摘要:

Diabetes incidence in BB rats is 60-80% and our aim was to investigate whether it is possible to characterize those rats destined to develop diabetes. While the genetic background as well as the environmental factors affecting BB-rat littermates are very similar, body weight reflects some existing variance. The study involved 151 BB rats, and the body weight of each animal was measured daily from birth. Thirty-four animals became diabetic before 100 days of age, and their body weight showed a 5-10% increase compared to the non-diabetic animals for each day of life from day 1 to day 45 (p values 0.0001 to 0.05). This increased body weight in individuals destined for diabetes was seen in both sexes. When investigating whether juvenile body weight has any predictive value, we found that the incidence of diabetes at 100 days of age increased from 22.5% to 46.7% (p<0.01) when the heaviest animals in each litter were selected, Insulin content in pancreas was examined at day 10 and 20, and was found to be significantly reduced in the BB rats with highest body weight compared with rest of the litter (p = 0.02 and p = 0.0005, respectively). The insulin concentration in peripheral blood was significantly reduced in the BB rats with highest body weight at 20 days of age (p = 0.002). When early and late diabetic BB rats were compared at time of diagnosis regarding blood glucose, degree of insulitis and number of small and large islets, no significant differences were found between the groups.

ISSN:0891-6934    

DOI:10.3109/08916939409010666

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Polyclonal B cell activation and the production of antibodies against a variety of autoantigens are features of systemic lupus erythematosus (SLE). Autoreactive B cells are found in healthy individuals but their numbers are probably regulated by cell death, after a few days, in the absence of proliferative stimuli. The process which achieves this regulation is known as apoptosis or programmed cell death. It has been postulated that in SLE patients dysfunction of apoptosis could result in the inappropriate longevity of autoreactive B cells, allowing autoantibody levels to reach pathogenic thresholds. This hypothesis has arisen as a result of studies revealing links between autoimmunity and two molecules which influence apoptosis. These are bcl-2 which enhances cell survival by inhibiting or delaying apoptosis and Fas, a cell surface molecule involved in the induction of apoptosis. Transgenic mice over expressing bcl-2 in their B cells showed polyclonal B cell expansion and their B cells showed extended survivialin vitro.After a few months these mice developed an autoimmune syndrome resembling SLE. Mice that carry thelprdisorder have defects in theFasgene. These mice, which do not express functional Fas molecules, suffer from an SLE-like autoimmune syndrome. Thus inappropriate expression of both bcl-2 and Fas can result in SLE-like autoimmune disease in mice. Research is now in progress to ascertain whether quantitative or functional abnormalities in these molecules exist in human SLE patients and contribute to the pathogenesis of the disease in some or all cases.

ISSN:0891-6934    

DOI:10.3109/08916939409010667

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

To investigate the mechanisms underlying the increased number of mast cells in autoimmune mice, the proliferative response of autoimmune mast cells to cytokines was examined. Bone marrow cells from autoimmune NZB mice produced scarcely any bone marrow derived mast cells (BMMCs) in the presence of interleukin 3 (IL-3), but were able to generate BMMCs when cultured with pokeweed mitogen-stimulated spleen cell conditioned medium (PWM-SCM). In contrast, NZB BMMCs showed very little proliferation in the presence of PWM-SCM, but proliferated strongly when cultured with stem cell factor (SCF). Non-autoimmune NZW BMMCs snowed a strong proliferative response to both IL-3 and PWM-SCM. but proliferated weakly in culture with SCF. Autoimmune NZB x NZW F, (B/W) BMMCs shared the proliferative activities of both NZB and NZW BMMCs, showing strong proliferation in response to IL-3, PWM-SCM and SCF. AH strains (including other non-autoimmune strains) except for NZW demonstrated synergism between PWM-SCM and SCF. This study suggests that the strong proliferative response of autoimmune mast cells to SCF plays a major role in, and that other cytokines are partially responsible for, increasing the number of mast cells in autoimmune mice. These mechanisms are discussed in relation to both constitutive and inducible hematopoiesis.

