Search PubMedSearch

Biomedical subjects

J F Brown

Publications and source records attributed to J F Brown.

At least 19 recordsLinked to original sources

Nitric oxide donors increase mucus gel thickness in rat stomach.

Instillation of the nitric oxide (NO) generator isosorbide dinitrate (0.1-1 mM) into the rat gastric lumen in vivo produced a dose-related increase in mucus gel thickness that was prevented by coadministration of oxyhaemoglobin (10 microM). Isosorbide dinitrate did not induce epithelial cell damage. S-Nitroso-N-acetyl-penicillamine (0.3 mM) and dibutyryl cyclic GMP (1 mM) also increased mucus thickness. These findings, along with the presence of NO synthase in the gastric mucosa, imply a role for NO in vivo in mediation of gastric mucus release.

Animals

Administration of anti-IL-4 monoclonal antibody 11B11 increases the resistance of mice to Listeria monocytogenes infection.

The role of endogenous IL-4 in resistance to Listeria monocytogenes infection was investigated by in vivo administration of an anti-IL-4 mAb (11B11). Mice treated with 0.01 to 0.4 mg of anti-IL-4 mAb before L. monocytogenes challenge demonstrated a significantly reduced peak bacterial burden in their livers and spleens and accelerated bacterial clearance from these organs. In addition, histopathologic damage to the liver was reduced. Maximal protection was achieved by i.p. injection of 0.1 mg of anti-IL-4 mAb 2 or 24 h before L. monocytogenes challenge; treatment with anti-IL-4 mAb after injection of L. monocytogenes had no effect on antilisterial resistance. Anti-IL-4 mAb-treated and control Listeria-infected mice exhibited similar patterns of IFN-gamma, IL-2, and IL-4 mRNA, as determined by polymerase chain reaction amplification of RNA extracted from spleen cells. In both anti-IL-4 mAb-treated and control mice, IFN-gamma, IL-2, and IL-4 mRNA were produced within 4 h after challenge. Cytokine mRNA levels were similar for anti-IL-4 mAb-treated and control mice, except for the greater amount of IFN-gamma mRNA in the anti-IL-4 mAb-treated mice at 4 h after L. monocytogenes challenge. IFN-gamma and IL-2 mRNA levels were sustained for at least 5 days, whereas IL-4 mRNA was undetectable by 3 days after challenge. There were no significant differences in the amounts of IL-4 and IFN-gamma detected in culture supernatants of spleen cells from anti-IL-4 mAb-treated and control Listeria-infected mice. These results suggest that endogenous IL-4, a cytokine thought to be produced principally by Th2 cells, has a deleterious effect on host defense against the facultative intracellular pathogen L. monocytogenes. Administration of an anti-IL-4 mAb increases antilisterial resistance without causing a detectable shift to a Th1 type of cytokine response.

Animals

Differential distribution of nitric oxide synthase between cell fractions isolated from the rat gastric mucosa.

Cells isolated from the rat gastric mucosa were resolved into two fractions on a percoll density gradient, and into five fractions using counterflow centrifugation (elutriation). Ca(2+)-dependent nitric oxide synthase (NOS) activity was found in the high density percoll fraction but not in the parietal cell enriched low density fraction. This activity was inhibited by NG-monomethyl-L-arginine with an IC50 of 3.7 microM. Cells in the elutriator fraction rich in mucous-epithelial cells exhibited the highest NOS activity, while the smaller cell fractions had no detectable NOS yet had the highest basal release of prostaglandin E2. The parietal cell enriched elutriator fraction again had low NOS activity. The activity of a constitutive NOS in the mucous-cell fraction may indicate a role of NO in the regulation of epithelial cell integrity or secretion.

Amino Acid Oxidoreductases

Dissociation of macrophage cytolysis and ability to transfer anti-listeria resistance by concanavalin A-stimulated spleen cells.

In this study, we determined whether spleen cells from Listeria monocytogenes-immunized mice were cytolytic for Listeria-infected macrophages. Spleen cells freshly obtained from immunized donors were unable to lyse Listeria-infected macrophages unless they were first stimulated in vitro for 2-3 days with Concanavalin A (ConA) or L. monocytogenes. Spleen cells from non-immunized mice developed cytolytic activity after incubation with ConA, but not with L. monocytogenes. Cytolytic spleen cells demonstrated an equivalent ability to lyse uninfected and Listeria-infected thioglycollate elicited peritoneal macrophages. Maximal cytolysis required co-incubation of effector and target cells for 18-20 h. Spleen cell culture supernatants did not lyse macrophages, suggesting that cytolysis required direct contact. Preincubation of immune spleen cells with ConA decreased their ability to transfer anti-listeria resistance in the spleens, but not the livers of recipient mice. Depletion of CD4+ or CD8+ cells did not significantly reduce the ability of ConA-incubated Listeria-immune spleen cells to transfer resistance. Despite being cytolytic for Listeria-immune infected macrophages, ConA-stimulated non-immune spleen cells did not transfer anti-listeria resistance. These results indicate that cytolytic cells can be generated by short-term incubation of spleen cells with antigen or mitogen. The dissociation between in vitro cytolytic activity and ability to transfer protection, however, suggests that the two biological activities are not inextricably linked.

