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Biomedical subjects

Y Sakatsume

Publications and source records attributed to Y Sakatsume.

18 recordsLinked to original sources
PubMed1996

Decrease in serum levels of thyroid hormone in patients with coronary heart disease.

The aim of this study was to evaluate the relationship between subclinical hypothyroidism and/or autoimmune thyroid disease and coronary heart disease (CHD). Ninety seven patients diagnosed as having CHD by a coronary angiography (CHD group) and 103 healthy subjects matched for age, sex and body mass index (control group) were included in the study. Thyroid function, thyroid autoantibodies and serum lipid concentrations were measured in the CHD and control groups. The CHD group exhibited significantly decreased serum free T3 (FT3) and free T4 (FT4) levels, and significantly increased serum TSH levels as compared with the control group, indicating a significant decrease in thyroid function in the CHD patients. Serum high density lipoprotein cholesterol (HDL-C) levels were significantly decreased in the CHD group. The incidence of subclinical hypothyroidism and thyroid autoantibodies was similar in both two groups. These observations were also true of women even after those who had diabetes mellitus (DM), hypertension (HT) and a smoking habit were excluded. This was not the case, however, in men without DM, HT, or a smoking habit. Patients with CHD had significantly lower serum levels of HDL-C than the control subjects, regardless of gender (P < 0.01). In the group with CHD, there was no difference between the serum lipid levels in patients with subclinical hypothyroidism and those with normal thyroid function. Female patients with CHD had significantly lower serum levels of thyroid hormone and HDL-C, but their subclinical hypothyroidism or thyroid autoimmunity did not seem to be related to the development of CHD.

Aged↗
PubMed1994

Disturbed lipid metabolism in patients with subclinical hypothyroidism: effect of L-thyroxine therapy.

To evaluate whether patients with subclinical hypothyroidism have a disturbance in lipid metabolism, and whether supplemental L-thyroxine (L-T4) therapy would improve their lipid parameters, we measured serum levels of thyroid hormones, TSH and lipid parameters in 34 patients with subclinical hypothyroidism before and 2 months after treatment with L-T4. Before treatment, patients with subclinical hypothyroidism had elevated serum low density lipoprotein cholesterol (LDL-C) concentrations compared with control subjects (P < 0.05). Overall, L-T4 therapy significantly decreased the serum level of TSH (P < 0.01), total cholesterol (TC; P < 0.02), high density lipoprotein cholesterol (P < 0.02), LDL-C (P < 0.05), and the ratio of apolipoprotein B to apolipoprotein A1 (P < 0.05). Lipid values in patients with basal serum TSH levels below 10 mU/l were not affected by L-T4 therapy, whereas serum levels of TC and LDL-C decreases significantly (P < 0.01) in patients with serum TSH levels above 10 mU/l. Thus, the L-T4 treatment appears to have a preventive effect on the disturbance of lipid metabolism in patients with subclinical hypothyroidism, especially in patients with serum TSH levels above 10 mU/l.

Adult↗
PubMed1991

Disturbance of thyroidal iodine metabolism in BB/W rat.

To investigate the thyroid function in Bio-Breeding Worcester (BB/W) rats, we have examined the iodine metabolism, serum TSH and thyroid hormone levels in 8- and 16-week-old BB/W and normal Wistar (W) rats. At 8 weeks of age, serum TSH levels were significantly higher in BB/W rats than in W rats, although there was no difference in the serum levels of free T3 and free T4. Furthermore, the thyroidal radioactive iodine incorporation at 48 h was significantly lower in BB/W rats, suggesting that they might have some defects in iodine organification. At 16 weeks of age, serum TSH levels were also significantly higher in BB/W rats than in W rats. Furthermore, serum TSH levels in 16-week-old BB/W rats were significantly higher than in 8-week-old BB/W rats. The thyroid weight was significantly greater in BB/W rats, probably due to the increased serum TSH. The thyroidal radioactive iodine uptake at 48 h and the iodine content in the thyroid homogenates were significantly lower in BB/W rats. These results suggest that BB/W rats have some defect in iodine metabolism resulting in impaired thyroid hormone synthesis.

