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Biomedical subjects

M Hattori

Publications and source records attributed to M Hattori.

At least 73 records · Page 4Linked to original sources

[A case of peritoneal papillary serous adenocarcinoma successfully treated by intraperitoneal consecutive administration of cisplatin].

The rare case of a 73-year-old woman with peritoneal papillary serous adenocarcinoma (PPSA), which was limited to the retroperitoneum, is described. She was admitted to our hospital because of vaginal bleeding and a pelvic mass. She had a total hysterectomy, double salpingo-oophorectomy, omentectomy, biopsy of the pelvic lymph nodes and subtotal tumorectomy. In immunohistochemical examinations, this tumor was diagnosed as PPSA, which was limited to the retroperitoneum without local or distant metastasis. Thereafter she received chemotherapy using a combination of cisplatin and cyclophosphamide at intervals of three weeks. Cisplatin was intraperitoneally administered in a divided dose of 20 mg from day 1 to day 4, and cyclophosphamide was intravenously infused in a dose of 500 mg on day 1. After three courses of this chemotherapy, a pathological complete response was observed and the only adverse effects were grade 1. In view of these advantages, this chemotherapy should be considered as first-line chemotherapy for aged patients with PPSA.

Adenocarcinoma, Papillary↗

Searching for preventive measures of cardiovascular events in aged Japanese taxi drivers--the daily rhythm of cardiovascular risk factors during a night duty day.

Previous studies have shown that Japanese taxi drivers are exposed to more risk factors and have a higher mortality rate due to cardiovascular disease than other occupational groups. We investigated the effect of night taxi driving with a view to preventing acute events of cardiovascular disease among aged taxi drivers. Twenty-nine taxi drivers (41-67 years old) were examined for urine normetanephrine/creatinine, von Willebrand factor, anti-thrombin III, t-plasminogen activator-plasminogen activator inhibitor 1-complex, hematocrit, blood glucose and blood pressure in the morning and at midnight during a duty day and in the following morning. At the same time, the blood pressure and blood glucose of 46 taxi drivers (43-67 years old) in the morning after a night duty with little sleep and in the morning after daytime work and subsequent night sleep were compared. The results obtained indicate that the aggravation of sympathetic nervous system functions with disturbed circadian rhythms, increased blood coagulation and blood concentration, endothelial injury and the elevation of blood glucose at midnight or the next morning were induced by their night work. These conditions are supposed to favour acute vascular events in aged taxi drivers. Preventive measures considered include social support for anticoagulant food and water intake, short exercise and walking as well as taking a rest and a nap during night work.

Adult↗

Complete nucleotide sequence of the prophage VT1-Sakai carrying the Shiga toxin 1 genes of the enterohemorrhagic Escherichia coli O157:H7 strain derived from the Sakai outbreak.

Shiga toxins 1 and 2 (Stx1 and Stx2) are encoded by prophages lysogenized in enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains. Lytic growth of the phage particles carrying the stx1 genes (stx1A and stx1B) of the EHEC O157:H7 strain RIMD 0509952, which was derived from the Sakai outbreak in 1996 in Japan, was induced after treatment with mitomycin C, but the plaque formation of the phage was not detected. We have determined the complete nucleotide sequence of the prophage VT1-Sakai. The integration site of the prophage was identified within the yehV gene at 47.7 min on the chromosome. The stx1 genes were downstream of the Q gene in the prophage genome, suggesting that their expression was regulated by the Q protein, the regulator of the late gene expression of the phage, which is similar to that of the stx1 or stx2 genes carried by the lambdoid phages reported previously. The sequences of the N gene and its recognition sites, nutL and nutR, were not homologous to those of the phages carrying the stx genes thus far reported, but they were very similar to those of bacteriophage phi21. The sequences of the repressor proteins, CI and Cro, that regulate expression of the early genes had low similarities with those of the known repressors of other phages, and their operator sequences were different from any sequence reported. These data suggest that multiple genetic recombination among bacteriophages with different immunities took place to generate the prophage VT1-Sakai. Comparison between the sequences of VT1-Sakai and lambda suggests that the ancestor of VT1-Sakai was produced by illegitimate excision, like lambda gal and bio phages.

Amino Acid Sequence↗

IP3 receptor-operated calcium entry.

This Perspective by Mikoshiba and Hattori is the third in a series on cellular calcium release mechanisms. The authors describe the regulated release of calcium from intracellular stores by the inositol 1,4,5 trisphosphate receptor (IP(3)R) and the relationship of this release mechanism to calcium influx from the extracellular milieu through store-operated calcium channels. They discuss a model proposing that intracellular and plasma membrane calcium channels are functionally and physically coupled.

