PubMed Health⌕ Search

Biomedical subjects

S Sato

Publications and source records attributed to S Sato.

At least 361 records · Page 20Linked to original sources
PubMed2000

Chloroplast development in Arabidopsis thaliana requires the nuclear-encoded transcription factor sigma B.

Development of plastids into chloroplasts, the organelles of photosynthesis, is triggered by light. However, little is known of the factors involved in the complex coordination of light-induced plastid gene expression, which must be directed by both nuclear and plastid genomes. We have isolated an Arabidopsis mutant, abc1, with impaired chloroplast development, which results in a pale green leaf phenotype. The mutated nuclear gene encodes a sigma factor, SigB, presumably for the eubacterial-like plastid RNA polymerase. Our results provide direct evidence that a nuclear-derived prokaryotic-like SigB protein, plays a critical role in the coordination of the two genomes for chloroplast development.

Arabidopsis↗
PubMed2000

An effective synthesis of isoorientin: the regioselective synthesis of a 6-C-glucosylflavone.

Isoorientin, a 6-C-beta-D-glucopyranosyl-3',4',5,7-tetrahydroxyflavone, was synthesized in a 15% overall yield, in ten steps, starting from the commercially available phloroacetophenone. The C-glucosyl phloroacetophenone derivative, a synthetic intermediate that contains a free hydroxyl group that is para to the glucosyl moiety, was obtained by hydrogenolysis by taking advantage of differences in the hydrogenolysis rates between a benzyl protecting group and a 2-methylbenzyl protecting group. Aldol condensation of the C-glucosyl phloroacetophenone derivative with 3,4-bis-benzyloxybenzaldehyde afforded the corresponding chalcone as a precursor of the 6-C-glucosyl flavone. Construction of the flavone system by application of I2-DMSO, followed by deprotection, yielded isoorientin.

Flavonoids↗
PubMed2000

Visualization, quantification and therapeutic evaluation of angiogenic vessels in cancer by synchrotron microangiography.

The usefulness of a synchrotron microangiography system for depicting, quantitating and therapeutically evaluating angiogenic vessels in cancer is illustrated. In 20 mice transplanted with murine colon cancer, sequential changes in the angiogenic vessels were determined by using synchrotron microangiography, using changes in tumor volume for reference. This system allowed the depiction and quantification of angiogenic vessels in the period from one to four weeks after transplantation. The effects of antiangiogenic therapy were evaluated by using a neutralizing antibody against vascular endothelial growth factor. The neutralizing antibody partially suppressed angiogenesis and tumor growth. Synchrotron microangiography is shown to be useful for the depiction, quantification and evaluation of angiogenic vessels in cancer.

Journal Article↗
PubMed2000

The conversion of 3-C-beta-D-galactopyranosyl phloroacetophenone to a spiroketal derivative.

Treatment of 3-C-beta-D-galactopyranosylphloroacetophenone in hot water with a catalytic amount of p-toluenesulfonic acid afforded a spiroketal compound as the main product. The chirality of the spiro carbon of the product was R, which is the opposite of the spiroketal obtained by the conversion of 3-C-beta-D-glucopyranosyl phloroacetophenone under identical conditions. The structure was determined by 1H-1H COSY, 1H-13C COSY, NOESY and HMBC spectroscopy.

Acetophenones↗
PubMed2000

Modulation of Akt kinase activity by binding to Hsp90.

Serine/threonine kinase Akt/PKB is a downstream effector molecule of phosphoinositide 3-kinase and is thought to mediate many biological actions toward anti-apoptotic responses. We found that Akt formed a complex with a 90-kDa heat-shock protein (Hsp90) in vivo. By constructing deletion mutants, we identified that amino acid residues 229-309 of Akt were involved in the binding to Hsp90 and amino acid residues 327-340 of Hsp90beta were involved in the binding to Akt. Inhibition of Akt-Hsp90 binding led to the dephosphorylation and inactivation of Akt, which increased sensitivity of the cells to apoptosis-inducing stimulus. The dephosphorylation of Akt was caused by an increase in protein phosphatase 2A (PP2A)-mediated dephosphorylation and not by a decrease in 3-phosphoinositide-dependent protein kinase-1-mediated phosphorylation. These results indicate that Hsp90 plays an important role in maintaining Akt kinase activity by preventing PP2A-mediated dephosphorylation.

Cell Line↗
PubMed2000

Post-ischemic hypothermia delayed neutrophil accumulation and microglial activation following transient focal ischemia in rats.

