Search PubMed⌕ Search

Biomedical subjects

Y Iwatani

Publications and source records attributed to Y Iwatani.

At least 19 recordsLinked to original sources
PubMed1992

Decreases in alpha beta T cell receptor negative T cells and CD8 cells, and an increase in CD4+ CD8+ cells in active Hashimoto's disease and subacute thyroiditis.

We examined peripheral lymphocyte subsets in patients with autoimmune thyroid disease, or subacute thyroiditis, in the active stage when possible. During destructive thyrotoxicosis arising from alpha beta T cell receptor (TCR) negative T (WT31-CD3+) cells and CD8 (CD4-CD8+) cells decreased and those of CD4+CD8+ cells increased slightly, resulting in proportional increases in CD4 (CD4+CD8-) cells, non-T, non-B (CD5-CD19-) cells, and the CD4/CD8 cell ratio. Changes were similar in active subacute thyroiditis. During stimulative thyrotoxicosis in active Graves' disease, the numbers of such T lymphocyte subsets were not changed, but only the number of CD5+ B (CD5+CD19+) cells increased markedly, resulting in proportional decreases in total T (CD3+) cells, alpha beta+ TCR T (WT31+CD3+) cells, CD8 cells, and non-T, non-B cells. A serial study of some of the patients showed opposite changes in alpha beta TCR- T cells, the CD4/CD8 cell ratio, and CD5+ B cells between the active stages of Graves' and Hashimoto's diseases. alpha beta TCR- T cells were mostly gamma delta TCR+ T (IIF2+ CD3+) cells in these patients. These data suggest that alpha beta TCR-T (gamma delta TCR+ T), CD8, and CD4+ CD8+ cells are important in thyroid destruction in Hashimoto's disease and subacute thyroiditis, and that CD5+ B cells are important in thyroid stimulation in Graves' disease.

Adult↗
PubMed1992

Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in patients with autoimmune thyroid disease were examined. NK activity was measured in a 4-hr 51Cr-release assay and the number of NK cells was analyzed with FITC-conjugated monoclonal antibodies by use of an automated flow cytometer. NK activity in patients with untreated Graves' disease (n = 25, 39.7 +/- 13.5%, P less than 0.05) and Hashimoto's thyroiditis (n = 18, 41.0 +/- 14.2%, P less than 0.05) was high compared to the activity in non-pregnant controls (n = 61, 32.6 +/- 15.0%). NK activity in patients with postpartum Graves' thyrotoxicosis (n = 11, 48.6 +/- 18.9%) was markedly increased compared to the activity in non-pregnant controls (P less than 0.01) and in postpartum controls (n = 29, 33.8 +/- 15.2%, P less than 0.05), although the mean ages of each group did not differ significantly. Moreover, NK activities in the thyrotoxic state were significantly higher than those in the euthyroid state in the same patients with postpartum Graves' thyrotoxicosis or with postpartum destructive thyrotoxicosis. The number of CD16 positive cells increased in patients with postpartum Graves' thyrotoxicosis. However the number of CD16 and CD57 positive cells were normal in all other groups of patients. These results indicate that an increase of NK activity is associated with exacerbation of autoimmune thyroid disease both in Hashimoto's thyroiditis and in Graves' disease and suggest that NK cells might have an important role for the control of disease activity in autoimmune thyroid disease.

Adult↗
PubMed1992

[Changes of differential leukocyte counts during pregnancy and in the postpartum period].

We examined differential leukocyte counts in peripheral blood from 177 pregnant and postpartum women with an automated leukocyte differential system, and compared them with those of 52 nonpregnant and non-postpartum women. The proportions and numbers of neutrophils and monocytes increased throughout pregnancy, returned to the non-pregnant levels within one month after delivery, and decreased transiently at 4 or 7 to 10 months postpartum. The proportions and numbers of lymphocytes and eosinophils decreased throughout pregnancy, and increased transiently at 4 to 10 months postpartum and one month postpartum, respectively. The proportion and number of basophils decreased during pregnancy and one month postpartum, and those of large unstained cells (LUC) decreased in the third trimester of pregnancy, and both returned to the non-pregnant levels at 4 months postpartum and within one month postpartum, respectively. These data indicate that differential leukocyte counts change dynamically during pregnancy and after delivery until 1 year postpartum.

Adult↗
PubMed1992

[Decrease of CD16 antigen density on granulocytes in chronic myeloid leukemia].

We examined the fluorescence intensity of CD16 antigen, which represents the density of CD16 antigen, on granulocytes by flow cytometry in 15 healthy subjects and 15 patients with neutrophilia due to inflammatory diseases and 10 patients with chronic myeloid leukemia (CML). The fluorescence intensity of CD16 antigen was significantly lower in patients with CML than in healthy subjects and also than in patients with neutrophilia. These data indicate that 1) density of CD16 antigen on granulocytes decrease in CML, and 2) analysis on the density of granulocyte CD16 antigen is useful for differential diagnosis of CML from inflammatory diseases with neutrophilia.

