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PubMed1999

Early and late results after thymectomy in myasthenia gravis: a retrospective study [correction of analysis].

BACKGROUND: This study aims to evaluate the early and late outcome of patients treated by surgery for myasthenia gravis and the diagnostic value of the Besinger Score, which is based on a correlation of severity of symptoms with specific antibodies to acetylcholine receptors, in the follow-up investigation after surgical therapy. METHODS: Between June 1984 and April 1992 thoracotomy was performed in 51 myasthenia gravis cases at our department. The retrospective analysis considered patients with (n = 13) or without thymoma (n = 38). The Besinger score was used to describe the severity of disease preoperatively and up to 5 years postoperatively. RESULTS: The Besinger score fell continually post surgery. Changes in relative serum concentrations of antibodies were similar to the Besinger score. Five years after thymectomy complete remission was diagnosed in 40% of the patients. The required dosage of pyridostigmine had fallen by two thirds after 5 years. Patients with follicular hyperplasia had significantly higher remission rates than those with thymoma. CONCLUSIONS: Surgery for myasthenia gravis is successful. The Besinger score well quantifies the severity of the disease.

Adolescent↗
PubMedDate not supplied

Temporary, but essential requirement of CD8+ T cells early in the pathogenesis of diabetes in BB rats as revealed by thymectomy and CD8 depletion.

Autoimmunity-prone BB rats demonstrate a T lymphocytopenia and abnormal T cell subset distribution. To test whether the life span of all T cells or only of certain subsets is reduced in BB rats, we thymectomised 8-week-old BB and PVG rats and subsequently assessed size and composition of the T cell population over a 6-week-period. In both strains, thymectomy (Tx) was followed by a decrease in peripheral T cell numbers, which was proportionally larger in BB rats. The decline of the Thy-1+ recent thymic migrant (RTM) T cell phenotype was similar in both strains. BB rats showed a rapid preferential loss of CD8+ and CD45RC+ T cells, whereas the relative loss of RT6+ T cells was proportional to that of all T cells and not significantly different from that in PVG rats. Tx at 8-week did not prevent diabetes. Tx of 4-week-old BB rats revealed essentially the same changes in peripheral T cell subset distribution as in 8-week-old animals. However, Tx at week 4 did prevent diabetes. Since this raised the possibility of a temporary requirement of CD8+ T cells for the development of diabetes, we performed CD8 depletions during different pre-diabetic intervals. We found that CD8 depletion from 4 to 8 and 4 to 14 weeks, but not from 8 to 14 weeks of age prevented diabetes. We conclude that the protective effect of early adult Tx is, at least in part, due to the rapid loss of CD8+ T cells, and that these cells are only required between 4 and 8 weeks of age for diabetes to develop in BB rats.

Aging↗
PubMed1996

Aod2, the locus controlling development of atrophy in neonatal thymectomy-induced autoimmune ovarian dysgenesis, co-localizes with Il2, Fgfb, and Idd3.

In genetically susceptible strains of mice, such as A/J and (C57BL/6J x A/J)F1 hybrids, neonatal thymectomy-induced autoimmune ovarian dysgenesis (AOD) is characterized by the development of antiovarian autoantibodies, oophoritis, and atrophy. Temporally, atrophy may be observed during and after the regression of inflammatory infiltrates from the ovary. Histologically, lesions appear as areas devoid of ovarian follicles in all stages of development that have been replaced by luteinized interstitial cells. We report here the mapping of Aod2, the locus that controls this phenotype, to mouse chromosomes 3 within a region encoding Il2 and Fgfb. Most significant, however, is the co-localization of Aod2 to Idd3, a susceptibility gene that plays a role in autoimmune insulin-dependent type 1 diabetes mellitus in the nonobese diabetic mouse.

Animals↗
PubMed1986

Changes in plasma vasopressin concentration in association with coronary artery surgery or thymectomy.

Plasma vasopressin concentrations in 14 patients undergoing coronary artery surgery were compared with those in eight patients undergoing thymectomy. Vasopressin concentrations increased similarly in both groups on sternotomy. A second, and more marked increase was noted in the patients requiring cardiopulmonary bypass. Haemodynamic stimuli could be responsible in both groups and might explain both the similarities and the differences between the groups.

Adult↗
PubMed2002

Differential effect of neonatal thymectomy on systemic and organ-specific autoimmune disease.

