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Biomedical subjects

N Seki

Publications and source records attributed to N Seki.

At least 163 records · Page 9Linked to original sources
PubMed1996

Prediction of the coding sequences of unidentified human genes. VI. The coding sequences of 80 new genes (KIAA0201-KIAA0280) deduced by analysis of cDNA clones from cell line KG-1 and brain.

In this series of projects of sequencing human cDNA clones which correspond to relatively long and nearly full-length transcripts, we newly determined the sequences of 80 clones, and predicted the coding sequences of the corresponding genes, named KIAA0201 to KIAA0280. Among the sequenced clones, 68 were obtained from human immature myeloid cell line KG-1 and 12 from human brain. The average size of the clones was 5.3 kb, and that of distinct ORFs in clones was 2.8 kb, corresponding to a protein of approximately 100 kDa. Computer search against the public databases indicated that the sequences of 22 genes were unrelated to any reported genes, while the remaining 58 genes carried sequences which show some similarities to known genes. Protein motifs that matched those in the PROSITE motif database were found in 25 genes and significant transmembrane domains were identified in 30 genes. Among the known genes to which significant similarity was shown, the genes that play key roles in regulation of developmental stages, apoptosis and cell-to-cell interaction were included. Taking into account of both the search data on sequence similarity and protein motifs, at least seven genes were considered to be related to transcriptional regulation and six genes to signal transduction. When the expression profiles of the cDNA clones were examined with different human tissues, about half of the clones from brain (5 of 11) showed significant tissue-specificity, while approximately 80% of the genes from KG-1 were expressed ubiquitously.

Amino Acid Sequence↗
PubMed1996

A gene map of the human genome.

The human genome is thought to harbor 50,000 to 100,000 genes, of which about half have been sampled to date in the form of expressed sequence tags. An international consortium was organized to develop and map gene-based sequence tagged site markers on a set of two radiation hybrid panels and a yeast artificial chromosome library. More than 16,000 human genes have been mapped relative to a framework map that contains about 1000 polymorphic genetic markers. The gene map unifies the existing genetic and physical maps with the nucleotide and protein sequence databases in a fashion that should speed the discovery of genes underlying inherited human disease. The integrated resource is available through a site on the World Wide Web at http://www.ncbi.nlm.nih.gov/SCIENCE96/.

Amino Acid Sequence↗
PubMed1996

Non-T cell-derived IL-4 plays an important role in IgE production induced by antigen resensitization and is resistant to FK506.

The present study investigates the role of non-T cell-derived IL-4 in IgE production. It is well known that IL-4 is generally produced by T cells and induces IgE production. We have demonstrated that non-T cells also produce IL-4 in vivo by injection with Ag following passive sensitization of mice with IgE. In contrast to its known potent immunosuppressive effects on T cells, FK506 only partially inhibited IL-4 produced by non-T cells; therefore, FK506 was found to be a useful tool for identifying a cell source of IL-4 production. We used this observation to examine the role of non-T cell-derived IL-4 in IgE production. The production of a high titer of IgE was induced by priming BALB/c mice with Ascaris suum extract and further enhanced by secondary immunization. The IgE production in this model was dependent on IL-4, since both primary and secondary IgE production were completely suppressed by injection with anti-IL-4 Ab. Although primary IgE production was completely inhibited by FK506, secondary IgE production was not inhibited. Furthermore, IL-4 induction in plasma was only partially inhibited by FK506 when the A. suum extract-primed mice were resensitized with Ag. These results indicate that IL-4 produced by non-T cells plays a crucial role in secondary IgE production.

Animals↗
PubMed1996

RN-tre identifies a family of tre-related proteins displaying a novel potential protein binding domain.