Following ischemia, inflammation has been demonstrated to be involved in the progression of the tissue damage. Intra-ischemic hypothermia has been shown to attenuate the adverse activities of neutrophils and microglia. We investigated whether neutrophil accumulation and/or microglial activation is attenuated in post-ischemic hypothermia following transient focal ischemia in rats. After 1 h of ischemia, the neutrophil accumulation and the microglial activation was evaluated immunohistochemically. Percent infarct area was compared at 1, 2, 3, 5, and 7 days after ischemia/reperfusion. In hypothermia, the neutrophil accumulation was delayed but not attenuated. In normothermia, the accumulation reached the peak at 2 days after ischemia. The peak shifted to 3 days in hypothermia. Similarly, the microglial activation was delayed in hypothermia. Comparison of the infarct area showed significant protection by hypothermia at 1 and 2 days after reperfusion. However, hypothermia failed to show significant protection after 3 days and later. These results show that the delayed neutrophil accumulation and the microglial activation can be responsible for the loss of persistent protection in post-ischemic hypothermia.

Animals↗
PubMed2000

Prevention of phosphatidylinositol 3'-kinase-Akt survival signaling pathway during topotecan-induced apoptosis.

The serine/threonine kinase Akt (also known as protein kinase B) is a downstream effector of phosphatidylinositol-3'-kinase [PI(3)K] that is recognized as the major mediator of survival signals that protect cells from undergoing apoptosis. In the course of examining the target molecules of the topoisomerase I inhibitor topotecan, we found that topotecan treatment promoted Akt dephosphorylation that led to the inactivation of Akt in human lung cancer A549 cells. Transfection of the constitutively active akt cDNA into A549 cells resulted in the reduction of the cytotoxic effect of topotecan, indicating that inhibition of the Akt pathway played an important role in exhibition of topotecan-mediated cytotoxic effects. Further analysis of Akt dephosphorylation revealed that topotecan treatment suppressed upstream kinases of Akt, 3-phosphoinositide-dependent protein kinase 1, and PI(3)K. Overall, the results demonstrate that topotecan exhibited its cytotoxic effects by down-regulating the PI(3)K-Akt survival signaling pathway in addition to inhibiting topoisomerase I.

3-Phosphoinositide-Dependent Protein Kinases↗
PubMed2000

Activation of HIF1alpha ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex.

Mutations in the VHL tumor suppressor gene result in constitutive expression of many hypoxia-inducible genes, at least in part because of increases in the cellular level of hypoxia-inducible transcription factor HIF1alpha, which in normal cells is rapidly ubiquitinated and degraded by the proteasome under normoxic conditions. The recent observation that the VHL protein is a subunit of an Skp1-Cul1/Cdc53-F-box (SCF)-like E3 ubiquitin ligase raised the possibility that VHL may be directly responsible for regulating cellular levels of HIF1alpha by targeting it for ubiquitination and proteolysis. In this report, we test this hypothesis directly. We report development of methods for production of the purified recombinant VHL complex and present direct biochemical evidence that it can function with an E1 ubiquitin-activating enzyme and E2 ubiquitin-conjugating enzyme to activate HIF1alpha ubiquitination in vitro. Our findings provide new insight into the function of the VHL tumor suppressor protein, and they provide a foundation for future investigations of the mechanisms underlying VHL regulation of oxygen-dependent gene expression.

Animals↗
PubMed2000

Plasma fibrinogen and coronary heart disease in urban Japanese.

There is little information on the relation of plasma fibrinogen concentration to the risk of coronary heart disease in Asians, including Japanese, whose plasma fibrinogen concentration has been reported to be low by Western standards. The authors conducted a prospective study with 4.8 years of follow-up of 11,977 men and women aged 21-89 years (mean value of fibrinogen = 267 mg/dl) living or working in Osaka, Japan, in 1990-1996 to examine the relation of plasma fibrinogen with the incidence of coronary heart disease (myocardial infarction and angina pectoris). Mean fibrinogen concentration was 293.6 mg/dl for men who developed coronary heart disease (n = 35) compared with 261.6 mg/dl for men free of coronary heart disease (n = 8,094; difference, p < 0.01), and 355.2 mg/dl for women who developed coronary heart disease (n = 6) compared with 276.8 mg/dl for women free of coronary heart disease (n = 3,842; difference, p < 0.01). With a Cox proportional hazards model to adjust for cardiovascular risk factors, the relative risk for the highest fibrinogen quartile (> or =295 mg/dl) compared with the lowest (<228 mg/dl) was 4.8 (95% confidence interval: 1.4, 16.8, p = 0.01) for coronary heart disease, and 3.8 (95% confidence interval: 1.1, 13.4, p = 0.04) for myocardial infarction. Plasma fibrinogen is useful to predict the risk of coronary heart disease among urban Japanese, whose mean plasma fibrinogen is relatively low.

