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Biomedical subjects

Y Iwatani

Publications and source records attributed to Y Iwatani.

At least 91 records · Page 5Linked to original sources
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

Marked increase of CD5 + B cells in hyperthyroid Graves' disease.

We examined the proportions of B lymphocytes bearing CD5 cell surface antigen (CD5+ B cells), which are capable of making autoantibodies, in peripheral blood from patients with various thyroid diseases. The level of CD5+ B cells was markedly increased (>9.0%) above the normal range (0.5-7.7%) in untreated, hyperthyroid patients with Graves' disease, although about 10% of the patients had no detectable serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb). However, the levels of CD5+ B cells were normal in untreated patients with destructive thyrotoxicosis due to aggravation of Hashimoto's thyroiditis or subacute thyroiditis. In patients with stimulated hyperthyroid Graves' disease the levels of CD5+ B cells were correlated with those of thyroid hormones and TRAb, all significantly increased. However, once hyperthyroidism was controlled by anti-thyroid drugs, CD5+ B cells were decreased, followed in turn by reduction of TRAb. We conclude that the proportion of CD5+ B cells is useful as a therapeutic index and for diagnosis of Graves' disease and its differentiation from destruction-induced thyrotoxicosis.

Adult↗
PubMed1989

Discordant changes in serum anti-TSH receptor antibody and antithyroid microsomal antibody during pregnancy in autoimmune thyroid diseases.

Immunological effect of pregnancy on the level of anti-TSH receptor antibody (TRAb) and antithyroid microsomal antibody (MCAb) was examined serially in twelve patients; ten with active Graves' disease treated with antithyroid drugs for some time during pregnancy, one with previous Graves' disease with stimulating type TRAb, and one with primary atrophic hypothyroidism with blocking type TRAb. TRAb was measured by radioreceptor assay (TSH-binding inhibitor immunoglobulin, TBII) and MCAb was determined by radioimmunoassay. Among the ten patients with active Graves' disease, TBII level decreased as pregnancy progressed in seven but increased during pregnancy in three, whereas MCAb level decreased uniformly during pregnancy in all ten patients. However, possible immunosuppressive effect of antithyroid drugs on these antibody levels could not be completely excluded in these patients. On the other hand, in the two consecutive pregnancies of the patient with previous Graves' disease, TBII level increased "spontaneously" to 10-fold the initial value at 30 weeks during the first pregnancy, while it did not show consistent increase or decrease during the second one. Another patient with primary hypothyroidism showed increase in TBII level during pregnancy to 5-fold the initial value at week 28. In contrast to these TBII changes, MCAb levels and immunoglobulin concentrations decreased consistently during pregnancy in these two patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1989

Cellular immunity as a valuable factor for prognostic prediction in patients with Graves' disease under antithyroid drug therapy.

Studies were performed on 42 unselected clinically euthyroid patients with Graves' disease under maintenance doses of antithyroid drugs for various clinical parameters to determine the remission rate and to investigate which parameters carry weight in determining the outcome of the disease and could be good predictive factors. T3 suppression test was performed in all patients, after which antithyroid drugs were discontinued and outcome of drug therapy was evaluated for 18-24 months. Patients were divided into two groups; group A, 12 patients, who stayed in remission and group B, 30, who had recurrence during the first year (0.5-9 months) after discontinuation of therapy. Duration of clinical history was not different between group A (mean 62.3 months) and group B (59.6 months), nor euthyroid periods before the test (15.5 months for group A and 17.6 months for group B). For thyroid specific parameters T4, T3, RT3U, TSH, thyroglobulin (Tg), thyroid suppressibility after T3 administration and goiter size; and anti-thyroglobulin antibody (TGHA), anti-thyroid microsomal antibody (MCHA), TSH-binding inhibitor immunoglobulins (TBII), thyroid-stimulating antibodies (TSAb), peripheral lymphocytes count and lymphocyte subsets [CD3, CD4, CD8, Leu7 and CD20 (B1)], as immunological parameters were analysed by linear discriminant analysis method to observe the significance in discriminating patients with or without remission and to evaluate the validity for predictive factors. (ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

[Laboratory tests for cellular immunology: flow cytometric analysis of lymphocyte subsets].

