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S Gordon

Publications and source records attributed to S Gordon.

At least 109 records · Page 6Linked to original sources
PubMed1999

Exposure-response relationships for work-related sensitization in workers exposed to rat urinary allergens: results from a pooled study.

BACKGROUND: Recent studies in a few industries have shown that the likelihood of IgE-mediated sensitization increases with increasing exposure. The shape of the exposure-response relationships and modification by age, sex, and smoking habit has hardly been studied. OBJECTIVE: The purpose of this study was to determine exposure sensitization relationships for rat sensitization and to evaluate the influence of atopy, smoking habits, and sex. METHODS: Data from 3 cross-sectional studies in The Netherlands, the United Kingdom, and Sweden were used and involved 1062 animal laboratory workers. Selection criteria were harmonized, and this resulted in a study population of 650 animal laboratory workers (60.6% female) with less than 4 years of exposure. Air allergen levels were assessed previously and converted on the basis of an interlaboratory allergen analysis comparison. Available sera were analyzed for the presence of specific antibodies against common allergens (house dust mite, cat, dog, and grass and birch pollen) and work-related allergens (rat and mouse urinary proteins). Questionnaire items on work-related respiratory symptoms, hours worked with rats per week, job performed, smoking habits, and sex were used in this analysis RESULTS: The prevalence of work-related sensitization to rat urinary allergens (IgE >0.7 KU/L) was 9.7 % (n = 63). Thirty-six of the sensitized workers had work-related symptoms (asthma or rhinitis). Two hundred forty-eight workers (38.2%) were atopic (defined as specific IgE to 1 of the common allergens). The sensitization rate increased with increasing air allergen exposure. Atopic workers exposed to low levels of allergen had a more than 3-fold increased sensitization risk compared with nonexposed atopic workers. For atopic subjects, the risk increased little with increasing exposure, whereas for nonatopic subjects, a steadily increasing risk was observed. Smoking and sex did not modify the sensitization risk. CONCLUSION: Rat urinary allergen-sensitization risk increased with increasing exposure intensity. Workers who were atopic had a clearly elevated sensitization risk at low allergen exposure levels.

Allergens↗
PubMed1999

Macrophage-restricted molecules: role in differentiation and activation.

Membrane antigens serve as excellent markers of murine macrophage (MO) differentiation in vivo and in vitro, and have yielded insights into novel MO functions in innate and acquired immunity. We review briefly the use of a range of monoclonal antibodies against MO which show restricted expression: F4/80, macrosialin and sialoadhesin. Differential display PCR strategies have made it possible to identify a novel MO-restricted membrane molecule, a murine MO C-type lectin (mMCL). The isolation of functionally active ab against known receptors such as the scavenger receptor, Class A (SR-A) has provided a key reagent to characterise the role of this molecule in adhesion, endocytosis, phagocytosis and in the regulation of cellular immunity. Studies in SR-A ko mice challenged with BCG and LPS show that the SR-A molecule helps to limit excessive production of cytokines such as TNFalpha by MO that have been activated by infection, and thus protects the host against septic shock.

Animals↗
PubMed1999

Potential role of the mannose receptor in antigen transport.

Potential endogenous ligands for the cysteine rich domain of the murine mannose receptor (MR) have been detected in marginal zone metallophilic macrophages in spleen and subcapsular sinus macrophages in lymph nodes of naive mice by immunohistochemistry using a Fc chimeric protein. Additional labelling was observed in follicular dendritic cells and migratory dendritic cells in immunised animals. Based on this labelling pattern and the identification of a soluble form of the MR in macrophage-conditioned media and mouse serum, we propose a novel role for this receptor in antigen transport.

Animals↗
PubMed1999

Class A scavenger receptors and the phagocytosis of apoptotic cells.

