The value of thymectomy in myasthenia gravis: a computer-assisted matched study.
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In the absence of a prospective randomized study of patients treated conservatively or with thymectomy, a computer-assisted retrospective matches study was devised. Of 563 patients treated for myasthenia gravis without thymoma up to 1965, 104 had thymectomy. With computer assistance, each surgical patient was matched with a medical patient on the basis of age, sex, and severity and duration of disease. On this basis 80 of the 104 surgical patients could be matched satisfactorily. There were 16 males and 64 females in each of the matched surgically treated and medical control groups. A complete remission was experienced by 27 of the 78 patients in the surgical group as compared to 6 of the medical group. Improvement was noted by 26 of 78 surgically treated patients and 13 of 78 receiving medical treatment. Survival for patients having thymectomy. Thirty-four patients in the medical group had died as compared to 11 in the surgical group. Comparison of survival in relation to sex, duration of symptoms, or age (less than 30 or less than 30 years) did not show a significant difference. Until more effective treatment is available for myasthenia gravis, thymectomy deserves consideration for both sexes, and with increased age or long duration of symptoms. (+info)
Cyclin D2 overexpression in transgenic mice induces thymic and epidermal hyperplasia whereas cyclin D3 expression results only in epidermal hyperplasia.
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In a previous report, we described the effects of cyclin D1 expression in epithelial tissues of transgenic mice. To study the involvement of D-type cyclins (D1, D2, and D3) in epithelial growth and differentiation and their putative role as oncogenes in skin, transgenic mice were developed which carry cyclin D2 or D3 genes driven by a keratin 5 promoter. As expected, both transgenic lines showed expression of these proteins in most of the squamous tissues analyzed. Epidermal proliferation increased in transgenic animals and basal cell hyperplasia was observed. All of the animals also had a minor thickening of the epidermis. The pattern of expression of keratin 1 and keratin 5 indicated that epidermal differentiation was not affected. Transgenic K5D2 mice developed mild thymic hyperplasia that reversed at 4 months of age. On the other hand, high expression of cyclin D3 in the thymus did not produce hyperplasia. This model provides in vivo evidence of the action of cyclin D2 and cyclin D3 as mediators of proliferation in squamous epithelial cells. A direct comparison among the three D-type cyclin transgenic mice suggests that cyclin D1 and cyclin D2 have similar roles in epithelial thymus cells. However, overexpression of each D-type cyclin produces a distinct phenotype in thymic epithelial cells. (+info)
Thymic hyperplasia as a source of ectopic ACTH production.
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A 26 year-old man with suspected Cushing's disease underwent transsphenoidal exploration of the pituitary without any evidence of microadenoma or hyperplasia. Progressive hypercortisolism necessitated bilateral adrenalectomy. Postoperatively, skin pigmentation gradually developed with a marked elevation of plasma ACTH levels, and CT scanning uncovered a thymic mass. Following removal of the thymic mass, skin pigmentation disappeared and plasma ACTH levels fell to normal. The excised mass was found to be a benign thymic hyperplasia without epithelial or carcinoid tumor cells. However, gel chromatography showed that the thymic tissue extract contained high ACTH content comparable to that of ectopic ACTH-producing tumors with a major component corresponding to ACTH(1-39). Northern blot analysis and in situ hybridization revealed the expression of proopiomelanocortin transcripts in lymphocytes of thymic hyperplasia. This report suggests that lymphocytes in thymic hyperplasia are the most likely site of deregulated ACTH expression causing ectopic ACTH syndrome. (+info)
Increased metabolic activity in the thymus gland studied with 18F-FDG PET: age dependency and frequency after chemotherapy.
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This study was designed to evaluate the age dependency of 18F-FDG uptake in the thymus and the frequency of PET confirmation of thymus hyperplasia after chemotherapy in cancer patients. METHODS: Whole-body FDG PET recordings of 168 patients were retrospectively examined for a retrosternal lesion in the anterior mediastinum that was attributable to the thymus. The patients were assigned to the following four groups: children with malignant lesions before the first therapy (group Ia; n = 15; mean age +/- SD, 11.9 +/- 3.7 y), children with malignant disease after chemotherapy (group Ib; n = 12; mean age, 10.3 +/- 5.0 y), adults with histologically confirmed malignant lymphoma before the first therapy (group IIa; n = 37; mean age, 43.9 +/- 16.7 y), and adult lymphoma patients 3 wk to 4 mo after chemotherapy (group IIb; n = 104; mean age, 40.9 +/- 14.6 y). RESULTS: Increased FDG accumulation in the thymus was seen in 11 patients (73%) of group Ia and 9 patients (75%) of group Ib. Thymus hyperplasia was found in 5 patients (5%) of group IIb. The eldest of these 5 patients was 25 y old. No increased FDG accumulation in the thymus was observed in any of the group IIa patients. In cases of visible FDG uptake in the thymus, standardized uptake values did not exceed 4. CONCLUSION: FDG accumulation in the thymus is a common finding in children and can occasionally be observed in young adults after chemotherapy. Knowledge of the characteristics of a typical retrosternal lesion in conjunction with the clinical history allows avoidance of diagnostic uncertainty and unnecessary procedures. (+info)
Thymic hyperplasia and lung carcinomas in a line of mice transgenic for keratin 5-driven HPV16 E6/E7 oncogenes.
