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Biomedical subjects

D Brown

Publications and source records attributed to D Brown.

At least 793 records · Page 44Linked to original sources

The contingent negative variation in a Go/No Go avoidance task: relationships with personality and subjective state.

Howard et al. (1982) reported an association in mentally abnormal offenders between psychometric impulsiveness and the degree of differentiation in the contingent negative variation (CNV) recorded at the vertex between Go and No Go conditions in a Go/No Go signalled avoidance task. The present study aimed to investigate whether this finding extended to two samples of young, healthy volunteers using a variety of impulsiveness-related measures. As well as examining the Go/No Go CNV recorded from the vertex, the present study investigated the Go/No Go CNV recorded bilaterally at central (C3 and C4: Experiment 1) and temporal (T3 and T4: Experiment 2) electrode derivations. The study also investigated relationships between the Go/No Go CNV and subjective state. including stress and arousal as measured by a mood-adjective checklist, as well as several task-related state measures. The Go CNV recorded at the vertex was found to relate to a variety of impulsiveness-related measures, in particular to Eysenck's Impulsivity, Venturesomeness and Psychoticism. The Go/No Go CNV recorded at temporal sites was more closely related to measures of Emotionality. While the Go CNV appears to be an electrocortical index of a neuropsychological system mediating subjective stress, the No Go CNV appears to index subjective arousal. Results are interpreted in terms of orthogonal 'primary' and 'secondary' appraisal processes (Folkman et al., 1979), and their implications for Gray's (1982) neuropsychological theory of anxiety and Tucker and Williamson's (1984) neural control systems model of human self-regulation are outlined.

Adolescent↗

Dual control over microvillus elongation during enterocyte development.

1. Previously determined logistic growth constants describing enterocyte microvillus development for a variety of species were analysed for possible interactions taking place between enterocyte migration rate (R) and the size of individual crypts (CD). 2. Microvillus elongation, the c-value of a logistic growth curve, was found to increase linearly with crypt depth and reciprocally with decreasing migration rate. The starting microvillus length of a basal crypt enterocyte, the a-value, also increased linearly with CD without being affected by R. 3. The mathematical equation describing the effects of CD and R on M, the maximal microvillus length, was M = 0.0016 CD + 0.073 CD/R, where M and CD are measured in micron and R in micron/hr. 4. The relationship found between R, CD and M is explained by suggesting that the crypt environment enables enterocytes to respond to an initiating signal imposed on cells as they begin to migrate onto villi. The possible nature of this putative signal is also discussed.

Animals↗

Theileria annulata sporozoite surface antigen expressed in Escherichia coli elicits neutralizing antibody.

Theileria annulata is an economically important protozoan parasite that threatens an estimated 250 million cattle with the disease tropical theileriosis. Development of a defined subunit vaccine is one means of trying to develop control measures against the disease. To this end we have characterized a surface antigen complex of the infective stage (sporozoite), by using a monoclonal antibody that neutralizes sporozoite infectivity in vitro. We have cloned the gene coding for this complex and have demonstrated that a fusion protein expressed from a fragment of this gene elicits strong neutralizing antibodies. Furthermore we provide data on the structure and expression of this gene. In particular we show that the region of the gene, expressed in one clone, codes for a protein segment relatively rich in proline residues. Also we demonstrate that expression of this gene appears to be stage specific, transcripts being present only in the sporoblast and sporozoite stages. The relevance of these findings to the production of a defined subunit vaccine is discussed.

Amino Acid Sequence↗

Subtypes of intercalated cells in rat kidney collecting duct defined by antibodies against erythroid band 3 and renal vacuolar H+-ATPase.

The cellular distributions of the kidney form of the erythrocyte band 3 chloride/bicarbonate exchanger and the kidney vacuolar H+-transporting ATPase were examined in rat kidney collecting duct by immunocytochemical staining of adjacent semithin sections. Polyclonal anti-peptide antibodies directed against two regions of murine erythroid band 3 gave a pattern of basolateral labeling similar to that seen with antibodies directed against the entire protein. In the medullary collecting duct almost all intercalated cells expressed basolateral membrane band 3 and displayed apical membrane H+-ATPase. In the cortical collecting duct and the connecting segment, band 3 labeling was restricted to a subpopulation of intercalcated cells. In the cortical collecting duct 46% of intercalated cells had apical H+-ATPase and basolateral band 3. Cells that had either basolateral or diffuse cytoplasmic staining for H+-ATPase were all band 3-negative and accounted for 53% of the intercalated cells. In addition, occasional intercalated cells with apical H+-ATPase appeared to lack basolateral band 3. These results demonstrate the coexpression of H+-ATPase and band 3 in opposite plasma membrane domains of a subpopulation of intercalated cells that are probably the acid-excreting (type A) cells. All other intercalated cells lacked immunoreactive band 3 and probably include the bicarbonate-excreting (type B) cells.

