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Showing papers by "Kyushu University published in 2000"


Journal ArticleDOI
Masahiro Irie1

3,623 citations


Journal ArticleDOI
01 Nov 2000-Diabetes
TL;DR: Both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs, which may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome.
Abstract: Recent studies have revealed that vascular cells can produce reactive oxygen species (ROS) through NAD(P)H oxidase, which may be involved in vascular injury. However, the pathological role of vascular NAD(P)H oxidase in diabetes or in the insulin-resistant state remains unknown. In this study, we examined the effect of high glucose level and free fatty acid (FFA) (palmitate) on ROS production in cultured aortic smooth muscle cells (SMCs) and endothelial cells (ECs) using electron spin resonance spectroscopy. Exposure of cultured SMCs or ECs to a high glucose level (400 mg/dl) for 72 h significantly increased the free radical production compared with low glucose level exposure (100 mg/dl). Treatment of the cells for 3 h with phorbol myristic acid (PMA), a protein kinase C (PKC) activator, also increased free radical production. This increase was restored to the control value by diphenylene iodonium, a NAD(P)H oxidase inhibitor, suggesting ROS production through PKC-dependent activation of NAD(P)H oxidase. The increase in free radical production by high glucose level exposure was completely restored by both diphenylene iodonium and GF109203X, a PKC-specific inhibitor. Exposure to palmitate (200 micromol/l) also increased free radical production, which was concomitant with increases in diacylglycerol level and PKC activity. Again, this increase was restored to the control value by both diphenylene iodonium and GF109203X. The present results suggest that both high glucose level and palmitate may stimulate ROS production through PKC-dependent activation of NAD(P)H oxidase in both vascular SMCs and ECs. This finding may be involved in the excessive acceleration of atherosclerosis in patients with diabetes and insulin resistance syndrome.

1,509 citations


Journal ArticleDOI
24 Aug 2000-Nature
TL;DR: It is shown that human SLAM (signalling lymphocyte-activation molecule), a recently discovered membrane glycoprotein expressed on some T and B cells, is a cellular receptor for measles virus, including the Edmonston strain.
Abstract: Measles virus continues to be a major killer of children, claiming roughly one million lives a year Measles virus infection causes profound immunosuppression, which makes measles patients susceptible to secondary infections accounting for high morbidity and mortality The Edmonston strain of measles virus, and vaccine strains derived from it, use as a cellular receptor human CD46 (refs 3, 4), which is expressed on all nucleated cells; however, most clinical isolates of measles virus cannot use CD46 as a receptor Here we show that human SLAM (signalling lymphocyte-activation molecule; also known as CDw150), a recently discovered membrane glycoprotein expressed on some T and B cells, is a cellular receptor for measles virus, including the Edmonston strain Transfection with a human SLAM complementary DNA enables non-susceptible cell lines to bind measles virus, support measles virus replication and develop cytopathic effects The distribution of SLAM on various cell lines is consistent with their susceptibility to clinical isolates of measles virus The identification of SLAM as a receptor for measles virus opens the way to a better understanding of the pathogenesis of measles virus infection, especially the immunosuppression induced by measles virus

927 citations


Journal ArticleDOI
24 Aug 2000-Nature
TL;DR: Findings indicate that LAMP-2 is critical for autophagy, and this theory is further substantiated by the finding that human Lamp-2 deficiency causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes.
Abstract: Lysosome-associated membrane protein-2 (LAMP-2) is a highly glycosylated protein and an important constituent of the lysosomal membrane Here we show that LAMP-2 deficiency in mice increases mortality between 20 and 40 days of age The surviving mice are fertile and have an almost normal life span Ultrastructurally, there is extensive accumulation of autophagic vacuoles in many tissues including liver, pancreas, spleen, kidney and skeletal and heart muscle In hepatocytes, the autophagic degradation of long-lived proteins is severely impaired Cardiac myocytes are ultrastructurally abnormal and heart contractility is severely reduced These findings indicate that LAMP-2 is critical for autophagy This theory is further substantiated by the finding that human LAMP-2 deficiency causing Danon's disease is associated with the accumulation of autophagic material in striated myocytes

