摘要:

Interactions between the immune and endocrine systems may have an important role in ovarian tum-origenesis. Neonatal thymectomy at 3 days of age (Tx-3) in (C3H/HeMs x 129/J) F, (C31) female mice results in an autoimmune ovarian dysgenesis then subsequent tumor formation. At 3 months of age the histology of the ovaries showed that approximately 60% of the Tx-3 mice (Tx-3 DO) had completely lost their oocytes and follicles so that a preponderance of interstitial-like cells remained. The remainder of the Tx-3 mice had atypical ovaries (Tx-3 AO). The vaginal cytology showed that both groups of Tx-3 mice became acyclic at an early age compared to the intact mice. Around 12 months of age, a high percentage of the dysgenic ovaries developed trabecular tumors. Plasma protein-related indicators of systemic inflammatory responses showed little change during the course of the autoimmune oophoritis or ovarian tumorigenesis. Levels of estradioL17β(E2) and testosterone (T) did not vary in the Tx-3 mice compared to those of the intact mice through 21 months of age but progesterone levels were lower during the exacerbation of the autoimmune oophoritis and tumor development. By 24 months of age levels of P increased while E, decreased. Apparently, the premature reproductive failure in these mice at a young-adult stage results from the early loss of the oocytes by the localized autoimmune insult to the ovaries. The autoimmune oophoritis may then be the primary trigger for the subsequent ovarian tumor formation and the tumors succeed in association with the altered hormonal milieu.

ISSN:0891-6934    

DOI:10.3109/08916939008993365

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Cell-mediated immunity (CMI) to myelin components has been implicated in Multiple Sclerosis (MS) pathogenesis: two targets were suggested, Myelin Basic Protein with controversial results and, more recently, gangliosides. In order to investigate their possible involvement, we have performed Leukocyte Migration inhibition (LMI) tests in the presence of human brain gangliosides. Thirty nine MS patients (twenty four bcing“definite”, according to McDonald and Halliday's classification), twenty nine patients with Other Neurological Diseases (OND), thirty six patients with Inflammatory diseases (ID) and forty healthy controls were tested. MS patients wcrc divided into two groups, depending on the clinical stage of the disease.The mean migration inhibiton percentage of the MS-attack group was found to be significantly different from the four others (p<0.01) (24.4±16.2 versus 10.9±8.5 in MS without attack, 4.4±12.9 in OND. 3.9±13.9 in ID and 11.1±12.1 in healthy subjects). LMI to gangliosides is therefore significantly increased during the attack stage in MS. These results support the notion of a Delayed Type Hypersensitiv-ity to these glycolipids during the active stage of the disease.

ISSN:0891-6934    

DOI:10.3109/08916939008993366

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Susceptibility to experimental autoimrnune thyroiditis (EAT) in mice is linked to the I-A subregion of the major histocompatibility complex (MHC). The present study was undertaken to assess the effectiveness of anti-I-Akmonoclonal antibody (MAb) 10–2.16 in preventing or arresting the development of EAT. Spleen cells from CBA/J or (CBA/J x Balb/c) Fl mice given 10–2.16 prior to sensitization with mouse thyro-globulin (MTg) and adjuvant could not transfer EAT to normal recipients, and cells from these mice did not proliferatein vitroto MTg. Donor CBA/J mice given 10–2.16 before immunization and recipients of cells from such mice produced little MTg-specific lgGl or IgG2b antibody but did produce nearly as much IgG2a as controls. The effects ofin vivotreatment with 10–2. 16 appear to be due to elimination of Ia + cells rather than to modulation of Ia or induction of suppressor T cells. When 10–2.16 was added toin vitrocultures it also prevented the proliferation and activation of sensitized CBA/J or Fl effector cell precursors. Other mAb specific for MHC class II gene products, but not associated with disease susceptibility, expressed by CBA/J (I-Ek) or FI (I-Ad) mice (14-4-4S or MK-D6 respectively), also preventedin vivosensitization, but did not blockin vitroactivation. Anti-I-Akwas also effective in preventing EAT if multiple injections of mAb were given to recipients of sensitized EAT effector cells. These studies indicate that Ia + cells are required for initial sensitization and activation of EAT effector cells and also contribute to the development of severe histopathologic lesions in the thyroid during the final effector stage of EAT.