Apoptotic cells are rarely seen in situ because of rapid clearance by phagocytes. A number of receptors have been implicated in the recognition and ingestion of dying cells. Class A scavenger receptors (SRs) are multi-domained membrane glycoproteins that can endocytose modified lipoproteins and bind a wide range of ligands. There is growing evidence that they contribute to several biological processes. We present data that suggest class A SRs are involved in the phagocytosis of apoptotic cells.

Animals↗
PubMed1999

Comparison of methods to assess airborne rat and mouse allergen levels. I. Analysis of air samples.

Airborne laboratory-animal allergens can be measured by several methods, but little is known about the effects of important differences in methodology. Therefore, methods used in research projects in The Netherlands, the UK, and Sweden were compared. Seventy-four sets of three parallel inhalable dust samples were taken by a single operator in animal facilities in the three countries, and analyzed in parallel by the three institutes for rat and mouse urinary allergen. Rat-allergen levels measured by RAST inhibition (UK) were 3000 and 1700 times higher than levels measured by enzyme immunoassay (EIA)-sandwich methods with polyclonal rabbit (The Netherlands) or monoclonal mouse (Sweden) antibodies, while the difference between the two EIA-sandwich methods was much smaller: a factor of 2.2. For mouse allergen, an inhibition radioimmunoassay (RIA) with rabbit antimouse antibodies (UK) gave 4.6 and 5.9 times higher concentrations than sandwich EIAs with rabbit polyclonal antibodies (Sweden and The Netherlands), while the difference between the two sandwich EIAs was, on average, 1.6-fold. Thus, although levels of rat and mouse aeroallergens are significantly correlated, the assay type gives large differences in absolute concentrations, and interlaboratory technical differences affect even the same assay type. Conversion factors can aid comparison between studies, and, in the long term, assay standardization is desirable.

Air Pollutants↗
PubMed1999

Comparison of methods to assess airborne rat and mouse allergen levels. II. Factors influencing antigen detection.

Potential factors influencing antigen detection in immunoassays for measuring rat or mouse aeroallergen (i.e., assay setup, antigen specificities, standard extracts used, and antigen decay) were investigated in a three-country study (the UK, The Netherlands, Sweden). An inhibition enzyme immunoassay (EIA) setup gave nominal rat urinary allergen (RUA) sample values seven times higher than a sandwich EIA setup utilizing identical antibodies and standards. In immunoblotting experiments, pooled patient serum and polyclonal rabbit antibodies partly detected different rat antigens; monoclonal antibody specificity could not be determined. Immunoblot detection of mouse urinary antigens (MUA) by the polyclonal rabbit antibodies from all laboratories was similar. In both the RUA and the MUA assays, urinary antigen standards were detected with similar potency, except purified Rat n 1, which was an inefficient inhibitor in the RUA RAST inhibition. In the sandwich EIA RUA assays, a rat room-dust extract was detected with 700800-fold less sensitivity than rat urine, whereas in the RAST RUA assay, dust inhibited equally with rat urine. Simulated decay did not decrease the potency of urinary antigen in any assay. Thus, assay setup and choice of detection antibodies strongly influence the nominal allergen levels. We recommend the use of standardized and characterized antibodies and standard extracts in sandwich EIAs to measure airborne rodent urinary allergens.

Air Pollutants↗
PubMed1999

Allergen exposure, atopy and smoking as determinants of allergy to rats in a cohort of laboratory employees.

