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Showing papers by "Osaka University published in 2004"


Journal ArticleDOI
TL;DR: Rapid progress that has recently improved the understanding of the molecular mechanisms that mediate TLR signalling is reviewed.
Abstract: One of the mechanisms by which the innate immune system senses the invasion of pathogenic microorganisms is through the Toll-like receptors (TLRs), which recognize specific molecular patterns that are present in microbial components. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also instructs the development of antigen-specific acquired immunity. Here, we review the rapid progress that has recently improved our understanding of the molecular mechanisms that mediate TLR signalling.

7,906 citations


Journal ArticleDOI
TL;DR: It is suggested that increased oxidative stress in accumulated fat is an early instigator of metabolic syndrome and that the redox state in adipose tissue is a potentially useful therapeutic target for obesity-associated metabolic syndrome.
Abstract: Obesity is a principal causative factor in the development of metabolic syndrome. Here we report that increased oxidative stress in accumulated fat is an important pathogenic mechanism of obesity-associated metabolic syndrome. Fat accumulation correlated with systemic oxidative stress in humans and mice. Production of ROS increased selectively in adipose tissue of obese mice, accompanied by augmented expression of NADPH oxidase and decreased expression of antioxidative enzymes. In cultured adipocytes, elevated levels of fatty acids increased oxidative stress via NADPH oxidase activation, and oxidative stress caused dysregulated production of adipocytokines (fat-derived hormones), including adiponectin, plasminogen activator inhibitor-1, IL-6, and monocyte chemotactic protein-1. Finally, in obese mice, treatment with NADPH oxidase inhibitor reduced ROS production in adipose tissue, attenuated the dysregulation of adipocytokines, and improved diabetes, hyperlipidemia, and hepatic steatosis. Collectively, our results suggest that increased oxidative stress in accumulated fat is an early instigator of metabolic syndrome and that the redox state in adipose tissue is a potentially useful therapeutic target for obesity-associated metabolic syndrome.

4,752 citations


Journal ArticleDOI
TL;DR: In this article, the authors identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling.
Abstract: Intracellular double-stranded RNA (dsRNA) is a chief sign of replication for many viruses. Host mechanisms detect the dsRNA and initiate antiviral responses. In this report, we identify retinoic acid inducible gene I (RIG-I), which encodes a DExD/H box RNA helicase that contains a caspase recruitment domain, as an essential regulator for dsRNA-induced signaling, as assessed by functional screening and assays. A helicase domain with intact ATPase activity was responsible for the dsRNA-mediated signaling. The caspase recruitment domain transmitted 'downstream' signals, resulting in the activation of transcription factors NF-kappaB and IRF-3. Subsequent gene activation by these factors induced antiviral functions, including type I interferon production. Thus, RIG-I is key in the detection and subsequent eradication of the replicating viral genomes.

3,775 citations


Journal ArticleDOI
TL;DR: Toll-like receptors have been established to play an essential role in the activation of innate immunity by recognizing specific patterns of microbial components and TIR domain-containing adaptors provide specificity of TLR signaling.

2,291 citations


Journal ArticleDOI
TL;DR: Significant differences in the relation of psychosocial factors to risk of myocardial infarction in 24767 people from 52 countries were found, suggesting that approaches aimed at modifying these factors should be developed.

2,110 citations


Journal ArticleDOI
16 Dec 2004-Nature
TL;DR: This finding represents a new component of the innate immune system and the acute phase response to infection and limits bacterial growth by sequestrating the iron-laden siderophore.
Abstract: Although iron is required to sustain life, its free concentration and metabolism have to be tightly regulated. This is achieved through a variety of iron-binding proteins including transferrin and ferritin. During infection, bacteria acquire much of their iron from the host by synthesizing siderophores that scavenge iron and transport it into the pathogen. We recently demonstrated that enterochelin, a bacterial catecholate siderophore, binds to the host protein lipocalin 2 (ref. 5). Here, we show that this event is pivotal in the innate immune response to bacterial infection. Upon encountering invading bacteria the Toll-like receptors on immune cells stimulate the transcription, translation and secretion of lipocalin 2; secreted lipocalin 2 then limits bacterial growth by sequestrating the iron-laden siderophore. Our finding represents a new component of the innate immune system and the acute phase response to infection.

