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Biomedical subjects

N Wood

Publications and source records attributed to N Wood.

At least 109 records · Page 6Linked to original sources

Toxic shock syndrome toxin-1 induces inositol phospholipid turnover, protein kinase C translocation, and calcium mobilization in human T cells.

Toxic shock syndrome toxin-1 (TSST-1) is a 22-kDa exotoxin produced by most Staphylococcus aureus strains responsible for toxic shock syndrome. TSST-1 is a mitogen for human T cells. The mechanism of T cell activation by TSST-1 was investigated. TSST-1 induced IL-2R expression, IL-2 synthesis, and proliferation in T cells in a monocyte-dependent fashion. Neither IL-1 nor IL-2, alone or in combination, substituted for monocytes in supporting TSST-1-induced mitogenesis. We investigated the mechanism by which TSST-1 induces initogenesis. TSST-1 failed to induce ADP-ribosylation of T cell membrane proteins. However, the toxin induced transient translocation of protein kinase C from cytosol to plasma membranes and also induced the mobilization of cellular Ca2+ stores in both PBMC and the Jurkat human tumor T cell line, suggesting that TSST-1 triggered inositol phospholipid turnover. This was directly demonstrated to be the case in both cellular preparations studied. TSST-1 induced the increased synthesis of the inositol phospholipid phosphatidyl inositol, phosphatidyl inositol-4 phosphate, and phosphoinositol inositol-4,5-bisphosphate, and induced the breakdown of inositol phospholipid as evidence by the accumulation of phosphatidic acid and inositol phosphates. We conclude that the action of TSST-1 involves the induction of inositol phospholipid turnover, protein kinase C activation, and mobilization of cellular Ca2+ stores. This effect is similar to that of mitogenic lectins and of anti-CD3 antibodies.

Adenosine Diphosphate Ribose↗

High-affinity interleukin-2 receptors on blood lymphocytes are decreased during active rheumatoid arthritis.

The expression of receptors for interleukin-2 (IL-2R) was examined in patients with active or inactive rheumatoid arthritis (RA) and in control subjects. Unstimulated blood lymphocytes from patients with active RA had increased levels of total IL-2R, as measured by Tac-positive cells, compared with the levels found in the other 2 groups. Mitogen-stimulated cells from patients with active RA expressed less IL-2R per cell, but the most striking feature was the failure to express high-affinity IL-2R. These changes could reflect persistent antigenic stimulation and explain the defective cell-mediated immunity in RA patients.

Adult↗

The Geriatric Mental State Examination as a case-finding instrument in the community.

The Geriatric Mental State Examination (GMS), a standardised psychiatric interview, and its computerised diagnostic system, AGECAT, have been applied to a large (1070) sample of subjects aged over 65 in Liverpool. In a split-half study of this sample, diagnostic scales within the GMS and a diagnostic index derived from them were tested for efficacy in cases of organic and early organic illness (mostly various stages of dementia) and depressive illness. Results demonstrated high levels of sensitivity and specificity, and positive predictive values were within the expected range when applied to these disorders, given their low prevalence in the community. The GMS, when used in this way, is a flexible and effective case-finding instrument.

Aged↗

Identification of human vascular endothelial cell/monocyte antigenic system using monoclonal antibodies.

Recent studies have suggested that non-major-histocompatibility-encoded antigens expressed preferentially on vascular endothelial cells and/or monocytes may act as immunogens leading to allograft rejection. In order to further characterize the antigens and to investigate the roles of interleukins in the induction of such antigens, three murine monoclonal antibodies (SK2H10, SK3A1, SK2F11) were produced against interferon-gamma-induced human umbilical vein endothelial cells. All three monoclonal antibodies reacted specifically with human endothelial cells cultured from umbilical veins as well as blood monocytes. Several human established cell lines with B, T, and erythroid/myeloid cell properties, as well as cell lines expressing HLA-class I and II antigens (SB, REH, HSB, K562 and HL-60) failed to react with these reagents, indicating that the binding structures on the endothelial/monocyte cell surface are distinct from HLA class I and II antigens. Furthermore, the binding characteristics of the three antibodies to endothelial cells, monocytes, and human monocytic cell line, U937, suggest that they recognize different determinants on the cell surface. Analysis of Ia-positive and Ia-negative clones of U937 demonstrated that the antibodies reacted strongly with the Ia-positive cells lines. The monoclonal SK2H10 reacted preferentially with phorbol esters-induced HL-60 and K562 cell lines; thus indicating that the antigens detected on the monocytes are associated with differentiation. These results indicate that these monoclonal antibodies to endothelial cells have specificities similar to those described for alloantisera defining the vascular endothelial cell/monocyte antigenic system and should facilitate definition of the biochemical and molecular nature of such antigens.