Eps8 is a recently identified SH3-containing substrate for tyrosine kinase receptors. To understand the role of eps8 in receptor-mediated signaling, we cloned cDNAs encoding proteins that bind to its SH3 domain. One of these cDNAs predicts the synthesis of an 828 amino acid protein with homology to the N-terminal region of the tre oncogene. We designated this protein RN-tre for Related to the N-terminus of tre. RN-tre is ubiquitously expressed and maps to 10p13, a region known to be involved in translocations in various leukemias. In addition, a 10p13 monosomy syndrome, characterized by developmental alterations, has been reported. The regional homology between RN-tre and tre, which is limited to their N-terminal portion, prompted us to investigate the origin of the tre oncogene transcriptional unit. We were able to show that tre is the fusion product of a 5' genetic element, homologous to RN-tre and a 3' element, encoding a de-ubiquinating enzyme. Moreover, we identified, within the N-terminus of RN-tre and tre, a domain (named TrH, for Tre Homology), which is conserved within several proteins from yeast to mammals and has protein-binding properties in vitro.

3T3 Cells↗
PubMed1996

Comparative genome mapping of the ataxia-telangiectasia region in mouse, rat, and Syrian hamster.

Chromosomal locations of the Atm (ataxia-telangiectasia (AT)-mutated) and Acat1 (mitochondrial acetoacetyl-CoA thiolase) genes in mouse, rat, and Syrian hamster were determined by direct R-banding FISH. Both genes were colocalized to the C-D band of mouse chromosome 9, the proximal end of q24.1 of rat chromosome 8, and qa4-qa5 of Syrian hamster chromosome 12. The regions in the mouse and rat were homologous to human chromosome 11q. Fine genetic linkage mapping of the mouse AT region was performed using the interspecific backcross mice. Atm, Acat1, and Npat, which is a new gene isolated from the AT region, and 12 flanking microsatellite DNA markers were examined. No recombinations were found among the Atm, Npat, Acat1, and D9Mit6 loci, and these loci were mapped 2.0 cM distal to D9Mit99 and 1.3 cM proximal to D9Mit102. Comparison of the linkage map of mouse chromosome 9 (MMU9) and that of human chromosome 11 (HSA11) indicates that there is a chromosomal rearrangement due to an inversion between Ets1 and Atm-Npat-Acat1 and that the inversion of MMU9 originated from the chromosomal breakage at the boundary between Gria4 and Atm-Npat-Acat1 on HSA11. This type of inversion appeared to be conserved in the three rodent species, mouse, rat, and Syrian hamster, using additional comparative mapping data with the Rck gene.

Acetyl-CoA C-Acetyltransferase↗
PubMed1996

Characterization of the transforming activity of p80, a hyperphosphorylated protein in a Ki-1 lymphoma cell line with chromosomal translocation t(2;5).

We have molecularly cloned a cDNA encoding a protein uniquely expressed and hyperphosphorylated at tyrosine residues in a Ki-1 lymphoma cell that contained chromosomal translocation t(2;5). The encoded protein p80 was shown to be generated by fusion of a protein-tyrosine kinase and a nucleolar protein B23/nucleophosmin (NPM). The coding sequence of this cDNA turned out to be virtually identical to that of the fusion cDNA for NPM-anaplastic lymphoma kinase (ALK) previously cloned from the transcript of the gene at the breakpoint of the same translocation. Overexpression of p80 in NIH 3T3 cells induced neoplastic transformation, suggesting that the p80 kinase is aberrantly activated. The normal form of p80 was predicted to be a receptor-type tyrosine kinase on the basis of its sequence similarity to the insulin receptor family of kinases. However, an immunofluorescence study using COS cells revealed that p80 was localized to the cytoplasm. Thus, subcellular translocation and activation of the tyrosine kinase presumably by its structural alteration would cause the malignant transformation. We also showed that a mutant p80 lacking the NPM portion was unable to transform NIH 3T3 cells. Thus, the NPM sequence is essential for the transforming activity, suggesting that the chromosomal translocation is responsible for the oncogenesis. Finally, Shc and insulin receptor substrate 1 (IRS-1) were tyrosine-phosphorylated and bound to p80 in p80-transformed cells. However, mutants of p80 that were defective for binding to and phosphorylation of Shc and insulin receptor substrate 1 could transform NIH 3T3 cells. Association of these mutants with GRB2 was still observed, suggesting that interaction of p80 with GRB2 but not with Shc or IRS-1 was relevant for cell transformation.