1,622 citations


Journal ArticleDOI
TL;DR: Results indicate that the Bcl-2 family of proteins not only regulates apoptosis, but also controls non-apoptotic programmed cell death that depends on the autophagy genes.
Abstract: Programmed cell death can be divided into several categories including type I (apoptosis) and type II (autophagic death). The Bcl-2 family of proteins are well-characterized regulators of apoptosis, and the multidomain pro-apoptotic members of this family, such as Bax and Bak, act as a mitochondrial gateway where a variety of apoptotic signals converge. Although embryonic fibroblasts from Bax/Bak double knockout mice are resistant to apoptosis, we found that these cells still underwent a non-apoptotic death after death stimulation. Electron microscopic and biochemical studies revealed that double knockout cell death was associated with autophagosomes/autolysosomes. This non-apoptotic death of double knockout cells was suppressed by inhibitors of autophagy, including 3-methyl adenine, was dependent on autophagic proteins APG5 and Beclin 1 (capable of binding to Bcl-2/Bcl-x(L)), and was also modulated by Bcl-x(L). These results indicate that the Bcl-2 family of proteins not only regulates apoptosis, but also controls non-apoptotic programmed cell death that depends on the autophagy genes.

1,394 citations


Journal ArticleDOI
TL;DR: Sutureless transplantation of carrier-free cell sheets composed of autologous oral mucosal epithelial cells may be used to reconstruct corneal surfaces and can restore vision in patients with bilateral severe disorders of the ocular surface.
Abstract: Background Ocular trauma or disease may lead to severe corneal opacification and, consequently, severe loss of vision as a result of complete loss of corneal epithelial stem cells. Transplantation of autologous corneal stem-cell sources is an alternative to allograft transplantation and does not require immunosuppression, but it is not possible in many cases in which bilateral disease produces total corneal stem-cell deficiency in both eyes. We studied the use of autologous oral mucosal epithelial cells as a source of cells for the reconstruction of the corneal surface. Methods We harvested 3-by-3-mm specimens of oral mucosal tissue from four patients with bilateral total corneal stem-cell deficiencies. Tissue-engineered epithelial-cell sheets were fabricated ex vivo by culturing harvested cells for two weeks on temperature-responsive cell-culture surfaces with 3T3 feeder cells that had been treated with mitomycin C. After conjunctival fibrovascular tissue had been surgically removed from the ocular surfa...

1,381 citations


Journal ArticleDOI
TL;DR: In this article, the authors have synthesized chemically modified titanium dioxide photocatalysts in which S (S4+) substitutes for some of the lattice titanium atoms, which showed strong absorption for visible light and high activities for degradation of methylene blue, 2-propanol in aqueous solution and partial oxidation of adamantane under irradiation at wavelengths longer than 440nm.
Abstract: Although titanium dioxide photocatalysts having anatase phase are a promising substrate for photodegradation of pollutants in water and air, their photocatalytic activities show only under ultraviolet (UV) light. For us to utilized a wide range of incident light such as solar light, development of the photocatalysts whose activities show under visible light is one of the most important strategies. We have synthesized chemically modified titanium dioxide photocatalysts in which S (S4+) substitutes for some of the lattice titanium atoms. They show strong absorption for visible light and high activities for degradation of methylene blue, 2-propanol in aqueous solution and partial oxidation of adamantane under irradiation at wavelengths longer than 440 nm. The oxidation state of the S atoms incorporated into the TiO2 particles is determined to be mainly S4+ from X-ray photoelectron spectra (XPS) spectra.