This study aimed to examine the relationship between exposure to rat urinary allergens, atopic status, smoking and the development of allergic symptoms and specific sensitization. It is a case-referent analysis of a cohort of 342 newly employed laboratory animal workers. Cases comprised persons developing symptoms of laboratory animal allergy or a positive skin prick test to rat urinary allergens; each was matched with up to two asymptomatic referents. Subjects were assigned to categories of exposure based on measurements of airborne rat urinary allergens. Of the cases, 80% reported that their symptoms started within 2 yrs of employment. The odds ratio (OR) for development of each symptom type (respiratory, eye or nose and skin) and of an immediate skin test reaction was increased in those with direct contact with rats. A gradient of increasing OR for the development of any such symptom across exposure categories was found; for respiratory symptoms and skin test reactions the OR for subjects in the highest exposure category were lower than those in intermediate categories, a pattern attenuated when the analysis was confined to outcomes developing within 2 yrs of first exposure. Atopy increased the OR of most outcomes as did cigarette smoking, although there was no evidence of a relationship between smoking and the development of a specific skin test reaction. In conclusion, allergen exposure was confirmed as the most important determinant of laboratory animal allergy; by implication, measures to reduce exposure may be the most effective means to reduce its incidence.

Adult↗
PubMed1999

A polyclonal outbreak of predominantly VanB vancomycin-resistant enterococci in northeast Ohio. Northeast Ohio Vancomycin-Resistant Enterococcus Surveillance Program.

We studied the molecular epidemiology of vancomycin-resistant enterococci (VRE) isolated in northeast Ohio during 1996 and examined the association between isolation of VRE from samples other than stool and antimicrobial purchases for five Cleveland hospitals. Susceptibility testing and pulsed-field gel electrophoresis were used to analyze 363 isolates from individual patients from 13 hospitals. Susceptibility testing indicated that 287 strains (79%) expressed the VanB phenotype and 76 (21%) expressed the VanA phenotype. The outbreak was polyclonal, with 30 total genotypes. Both VanA and VanB VRE demonstrated multiple genotypes. One genotype was present in all hospitals, suggesting spread between hospitals. For five teaching hospitals, rates of isolation from non-stool sources and from blood correlated positively with purchases of ticarcillin/clavulanic acid (P = .005). In summary, this outbreak demonstrates transmission of VRE between several hospitals in a geographic region and suggests that use of certain beta-lactam antibiotics may be associated with an increased prevalence of VRE.

Disease Outbreaks↗
PubMed1999

Lymphocyte subpopulations in lymphoid organs of rats after acute resistance exercise.

PURPOSE: The ability of aerobic exercise to change lymphocyte subpopulation distributions is well documented; much less is known about resistance exercise. The purpose of this experiment was to determine the effects of an acute bout of resistance exercise on lymphocyte subpopulations in primary and secondary lymphoid compartments. METHODS: Male rats were operantly conditioned to climb a ladder while carrying weights that were progressively increased to equal body weight. During the acute session, rats performed repetitive climbs until exhaustion. Thymus, spleen, blood, and axial and inguinal lymph nodes were removed; leukocytes were isolated and incubated with monoclonal antibodies against differentiation markers, activation antigens, and adhesion molecules. RESULTS: Exercised versus control rats had greater numbers of leukocytes in the thymus, axial, and inguinal nodes but not in the blood or spleen. The percentage of CD4+ cells increased after exercise in the thymus, spleen, and blood. The percentages of cells expressing the integrin LFA-1beta were elevated in all the tissues except inguinal lymph nodes. In addition, more leukocytes from exercised than nonexercised rats expressed detectable numbers of activation markers, IL-2 receptor-alpha and MHC class II molecules; however, as indicated by proliferating cell nuclear antigen analysis, the cells were not actively dividing at the time of assay. CONCLUSIONS: Based on these and published data, it appears that a single bout of resistance exercise can affect lymphoid cell subpopulations probably by inducing changes in leukocyte trafficking.

Animals↗
PubMed1999

Phylogenetic analysis of Ureaplasma urealyticum--support for the establishment of a new species, Ureaplasma parvum.

