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Biomedical subjects

S Gordon

Publications and source records attributed to S Gordon.

At least 199 records · Page 11Linked to original sources
PubMed1996

Molecular cloning of F4/80, a murine macrophage-restricted cell surface glycoprotein with homology to the G-protein-linked transmembrane 7 hormone receptor family.

F4/80 is a monoclonal antibody that recognizes a murine macrophage-restricted cell surface glycoprotein and has been extensively used to characterize macrophage populations in a wide range of immunological studies. Apart from the tightly regulated pattern of expression of the F4/80 antigen, little is known about its possible role in macrophage differentiation and function. We have sought to characterize the molecule at the molecular level, through the isolation of cDNA clones, and now describe the sequence of the F4/80 protein. The primary amino acid sequence demonstrates homology to two protein superfamilies. The NH2-terminal region consists of seven epidermal growth factor-like domains, separated by approximately 300 amino acids from a COOH-terminal region that shows homology to members of the seven transmembrane-spanning family of hormone receptors. The potential role of these distinct domains is discussed with respect to the possible function of the F4/80 molecule.

Amino Acid Sequence↗
PubMed1996

Implantable LVAD infections: implications for permanent use of the device.

BACKGROUND: Infection in implantable left ventricular assist device (LVAD) patients is common and has serious implications regarding permanent use of the LVAD. METHODS: Thirty-three patients had HeartMate LVAD insertion as a bridge to heart transplantation. The mean length of hospital stay was 8 days before LVAD insertion. Before insertion 6 patients (18%) had positive pulmonary cultures and 5 patients (15%) had bacteremia. RESULTS: During LVAD support 18 patients (55%) had bloodstream infection. Of 24 patients (73%) successfully bridged to transplantation, 12 (50%) had positive blood cultures including Staphylococcus species (n = 9), Candida (n = 3), Pseudomonas (n = 2), and Enterococcus (n = 2). Infectious complications encountered in this series included driveline infection requiring surgical revision, septic embolus, "cleared" device infection, "suppressed" device infection, and LVAD infection treated by device removal in 1 patient and device exchange in another. CONCLUSIONS: Infection in implantable LVAD patients is common, especially in patients in whom multiple organ failure develops, requiring prolonged stay in the intensive care unit. Strategies are needed to prevent these infections in recipients of the permanent LVADs because treatment of an established infection is difficult and expensive.

Adult↗
PubMed1996

Sexual abuse evaluations in the emergency department: is the history reliable?

The authors assessed agreement on perpetrator identification obtained at two interviews of child victims of sexual abuse. We reviewed charts for 141 children who had undergone both a screening interview by an emergency department physician and an investigative interview by an interdisciplinary team specializing in child sexual abuse evaluation. For 107 (76%) cases, information was consistent; for instance, identification occurred at both interviews or at neither interview. Of the 38 children not identifying the perpetrator at the screening interview, 17 (45%) made disclosure at the investigative interview. Children who made disclosure only at the investigative interview were more likely to have refused to speak to the physician in the emergency department (p = .001). No significant differences were found when data for interview site and perpetrator identification were analyzed by gender of child, time interval between assault and screening interview, time interval between the two interviews, relationship of the alleged perpetrator to the child, performance of the investigative interview on an inpatient versus outpatient basis, and report of genital contact. In conclusion, perpetrator identification obtained during emergency department screening interviews usually agreed with information obtained at the subsequent investigative interview. The investigative interview was most helpful in identification of perpetrators when the child was not the source of the history obtained in the emergency department.

Child↗
PubMed1996

Macrophage membrane molecules: markers of tissue differentiation and heterogeneity.

Monoclonal antibodies directed against murine macrophage differentiation antigens provide tools to characterize novel glycoproteins, their expression by different macrophage subpopulations in situ and regulation by cytokines and other agents in vitro. Studies are in progress to determine ligands for these molecules, and to establish possible functions. We summarize current knowledge of the following molecules: F4/80, a glycoprotein with homology to the G-protein linked transmembrane 7 hormone receptor family; macrosialin, a member of the lysosomal-associated membrane protein [lamp] family with a macrophage-specific mucin-like extracellular domain also present in its human homologue, CD68; sialoadhesin, a sialic acid binding lectin with multiple Ig superfamily domains; mannosyl receptor, a lectin-like molecule with multiple C-type lectin domains; type 3 complement receptor, a beta 2 integrin involved in cell migration and adhesion; scavenger receptor, a transmembrane homotrimer with a collagenous domain.

Animals↗
PubMed1996

HIV-1 envelope glycoprotein gp120 down-regulates CD4 expression in primary human macrophages through induction of endogenous tumour necrosis factor-alpha.