Flow Cytometry↗
PubMed1991

Changes in natural killer cell activity in normal pregnant and postpartum women: increases in the first trimester and postpartum period and decrease in late pregnancy.

Changes in the activity and number of natural killer (NK) cells in peripheral blood in normal pregnant and postpartum women were examined. NK activity was measured in a 4-h 51Cr-release assay and evaluated by conventional relative lytic units and absolute lytic units which represent the total NK activity within a fixed volume of circulating blood. The number of NK cells was analyzed with FITC-conjugated monoclonal antibodies and by use of an automated flow cytometer. Unexpectedly, the relative NK activity increased in the first trimester and also for 1 month postpartum compared to the activity in normal non-pregnant controls. On the other hand, absolute NK activity decreased in the third trimester compared to the activity in normal non-pregnant controls. The percentage of CD57+ cells decreased in the second trimester, but the percentage of CD16+ cells did not change during pregnancy or the postpartum period. The absolute counts of CD57+ cells and CD16+ cells decreased in the second and third trimesters and increased transiently in the postpartum period. These findings indicate that the increased NK activity in the first trimester and at 1 month postpartum is induced by increased cytotoxic activity of individual NK cells, and that the decreased NK activity in late pregnancy is induced by a decrease in the numbers of NK cells. These physiological changes may play an important role in implantation in early pregnancy, protection of the fetal allograft in late pregnancy and in the natural defense against infection during the puerperal period.

Adult↗
PubMed1991

Detection of thyroid microsomal and thyroglobulin antibodies by new sensitive radioimmunoassay in Hashimoto's disease; comparison with conventional hemagglutination assay.

We evaluated clinical usefulness of thyroid microsomal antibody (MCAb) and thyroglobulin antibody (TGAb) measured by new sensitive radioimmunoassays (RIA). These assays are simple and reproducible; the intra- and inter-assay coefficients of variation were 3.6-6.8% and 6.6-13.2% in the MCAb assay, and 3.2-7.7% and 7.6-12.3% in the TGAb assay, respectively. In 126 patients with Hashimoto's disease, the antibody activity determined by this RIA correlated with that determined by the hemagglutination assay (HA) (r = 0.848 for MCAb, r = 0.686 for TGAb, p less than 0.001). MCAb was detected by RIA in all of 115 HA-positive and 4 of 11 HA-negative patients, and TGAb by RIA in all of 84 HA-positive and 29 of 42 HA-negative patients: the prevalence of MCAb was 94% and that of TGAb was 90% in the disease. Moreover, some showed high antibody activity only in RIA. In another group of 14 patients with biopsy-proved Hashimoto's disease with no antibody activity by routine HA tests, serum MCAb was detected in 3 (21%), TGAb in 11 (79%), and both activities in 2 (14%). Our results indicate that (1) the RIA tests are more sensitive than the conventional HA test, and that (2) the present RIA test for TGAb is more sensitive than that for MCAb in detecting autoimmune abnormalities, especially in patients with biopsy-proved Hashimoto's disease who give negative results in the HA test.

Adult↗
PubMed1991

[Effect of plasma on analysis of lymphocyte subsets].

We examined the effect of plasma on the analysis of lymphocyte subsets with a flow cytometer using whole blood cells. Removal of plasma from whole blood by washing them before labelling the lymphocytes with fluorescein-conjugated antibodies reduced the proportion of CD5+CD19+ cells and increased the proportions of CD16+ CD57- and CD16+ CD57+ cells, as compared with those measured without washing, but did not change the proportions of CD5+ CD19-, CD5- CD19+, CD4+ CD8-, CD4- CD8+ and CD16- CD57+ cells. Removal of plasma from whole blood also reduced the fluorescence intensity of CD4 and CD5 antigens and increased that of CD8, CD16, CD19 and CD57 antigens on each lymphocyte subsets. Characteristics of the changed lymphocyte subsets were to have a surface antigen with weak immunofluorescence on the flow cytometric analysis such as CD5 and CD16, and to have an unclear borderline between the positive and negative cells. Therefore, even slight changes in the fluorescence intensity of these antigens could change the proportion of CD5+ CD19+, CD16+ CD57- and CD16+ CD57+ cells. However, these changes were not observed, when using the washed blood cells as samples after readdition of plasma to them. These data suggest that removal of plasma from blood before labelling the lymphocytes with fluorescein-conjugated antibodies is necessary to make the sample condition equal for flow cytometric analysis of lymphocyte subsets.

Adult↗
PubMed1990

CD4 cells from patients with autoimmune thyroid disease secrete interferon gamma after stimulation by thyroid microsomal antigen; CD8 cells suppress this secretion.

