Biomedical subjects

N Seki

Publications and source records attributed to N Seki.

At least 127 records · Page 7Linked to original sources

PubMed1998

Characterization of a human homolog (BACH1) of the mouse Bach1 gene encoding a BTB-basic leucine zipper transcription factor and its mapping to chromosome 21q22.1.

Clinical interest in the genes on human chromosome 21, especially with respect to Down syndrome (DS), has provided a strong impetus for the creation of a transcript map of this chromosome. In an effort to identify new human genes on the basis of cDNA analysis, we found several cDNA clones that corresponded to chromosome 21-specific transcripts. One of these, ha2303, showed strong similarity to the murine transcription factor Bach1. We subsequently determined the entire nucleotide sequence of this cDNA clone and found it to contain the whole coding sequence. The gene, termed BACH1, encodes a 736-amino-acid polypeptide with 80.3% identity to the murine Bach1 protein and contains a Cap'n'collar (CNC)-type basic leucine zipper (bZip) domain and a protein interaction motif, the BTB domain. Northern blot analysis revealed that BACH1 was expressed in all tissues examined. Mapping using the NotI restriction map and the YAC contig map showed that the BACH1 gene is located at 21q22.1 between the NotI sites LA329 (D21S338) and LL60 (D21S389) and within approximately 400 kb of LA329. Both the prospective function and the chromosomal location suggest that this gene may be a DS candidate gene, contributing to certain DS phenotypes, and is possibly involved in certain features of monosomy 21.

Amino Acid Sequence↗

PubMed1998

DPC4 splice variants in neuroblastoma.

One of the loci for neuroblastoma suppressor genes is chromosome 18q21 where the DPC4 tumor suppressor gene, as well as the DCC and MADR2 genes, is located. DPC4 is a molecule of the TGF-beta signal which regulates differentiation of the neural crest precursor cells from which neuroblastoma originates. During the search for the significance of DPC4 as a candidate neuroblastoma suppressor gene, we found that there are at least two variant forms of the DPC4 transcripts by using the reverse-transcriptase-PCR procedure. The subsequent sequencing analysis has revealed that one is missing exons 5 and 6 and the other is missing exons 4-6. Both splice variants were frequently observed in neuroblastomas and at low levels in normal tissues. Though the functional role of the DPC4 splice variants is unknown, they might be important in regulating the TGF-beta signaling not only in neuroblastomas but also in other tumors and normal tissues.

Alternative Splicing↗

PubMed1998

Discovery of FR115092: a novel antinephritic agent.

A series of dapsone-related 4-aminopheynl and 2-aminothiazolyl derivatives was prepared, and their antinephritic activity and blood toxicity were evaluated. 5-(2-Pyridylsulfonyl)-2-thiazolamine (FR115092, 26) was effective against two nephritis models, namely graft-versus-host disease (GVHD) and autoimmune W/BF1 mice, and showed none of the blood toxicity observed with dapsone.

Anemia↗

PubMed1998

Strain difference in the induction of T-cell activation-associated, interferon gamma-dependent hepatic injury in mice.

