Gene/Protein Disease Symptom Drug Enzyme Compound
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 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have explored scid mice as an in vivo model to study lymphocyte function and autoantibody production in patients with autoimmune thyroiditis and thyroid peroxidase (hTPO) autoantibodies. Patient's peripheral blood mononuclear cells (PBMC) were transplanted into scid mice via intraperitoneal injections and human immunoglobulin G (hIgG) and thyroid autoantibody levels in the murine sera were monitored for a minimum of 3 months after transplantation. Human IgG reached maximum serum levels of > 3,000 micrograms/ml (mean +/- SEM = 1,199 +/- 354 micrograms/ml) after an average of 6.5 weeks. In reconstituted mice (hereafter named At-Scid-hu) substantial titers of anti-hTPO of up to 0.51 (ELISA index, normal range < 0.02) were observed over a period of 1-2 months, followed by a gradual decline. Immunization of AT-Scid-hu mice with immunogenic, recombinant human hTPO (rec-hTPO) failed to enhance hTPO-Ab levels. Furthermore, there was no correlation between the magnitude of human IgG in the murine serum and concomitant levels of anti-hTPO. Murine thyroid function was unaffected by the transplantation of PBMC, as evidenced by normal serum thyroxine (T4) levels, and lack of specific pathologic changes in the thyroid. These data indicate, for the first time, the potential for longer-term human thyroid autoantibody secretion in the scid mouse reconstitution model allowing for further investigation of the regulatory factors inpinging on the human B cells surviving in the murine environment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characteristics of long-term human thyroid peroxidase autoantibody secretion in scid mice transplanted with lymphocytes from patients with autoimmune thyroiditis. 142 61

We investigated the serial changes in the plasma levels of anti-thyroglobulin antibody (ATA) by solid-phase enzyme immunoassay, thyroid hormones and blood glucose, since spontaneous occurring lymphocytic thyroiditis (LT) has been found in spontaneously diabetic Bio Breeding/Worcester (BB/W) rat. We also observed the correlation between these levels and histological findings in the thyroid gland. The incidence of diabetes was 0% in 5 week old rats (group A), 70% in 11 week old rats (group B), and 86% in 20 week old rats (group C), while LT was observed in 0% in group A, 20% in group B and 48% in group C. Although the incidence of both increased with age, there was no link between LT and diabetes. Plasma ATA levels were 91.4 +/- 28.5 (OD492 X 1,000, mean +/- SEM) in the control (14 week old Wistar Furth) rats. 49.5 +/- 15.4 in group A, 197.8 +/- 41.5 in group B, and 376.7 +/- 48.7 in group C, again showing a clear increase with age. In group C, the plasma levels of ATA in rats with LT were significantly higher than those without LT. In addition, 6 out of 11 rats without LT had abnormaly high ATA levels. In group C, the plasma levels of free 3,5,3'-triiodothyronine (FT3) and total thyroxine (TT4), and also the FT3/TT4 ratio were significantly lower and the plasma levels of blood glucose were higher than in the other groups. There was no difference between the plasma thyroid hormone levels in rats with LT and those without LT. These studies suggest that LT may occur independently of insulitis, namely diabetes, ATA levels and the incidence of LT increase with age, the site of ATA production may not be confined to the thyroid gland, and the derangement of glucose metabolism may be one of the factors in the decrease in plasma thyroid hormone. The BB/W rat is not only a useful animal model to use in exploring the pathogenesis of human insulin-dependent diabetes mellitus, but also spontaneous autoimmune thyroiditis.
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PMID:Spontaneous autoimmune thyroiditis in Bio Breeding/Worcester (BB/W) rat. 355 49

