Search

Introduction Heart failure (HF) is a clinical syndrome associated with diverse metabolic disturbances. Recent studies including ours suggest that skeletal muscle plays an important role in the pathogenesis of chronic HF and chronic kidney disease (CKD). However, the effect of renal function on skeletal muscle mass in HF remains unclear. Purpose The purpose of this study was to investigate the impact of chronic kidney disease on appendicular skeletal muscle mass in hospitalized patients with acute HF (AHF). Methods We assessed lean body mass by dual energy X-ray absorptiometry in 418 hospitalized patients with AHF (age 71±13, left ventricular ejection fraction (LVEF) 39±17%, estimated glomerular filtration rate (eGFR) at discharge 46±19 mL/min/1.73 m2). Low appendicular skeletal muscle mass index (ASMI, appendicular skeletal muscle mass/height2) was defined according to the Asia Working Group for Sarcopenia criteria ( Results CKD was observed in 77% of hospitalized patients with AHF (eGFR ≥60 mL/min/1.73 m2, n=96, 23%, eGFR 30–59 mL/min/1.73 m2, n=233, 56%, eGFR Conclusions CKD was associated with decreased skeletal muscle mass in hospitalized patients with AHF. CKD and skeletal muscle mass independently correlated with mortality after AHF episode. The cross link between kidney and skeletal muscle might play an important role in the pathogenesis of AHF. Funding Acknowledgement Type of funding sources: None.

We have investigated the electronic structure evolution with F doping in $\mathrm{Pr}{\mathrm{O}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}\mathrm{Bi}{\mathrm{S}}_{2}$ ($x=0.0,0.3,0.5$) by means of angle-resolved photoemission spectroscopy. Undoped $\mathrm{Pr}\mathrm{O}\mathrm{Bi}{\mathrm{S}}_{2}$ exhibits Fermi surface (FS) pockets around the $X$ point which can be associated with electron doping due to the ${\mathrm{Pr}}^{3+}/{\mathrm{Pr}}^{4+}$ mixed valence. At $x=0.3$, the FS pockets are expanded, and their area is almost consistent with the F doping level. Interestingly, horizontal segments facing each other in the rectangular FS pockets lose their spectral weight. The partial suppression of the FS pockets suggests possible anisotropic charge fluctuations around $x=0.3$. At $x=0.5$, the FS area is much smaller than the expected value as commonly observed for $\mathrm{Ce}{\mathrm{O}}_{0.5}{\mathrm{F}}_{0.5}\mathrm{Bi}{\mathrm{S}}_{2}$ and $\mathrm{Nd}{\mathrm{O}}_{0.5}{\mathrm{F}}_{0.5}\mathrm{Bi}{\mathrm{S}}_{2}$. In addition, the highly depleted spectral weight at the FS pockets would be consistent with evident charge fluctuations driven by atomic disorder in the $\mathrm{Bi}{\mathrm{S}}_{2}$ network.

Single nucleotide polymorphisms in drug metabolizing Cytochrome P450 (CYP) enzymes are important contributors to inter-individual differences in drug metabolism leading to adverse drug reactions. Despite their extensive characterization and importance in pharmacogenetics of clinical drugs, the structural basis of CYP polymorphisms has remained scant. Here we report the crystal structures of human CYP2C9 and its polymorphic variants, *3 (I359L) and *30 (A477T), with an anti-hypertensive drug losartan. The structures show distinct interaction and occupation of losartan in the active site, the access channel and the peripheral binding site. The I359L substitution located far away from the active site remarkably altered the residue sidechains near the active site and the access channel. Whereas the T477 substitution illustrated hydrogen-bonding interaction with the reoriented sidechain of Q214. The results provide structural insights into reduced catalytic activity of the CYP2C9 variants and have important implications for understanding genetic polymorphisms in CYP-mediated drug metabolism.

Statin-related myopathy (SRM) is a clinically important adverse reaction. Recent pharmacogenetic research, mainly in non-Asian populations, have indicated clinical relevance of some of genetic biomarkers to SRM, but predictive markers for SRM in Asian populations including Japanese has not yet been established. This study was aimed to identify clinically important genetic markers associated with SRM in Japanese patients. Allele frequencies of the three reported candidate markers — SLCO1B1 rs4149056, RYR2 rs2819742, and GATM rs9806699 — and carrier frequencies of HLA types were compared between patients with SRM patients (n = 52) and healthy Japanese subjects (n = 2878 or 86 (for rs9806699) as controls). No significant association of RYR2, SLCO1B1, and GATM variants with SRM were observed in our Japanese patients, but a significant association was detected for HLA-DRB1*04:06 with SRM (odds ratio: 3.19; 95% confidence interval: 1.53–6.66). This study suggested that HLA-DRB1*04:06 might be associated with SRM onset in a Japanese population. Further studies are required to validate these results.