A single intravenous injection of concanavalin A (Con A) induces T-cell activation-associated inflammatory injury selectively in the liver. This study investigated the strain difference in the development of Con A-induced hepatic injury. Normal C57BL/6 and BALB/c spleen cells produced comparable levels of T-cell-derived lymphokines (interferon gamma [IFN-gamma], tumor necrosis factor alpha [TNF-alpha], and interleukin-2 [IL-2]) following in vitro stimulation with Con A. A single intravenous injection of Con A to C57BL/6 mice induced the plasma levels of TNF-alpha and IL-2 comparable with or slightly higher than those observed in BALB/c mice, whereas the same treatment resulted in an apparently lower level of IFN-gamma production in C57BL/6 mice. RNA from livers of Con A-treated C57BL/6 mice exhibited lower levels of IFN-gamma mRNA than RNA of BALB/c livers. Unexpectedly, a dramatic difference in the severity of hepatic injury was observed between C57BL/6 and BALB/c. Namely, the peak alanine transaminase (ALT) level was more than 15,000 U/L and inducible as early as 8 hours after injection of 0.2 mg Con A per mouse in the C57BL/6 strain, whereas the peak was approximately 3,000 U/L and induced as late as 24 hours after Con A injection in the BALB/c strain. The increase in plasma ALT levels was limited to less than 10% by injection of anti-IFN-gamma monoclonal antibody (mAb) in both strains. The C57BL/6 strain inducing lower levels of IFN-gamma exhibited higher IFN-gamma responsiveness as exemplified by the intrahepatic expression of an IFN-gamma-inducible gene, an inducible type of nitric oxide (NO) synthase (iNOS). These results indicate that, while IFN-gamma produced in vivo by activated T cells induces hepatic injury, there exists a striking strain difference in the induction of IFN-gamma-dependent hepatic injury.

Alanine Transaminase↗

PubMed1998

Different angiogenic pathways in human cervical cancers.

OBJECTIVE: The objective of this study is to clarify the association between the expression of two types angiogenic factors, vascular endothelial growth factor (VEGF) and platelet-derived endothelial cell growth factor (PD-ECGF)/thymidine phosphorylase(dThdPase) and clinicopathological features, including tumor angiogenesis, in cervical cancers. METHODS: The expression of VEGF and PD-ECGF was evaluated by immunohistochemical staining of tumor specimens from 73 patients with stage Ib-IIb cervical cancer (51, squamous cell carcinoma; 19, adenocarcinoma; 3, adenosquamous carcinoma) who underwent radical hysterectomy. The microvessel density was assessed by immunostaining for factor VIII-related antigen in the most neovascularized area. RESULTS: The microvessel density in adenocarcinomas was significantly higher than that in squamous cell carcinomas (P < 0.01). The intensity of VEGF expression in adenocarcinomas was significantly stronger than that in squamous cell carcinomas (P < 0.05). In contrast, the expression of PD-ECGF in squamous cell carcinomas was significantly higher than that in adenocarcinomas (P < 0.0001) and adenosquamous carcinomas (P < 0.01). There was an inverse relationship between VEGF expression and PD-ECGF expression among all patients studied (P < 0.001). The microvessel density was significantly correlated with the intensity of VEGF expression (P < 0.05). In contrast, there was no correlation between the microvessel density and the expression of PD-ECGF. CONCLUSIONS: The expression of VEGF appears to be involved in the promotion of angiogenesis in cervical cancers. Furthermore, we propose that angiogenic pathways may be different in different types of cervical cancers.

Adenocarcinoma↗

PubMed1998

Isolation, tissue expression, and chromosomal assignment of human RGS5, a novel G-protein signaling regulator gene.

The regulator of G-protein signaling (RGS) proteins have recently been identified as signal transduction molecules which have structural homology to SST2 of Saccharomyces cerevisiae and EGL-10 of Caenorhabditis elegans. Multiple genes homologous to SST2 are present in higher eukaryotes, and the group of these genes is termed the RGS family. RGS proteins are involved in the regulation of heterotrimeric G-proteins by acting as GTPase-activators. A putative new member of the RGS family was isolated from a neuroblastoma cDNA library. The amino acid sequence deduced from the cDNA possessed all consensus motifs of the RGS domain and showed closest homology to mouse RGS5 (90% identical), indicating that it was human RGS5 (hRGS5). The messenger RNA of hRGS5 was abundantly expressed in heart, lung, skeletal muscle, and small intestine, and at low levels in brain, placenta, liver, colon, and leukocytes. The chromosome localization of the gene in the 1q23 region was determined by a monochromosomal hybrid panel and a radiation hybrid panel.

Amino Acid Sequence↗

PubMed1998

Assignment of the ZIP kinase gene to human chromosome 19p13.3 by somatic hybrid analysis and fluorescence in-situ hybridization.