Animals↗
PubMed1991

The effect of xenotransplantation of human thyroid tissue following radioactive iodine-induced thyroid ablation on thyroid function in the nude mouse.

We have attempted to determine whether xenotransplanted human thyroid tissue into nude mice would act as a physiological substitute for the mouse thyroid gland after the mice had been rendered hypothyroid, using radioactive iodine (131I). The dosage of 0.2 millicuries of 131I was given to each mouse. The xenotransplantations of human thyroid tissue, i.e., normal, Graves' and nontoxic multinodular goitre, were carried out three weeks after radioactive ablation. The values of TSH in all mice rose to high levels (71 +/- 15.6 ng/ml, +/- SD) by three weeks after 131I administration. The TSH values in the mice declined rapidly and reached normal levels by 3-5 weeks after xenotransplantation. In addition, the serum T4 values were generally in the euthyroid range by 3-6 weeks after xenotransplantation. There were no marked differences in the changes of serum T4 and TSH when the three groups were compared. These results indicated that the xenografted human thyroid tissue permitted a return to a normal feedback system as reflected by normal serum TSH and T4 values in the animals. The Graves' thyroid tissue reverted to normal physiological function when removed from its human (abnormal) immune environment, signifying that Graves' thyrocytes are mere passive captives to immune events. This model should prove to be useful in the study of human thyroid physiology and pathophysiology.

Animals↗
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

Effects of recombinant human interferon gamma on human thyroid tissues from patients with Graves' disease and normal subjects transplanted into nude mice.

We have attempted to determine whether interferon gamma (IFN gamma) would enhance, sustain or induce autoimmune thyroid disease (AITD) in xenotransplanted thyroid tissue from patients with Graves' disease or normal persons (actually paranodular tissue) in nude athymic mice, in the absence of an intact immune system. A dosage of 4000 U/mouse of human IFN gamma (hIFN gamma) was injected intraperitoneally daily for six consecutive weeks into the xenotransplanted mice. The parameters measured included the free T4 index, thyroid autoantibodies and TSH during the course of hIFN gamma injections. Thyroid epithelial cell (TEC) HLA-DR expression was measured in the thyroid tissue before xenotransplantation and at sacrifice; in addition, light and electron microscopic studies were carried out at those times. There were no significant differences in thyroid function between the control results and those obtained with hIFN gamma in either group of tissues. TEC HLA-DR expression was significantly increased by hIFN gamma in the normal group, but insignificantly in the Graves' group. In both light and electron microscopic observations, Graves' tissue (whether or not treated with hIFN gamma) was indistinguishable at sacrifice from normal thyroid tissue. The appearance had markedly altered from the same Graves' tissue examined at the time of the initial human surgery, which then showed the usual histological appearance of this disorder. We conclude that IFN gamma induced HLA-DR expression alone is not sufficient to sustain the ongoing process of AITD in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

The mechanism for the discrepancy between serum total and free thyroxine values induced by autoantibodies: report on two patients with Graves' disease.

The sera from two patients with Graves' disease gave abnormally high serum free T4 values as compared with the total T4 and other hormone values, suggesting the presence of autoantibodies to labelled T4 analogue used in the Amersham free T4 assay kit. The autoantibodies appeared to develop after the initiation of methimazole therapy and disappeared again after the cessation of methimazole. This binding activity to labelled T4 analogue was demonstrated to be in the immunoglobulin G with a kappa light chain isotype in both sera, and was displaced by unlabelled T4 in a dose-dependent manner. The binding of immunoglobulin G purified from these sera to labelled T4 or T4 analogue was found to be almost identical to that of the corresponding serum binding. Since the specific radioactivity of labelled T4 analogue used in the Amersham free T4 assay kit is about 10 times higher than that of the labelled T4 in the Amersham total T4 assay kit, serum free T4 determinations are much more vulnerable to thyroid hormone autoantibodies. Thus, in the presence of autoantibodies, a large discrepancy develops between free T4 and total T4 values.

Adult↗
PubMed1990

Effects of supernatants of peripheral blood mononuclear cells stimulated by thyroid microsomal antigen on thyrocyte HLA-dr expression in vitro.

