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Biomedical subjects

T Fujihira

Publications and source records attributed to T Fujihira.

36 records · Page 2Linked to original sources
PubMed1992

A kindred of multiple endocrine neoplasia type 2B.

We describe familial cases of multiple endocrine neoplasia (MEN) 2B: A 48-year-old man is the proband. He had pheochromocytoma, medullary thyroid carcinomas (MTCs), parathyroid hyperplasia, mucosal neuromas, eversion of eyelids and Marfanoid appearance, and then underwent adrenalectomy and total thyroidectomy. Family screening revealed that his two daughters (10 and 8 years old) had mucosal neuromas and increased serum calcitonin (CT). Both of them had MTCs but no pheochromocytoma, and their MTCs were surgically removed. The father and his children have been in favorable condition since the operations. Southern blot analysis with 33 polymorphic DNA probes was done in MTCs obtained from two daughters. An RBP3 (10q11.2) locus linked to a predisposing gene on chromosome 10 was uninformative in either patient because of constitutional homozygosity. Loss of heterozygosity at the MYCL1 locus on chromosome 1p32 was observed in MTC from the younger sister, but no loss of heterozygosity was recognized in other loci examined. Deletion of the 1p32 locus may play a role in the development of MEN 2B.

Adrenal Gland Neoplasms↗
PubMed1990

Interleukin-4 as a potent inhibitor of bone resorption.

A possible role of interleukin-4 (IL-4) in the regulation of bone turnover was assessed by employing a 45Ca prelabeled-fetal mouse long bone culture system. IL-4 inhibited the bone resorption stimulated by parathyroid hormone (PTH), PTH related protein (PTHrP), 1 alpha, 25, dihydroxy-vitamin D3 [1 alpha, 25 (OH)2 D3], interleukin-1 alpha and - 1 beta (IL-1 alpha, IL-1 beta) and prostaglandin E2 (PGE2). Anti-IL-4 on monoclonal antibody abolished the inhibitory effect of IL-4 on the bone resorption. These results suggest that IL-4 may play an important role on the inhibitory regulation of bone resorption.

Animals↗
PubMed1989

[Significance of circulating anti-thyroid stimulating hormone (TSH) receptor antibodies in patients with autoimmune thyroid diseases--thyroid stimulation blocking antibody in patients with Graves' disease].

It is a well-known fact that a thyroid stimulation blocking antibody (TSBAb) may play an important role in primary hypothyroidism. However, it has rarely been reported that TSBAb appears in only a few cases of Graves' disease which became hypothyroidism in their clinical courses. We examined TSBAb in 120 sera from 79 cases with Graves' disease before or while under methimazole (MMI)-treatment. TSBAb value was expressed as the percentage inhibition of TSH-stimulated cAMP response of porcine thyroid cells by the patient's IgG. TSBAb was positive in 9 cases (11.4%) of 79 cases of Graves' disease. In 6 of the 9 cases, TSBAb was detected at the untreated period. In the other 2 of the 9 cases, it was detected during the exacerbation related with their pregnancy. It was difficult to control Graves' disease in all 9 cases. These results suggest that TSBAb appears not only in primary hypothyroidism but also even in the hyperthyroid state of Graves' disease, and that the combination of TSAb and TSBAb may regulate the pathogenesis of Graves' disease.

Adult↗
PubMed1989

Circulating monocyte (macrophage)-specific antibodies in patients with autoimmune thyroid diseases.

We investigated the presence of circulating monocyte-specific antibodies (monocytotoxic activities) by a complement-dependent cytotoxicity test and the relations between these monocytotoxic activities and other immunological indices in patients with autoimmune thyroid diseases. Antibodies reactive for monocytes (macrophages) were found in the sera from patients with autoimmune thyroid diseases. These antibodies were present in both IgG and IgM fractions and specific for monocytes since they were absorbed by monocytes but not by lymphocytes or granulocytes; furthermore, lymphocytotoxic and granulocytotoxic activities were not changed after the absorption of the sample sera by monocytes. Also, these antibodies did not have cross-reactivity to thyroid-specific antigens demonstrated by absorption tests and their specificity was different from anti HLA-DR antibody demonstrated by a flow cytofluorometric analysis. Monocyte-specific antibodies are reactive for autologous monocytes as well as allogenic monocytes. Patients who had positive monocytotoxic activities had high levels of TSH receptor antibodies (TRAb) and antimicrosomal antibodies in Graves' disease, and monocytotoxic activities were significantly correlated with the levels of TRAb in Graves' disease. These results suggest that the monocyte-specific antibodies (monocytotoxic activities) were significantly correlated with the immunological activities in Graves' disease.

