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Thermally triggered shrinking rates of poly(N-isopropyl-acrylamide) (PNIPA) -based organic-inorganic hydrogel could be accelerated by applying the ice templating method. Freezing and subsequent rehydration of gels is an effective way to prepare the porous polymer network that leads to rapid expelling of pore water. The shrinking coefficients obtained by fitting Fick's law to the data increased two orders of magnitude as compared with the conventional gel before freezing. The microstructure of gels generated during freezing gels had advantage to expel the pore water rapidly probably due to the PNIPA aggregation through the hydrophobic interaction.

Statins have been reported to protect against end-organ damage in essential hypertension; however, detailed mechanisms underlying organ-protective actions of statins remain unclear. Statins can exert pleiotropic effects aside from lowering cholesterol and blood pressure levels through several different pathways, which may lead to distinct patterns of changes in gene expression in vital end-organs. The aim of the present study was to systemically evaluate gene expression changes in three major end-organs (the brain, heart and kidney) induced by atorvastatin at a dose that altered neither blood pressure nor plasma total cholesterol levels. The stroke-prone spontaneously hypertensive (SHRSP) rats, an established model of hypertension and end-organ damage, was treated with atorvastatin (15 mg/kg/day) for 4 weeks from 12 to 16 weeks of age. DNA microarray technology was used to identify gene expression changes in three end-organs. In the current experimental setting, 4 weeks of atorvastatin treatment lowered plasma levels of non-esterified fatty acid significantly (P=0.0012) and triglyceride modestly (P=0.07) without altering blood pressure and plasma total cholesterol levels in male SHRSP rats. The level of expression of a number of genes was changed in an organ-specific manner after 4 weeks of drug administration to SHRSP rats. Among the end-organs studied, the most prominent alteration in gene expression was observed in the heart. The identical treatment protocol was applied to age-matched normotensive control rats, Wistar Kyoto rats, and this also caused a number of genes to be differentially expressed in an organ-specific manner. These results provide new insights into the mechanisms underlying the potential efficacy of statins in protecting against end-organ damage in essential hypertension and thus lay the foundation for future studies.

To systematically evaluate genetic susceptibility to type 2 diabetes (T2D) in “candidate” regions on chromosomes 1q, 3q and 12q, we examined disease association by using a total of 2,083 SNPs in two-step screening; a screening panel comprised 473 cases and 285 controls and an extended (or combined) panel involved 658 cases and 474 controls. For the total interval screened (40.9 Mb), suggestive evidence of association was provided for several annotated gene loci. For example, in the MCF2L2 gene on 3q, a significant association (a nominal P value of 0.00009) was observed when logistic regression analysis was performed for three associated SNPs (rs684846, rs35069869 and rs35368790) that belonged to different LD groups. Also, in the SLC15A4 gene on 12q, rs3765108 showed a marginally significant association with an overall estimated odds ratio of 0.79 (P = 0.001). No significant association was found for known candidate gene loci on 3q, such as ADIPOQ and IGF2BP2. Using the available samples, we have observed disease associations of SNPs derived from two novel gene loci in the Japanese population through high-density searches of diabetes susceptibility in three chromosomal regions. Independent replication will clarify the etiological relevance of these genomic loci to T2D.

In tests, Chromobacterium violaceum ATCC 12472 produced several N-acyl-L-homoserine lactones (AHLs). Of these, N-(3-hydroxydecanoyl)-L-homoserine lactone was dominant, and controlled violacein production by quorum sensing. Strain VIR07, an AHL-deficient mutant, did not produce violacein. Violacein production in VIR07 was induced by adding long-chain AHLs (C10-C16), but was inhibited by adding short-chain AHLs (C4-C8). Strain VIR07 showed the response of violacein production when AHLs diffused from a variety of AHL-producing bacteria on agar plates, and thus might be a useful biosensor for recognizing exogenous AHLs.

A number of gram-negative bacteria have a quorum-sensing system and produce N -acyl- l -homoserine lactone (AHL) that they use them as a quorum-sensing signal molecule. Pantoea ananatis is reported as a common colonist of wheat heads at ripening and causes center rot of onion. In this study, we demonstrated that P. ananatis SK-1 produced two AHLs, N -hexanoyl- l -homoserine lactone (C6-HSL) and N -(3-oxohexanoyl)- l -homoserine lactone (3-oxo-C6-HSL). We cloned the AHL-synthase gene ( eanI ) and AHL-receptor gene ( eanR ) and revealed that the deduced amino acid sequence of EanI/EanR showed high identity to those of EsaI/EsaR from P. stewartii . EanR repressed the ean box sequence and the addition of AHLs resulted in derepression of ean box. Inactivation of the chromosomal eanI gene in SK-1 caused disruption of exopolysaccharide (EPS) biosynthesis, biofilm formation, and infection of onion leaves, which were recovered by adding exogenous 3-oxo-C6-HSL. These results demonstrated that the quorum-sensing system involved the biosynthesis of EPS, biofilm formation, and infection of onion leaves in P. ananatis SK-1.

