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Biomedical subjects

N Amino

Publications and source records attributed to N Amino.

At least 217 records · Page 12Linked to original sources

Physiologic thyroid activation in normal early pregnancy is induced by circulating hCG.

In normal early pregnancy, serum free thyroxine (T4) increases and serum TSH decreases, indicating that the thyroid gland is activated physiologically. To identify the factor responsible for this thyroid activation, we measured the serum thyroid-stimulating activity in comparison with the serum level of hCG in 39 normal women in early pregnancy. Serum thyroid-stimulating activity was measured by a sensitive cyclic adenosine 3',5'-monophosphate (cAMP) accumulation assay using a rat thyroid cell line (FRTL-5). Thyroid-stimulating activity was detected in 37 women (95%), and the activities of individuals correlated positively with their serum free T4 levels (r = 0.474; P less than .01) and negatively with their serum TSH levels (r = -0.376; P less than .02). Moreover, serum thyroid-stimulating activity correlated closely with the serum hCG level (r = 0.741; P less than .001), but was completely abolished by pre-treatment of the sera with hCG antibodies. These data indicate that in normal early pregnancy, the thyroid gland is physiologically activated by serum hCG, which has intrinsic thyroid-stimulating activity.

Animals↗

[Development of ELISPOT assay for thyroid autoantibody-producing cells].

A new assay system for detection of thyroid-autoantibody-producing cells was developed. This assay is based on the ELISPOT method with antigen-coated nitrocellulose membranes in 96-well microfilter plates. This was more sensitive than conventional methods such as a radioimmunoassay and a passive agglutination method for detection of thyroid-autoantibody production. The coefficients of inter- and intra-assay variations for antibody-producing cells were less than 6.5%. Thus, this assay system can be used to analyse the thyroid-specific immunological abnormalities as a routine test.

Agglutination Tests↗

[Correlation between intracellular alkaline phosphatase activities and incidence of toxic granules in neutrophilia].

We examined the intracellular alkaline phosphatase (NIAP) activities in peripheral neutrophils in 15 healthy subjects and 15 patients with inflammatory diseases, and compared them with the percentages of neutrophils with cytoplasmic toxic granules (NTG), which is thought to be induced by infection. NIAP activities were markedly increased in patients and significantly correlated with the percentages of NTG. These data indicate that measurement of NIAP activity is useful for the diagnosis of infections and/or inflammatory diseases.

Alkaline Phosphatase↗

[Intracellular alkaline phosphatase activities in myelodysplastic syndrome].

We examined the intracellular alkaline phosphatase (NIAP) activities in peripheral neutrophils in 15 normal controls, 4 patients with myelodysplastic syndrome, and 4 with chronic myeloid leukemia. NIAP activities were decreased in myelodysplastic syndrome in comparing to normal controls (p less than 0.01). These data suggest that measurement of NIAP activity is useful for supporting a diagnosis of myelodysplastic syndrome.

Alkaline Phosphatase↗

Thyroxine requirement during pregnancy for replacement therapy of hypothyroidism.

We examined the dose requirements of thyroxine (T4) and desiccated thyroid during eight pregnancies of six women who had undergone total thyroidectomy for thyroid carcinoma. In five pregnancies from four patients treated with T4, serum free T4, which was measured by a newly developed radioimmunoassay, decreased during pregnancy but increased above the normal range after delivery. Consistent with these changes in free T4, serum TSH (measured by a highly sensitive immunoradiometric assay) increased during pregnancy but returned to an undetectable level after delivery, with one exception. The serum triiodothyronine (T3)-to-T4 ratio, which is related to peripheral conversion of T4 to T3, was lower in patients treated with T4 than in normal controls, regardless of pregnancy. The ratio decreased further during pregnancy, and so relative deficiency of T3 during pregnancy was suspected, especially in T4-treated patients. On the other hand, in two pregnancies from two other patients treated with desiccated thyroid at a dose most equivalent to that of T4, serum free T4 decreased to a low-normal value during gestation but returned to the normal range after delivery, whereas serum TSH scarcely changed during pregnancy. These findings indicate that replacement therapy for pregnant patients with hypothyroidism after total thyroidectomy should include an increased dose of T4; in contrast, the dose of desiccated thyroid need not be changed.