ISSN:0891-6934    

DOI:10.3109/08916939409010668

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We prepared a series of overlapping peptides (29 in total, 20 amino acids each) containing the sequence of the entire extracellular domain of the human TSH receptor. Three peptides (181-200, 376-394, and EC3 (629-639)) bound IgG from patients with Graves' disease in an enzyme linked immunoassay. Peptide 181-200 bound IgG from 9 of 10, EC3 from 8 of 10, and 376-394 from 6 of 10 patients respectively, compared to 0 of 9 controls. We affinity purified TSHr auto-antibodies from four Graves' patients using the three above noted peptides bound to epoxy-activated sepharose. Thyroid stimulating activity was enriched in the bound fraction from at least two of the three peptide affinity columns in each of the four patients, although the pattern of affinity enrichment differed between patients. One patient was found to possess a combination of stimulatory and inhibitory TSHr antibodies and, after affinity purification, the anti-3 76-394 and anti-EC3 fractions were enriched in stimulatory activity, suggesting that those regions of the receptor were epitopes for stimulatory antibodies. However, affinity purification against peptide 181-200 produced an IgG preparation that was not stimulatory, but was a potent thyroid inhibitor. Thus, we have not only partially purified TSHr auto-antibodies, but also successfully separated stimulatory and inhibitory antibodies from a single patient using combination TSHr peptide affinity.

ISSN:0891-6934    

DOI:10.3109/08916939409010669

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

We have compared the frequencies of T cells expressing each of four different T cell receptor (TCR) Vβsegements in lamina propria and peripheral blood lymphocytes of 12 Crohn's disease (CD), six ulcerative colitis (UC), and 10 control patients in an attempt to identify disease-specific changes. The frequencies of CD4 + and CD8 + cells reacting with each of four fluoresccinated TCR-specific monoclonal antibodies directed against Vβ5, Vβ6.7a, Vβ8, and Vβ12 were determined by flow cytometry. There was no difference among the groups in the average frequency of any single Vβsegment in either the CD4 + or CD8 + subpopulations. However, when the sum of the differences in VP frequencies (Δscore) between peripheral blood lymphocytes (PBL) and lamina propria lymphocytes (LPL) were determined for each individual, significant differences were observed between the CD4 + and CD8 + populations and among the patient groups. In all three patient groups, there were significant individual differences between LPL and PBL in the frequencies of CD8 + and CD4 + cells reacting with the four Vβ-specific mAb. In Controls and UC, this difference was, on average, two-fold greater in CD8 + cells than in CD4 +. In CD, however, this difference was, on average, the same for CD8 + and CD4 + cells. These observations suggest that (1) the human colonic LPL TCR repertoire is normally different from that of PBL, especially in the CD8 + population and (2) there is an alteration in the LPL TCR repertoire in CD which is not observed in Controls or UC.

ISSN:0891-6934    

DOI:10.3109/08916939409010670

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Systemic sclerosis (SSc) is an autoimmune connective tissue disease of unknown etiology in which aberrant fibroblast function results in fibrosis of the skin and internal organs. A distinguishing feature of dermal fibroblasts cultured from SSc lesions is that they produce constitutively, i.e., without exogenous stimulation, as much as 30-fold more interleukin-6 (IL-6) than do normal fibroblasts. The present study indicates that the mechanism of constitutive IL-6 secretion involves the accumulation of IL-6 mRNA in affected SSc fibroblasts, mediated by the constitutive binding of nuclear factors to the IL-6 promoter. DNA-protein complexes formed using nuclear extracts of constitutively expressing cells are distinct from those using extracts of normal cells, with or without exogenous stimulation of IL-6; thus, the mechanisms which regulate constitutive and inducible IL-6 gene expression are apparently distinct. The data also demonstrate that dermal fibroblasts respond very rapidly to IL-6 by increasing expression of the IL-6 gene, thus suggesting a mechanism for the establishment and/or persistence of constitutive expression. The constitutive secretion of IL-6 may play an important role in the perpetuation of the local immune dysregulation and fibroblast activation in the SSc lesion.