Adolescent↗
PubMed1989

Immunological abnormality of peripheral blood B cells in patients with autoimmune thyroid disease.

We investigated the response to immunoglobulin G-secreting cells (ISC) by peripheral blood mononuclear cells (PB-MNC) and purified B cells following stimulation with Staphylococcus aureus Cowan 1 (SAC) or with B cell stimulatory factor 2 (interleukin 6: IL-6), using the reverse hemolytic plaque assay in an attempt to clarify the immunological functions of peripheral blood B cells in patients with autoimmune thyroid disease (AITD). ISC response by PB-MNC following stimulation with SAC was significantly decreased in patients in the hyperthyroid state of Graves' disease and Hashimoto's thyroiditis as compared with that of normal controls. The difference in SAC-response was not significant between patients with euthyroid state of Graves' disease and normal controls. ISC response by PB-MNC following stimulation with SAC exhibited a reciprocal relationship to TRAb in patients with Graves' disease. Using purified B cells, some spontaneous ISC response without SAC stimulation was observed in patients in the hyperthyroid state of Graves' disease and Hashimoto's thyroiditis. This spontaneous ISC response was further enhanced by IL-6. These results suggest that in organ-specific autoimmune diseases such as AITD, immunological abnormalities exist in B cells and some B cells are nonspecifically activated in the immunologically active state.

Antibody-Producing Cells↗
PubMed1988

Production of bone-resorbing activity corresponding to interleukin-1 alpha by adult T-cell leukemia cells in humans.

The physicochemical properties and relationship of bone-resorbing activity and interleukin 1 (IL-1) produced by adult T-cell leukemia (ATL) cells and cell line were studied in vitro. The culture supernatant of ATL cell line, MT2, and peripheral blood lymphocytes freshly obtained from ATL patients had both IL-1 activity detected by the stimulation of murine thymocyte-proliferative responses and bone-resorbing activity detected by the stimulation of 45Ca release from prelabeled murine fetal bones. By Sephacryl S-200 column chromatography, both activities were eluted as a single peak at approximately Mr 15,000. By the chromatofocusing technique, the isoelectric point values of both activities were estimated as pH 4.8 and 5.2. Furthermore, both activities were absorbed with rabbit anti-IL-1 alpha antiserum, but not with anti-IL-1 beta antiserum. These results suggest that ATL cells and cell line produce bone-resorbing activity which corresponds to IL-1 alpha and that this IL-1 alpha is one of the most important causes of hypercalcemia in ATL patients.

Biological Assay↗
PubMed1987

[Circulating HLA-DR (Ia) positive T cells and T cell activation by thyroglobulin, thyroid microsome and TSH-receptor in autoimmune thyroid diseases].

HLA-DR antigens are not expressed on normal circulating T lymphocytes, but recently it has become apparent that HLA-DR antigens are expressed on immunologically activated T lymphocytes, as well as monocytes, macrophages, and B lymphocytes. Namely, the HLA-DR antigens are considered to be one of the activated T cell antigens. It is apparent from the previous studies that increased numbers of HLA-DR positive T cells frequently appear in the circulation in systemic autoimmune diseases, such as RA and SLE. Furthermore, in such diseases, it is reported that the variations in circulating HLA-DR positive T cells are related to the activity of the diseases. In this communication, we examined the variations in HLA-DR positive T cells in the peripheral blood of the patients with autoimmune thyroid diseases. HLA-DR positive T cells were detected by cytotoxicity test using anti HLA-DR mouse monoclonal antibody (Leu-HLA-DR antibody) and rabbit complement. The results indicate that; 1) The percentage of HLA-DR positive T cells were increased in the patients with autoimmune thyroid diseases. 2) The changes of HLA-DR positive T cells accompanied with the stimulation by non-specific mitogens in vitro in autoimmune thyroid diseases did not differ from those in the normal controls. 3) The percentage of HLA-DR positive T cells increased by the stimulation of TSH-receptor and thyroid microsome in Graves' disease, on the other hand, it occurred by the stimulation of thyroglobulin and thyroid microsome in Hashimoto's thyroiditis. 4) The percentage of HLA-DR positive T cells were correlated with TRAb (TSH receptor Ab assayed by Smith's kit) in Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

[Circulating monocyte (macrophage)-specific antibodies in patients with autoimmune thyroid diseases].

