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Biomedical subjects

Y Iwatani

Publications and source records attributed to Y Iwatani.

At least 55 records · Page 3Linked to original sources
PubMed1996

A sustained increase in beta-adrenoceptors during long-term therapy with metoprolol and bisoprolol in patients with heart failure from idiopathic dilated cardiomyopathy.

Effects of long-term therapy with beta 1-selective antagonists (metoprolol, bisoprolol) on beta-adrenoceptors in lymphocytes of patients with idiopathic dilated cardiomyopathy (DCM) were examined. There was a significant reduction in the number of lymphocyte beta-adrenoceptors in patients with DCM compared to that in healthy volunteers, as demonstrated by a selective decrease in maximum number of binding sites (Bmax) for (-)-[125I]iodocyanopindolol (CYP). A therapy with metoprolol and bisoprolol in these patients caused a marked increase in lymphocyte beta-adrenoceptor density. The significant increase was observed from 2 or 3 months after the start of therapy with these drugs, and it was maintained during the therapy for 24 months. The left ventricular ejection fraction in patients with DCM was improved by the long-term therapy with metoprolol and bisoprolol, and this effect seems to be correlated with an observed enhancement of lymphocyte beta-adrenoceptors in the time course. Also, the increase in lymphocyte beta-adrenoceptors appears to be correlated with a gradual amelioration in circulating catecholamine levels by the long-term therapy with beta-adrenoceptor antagonists in patients with DCM. Thus, the present study suggests that beta-adrenoceptors in lymphocytes of patients with DCM are up-regulated by a long-term therapy with metoprolol and bisoprolol.

Adrenergic beta-2 Receptor Antagonists↗
PubMed1996

Studies on unusual cytoplasmic structures which contain rabies virus envelope proteins.

We investigated unusual structures produced in BHK-21 cells infected with rabies virus (HEP-Flury strain). Sellers' staining of the cells revealed, in addition to Negri body-like structures (inclusion bodies), production of a fuchsin-stained cytoplasmic structure (FCPS) which encircled the nucleus. The frequency of the FCPS-forming cells increased as replication progressed. The FCPS was different from the inclusion body because the former contained the viral glycoprotein (G) and matrix protein (M2) antigens, while the latter contained nucleocapsid antigens. In the early phase of infection, we observed accumulation of viral envelope antigens in a cytoplasmic structure that was considered to be expanded rough endoplasmic reticulum (rER) because of its concomitant increase in BiP content. Time-course studies suggested that the envelope antigen-containing structure, which was not stained with basic fuchsin, translocated to the perinuclear region to form the FCPS. FCPS formation was dependent on incubation temperature and was decreased at 30 degrees C, while the development of virus-induced cytopathic effect (CPE) was delayed. When the incubation temperature was shifted up to 37 degrees C, FCPS formation was induced again and progression of CPE was accelerated in approximate proportion to the increasing number of FCPS-positive cells. From these studies, we conclude that viral G proteins gradually accumulate in the rER with M2 protein and the expanded rER converts eventually into the FCPS, which may be closely related to accelerated host cell death.

Animals↗
PubMed1996

Changes in soluble CD4 and CD8 proteins in healthy pregnant and postpartum women.

PROBLEM: We examined physiological changes in serum levels of soluble CD4 (sCD4) and soluble CD8 (sCD8) during pregnancy and 1-12 months postpartum to study changes in the maternal immune system during and after pregnancy. METHOD: The serum concentrations of sCD4 and sCD8 were measured by enzyme immunoassay in the sera separated from blood samples withdrawn from healthy women in the 1st, 2nd, and 3rd trimesters of pregnancy and 1, 4, 7, and 10-12 months postpartum (n = 182) and healthy non-pregnant women (n = 25), and in 90 of the women, the changes in sCD4 and sCD8 were compared with changes in the number of peripheral CD4+ and CD8+ cells measured by flow cytometry. RESULTS: The serum concentration of sCD4 decreased throughout pregnancy, from the first trimester, and recovered gradually after delivery. The serum concentration of sCD8 did not change significantly during or after pregnancy compared to the concentration in the non-pregnant controls, but the concentration 1 month postpartum was significantly higher than that in the 3rd trimester. The number of CD4+ and cd8+ cells decreased during pregnancy but did not change significantly after delivery. Interestingly, the ratio of the serum sCD4 level to the number of CD4+ cells decreased and the ratio of the sCD8 level to the number of CD8+ cells increased in the first and second trimesters of pregnancy, but these ratios were within the normal range from the third trimester of pregnancy to 10-12 months postpartum. CONCLUSIONS: Decreases in serum sCD4 concentration and in the ratio sCD4/CD4+ cells, and an increase in the ratio sCD8/CD8+ cells may be important factors in the immunological changes that occur during pregnancy.