We have investigated the electronic properties of ${\mathrm{BiS}}_{2}$-based superconductors by using x-ray photoemission spectroscopy (XPS). In going from $x=0.3$ to 0.5 in ${\mathrm{PrO}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}{\mathrm{BiS}}_{2}$, the Pr $3d$ and Pr $4d$ peaks are shifted by $\ensuremath{\sim}0.10\ifmmode\pm\else\textpm\fi{}0.05$ eV from the Fermi level, partially consistent with the electron doping. In ${\mathrm{PrO}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}{\mathrm{BiS}}_{2}$, the ${\mathrm{Pr}}^{3+}\ensuremath{-}{\mathrm{Pr}}^{4+}$ mixed valence remains unchanged with the electron doping from $x=0.3$ to 0.5. In ${\mathrm{CeO}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}{\mathrm{BiS}}_{2}$, the doped electrons for $x=0.5$ almost suppress the ${\mathrm{Ce}}^{3+}\ensuremath{-}{\mathrm{Ce}}^{4+}$ valence fluctuation. Although the core-level peaks are also shifted by $\ensuremath{\sim}0.10\ifmmode\pm\else\textpm\fi{}0.05$ eV towards the higher-binding-energy side with the electron doping from $x=0$ to 0.5 in ${\mathrm{CeO}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}{\mathrm{BiS}}_{2}$, the Bi $4{f}_{7/2}$ binding-energy shift is higher in the Pr system compared with the Ce system. The present results suggest that the doped electrons increase orbital occupations in the rare-earth $4f$ orbitals at the valence band and show valence fluctuations differently in the two systems.

A field-reversed configuration (FRC) plasma is a high-beta elongated compact toroid only with a poloidal field. Since the plasma torus does not link with confinement coil and vacuum vessel, the FRC can be translated from the formation region to confinement region along the external guide field. In this work, the effects of particle, flux and energy supply to the FRC due to the interaction with background neutral particles has been investigated. Translating an FRC plasma through a neutral gas background is equivalent to the injection of neutral beam end-on into the FRC. The experiments were performed on NUCTE-III and NUCTE-III/T. Due to the effects of back ground particle injection during translation process, the loss rate of particle, flux and energy were reduced.

In the field-reversed configuration (FRC) plasma, rotational instability with toroidal mode number n = 2 is known as a sole destructive MHD instability. Though an ideal FRC is unstable for higher n interchange instabilities, those have never been observed in past experiments. As a possible stabilized mechanism, self-generated toroidal rotation and its shear have been investigated experimentally.

Presented is a report of a panel discussion held as part of the ISA 2006 Sankyo Forum titled "A Trilogy of Primary Prevention Statin Trials--The Impact of These Landmark Studies on Clinical Practice," Rome, Italy, June 2006. The themes of the panel discussion were the design features of three trials, WOSCOPS, AFCAPS/TexCAPS, and Japan's MEGA Study; comparison of their primary endpoints; and the implications of their results. Among the topics discussed by the panel of experts from Japan, USA, and UK were observations on the benefits associated with pravastatin at low dose as demonstrated in the MEGA Study as well as that study's implications for women, who represented the majority of subjects. Several suggestions were put forth to explain how the low dose used in MEGA elicited similar LDL-C reductions to those observed in WOSCOPS and AFCAPS/TexCAPS at higher doses including the body size hypothesis, genetic variation, and statin-diet interaction. It was felt that in Japan, the current guidelines are adequate; there seemed no merit in radically reducing LDL-C levels since in the Japanese population the risk is generally low. Japanese physicians tend to use small doses of statin and believe that these are effective in lowering cholesterol sufficiently with few side effects and encourage good compliance.

Aim: To construct a simple, low-cost typing method for the surrogate marker of HLA-A*31:01, a risk factor for carbamazepine (CBZ) related Stevens–Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Materials & methods: DNAs from Japanese SJS/TEN patients were used for genotyping and developing the assay. Results: HLA-A*31:01 was confirmed to be significantly associated with definite/probable cases of CBZ-related SJS/TEN (p = 0.0040). Three single nucleotide polymorphisms, rs1150738, rs3869066 and rs259945, were in absolute linkage disequilibrium with HLA-A*31:01 in 210 Japanese SJS/TEN patients. Robust genotyping of rs3869066 in ZNRD1-AS1 was developed using polymerase chain reaction-restriction fragment length polymorphism assays. Conclusion: Single nucleotide polymorphism genotyping is less time consuming and cheaper than conventional HLA typing, and would be useful for identifying Japanese patients at risk of CBZ-related SJS/TEN.

We have tested a field-reversed configuration (FRC) formation with a spheromak injection for the first time. In this method, initial pre-ionized plasma is injected as a magnetized spheromak-like plasmoid into the discharge chamber prior to main field reversal. The FRC plasma with an electron density of 1.3 × 1021 m−3, a separatrix radius of 0.04 m and a plasma length of 0.8 m was produced successfully in initial background plasma of about 1.6 × 1019 m−3 by spheromak injection. The density is about one third of the conventional formed by the z-ionized method.