1,226 citations


Journal ArticleDOI
TL;DR: The link of adiponectin to visceral adiposity, insulin resistance, and vascular diseases is discussed, and this novel adipocytokine has plural biofunctions, such as antidiabetic, antiatherosclerotic, and antiinflammatory functions.
Abstract: In this review article, the crucial roles of adipocytes in the development of so-called metabolic syndrome and vascular disease are reviewed, focusing on adipocyte-derived bioactive substances, adipocytokines. Recent progress in adipocyte biology shows that adipocytes are not merely energy-storing cells but that they secrete a variety of hormones cytokines, growth factors, and other bioactive substances. To search for novel adipocytokines by the large-scale random sequence analysis of expressed genes in adipocytes, we identified an adipose-specific collagen-like molecule, adiponectin. This novel adipocytokine has plural biofunctions, such as antidiabetic, antiatherosclerotic, and antiinflammatory functions. Adiponectin plasma levels decrease with the accumulation of visceral adipose tissue. In this review, we discuss the link of adiponectin to visceral adiposity, insulin resistance, and vascular diseases.

1,179 citations


Journal ArticleDOI
TL;DR: Vibrios harbour a wealth of diverse genomes as revealed by different genomic techniques including amplified fragment length polymorphism, multilocus sequence typing, repetetive extragenic palindrome PCR, ribotyping, and whole-genome sequencing, which are probably important driving forces in the evolution and speciation of vibrios.
Abstract: Vibrios are ubiquitous and abundant in the aquatic environment. A high abundance of vibrios is also detected in tissues and/or organs of various marine algae and animals, e.g., abalones, bivalves, corals, fish, shrimp, sponges, squid, and zooplankton. Vibrios harbour a wealth of diverse genomes as revealed by different genomic techniques including amplified fragment length polymorphism, multilocus sequence typing, repetetive extragenic palindrome PCR, ribotyping, and whole-genome sequencing. The 74 species of this group are distributed among four different families, i.e., Enterovibrionaceae, Photobacteriaceae, Salinivibrionaceae, and Vibrionaceae. Two new genera, i.e., Enterovibrio norvegicus and Grimontia hollisae, and 20 novel species, i.e., Enterovibrio coralii, Photobacterium eurosenbergii, V. brasiliensis, V. chagasii, V. coralliillyticus, V. crassostreae, V. fortis, V. gallicus, V. hepatarius, V. hispanicus, V. kanaloaei, V. neonatus, V. neptunius, V. pomeroyi, V. pacinii, V. rotiferianus, V. superstes, V. tasmaniensis, V. ezurae, and V. xuii, have been described in the last few years. Comparative genome analyses have already revealed a variety of genomic events, including mutations, chromosomal rearrangements, loss of genes by decay or deletion, and gene acquisitions through duplication or horizontal transfer (e.g., in the acquisition of bacteriophages, pathogenicity islands, and super-integrons), that are probably important driving forces in the evolution and speciation of vibrios. Whole-genome sequencing and comparative genomics through the application of, e.g., microarrays will facilitate the investigation of the gene repertoire at the species level. Based on such new genomic information, the taxonomy and the species concept for vibrios will be reviewed in the next years.

Journal ArticleDOI
TL;DR: In this article, the authors studied the thermodynamic properties and phase structures of topological black holes in Einstein theory with a Gauss-Bonnet term and a negative cosmological constant.
Abstract: We study the thermodynamic properties and phase structures of topological black holes in Einstein theory with a Gauss-Bonnet term and a negative cosmological constant. The event horizon of these topological black holes can be a hypersurface with positive, zero, or negative constant curvature. When the horizon is a zero curvature hypersurface, the thermodynamic properties of black holes are completely the same as those of black holes without the Gauss-Bonnet term, although the two black hole solutions are quite different. When the horizon is a negative constant curvature hypersurface, the thermodynamic properties of the Gauss-Bonnet black holes are qualitatively similar to those of black holes without the Gauss-Bonnet term. When the event horizon is a hypersurface with positive constant curvature, we find that the thermodynamic properties and phase structures of black holes drastically depend on the spacetime dimension d and the coefficient of the Gauss-Bonnet term: when dgreater than or equal to6, the properties of black holes are also qualitatively similar to the case without the Gauss-Bonnet term, but when d=5, a new phase of locally stable small blacks holes occurs under a critical value of the Gauss-Bonnet coefficient, and beyond the critical value, the black holes are always thermodynamically stable. However, the locally stable small black hole is not globally preferred; instead a thermal anti-de Sitter space is globally preferred. We find that there is a minimal horizon radius, below which the Hawking-Page phase transition will not occur since for these black holes the thermal anti-de Sitter space is always globally preferred.