Adult↗
PubMed1995

Study on an antibody against F1F2 fragment of human factor V in a patient with Hashimoto's disease and bullous pemphigoid.

We found a 81-year-old man with Hashimoto's disease and bullous pemphigoid whose activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged. Mixing studies with normal plasma failed to correct APTT and PT, suggesting the presence of circulating inhibitor. The patient's factor V activity was 11% of normal control and was not corrected by mixing with normal plasma, indicating the presence of an inhibitor against factor V. This inhibitory activity was observed up to 32 times dilution of the patient's plasma. The inhibitor activity against factor V was not detected in the fraction of the patient's plasma that passed through Protein A Sepharose, but detected in the elution with glycine-HCl buffer. Furthermore, using SDS-PAGE and immunoblotting method, purified IgG from the patient's plasma reacted with a protein with molecular weight (74KD) equivalent to F1F2 of factor Va which was activated by thrombin. The inhibitory activity was associated with IgG4 subclass. These data indicate that the inhibitor was IgG antibody which inhibit F1F2 of factor V. Autoimmune mechanism was strongly suggested for the development of the antibody.

Aged↗
PubMed1995

Euthyroid Graves' disease showing no thyroid abnormalities except positive thyroid-stimulating antibody (TSAb): two case reports.

We report two cases of euthyroid Graves' disease in women who had ophthalmopathy without previous history of hyperthyroidism. Enlargement of extraocular muscles was observed by magnetic resonance imaging (MRI). The patients had no thyroid enlargement and their serum concentrations of free T4, free T3, and TSH were normal. The sera were negative for antithyroid microsomal and thyrogobulin antibodies, and anti-TSH receptor antibodies measured by radioreceptor assay. T3 suppression test results were normal. Only thyroid-stimulating antibody (TSAb) measured by sensitive bioassay was positive. These findings indicate that sensitive TSAb is the most useful laboratory test in the diagnosis of euthyroid Graves' disease.

Adult↗
PubMed1995

Hashimoto thyroiditis: correlation of MR imaging signal intensity with histopathologic findings and thyroid function test results.

PURPOSE: To assess the clinical usefulness of magnetic resonance (MR) imaging of the thyroid gland in Hashimoto thyroiditis. MATERIALS AND METHODS: Signal intensity ratios on spin-echo T1-, proton-density-, and T2-weighted images were measured prospectively in 37 patients with Hashimoto thyroiditis (33 women, four men; mean age, 51 years) and in 10 patients with thyroid lymphoma (six women, four men; mean age, 68 years). Signal intensity ratios were correlated with histopathologic findings and thyroid function test results with stepwise regression analysis. Diagnosis of lymphoma with signal intensity ratios was compared with morphologic diagnosis by using receiver operating characteristic curves. RESULTS: A proton-density-weighted signal intensity ratio of 1.54 or higher indicated hypothyroidism (R = .445, P = .008; 29% sensitivity [two of seven patients]). A T2-weighted signal intensity ratio of 5.08 or higher suggested advanced glandular destruction (R = .677, P < .001). Diagnosis by each observer was better than diagnosis with signal intensity ratios. CONCLUSION: MR imaging results can reflect thyroid function and histopathologic findings in the thyroid gland and help discriminate malignant lymphoma from Hashimoto thyroiditis.

Adult↗
PubMed1995

Significance of thyroid stimulating antibody and long term follow up in patients with euthyroid Graves' disease.

We examined 13 patients with euthyroid Graves' disease suspected ophthalmologically, by comparing them with 20 patients with untreated Graves' disease and by following them up for 5 to 10 years. They had Graves' ophthalmopathy (NOSPECS class II-IV) without other ocular diseases, normal levels of serum thyroid hormones, and no previous history of Graves' disease. Proptosis in euthyroid Graves' disease was not significantly different from that in untreated Graves' disease. In 3 patients with euthyroid Graves' disease, TSH was suppressed. There was either no TSH response to TRH or it was low in 7 of 12 patients examined. The result of a T3-suppression test was abnormal in 8 of 11 patients examined. Titers of serum TGHA, MCHA, TSH-binding inhibitory immunoglobulin (TBII), and thyroid stimulating antibody (TSAb) were significantly lower in patients with euthyroid Graves' disease compared than in patients with untreated Graves' disease. TSAb, however, was positive in 12 of 13 (92%) patients. In spite of positive TSAb, 9 of 13 patients with euthyroid Graves' disease had normal radioactive iodine uptake (RAIU). During the observation period, various abnormalities in thyroid function developed: persistent hyperthyroidism in 5 patients (38%), transient thyrotoxicosis in 2 (15%) and transient hypothyroidism in 1 (8%). We conclude that euthyroid Graves' disease is a subtype of Graves' disease that minimally develops thyrotoxicosis in spite of the existence of TSAb due to some mechanism inhibiting thyroid growth or stimulation, and that the measurement of TSAb provides a useful marker for the diagnosis of this disease.