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Human Papillomavirus type 16 (HPV-16) is the cause of both benign lesions and ano-genital cancers. In HPV-associated cancers the transforming properties of the expressed viral E6 and E7 proteins have been revealed by a number of different assays. We have generated transgenic mice expressing HPV-16 E6/E7 genes under the control of the murine keratin 5 gene promoter, which should confer cell-type specific expression in the basal cells of squamous stratified epithelia. Transgenic mice developed thymic hyperplasia and lung neoplasia with 100% frequency, the thymus showing a size increase at 2 months and reaching the maximum dimension at 6 months, when lung carcinomas appeared. After this time the size of hyperplastic thymi decreased, while malignant formations invaded the mediastinal area. Hepatic metastasis could be also observed in some of the animals at the autopsy and death invariably occurred around 10-11 months of age. (+info)
Mucosa-associated lymphoid tissue of the thymus hyperplasia vs lymphoma.
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In the thymus, the relationship between lymphofollicular hyperplasia and mucosa-associated lymphoid tissue (MALT)-type lymphoma is uncertain. We analyzed 14 cases with a diagnosis of thymic follicular hyperplasia in patients with connective tissue disease (n = 2), myasthenia gravis (n = 11), or both (n = 1). In 11 cases, well-defined reactive lymphoid follicles were surrounded by a continuous layer of medullary epithelial cells. A polyclonal rearrangement of the immunoglobulin heavy chain gene (IgH) was observed. In 3 cases, ill-defined lymphoid follicles with sheets of centrocytic-like B cells disrupting the medullary cytokeratin epithelial network were observed on certain sections. These cells expressed the phenotypic features of memory B cells with CD20, CD79a, and bcl-2 positivity and CD5, CD10, CD23, and bcl-6 negativity, and a monoclonal rearrangement of the IgH gene was detected. Appropriate sampling, cytokeratin staining, and molecular analyses may help to identify early MALT-type lymphoma developing in the setting of thymic lymphofollicular hyperplasia. (+info)
CDS1 and promoter single nucleotide polymorphisms of the CTLA-4 gene in human myasthenia gravis.
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The cytotoxic T lymphocyte associated protein 4 (CTLA-4) gene (Ctla-4) is a candidate gene for autoimmune disease. We here report results of two single nucleotide polymorphisms (SNPs) in the Ctla-4, a +49 A/G SNP in CDS1 and a C/T promoter SNP at position -318. There were no differences in these two SNPs between patients and healthy individuals. The frequency of allele G and genotype G/G at position +49 in CDS1 was increased in patients with thymoma when compared with patients with normal and hyperplastic thymic histopathology. Patients with the G/G genotype had signs of immune activation manifested as higher levels of serum IL-1beta and higher percentage of CD28(+) T lymphocytes. There was a strong linkage between the 86bp allele in the 3'-UTR and the A(+49) allele in CDS1. Our results suggest that the SNP at position +49 in CDS1 might be associated with the manifestations of MG. (+info)
The influence of preoperative drug treatment on the extent of hyperplasia of the thymus in primary thyrotoxicosis.
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Thymic biopsies taken from women at the beginning of the operation of subtotal thyroidectomy were studied by the point-counting histometric technique. In all patients with primary thyrotoxicosis, the thymus is hyperplastic. After pretreatment with antithyroid drugs, the pattern of thymic involution with age is similar to, but at higher levels, than that in control groups of patients with non-toxic goitre in whom there is no evidence of immunological abnormality. By contrast, after propranolol pretreatment very little age involution is seen. The differences in the appearance of the thymus in female primary thyrotoxixosis patients prepared for operation with different drug treatment regimes are probably related to the pharmacological actions of the drugs and may indicate an interaction between primary immunological and secondary endocrinological factors in the disease process. (+info)