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J F Brown

Publications and source records attributed to J F Brown.

At least 37 records · Page 2Linked to original sources
PubMed1996

Evaluating the impact of exposure to environmental contaminants on human health.

Humans are exposed daily to low concentrations of many different chemical substances, natural and some man-made. Although many of these substances can be toxic at high levels, typical exposures are far below the effect levels. The responses produced by man-made aromatic hydrocarbon receptor agonists, such as dioxins, polychlorinated dibenzofurans, coplanar polychlorinated biphenyls, and polycyclic aromatic hydrocarbons, are also produced, often to greater extents [corrected], by naturally occurring constituents of fried meat, cabbage, broccoli, cauliflower, cocoa, and curry. Our society seems to be concerned about the health risks associated only with the synthetic chemicals, regardless of their proportional contribution to the total agonist activity, and regulates on the basis of such concerns. It would be more protective of the public health to determine acceptable concentrations for each type of response, regardless of the origin of the inducing agent, and issue advisories or regulations accordingly.

Animals↗
PubMed1995

The PiGMaP consortium linkage map of the pig (Sus scrofa).

A linkage map of the porcine genome has been developed by segregation analysis of 239 genetic markers. Eighty-one of these markers correspond to known genes. Linkage groups have been assigned to all 18 autosomes plus the X Chromosome (Chr). As 69 of the markers on the linkage map have also been mapped physically (by others), there is significant integration of linkage and physical map data. Six informative markers failed to show linkage to these maps. As in other species, the genetic map of the heterogametic sex (male) was significantly shorter (approximately 16.5 Morgans) than the genetic map of the homogametic sex (female) (approximately 21.5 Morgans). The sex-averaged genetic map of the pig was estimated to be approximately 18 Morgans in length. Mapping information for 61 Type I loci (genes) enhances the contribution of the pig gene map to comparative gene mapping. Because the linkage map incorporates both highly polymorphic Type II loci, predominantly microsatellites, and Type I loci, it will be useful both for large experiments to map quantitative trait loci and for the subsequent isolation of trait genes following a comparative and candidate gene approach.

Animals↗
PubMed1994

Lipopolysaccharide induces Ca(2+)-independent nitric oxide synthase activity in rat gastric mucosal cells.

Ca(2+)-independent nitric oxide synthase was detected in gastric mucosal cells isolated from rats injected 4 h previously with Escherichia coli lipopolysaccharide (3 mg/kg i.v.). Induced nitric oxide synthase was located in an elutriated cell fraction of intermediate size which contained epithelial cells, but was absent from the parietal cell fraction. Administration of dexamethasone (2 mg/kg i.p.) 1 h before lipopolysaccharide inhibited the appearance of Ca(2+)-independent nitric oxide synthase, and prevented the observed reduction in cell viability (trypan blue exclusion). Ca(2+)-independent nitric oxide synthase activity can thus be induced in certain cells of the gastric mucosa, and may contribute to gastric pathologies where there is activation of the immune system.

Amino Acid Oxidoreductases↗
PubMed1994

Administration of anti-granulocyte mAb RB6-8C5 impairs the resistance of mice to Listeria monocytogenes infection.

Mice injected i.p. with RB6-8C5 mAb experienced a profound depletion of neutrophils in the bloodstream and spleen and significant impairment of their resistance to experimental infection with Listeria monocytogenes. Control mice survived i.v. inoculation with 5 x 10(4) L. monocytogenes; whereas, most RB6-8C5 mAb-treated mice inoculated i.v. with as few as 10 L. monocytogenes died within 6 days. RB6-8C5 mAb treatment was particularly deleterious when given within the first 24 h after i.v. inoculation with L. monocytogenes; however, some adverse effect was observed even when administration was delayed until 3 or 5 days after bacterial inoculation. Histopathologic examination of the livers of RB6-8C5 mAb-treated mice revealed necrotic foci that were characterized by few inflammatory cells and massive numbers of Gram-positive bacteria within hepatocytes. Additional evidence that the effects of RB6-8C5 mAb administration were chiefly due to neutrophil depletion include: 1) the effects of RB6-8C5 mAb treatment occurred more rapidly than what is generally seen in mice treated with anti-T cell mAbs, 2) similar results were observed with normal and scid mice, 3) RB6-8C5 mAb administration did not diminish delayed-type hypersensitivity nor the ability of spleen cells from immunized mice to transfer resistance, and 4) natural killer cell activity was unaffected by RB6-8C5 mAb administration. The results of this study provide additional evidence in support of the importance of neutrophils in the early stage of innate resistance to murine listeriosis.

Animals↗
PubMed1994

Recombinant interleukin-12 enhances resistance of mice to Listeria monocytogenes infection.

