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Biomedical subjects

A J Edwards

Publications and source records attributed to A J Edwards.

At least 55 records · Page 3Linked to original sources
PubMed1990

In vivo cellular tropism of human T-cell leukemia virus type 1.

To establish the phenotype of human T-cell leukemia virus type 1 (HTLV-1)-infected cells in peripheral blood, the polymerase chain reaction was used to detect and quantitate viral DNA in subpopulations of leukocytes obtained from patients with tropical spastic paraparesis and asymptomatic carriers. HTLV-1 could not be detected in peripheral blood mononuclear cells thoroughly depleted of T lymphocytes (E- CD3-), nor could it be detected in highly enriched populations of B lymphocytes (E- CD19+), monocytes (E- CD14+), or natural killer cells (E- CD16+). T lymphocytes were strongly positive for HTLV-1, and fractionation of this population revealed that 90 to 99% of the HTLV-1 DNA segregated with the CD4+ CD8- and CD45RO+ subsets. No difference between the cell type distribution of HTLV-1 in the asymptomatic carrier and the subjects with tropical spastic paraparesis was evident. Southern hybridization of genomic DNA prepared from the peripheral blood of HTLV-1 carriers indicated that up to 10% of circulating leukocytes may carry the HTLV-1 provirus.

Blotting, Southern↗
PubMed1990

Risk management information for HIV infection.

This article discusses HIV infection in terms of the risk manager's information needs in the health care environment. The malpractice problem, increasing workman's compensation suits, the greater role of the ombudsman, implementation of the National Practitioner Data Bank, and the Joint Commission on Accreditation of Health Care Organizations' (JCAHO) emphasis on clinical excellence are conditions which have given greater importance to the risk manager's position. Included in this article are hedges to retrieve various components of risk management and a select bibliography from AIDSLINE.

Communicable Disease Control↗
PubMed1990

Systemic migration of dendritic cells during contact sensitization.

Twenty-four hours after skin painting mice on the flank with the contact sensitizer fluorescein isothiocyanate (FITC), the number of dendritic cells (DC) increased sharply, not only in draining but also in contralateral (CLN) and distant lymph nodes. High levels of antigen were detected on up to 50% of DC isolated from draining lymph nodes (DLN), and these cells were potent stimulators of naive T cells in vitro. Less than 3% of DC from contralateral and distant lymph nodes carried detectable antigen and did not induce significant T-cell proliferation. A significant number of DC had migrated to draining, contralateral and distant lymph nodes without acquiring detectable antigen. This indicates that there is a systemic signal causing the movement of DC to lymph nodes. This appears to be independent of mature T cells, as the systemic migration of DC also occurred in nude mice.

Animals↗
PubMed1989

Accumulation of 111In-neutrophils in rabbit skin in allergic and non-allergic inflammatory reactions in vivo. Inhibition by neutrophil pretreatment in vitro with a monoclonal antibody recognizing the CD18 antigen.

The mAb 60.3 recognizes the neutrophil CD18 Ag. We have investigated the effect of in vitro pretreatment of radiolabeled neutrophils with mAb 60.3 on their accumulation in vivo. Further, we have compared the in vivo effects of mAb 60.3 with its effects on neutrophil adherence in vitro. Neutrophil accumulation in vivo was measured in response to: 1) exogenous mediators FMLP, C5a des Arg, LTB4 and IL-1; 2) endogenous mediators generated in a non-allergic inflammatory reaction induced by zymosan; and 3) endogenous mediators generated in two allergic inflammatory reactions, a passive cutaneous anaphylactic reaction and a reversed passive Arthus reaction in rabbit skin. Pretreatment of neutrophils with mAb 60.3 inhibited their accumulation in all the responses. The results demonstrate that there is a common mechanism mediating neutrophil accumulation in these inflammatory reactions. Neutrophils pretreated with mAb 60.3 were also unresponsive to chemoattractants in in vitro adherence assays. However, the antibody-treated neutrophils responded normally to FMLP and C5a with respect to granular enzyme release. These results suggest that the basal expression of CD18 Ag is important for the adherence of neutrophils to microvascular endothelial cells stimulated by the local generation, or administration, of chemical mediators in vivo. Despite the fact that mediators such as FMLP can increase CD18 expression in vitro, it appears more likely that such mediators act in vivo by inducing a conformational change in the basally expressed neutrophil adhesive molecules.

Animals↗
PubMed1988

Infection of B lymphocytes by the human immunodeficiency virus and their susceptibility to cytotoxic cells.

