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Biomedical subjects

Jun Sasaki

Publications and source records attributed to Jun Sasaki.

At least 19 recordsLinked to original sources
PubMed2007

Effect of rosuvastatin 5-20mg on triglycerides and other lipid parameters in Japanese patients with hypertriglyceridemia.

To evaluate the potential dose effect of rosuvastatin on triglyceride (TG) levels in Japanese hypertriglyceridemic patients, we randomized 154 patients with TG levels of >or=200 and <800 mg/dL to 8 weeks of treatment with rosuvastatin 5, 10 or 20mg once daily; bezafibrate 200mg twice daily; or placebo. Compared with placebo, TG was reduced by 30.1% with rosuvastatin 5mg, 30.1% with 10mg and 32.3% with 20mg (all p<or=0.0001), with no evidence of a dose effect. Changes in TG were evident after 2 weeks of treatment and maintained thereafter. In a benchmark comparison, rosuvastatin across its dose range reduced TG by 29.1-31.1% from baseline versus 45.4% for bezafibrate. Compared with bezafibrate, rosuvastatin was superior with respect to changes in non-high-density lipoprotein cholesterol (non-HDL-C, -36.8 to -44.3% for rosuvastatin versus -2.0% for bezafibrate), low-density lipoprotein cholesterol (-31.9 to -41.0% versus +29.3%), total cholesterol (-27.1 to -33.3% versus +2.1%), although smaller improvements in HDL-C (12.4-16.7% versus 19.6%) were observed. Rosuvastatin also produced superior dose-related decreases in median high-sensitivity C-reactive protein (22.9-38.5%). Treatment was well tolerated in both rosuvastatin and bezafibrate patients, with clinically important increases in alanine aminotransferase being rare, no adverse effect on renal function being observed and no cases of myopathy or rhabdomyolysis being reported. The current study does not suggest a dose-related effect of rosuvastatin in lowering TG in hypertriglyceridemic Japanese patients, although dose-related improvements in other elements of the atherogenic lipid profile were observed.

Apolipoproteins↗
PubMed2006

Laser-induced transient grating analysis of dynamics of interaction between sensory rhodopsin II D75N and the HtrII transducer.

The interaction between sensory rhodopsin II (SRII) and its transducer HtrII was studied by the time-resolved laser-induced transient grating method using the D75N mutant of SRII, which exhibits minimal visible light absorption changes during its photocycle, but mediates normal phototaxis responses. Flash-induced transient absorption spectra of transducer-free D75N and D75N joined to 120 amino-acid residues of the N-terminal part of the SRII transducer protein HtrII (DeltaHtrII) showed only one spectrally distinct K-like intermediate in their photocycles, but the transient grating method resolved four intermediates (K(1)-K(4)) distinct in their volumes. D75N bound to HtrII exhibited one additional slower kinetic species, which persists after complete recovery of the initial state as assessed by absorption changes in the UV-visible region. The kinetics indicate a conformationally changed form of the transducer portion (designated Tr*), which persists after the photoreceptor returns to the unphotolyzed state. The largest conformational change in the DeltaHtrII portion was found to cause a DeltaHtrII-dependent increase in volume rising in 8 micros in the K(4) state and a drastic decrease in the diffusion coefficient (D) of K(4) relatively to those of the unphotolyzed state and Tr*. The magnitude of the decrease in D indicates a large structural change, presumably in the solvent-exposed HAMP domain of DeltaHtrII, where rearrangement of interacting molecules in the solvent would substantially change friction between the protein and the solvent.

Archaeal Proteins↗
PubMed2006

Risk of coronary events in Japanese patients with both hypercholesterolemia and type 2 diabetes mellitus on low-dose simvastatin therapy: implication from Japan Lipid Intervention Trial (J-LIT).