Adult↗
PubMed2000

Identification of thioether intermediates in the reductive transformation of gonyautoxins into saxitoxins by thiols.

O-Sulfate group of gonyautoxin I and IV is transformed into methylene to form neosaxitoxin by thiols such as glutathione, a common cellular scavenger, in mild conditions. We isolated the intermediate of this conversion and propose that this reaction proceeds through formation of thiohemiketal, 1,2 shift to form stable thioether intermediate, and then redox exchange at sulfur atom to form the final product.

Animals↗
PubMed2000

Usefulness of mass screening for ovarian carcinoma using transvaginal ultrasonography.

BACKGROUND: International Federation of Gynecology and Obstetrics Stage I ovarian carcinoma, which has the worst prognosis among all types of gynecologic carcinoma, has a high cure rate as has been reported, but early diagnosis is difficult and to the authors' knowledge screening methods have not been established. Since 1989, the authors have performed transvaginal ultrasonography (TVS) as a form of screening for ovarian carcinoma. The purpose of the current study was to summarize and evaluate screening results for the last 10 years with respect to ovarian carcinoma diagnosis and risk factors. METHODS: Primary screening by TVS was performed in asymptomatic women who participated in annual uterine cervical carcinoma screening. Four scanning sections by TVS were established and all sonograms were recorded. Women with abnormal sonograms (a mass > 30 mm in greatest dimension or a mass with a mixed pattern) received secondary screening and closer examination with a tumor marker and an imaging diagnostic examination. Laparotomy was conducted on all masses with a greatest dimension of >/= 60 mm or on suspected malignant masses. Subject information-related risk factors also were recorded. RESULTS: Subjects were 183,034 women who participated in primary screening. Of these women, 51,550 were undergoing screening for the first time. The time required for primary screening was 1 minute per subject. Secondary screening was required for 5309 participants (10.3%) and surgery was performed on 324 participants. Twenty-two primary tumors and 2 metastatic tumors were detected for a diagnostic rate of 0.047%. Of the 22 primary tumors, 17 (77.3%) were classified as Stage I carcinoma, with tumor markers positive only for 5 (29.4%). The percentage of the total number of Stage I ovarian carcinoma cases increased after the induction of screening from 29.7% to 58.8%. CONCLUSIONS: These results are significant in that 77.3% of the primary ovarian carcinomas found during the current screening were of curable Stage I. Increased use of TVS screening for ovarian carcinoma may increase the chance for early diagnosis and decrease the mortality of the disease.

Adult↗
PubMed2000

A role for p27/Kip1 in the control of cerebellar granule cell precursor proliferation.

During development, control of proliferation of neuronal precursor cells plays a crucial role in determining the number of neurons. Proliferation is driven by mitogens, but how it is terminated remains a mystery. In this study, we examined the role of cyclin-dependent kinase inhibitors in the control of proliferation of cerebellar granule cell precursors (GCPs). Among the inhibitors we examined, only p27/Kip1 (p27) was expressed at significant levels in cells of the granule cell lineage in the developing and adult cerebellum. In developing cerebella, p27 was expressed in the external germinal layer (the deeper regions), the molecular layer, and the granule layer. In adult cerebella, p27 was expressed in the cells of the granule layer. We isolated and purified GCPs from cerebella of developing mice and examined their bromodeoxyuridine (BrdU) uptake and p27 expression at various times. We found that there was an inverse correlation between BrdU uptake and p27 expression. Even in the presence of saturating amounts of Sonic hedgehog, a potent mitogen, the cells eventually stopped dividing and differentiated, expressing p27 strongly. We also examined mice in which one or both copies of the p27 gene have been inactivated by targeted gene disruption and found that their cerebella were larger than those of wild-type mice. In cell cultures, GCPs prepared from p27-deficient mice showed enhanced proliferation compared with GCPs from wild-type mice. Taken together, these results suggest that there is an intracellular mechanism that stops GCP division and causes GCPs to differentiate and that p27 is part of this mechanism.

Age Factors↗
PubMed2000

Effect of P(2)' site tryptophan and P(20)' site deletion of Momordica charantia trypsin inhibitor II on inhibition of proteinases.