Animals

Details please...

Explore the source record for details and available documents.

Blood Glucose

Effects of recombinant human interleukin-6 alone and in combination with recombinant interleukin-1 alpha and tumor necrosis factor alpha on antibacterial resistance in mice.

In this study, recombinant human interleukin-6 (rIL-6) was tested for its ability to alter the resistance of mice to experimental Listeria monocytogenes infection. Single bolus or repeated injections of rIL-6 by itself did not increase antilisteria resistance. When rIL-6 was injected in combination with suboptimal concentrations of rIL-1 alpha and tumor necrosis factor alpha (rTNF-alpha), it did not augment their abilities to mediate protection in the spleen and had a marginal effect on the level of protection in the liver. Injection of rIL-6 together with protective doses of rIL-1 alpha did not diminish the protection stimulated by the latter. Unlike rIL-1 alpha and recombinant tumor necrosis factor alpha, rIL-6 appears to have little ability to elevate antibacterial resistance.

Animals

Early expression of cytokine mRNA in mice infected with Listeria monocytogenes.

Protective immunity first becomes evident at 3 to 4 days after inoculation of mice with a sublethal dose of Listeria monocytogenes. Recent evidence suggests that production of gamma interferon (IFN-gamma) occurs earlier (within the first 24 h of infection). The purpose of this study was to define better the sequence of cytokine mRNA expression during the early stages of L. monocytogenes infection. Cytokine mRNA expression was detected by polymerase chain reaction-assisted amplification of RNA extracted from the spleen cells of individual mice euthanized at 0.5 to 120 h after L. monocytogenes challenge. By using this method, mRNAs for tumor necrosis factor alpha, interleukin-1 alpha (IL-1 alpha), IL-2, IL-4, IL-5, and IFN-gamma were detected in RNA from the spleen cells of uninfected mice. The intensity of the bands for IFN-gamma, however, was increased greatly at 16 h after intravenous injection of 5 x 10(4) CFU (nearly 1 50% lethal dose) of L. monocytogenes. IL-6 and granulocyte-macrophage colony-stimulating factor mRNAs were not detected in spleen cell RNA from uninfected mice but were induced within 30 and 60 min, respectively, after inoculation with L. monocytogenes. Increased amounts of mRNAs for IFN-gamma, IL-6, and granulocyte-macrophage colony-stimulating factor were detected after injection of viable, but not killed, L. monocytogenes. IL-3 mRNA was not detected at any time in RNA extracted from the spleen cells of uninfected or L. monocytogenes infected mice. These results suggest that infection with L. monocytogenes elicits a detectable cytokine mRNA response within the first few hours of infection.

Animals

Diseases and parasites of red foxes, gray foxes, and coyotes from commercial sources selling to fox-chasing enclosures.

Fifty-six red foxes (Vulpes vulpes), 18 gray foxes (Urocyon cinereoargenteus), and 13 coyotes (Canis latrans) obtained by the South Carolina Wildlife and Marine Resources Department during an investigation of suspected illegal wildlife translocation were examined for diseases and parasites. Red foxes and coyotes were confiscated from an animal dealer based in Ohio (USA), and gray foxes were purchased from an animal dealer in Indiana (USA). Emphasis was placed on detection of pathogens representing potential health risks to native wildlife, domestic animals, or humans. All animals were negative for rabies; however, 15 gray foxes were incubating canine distemper at necropsy. Serologic tests disclosed antibodies to canine parvovirus, canine distemper virus, canine adenovirus, canine coronavirus, canine herpesvirus, and canine parainfluenza virus in one or more host species. Twenty-three species of parasites (two protozoans, three trematodes, four cestodes, eleven nematodes, and three arthropods) were found, including species with substantial pathogenic capabilities. Echinococcus multilocularis, a recognized human pathogen not enzootic in the southeastern United States, was found in red foxes. Based on this information, we conclude that the increasingly common practice of wild canid translocation for stocking fox-chasing enclosures poses potential health risks to indigenous wildlife, domestic animals, and humans and, therefore, is biologically hazardous.

Animals

Update: drug therapy for acute myocardial infarction.