Supernatants of 5 day cultures of peripheral blood mononuclear cells (PBMC) stimulated by thyroid microsomal antigens (TMA), and liver microsomal antigens (LMA) have been utilized to induce HLA-DR expression on human thyroid epithelial cells (TEC). The PBMC were obtained from 8 normal control persons and 13 patients with autoimmune thyroid disease (AITD) (7 Graves' disease and 6 Hashimoto's thyroiditis). The TEC HLA-DR expression was measured by an enzyme-linked immunosorbent assay (ELISA) technique. TEC HLA-DR expression was calculated as follows: (experimental optical density-control optical density) x 10(3): TEC HLA-DR index: % HLA-DR expression of IFN gamma 100 U/ml stimulation; and stimulation index (SI): TEC HLA-DR expression index induced by PBMC supernatants with antigen stimulation/TEC HLA-DR expression index induced by PBMC supernatants without antigen stimulation x 100. Supernatants without antigen stimulation from both normal control subjects and patients were able to induce TEC HLA-DR expression only minimally: 36.7 +/- 32.6 (mean +/- SD) TEC HLA-DR index for normal controls and 21.3 +/- 15.5 TEC HLA-DR index for AITD (not significant). The SI curves of both TMA and LMA were significantly different between control and AITD using two-way ANOVA test (p less than 0.01). TMA-stimulated PBMC supernatants from the patients increased TEC HLA-DR expression when compared to basal level using paired t-test; TMA 1 ng/ml, SI 179 +/- 99, less than 0.05.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1990

Peripheral blood T lymphocyte sensitization to thyroid microsomal antigen from patients with Graves' disease negative for circulating anti-thyroid microsomal antibodies.

We have studied thyrocyte HLA-DR expression induced by supernatants of peripheral blood mononuclear cells (PBMC) stimulated by thyroid microsomal antigen (TMA), as an index of sensitization of the T lymphocyte in autoimmune thyroid diseases; we have studied PBMC from 11 normal control persons and 19 patients with Graves' disease (GD) in whom serum anti-thyroid microsomal antibodies (AMA) were either not detectable (9 patients) or were positive (10 patients). Thyrocyte HLA-DR induction in response to TMA-treated PBMC supernatants from GD was significantly different from that of normal controls (p less than 0.05, ANOVA). TMA-stimulated GD PBMC supernatants increased thyrocyte HLA-DR index [TMA 1 ng/ml, SI 143 +/- 82 (mean +/- SD), p less than 0.05], but normal PBMC supernatants did not. However there was no significant difference in response in terms of the thyrocyte HLA-DR expression induced by TMA-stimulated PBMC supernatants between AMA seronegative vs seropositive GD. These results suggest the possibility of some dissociation of the activities of T lymphocytes and B lymphocytes in patients with GD in response to thyroid microsomal antigen with or without anti-thyroid microsomal antibodies.

Adult↗
PubMed1990

Serum interferon gamma levels in autoimmune thyroid disease.

The lymphokine, interferon gamma (IFN gamma) is considered to play an important role in the development of autoimmune thyroid disease (AITD); the main source of IFN gamma has been shown to be CD4 cells when stimulated by soluble antigen. We have measured the serum IFN gamma concentration in 42 patients with AITD (24 Graves' disease and 18 Hashimoto's thyroiditis) and 9 normal control subjects, using a sandwich enzyme-linked immunosorbent assay (ELISA) (detectable limit, 1 IU/ml). One of normal controls, 14 of the 24 patients with Graves' disease, and 5 of the 18 patients with Hashimoto's thyroiditis had detectable IFN gamma levels. Patients with Graves' disease were found to have higher concentrations of serum IFN gamma (11.6 +/- 15.8 IU/ml, mean +/- SD) than normal controls (1.1 +/- 0.3 IU/ml). However, the values in patients with Hashimoto's thyroiditis (9.4 +/- 15.5 IU/ml) were not significant when compared to those in normal controls. Serum IFN gamma values in patients with AITD did not correlate with serum anti thyroid autoantibodies (antithyroglobulin, antithyroid microsomal antibody, or TSH binding inhibitory immunoglobulin activity) or with thyroid function. Thus, increased in vivo production of IFN gamma in Graves' disease as evidenced in these serum concentrations might reflect T cell activity, but does not appear to be an accurate reflection of intrathyroidal events.

