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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 613 records · Page 34Linked to original sources
PubMed1992

Paralytic poliomyelitis in England and Wales, 1985-91.

OBJECTIVES: To ascertain all cases of paralytic poliomyelitis in England and Wales during 1985-91 and to determine the source of infection in each case. DESIGN: Descriptive study of cases reported between 1985 and 1991. SETTING: All health districts in England and Wales. SUBJECTS: Patients normally resident in England and Wales whose clinical features were consistent with paralytic poliomyelitis or with laboratory evidence of recent poliovirus infection and compatible symptoms. MAIN OUTCOME MEASURES: Clinical, epidemiological, and laboratory features in identified cases. RESULTS: Of 54 suspected cases of poliomyelitis, 33 were excluded, leaving 21 cases, of which 13 were vaccine associated (nine recipient and four contact) cases, five were imported cases, and three were cases whose source of infection was unknown. No cases due to indigenous wild polioviruses were identified; two were imported cases due to wild viruses. One patient died during the acute phase of the illness, and two children with previously unrecognised severe congenital immune deficiency died between one and two months after the onset of paralysis after the first or second dose of oral polio vaccine. The estimated risk of vaccine associated paralysis is 1.46 per million for the first dose, 0.49 for the second, zero for the third and fourth doses, and 0.33 for the fifth. CONCLUSIONS: Indigenous wild poliovirus seems to have been eradicated, although wild virus may be imported; improved surveillance of suspected cases including immediate notification and characterisation of the virus to ensure that eradication is maintained is essential.

Adolescent↗
PubMed1992

Clonally related IgM rheumatoid factors undergo affinity maturation in the rheumatoid synovial tissue.

Using hybridoma technology we established a panel of human monoclonal rheumatoid factors (RF) from the synovial tissues of two patients with rheumatoid arthritis (RA), and one patient with polyarticular juvenile RA. Nucleotide sequence analysis of the V regions of these RF indicates that two independently derived antibodies from one of the RA patients are clonally related. One of these antibodies appears to be close to germ-line configuration, whereas the other has accumulated a total of 36 substitutions in both H and L chains. Measurements of the affinity for human IgG of the two RF show that the extensively mutated RF has 100-fold higher affinity for IgG than the RF close to germline. These findings indicate that IgM RF in RA can undergo affinity maturation and suggest that certain RF may be the product of an Ag-driven immune response.

Amino Acid Sequence↗
PubMed1992

A ubiquitous 64-kDa protein is a component of a chloride channel of plasma and intracellular membranes.

Chloride channels are present in the plasma and intracellular membranes of most cells. Previously, using the ligand indanyloxyacetic acid (IAA), we purified four major proteins from bovine kidney cortex membrane vesicles. These proteins gave rise to chloride channel activity when reconstituted into phospholipid vesicles. Two of these proteins (97 and 27 kDa) were found to be drug-binding proteins by N-terminal sequence analysis. Antibodies raised to the 64-kDa protein stained only this protein on immunoblots, and only this protein was present after purification on an immunoaffinity column. In addition, these same antibodies were able to deplete IAA-94 inhibitable chloride channel activity from solubilized kidney membranes. Of fractions obtained from the gel filtration of solubilized kidney membranes, only those containing this 64-kDa protein exhibited measurable chloride channel activity. Immunoblots of a variety of species and cell types, both epithelial and nonepithelial, revealed that this protein is ubiquitous and highly conserved. Immunocytochemistry in CFPAC-1 cells revealed staining for this protein on the apical plasma membrane and in the membranes of intracellular organelles. These results demonstrate that the integral membrane protein p64 is a component of chloride channels present in both epithelial plasma membrane and the membranes of intracellular organelles.

Amino Acid Sequence↗
PubMed1992

Selectively amplified expression of an isoform of the vacuolar H(+)-ATPase 56-kilodalton subunit in renal intercalated cells.

The intercalated cells of the kidney collecting duct are specialized for physiologically regulated proton transport. In these cells, a vacuolar H(+)-ATPase is expressed at enormous levels in a polarized distribution on the plasma membrane, enabling it to serve in transepithelial H+ transport. In contrast, in most eukaryotic cells, vacuolar H(+)-ATPases reside principally in intracellular compartments to effect vacuolar acidification. To investigate the basis for the selective amplification of the proton pump in intercalated cells, we isolated and sequenced cDNA clones for two isoforms of the approximately 56-kDa subunit of the H(+)-ATPase and examined their expression in various tissues. The predicted amino acid sequence of the isoforms was highly conserved in the internal region but diverged in the amino and carboxyl termini. mRNA hybridization to a cDNA probe for one isoform (the "kidney" isoform) was detected only in kidney cortex and medulla, whereas mRNA hybridization to the other isoform of the approximately 56-kDa subunit and to the H(+)-ATPase 31-kDa subunit was found in the kidney and other tissues. Immunocytochemistry of rat kidney with an antibody specific to the kidney isoform revealed intense staining only in the intercalated cells. Staining was absent from proximal tubule and thick ascending limb, where H(+)-ATPase was detected with a monoclonal antibody to the 31-kDa subunit of the H(+)-ATPase. This example of specific amplification of an isoform of one subunit of the vacuolar H(+)-ATPase being limited to a specific cell type suggests that the selective expression of the kidney isoform of the approximately 56-kDa subunit may confer the capacity for amplification and other specialized functions of the vacuolar H(+)-ATPase in the renal intercalated cell.

Adult↗