摘要:

The nonobese diabetic (NOD) mouse develops diabetes spontaneously due to autoimmune destruction of the pancreatic islets with a higher incidence in the female than the male. Prolactin (PRL), a hormone whose role has been previously focused on reproduction and lactation has been demonstrated to influence immune responses. In this study, we investigated the effect of hypoprolactinemia and hyperprolactinemia on the incidence of diabetes in male and female NOD mice. Our hypoprolactinemia model was induced from the time of weaning (21 days of age) to 112 days of age by daily injections of 200μmlg of bromocriptine (CB-154). A hyperprolactinemic model was induced by a syngeneic anterior pituitary transplant (APT) to the kidney capsule at 35 days of age and maintained until 112 days of age. Additional experimental groups were also investigated. A group of males received pituitary transplants combined with daily subcutaneous injections of CB-154. A group of females treated with CB-154 was also given daily subcutaneous injections of 30μmlg of oPRL. An ovariectomized (OVX-Control) group of females was also established to serve as a second control for the OVX-APT group. Bromocriptine administration did not significantly decrase plasma PRL levels compared to controls (CTRL) while APT animals had plasma PRL levels that were significantly higher (P0.0001). From these results we conclude that PRL can modulate the incidence of diabetes in NOD mice and hyperprolactinemia augments the autoimmune response leading to the development of diabetes.

ISSN:0891-6934    

DOI:10.3109/08916939409007991

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Tumour necrosis factor (TNF) has been implicated in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). To investigate a possible role for TNF in IDDM we compared endogenous TNF production in two lines of non-obese diabetic (NOD) mice, NOD/Lt and NOD/WEHI, that have a high and low incidence of diabetes, respectively. Preliminary experiments had shown that the lower syngeneic mixed lymphocyte reaction (SMLR) in NOD/Lt mice could be corrected by TNF-α. Plasma TNF-αwas measured in 8 week-old female non-diabetic mice primed with 1000 units IV of murine interferon gamma (IFN-γ) followed after 3 hours by 5μmlg IV of lipopolysaccharide (LPS). Two hours later plasma was collected and TNF measured by ELISA. Plasma TNF in NOD/Lt mice was 9.2>2.4ng/ml (meanseM, n= 16) compared to 2.5>0.5 ng/ml in NOD/WEHI mice (n= 15) and 7.6>1.0ng/ml in BALB/c mice (n= 14). Time course studies demonstrated higher levels of both immunoreactive and bioactive TNF in NOD/Lt compared to NOD/WEHI mice up to 4 hours post-stimulation. A separate group of female NOD/Lt mice had IFN-γ/LPS-stimulated plasma TNF-αmeasured at 10 weeks and were followed to age 30 weeks. The mean stimulated plasma TNF-αlevel wsa consistently higher in those mice that developed diabetes compared to those that remained non-diabetic, the difference being significant when mice were 21 weeks of age. These results suggest that endogenous TNF-αproduction may be a trait marker of IDDM susceptibility.

ISSN:0891-6934    

DOI:10.3109/08916939409007992

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Anticardiolipin (ACL) antibodies and interleukin-6 (IL-6) in cerebrospinal fluid (CSF) may be involved in the mechanism of lupus patients with central nervous system (CNS) involvement. ACL antibodies of 3 isotypes and IL-6 were measured in paired CSF and serum samples from 14 lupus patients with CNS involvement, 5 lupus patients without CNS involvement and 7 patients with non-inflammatory neurological diseases. ACL antibodies, IgG and IgM isotypes, and IL-6 were significantly increased in CSF from lupus patients with CNS involvement as compared with other 2 groups of patients. Both ACL antibodies and IL-6 decreased after neurological activity subsided. These results suggest increased ACL antibodies and IL-6 in CSF are involved in immune responses within CNS in lupus patients. Quantitation of CSF ACL antibodies may be helpful in evaluating neurological activity of lupus patients with CNS involvement.

