[Percutaneous hepatic infarction therapy (PIT)].
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Aged↗
Biomedical subjects
S Sato
Publications and source records attributed to S Sato.
p53 gene status and chemosensitivity in ovarian cancer.
Recent studies suggest that drug induced apoptosis relates to the sensitivity. p53 gene, which has a pivotal role in inducing apoptosis, frequently mutates in ovarian cancer. Therefore, p53 gene status and chemosensitivity in epithelial ovarian cancer is discussed. Nonresponders to chemotherapy had mutations of the p53 gene more frequently (83% for nonresponders vs. 16% for responders) in patients with epithelial ovarian cancer undergoing platinum-base chemotherapy. Apoptotic index was significantly greater in tumors with wild-type p53 gene than those without the gene. p53 gene transduction markedly enhanced the sensitivity to cisplatin (CDDP) and CDDP-induced apoptosis, but did not affect the sensitivity to paclitaxel (PTX) nor PTX-induced apoptosis in ovarian cancer cells without p53 gene. The combination treatment with a recombinant adenovirus carrying a wild-type p53 gene (AxCAp53) and CDDP significantly suppressed tumor growth of ovarian cancer cells with and without p53 gene, compared with a single treatment of either AxCAp53 or CDDP in ovarian cancer xenograft. Apoptotic index was significantly higher and proliferating cell nuclear antigen labeling index was relatively lower in an ovarian cancer xenograft without p53 gene receiving combination treatment, compared with a single treatment of either CDDP or AxCAp53, suggesting that the transduction of p53 gene induces apoptosis, but does not enhance the DNA repair system. A significant survival advantage was observed in the combination treatment compared with other treatments in carcinoma peritonitis models. In conclusion, p53 gene status contributes the sensitivity to CDDP in ovarian cancer. Additionally, combination treatment of p53 gene transduction and CDDP may be an effective therapeutic modality for ovarian cancer without wild-type p53 gene.
Adenocarcinoma↗
[Functional genomics in Arabidopsis thaliana].
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Arabidopsis↗
[Quantitative evaluation of esophageal scintigraphy in systemic sclerosis].
BACKGROUND: Esophageal involvement by systemic sclerosis (SSc) is frequent. The purpose of this study was to evaluate esophageal motility disorders quantitatively. METHODS: We investigate esophageal scintigraphy in 22 patients with SSc. Esophageal scintigraphy was obtained with swallowing physiological saline in supine position, and swallowing soup in supine and sitting positions. Data was acquired with 0.5 sec per frame for 192 frames in the anterior view. We employed a condensed image as a visual evaluation, half-life and retention rate as a quantitative evaluation, which were obtained from time-activity curves generated from regions of interest on the whole esophagus. The half-life and retention rate were compared with classification of Barnett, stages of SSc, and modified Rodnan total skin score (TSS). RESULTS: No significant differences were seen in classification of Barnett and the stages of SSc. No significant difference was seen between swallowing water and soup in the supine position. The retention rate was significantly prolonged in the supine position than in the sitting position. The retention rate of soup study in the sitting position correlated with TSS (r = 0.61). CONCLUSION: Esophageal scintigraphy in the sitting position is useful in evaluation of esophageal motility in SSc.
Adult↗
[Relationship between the fecal mutagenicity and metal content, smoking habit and dietary intake].
OBJECTIVE: The study was carried out to collect basic data on exposure of mucous cells of the large intestine to mutagens by investigating the genotoxicity of fecal samples from the urban population. Simultaneously, relations with food intake (food groups and nutritive components), lifestyle factors and fecal metal content was investigated. METHODS: A total of 199 self-collected fecal samples from middle aged healthy volunteer living in urban areas of Osaka city were freeze-dried and ground in a mill. The mutagenicity of aqueous extracts of the ground samples was measured by the umu-test. Metal content of the feces was analysed by atomic absorption spectrophotometlly. On the day previous to the feces collection, the contents of meals were recorded and confirmed by interview with a dietitian. Quantification of nutritive components was carried out using the 4th edition of the Japan Food Standard Vomposition Table. RESULTS: Mutagenicity of feces was higher in males than in females, and in those aged 40-49 years than 50-69 years in males but not females. Large differences were found for content of 8 metals in the feces; concentrations were in the decreasing order of calcium, potassium, magnesium, sodium, zinc, iron, manganese and copper, the highest being 20.4 mg for calcium and the lowest was 53.5 micrograms for copper. Between the metal contents and mutagenicity, values for zinc and iron showed positive correlations and for sodium a negative correlation under S9(+) conditions. A weak but significant correlation was observed between the numbers of cigarettes smoked per day and S9 (+) mutagenicity. However we could not find any relation with food groups or nutritive components. CONCLUSION: It is well known that human feces contain many mutagens and carcinogens and that these can act directly on the mucous membrane of large intestine. Therefore, it is very important to estimate exposure levels. From the present data we can conclude that relations between mutation-activity of the feces and diet are complex. Their elucidation will require a large number of volunteers who have similar living conditions to obtain appropriate data.