Acute myocardial infarction is potentially a highly treatable disease. Immediate interventions are directed to decreasing tissue hypoxia with oxygen and improving bloodflow to ischemic myocardium using nitrates and thrombolytic agents. Cardiac workload should be reduced by eliminating endogenous catecholamine release with analgesia and sedation, and beta blockade in patients without CHF to decrease heart rate and myocardial oxygen demand. Treatment of the complications of AMI include dysrhythmia prophylaxis, monitoring and specific therapy. Treatment of pump failure includes using vasodilators, vasopressors and positive inotropic agents. Early recognition and timely initiation of appropriate therapy should be every physician's goal.

Humans

Regulation of chorismate mutase in Saccharomyces cerevisiae.

The Saccharomyces cerevisiae ARO7 gene was cloned by screening a wild-type gene bank for complementation of an aro7 auxotrophic mutant. In vitro mutagenesis of the isolated plasmid (pJFB1) gave several transformants resistant to levels of the phenylalanine analogue 2-thienylalanine inhibitory to the wild-type transformant. Chorismate mutase assays indicated that two of the mutants (J14-26IV6 and J14-26IV9) were resistant to feedback inhibition by tyrosine displayed by wild-type strains. Analysis of the effect of other aromatic amino acids on chorismate mutase activity showed that tryptophan counteracted this inhibition. Analysis of the effect of tyrosine in the growth medium on enzyme activity indicated that the wild-type ARO7 gene was repressed by tyrosine, a phenomenon not previously reported. Two of the 2-thienylalanine resistant mutants (J14-26IV3 and J14-26IV9) appeared to be resistant to this repression. Transcriptional analysis confirmed that the level of ARO7 transcript decreased with increasing tyrosine concentration. In stain J14-26IV9 the ARO7 transcript level was not affected. J14-26IV9, therefore, appears to be a double mutant, resistant to both feedback inhibition and repression by tyrosine.

Chorismate Mutase

Human body burden of polychlorinated dibenzofurans associated with toxicity based on the yusho and yucheng incidents.

The polychlorinated dibenzofurans (PCDFs) are one group of man-made toxicants for which reasonably extensive data exist relevant to dose-response relationships in humans. Examination of contaminated food oil consumption from the yusho (Japan) poisoning incident indicates the mean uptake or body burden of 2, 3, 4, 7, 8-pentachlorodibenzofuran (PnCDF) equivalents (PEQ) associated with nausea and anorexia to be 4.4 micrograms/kg body wt and that associated with chloracne to be 5.9 micrograms/kg. For the yucheng (Taiwan) poisoning incident, blood measurements for chloracne show a similar body burden of 4.0 micrograms/kg. The latter value is toxicologically equivalent to a 2,3,7,8-tetrachlorodibenzo-p-dioxin equivalent (TEQ) body burden of 2.0 micrograms/kg body wt or about 150 micrograms for an adult person. This corresponds to an adipose tissue level of about 10 micrograms/kg fat, and is comparable to that known to cause chloracne in rhesus monkeys. These body burdens on a TEQ basis are more than 200 times higher than the average current levels of PCDDs/PCDFs found in North American populations and are the first to relate human body burdens of PCDFs with a known effect and to compare them to animal data. Since the effects reported may not be the most sensitive indicator of human toxicity, lower body burdens could be associated with more subtle toxicological events.

Adolescent

Effects of purified anti-Lyt-2 mAb treatment on murine listeriosis: comparative roles of Lyt-2+ and L3T4+ cells in resistance to primary and secondary infection, delayed-type hypersensitivity and adoptive transfer of resistance.

Mice treated with purified anti-Lyt-2 monoclonal antibody (mAb) displayed a delayed ability to eliminate a primary Listeria monocytogenes infection from their spleens. Elimination of listeriae from the liver was unimpaired by anti-Lyt-2 mAb treatment. Treatment with anti-L3T4 mAb, alone or in combination with anti-Lyt-2 mAb, resulted in similar increases in the numbers of listeriae recovered from the spleens at 7 days after challenge. Listeria-infected mice that had been treated with anti-Lyt-2 mAb alone developed a strong delayed-type hypersensitivity (DTH) response, although it was significantly reduced as compared to control listeria-infected mice. In contrast, treatment with anti-L3T4 mAb severely impaired the development of DTH in listeria-infected mice. Treatment with anti-Lyt-2 mAb and anti-L3T4 mAb, singly or in combination, did not prevent mice from developing increased anti-listeria resistance if they were then immunized with a sublethal dose of L. monocytogenes. Treatment of mice with anti-Lyt-2 mAb or anti-L3T4 mAb before immunization, however, reduced the ability of their spleen cells to transfer anti-listeria resistance to recipient mice. These results indicate that Lyt-2+ cells make substantial contributions to the resistance of mice to primary L. monocytogenes infection, and to the ability of spleen cells from listeria-immunized mice to transfer resistance to naive recipients.