Essential hypertension is one of the most common, complex diseases, of which considerable efforts have been made to unravel the pathophysiological mechanisms. Over the last decade, multiple genome-wide linkage analyses have been conducted using 300-900 microsatellite markers but no single study has yielded definitive evidence for 'principal' hypertension susceptibility gene(s). Here, we performed a three-tiered, high-density association study of hypertension, which has been recently made possible. For tier 1, we genotyped 80 795 SNPs distributed throughout the genome in 188 male hypertensive subjects and two general population control groups (752 subjects per group). For tier 2 (752 hypertensive and 752 normotensive subjects), we genotyped a panel of 2676 SNPs selected (odds ratio >or= 1.4 and P

Significant evidence of linkage to type 2 diabetes (T2D) has been shown in a relatively broad region on chromosome 20q, where the hepatocyte nuclear factor-4α ( HNF4A ) has been noted as a positional candidate. To systematically evaluate genetic susceptibility to T2D in the relevant region, we examined the disease association by using 1145 SNPs in two-step screening in the Japanese population. The marker screening enabled us to identify significant disease association in the lipopolysaccharide binding protein ( LBP ) but not in the HNF4A locus. In a 17.7-Mb interval screened, the strongest association was identified for a SNP, rs2232592, located in the intron of LBP , with an estimated odds ratio of 1.73 (95% CI 1.30–2.31) ( P = 0.0002) in the whole study panel involving 675 case and 474 control subjects. Our data suggest that the LBP gene may confer genetic susceptibility to T2D and this warrants further replication study.

Angiotensin-converting enzyme (ACE) 2, a newly emerging component of the renin-angiotensin system, is presumed to be a counterregulator against ACE in generating and degrading angiotensin II. It remains to be elucidated how mRNA levels of these two genes are quantitatively regulated in the kidney and also what kind of clinicopathological characteristics could influence the gene expressions in humans. Seventy-eight cases of biopsy-proven renal conditions were examined in detail. Total RNA from a small part of each renal cortical biopsy specimen was reverse transcribed, and the resultant cDNA was amplified for ACE, ACE2, and glyceraldehyde-3-phosphate dehydrogenase with a real-time PCR system. Then we investigated the relationship between clinicopathological variables and mRNA levels adjusted for glyceraldehyde-3-phosphate dehydrogenase. Statistically significant correlation was not observed between any clinicopathological variables and either of the gene expressions by pairwise comparison. However, a strong correlation was observed between the gene expressions of ACE and those of ACE2. Moreover, the ACE to ACE2 ratio was significantly higher in subjects with hypertension (HT) than that in subjects without HT. Whereas parameters of renal function, e.g. urinary protein excretion (UPE) and creatinine clearance (Ccr), are not significantly related to the ACE to ACE2 ratio as a whole, the HT status may reflect disease-induced deterioration of renal function. That is, UPE and Ccr of subjects with HT are significantly different from those without HT, in which a significant correlation is also observed between UPE and Ccr. Finally, stepwise regression analysis further revealed that only the HT status is an independent confounding determinant of the ACE to ACE2 ratio among the variables tested. Our data suggest that ACE2 might play an important role in maintaining a balanced status of local renin-angiotensin system synergistically with ACE by counterregulatory effects confounded by the presence of hypertension. Thus, ACE2 may exert pivotal effects on cardiovascular and renal conditions.

The Malay people are an important ethnic composition in Southeast Asia, but their genetic make-up and population structure remain poorly studied. Here we conducted a genome-wide study of four geographical Malay populations: Peninsular Malaysian Malay (PMM), Singaporean Malay (SGM), Indonesian Malay (IDM) and Sri Lankan Malay (SLM). All the four Malay populations showed substantial admixture with multiple ancestries. We identified four major ancestral components in Malay populations: Austronesian (17%–62%), Proto-Malay (15%–31%), East Asian (4%–16%) and South Asian (3%–34%). Approximately 34% of the genetic makeup of SLM is of South Asian ancestry, resulting in its distinct genetic pattern compared with the other three Malay populations. Besides, substantial differentiation was observed between the Malay populations from the north and the south and between those from the west and the east. In summary, this study revealed that the genetic identity of the Malays comprises a mixed entity of multiple ancestries represented by Austronesian, Proto-Malay, East Asian and South Asian, with most of the admixture events estimated to have occurred 175 to 1,500 years ago, which in turn suggests that geographical isolation and independent admixture have significantly shaped the genetic architectures and the diversity of the Malay populations.

Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P < 5 × 10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7 single-nucleotide polymorphisms are with low frequency (MAF < 5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians.

Inclusion complex between cyclodextrins (CDs) and bacterial signal molecules is responsible for inhibitory effects on quorum sensing (QS). Since many bacteria have QS system for controlling gene expression in response to cell population density by means of signal molecules, an intercept of the QS signal onto the CDs can be a general method to control transcription of the QS-regulated genes. The QS in the opportunistic pathogen Serratia marcescens could be artificially controlled by trapping the QS signal N-acylhomoserine lactones (AHLs) onto the CDs because AHLs are known to work as a common QS signal in gram negative bacteria. After S. marcescens was cultured in the presence of 10 mM 2−hydroxypropyl-β-CD (HP-β-CD), the relative prodigiosin production could be reduced to approximately 0.86. Nonspecific adsorption of AHLs onto the cellulose ether gel sheets was very little because the relative production of prodigiosin remained 0.95–1.00 after the immersion of the gel sheets in the liquid medium throughout the cell culture. Addition of both anionic carboxymethyl cellulose gel sheets and 10 mM HP-β-CD in the culture medium effectively controlled the relative prodigiosin production to approximately 0.56. This result suggested that the ionic interaction between acceptor molecules and the AHLs could stabilize the inclusion complex and then block the sequential QS-regulated process. Moreover, CD-immobilized polymer gel sheets have high potential for the QS regulation because HP-β-CD-immobilized hydroxypropyl cellulose or hydroxypropyl methyl cellulose gel sheets effectively controlled the prodigiosin production.

The spontaneously hypertensive rat (SHR) is a model of human insulin resistance syndrome. Quantitative trait loci for cellular defects in glucose and fatty acid metabolism have been mapped to an overlapping region of rat chromosome (RNO) RNO4 in SHR of the National Institute of Health colony, where a deletion in the Cd36 gene has been implicated as the causative mutation of insulin resistance. The present study has examined the potential presence of RNO4 linkage to a series of metabolic phenotypes in F2 progeny derived from SHR of a Japanese colony (SHR/Izm) without the Cd36 mutation. Our data demonstrate that ‘major’ insulin resistance gene(s) are unlikely to exist on RNO4 in SHR/Izm and in vitro phenotypes measured in isolated adipocytes do not cosegregate in the F2 population studied. Thus, it seems to be difficult to explain the underlying genetic mechanisms of insulin resistance by a single major gene on RNO4.

Cardiac hypertrophy and left ventricular hypertrophy are known to be substantially controlled by genetic factors. As an experimental model, we undertook genome-wide screens for cardiac mass in F2 populations bred from the stroke-prone spontaneously hypertensive rats (SHRSP) and normal spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) of a Japanese colony. Two F2 cohorts were independently produced: F2(SHRSP x WKY) (110 male and 110 female rats) and F2(SHR x WKY) (151 male rats). The ratio of heart weight to body weight (Hw/Bw) was evaluated at 12 months of age in F2(SHRSP x WKY) after salt-loading for 7 months, and at around 15 weeks of age in F2(SHR x WKY) who had been fed a normal rat chow diet. Subsequent to an initial screen with 251 markers in F2(SHRSP x WKY) male progeny, 170 and 161 markers were selected and characterized in F2(SHRSP x WKY) female progeny and F2(SHR x WKY) male progeny, respectively. Markers from four chromosomal regions showed suggestive or significant linkage to Hw/Bw. The strongest and the most consistent linkage was found in the vicinity of D3Mgh16 on rat chromosome (RNO) 3 (a maximal log of the odds score reached 4.0 to 6.6 across the F2 populations studied). In the other three regions on RNO6, RNO10 and RNO13, the degree of linkage was more prominent in either males or females. These data provide solid evidence for a "principal" RNO3 quantitative trait loci regulating Hw/Bw in SHRSP and SHR, and also suggest the possible presence of sexual dimorphism in regard to genetic susceptibility for cardiac hypertrophy.