Female↗

Improvement of infiltrative ophthalmopathy in parallel with decrease of thyroid-stimulating antibody (TSAb) activity in two patients with hypothyroid Graves' disease.

Two patients with primary hypothyroidism associated with infiltrative ophthalmopathy without previous history of hyperthyroidism are presented. Anti-TSH receptor antibodies (TRAb) were detected by radioreceptor assay (TBII), and unexpectedly their biological activity was not of a blocking (TSBAb), but of a thyroid-stimulating type (TSAb). After the initiation of levothyroxine therapy, the TBII and TSAb activities both decreased gradually with normalization of the elevated TSH level. The inflammatory eye signs improved strikingly in parallel with decrease of these antibody activities. These data indicate that (1) TRAb in primary hypothyroidism do not always show TSAb activity, (2) the decrease in TRAb following levothyroxine therapy in these patients appeared to correlate with suppression of TSH, (3) changes in infiltrative ophthalmopathy were associated with that of TSAb even in primary hypothyroidism, and (4) the hypothyroidism in these patients is justifiably diagnosed as "hypothyroid Graves' disease". TSAb might be somewhat related to the pathogenesis of ophthalmopathy in autoimmune thyroid diseases.

Antibodies↗

Intrathyroidal HLA-DR-positive lymphocytes in Hashimoto's disease: increases in CD8 and Leu7 cells.

The peripheral and intrathyroidal HLA-DR-positive (DR+) lymphocyte subsets that were activated in vivo in patients with Hashimoto's disease (HD) were examined by two-color flow cytometry with monoclonal antibodies against CD3, CD4, CD8, Leu7, CD19, and HLA-DR antigens. The proportions of total DR+ cells in peripheral lymphocytes and the proportions of DR+ cells in the CD3+, CD4+, and Leu7+ lymphocytes were higher in patients with HD than in normal controls. Furthermore, the proportions of total DR+ cells among intrathyroidal lymphocytes isolated from thyroid tissue of individuals with HD were higher than those in their peripheral lymphocytes. Interestingly, the proportions of DR+ cells among the CD3+, CD8+, and Leu7+ lymphocytes in the thyroid were greatly increased. These data indicate that (i) CD3+ T, especially CD4+ T helper/inducer, lymphocytes and Leu7+ NK/K cells are activated in peripheral blood in Hashimoto's disease and that (ii) CD3+ T, especially CD8+ T suppressor/cytotoxic, lymphocytes and Leu7+ NK/K cells are predominantly activated in Hashimoto's goiter, suggesting an increase of cell-mediated cytotoxicity in the thyroid in Hashimoto's disease.

Adult↗

Peripheral large granular lymphocytes in normal pregnant and postpartum women: decrease in late pregnancy and dynamic change in the puerperium.

Large granular lymphocytes (LGLs) have a variety of cytotoxic activities of NK, K and cytotoxic T lymphocytes, suggesting that their morphology is indicative of lytic function. In non-pregnant normal control women (n = 48), the number of LGLs was 0.30 +/- 0.14 x 10(9)/l and the proportion of LGLs in their peripheral lymphocyte fraction was 14.0 +/- 5.4%. The number and proportion of LGLs were significantly decreased in the third trimester of pregnancy (n = 32; 0.19 +/- 0.08 x 10(9)/l, P less than 0.01, and 11.7 +/- 3.8%, P less than 0.05), although an unexpected increase in the proportion of LGLs was observed in the first trimester of pregnancy (n = 24; 17.5 +/- 6.5%, P less than 0.05). After delivery, the number and proportion of LGLs increased rapidly to restore the non-pregnant levels and showed a marked increase in LGL count 4 months postpartum. These data suggest that lymphocyte-mediated cytotoxicity decreases in late pregnancy and increase dynamically after delivery to restore the non-pregnant state.

Antibody-Dependent Cell Cytotoxicity↗

Peripheral K cells in normal human pregnancy: decrease during pregnancy and increase after delivery.