Flow cytometric analysis for lymphocyte subsets provides two kinds of data: proportion of fluorescence-positive cells (lymphocyte subsets) and the fluorescence intensity. For proportional analysis of lymphocyte subsets, lymphocytes are fractionated with a conventional gate window in scatter analysis, but if activated or enlarged lymphocytes are examined, lymphocytes should be fractionated with an extended gate window. On the other hand, fluorescence intensity of a lymphocyte subset, which represents density of cell surface antigen detected by fluorescence-conjugated specific antibody, is not measured in routine tests yet. However, data on fluorescence intensity are often more valuable than the proportions of lymphocyte subsets: e.g., decrease in fluorescence intensity, but not in proportion, of CD8+ cells in active Graves' disease, and marked decrease in fluorescence intensity of OKT4+ cells in a carrier of familial OKT 4 epitope deficiency. Furthermore, two-color flow cytometry has enabled to measure more valuable, classified subsets of lymphocytes than single color flow cytometry. For example, measurement of peripheral CD5 (Leu-1)+ B cells is very useful for diagnosis of Graves' disease and its differentiation from destruction-induced thyrotoxicosis. In conclusion, we showed that measurement of fluorescence intensity of lymphocyte subsets and two-color flow cytometry are useful for laboratory tests of lymphocyte subsets.

Flow Cytometry↗
PubMed1988

Universal predictive criteria for neonatal overt thyrotoxicosis requiring treatment.

The universal predictive criteria for neonatal overt thyrotoxicosis requiring treatment were examined in 108 neonates (including a pair of twins) born to mothers with Graves' disease (36 patients under treatment with antithyroid drugs [group A] and 71 in remission [group B]). Anti-thyroid-stimulating hormone (TSH) receptor antibody activity was measured by both radioreceptor assay (TSH-binding inhibitor immunoglobulin [TBII]) and biologic stimulation assay (thyroid stimulating antibody [TSAb]). For generalization of the predictive criteria, the expression of TBII activity was standardized using standard serum made taking units of Medical Research Council long-acting thyroid stimulator, standard B as a reference, and expression of TSAb activity was standardized using bovine TSH as a standard. TBII activity was positive in 22 mothers at delivery, and TSAb activity was positive in 18. In 12 cases, both activities were positive. Both the TBII and the TSAb activity of maternal serum at delivery correlated well with that of the cord serum. Neonatal thyrotoxicosis occurred in 9 of 108 neonates (8%), of whom five (5%) had clinical overt symptoms requiring antithyroid drug treatment. In all nine cases the TBII and TSAb activities were both positive, but no neonate without TBII or TSAb activity developed thyrotoxicosis. The prediction rate (42%) of neonatal overt thyrotoxicosis was higher when both TBII and TSAb were measured than when only TBII (23%) or TSAb (28%) was measured. Clinical overt thyrotoxicosis could be predicted in five of six neonates (83%) of mothers when the cutoff levels of antibody activities were increased to a TBII activity of above 8 U/ml and TSAb activity of above 1.0 TSH microUEq.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1988

Effects of different sample preparations on enumeration of large granular lymphocytes (LGLs), and demonstration of a sex difference of LGLs.

Peripheral natural killer (NK) cells were identified by their morphologic appearance as large granular lymphocytes (LGLs) in a cytocentrifuged or spun blood film but not in thin wedge blood film. The authors studied the effect of different methods of sample preparation and staining on the enumeration of peripheral human LGLs as a routine test. In the blood film made from anticoagulated venous blood, LGLs were scattered in a field and sometimes deformed by compression of erythrocytes. In a blood film made from mononuclear cells, LGLs were shrunken, rendering it difficult to always identify cytoplasmic granules. In contrast, LGLs were easily and accurately identified in a blood film made from leukocyte-rich plasma, displaying none of the above artifacts. As well, the percentage of LGLs obtained was similar to that obtained from a blood film made from anticoagulated venous blood. In addition, May-Grünwald-Giemsa (MGG) stained azurophilic granules more clearly than did Giemsa above. As a result of these observations, a blood film that was made from leukocyte-rich plasma and that was stained by MGG was considered to be most suitable for the routine enumeration of LGL. Using this method, the authors found a significant correlation between the percentages of LGLs and Leu-7+ cells in the same subjects (r = 0.71; n = 22; P less than 0.001) and also a significant sex difference in the percentages of peripheral LGLs, which were significantly lower in women (17.0 +/- 3.6%; n = 35; P less than 0.05) than in men (19.5 +/- 5.3%; n = 20). Furthermore, the percentage of LGLs with abundant cytoplasmic granules, which might have greater NK activity, was also significantly lower in women (15.9 +/- 3.1%; n = 35; P less than 0.01) than in men (17.9 +/- 4.0%; n = 20).

Adult↗
PubMed1988

Changes of lymphocyte subsets in normal pregnant and postpartum women: postpartum increase in NK/K (Leu 7) cells.

Changes in lymphocyte subsets in whole blood of normal pregnant and postpartum women were examined by flow cytometry with an automated leukocyte differential system. From the first trimester and throughout pregnancy, the absolute counts of T(CD3) and B(CD20) and T-cell subsets (CD4, CD8) decreased with a decrease in the absolute lymphocyte count, although the proportions of these cells remained unchanged except for a decrease in the percentage of T helper-inducer (CD4) cells in the first trimester. On the contrary, the percentage of NK/K (Leu 7) cells, but not of NK/K (CD16) cells, increased in the first trimester and then both gradually decreased in the second and third trimesters. In the postpartum period, the percentages and absolute counts of T(CD3) and NK/K (Leu 7) cells, but not of other cells, increased transiently. These changes of lymphocyte subsets may indicate suppression of immunological activity during pregnancy and its "increase" in the postpartum period.