Type 2 diabetes mellitus is a heterogeneous disorder, and the development of type 2 diabetes mellitus is associated with both insulin secretion defect and insulin resistance. The primary metabolic defect leading to type 2 diabetes mellitus has been thought to be varied among populations, especially in Japanese and Caucasians. Here, we have done the genome-wide scan for type 2 diabetes mellitus using 102 affected Japanese sib-pairs to identify the genetic factors predisposing to type 2 diabetes mellitus. Nonparametric linkage analysis showed one suggestive evidence for linkage to 11p13-p12 [D11S905: two-point maximum LOD score (MLS) of 2.89 and multipoint MLS of 2.32] and one nominally significant evidence for linkage to 6q15-q16 (D6S462: two-point MLS of 2.02). Interestingly, the 11p13-p12 region was reported to be a susceptibility locus for Japanese type 2 diabetes mellitus with suggestive evidence of linkage, and D11S905 was within 5 cM to D11S935 with the highest MLS in the previous linkage analysis reported. The only overlapped susceptibility region with suggestive evidence of linkage for Japanese type 2 diabetes mellitus was D11S935-D11S905 among the three reports including this study. These results taken together suggest that a susceptibility gene for type 2 diabetes mellitus in Japanese will reside in 11p13-p12.

Although several quantitative trait loci for blood pressure have been reported in stroke-prone spontaneously hypertensive rats (SHRSP), the results are not always concordant among different crosses. To evaluate potential confounding factors in linkage analysis, we performed genome-wide screens in F2 populations derived from SHRSP and Wistar-Kyoto rats of a Japanese colony.Two F cohorts were independently produced: F2-1 (110 male and 110 female rats), and F2-2 (174 male and 184 female rats). Blood pressure was measured longitudinally (from 2 to 5 months of age and 1 month after salt-loading) in F2-1, while it was measured at 13 weeks of age in F2-2. Subsequent to an initial screen with 251 markers in F2-1 male progeny, 170 markers were selected and characterized in the remaining populations.When 578 rats were analyzed together, markers from five chromosomal regions showed significant linkage to blood pressure at 13 weeks of age. The strongest and the most consistent linkage was found on rat chromosome 1 (a maximal log of the odds score reached 8.3). In the other regions, the degree of linkage was more prominent in either of sexes. Some evidence of age-specific and sex-specific linkage was detected in five additional regions in the F2-1 cohort. In the Japanese colony, however, there was no significant linkage to several chromosomal regions previously reported in other SHRSP colonies.Our data provide solid evidence of a chromosome-1 linkage and demonstrate the importance of aging, sex, and dietary manipulation in linkage analysis. Also, the combination of parental rat strains seems to be critical when searching for blood pressure quantitative trait loci.

We have witnessed great success in the identification of new type 2 diabetes susceptibility loci through genome‐wide association (GWA) analysis in the past 5 years. The number of loci robustly implicated in type 2 diabetes risk; that is, those that have attained a genome‐wide significance level (P 50 today. As these GWA studies were carried out almost exclusively in European‐descent populations, studies in non‐European populations will allow us to assess the relevance of the findings to other ethnic groups. To address this point, a consortium‐based GWA meta‐analysis of type 2 diabetes was recently carried out in East Asians with a multistage study design (involving >25,000 cases and >29,000 controls in total)1; eight new loci were confirmed to significantly associate with type 2 diabetes. This large‐scale GWA meta‐analysis was principally carried out in the Asian Genetic Epidemiology Network (AGEN), in which our group participated together with investigators from Japan, Korea, China, Taiwan, Singapore and the USA.

The properties of cationic surfactant-clay mixtures were examined by measurements of the electric conductivity, absorption spectra, and X-ray diffraction patterns. The orientation of N-[[4-(aminoiminomethyl)amino]butyl]dodecanamide (DAG) as a intercalated cationic surfactant and the thickness of the interlayer space of clay using Na-saponite (Sumecton SA) were investigated. DAG molecules were intercalated in a 1 nm gap in the interlayer space of clay. It is speculated that alkyl groups of the surfactant molecules are placed not parallel, but inclined slightly vertical to the internal surface of Na-saponite.