A cDNA for a putative member of the serine/threonine kinase family was cloned from an adult human testis cDNA library. The predicted translation product was identical to ZIP kinase, which has been suggested to play an important role in the induction of apoptosis. The messenger RNA was ubiquitously expressed in various tissues. The chromosomal location of the gene was determined by fluorescence in-situ hybridization and polymerase chain reaction-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel. This gene was mapped on the q13.3 region of chromosome 19.

Adult↗

PubMed1998

Cloning, expression analysis, and chromosomal localization of HIP1R, an isolog of huntingtin interacting protein (HIP1).

Huntington disease (HD) is an inherited neurodegenerative disorder which is associated with CAG expansion in the coding region of the gene for huntingtin protein. Recently, a huntingtin interacting protein, HIP1, was isolated by the yeast two-hybrid system. Here we report the isolation of a cDNA clone for HIP1R (huntingtin interacting protein-1 related), which encodes a predicted protein product sharing a striking homology with HIP1. RT-PCR analysis showed that the messenger RNA was ubiquitously expressed in various human tissues. Based on PCR-assisted analysis of a radiation hybrid panel and fluorescence in situ hybridization, HIP1R was localized to the q24 region of chromosome 12.

Adaptor Proteins, Signal Transducing↗

PubMed1998

Isolation, tissue expression, and chromosomal assignment of a novel human gene which encodes a protein with RING finger motif.

We identified a novel gene encoding a RING finger (C3HC4-type zinc finger) protein from a human neuroblastoma full-length enriched cDNA library. This cDNA clone consists of 1919 nucleotides with an open reading frame of a 485-amino acid protein. From reverse transcription (RT)-polymerase chain reaction (PCR) analysis, the messenger RNA was ubiquitously expressed in various human adult tissues. The chromosomal location of the gene was determined on the chromosome 6p21.3 region by PCR-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel.

Adult↗

PubMed1998

Chromosomal assignment of the gene for human DNA-PKcs interacting protein (KIP) on chromosome 15q25.3-q26.1 by somatic hybrid analysis and fluorescence in situ hybridization.

We report the chromosomal location of the gene for DNA-PKcs interacting protein KIP. Based on fluorescence in situ hybridization and polymerase chain reaction (PCR)-based analyses with both a human/rodent monochromosomal hybrid cell panel and a radiation hybrid mapping panel, this gene was mapped to q25.3-q26.1 region on chromosome 15.

Calcium-Binding Proteins↗

PubMed1998

Laparoscopic removal of a large gastric trichobezoar.

A large trichobezoar has been traditionally removed by open surgery, which has entailed an upper abdominal incision. With the advent of laparoscopic surgery, it became feasible to retrieve a foreign body from the stomach without the necessity of a large skin incision in the upper abdomen. A 7-year-old girl presenting with abdominal pain, nausea, and appetite loss was admitted and evaluated. Results of an upper gastrointestinal series showed a large mass in the stomach that extended into the duodenum. Endoscopical removal had been tried twice under general anesthesia and resulted only in the retrieval of the small portion of the trichobezoar in the duodenum; total removal seemed impossible with endoscopic techniques. Laparoscopic removal was then under-taken to avoid the surgical scar in the upper abdomen. The trichobezoar was successfully retrieved through a gastrotomy and removed via a small suprapubic incision. This approach may be the treatment of choice for future cases of trichobezoar when surgery is indicated.

Bezoars↗

PubMed1998

A distamycin A-inducible fragile site, FRA8E, located in the region of the hereditary multiple exostoses gene, is not involved in HPV16 DNA integration and amplification.

