Composite activities on B cells of products released by T cells activated by concanavalin A.

Supernatants from murine spleen cells cultured for 48 h in the presence of 1.0 μg of concanavalin A (Con A) induced polyclonal antibody synthesis in cultures of spleen cells from both normal and athymic mice in the absence of exogeneous antigen. Moreover, the Con A-induced supernatant rescued B cells which had been rendered unresponsive by a tolerogen [haptenated poly(D Glu,D Lys)]. The capacity of the supernatant to induce cell proliferation was studied under both high and low-density culture conditions. In contrast to antibody secretion, proliferation was only detectable in low-density cultures. The Con A-induced supernatant also contained suppressive components, since the primary anti-sheep red blood cell (SRBC) response was markedly suppressed when the antigen added to cultures consisted of SRBC which had previously been used for absorbing the supernatants. Absorbed supernatants displayed enhanced helper activity indicating that only the suppressor component was removable by antigen. The suppressive component was eluted from erythrocytes with ammonium thiocyanate and was itself strongly suppressive when added to cultures with fresh erythrocytes. Furthermore, the suppressive component proved to be highly antigen-specific, as the SRBC-absorbed factor did not affect the response to horse RBC. The results indicate that supernatants from Con A-activated spleen cells contain both helper and suppressor factors, the latter having easily demonstrable antigen specificity. They further suggest that a nonantigen-derived signal is sufficient to trigger both proliferation and antibody synthesis by B cells.     

A new HLA-A allele, HLA-A*6824, identified in three unrelated individuals

A novel allele, human leukocyte antigen (HLA)-A*6824, has been identified in three unrelated individuals of northwestern European origin in a period of less than 4 months, implying that this allele may be quite common in this population. HLA-A*6824 differs from A*680102 by a single nucleotide change at position 275 in exon 2, which results in a conservative amino acid substitution from lysine to arginine in the peptide-binding groove at codon 68.     

Bronchitis symptoms in young teenagers who actively or passively smoke cigarettes

This study was undertaken to examine the prevalence of bronchitis (cough with phlegm) symptoms in teenagers who either smoked cigarettes on a regular basis (active smokers) or were non-smokers but who are exposed to passive smoking (passive smokers) in the home. The study was undertaken in 1995 and repeated in 1998. The 1995 study was a cross sectional questionnaire survey of smoking habits in secondary school children aged 13-14 years and was undertaken as part of the ISAAC questionnaire survey. Thirty representative and randomly selected schools from throughout the Republic of Ireland took part in the study. In the 1995 study, 3066 students completed a questionnaire on their current smoking habits and symptoms of cough and phlegm. We found that 634 (20.7%) of these young teenagers actively smoked cigarettes with significantly more females smoking than males with 23.3% of girls compared to 17.6% boys (p = 0.0001). We found that 46.3% of non-smoking children were exposed to smoking in the home (passive smokers) with parental smoking accounting for most of the passive smoking. Bronchitis symptoms were more commonly reported in active smokers compared to non-smokers with an odds ratio of 3.02 (95% CI 2.34-3.88) (p < 0.0001) or in passive smokers compared to those not exposed to smoking with odds ratio of 1.82 (95% CI 1.32-2.52) (p < 0.0001). The 1998 study showed similar results for smoking habits, passive smoking and prevalence of bronchitis symptoms as with the 1995 study. These results document that increased bronchitis symptoms occur in teenagers exposed to active or passive smoking.     

Daily versus thrice-weekly interferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C in HIV-infected persons: a multicenter randomized controlled trial

Among HIV-infected persons, chronic hepatitis C virus (HCV) infection causes substantial morbidity and mortality. However, few studies have evaluated the safety and efficacy of interferon alfa (IFN) and ribavirin (RBV) therapy in co-infected persons. Accordingly, a randomized, controlled, open-label, multicenter trial was conducted to establish the safety, tolerability, and efficacy of IFN alfa-2b 3 mIU daily plus RBV 800 mg/d compared with IFN alfa-2b 3 mIU thrice weekly (TIW) plus RBV 800 mg/d in HCV treatment-naive, HIV-infected subjects with compensated liver disease and stable HIV disease. The primary endpoint was sustained virologic response (SVR), defined as an undetectable HCV RNA level 24 weeks after discontinuation of HCV therapy. At study entry, subjects in both groups were similar with respect to age, gender, HCV genotype, and HIV disease status. Of 180 randomized subjects, 162 received at least 1 dose of study medication, constituting the modified intention-to-treat population. After 12 weeks of therapy, 122 (75%) had serum HCV RNA levels assessed; of these subjects, early virologic response (undetectable HCV RNA or >2 log10 decrease from baseline) was observed in 33 (42%) and 13 (16%) of subjects taking daily and TIW IFN, respectively (P < 0.001). SVR was observed in 15 (19.0%) and 7 (8.4%) of subjects taking daily and TIW IFN, respectively (P = 0.05). Adverse events were similar in both groups. However, while no deaths or opportunistic infections were observed, nearly 30% of subjects stopped treatment due to adverse events and 7 subjects experienced a serious adverse event. In conclusion, SVR was achieved in 19% of HIV/HCV coinfected subjects treated with daily IFN plus RBV, but the effectiveness of therapy was substantially diminished by relatively high rates of treatment-related toxicity.     

