Clozapine--a dangerous drug in a clozapine-naïve subject.

Clozapine is a uniquely effective antipsychotic, but is very toxic in clozapine-naïve subjects. A 34-year-old male patient in a mental health facility, who was not prescribed clozapine, took 350 mg clozapine obtained from another patient at night. He was found dead the next morning.

Thirty years with Fc(sigma)R.

In his talk Henry Metzger [H. Metzger et al., Immunol.

Microheterogeneity of alpha 1-antitrypsin in relation to the concentration of its complex with immunoglobulin A in the sera of patients with rheumatoid arthritis.

Objective: Serum alpha 1-antitrypsin (alpha 1AT) is an acute-phase glycoprotein which contains three carbohydrate side chains, N-glycosidically linked to the asparagine molecules (Asn46, Asn83 and Asn247) of the single polypeptide unit. "Microheterogeneity", which is a varying proportion of bi- or triantennary heteroglycans attached to the glycosylation sites, has been observed in various inflammatory states including rheumatoid arthritis (RA), and may influence the properties of alpha 1AT.

Methods: In this study, we used affinity immunoelectrophoresis with the lectin concanavalin A (ConA) to investigate the possible role of alpha 1AT microheterogeneity in IgA-alpha 1AT complex formation.

Levels of substance P and IgE decapeptide in nasal polyp fluid and matching sera: a preliminary study.

Sixteen unselected patients with nasal polyps had the levels of substance P and IgE decapeptide measured by ELISA in the oedema fluids and their matched sera. All 16 samples had low levels of substance P in their sera and had high level of substance P in eight samples of nasal polyp oedema. There was a considerable variation in the values of IgE decapeptide found in the sera but 14 polyp oedema fluids had high levels of IgE decapeptide.

Cross-linking of a sequential epitope within the beta-chain of HLA-DR/DP molecules suppressing B lymphocyte growth and inducing homotypic cell aggregation.

A monoclonal antibody (SU2) directed against HLA class II antigens has been produced by immunizing BALB/c mice with a lymphoblastoid cell line, RPMI-8866 cells. The specificity of this mAb has been determined using a panel of HLA class II transfectants. SU2 stained all HLA-DR and HLA-DP transfectants tested, but reacted with only one HLA-DQ (HLA-DQw2).

Epitope mapping of the site(s) of binding of Fc epsilon RII/CD23 within human IgE. Determination of the B lymphocyte-binding sites by use of synthetic peptides and anti-peptide antibodies representative of linear Fc sequences.

The work undertaken has investigated the structure-function relationship between IgE and its low affinity receptor on B lymphocytes. To identify sites on the IgE molecule which interact with the low affinity receptor (Fc epsilon RII/CD23), 10 different peptide sequences within the CH2, CH3 and CH4 domains of human IgE were selected according to charge, overall hydrophobicity and possible accessibility on native IgE sequences. Peptides representative of these were synthesized by the solid phase procedure; and their cytophilic activities were examined by determining their capacity to inhibit the binding of radiolabelled or erythrocyte-bound IgE to a Fc epsilon RII/CD23 positive B cell line (RPMI-8866).

Production and characterization of two murine monoclonal antibodies directed against epitopes exclusive to soluble fragments of Fc epsilon RII/CD23.

Two murine monoclonal antibodies (mAb) designated as SU1 and SU3 directed against soluble Fc epsilon RII/CD23 have been generated by fusing X.63.AG.

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.

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.

Effect of human IgG1 peptides on the antigen-specific antibody response of mice in vivo.

The effect of synthetic peptides--corresponding to the amino acid sequences 289-301 (Y48) and 293-301 (Y91) within the CH-2 domain in the human IgG1 was studied on the oxazolone-specific primary and secondary antibody response isotype distribution and on the sheep erythrocyte (SRBC)-specific primary IgM response. High responder (Balb/c) and low responder (C57Bl/6) mice to oxazolone hapten were treated intraperitoneally with various doses of peptides simultaneously with the first and second contact sensitization. The relative levels of oxazolone-specific IgM, IgG3, IgG1, IgG2a and IgG2b antibodies were determined by a solid phase radioimmunoassay.

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.

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.

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.

Modulatory effect of synthetic human IgG Fc peptides on the in vitro immune response of murine spleen cells.

Synthetic peptides representative of defined surface-exposed sequences within the CH-2 and CH-3 domains of human IgG1 induce IgM production by murine spleen cells, even in cultures depleted of T-lymphocytes. This stimulation was not altered by simultaneous administration of dextran sulphate in suboptimal concentration, its effect being additive to that of the peptides. Cell proliferation was augmented only at 10(-4) M doses of peptides.

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.

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.