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H Nishimori

Publications and source records attributed to H Nishimori.

At least 19 recordsLinked to original sources
PubMed1999

Molecular cloning, mapping, and characterization of a novel human gene, MTA1-L1, showing homology to a metastasis-associated gene, MTA1.

Through large-scale sequencing of clones randomly selected from libraries of human cDNAs, we have isolated a novel human gene encoding a product with 59.6% identity in amino acid sequence to human MTA1, a protein associated with tumor invasion and metastasis. This cDNA, named MTA1-L1 (MTA1 like 1), consists of 2736 nucleotides with an open reading frame encoding 668 amino acids. A single 3.0-kb transcript of MTA1-L1 was expressed ubiquitously on Northern blots. Structural analysis of the MTA1-L1 gene revealed 18 exons spanning 8.1 kb of genomic DNA. We assigned the MTA1-L1 locus to chromosomal band 11q12-13.1 by fluorescence in situ hybridization.

Amino Acid Sequence↗
PubMed1999

Association of ulcerative colitis with rare VNTR alleles of the human intestinal mucin gene, MUC3.

Ulcerative colitis (UC), a common form of inflammatory bowel disease, is a multifactorial disorder with significant genetic influence. Recently, evidence of linkage on chromosome 7q near the intestinal mucin gene MUC3 was reported by an affected sib-pair analysis. Previous reports indicate a possible mucin abnormality in UC patients, but whether genetic differences in a specific mucin gene are associated with UC is unknown. Here we analysed polymorphisms of variable number of tandem repeats (VNTRs) within this gene using DNAs obtained from 243 Japanese (75 patients with UC and 168 controls), and to confirm the result we undertook a two-stage examination using 328 Caucasian samples (72 and 85 with UC in the first and second stages, respectively, and 171 controls). When the frequency of patients carrying one or two rare VNTR alleles was compared with that of controls, a significant increase was found first in Japanese patients (odds ratio 2.72, 95% CI 1.17-6.32, P = 0. 0308). In Caucasians, the odds ratio was 2.80 (95% CI 1.36-5.75, P = 0.0079) in the first stage, 2.43 (95% CI 1.20-4.92, P = 0.0196) in the second stage and 2.60 (95% CI 1.41-4.80, P = 0.0024) in total. The overall odds ratio was 2.64 (95% CI 1.60-4.33, P = 0.0001). This result suggests that rare alleles of the MUC3 gene may confer genetic predisposition to UC.

Alleles↗
PubMed1999

Identification of BAIAP2 (BAI-associated protein 2), a novel human homologue of hamster IRSp53, whose SH3 domain interacts with the cytoplasmic domain of BAI1.

BAI1 (brain-specific angiogenesis inhibitor 1) was originally isolated as a p53-target gene specifically expressed in brain. To clarify its function, we have been searching for cellular proteins that associate with the cytoplasmic domain of BAI1. Using its intracellular carboxyl terminus as "bait" in a yeast two-hybrid system, we isolated a cDNA clone named BAIAP2 whose nucleotide sequence would encode a 521-amino acid protein showing significant homology to a 58/53-kDa substrate of insulin-receptor kinase in the hamster. As the expression profile of BAIAP2 examined by Northern blot analysis was almost identical to that of BAI1, BAIAP2 appears to be active mainly in neurons. In vitro binding assays confirmed that a proline-rich cytoplasmic fragment of BAI1 interacted with the Src homology 3 (SH3) domain of BAIAP2. Double-color immunofluorescent analysis revealed that BAIAP2 was localized at the cytoplasmic membrane when it was coexpressed with BAI1 in COS-7 cells; BAIAP2 not associated with BAI1 was diffused in the cytoplasm. Predominant localization of BAI1 protein in a sub-cellular fraction enriched in growth cones indicated a possible role of BAI1 as a cell adhesion molecule inducing growth cone guidance. As a protein partner of BAI1, BAIAP2 may represent an important link between membrane and cytoskeleton in the process of neuronal growth.

Amino Acid Sequence↗
PubMed1999

Recombinant adenovirus expressing wild-type p53 is antiangiogenic: a proposed mechanism for bystander effect.

