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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 379 records · Page 21Linked to original sources
PubMed1996

The 1990 Florida Dental Investigation: theory and fact.

Controversy remains about the Centers for Disease Control and Prevention's (CDC) conclusion that a dentist in Florida transmitted human immunodeficiency virus to six of his patients in the late 1980s. The most vocal doubt has come from journalists affiliated with the television program 60 Minutes. Although unanswered questions about the case remain, the evidence continues to overwhelmingly support the CDC's theory. The criticism of the CDC investigation consists largely of assertions that contrary evidence theoretically might exist.

Acquired Immunodeficiency Syndrome↗
PubMed1996

A clinical evaluation of a new method for HBV DNA quantitation in patients with chronic hepatitis B.

Selection of HBsAg-positive patients for antiviral therapy requires an estimation of disease activity and viral replication. Serum transaminases and histological analysis are commonly used to assess disease activity, and viral replication is assessed by serological testing of HBeAg and serum hepatitis B virus (HBV) DNA. Dot blot hybridisation may be insufficiently sensitive to corroborate low-grade replication in patients with active hepatitis, and polymerase chain reaction (PCR) may be testing too sensitive for this role. Theoretically an assay of intermediate sensitivity is therefore required. Our aim was to evaluate whether the branched chain DNA (bDNA) assay would fulfil this function. Seventy-one HBsAg-positive patients were tested for HBV DNA by the bDNA assay; 64 were also tested by dot blot hybridisation and, when appropriate, also by PCR. Thirty-seven (52%) patients were positive for HBV DNA by the bDNA assay. HBV DNA was detected in the majority (21/28; 75%) of HBeAg-positive patients but also in 14 of 36 (39%) anti-HBe-positive patients. HBV DNA was detected by the bDNA assay in 20 of 48 (42%) patients negative for HBV DNA by dot blot hybridisation assay. All patients positive for HBV DNA by dot blot hybridisation were also positive by the bDNA assay. Sixteen of twenty-five (64%) patients negative for HBV DNA by the bDNA assay were positive for HBV DNA by PCR. The bDNA assay is a sensitive and reliable method for the detection of HBV DNA. As nucleoside analogue therapy becomes more widely available, the assay should provide a useful tool for the selection for and monitoring of patients on antiviral therapy.

Adult↗
PubMed1996

Glycosylphosphatidylinositol-anchored H-2Db molecules are defective in antigen processing and presentation to cytotoxic T lymphocytes.

Glycosylphosphatidylinositol-anchored (GPI)-Db molecules are defective in mediating cytotoxic T lymphocytes (CTL) lysis of transfected lymphoma cells, compared to their transmembrane (TM) counterpart. This defect is manifest when antigenic peptide must be processed and presented through the endogenous pathway. These same transfectants can be lysed by allospecific CTL, or by antigen-specific Db-restricted CTL when pulsed with appropriate exogenous synthetic peptide, demonstrating that they can bind and present peptide for CTL-mediated lympholysis. The defect apparently results from differences between GPI-Db and TM-Db assembly and transport, or from differences in membrane topology that affect CD8+ CTL recognition of major histocompatibility complex/peptide complex.

Animals↗
PubMed1996

Antigen retrieval in cryostat tissue sections and cultured cells by treatment with sodium dodecyl sulfate (SDS).

A simple method for antigen retrieval in tissue sections and cell cultures is described. Because many antibodies recognize denatured proteins on western blots, but are poorly reactive by immunocytochemistry, the effect of applying sodium dodecyl sulfate (SDS) to cryostat sections of tissues and to cell cultures prior to immunostaining was examined. In many cases, a 5-min pretreatment with 1% SDS produced a dramatic increase in staining intensity by indirect immunofluorescence. Among the antibodies tested that showed a positive effect of SDS were an anti-Na/K-ATPase monoclonal antibody, an anti-AE1/2 anion exchanger polyclonal antipeptide antibody, a monoclonal anti-caveolin antibody, and an anti-rab4 monoclonal antibody. In other cases, including antibodies against gp330, aquaporin 1, and aquaporin 2, no effect of SDS was detected. The results show that SDS treatment can be used as a simple method of antigen retrieval in cryostat sections and on cultured cells. In some cases, antigens were not detectable without pretreatment with SDS.

Animals↗
PubMed1996

Sequence conservation and expression of the gene encoding the outer capsid glycoprotein among human group C rotaviruses of global distribution.

Group C rotaviruses have been identified recently from fecal samples of children with diarrhea in the United States. Using reverse transcriptasepolymerase chain reaction and sequence analysis, we sequenced gene 8s encoding VP7 from two U.S. strains (RI-1 and RI-2), and eight other strains isolated from patients on four continents, and compared these with the sequences of four published strains. The gene 8s of the 14 strains were remarkably conserved in size and in predicted primary and secondary structures. When the sequences of the human VP7s were compared with that of the prototype porcine Cowden strain, six regions were found variable in both deduced primary and predicted secondary structures, four of which were predicted to be hydrophilic and might determine serotype specificity. Gene 8 of the human S-1 strain was further characterized by expression in recombinant baculoviruses. The expressed product was immunogenic but failed to elicit neutralizing antibodies. Our sequence analysis indicates that all the human strains characterized to date belong to a single G genotype, which may constitute a single G serotype, pending further antigenic analysis. Whether the human strains and the Cowden strain are the same serotype remains to be determined.