3T3 Cells↗
PubMed1996

Chromosome mapping of human (ZNF179), mouse, and rat genes for brain finger protein (bfp), a member of the RING finger family.

The bfp, a member of the RING finger family, has been shown to be predominantly expressed in brain and up-regulated in neural differentiation of P19 embryonic carcinoma cells. Chromosome mapping of the bfp gene by fluorescence in situ hybridization reveals that human BFP (ZNF179) is located at 17p11.2, mouse Bfp at 11B1.3, and rat BFP at 10q22. These results provide additional evidence that the mouse 11B region displays conserved linkage homology with the 17p11.2 region of the human genome and the 10q22 region of the rate genome.

Amino Acid Sequence↗
PubMed1996

Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1.

As part of our continuing efforts to accumulate information on the coding region of unidentified human genes, we newly determined the sequences of 40 cDNA clones of human cell line KG-1 which correspond to relatively long and nearly full-length transcripts, and predicted the coding sequences of the corresponding genes, named KIAA0161 to 0200. The average size of the cDNA clones analyzed was approximately 5.0 kb. A computer search of the sequences in public databases indicated that the sequences of 20 genes were unrelated to any reported genes, while the remaining 20 genes carried sequences which show some similarities to known genes. Among the genes in the latter category, KIAA0167 contained a Zn-finger motif with significant structural similarity to that of the yeast transcription factor GCS1, and KIAA0189 was classified into the RhoGAP gene family. Stretches of typical CAG (Gln) repeats, which were often correlated with genetic disorders, were found in KIAA0181 and KIAA0192. Another novel repeat composed of alternating Arg and Glu was identified in KIAA0182. Northern hybridization analysis demonstrated that 10 genes are expressed in a cell- or tissue-specific manner.

Amino Acid Sequence↗
PubMed1996

Identification of a novel human gene containing the tetratricopeptide repeat domain from the Down syndrome region of chromosome 21.

The Down syndrome (DS) region on chromosome 21, which is responsible for the DS main features, has been defined by analysis of DS patients with partial trisomy 21. Within the DS region, we constructed a 1.6-Mb P1 contig map previously. To isolate gene fragments from the 1.6-Mb region, we performed direct cDNA library screening and exon trapping using the P1 clones and a human fetal brain cDNA library, and obtained 67 cDNA fragments and 52 possible exons. Among them, 23 cDNA fragments and 4 exons were interpreted to be derived from a single gene by localization on P1 clones and by Northern analysis. To obtain the full-length cDNA sequence, longer cDNA clones were further screened from another human cDNA library which was enriched with longer cDNA species. These clones were sequenced and assembled to a sequence of 9045 bp. This transcribed sequence encodes a novel 2025 amino-acid protein containing tetratricopeptide repeat (TPR) motifs and therefore the gene was designated as TPRD (a gene containing the TPR motifs on the Down syndrome region). The TPR domain has been found in a certain protein phosphatase and in other proteins involved in the regulation of RNA synthesis or mitosis. The TPRD gene, the novel gene which was proved to be in the 1.6-Mb region and to have the interesting features described above, is a candidate for genes responsible for the DS phenotypes.

Amino Acid Sequence↗
PubMed1996

Critical involvement of interferon gamma in the pathogenesis of T-cell activation-associated hepatitis and regulatory mechanisms of interleukin-6 for the manifestations of hepatitis.