Adult↗
Interleukin 18 levels reflect the severity of acute pancreatitis.
The serum interleukin 18 (IL-18) levels were significantly increased in cases of acute pancreatitis, corresponding to the severity of the disease. The IL-18 levels were also significantly correlated with the serum tumor necrosis factor alpha (TNF-alpha) and bilirubin levels. The possible involvement of IL-18 in the development of liver dysfunction in acute pancreatitis is suggested.
Acute Disease↗
Heart rate variability during long truck driving work.
We recorded ambulatory electrocardiograms of 6 long distance truck drivers during their work period in order to observe the affect of autonomic nervous function and symptoms while doing their work. We also recorded their work patterns every minute. The RR50 value and the LFP/HFP ratio were calculated every two minutes based on R-R interval data. RR50 was significantly higher during taking naps than during other periods of work shifts, while, the LFP/HFP ratio showed significantly lower during taking naps than during other periods of work shifts. RR50 in the morning was significantly higher than that in the afternoon. On the contrary, the LFP/HFP ratio showed opposite tendency. Only on the times of driving, RR50 was significantly higher in the morning than that in the afternoon. On the other hand, the LFP/HFP ratio showed an opposite tendency. These results show that the parasympathetic nervous activities were more dominant than sympathetic nervous activities in the morning during the subjects were doing long distance truck driving including midnight work. Driving while in high parasympathetic nervous activity levels may add to cardiovascular stress and lead to drowsiness. And this may result in disrupted attention. It is necessary to decrease work time and improve working conditions of truck drivers working long-hour shifts.
Adult↗
[Role of cell adhesion molecules in wound healing].
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Animals↗
Complete structure of the chloroplast genome of a legume, Lotus japonicus.
The nucleotide sequence of the entire chloroplast genome (150,519 bp) of a legume, Lotus japonicus, has been determined. The circular double-stranded DNA contains a pair of inverted repeats of 25,156 bp which are separated by a small and a large single copy region of 18,271 bp and 81,936 bp, respectively. A total of 84 predicted protein-coding genes including 7 genes duplicated in the inverted repeat regions, 4 ribosomal RNA genes and 37 tRNA genes (30 gene species) representing 20 amino acids species were assigned on the genome based on similarity to genes previously identified in other chloroplasts. All the predicted genes were conserved among dicot plants except that rpl22, a gene encoding chloroplast ribosomal protein CL22, was missing in L. japonicus. Inversion of a 51-kb segment spanning rbcL to rpsl6 (positions 5161-56,176) in the large single copy region was observed in the chloroplast genome of L. japonicus. The sequence data and gene information are available on our World Wide Web database at http://www.kazusa.or.jp/en/plant/database.html.
Amino Acids↗
Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti.
The complete nucleotide sequence of the genome of a symbiotic bacterium Mesorhizobium loti strain MAFF303099 was determined. The genome of M. loti consisted of a single chromosome (7,036,071 bp) and two plasmids, designated as pMLa (351,911 bp) and pMLb (208, 315 bp). The chromosome comprises 6752 potential protein-coding genes, two sets of rRNA genes and 50 tRNA genes representing 47 tRNA species. Fifty-four percent of the potential protein genes showed sequence similarity to genes of known function, 21% to hypothetical genes, and the remaining 25% had no apparent similarity to reported genes. A 611-kb DNA segment, a highly probable candidate of a symbiotic island, was identified, and 30 genes for nitrogen fixation and 24 genes for nodulation were assigned in this region. Codon usage analysis suggested that the symbiotic island as well as the plasmids originated and were transmitted from other genetic systems. The genomes of two plasmids, pMLa and pMLb, contained 320 and 209 potential protein-coding genes, respectively, for a variety of biological functions. These include genes for the ABC-transporter system, phosphate assimilation, two-component system, DNA replication and conjugation, but only one gene for nodulation was identified.
ATP-Binding Cassette Transporters↗
Complete genome structure of the nitrogen-fixing symbiotic bacterium Mesorhizobium loti (supplement).
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Base Sequence↗
Pigment cell-specific expression of the tyrosinase gene in ascidians has a different regulatory mechanism from vertebrates.