The structural property and interfacial morphology have been investigated for the Ca 2 Si/Mg 2 Si interface. The Ca 2 Si layers were grown on Mg 2 Si layers by heat treatment of the Mg 2 Si/Si substrates in Ca vapor. It is found that the CaMgSi phase is formed at the Ca 2 Si/Mg 2 Si interface. The structural property of the resultant silicides was examined by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The chemical composition of the layers was examined by energy dispersion spectroscopy (EDS). In addition, the chemical analysis by X-ray photoelectron spectroscopy (XPS) revealed the Mg segregation on the silicide surface. The growth mechanism of Ca 2 Si on Mg 2 Si/Si is also discussed.

Background Patients with lipoprotein lipase (LPL) deficiency had been generally thought to be spared accelerated atherosclerosis in spite of a marked elevation of plasma triglyceride levels. However, it has been recently reported that some heterozygous and homozygous LPL-deficient patients are associated with premature atherosclerosis. In this paper, we report a 55-year-old type I hyperlipidaemic patient with a novel missense mutation in the LPL gene. Patient and results The patient had suffered from coronary artery disease, abdominal aortic aneurysm, and stenoses of the bilateral renal arteries and superficial femoral arteries. Sequencing of the genomic DNA revealed that the patient was a homozygote for the mutation, a G to C transition at nucleotide position 1069 in the exon 6, resulting in an amino acid substitution of Phe for Leu303 (L303F). Approximately ∼6% and ∼40% of normal LPL activity and LPL mass, respectively, were detected in the patient's postheparin plasma. An in vitro expression study demonstrated that COS7 cells transfected with L303F mutant cDNA produced a 40% amount of LPL protein in cell lysates compared with normal cDNA, but no protein was detected in the media. Lipoprotein lipase activity was completely absent in both lysates and media of the cells transfected with the mutant cDNA, suggesting that this mutation in the LPL gene results in the production of a functionally inactive protein. Conclusion This case suggests that the LPL missense mutation (L303F), which impairs lipolysis but preserves the LPL mass, is proatherogenic.

Board-to-board optical interconnection between optical waveguide channels is suitable for high-speed optoelectronic printed wiring boards (OE-PWBs). Here, we propose a novel optical interconnection method based on plug-in alignment between an optical waveguide plug (OWP) and a micro hole array (MHA). The OWP and MHA are prepared from UV-curable resin and fabricated by the mask transfer method. As they are well-aligned on the optical waveguide channels of the OE-PWBs, both optical circuits of the OE-PWBs can be interconnected easily. From experimental results, we found that the plug-in alignment technique is promising for board-to-board optical interconnection.

In most region extraction methods using the Active Contour Model (ACM, Snakes), the entire area of a target object is treated as a single region, and an ACM is deformed locally by image properties around the contour. For these reasons, it is difficult for these methods to extract accurately an object area that has intricate distributions of image properties. In response to this difficulty, to introduce wide-ranging image properties into the extraction process, it has been proposed to control an ACM by the statistical characteristics of image properties in the object and background regions. However, this approach is unsuitable when image properties vary widely with location in each region. In this paper, to overcome this problem, a novel region extraction method is proposed. The proposed method makes multiple ACMs compete with each other and each ACM extract a subregion of uniform image properties, and, as a result, the method extracts the entire area of an object as a set of several subregions. In the proposed method, first, a few initial curves are set in the object and background regions. Each initial curve is divided into several segments, and multiple initial ACMs are made by dilating these segments. Second, at each ACM, the density function of image properties is estimated, and for each control point on a contour, the likelihood with respect to every ACM region is determined. Based on this likelihood, each ACM is controlled and multiple ACMs compete with each other. © 2001 Scripta Technica, Syst Comp Jpn, 32(5): 1–11, 2001

Cardiac sarcoidosis occurs in 1-5% of sarcoidosis patients. We previously reported a significant increase of the uncommon TNFA (tumor necrosis factor alpha) allele, TNFA2 with cardiac sarcoidosis in Japanese. In order to precisely localize the susceptible locus for cardiac sarcoidosis within the HLA region, genetic polymorphisms of classical HLA genes, non-classical HLA class II genes such as HLA-DMA and -DMB genes and several genes involved in the class I-mediated antigen presentation pathway (TAP1, TAP2, LMP2 and LMP7) were investigated. Further, association analyses using four polymorphic microsatellite markers located around the TAP1 and TNFA genes were also carried out. As a result, HLA-DQB1*0601 was found to be the most significantly associated allele, being more significantly increased than TNFA2. No significant increase of the DR52-associated DRB1 alleles (DRB1*03, 05, 06 and 08), which was suggested to be primarily associated with lung sarcoidosis, was observed in cardiac sarcoidosis. A primary role of DQB1*0601 in determination of the susceptibility to cardiac sarcoidosis was supported by association analysis using four polymorphic microsatellite markers, in which only the TAP1 microsatellite locus, the nearest marker to the DQB1 gene among the microsatellites tested, displayed a significant positive association with cardiac sarcoidosis. On the other hand, the HLA-DQB1*0501-DQA1*0101-DRB1*0101-B7 haplotype showed a negative association with the disease, as similarly observed in lung sarcoidosis. Thus, molecular mechanism for controlling the development of the disease related to HLA molecules are different between cardiac and lung sarcoidosis, whereas those for conferring a resistant trait may be similar to each other.