Adult↗
PubMed1988

Long term follow-up and HLA association in patients with postpartum hypothyroidism.

The long term clinical outcome of postpartum hypothyroidism was investigated by follow-up studies of 44 patients (59 postpartum episodes; mean age of mothers at delivery, 28.2 yr) 5 or more yr later (mean interval after delivery, 8.7 yr; range, 5-16 yr). Forty-nine episodes (83%) in 34 women were followed by recovery within 1 yr postpartum, and those women remained euthyroid thereafter (group A); 10 women [10 episodes (17%)] developed permanent hypothyroidism during the follow-up period (group B). Five women in group B recovered during the first year, but became hypothyroid again later, the other 5 women in Group B remained persistently hypothyroid. HLA typing revealed significantly higher frequencies of HLA-DR3, -DRW8, -DRW9, -A26, -BW46, and -BW67, and significantly lower frequencies of HLA-DR2, -BW52, -BW62, and -CW7 in women with postpartum hypothyroidism than in normal women. Of 9 women with postpartum hypothyroidism who had HLA-DRW9 and/or -B51 associated with antithyroglobulin-antibody titers of 2(3) X 10 or higher, 6 developed permanent hypothyroidism. We conclude that long term follow-up is essential for women of postpartum hypothyroidism because of the risk of permanent hypothyroidism. The results suggest that some immunogenetic factors may be related to the etiology of postpartum hypothyroidism and that women with HLA-DRW9 and/or -B51 and higher titers of antithyroglobulin antibody are likely to develop permanent hypothyroidism.

Adult↗
PubMed1988

Studies of the effect of suppressor T lymphocytes on the induction of antithyroid microsomal antibody-secreting cells in autoimmune thyroid disease.

The suppressor function in CD8 (suppressor/cytotoxic) T lymphocytes from patients with autoimmune thyroid disease and normal subjects has been studied. CD8 and CD4 (helper/inducer) cells were separated by the panning method. Patient's non-T cells and autologous CD4 cells were cultured with or without autologous or allogeneic CD8 cells in the presence of either pokeweed mitogen or Staphylococcus aureus strain Cowan 1 plus human thyroid microsomal antigen. Antithyroid microsomal antibody (AMA) and total immunoglobulin G (IgG)-secreting non-T cells were measured by enzyme-linked immunosorbent spot assay. With pokeweed mitogen stimulation, the suppressor effect of CD8 cells from patients with serum AMA on the induction of AMA (of IgG type)-secreting cells was significantly less than that of CD8 cells from normal subjects. CD8 cells from patients with no serum AMA suppressed the induction of AMA-secreting cells as much as did normal CD8 cells. CD8 cells from both patients and normal subjects suppressed the induction of IgG-secreting cells equally well. On the other hand, with the combination of S. aureus strain Cowan 1 and human thyroid microsomal antigen (1 mg/L) stimulation, CD8 cells from both normal subjects and patients only slightly suppressed the induction of IgG-secreting cells. However, under these circumstances, once again, CD8 cells from both normal subjects and patients with no serum AMA suppressed the induction of AMA-secreting cells, whereas CD8 cells from patients with serum AMA suppressed the induction of the AMA-secreting cells significantly less. Higher TMc concentrations enhanced the suppressor effect of CD8 cells from patients with serum AMA on the induction of AMA-secreting cells. Furthermore, Concanavalin A, when added to the stimuli described above, further inhibited the induction of both AMA- and IgG-secreting cells by CD8 cells from patients with serum AMA. There thus appears to be a relative defect of antigen-specific suppressor T lymphocyte function in CD8 cells from patients with autoimmune thyroid disease, which may result in the presence of autoantibody-secreting cells in those patients.

Adult↗
PubMed1988

In vitro induction of anti-thyroid microsomal antibody-secreting cells in peripheral blood mononuclear cells from normal subjects.