Angiogenesis is required for the growth and progression of malignancies. Recent studies have demonstrated that genetic alterations may accompany acquisition of the angiogenic phenotype. The tumor suppressor gene p53 is most frequently mutated in human cancers and is also known to be a transcriptional regulator of a variety of genes. Here, we investigated the antiangiogenic effect of the wild-type p53 (wt-p53) gene transfer on a human non-small cell lung cancer cell line. Mutant p53-expressing H226Br non-small cell lung cancer cells were transduced with the wt-p53 gene using a recombinant adenoviral vector (Ad5CMVp53) and applied to semiquantitative reverse transcription-PCRs for the detection of altered mRNA expression of angiogenic and/or antiangiogenic factors. In vivo neovascularization assay of Ad5CMVp53-infected cells was then performed using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice. We also evaluated the effect of Ad5CMVp53-infected H226Br cells on nontransduced tumor cells in vivo by s.c. inoculating mixture of cells into nu/nu mice. Ad5CMVp53 infection markedly inhibited the expression of an angiogenic factor, vascular endothelial growth factor, and increased the expression of a novel antiangiogenic factor, brain-specific angiogenesis inhibitor 1, resulting in reduced neovascularization in vivo. Mixing experiments showed that tumor cells transduced with the wt-p53 gene inhibited the in vivo tumor growth of adjacent nontransduced cells. Our data suggest that a recombinant adenovirus expressing the wt-p53 gene is antiangiogenic, which may explain, in part, the mechanism of the bystander effect induced by the wt-p53 gene transfer on adjacent tumor cells.

Adenoviruses, Human↗
PubMed1998

A missense mutation of mouse OCTN2, a sodium-dependent carnitine cotransporter, in the juvenile visceral steatosis mouse.

Carnitine is an essential cofactor for the mitochondrial beta-oxidation of long-chain fatty acids. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, is inherited in an autosomal recessive manner. Recently, a human OCTN2 gene encoding a sodium-dependent carnitine cotransporter was isolated and mapped to human chromosome 5q31. Since the mouse jvs locus was assigned to the region of chromosome 11 where it is syntenic to human chromosome 5q31, we isolated the mouse octn2 gene and screened for its mutation in the jvs mouse. DNA sequencing analysis disclosed a missense mutation from CTG (Leu) to CGG (Arg) at codon 352 located within the sixth transmembrane domain of octn2. This amino acid replacement possibly causes the conformational change of the protein that leads to dysfunction of the gene product. Hence, we conclude that octn2 is a candidate gene responsible for the JVS mouse.

Amino Acid Sequence↗
PubMed1998

Cloning and characterization of BAP3 (BAI-associated protein 3), a C2 domain-containing protein that interacts with BAI1.

BAI1 (brain-specific angiogenesis inhibitor 1), a p53-target gene specifically expressed in brain, encodes a seven-span transmembrane protein considered to be a member of the secretin receptor family. Using a two-hybrid system, we isolated a cDNA encoding a product that interacts with the cytoplasmic region of BAI1 and designated it BAP3 (BAI1-associated protein 3). The BAP3 product is a novel C2 domain-containing molecule with homology to Munc13 and synaptotagmin. As with Munc13, BAP3 is expressed predominantly in brain. Deletion-mutant analysis revealed that the interaction between BAI1 and BAP3 was not mediated by the C2 domains. Its predominant expression in brain and homology to Munc13 indicate that BAP3, by interacting with BAI1, might be involved in some neuronal function such as regulating release of neurotransmitters.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Cloning and characterization of BAI-associated protein 1: a PDZ domain-containing protein that interacts with BAI1.

Brain-specific angiogenesis inhibitor 1 (BAI1), which is a p53-target gene specifically expressed in brain, encodes a seven-span transmembrane protein. Using a two-hybrid system, we isolated a cDNA that encodes a protein, named BAP1 (BAI1-associated protein), which interacts with the cytoplasmic region of BAI1. BAP1 is a novel member of the MAGUK (membrane-associated guanylate kinase homologue) family; it possesses a guanylate kinase domain, WW domains, and multiple PDZ domains. Interaction between BAI1 and BAP1 was mediated by a QTEV motif in the carboxy-terminal region of BAI1 and PDZ domains of BAP1. By immunocytochemical analysis of COS-7 cells transfected with BAI1 and BAP1, both products were co-localized at the cytoplasmic membrane, especially at cell-cell junctions. Cells transfected with BAI1 formed filopodia-like cytoplasmic extensions. These results suggest that BAI1 and BAP1 might be involved in cell adhesion and signal transduction in brain.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Reduced expression and rare genomic alteration of nm23-H1 in human hepatocellular carcinoma and hepatoma cell lines.