Tyrosinase is the key enzyme required for the synthesis of melanin pigments. Sequence comparison and functional analysis of the 5' upstream regions of vertebrate tyrosinase genes have revealed the importance of conserved E-box motifs in regulating their specific expression in pigment cells, optic cup-derived retinal pigment epithelium (RPE) and neural crest-derived melanocytes. In ascidians (more basal protochordates), two pigment cells that resemble vertebrate RPE cells are formed and specifically express the orthologous tyrosinase gene (HrTyr) in the cerebral vesicle located at the anterior end of the neural tube. To define regulatory sequences required for pigment cell-lineage-specific expression of HrTyr during embryogenesis, a series of mutations of the 5' upstream region of HrTyr were fused to the lacZ reporter gene and were microinjected into fertilized eggs. We found that the -152bp upstream of the translational start site is essential for expression in pigment cell precursors of tailbud-stage embryos. Further, additional positive and unique restriction elements were identified in the region up to -1.8kb. Surprisingly, in the -152bp minimal promoter or in other regions with regulatory activities, there are no E-box motifs or sequences correlating with other conserved elements regulating vertebrate tyrosinase promoters. The possibility that Pax proteins regulate HrTyr expression is also discussed.
Amino Acid Sequence↗
Serological analysis of BALB/C methylcholanthrene sarcoma Meth A by SEREX: identification of a cancer/testis antigen.
Antigens of BALB/c methylcholanthrene-induced fibrosarcoma Meth A recognized by the host humoral immune response were investigated by serological analysis of antigens by recombinant expression cloning (SEREX). Immunoscreening a cDNA library from Meth A (Kgamma) cells (Meth A retrovirally transfected with murine IFN-gamma cDNA) with sera from BALB/c mice growing parental Meth A transplants identified 10 antigens. One of them, OY-MS-4, showed characteristics of a cancer/testis (CT) antigen. Nucleotide sequence analysis revealed that OY-MS-4 was identical to a mouse placenta and embryonic expression gene (pem) known to be selectively expressed during embryogenesis and in transformed cell lines. In adult mice, expression of OY-MS-4 was restricted to testis and placenta. Four of 6 methylcholanthrene-induced fibrosarcomas in BALB/c mice showed strong expression of OY-MS-4. In 6 T-cell leukemias, only a dimethylbenzanthracene-induced leukemia, EL4 (C57BL), showed strong expression. Two other tumors, A20.2J and P815, induced by ethylnitrosourea and methylcholanthrene, respectively, also strongly expressed OY-MS-4. The other 9 gene products identified in Meth A by SEREX were expressed in all 15 tumors tested and in a range of normal tissues. Sequence analysis of cDNA inserts coding for the SEREX-defined antigens showed no evidence of mutation. Despite the expression of OY-MS-1-10 antigens in methylcholanthrene sarcomas other than Meth A, no antibody was detected in the sera of mice bearing these other sarcomas. The basis for the unique immunogenicity of OY-MS-1-10 presented by Meth A, but not by other syngeneic tumors expressing these gene products, is unknown.
Amino Acid Sequence↗
Synergy and cross-tolerance between toll-like receptor (TLR) 2- and TLR4-mediated signaling pathways.
A family of Toll-like receptor (TLR) mediates the cellular response to bacterial cell wall components; murine TLR2 and TLR4 recognize mycoplasmal lipopeptides (macrophage-activating lipopeptides, 2 kDa (MALP-2)) and LPS, respectively. Costimulation of mouse peritoneal macrophages with MALP-2 and LPS results in a marked increase in TNF-alpha production, showing the synergy between TLR2- and TLR4-mediated signaling pathways. Macrophages pretreated with LPS show hyporesponsiveness to the second LPS stimulation, termed LPS tolerance. The LPS tolerance has recently been shown to be primarily due to the down-regulation of surface expression of the TLR4-MD2 complex. When macrophages were treated with MALP-2, the cells showed hyporesponsiveness to the second MALP-2 stimulation, like LPS tolerance. Furthermore, macrophages pretreated with MALP-2 showed reduced production of TNF-alpha in response to LPS. LPS-induced activation of both NF-kappaB and c-Jun NH(2)-terminal kinase was severely impaired in MALP-2-pretreated cells. However, MALP-2-pretreated macrophages did not show any reduction in surface expression of the TLR4-MD2 complex. These findings indicate that LPS-induced LPS tolerance mainly occurs through the down-regulation of surface expression of the TLR4-MD2 complex; in contrast, MALP-2-induced LPS tolerance is due to modulation of the downstream cytoplasmic signaling pathways.