The rare fragile site is a specific point on a chromosome that is expressed as an isochromatid gap or break under certain conditions of cell culture and is inherited in a Mendelian codominant fashion. Five folate-sensitive fragile sites were cloned, and the molecular basis of fragile site mutation was shown to be a new class of mutation, called dynamic mutation, resulting from an allelic expansion of (CCG)n repeats. The mechanism responsible for other types of rare fragile sites, i.e., distamycin A-inducible and BrdU-requiring, is unknown, although cytogenetic studies suggested that these fragile sites play a mechanistic role in breakage and recombination and may also be integration and modification sites of foreign viral DNA genomes. A distamycin A-inducible fragile site, FRA8E, is mapped to 8q24.1 in which various loci implicated in genomic instability are located. Here we identified a YAC clone spanning both FRA8E and the hereditary multiple exostosis (EXT1) gene, using fluorescence in situ hybridization (FISH) analysis of a yeast artificial chromosome (YAC) contig. By using P1 clones as probes, the FRA8E locus was further localized to a 400-kb region including the EXT1 gene. Furthermore, the integration and amplification site of human papillomavirus 16 DNA in the ASCC (argyrophil small cell carcinoma) cells were shown not to coincide with FRA8E, but to be involved in an extensively broad genomic region of 8q24.1, including the c-myc gene.

Chromosome Fragile Sites↗

PubMed1998

CD44 exon v6 correlates with cellular differentiation but not with progression and metastasis of cervical cancer.

The purpose of this study was to investigate whether CD44v6 expression correlates with progression or metastasis of cervical cancer. The presence of mRNA for CD44v6 was examined, the association with clinicopathological features was assessed in 80 patients with cervical cancer by reverse transcriptase-polymerase chain reaction (RT-PCR) and subsequent Southern blot hybridisation with an oligonucleotide probe specific for v6. The standard form of CD44 was expressed in all specimens and 53 of 80 cervical cancers expressed an isoform containing exon v6 in combination with other variant exons. In addition, longer size transcripts of more than 1350 bp (long form) were identified in 22 of the 53 CD44v6 positive patients. The expression of CD44v6 and CD44v6 long form in squamous cell carcinomas was significantly higher than that in non-squamous cell carcinomas (P < 0.001). The expression of CD44v6 long form in histological grade 1 and 2 was significantly higher than that in grade 3 (P < 0.05). 47 patients in stage Ib-IIb cervical cancers were treated by radical hysterectomy and pelvic lymphadenectomy. We did not find any association between the expression of the long form or the short form of CD44v6 and any pathological features, except for histological cell type. These findings suggest that the regulation of CD44v6 seems to be different between different histological cell types and different tumour grades, and the expression of CD44v6 might not be implicated in the progression and metastasis of cervical cancer.

Adenocarcinoma↗

PubMed1998

Polymorphism of the 5'-flanking region of the human tumor necrosis factor (TNF)-alpha gene in Japanese.

Polymorphism of the 5'-flanking promoter/enhancer region of the TNF-alpha gene in Japanese is not well understood. To better understand it, we have determined the 1,358 base pair sequence of the 5'-flanking region of the TNF-alpha gene in nine Japanese, and identified three new polymorphisms at positions 1,031 (T to C change, termed as -1,031C), -863 (C to A, -863A), and -857 (C to T, -857T), with the former two in one allele. The level of TNF-alpha production by concanavalin A (Con A)-activated peripheral blood mononuclear cells from the five donors possessing at least one new allele was 1.8-fold higher than that from the remaining four donors with the dominant allele. The transcriptional promoter activity of the 1,031C/-863A or -857T allele in response to Con A stimulation was 2.0 or 1.7-fold higher than that of the dominant allele, respectively. The allele frequencies of -1,031C, -863A, -857T, -308A (G to A), and -238A (G to A) (the latter two were previously reported) in 575 healthy Japanese were 16.0, 14.0, 17.7, 1.7 and 2.0%, respectively. The -1,031C/-863A or -857T allele was in significant linkage disequilibrium with HLA-B61, -B39 and -DRB1*0901, or with HLA-B54, -B35, -B59, and -DRB1*0405, respectively. The newly identified alleles observed in a relatively large proportion of Japanese may be related to differences in levels of TNF-alpha production in immune responses to various stimuli among individuals.