Adult↗
PubMed1995

Long-term effects of thyroid hormone on lymphocyte subsets in spleens and thymuses of mice.

We examined the effects of the long-term administration to mice of thyroid hormone or propylthiouracil (PTU) on lymphocyte subsets in spleens, and thymuses to clarify whether hyperthyroxinemia itself causes the changes in lymphocyte subsets, such as the marked increase in CD5+ B cells and decrease in natural killer (NK) cells, observed in hyperthyroid Graves' disease. Both the number and proportion of splenic NK (Thy-1+ asialo GM1+) cells were increased in hyperthyroxinemic mice treated with thyroxine (T4) for both short and long terms (8 and 32 weeks, respectively), those of splenic and thymic T (CD5+ sIgM-) cells and CD5-B cells were increased only in hypothyroxinemic mice treated with PTU for 32 weeks, compared with those in euthyroid mice. These data indicate that 1) long-term hyperthyroxinemia increases splenic and thymic T cells and splenic NK cells, but not CD5+ B cells, in mice, 2) long-term hypothyroxinemia induced by PTU treatment increases splenic B cells and CD5- B cells, and 3) hyperthyroxinemia itself does not cause the changes in CD5+ B cells and NK cells, which are observed in hyperthyroid Graves' disease, in mice.

Animals↗
PubMed1994

Prediction of post-partum Graves' thyrotoxicosis by measurement of thyroid stimulating antibody in early pregnancy.

OBJECTIVE: Autoimmune thyroid diseases often occur after delivery. However, it has been difficult to predict who will develop Graves' thyrotoxicosis after delivery. We tried to establish a systematic method for predicting post-partum onset of Graves' thyrotoxicosis. DESIGN: We followed up the pregnant women with antithyroid microsomal antibody (MCAb) from early pregnancy to the post-partum period and analysed the relation between the activities of thyroid stimulating antibodies (TSAb) in early pregnancy and post-partum occurrence of Graves' disease. PATIENTS: Seventy-one women with positive MCAb in early pregnancy were studied. They were randomly selected from 262 MCAb-positive subjects found in 3405 consecutive early pregnant women who attended our maternity clinic during the last ten years. MEASUREMENTS: MCAb was measured with a commercially available agglutination kit. For 71 MCAb-positive subjects, TSH-binding inhibitory immunoglobulin (TBII) and TSAb were measured in early pregnancy, and serially until 6 months after delivery for the subjects with either positive TBII or TSAb. Thyroid function and goitre size were recorded at every observation. RESULTS: Among the 71 subjects, 7 showed positive TSAb in early pregnancy without any thyroid dysfunction; all 7 developed thyroid dysfunction in the post-partum period. Five of them (70% of TSAb-positive subjects) developed Graves' disease, two showing persistence and three transiently. None of 64 TSAb-negative subjects developed Graves' thyrotoxicosis, though 44 developed various types of thyroid dysfunction as a result of post-partum autoimmune thyroiditis. CONCLUSION: The individuals at high risk of post-partum onset of Graves' thyrotoxicosis can be found early in their pregnancy by the detection of TSAb. Overall occurrence of post-partum Graves' disease in the general population is estimated above 0.54%, that is, one in 200 post-partum women may develop Graves' thyrotoxicosis, although thyrotoxicosis may be transient in half of the patients.

Autoantibodies↗
PubMed1994

Prevalence of postpartum onset of disease within patients with Graves' disease of child-bearing age.

To assess the prevalence of postpartum onset of disease among the patients with Graves' disease, we performed a retrospective examination of 289 consecutive female patients with Graves' disease who attended our thyroid clinic. Of these patients, 92 were female of child-bearing age (20-39 y.o.) who have had one or more deliveries, and at least 37 patients revealed clear evidences of postpartum onset of the disease. That is, at least 40% of Graves' patients of 20-39 y.o. developed their disease during the postpartum period.

Adult↗
PubMed1994

Reducing effect of nadolol on serum levels of free thyroid hormones in hyperthyroidism.

We evaluated the effect of the beta-adrenergic receptor blocking agent nadolol on serum levels of free thyroid hormones in 20 untreated patients with Graves' disease, aged between 17 and 57 years (mean +/- SD, 32.9 +/- 10.5). All the patients were treated with 30 mg of nadolol alone once-daily for 2 weeks, and clinical and laboratory parameters before and after the treatment were compared. Systolic blood pressure was depressed significantly (P < 0.001) from 132.7 +/- 11.1 mmHg to 122.8 +/- 10.9 mmHg. The resting pulse rate was also reduced significantly (from 110.3 +/- 9.2/min to 86.0 +/- 13.2/min, P < 0.001). Serum free thyroxine levels were reduced significantly from 7.1 +/- 3.1 ng/dl to 5.7 +/- 3.6 ng/dl (P < 0.05) and serum free triiodothyronine levels were reduced from 21.9 +/- 5.6 pg/ml to 17.2 +/- 6.9 pg/ml (P < 0.01). In the present study, the beta-adrenergic receptor blocking agent nadolol was newly found to have a reducing effect on serum free thyroxine, as well as free triiodothyronine concentrations.

