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Biomedical subjects

T Fujihira

Publications and source records attributed to T Fujihira.

At least 19 recordsLinked to original sources
PubMed1997

Parathyroid hormone-related peptide-(1-34) [PTHrP-(1-34)] induces vasopressin release from the rat supraoptic nucleus in vitro through a novel receptor distinct from a type I or type II PTH/PTHrP receptor.

PTH and PTH-related peptide (PTHrP) bind to a type I PTH/PTHrP receptor expressed in bone and kidney or a type II receptor in nonclassical target tissue with equal affinity and similar bioactivities. PTHrP is abundant in the central nervous system, but its physiological role remains unknown. Herein, we examined the role of PTHrP-(1-34) on arginine vasopressin (AVP) release from the rat supraoptic nucleus (SON). Application of PTHrP-(1-34) to SON slices caused an increase in AVP release in a concentration-dependent manner. Neither PTHrP-(7-34) nor PTH-(1-34) had any effect on AVP release from the SON. PTHrP-(1-34)-induced AVP release was antagonized by a large excess of PTHrP-(7-34) and by H89, an inhibitor of cAMP-dependent protein kinase (A kinase), but not by PTH-(1-34) or PTH-(13-34). PTHrP-(1-34), but not PTH-(1-34), also dose-dependently increased the levels of cAMP in the SON. 125I-Labeled PTHrP-(1-34) bound specifically to crude membranes isolated from the SON. Scatchard analysis showed a single class of binding sites for PTHrP-(1-34) with a Kd of 36.4 nM and a maximum binding capacity of 3.94 pmol/mg protein. No specific binding for 125I-labeled PTH-(1-34) was noted. The binding of 125I-labeled PTHrP-(1-34) was displaced by unlabeled PTHrP-(1-34) and unlabeled PTHrP-(7-34), but not by unlabeled PTH-(1-34). These findings suggest that PTHrP-(1-34), but not PTH-(1-34), causes the release of AVP from the SON through a novel receptor distinct from type I or II PTH/PTHrP receptors.

Animals↗
PubMed1997

A case of active acromegalic woman with a marked increase in serum insulin-like growth factor-1 levels after delivery.

Pregnancy in a woman with active acromegaly is very rare, because amenorrhea, due to hyperprolactinemia and disturbed pituitary gonadotropin secretion may cause infertility. We report a 28-year-old pregnant woman with untreated acromegaly, who was followed up from early pregnancy to delivery. Her pregnancy was uneventful, and she went into spontaneous labor at 38 weeks and delivered a normal infant. Her serum GH levels were further increased in late pregnancy, followed by decreased in postpartum periods, which may be associated with enlargement of pituitary adenoma during pregnancy. In contrast with serum GH, her serum insulin-like growth factor-1 (IGF-1) levels were dissociated with her serum GH levels during late pregnant and postpartum period. Her serum GH and IGF-1 levels in late pregnancy were different from the levels in pregnant women with acromegaly reported previously.

Acromegaly↗
PubMed1996

Ileocolic intussusception in adult due to malignant lymphoma in the cecum with intramural metastasis.

A rare adult case of intussusception caused by malignant lymphoma of the cecum with intramural metastasis is reported. The patient was a 24-year-old man. Ileocolic intussusception was diagnosed by characteristic findings on abdominal computed tomography. Endoscopic examination revealed a massive protuberant tumor, 3 cm in diameter, and a semipedunculated polyp, 1 cm in diameter, in the cecum, which had caused the ileocolic intussusception. Endoscopic biopsy specimens failed to yield a definitive diagnosis histologically, but right hemicolectomy with lymph node dissection was performed. On histologic examination of the surgical specimens, both the tumor and the polyp were diagnosed as diffuse lymphoma of medium-sized cell type, and no lymph node involvement was found. The patient responded well to surgical and chemotherapeutic treatment, and has had no recurrence of malignant lymphoma in the 2 years since the surgical treatment. This was a very rare case of an intussusception in an adult patient due to malignant lymphoma in the cecum with intramural metastasis and without lymph node involvement.

