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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 235 records · Page 13Linked to original sources

Variation in rat urinary aeroallergen levels explained by differences in site, task and exposure group.

We describe how much of the variation in rat urinary aeroallergen (RUA) levels may be explained by differences in site and exposure group in research establishments and we identify task categories associated with high RUA levels. In this population 73% of the variability in RUA levels could be explained by exposure group, site and their interaction term. Exposure group alone explained the majority of the variation (69%). The task category associated with the highest RUA level was cleaning out, followed by indirect contact with rats and handling rats. The task categories associated with the lowest levels were slide production, post mortem and experiments. These results may help choose appropriate exposure measures for epidemiological studies in research establishments in the future and may help reduce the incidence of laboratory animal allergy.

Allergens↗

Molecular immunobiology of macrophages: recent progress.

Macrophage molecules involved in adhesion, signalling, secretion and interactions with pathogens and T-helper lymphocytes have been cloned and defined using monoclonal antibodies and genetic disruption. Studies of the regulation of macrophage differentiation and activation by cytokines have yielded insights into the heterogeneity of their functions in natural and acquired immunity, including immunity to infections by mycobacteria and HIV.

Animals↗

Tissue-specific targeting of cytokine unresponsiveness in transgenic mice.

The ubiquitous cellular distribution of certain cytokine receptors has hampered attempts to define the physiologically important cell-specific functions of cytokines in vivo. Herein, we report the generation of transgenic mice that express a dominant-negative IFN gamma receptor alpha chain mutant under the control of either the human lysozyme promoter or the murine lck proximal promoter, which display tissue-specific unresponsiveness in the macrophage or T cell compartments, respectively, to the pleiotropic cytokine, IFN gamma. We utilize these mice to identify previously undefined cellular targets of IFN gamma action in the development of a murine antimicrobial response and the mixed lymphocyte reaction. Moreover, we identify the macrophage as a critical responsive cell in manifesting the effects of IFN gamma in regulating CD4+ T helper subset development. These studies thus represent a novel approach to studying the cell-specific actions of an endogenously produced pleiotropic cytokine in vivo.

Animals↗

An outbreak of campylobacter food poisoning in a health care setting.

An outbreak of campylobacter food poisoning in a group of health care workers is reported. The outbreak involved 12 of 31 staff members attending a departmental party. Investigations revealed that a chicken dish was the most likely vehicle of infection. The relative risk of developing symptoms after eating this dish was 6.15 (P < 0.002). Further investigation established that not only had the cooking instructions been misunderstood but storage of the the food the morning of the party did not comply with Department of Health guidelines. The outbreak was associated with considerable morbidity and cost. It is important that health care workers other than professional catering staff are aware of the guidelines available to ensure the correct preparation and storage of food if such events are to be held in hospital departments. It is also important that manufacturers of chicken products ensure that labelling regarding further cooking is clear and in large print.

Campylobacter Infections↗

Influences of chronic cholangiohepatitis and cholestasis on hepatic metabolism of benzo[a]pyrene in white suckers (Catostomus commersoni) from industrially polluted areas of Lake Ontario.

White suckers from polluted regions of western Lake Ontario have an increased prevalence of cholangiocellular and hepatocellular and hepatocellular neoplasms associated with an idiopathic chronic cholangiohepatitis. We examined the hypothesis that bile duct obstructions and cholestasis in these fish might increase the susceptibility of liver to administered benzo[a]pyrene (B[a]P). Cytosolic glutathione S-transferase (GST) activity (CDNB) was reduced in obstructed liver to 45% of activity in adjacent unobstructed liver. At micromolar concentrations, chenodeoxycholic acid, deoxycholic acid, bilirubin and haematin each inhibited GST activity of hepatic cytosolic and S-hexylglutatione-affinity-purified GST preparations from unobstructed liver. Liver cytosol and affinity-purified hepatic GSTs from normal white sucker liver reduced DNA binding of 3H-benzo[a]-pyrene-7,8-diol-9,10-epoxide (3H-BPDE) after preincubation in vitro in the presence of 5 mM GSH. Under these conditions, cytosol from adjacent unobstructed liver had a moderately stronger protective activity against DNA binding by BPDE (16.4 +/- 1.3 pmol BPDE/mg DNA) than did cytosol from obstructed liver (20.6 +/- 1.6 pmol BPDE/mg DNA). Suckers with obstructed livers identified by laparotomy were orally administered 3H-benzo[a]pyrene (3H-B[a]P) (0.2 mmol/kg) or unlabelled B[a]P (2.0 mg/kg) and the level of B[a]P macromolecular binding was analyzed in liver tissue by liquid scintillation counting and by immunohistochemistry with antibodies to BPDE-DNA adducts. Covalent binding of 3H-B[a]P to hepatic protein was 30% less in adjacent unobstructed liver compared to obstructed liver; however, there was no significant difference in the levels of 3H-B[a]P bound to DNA in the obstructed lobes compared with non-obstructed adjacent liver. These studies demonstrate that some endogenous non-substrate ligands that accumulate during cholestasis can reduce hepatic GST activity in white suckers. While these changes are insufficient to influence total 3H-B[a]P-DNA adducts in obstructed liver, the preferential localization of BPDE-DNA adducts in GST-deficient hyperplastic biliary tracts suggests that cholangiohepatitis might increase susceptibility to cholangiolar neoplasia in fish exposed to genotoxic polycyclic aromatic hydrocarbons.

Animals↗

Lipopolysaccharide (LPS) down-regulates CD4 expression in primary human macrophages through induction of endogenous tumour necrosis factor (TNF) and IL-1 beta.