Momordica charantia trypsin inhibitor II (MCTI-II) inhibits the amidolytic activity of factor Xa with a K(i) value 10-100-fold smaller than those of other squash family inhibitors. It also inhibits factor X activation mediated by factor VIIa-tissue factor complex or factor IXa. Comparison of other squash family inhibitors reveal Trp at position 7 (P(2)') and a deletion at position 25 (P(20)') are characteristics of MCTI-II. In order to elucidate the effect of these positions on the inhibitory activity, we chemically synthesized three inhibitors: S-MCTI-II whose amino acid sequence is identical to natural MCTI-II, S-MCTI-II(7L) whose P(2)'(Trp) is substituted with Leu, and S-MCTI-II(25N) whose P(20)'(deletion) is filled with Asn. The dissociation constants of the complexes of human factor Xa with S-MCTI-II, S-MCTI-II(7L), and S-MCTI-II(25N) were 1.3x10(-6) M, 2.8x10(-5) M, and 7.3x10(-6) M, respectively. They inhibited factor X activation mediated by factor VIIa with the same degree. As in the case of natural MCTI-II, S-MCTI-II suppressed factor X activation mediated by factor IXa, while S-MCTI-II(7L) and S-MCTI-II(25N) did not. Both the Trp at the P(2)' position and deletion at the P(20)' position are thus likely required for the inhibition of factor Xa, trypsin, and factor IXa, while these two positions do not affect factor X activation initiated by the factor VIIa-tissue factor complex.

Amino Acid Sequence↗
PubMed2000

A large scale analysis of cDNA in Arabidopsis thaliana: generation of 12,028 non-redundant expressed sequence tags from normalized and size-selected cDNA libraries.

For comprehensive analysis of genes expressed in the model dicotyledonous plant, Arabidopsis thaliana, expressed sequence tags (ESTs) were accumulated. Normalized and size-selected cDNA libraries were constructed from aboveground organs, flower buds, roots, green siliques and liquid-cultured seedlings, respectively, and a total of 14,026 5'-end ESTs and 39,207 3'-end ESTs were obtained. The 3'-end ESTs could be clustered into 12,028 non-redundant groups. Similarity search of the non-redundant ESTs against the public non-redundant protein database indicated that 4816 groups show similarity to genes of known function, 1864 to hypothetical genes, and the remaining 5348 are novel sequences. Gene coverage by the non-redundant ESTs was analyzed using the annotated genomic sequences of approximately 10 Mb on chromosomes 3 and 5. A total of 923 regions were hit by at least one EST, among which only 499 regions were hit by the ESTs deposited in the public database. The result indicates that the EST source generated in this project complements the EST data in the public database and facilitates new gene discovery.

Arabidopsis↗
PubMed2000

Structural analysis of Arabidopsis thaliana chromosome 3. II. Sequence features of the 4,251,695 bp regions covered by 90 P1, TAC and BAC clones.

To deduce the entire sequence of the top arm of the Arabidopsis thaliana chromosome 3, the sequence determination was performed on a total of 90 P1, TAC and BAC clones chosen according to our sequencing strategy. Sequence features of the resulting 4,251,695 bp regions were analyzed with various computer programs for similarity search and gene modeling. As a result, a total of 941 potential protein-coding genes were identified. The average density of the genes identified was 1 gene per 4210 bp. Introns were observed in 73% of the genes, and the average number per gene and the average length of the introns were 3.6 and 159 bp, respectively. These sequence features are essentially identical to those of chromosomes 3 and 5 in our previous reports. The regions also contained 14 tRNA genes when searched by similarity to reported tRNA genes and the tRNA scan-SE program. The sequence data and information on the potential genes are available through the World Wide Web database KAOS (Kazusa Arabidopsis data Opening Site) at http://www.kazusa.or.jp/kaos/.

Arabidopsis↗
PubMed2000

Cytological and immunological changes in bronchoalveolar lavage fluid and histological observation of lung lesions in pigs immunized with Mycoplasma hyopneumoniae inactivated vaccine prepared from broth culture supernate.

We have compared the cytology of bronchoalveolar lavage fluid (BALF) and the pathology of lung lesions in pigs immunized with/without Mycoplasma hyopneumoniae inactivated vaccine prepared from broth culture supernate on experimental infection. Numbers of total cells, macrophages, neutrophils and lymphocytes have decreased in BALF of vaccinated pigs following infection. The mean percentage of lung lesions, inflammatory cell infiltration into the airways and T cells accumulation around the bronchi were reduced in vaccinated pigs. The levels of tumor necrosis factor (TNF)-alpha also decreased in vaccinated pigs. These results suggest that the vaccination may contribute to decrease TNF-alpha production, and therefore, inflammatory cell responses in the lung due to M. hyopneumoniae infection were suppressed, resulting in fewer lung lesions.

Animals↗