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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 271 records · Page 15Linked to original sources
PubMed1994

HIV-1 induces tumour necrosis factor and IL-1 gene expression in primary human macrophages independent of productive infection.

Cytokines such as tumour necrosis factor-alpha (TNF-alpha) and IL-1 beta may play a role in immunopathogenesis of AIDS. We studied early effects (0.5-48 h) of monocytotropic (ADA) or lymphotropic (IIIB) strains of HIV-1 on TNF-alpha and IL-1 beta mRNA expression in primary human macrophages by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. Three-day-old monocyte-derived macrophages were exposed either to tissue culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 0.05) or to control supernatants free of virions and gp120. ADA strain, but not IIIB, replicated in primary tissue culture-differentiated macrophages (TCDM). Soluble CD4 (sCD4) was used to inhibit binding of both strains to macrophages. We found that TNF-alpha and IL-1 beta gene expression was induced by both strains 0.5-3 h after addition of virus, and that enhanced expression of both cytokines was inhibited by sCD4. We conclude that CD4-dependent binding to the cell surface is sufficient to enhance TNF-alpha and IL-1 beta mRNA, whereas productive viral replication in primary human macrophages is not required. Therefore, similar pathways regulate gene expression of TNF-alpha and IL-1 beta by macrophages during initial infection by HIV-1 in vitro.

Base Sequence↗
PubMed1994

The application of luciferase as a reporter of environmental regulation of gene expression in mycobacteria.

This paper describes the construction of pSG10, the first mycobacterial promoter probe shuttle vector to use the structural gene of a bacterial luciferase as a reporter gene. To examine the utility of using bacterial luciferase to measure gene expression in mycobacteria, the authors have used this vector to monitor the induction of the acetamidase gene promoter of Mycobacterium smegmatis. Luciferase proved to be a rapid, sensitive and easily assayable reporter of changes in gene activity in response to environment in mycobacteria.

Acetamides↗
PubMed1994

Work related symptoms, sensitisation, and estimated exposure in workers not previously exposed to laboratory rats.

Findings are presented from the initial cross sectional phase of a cohort study of employees exposed to laboratory rats. Of 366 eligible workers at four sites 323 (88%) were surveyed; symptoms assessed by self completed questionnaire and sensitisation measured by the response to skin prick tests were related to intensity of exposure both to total dust and to rat urinary aeroallergen. Among 238 workers, without previous occupational exposure to rats, work related symptoms, which started after first employment at the site were related to exposure intensity (expressed either in terms of dust or of aeroallergen) at the time of onset of symptoms. These relations were stronger in atopic subjects but were unrelated to smoking. Positive skin tests to rat urinary extract were also more frequent with increased exposure, a relation found in both atopic subjects and in smokers. There was a strong association between work related symptoms and specific sensitisation.

Adult↗
PubMed1994

Exposure to dust and rat urinary aeroallergens in research establishments.

As part of an epidemiological study rat urinary aeroallergen (RUA) and total dust concentrations were measured at three research establishments. Personal RUA measurements in nine exposure groups over a workshift showed highest exposure for animal technicians (geometric mean (GM) = 32.4 micrograms/m3) and lowest for workers in slide production and office (GM > or = 0.1 micrograms/m3). Except for slide production workers, contact with rats, their tissues, faeces, or urine comprised less than half the work shift. Exposure during contact with rats was considerably higher. Personal RUA measurements in nine task categories showed high RUA concentrations for handling rats (GM = 68.0 micrograms/m3) and cleaning out (GM = 53.6 micrograms/m3). Traces of RUA could still be measured in tearooms inside and near offices outside the animal houses. Total dust concentrations were low.

Allergens↗
PubMed1994

Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis.