Autoantibodies↗
PubMed1989

Nontoxic nodular goiter and papillary thyroid carcinoma are not associated with peripheral blood lymphocyte sensitization to thyroid cells.

We tested the claim that uni- and multinodular goiter (UNG and MNG) and papillary carcinoma (PC) of the thyroid are autoimmune thyroid diseases (AITD) similar to Graves' disease (GD) and Hashimoto's thyroiditis (HT). The expression of HLA-DR on cultured thyroid epithelial cells (thyrocytes) from UNG, MNG, and PC after coculture with autologous peripheral blood mononuclear cells (PBMC) was compared with that on GD and HT cells. The thyrocytes also were cultured with interferon-gamma (IFN gamma) alone. A cytotoxicity assay involving 51Cr-labeled thyrocytes, anti-HLA-DR, and complement was used to determine HLA-DR expression. Stimulation of thyrocytes with 200 U/mL IFN gamma induced HLA-DR (expressed as a cytotoxicity index) equally well on all thyrocytes [AITD (n = 6): IFN gamma, 23.8 +/- 7.7 (+/- SD); unstimulated, 3.6 +/- 2.0; UNG (n = 6), MNG (n = 9), and PC (n = 5): IFN gamma, 22.5 +/- 4.7; unstimulated, 4.0 +/- 3.0]. When cocultured with autologous PBMC, the values were: AITD, 24.9 +/- 10.1; UNG, MNG, and PC, 3.8 +/- 3.7 (P less than 0.001). The supernatants from the AITD cocultures had higher IFN gamma concentrations (by RIA) than those from the other cocultures. We conclude that in UNG, MNG, and PC, the peripheral blood helper T-lymphocytes are not sensitized to thyrocyte membrane antigen(s); consequently, little if any IFN gamma is produced in cocultures, and hence, there is no increase in thyrocyte HLA-DR expression, unlike the situation in AITD (GD and HT). Thus, UNG, MNG, and PC are not primarily autoimmune in nature, as defined by a lack of sensitization of the PBMC of such patients to thyroid antigen(s).

Antigens, Surface↗
PubMed1987

[Development of highly sensitive assays of antithyroid microsomal antibodies and their clinical application--solid type ELISA using the avidin-biotin system].

We have developed new type of ELISA using avidin-biotin (AB) system in measuring antithyroid microsomal antibody (AMA). In the first method, AMA was detected by biotinylated anti-IgG (Indirect AB-ELISA) and in the second AMA was detected by biotinylated microsome antigen (Sandwich AB-ELISA). In the both methods, avidin-peroxidase was then added and peroxidase activity remained on the wells of a microplate was measured. In the study of samples from patients with Graves' disease with negative MCHA test (n = 39) and normal controls (n = 19), Indirect AB-ELISA showed a higher OD492 in Graves' patients than normal controls (p less than 0.01), whereas Sandwich AB-ELISA did not. In the study of patients with chronic thyroiditis which was confirmed by fine needle aspiration biopsy, 7 out of 9 samples with negative MCHA test and all of 11 with weakly positive MCHA test were positive in the Indirect AB-ELISA. These studies demonstrated the superior sensitivity of Indirect AB-ELISA than the other methods. Then the samples from patients with various kinds of diseases and negative MCHA test were assessed using this method. Forty-eight in 60 cases (80.0%) of Graves' disease, 3 in 4 cases (75%) of chronic thyroiditis, 6 in 7 cases (85.7%) of simple goiter, 7 in 8 cases (87.5%) of thyroid cancer, 2 in 9 cases (22.2%) of thyroid adenoma and 1 in 6 cases (16.7%) of pituitary hypothyroidism showed AMA activity. Therefore, autoimmune phenomena are far more common in various thyroid diseases than it has been previously recognized.

Autoantibodies↗
PubMed1987

Spontaneous in vitro production of thyroglobulin specific helper factor in patients with autoimmune thyroid diseases.