ISSN:0891-6934    

DOI:10.3109/08916939409007993

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Collagen-Induced Arthritis (CIA) is an experimentally induced and genetically controlled animal model of chronic joint inflammation. In rats, there are informative strain differences in susceptibility to CIA. DA rats (RTlavl) develop severe CIA after immunization with bovine (BII), chick (CII), or homologous rat (RII) type II collagens. In contrast, the MHC-congenic DA.IN(BN) and WF.IN(BN) rats (RTln) are relatively resistant to CIA and develop moderate CIA in response to immunization with CII but not BII or RII. We previously found that simultaneous infection with rat cytomegalovirus (RCMV) greatly exacerbates the severity of arthritis that develops in BII-immunized DA rats. To examine the mechanism of RCMV amplification of CIA, the effect of simultaneous infection with RCMV on arthritis and autoimmunity to type II collagen was determined in WF.1N and DA.IN rats after immunization with BII, CII and RII. RCMV increased the incidence of CIA and the level of autoimmunity to type II collagen (skin-testing and IgG antibody titer) selectively in DA.IN and WF.1N rats immunized with CII, but not in littermates immunized with BII, although the transient reversal of CD4+/CD8+mononuclear cell ratios in peripheral blood that is associated with RCMV infection occurred equally in both BII- and CII- immunized DA. IN rats. Likewise, RCMV infection moderately increased the levels of anti-RII autoimmunity and arthritis in DA rats sub-optimally immunized with RII but had no consistent effect on either anti-RII immunity or arthritis in RII-immunized DA.IN and WF.ln rats. The data show that RCMV augments arthritis only in rats that are gentically susceptible to CIA and that are appropriately immunized with a species of type II collagen that is arthritogenic for the MHC-haplotype being tested. Two possible mechanisms are suggested by these data: RCMV-associated increases in anti-RII autoimmunity in rats with CIA may result from amino acid sequence homologies between RCMV and type II collagen; alternatively, virus-induced pro-inflammatory cytokines may activate RH-reactive lymphocytes thereby potentiating autoimmunity and arthritis.

ISSN:0891-6934    

DOI:10.3109/08916939409007994

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

While attempting to evaluate CDS + and CD5 - anti-DNA-secreting plaque-forming cells (PFC) in patients with systemic lupus erythematosus (SLE), significant numbers of PFC against control sheep erythrocytes (ShE) treated with poly-L-lysine (PLL) but not further conjugated with single-stranded (ss) or double-stranded (ds) DNA were noted. Numbers of PFC obtained using PLL-ShE, ssDNA-ShE and dsDNA-ShE were not significantly different, all reactivity to DNA apparently being accounted for by binding of antibodies to PLL-treated ShE. Nevertheless, anti-PLL-PFC could be inhibited by soluble dsDNA included in the plaque assay. These findings might be explained by cationic anti-DNA antibodies binding non-specifically to anionic PLL. Control healthy subjects gave few PFC against PLL-ShE, ssDNA-ShE or dsDNA-ShE. Anti-PLL-PFC appeared to be related to disease activity, with higher numbers of both CD5 + and CD5 - PFC in patients with clinically active SLE.

ISSN:0891-6934    

DOI:10.3109/08916939409007995

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Several genomic polymorphisms at the insulin(INS)gene and its flanking regions were analyzed in 197 unrelated Caucasian patients affected by insulin-depenent diabetes (IDDM) and 159 ethnically matched, normal controls ascertained from the South-Eastern United States. We found that the frequency of homozygotes for the common variant at the insulin gene was significantly increased in the diabetic population (RR = 2.0, p<0.005). However, the polymorphisms in the 5′and 3′regions flanking theINSwere not significantly associated with IDDM. These results suggest that the IDDM susceptibility locus on chromosome 11p is located within the region extending from the 5′VNTR to the 3′end of theINSgene. We determined theHLA-DQB1genotypes by denaturing gradient gel electrophoresis (DGGE) and/or sequence-specific primers (SSP) techniques to assess the possible interactions betweenINSand HLA.DQB1*0302had the strongest predisposing effect on IDDM susceptibility (RR = 9.3) andDQB1*0602the strongest protective effect (RR = 0.02). However, a significant predisposing effect ofDQB1*020/could be demonstrated only after removal of the effects ofDQB1*0302andDQB1*0602.Analyses of the genotypes revealed that all genotypes containing 0602 were protective and that the heterozygous genotype 0201/0302 and homozygous genotype 0302/0302 confer the highest risk (RR = 20.9 and 12.9 respectively). However, heterozygous genotypes 0302/X (X excludes 0201,0302 and 0602) have a significantly lower predisposing risk. Similarly, there is heterogeneity in risk between predisposing 0201/0201 homozygous individuals and protective 0201/X individuals. When subjects were stratified by HLA genotypes, the relative risks conferred byINSdid not vary, thus suggesting that the susceptibility effects conferred by HLA andINSare additive rather than interactive.