In this study, the phylogenetic relationships between the two biovars and 14 serovars of Ureaplasma urealyticum were studied using the sequences of four different genes or genetic regions, namely: 16S rRNA genes; 16S-23S rRNA gene spacer regions; urease gene subunits ureA, ureB, partial ureC and adjoining regions upstream of ureA, ureA-ureB spacer and ureB-ureC spacer; the 5'-ends of the multiple-banded antigen (MBA) genes. U. urealyticum genotypes, based on all four genomic sequences, could be clearly separated into two clusters corresponding with currently recognized biovars 1 and 2. Sequences were generally conserved within each biovar. However, there was heterogeneity within the 5'-end regions of the MBA genes of the four serovars of biovar 1; the sequence of serovar 3 was identical with the previously published sequence and differed by only three bases from that of serovar 14; but there were significant differences between the sequences of serovars 3 and 14 and those of serovars 1 and 6. Based on the phylogenetic analysis, support is given to previous recommendations that the two biovars of U. urealyticum be classified as distinct species, namely U. parvum and U. urealyticum for biovars 1 and 2, respectively. In the future, the relationship between the new species and clinical manifestations of ureaplasma infections should be studied.

5' Untranslated Regions↗
PubMed1999

Comparative analysis and serovar-specific identification of multiple-banded antigen genes of Ureaplasma urealyticum biovar 1.

Ureaplasma urealyticum is a causative agent of nongonococcal urethritis and is implicated in the pathogenesis of several other diseases. The species is divided into 14 serovars and two biovars, of which biovar 1 is most commonly isolated from clinical specimens. Reported associations between individual serovars and diseases have been difficult to confirm because of practical difficulties with serotyping. The multiple-banded antigen (MBA) is the predominant U. urealyticum antigen recognized during infections in humans and probably has a significant role in virulence. The 5' end of the MBA gene is relatively conserved but contains biovar, and possibly serovar, specificity. The 5' ends of the MBA genes of standard strains of U. urealyticum biovar 1, consisting of serovars 1, 3, 6, and 14, were amplified, cloned into pUC19, and sequenced to identify serovar-specific differences. The 5' end of the MBA gene sequence of serovar 3 was identical with the previously published sequence and differed by only three bases from that of serovar 14. Significant differences between the MBA gene sequences allowed biovar 1 to be divided into two subgroups, containing serovars 3/14 and serovars 1 and 6, respectively, using primers UMS-125-UMA269 and UMS-125-UMA269'. Serovars 1 and 6 were distinguished by restriction enzyme analysis of the amplicon and/or by PCR specific for serovar 6. These methods were used to identify and type U. urealyticum in 185 (46.3%) of 400 genital specimens from women. Biovar 1 was detected in 89.2% and biovar 2 in 18.3% of positive specimens. Of 165 specimens containing U. urealyticum biovar 1, 22.2% contained more than one serovar and 46.7, 46.1, and 25.5% contained serovars 1, 3/14, and 6, respectively. U. urealyticum was found in a significantly higher proportion of pregnant women than in sex workers and other women attending a sexually transmissible diseases clinic (P < 0.01). The methods described are relatively rapid, practicable, and specific for serotyping isolates and for direct detection and identification of individual serovars in clinical specimens containing U. urealyticum biovar 1.

Antigens, Bacterial↗
PubMed1999

Analysis of macrophage scavenger receptor (SR-A) expression in human aortic atherosclerotic lesions.

The class A scavenger receptors (SR-As) are trimeric, integral membrane glycoproteins that exhibit unusually broad ligand-binding properties. A number of studies have suggested that these receptors may play an important role in host defense and in many macrophage-associated pathological processes, including atherosclerosis and Alzheimer's disease. The study of the expression and function of these receptors in human disease has been hampered by the lack of suitable antibodies recognizing human SR-A. This has generated questions regarding the nature of receptors responsible for scavenger receptor activity detected in a variety of cell types, including monocytes, macrophages, smooth muscle cells, and endothelial cells. To address these questions, we have produced high-titer antisera recognizing human SR-A by using mice deficient for SR-A (SR-A -/-). We show that SR-A -/- mice produce a significantly higher-titer immune response than do wild-type (SR-A +/+) littermates, with antisera of the former having a broad species reactivity and recognizing SR-A from humans, mice, and rabbits. The antisera recognize both type I and II SR-A in a wide range of immunological techniques. Using these antisera we show that the expression of SR-A protein is induced during monocyte to macrophage differentiation and that SR-A mediates 80% of the uptake of acetylated low density lipoprotein by human monocyte-derived macrophages. We also establish that human SR-A is expressed by tissue macrophages in liver and lung and by macrophage-derived foam cells within aortic atherosclerotic lesions, with little detectable expression by smooth muscle cells or aortic endothelium.

