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T Nishi

Publications and source records attributed to T Nishi.

At least 91 records · Page 5Linked to original sources
PubMed1999

Human histamine H2 receptor gene: multiple transcription initiation and tissue-specific expression.

We have characterized the genomic structure of 12.3 kb of the 5'-flanking region of the human histamine H2 receptor gene. The multiple transcription initiation sites of the human histamine H2 receptor gene were mapped utilizing the 5'-end cap structure of mRNA. We found that a 85 bp segment (-610-(-)525 bp) immediately upstream of the initiation site exhibits a strong promoter activity in the gastric adenocarcinoma, MNK45, expressing human histamine H2 receptor. A 4.8 kb transcript of the human histamine H2 receptor gene was found in the placenta, spinal cord, lymph node and bone marrow in addition to the previously reported tissues including the heart, brain and stomach, whereas a 1.8 kb transcript was observed in almost all tissues examined. 3'-rapid amplification of cDNA ends revealed the corresponding length of the 3'-untranslated region. These results suggest that the 3'-untranslated region may be involved in the differential expression.

Base Sequence↗
PubMed1999

Transmembrane topography of the 100-kDa a subunit (Vph1p) of the yeast vacuolar proton-translocating ATPase.

The membrane topography of the yeast vacuolar proton-translocating ATPase a subunit (Vph1p) has been investigated using cysteine-scanning mutagenesis. A Cys-less form of Vph1p lacking the seven endogenous cysteines was constructed and shown to have 80% of wild type activity. Single cysteine residues were introduced at 13 sites within the Cys-less mutant, with 12 mutants showing greater than 70% of wild type activity. To evaluate their disposition with respect to the membrane, vacuoles were treated in the presence or absence of the impermeant sulfhydryl reagent 4-acetamido-4'-maleimidylstilbene-2,2'-disulfonic acid (AMS) followed by the membrane permeable sulfhydryl reagent 3-(N-maleimidylpropionyl) biocytin (MPB). Three of the 12 active cysteine mutants were not labeled by MPB. The mutants E3C, D89C, T161C, S266C, N447C, K450C, and S703C were labeled by MPB in an AMS-protectable manner, suggesting a cytoplasmic orientation, whereas G602C and S840C showed minimal protection by AMS, suggesting a lumenal orientation. Factor Xa cleavage sites were introduced at His-499, Leu-560, and Pro-606. Cleavage at 560 was observed in the absence of detergent, suggesting a cytoplasmic orientation for this site. Based on these results, we propose a model of the a subunit containing nine transmembrane segments, with the amino terminus facing the cytoplasm and the carboxyl terminus facing the lumen.

Cysteine↗
PubMed1999

Overexpression of striatal enriched phosphatase (STEP) promotes the neurite outgrowth induced by a cAMP analogue in PC12 cells.

A cytoplasmic protein tyrosine phosphatase (PTPase) designated as striatal enriched phosphatase with a molecular weight of 46 kDa (STEP46) is highly expressed in striatal neurons with dopamine D1-receptors. To examine the hypothesis that STEP46 is involved in the neuronal functions modulated by the cyclic adenosine 3', 5'-monophosphate (cAMP)-signaling system, we introduced the complementary DNA of STEP46 into the pheochromocytoma cell line PC12, which exhibits neuronal differentiation characterized by neurite outgrowth in response to cAMP and nerve growth factor stimulation, and we established subclonal cell lines that constitutively overexpress STEP46 protein with PTPase activity. The subclones expressing STEP46 showed increased neurite outgrowth during differentiation induced by a cAMP analogue (dibutyryl cAMP). The positive regulatory role of STEP46 in the cAMP-induced neuronal differentiation of PC12 cells indicates that STEP46 may play a role in neuronal processes modulated by the cAMP-signaling cascade as a PTPase.

Animals↗
PubMed1999

Combined NK1 and NK2 tachykinin receptor antagonists: synthesis and structure-activity relationships of novel oxazolidine analogues.

We report herein the synthesis and structure-activity relationships of a series of novel oxazolidine analogues with regards to NK1 and NK2 tachykinin receptor binding affinity. Among this series of oxazolidine analogues, some compounds exhibited excellent high binding affinities for both NK1 and NK2 receptors. In addition, we describe the inhibitory effect in vivo on SP-induced airway vascular hyperpermeability and NKA-induced bronchoconstriction in guinea pigs.