ISSN:0891-6934    

DOI:10.3109/08916939409007996

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Many autoantibodies have been described in HIV-infected individuals. We have examined the incidence, associations and prognostic significance of anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA) and anti-glomerular basement membrane (GBM) antibodies in individuals with HIV infections.One hundred and five patients, with asymptomatic infections (n = 37), AIDS-related complex (n = 32) or AIDS (n = 36) were studied. Plasma from 24 of these (23%) were postive for ANA: most demonstrated speckled fluorescence (n = 21) and were of low titre (1 + in 18). ANCA were demonstrated by IIF in 18 individuals (17%) and all fluorescent patterns were seen; 6 of these plasma were also positive in the ELISAs for antibodies to proteinase 3, myeloperoxidase or elastase. Thirteen plasma were positive for ANCA in the neutrophil cytoplasm ELISA; 10 of these were also positive in the specific ELISAs. A total of 30 plasma bound to proteinase 3, myeloperoxidase or elastase in specific ELISAs, in 6 cases with 2 specificities. Finally, 18 plasma (17%) contained anti-GBM antibodies by ELISA, but none of 4 plasma tested in inhibition assays was specific. ANA, ANCA and anti-GBM antibodies were not uncommon in HIV-infected individuals but the presence of these antibodies was not associated with the clinical manifestations of the corresponding autoimmune diseases. In addition, there was no correlation between the demonstration of these antibodies and the immunological status of the individual (apart from a correlation between CD4 counts less than 400/ul with anti-GBM antibodies), the presence of an opportunistic infection, the development of malignancy or reduced survival.Some of these antibodies may arise from polyclonal activation, or be due to“sticky”serum since we have shown that the presence of anti-GBM antibodies correlated with the demonstration of ANCA by ELISA. These antibodies are not more common in hypergammaglobulinemic plasma but some may be due to heat-treatment of the plasma.The clinician caring for HIV-infected individuals needs to be aware of these“false-positive”antibody results.

ISSN:0891-6934    

DOI:10.3109/08916939409007997

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We have determined the incidence of autoimmune thyroid disorders in patients with Addison's disease. The material comprised 212 patients, 128 women and 84 men, aged 9-74 years. In 58 patients tuberculosis and in six patients other adrenal disorders were diagnosed. In the remaining 148 patients the auto-immune mechanism was the most probable cause of adrenocrotical insufficiency. In order to evaluate the thyroid abnormalities seen in patients with Addison's disease the T3, T4(RIA), TSH (ELISA) and anti-thyroid autoantibodies were determined apart from routine clinical examination. Antimicrosomal, anti-thyroglobulin and anti-thyroperoxidase antibodies were measured in 91, 188 and 81 cases respectively. Thyrotoxicosis was diagnosed in 17 and primary hypothyroidism in 18 cases. Moreover, eight patients had evidence of subclinical hypothyroidism. The anti-thyroglobulin antibodies with titer ranging from 1 : 80 to 1 : 10 000 were detected in 66 patients, whereas antimicrosomal antibodies were found in 51 patients at a titer ranging from 1 : 80 to 1 : 9720. Autoantibodies against thyroid peroxidase were found in sera of 67 patients, with titer ranging from 1 : 2000 to 1 : 25 6000.

ISSN:0891-6934    

DOI:10.3109/08916939409007998

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Bullous pemphigoid (BP) is an autoimmune blistering disease characterized in part by the presence of tissue-bound and circulating antibodies (mostly of IgG) to the basement membrane zone (BMZ). We previously reported that IgG subclasses of BP antibodies were IgG1, IgG2and IgG4, and that only BP IgG1fixed complements. In this study, we examined whether BP IgG sub-classes bound to the same epitope of BP antigen or a different epitope. In an inhibition immunofluorescence studies, the complement fixing capability of IgG1was inhibited by the pretreatment with IgG4and partially inhibited by IgG2. On immunoblot analysis, IgG1and IgG4were bound to the same MW of BP antigen. In enzyme-linked immunosorbent assay (ELISA), the binding capability of IgG subclass fractions from patients with BP to synthetic peptide PI-2, exceeding normal IgG subclass fractions was seen in five IgG1, one IgG2and two IgG4, from eight BP patients. The binding capability of IgG subclass fractions from the patients with BP to Pl-1, exceeding the normal IgG fractions was seen in two IgG1, three IgG2and one IgG4from ten BP patients. On inhibition ELISA, the binding activity to Pl-2 of IgG4was partially inhibited by the pretreatment of IgG1and IgG2. These findings suggest that BP IgG1, IgG2and IgG4could bind to the same epitope though considerable variation occurred between patients.

ISSN:0891-6934    

DOI:10.3109/08916939409007999

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939409008000

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor