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It is well established that gluten-free diet reduces the incidence of type 1 diabetes mellitus (T1D) in non-obese diabetic (NOD) mice, though the mechanism is not known. However, regulatory T cells (Treg) are likely to play an important role. Also, it is known that dietary gluten induces an intestinal increase in the bacterium Lactococcus garvieae, but the importance of this phenomenon for T1D development is doubtful. Our hypothesis is that gluten is responsible for mediating its effect on T1D through the influence on Treg development independent of gluten-induced Lactococci. Four groups of female NOD and BALB/c mice of 3 week old were fed either a gluten-free diet or a standard diet. Lactococcus garvieae or saline water was administered per oral to one of each dietary group. Spleen and Peyer′s patches were sampled from BALB/c mice for flow cytometric monitoring of IL-10 and Treg. NOD mice were diagnosed diabetic with blood glucose level >12 mmol/l. Dietary gluten significantly decreased the occurrence of Tregs by 10–15% ( P < 0.05) in mice compared with those fed a standard diet. These results and the diabetes incidence were independent of the gluten-induced bacterial factor Lactococci. The prevalence of Treg was 5- to 10-fold more abundant in the Peyer′s patches than in the spleen ( P < 0.001). In conclusion, dietary gluten has a significant negative quantitative impact on the generation of Treg in mice, independent of gluten-induced Lactococcus garvieae, and Treg are far more abundant in Peyer′s patches than in the spleen. [ABSTRACT FROM AUTHOR]

The aim of this study was to measure the direct release of nitric oxide (NO) from the porcine mitral valve using a NO microelectrode. Furthermore, the expression and localization of endothelial nitric oxide synthase (eNOS) in the mitral valve was studied using immunohistochemistry, Western blotting and RT-PCR. Results show that bradykinin increases NO release from mitral valves (ΔBradykinin: 33.71 ± 10.41 nm NO, P < 0.001, n = 10), whereas N-nitro-l-arginine methyl esther (l-NAME) decreases NO release when compared with basal level (Δl-NAME: 82.69 ± 15.66 nm NO, P < 0.005, n = 4). Both protein and mRNA expression of eNOS in mitral valves and in isolated valvular endothelial cells suggest that the NO release is mainly associated with the mitral valve endothelium. It is concluded that direct NO release from porcine mitral valves coincides with eNOS expression. This study documents useful techniques for investigations into the role of local NO release in mitral valve diseases. [ABSTRACT FROM AUTHOR]

Studies on the immune response against hapten-autologous protein carriers in mice, guinea-pigs and rabbits have shown that the new antigenic determinants introduced in the carrier molecule by the hapten coupling reaction play an important role in the induction of both immunity and tolerance to these conjugates. The present experiments were designed to elucidate the specificity of the new antigenic determinants induced (1) by different haptens through the same coupling procedure and (2) by the same hapten coupled by different procedures. The results showed that both the nature of the hapten and the coupling procedure played a role in the serological specificity of the new antigenic determinants. [ABSTRACT FROM AUTHOR]

Mink persistently infected with Aleutian disease virus (ADV) develop plasmacytosis (hypergammaglobulinaemia) and immune complex disease. Mink of different colour phases were Infected with different strains of ADV and bled at different limes alter infection. The average antibody affinities (Kav) were measured in the sera and found to fall in the range of 2 × 109-2 × 1010 M-1, thus indicating good-quality antibodies. In sera of non-Aleutian genotype mink a decline in Kav during development of plasmacytosis was observed. Moreover, the antibody heterogeneity (α values) tended to decrease during the disease progress. In contrast, the Kav values in sera of infected Aleutian genotype mink remained relatively high after hypergammaglobulinaemia developed, and the antibody heterogeneity for certain of the mink sera indicated restricted heterogeneity (high α values). In agreement with the clonal selection theory. low virus burden (for instance, during infection with a low-virulence ADV strain) generated relatively higher affinity antibodies than a high virus burden liar instance, the highly virulent Utah I strain of ADV). Furthermore. antibodies present in low concentration were of higher affinity than antibodies present in high concentrations. The relatively high affinity antibodies found in this study indicate that if the immune complex disease seen in AD is caused by virus-anti-virus antibodies, good-quality antibodies are likely to he responsible for the pathological findings. [ABSTRACT FROM AUTHOR]