Animals↗

Carbamazepine compared to haloperidol in acute mania.

In a double-blind, between-patient clinical trial carbamazepine (CBZ) (n = 8) was compared to haloperidol (HP) (n = 9) in patients presenting with mania (DSM III). Seven patients on HP and 2 on CBZ failed to complete 4 weeks treatment. In 4 of the HP group this was because of extrapyramidal side-effects (EPS). Two patients on CBZ and 2 on HP were withdrawn because of lack of efficacy. Statistically significant clinical improvement was seen in both groups within the first 2 weeks of treatment with HP acting more quickly. In addition to EPS which occurred in HP patients, drowsiness was experienced in 4 on CBZ and 3 on HP, and gastrointestinal symptoms in 3 on CBZ. No serious haematological changes, nor abnormalities in clinical chemistry occurred in either group. We conclude that CBZ appears to be a potentially useful drug in the treatment of acute mania.

Acute Disease↗

Cohort and case-control analyses of workers exposed to vinyl chloride: an update.

The mortality in a cohort of workers at a vinyl chloride polymerization plant has been updated, extending the period of observation in the original study from 1974 to 1986. Workers at this plant may have been exposed to vinyl chloride monomer and/or polyvinyl chloride dust, or may have had no exposure to either substance. Seventy-six percent of the work force worked in jobs with potential exposure to vinyl chloride monomer. Among the total cohort, statistically significant excess risks were observed for liver, lung, and brain cancer. For the subcohort of workers exposed to vinyl chloride monomer, the standardized mortality ratio (SMR) for liver cancer was 333 (90% confidence interval (CI) 202 to 521). However, there were no significant excesses of either brain (SMR = 145, 90% CI 78 to 249) or lung cancer (SMR = 115, 90% CI 96 to 141). To investigate dose response, nested case-control studies for liver, brain, and lung cancer were conducted among the total cohort (including the nonexposed). For these studies there were two exposure variables, cumulative dose of vinyl chloride monomer and cumulative dose of polyvinyl chloride dust. Cumulative dose was defined as the product of level and duration of exposure. The only significant association between disease risk and cumulative dose was for liver cancer and cumulative dose of vinyl chloride monomer. Further division of the liver cancers into angiosarcoma (n = 12) and other liver cancers (n = 7), based on review of death certificates and medical records, showed that the dose response existed only for angiosarcomas.

Brain Neoplasms↗

Parasite-specific T cell responses of sheep following live infection with the gastric nematode Haemonchus contortus.

Helper T cell lines recognizing antigen in the context of MHC Class II molecules were generated from peripheral blood mononuclear cells (PBMC) of sheep undergoing a primary or secondary infection with the nematode parasite Haemonchus contortus. The lines were used to identify 15-18, 25-29, 70-80 and greater than 100 kD immunodominant parasite larval antigens fractionated by SDS-PAGE under reducing conditions. Non-specific mitogenic activity in the antigen fractions was not detected. During primary infection PBMC did not respond to soluble antigens or those fractionated on SDS-PAGE, whereas T cell lines generated from these PBMC responded well. T cell lines and PBMC derived after a secondary infection responded similarly to fractionated larval antigen. This indicated that (a) the T cell lines had retained their antigen specificities (as represented by autologous PBMC reactivity) in spite of in-vitro cycles of restimulation with whole larval soluble antigen and subsequent expansion in recombinant human IL-2, and (b) proliferation of the antigen-specific PBMC was predominantly due to helper T cells. Variations between individual sheep in response to fractionated larval antigens was also observed. The pattern of helper T cell reactivity to SDS-PAGE larval antigens correlated poorly with B cell reactivity in the same animals by serum antibody Western blot analysis. These results demonstrate that helper T cell epitopes can be mapped in complex parasite antigen preparations in sheep and that this approach will be useful in the identification of parasite protective antigens in helminthiasis where the cellular or humoral nature of protection is not clearly defined.

Animals↗

Isolation of a gene that down-regulates nitrate assimilation and influences another regulatory gene in the same system.

Glutamine is the preferred source of nitrogen of Neurospora crassa. In its presence and that of the gene product of MS5 (nmr-1), the fungus represses the assimilation of less preferred forms of nitrogen, such as nitrate. In the absence of glutamine and the presence of the product of gene nit-2, less preferred forms of nitrogen are assimilated as long as a specific pathway for their assimilation is induced. We report here the isolation, from a cosmid bank, of a gene that complements MS5 and can also complement nit-2. We speculate that this result suggests an interaction between the MS5 and nit-2 gene products and that this is important in the regulation of nitrate assimilation.

Cosmids↗

Meningitis in the newborn--a 14 year review.

A 14 year review of meningitis in babies showed that overall mortality and survival without handicap has not improved. The failure to improve the prognosis of these babies during a period when overall perinatal mortality fell rapidly is because smaller babies are being affected and different organisms are being cultured.

Humans↗

Vesicle recycling and cell-specific function in kidney epithelial cells.

Epithelial cell function depends on the precise delivery of newly synthesized and recycled membrane components to specific plasma membrane domains. The establishment and maintenance of apical and basolateral plasma membrane domains of quite distinct composition enable epithelia to undertake the vectorial transport of fluid, ions, and a variety of other molecules from one compartment to another. In many epithelia this capacity for transepithelial transport can be rapidly and reversibly modulated by prevailing physiological conditions. For example, in the collecting duct of the kidney the two epithelial cell types have both evolved efficient systems that enable such alterations in cell-specific function to occur in response to different stimuli. In both vasopressin-sensitive principal cells and the acid-secreting intercalated cells, specialized membrane patches containing water channels and proton pumps, respectively, are inserted into and removed from plasma membranes on demand and thus dramatically alter the properties of plasma membranes in these cells. Although the basic mechanism in both cells is the recycling of vesicles containing the membrane components of interest, the specific details of the process appear different in the two cell types. In the principal cell vesicle recycling is induced by a specific hormone, vasopressin, and involves clathrin-coated vesicles in the endocytotic step of the cycle. The vesicles that deliver water channels to the cell surface have not yet been identified. In the intercalated cell the transporting vesicles are highly specialized and are coated with the cytoplasmic domains of proton pumps. These vesicles do not have a clathrin coat and therefore represent a distinct class of coated vesicle. As more becomes known about transporting vesicles that are involved in different functions within the cell, it is becoming increasingly clear that it is no longer valid to separate vesicles simply into coated, i.e. clathrin-coated, and smooth vesicles. Three types of coating material have already been described on so-called coated vesicles (1, 14, 24), and it is likely that as our ability to detect the cytoplasmic domains of more proteins involved in intracellular transport increases, we will find that all vesicles are coated, but some are more coated than others. These coating molecules will include the cytoplasmic domains of proteins that are being delivered by the vesicles, as well as specific proteins that are involved in vesicle targeting, vesicle movement, and vesicle fusion or fission.

Animals↗

Colchicine-induced redistribution of an apical membrane glycoprotein (gp330) in proximal tubules.

Factors governing the selective, polarized insertion of membrane proteins are poorly understood, but some studies have suggested that microtubules are involved in the generation and maintenance of cell polarity. We have examined by immunocytochemistry the effect of the microtubule-disrupting agent, colchicine, on the cellular distribution of an endogenous glycoprotein, gp330, which is normally inserted only into the apical plasma membrane of proximal tubule epithelial cells. In control rats, gp330 was localized in the brush border and in apical invaginations and vesicles. Six hours after injection of colchicine, however, vesicles containing gp330 were dispersed throughout the entire cytoplasm of the cell. Many vesicles were packed into basolateral infoldings, close to the plasma membrane, but there was no significant insertion of gp330 into the basolateral membrane. When rabbit anti-gp330 antiserum was injected intravenously into colchicine-treated rats, immune complexes appeared in the glomerular basement membrane but could not be detected in peritubular basement membranes. This supports the conclusion that colchicine treatment does not result in the insertion of gp330 into the basolateral plasma membrane of proximal tubule cells. Our results indicate that although microtubules are involved in the accumulation of gp330-containing vesicles at the apical pole of the cell, other factors must be required for fusion with the plasma membrane to occur.

Animals↗

Membrane recycling and epithelial cell function.

The plasma membrane composition of virtually all eucaryotic cells is established, maintained, and modified by the process of membrane recycling. Specific plasma membrane components are inserted by exocytosis of transport vesicles, and are removed by endocytosis of segments of the membrane in which particular proteins are concentrated. In the kidney collecting duct, vasopressin induces the cycling of vesicles that are thought to carry water channels to and from the apical plasma membrane of principal cells, thus modulating the water permeability of this membrane. In the intercalated cells of the collecting duct, hydrogen ion secretion is controlled by the recycling of vesicles carrying proton pumps to and from the plasma membrane. In both cell types, "coated" carrier vesicles are involved, but whereas clathrin-coated vesicles participate in water channel recycling, the vesicles in intercalated cells are coated with the cytoplasmic domains of proton pumps. Following a brief outline of membrane recycling in general, this review summarizes previous data on membrane recycling in the collecting duct and related transporting epithelia and discusses some selected points relating to the role of membrane recycling and cell-specific function in the collecting duct.

Animals↗

Immunocytochemical localization of Na+ channels in rat kidney medulla.

Amiloride-sensitive Na+ channels were localized in semithin frozen sections of rat renal medullary collecting ducts, using polyclonal antibodies directed against purified bovine kidney Na+ channel protein. The apical plasma membrane of collecting duct principal cells was heavily stained by indirect immunofluorescence, whereas intercalated cells were negative. Basolateral plasma membranes of both cell types were unstained, as were subapical vesicles in the cytoplasm of these cells. In the thick ascending limb of Henle, some scattered granular fluorescence was seen in the cytoplasm and close to the apical pole of epithelial cells, suggesting the presence of antigenic sites associated with some membrane domains in these cells. No staining was detected in thin limbs of Henle, or in proximal tubules in the outer medulla. These results show that amiloride-sensitive sodium channels are located predominantly on the apical plasma membrane of medullary collecting duct principal cells, the cells that are involved in Na+ homeostasis in this region of the kidney.

Animals↗

Superovulation and early embryo development in the adult mouse after prenatal exposure to diethylstilboestrol.

Pregnant mice were injected subcutaneously with diethylstilboestrol (DES: 10 micrograms/kg body weight in 0.1 ml corn oil) or corn oil alone on Day 15 or 16 of gestation (Day 1 = day of copulatory plug) and allowed to give birth. Female progeny from control and DES-exposed animals were superovulated with exogenous gonadotrophins at 6-8 weeks of age. In-vivo results indicated that the total number of ovulated ova, 2-cell embryos and blastocysts were significantly increased in DES-exposed progeny but that there was a decline in developmental potential from the ovulated ova stage to the blastocyst stage in these animals. However, there was no significant difference in the in-vitro development of 2-cell embryos to the blastocyst stage between control and DES-exposed animals. These results indicate that the ovaries of mice exposed in utero to DES are capable of responding to exogenous gonadotrophins and that second generation progeny have the potential for normal development to the early postblastocyst stage of embryogenesis. The in-vivo decline in developmental potential may be attributable to reproductive tract abnormalities rather than ova/embryo defects.

Animals↗

High resolution 2-dimensional mapping of protease activities.

Proteases are secreted by wide variety of cells and are involved in many important processes. The qualitative analysis of these activities from small volumes of conditioned media is often difficult and limited to a description of apparent molecular weights. Here we report the application of a 2-dimensional system with the capability to resolve and identify subtle alterations of post translational modifications of individual activities.

Electrophoresis, Gel, Two-Dimensional↗

Comparison of three-day butoconazole treatment with seven-day miconazole treatment for vulvovaginal candidiasis.

In this multicenter, parallel, randomized, investigator-blind trial, we compared the safety and efficacy of a three-day regimen of 2% butoconazole vaginal cream with those of a seven-day regimen of 2% miconazole vaginal cream. Enrolled were 271 nonpregnant women with vulvovaginal candidiasis. Each patient administered her assigned study medication to the posterior vaginal fornix for three or seven consecutive nights. All 271 patients were included in the safety evaluation, and 225 (111 receiving butoconazole and 114 receiving miconazole) were included in the efficacy evaluation. Eight to ten days after treatment completion, 88% of the butoconazole-treated patients and 91% of the miconazole-treated patients were Candida negative; 80% of the butoconazole-treated patients and 82% of the miconazole-treated patients were considered clinically cured. Thirty days after treatment completion, 73% of the butoconazole-treated patients and 69% of the miconazole-treated patients remained Candida negative; 78% of the butoconazole-treated patients and 80% of the miconazole-treated patients remained free of clinical symptoms of vulvovaginitis. None of the differences between the two treatment groups was statistically significant. Six patients (four receiving butoconazole and two receiving miconazole) reported increased symptoms of vulvovaginal irritation, and three of them (two receiving butoconazole and one receiving miconazole) withdrew from the trial. Thus, the efficacy and safety of the three-day butoconazole treatment regimen were equivalent to those of the seven-day miconazole treatment regimen. The advantage of the shorter butoconazole treatment is increased patient compliance with maintenance of high efficacy.

Administration, Intravaginal↗