ISSN:0891-6934    

DOI:10.3109/08916939008993367

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The relationship between spectrotype and IgG subclass of autoantibodies to thyroglobulin (Tg) and thyroid peroxidase (TPO) has been investigated using sera from Hashimoto and Graves' patients. Isoelectric focussing (IEF) was carried out in gels over the range pI 3.5–9.5 followed by transblotting to nitrocellulose and probing the filters using125I-labelled TPO and Tg. As has been shown previously for Tg antibodies, TPO antibody focussed over different pl values in different patients but the spectrotypes for individuals were constant over 2–5 years. Further, the pI values for TPO and Tg autoantibodies appeared to be related to IgG subclass, for example IgGl Tg antibodies tended to focus nearer the cathode (PI 8.0–9.5) than IgG4 antibodies (PI 6.5–8.5) while antibodies of subclasses IgGl +2 + 4 produced spectrotypes covering a broad pI range (5.7–9.5). Consequently, it seems likely that the characteristic spectrotypes described by others for Tg autoantibodies. and those we now report for TPO antibodies, reflect the IgG subclass“fingerprints”which we suggest may be a measure of the ability of an individual to respond to different epitopes on these two thyroid antigens.

ISSN:0891-6934    

DOI:10.3109/08916939008993368

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Only one out of 57A-/ A-rabbits immunized with rat or guinea-pig myelin developed clinical signs suggestive of EAE. On the contrary, clinical signs of acute or chronic EAE were found in two thirds of the 102A + /A+andA + /A -rabbits immunized in the same way. About one third of the diseased animals had reversible acute EAE, another third died paralysed and the last third developed chronic progressive or relapsing EAE. Incidence and severity of EAE symptoms were positively correlated with age and no significant difference was observed between males and females.Cellular and humoral anti-myelin responses were stronger in A+than in A−rabbits. Anti-A antibodies, on the contrary, were only detected in A−rabbits. The A+rabbits did not make Anti-A at any time. Anti-A antibodies increased early, in A−rabbits, after immunization with myelin (11–30 days) and were later replaced by a low, but specific, anti-myelin response (60–90 days).The gene responsible for the susceptibility to EAE is autosomal and dominant over resistance. This gene must be closely linked to theAlocus or might be theAgene itself. The low susceptibility of A−rabbits to the disease could be, in this last case, a consequence of the competition between the early anti-A and the normal anti-myelin immune responses, both induced by the injection of myelin.

ISSN:0891-6934    

DOI:10.3109/08916939008993369

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

MRL/lpr mouse-derived interleukin-3 (IL-3)-mimetic monoclonal antibodies were examined for their binding sites. One of these five antibodies (B10, F8, F9, F12, H 11), F9 interacted with the IL-3 receptor, as if it were an anti-idiotypic antibody; the IL-3-mimetic activity of F9 was blocked by a neutralizing rat monoclonal anti-IL-3 antibody. IL-3 mRNA was not detected in hybridoma F9, as analyzed by the SI protection assay, Thus, the activity neutralized by the rat antibody is of the F9 antibody itself but not the IL-3 type. Such blocking was not observed with the IL-3-mimetic activity of the other MRL/lpr-derived monoclonal antibodies. On the other hand, the binding of all these monoclonal antibodies to IL-3-depen-dent cells was inhibited by each other andvice versa, as analyzed by two-color flow cytometry. This indicates that the binding sites of the five monoclonal antibodies are located so close to each other that the binding of one would interfere with the binding of any one of the others (since the binding experiment was done on ice, it is unlikely that the inhibition is due to down-modulation of the receptors). Taken together the results obtained by the enzyme digestion study, we discussed that all five IL-3-mimetic monoclonal antibodies are directed to the IL-3 receptor, but only F9 binds to the portion directly responsible for the binding of IL-3 and the other antibodies (B10, F8, F12, H11) bind to different portions, respectively, which are adjacent or overlapping to the binding site of F9.