Animals↗
PubMed1999

Cloning and functional characterization of the 5'-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene. Essential role of 5'-untranslated region in tissue-specific expression.

The human monocyte chemoattractant protein-1 receptor designated hCCR2 is an essential co-receptor in cell entry by the human immunodeficiency virus as well as a receptor for monocyte chemoattractant protein-1, a member of the family of C-C chemokines that mediate monocyte chemotaxis. To elucidate the molecular mechanisms underlying the transcriptional regulation of hCCR2, we cloned and sequenced the hCCR2 gene; it was approximately 8 kilobase pairs in length and consisted of three exons divided by two introns. In the 5'-flanking region, there were the typical mammalian promoter consensus elements, a CAAT box and a TATA box, resulting in a single transcription initiation site. In addition, we found clustered tissue-specific cis-regulatory elements such as GATA consensus sequences, Oct-1 binding sequences, and CAAT/enhancer-binding protein binding sequences. Luciferase assays with various promoter deletions and gel mobility shift assays indicated that three cis-regulatory elements located within the region from -89 to +118 are required for basal activity in THP-1 cells. One element is an octamer sequence 36-base pair upstream from the TATA box; it binds mainly to Oct-1 and is capable of increasing transcriptional activity. The other two elements, which are tandem recognition sites of the CAAT/enhancer-binding protein family, are located in the 5'-untranslated region and account for the transcriptional activation as well as the tissue specificity of hCCR2.

5' Untranslated Regions↗
PubMed1999

Blockade of kit signaling induces transdifferentiation of interstitial cells of cajal to a smooth muscle phenotype.

BACKGROUND & AIMS: Interstitial cells of Cajal (ICC) serve as pacemaker cells and mediators of neurotransmission from the enteric nervous system to gastrointestinal muscles. ICC develop from mesenchymal cells that express c-Kit, and signaling via Kit receptors is necessary for normal development of ICC. We studied the fate of functionally developed ICC after blockade of Kit receptors to determine whether ICC undergo cell death or whether the phenotype of the cells is modified. The fate of undeveloped ICC was also investigated. METHODS: Neutralizing, anti-Kit monoclonal antibody (ACK2) was administered to mice for 8 days after birth. ICC in the small intestine were examined by immunohistochemistry and electron microscopy. Occurrence of apoptosis was also assayed. RESULTS: When Kit receptors were blocked, ICC nearly disappeared from the small intestine. Apoptosis was not detected in regions where ICC are normally distributed. Remaining Kit-immunopositive cells in the pacemaker region of the small intestine developed ultrastructural features similar to smooth muscle cells, including prominent filament bundles and expression of the muscle-specific intermediate filament protein, desmin, and smooth muscle myosin. ICC of the deep muscular plexus normally develop after birth in the mouse. Precursors of these cells remained in an undifferentiated state when Kit was blocked. CONCLUSIONS: These data, along with previous studies showing that ICC in the pacemaker region of the small intestine and longitudinal muscle cells develop from the same Kit-immunopositive precursor cells, suggest inherent plasticity between the ICC and smooth muscle cells that is regulated by Kit-dependent cell signaling.

Animals↗
PubMed1999

Ossifying fibromyxoid tumor of soft parts in a child: a case report.

Ossifying fibromyxoid tumor (OFMT) is a relatively rare tumor, most of which occur in adults with preferential localization in subcutis or muscles of the extremeties. Although Schwannian or cartilage origin has been suggested, histogenesis of this tumor still is unclear. The authors present a 6-year-old girl with retroperitoneal OFMT showing paraspinal extension, who is alive and tumor free 9 years after excision. The current case is the youngest reported patient showing unusual deep trunk site with surgically identified association with the spinal nerve. Both the clinical and histopathologic features strongly suggested Schwannian origin of this tumor.

Child↗
PubMed1999

Analysis of 1,992 patients with anorectal malformations over the past two decades in Japan. Steering Committee of Japanese Study Group of Anorectal Anomalies.