Animals

Growth at reduced temperatures increases the virulence of Listeria monocytogenes for intravenously but not intragastrically inoculated mice.

Growth of three clinical isolates (Scott A, Murray B, and F5380) and one laboratory strain (EGD) of L. monocytogenes at 4 degrees C significantly increased their virulence for intravenously injected mice. Using the EGD strain for subsequent experiments, we determined that growth at either 4 degrees or 22 degrees C enhanced the growth of listeria in the spleen and liver. Similar numbers of listeriae were recovered from the spleens and livers of mice during the first 48 h after i.v. injection of strain EGD grown at 37 degrees C or 4 degrees C. At later timepoints (3-6 days), significantly more listeriae were recovered from the spleens and livers of mice injected i.v. with strain EGD grown at 4 degrees C. In contrast, L. monocytogenes EGD grown at 37 degrees C and 4 degrees C demonstrated similar abilities to survive in the gastrointestinal tract, to translocate to the mesenteric lymph nodes, and to disseminate to the spleen and liver in intragastrically inoculated mice. Listeria monocytogenes EGD grown at 4 degrees C released less hemolysin into the culture medium than did this strain when grown at 22 degrees C and 37 degrees C. Transfer to fresh broth and incubation at 37 degrees C for 2 h increased the release, to similar levels, of hemolysin from L. monocytogenes EGD grown at 4 degrees, 22 degrees, and 37 degrees C. Temperature-induced differences in virulence, therefore, may not reflect the amount of hemolysin released.

Animals

Administration of purified anti-L3T4 monoclonal antibody impairs the resistance of mice to Listeria monocytogenes infection.

Anti-L3T4 monoclonal antibody (GK1.5) treatment significantly impaired the antilisteria resistance of mice as manifested by increased recovery of listeriae from the spleens and livers of anti-L3T4-treated mice and by greater severity of damage to the liver and other organs. Anti-L3T4-treated mice demonstrated a profound decrease in their T cell-mediated responses to Listeria monocytogenes and its products; they failed to develop delayed type hypersensitivity to soluble listeria antigens in vivo, and their spleen cells proliferated poorly in response to stimulation by either mitogens or listeria antigens in vitro. Spleen cells from control listeria-infected mice produced significant amounts of gamma interferon when stimulated with listeria antigens in vitro, whereas under the same conditions spleen cells from anti-L3T4-treated listeria-infected mice failed to produce detectable gamma interferon. Anti-L3T4 treatment resulted in a slight increase in serum colony-stimulating activity as compared with control listeria-infected mice, probably as a result of the increased bacterial burden in these animals. Despite the dramatic decrease in T-cell activities, anti-L3T4-treated mice succeeded in clearing L. monocytogenes from the spleen and liver in a manner that was only slightly delayed as compared with control listeria-infected mice. In addition, anti-L3T4-treated listeria-immunized mice exhibited a moderate degree of enhanced resistance to rechallenge with L. monocytogenes, and their spleen cells were able to transfer a limited degree of antilisteria resistance to naive recipient mice. Both of these responses, however, were diminished as compared with those of control listeria-immunized mice in the same experiments. Although these observations establish a critical role for L3T4+ cells in the development of maximal resistance to listeriosis, they also suggest that compensatory mechanisms may allow mice to develop considerable antilisteria resistance even when L3T4+ cell activities are substantially reduced.

Animals

Effects of growth temperature on the ingestion and killing of clinical isolates of Listeria monocytogenes by human neutrophils.

In this study, we compared three human isolates (F5380, Scott A, and Murray B) and one laboratory strain (EGD) of Listeria monocytogenes for their resistance to ingestion and killing by human neutrophils. We observed no substantial difference in killing among these strains when they were grown at 37 degrees C. Because it is likely that listerial growth occurs at lower temperatures during food-borne outbreaks of listeriosis, we also compared these strains after they were grown at 22 and 4 degrees C. A general reduction in the ability of human neutrophils to kill L. monocytogenes was observed as the temperature at which the listeriae were grown decreased. Growth at 4 degrees C significantly decreased the killing of all four strains of L. monocytogenes by human neutrophils; two strains (EGD and F5380) were more resistant to killing than were the other two strains (Scott A and Murray B). No obvious relationship was noted between the chemiluminescence response of neutrophils to opsonized listeriae and the ability of the neutrophils to kill listeriae in vitro. Growth at 4 degrees C, however, significantly increased the resistance of L. monocytogenes to killing by hydrogen peroxide.

Humans