Alleles↗

PubMed1998

Congenital megalourethra: a case report.

We describe a case of a male infant with a scaphoid megalourethra. A physical examination showed a large, flabby phallus with bilateral undescended testes. The corpus spongiosum was absent with normal corpora cavernosa. Urethrography showed a crescent-shaped dilatation of the anterior urethra. Further examination revealed an association with concomitant urogenital anomalies, right renal hypoplasia-dysplasia, bilateral vesicoureteral reflux and the prune-belly syndrome. A urethroplasty with resection of the excess urethral tissue and reconstruction of the urethra was performed. There was a satisfactory surgical result and the patient now voids without difficulty.

Cystoscopy↗

PubMed1998

Studies on anti-inflammatory agents. VI. Synthesis and pharmacological properties of 2,3-diarylthiophenes.

A series of novel 5-substituted-2,3-diarylthiophenes has been synthesized and found to be active in the rat adjuvant arthritis (AA) model and/or in the yeast-induced hyperalgesia (Randall-Selitto) assay. Among the compounds synthesized herein, 2-(4-fluorophenyl)-3-[4-(methylsulfonyl)phenyl]-5-(trifluoromethyl)thiop hene (6a) exhibited the most potent activities on AA, collagen-induced arthritis (CIA) and the delayed-type hypersensitivity response to type II collagen. 5-Bromo-2-[4-(methylamino)phenyl]-3-[4-(methylsulfinyl)phenyl]thiophene (38) is also a potent inhibitor of AA, CIA, hyperalgesia and in vitro tumor necrosis factor-alpha production.

Adjuvants, Immunologic↗

PubMed1998

A new derivatizing agent, trimethylammoniopropyl methanethiosulphonate, is efficient for preparation of recombinant brain-derived neurotrophic factor from inclusion bodies.

Derivatization with trimethylammoniopropyl methanethiosulphonate (TAPS-sulphonate) enabled brain-derived neurotrophic factor (BDNF) to be prepared efficiently from Escherichia coli inclusion bodies. Reduced BDNF obtained from inclusion bodies solubilized by urea and reduced by dithiothreitol was suggested to form a complex with itself or with other compounds such as lipids. It could hardly be adsorbed on to cation-exchange resin for partial purification prior to a refolding reaction. Reversible derivatization of cysteine residues was tested as a method of dissociating BDNF from such complexes. However, even if a methyl or aminoethyl group was introduced, BDNF could not be dissociated readily. Derivatization with TAPS-sulphonate brought about good dissociation of BDNF, and more than 50% adsorbed on to the cation-exchange resin. BDNF derivatized with TAPS-sulphonate refolded well, and the refolded samples showed the same biological activity as purified BDNF. Derivatization with TAPS-sulphonate would increase the intermolecular repulsion of BDNF, due to the positively charged character of the quaternized amine, and inhibit complex formation. Thus, TAPS-sulphonate is effective for the preparation of BDNF under denatured conditions.

Brain-Derived Neurotrophic Factor↗

PubMed1997

Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro.

As a part of our project for accumulating sequence information of the coding regions of unidentified human genes, we herein report the sequence features of 78 new cDNA clones isolated from human brain cDNA libraries as those which may code for large proteins. The sequence data showed that the average size of the cDNA inserts and their open reading frames was 6.0 kb and 2.8 kb (925 amino acid residues), respectively, and these clones produced the corresponding sizes of protein products in an in vitro transcription/translation system. Homology search against the public databases indicated that the predicted coding sequences of 68 genes contained sequences similar to known genes, 69% of which (47 genes) were related to cell signaling/communication, nucleic acid management, and cell structure/motility. The expression profiles of these genes in 14 different tissues have been analyzed by the reverse transcription-coupled polymerase chain reaction method, and 8 genes were found to be predominantly expressed in the brain.

Brain Chemistry↗