Antibodies, Monoclonal↗

Range of mental illness among the elderly in the community. Prevalence in Liverpool using the GMS-AGECAT package.

A sample of 1070 elderly persons aged over 65 living in the Liverpool community was interviewed using the community version of the Geriatric Mental State (GMS) and the findings processed to provide a computerised diagnosis by AGECAT. Levels of organic disorder, probably dementia, reached 5.2%, intermediate between those of London and New York derived from previous studies. Levels for depressive illness overall were below those of other studies at 11.3% while levels for neurotic disorder were much the same at 2.4%. The rise in the prevalence of dementia with age was further confirmed. The GMS AGECAT Package provides a method for standardising both the collection of data and the diagnostic process for comparative epidemiological studies and other research.

Aged↗

Induction of IgE synthesis in normal human B cells. Sequential requirements for activation by an alloreactive T cell clone and IgE-potentiating factors.

Two human alloreactive T cell clones were established from a one-way mixed lymphocyte culture involving two nonatopic donors, and were assessed for their capacity to induce IgE synthesis by B cells obtained from the original stimulator. The two alloreactive T cell clones studied induced IgG but not IgE synthesis in normal B cells. However, one of the two clones, clone 2H6, induced IgE synthesis in the presence of supernatants from T cell lines derived from patients with the hyper-IgE syndrome (HIE), and enriched for T cells bearing receptors for IgE. These supernatants by themselves caused no IgE synthesis in nonatopic B cells. The potentiating factors in these supernatants were shown to bind to IgE. Time sequence experiments indicated that interaction of the B cells with the alloreactive clone 2H6 renders them responsive to the action of the IgE-potentiating factors. These results indicate that induction of IgE synthesis in normal B cells involves at least two sequential T cell derived signals. Furthermore, T cell clones are heterogenous in their capacity to provide these signals.

B-Lymphocytes↗

Circulating IgG autoantibodies to IgE in atopic syndromes.

Sera from nonatopic healthy donors and patients with hyper-IgE syndrome, allergic respiratory disease, i.e., allergic rhinitis and asthma, and atopic dermatitis were assayed for the presence of IgG and IgM antibodies to IgE. The assay used was based on an ELISA method that measured the binding of IgG or IgM in test sera to myeloma IgE (PS)-coated microtiter wells. The levels of IgG anti-IgE but not of IgM anti-IgE were elevated in patient sera of all three categories tested. The same sera failed to demonstrate increased levels of IgG anti-IgM or IgG anti-IgA. Significant IgG anti-IgE activity remained after absorption of patient sera over pooled human IgG F(ab')2 Sepharose. The IgG anti-IgE activity appeared to be directed toward the Fc portion of IgE because absorption of positive sera over IgE (ADZ) Sepharose but not over myeloma IgG Sepharose completely removed their reactivity with IgE (PS) and because sera from atopic individuals but not from normal subjects contained IgG anti-IgE activity against the protein backbone of the Fc portion of IgE synthesized from a fragment of the cloned gene of human myeloma IgE (ND) heavy chain. Regression analysis demonstrated a weak but significant correlation (r = 0.31; p less than 0.05) between serum IgE levels and IgG anti-IgE activity. Fractionation of sera from the three patient categories by gel filtration over Sepharose 6B revealed that IgG anti-IgE activity was present both as monomeric IgG and in IgE containing immune complexes (IC). Intermediate molecular size IC (between 7S and 19S) were present in all three patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

Potentiation of human immunoglobulin E synthesis by plasma immunoglobulin E binding factors from patients with the hyperimmunoglobulin E syndrome.