Animals↗

Genome sequence of the endocellular bacterial symbiont of aphids Buchnera sp. APS.

Almost all aphid species (Homoptera, Insecta) have 60-80 huge cells called bacteriocytes, within which are round-shaped bacteria that are designated Buchnera. These bacteria are maternally transmitted to eggs and embryos through host generations, and the mutualism between the host and the bacteria is so obligate that neither can reproduce independently. Buchnera is a close relative of Escherichia coli, but it contains more than 100 genomic copies per cell, and its genome size is only a seventh of that of E. coli. Here we report the complete genome sequence of Buchnera sp. strain APS, which is composed of one 640,681-base-pair chromosome and two small plasmids. There are genes for the biosyntheses of amino acids essential for the hosts in the genome, but those for non-essential amino acids are missing, indicating complementarity and syntrophy between the host and the symbiont. In addition, Buchnera lacks genes for the biosynthesis of cell-surface components, including lipopolysaccharides and phospholipids, regulator genes and genes involved in defence of the cell. These results indicate that Buchnera is completely symbiotic and viable only in its limited niche, the bacteriocyte.

Aerobiosis↗

Identification and characterization of a 500-kb homozygously deleted region at 1p36.2-p36.3 in a neuroblastoma cell line.

Loss of heterozygosity of the distal region of chromosome 1p where tumor suppressor gene(s) might harbor is frequently observed in many human cancers including neuroblastoma (NBL) with MYCN amplification and poor prognosis. We have identified for the first time a homozygously deleted region at the marker D1S244 within the smallest region of overlap at 1p36.2-p36.3 in two NBL cell lines, NB-1 and NB-C201 (MASS-NB-SCH1), although our genotyping has suggested the possibility that both lines are derived from the same origin. The 800-kb PAC contig covering the entire region of homozygous deletion was made and partially sequenced (about 60%). The estimated length of the deleted region was 500 kb. We have, thus far, identified six genes within the region which include three known genes (DFF45, PGD, and CORT) as well as three other genes which have been reported during processing our present project for the last 3(1/2) years (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14). They include the genes related to apoptosis, glucose metabolism, ubiquitin-proteasome pathway, a neuronal microtubule-associated motor molecule and biogenesis of peroxisome. At least three genes (HDNB1/UFD2, KIAA0591F/KIF1B-beta, and PEX14) were differentially expressed at high levels in favorable and at low levels in unfavorable subsets of primary neuroblastoma. Since the 1p distal region is reported to be imprinted, those differentially expressed genes could be the new members of the candidate NBL suppressor, although RT-PCR-SSCP analysis has demonstrated infrequent mutation of the genes so far identified. Full-sequencing and gene prediction for the region of homozygous deletion would elucidate more detailed structure of this region and might lead to discovery of additional candidate genes. Oncogene (2000) 19, 4302 - 4307

Carrier Proteins↗

Regulated cleavage of a contact-mediated axon repellent.

Contact-mediated axon repulsion by ephrins raises an unresolved question: these cell surface ligands form a high-affinity multivalent complex with their receptors present on axons, yet rather than being bound, axons can be rapidly repelled. We show here that ephrin-A2 forms a stable complex with the metalloprotease Kuzbanian, involving interactions outside the cleavage region and the protease domain. Eph receptor binding triggered ephrin-A2 cleavage in a localized reaction specific to the cognate ligand. A cleavage-inhibiting mutation in ephrin-A2 delayed axon withdrawal. These studies reveal mechanisms for protease recognition and control of cell surface proteins, and, for ephrin-A2, they may provide a means for efficient axon detachment and termination of signaling.

Amino Acid Motifs↗

Chymase mediates mast cell-induced angiogenesis in hamster sponge granulomas.

We investigated the contribution of mast cell chymase in mast cell-dependent angiogenesis using the hamster sponge-implant model, where angiogenesis in the granulation tissue surrounding the subcutaneously implanted sponge was evaluated by measuring the hemoglobin content. Daily local injection of compound 48/80 (3-100 microg/site/day), a potent mast cell activator, induced formation of granulomas and angiogenesis in time- and dose-dependent manners. This angiogenic response was inhibited by chymase inhibitors including chymostatin (> or = 1 nmol/site/day), soybean trypsin inhibitor (SBTI; > or = 1.4 nmol/site/day) and lima bean trypsin inhibitor (LBTI; > or = 3.3 nmol/site/day), but not by a tryptase inhibitor like leupeptin (> or = 700 nmol/site/day). Although pyrilamine (> or = 2,580 nmol/site/day), a histamine H1 receptor antagonist, and protamine (300 microg/site/day) also inhibited angiogenesis, these effects were much less pronounced than those by chymase inhibitors. Furthermore, antigen-induced angiogenesis in hamsters pre-sensitized with ovalbumin was also inhibited by the chymase inhibitors by 60-70%. Our results suggest that chymase is a major mediator in mast cell-mediated angiogenesis.