860 citations


Journal ArticleDOI
24 Aug 2000-Nature
TL;DR: It is concluded that primary LAMP-2 deficiency is the cause of Danon disease and this is the first example of human cardiopathy–myopathy that is caused by mutations in a lysosomal structural protein rather than an enzymatic protein.
Abstract: "Lysosomal glycogen storage disease with normal acid maltase" which was originally described by Danon et al., is characterized clinically by cardiomyopathy, myopathy and variable mental retardation. The pathological hallmark of the disease is intracytoplasmic vacuoles containing autophagic material and glycogen in skeletal and cardiac muscle cells. Sarcolemmal proteins and basal lamina are associated with the vacuolar membranes. Here we report ten unrelated patients, including one of the patients from the original case report, who have primary deficiencies of LAMP-2, a principal lysosomal membrane protein. From these results and the finding that LAMP-2-deficient mice manifest a similar vacuolar cardioskeletal myopathy, we conclude that primary LAMP-2 deficiency is the cause of Danon disease. To our knowledge this is the first example of human cardiopathy-myopathy that is caused by mutations in a lysosomal structural protein rather than an enzymatic protein.

844 citations


Journal ArticleDOI
TL;DR: A comprehensive system to examine two-hybrid interactions in all of the possible combinations between proteins of Saccharomyces cerevisiae will provide many leads for integration of various cellular functions and serve as a major driving force in the completion of the protein-protein interaction map.
Abstract: tions, constituting '10% of the total to be tested, has revealed 183 independent two-hybrid interactions, more than half of which are entirely novel. Notably, the obtained binary data allow us to extract more complex interaction networks, including the one that may explain a currently unsolved mechanism for the connection between distinct steps of vesicular transport. The approach de- scribed here thus will provide many leads for integration of various cellular functions and serve as a major driving force in the com- pletion of the protein-protein interaction map.

837 citations


Journal ArticleDOI
TL;DR: The available evidence support the role of oxidative stress in ischemia-reperfusion injury and emphasize the importance of antioxidant mechanisms in cardioprotection.
Abstract: Background: Myocardial ischemia–reperfusion represents a clinically relevant problem associated with thrombolysis, angioplasty and coronary bypass surgery. Injury of myocardium due to ischemia–reperfusion includes cardiac contractile dysfunction, arrhythmias as well as irreversible myocyte damage. These changes are considered to be the consequence of imbalance between the formation of oxidants and the availability of endogenous antioxidants in the heart. Observations: An increase in the formation of reactive oxygen species during ischemia–reperfusion and the adverse effects of oxyradicals on myocardium have now been well established by both direct and indirect measurements. Although several experimental studies as well as clinical trials have demonstrated the cardioprotective effects of antioxidants, some studies have failed to substantiate the results. Nonetheless, it is becoming evident that some of the endogenous antioxidants such as glutathione peroxidase, superoxide dismutase, and catalase act as a primary defense mechanism whereas the others including vitamin E may play a secondary role for attenuating the ischemia–reperfusion injury. The importance of various endogenous antioxidants in suppressing oxidative stress is evident from the depression in their activities and the inhibition of cardiac alterations which they produce during ischemia–reperfusion injury. The effects of an antioxidant thiol containing compound, N -acetylcysteine, and ischemic preconditioning were shown to be similar in preventing changes in the ischemic-reperfused hearts. Conclusions: The available evidence support the role of oxidative stress in ischemia–reperfusion injury and emphasize the importance of antioxidant mechanisms in cardioprotection.