The T4 molecule (CD4) is an important component of the human immunodeficiency virus (HIV) receptor. As yet, no other component has been demonstrated. We report here that two cell lines, a B lymphoblastoid cell line (Gupta) and a glial cell line (HEB) derived from human embryonal brain tissue, are productively infectable with two distinct isolates of HIV as judged by electron microscopy and immunological and virological studies. These two cell lines do not display detectable surface CD4 glycoprotein. However, using S1 nuclease analysis, we have found that both cell lines do express low levels of CD4 mRNA. Neither of them produced syncytia formation upon HIV infection, a recognized feature of HIV-infected cells strongly expressing the CD4 glycoprotein. It is conceivable that the CD4 mRNA is translated, resulting in meager surface expression of CD4 molecules undetectable by conventional techniques. Therefore, infection with HIV may be one of the most sensitive methods of demonstrating low levels of CD4 expression by human cells. Furthermore, HIV-infected Gupta cells have here been shown to be more susceptible to the lytic activity of natural killer (NK) cells than their uninfected counterparts. These phenomena may be important for pathogenesis of HIV-associated disorders.

Antibodies, Monoclonal↗
PubMed1988

Blocking of acquisition and presentation of antigen by dendritic cells with cyclosporine. Studies with fluorescein isothiocyanate.

The effect of cyclosporine on the acquisition and presentation of antigen by dendritic cells (DC) was examined. Mice skin-painted with the contact sensitizer FITC received 100 mg/kg of CsA orally on the day before and the day of sensitization. This blocked the development of delayed hypersensitivity as measured by ear-swelling on challenge with antigen on day 6. The antigen-presenting DC in the draining lymph nodes 24 hr after skin painting were studied. The numbers of DC within the lymph node more than doubled after skin painting and this was not altered by the treatment with CsA. The DC from normal skin-painted animals showed a biphasic distribution of antigen, with more than half the cells acquiring high levels of antigen and the remainder having low amounts. In the animals treated with CsA most cells had low levels of antigen. The DC from untreated animals stimulated primary proliferative responses of syngeneic lymphocytes in vitro and initiated delayed hypersensitivity in recipient animals, but the DC from CsA-treated animals did not stimulate immune responses. Cyclosporine may, therefore, prevent acquisition and presentation of antigen by DC in addition to any direct effects on T and B cells.

Animals↗
PubMed1987

Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies.

We have examined the cells involved in the development of contact sensitivity to FITC in CBA mice. After skin painting with antigen, the number of dendritic cells (DC) in the draining lymph nodes increased by 30 min, was maximal at 48 h, and returned to normal by 6 d. Derivation of some DC from Langerhans' cells of the skin was indicated from the presence of Birbeck granules observed in some DC isolated 24 h after skin painting. The DC acquired FITC and by 8 h there were two populations, one highly fluorescent and the other less fluorescent. The highly fluorescent cells were present between 8 h and 3 d after sensitization, and during this period the DC were potent at initiating primary proliferative responses of normal syngeneic T lymphocytes in vitro. Between days 3 and 5 the numbers of lymphocytes in the draining lymph node increased. During this period purified T lymphocytes did not express detectable levels of antigen, but enriched B cell populations expressed antigen transiently on day 1, 2, or 3 after exposure to antigen. The results showed that, during a 3-d period after exposure to antigen, DC expressed antigen and stimulated T cell proliferation. We speculate that low amounts of FITC binding selectively to veiled cells or lymph node DC in the first hours after exposure to antigen are not immunogenic but that Langerhans' cells acquire high levels of antigen, enter the nodes, and initiate immune responses.

Actin Cytoskeleton↗
PubMed1987

T4 lymphopenia in human tuberculosis.

Lymphocyte subpopulations in vitro in 13 patients with bacteriologically-proven tuberculosis and 12 matched controls, by immunofluorescence using monoclonal antibodies have been studied. Active tuberculosis was associated with significant reductions in absolute numbers of total T (Leu 4 or 1+), T4 (Leu 3a+) and B (Leu 12+) lymphocytes, but there were no significant differences in total T8 (Leu 2a+) counts. In two patients, T4-lymphopenia was sufficiently profound to cause reversal of T4: T8 ratio (less than 1.2). These changes were not related to the radiological extent of the disease or size of the Mantoux reaction. Normal ranges for the different classes of lymphocytes were readily restored by chemotherapy.

B-Lymphocytes↗
PubMed1986

Preferred provider organizations: an overview.

This article examines Preferred Provider Organizations--a recently developing alternative form of health care organization. Current problems in the health care system, together with the structure, purpose, and benefits resulting from Preferred Provider Organizations are discussed. The contents of the File HEALTH database are compared with other business and legal databases for unique coverage of this topic.

