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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 631 records · Page 35Linked to original sources
PubMed1992

Antibody against the Leu-CAM beta-chain (CD18) promotes both LFA-1- and CR3-dependent adhesion events.

The Leukocytic cell-adhesion molecule (beta 2 integrin) family of adhesion molecules play a key role in the intercellular adhesive interactions necessary for normal immune cell function. In this study, we report an antibody that recognizes an epitope on the Leukocytic cell-adhesion molecule common beta-chain (CD18) and promotes both lymphocyte function-associated Ag-1- and CR3-dependent adhesion events. The antibody recognizes a temperature-sensitive epitope that is not dependent on the presence of divalent cations. It is proposed that antibody binding promotes a conformational change in both lymphocyte function-associated Ag-1 and CR3, which may mimic a natural activation mechanism, resulting in increased cellular adhesion.

Antibodies, Monoclonal↗
PubMed1992

Proteinases inhibit H(+)-ATPase and Na+/H+ exchange but not water transport in apical and endosomal membranes from rat proximal tubule.

A marked increase in water permeability can be induced in Xenopus oocytes by injection of mRNA from tissues that express water channels, suggesting that the water channel is a protein. In view of this and previous reports which showed that proteinases may interfere with mercurial inhibition of water transport in red blood cells (RBC), we examined the influence of trypsin, chymotrypsin, papain, pronase, subtilisin and thermolysin on water permeability as well as on ATPase activity, H(+)-pump, passive H+ conductance, and Na+/H+ exchange in apical brush-border vesicles (BBMV) and endosomal (EV) vesicles from rat renal cortex. H+ transport was measured by Acridine orange fluorescence quenching and water transport by stopped-flow light scattering. As measured by potential-driven H+ accumulation in BBMV and EV, proteinase treatment had little effect on vesicle integrity. In BBMV, ecto-ATPase activity was inhibited by 15-30%, Na+/H+ exchange by 20-55%, and H+ conductance was unchanged. Osmotic water permeability (Pf) was 570 microns/s and was inhibited 85-90% by 0.6 mM HgCl2; proteinase treatment did not affect Pf or the HgCl2 inhibition. In EV, NEM-sensitive H+ accumulation and ATPase activity were inhibited by greater than 95%. Pf (140 microns/s) and HgCl2 inhibition (75-85%) were not influenced by proteinase treatment. SDS-PAGE showed selective digestion of multiple polypeptides by proteinases. These results confirm the presence of water channels in BBMV and EV and demonstrate selective inhibition of ATPase function and Na+/H+ exchange by proteinase digestion. The lack of effect of proteinases on water transport by mercurials. We conclude that the water channel may be a small integral membrane protein which, unlike the H(+)-ATPase and Na+/H+ exchanger, has no functionally important membrane domains that are sensitive to proteolysis.

Animals↗
PubMed1992

The pathology of hepatitis C.

To determine the histologic pattern of hepatitis C, 54 liver biopsy specimens from 45 patients with a clinicopathological diagnosis of hepatitis C were studied. All patients were seropositive for antibody to hepatitis C virus by second-generation testing. Both transfusion-related and sporadic cases were included. More than half the samples showed chronic hepatitis without cirrhosis, whereas 44% showed developing or fully established cirrhosis. A histological pattern of mild chronic hepatitis with portal lymphoid follicles and varying degrees of lobular activity was found in many of the patients. Lymphoid aggregates or follicles were seen in 78% of biopsy specimens, but aggregates, less prominent than in hepatitis C, were also seen in 14 of 27 samples (52%) from patients with hepatitis B. We conclude that a characteristic histological pattern exists in chronic hepatitis C, that this pattern is not always found and that prominent lymphoid follicles, though not unique to hepatitis C, provide a useful diagnostic clue.

Adult↗
PubMed1992

Absence of hepatitis B virus precore mutants in patients with chronic hepatitis B responding to interferon-alpha.

