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Biomedical subjects

D R Stanworth

Publications and source records attributed to D R Stanworth.

At least 19 recordsLinked to original sources
PubMed1992

Synthetic peptides comprising defined sequences of CH-2 and CH-3 domains of human IgG1 induce prostaglandin E2 production from human peripheral blood mononuclear cells.

Synthetic peptides Y48 and Y75 comprising sequences at exposed sites within the CH-2 and CH-3 domains of human IgG1 at a concentration of 10(-5) M, increase PGE2 production by human peripheral blood mononuclear cell (PBMC) cultures. An increase of leukocyte migration inhibitory factor (LMIF) production in PBMC cultures--as a result of synthetic peptide treatment--was also observed. This LMIF activity, to some extent, is attributed to the PGE2 production by the cells; the inhibition of leukocyte migration being abolished by the presence of indomethacine or antibody to PGE2.

Cell Migration Inhibition↗
PubMed1992

Anti-IgG autoantibodies in HIV-infected hemophilia patients.

Sera of 76 HIV-negative hemophilia patients, 103 HIV-positive (HIV+) hemophilia patients free of AIDS or AIDS related complex (ARC), and 32 HIV+ hemophilia patients with AIDS/ARC were tested for four different anti-IgG activities. IgG-anti-F(ab')2 gamma, IgM-anti-F(ab')2 gamma, and IgG-anti-Fc gamma serum activities were significantly associated with the clinical stage of HIV infection, whereas IgM-anti-Fc gamma was not. IgG-anti-F(ab')2 gamma activity was found to be caused by cross-reaction of anti-HIV antibody with an epitope within the constant CH1 domain of human IgG. HIV+ hemophilia patients with severe thrombocytopenia (less than 50,000/microliters platelet counts) had significantly higher IgM-anti-IgG activity than patients with greater than 50,000/microliters platelets. Because anti-IgG antibodies possess immunoregulatory properties, our results may serve as a possible explanation for the frequent B cell disorders encountered in HIV-infected patients.

AIDS-Related Complex↗
PubMed1991

Affinity-purified soluble Fc epsilon RII/CD23 derived from RPMI-8866 cells induces histamine release from human nasal polyp mast cells through a non-IgE-mediated mechanism.

Soluble Fc epsilon RII/CD23 (IgE-binding factor) is released spontaneously from activated B cells and most EBV-immortalised B cell lines. We have purified soluble Fc epsilon RII/CD23 from culture supernatants of RPMI-8866 cells on an IgE Sepharose column, and studied its ability to release histamine from human nasal polyp mast cells. Soluble Fc epsilon RII/CD23 induces release of a significant amount of histamine from nasal polyp mast cells in a dose-dependent manner. IgE, and a monoclonal antibody specific for the soluble form of this receptor, were shown to neutralise this effect. It was found that soluble Fc epsilon RII/CD23 was still capable of triggering histamine release from nasal polyp mast cells from which IgE had been eluted by incubation in a low pH buffer, suggesting that a non-IgE mediated mechanism was responsible for this effect.

Animals↗
PubMed1991

The association and predictive value of the complex immunoglobulin A-alpha 1-antitrypsin in the development of erosions in early rheumatoid arthritis.

Immunoglobulin A-alpha 1 antitrypsin complex (IgA-AT), its constituent components and nine other clinical or laboratory variables were measured in thirty-three patients with early, non-erosive rheumatoid arthritis (RA) in order to assess their value in predicting the subsequent development of erosions. After 12 months, eighteen patients had developed erosions. Comparison of variables measured at outset between the group of patients subsequently developing erosions and those not, showed only the complex IgA-AT level to be significantly different, the mean being higher in the erosive group. In the subgroup of patients with high IgA-AT levels (greater than 3.0 arbitary units) all developed erosions. The possible therapeutic implications of these findings are discussed.

Arthritis, Rheumatoid↗
PubMed1991

Affinity-purified soluble Fc epsilon RII/CD23 derived from a culture supernatant of an EBV-immortalized B-cell line induced a monophasic fever in rabbits.

A soluble form of Fc epsilon RII/CD23 is spontaneously released from most lymphoblastoid cell lines established by the Epstein-Barr virus (EBV). Such a product was purified on an IgE-Sepharose column and its pyrogenic effect was investigated in rabbits. This preparation induced a monophasic fever in rabbits, with a peak response appearing 75 min after injection. Since IgE was found to be capable of abrogating such an effect, it is suggested that IgE might be involved in the control of the effectiveness of this soluble protein.

Animals↗
PubMed1990

Allergy treatment with a peptide vaccine.

An antiserum, obtained by immunising rabbits with a human peptide-protein conjugate, was shown to inhibit histamine release from rat mast cells both in vitro and in vivo. Immunisation of sensitised rats with the same peptide reduced IgE antibody formation and serum histamine concentration, and abolished systemic anaphylactic reactions in response to allergen challenge. This peptide may form the basis of a vaccine in a new approach to the immunotherapy of atopic disease.

Animals↗
PubMed1990

Functional implication for the topographical relationship between MHC class II and the low-affinity IgE receptor: occupancy of CD23 prevents B lymphocytes from stimulating allogeneic mixed lymphocyte responses.