We investigated the presence of circulating monocyte-specific antibodies (monocytotoxic activities) by cytotoxicity tests and also the relationships between these monocytotoxic activities and the clinical data in autoimmune thyroid diseases. Subjects of this investigation include 16 patients with Graves' disease, 20 patients with Hashimoto's thyroiditis and 10 normal controls. To obtain monocyte-rich population, peripheral blood mononuclear cells of type 0 healthy donor were incubated on culture dishes for 12 hours and dish adherent cells were separated by pipetting. These monocyte-rich population were incubated with sample sera which were previously absorbed by lymphocytes of many different kinds of HLA types to eliminate anti-lymphocyte antibodies, and thereafter cytotoxicity tests were performed by adding rabbit complements. The monocytotoxic activities were expressed by %cytotoxicities and the value of %cytotoxicity over 3.9% (mean + 4SD of %cytotoxicities of normal controls) was considered to be positive in monocytotoxic activity. The results indicate that; 1) 8 patients (50%) of Graves' disease and 10 patients (50%) of Hashimoto's thyroiditis had positive values of monocytotoxic activity. 2) These positive values of monocytotoxic activity were markedly decreased after absorption of sample sera by monocytes, and these patients who had positive values of monocytotoxic activities to allogenic monocytes also had positive values of monocytotoxic activities to autologous monocytes. 3) Patients who had positive monocytotoxic activities also had high levels of TSH receptor antibody (TRAb) and anti-microsomal antibody, besides, monocytotoxic activity was significantly correlated with levels of TRAb in Graves' disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗
PubMed1987

Existence and immunological significance of circulating Ia+T cells in autoimmune thyroid diseases.

We investigated the percentage of circulating HLA-DR antigen positive (Ia antigen positive: Ia+) T cells and the additive proliferation by non-specific mitogens and thyroid-specific antigens by means of a cytotoxicity test in autoimmune thyroid diseases. Furthermore, we studied the stimulative function of circulating Ia+T cells in autologous mixed lymphocyte reactions. %Ia+T cells were significantly increased in patients with autoimmune thyroid diseases compared with those in normal controls. They were additionally increased by the stimulation of TSH-receptor or thyroid-microsome in patients with Graves' disease, and by the stimulation of thyroglobulin and thyroid-microsome in patients with Hashimoto's thyroiditis. As to the cellular immune function, circulating Ia+T cells stimulated Ia-T cells in autologous MLR in patients with autoimmune thyroid diseases. These data suggest that some of the T cells are already activated in vivo, that the activation of T cells may be by thyroid-specific antigens, and that these activated (Ia+) T cells may be able sequentially to induce the activation of inactivated (Ia-) T cells in autoimmune thyroid diseases.

Cytotoxicity Tests, Immunologic↗
PubMed1986

Autopsy findings of the coronary arteries of variant angina with Raynaud's phenomenon of the tongue.

A 42 year old man with variant angina occasionally associated with syncopal attacks died of acute myocardial infarction 17 months after the onset of angina. Prior to the onset of variant angina, he had Raynaud's phenomenon of the tongue for 2 years. Both Valsalva maneuver and hyperventilation could repeatedly provoke chest pain and ST segment elevation in leads II, III and aVF. The infusion of prostaglandin E1 at a rate of 0.05 microgram/kg/min, was able to prevent the attack of variant angina induced by these maneuvers. Although coronary angiography performed 15 months prior to death revealed no organic lesions except for complete spastic occlusion at segment 1 following intravenous ergonovine, autopsy revealed marked intimal proliferation and accumulation of abundant glycosaminoglycans in three coronary vessels, as well as in small and muscular arteries of other organs. This suggests that a rapid systemic progression of narrowing due to proliferation of the intima might occur in some cases of variant angina.

Adult↗
PubMed1985

Primary malignant lymphoma of the thyroid in a patient with long-standing Graves' disease.

We have recently encountered a patient with rapidly enlarging thyroid masses histologically diagnosed as diffuse histiocytic lymphoma which developed in the active course of Graves' disease. The primary thyroid lymphoma has been in complete remission after local radiation therapy. The association of Hashimoto's thyroiditis and thyroid lymphoma has well been recognized. Meanwhile, data have accumulated to demonstrate that Hashimoto's thyroiditis and Graves' disease share possible similar causal immunological abnormalities and are closely related entities. However, the association of Graves' disease and primary thyroid lymphoma has never been reported, as far as we know. Therefore, this case may be the first one that supports the natural concept that thyroid lymphoma develops from pre-existing Graves' disease secondary to the similar immunological abnormalities in Hashimoto's thyroiditis.