We investigated the expression and genomic alteration of nm23-H1 (which encodes a nucleoside diphosphate, kinase A) in 12 human hepatocellular carcinomas (HCCs) and four hepatoma cell lines. The expression of nm23-H1 protein was significantly reduced in HCCs with intrahepatic metastasis (72%) compared with expression in HCCs without intrahepatic metastasis (38%). However, in two of three HCCs examined that had marked reduction of nm23-H1 protein, the nm23-H1 mRNA level was not reduced. A hepatoma cell line, HLF (phenotype, poorly differentiated carcinoma) revealed marked reduction of nm23-H1 protein compared with two other hepatoma cell lines, HuH-1 and HuH-2, although the mRNA level was similar in the three cell lines. No allelic deletion of the nm23-H1 gene was detected in the 12 HCCs examined. No point mutation in the coding region of the nm23-H1 gene was observed in any of the 12 HCCs or the four hepatoma cell lines. These findings suggest that: (i) the expression of nm23-H1 protein is inversely associated with high metastatic potential of HCC, (ii) regulation of nm23-H1 expression may occasionally occur at both the transcriptional and post-transcriptional levels in HCC; and (iii) genomic alteration of nm23-H1 is a rare event in HCC.

Adult↗
PubMed1998

Assessment of internal thoracic artery graft with intraoperative color Doppler ultrasonography.

BACKGROUND: Intraoperative ultrasonography has the potential to provide anatomic and functional information about internal thoracic artery (ITA) graft, but this potential has been hindered by the relatively large standard probe. In this study, we used a color Doppler microprobe to evaluate ITA grafts. METHODS: The subjects were 15 consecutive patients who underwent elective coronary artery bypass grafting either with cardiopulmonary bypass (n = 14) or without (n = 1). All patients underwent anastomosis of the left ITA to the left anterior descending artery. The ITA graft was assessed before the chest was closed, with the microprobe placed directly on the graft. RESULTS: A good-quality color Doppler image of the ITA graft was easily obtained in all 15 patients within a few minutes. The ITA graft function was assessed by analyzing the shape of the pulsed Doppler wave. All ITA grafts were patent, and the mean graft diameter was 1.8 +/- 0.04 mm. The peak systolic velocity, peak diastolic velocity, and mean velocity were 52.0 +/- 14.9 cm/s, 58.3 +/- 22.4 cm/s, and 36.5 +/- 10.9 cm/s, respectively. The ratio of peak diastolic velocity to peak systolic velocity was 1.24 +/- 0.66. The ITA graft seemed to function well when the biphasic diastolic predominant flow appeared. The mean blood flow was 55.1 +/- 22.0 mL/min. CONCLUSIONS: Intraoperative ultrasonography using the microprobe provides adequate anatomic and hemodynamic information regarding ITA grafts. As the Doppler flow evaluation has high sensitivity and specificity, we suggest that intraoperative ultrasonography is useful for the assessment of these grafts.

Anastomosis, Surgical↗
PubMed1998

High colony forming capacity of primary cultured hepatocytes as a dominant trait in hepatocarcinogenesis-susceptible and resistant mouse strains.