Precore defective HBV mutants may gradually prevail because of immune selection and explain spontaneous seroconversion from HBeAg to anti-HBe in HBV carriers. We have analyzed whether the presence of precore HBV mutants is a determinant of responsiveness to interferon-alpha therapy. Fifteen carriers (nine responders and six nonresponders) who were treated with interferon-alpha were examined. Serum samples were collected before and after therapy. After extraction of DNA, the precore region was amplified by the polymerase chain reaction, and the product was identified by gel electrophoresis and ethidium bromide staining and then Southern blotting and molecular hybridization. The amplified products in all patients were asymmetrically amplified by a modified polymerase chain reaction, and the precore region was directly sequenced. All patients were HBV DNA positive initially. Circulating HBeAg-negative mutants were not identified before treatment in either responders or nonresponders. All nine responders were negative for HBV DNA in serum by dot blot during or after treatment, but seven remained positive by polymerase chain amplification and Southern-blot hybridization. All of the nonresponders remained positive for HBV DNA by dot blot. A silent mutation involving the substitution of an A for G at position 1888 was found in seven carriers; however, no HBeAg-negative mutants were detected in the follow-up of either responders or nonresponders to interferon-alpha.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Involvement of a neutral glycolipid in differential cell adhesion in the Xenopus blastula.

Many different molecular species mediate cell adhesion during embryonic development. These can have either protein or carbohydrate functional groups, which can act in either a homophilic or a heterophilic manner, and often in concert. We report here that a monoclonal antibody, M4B, raised against Xenopus blastomere membranes, inhibits the calcium-dependent adhesion of dissociated blastomeres. M4B maintains its inhibitory effect on adhesion when converted into univalent fragments, and specifically affects calcium-dependent adhesion. The antigen is regulated in both space and time during early development. It is found on cell surfaces throughout the egg to blastula stages, but is more concentrated on cells in the animal and marginal zones of the blastula. It is dramatically downregulated during gastrulation, and becomes largely restricted to gut epithelium by the larval stages. We show also that M4B function is spatially differentiated at the blastula stage, since it inhibits the aggregation of dissociated animal cells to a greater extent than vegetal cells. This membrane antigen may therefore play a role in the differential adhesion observed between different regions of the blastula, and which we presume to underlie the segregation of the primary germ layers during gastrulation. M4B recognizes a complex of plasma membrane glycolipids. Periodate treatment destroys the ability of these glycolipids to react with the antibody, indicating that the epitope resides in the carbohydrate moiety of the glycolipids. Chemical characterization shows that it is a neutral glycolipid, and that the major component is of the glycoglycerolipid, rather than the more common glycosphingolipid class. Blocking experiments with oligosaccharides of defined structure, and antibody crossreactivity show that the M4B antibody does not recognize several known embryonic carbohydrate antigens. These results demonstrate that M4B antibody recognizes a novel group of developmentally regulated glycolipids which function in calcium-dependent cell--cell adhesion in the Xenopus blastula.

Animals↗
PubMed1992

Effects of gallium on bone in the rat.

Gallium nitrate lowers the serum calcium in patients with hypercalcemia caused by malignancy and is available for clinical use. The mechanism for the hypocalcemic action is unknown, however. The present studies were undertaken to determine the effects of gallium on bone metabolism. Normal male rats were implanted subcutaneously with mineralized allogeneic bone matrix. Histomorphometry of the implants and of tibiae was determined after three doses of tetracycline administered at intervals of 1 week. Gallium as nitrate was administered daily by intraperitoneal injection at doses of 0.9, 1.8, and 3.6 mg elemental gallium per kg body weight for 21 days in one study and at 3.5 mg/kg for 33 days in a second study. All the gallium-treated rats gained weight. Rats given gallium at doses of 3.5 mg/kg or more grew at a lower rate than untreated controls (-7 and -10% at doses of 3.5 and 3.6 mg/kg, respectively; p less than 0.05). At a dose of 0.9 mg/kg, gallium did not inhibit bone resorption or lower serum calcium but inhibited bone formation by 32% and bone apposition by 36% at the endosteal surface of the tibia. At a dose of 1.8 mg/kg, gallium produced modest hypocalcemia, prevented a rise in circulating 1,25-dihydroxyvitamin D [1,25-(OH)2D], inhibited bone resorption in implants, and inhibited bone formation by 19% and bone apposition by 18%. At a dose of 3.5 mg/kg, gallium lowered the serum calcium and serum 1,25-(OH)2D, inhibited growth, and accentuated the antiresorptive and antiformative effects seen at the two lower doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Improved diagnosis of chronic hepatitis C virus infection by detection of antibody to multiple epitopes: confirmation by antibody to synthetic oligopeptides.

