Biomedical subjects

Y Kasuga

Publications and source records attributed to Y Kasuga.

At least 55 records · Page 3Linked to original sources

PubMed1993

The outcome of patients with thyroid carcinoma and Graves' disease.

A total 847 consecutive patients with Graves' disease who underwent thyroidectomy between 1965 and 1990 were found to have a 4.3% incidence of coincident carcinoma of the thyroid. In 68.2% of these cases the tumors were less than 1 cm in diameter and were detected in only 7 patients (19.4%) prior to surgery. Dissection of the regional lymph nodes was necessary in only 11 patients. A review of the patients in 1990 revealed no carcinoma-related deaths with metastases occurring most commonly in the patients with larger tumors and in those whose cancer had been detected prior to thyroidectomy. Although the detection of potential tumors occurring with Graves' disease using preoperative echogram may be of interest, our results suggest that occult microcarcinoma occurring coincidentally with Graves' disease is not clinically significant as it did not cause any recurrence in this study. Moreover, there was no evidence to suggest that Graves' disease was associated with the increased or rapid growth of these tumors.

Adenocarcinoma↗

PubMed1993

Primary scirrhous carcinoma of the nipple with symptoms simulating Paget's disease: report of a case.

We report herein an extremely rare case of primary scirrhous carcinoma of the nipple, being of particular interest in that the patient presented with symptoms very similar to those of Paget's disease. The carcinoma cells were detected by aspiration biopsy cytology rather than by touch smear, although both were performed to differentiate this lesion from Paget's disease and other diseases of the nipple. Thus, we recommend that both touch smear and aspiration biopsy cytology should be performed for all patients presenting with symptoms such as those observed in this case to rule out the possibility of scirrhous carcinoma of the nipple or Paget's disease.

Adenocarcinoma, Scirrhous↗

PubMed1993

Development of hypothyroidism with thyroid stimulation blocking antibody long after treatment with antithyroid drugs in a patient with hyperthyroid Graves' disease: a case report.

We observed a patient manifesting spontaneous hypothyroidism with thyroid stimulation blocking antibody (TSBAb) long after treatment with antithyroid drugs (ATDs) for hyperthyroid Graves' disease. A 19-year-old female with Graves' disease was treated with ATDs for approximately 2 years; after cessation of ATDs, hyperthyroidism did not recur. Nine years later, she was again seen in our hospital because of symptoms indicative of hypothyroidism. Thyroid hormone replacement was commenced after laboratory confirmation of hypothyroidism. TSH-binding inhibitor immunoglobulin and TSBAb were both positive, while thyroid stimulating antibody (TSAb) was negative, at the time of diagnosis of hypothyroidism. These results indicated that the alterations in thyroid function in this patient appeared to relate to the presumed decline in the activity of TSAb and the appearance of TSBAb years after ATDs administration had been discontinued.

Adult↗

PubMed1993

Clinical evaluation of upper mediastinal dissection for differentiated thyroid carcinoma.

BACKGROUND: An extensive upper mediastinal dissection in advanced differentiated thyroid carcinoma is occasionally required. This investigation was undertaken to clarify the indications for mediastinal lymph node dissection and the route of upper mediastinal metastases. METHODS: Twenty-one patients with differentiated thyroid cancer, who underwent their first radical operations with mediastinal dissection through a partial midline sternotomy, were enrolled in this study. Of 21 patients, 10 (48%) were found to have mediastinal lymph node metastases. RESULTS: The tumor size in the group with metastatic disease was much bigger than that in the group without metastatic disease. Histologic type and age were similar between the two groups. The extent of cervical lymph node metastases was more significant in the group with metastatic disease; in particular, all 10 patients showed more than two metastatic nodes along the internal jugular vein of the tumor-free side. CONCLUSIONS: This study indicates that metastases to the internal jugular chain on the side contralateral to the primary tumor would be an extremely important factor for indication of extensive upper mediastinal lymph node dissection after median partial sternotomy in patients with differentiated thyroid carcinoma.

Adolescent↗

PubMed1992

Evidence of intrathyroidal accumulation of TSH receptor antibody in Graves' disease.