When hepatocytes isolated from mouse liver are cultivated in vitro, a small fraction of cells can survive, forming colonies, while most cells die within a few weeks. We compared the colony forming capacity of hepatocytes in three mouse strains; two strains susceptible for hepatocarcinogenesis, C3H/HeJ (C3) and DBA/2J mice (D2), and one resistant strain, C57BL/6J mice (B6). The colony forming capacity was about 3:2:1 for D2, C3 and B6 at the 4th week after start of culture, indicating that this capacity correlated with the susceptibility to tumor induction. When the colony forming capacity was compared in F1 hybrids between the three strains, the high colony forming capacity was dominant, again resembling the trait for hepatocarcinogenesis. In F1 hybrids between the two susceptible strains, the colony numbers were more than those of the parental strains, indicating the high colony forming capacity of the two susceptible strains to be additive. During 4 weeks of culture period, the cells continuously proliferated, but fairly large numbers of cells died, some showing characteristics of apoptosis and others of lysis. Although the proliferation rate was not different among the three strains until the 2 week time point, it was significantly lower in B6 than in C3 or D2 strains by the 4th week. On the other hand, the cell death rate was lower in D2 cells than in B6 or C3 cells after 2 weeks. These results indicate that the genetic background affects proliferation and death rates of cultured hepatocytes, which may be related to the different colony forming capacity of these three strains.

Animals↗
PubMed1998

Cloning of TCFL5 encoding a novel human basic helix-loop-helix motif protein that is specifically expressed in primary spermatocytes at the pachytene stage.

We have isolated a novel human gene that is expressed specifically in primary spermatocytes in the testis. The cDNA contains an open reading frame of 1356 bp, encoding a 452-amino-acid protein that includes a basic Helix-Loop-Helix (bHLH) motif. The gene, which was mapped to chromosome region 20q13.3-->qter by fluorescence in situ hybridization, consists of six exons and spans approximately 24 kb of genomic DNA. Immunohistochemical staining located the gene product exclusively in cell nuclei of primary spermatocytes at the pachytene stage, but not in those at the leptonema stage. We named this gene TCFL5 (transcription factor-like 5, basic helix-loop-helix). The cell-type and stage-specific expression of TCFL5 indicates that this protein may function in a crucial role in spermatogenesis as a transcription factor by regulating cell proliferation or differentiation of cells through binding to a specific DNA sequence like other bHLH molecules.

Animals↗
PubMed1998

[Fundamental and clinical studies on tazobactam/piperacillin in the pediatric field].

Pharmacokinetics, efficacy and safety of tazobactam/piperacillin (TAZ/PIPC), a new beta-lactamase inhibitor combined with a penicillin antibiotic, were studied in pediatrics and the following results were obtained. 1) Serum concentration and urinary excretion of TAZ/PIPC after intravenous administration at a dose of 46 mg/kg to one child were investigated. Serum half-lives were 0.5 hours for TAZ and 0.6 hours for PIPC, while the urinary recovery rates in the first 6 hours after administration, were 61.6% and 56.3% respectively. 2) TAZ/PIPC was administered at a dose of 46.0-73.5 mg/kg t.i.d. for 3-13 days to 10 patients, 6 with respiratory infection, 1 with pharyngotonsillitis, 1 with pertussis and 2 with soft tissue infection of skin. Clinical response were excellent in 5 cases and good in 5 cases, and the efficacy rate was 100%. Bacteriologically, 2 strains (Staphylococcus aureus and Streptococcus pyogenes) isolated from 2 patients were eradicated after the treatment. As for adverse reaction, mild skin rash was observed in 1 case but disappeared within 2 days after withdrawal of the drug. As for abnormal laboratory test results decrease in neutrophiles and increase in eosinophiles in each 1 case were observed, which were, however, normalized after administration. From the above results, tazobactam/piperacillin was considered to be a useful antibiotic in the pediatric field.

Bacterial Infections↗
PubMed1997

Cloning of P2XM, a novel human P2X receptor gene regulated by p53.

Through cloning of functional p53-binding sites (p53-tagged sites) from the human genome, we isolated a novel gene inducible by wild-type p53. Its cDNA sequence contained an open reading frame encoding a 431-amino acid peptide that showed a significant homology with members of the P2X family. This protein also revealed a similarity to RP-2, a gene activated in thymocytes undergoing programmed cell death. Northern blot analysis showed that it was expressed predominantly in skeletal muscle. Hence, we designated the gene P2XM (P2X specifically expressed in skeletal muscle). P2XM was localized to chromosomal band 22q11, where frequent loss of heterozygosity has been observed in rhabdoid tumors. Although we detected no genetic alteration in the coding sequences, one of four rhabdomyosarcoma cell lines examined had completely lost expression of this gene. Furthermore, a minor splice variant lacking a part of exon 1 that would encode residues corresponding to transmembrane domain M1 was relatively more abundant in two of seven sarcoma cell lines, one of which was derived from a rhabdomyosarcoma, and the other was derived from an osteosarcoma. The results suggest that P2XM may play a significant role in the proliferation and/or differentiation of skeletal muscle cells and that its altered expression may be involved in the development of some sarcomas.