Peripheral blood levels of K cells were measured in normal pregnant and post-partum women by a plaque-forming cell technique that detects K cells on the basis of their activity of antibody-dependent cell-mediated cytotoxicity (ADCC). Peripheral K cells decreased throughout normal pregnancy (n = 46; 7.8 +/- 3.4%, P less than 0.01; 0.13 +/- 0.08 X 10(9)/l, P less than 0.001) and increased in the post-partum period (n = 17; 14.2 +/- 6.1%, P less than 0.05; 0.32 +/- 0.20 X 10(9)/l, P less than 0.01) in comparison with those in normal non-pregnant controls (n = 29; 10.5 +/- 4.2%; 0.20 +/- 0.09 X 10(9)/l). These findings suggest that a decrease of K cells during pregnancy may contribute in part to maternal acceptance of the fetal allograft and that the post-partum increase of K cells may represent a post-partum increase of cell-mediated cytotoxicity, which may contribute to natural defense against puerperal infection.

Adult↗

Peripheral self-tolerance and autoimmunity: the protective role of expression of class II major histocompatibility antigens on non-lymphoid cells.

Immunologic self-tolerance is achieved mainly during development by clonal deletion in the thymus of T lymphocytes with receptors specific for self-antigens and with associated T-cell markers CD4/CD8. However, T cells expressing a low level of these markers are allowed into the periphery still bearing their autospecific receptors. Such clonal deletion, induced by cells bearing the class II antigens coded for by major histocompatibility complex (MHC) in the thymus, does not remove all autoreactive T cells specific for antigens of differentiated tissue expressed extrathymically. However, these autoreactive T cells are silent in the periphery. Peripheral non-lymphoid cells (e.g., endocrine cells) can induce antigen-specific unresponsiveness in T cells and can specifically suppress production of autoantibody against their antigens when the non-lymphoid cells express class II MHC antigens on their surface. This class II MHC expression is induced by interferon-gamma produced by T cells as a result of various immune responses, such as autoimmune reaction. Thus, the expression of class II MHC antigens on non-lymphoid cells may serve as a peripheral mechanism for the induction and maintenance of self-tolerance in autoreactive T cells that escape negative selection in the thymus or that are specific for extrathymic tissue antigens, in a fail-safe mechanism against autoimmunity. Some autoimmune diseases, especially organ-specific ones, might be caused by a defect in this fail-safe mechanism.

Autoimmune Diseases↗

Effective method for prediction of transient hypothyroidism in neonates born to mothers with chronic thyroiditis.

An effective method of prediction of neonatal transient hypothyroidism was examined in 105 neonates (including a pair of twins) born to mothers with chronic thyroiditis (92 mothers with goitrous Hashimoto's disease and 12 with primary atrophic hypothyroidism). Antithyroid microsomal antibody was measured by a hemagglutination technique (MCHA), and antithyroid-stimulating hormone (TSH) receptor antibody by both radioreceptor assay (TBII) and biologic thyroid-stimulation blocking assay (TSBAb). For generalization of predictive criteria, the expression of TBII activity was standardized using standard serum made taking units of MRC-LATS-standard B as a reference, and that of TSBAb activity was standardized as the degree of dilution with normal pooled serum to attain 50% inhibition of TSH (100 microU/ml)-induced cyclic adenosine monophosphate increase (TSBAb50). The MCHA titer in maternal serum at delivery correlated well with that of the corresponding cord serum, but not with the free thyroxine (T4) index or the TSH level in cord serum. TBII activity was positive in only 4 of 12 mothers with primary atrophic hypothyroidism, TSBAb activity was also positive only in these four mothers, and neonatal thyroid dysfunction was observed in three of their neonates. Two of these neonates developed transient hypothyroidism requiring T4 treatment, and the t third developed mild transient hyperthyrotropinemia with normal T4 and triidothyronine levels. The mothers whose neonates showed transient hypothyroidism had TBII activities of more than 300 U/ml and TSBAb50 activities of more than 300. Ninety-two mothers with goitrous Hashimoto's disease had neither TBII nor TSBAb activity, irrespective of their thyroid function, and delivered euthyroid babies.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

Evaluation of TSH receptor antibody by 'natural in vivo human assay' in neonates born to mothers with Graves' disease.