A single intravenous injection of concanavalin A (Con A) induces T-cell activation and an acute hepatitis in mice. This study investigated the role of interferon gamma (IFN-gamma) in the pathogenesis of this hepatitis model. Striking increases in the plasma levels of various cytokines, including tumor necrosis factor (TNF), interleukin-2 (IL-2), and IFN-gamma, were detected before the increase in plasma aminotransferase levels induced by Con A injection. TNF levels peaked within 2 hours, whereas IFN-gamma levels peaked at 6 hours after Con A injection. In contrast to a sharp peak of TNF levels, high IFN-gamma levels were detected for a more prolonged period. Passive immunization with anti-IFN-gamma monoclonal antibody (MAb) conferred a dose-dependent protection against liver injury in this model. This protection was observed when anti-IFN-gamma MAb was administered at least 30 minutes before Con A injection but not when given 1 hour after Con A injection. The protection from Con A-induced hepatitis was also induced by administration of rIL-6 before Con A injection. rIL-6 treatment induced significant albeit incomplete inhibition of IFN-gamma and TNF production, whereas this regimen did not affect IL-2 production. Despite striking protective effects of rIL-6 or anti-IFN-gamma MAb, comparable levels of cellular (both T cell and polymorphonuclear cell) infiltration were detected in liver sections from animals untreated, or treated with either rIL-6 or anti-IFN-gamma MAb. Moreover, electron microscopic examination showed that infiltrating T cells exhibited a blastoid appearance in all groups. These results indicate that IFN-gamma plays a critical role in the development of Con A-induced acute hepatitis and suggest that IL-6 administration can regulate the manifestation of hepatitis through mechanisms including the reduced production of inflammatory cytokines such as IFN-gamma.

Animals↗
PubMed1996

Human tumor rejection antigens MAGE.

Characterization of the MAGE genes has facilitated a molecular approach to identification of the genes encoding tumor-rejection antigens expressed on human cancer cells. MAGE proteins are normal tissue antigens compartmentalized in testicular cells that play an important role in the early phase of spermatogenesis. MAGE-1, -2, -3, -4, and -6 genes are preferentially expressed in many different cancers at both the mRNA and protein levels. More than half of human cancers of various histologic type express at least one of these MAGE genes. Demethylation induces MAGE antigens in cells, suggesting that MAGE genes are important developmentally regulated genes under methylating control. Thus, genetic instability in cells causing loss of this methylating control could result in the preferential expression of MAGE genes in cancer cells. Therefore, MAGE gene products may be appropriate target molecules for development of new cancer vaccine.

Amino Acid Sequence↗
PubMed1996

Identification and characterization of a new gene physically linked to the ATM gene.

Ataxia telangiectasia (AT) is an autosomal recessive disease of unknown etiology associated with cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, and hypersensitivity to ionizing radiation. Although AT has been divided into four complementation groups by its radioresistant-DNA synthesis phenotype, the ATM gene has been isolated as the candidate gene responsible for all AT groups. We identified a new gene, designated NPAT, from the major AT locus on human chromosome 11q22-q23. The gene encoded a 1421-amino-acid protein containing nuclear localization signals and phosphorylation target sites by cyclin-dependent protein kinases associated with E2F. The messenger RNA of NPAT was detected in all human tissues examined, and its genomic sequence was strongly conserved through eukaryotes, suggesting that the NPAT gene may be essential for cell maintenance and may be a member of the housekeeping genes. Analysis of the genomic region of NPAT surprisingly revealed that the gene existed only 0.5 kb apart from the 5' end of the ATM transcript with opposite transcriptional direction. It may be possible to propose the idea that the promoter region could be shared by both housekeeping genes and that each gene could influence the expression of the other.

Amino Acid Sequence↗
PubMed1996

Activity immediately before the onset of non-fatal myocardial infarction and sudden cardiac death.