BACKGROUND: Cardiac hypertrophy is associated with elevated intracardiac angiotensin-converting enzyme activity, which may contribute to diastolic dysfunction. METHODS AND RESULTS: We infused enalaprilat (0.05 mg/min) for 15 minutes into the left coronary arteries of 20 adult patients with left ventricular (LV) hypertrophy due to aortic stenosis (mean aortic valve area, 0.7 +/- 0.2 cm2) and 10 patients with dilated cardiomyopathy (mean ejection fraction, 35 +/- 4%) and assessed (1) simultaneous changes in LV micromanometer pressure and dimensions, (2) LV regional wall motion analyzed by the area method, and (3) Doppler flow-velocity profiles. Systemic neurohormonal activation did not occur with the selective left coronary artery infusion; there were no changes in plasma renin activity, angiotensin-converting enzyme activity, or atrial natriuretic peptide. In patients with aortic stenosis, LV end-diastolic pressure declined from 25 +/- 2 to 20 +/- 2 mm Hg (P < .05). LV pressure-volume and LV pressure-dimension relations showed downward shifts by ventriculography and echocardiography, respectively, indicating improved diastolic distensibility. Regional area change during isovolumic relaxation increased in the anterior segments perfused with enalaprilat but decreased in the inferior segments, indicating acceleration of isovolumic relaxation in the anterior segments and reciprocal shortening in the inferior segments. Regional peak filling rate increased in the anterior segments but not in the inferior segments, and the regional area stiffness constant decreased in the anterior segments but not in the inferior segments. There were no changes in heart rate, cardiac output, or right atrial pressure, excluding alterations in right ventricular/pericardial constraint. In contrast, in the patients with dilated cardiomyopathy the decrease in LV end-diastolic pressure from 22 +/- 2 to 18 +/- 2 mm Hg (P < .05) was accompanied by a significant fall in right atrial pressure (9 +/- 1 to 6 +/- 1 mm Hg), implicating alterations in pericardial constraint. The patients with dilated cardiomyopathy showed no improvement in regional diastolic relaxation, filling, or distensibility. CONCLUSIONS: Intracoronary enalaprilat at a dosage that did not cause systemic neurohormonal activation improved LV diastolic chamber distensibility and regional relaxation and filling in patients with LV hypertrophy due to aortic stenosis. In contrast, these effects of intracoronary enalaprilat on diastolic function were not observed in patients with dilated cardiomyopathy who did not have concentric hypertrophy. These observations support the hypothesis that the cardiac renin-angiotensin system is activated in patients with concentric pressure-overload hypertrophy and that this activation may contribute to impaired diastolic function.

Aged↗
PubMed1994

Macrophage recruitment during limb development and wound healing in the embryonic and foetal mouse.

Macrophages play a pivotal role in the adult inflammatory response to wounding. They are directly responsible for cellular debridement and, by providing a source of growth factors and cytokines, they recruit other inflammatory and fibroblastic cells and influence cell proliferation and tissue remodelling. In this paper we investigate the role of macrophages in clearing areas of programmed cell death in the developing embryo and also their role in embryonic and foetal wound healing. Immunocytochemistry using the monocyte/macrophage-specific monoclonal antibody, F4/80, reveals a close association between areas of programmed cell death in the remodelling interdigital regions of the mouse footplate and of F4/80-positive cells, suggesting that monocyte-derived macrophages, and not locally recruited fibroblastic cells, as previously believed, are responsible for phagocytosing and clearing areas of interdigital apoptosis. Our studies of wound healing reveal that macrophages are not recruited to, and therefore cannot be playing an active role in the healing of, excisional wounds made in the mouse embryo at any stage up until E14.5. Beyond this transition stage we see a significant recruitment of macrophages within 12 hours of wounding. We find that macrophages can be attracted to wounds in earlier embryos if the wound results in significant cell death such as after burning.

Animals↗
PubMed1994

Murine erythroleukemia (MEL) cells bear ligands for the sialoadhesin and erythroblast receptor macrophage hemagglutinins.

While many studies of erythropoiesis have focused on interactions between developing cells and the extracellular matrix, scant attention has been paid to the role of erythroid-macrophage interactions in this process. Murine erythroleukemia (MEL) cell lines have been used extensively in these studies to define erythroid adhesion events. In this study, we compared the adhesion to both fibronectin and macrophages of MEL cells and primary fetal liver erythroblasts. The avidity of MEL cells for purified mouse fibronectin was greater than that of the primary cells. In addition, we have shown that MEL cells carry ligands/counter-receptors for sialoadhesin (Sn) and the erythroblast receptor (EbR), two hemagglutinins expressed by hematopoietic stromal macrophages. These two macrophage-binding activities were independent of erythroid fibronectin-binding activity. Proteolysis of MEL cell surface receptors was necessary to reveal these activities, with this process providing a means for using MEL cells as ligand cells in studies of macrophage hemagglutinins. While erythroid adhesion to fibronectin and components of the extracellular matrix may be of importance in early erythropoiesis, hemagglutinin-expressing stromal macrophages provide the appropriate microenvironmental niche for the terminal stages of erythropoiesis preceding the release of enucleated cells into the circulation.