781 citations


Journal ArticleDOI
17 Mar 2000-Science
TL;DR: Efficient electrophilic metalation of aromatic C-H bonds leading to new C-C bond formation through regio- and stereoselective addition to alkynes and alkenes has been realized by a catalytic amount of palladium( II) or platinum(II) compounds in a mixed solvent containing trifluoroacetic acid at room temperature.
Abstract: Efficient electrophilic metalation of aromatic C-H bonds leading to new C-C bond formation through regio- and stereoselective addition to alkynes and alkenes has been realized by a catalytic amount (0.02 to 5 mole percent) of palladium(II) or platinum(II) compounds in a mixed solvent containing trifluoroacetic acid at room temperature. Various arenes undergo unexpected selective trans hydroarylation to terminal or internal CcC bonds inter- and intramolecularly with high efficiency (up to a turnover number of 4500 for palladium), especially for electron-rich arenes, giving thermodynamically unfavorable cis-alkenes, and the oxygen- and nitrogen-containing heterocycles. The simplicity, generality, and efficiency of this process should be very attractive to the possible industrial application for the functionalization of arenes.

731 citations


Journal ArticleDOI
TL;DR: Results indicate that H(2)O(2), derived from endothelial NO synthase (eNOS) is an EDHF in mouse small mesenteric arteries and that eNOS is a major source of the reactive oxygen species.
Abstract: The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several endothelium-derived relaxing factors, such as prostacyclin, nitric oxide (NO), and the previously unidentified endothelium-derived hyperpolarizing factor (EDHF). In this study, we examined our hypothesis that hydrogen peroxide (H(2)O(2)) derived from endothelial NO synthase (eNOS) is an EDHF. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine (ACh) were markedly attenuated in small mesenteric arteries from eNOS knockout (eNOS-KO) mice. In the eNOS-KO mice, vasodilating and hyperpolarizing responses of vascular smooth muscle per se were fairly well preserved, as was the increase in intracellular calcium in endothelial cells in response to ACh. Antihypertensive treatment with hydralazine failed to improve the EDHF-mediated relaxation. Catalase, which dismutates H(2)O(2) to form water and oxygen, inhibited EDHF-mediated relaxation and hyperpolarization, but it did not affect endothelium-independent relaxation following treatment with the K(+) channel opener levcromakalim. Exogenous H(2)O(2) elicited similar relaxation and hyperpolarization in endothelium-stripped arteries. Finally, laser confocal microscopic examination with peroxide-sensitive fluorescence dye demonstrated that the endothelium produced H(2)O(2) upon stimulation by ACh and that the H(2)O(2) production was markedly reduced in eNOS-KO mice. These results indicate that H(2)O(2) is an EDHF in mouse small mesenteric arteries and that eNOS is a major source of the reactive oxygen species.

716 citations


Journal ArticleDOI
TL;DR: Results suggest that specific degradation of cyclin E and p27Kip1 is mediated by the SCFSkp2 ubiquitin ligase complex, and that Skp2 may control chromosome replication and centrosome duplication by determining the abundance of cell cycle regulators.
Abstract: The ubiquitin-proteasome pathway plays an important role in control of the abundance of cell cycle regulators. Mice lacking Skp2, an F-box protein and substrate recognition component of an Skp1-Cullin-F-box protein (SCF) ubiquitin ligase, were generated. Although Skp2(-/-) animals are viable, cells in the mutant mice contain markedly enlarged nuclei with polyploidy and multiple centrosomes, and show a reduced growth rate and increased apoptosis. Skp2(-/-) cells also exhibit increased accumulation of both cyclin E and p27(Kip1). The elimination of cyclin E during S and G(2) phases is impaired in Skp2(-/-) cells, resulting in loss of cyclin E periodicity. Biochemical studies showed that Skp2 interacts specifically with cyclin E and thereby promotes its ubiquitylation and degradation both in vivo and in vitro. These results suggest that specific degradation of cyclin E and p27(Kip1) is mediated by the SCF(Skp2) ubiquitin ligase complex, and that Skp2 may control chromosome replication and centrosome duplication by determining the abundance of cell cycle regulators.

