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T Fujihira

Publications and source records attributed to T Fujihira.

At least 19 recordsLinked to original sources
PubMed2006

Evidence for involvement of glial cell activity in the control of extracellular D-serine contents in the rat brain.

The continuous intra-cortical infusion of a glia toxin, fluorocitrate, at the concentration of 1 mM caused a decrease in the cortical extracellular contents of an intrinsic coagonist for the N-methyl-D-aspartate (NMDA) type glutamate receptor, D-serine, by peaking at 40 min by -25% but produced an increase in those of glycine and L-serine. The attenuated glial activity by fluorocitrate was verified by a marked reduction in the extracellular glutamine contents. The present findings suggest that a group of glial cells such as a population of the protoplasmic astrocytes could, at least in part, participate differently in the regulation of the extracellular release of D-serine and another NMDA coagonist glycine in the medial frontal cortex of the rat.

Animals↗
PubMed2000

Centrally administered murine-leptin stimulates the hypothalamus-pituitary- adrenal axis through arginine-vasopressin.

Starvation induces a decrease in circulating leptin levels and activation of the hypothalamus-pituitary-adrenal (HPA) axis. Leptin inhibits the HPA axis in unfed rodents or genetically leptin-deficient ob/ob mice, whereas it stimulates corticotropin-releasing hormone (CRH) gene expression in the paraventricular nucleus (PVN). However, the interactions between leptin, CRH and the HPA axis are poorly understood and are likely to be complex. We recently demonstrated that central leptin administration caused increases in plasma arginine-vasopressin (AVP) and AVP gene expression of the PVN in nonstressful rats. AVP stimulates the release of adrenocorticotropic hormone (ACTH), but it also potentiates the action of CRH on ACTH release. In this study, we investigated the effects of leptin on plasma ACTH and corticosterone levels, CRH mRNA of the PVN and proopiomelanocortin (POMC) mRNA of the pituitary in nonstrained rats. Intracerebroventricularly administered leptin caused increases in plasma ACTH and corticosterone levels in dose-dependent manners. In Northern blot analyses, the leptin injection induced significant increases in the expression of CRH mRNA in the PVN and POMC mRNA in the pituitary. The increased plasma ACTH and corticosterone levels by leptin were attenuated with intracerebroventricular pretreatment of a V(1a) receptor antagonist (OPC-21268) or a V(1a)/V(1b) receptor antagonist (dP[Tyr(Me)(2)]AVP), but not with that of a V(2) receptor antagonist (OPC-31260). The leptin-induced CRH mRNA expression in the PVN and POMC mRNA expression in the pituitary were also reduced by the pretreatment with OPC-21268 and dP[Tyr(Me)(2)]AVP. These results suggest that intracerebroventricular leptin administration activates the HPA axis by AVP receptor activation through V(1a) receptors in the PVN which in turn activates CRH neurons to drive ACTH and corticosterone secretion in concert with AVP in nonstrained rats.

Adrenocorticotropic Hormone↗
PubMed1999

Comparison of recombinant human thyrotropin receptors versus porcine thyrotropin receptors in the thyrotropin binding inhibition assay for thyrotropin receptor autoantibodies.

Thyrotropin receptor autoantibodies (TRAb) are most commonly measured in a thyrotropin-binding inhibition (TBI) assay using solubilized porcine thyrotropin receptors (pTSHR). Recently, we reported modifications in recombinant human thyrotropin receptor (hTSHR) production and extraction that made substitution of this antigen for the pTSHR practical. We now report the first comparison of the behavior in a TBI assay of the recombinant, solubilized hTSHR with the pTSHR in a large series of clinically characterized patients with autoimmune thyroid disease. We studied 227 patients with Graves' disease (32 untreated patients, 156 patients receiving antithyroid medications, 24 patients in remission, 9 patients with recurrence of disease, and 6 thyroidectomized patients), as well as 32 patients with Hashimoto's thyroiditis and 28 normal individuals. In patients with untreated Graves' disease, 29 of 32 (90.6%) were TBI positive with either antigen, although two sera gave discrepant data in the two assay. Of the patients receiving antithyroid drugs, 94 of 156 (60.3%) were positive with the pTSHR and 106 of 156 (67.9%) were positive with the hTSHR TBI assay (p < 0.05%). In all other respects, however, there was no difference between the two TBI assays. Neither assay performed well in providing clinical guidance in the remission or relapse of disease. Of the 24 Graves' patients in remission, 75.0% and 79.2% were TBI negative with the hTSHR and pTSHR assays, respectively. The TBI assay at the time of relapse was even less informative; 6 of 9 (66.7%) being TBI negative in the pTSHR assay and 3/9 (33.3%) being negative in the hTSHR assay. In TBI assays with both species of TSHR, 3 of 32 hypothyroid patients with Hashimoto's thyroiditis were TBI positive. In summary, production of the recombinant hTSHR is now a practical reality and this antigen can clearly substitute at least as well for the pTSHR in the imperfect, although most commonly used, TBI assay. It is, therefore, likely that the hTSHR will supplant the pTSHR in this important assay. However, the use of the hTSHR rather than pTSHR does not appear to provide a major advantage, at least in terms of TBI assay sensitivity, specificity and predictive value.

Animals↗
PubMed1999

Centrally administered murine leptin stimulates plasma arginine-vasopressin secretion and increases the level of mRNA expression in the supraoptic nucleus of conscious rats.

The product of the ob gene protein, leptin, has been suggested to function as an endogenous mediator of the cardiovascular system via sympathetic nerve activity. Moreover, extensive distribution of leptin receptor-like immunoreactivity has been demonstrated in the choroid plexus, cerebral cortex, hippocampus, thalamus and hypothalamus, especially in the paraventricular nucleus (PVN) and supraoptic nucleus (SON). In this study, we have investigated the in vivo effects of leptin on plasma arginine-vasopressin (AVP) secretion and the level of AVP messenger ribonucleotic acid (AVP mRNA) in the SON of conscious rats. Intracerebroventricularly administered leptin increased plasma AVP concentration in a dose-dependent manner (0-400 pmol/rat). The maximal effect was obtained at 15 min after the administration of leptin. Furthermore, in Northern blot analyses, the levels of AVP mRNa in the SON increased approximately 2-fold from the basal level after the administration of leptin. AVP mRNA expression in the PVN was also increased by leptin. However, leptin had no effects on plasma oxytocin (OXT) secretion and OXT gene expression in the SON. In conclusion, leptin is involved in AVP secretion via the central nervous system, however, its physiological role is unknown.

Animals↗
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↗