Psoriasis vulgaris is associated with the HLA-Cw6 and Cw7 antigens. We have previously narrowed down the critical region most likely to contain the psoriasis vulgaris gene to 111 kb spanning 89 kb to 200 kb telomeric of the HLA-C locus by microsatellite mapping. This segment includes three known genes (POU5F1, SC1 and S) and four new expressed genes. Among them, SC1 (TCF19) is the cell growth regulated gene possibly with trans-activator activity. Since psoriasis vulgaris is a common skin disorder characterized by hyperproliferation of epidermal cells, it is tempting to speculate that the SCI gene is one of the strong candidate genes responsible for the development of psoriasis vulgaris. Here, we investigated genetic polymorphisms in the SC1 gene by direct DNA sequencing and polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) techniques. Three single nucleotide polymorphisms in exon 2, two of which are accompanied by amino-acid substitutions, were identified. Further, one 4-bp deletion polymorphism was detected around the acceptor site of the lariat-shaped structure necessary for RNA splicing in intron 2. No significant difference in the dimorphic or haplotypic distribution at these four polymorphic sites was observed between the patients with psoriasis vulgaris and healthy controls. This suggests that the susceptible gene for psoriasis vulgaris is not the SC1 gene itself, although a unique homozygous haplotype was identified in the patients.

A unique subclone of a bone marrow-derived stromal cell line, BMS2.4, produces soluble factors that inhibit proliferation of several types of hematopoietic cell lines. An understanding of these molecules may be informative about negative regulatory circuits that can potentially limit blood cell formation. We used expression cloning to identify interleukin-6 (IL-6) as one factor that suppressed growth of a pre-B–cell variant line, 1A9-M. Moreover, IL-6 induced macrophage-differentiation and apoptosis of 1A9-M cells. During this process, IL-6 downregulated expression of BCL2 in 1A9-M cells and stimulated BCL-XL expression, but had no effect on p53, Bax, or Bak gene expression. Mechanisms for transduction of IL-6–induced signals were then evaluated in IL-6–stimulated 1A9-M cells. Whereas the signal transducer and activator of transcription 3 (Stat3) was phosphorylated and activated, there was no effect on either Stat1 or Stat5. The importance of BCL2 and Stat3 on IL-6–induced macrophage-differentiation and apoptosis was studied with 1A9-M cells expressing human BCL2 or a dominant-negative form of Stat3, respectively. IL-6–induced apoptosis, but not macrophage-differentiation, was blocked by continuously expressed BCL2. A dominant-negative form of Stat3 inhibited both macrophage-differentiation and apoptosis induced by IL-6. However, diminished Stat3 activity did not prevent IL-6–induced downregulation of the BCL2 gene. Therefore, activation of Stat3 is essential for IL-6–induced macrophage-differentiation and programmed cell death in this model. Whereas overexpression of BCL2 abrogates the apoptotic response, Stat3-independent signals appear to downregulate expression of the BCL2 gene.

The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). Pik3r1-/- mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes. Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). This mechanism seems to be responsible for the phenotype of Pik3r1-/- mice, namely increased glucose transport and hypoglycaemia. Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vivo.

The magnetic configuration of a field-reversed configuration (FRC) has a center closed region and open field region. Because of this geometrical property, an FRC can be translated from a formation ...

In the production of vapor-grown carbon fibers, ultrafine iron catalyst particles play an important role in the elongation process of the fibers. The activity of the catalyst particles depends strongly on their sizes. Therefore, in this work, ultrafine iron catalyst particles were produced under various reaction conditions using the liquid pulse injection technique, and were collected to investigate the influence of the reaction conditions on the size distribution of the obtained particles. The varied conditions were, the concentration and amount of ferrocene, which was used as the source of the catalyst material, and the velocity of the carrier gas at a fixed temperature. Each of them had a significant influence on the size distribution. From the obtained distribution curves, the relationship between the amount of catalyst particles having diameters in the range 20–30 nm, and the yield of fibers produced under the same set of reaction conditions was investigated. It was found that the yield increases with the increase in the number of catalyst particles in the size range from 20 to 30 nm. Furthermore, a model was developed to predict the size distribution of particles produced under various reaction conditions. This model was found to well represent the experimental data.