Although a variety of techniques have been devised to assess salt sensitivity, most have proven cumbersome from a methodological perspective. We therefore attempted to develop a 2-week method by which participants could be tested in an outpatient setting without requirement of a strict dietary regimen. In this method, subjects take 140 mEq of an NaCl supplement per day for 1 week and 25 mg of hydrochlorothiazide daily for another week while maintaining their customary diet. In our first trial, 8 healthy volunteers submitted to this method, as well as to a widely-used rapid volume expansion and contraction protocol. Blood pressure measurements, blood sampling and 24-h urine collection were performed before, in the middle of, and after each intervention. There was a fair correlation (r = 0.69) between the two protocols with respect to the changes in mean blood pressure (deltaMBP), a measure of salt sensitivity. In our second trial, we tested the method on 82 Japanese subjects who had never been treated with antihypertensive drugs. DeltaMBP was significantly correlated with plasma renin activity (PRA) during salt loading (r = 0.52, p < 0.0001) and with the changes in atrial natriuretic peptide (deltaANP) (r = -0.34, p = 0.0018). When total subjects were divided into two subgroups by age, a similar tendency of correlation was observed. Age, PRA during salt loading, deltaANP, and delta norepinephrine were proven to be significant predictors of salt sensitivity and accounted for 46% of the deltaMBP variances. Based on these results, the dietary method presented here seems to be applicable for a population-based survey. Our preliminary data also suggest that PRA and ANP would be of predictive value in the salt sensitivity test.

Hypertension is considered to be a complex trait to which genetic, environmental, and demographic factors contribute interactively. Recently, molecular genetic studies have achieved remarkable success in the elucidation of causative mutations in several Mendelian hypertensive disorders in which single nucleotide polymorphisms (SNPs) disrupt the function of single genes, thereby leading to unambiguous phenotypes. It seems unlikely, however, that such a simple base-substitution is the primary mechanism in cases of essential hypertension, even if SNPs modify the relevant gene function to some extent. Despite the enormous efforts made to date, no consistent association between any of the candidate genes and essential hypertension has been established. One plausible explanation is that because individual genes play a modest role in the pathogenesis of hypertension, confounding variables, whether individual (sex, ethnic origin, etc.) or environmental, may decrease the chance of identifying a causative relation between the genes and hypertension, depending on the populations studied. Several approaches can be proposed to overcome this problem, including long-term follow-up of clinical events collected to attain sufficient phenotypic information and statistical power. With the recent advances in high-throughput genotyping techniques and bioinformatic strategies, it has become possible to perform even SNP-based genome-wide screening. At present, however, the need for identification of susceptibility genes for hypertension still poses a great and unanswered challenge. Nonetheless, we believe that a precise understanding of the manner in which genetic variations affect hypertension can be achieved, and that clarification of the associated phenotypes will lead to the development of effective preventive and treatment strategies.

We fabricated 2.1GHz TM010-mode microwave resonators with (Bi, Pb)2Sr2Ca2Cu3Ox (Bi2223) superconducting thick films on a Ba(Sn, Mg, Ta)O3 dielectric disk with a relative dielectric constant of er=24. The Bi2223 thick films were screen-printed on both sides of the dielectric disk and subjected to a double repetition of cold isostatic pressing at 0.4GPa and sintering at various temperatures ranging from 820 to 840°C. An increase of the sintering temperature raises the Bi2223 phase purity up to 98% on the surfaces of the thick films, but high-temperature sintering above 830°C causes a chemical reaction at the interface between the Bi2223 thick film and the dielectric disk. An optimization of the sintering temperature to 830°C gives the unloaded quality factors Qu as much as 74, 000 at 70K and 158, 000 at 25K, which correspond to surface resistances Rs of 0.34 and 0.15mΩ for Bi2223 thick films, respectively. These values are approximately 20 times higher than those for the resonator using Ag electrodes with the same structure.