Alternative Splicing↗
PubMed1997

Genetic dissection of susceptibility to murine ovarian teratomas that originate from parthenogenetic oocytes.

The LT/Sv mouse strain is characterized by its abnormally high incidence of spontaneous ovarian teratomas. These tumors have been shown to originate from parthenogenetic oocytes, which are spontaneously induced to divide. Both spontaneous parthenogenesis and ovarian teratomas are extremely rare for other mouse strains, including C57BL/6J. To identify the genes responsible for this unique phenotype of female LT/Sv mice, we performed linkage analysis of female (C57BL/6J x LT/Sv)F2 mice. A locus on chromosome 6 designated Ots1 (ovarian teratoma susceptibility) was identified as the single major locus that increases the frequency of teratomas in a semidominant manner.

Animals↗
PubMed1997

GML sensitizes cancer cells to Taxol by induction of apoptosis.

Recently we identified a novel gene, gml, whose expression is regulated in a p53-dependent manner and found that gml expression was correlated with the sensitivity of esophageal cancer cells to anticancer drugs. To further investigate the biological mechanism of gml in determining the chemosensitivity of cancer cells to clinically useful agents, we introduced gml cDNA into TE10, an esophageal cancer cell line that lacks endogenous gml expression. In two resulting stable cell lines which expressed gml cDNA in the absence of wildtype p53, cell death occurred within 6 h after treatment with Taxol. TE10 parent cells or TE10 cells transfected with vector alone displayed relative resistance for 36 h. Induction of gml did not by itself affect viability. Morphological analysis confirmed that the increased chemosensitivity to Taxol conferred by gml was due to apoptosis. These data suggest that reduced expression of gml is likely to be associated with poor response rates to chemotherapy, and that an assay for gml expression might serve a clinical purpose as a predictor of chemotherapeutic sensitivity.

Antineoplastic Agents, Phytogenic↗
PubMed1997

A novel brain-specific p53-target gene, BAI1, containing thrombospondin type 1 repeats inhibits experimental angiogenesis.

The genetic alteration of p53 is associated with neovascularization during progression of glioma to its more malignant form, glioblastoma. Hence, one or more of the genes transactivated by p53 is likely to function as an angiogenesis inhibitors. We isolated a novel p53-inducible gene that encodes a 1584-amino-acid product containing five thrombospondin type 1 (TSP-type 1) repeats and is specifically expressed in the brain. A recombinant protein corresponding to the TSP-type 1 repeats of this gene product inhibited in vivo neovascularization induced by bFGF in the rat cornea. The expression of this gene, designated BAI1 (brain-specific angiogenesis inhibitor 1) was absent or significantly reduced in eight of nine glioblastoma cell lines, suggesting BAI1 plays a significant role in angiogenesis inhibition, as a mediator of p53.

Amino Acid Sequence↗
PubMed1997

Cloning and characterization of BAI2 and BAI3, novel genes homologous to brain-specific angiogenesis inhibitor 1 (BAI1).

We have identified two novel human genes homologous to BAI1 (brain-specific angiogenesis inhibitor 1), an angiogenesis inhibitor that is a candidate for involvement in development of glioblastoma. Like BAI1, these two genes, designated BAI2 and BAI3, were specifically expressed in brain, and are likely to be expressed in the same type of cells. However, in spite of similar tissue specificity among the three BAI genes, only BAI1 is transcriptionally regulated by p53. BAI3 expression was absent in two of nine glioblastoma cell lines examined and was significantly reduced in three of the remaining seven. These data suggest that members of this novel gene family may play important roles in suppression of glioblastoma. BAI1, BAI2 and BAI3 were mapped to 8q24, 1p35 and 6q12, respectively.

Astrocytes↗