Animals↗
Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana.
The genome of the model plant Arabidopsis thaliana has been sequenced by an international collaboration, The Arabidopsis Genome Initiative. Here we report the complete sequence of chromosome 5. This chromosome is 26 megabases long; it is the second largest Arabidopsis chromosome and represents 21% of the sequenced regions of the genome. The sequence of chromosomes 2 and 4 have been reported previously and that of chromosomes 1 and 3, together with an analysis of the complete genome sequence, are reported in this issue. Analysis of the sequence of chromosome 5 yields further insights into centromere structure and the sequence determinants of heterochromatin condensation. The 5,874 genes encoded on chromosome 5 reveal several new functions in plants, and the patterns of gene organization provide insights into the mechanisms and extent of genome evolution in plants.
Animals↗
A Toll-like receptor recognizes bacterial DNA.
DNA from bacteria has stimulatory effects on mammalian immune cells, which depend on the presence of unmethylated CpG dinucleotides in the bacterial DNA. In contrast, mammalian DNA has a low frequency of CpG dinucleotides, and these are mostly methylated; therefore, mammalian DNA does not have immuno-stimulatory activity. CpG DNA induces a strong T-helper-1-like inflammatory response. Accumulating evidence has revealed the therapeutic potential of CpG DNA as adjuvants for vaccination strategies for cancer, allergy and infectious diseases. Despite its promising clinical use, the molecular mechanism by which CpG DNA activates immune cells remains unclear. Here we show that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9. TLR9-deficient (TLR9-/-) mice did not show any response to CpG DNA, including proliferation of splenocytes, inflammatory cytokine production from macrophages and maturation of dendritic cells. TLR9-/- mice showed resistance to the lethal effect of CpG DNA without any elevation of serum pro-inflammatory cytokine levels. The in vivo CpG-DNA-mediated T-helper type-1 response was also abolished in TLR9-/- mice. Thus, vertebrate immune systems appear to have evolved a specific Toll-like receptor that distinguishes bacterial DNA from self-DNA.
Adaptor Proteins, Signal Transducing↗
Synthesis of C-pentopyranosylphloroacetophenone derivatives and their anomerization.
A 3-C-beta-D-xylopyranosylphloroacetophenone derivative was synthesized via reaction of 2,3,4-tri-O-benzyl-alpha-D-xylopyranosyl fluoride and 2,4-di-O-benzylphloroacetophenone in the presence of boron trifluoride diethyl etherate. Alternatively, the reaction of 2,3,4-tri-O-benzyl-beta-L-arabinopyranosyl fluoride with 2,4-di-O-benzylphloroacetophenone afforded both the 3-C-alpha-L- and the 3-C-beta-L-arabinopyranosylphloroacetophenone derivatives under identical reaction conditions. The C-beta-L-arabinoside, the thermodynanic product, was produced via anomerization of the C-alpha-L-arabinoside, the kinetic product during the reaction. The composition of this product mixture is apparently dictated by both 1,3-diaxial and 2,4-diaxial interactions.
Acetophenones↗
Quantitative genetic variation in CD19 expression correlates with autoimmunity.
Signaling thresholds influence the balance between humoral immunity and autoimmunity. Cell surface CD19 regulates intrinsic and Ag receptor-induced B lymphocyte signaling thresholds, and transgenic mice that overexpress CD19 by 3-fold generate spontaneous autoantibodies in a genetic background not associated with autoimmunity. To quantify the extent that genetically determined differences in expression of a single cell surface molecule can influence autoantibody production, we have assessed autoimmunity in a C57BL/6-transgenic mouse line with subtle 15-29% increases in CD19 cell surface expression (CD19 transgenic). Antinuclear Abs, especially anti-spindle pole Abs, rheumatoid factor, and autoantibodies for ssDNA, dsDNA, and histone were produced in these transgenic mice, but not littermate controls. This demonstrates that small changes in CD19 expression can induce autoantibody production. Remarkably, similar changes in CD19 expression were found on B cells from patients with systemic sclerosis, a multisystem disorder of connective tissue with autoantibody production. CD19 density on blood B cells from systemic sclerosis patients was significantly ( approximately 20%) higher compared with normal individuals, whereas CD20, CD22, and CD40 expression were normal. These results suggest that modest changes in the expression or function of regulatory molecules such as CD19 may shift the balance between tolerance and immunity to autoimmunity. Thereby autoimmune disease may result from a collection of subtle multigenic alterations that could include incremental density changes in cell surface signaling molecules.
Adult↗