Journal ArticleDOI
TL;DR: It is shown that TLR-mediated IFN-α induction requires the formation of a complex consisting of MyD88, TRAF6 and IRF7 as well as TRAF 6-dependent ubiquitination.
Abstract: Toll-like receptors (TLRs) are involved in the recognition of microbial pathogens. A subset of TLRs, TLR7, TLR8 and TLR9, induces antiviral responses by producing interferon-alpha (IFN-alpha). Production of IFN-alpha is dependent on the Toll-interleukin-1 receptor domain-containing adaptor MyD88. Here we show that MyD88 formed a complex with the transcription factor IRF7 but not with IRF3. The death domain of MyD88 interacted with an inhibitory domain of IRF7, and this interaction resulted in activation of the IFN-alpha-dependent promoters. Furthermore, the adaptor molecule TRAF6 also bound and activated IRF7. Ubiquitin ligase activity of TRAF6 was required for IRF7 activation. These results indicate that TLR-mediated IFN-alpha induction requires the formation of a complex consisting of MyD88, TRAF6 and IRF7 as well as TRAF6-dependent ubiquitination.

Journal ArticleDOI
21 May 2004-Science
TL;DR: It is reported that tingible body macrophages in the germinal centers of the spleen and lymph nodes strongly express MFG-E8, a protein that binds to apoptotic cells by recognizing phosphatidylserine and that enhances the engulfment of apoptosis cells by macrophage.
Abstract: Apoptotic cells expose phosphatidylserine and are swiftly engulfed by macrophages. Milk fat globule epidermal growth factor (EGF) factor 8 (MFG-E8) is a protein that binds to apoptotic cells by recognizing phosphatidylserine and that enhances the engulfment of apoptotic cells by macrophages. We report that tingible body macrophages in the germinal centers of the spleen and lymph nodes strongly express MFG-E8. Many apoptotic lymphocytes were found on the MFG-E8-/- tingible body macrophages, but they were not efficiently engulfed. The MFG-E8-/- mice developed splenomegaly, with the formation of numerous germinal centers, and suffered from glomerulonephritis as a result of autoantibody production. These data demonstrate that MFG-E8 has a critical role in removing apoptotic B cells in the germinal centers and that its failure can lead to autoimmune diseases.

Journal ArticleDOI
TL;DR: Direct observation of current-driven magnetic domain wall (DW) displacement by using a well-defined single DW in a microfabricated magnetic wire with submicron width is reported.
Abstract: We report direct observation of current-driven magnetic domain wall (DW) displacement by using a well-defined single DW in a microfabricated magnetic wire with submicron width. Magnetic force microscopy visualizes that a single DW introduced in a wire is displaced back and forth by positive and negative pulsed current, respectively. The direct observation gives quantitative information on the DW displacement as a function of the intensity and the duration of the pulsed current. The result is discussed in terms of the spin-transfer mechanism.

Journal ArticleDOI
TL;DR: The protective effects of Probiotics are mediated by their own DNA rather than by their metabolites or ability to colonize the colon, and live microorganisms are not required to attenuate experimental colitis because nonviable probiotics are equally effective.

Journal ArticleDOI
TL;DR: The present Pd catalyst does not require additives to complete the catalytic cycle, and the diameters of the generated Pd nanoclusters can be controlled upon acting on the alcohol substrates used.
Abstract: Treatment of a stoichiometric hydroxyapatite (HAP), Ca10(PO4)6(OH)2, with PdCl2(PhCN)2 gives a new type of palladium-grafted hydroxyapatite. Analysis by means of powder X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), energy-dispersive X-ray (EDX), IR, and Pd K-edge X-ray absorption fine structure (XAFS) proves that a monomeric PdCl2 species is chemisorbed on the HAP surface, which is readily transformed into Pd nanoclusters with a narrow size distribution in the presence of alcohol. Nanoclustered Pd0 species can effectively promote the alcohol oxidation under an atmospheric O2 pressure, giving a remarkably high turnover number (TON) of up to 236,000 with an excellent turnover frequency (TOF) of approximately 9800 h(-1) for a 250-mmol-scale oxidation of 1-phenylethanol under solvent-free conditions. In addition to advantages such as a simple workup procedure and the ability to recycle the catalyst, the present Pd catalyst does not require additives to complete the catalytic cycle. The diameters of the generated Pd nanoclusters can be controlled upon acting on the alcohol substrates used. Oxidation of alcohols is proposed to occur primarily on low-coordination sites within a regular arrangement of the Pd nanocluster by performing calculations on the palladium crystallites.