Adult↗
PubMed1996

Expression of nm23-H1 in prostatic intraepithelial neoplasia and adenocarcinoma.

The product of the nm23-H1 gene has been reported to be related to the metastatic potential of several tumors. Although several studies have characterized the expression of the nm23-H1 gene product in prostatic adenocarcinoma, little is known of the expression of this protein in prostatic intraepithelial neoplasia (PIN), a putative precancerous lesion. The authors used immunohistochemistry to examine the expression of the nm23-H1 protein in PIN as well as benign and malignant prostatic tissue. A monoclonal antibody to nm23-H1 (Novocastra, Newcastle upon Tyne, UK, clone 37.6) and a biotin/strepavidin detection system were used for antigen localization. Weak to moderate immunostaining was consistently detected in the benign glandular epithelium of 28 radical prostatectomy specimens. In contrast, strong immunostaining was detected in the glandular epithelium in PIN lesions of 19 radical prostatectomy specimens examined. Strong immunostaining was also frequently detected in the malignant cells of 39 localized prostatic adenocarcinomas, as well as 7 metastatic lesions. These findings show a phenotypic similarity of PIN to prostatic adenocarcinoma with respect to nm23-H1 expression. Furthermore, strong expression of nm23-H1 likely represents an early event in the development of prostatic adenocarcinoma.

Adenocarcinoma↗
PubMed1996

Quantitative assessment of hepatitis C virus RNA and IgM antibodies to hepatitis C core in chronic hepatitis C.

BACKGROUND/AIMS: IgM antibodies to hepatitis C virus have been found in a variable proportion of patients with chronic hepatitis C. We have evaluated whether IgM anti-core antibodies correlate with viraemia or hepatic injury in chronic hepatitis C. METHODS: Serum from 106 patients with chronic hepatitis C with varying stages of disease were tested for IgM anti-core hepatitis C virus by immunoassay. All patients were seropositive for IgG antibody to hepatitis C virus by second-generation ELISA; 25 had histologic cirrhosis and 57 chronic hepatitis. IgM anti-core was detected in 84/106 (79.2%) patients. HCV-RNA was tested by branched (bDNA) signal amplification assay or by polymerase chain reaction in 92 patients. RESULTS: All IgM-anti-HCV positive patients had detectable HCV-RNA. Seventy of 87 (80.5%) HCV-RNA-positive patients were IgM anti-core positive. Levels of IgM anti-HCV were significantly higher in patients with HCV-RNA detected by bDNA than in those who were bDNA negative, but there was no correlation between HCV-RNA concentrations and IgM anti-HCV levels. Of the 84 patients with positive results for IgM anti-core hepatitis C virus, 59 (70.2%) had abnormal alanine aminotransferase levels. The levels of IgM anti-core hepatitis C virus were likewise significantly higher in those with abnormal alanine aminotransferase levels. There was no difference in the percentage of patients with a positive IgM anti-HCV, or in levels of IgM anti-core hepatitis C virus in those with chronic hepatitis versus cirrhosis. CONCLUSIONS: These data suggest that the majority of patients with chronic hepatitis C virus infection are IgM anti-core hepatitis C virus positive, and the detection seems to be associated with viral replication and biochemical evidence of hepatic necrosis. IgM anti-core hepatitis testing may prove useful as an adjunct in the clinical assessment of patients with chronic hepatitis C.

Adolescent↗
PubMed1996

Ethics and LAVH.

Explore the source record for details and available documents.

Ethics, Medical↗
PubMed1996

Measles immunity and response to revaccination among secondary school children in Cumbria.

The prevalence of antibody to measles virus in 759 children aged 11-18 years attending a secondary school in Cumbria was measured using a salivary IgG antibody capture assay. Serum IgG antibody levels were measured using a plaque reduction neutralization assay in subjects whose saliva was antibody negative. Vaccination histories were obtained from the child health computer and general practice record. A total of 662 pupils (87% of those tested) had detectable measles-specific IgG in saliva. Of the remaining 97, 82 provided blood samples and 29 had serum neutralizing antibody levels above 200 mIU/ml. Afer adjusting for non-participation rates, the proportion considered non-immune (no IgG in saliva and < or = 200 mIU/ml in serum) was 9% overall, ranging from 6% in vaccinated children to 20% in unvaccinated children. Measles-mumps-rubella vaccine was given to 50 children of whom 38 provided post-vaccination serum and 32 saliva samples. Thirty (79%) had a fourfold or greater rise in serum neutralizing antibody and 28 (88%) developed IgG antibody in saliva. Half of the children considered non-immune by antibody testing would have been overlooked in a selective vaccination programme targeted at those without a history of prior vaccination. A programme targeted at all school children should substantially reduce the proportion non-immune since a primary or booster response was achieved in three quarters of previously vaccinated children with low antibody levels and in all unvaccinated children. While it is feasible to screen a school-sized population for immunity to measles relatively quickly using a salivary IgG assay, a simple inexpensive field assay would need to be developed before salivary screening and selective vaccination could substitute for universal vaccination of populations at risk of measles outbreaks. The salivary IgG assay provided a sensitive measure of a booster response to vaccination.

