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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 253 records · Page 14Linked to original sources
PubMed1995

Bioavailability comparison between albendazole and albendazole sulphoxide in rats and man.

Albendazole (ABZ) is a broad spectrum anthelmintic benzimidazole with very low bioavailability, and its activity is due to its main metabolite, Albendazole sulphoxide (ABZS). This work demonstrates the improvement of bioavailability when the ABZS is directly administered, compared with the ABZ administration, both orally given. This observation may be used as an interesting target in the design of new drugs with antihelmintic activity in systemic diseases, using ABZS as a parent drug.

Adult↗
PubMed1994

Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains.

Sialoadhesin is a macrophage-restricted adhesion molecule of 185 kDa that mediates sialic acid-dependent binding to cells. It is expressed strongly by macrophages in lymphoid and haemopoietic tissues where it is likely to mediate cell-cell interactions. Here we report the molecular cloning of murine sialoadhesin and show that it is a new member of the immunoglobulin (Ig) superfamily with 17 Ig-like domains. COS cells transfected with a cDNA encoding full-length sialoadhesin bound mouse bone marrow cells in a sialic acid-dependent manner. Alternatively spliced cDNAs, predicting soluble forms of sialoadhesin containing the first three or 16 Ig-like domains of sialoadhesin, were expressed in COS cells and the respective proteins purified. When immobilized on plastic, the 16-domain form bound cells in a sialic acid-dependent manner, suggesting that sialoadhesin can function in both secreted and membrane-bound forms. The most similar proteins in the database were CD22, myelin-associated glycoprotein, Schwann cell myelin protein and CD33. Like sialoadhesin, CD22 mediates sialic acid-dependent cell adhesion. The sequence similarity of sialoadhesin to CD22 and related members of the Ig superfamily indicates the existence of a novel family of sialic acid binding proteins involved in cell-cell interactions.

Amino Acid Sequence↗
PubMed1994

Use of surface molecules and receptors for studying macrophages and mononuclear phagocytes.

Members of the mononuclear phagocyte system use their extensive repertoire of cell surface receptors to interact with their external environment. A number of different assays are available for the study of these molecules and their many functions. In this paper we describe how monoclonal antibodies may be generated against macrophage molecules, and discuss how screening strategies aimed at producing functionally active reagents may be devised. Using the macrophage mannose and scavenger receptors as examples, we describe assays for determining macrophage adhesion to culture plastic surfaces, endocytosis of soluble ligands and phagocytosis of particles in vitro. These assays may be used in the production of inhibitory monoclonal antibodies, as well as in studies of the regulation of macrophage phenotype and activity.

Animals↗
PubMed1994

Th2 cytokines in AIDS.

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Acquired Immunodeficiency Syndrome↗
PubMed1994

Macrophage-colony-stimulating factor selectively enhances macrophage scavenger receptor expression and function.

Regulation of macrophage scavenger receptor (MSR) activity may be an important determinant of the extent of atherogenesis. The effect of macrophage-colony-stimulating factor (M-CSF) on this pathway was studied using a recently developed monoclonal antibody to murine MSR. M-CSF markedly and selectively increased MSR synthesis in murine macrophages: posttranslationally, the receptor appeared more stable and shifted to a predominantly surface distribution. Functionally, M-CSF enhanced modified lipoprotein uptake and increased divalent cation-independent adhesion in vitro. These results suggest a plausible mechanism whereby M-CSF production in the atheromatous plaque microenvironment could promote the recruitment and retention of mononuclear phagocytes and subsequent foam cell formation.

Animals↗
PubMed1994

Interleukin-13 alters the activation state of murine macrophages in vitro: comparison with interleukin-4 and interferon-gamma.

Interleukin (IL)-13 is a newly described cytokine expressed by activated lymphocytes. We examined the effects of the murine recombinant cytokine on the phenotype and activation status of elicited peritoneal macrophages (M phi), concentrating on activities which are known to be modulated by interferon-gamma and IL-4. IL-13 markedly suppressed nitric oxide release and to a lesser extent secretion of the pro-inflammatory cytokine tumor necrosis factor-alpha. However, antimicrobial capacity was not completely jeopardized as the respiratory burst was unaffected, and indeed the enhanced expression of M phi mannose receptor and major histocompatibility class II, and regulation of sialoadhesin, the M phi sialic acid-specific receptor involved in hemopoietic and lymphoid interactions, suggest that these cells are not simply deactivated, but primed for an active role in immune and inflammatory responses. These activities closely mimic those of IL-4, but mediation of the effects by IL-4 was discounted by the use of a neutralizing monoclonal antibody. Thus, IL-13, like IL-4, is a cytokine which has complex effects on M phi behavior, inducing activities characteristic of both activation and deactivation.

Animals↗
PubMed1994

A rabbit ear model for cold stress testing.