Cholesteryl ester transfer protein (CETP) deficiency is the most common cause of hyperalphalipoproteinemia in Japan. However, the genetic basis of this disorder has not been fully characterized. We have studied a 49-year-old Japanese male presenting with total cholesterol, HDL-cholesterol, and apolipoprotein A-I levels of 300, 236, and 233 mg/dl, respectively, and total absence of CETP activity and mass in plasma. Sequence analysis of the patient's CETP gene revealed that the splice donor consensus GT was substituted by GG in intron 10 (intron 10 splice defect) and by AT in intron 14 (intron 14 splice defect). Restriction digestion of PCR-amplified DNA using NdeI and MaeIII established that the patient was a compound heterozygote for both gene defects. Sequencing of cDNA amplified by RT-PCR from the patient's monocyte-derived macrophage RNA demonstrated abnormal splicing with deletion of exon 10 as well as alternative splicing at a native AG site located 31 nucleotides 5' of the normal splice acceptor in intron 13. Thus, the intron 10 splice defect results in exon 10 skipping and the insertion of a 31 bp fragment between exon 13 and exon 14, which contains an in frame stop codon. The presence of abnormally spliced mRNA was further confirmed by amplification of patient cDNA using CETP specific primers. Abnormal splicing of exon 14 as a result of the intron 14 splice defect was not detected, indicating potential unstable CETP mRNA derived from that mutation. These findings demonstrate that a novel splice site mutation in intron 10 of the CETP gene results in the skipping of exon 10, as well as disruption of downstream splicing at intron 13 identifying a novel mechanism leading to CETP deficiency.

Simultaneous quantification methods and sample preparation methods for five typical biogenic amines (5-hydroxytryptamine, dopamine, epinephrine, norepinephrine, and octopamine), one precursor (tyramine), and three metabolites (N-acetyldopamine, N-acetyloctopamine, and synephrine) using HPLC with an electrochemical detector were developed. These methods were applied to investigating the distribution of these amine derivatives in the central nervous system of last instar of Spodoptera litura. In the central nervous system, all amines listed above were detected; among those, N-acetyldopamine and N-acetyloctopamine existed at relatively high levels rather than their free-amines. Chlordimeform, a potent antifeedant, caused an increase in N-acetyldopamine levels in cerebral and suboesophageal ganglia and a decrease in 5-hydroxytryptamine and N-acetyloctopamine levels in the cerebral, suboesophageal, and thoracic ganglia. On the other hand, aristolochic acid I, a newly found antifeedant from Aristolochia albida, did not cause any statistically significant change in any amine levels, except for dopamine and 5-hydroxytryptamine in suboesophageal ganglia and tyramine in thoracic ganglia. From these results, it has been suggested that chlordimeform and aristolochic acid I each had a different mode of antifeedant activity against S. litura.

Six haploid plants of radish were obtained via alien monosomic addition lines (2n = 19). One plant was derived from anther culture of an Raphanus sativus-Brassica oleracea addition line, one plant from the selected smaller seed of an R. sativus-Sinapis arvensis addition line and four plants from an R. sativus-B. rapa addition line. During metaphase I of pollen mother cells, two plants exhibited the chromosome pairing of (0-3)II+ (3-9)I, three showed (0-1)III + (0-3)II + (3-9)I and the remaining plant (0-2)II + (5-9)I. Trivalents seemed to be formed by the pairing between two larger chromosomes and the smaller one with somewhat loose pairing. All haploid plants were inferior to the radish cv. ‘Shogoin’ (2n = 18) with respect to vegetative growth. Their flowers were smaller, with sterile pollen grains, but a few normal flowers with fertile pollen sporadically developed and then produced a few seeds. It is suggested that the radish genome (R, n = 9) might comprise three pairs of homoeologous chromosomes, with the remaining three chromosomes carrying the homologous region(s) that results in a trivalent formation.

Dilated cardiomyopathy (DCM), a common cause of heart failure, is characterized by cardiac dilation and reduced left ventricular ejection fraction, but the underlying mechanisms remain unclear. To investigate the mechanistic basis, we performed global metabolomic analysis of myocardial tissues from the left ventricles of J2N-k cardiomyopathic hamsters. This model exhibits symptoms similar to those of human DCM, owing to the deletion of the δ-sarcoglycan gene. Charged and lipid metabolites were measured by capillary electrophoresis mass spectrometry (MS) and liquid chromatography MS(/MS), respectively, and J2N-k hamsters were compared with J2N-n healthy controls at 4 (presymptomatic phase) and 16 weeks (symptomatic) of age. Disturbances in membrane phospholipid homeostasis were initiated during the presymptomatic phase. Significantly different levels of charged metabolites, occurring mainly in the symptomatic phase, were mapped to primary metabolic pathways. Reduced levels of metabolites in glycolysis, the pentose phosphate pathway, and the tricarboxylic acid cycle, together with large decreases in major triacylglycerol levels, suggested that decreased energy production leads to cardiac contractile dysfunction in the symptomatic phase. A mild reduction in glutathione and a compensatory increase in ophthalmate levels suggest increased oxidative stress in diseased tissues, which was confirmed by histochemical staining. Increased levels of 4 eicosanoids, including prostaglandin (PG) E 2 and 6-keto-PGF 1α , in the symptomatic phase suggested activation of the protective response pathways. These results provide mechanistic insights into DCM pathogenesis and may help identify new targets for therapeutic intervention and diagnosis.

