to cause a change from a Type II to a Type I or III beta-turn. Space-filling models of the beta-turn (residues 46-49) in the normal, mutant and partial revertant epsilon-subunits indicate that the peptide oxygen between Pro-47 and Gly-48 is in a different position to the peptide oxygen between Pro-47 and Asp-48 and that the substitution of Pro-47 by either Ser or Thr restores an oxygen close to the original position. It is suggested that the peptide oxygen between Pro-47 and Gly-48 of the epsilon-subunit is involved either structurally in inter-subunit H-bonding or directly in proton movements through the F1-ATPase.

Alleles↗
PubMed1987

Altered translation of the uncC gene coding for the epsilon subunit of the F1F0-ATPase of Escherichia coli.

The nucleotide sequence of the previously described uncC424 allele was determined and found to be the same as that of a wild-type uncC gene. However, a G----A change occurred 7 nucleotides upstream from the translation start codon, changing the putative Shine-Dalgarno sequence from GAGG to GAAG. Four revertant strains were examined. In one revertant, which had normal growth and membrane properties, a single base deletion had occurred to re-form the Shine-Dalgarno sequence GAGG 1 nucleotide closer to the translation start codon. A second revertant had a single base deletion in the preceding uncD gene, causing an extension of the beta subunit by 6 amino acids and an increase, presumably by translational coupling, in the amount of epsilon subunit. The third and fourth revertant strains were phenotypically similar and had either C----T or G----T changes 18 or 19 nucleotides, respectively, upstream from the translation start codon.

Base Sequence↗
PubMed1986

The plasma protein binding of metoclopramide in health and renal disease.

The plasma protein binding of metoclopramide was measured after addition of the drug (60 ng ml-1) to plasma from 18 patients with renal disease and 18 age and sex matched healthy individuals. The mean free fraction in renal disease (0.59 range 0.41-0.71) was not significantly different from controls (mean 0.6 range 0.56-0.69). In both groups the binding ratio of metoclopramide was significantly related to plasma alpha 1-acid glycoprotein (AAG) concentration but not to albumin or plasma non-esterified fatty acids concentration. Metoclopramide bound to human serum albumin (HSA) to a limited extent and to human AAG to a greater extent indicating that AAG is the major binding protein for the drug in plasma.

Blood Proteins↗
PubMed1985

Characteristics of P2 (nucleotide) receptors mediating contraction and relaxation of rat aortic strips: possible physiological relevance.

ATP and ADP relaxed rat aortic strips precontracted with noradrenaline by an endothelium-dependent mechanism. 5'-AMP was much less potent and adenosine was essentially without effect. The metabolically stable analogues alpha,beta-methylene ATP and beta,gamma-methylene ATP further contracted precontracted aorta. Aortic strips, which had not been precontracted with noradrenaline, contracted when exposed to either ATP or alpha,beta-methylene ATP, the latter nucleotide being much more potent than the former. Removal of the endothelium increased the contractions to ATP. ANAPP3 had no effect on the endothelium-dependent relaxations produced by ATP but it antagonized contractions produced by alpha,beta-methylene ATP. These results provide evidence for the possible existence of two subtypes of P2 receptors in rat aorta; a P2 receptor mediating contraction residing on smooth muscle which can be antagonized by ANAPP3 and where alpha,beta-methylene ATP is more potent than ATP, and a P2 receptor mediating relaxation located on the endothelium which cannot be antagonized by ANAPP3 and where ATP is much more potent than alpha,beta-methylene ATP.

Adenosine Diphosphate↗
PubMed1985

Transition stages of molecular drive in multiple-copy DNA families in Drosophila.

Multigene and non-genic DNA families are in a state of turnover and hence are continually being replaced throughout a population by new variant repeats. To quantify such molecular processes, in the absence of selection, it is necessary to find and compare stages of transistion during the homogenization of at least two non-genic families evolving in parallel in a closely related group of species. Detailed sequence analysis of patterns of variation, at each nucleotide position considered independently, amongst repeats of two tandem DNA families from seven related Drosophila species, reveals all stages of transition during the spread of randomly produced variant repeats. Variant repeats are found at different stages of homogenization and fixation in a population, irrespective of the loci, chromosomes or individuals from which they were cloned. Differences between the families in the relatively small number of variants at each transition stage and the greater number of fully homogenized and fixed variants between species of greater divergence indicate that the process of spread (molecular drive) is rapid relative to the mutation rate and occurs at seemingly different constant rates for each family. Occasional gene conversions, in addition to unequal exchanges, have contributed to family turnover. The significance of these results to the evolution of functional multigene families and divergence and conservation of sequences is discussed.

Journal Article↗
PubMed1985

The ex vivo plasma protein binding of theophylline in renal disease.

The plasma protein binding of theophylline was measured in 21 patients with renal disease and 21 healthy age and sex matched controls. The percentage of theophylline unbound to plasma was greater in patients with nephrotic syndrome and in chronic renal failure than in controls. In nephrotic syndrome the impairment of drug binding mirrored the marked degree of hypoalbuminaemia seen in this condition but in chronic renal failure the impairment of protein binding was greater than would be expected from the plasma albumin concentration changes. The percentage of theophylline free in plasma in renal disease may be increased (by as much as 50%). Such changes should be taken into account in interpreting the relationship between total plasma theophylline concentration and drug effect in renal disease.

Adult↗