704 citations


Journal ArticleDOI
TL;DR: In this article, the structures and magnetism of complex-based metal assemblies derived from [M(CN) 6 ] n − (M=Cr 3+, Mn 3+, Fe 3+ and Co 3+ ), Fe 2+ ; n =3, 4) and coordinatively unsaturated [M A (L) x ] m + (M A =Mn 2+, Ni 2+, Cu 2+ and Mn 3+, Fe 3+, and L=polyamine ligand, salen 2− derivatives) are reviewed.

Journal ArticleDOI
TL;DR: The present review attempts to provide an insight into general knowledge available for class IIa bacteriocins and discusses common features and recent findings concerning these substances.
Abstract: In the last decade, a variety of ribosomally synthesized antimicrobial peptides or bacteriocins produced by lactic acid bacteria have been identified and characterized. As a result of these studies, insight has been gained into fundamental aspects of biology and biochemistry such as producer self protection, membrane-protein interactions, and protein modification and secretion. Moreover, it has become evident that these peptides may be developed into useful antimicrobial additives. Class IIa bacteriocins can be considered as the major subgroup of bacteriocins from lactic acid bacteria, not only because of their large number, but also because of their activities and potential applications. They have first attracted particular attention as listericidal compounds and are now believed to be the next in line if more bacteriocins are to be approved in the future. The present review attempts to provide an insight into general knowledge available for class IIa bacteriocins and discusses common features and recent findings concerning these substances.

Journal ArticleDOI
TL;DR: A critical role for CD26 is revealed in physiological glucose homeostasis, and it is established as a potential target for therapy in type II diabetes.
Abstract: A subset of prolyl oligopeptidases, including dipeptidyl-peptidase IV (DPP IV or CD26, EC 3.4.14.5), specifically cleave off N-terminal dipeptides from substrates having proline or alanine in amino acid position 2. This enzyme activity has been implicated in the regulation of the biological activity of multiple hormones and chemokines, including the insulinotropic peptides glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Targeted inactivation of the CD26 gene yielded healthy mice that have normal blood glucose levels in the fasted state, but reduced glycemic excursion after a glucose challenge. Levels of glucose-stimulated circulating insulin and the intact insulinotropic form of GLP-1 are increased in CD26−/− mice. A pharmacological inhibitor of DPP IV enzymatic activity improved glucose tolerance in wild-type, but not in CD26−/−, mice. This inhibitor also improved glucose tolerance in GLP-1 receptor−/− mice, indicating that CD26 contributes to blood glucose regulation by controlling the activity of GLP-1 as well as additional substrates. These data reveal a critical role for CD26 in physiological glucose homeostasis, and establish it as a potential target for therapy in type II diabetes.

Journal ArticleDOI
03 Mar 2000-Cell
TL;DR: In this article, the NMR structure of a general import receptor, rat Tom20, in a complex with a presequence peptide derived from rat aldehyde dehydrogenase was reported.

Journal ArticleDOI
TL;DR: Targeted disruption of Chk1 in mice showed that ChK1(-/-) embryos exhibit gross morphologic abnormalities in nuclei as early as the blastocyst stage, which may indicate that Chk 1 is indispensable for cell proliferation and survival through maintaining the G(2) checkpoint in mammals.
Abstract: The recent discovery of checkpoint kinases has suggested the conservation of checkpoint mechanisms between yeast and mammals. In yeast, the protein kinase Chk1 is thought to mediate signaling associated with the DNA damage checkpoint of the cell cycle. However, the function of Chk1 in mammals has remained unknown. Targeted disruption of Chk1 in mice showed that Chk1(-/-) embryos exhibit gross morphologic abnormalities in nuclei as early as the blastocyst stage. In culture, Chk1(-/-) blastocysts showed a severe defect in outgrowth of the inner cell mass and died of apoptosis. DNA replication block and DNA damage failed to arrest the cell cycle before initiation of mitosis in Chk1(-/-) embryos. These results may indicate that Chk1 is indispensable for cell proliferation and survival through maintaining the G(2) checkpoint in mammals.