To examine the hypothesis that the pathway of adaptation to high altitude in natives differs considerably from that in newcomers, we measured maximal O2 uptake (VO2max), minute ventilation, anaerobic threshold (AT), blood lactate, and blood gases during maximal exercise in 17 lifelong Tibetan residents and 14 acclimatized Han Chinese newcomers living at the altitude of 4,700 m. The two groups were similar in age, height, and weight, and the subjects were nonathletes. Although VO2max was significantly lower in the Tibetans than in the Hans (30.4 +/- 1.5 vs. 36.0 +/- 1.9 ml.min-1.kg-1 STPD; P < 0.05), at maximal exercise effort the exercise workload was greater (167.7 +/- 4.2 vs. 150.0 +/- 5.9 W; P < 0.05). The mean AT values (in % VO2max) in the Tibetan and Han subjects were 84.1 and 61.6%, respectively (P < 0.01). Minute ventilation at maximal exercise was significantly lower in the Tibetans than in the Hans (68.4 +/- 3.4 vs. 79.7 +/- 4.1 l/min BTPS; P < 0.05), whereas heart rate at maximal effort was equivalent in the two groups. The Tibetans showed lower blood lactate value than did the Hans both before and at the end of exercise. We conclude that the Tibetan natives have higher exercise performance and AT but lower VO2max and blood lactate concentration than do acclimatized Han newcomers. These results may reflect the effects of genetic or peripheral adaptation factors in the Tibetan natives.

In most interspecific hybridization among diploid Brassica species (n = 8, 9, 10), few or no hybrids are obtained, and the three crosses of tetraploid (n = 17, 18, 19) by diploid species are usually only partially successful, especially in one of the reciprocal crosses. Such a cross-incompatibility complex is explained in this paper by a polar-nuclei activation (PNA) hypothesis which proposes two reversible functions, a normal reproduction and a sexual barrier, of double fertilization in higher plants. The first, i.e. the relative activating value (AV) of diploid species, was estimated as 1.0–3.5, whereas that of tetraploid species was 2.7–5.2. In addition, crosses with a polar nuclei activation index (AI) of about 15–87 % were compatible but those beyond the two limits were incompatible, 50 % of those showing normal seed development after self-pollination.

Activated sludge mixed cultures were cultivated with a glucose containing substrate in order to investigate the relationship between the feeding pattern (continuous or intermittent feeding) and the glycogen reservation capacity of activated sludge. An experimental method to measure the maximum capacity of glycogen reservation in the sludge was developed. Sludge with higher glycogen reservation capacity has an ability to synthesize glycogen faster, which ensures the higher glucose uptake. Therefore, sludge which has high glycogen reservation capacity becomes predominant in intermittently fed reactors. When the feeding pattern was changed from continuous feeding to intermittent feeding, a filamentous bacterium, Type 1701, started to decrease and a gram positive tetrad coccus became predominant. When the feeding pattern was returned to continuous feeding, Type 1701 re-appeared. Type 1701 has lower glycogen reservation capacity than the tetrad coccus. Therefore, the former cannot dominate over the latter in intermittently fed reactors.

For the development of a new cytoplasmic male sterility (CMS) system in Brassica rapa (2n= 20, AA), intergeneric hybridization was performed in Eruca sativa (2n= 22, EE)×B. rapa. The original amphihaploid F1 plant (2n= 21, EA) generated via embryo rescue produced a sesquidiploid F1 plant (2n= 31, EAA), from which the alloplasmic F3 plants were generated. In F3, some progenies with malformed anthers were maintained as male-sterile lines up to the F5 generation. In the F6 and F7 generations, the alloplasmic male-sterile plants were bred by backcrossing to several B. rapa genotypes and were then classified into the three distinctive types: petaloid, antherless and brown anther, in addition to three intermediate types between them. By southern blot analysis, each plant of the petaloid and antherless types was shown to carry the cytoplasm genome of E. sativa. These male-sterile plants produced as many viable seeds as the corresponding male-fertile plants, although their nectary gland development was minimal. Consequently, CMS lines of the petaloid and antherless types with enhanced seed fertility and nectary gland development could provide promising plant materials for F1 seed production in B. rapa.

The transforming activity of the human fyn protein, p59fyn, which is a kinase of the src family, was investigated by testing the effect of recombinant avian retrovirus (Fyn virus) expressing p59fyn on chickens or cultured chicken embryo fibroblast (CEF) cells. The Fyn virus did not induce transformed foci. After several passages of the virus stock on CEF cells, however, a few foci were detected in the presence of dimethyl sulfoxide. Chickens inoculated with Fyn virus at the stage of 12-day-old embryos developed fibrosarcomas 3 to 6 weeks after hatching. The viruses obtained from these foci and from one of the tumor tissues showed high transforming activity in the presence of dimethyl sulfoxide, suggesting that these viruses carry spontaneous mutations of the fyn gene. Four fyn genes from CEF DNAs infected with transforming viruses were molecularly cloned, and their products were confirmed to possess transforming activity. DNA sequence analysis of the fyn genes showed that two of the four mutants have Thr instead of Ile at position 338 in the kinase domain. The other two mutants carry deletions of 78 and 108 base pairs, respectively, which result in complete loss of region C of SH2. The overall level of proteins containing phosphotyrosine was significantly higher in transformed cells than in normal CEF cells. Our data indicate that when expressed at high levels in a retrovirus, normal p59fyn cannot cause cellular transformation, but that mutant p59fyn with either a single amino acid substitution in the kinase domain or a deletion including region C produces a transforming protein, perhaps due to enhanced tyrosine kinase activity. This is the first observation that deletion of region C can unmask the potential transforming activity of a src family kinase.