To clarify the intrathyroidal accumulation of TSH receptor antibody (TR-ab) produced in the thyroid, adrenalin was injected directly into the thyroid artery of patients with Graves' disease during surgery, allowing serial determination of the TR-ab levels in the thyroidal venous blood. Nine surgical patients (3M and 6F) with Graves' disease and receiving anti-thyroid drugs preoperatively for a period of one to four years were enrolled in this study. Comparison between pre- and posttreatment TR-ab levels revealed continuous increments from the pretreatment levels within 15 min of the injection in five (55.6%) of the nine patients. In three of the five patients, TR-ab levels that had been negative before adrenalin injection became positive 1 min after injection. It is assumed that the increase in the TR-ab level is due to adrenalin-induced constriction of the capillaries in the thyroid tissues, resulting in a voluminous flow of the TR-ab retained in the thyroid into the vein. These findings indicate that the TR-ab level in the peripheral blood does not necessarily reflect precisely the abnormal immunological condition in the Graves' thyroid.

Adolescent↗

PubMed1991

The problems encountered in the surgical management of primary hyperparathyroidism.

The problems encountered in the diagnosis and treatment of primary hyperparathyroidism were studied in 69 cases. The accuracy of imaging for hyperplasia was less than that for adenoma or carcinoma and the major causes for multiple operations were a failure to locate the four glands and mediastinal adenoma. The intravenous administration of high doses of calcitonin could reduce the serum calcium level of patients in hypercalcemic crisis. Carcinoma required ipsilateral modified radical neck dissection because of lymph node metastases, and non-medullary thyroid carcinoma was often associated with primary hyperparathyroidism. We found removal of the parathyroid adenoma and biopsy or extirpation of only one macroscopically normal gland to be a fully satisfactory procedure after bilateral neck exploration and attempting to identify at least four glands.

Adenoma↗

PubMed1991

Interleukin 2-activated killer cells do not mediate autologous thyrocyte lysis in autoimmune thyroid disease in vitro.

Because of interest in IL-2, and IL-2-activated killer cell-induced hypothyroidism in humans, we attempted to study an in vitro system that might prove to illuminate this disorder. We have thus studied interleukin 2 (IL-2--0, 12.5, 25, or 50 U/mL) activated killer cell-mediated autologous thyrocyte lysis, as well as cytotoxic activity in IL-2-stimulated mononuclear cell supernatants in 7 patients with autoimmune thyroid disease (2 Graves' disease and 5 Hashimoto's thyroiditis) using the 51Cr release assay. Controls included 14 patients with nonautoimmune thyroid disease (3 nontoxic goiter, 8 follicular thyroid adenoma, 2 papillary thyroid carcinoma, and 1 medullary carcinoma of the thyroid). Soluble IL-2 receptor (sIL-2R) in supernatants of peripheral mononuclear cells stimulated by IL-2 from these patients also was measured. Whereas in the control preparations, IL-2-activated killer cell activity was increased in a dose-dependent fashion relative to the IL-2 concentration, as well as to the effector cell/target cell ratio, in preparations from patients with autoimmune thyroid disease, this activity was not elevated as the IL-2 concentration was increased. The susceptibility of thyrocytes to the lytic effect of IL-2-activated killer cells was higher in controls than that in autoimmune thyroid disease (at concentrations of IL-2 of 0, 12.5, 25, and 50 U/mL) (p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1991

Studies of CD4+ (helper/inducer) T lymphocytes in autoimmune thyroid disease: demonstration of specific induction in response to thyroid peroxidase (TPO) in vitro and its relationship with thyroid status in vivo.

We have studied by flow cytometric analysis the antigen specific activation of CD4+ (helper/inducer) T lymphocytes by purified human thyroid peroxidase (TPO). Peripheral blood mononuclear cells were obtained from 26 patients with Graves' disease (GD), 16 with Hashimoto's thyroiditis (HT), 7 with nontoxic nodular goiter (NG), and 14 normal subjects (N). Cells were cultured for 7 days in the presence or absence of TPO at final concentrations of 3, 30, and 300 ng/mL. When harvested, cells were reacted with an FITC-conjugated anti-CD4 and a PE-conjugated anti-HLA-DR murine monoclonal antibodies. The percentage of HLA-DR+ CD4+ cells (activated CD4+ cells) was determined by a flow cytometer. In the absence of TPO, CD4+ cells had been activated without any specific stimulant. This is known as the autologous mixed lymphocyte reaction (AMLR). In the AMLR, CD4+ cells from GD and HT were less activated compared to those from NG and N. Results of TPO-specific activation were expressed as an incremental increase of activated CD4+ cells (II) (percentage of activated CD4+ cells cultured with TPO minus percentage of activated CD4+ cells cultured without TPO). II of N, GD, HT, and NG were 0.37 +/- 0.21, 2.20 +/- 0.45,** 2.0 +/- 0.66,* and 0.35 +/- 0.27 (mean +/- SEM), respectively (**p less than 0.01; *p less than 0.05 vs N). When patients were further subdivided, the highest mean II was found in patients with hyperthyroid GD (p less than 0.01), followed by euthyroid HT (p less than 0.05) and euthyroid GD (p less than 0.05), however there was no significant difference between hypothyroid HT and N. In conclusion (1) AMLR reactivity of CD4+ cells from GD and HT was impaired, (2) however, CD4+ cells from both GD and HT were significantly more induced by TPO compared to N, and (3) this induction depends, in part, on the in vivo thyroid status.