Among immunological abnormalities present in human immunodeficiency virus type 1 (HIV-1)-infected individuals are dysregulation of cytokine production and CD4 down-regulation in both T-helper cells and monocytes/macrophages. The HIV-1 envelope glycoprotein 120 (gp120) has the ability to induce different cytokines in peripheral blood mononuclear cells and in monocytes/macrophages in vitro which in some instances have been reported to down-regulate macrophage CD4 expression. This study provides evidence that HIV-1 recombinant gp120 (rgp120) down-regulates both surface and total CD4 expression in primary tissue culture-differentiated macrophages (TCDM) at the level of transcription. The CD4 down-regulation observed in TCDM occurred between 6 and 12 hr after rgp120 treatment preceded by a peak of endogenous tumour necrosis factor-alpha (TNF-alpha) observed at 3-6 hr post-treatment. We demonstrate that the TCDM CD4 down-regulation observed after rgp120 treatment was inhibited by the use of an anti-huTNF-alpha monoclonal antibody (mAb), but not by mAb directed against other cytokines induced by rgp120, such as interleukin-1 beta (IL-1 beta) and interferon-alpha (IFN-alpha). The present findings roughly parallel those observed both in the sera of patients and in the monocytes/macrophages isolated from HIV-positive individuals, suggesting that gp120 by stimulating endogenous TNF-alpha production could be a good candidate for the CD4 down-regulation observed in the monocytes/macrophages of HIV-1-infected individuals. In contrast to CD4 down-regulation in HIV-infected lymphocytes, which results from a direct effect of viral genes on CD4 expression, soluble factors such as cytokines induced during HIV infection might explain the monocyte/macrophage CD4 dysregulation observed in acquired immune deficiency syndrome.

Antibodies, Monoclonal↗
PubMed1996

Antifungal susceptibility testing using the E test: comparison with the broth macrodilution technique.

The National Committee for Clinical Laboratory Standards reference broth macrodilution method for antifungal susceptibility testing was compared with the E test by testing 86 clinical isolates of Candida spp. and Cryptococcus neoformans. The MIC agreement rates for the two methods for Candida spp. were 73-89% within +/-1 doubling dilution and 87-100% within +/-2 dilutions. For C. neoformans, agreement within +/-1 dilution was > 70% for all the agents tested except fluconazole for which agreement was 35%. Our data support the further evaluation of the E test as an alternative method for antifungal susceptibility testing. However, E test MICs of fluconazole for C. neoformans, particularly C. neoformans var. gattii should be interpreted with caution, as falsely elevated MICs may occur.

Antifungal Agents↗
PubMed1996

Toxicology screening in adolescent trauma.

We sought to define the prevalence of positive drug screens in adolescent victims of major trauma. The records of 125 consecutive adolescent patients presenting with major trauma to an inner-city trauma center during the last nine months of 1990 were reviewed. Eighty-five (68%) received urine toxicology screens for alcohol and illicit drugs. Twenty-one (25%) of screened patients had a positive urine drug screen. The most commonly detected drugs were alcohol, cocaine, and opiates. Gender, race, mechanism of injury, mental status at presentation, injury severity score, and revised trauma score were not associated with a positive drug screen. We conclude that: 1) 25% of screened adolescent victims of major trauma seen at an inner-city trauma center had positive urine toxicology screens for alcohol or illicit drugs. 2) As none of the study variables was associated with a positive drug screen, selective drug screening cannot be supported.

Adolescent↗
PubMed1996

Collagenous macrophage scavenger receptors.

Collagen, the most abundant protein in the human body, is a major constituent of extracellular matrix. Among macrophage membrane proteins, type I and II scavenger receptors and MARCO contain a collagenous domain. Analysis of type I and II receptor knockout mice and histochemical studies indicate that these proteins play roles in scavenger, adhesion and host defense functions of macrophages.

Animals↗
PubMed1996

Tumor necrosis factor alpha inhibits entry of human immunodeficiency virus type 1 into primary human macrophages: a selective role for the 75-kilodalton receptor.

The proinflammatory cytokine tumor necrosis factor alpha (TNFalpha) is readily detected after human immunodeficiency virus type 1 (HIV-1) infection of primary macrophages in vitro and is present in plasma and tissues of patients with AIDS. Previous studies have shown that human recombinant TNFalpha (hrTNFalpha) enhances HIV replication in both chronically infected promonocytic and T-lymphoid cell lines in vitro. We report here that in contrast to untreated tissue culture-differentiated macrophages (TCDM), in which the proviral long terminal repeat (LTR) could be detected as soon as 8 h postinfection by a PCR assay, TCDM pretreatment for 3 days by hrTNFalpha markedly delayed its appearance until 72 h after infection with the HIV-1 Ada monocytotropic strain. Moreover the inhibition of formation of the proviral LTR in HIV-1-infected TCDM was directly proportional to the concentration of hrTNFalpha used. To determine if the inhibition of LTR formation results from blockade of viral entry, we performed a reverse transcription PCR assay to detect intracellular genomic viral RNA as early as 2 h after infection. Pretreatment of primary TCDM by hrTNFalpha for 3 days and even for only 2 h inhibits 75% of the viral entry into the cells. The inhibition of viral entry by hrTNFalpha was totally abolished by the use of anti-human TNFalpha monoclonal antibody. By using TNFalpha mutants specific for each human TNFalpha receptor, we showed that the inhibition of HIV-1 entry into TCDM was mediated not through the 55-kDa TNF receptor but through the 75-kDa TNF receptor. Although prolonged (1 to 5 days) TNFalpha treatment can downregulate CD4 expression in primary human TCDM, surface CD4 levels were not reduced by 2 h of treatment and was therefore not a limiting step for HIV-1 entry. In contrast to the inhibition of viral entry into primary TCDM, pretreatment with hrTNFalpha did not modify HIV-1 entry into phytohemagglutinin A-activated peripheral blood lymphocytes. TNFalpha-pretreatment inhibited HIV-1 replication in primary TCDM but not in phytohemagglutinin A-activated peripheral blood lymphocytes as assessed by decreased reverse transcriptase activity in culture supernatants. These results demonstrate that TNFalpha is able to enhance host cellular resistance to HIV-1 infection and that selective inhibition of HIV-1 entry into primary TCDM by TNFalpha involves the 75-kDa TNF receptor but not the 55-kDa TNF receptor.