Adult↗
PubMed1995

Stimulatory effect of interleukin-1 alpha on proliferation through a Ca2+/calmodulin-dependent pathway of a human thyroid carcinoma cell line, NIM 1.

NIM 1 cells, a human thyroid cell line established from a patient with thyroid papillary adenocarcinoma, produce cytokines such as interleukin-1 alpha (IL-1 alpha) and granulocyte-colony stimulating factor. In the present study, we investigated the signal transduction pathway in the proliferation of NIM 1 cells evoked by IL-1 alpha. Incubation of NIM 1 cells with IL-1 alpha for 48 h increased the incorporation of 3H-thymidine (3H-TdR). The stimulatory effect of IL-1 alpha was evident at 0.01 ng/ml and the maximal effect was seen at 10 ng/ml. IL-1 alpha evoked an influx of 45Ca into NIM 1 cells within 3 min in a concentration-dependent manner (0.01-1 ng/ml). These stimulatory effects of IL-1 alpha on both 3H-TdR incorporation and 45Ca influx were similarly inhibited by nicardipine, an inhibitor of voltage-dependent Ca2+ channels, in a concentration-dependent manner (10-1000 nM). The stimulatory effect of IL-1 alpha on 3H-TdR incorporation was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), an antagonist of calmodulin, but not by 1-(5-isoquinoline sulfonyl)-2-methylpiperazine (H-7), an inhibitor of protein kinase C. While the culture medium initially contained 0.75 mM Ca2+, inhibition of 3H-TdR incorporation by nicardipine and W-7 under these baseline conditions was also recognized. These results suggest that IL-1 alpha stimulates cell proliferation through a Ca2+/calmodulin-dependent pathway in NIM 1 cells.

Biological Transport↗
PubMed1995

Siblings with ACTH insensitivity due to lack of ACTH binding to the receptor.

We report two siblings, a 9-year-old boy and 4-year-old girl, with ACTH insensitivity. They were referred to our hospital because of pigmentation of the skin. They had normal plasma cortisol and urinary 17-OHCS levels despite markedly high plasma ACTH, and these did not respond to consecutive 3-day ACTH-Z administration, but plasma aldosterone responded normally to increased plasma renin activity after a low sodium diet. We examined the characteristics of ACTH receptors in peripheral blood mononuclear leukocytes (MNLs) obtained from the patients and their family. Adenylate cyclase generation caused by an addition of ACTH did not occur in MNLs from the patients. In studies on ACTH binding to MNLs, a lack of high-affinity ACTH binding was observed in the patients. These results suggest that the patients have a defect in ACTH binding to the receptors, resulting in ACTH insensitivity. The reason for this defect in ACTH binding remains unclear because no significant mutation in the ACTH receptor DNA sequence was detected in the MNLs of these patients.

17-Hydroxycorticosteroids↗
PubMed1995

Germ line mutation in the RET proto-oncogene associated with familial multiple endocrine neoplasia type 2B: a case report.

Multiple endocrine neoplasia type 2 (MEN 2) is a dominantly inherited cancer syndrome. MEN 2B is characterized by the combined occurrence of medullary thyroid carcinoma (MTC), pheochromocytoma, mucosal neuroma and Marfanoid habitus. Recently, a missense mutation in codon 918 of the proto-RET has been reported in the germ line of apparently distinct families with MEN 2B. In the present paper we first show a familial case of MEN 2B in Japan also to be associated with a germ line mutation in codon 918 of the proto-RET. The mutation was the substitution of a threonine for a methionine in the tyrosine kinase domain of the protein. The germ-like mutations of the proto-RET in MEN 2A and MEN 2B are the first examples of a dominantly acting oncogenic point mutation initiating human hereditary neoplasia.

Adrenal Gland Neoplasms↗
PubMed1994

The receptor, metabolism and effects of androgen in osteoblastic MC3T3-E1 cells.