Hypercholesterolemic patients with type 2 diabetes mellitus are at increased risk of coronary heart disease (CHD); however, direct evidence is very limited in Japanese patients. The J-LIT is the first nationwide study conducted to assess the relationship between serum lipid levels and development of coronary events in Japanese hypercholesterolemic patients. We analyzed the coronary events in the J-LIT study subjects by having type 2 diabetes or not. Of the total 41,801 subjects without prior CHD who received open-label simvastatin, 5mg/day, 6554 (male 40.2%, age 57.8+/-7.8) subjects had type 2 diabetes, while 35,247 (male 30.0%, age 57.8+/-7.9) did not. In this analysis, relative coronary event risks based on a 0.26 mmol/l (10mg/dl) increase in low density lipoprotein-cholesterol (LDL-C), were similar between hypercholesterolemic subjects with and without type 2 diabetes (17.3% versus 19.4%). Although all subjects were treated with simvastatin, the subjects with type 2 diabetes have significantly more coronary events compared to the subjects without type 2 diabetes (1.80/1000 and 0.76/1000 patient-years, respectively). Given the results above, to reduce the risk of coronary events in Japanese patients with both hypercholesterolemia and type 2 diabetes, careful and strict cholesterol management is needed in addition to the control of blood glucose.

Adult↗
PubMed2006

[Nodular goiter].

Explore the source record for details and available documents.

Cytodiagnosis↗
PubMed2006

Reverse genetics system for introduction of site-specific mutations into the double-stranded RNA genome of infectious rotavirus.

We describe here the successful establishment of a reverse genetics system for rotavirus (RV), a member of the Reoviridae family whose genome consists of 10-12 segmented dsRNA. The system is based on the recombinant vaccinia virus T7 RNA polymerase-driven procedure for supplying artificial viral mRNA in the cytoplasm. With the aid of helper virus (human RV strain KU) infection, intracellularly transcribed full-length VP4 mRNA of simian RV strain SA11 resulted in the rescue of the KU-based transfectant virus carrying the SA11 VP4 RNA segment derived from cDNA. In addition to the rescued transfectant virus with the authentic SA11 VP4 gene, three more infectious RV transfectants, into which silent mutation(s) were introduced to destroy both or one of the two restriction enzyme sites as gene markers in the SA11 VP4 genome, were also rescued with this method. The ability to artificially manipulate the RV genome will greatly increase the understanding of the replication and the pathogenicity of RV and will provide a tool for the design of attenuated vaccine vectors.

Animals↗
PubMed2006

Ferromagnetic ordering in a new nickel polyborate NiB12O14(OH)10.

A new nickel polyborate, NiB12O14(OH)10 was synthesized using boric acid as a flux. This material has two-dimensional borate layers with a quasi-square lattice of Ni2+. The Ni2+ ions locate in the plane of the two-dimensional layer, bridged through BnO(n+1) chains in the plane and connected with the three-membered ring borate groups out of the plane. The dc and ac magnetic susceptibility, magnetization and specific heat measurements show that this material undergoes a weak ferromagnetic phase transition at Tc = 5.8 K. At T < Tc, a metamagnetic phase transition is observed at about 5 T, associated by a spin-flop, suggesting the ferromagnetic ordering is induced by an antiferromagnetic interaction. A broad maximum in the ac susceptibility at TM = 23-24 K indicates an intermediate short-range ordering.

Journal Article↗
PubMed2006

Regulation of cancer-related growth factor expression by artificial zinc-finger proteins.

One attractive approach to anticancer therapy is repression of expression of vascular endothelial growth factor (VEGF) gene, which is a potent target for prevention of tumor growth. To achieve this, artificial transcription factors (ATF) designed for VEGF gene regulation were fused to cell-penetrating peptides (CPPs). We demonstrated ATFs fused to CPPs, designated CPP-ATFs or designed regulatory proteins (DRPs), could penetrate into mammalian cells and transiently repress expression of a reporter gene, which was under control of the VEGF promoter/5'-UTR. We discuss gene-regulatory properties of CPP-ATFs in detail.