Antigens, CD↗
PubMed1996

Cytokine regulation of the macrophage (M phi) system studied using the colony stimulating factor-1-deficient op/op mouse.

The macrophage (M phi) lineage is more complex than other myeloid lineages of hematopoietic cells and includes strikingly different end cells such as Kupffer cells, alveolar M phi, histiocytes, serosal M phi, synovial type A cells, microglia, osteoclasts, and possibly dendritic cells. These cells are formed under the influence of primary M phi growth factors such as colony stimulating factor (CSF)-1, granulocyte-M phi (GM)-CSF, and interleukin-3. The dissection of the system has been greatly facilitated by discovery of the osteopetrotic op/op mouse, which has a spontaneous knockout of the gene for CSF-1 and possesses generalized but differential deficiency of various local subpopulations of M phi. Studies using this model indicate that the M phi lineage is split into CSF-1-dependent and CSF-1-independent cells that are largely independently regulated. These contribute variably to different local populations and have largely, but not totally, overlapping functions. Both CSF-1 and GM-CSF are responsible for transition of cells of the M phi lineage from bone marrow to blood, and from blood to tissues, and have a critical extramedullary role. Regulation of the M phi system by CSF-1 is complex, with some local populations dependent on circulating CSF-1 and some supported exclusively by locally produced CSF-1. Colony stimulating factor-1-dependent M phi are not required for the generation of a specific immune response. Instead, most likely they play a regulatory role in various tissue reactions including responses to bacterial infection, neoplasia, and atherosclerosis. A hypothetical major role of CSF-1-independent M phi is to collaborate with lymphocytes in mounting an immune response. These issues need further exploration using animals with knockouts of genes for other M phi growth and activation factors and their receptors.

Animals↗
PubMed1996

Manchester and Oxford Universities Scale for the Psychopathological Assessment of Dementia (MOUSEPAD).

BACKGROUND: There is increasing awareness of the importance of psychopathological and behavioural changes in dementia and a need for an instrument to measure these features which achieves an appropriate compromise between brevity and breadth. We describe a newly developed 59-item instrument: the MOUSEPAD. METHOD: Reliability, sensitivity and validity were examined with 30 carers, each of whom was interviewed four times over six weeks. RESULTS: For different symptom groups, kappa ranged from 0.43 to 0.93 for test-retest reliability, from 0.56 to 1.0 for inter-rater reliability, and from 0.43 to 0.67 for the validation study. CONCLUSIONS: The scale may be useful as an outcome measure in drug trials, for correlating psychopathological and behavioural changes with post-mortem findings, and in epidemiological surveys.

Aged↗
PubMed1996

Breath measurements as volatile organic compound biomarkers.

A brief review of the uses of breath analysis in studies of environmental exposure to volatile organic compounds (VOCs) is provided. The U.S. Environmental Protection Agency's large-scale Total Exposure Assessment Methodology Studies have measured concentrations of 32 target VOCs in the exhaled breath of about 800 residents of various U.S. cities. Since the previous 12-hr integrated personal air exposures to the same chemicals were also measured, the relation between exposure and body burden is illuminated. Another major use of the breath measurements has been to detect unmeasured pathways of exposure; the major impact of active smoking on exposure to benzene and styrene was detected in this way. Following the earlier field studies, a series of chamber studies have provided estimates of several important physiological parameters. Among these are the fraction, f, of the inhaled chemical that is exhaled under steady-state conditions and the residence times. tau i in several body compartments, which may be associated with the blood (or liver), organs, muscle, and fat. Most of the targeted VOCs appear to have similar residence times of a few minutes, 30 min, several hours, and several days in the respective tissue groups. Knowledge of these parameters can be helpful in estimating body burden from exposure or vice versa and in planning environmental studies, particularly in setting times to monitor breath in studies of the variation with time of body burden. Improvements in breath methods have made it possible to study short-term peak exposure situations such as filling a gas tank or taking a shower in contaminated water.

Biomarkers↗