Journal ArticleDOI
Takeshi Nagai1
TL;DR: In this article, type I collagen was prepared from fish skin, bone and fin, respectively, and the denaturation temperatures of these collagens were as follows: skin collagen (250-265°C), bone collagen (295-300°C) and fin collagen (280-291°C).

Journal ArticleDOI
06 Apr 2000-Nature
TL;DR: Genes related to Cdt1 have been found in Metazoa and plants, suggesting that the cooperation of Cdc6/Cdc18 with Cdt 1 to load MCM proteins onto chromatin may be a generally conserved feature of DNA licensing in eukaryotes.
Abstract: To maintain genome stability in eukaryotic cells, DNA is licensed for replication only after the cell has completed mitosis, ensuring that DNA synthesis (S phase) occurs once every cell cycle1. This licensing control is thought to require the protein Cdc6 (Cdc18 in fission yeast) as a mediator for association of minichromosome maintenance (MCM) proteins with chromatin2,3,4,5,6,7,8,9,10. The control is overridden in fission yeast by overexpressing Cdc18 (ref. 11) which leads to continued DNA synthesis in the absence of mitosis12. Other factors acting in this control have been postulated13 and we have used a re-replication assay to identify Cdt1 (ref. 14) as one such factor. Cdt1 cooperates with Cdc18 to promote DNA replication, interacts with Cdc18, is located in the nucleus, and its concentration peaks as cells finish mitosis and proceed to S phase. Both Cdc18 and Cdt1 are required to load the MCM protein Cdc21 onto chromatin at the end of mitosis and this is necessary to initiate DNA replication. Genes related to Cdt1 have been found in Metazoa and plants (A. Whitaker, I. Roysman and T. Orr-Weaver, personal communication), suggesting that the cooperation of Cdc6/Cdc18 with Cdt1 to load MCM proteins onto chromatin may be a generally conserved feature of DNA licensing in eukaryotes.

Journal ArticleDOI
TL;DR: Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction, likely to be important promoters of human asthma.
Abstract: Asthma and atopy show epidemiological association and are biologically linked by T-helper type 2 (T(h)2) cytokine-driven inflammatory mechanisms IL-4 operates through the IL-4 receptor (IL-4R, a heterodimer of IL-4Ralpha and either gammac or IL-13Ralpha1) and IL-13 operates through IL-13R (a heterodimer of IL-4Ralpha and IL-13Ralpha1) to promote IgE synthesis and IgE-based mucosal inflammation which typify atopy Recent animal model data suggest that IL-13 is a central cytokine in promoting asthma, through the stimulation of bronchial epithelial mucus secretion and smooth muscle hyper-reactivity We investigated the role of common genetic variants of IL-13 and IL-13Ralpha1 in human asthma, considering IgE levels A novel variant of human IL-13, Gln110Arg, on chromosome 5q31, associated with asthma rather than IgE levels in case-control populations from Britain and Japan [peak odds ratio (OR) = 231, 95% CI 133-400]; the variant also predicted asthma and higher serum IL-13 levels in a general, Japanese paediatric population Immunohistochemistry demonstrated that both subunits of IL-13R are prominently expressed in bronchial epithelium and smooth muscle from asthmatic subjects Detailed molecular modelling analyses indicate that residue 110 of IL-13, the site of the charge-modifying variants Arg and Gln, is important in the internal constitution of the ligand and crucial in ligand-receptor interaction A non-coding variant of IL-13Ralpha1, A1398G, on chromosome Xq13, associated primarily with high IgE levels (OR = 3 38 in males, 110 in females) rather than asthma Thus, certain variants of IL-13 signalling are likely to be important promoters of human asthma; detailed functional analysis of their actions is needed