Aged↗
PubMed1985

Evidence of bone resorption-stimulating factor in adult T-cell leukemia.

Adult T-cell leukemia (ATL) is known to be frequently accompanied by hypercalcemia, but the mechanisms responsible for hypercalcemia in this disorder are not fully understood. We have recently experienced two male patients (25 and 36 yr old) with ATL diagnosed from typical leukemic cells with grooved and folded nucleus, surface marker, anti-ATLA antibody etc. Serum calcium levels of these patients were 16.4 and 21.4 mg/dl, respectively, with no radiological evidence of bone destruction. Peripheral blood leukemic lymphocytes from these patients were purified by the Ficoll-Hypaque method and cultured at a concentration of 1.5 X 10(6) cells/ml for 3 days on F-10 medium supplemented with 10% fetal calf serum. The supernatant fluids from the cell cultures were bioassayed for bone resorption-stimulating activity (BRSA) by an assay based on the release of 45Ca from prelabeled fetal mouse forearm bones in organ culture according to Raisz's method. The supernatant fluid of cultures from both patients which showed marked BRSA was nondialyzable through a dialysis membrane with a molecular weight cutoff of 3500. Parathyroid hormone and prostaglandins were not detectable in the supernatant fluids of the leukemic cell cultures. In one patient, BRSA was measured twice and found to be decreased to a normal level when the patient was in hematological remission with a normal calcium level (8.3 mg/dl). These results suggest that the hypercalcemia observed in patients with ATL is due, in part, to a bone resorption-stimulating factor which is produced by leukemic T-cell lymphocytes.

Adult↗
PubMed1979

Effect of bradykinin to cyclic AMP levels and response of murine lymphocytes.

No information is available on the pharmacological effect of bradykinin to lymphocytes and immunological responses of them. In this study it was clarified that bradykinin as well as histamine elevated cyclic adenosine 3',5' monophosphate (cAMP) levels of murine splenic or lymph node lymphocytes and mature thymocytes (cortisone-resistant thymus), but did not increase cAMP levels of immature thymocytes as well as histamine. The increased cAMP ratios in T cell-enriched splenic lymphocytes by the impulse of bradykinin were higher than that in splenic and lymph node lymphoid cells by the stimulation of bradykinin. It was also demonstrated that bradykinin as well as histamine suppressed DNA synthesis by mitogenic (PHA-P, Con-A) stimulation of splenic lymphocytes, but not a effect to the response of lymphocytes by mitogenic (LPS) stimulation was observed. These facts suggest that bradykinin may play an important role in the regulation of immunologic lymphocyte responses.

Animals↗
PubMedDate not supplied

Clinical significance of anti-TSH antibody in sera from patients with Graves' disease and other thyroid disorders.

In a survey of patients having anti-TSH antibody (TSH Ab), data from 167 subjects were collected from 8 Japanese Institutions. They were divided into a high TSH Ab group consisting of 63 cases; since the means of assay was via a subnormal thyrotropin binding inhibitor immunoglobulin (TBII) assay, this group had TBII values less than -20%. An additional low TSH Ab group was made up of 104 cases. Out of a total of 11,211 patients, the incidence of TSH Ab for the high and low groups were 0.57% and 13.4%, respectively. More than 95% of these TSH Ab carriers had Graves' disease or some other autoimmune thyroid disorder, and anti-thyroglobulin and anti-thyroid microsomal antibodies were detected similarly in both groups. It was significant that TSH receptor antibodies could also be detected in both groups, namely, thyroid stimulating antibody and long acting thyroid stimulator (LATS) in 4 of 9 patients in the high TSH Ab group and TBII in 55 of 104 in the low TSH Ab group, respectively. The high TSH Ab levels tended to persist, but 26% of cases showed disappearance or appearance of the antibody during the observation period. In one Graves' patient, a moderate TBII activity (64.2%) was followed by markedly elevated TSH Ab (TBII: -83.4%) within 2 months. The TSH Ab in the low TSH Ab group disappeared in most cases. Also, fluctuations in TSH Ab did not always parallel those seen for TBII and reciprocal fluctuation pattern (transient or otherwise) were observed in 33%. In conclusion, anti-TSH antibody is produced frequently in patients with either Graves' disease or some other autoimmune thyroid disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