Neonatal thyrotoxicosis induced by transferred TSH receptor antibody (TRAb) is the ideal human in-vivo experimental system for the evaluation of TRAb. The clinical significance of circulating TRAb in Graves' disease was evaluated by this 'natural in-vivo human assay'. TRAb activity in vitro was measured by radioreceptor assay (thyrotrophin-binding inhibitor immunoglobulin, TBII) and sensitive cAMP accumulation assay using FRTL-5 cells (thyroid-stimulating antibody, TSAb). Further, the binding-stimulation index (B-S index) was newly introduced, which was the most useful indicator for prediction of neonatal thyrotoxicosis, calculated as the product of TBII and TSAb (Tamaki et al., 1988a). Maternal serum TRAb indices showed highly significant correlations with the serum free T4 index (FT4I) and free T3 index (FT3I) in neonates (5-10 days after birth) born to 20 mothers with Graves' disease who had positive TBII and/or TSAb (FT4I: r = 0.825 for TBII, r = 0.908 for TSAb, r = 0.944 for the B-S index, P less than 0.001; FT3I: r = 0.622 for TBII, P less than 0.01, r = 0.812 for TSAb, r = 0.791 for the B-S index, P less than 0.001; n = 20). In contrast, in 57 untreated adult patients with hyperthyroid Graves' disease, the FT4I and FT3I levels were not correlated with any of the TRAb indices. The linear regression relationship between the B-S index and FT4I found in neonates was applied to values in adult patients with Graves' disease, and the patients were divided into three groups on the basis of the 95% confidence limit: high, normal, and low responders of thyroid hormone (FT4I) secretion to the B-S index. FT4I and the ratio of FT4I to the B-S index were highest and the TRAb indices were lowest in the high responders, while FT4I and the FT4I/B-S index ratio were lowest and the TRAb indices were highest in the low responders. The FT4I/B-S index ratio was inversely correlated with the titres of antithyroid microsomal antibody in all the adult patients with untreated Graves' disease (r = -0.288, P less than 0.05). The results suggest that in-vitro assays using animal thyroid cells and cAMP as an index of response are suitable for detecting circulating thyroid stimulating activity in vivo. Secretion of thyroid hormones in Graves' disease may be regulated not only by circulating thyroid-stimulating antibodies but also by intrathyroidal stimulatory factors or by inhibitory or destructive factors.

Antibodies↗

Incidences of antibodies to Yersinia enterocolitica: high incidence of serotype O5 in autoimmune thyroid diseases in Japan.

Antibodies to Yersinia enterocolitica serotype O3, O5, O6 and O9 were measured by the micro-agglutination method in 445 healthy subjects and patients with Grave's disease (n = 70), Hashimoto's disease (n = 45) and thyroid tumor (n = 29). In contrast to previous reports, the incidence of antibodies to serotype O3 in each group of patients with thyroid diseases was not significantly different from that in healthy subjects. However, the incidence of antibodies to serotype O5 was significantly higher in patients with Graves' disease (81.4%, P less than 0.001) and Hashimoto's disease (91.1%, P less than 0.001) than in healthy subjects (258.9%). Significantly increased incidence of antibodies to serotypes O6 and O9 was observed only in patients with Hashimoto's disease (40.0% and 51.1% vs healthy subjects 24.7% and 29.9%, respectively). Patients with thyroid tumor showed no increase in any serotype of Yersinia enterocolitica. No correlations was found between the titers of anti-Yersinia antibodies and anti-thyroglobulin or anti-microsomal antibodies. These data indicate an association between thyroid autoimmunity and antibodies to Yersinia enterocolitica. These results are different from those in reports from other countries, suggesting that serotype specificity may be influenced by racial or genetic factors.

Antibodies, Bacterial↗

Subacute thyroiditis associated with systemic multi-organ disorders.

Subacute thyroiditis is generally thought to be a self-limited inflammatory disease of the thyroid gland. This paper describes serial observations on the clinical course of a typical patient with subacute thyroiditis. This patient showed specific features of destructive thyrotoxicosis with increases in the serum levels of acute phase reactants and in the erythrocyte sedimentation rate. She also showed signs of liver dysfunction [slightly increased alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (gamma-GTP), and leucine aminopeptidase (LAP)], slight anemia, glucose intolerance, increased pancreatic enzymes, splenomegaly, and an increase in peripheral Leu 7 positive (NK/K) cells. These abnormalities all improved with recovery from disease. These findings indicate that in this patient with subacute thyroiditis inflammation is not limited to the thyroid gland but also involves the liver, pancreas and spleen. Thus the subacute thyroiditis in this patient may be a systemic multi-organ disease.

Female↗