Journal ArticleDOI
TL;DR: In this paper, the photocycloreversion reactions in the single-crystalline phase were observed in a closed-ring isomer of 1,2-Bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene.
Abstract: 1,2-Bis(2-methyl-5-phenyl-3-thienyl)perfluorocyclopentene (1a) and their derivatives, 1,2-bis(2-methyl-5-p-tolyl-3-thienyl)perfluorocyclopentene (2a) and 1,2-bis(2-methyl-5-p-tert-butylphenyl-3-thienyl)perfluorocyclopentene (3a), were found to undergo reversible photochromic reactions in the single-crystalline phase. Upon irradiation with 366 nm light the single crystals turned blue. The blue colored crystals returned to colorless by irradiation with visible light (λ > 480 nm). The substituents at para positions of the phenyl groups did not affect the rates of photocyclization reactions both in the single-crystalline phase and in hexane. Activation energies of the photocyclization reactions were almost zero. On the other hand, activation energies as much as 5−10 kJ mol-1 were observed in the photocycloreversion reactions in the single-crystalline phase. These values were smaller than those observed in solution, ca. 16 kJ mol-1. Slow thermal cycloreversion reaction of the closed-ring isomer (1b) was observ...

Journal ArticleDOI
TL;DR: A simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators to test the estrogenic activity of chemicals.
Abstract: One of the urgent tasks in understanding endocrine disruptors (EDs) is to compile a list of suspected substances among the huge number of chemicals by using the screening test method. We developed a simple and rapid screening method using the yeast two-hybrid system based on the ligand-dependent interaction of nuclear hormone receptors with coactivators. To date, we have tested the estrogenic activity of more than 500 chemicals including natural substances, medicines, pesticides, and industrial chemicals. 64 compounds were evaluated as positive, and most of these demonstrated a common structure; phenol with a hydrophobic moiety at the para-position without bulky groups at the ortho-position. These results are expected to facilitate further risk assessment of chemicals.

Book
11 May 2000
TL;DR: In this article, the properties of gradient index glass, laser glass, nonlinear optical glass, magneto-optical glass and nonlinear nonlinear polysilicon glass are investigated. But they do not consider nonlinear glass.
Abstract: 1 Glass properties 2 Gradient index glass 3 Laser glass 4 Nonlinear optical glass 5 Magneto-optical glass

Journal ArticleDOI
TL;DR: There was a significant positive relation between myocardial ROS level and left ventricular contractile dysfunction and, in the failing myocardium, *OH was produced as a reactive product of *O(2)(-) and H(2)O( 2), which might play an important role inleft ventricular failure.
Abstract: —Experimental and clinical studies have suggested an increased production of reactive oxygen species (ROS) in the failing myocardium. The present study aimed to obtain direct evidence for increased ROS and to determine the contribution of superoxide anion (·O2−), H2O2, and hydroxy radical (·OH) in failing myocardial tissue. Heart failure was produced in adult mongrel dogs by rapid ventricular pacing at 240 bpm for 4 weeks. To assess the production of ROS directly, freeze-clamped myocardial tissue homogenates were reacted with the nitroxide radical, 4-hydroxy-2,2,6,6,-tetramethyl-piperidine- N -oxyl, and its spin signals were detected by electron spin resonance spectroscopy. The rate of electron spin resonance signal decay, proportional to ·OH level, was significantly increased in heart failure, which was inhibited by the addition of dimethylthiourea (·OH scavenger) into the reaction mixture. Increased ·OH in the failing heart was abolished to the same extent in the presence of desferrioxamine (iron chelator), catalase (H2O2 scavenger), and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron; LaMotte) (·O2− scavenger), indicating that ·OH originated from H2O2 and ·O2−. Further, ·O2− produced in normal myocardium in the presence of antimycin A (mitochondrial complex III inhibitor) could reproduce the increase of H2O2 and ·OH seen in the failing tissue. There was a significant positive relation between myocardial ROS level and left ventricular contractile dysfunction. In conclusion, in the failing myocardium, ·OH was produced as a reactive product of ·O2− and H2O2, which might play an important role in left ventricular failure.