Journal ArticleDOI
TL;DR: Caspase-4 can function as an ER stress-specific caspase in humans, and may be involved in pathogenesis of Alzheimer's disease.
Abstract: Recent studies have suggested that neuronal death in Alzheimer's disease or ischemia could arise from dysfunction of the endoplasmic reticulum (ER). Although caspase-12 has been implicated in ER stress-induced apoptosis and amyloid-β (Aβ)–induced apoptosis in rodents, it is controversial whether similar mechanisms operate in humans. We found that human caspase-4, a member of caspase-1 subfamily that includes caspase-12, is localized to the ER membrane, and is cleaved when cells are treated with ER stress-inducing reagents, but not with other apoptotic reagents. Cleavage of caspase-4 is not affected by overexpression of Bcl-2, which prevents signal transduction on the mitochondria, suggesting that caspase-4 is primarily activated in ER stress-induced apoptosis. Furthermore, a reduction of caspase-4 expression by small interfering RNA decreases ER stress-induced apoptosis in some cell lines, but not other ER stress-independent apoptosis. Caspase-4 is also cleaved by administration of Aβ, and Aβ-induced apoptosis is reduced by small interfering RNAs to caspase-4. Thus, caspase-4 can function as an ER stress-specific caspase in humans, and may be involved in pathogenesis of Alzheimer's disease.

Journal ArticleDOI
TL;DR: A self-contained theory of the domain wall dynamics in ferromagnets under finite electric current is presented and the momentum-transfer effect dominates, and the threshold current for wall motion is proportional to V(0)/rho(w), V0 being the pinning potential.
Abstract: A self-contained theory of the domain wall dynamics in ferromagnets under finite electric current is presented. The current has two effects: one is momentum transfer, which is proportional to the charge current and wall resistivity (rho(w)); the other is spin transfer, proportional to spin current. For thick walls, as in metallic wires, the latter dominates and the threshold current for wall motion is determined by the hard-axis magnetic anisotropy, except for the case of very strong pinning. For thin walls, as in nanocontacts and magnetic semiconductors, the momentum-transfer effect dominates, and the threshold current is proportional to V(0)/rho(w), V0 being the pinning potential.

Journal ArticleDOI
04 Nov 2004-Nature
TL;DR: The atomic basis for allosteric regulation of the conformation and affinity for ligand of the integrin ectodomain is defined, and how fibrinogen-mimetic therapeutics bind to platelet integrin αIIbβ3 is defined.
Abstract: Integrins are important adhesion receptors in all Metazoa that transmit conformational change bidirectionally across the membrane. Integrin alpha and beta subunits form a head and two long legs in the ectodomain and span the membrane. Here, we define with crystal structures the atomic basis for allosteric regulation of the conformation and affinity for ligand of the integrin ectodomain, and how fibrinogen-mimetic therapeutics bind to platelet integrin alpha(IIb)beta3. Allostery in the beta3 I domain alters three metal binding sites, associated loops and alpha1- and alpha7-helices. Piston-like displacement of the alpha7-helix causes a 62 degrees reorientation between the beta3 I and hybrid domains. Transmission through the rigidly connected plexin/semaphorin/integrin (PSI) domain in the upper beta3 leg causes a 70 A separation between the knees of the alpha and beta legs. Allostery in the head thus disrupts interaction between the legs in a previously described low-affinity bent integrin conformation, and leg extension positions the high-affinity head far above the cell surface.