The effect of recombinant murine IL-12 (rIL-12) or anti-IL-12 antibody administration on resistance to murine listeriosis was investigated. Mice given a single 0.5 micrograms dose of rIL-12 had 1.5 log10 fewer listeriae in their spleens and livers as compared with control infected mice 3 days after L. monocytogenes challenge. Conversely, administration of anti-IL-12 IgG caused an equivalent increase in the cfu of L. monocytogenes recovered from the spleens and livers as compared to control mice. This is the first report of such a protective effect from a single dose of rIL-12. Treatment of uninfected mice with rIL-12 induced IFN-gamma mRNA production in their livers. Infection of mice with L. monocytogenes caused a similar increase in IFN-gamma mRNA levels that was not increased further by concurrent treatment with rIL-12. Treatment of mice with an anti-IFN-gamma MAb eliminated the protective effect of IL-12 on Listeria infection. Expression of TNF-alpha, IL-10 and IL-12p40 mRNA in L. monocytogenes-infected mice were not significantly altered by administration of either anti-IL-12 IgG or rIL-12. rIL-12 administration was associated with increased serum AST levels, a measure of liver damage, 1 day after treatment in L. monocytogenes-infected mice. In addition, rIL-12 administration was associated with the increased presence of small inflammatory foci and necrotic hepatocytes in both infected and uninfected mice, suggesting a proinflammatory role for IL-12 in the liver.

Animals↗
PubMed1994

Administration of antigranulocyte monoclonal antibody RB6-8C5 prevents expression of acquired resistance to Listeria monocytogenes infection in previously immunized mice.

Recent studies have established the importance of neutrophils in innate resistance to Listeria monocytogenes infection in mice. The purpose of this study was to determine the importance of neutrophils in acquired resistance to L. monocytogenes infection. Previously immunized mice that were depleted of neutrophils by administration of the antigranulocyte monoclonal antibody RB6-8C5 demonstrated less resistance to L. monocytogenes challenge than did nonimmunized control mice. In contrast, immunized control mice exhibited a heightened resistance to rechallenge, as expected. These results suggest that neutrophils make previously unrecognized contributions to acquired immunity to a facultative intracellular pathogen.

Animals↗
PubMed1994

Treatment with anti-interleukin-10 monoclonal antibody enhances early resistance to but impairs complete clearance of Listeria monocytogenes infection in mice.

Mice that received an anti-interleukin-10 (anti-IL-10) neutralizing monoclonal antibody (MAb) (SXC-1) prior to infection with Listeria monocytogenes initially demonstrated resistance to the infection, as indicated by reduced recovery of L. monocytogenes from their spleens and livers during the first 5 days after challenge. Anti-IL-10 MAb-treated mice then demonstrated reduced resistance during the later stage of infection, as indicated by persistent infection with L. monocytogenes in their livers 11 days after challenge. Aspartate aminotransferase (AST) levels (a measure of liver damage) in the sera of control mice increased between 1 and 5 days after challenge, while anti-IL-10 MAb-treated mice maintained lower AST levels. At 7 days after challenge, AST levels in the sera of control mice decreased as the numbers of organisms declined. In contrast, AST levels increased as the infections persisted in anti-IL-10 MAb-treated mice. The AST levels in serum reflected liver histopathology as anti-IL-10 MAb-treated mice exhibited fewer granulomatous lesions and less necrosis of liver tissue than the control mice during the first 5 days after challenge. Anti-IL-10 MAb treatment altered the expression of inflammatory cytokine mRNAs during L. monocytogenes infection. Control MAb-treated mice exhibited increased expression of tumor necrosis factor alpha and granulocyte-macrophage colony-stimulating factor mRNA in their lives during L. monocytogenes infection, but this increase did not occur in anti-IL-10 MAb-treated mice. Gamma interferon mRNA expression in the livers of the control MAb-treated mice was increased between 1 and 5 days after L. monocytogenes challenge and then decreased at 7 days after challenge. In contrast, gamma interferon mRNA expression in the livers of anti-IL-10 MAb-treated mice was not decreased until 7 days after challenge. These results indicate that endogenous IL-10 has both beneficial and detrimental effects on the host response to L. monocytogenes infection in mice.

Animals↗
PubMed1994

Nitric oxide synthase activity, viability and cyclic GMP levels in rat colonic epithelial cells: effect of endotoxin challenge.

The present study has examined whether epithelial cells could be a source of the inducible form of nitric oxide synthase (iNOS) in the colon of rats challenged with E. coli lipopolysaccharide and whether such excessive endogenous nitric oxide (NO) or exogenous NO released from NO donors could affect their viability. Epithelial cells were isolated from rat colon, and cell viability was determined by trypan blue exclusion. The appearance of a calcium-independent iNOS determined by the conversion of radiolabeled L-arginine to citrulline was observed in cells harvested from lipoplysaccharide (3 mg/kg for 4 hr)-treated rats, with a 10-fold increase in total NOS activity compared with control. This was accompanied by a 3-fold decrease in epithelial cell viability. Levels of iNOS and of cellular injury were not significantly affected in rats made neutropenic by the administration of antineutrophil serum. Induction of NOS was also associated with an increase in epithelial cyclic guanylate monophosphate levels. Both iNOS activity and cell injury were inhibited by in vivo pretreatment with dexamethasone (1 mg/kg i.v., for 4 hr) or the NOS inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg s.c.) in a dose that itself reduced viability. The incubation of epithelial cells with the NO donors, nitroprusside, S-nitroso-N-acetyl penicillamine or S-nitroso-N-glutathione (0.1-1 mM) produced concentration-dependent cytotoxicity. These findings indicate that the induction of NOS in colonic epithelial cells is not dependent upon infiltration of neutrophils and is accompanied by a reduction in cellular viability, an effect mimicked in vitro by NO donors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Oxidoreductases↗
PubMed1994

Incorporating computer-based learning in a medical school environment.