BACKGROUND/PURPOSE: This report describes the results of a group study of the Japanese Study Group of Anorectal Anomolies (JSGA) to determine the relative incidence of specific types of anorectal anomaly in Japan, and includes discussion of rectourethral fistula regarding the relationship between the levels of the fistula and blind end of the rectum, low type deformity, rare types, and associated anomalies. METHODS: A total of 1,992 patients (1,183 boys and 809 girls) registered from 1976 to 1995 were analyzed. RESULTS: High-type deformities accounted for 26.0% of cases, intermediate 10.7%, low 57.2%, miscellaneous 4.5% and unclassified 1.8%. The most frequent deformity was male anocutaneous fistula (n = 364), followed by male rectourethral fistula (n = 333), and female anovestibular fistula (n = 241). There were 42 rectovesical fistulas in boys and 93 rectocloacal fistulas in girls. Covered anus complete occurred at the same frequency (10.1% of low deformities) as covered anal stenosis. In rectourethral fistula, the blind end of the rectum lay at or above the level of the P-C line in 40.3% of cases, at or above the M line in 39.6% and at the vicinity of the I line in 20.2%, respectively. There was no parallel relationship between the site of the fistula opening and the level of the rectal pouch. The overall incidence of patients having one or more associated anomalies was 45.2%: 70.6% in high deformity, 60.7% in intermediate, and 31.3% in low. The rate of association of Down's syndrome with deformities without fistula (40.3%) was significantly higher than with deformities with fistula (0.3%). CONCLUSIONS: Rectovesical fistula and covered anus complete were not infrequent deformities in this series. We consider that at least 20% of rectourethral fistula should be categorized as intermediate or low deformity from the viewpoint of the position of the rectal pouch. A significant preponderance of Down's syndrome in the deformities without fistula suggests that further investigation of associated anomalies in comparision with other congenital diseases may provide insights into the pathogenesis of anorectal malformation in the field of molecular genetics.

Anal Canal↗
PubMed1999

Clinical features of isolated noncompaction of the ventricular myocardium: long-term clinical course, hemodynamic properties, and genetic background.

OBJECTIVES: A nationwide survey was conducted to clarify the clinical features of isolated noncompaction of the ventricular myocardium (INVM) in Japanese children in comparison with features previously described in patients with INVM. BACKGROUND: Isolated noncompaction of the ventricular myocardium is a rare disorder characterized by an excessively prominent trabecular meshwork. It is accompanied by depressed ventricular function, systemic embolism and ventricular arrhythmia. METHODS: A questionnaire specifically designed for this study was sent to 150 hospitals in Japan where a pediatric cardiology division exists. RESULTS: Twenty-seven patients were diagnosed by two-dimensional echocardiography, their ages ranging from one week to 15 years at presentation, with follow-up lasting as long as 17 years. The gross anatomical appearance and the extension of noncompacted myocardium predominantly at the apex observed on two-dimensional echocardiograms were similar to observations reported previously. Dissimilarities included a greater number of asymptomatic patients at initial presentation, a longer clinical course with gradually depressed left ventricular function, no systemic embolism, and rare ventricular tachycardia in the Japanese children. Cardiac catheterization disclosed normal left ventricular end-diastolic volume and increased left ventricular end-diastolic pressure in most cases, consistent with restrictive hemodynamics. A higher incidence of Wolff-Parkinson-White syndrome was found in the children, whereas left bundle branch block was rarer than reported in adults. Familial recurrence was high (44%) and included many women. CONCLUSIONS: In Japanese children, INVM can be found by screening examinations at asymptomatic stage, and it might have a longer dinical course with gradually depressed left ventricular function and restrictive hemodynamics. The pattern of familial recurrence we observed implies that INVM is a distinctive clinical entity with a heterogeneous genetic background.

Adolescent↗
PubMed1999

Three secoiridoid glucosides from Jasminum nudiflorum.

Phytochemical study of the leaves and stems of Jasminum nudiflorum has led to the isolation of three secoiridoid glucosides, jasnudiflosides A-C (1-3). The structures of these compounds were elucidated on the basis of chemical and spectroscopic evidence.

Carbohydrate Conformation↗
PubMed1999

Participation of Bcl-2/Bax-alpha in glutamate-induced apoptosis of human glioblastoma cells.

Glutamate has been shown to function as a toxic agent in neuronal and glial cells, as well as an excitatory neurotransmitter throughout the central nervous system. In the present study, we examined the effect of increasing glutamate concentration on the induction of apoptosis in the two human glioblastoma cell lines GB-4 and GB-12. Glutamate exposure caused cell death of GB-4 and GB-12 in a dose-dependent manner. The cells were found to die via apoptosis in response to glutamate based on the following criteria: propidium iodide (PI) staining, H-E staining, electron microscopic analysis, and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. The glutamate-induced apoptosis appears to involve the modulation of Bcl-2 family gene products such as Bcl-2, Bcl-xL, and Bax-alpha. Both Bcl-2 and Bcl-xL were down-regulated by glutamate at 24 h and further at 48 h. The apoptosis-promoting product p21 Bax-alpha was also down-regulated in GB-12 but slightly up-regulated in GB-4, accompanied by generation of variant form of p18 Bax-alpha in both cell lines. These findings suggest that glutamate toxicity results in cellular death via an apoptotic mechanism which appears to involve the Bcl-2/Bax-alpha molecular complex.