Angiogenesis Inhibitors↗
PubMed2006

Osteopontin participates in Th1-mediated host resistance against nonlethal malaria parasite Plasmodium chabaudi chabaudi infection in mice.

Osteopontin (OPN) knockout mice (OPN-KO mice) died of Plasmodium chabaudi chabaudi infection, although wild-type (WT) mice had self-limiting infections. OPN was detected in the WT mice at 2 days postinfection. OPN-KO mice produced significantly smaller amounts of interleukin-12 and gamma interferon than WT mice produced. These results suggested that OPN is involved in Th1-mediated immunity against malaria infection.

Animals↗
PubMed2006

Gender difference in coronary events in relation to risk factors in Japanese hypercholesterolemic patients treated with low-dose simvastatin.

BACKGROUND: Gender differences between the risk factors for coronary heart disease and coronary events were examined in the Japan Lipid Intervention Trial, a 6-year observational study. METHODS AND RESULTS: Men (12,575) and women (27,013) were analyzed for risk of coronary events (acute myocardial infarction and sudden cardiac death). Simvastatin reduced serum low-density lipoprotein cholesterol (LDL-C) by 27% in both genders, and increased serum high-density lipoprotein cholesterol (HDL-C) in men (5%) and women (4%). The incidence of coronary events was lower in women (0.64/1,000 patient-years) than in men (1.57/1,000 patient-years). The risk of coronary events increased by 18% in men and 21% in women with each 10 mg/dl elevation of LDL-C, and decreased by 39% in men and 33% in women with each 10 mg/dl elevation of HDL-C. The risk increased proportionally with aging in women, but not in men. Diabetes mellitus (DM) was more strongly related to the risk of coronary events for women (relative risk 3.07) than for men (relative risk 1.58). CONCLUSIONS: The incidence of coronary events is lower in women. Serum LDL-C is related to an increased risk of coronary events to the same extent in both genders. DM seems to be a more important risk factor in women, trading off the lower risk of coronary events among them.

Adult↗
PubMed2006

Molecular cloning and characterization of an enzyme hydrolyzing p-nitrophenyl alpha-D-glucoside from Bacillus stearothermophilus SA0301.

Bacillus stearothermophilus SA0301 produces an extracellular oligo-1,6-glucosidase (bsO16G) that also hydrolyzes p-nitrophenyl alpha-D-glucoside (Tonozuka et al., J. Appl. Glycosci., 45, 397-400 (1998)). We cloned a gene for an enzyme hydrolyzing p-nitrophenyl alpha-D-glucoside, which was different from the one mentioned above, from B. stearothermophilus SA0301. The k(0)/K(m) values of bsO16G for isomaltotriose and isomaltose were 13.2 and 1.39 s(-1).mM(-1) respectively, while the newly cloned enzyme did not hydrolyze isomaltotriose, and the k(0)/K(m) value for isomaltose was 0.81 s(-1).mM(-1). The primary structure of the cloned enzyme more closely resembled those of trehalose-6-phosphate hydrolases than those of oligo-1,6-glucosidases, and the cloned enzyme hydrolyzed trehalose 6-phosphate. An open reading frame encoding a protein homologous to the trehalose-specific IIBC component of the phopshotransferase system was also found upstream of the gene for this enzyme.

Amino Acid Sequence↗
PubMed2006

Two cognitions observed in Taijin-Kyofusho and social anxiety symptoms.

The offensive type is most characteristic in four types of social fear or anxiety in Japan, Taijin-kyofusho. This type is characterized by cognitions of other-offending and avoidance-by-others. The present purpose was to investigate which cognition is more important in the pathogenesis of the Offensive type. 220 undergraduates completed the Other-offending Cognition and the Avoidance-by-others Cognition Scale, the Interaction Anxiety Scale, and Audience Anxiety Scale. Partial correlations, controlling for each cognition in turn, showed a significant association only between scores on Social Anxiety Disorder and the other-offending cognition. Change in the other-offending cognition may have therapeutic importance.