Animals↗

Sequence-based structural features between Kvlqt1 and Tapa1 on mouse chromosome 7F4/F5 corresponding to the Beckwith-Wiedemann syndrome region on human 11p15.5: long-stretches of unusually well conserved intronic sequences of kvlqt1 between mouse and human.

Mouse chromosome 7F4/F5 is a syntenic locus of human 11p15.5 in which many imprinted genes are clustered. Transmission of aberrant human 11p15.5 or duplicated 11p causes Beckwith-Wiedemann syndrome (BWS) depending on which parent the chromosome is derived from. To analyze a syntenic mouse locus corresponding to human 11p15.5, mouse BAC contigs were constructed between Nap2 and Tapa1, in which 390 kb was sequenced between Kvlqt1 and Tapa1. An unexpected finding was that of highly conserved intronic sequences of Kvlqt1 between mouse and human, and their homologies came up to at least 160 kb because the length of this gene extended to 350 kb, suggesting the possibility of some functional constraint due to transcriptional and/or post-transcriptional regulation of this region. Many expressed sequence tags (ESTs) were mapped on this locus. Three genes, Lit1 (Kvlqt1-AS), Mtr1 and Tssc4, were identified and characterized. Lit1 is an antisense-transcript of Kvlqt1 and paternally expressed and maternally methylated throughout the developmental stage. The position where Lit1 exists corresponded to a highly conserved region between mouse and human. This transcript extends at least 60 kb from downstream to upstream of exon 10 in Kvlqt1. Tssc4 and Mtr1 carried putative open reading frames but neither was imprinted. Further characterization of this locus based on the sequence comparison between mouse and human will contribute valuable information towards resolving the mechanism of the occurrence of BWS and the associated childhood tumor.

Alleles↗

A novel gene, DSCR5, from the distal Down syndrome critical region on chromosome 21q22.2.

Based on a detailed sequence of the distal Down syndrome critical region (DSCR), we predicted and molecularly cloned a novel gene, designated DSCR5. We determined the sequences of expressed sequence tags (ESTs) that almost matched the predicted cDNA sequence of DSCR5. Northern blot analysis showed that DSCR5 is expressed in several tissues including the liver, skeletal muscle, heart, pancreas and testis. To determine the 5'-end of DSCR5, the oligo-capping method was employed. Combining the EST sequence data and that from the oligo-capping experiments, we obtained the full-length cDNA sequence of DSCR5. DSCR5 had at least four types of alternatively spliced variants. According to the number of exons, they could be classified into two subtypes: DSCR5alpha and DSCR5beta. DSCR5alpha includes three splice variant subtypes, DSCR5alpha1, alpha2 and alpha3, which each has different first non-coding exon. In addition, the most abundantly isolated form, DSCR5alpha1, shows microheterogeneity of the mRNA start site. Comparison of the sequences between the predicted cDNA and the molecularly cloned cDNA revealed that the computer programs had limited validity to correctly predict the terminal exons. Thus, molecular cloning should always be required to complement the inadequacy of the computer predictions.

Alternative Splicing↗

Newly identified repeat sequences, derived from human chromosome 21qter, are also localized in the subtelomeric region of particular chromosomes and 2q13, and are conserved in the chimpanzee genome.

Subtelomeric regions have been a target of structural and functional studies of human chromosomes. Markers having a defined structure are especially useful to such studies. Here, we report 93 bp tandem repeat sequences found in the subtelomeric region of human chromosome 21q. They were also detected in the telomeric region of several other chromosomes. Interestingly, the repeat was also found in the 2q13 region which is known to be a position of chromosomal fusion, a major difference between the human and chimpanzee karyotypes. To the best of our knowledge, this repetitive sequence is a new member of human subtelomeric interspersed repeats.

Animals↗

Comparison of whole genome sequences of Chlamydia pneumoniae J138 from Japan and CWL029 from USA.

Chlamydia pneumoniae is a widespread pathogen of humans causing pneumonia and bronchitis. There are many reports of an association between C.PNEUMONIAE: infection and atherosclerosis. We determined the whole genome sequence of C.PNEUMONIAE: strain J138 isolated in Japan in 1994 and compared it with the sequence of strain CWL029 isolated in the USA before 1987. The J138 circular chromosome consists of 1 226 565 nt (40.7% G+C) with 1072 likely protein-coding genes that is 3665 nt shorter than the CWL029 genome. Plasmids, phage- or transposon-like sequences were not identified. The overall genomic organization, gene order and predicted proteomes of the two strains are very similar, suggesting a high level of structural and functional conservation between the two unrelated isolates. The most conspicuous differences in the J138 genome relative to the CWL029 genome are the absence of five DNA segments, ranging in size from 89 to 1649 nt, and the presence of three DNA segments, ranging from 27 to 84 nt. The complex organization of these 'different zones' may be attributable to a unique system of recombination.