The regulation of CD4 expression on macrophages and its role in immune cell interactions remain obscure. In contrast with primary lymphocytes, primary macrophages express only low amounts of surface CD4, which is regulated differentially for example by adherence in vitro. We report that addition of LPS for 1-5 days to human blood monocyte tissue culture-derived macrophages (TCDM) down-regulates both surface CD4 expression and total cellular CD4 antigen content as measured by flow cytometry and Western blot analysis. TNF-alpha and IL-1 beta, proinflammatory cytokines which are both induced by LPS, also down-regulate surface and total CD4 expression in TCDM. This down-regulation of CD4 expression by LPS, TNF-alpha, and IL-1 beta occurs at the level of transcription. The decreased macrophage CD4 expression induced by LPS was blocked by MoAbs directed against human TNF-alpha and IL-1 beta, demonstrating that LPS acts on CD4 expression through induction of endogenous TNF-alpha and IL-1 beta. Conversely, neither LPS nor TNF-alpha and IL-1 beta were able to modulate surface CD4 expression on quiescent or phytohaemagglutinin (PHA)-activated lymphocytes. Of other cytokines and growth factors tested, Th2 cytokines (IL-4, IL-10, IL-13), chemokines (MCP-1, MIP-1 alpha, RANTES), and macrophage colony-stimulating factor did not alter CD4 expression in primary macrophages; granulocyte-monocyte colony-stimulating factor and the prototypal Th1 cytokine interferon-gamma (IFN-gamma) modulated surface CD4 expression only after prolonged treatment (5 days). Our results show that LPS, TNF-alpha and IL-1 beta selectively down-regulate CD4 expression in primary human macrophages, and that decreased CD4 expression induced by LPS results from endogenous secretion of TNF-alpha and IL-1 beta by the macrophages.

Adjuvants, Immunologic↗

The alpha-glucosidase inhibitor N-butyldeoxynojirimycin inhibits human immunodeficiency virus entry at the level of post-CD4 binding.

The alpha-glucosidase inhibitor N-butyldeoxynojirimycin (NB-DNJ) is a potent inhibitor of human immunodeficiency virus (HIV) replication and syncytium formation in vitro. However, the exact mechanism of action of NB-DNJ remains to be determined. In this study we have examined the impairment of HIV infectivity mediated by NB-DNJ. By two independent HIV entry assays [PCR-based HIV entry assay and entry of Cocal(HIV) pseudotypes], the reduction in infectivity was found to be due to an impairment of viral entry. No effect of NB-DNJ treatment was seen on the kinetics of the interaction between gp120 and CD4 (surface plasmon resonance; BIAcore) or on the binding of virus particles to H9 cells (using radiolabeled virions). We therefore conclude that a major mechanism of action of NB-DNJ as an inhibitor of HIV replication is the impairment of viral entry at the level of post-CD4 binding, due to an effect on viral envelope components.

1-Deoxynojirimycin↗

Sialoadhesin binds preferentially to cells of the granulocytic lineage.

Sialoadhesin is a macrophage-restricted, sialic acid-dependent receptor of 185 kD that binds to the oligosaccharide sequence NeuAc alpha 2,3Gal on cell surface glycoconjugates. Recent cDNA cloning has shown that sialoadhesin is a new member of the immunoglobulin superfamily with sequence similarity to CD22, a sialic acid-dependent receptor of B lymphocytes. Sialoadhesin has been implicated in cellular interactions of stromal macrophages with developing myeloid cells. In this study, direct evidence for this interaction was obtained in cell-cell binding assays using both native and recombinant forms of the protein. In all assays, sialoadhesin exhibited specific, differential binding to various murine cell populations of hemopoietic origin. In rank order, sialoadhesin bound neutrophils > bone marrow cells = blood leukocytes > lymphocytes > thymocytes. Single-cell analyses confirmed that sialoadhesin selectively bound myeloid cells in complex cell mixtures obtained from the bone marrow and blood. In comparison, a recombinant Fc-chimeric form of murine CD22 showed high binding to B and T lymphocytes, but very low binding to immature and mature myeloid cells. These results are consistent with the notion that sialoadhesin in involved in interactions with granulocytes at different stages of their life histories.

Animals↗

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Education, Nursing, Associate↗

Complications and results of 361 hysterectomies performed at laparoscopy.

BACKGROUND: Before the appropriate use of laparoscopy in hysterectomy can be determined, it is necessary to evaluate the results, including complications. There must also be an accepted classification system to facilitate accurate comparison to total abdominal hysterectomy. STUDY DESIGN: We retrospectively evaluated the charts of 361 women who underwent hysterectomy for various benign pathologic conditions. Intraoperative and postoperative complication rates for hysterectomy performed at operative laparoscopy were examined. The hysterectomies were classified as one of four types according to the number of steps performed laparoscopically. All women were candidates for total abdominal hysterectomy, but not vaginal hysterectomy. RESULTS: The overall complication rate for hysterectomy performed at operative laparoscopy was 11.1 percent. Most complications were minor, including cystitis (1.66 percent), transient high fever (1.39 percent), abdominal wall ecchymosis (1.12 percent), and pneumonia and bronchitis (1.12 percent). There was no correlation between the type of laparoscopic hysterectomy performed and the complication rate. CONCLUSIONS: Our rate of intraoperative and postoperative complications associated with laparoscopic hysterectomy compares favorably with published complication rates for vaginal and abdominal hysterectomy.

Abdominal Muscles↗