Animals↗
PubMed1994

[Malignant nictitating membrane tumors in dogs and cats].

Tumours of the third eyelid in 47 dogs and five cats were examined histopathologically. The clinical observations leading to the tumour diagnosis are presented. The tumours were seen more frequently in the dachshund breed, the affected cats belonged to the European Short-hair breed. The diagnosed tumours of the third eyelid could be histologically classified as adenomas and adenocarcinomas of the gland of the third eyelid, malignant melanomas, squamous cell papillomas and carcinomas of the nictitating membrane, several soft tissue tumours and some cases of pseudoneoplastic hypertrophy of the gland of the third eyelid. Local recurrence of tumour occurred in eight dogs and two cats after resection. Tumour metastasis was confirmed in three dogs. The clinical procedure recommended for avoidance of recurrence is discussed. The differential diagnosis of the malignancies of the third eyelid is described. Questionnaires were designed for the animal owners in an attempt to identify etiopathogenetically important factors, the results of which are discussed.

Adenocarcinoma↗
PubMed1994

Naked megakaryocyte nuclei in bone marrows of patients with acquired immunodeficiency syndrome: a somewhat specific finding.

Naked megakaryocyte nuclei (NMN) were studied retrospectively in 100 bone marrow biopsy sections and aspirates from patients with acquired immunodeficiency syndrome (AIDS) and 124 non-AIDS controls. An NMN score was developed to semiquantitate the NMN. The AIDS bone marrows had an incidence of 97% and a mean NMN score of 2.24 which was a higher incidence and score than the control groups and was statistically significant. The control groups consisted of 20 chronic myeloproliferative disorders (incidence of 70% and score of 1.4); 24 cases of acute myelogenous leukemia and myelodysplastic syndrome (incidence of 29.2% and 0.46 score); 22 cases of non-AIDS immune thrombocytopenic purpura (incidence of 50% and 0.82 score); 11 cases of acute lymphocytic leukemia (0% incidence); 21 cases of anemia (52.4% incidence and 0.7 score); and 26 cases of lymphoma staging (35% incidence and 0.35 score). It is concluded that NMN are a very frequent and, with a high score, a specific finding in AIDS bone marrow examinations.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Interleukin 13 inhibits human immunodeficiency virus type 1 production in primary blood-derived human macrophages in vitro.

The mechanisms by which cellular immunity maintains the asymptomatic state after human immunodeficiency virus type 1 (HIV-1) infection are poorly understood. CD4+ T lymphocytes play a complex role in regulating anti-HIV effector pathways, including activation of macrophages, which are themselves implicated in clinical latency and pathogenesis of symptomatic acquired immune deficiency syndrome. We have found that a newly identified T helper type 2 lymphokine, interleukin 13 (IL-13), inhibits HIV-1ADA and Ba-L replication in primary tissue culture-derived macrophages but not in peripheral blood lymphocytes. Viral production in cells was measured by viral protein (p24) and reverse transcriptase levels, while entry was assessed by proviral DNA analysis at timed intervals after infection. Inhibition by IL-13 was dose and time dependent and not mediated through altered viral entry, reverse transcription, or viral release. IL-13 is therefore a candidate cytokine for the suppression of HIV infection within monocytes and macrophages in vivo.

Base Sequence↗
PubMed1993

Divalent cation-independent macrophage adhesion inhibited by monoclonal antibody to murine scavenger receptor.

Macrophages interact with other cells and components of the extracellular environment by means of adhesion receptors. Adhesion to artificial substrata in vitro facilitates isolation of macrophages, and has been used to generate antibodies that inhibit their migration in vivo. Unlike other cell types, macrophages attach to tissue culture plastic in the absence of divalent cations. Here we use an adhesion assay exploiting this property to isolate a rat monoclonal antibody, 2F8, which totally inhibits divalent cation-independent adhesion of murine macrophages to tissue culture plastic in the presence of fetal calf serum. Immunoprecipitation from macrophages and stably transfected Chinese hamster ovary cells revealed that the antigen recognized by monoclonal 2F8 is identical to murine macrophage scavenger receptor. We propose a novel function for this molecule, previously described as an endocytic receptor, thus providing a mechanism for mononuclear phagocyte recruitment to and retention in ligand-rich tissues such as in atherosclerotic lesions.

Animals↗