To extract object regions from images, the methods using region-based active contour model (ACM) have been proposed. By controlling ACM with the statistical characteristics of the image properties, these methods effect robust region extraction. However the existing methods require redundant processing and cannot adapt to complex scene images. To overcome these problems, we propose a new method for controlling region-based ACM. In the proposed method, a definite area is set along an object boundary. This area is partitioned into several subareas, and they, are iteratively deformed to make the image properties be uniform in each subarea. As a result of this clustering on the definite area, the image properties in a necessary and sufficient area can be effectively reflected on ACM control, and efficient and accurate region extraction can be achieved.

Adiponectin is a new member of adipocyte derived proteins belonging to the soluble defence collagens.1 Plasma adiponectin concentrations in obese subjects are decreased in spite of an adipose specific expression.1 More interestingly, the patients with chronic coronary artery disease exhibited lower plasma adiponectin concentrations compared to body mass index (BMI) matched control subjects.2 On the other hand, adiponectin accumulates in the vascular subendothelial space when the endothelial barrier is damaged.3 In vitro, adiponectin suppresses the expression of adhesion molecules in the vascular endothelial cells and cytokine production from macrophages.2,4 Therefore, the molecule may be involved in the inflammation and tissue repairing processes. Acute coronary syndrome is often precipitated by acute thrombosis.5 It is commonly accepted that the rupture or the erosion of plaques by the inflammatory process leads to coronary thrombosis and acute myocardial infarction (AMI). The C reactive protein (CRP) concentrations in the acute phase are suggested to reflect pre-existing coronary plaque instability associated with the onset of AMI. The significance of adiponectin in acute coronary syndrome has never been investigated. In the present study, we examined the serial change in plasma adiponectin concentrations and its relation to plasma CRP concentration in …

Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic subjects (FDR) as well as 40 healthy control subjects (CON) without a known family history of diabetes. Insulin sensitivity (Si) was studied with the minimal model, and measurements of adiponectin, metabolic variables, inflammatory markers, and endothelial injury markers, as well as lipoprotein concentrations, were performed. FDR were insulin resistant (3.3 ± 2.4 vs. 4.5 ± 2.6 × 10−4 × min−1 per μU/ml [mean ± SD], P < 0.01), and their circulating plasma adiponectin levels (6.6 ± 1.8 vs. 8.1 ± 3.0 μg/ml, P < 0.03) were decreased. After adjustments for age in FDR, adiponectin levels were negatively correlated with fasting proinsulin (r −0.64, P < 0.001), plasminogen activator inhibitor (PAI)-1 activity (r −0.56, P < 0.001), fasting insulin (r −0.55, P < 0.001), and acute insulin response (r −0.40, P < 0.05); they were positively related to HDL cholesterol (r 0.48, P < 0.01) and Si (r 0.41, P < 0.01). Furthermore, when adjusted for age, waist, and Si, adiponectin was associated with HDL cholesterol and proinsulin, which explained 51% of the variation in adiponectin in multiple regression analyses in that group. In conclusion, circulating plasma adiponectin levels were decreased in nonobese but insulin-resistant FDR and, in addition, related to several facets of the insulin resistance syndrome (IRS). Thus, hypoadiponectinemia may be an important component of the association between cardiovascular disease and IRS.

Many studies have reported the cholesterol-lowering, anti-lipogenic, anti-obesity and anti-hypertensive effects of soy protein. Adipose tissue-specific plasma protein, adiponectin, has anti-atherogenic and anti-insulin-resistance properties. Here, we investigated the effects of soy protein diet on body fat composition, plasma glucose, lipid and adiponectin levels and expression of genes involved in glucose and fatty acid metabolism in obese KK-A y mice. Body weights and adipose tissue weights of mesenteric, epididymal, and brown fat were lower in mice on calorie-restricted diet containing soy protein isolate. Plasma cholesterol, triglyceride, free fatty acid, and glucose levels were also decreased by this diet. Body fat content and plasma glucose levels in mice on a soy protein isolate diet were still lower than those treated with an isocaloric casein-protein-diet. Among the genes related to glucose and fatty acid metabolism, adiponectin mRNA levels in adipose tissue and adiponectin plasma concentrations were elevated in mice on a calorie-restricted diet, although there were no significant differences between soy protein and casein protein groups. Our results indicate that that soy protein diet decreased body fat content and plasma glucose levels more effectively than isocaloric casein-protein diet in obese mice.