Incidence and outcome of chronic graft-versus-host disease using National Institutes of Health consensus criteria.

Chronic graft-versus-host disease (cGVHD), a common complication after stem cell transplant (SCT), has an impact on morbidity and survival. Previous classification of cGVHD has not been reproducible or prognostic for nonrelapse mortality (NRM). Recently the National Institutes of Health (NIH) consensus criteria were proposed, but the ability of this classification to predict outcome of various subtypes of cGVHD is unknown. Patients (N = 110) undergoing an SCT for a hematologic malignancy and surviving until day 100 posttransplant from 2001 to 2003 were studied. The overall survival (OS) using a landmark analysis at day 100 was 44% versus 66% (no GVHD vs. GVHD, P = .026). The OS of patients with various types of GVHD as proposed by the NIH criteria were significantly different (P < .0001). In a univariate analyses, this was more apparent when patients with any acute features of GVHD were compared to classic cGVHD (3-year OS 46% vs. 68%, P = .033). The 3-year NRM for the entire cohort was 21%, and was not affected by presence or absence of GVHD or subtypes of GVHD. In a multivariable analysis, extensive cGVHD (hazard ratio [HR] 0.35, P = .015) and having any acute feature of GVHD after day 100 (HR 3.36, P = .0144) were significant independent predictors of survival. The OS with different NIH subtypes of GVHD after day 100 from SCT varies, and is superior for patients with classic cGVHD.     

Quantitative immunoassay of Treponema denticola serovar C in adult periodontitis.

Murine monoclonal antibodies specific for Treponema denticola serovar C were produced and characterized in this study. An immunoassay was then developed by using these monoclonal antibodies, and the T. denticola serovar C antigen content of subgingival plaque was quantitated for samples taken from patients with periodontitis and healthy volunteers. The human subgingival plaque samples were grouped by severity of disease and pocket depth measurements at the collection site. The T. denticola serovar C content per milligram of subgingival plaque from deep pockets (greater than 6 mm) of patients with severe periodontitis was found to be twice that of samples collected from deep pockets (4 to 6 mm) of patients with moderate periodontitis or samples collected from healthy subjects (pocket depth, less than 4 mm).     

Identification of a major antigenic epitope on CNBr-fragment 11 of type II collagen recognized by murine autoreactive B cells.

Immunization of certain strains of mice with native type II collagen (CII) induces both development of arthritis and an antibody response to autologous CII. The autoantibody response in a high-responder strain, the DBA/1 mouse, has been described earlier, and a number of monoclonal antibodies have been characterized for arthritogenicity and autoreactive binding to cartilage in vivo and in vitro. Here we map the antigenic epitope of one of these arthritogenic monoclonal antibodies (CII-C1). It belongs to a group of antibodies recognizing the CNBr fragment alpha 1(II)-CB11 of CII. Using the enzyme-linked immunosorbent assay technique, we show that the antibody reacts only with native, triplehelical CII, but not with other collagens. The antibody is able to stain specifically the CB11 fragment by immunoblotting, suggesting some partial renaturation of the CNBr fragment into triple-helical structures after blotting. The binding site of CII-C1 on CB11 was further focused by rotary shadowing of antibody-labeled CII to a site 89 +/- 8 nm from the amino end of CII, corresponding to the middle of CB11. This location was confirmed by cleavage of CB11 with trypsin, separation of the tryptic peptides by high-performance liquid chromatography and dot-blot analysis of the antigenic peptides with the CII-C1 antibody. Sequencing of the single positive peptide located the antigenic epitope within the sequence GFAGQAGPAGATGAPGRP (residues 316-333). Assuming 0.29 nm per residue, this corresponds to a position within 92-96.5 nm from NH2 terminal end of CII. Apart from glycine residues, which are not exposed on the triple-helical structure, only two amino acid residues (F-x-y-Q) are conserved in CII from different species but are not found in the triple-helix of other collagens except type IV collagen. Therefore, this structure is likely to be of critical importance for the binding of the CII-C1 antibody. Of potential importance is that this structure is also found in certain other arthritogenic proteins such as 65-kDa mycobacterial protein, in CMV and EBV.