The TRH test, using synthetic TRH (TSH-releasing hormone) is the most sensitive test for the assessment of thyroid function. It may show elevated basal TSH and/or an exaggerated TSH response to TRH, despite normal thyroid hormone levels (T4, FT4I, T3). This condition is termed "preclinical hypothyroidism" (pc hypo). Thyroid hormone levels, the clinical index of Billewicz and metabolic impact on target tissues were studied prospectively in 38 pc hypo women and compared with 20 controls matched for age, weight and sex and 9 patients with overt hypothyroidism. For metabolic evaluation at the tissue site two new metabolic tests were developed and standardized, the systolic time intervals (STI) and sex-hormone-binding globulin (SHBG), which were used in conjunction with the ankle reflex time (ART) and lipids (cholesterol and triglycerides). The thyroid hormones T4, FT4I and T3 in pc hypo (77.8 +/- 2.0 nmol/l; 71.8 +/- 2.3; 1.92 +/- 0.07 nmol/l respectively; mean +/- SEM) were within the normal range (by definition), but significantly lower in comparison with the normal controls (105.5 +/- 3.3 nmol/l; 97.8 +/- 3.1; 2.91 +/- 0.12 nmol/l respectively; p less than 0.001). The clinical index and metabolic parameters SHBG and ART showed significant hypothyroid changes. STI (measured as preejection period) and lipids were not yet significantly different from the controls despite a hypothyroid tendency in many single individuals. The etiology in 144 patients with pc hypo (out of 2969 TRH tests) was analysed and the following causes identified: a) treated hyperthyroidism (38 after radioiodine, 5 after partial thyroidectomy, 5 after antithyroid drugs, 5 after radioiodine and partial thyroidectomy); b) simple goiter (7 without and 21 after partial thyroidectomy); c) autoimmune thyroiditis (27); d) other causes such as subacute thyroiditis (10); Riedel's thyroiditis (2), dyshormogenesis (2), drugs (6), treated toxic adenomas (2); e) etiology unknown or not identified (14).
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PMID:[Metabolic evaluation and etiology of "preclinical hypothyroidism": a preliminary report]. 719 52

We have examined the hTcR V gene family use of T-cells present in the aspiration thyroid biopsy specimens of patients with hyperthyroid Graves' disease (n = 8) and Hashimoto's autoimmune thyroiditis (n = 5). Nine of the 13 specimens had cytologically identified thyroid follicular cells, and 12 of the 13 contained human thyroglobulin-specific mRNA, confirming successful sampling. Of 18 hTcR V alpha and 19 hTCR V beta gene families tested for in the individual aspirates, a mean +/- SEM of 6.8 +/- 0.9 V alpha and 9.6 +/- 1.4 V beta gene families were present in the Graves' aspirates, while 12.2 +/- 1.7 and 16.8 +/- 0.4 V alpha and V beta gene families were present in the aspirates of patients with Hashimoto's thyroiditis. These samples, which offer a window onto the natural history of autoimmune thyroid disease, demonstrate significant hTcR V alpha and beta gene restriction in hyperthyroid Graves' disease, but much less restriction of both V alpha and V beta gene families in Hashimoto's disease. Such data extend our earlier information based only on examination of highly selected surgical specimens of patients with autoimmune thyroid disease to the much more typical patient. We conclude that hTcR V gene restriction of varying degrees is present in the majority of patients with autoimmune thyroid disease, but appears to be more easily detected in Graves', rather that Hashimoto's, disease.
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PMID:T-cell receptor V gene use in autoimmune thyroid disease: direct assessment by thyroid aspiration. 844 22

Clinical and laboratory characteristics of chronic autoimune thyroiditis were analysed in sixty-seven patients (55 girls). At the time of diagnosis the mean +/- SEM age of 67 patients was 11.6 +/- 2.9 years. Diagnosis of the disease was based on the findings of the enlarged thyroid gland on palpation and positive thyroglobulin and/or microsomal antibodies. The assessment of thyroid function was based on clinical diagnosis and on the levels of thyroid-stimulating hormone and thyroxine. Initially 36 (53.7%) of 67 patients were euthyroid, 15 (22.4%) were hyperthyroid and 16 (23.9%) were hypothyroid. In addition to the well known clinical signs of chronic autoimmune thyroiditis, the palpable lymh nodes in the immediate proximity of the thyroid gland were found in high frequency (47%) in our patients with euthyroid or hyperthyroid goiter. The thyroid function was followed-up in fifty-three patients for an average of 2.6 (0,3-7) years. No progression to hypothyroidism was clinically observed, or demonstrated by laboratory findings in euthyroid patients. In seven patients with subclinical hypothyroidism at the time of diagnosis spontaneous recoveries of thyroid function occurred. The majority of hyperthyroid patients (80%) required a prolonged antithyroid treatment. In all patients with clinical and laboratory signs of hypothyroidism the replacement therapy with thyroxine was started at the time of diagnosis.
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PMID:[Clinical and laboratory characteristics of chronic autoimmune thyroiditis in children and adolescents]. 1797 95