Apoptosis↗
PubMed1999

Synthesis of 2-phenylbenzofuran derivatives as testosterone 5 alpha-reductase inhibitor.

A series of 2-phenylbenzofuran derivatives with a carbamoyl, alkylamino, or alkyloxy group at the 5 or 6 position of the benzofuran ring were synthesized and evaluated for rat and human testosterone 5 alpha-reductase inhibitory activities in vitro. Against rat enzyme, the carbamoyl derivatives had more potent inhibitory activities than the alkylamino or alkyloxy derivatives, and the 6-carbamoyl derivatives tended to be more potent than the 5-carbamoyl derivatives. Against human enzyme, the 6-substituted derivatives had more potent inhibitory activities than the 5-substituted derivatives. The 6-carbamoyl and 6-alkylamino derivatives tended to show stronger inhibitory activities against human type 1 enzyme than against type 2 enzyme, but they were not largely selective.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1999

Guanidinated casein hydrolysate stimulation of cholecystokinin release via pancreatic enzyme- and cholinergic-independent mechanisms in rats.

We had demonstrated that a peptic hydrolysate of guanidinated casein that is made from casein by the conversion of lysine to homoarginine stimulated pancreatic exocrine secretion in rats with chronic bile-pancreatic juice (BPJ) diversion from the proximal small intestine. This modified protein also stimulated cholecystokinin (CCK) release from dispersed rat intestinal cells. In this study, we found that guanidinated casein hydrolysate stimulates CCK release in chronic BPJ-diverted rats with cholinergic control blocked by atropine. Intraduodenal guanidinated casein hydrolysate increased portal plasma CCK concentration and pancreatic secretion in atropine-treated BPJ-diverted rats. In contrast, the portal plasma CCK concentration was not increased by intact casein hydrolysate. We conclude that guanidinated casein hydrolysate directly stimulates CCK release from the intestine via some cholinergic-independent mechanism, and an increase of the pancreatic exocrine secretion is regulated by CCK released by guanidinated casein hydrolysate. A guanidyl residue is likely to be involved in this control.

Animals↗
PubMed1999

Expression of p120 nucleolar proliferating antigen in human gliomas and growth suppression of glioma cells by p120 ribozyme vector.

p120 is a nucleolar proliferating antigen which is expressed in tumor cells but not normal resting cells. The expression and localization of p120 in human gliomas were studied by Northern blot analysis, Western blot analysis and immunohistochemistry. All five of the glioma cell lines and all of the glioma specimens we investigated expressed p120 at both the mRNA and protein levels. p120 expression was not detected in adjacent brain tissues. A ribozyme vector was constructed to cleave the first GUC sequence in the coding region of p120 mRNA. This p120 ribozyme vector was transfected into the glioma cell line SF188, which expresses p120. The reduced p120 expression of the transfectant at both the mRNA and protein levels was confirmed. An MTT assay indicated that the transfected cells grew more slowly than control cells. These results indicate that i) p120 has an important role in the proliferation of gliomas, and ii) the ribozyme against p120 mRNA can suppress glioma cell growth.

Base Sequence↗
PubMed1999

Frequent expression of inducible nitric oxide synthase in esophageal squamous cell carcinomas.

Nitric oxide (NO) plays important biological roles in cardiovascular, nervous and immune systems, and is synthesized by nitric oxide synthase (NOS). Intracellular NO is known to cause DNA damage as a mutagen. We examined the expression of cytokine-inducible NOS (iNOS) in human esophageal squamous cell carcinomas. Weak iNOS immunoreactivity was seen in the basal and parabasal layers of non-neoplastic esophageal stratified squamous epithelium. iNOS expression was detected in 50 (87.7%) of the 57 esophageal squamous cell carcinomas, regardless of the depth of tumor invasion, histological differentiation and lymph node status. Early-stage cancers, i.e. mucosal squamous cell carcinomas, also showed significant iNOS expression. We speculate that increased iNOS expression is associated with the carcinogenesis of human esophageal cancer.

Adult↗