Thymectomy on day 3 after birth (d3tx) depletes CD4+CD25+ regulatory T cells leading to multiple independent organ-specific autoimmune diseases. However, systemic autoimmune disease such as systemic lupus erythematosus has not been reported in d3tx mice. Herein, we investigate the effect of d3tx on spontaneous autoantibody response and immune complex glomerulonephritis (GN) in the lupus-prone (SWR x NZB)F1 (SNF1) mice. The d3tx SNF1 mice developed accelerated antibody responses to double-stranded DNA and DNA-histone complexes, and an increased frequency of activated CD4+ T cells. Unexpectedly, the renal histopathology and mortality from GN were significantly ameliorated in d3tx SNF1 mice, which concomitantly exhibited a Th2-biased antibody response. By 16 weeks, the d3tx mice had higher levels of total and autoantigen-specific IgG1, and at 12 months, the autoantigen-specific IgG2a was significantly below that of the sham thymectomized mice. These differences corresponded with reduction in total and autoantigen-specific IgG2a in the renal eluates of the d3tx mice. In addition, while all the mice had immune complex deposition in the mesangium and peripheral capillary loops of the glomeruli, IgG2a and C3 deposits restricted to the mesangial regions alone were more frequent in d3tx mice. D3tx SNF1 mice, protected from lupus-like GN, developed organ-specific autoimmune responses and diseases including prostatitis, orchitis and oophoritis, and antibodies to prostate, cardiac and skeletal muscle antigens. Therefore, d3tx paradoxically protects SNF1 mice from genetically prone lupus-like GN, yet promotes de novo organ-specific autoimmunity.

Animals↗
PubMed1975

The effect of neonatal thymectomy on Tamiami virus-induced central nervous system disease.

Tamiami virus, a member of the arenavirus group, produces an acute CNS disease in suckling mice manifested primarily by cerebellar ataxia, paralysis, convulsions, and death. Animals that survive are left with an asymptomatic cerebellar heterotopia. Neonatal thymectomy prevents both acute CNS disease and the resultant cerebellar heterotopia despite equivalent titers of virus and concentrations of viral antigen in the brains of both thymectomized and nonthymectomized infected mice. Inflammatory CNS disease and cerebellar germinal cell necrosis do not develop in thymectomized mice examined more than three months after infection. Viremia and complement-fixing antibody occur in both groups of mice with slightly higher antibody titers in nonthymectomized mice. Tamiami virus-induced cerebellar heterotopia appears to be immunologically-mediated, but the immunopathologic cerebellar lesion differs from the frank necrosis of the brain produced by both Tacaribe and LCM virus in newborn mice.

Animals↗
PubMed1980

Tolerance to allogeneic and to xenogeneic heart grafts provided by thymectomy of adult mice combined with donor cell and cyclophosphamide inoculation.

A new method of induction of tolerance to allogeneic and to xenogeneic cells is presented. It includes thymectomy of adult mice followed 1 month later by the injection of 1 X 10(8) spleen cells i.v. and i.p. administration of 200 mg of cyclophosphamide per kg 1 day after cells. This method induced prolonged survival of heterotopically transplanted neonatal C57BL/6 murine heart grafts (more than 8 months) and of August rat heart grafts (more than 2 months) in CBA mice. Tolerance to allo- or xenoantigens was formed at the cell level. Experimental animals did not produce allo- or xenohemagglutinins after graft implantation. Spleen cells of mice with surviving C57BL/6 heart grafts did not respond to C57BL/6 cells in mixed lymphocyte culture (MLC) reaction. Lymphoid cell chimerism was not observed in animals tolerant to alloantigens.

Animals↗
PubMed1992

Skin xenograft rejection in Xenopus--immunohistology and effect of thymectomy.

Immunohistology, using the T-lineage-specific monoclonal antibody XT-1 and an anti-IgM mAb, illustrates differences in the cellular basis of skin allograft and xenograft destruction displayed by control froglets (X. laevis). Thus T cells predominate within allografts, whereas B-lineage cells accumulate under xenografts (from X. tropicalis). The possibility that T cells do not play a central role in mediating xenograft rejection is consistent with the finding that early thymectomy (at 7 days) has minimal effect on rejection end points of X. tropicalis transplants. However, rejection of skin from a "phylogenetically less distant" xenogeneic species (X. borealis) is shown here to be impaired in early thymectomized X. laevis. Differences in the extent to which the thymus has been shown to influence skin xenograft rejection in Xenopus are discussed.

Animals↗
PubMed1999

The effect of thymectomy on tolerance induction and cardiac allograft vasculopathy in a miniature swine heart/kidney transplantation model.