Secretion of immunoglobulin G (IgG) and IgM antithyroid microsomal antibodies (AMA) was induced in vitro by coculturing non-T cells (B lymphocytes) and autologous CD4 (helper/inducer) cells from normal subjects stimulated with pokeweed mitogen (PWM) or a combination of human thyroid microsomal antigen (McAg) and Staphylococcus aureus Cowan I (SAC) strain. With PWM stimulation, AMA production was induced in more IgM-secreting cells (AMA-M) than IgG-secreting cells (AMA-G). However, McAg plus SAC stimulation resulted in similar numbers of AMA-G- and AMA-M-secreting cells. PWM induced a significantly greater number of both AMA-M (and generalized IgM)-secreting cells than did McAg plus SAC, while the number of AMA-G-secreting cells induced by the two stimuli were similar. There were no significant differences between autologous or allogeneic CD4 cells from normal subjects or patients with autoimmune thyroid disease (AITD) when cocultured with B cells from normal subjects in terms of helper activity in the induction of AMA-M- or IgM-secreting cells with PWM stimulation. However, with McAg plus SAC, CD4 cells from patients with AITD induced a significantly greater number of AMA-M-secreting cells than did autologous or allogeneic CD4 cells from normal subjects. There was no difference in helper activity between autologous and allogeneic normal CD4 cells in the induction of generalized IgM-secreting cells regardless of the stimulus used. Normal autologous or allogeneic CD8 (suppressor/cytotoxic) cells cocultured with normal B cells and autologous CD4 cells suppressed the induction of AMA-M-secreting cells by PWM stimulation. On the other hand, CD8 cells from patients with AITD suppressed the induction of AMA-M-secreting cells significantly less effectively. All CD8 cells suppressed the induction of IgM-secreting cells equally well. We conclude that 1) B lymphocytes from normal subjects are capable of producing autoantibodies in vitro in the presence of CD4 cells; 2) the helper activity of CD4 cells from patients with AITD to induce AMA-M secreting cells is greater than that of normal CD4 cells with thyroid antigen stimulation; and 3) this helper activity may be due to relatively impaired suppressor activity in thyroid antigen-specific CD8 cells from patients with AITD, whereas the immunoregulatory function of CD8 cells from normal subjects appears to play an important role in the maintenance of self-tolerance.

Adult↗
PubMed1988

Increase in antideoxyribonucleic acid antibody titer in postpartum aggravation of autoimmune thyroid disease.

Serum antidouble stranded DNA antibody levels were measured during pregnancy and after delivery in women who had postpartum exacerbations of Graves' and Hashimoto's diseases. The changes in serum anti-DNA antibody levels closely paralleled those in the serum free T4 index, significantly increasing in the thyrotoxic phase 3-8 months postpartum in women with postpartum exacerbations of thyrotoxicosis due to Graves' disease and 1-3 months postpartum in women with postpartum destructive thyrotoxicosis of Graves' and Hashimoto's diseases. No change in anti-DNA antibody level was found in women with no postpartum exacerbations of thyroid diseases, nor could we demonstrate significant increases in serum anti-DNA antibody titers in patients with thyrotoxicosis due to subacute thyroiditis or in normal pregnant and postpartum women. The changes in serum anti-DNA antibody titers may reflect some generalized immunological abnormality in women who have postpartum exacerbations of Graves' or Hashimoto's diseases.

Adult↗
PubMed1988

Increase in peripheral large granular lymphocytes in postpartum autoimmune thyroiditis.

In order to elucidate the mechanism of postpartum aggravation of autoimmune thyroid disease (AITD), we serially examined the change in the proportion of peripheral large granular lymphocytes (LGL), which have activities of NK, K and/or cytotoxic T cells, in their postpartum period. Within 6 months postpartum, the percentage of LGL increased transiently in patients with AITD who remained euthyroid, or developed destructive thyrotoxicosis and/or hypothyroidism due to thyroiditis and even in normal controls. These changes in the LGL percentage were more obvious in the patients who had marked postpartum thyroid dysfunction. In contrast, we did not find a definite increase in the LGL percentage within 6 months postpartum in patients with Graves' disease who relapsed into Graves' thyrotoxicosis. These deta suggest that the increase in LGL in the postpartum period may be related to the induction of postpartum destructive thyrotoxicosis and/or hypothyroidism in AITD.

Female↗
PubMed1988

Production of antigen specific procoagulant activity; effect of various culture supernatants.

Culture supernatants (CS) of peripheral blood mononuclear cells (PBM) from normal subjects and patients with autoimmune thyroid disease (AITD) have been tested for procoagulant inducing activity. CS of PBM from patients with AITD stimulated with solubilized thyroid antigen induced significantly greater procoagulant activity (PCA) in a human monocyte-like cell line, U937, than CS of PBM from normal subjects similarly tested, suggesting that PBM from patients released a procoagulant inducing factor(s) into ambient fluid in response to thyroid antigen stimulation. There was a significant correlation between PCA inducing activity in PBM and that in CS from those same PBM cultures. CS from normal T lymphocytes stimulated with large amounts of thyroid antigen (putative suppressor factor) had no suppressive effect on thyroid antigen-induced PCA production in PBM from patients with AITD. These observations suggest that the helper activity for antigen-induced PCA production appears to be mediated, at least in part, by soluble factor(s); conversely, these helper cells were not apparently subject to suppressor influences under these circumstances.

Adolescent↗