Following the observation of Bonnefoy et al. (J. Exp. Med. 1988. 167:57), that the low-affinity IgE receptor (CD23) on B lymphocytes can be coupled (with the use of chemical cross-linking reagents) to major histocompatibility complex (MHC) class II DR molecules, we now report that ligands binding within the lectin-homology region of CD23 prevent B cells from stimulating allogeneic mixed lymphocyte responses. Ligands capable of blocking mixed lymphocyte responses include the anti-CD23 antibodies MHM6 and EBVCS 4 but not EBVCS 1 and 5. IgE itself, and small peptides representing sequences within the CH3 domain of IgE. The detailed topographical relationship between CD23 and MHC class II on the B lymphocyte surface was examined using dual immuno-fluorescence labeling of cells and direct visualization of the staining by confocal laser scanning microscopy. On transformed B lymphoblasts, the two antigens were seen to co-localize in discrete patches; on normal B cells which had been cultured for 2 days with interleukin 4, CD23 and MHC class II converged at a single pole which exhibited a tendency to pseudopod formation and provided a focus for homotypic cell-cell interactions. The possibility that CD23 could serve as a co-stimulatory-adhesion molecule in antigen presentation by B lymphocytes is discussed with special reference to a potential role in the regulation of IgE synthesis.

Antibodies, Monoclonal↗
PubMed1989

Anti-viral antibodies in HIV (HTLV-III) infection possess auto-antibody activity against a CH1 domain determinant in human IgG: possible immunological consequences.

Two regions of the envelope glycoprotein gp120 of the human immunodeficiency virus were shown to have a significant degree of homology to human immunoglobulin-gamma heavy-chain constant domains. We have now synthesized three short linear peptides, the first representing a sequence within the CH1 domain, the second an analogue of it, and the third representative of a region within the viral gp120. Polyclonal antibodies against these peptides were raised in rabbits and used to demonstrate that they all reacted well with human native IgG. Vice-versa, we observed the reaction of these antisera to the virus in an ELISA system. The proportion of sera reacting with the human gamma-chain peptide was significantly higher in HIV-positive individuals than in HIV-negative individuals, suggesting production of anti-viral antibodies in AIDS patients with auto-antibody activity against a CH1 domain determinant in human IgG.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Sulphasalazine therapy in ankylosing spondylitis: its effect on disease activity, immunoglobulin A and the complex immunoglobulin A-alpha-1-antitrypsin.

Serum levels of immunoglobulin A (IgA) and the complex immunoglobulin A-alpha 1 antitrypsin (IgA-alpha 1AT) were measured at the commencement and after 3 months of a double-blind, placebo-controlled trial of sulphasalazine (SAS) in patients with active ankylosing spondylitis (AS). Twenty-eight patients were evaluated, 15 on sulphasalazine, 13 on placebo. Significant falls were seen in both IgA (p less than 0.01) and IgA-alpha 1AT (p less than 0.001) in the actively treated patients. In addition, significant improvement in clinical and laboratory measures of disease were observed. It is concluded that SAS is effective in AS and modulates the immune response.

Adult↗
PubMed1989

The incidence of IgE and IgG antibodies to chlorhexidine.

IgE antibodies to the antiseptic agent chlorhexidine have recently been detected in the majority of sera from a small group of predominantly Japanese individuals showing anaphylactic-type adverse reactions towards chlorhexidine. In this study the prevalence of IgE and IgG antibodies with specificity for chlorhexidine was investigated in groups of Japanese and British individuals. The RAST data, using a better defined semi-chlorhexidine-HSA antigen than previously employed, revealed that chlorhexidine-specific IgE was only detected in Japanese individuals who had experienced anaphylactic-type reactions and was not detected in groups of Japanese nurses and patients, or in groups of British nurses and hospital staff, all in regular contact with chlorhexidine. A group of British blood donors was also negative. In contrast, IgG antibodies were detected not only in sera from chlorhexidine-sensitive Japanese patients, but also in several sera from Japanese nurses, non-sensitive Japanese patients and several British individuals. The possible reasons for these observations are discussed.

Adult↗
PubMed1989

IgA-alpha 1 antitrypsin complexes in ankylosing spondylitis.

A study of 95 serum samples from 61 patients with ankylosing spondylitis (AS) showed that 21 patients (34%) had raised levels of IgA-alpha 1 antitrypsin complexes. These were associated with active disease as measured by a clinical index and also with erythrocyte sedimentation rate, C reactive protein, and serum IgA. In particular, an association was noted between 'extraspinal' manifestations of AS such as synovitis, uveitis, and active inflammatory properties of these complexes. It is suggested that these complexes may have a role in the pathogenesis of such clinical manifestations.

Adult↗
PubMed1988

Synergistic enhancement of histamine release from rat peritoneal mast cells by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate is not reflected by corresponding changes in phospholipid turnover.

In an attempt to elucidate further the relationship between changes in phospholipid metabolism in, and histamine secretion from, purified rat peritoneal mast cells, the effects of the phorbol diester 12-O-tetradecanoylphorbol 13-acetate (TPA) on these responses in stimulated and unstimulated cells was investigated. TPA caused a dose-dependent increase in the incorporation of 32PO4(3-) into the mast cell phospholipids; phosphatidic acid (PA) and phosphatidylcholine (PC), but not phosphatidylinositol (PI). TPA synergistically enhanced histamine release from cells stimulated by anti-immunoglobulin E (IgE) and the calcium ionophore A23187, reducing its ED50 from 150 nM to 40 nM, but did not alter histamine release from cells stimulated by compound 48/80. The effect of TPA on the changes in 32PO4(3-) incorporation into phospholipids associated with the above secretagogues did not, however, correlate well with the observed effects on histamine secretion induced by the same secretagogues. These observations are discussed in relation to the known effects of phorbol esters upon both secretory processes and phospholipid metabolism in other tissues.

Animals↗