The production of interferon gamma (IFN gamma) by peripheral blood mononuclear cells (PBMC) from normal persons and patients with autoimmune thyroid disease (AITD) has been studied in vitro either spontaneously or after stimulation with thyroid microsomal antigen (TMc) or liver microsomal antigen (LMc). The numbers of IFN gamma secreting cells were measured by a spot-ELISA technique. AITD PBMC spontaneously contained significantly more IFN gamma secreting cells than did normal control PBMC. Moreover, TMc antigen caused a significantly greater number of IFN gamma secreting cells in AITD PBMC than did LMc antigen, whereas there was no significant difference between the two antigens in the normal control PBMC preparations. Thus TMc antigen caused a stimulation of the number of IFN gamma secreting cells only in the AITD PBMC and not in the normal PBMC. CD4 plus B cells or CD4 cells alone (with monocytes in both instances) contained more IFN gamma secreting cells under unstimulated conditions than did CD8 cells in both groups. AITD CD4 plus B cells (or CD4 cells) contained more IFN gamma secreting cells than did normal cells, but there was no significant difference between both groups in terms of the number of CD8 IFN gamma secreting cells. Normal CD4 plus B cells (or CD4 cells) responded to TMc antigen significantly more than did total normal PBMC at 10 and 1,000 ng/ml TMc. This was not the case when patients' CD4 plus B cells (or CD4 cells) were compared with patients' total PBMC, in which there were no significant differences. This suggests that CD8 suppressor activity was inadequate in AITD and thus the deletion of CD8 cells did not result in an increase in IFN gamma secreting cells. When TMc antigen was added to AITD CD8 cells, there was a significant diminution of IFN gamma secreting cell numbers at 10 and 1,000 ng/ml TMc. Moreover, adding autologous CD8 cells to CD4 plus B cells resulted in a significant suppression of IFN gamma production at 100 and 1,000 ng/ml TMc in both groups. AITD CD8 cells appeared to be somewhat less effective than normal CD8 cells, but this did not reach significance. It is thus concluded that AITD CD4 cells respond specifically to TMc antigen. CD4 production of IFN gamma appears to be suppressed by CD8 cells activated with antigen and the CD8 cells appear to be involved in the regulation of IFN gamma production by the CD4 cells.

Adult↗
PubMed1990

[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↗
PubMed1990

[Determination of hepatitis B virus pre-S 2 antigen by reversed passive hemagglutination and its clinical significance].

Pre-S 2 antigen has been distinct as one of the hepatitis B virus (HBV) markers recently. We detected Pre-S 2 antigen by reversed passive hemagglutination (R-PHA) in 98 samples and investigated the correlation between Pre-S 2 antigen and other HBV markers. Forty-two samples in 98 surface(s) antigen positive samples were positive for Pre-S 2 antigen (42.9%). Nineteen samples in 21 e antigen positive samples and 20 samples in 74 e antibody samples were positive for Pre-S 2 antigen (90.5% and 27.0% respectively). Pre-S 2 antigen titers by half quantitative 2n dilution method ranged from 256 to 2048 or more in e antigen positive samples and from 8 to 64 in e antibody positive samples. They showed two-peak distributions. There were no significant correlation between Pre-S 2 antigen titers and GPT values. In conclusion, determination of Pre-S 2 antigen might be one of the useful indexes of proliferation of HBV.

Adult↗
PubMed1989

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↗
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↗
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

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↗
PubMed1987

Immunomodulatory effect of the treatment of Graves' disease on antigen-specific monocyte procoagulant activity production.

The monocyte procoagulant activity (PCA) production assay has been shown to be a good parameter of cell-mediated immunity. We have studied antigen-specific PCA production in peripheral blood mononuclear cells from patients with Graves' disease to determine the effect of the treatment on the cell-mediated immune response. Peripheral blood mononuclear cells from patients with untreated or relapsed Graves' disease produced significantly greater PCA with thyroid antigen stimulation than those from normal subjects. Patients both on antithyroid drugs in the hyperthyroid state and within 3 months post-131I therapy also produced significantly larger amount of PCA than normal subjects. However, there was no significant difference in PCA production with thyroid antigen stimulation between normal subjects and patients on anti-thyroid drugs in the euthyroid state, or patients over 3 months post-131I therapy. The ratio of positive to negative PCA production in patients on anti-thyroid drugs in the euthyroid state or over 3 months post-131I therapy was significantly lower than in untreated or relapsed Graves' disease patients. Mononuclear cells from patients on propylthiouracil responded to propylthiouracil in vitro by production of PCA. Cells from normal subjects, untreated Graves' disease patients, or patients with Hashimoto's thyroiditis did not produce PCA with propylthiouracil stimulation. Mononuclear cells from patients who were on propylthiouracil for more than 3 months produced greater PCA than those on the drug for less than 3 months, suggesting sensitization of lymphocytes to propylthiouracil during the course of treatment. However, after 131I therapy, they gradually became unresponsive to propylthiouracil. This study has shown that the activity of the antigen-specific response assessed by PCA production in mononuclear cells from Graves' disease patients declined after treatment, suggesting that the treatment exerted immunomodulatory effects.

Adolescent↗