A rabbit ear model resembling the human digit was studied to determine the vascular response of the rabbit ear to a cold stress. Following moderate cooling (10 minutes at 5 degrees - 8 degrees C), auricular blood flow and cutaneous perfusion were reduced. This decrease was reversed by 30 minutes of warming. The response in the rabbit ear to cold stress is similar to that of normal human digits. The similarities between the control of the circulation in human digits and rabbit ears may result from the similarities in digital and auricular vascular receptors and receptor subtypes. Verification of the rabbit model provides an experimental method for obtaining important data regarding digital pathophysiology and the treatment of cold intolerance. Further study with this model will provide clinically relevant information regarding the pathophysiology of digital thermoregulatory abnormalities.

Animals↗
PubMed1994

The kinetics of human immunodeficiency virus reverse transcription are slower in primary human macrophages than in a lymphoid cell line.

Reverse transcription is a critical event in the life of a retrovirus and a potential determinant of viral infectivity. The kinetics of "endogenous" reactions are relatively well defined but little is known about HIV reverse transcription during infection. In this report, we have estimated the rate and efficiency of HIV-1 reverse transcription in primary macrophages and H9 lymphoid cells using quantitative PCR to detect intermediate cDNA structures. DNA synthesis is completed 12-16 hr after infection of H9 cells, but requires more than 36 hr in M phi, owing to slower rates of extension and template switching. Reverse transcription was inefficient in both cell types and in H9 cells the kinetics were sufficiently well resolved to estimate that only one in three transcripts initiated were extended to full-length viral DNA. Slower DNA synthesis largely accounts for the longer replicative cycle of HIV in macrophages. The rate of reverse transcription, which may depend upon levels of deoxynucleotide triphosphate substrates, is a potential factor in modulating the permissiveness of macrophage populations in vivo.

Base Sequence↗
PubMed1994

Upregulation of the macrophage scavenger receptor in response to different forms of injury in the CNS.

The monoclonal antibody 2F8 was used to localize the macrophage scavenger receptor by immunohistochemistry. In control adult mice, macrophage scavenger receptor expression in the brain was restricted to stromal and epiplexus macrophages of the choroid plexus, meningeal macrophages and to perivascular sites. Microglia did not express the receptor. In the developing mouse brain, macrophage scavenger receptor expression was high on meningeal macrophages and detectable on immature microglia in the supraventricular corpus callosum, cingulum, cavum septum and the periaqueductal area. In the aged mouse brain, the pattern of macrophage scavenger receptor expression was no different from that in the young adult brain. Macrophage scavenger receptor expression on resident microglia and recruited macrophages was detected 24 h after an intrahippocampal injection of either lipopolysaccharide or kainic acid. Macrophage scavenger receptor expression was also detected in microglia 3 days after optic nerve crush both in the nerve segment distal to the crush site and in the superior colliculus. These studies indicate a potential role for the macrophage scavenger receptor in the CNS in the clearance of debris during acute neuronal degeneration.

Animals↗
PubMed1994

Murine M phi scavenger receptor: adhesion function and expression.

In the absence of divalent cations M phi lose their spread morphology but remain adherent to tissue culture treated plastic. We have exploited this property of M phi adhesion in vitro, to isolate a rat monoclonal 2F8, which totally inhibits the divalent cation-independent adhesion of M phi to tissue culture treated plastic and is partly responsible for the trypsin-resistant adhesion of M phi to the same substratum. Immunoprecipitation from macrophages and stably transfected Chinese Hamster Ovary Cells revealed that the antigen recognised by monoclonal antibody 2F8 is identical to the murine macrophage scavenger receptor. Macrophage scavenger receptors are trimeric integral membrane glycoproteins which have been implicated in various macrophage functions including uptake of oxidised lipoprotein and the formation of foam cells in atherosclerotic lesions. We have used monoclonal antibody 2F8 to explore the expression of murine macrophage scavenger receptor in lymphoid and non-lymphoid organs of the normal adult mouse and to examine the contribution of macrophage scavenger receptor to macrophage adhesion within tissues.

Animals↗
PubMed1994

Cytokine and growth factor regulation of macrophage scavenger receptor expression and function.

Regulation of macrophage scavenger receptor (MSR) activity may be an important determinant of the extent of atherogenesis and the efficacy of host defense. The effect of M-CSF on this pathway was studied using a recently developed monoclonal antibody to murine MSR. M-CSF markedly and selectively increased MSR synthesis in murine macrophages (M phi); post-translationally the receptor appeared more stable and shifted to a predominantly surface distribution. Functionally M-CSF enhanced modified lipoprotein uptake and increased divalent cation-independent adhesion in vitro. These results suggest a plausible mechanism whereby M-CSF production in the atheromatous plaque microenvironment could promote the recruitment and retention of mononuclear phagocytes and subsequent foam cell formation. In addition, the Th1 cytokine (gamma-interferon) and Th2 cytokine (interleukin-4) had differential effects on MSR glycosylation in vitro suggesting a further possible regulatory role by these lymphokines on macrophage MSR function.

Arteriosclerosis↗
PubMed1994

BCG-induced granuloma formation in murine tissues.