ISSN:0891-6934    

DOI:10.3109/08916939008993370

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The characteristics of autoantibodies reactive with bovine (b) TSH were examined in the sera of six patients with Graves' disease selected on the basis of highly negative values in the TSH receptor assay. Test sera were incubated with other125I-labeled pituitary glycoprotein hormones and their isolated subunits (αandβ) [human (h) TSH, bTSH, porcine (p) TSH. pFSH, bFSH, bLH and equine (e) chorionic gonadotropin (CG)] (purity was confirmed by gel-filtration on Sephadex G-100 and SDS-PAGE), and the antibody bound fraction was precipitated by the addition of anti-human gamma-globulin (goat). Almost all sera showed detectable binding to bTSH, pTSH, pFSH, pTSH-α, bFSH-α, bLH-α, but not to hTSH, hTSH-α, hTSH-β, hFSH, hLH. hCG, pTSH-β, bLH-β, eCG-α. Exceptions were very low binding to bLH-βby one serum and to pTSH-βby two sera. The level of binding (B/T%) of the patients' sera to pTSH-α, bFSH-α, and bLH-α, was 3.0–17.7%, 2.6–45.3% and 2.2–39.0%. respectively; that of sera from normal healthy adults was 1.9±0.3%, 0.8±0.2% and 0.9±0.2% (mean±SD), respectively. These results indicate that the TSH antibodies recognize mainly an epitope in theαsubunit of bovine and procine pituitary glycoprotein hormones (TSH, FSH, LH).

ISSN:0891-6934    

DOI:10.3109/08916939008993371

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

Antibodies to islet antigens are useful markers of the pathological process that results in destruction of beta cells in type I diabetes. The targets of these antibodies, however, are not well characterized and their role in the pathological process remains to be established. To better understand the range of antigens recognized by autoantibodies in type I diabetes mellitus, we carried out immunoblotting on protein extracts from human islets and rat insulinomas. Using this approach high titer antibodies specific for islet antigens were detected in 20/28 sera from recent onset type I diabetics and were infrequent (4/28) in sera from age-matched controls. Sera from diabetics reacted with multiple antigens at titers from 1/100–1/4000 while control sera usually bound a single band at lower dilutions. Although antigens of M, 52, 84, 116 and 150 kilodalton were recognized most frequently, no antigen was bound by more than 50% of diabetic sera. Some of these antigens enriched in the membrane fraction while others were not. The data demonstrate that a heterogeneous group of islet antigens is recognized by autoantibodies present at the onset of type I diabetes when islet destruction is complete. These findings contrast previous reports using immunoprecipi-tation with undiluted sera that principally identify a 64 kDa islet antigen. Thus, the immunoblot technique detects a different set of reactivities than previously identified by immunoprecipitation. The pattern of multiple reactivities with both surface and cytoplasmic antigens suggest that many autoantibodies may be generated by beta cell destruction and some of these may amplify the ongoing immune response.

ISSN:0891-6934    

DOI:10.3109/08916939008993372

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The expression of surface markers of T cell subsets in the peripheral blood of 30 Graves' disease patients was investigated pre and post therapy using two colour flow cytometry. Reduced numbers of total, helper/inducer and suppressor/cytotoxic T cells were found in untreated Graves' patients. Numbers of suppressor-inducer T cells which are associated with maintaining the normal immune response, did not differ significantly between untreated Graves' patients and controls. Although 8 weeks' Carbimazole therapy reversed the changes in total, helper/inducer and suppressor/cytotoxic T cells, PTU or131I therapy did not. While suppressor-inducer T cell numbers were not affected by Carbimazole or PTU therapy,l31I treatment caused a decrease in suppressor-inducer T cell numbers.

ISSN:0891-6934    

DOI:10.3109/08916939008993373

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor

摘要:

The subclass pattern of red cell bound IgG autoantibody was studied in 304 patients on 426 occasions. Subclass interrelationships with time, other cell bound immunoglobulins (IgM, IgA), amount of bound IgG and serum haptoglobin levels were investigated using population proportions; because of the multiple statistical tests, P<0.01 was required for significance.IgGl was most common, being found in 98% of cases and as the sole subclass in 64%; multiple subclasses occurred in 34.5%. The IgG subclass pattern possibly changed with time (P2 and800 and<400 molecules IgG per red cell respectively). Multiple subclasses (P0.01), but not IgG3, were possibly associated with low haptoglobin levels; significance was reached, however, if the multiple immunoglobulin effect was ignored. IgG subclass interrelationships are clearly complex and require strictly defined populations for their study.

ISSN:0891-6934    

DOI:10.3109/08916939008993374

出版商:Taylor&Francis    

年代:1990

数据来源: Taylor