Journal ArticleDOI
21 Jan 2000-Science
TL;DR: The chloroplast membrane of higher plants contains an unusually high concentration of trienoic fatty acids as mentioned in this paper, while plants grown in colder temperatures have a higher content of trienoisophoric fatty acids.
Abstract: The chloroplast membrane of higher plants contains an unusually high concentration of trienoic fatty acids Plants grown in colder temperatures have a higher content of trienoic fatty acids Transgenic tobacco plants in which the gene encoding chloroplast omega-3 fatty acid desaturase, which synthesizes trienoic fatty acids, was silenced contained a lower level of trienoic fatty acids than wild-type plants and were better able to acclimate to higher temperatures

Journal ArticleDOI
TL;DR: Inferring genetic network architecture from time series data of gene expression patterns is an important topic in bioinformatics and inference algorithms based on the Boolean network were proposed, but were not sufficient as a model of a genetic network.
Abstract: Motivation: Inferring genetic network architecture from time series data of gene expression patterns is an important topic in bioinformatics. Although inference algorithms based on the Boolean network were proposed, the Boolean network was not sufficient as a model of a genetic network. Results: First, a Boolean network model with noise is proposed, together with an inference algorithm for it. Next, a qualitative network model is proposed, in which regulation rules are represented as qualitative rules and embedded in the network structure. Algorithms are also presented for inferring qualitative relations from time series data. Then, an algorithm for inferring S-systems (synergistic and saturable systems) from time series data is presented, where S-systems are based on a particular kind of nonlinear differential equation and have been applied to the analysis of various biological systems. Theoretical results are shown for Boolean networks with noises and simple qualitative networks. Computational results are shown for Boolean networks with noises and S-systems, where real data are not used because the proposed models are still conceptual and the quantity and quality of currently available data are not enough for the application of the proposed methods.

Journal ArticleDOI
15 May 2000-Cancer
TL;DR: This study investigated VEGF expression and microvessel density (MVD) in ductal pancreatic adenocarcinoma and examined the correlations among V EGF expression, clinicopathologic factors, and clinical outcome.
Abstract: BACKGROUND Vascular endothelial growth factor (VEGF), a recently identified growth factor with significant angiogenic properties, is a multifunctional angiogenic cytokine that is expressed in many tumors. High VEGF expression has been shown to correlate with the incidence of metastasis and poor prognosis in various cancers. In this study, the authors investigated VEGF expression and microvessel density (MVD) in ductal pancreatic adenocarcinoma and examined the correlations among VEGF expression, clinicopathologic factors, and clinical outcome. The authors especially focused on the correlation between VEGF expression and liver metastasis. METHODS Paraffin embedded tumor specimens of 142 surgically resected pancreas carcinoma were immunohistochemically stained for VEGF and MVD. The correlations among VEGF expression and MVD, clinicopathologic factors, and clinical outcome were then statistically analyzed. RESULTS One hundred thirty-two (93%) of 142 ductal pancreatic adenocarcinomas were positive for VEGF protein by immunohistochemistry. A significant correlation was observed between VEGF positivity and MVD (P < 0.0001). Multivariate logistic regression analysis indicated a significant association between high VEGF expression and liver metastasis (P = 0.010) but no other factors, such as age, tumor size, histologic type, lymph node metastasis, venous invasion, neural invasion, peritoneal metastasis, or local recurrence. Patients with tumors that showed moderate or high VEGF expression had significantly shorter survival than patients with low VEGF expression or none at all in their tumors (P < 0.05). CONCLUSIONS These results indicate that VEGF expression is closely correlated with MVD and seems to be an important predictor for both liver metastasis and poor prognosis in ductal pancreatic adenocarcinoma. Cancer 2000;88:2239–45. © 2000 American Cancer Society.