We investigated the androgen receptor (AR), metabolism and effects of androgens in osteoblastic MC3T3-E1 cells. AR was proved as a transcript of a 10-kb mRNA and as a 110-kDa protein. An immunocytochemical study showed that AR was located mainly in the nuclei. Specific binding of [3H]DHT was observed in both the nuclear and cytosol fractions. MC3T3-E1 cells possessed approximately 1190 binding sites per cell and most of the sites (1150 sites) situated in the nucleus. The apparent Kd value in the nuclear fraction was 1.35 nM for [3H]DHT binding, and it was similar to that for [3H]testosterone. In the competition analysis, there was not much difference in the displacement of the [3H]DHT binding from AR between the addition of radioinert DHT and testosterone. In studies of 5 alpha-reductase activity and aromatase activity of the cells, both activities were lower than the respective values in classical androgen target tissues. Androgens stimulated the incorporation of [3H]thymidine into the cell, and DHT and testosterone had a similar potency on the cell proliferation. Thus, these results suggest testosterone itself acts mainly on the osteoblasts without conversion to DHT.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1994

Familial primary hyperparathyroidism complicated with Wilms' tumor.

We describe a familial occurrence of primary hyperparathyroidism. The proband is a 60-year-old woman who had a parathyroid adenoma. Her older sister had a parathyroid adenoma with cementifying jaw fibroma and her younger sister died of parathyroid adenocarcinoma with pulmonary metastasis at the age of 38. We have not yet obtained evidence for other endocrine disorders suggesting multiple endocrine neoplasia (MEN) in this pedigree. The proband is complicated with Wilms' tumor. It is now widely accepted that respective predisposed genes of MEN type 1 and Wilms' tumor, and PTH gene are located on chromosome 11. The manifestation observed in this case may be related to mutational abnormalities on chromosome 11.

Adenocarcinoma↗
PubMed1992

Characterization of a minimal promoter element required for transcription of the mouse type II beta regulatory subunit (RII beta) of cAMP-dependent protein kinase.

The 5'-flanking DNA of the mouse RII beta subunit of the cAMP-dependent protein kinase gene was characterized by transient transfection of RII beta-CAT constructs into mouse neuroblastoma cells (NB2a) and Chinese hamster ovary (CHO) cells and by gel mobility shift and footprinting assays. The minimal promoter of the RII beta gene was composed of two adjacent functional elements. A 3'-element which supported enhanced CAT activity was located between base pairs (bp) -267/-168 from the translation initiation start site. CAT plasmids containing these RII beta sequences showed 12- and 16-fold increased CAT activity in the NB2a and CHO cells, respectively, compared to the basic CAT vector. Plasmids containing 20 additional bp 5' to the -267/-168 fragment showed 2-fold more CAT activity than the shorter fragment in NB2a cells, while CAT activity in CHO cells was nearly the same for both constructs. CAT plasmids containing only this 20-bp fragment showed 9- and 13-fold increased CAT activity in NB2a and CHO cells, respectively. The core promoter of the RII beta gene lacked classical TATA and CAT sequences, but contained 3 copies of the Sp1 core consensus sequence. Gel mobility shift assays using 32P-labeled 5'-flanking DNA containing bp -291/-49 and nuclear extracts from NB2a and CHO cells displayed several retarded bands in the gels suggesting complex formation with nuclear DNA-binding factors. Unlabeled DNA containing bp -291/-49 blocked the appearance of all retarded bands. Competition using an oligonucleotide corresponding to the Sp1 DNA-binding site effectively blocked the appearance of the two more slowly migrating bands but did not affect the major rapidly migrating bands. DNase I footprinting analysis using purified Sp1 protein confirmed that Sp1 could bind to the Sp1 sites. Methylation interference and mutational analysis showed that one of the faster migrating bands was the result of factor binding to the DNA sequence adjacent to the Sp1 sites. Additional tissue-specific nuclear-binding factor sequences were detected upstream of the core promoter. Our data suggest that the core promoter of the RII beta gene can initiate transcription from the DNA around the Sp1 sites but that there are tissue-specific nuclear factor-binding sites located distal to the Sp1 sites.

Animals↗
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↗