Mink persistently infected with Aleutian disease virus (ADV) develop hypergammaglobulinaemia and immune complex disease. Radiolabelled antibodies from mink infected with ADV-G, DK, Pullman, and Utah I strains of ADV were reacted against all four ADV strains in radioimmunoassay (RIA). The amount anti-ADV antibody in two equally hypergammaglobulinaemic serum pools varied from 13% (anti-Pullman) to 57% (anti-Utah I). Serum pools from two other sources (anti-DK and anti-ADV-G), although less hypergammaglobulinaemic, had 5% and 13%, respectively, indicating that 43-95% of the Ig in the sera of mink with AD was not specific antibody to ADV structural antigens. The possibility of a general polyclonal activation of the humoral immune system is being discussed. Comparison of plateau RIA binding levels for the four serum pools against the four viral antigens suggested three patterns of reactivity: DK anti Utah I reacted similarly, but Pullman and ADV-G reacted serologically different. [ABSTRACT FROM AUTHOR]

Human antibodies to streptococcal groups A and C carbohydrates were measured quantitatively with a radioimmunoassay using tyrosylated 125I carbohydrate. Analysis of acute and convalescent sera from people with groups A or C streplococcal pharyngeal infection or persistent carriage revealed a significant rise in antibodies. Inhibition reactions with the cold carbohydrate indicated the specificity of the elicited antibodies, in some instances, group C as well as group A antibodies occurred after group A pharyngeal infections. Further clinical and epidemiological studies are required to determine the significance of group-specific antibodies. Antistreptolysin-O (ASO) rises were observed in individuals with group C antibody responses after persistent group C pharyngeal carriage. For this reason, epidemiological surveys that rely primarily on ASO surveys to determine the incidence of group A streplococcal infections must be interpreted with caution, at least in the developing countries, where group C pharyngeal carriage is common. [ABSTRACT FROM AUTHOR]

One hundred and five rabbits were immunized with a streptococcal group A or C vaccine. An anti-antibody production in relation to the antistreptococcal antibody production was measured by two methods, the latex fixation test and the sensitized sheep erythrocyte test (the Waaler-Rose test). The anti-antibody production was correlated to the amount of precipitating and agglutinating antistreptococcal antibodies, antibody restriction, and γ-globulin allotypes within the a locus. Anti-antibodies measured by the Waaler-Rose test showed no correlation with any of the variables mentioned. The anti-antibody production measured by the latex fixation test showed a correlation with antibody restriction; that is, a positive latex reaction was found in a higher percentage of rabbits with a homogeneous or restricted heterogeneous antibody response to streptococcal carbohydrate antigens than in rabbits with a heterogeneous antibody response. Possible mechanisms underlying the production of anti-antibodies are discussed. [ABSTRACT FROM AUTHOR]

One hundred and five rabbits were immunized with a streptococcal group A and C vaccine. About 50% of the rabbits died during the immunization, mainly of unknown causes. The amounts of precipitating and agglutinating antibodies, antibody restriction, and γ-globulin allotypes within the a locus were determined and correlated with one another. The mean precipitin and agglutinin titers of the rabbit antisera with some kind of restricted response in almost all case were higher than the titers of the antisera from the rabbits with a heterogeneous response, but the difference was significant in only a few cases. No significant correlation was found between allotypic markers and the other variables mentioned. [ABSTRACT FROM AUTHOR]

The degree of uptake of DNP 125I-HSA (= DNP ∗HSA) conjugates by mouse peritoneal exudate (PE) cells in vivo and their retention in the spleen, and liver depended on the density of hapten per carrier molecule. Forty to 400 times more DNP29∗HSA and DNP39∗HSA were ingested by PE cells as compared to HSA alone. Significantly more DNP29∗HSA and DNP39∗HSA persisted in the spleen and liver after intraperitoneal injection than ∗HSA, DNP6∗HSA or DNP11∗HSA. ∗HSA, DNP6∗HSA, and DNP11∗HSA were rapidly catabolized after uptake in macrophages in vitro, but a small amount of these antigens was associated with the cells. About 50% of the ∗HSA was membrane-bound. ∗HSA conjugated with DNP29 or DNP39 was more rapidly catabolized by PE cells than when it was present in low-density hapten-carrier conjugates. More of the high-density conjugates were associated with the PE cells than was the case with the other conjugates, and again about 50% of the radioactivity was membrane-bound. Thus, the degree of metabolism and persistence of ∗FISA in vitro was also related to the density of hapten on the carrier. [ABSTRACT FROM AUTHOR]

Antibody formation in rabbits against sheep erythrocytes (SRBC) was suppressed after injection of anti-SRBC IgG. Suppression did not occur, however, if the injected IgG had an allotypic marker to which the rabbits possessed circulating antibody. [ABSTRACT FROM AUTHOR]