Affinity-purified IgE-binding factors from the plasma of patients with the hyper IgE syndrome (HIE) were assessed for their capacity to enhance IgE synthesis by B cells derived from patients with allergic rhinitis or normal nonatopic donors. IgE-binding factors from three of four HIE patients enhanced IgE synthesis by B cells from patients with perennial allergic rhinitis, or with seasonal allergic rhinitis (SAR) and recent pollen exposure, but did not enhance IgE synthesis by B cells from nonatopic donors or from SAR patients with no recent pollen exposure. IgG synthesis was not affected by HIE IgE binding factors. In contrast, IgE binding factors from three of three nonatopic donors failed to enhance IgE or IgG synthesis. Plasma IgE-binding factors from the fourth patient with HIE contained a mixture of IgE-potentiating activity and IgE-suppressive activity. These two activities could be separated on concanavalin A Sepharose or peanut agglutinin agarose columns. Human IgE potentiating factor, but not IgE suppressive factor, had affinity for concanavalin A but not peanut agglutinin and fractionated into two peaks on gel filtration over Sephadex G-75: one peak with a molecular size of approximately 15,000 D and the other with a molecular size of approximately 60,000 D. The isolation of functional IgE binding factors which potentiate IgE synthesis from the plasma of patients with HIE suggests that IgE-binding factors play an important role in the in vivo regulation of IgE synthesis in man.

B-Lymphocytes↗

Childhood leukemia with simultaneously expressed myeloid and lymphoid markers suggesting stem cell origin.

A case study is presented of a leukemic patient whose cells express markers of both myeloid and lymphoid cells. Cells were identified from bone marrow which expressed either myeloid antigens, lymphoid antigens, or both myeloid and lymphoid antigens, indicating a possible common stem cell capable of differentiating along either a lymphoid or myeloid cell lineage. Using specific monoclonal antibodies, 40-70% of the cells were reactive with anti-T-cell antibodies, 50% of the cells were reactive with antibodies to the common ALL antigen (CALLA), and 80-90% of the cells were reactive with antibodies directed against myeloid antigens. Using double staining techniques, some cells were found to demonstrate only myeloid markers; others, only lymphoid markers; and others, both myeloid and lymphoid markers. These results suggest that a common stem cell is capable of differentiating along both lymphoid and myeloid lineages.

Antibodies, Monoclonal↗

Aetiology and incidence of facial fractures in adults.

The incidence, aetiology and trends in fractures of the facial bones occurring in the years 1965, 1970, 1975 and 1980 in the Grampian Region of Scotland are reported. A 2.7 fold increase in incidence occurred during this period. Males are seen to be most at risk and an increase in assault and sports-related trauma is seen. Offshore oil exploration developed during this period and its effects are discussed. Attention is drawn to the differences in the aetiology of right and left malar fractures.

Adult↗

Cellular basis of defective cell-mediated lympholysis in atopic dermatitis.

Peripheral blood lymphocytes (PBL) from patients with atopic dermatitis (A.D.) were examined for their capacity to generate cytotoxic T lymphocytes (CTL) during mixed lymphocyte cultures (MLC). Cell-mediated lympholysis (CML) activity, but not proliferative response during MLC, was significantly decreased (p less than 0.01) in patients with A.D. (n = 19) compared with normal controls (n = 19) or patients with other skin diseases (n = 14). Regression analysis revealed a significant correlation (p less than 0.001) between CML activity and the percentage of circulating T8+ suppressor/cytotoxic T cells. Deficient CML activity in A.D. patients, however, was not corrected when isolated autologous T4+ and T8+ cells were recombined at a normal ratio (2:1) of T4+ to T8+ cells. Examination of CML activity in co-cultures of isolated T4+ and T8+ cells obtained from two A.D. patients and their respective HLA-identical healthy siblings indicated that the defect in CML resided in both the helper/inducer T4+ cells and the effector T8+ cells. The defective cytotoxic T cell function reported in the present study may account for the increased susceptibility of patients with A.D. to develop severe viral infections.

Adolescent↗

Immunoregulatory T cell abnormalities in mucocutaneous lymph node syndrome.

We recently demonstrated that during the acute phase of mucocutaneous lymph node syndrome (MCLS)3 there was a significant reduction in circulating T8+ suppressor/cytotoxic T cells and an increased number of Ia/Dr-bearing T4+ T cells, which suggests the presence of circulating activated helper T cells (1). Furthermore, the vast majority of patients with acute MCLS had a significantly elevated number of circulating B cells spontaneously secreting IgG and IgM. In the present study, the possible role of the immunoregulatory T cell abnormalities in the polyclonal B cell activation was investigated by assaying the ability of T cells and T cell factors from patients with acute MCLS to induce immunoglobulin production by normal B lymphocytes. We also examined the capacity of normal T cells to suppress immunoglobulin production by activated B cells from patients with acute MCLS.

Antibody-Producing Cells↗