Information Services↗
PubMed1986

Non-adherent, low-density cells from human peripheral blood contain dendritic cells and monocytes, both with veiled morphology.

Dendritic cells (DC) from human peripheral blood, known to adhere transiently and to become non-adherent by 16 hr, can be separated in the low-density interface on hypertonic Metrizamide gradients. Many more low-density cells (5.8% of the mononuclear cells separated on Ficoll) were obtained from the population that was non-adherent after only 90 min. Over 95% of these low-density cells had veiled morphology. A proportion were monocytes by phenotypic and phagocytic properties. One-third of the cells (on average) were DC on the basis of lack of monocyte phenotype and of potency as stimulators in the mixed lymphocyte reaction. Including both the 16 hr and 90 min non-adherent cells, over 2% of the mononuclear cells isolated from human peripheral blood may be DC.

5'-Nucleotidase↗
PubMed1986

Dendritic cells and the initiation of contact sensitivity to fluorescein isothiocyanate.

Lymph node cells taken 24 hr after skin-painting mice with the contact sensitizer fluorescein isothiocyanate (FITC) induce delayed-type hypersensitivity in recipient mice. Skin-painting increased the number of dendritic cells (DC) in the draining lymph nodes without significantly changing the number of lymphocytes at 24 hr. The antigen was preferentially located on the DC. Raising the dose of FITC increased both the number of DC and the amount per cell. The addition of these DC to syngeneic lymph node cells at a ratio as low as 1:300 initiated proliferative responses in vitro. The level of proliferation was related to the amount of antigen on the DC. Mice given 50,000 of these fluorescent DC developed specific contact sensitivity reactions. DC exposed in vitro to FITC also acquired antigen and were able to initiate proliferative responses in vitro and to sensitize recipient mice. The DC may therefore be the prime cell involved in the induction of delayed-type hypersensitivity.

Animals↗
PubMed1985

Defective low-density cells of dendritic morphology from the blood of patients with common variable hypogammaglobulinaemia: low immunoglobulin production on stimulation of normal B cells.

Low-density cells (LDC) of dendritic morphology from the blood of patients with common variable (late-onset) hypogammaglobulinaemia (CVH) did not induce allogeneic immunoglobulin production by normal B cells unlike LDC from normal blood. When LDC from patients were treated with pokeweed mitogen (PWM), a lower allogeneic secretion of IgM and IgG was induced in normal B cells than that induced by allogeneic normal LDC treated with PWM. B cells from hypogammaglobulinaemic patients were non-responsive to both normal and patient LDC treated with PWM under all conditions tested.

Agammaglobulinemia↗
PubMed1984

Changes in the populations of lymphoid cells in human peripheral blood following physical exercise.

Marked lymphocytosis occurs after exercise. In a study of healthy volunteers this was dominated by one population lacking T cell and B cell determinants and another expressing the Leu 2a phenotype (cytotoxic/suppressor). Lymphocytes from two individuals were characterised further and a near five-fold increase in cells expressing antigens associated with natural killer (NK) cells (Leu 7 and Leu 11) was noted. In addition, these emergent lymphocytes, unlike most T cells, lacked acid alpha-naphthyl esterase activity. In functional studies, exercise led to significantly greater NK activity but, in spite of altering the distribution of lymphocyte subpopulations, there was no detectable change in the proliferative response to the T cell mitogen, concanavalin A, over a wide range of cell concentration, mitogen dose and time. The numbers of low density macrophages and dendritic cells increased concomitantly with the increase in total lymphocytes. We conclude that exercise increases the proportion of circulating NK cells and cells expressing the Leu 2a phenotype.

Cell Separation↗
PubMed1983

Synergistic killing of human leukaemic lymphoblasts by glucocorticoids and cytosine arabinoside.

Previous work has shown that the lethal effects of glucocorticoids on the human lymphoblastoid cell line, CEM-C7, are antagonized by the simultaneous presence of 1-beta-D-arabinofuranosylcytosine (Ara-C). A possible cell cycle mechanism prompted further studies using flow microfluorimetry. We now report that (1) Ara-C (10-100 nM) blocks cells in S-phase and (2) the block is reversible after the drug is removed. A second treatment protocol, in which glucocorticoid is added to cells recovering from the effects of 24 h exposure to Ara-C, results in a clear synergism between the 2 drugs. This synergism is observed over a range of concentrations (5-100 nM), but is most significant at low doses, where inhibition of cell growth by Ara-C occurs but cell killing is minimal. Prior treatment with Ara-C increases the number of cells killed in the presence of steroid during the period 12-24 h after removal of the S-phase block. Combinations of Ara-C and steroid can thus be either synergistic or antagonistic, depending on the drug scheduling.

Cell Cycle↗