Base Composition↗

The DNA sequence of human chromosome 21.

Chromosome 21 is the smallest human autosome. An extra copy of chromosome 21 causes Down syndrome, the most frequent genetic cause of significant mental retardation, which affects up to 1 in 700 live births. Several anonymous loci for monogenic disorders and predispositions for common complex disorders have also been mapped to this chromosome, and loss of heterozygosity has been observed in regions associated with solid tumours. Here we report the sequence and gene catalogue of the long arm of chromosome 21. We have sequenced 33,546,361 base pairs (bp) of DNA with very high accuracy, the largest contig being 25,491,867 bp. Only three small clone gaps and seven sequencing gaps remain, comprising about 100 kilobases. Thus, we achieved 99.7% coverage of 21q. We also sequenced 281,116 bp from the short arm. The structural features identified include duplications that are probably involved in chromosomal abnormalities and repeat structures in the telomeric and pericentromeric regions. Analysis of the chromosome revealed 127 known genes, 98 predicted genes and 59 pseudogenes.

Base Sequence↗

The human and mouse Period1 genes: five well-conserved E-boxes additively contribute to the enhancement of mPer1 transcription.

The clock gene, Period1, from human and mouse was sequenced and characterized. Both human PERIOD1 (human PER1) and mouse Period1 (mouse Per1) consisted of 23 exons spanning approximately 16 kb, and their structures showed strong similarity to each other. For example, six highly conserved regions were identified in the 5' upstream sequences. These conserved segments exhibited 77-88% identity and possessed several potential regulatory elements including five E-boxes (the binding site of the CLOCK-BMAL1 complex) and four cyclic AMP response elements. Transient transfection assays using a mPer1-luciferase fusion gene revealed that each of the conserved E-boxes additively functions as an enhancer for the transactivation of mPer1 by mCLOCK and mBMAL1.

ARNTL Transcription Factors↗

Criteria for gene identification and features of genome organization: analysis of 6.5 Mb of DNA sequence from human chromosome 21.

To establish criteria for and the limitations of novel gene identification, to identify novel genes of potential relevance to Down Syndrome and to investigate features of genome organization, 6. 550kb. In total, 41 novel gene models were predicted, and for a subset of these, RT-PCR experiments helped to verify and refine the models, and were used to assess expression in early development and in adult brain regions of potential relevance to Down syndrome. Results suggest generally low and/or restricted patterns of expression, and also reveal examples of complex alternative processing, especially in brain, that may have important implications for regulation of protein function. Analysis of complete gene structures of the known genes identified a number of very large introns, a number of very short intergenic distances, and at least one potentially bi-directional promoter. At least 3/4 of known genes and 1/2 of predicted genes are associated with CpG islands. For novel genes, three cases of overlapping genes are predicted. Results of these analyses illustrate some of the complexities inherent in mammalian genome organization and some of the limitations of current sequence analysis technologies. They also doubled the number of potential genes within the region.

Adult↗

Inhibition of nitric oxide release by an aqueous extract of Tinospora tuberculata.

An aqueous extract of Tinospora tuberculata stems was found to scavenge nitric oxide (NO) in vitro in both cell and cell-free systems. When the aqueous extract was added to lipopolysaccharide-stimulated murine macrophages, it inhibited NO release dose-dependently, and similar activity was found in a cell-free system using sodium nitroprusside as a NO donor. These findings may help to explain, in part, certain pharmacological activities of Tinospora tuberculata.

Animals↗

Identification of the homozygously deleted region at chromosome 1p36.2 in human neuroblastoma.

BACKGROUND: We have identified for the first time a homozygously deleted region within the smallest region of overlap at 1p36.2-3 in two neuroblastoma cell lines. PROCEDURE: The 800-kb PAC contig covering the entire homozygously deleted region was made and sequenced. To date, approximately 70% of sequencing has been accomplished, and the estimated length of the deleted region was 500 kb. RESULTS: Currently, we have found six genes within the region, which include three known genes as well as three other genes that have been reported during processing of our present project for the last 3(1/2) years. We report here the results of expression and mutation analyses of those genes. CONCLUSIONS: Full sequencing for the region of homozygous deletion as well as further analyses of the genes mapped within the region may reveal whether or not there is a neuroblastoma suppressor gene as proposed by the Knudson's two-hit hypothesis.

Child, Preschool↗