BCG infection of mice provides a convenient model to study natural and cellular immunity to mycobacteria and the mechanisms of granuloma formation and repair. We have used a range of macrophage (M phi) membrane molecules and secretory products to investigate resident M phi-pathogen interactions and T lymphocyte-dependent recruitment and activation of M phi in different tissues of immature, normal adult and gamma interferon deficient animals. In situ hybridization (ISH), RT-PCR and immunocytochemical analysis of M phi gene and product expression have been correlated with in vitro study of endocytic and secretory activity in which biogel polyacrylamide bead-elicited peritoneal M phi are exposed to Th1 and Th2 cytokines, LPS, BCG and other stimuli. The role of resident and newly recruited M phi responding to BCG in liver, spleen, lung and brain has been defined by means of antigen markers expressed by M phi (F4/80, 7/4, CR3, macrosialin, sialoadhesin and scavenger receptor) and/or T and B lymphoid cells (MHC Class II, CD4, CD8, B220). Heterogeneity in M phi secretory activity was revealed by ISH analysis of lysozyme, TNF-alpha, IL-1 IL-6 and MCP-1, by in vitro assay of NO and superoxide anion production, and by RT-PCR studies of Th1 (interferon gamma) and Th2 (IL-4, IL-13, IL-10) lymphokine mRNA in tissues. Our studies confirm the importance of interferon gamma as a critical mediator of host resistance to mycobacterial infection and raise intriguing questions in regard to T cell and M phi functional heterogeneity in distinct tissue microenvironments.

Animals↗
PubMed1994

Interleukin-10 inhibits initial reverse transcription of human immunodeficiency virus type 1 and mediates a virostatic latent state in primary blood-derived human macrophages in vitro.

Interleukin-10 (IL-10), a product of T lymphocytes, B cells and macrophages, participates in Th-2 immune responses and modulates macrophage functions including possible interactions with pathogens. We have found that Chinese hamster ovary cell-derived human recombinant (hr) IL-10 inhibits human immunodeficiency virus type 1 strains Ada and Ba-L (HIV-1ADA and HIV-1Ba-L) replication in primary tissue culture-derived macrophages in a dose-dependent manner. Inhibition by IL-10 treatment (> 5 U/ml) was effective 72 h before or 24 h after infection and cytokine activity blocked by anti-hrIL-10 antibody (19F1), or lost after heat inactivation of IL-10. Viral production was measured by determining p24 and reverse transcriptase levels while reverse transcription kinetics for the long terminal repeat (LTR) and gag were assessed at timed intervals after infection and quantified by 32P end-labelling. IL-10 inhibited early steps of infection without modulating cell surface CD4+ levels. The onset of LTR reverse transcription was delayed by 4 to 8 h and the number of LTR transcripts was decreased by 77% at 24 h and by 87% 48 h after infection. IL-10 effects were reversible; after cytokine washout, cells treated before infection showed lower levels of virus compared with those treated after infection. IL-10 biological activity was confirmed in three virus-independent assays. These results demonstrate IL-10 decreases HIV-1 reverse transcription upon macrophage infection and subsequently mediates viral latency in vitro. Therefore, IL-10 may be involved in the effective control of HIV-1-infected macrophages in vivo.

Animals↗
PubMed1994

Definition of the range and distribution of human immunodeficiency virus macrophage tropism using PCR-based infectivity measurements.

The tropism of human immunodeficiency virus (HIV) for macrophages (m phi) is a well recognized phenomenon, but the range and distribution of m phi-tropic phenotypes have not been defined by quantitative means. This study uses a PCR-based infectivity assay to derive an index of m phi tropism for several common strains of HIV. The results show that m phi tropism varies over about six orders of magnitude and that the most m phi-tropic strains have a higher infectivity for m phi than for peripheral blood lymphocytes. Strains were distributed throughout this range, suggesting that m phi tropism is a continuously variable phenotypic property. Although the degree of tropism was strongly influenced by the mode of isolation and propagation of virus strains, there was no evidence for the existence of distinct m phi-tropic or non-m phi-tropic phenotypes. Finally, the tropism of two selected strains was found to be determined by an early step in replication, probably virus entry.

Base Sequence↗
PubMed1994

Measurement of airborne rat urinary allergen in an epidemiological study.

The suitability of radioallergosorbent test (RAST) inhibition to quantify occupational exposure to rat urinary aeroallergen (RUA) has been assessed. When using a constant pool of rat allergic sera, the reproducibility of the assay over 1 year was comparable to that reported for other immunoassays; at 50% RAST inhibition the inter-assay coefficient of variation (CV) was 7.0% and the intra-assay CV was 3.0%. The assay was highly specific for rat urine; mouse urine was 1100-fold less potent at inhibiting the rat urine RAST system. Significant inter-assay variation in the 'high' control was not due to batch variation and was relatively small when compared with the variation in RUA concentrations in the occupational environment. Measurement of workplace RUA exposure demonstrated that those directly involved in the care of rats experienced the highest RUA exposure of the nine occupational groups studied (animal technicians GM = 23.10 micrograms/m3), dead animals (e.g. post mortem GM = 1.60 micrograms/m3, scientists GM = 0.67 microgram/m3) and rat tissue (e.g. slide production GM = 0.04 microgram/m3). In view of the complexity of rat allergens, RAST inhibition is an appropriate method for the quantification of occupational exposure to rats.

Air Pollution, Indoor↗