BACKGROUND: We have previously demonstrated that MHC class I disparate hearts transplanted into miniature swine treated with a short course of cyclosporine developed florid cardiac allograft vasculopathy (CAV) and were rejected within 55 days. However, when a donor-specific kidney is cotransplanted with the heart allograft, recipients become tolerant to donor antigen and accept both allografts long-term without the development of CAV. In the present study, we have investigated the role of the host thymus in the induction of tolerance and prevention of CAV in heart/kidney recipients. METHODS: Total thymectomies were performed in six animals (postoperative day [POD]-21), which on day 0 received either an isolated MHC class I disparate heart allograft (n=3) or combined class I disparate heart and kidney allografts (n=3), followed in both cases by a 12-day course of cyclosporine (POD 0-11). Graft survival and the development of CAV in these thymectomized recipients were compared to the same parameters in non-thymectomized, cyclosporine-treated recipients bearing either class I disparate heart allografts (n=5) or heart and kidney allografts (n=4). RESULTS: In the group of animals bearing isolated class I disparate heart allografts, the thymectomized recipients rejected their allografts earlier (POD 8, 22, 27) than the non-thymectomized recipients (POD 33,35,45,47,55). The donor hearts in both the thymectomized and non-thymectomized animals developed florid CAV. In the group of animals bearing combined class I disparate heart and kidney allografts, the nonthymectomized recipients accepted both donor organs long term with no evidence of CAV. In contrast, none of the thymectomized heart/kidney recipients survived >100 days, and they all developed the intimal proliferation of CAV. CONCLUSION: Thymic-dependent mechanisms are necessary for the induction of acquired tolerance and prevention of CAV in porcine heart/kidney recipients.

Animals↗
PubMed1978

Effect of bursectomy and thymectomy on Pasteurella multocida infection in chickens.

The effects of various treatments on the immune response of chickens to vaccine prepared from Pasteurella multocida strain P1059 were investigated. The treatments, given on or before the day of hatching, consisted of surgical bursectomy (SB), hormonal bursectomy (HB), surgical thymectomy (ST) and X-irradiation (X). In chickens subjected to SB, SBX or HB before vaccination, the production of agglutinin and immunoglobulin was impaired, but the production of resistance against challenge was not. In chickens subjected to ST or STX before vaccination, the production of agglutinin and immunoglobulin was unimpaired, but the production of resistance against challenge was diminished. Protection was therefore thymus-dependent.

Agglutinins↗
PubMed1991

Genetic studies on experimental autoimmune gastritis induced by neonatal thymectomy using recombinant inbred strains between a high-incidence strain, BALB/c, and a low-incidence strain, DBA/2.

Thymectomy on day 3 after birth induced autoimmune gastritis (AIG) at the age of 2 months in 51-73% of BALB/c mice, and in only 3-5% of DBA/2 mice. AIG was detected by histological and serological (immunofluorescence staining for detecting anti-parietal cell autoantibody) examination. However, autoantibody was weakly positive in almost all of these DBA/2 mice when measured by ELISA using extract of murine gastric mucosa as the antigen. To investigate genetically the mechanism controlling the incidence of AIG, II recombinant inbred strains established by brother-sister mating of (BALB/c x DBA/2) F2 mice (C x D2 strains) were used. Among 26 markers tested, the Mls-1 locus on BALB/c chromosome 1 and the Hc locus coding a complement component (C5) on BALB/c chromosome 2 were found to be associated with high susceptibility to AIG. However, if one or both of the loci were of DBA/2 origin, mice showed medium or low susceptibility to AIG. For further analysis, F1, F2 and back-cross generations of these two strains were tested, but segregation of a single susceptibility or insusceptibility gene was not obtained. Taken together, it seems probable that two or more genes are involved in the induction mechanism of AIG. We did not detect C5 deposition in AIG lesions, nor complement-dependent cytotoxic antibody to parietal cells in serum from AIG mice. However, injection of irradiated spleen cells of DBA/2 mice into BALB/c mice thymectomized on day 3 augmented the incidence of AIG from 71 to 100%, but not that of oophoritis (33%). A relationship between Mls-1a determinants and the pathogenesis of AIG was further suggested from the fact that V beta 6 TcR-expressing T cells increased in number in AIG-bearing compared with normal BALB/c mice.

Animals↗
PubMed1986

Pure red cell aplasia and thymoma: demonstration of persisting inhibition of erythropoiesis after thymectomy and resolution after immune suppressive treatment.

A 61 year-old woman presented with general malaise, hair loss, pure red cell aplasia (PRCA) and thymoma: no growth of erythropoietic colonies in vitro (BFU-E) was observed in the presence of her own serum. The thymoma was removed: after the operation no improvement of her anaemic condition was observed and colony growth was very poor, although T-depleted narrow preparations showed a modest BFU-E formation in autologous serum. Following treatment with azathioprine, a complete recovery was seen, associated with normal BFU-E formation in vitro. This observation suggests that a complex inhibition of erythropoiesis may operate in PRCA involving both humoral and cellular factors; thymectomy alone may not be sufficient to restore haemopoiesis, but has to be followed by immune suppressive treatment.