To investigate triggers for the occurrence of acute myocardial infarction (AMI) and sudden cardiac death (SCD), we examined the activities immediately before the time of onset in 149 cases of non-fatal AMI and 110 cases of SCD. All of the cases in which death occurred within 24 h from the onset of the underlying cause were considered SCD as long as the cause of death was of cardiac origin or unknown. We calculated the average time which is spent on each activity in the life cycle of Japanese people and estimated the number of incidence of each activity assuming a uniform distribution. Estimated values and actual values were compared. The results were as follows: 1) The incidence of non-fatal AMI and SCD was low while sleeping or resting or doing light work, and was high while using the toilet or doing sport or heavy work. 2) the incidence of SCD was also high even during moderate exertion, such as taking a bath or, walking or cycling, and it was significantly higher than that in the group of non-fatal AMI. 3) The incidence of non-fatal AMI was high while eating or drinking. 4) Many of the patients with SCD had past histories of circulatory diseases, compared to those with non-fatal AMI. This difference in past histories may account for the high incidence of SCD during moderate exertion.

Activities of Daily Living↗
PubMed1996

Manifestation of subclinical diabetes insipidus due to pituitary tumor during pregnancy.

We describe a case of diabetes insipidus (DI) due to a pituitary tumor in a 33-year-old pregnant woman who developed a sudden onset of polyuria (over 8 l/day) and polydipsia at 30 weeks of gestation. Her plasma concentration of vasopressin (AVP) was low compared with high serum osmolality (298 mOsm/kg), and her urine output was well controlled by treatment with desmopressin acetate (DDAVP). Cranial magnetic resonance imaging (MRI) demonstrated a 1.8 x 1.2-cm pituitary tumor, but she did not have any disturbance in the release of anterior pituitary hormones. The serum concentration of cystine aminopeptidase (CAP) was within the normal range for a woman at 34 weeks of gestation. After an uncomplicated delivery of a healthy girl, her polyuria gradually resolved. The size of the pituitary tumor gradually decreased in parallel to a reduction in her urine output, but a silent hemorrhage was detected in her pituitary gland 4 weeks after the delivery. Although pregnancy is sometimes associated with central DI, the occurrence of DI due to pituitary tumor under pregnancy is rare. The basal AVP recovered to within the normal range, but the low response of AVP secretion to high osmolality persisted. In this case, pregnancy may affect the manifestation of subclinical DI. This case may therefore enhance our understanding of the mechanisms of DI during pregnancy.

Adenoma↗
PubMed1995

Isolation of human purH gene expressed in the rodent transformant cells by subtractive enrichment of 3'-untranslated region of human transcript.

A subtraction procedure was developed for identification and isolation of a human gene transcribed in mouse transformant cells. The procedure was based on subtractive enrichment of the products that were amplified by the combination of reverse transcription and polymerase chain reaction from the 3'-untranslated region (3'-UTR) of human poly(A)+ RNA expressed in the mouse transformant cells. To assess the ability and usefulness of the procedure, we attempted to recover the human purH gene from a mouse transformant cell line, which was originally established by functional complementation using the human metaphase chromosome-mediated gene transfer technique from a mouse purH-negative mutant cell line. Using our procedure, a part of the human transcript in the transformant cells was successfully identified and isolated. The full-length cDNA was isolated using the 3'-UTR clone as a probe, and its biological activity was confirmed by introducing it into the mouse purH-negative mutant cells.

Acyltransferases↗
PubMed1995

A human homolog of the mitochondrial protein import receptor Mom19 can assemble with the yeast mitochondrial receptor complex.

Import of preproteins into mitochondria requires transport machineries in both mitochondrial membranes that have been characterized in Saccharomyces cerevisiae and Neurospora crassa. By cDNA analysis, we identified a human protein of 16 kDa with significant overall homology to the fungal mitochondrial import receptor Mom19, including the three typical characteristics: a hydrophobic N-terminal segment, a tetratrico peptide motif in the middle and a negatively charged C-terminus. The human Mom19 homolog is expressed in all tissues analyzed. When synthesized in vitro, the human Mom19 homolog is targeted to isolated yeast mitochondria and specifically associates with the outer membrane receptor complex, suggesting that indeed a mitochondrial import receptor was identified.

Amino Acid Sequence↗