Actins↗
PubMed1999

Rapid recruitment of late endosomes and lysosomes in mouse macrophages ingesting Candida albicans.

Candida albicans is an important opportunistic pathogen, whose interaction with cells of the immune system, in particular macrophages (MO), is poorly understood. In order to learn more about the nature of the infectious mechanism, internalisation of Candida albicans was studied in mouse MO by confocal immunofluorescence and electron microscopy in comparison with latex beads of similar size, which were coated with mannosyl-lipoarabinomannan (ManLAM) to target the MO mannose receptor (MR). Uptake of Candida yeasts had characteristics of phagocytosis, required intact actin filaments, and depended on the activity of protein kinase C (PKC). Candida phagosomes rapidly attracted lysosome-associated membrane protein (Lamp)-rich vacuoles, indicative of fusion with late endosomes and lysosomes. Rapid recruitment of late endosomes and lysosomes could be observed regardless of heat-inactivation or serum-opsonisation of Candida, but did not follow binding of the mannosylated-beads to MO, which suggest that this phenotype is not MR-specific. The yeasts developed germ tubes within phagolysosomes, distended their membranes and escaped, destroying the non-activated MO. The filamentous form of Candida could penetrate intact MO even when phagocytosis was blocked, and also attracted Lamp-rich organelles. Inhibition of lysosomal acidification and associated lysosomal fusion reduced germ tube formation of Candida within the phagolysosomes. These data suggest that rapid recruitment of late endocytic/lysosomal compartments by internalizing C. albicans favours survival and virulence of this pathogen.

Acids↗
PubMed1999

Nursing and Wit.

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Drama↗
PubMed1999

Targeted intervention to improve compliance in an urban hemodialysis population.

Noncompliance impacts the successful delivery of care to the "urban" ESRD population. It is our belief that noncompliance can be an extension of the dysfunctional coping mechanisms of patients who lack adequate psychosocial support. In this article, we have described a pilot program providing on-site, targeted intervention for patients identified at increased risk for poor clinical outcomes, based on failure to comply with the prescribed dialysis treatment prescription. This collaboration between our "nephrology practice," an outpatient "HD facility," and a "C-L psychiatry service" has resulted in extremely low no-show rates in an urban dialysis population. We have also discovered an opportunity for reducing hospitalizations. Targeted intervention can improve compliance and prove to be cost effective.

Algorithms↗
PubMed1998

Functional comparison of the murine macrosialin and human CD68 promoters in macrophage and nonmacrophage cell lines.

The glycoprotein macrosialin is expressed specifically in murine monocytes and macrophages. In the murine genome the macrosialin gene lies 877 bp 3' of the ubiquitously expressed elongation initiation factor 4A1 (eIF-4AI) gene on chromosome 11. The macrosialin gene promoter directs high-level expression in transiently transfected murine macrophage cell lines, but significant levels of expression are seen in nonmacrophage cell lines. The first intron of the gene encoding the human homologue of macrosialin, CD68, directs macrophage-specific expression when cloned downstream of the human CD68 gene promoter. Despite sharing extensive sequence homology with the human CD68 gene first intron, the murine macrosialin gene first intron does not act as a macrophage-specific enhancer when cloned downstream of the human CD68 or murine macrosialin promoters. We conclude that the genetic elements that are responsible for macrophage-specific gene expression are organized differently in the murine and human CD68 genes.

Animals↗