Serum samples from 226 patients covering a wide spectrum of liver disease were tested for antibodies to hepatitis C virus (HCV) using both first and second generation enzyme linked immunosorbent assays. Selected sera were also tested by peptide immunoassays, by the four-antigen recombinant immunoblot assay (RIBA II), and for viral genome by the polymerase chain reaction. Antibody to c100-3 was detected in 61% of patients with chronic non-A, non-B (NANB) hepatitis and/or 46.5% with presumed NANB-related cirrhosis by the first generation test. These figures increased to 77% and 58% when antibodies to recombinant structural and non-structural HCV antigens were sought by the second generation assay. Supplemental testing against peptide Sp75 and Sp65/sp67 confirmed that reactivity of sera by second generation assays was due to antibodies to the additional structural and non-structural antigens. Samples negative by the first generation assay were not confirmed by the supplemental assay using peptides Sp75 and Sp65/Sp67. HCV RNA was detected in 60% of the anti-HCV positive sera tested, most of which were also RIBA II positive. Our findings confirm that the introduction of the structural and non-structural antigens, especially the putative nucleocapsid protein, improves sensitivity of detection of antibodies to HCV, and facilitates diagnosis in patients with "cryptogenic" chronic hepatitis.

Antigens, Viral↗
PubMed1992

Clozapine prevents recurrence of psychosis in Parkinson's disease.

Psychosis secondary to dopaminergic therapy can limit the ability to manage motor symptoms of advanced Parkinson's disease (PD). We report the results of an open label 3-month trial that evaluated the antipsychotic effects of clozapine in eight PD patients with drug-induced psychosis. Response was quantified using a simplified brief psychiatric rating scale and two PD scales. Clozapine significantly improved psychiatric scores at low doses. The use of every other day regimens (not previously utilized) led to good control of symptoms and minimized side effects. Clozapine also had a positive sleep effect in four patients and improved dyskinesia in one. Finally, this treatment prevented recurrence of psychosis while levodopa doses were significantly increased and while other antiparkinsonian medications were added. Motor disability related to PD improved as a result of these treatment adjustments. We conclude that clozapine is effective in treating drug-induced psychosis in PD and allows for safe optimization of antiparkinsonian therapy.

Activities of Daily Living↗
PubMed1992

Diagnosis of the acute ischaemic heart by ion elution from myocardium.

The post-mortem diagnosis of acute myocardial ischaemia may be difficult to establish in the absence of morphological changes in the myocardium or recent coronary thrombosis. Ischaemic cell injury leads to potassium (K) efflux and sodium (Na) influx and, if the blood is still circulating, the K:Na ratio of the tissue falls. In this study, the K:Na ratio was measured by eluting the ions from samples of myocardium and assaying the eluate. The method yields similar results to those obtained by a previous method, in which myocardial samples were homogenized. The K:Na ratios on samples of horizontal slices through the heart were plotted on maps of the slices. A low K:Na ratio corresponded to, but extended beyond, areas where there was morphological evidence of ischaemia. The method is simple and may be of use in routine practice.

Acute Disease↗
PubMed1992

Multiple resistance to sulfonylureas and imidazolinones conferred by an acetohydroxyacid synthase gene with separate mutations for selective resistance.

The acetohydroxyacid synthase (AHAS) gene from the Arabidopsis thaliana mutant line GH90 carrying the imidazolinone resistance allele imr1 was cloned. Expression of the AHAS gene under the control of the CaMV 35S promoter in transgenic tobacco resulted in selective imidazolinone resistance, confirming that the single base-pair change found near the 3' end of the coding region of this gene is responsible for imidazolinone resistance. A chimeric AHAS gene containing both the imr1 mutation and the csr1 mutation, responsible for selective resistance to sulfonylurea herbicides, was constructed. It conferred on transgenic tobacco plants resistance to both sulfonylurea and imidazolinone herbicides. The data illustrate that a multiple-resistance phenotype can be achieved in an AHAS gene through combinations of separate mutations, each of which individually confers resistance to only one class of herbicides.

Acetolactate Synthase↗