Adolescent↗
PubMed2006

Benefits of negative thinking and negative affect: analyses of answers to an open-ended question by Japanese undergraduates.

What are the benefits of negative thinking and negative affect? Although previous studies in evolutionary psychology, social psychology, and clinical psychology have clarified the question, there has been no definitive study asking people directly about the perceived benefits. In the present study, 119 Japanese undergraduates were asked how they recognized the benefits of negative thinking and negative affect. Their answers were analyzed qualitatively. The answers were arranged into 30 smaller categories and 12 superordinate ones. The benefits were divided into "benefits to the self" and "benefits to interpersonal relations". Finally, the conditions necessary for the negative thinking and negative affect being benign, and possible cultural differences, were discussed.

Adolescent↗
PubMed2006

Statins: beneficial or adverse for glucose metabolism.

Large-scale clinical trials have established that statin use for lowering blood cholesterol is beneficial in reducing atherosclerotic cardiovascular diseases in different populations. However, the general reputation of statins seems to be clouded by a potential adverse effect of a class of statins on glucose metabolism. This paper reviewed clinical data of statins regarding the effects on diabetes mellitus and glucose metabolism. At least five randomized controlled studies, primarily investigating the protective effect of statins on the risk of cardiovascular diseases, have addressed the effect of statins on glucose metabolism in Western countries. One study showed that pravastatin (40 mg/day) was protective against the development of diabetes mellitus. Two studies of atorvastatin (10 mg/day) and one study of simvastatin (40 mg/day) showed no measurable effect of these regimens on the risk of diabetes mellitus or the clinical course of diabetes mellitus. One study of atorvastatin (80 mg/day) versus pravastatin (40 mg/day) suggested a deterioration of glucose metabolism associated with a high dose of atorvastatin. In Japan, a few case reports have noted a potential adverse effect of atorvastatin on glycemic control in patients with diabetes mellitus; however, seven clinical trials have showed no such effect of atorvastatin although these studies were relatively small in size and short in follow-up. Only one of the two observational studies suggested a possible adverse effect of atorvastatin on glycemic control. Evidence is extremely limited regarding atorvastatin use and deterioration in glycemic control, and further studies are needed to draw a conclusion on this issue.

Atorvastatin↗
PubMed2006

Prevalence of metabolic syndrome in the general Japanese population in 2000.

To determine the prevalence of metabolic syndrome in the Japanese general population, we analyzed data from a nationwide survey conducted in 2000. According to the Japanese new diagnostic criteria for metabolic syndrome in 2005, we analyzed 3,264 people aged from 20 to 79 (men, 1,917; women, 1,347) from the total participants. The incidence of metabolic syndrome was 7.8%. Men had a higher incidence (12.1%) than women (1.7%). Most of the women satisfying the criteria were 50 years old or over, while the incidence in men started to rise from their 30s. When we applied the criteria of Adult Treatment Panel III, the incidence was about 3-fold higher. In this population visceral obesity was associated with metabolic abnormalities, such as higher LDL-cholesterol, triglyceride, glucose, and blood pressure and lower HDL-cholesterol. Thus we determined the incidence of metabolic syndrome and each metabolic abnormality in the Japanese general population in 2000 and found an association of visceral obesity with metabolic abnormalities. Intervention to reduce the incidence of metabolic syndrome in Japan is necessary to reduce the risk of cardiovascular disease.

Adult↗
PubMed2006

Treatment of hyperlipidemia from Japanese evidence.