Patients with lipoprotein lipase (LPL) deficiency had been generally thought to be spared accelerated atherosclerosis in spite of a marked elevation of plasma triglyceride levels. However, it has been recently reported that some heterozygous and homozygous LPL-deficient patients are associated with premature atherosclerosis. In this paper, we report a 55-year-old type I hyperlipidaemic patient with a novel missense mutation in the LPL gene.The patient had suffered from coronary artery disease, abdominal aortic aneurysm, and stenoses of the bilateral renal arteries and superficial femoral arteries. Sequencing of the genomic DNA revealed that the patient was a homozygote for the mutation, a G to C transition at nucleotide position 1069 in the exon 6, resulting in an amino acid substitution of Phe for Leu303 (L303F). Approximately 6% and approximately 40% of normal LPL activity and LPL mass, respectively, were detected in the patient's postheparin plasma. An in vitro expression study demonstrated that COS7 cells transfected with L303F mutant cDNA produced a 40% amount of LPL protein in cell lysates compared with normal cDNA, but no protein was detected in the media. Lipoprotein lipase activity was completely absent in both lysates and media of the cells transfected with the mutant cDNA, suggesting that this mutation in the LPL gene results in the production of a functionally inactive protein.This case suggests that the LPL missense mutation (L303F), which impairs lipolysis but preserves the LPL mass, is proatherogenic.

We propose an object oriented reference model with several middleware tools, which includes OODB, GUI libraries, and CORBA. It is approved that a software structure with a framework brings various advantages. However unplanned combinations of the different frameworks often cause the problem, which greatly decrease their expected effectiveness. We therefore propose MVIm (Model-View-Interface manager) model to escape from this problem. Since the interface manager indirectly combines between middleware, we can effectively use the middleware without bad interference.

Although various bonding methods have been developed for flip-chip assembly, most of them cannot be applied to smaller pitch interconnection for the next generation. In the present study, a new bonding method, the surface activated bonding (SAB) is introduced. The feasibility of the SAB for bump bonding was investigated by some experiments. The Au electroplated bumps were prepared for experiments. The three different types of material, Au, Cu, and Al were used as contact metals. The reliability of interconnections was tested in temperature storage. As a result, we could achieved the bonding of microbumps with high strength and good electrical connection. It was also found that in the case of bump bonding, SAB can be done under relatively high vacuum pressure condition.

For interactive image manipulation, a new region extraction method using active contour models (ACM) is proposed. In this method, to improve extraction accuracy, multiple ACMs controlled by the statistical characteristics of image data are applied to the region of a single object. These ACMs compete with each other and each ACM extracts a subregion of uniform image properties. As a result of this competition, the entire region of the object is extracted as a set of several subregions. In addition, to lighten the load of the initial ACM settings, a procedure for making multiple initial ACMs from a few initial curves is also proposed. In this procedure, a few initial curves are set in an image, each initial curve is divided into several segments at the optimal loci, and multiple initial ACMs are made by dilating these segments.

For accurate region extraction, region-based active contour models (ACM) have been proposed. Compared with ordinary ACM, they require heavier loads of initial settings and further processing time. Considering these problems, for effective and efficient extraction, we propose a new region-based ACM. In the proposed method, first, users draw an initial curve in an object. Along this curve, definite length scanlines are set perpendicular to the initial curve and across the object contour. Depending on the image properties around scanlines, the scanlines are separated into several groups and each group is divided into two subregions (object and background regions). Scanline grouping and group dividing are iterated until the image properties are sufficiently uniform in each subregion. Through this clustering, a region along an object contour is segmented into subregions of uniform image properties, and consequently the image properties in a necessary and sufficient area are introduced into the extraction process effectively.

For interactive image manipulation, a new region extraction method using active contour model (ACM) is proposed. In this method, to the region of a single object, multiple ACMs controlled by the statistical characteristics of image data are applied. These ACMs compete with each other, and each ACM extracts a subregion of uniform image properties. The entire region of the object is extracted as a set of several subregions. This method requires multiple initial ACMs set. To ease this initial setting, a procedure for making initial ACMs from a few initial curves is also proposed. In this procedure, a few initial curves are set in an image, each initial curve is divided into appropriate number segments at the optimal loci, and multiple initial ACMs are made by dilating these segments.

In this article, we propose an object tracking method using a neural network which represents the shape of an object based on the object's color information. We previously proposed a specific form of multiple-layered neural network which has a suitable structure to represent an object's shape. This network (shape representation network, SRN) originally was developed to deal with black and white images but it is extended for color images in this article. SRN is capable of representing objects of various kinds of shape and color with an arbitrary degree of blurring. Its learning capability enables automatic model construction for various shapes including their color information. To perform object tracking with color information, we introduce Mahalanobis distance in color space and improve the tracking performance. Some experiments are performed to evaluate the performance of the proposed method using real image sequences.