We have investigated regulatory cell abnormalities in patients with autoimmune thyroid diseases through in vitro thyroglobulin (Tg) specific helper factor production. Helper activities were measured in the mice spleen cell assays, using hapten-carrier system. Peripheral blood leukocytes (PBL) from 5 out of 6 patients produced the Tg specific helper factor not only when they were stimulated in vitro with Tg but also when they were not stimulated. On the contrary, normal PBL did not produce the factor when they were not stimulated in vitro. However, 3 out of 5 normal PBL did produce the factor when they were stimulated in vitro with Tg. From several lines of studies, this helper factor was specific for Tg in its production and action. From these results it is concluded that (a) Tg specific helper T cells are already activated in vivo in patients with autoimmune thyroid diseases, indicating the presence of immunoregulatory abnormalities in these patients, and that (b) normal PBL have a potential to produce this helper factor when they are appropriately stimulated.

Biological Assay↗
PubMed1986

Spontaneous autoimmune thyroiditis in Bio Breeding/Worcester (BB/W) rat.

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.

Age Factors↗
PubMed1986

Interference with thyrotropin receptor antibody determination by a spuriously occurring anti-bovine TSH antibody.

Abnormally negative values of thyrotropin binding inhibitor immunoglobulin (TBII) were found in the sera from a patient with Graves' disease. This was due to the presence of potent bovine TSH (bTSH) binding activity in the sera. This activity was demonstrated to be in immunoglobulin G (IgG) with a lambda light chain isotype, which was shown to have an affinity for bTSH with a Ka value of 3.5 X 10(10) M-1 and a maximum binding capacity of 1.1 X 10(-14) M/mg IgG. F(ab')2 fragments obtained through pepsin digestion from the patient's IgG retained bTSH binding activity. [125I] bTSH binding to this IgG was inhibited by the TSH receptor. The inhibition was not completely competitive, suggesting the presence of different binding sites for this IgG and the TSH receptor on the TSH molecule. This IgG, however, could not bind labelled human TSH (hTSH). Since neither TSH nor other pituitary derivatives had ever been given to the patient, this bTSH binding activity was considered to be due to a spuriously occurring anti-bTSH antibody.

Adult↗
PubMed1986

Decreased serum thyroglobulin levels in the late stage of pregnancy.

Serum thyroglobulin levels were serially measured in 25 normal pregnant women to evaluate thyroidal activity during normal pregnancy. Measurements included serum T3, T4, free T4, TBG, and TSH. Tg and FT4 levels were found to be decreased in the third trimester when compared with those of the first trimester and with those of normal non-pregnant individuals (P less than 0.01). TSH levels were higher than normal in pregnant women at all stages of pregnancy, with a significant rise at the third trimester. These findings suggest the presence of a subclinical hypothyroid state in the late stage of normal pregnancy.

Female↗
PubMedDate not supplied

Lack of response of peripheral blood mononuclear cells to thyroid microsomal antigen in nontoxic nodular goiters.

The production of interferon gamma (IFN gamma) by peripheral blood mononuclear cells (PBMC) from patients with nontoxic nodular goiter (NTNG), autoimmune thyroid disease (AITD), and normal persons (NL) has been studied in vitro, with the express object of comparing NTNG and AITD. PBMC were cultured with thyroid microsomal antigen (TMc), thyroglobulin (Tg), and liver microsomal antigen (LMc) at concentrations of 0, 1, 10, 100, and 1000 ng/ml for two days. IFN gamma was measured by a spot-ELISA technique which determines the number of cells secreting IFN gamma. There were no significant differences in the basal numbers of IFN gamma secreting cells between NL, AITD, and NTNG PBMC in this study. In AITD PBMC, TMc antigen caused a significant increase in the number of IFN gamma secreting cells, compared with the numbers in unstimulated AITD PBMC (percent IFN gamma secreting cells), whereas Tg and LMc antigen caused a significant decrease in all groups. The maximal percentage change in IFN gamma secreting cells (i.e., compared to unstimulated PBMC) did not increase significantly in NTNG in response to TMc antigen, in contrast to the AITD PBMC. Based on these findings, it is concluded that NTNG PBMC are not sensitized to the thyroid antigens tested; this is unlike the findings from AITD PBMC.

Adolescent↗