The treatment of hyperlipidemia is aimed at preventing cardiovascular disease (CVD) and coronary heart disease (CHD). As the incidence of CHD in Japan is about one-third lower and that of stroke is two-fold higher compared to Western countries, and the doses of lipid-lowering drugs used in foreign randomized controlled clinical trials (RCTs) are much higher than in general use in Japan, it remains unclear whether the results of RCTs conducted in Western countries could be extrapolated to Japanese patients. Recently, two major large-scale, prospective, RCTs in Japanese hypercholesterolmic patients, the Management of Elevated Cholesterol in the Primary Prevention of Adult Japanese (MEGA) study and the Japan EPA Lipid Intervention Study (JELIS), have been reported. Japanese epidemiological studies and Japanese clinical studies are reviewed. The evidence suggests that hypercholesterolemia, hypertriglyceridemia, and low HDL-cholesterol are strongly associated with increased CHD risk. Lipid-lowering medication shows beneficial effects even in low-risk populations; however, the data did not support that lower cholesterol is better. The safety and efficacy of hyperlipidemia treatment in Japanese patients are discussed.

Asian People↗
PubMed2005

Photochromicity of Anabaena sensory rhodopsin, an atypical microbial receptor with a cis-retinal light-adapted form.

We characterize changes in isomeric states of the retinylidene chromophore during light-dark adaptation and photochemical reactions of Anabaena (Nostoc) sp. PCC7120 sensory rhodopsin (ASR). The results show that ASR represents a new type of microbial rhodopsin with a number of unusual characteristics. The three most striking are: (i) a primarily all-trans configuration of retinal in the dark-adapted state and (ii) a primarily 13-cis light-adapted state with a blue-shifted and lower extinction absorption spectrum, opposite of the case of bacteriorhodopsin; and (iii) efficient reversible light-induced interconversion between the 13-cis and all-trans unphotolyzed states of the pigment. The relative amount of ASR with cis and trans chromophore forms depends on the wavelength of illumination, providing a mechanism for single-pigment color sensing analogous to that of phytochrome pigments. In addition ASR exhibits unusually slow formation of L-like and M-like intermediates, with a dominant accumulation of M during the photocycle. Co-expression of ASR with its putative cytoplasmic transducer protein shifts the absorption maximum and strongly decreases the rate of dark adaptation of ASR, confirming interaction between the two proteins. Thus ASR, the first non-haloarchaeal sensory rhodopsin characterized, demonstrates the diversity of photochemistry of microbial rhodopsins. Its photochromic properties and the position of its two ground state absorption maxima suggest it as a candidate for controlling differential photosynthetic light-harvesting pigment synthesis (chromatic adaptation) or other color-sensitive physiological responses in Anabaena cells.

Anabaena↗
PubMed2005

The 5'-terminal region of the Aichi virus genome encodes cis-acting replication elements required for positive- and negative-strand RNA synthesis.

Aichi virus is a member of the family Picornaviridae. It has already been shown that three stem-loop structures (SL-A, SL-B, and SL-C, from the 5' end) formed at the 5' end of the genome are critical elements for viral RNA replication. In this study, we further characterized the 5'-terminal cis-acting replication elements. We found that an additional structural element, a pseudoknot structure, is formed through base-pairing interaction between the loop segment of SL-B (nucleotides [nt] 57 to 60) and a sequence downstream of SL-C (nt 112 to 115) and showed that the formation of this pseudoknot is critical for viral RNA replication. Mapping of the 5'-terminal sequence of the Aichi virus genome required for RNA replication using a series of Aichi virus-encephalomyocarditis virus chimera replicons indicated that the 5'-end 115 nucleotides including the pseudoknot structure are the minimum requirement for RNA replication. Using the cell-free translation-replication system, we examined the abilities of viral RNAs with a lethal mutation in the 5'-terminal structural elements to synthesize negative- and positive-strand RNAs. The results showed that the formation of three stem-loops and the pseudoknot structure at the 5' end of the genome is required for negative-strand RNA synthesis. In addition, specific nucleotide sequences in the stem of SL-A or its complementary sequences at the 3' end of the negative-strand were shown to be critical for the initiation of positive-strand RNA synthesis but not for that of negative-strand synthesis. Thus, the 5' end of the Aichi virus genome encodes elements important for not only negative-strand synthesis but also positive-strand synthesis.

Animals↗