Adolescent↗
PubMed1993

Shedding of Gs protein (a soluble form of the viral glycoprotein) by the rabies virus-infected BHK-21 cells.

We investigated a possible mechanism of G protein shedding occurring in the rabies virus-infected BHK-21 cell cultures. Quantitative analysis showed that about 10% of the newly synthesized G proteins were shed from the cells as Gs protein, a soluble form of G protein which lacked the C-terminal anchoring region of the protein, into the culture medium. Pulse-chase experiments revealed that the release of tritium-labeled Gs proteins began soon after the synthesis, but ceased after a short time (within about 2 hr). On the other hand, the release of the virion-associated G protein began 30 to 60 min behind the start of Gs protein shedding and continued for more than 10 hr. Gs protein could not be detected in the cells by biochemical and immunological methods at the time when large amounts of Gs protein were actively being shed. With an antiserum against the C-terminal of G protein we could detect in the cell a polypeptide having a size that is seemingly the same as that which was lost from Gs protein. These results suggest that Gs proteins are generated by a proteolytic cleavage of newly synthesized G proteins, and the cleavage seems to be stopped at a certain stage of the G protein maturation.

Amino Acid Sequence↗
PubMed1993

Intrathyroidal lymphocyte subsets, including unusual CD4+ CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells, in autoimmune thyroid disease.

Intrathyroidal lymphocyte subsets were analysed in 13 euthyroid patients with autoimmune thyroid disease by two-colour flow cytometry and compared with subsets in peripheral blood. In both Graves' and Hashimoto's diseases, proportions of intrathyroidal CD5- B cells were higher than in peripheral blood. The numbers of such cells were correlated with serum levels of anti-thyroid microsomal antibodies. Proportions of T cells bearing alpha beta chains of T cell receptors (TCR alpha beta+ T; T alpha beta) and CD16+CD57+ natural killer (NK) cells were lower in the thyroid, but proportions of CD3hiTCR alpha beta-TCR gamma delta+ (T gamma delta) cells were not different. Proportions of CD4+Leu-8- helper T cells and CD4+CD57+ germinal centre T cells were higher and proportions of CD4+Leu-8+ suppressor-inducer T cells and CD8+CD57+ or CD8+CD11b+ suppressor T cells were lower than in the blood in both diseases. Proportions of CD5+ B cells were high in Graves' disease, and proportions of CD8+CD11b- cytotoxic T cells were high in Hashimoto's disease. Unexpectedly, CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells were present in thyroid tissues of both diseases. These findings suggest that: (i) an imbalance in the numbers of regulatory T cells and of NK cells that had appeared in the thyroid resulted in the proliferation of CD5- B cells, which were related to thyroid autoantibody production; (ii) CD5+ B cells and cytotoxic T cells are important for the different pathological features in Graves' and Hashimoto's diseases, respectively; and (iii) intrathyroidal CD4+CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells may be related to the pathogenesis of autoimmune thyroid disease.

Adolescent↗
PubMed1993

Recurrence of thyrotoxicosis after attack of allergic rhinitis in patients with Graves' disease.

Graves' disease is frequently aggravated during antithyroid drug therapy; however, little is known of its aggravating factors. We studied 83 patients with Graves' disease who were euthyroid for at least 6 months under antithyroid maintenance therapy, and we examined the relationship between thyrotoxicosis relapse, attack of allergic rhinitis, and peripheral eosinophil increase. Forty-one patients showed thyrotoxicosis relapse; of these, 22 (54%) showed peripheral eosinophil increase, and 14 (34%) had attacks of allergic rhinitis. In the remaining 42 patients without thyrotoxicosis relapse, only 4 (10%, P < 0.001) showed an increase in peripheral eosinophils, and only 3 (7%, P < 0.01) had allergic rhinitis. Recurrence of thyrotoxicosis was observed with the increase in serum levels of TSH-receptor antibodies and increase in eosinophils 2 months after the attack of allergic rhinitis. Three patients with seasonal allergic rhinitis showed thyrotoxicosis relapse at the same time of year within 2 consecutive years. Our findings indicate that allergic rhinitis can be an aggravating factor of Graves' disease and suggest that the preceding increase in peripheral eosinophils can be a predictive indicator of recurrence of thyrotoxicosis during antithyroid drug therapy.

Adolescent↗