Journal ArticleDOI
TL;DR: Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA, and the adverse events were not dose dependent.
Abstract: Objective Interleukin-6 (IL-6) is a pleiotropic cytokine that regulates the immune response, inflammation, and hematopoiesis. Overproduction of IL-6 plays pathologic roles in rheumatoid arthritis (RA), and the blockade of IL-6 may be therapeutically effective for the disease. This study was undertaken to evaluate the safety and efficacy of a humanized anti–IL-6 receptor antibody, MRA, in patients with RA. Methods In a multicenter, double-blind, placebo-controlled trial, 164 patients with refractory RA were randomized to receive either MRA (4 mg/kg body weight or 8 mg/kg body weight) or placebo. MRA was administered intravenously every 4 weeks for a total of 3 months. The clinical responses were measured using the American College of Rheumatology (ACR) criteria. Results Treatment with MRA reduced disease activity in a dose-dependent manner. At 3 months, 78% of patients in the 8-mg group, 57% in the 4-mg group, and 11% in the placebo group achieved at least a 20% improvement in disease activity according to the ACR criteria (an ACR20 response) (P < 0.001 for 8-mg group versus placebo). Forty percent of patients in the 8-mg group and 1.9% in the placebo group achieved an ACR50 response (P < 0.001). The overall incidences of adverse events were 56%, 59%, and 51% in the placebo, 4-mg, and 8-mg groups, respectively, and the adverse events were not dose dependent. A blood cholesterol increase was observed in 44.0% of the patients. Liver function disorders and decreases in white blood cell counts were also observed, but these were mild and transient. There was no increase in antinuclear antibodies or anti-DNA antibodies. Anti-MRA antibodies were detected in 2 patients. Conclusion Treatment with MRA was generally well tolerated and significantly reduced the disease activity of RA.

Journal ArticleDOI
TL;DR: In this paper, two English-speaking "Robovie" robots interacted with first and sixth-grade pupils at the perimeter of their respective classrooms, using wireless identification tags and sensors to identify and interact with children who came near them.
Abstract: Robots increasingly have the potential to interact with people in daily life. It is believed that, based on this ability, they will play an essential role in human society in the not-so-distant future. This article examined the proposition that robots could form relationships with children and that children might learn from robots as they learn from other children. In this article, this idea is studied in an 18-day field trial held at a Japanese elementary school. Two English-speaking "Robovie" robots interacted with first- and sixth-grade pupils at the perimeter of their respective classrooms. Using wireless identification tags and sensors, these robots identified and interacted with children who came near them. The robots gestured and spoke English with the children, using a vocabulary of about 300 sentences for speaking and 50 words for recognition. The children were given a brief picture-word matching English test at the start of the trial, after 1 week and after 2 weeks. Interactions were counted using the tags, and video and audio were recorded. In the majority of cases, a child's friends were present during the interactions. Interaction with the robot was frequent in the 1st week, and then it fell off sharply by the 2nd week. Nonetheless, some children continued to interact with the robot. Interaction time during the 2nd week predicted improvements in English skill at the posttest, controlling for pretest scores. Further analyses indicate that the robots may have been more successful in establishing common ground and influence when the children already had some initial proficiency or interest in English. These results suggest that interactive robots should be designed to have something in common with their users, providing a social as well as technical challenge.

Journal ArticleDOI
TL;DR: The similarities in the phenotypes of the MILI- and MVH-deficient mice and in the physical binding properties of MILI and MVh indicate a functional association of these proteins in post-transcriptional regulation, and indicate that MILI is essential for the differentiation of spermatocytes.
Abstract: The piwi family genes, which are defined by conserved PAZ and Piwi domains, play important roles in stem cell self-renewal, RNA silencing, and translational regulation in various organisms. To reveal the function of the mammalian homolog of piwi, we produced and analyzed mice with targeted mutations in the Mili gene, which is one of three mouse homologs of piwi. Spermatogenesis in the MILI-null mice was blocked completely at the early prophase of the first meiosis, from the zygotene to early pachytene, and the mice were sterile. However, primordial germ cell development and female germ cell production were not disturbed. Furthermore, MILI bound to MVH, which is an essential factor during the early spermatocyte stage. The similarities in the phenotypes of the MILI- and MVH-deficient mice and in the physical binding properties of MILI and MVH indicate a functional association of these proteins in post-transcriptional regulation. These data indicate that MILI is essential for the differentiation of spermatocytes.