Journal ArticleDOI
TL;DR: The sensitivity of DNA detection was improved to 10 zmol by reducing the amount of immobilized DNA probe and protecting the uncovered surface of the electrode with 2-mercaptoethanol, and dA20 and the yeast choline transport gene were quantitated at the subpicomole level.
Abstract: Naphthalene diimide derivative 1 carrying ferrocenyl moieties at the termini of imide substituents binds intact calf thymus DNA 4 times more strongly than the denatured DNA, and its complex with the intact DNA dissociates 80 times more slowly than that with the denatured DNA. On the basis of these observations, ligand 1 was applied to a probe of electrochemical DNA sensing. A thiol-linked single-stranded DNA probe was immobilized through the S−Au bonding to 20−30 pmol/mm2 on a gold electrode. Following hybridization with the complementary DNA, the electrode was soaked in a solution containing 1 (intercalation step) and then washed with buffer for 5 s. The cyclic voltammogram and differential pulse voltammogram for this electrode gave an electrochemical signal due to the redox reaction of 1 that was bound to the double-stranded DNA on the electrode. Thus, dA20 and the yeast choline transport gene were quantitated at the subpicomole level. The sensitivity of DNA detection was improved to 10 zmol by reducing...

Journal ArticleDOI
01 Jan 2000-Carbon
TL;DR: The recent development of de-SOx and de-NOx using activated carbon fibers (ACF) in Japan is introduced in this paper, comparing it with the conventional commercialized system.

Journal ArticleDOI
13 Oct 2000-Cell
TL;DR: It is shown that the mdm2 gene is also regulated by the Ras-driven Raf/MEK/MAP kinase pathway, in a p53-independent manner, and may play a key role in suppressing p53 during tumor development and treatment.

Journal ArticleDOI
TL;DR: The pathogenesis of GC-induced osteoporosis and its prevention and treatment is summarized, with a focus on rheumatoid arthritis patients.
Abstract: Glucocorticoid- (GC-) induced osteoporosis and an increased risk of fractures are one of the most serious problems for patient using long-term GC therapy, such as those with rheumatoid arthritis, autoimmune diseases, inflammatory bowel diseases, bronchial asthma, and chronic lung diseases. GCs are known to affect both bone formation and resorption. In rheumatoid arthritis, the etiology of bone loss is multifactorial, including local inflammation around joints, release of bone-absorbing cytokines, physical inactivity, and malnutrition, in addition to the use of GC. Two guidelines have been published, by the American College of Rheumatology Task Force in 1966 and by the UK Consensus Group in 1998. Both guidelines recommend that patients 'receiving GC therapy at doses of 7.5 mg/day of prednisolone or more for 6 months or longer should have their bone mineral density measured and begin preventive therapies. Calcium and vitamin D supplements, sex hormone replacement, and weight-bearing exercise are the first-line therapies. For patients who are unable to take sex hormone replacement therapy (HRT), bisphosphonates are recommended by both guidelines. In this article, we briefly summarize the pathogenesis of GC-induced osteoporosis and its prevention and treatment.

Journal ArticleDOI
TL;DR: In this article, equal channel angular (ECA) pressing at room temperature was used to reduce the grain sizes of six commercial aluminum-based alloys (1100, 2024, 3004, 5083, 6061, and 7075) to within a submicrometer range.
Abstract: Using equal-channel angular (ECA) pressing at room temperature, the grain sizes of six different commercial aluminum-based alloys (1100, 2024, 3004, 5083, 6061, and 7075) were reduced to within the submicrometer range. These grains were reasonably stable up to annealing temperatures of ∼200 °C and the submicrometer grains were retained in the 2024 and 7075 alloys to annealing temperatures of 300 °C. Tensile testing after ECA pressing through a single pass, equivalent to the introduction of a strain of ∼1, showed there is a significant increase in the values of the 0.2 pct proof stress and the ultimate tensile stress (UTS) for each alloy with a corresponding reduction in the elongations to failure. It is demonstrated that the magnitudes of these stresses scale with the square root of the Mg content in each alloy. Similar values for the proof stresses and the UTS were attained at the same equivalent strains in samples subjected to cold rolling, but the elongations to failure were higher after ECA pressing to equivalent strains >1 because of the introduction of a very small grain size. Detailed results for the 1100 and 3004 alloys show good agreement with the standard Hall-Petch relationship.