ISSN:0891-6934    

DOI:10.3109/08916939409010671

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Several lines of evidence support an etiological role of iodine for the initiation and perpetuation of autoimmune thyroid disease. However, varying relapse rates after increased iodine supplementation have been reported for Graves' disease. Furthermore the effects of iodine on the intensity of human autoimmune thyroiditis have previously only been investigated by indirect parameters and actions of iodine on thyroid function and a possible enhancement of the intrathyroidal autoimmune process in Graves' disease are difficult to separate in previous studies. Moreover lymphocytic thyroiditis in animal models has always been induced by considerably higher iodine doses as those used in in vivo studies. Therefore we investigated the effect of low and high iodine concentrations on the intensity of the intrathyroidal autoimmune process in Graves' disease.The intensity of intrathyroidal infiltration by lymphocytes, memory T cells, plasma cells and antigen presenting cells was determined by quantitative immunohistologic methods in 38 Graves' disease patients. 12 patients received additional preoperative iodine (group II) and 26 were treated with thiourelene antithyroid drugs only (group I). Urinary and intrathyroidal iodine concentrations were determined by a modified cer arsenit method in both groups.Application of high iodine doses in group II induced a significant increase of kappa and lambda positive plasma cells and interdigitating reticulum cells. This was not observed for activated T cells. There was no correlation between the extent of intrathyroidal infiltration by activated T cells, plasma cells and antigen presenting cells, and intrathyoidal or urinary iodine or intrathyoidal iodine concentrations in group I.High iodine doses therefore aggravate the intrathyoidal autoimmune process in Graves' disease by inducing an accumulation of immunocompetent cells involved in antigen presentation and antibody production. Howerver variations of iodine concentrations within the range encountered during antithyroid treatment do not seem to influence the number of intrathyoidal immunocompetent cells in established Graves' disease.

ISSN:0891-6934    

DOI:10.3109/08916939409010672

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Sera from myasthenia gravis (MG) patients with thymoma were examined in Western blot for the presence of antibodies to proteins in the sarcoplasmic reticulum (SR) of cardiac muscle. Fourteen of 30 MG thymoma sera had IgG antibodies to a protein with the same electrophoretic mobility as cardiac muscle ryanodine receptor (RyR). Anti-cardiac RyR antibodies were not detected in any of the 45 sera from MG patients without thymoma. The same 14 MG thymoma sera, but none of the others, bound to RyR from skeletal muscle as well. Neutralization experiments showed that the anti-RyR antibodies in MG patient cross-reacted with cardiac and skeletal muscle RyR. Since skeletal and cardiac muscle RyRs are antigenically different, our findings may indicate that autoantibodies to RyR in MG originate by sensitization to a peptide shared by cardiac and skeletal muscle RyR, rather than to the complete native RyR.

ISSN:0891-6934    

DOI:10.3109/08916939409010673

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

摘要:

Synovial fluid aspirated from 34 patients with symptomatic rheumatoid arthritis (RA) was evaluated for the presence of human cytomegalovirus (CMV) genomic material using polymerase chain reaction (PCR), and for levels of interleukin 8 (IL-8) and IL-6 using enzyme-linked immunoadsorbence assay. IL-8 and IL-6 levels were significantly higher in CMV DNA-positive RA patients than CMV DNA-negative RA patients and at least 10-fold higher than in both corresponding control groups of patients with osteoarthritis (OA). These findings suggest an association between elevated IL-8 and IL-6 levels and the presence of the CMV genome in RA patients.

ISSN:0891-6934    

DOI:10.3109/08916939409010674

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor

ISSN:0891-6934    

DOI:10.3109/08916939409010675

出版商:Taylor&Francis    

年代:1994

数据来源: Taylor