A systematic multifaceted approach is effective in integrating computer-based learning in a medical school environment. The need to educate medical students in computer use, the growing economic constraints facing many medical schools, and the permeation of computer technology in the medical profession encourage collaboration across academic disciplines and services to meet well identified instructional needs through computer-based learning.

Attitude↗
PubMed1993

The nitric oxide donor, S-nitroso-N-acetyl-penicillamine, inhibits secretory activity in rat isolated parietal cells.

Accumulation of the weak base aminopyrine was used as an index of acid secretory activity in rat isolated parietal cells. The nitric oxide (NO) donor, S-nitroso-N-acetyl-penicillamine (SNAP) caused a dose-dependent inhibition of aminopyrine accumulation (half-maximally effective concentration 247 microM) which was accompanied by an increase in guanosine 3',5'-cyclic monophosphate (cGMP) but no decrease in cell viability (trypan blue), glucose oxidation or adenosine 3',5'-cyclic monophosphate (cAMP) content. Oxyhaemoglobin (37 microM), which scavenges NO, significantly reduced the inhibitory effect of SNAP (1 mM). Prior exposure of intact cells to SNAP also reduced aminopyrine accumulation in response to ATP in permeabilised cells, an effect prevented by Rp-8-bromoguanosine 3',5'-monophosphorothioate, which inhibits activation of cGMP-dependent protein kinase, but not by the Sp-isomer. NO thus inhibits secretory activity in rat parietal cells by a specific interaction that may involve cGMP.

Adenosine Triphosphate↗
PubMed1993

Nitric oxide synthase induction and intestinal epithelial cell viability in rats.

The present study determined the presence of constitutive and inducible nitric oxide (NO) synthase activities in intestinal isolated epithelial cells and the effects of NO induction on intestinal epithelial cell viability. Epithelial cells were isolated from rat proximal small intestine by dispersion using citrate and EDTA. Constitutive NO synthase activity, determined by [14C]arginine conversion to citrulline that was inhibited by in vitro incubation with the arginine analogue NG-monomethyl-L-arginine (L-NMMA; 300 microM) or ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA; 1 mM), was observed in these cells. Administration of Escherichia coli lipopolysaccharide (LPS; 3 mg/kg iv) significantly augmented NO synthase activity (determined 4 h later), which was inhibited in vitro by incubation with L-NMMA but not by EGTA. The highest level of constitutive and inducible NO synthase activity occurred in intestinal villus cells, and the lowest was in crypt cells. Induction of NO synthase activity was associated with a decrease in cellular viability as assessed by a decrease in trypan blue exclusion. Dexamethasone pretreatment (1 mg/kg iv 2 h before LPS administration) significantly reduced both induction of NO synthase activity and the reduction in cellular viability. Likewise concurrent administration of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (10 mg/kg sc) ameliorated the reduction in cell viability induced by LPS administration, an effect abolished by pretreatment with the NO substrate L-arginine (350 mg/kg sc). Whereas constitutively formed NO may have a physiological role in these cells, the results in this study suggest that induction of NO synthase in epithelial cells may represent a mechanism of local intestinal damage.

Amino Acid Oxidoreductases↗
PubMed1993

Nitric oxide generators and cGMP stimulate mucus secretion by rat gastric mucosal cells.

The effect of nitric oxide (NO) donors on the release of mucus from a suspension of isolated gastric cells was investigated by using an enzyme-linked immunosorbent assay for rat gastric mucin. Isosorbide dinitrate (ISDN, 0.1-2 mM) produced a dose-related stimulation of mucus secretion, without affecting the viability of the isolated cells as determined by trypan blue exclusion or acid phosphatase release. In a comparable concentration range to that stimulating mucus release, ISDN elevated the guanosine 3',5'-cyclic monophosphate (cGMP) content of cell suspensions enriched with mucous cells. The nitrosothiol S-nitroso-N-acetylpenicillamine (0.3 mM), which spontaneously liberates NO, likewise stimulated mucus release, and this action was blocked by 10 microM oxyhemoglobin, which scavenges NO. Nitroprusside (1 mM), dibutyryl cGMP (0.01-1 mM), and the cGMP phosphodiesterase inhibitor M & B 22948 (0.1 mM) also increased mucus release. Thus generators of NO stimulate mucus secretion by rat gastric mucosal cells, which may reflect the elevation of intracellular cGMP. These findings, along with the presence of NO synthase in the gastric epithelial cells, suggest an effector role for NO in mediation of gastric mucus release.

Animals↗