Journal ArticleDOI
TL;DR: Hypoadiponectinemia is closely associated with the clinical phenotype of the metabolic syndrome and measuring the plasma concentration of adiponectin may be useful for management of the metabolism syndrome.
Abstract: Background The metabolic syndrome, a cluster of abdominal obesity, dyslipidemia, hypertension and hyperglycemia, is a common basis for atherosclerotic vascular diseases in industrial countries exposed to overnutrition. Adiponectin is an adipose-derived plasma protein with anti-atherogenic and insulin-sensitizing activities. Methods and Results A total of 661 Japanese adults (479 men, 53±10 years; 182 women 56±10 years) were enrolled. Plasma adiponectin concentrations correlated negatively with waist circumference, visceral fat area, serum triglyceride concentration, fasting plasma glucose, fasting plasma insulin, and systolic and diastolic blood pressure in both sexes. A positive correlation was found between plasma adiponectin and high-density lipoprotein cholesterol concentrations in both sexes. The mean number of components of the metabolic syndrome increased as the plasma adiponectin concentration decreased: 2.57±1.34 for men and 2.00±1.51 for women with adiponectin concentrations <4.0 μg/ml. In all, 52.3% of men and 37.5% of women with adiponectin concentrations <4.0 μg/ml fulfilled the criteria for metabolic syndrome. Conclusion Hypoadiponectinemia is closely associated with the clinical phenotype of the metabolic syndrome and measuring the plasma concentration of adiponectin may be useful for management of the metabolic syndrome. (Circ J 2004; 68: 975 - 981)

Journal ArticleDOI
TL;DR: Data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells.

Journal ArticleDOI
01 Jul 2004-Immunity
TL;DR: It is concluded that the TLR9/MyD88 pathway mediates antiviral cytokine responses by IPC, DC, and possibly other cell types, which are coordinated to promote effective NK cell function and MCMV clearance.

Journal ArticleDOI
TL;DR: In this paper, the spectral peak energy (Ep) and peak luminosity were derived by combining the data of Ep and the peak luminosities by BeppoSAX and BATSE and derived a GRB formation rate as a function of the redshift.
Abstract: We estimate a gamma-ray burst (GRB) formation rate based on the new relation between the spectral peak energy (Ep) and the peak luminosity. The new relation is derived by combining the data of Ep and the peak luminosities by BeppoSAX and BATSE, and it looks considerably tighter and more reliable than the relations suggested by the previous works. Using the new Ep-luminosity relation, we estimate redshifts of the 689 GRBs without known distances in the BATSE catalog and derive a GRB formation rate as a function of the redshift. For the redshift range of 0 ≤ z ≤ 2, the GRB formation rate increases and is well correlated with the star formation rate, while it keeps constant toward z ~ 12. We also discuss the luminosity function and the redshift dependence of the intrinsic luminosity (luminosity evolution).

Journal ArticleDOI
15 Feb 2004-Blood
TL;DR: Though TLR9/MyD88-deficiency abrogates IPC responses to HSV-1 in vitro, mice lacking either MyD88 orTLR9 are capable of controlling HSV -1 replication in vivo after local infection, demonstrating that TLR 9- and MyD 88-independent pathways in cells other than IPCs can effectively compensate for defective IPC responders.

Journal ArticleDOI
01 Oct 2004-Immunity
TL;DR: It is demonstrated that TGF-β signaling in tumor infiltrating T lymphocytes controls the growth of dysplastic epithelial cells in experimental colorectal cancer, as determined by histology and a novel system for high-resolution chromoendoscopy.

Journal ArticleDOI
TL;DR: The proposed algorithm for nonlinear receding horizon control is applied to a two-link arm whose dynamics is highly nonlinear and is shown to be bounded under some conditions.