Adolescent↗

PubMed1991

Multiple pulmonary hyalinizing granulomas associated with systemic idiopathic fibrosis.

A 41-year-old man with progressive nodular infiltration of the lung of about 2 years' duration died of cardiac and respiratory failure. Autopsy revealed bilateral multiple pulmonary hyalinizing granulomas (PHGs) diagnosed on the basis of the characteristic dense hyaline collagen bundles with nonspecific inflammatory infiltration. Constrictive pericarditis, retroperitoneal fibrosis, mediastinal fibrosis, fibrous thickening of the peritoneal and pleural surfaces, and fibrosis of soft tissue of the neck, flank, and hepatic hilar region were present, therefore, a diagnosis of systemic idiopathic fibrosis was made. The patient had anti-thyroglobulin and anti-thyroid microsomal antibodies and lymphocytic thyroiditis. The inflammatory process of PHG of the present case was active and the clinical course was progressive. PHG seems to be a lesion belonging to the systemic idiopathic fibrosis complex. Immunologic abnormalities may be related to PHG and systemic idiopathic fibrosis.

Adult↗

PubMed1991

Effects of recombinant human interleukin-2 and tumor necrosis factor-alpha with or without interferon-gamma on human thyroid tissues from patients with Graves' disease and from normal subjects xenografted into nude mice.

We have compared the effects of interleukin-2 (IL-2) or tumor necrosis factor-alpha (TNF alpha) administration with or without interferon-gamma (IFN gamma) on Graves' and normal thyroid tissue xenografts in the nude mouse (in the absence of an intact immune system) in terms of possible functional, immunological, or histological changes. The dosages of recombinant human IL-2, TNF alpha, and IFN gamma given to each mouse were 250, 800, and 4000 U, respectively; they were injected ip daily for 6 consecutive weeks. The parameters measured included the free T4 index, thyroid autoantibodies, and mouse TSH during the course of the study. Thyroid epithelial cell (TEC) HLA-DR expression was measured in thyroid tissue before xenotransplantation and at death; in addition, light microscopic studies were carried out at those times. There were no significant differences in thyroid function between the results in unstimulated (control) animals and those obtained with cytokine administration in either group of tissues, with the exception of the group receiving TNF alpha together with IFN gamma; in this latter group, the free T4 index declined significantly 4-6 weeks after commencement of treatment in the animals with normal thyroid tissue xenografts. The reduction of thyroid function induced by the combination of IFN gamma and TNF alpha observed in normal thyroid tissue may be due to inhibition of thyroperoxidase and thyroglobulin gene transcription. However, there was no such effect on the Graves' thyroid tissue xenografts, perhaps because of down-regulation of this tissue in response to cytokines, after having been released from long term in vivo immune stimulation. On the other hand, TNF alpha plus IFN gamma induced TEC HLA-DR expression on both types of thyroid xenografts at death, although IL-2 alone did not induce HLA-DR expression, and IFN gamma induced TEC significantly only on normal thyroid xenografts (but not on Graves' xenografts). In light microscopic examination, Graves' thyroid xenografts treated with IL-2 alone or TNF alpha plus IFN gamma appeared normal at death. In addition, normal thyroid xenografts treated with the same cytokines did not show discernible differences compared to those at human surgery or when the xenografts were untreated at death. We conclude that Graves' TEC did not differ from normal TEC in any significant fashion at the time of death, aside from a reduced responsiveness to the stimuli applied.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Two cases of acute pseudogout attack following parathyroidectomy.