Antibody Formation↗
PubMed1993

Case report: spontaneous pregnancy following thymectomy for myasthenia gravis associated with premature ovarian failure.

We report the case of a 29-year-old woman who was diagnosed to have premature ovarian failure (POF) and myasthenia gravis at the age of 27 years. She was treated by thymectomy and pyridostigmine. Hormone replacement was started after the operation and she subsequently conceived spontaneously. We believe this is the first report of a spontaneous pregnancy after the diagnosis of POF associated with myasthenia gravis.

Adult↗
PubMed1976

Membrane bound IgG on erythroblasts in pure red cell aplasia following thymectomy. A case report.

A case of pure red cell aplasia appearing 6 months following thymectomy is reported in a 43-year-old man. Immunofluorescence studies of the patient's bone marrow have demonstrated the presence of membrane-bound IgG on the majority of erythroblasts and some mature erythrocytes. It is suggested that the IgG represents anti-erythroid autoantibodies. The number of Ig-bearing lymphocytes in peripheral blood was decreased as was the level of immunoglobulins indicating a B-lymphocyte deficiency. T-lymphocyte functions were without remarks. The patient was initially treated with corticosteroids and oxymetholone. He responded well to this therapy but relapsed 9 month later. Cyclophosphamide treatment was started and followed by a complete haematologic remission.

Adult↗
PubMed1993

Interspecies-specific ovarian autoantigens involved in neonatal thymectomy-induced murine autoimmune oophoritis.

PROBLEM: Thymectomy of mice on day 3 after birth (3d-Tx) gives rise to the appearance of a particular type of ovarian lesion known as experimental autoimmune oophoritis (AIO). METHOD: In the present study, the spleen cells from BALB/c mice having undergone 3 day-Tx AIO were fused with X63-Ag8-6.5.3 myeloma cells, and a number of hybridoma clones producing autoantibodies against ovarian tissue were established. RESULTS: On the basis of immunohistochemical and protein-chemical analysis, two independent clones, designated at T2.2 and S1.6, were found to react with interstitial tissues surrounding the follicles. These monoclonal antibodies showed broad cross-species reactivity, in that they recognized similar antigenic macromolecules in the rat, pig, human, and mouse. The antigenic determinants were strongly resistant to heat and acid, especially to the treatment of periodic acid, indicating that the antigenic determinants had no relation with carbohydrate components. CONCLUSIONS: By antibody affinity chromatography, two kinds of autoantigens were identified. SDS-PAGE, under reduced or nonreduced conditions, revealed an 80/85 kDa protein for T2.2, and an 82 kDa for S1.6, respectively.

Animals↗
PubMed1975

Influence of neonatal thymectomy on blood pressure and hypertensive vascular disease in rats with renal hypertension.

The effect of neonatal thymectomy on the degree and prognosis of hypertension and on the vascular lesions in rats with renal hypertension was studied. There were no differences between thymectomized and sham operated hypertensive rats. The degree of hypertension, the frequency of spontaneous death and heart infarcts were the same in both groups. The occurrence and degree of perivascular cell infiltrations, deposits of perivascular connective tissue and fibrinoid degenerations of the media were found to be the same in both the thymectomized and the sham operated hypertensive animals. The results do not support the assumption that delayed type immune reactions are important in the pathogenesis of hypertensive vascular disease in renal hypertensive rats.

Animals↗
PubMed1981

Thymic abnormalities: antigen or antibody? Response to thymectomy in myasthenia gravis.

The therapeutic value of thymectomy for myasthenia is still questioned although it retains an important place among management modalities that strive for sustained remission. Questions derive from uncertainty as to appropriate timing, variable extent of resection and quantitation of response. Forty-seven patients, followed one to seven years, underwent an extended transsternal or combined transcervical-transsternal procedure with anterior mediastinal exenteration. Sixteen have been in complete remission from six months to six years, four are asymptomatic on occasional pyridostigmine and eight are significantly improved. Evaluation of thymic pathology (hyperplasic, involuted areas, and thymoma) included a search for thymic myoid cells by fluorescence cytochemistry. Antibodies to acetylcholine receptor present in 38 of 43, decreased post-operatively to normal in four, by 50% to 80% in 14, by 20 to 50% in three and were unchanged in 14. Most remissions occurred in young women with noninvoluted hyperplastic glands and variably high anti-AChR titers which dropped toward normal in seven of 15. These results encourage us to utilize this procedure routinely.

Adolescent↗