Adolescent↗
PubMed1996

A study of maternally derived measles antibody in infants born to naturally infected and vaccinated women.

Maternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean titres were significantly higher in the unvaccinated than in the vaccinated mothers (P < 0.001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.

Adult↗
PubMed1996

Methodological considerations in participant event monitoring of low-base-rate events in health psychology: children's injuries as a model.

The present article outlines the advantages of the participant event monitoring methodology for the investigation of unpredictable, low-base-rate events in children. Several methods for assessing the quality of participant event monitoring data are advanced with a data set showing participant event monitoring of children's minor injuries by 61 children and their mothers. Child-mother correspondence and debriefing data suggest good accuracy for frequency estimates. Home- and laboratory-based simulations illustrate the participant event monitors' accuracy for major details. Traditional measures of data quality show good overall coder and test-retest reliability, and cross-observer reports show acceptable estimates of validity for objective aspects of the events and the expected lower estimates for the more subjective aspects. Conceptual and pragmatic difficulties of the method are considered, and suggestions for future research are advanced.

Accident Prevention↗
PubMed1996

Long-term treatment of growth retarded children with chronic renal insufficiency, with recombinant human growth hormone.

Long-term (5 years) treatment of 20 growth-retarded pre-pubertal children with chronic renal insufficiency (CRI) led to a significant (P < 0.00005) improvement in standardized height from -2.6 at baseline to -0.7 at five years. Eight patients were paused after reaching target height (50th centile midparental height) and 4 (50%) required re-initiation of recombinant human growth hormone (rhGH) because of a substantial decrease in standardized height. Growth potential was not adversely impacted with a delta height age (HA) minus delta bone age (BA) at five years of +0.5 (N = 8). The mean calculated CCr decreased from 32.2 +/- 15.2 ml/min/1.73 m2 at baseline to 24.6 +/- 14.7 ml/min/1.73 m2 at five years (P = 0.04), which would be consistent with the natural history of CRI in children. Despite the absence of clinical consequences, the increase in the mean fasting and two-hour post-prandial plasma insulin levels during treatment compared to baseline requires further investigation. The only clinically significant adverse event potentially related to rhGH was the development of avascular necrosis of the femoral head during the fourth year of treatment in one patient. Long-term rhGH treatment in children with CRI improves the potential of children with CRI achieving target adult height.

Child↗
PubMed1996

Localization of the thiazide sensitive Na-Cl cotransporter, rTSC1 in the rat kidney.

A thiazide sensitive Na-Cl cotransporter, rTSC1, has recently been cloned from a rat kidney cortex cDNA library. The molecular regulation and nephron localization of this protein is unknown. The purpose of this study was to examine the nephron distribution and subcellular localization of the rTSC1 protein in the rat kidney. In situ hybridization showed rTSC1 transcripts were localized to short, convoluted tubule segments in the kidney cortex. Polyclonal antibodies raised against a 110 amino acid segment from the amino terminus of rTSC1 recognized three major bands of 135, 140 and 155 kDa on Western blotting of membrane protein from cortex but not outer medulla of the rat kidney. Immunofluorescence studies using the antibody alone and in double labeling experiments with antibodies against the H+ ATPase and calbindin D28, showed intense labeling of apical membranes in the distal nephron beginning in the initial distal convoluted tubule and terminating within the connecting tubule. The intensity of labeling diminished from proximal to distal sites along the distal tubule. Ultrastructural studies by immunoelectron microscopy showed the cotransporter protein to be localized predominately on apical microvilli of the distal convoluted tubule cells. These results are consistent with rTSC1 encoding the apical thiazide sensitive Na-Cl cotransporter in the distal tubule.

Animals↗
PubMed1996

Acidification of the male reproductive tract by a proton pumping (H+)-ATPase.

An acidic luminal pH (ref. 1-3) is involved in sperm maturation, and in maintaining sperm in an immotile state in the epididymis and vas deferens (2,4-6). Neutralization by prostatic fluid is one of a complex series of events that triggers sperm motility (2,7,8). Failure of the acidification mechanism might, therefore, result in poor sperm maturation, premature motility and infertility. We have shown that a vacuolar (H+)-ATPase is expressed at high levels on the luminal plasma membrane of specialized cells in the epididymis (9), which closely resemble acid-secreting kidney intercalated cells (10,11). We now show that similar cells are also present in the vas deferens, and that a bafilomycin-sensitive proton flux can be detected using a noninvasive proton-selective vibrating probe. Up to 80% of the net proton secretion in the vas deferens is inhibited by bafilomycin, consistent with a major role of a vacuolar-type (H+)-ATPase in this process. This acidification mechanism is a potential target for novel strategies aimed at modulating the acidification capacity of parts of the male reproductive tract and, therefore, in regulating male fertility.

Animals↗