Two cases of acute attack of pseudogout associated with primary hyperparathyroidism are reported. Case 1 suffered from acute pain and swelling of the right ankle and dorsal of the right foot. Case 2 suffered from unknown fever and pain of the bilateral jaw, shoulder, elbow, wrist and knee joints. Postoperative radiological studies revealed the association of chondrocalcinosis in both cases. Synovial fluid in case 2 was aspirated and analyzed for calcium pyrophosphate dihydrate crystal by microscopic examination.

Acute Disease↗

PubMed1991

Anti-triiodothyronine autoantibodies in a euthyroid woman: confirmation of immunoglobulin G antibodies employing protein A column chromatography.

The presence of thyroid hormone autoantibodies was investigated in a 48-year-old non-goitrous woman with high levels of serum total T3 and free T3. Her other thyroid function tests were normal. The presence of thyroid hormone autoantibodies were assessed in serum, acid-charcoal treated serum, IgG fractions and in a purified IgG fraction. the IgG fraction was separated from serum by a protein A-Sepharose CL-4B column chromatography and purified by gel filtration chromatography using Sephacryl S 200. Sera from normal individuals were used as controls. The results showed that the increased serum total and free T3 levels were caused by the presence of anti-T3 IgG autoantibodies. The results also indicate that protein A column chromatography is useful as a screening method for gross qualitative analyses of thyroid hormone autoantibodies.

Autoantibodies↗

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↗

PubMed1991

[Clinical evaluation of operative procedure for differentiated carcinoma of isthmus of the thyroid].

We studied 19 patients who had undergone operation for differentiated carcinoma of isthmus of the thyroid in Shinshu University Hospital from 1967 to 1986. Regarding the operations, total thyroidectomy was performed in 6 cases, subtotal thyroidectomy in 8 cases, lobectomy in one case and isthmectomy in 4 cases. In 12 cases, lymph node dissection was carried out. Among these 12 cases, 6 cases (50%) had evidence of metastasis. Intraglandular metastasis was found in 3 cases. There were no relationship between tumor size and nodal metastasis. From these results, we do not think that total thyroidectomy is indicated in the case of differentiated carcinoma of isthmus of the thyroid. In conclusion, subtotal thyroidectomy with bilateral modified radical neck dissection is sufficient as the operative procedure for differentiated carcinoma of isthmus of the thyroid.

Adenocarcinoma↗

PubMed1990

Clinical and immunological studies on patients with Graves' disease preoperatively treated with corticosteroids and iodides.

The purpose of this study was to evaluate the acute effects of corticosteroid and iodide preoperative therapy in patients with Graves' disease in terms of thyroid function and immunological parameters. The above combination was prescribed for 4 patients who had experienced severe side effects from antithyroid drugs (ATD) in order to reduce the possibility of post-thyroidectomy thyroid storm. Corticosteroids were employed daily for four days, and iodides were given daily for two weeks prior to thyroidectomy. The free T3 values decreased rapidly to euthyroid levels following the administration of both drugs, although the free T4 values were still much higher than normal in 3 of the 4 patients at the time of surgery. By comparison, 3 of 8 patients treated with ATD also had thyroid hormone levels above normal. Studies of lymphocyte subsets revealed that the percentage of helper T cells was significantly less in the corticosteroid-iodide treatment group than in the control and ATD groups. It is thus possible that postoperative thyroid storm might be prevented through corticosteroid-iodide therapy by virtue of the reduction of free T3 values to within the normal range by the time of surgery. The acute suppression of helper T cells was another results of this form of therapy observed.

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

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

Cytophagic histiocytic panniculitis evolving into total lipodystrophy.

A 15-year-old boy had persistent fever with severe neutropenia, thrombocytopenia, coagulation disorder, and marked elevation of lactate dehydrogenase values. A diagnosis of cytophagic histiocytic panniculitis was made after repeated skin biopsies. Three years after onset, he gradually lost 20 kg in body weight, and both skin and bone marrow specimens revealed degenerative changes of fatty tissue without any inflammatory cells. These findings suggest that total lipodystrophy syndrome results from the inflammatory destructive process of adipose tissue. To our knowledge, our report is the first to show, in a series of histologic studies, that an inflammatory destructive process may be involved in some cases of total lipodystrophy syndrome.

Adolescent↗