Introduction American Diabetes Association (ADA) has officially endorsed glycosylated haemoglobin (HbA 1c ) as a diagnostic tool. The recommended cut-off for diagnosing diabetes is ≥6.5%. Objectives To compare use of HbA 1c and fasting plasma glucose (FPG) to diagnose diabetes in an urban Sri Lankan community. Methods This cross-sectional study is based on baseline data from a prospective study on non-communicable diseases in randomly selected individuals aged 35-64 years in a selected community. HbA 1c was measured by National Glycohaemoglobin Standardization Program certified Bio Rad Variant HbA 1c HPLC method. Diagnostic performance of HbA 1c was evaluated in those without previous diabetes. Receiver Operating Characteristic Curve was used to identify optimum HbA 1c threshold. Results We studied 2516 individuals with no previous history of diabetes. Of these 53.8% were women. Mean age was 52±7.9 years. FPG was ≥7mmol/l in 245(9.7%). HbA 1c was ≥6.5% in 173(6.9%). Concordance between FPG and HbA 1c was 95% (both criteria positive: 5.8%; both criteria negative: 89.2%). Compared to FPG, HbA 1c cut-off of ≥6.5% had specificity of 98.9% (95% CI 98.3-99.3) and sensitivity of 60% (95% CI 53.6-66.2). Positive and negative predictive values were 85% (95% CI 78.8-89.9) and 95.8% (95% CI 94.9-96.6), respectively. Compared to FPG, optimum HbA 1c threshold for diagnosing diabetes was 5.9% (sensitivity: 84%; specificity: 88.8%; area under the curve: 0.91). Conclusions In the study population, detection of diabetes with ADA recommended HbA 1c criterion was 29% less than with FPG criterion. Compared to FPG, HbA 1c had high specificity but sensitivity was low. Further research is needed to refine the optimum HbA 1c threshold in Sri Lankans.

Background/Objective The 16q12.2 locus in the first intron of FTO has been robustly associated with body mass index (BMI) and type 2 diabetes in genome-wide association studies (GWAS). To improve the resolution of fine-scale mapping at FTO, we performed a systematic approach consisting of two parts. Methods The first part is to partition the associated variants into linkage disequilibrium (LD) clusters, followed by conditional and haplotype analyses. The second part is to filter the list of potential causal variants through trans-ethnic comparison. Results We first examined the LD relationship between FTO SNPs showing significant association with type 2 diabetes in Japanese GWAS and between those previously reported in European GWAS. We could partition all the assayed or imputed SNPs showing significant association in the target FTO region into 7 LD clusters. Assaying 9 selected SNPs in 4 Asian-descent populations—Japanese, Vietnamese, Sri Lankan and Chinese (n≤26,109 for BMI association and n≤24,079 for type 2 diabetes association), we identified a responsible haplotype tagged by a cluster of SNPs and successfully narrowed the list of potential causal variants to 25 SNPs, which are the smallest in number among the studies conducted to date for FTO. Conclusions Our data support that the power to resolve the causal variants from those in strong LD increases consistently when three distant populations—Europeans, Asians and Africans—are included in the follow-up study. It has to be noted that this fine-mapping approach has the advantage of applicability to the existing GWAS data set in combination with direct genotyping of selected variants.

Aims/Introduction: Resistin, an inflammatory cytokine, might be involved in the development of atherosclerosis. In a recent paper, we showed that resistin polymorphism might be a risk marker for stroke susceptibility in Japanese type 2 diabetic patients. We tested whether the serum resistin levels might be also a risk marker of stroke independently from RETN polymorphism. Materials and Methods: Type 2 diabetic outpatients from our hospitals were enrolled. Patients (n = 89) with a history of coronary heart disease and stroke, and randomly selected controls (n = 178) matched for sex and age, but without a history of coronary heart disease and stroke, were examined for polymorphism ‐420 (C>G) and cytokines levels. Results: Serum resistin levels were significantly higher in patients with cardiovascular diseases (CVD) than in those without CVD (P = 0.024), and were highest in patients with stroke among the CVD. In multiple logistic regression analysis, serum resistin levels was an independent risk marker of stroke even after adjusted by RETN polymorphism, age, sex, body mass index, HbA1c, systolic and diastolic blood pressure, triglyceride, low density lipoprotein cholesterol, high density lipoprotein cholesterol, creatinine, history of coronary heart disease, treatment of insulin, sulfonylurea and aspirin (odds ratio 1.33, 95% confidence interval [CI] 1.02–1.73, P = 0.039). The enrolled patients were divided by their serum resistin levels (high or low group) and their genotypes (CC, CG, GG at ‐420) into six groups. Patients with the GG genotype and high resistin levels showed the highest odds ratio, 5.69 (95% CI 1.24–26.1), compared with the group with CC and low levels. Conclusions: The results suggest that serum resistin levels might be a good marker of susceptibility to stroke as well as RETN polymorphism. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.00040.x, 2010)

The 9p21 region has been pointed out by the genome-wide association studies as a hot spot for disease-associated variants. Most of the diseases linked with the locus are aging-related conditions, such us cardiovascular disease, diabetes and cancer. Centenarians are known to present a reduced risk and delayed onset for these conditions. Here, we aimed to assess if the 9p21 variants contribute to this protection by possibly altering basic aging mechanisms.We genotyped 15 tag single-nucleotide polymorphisms (SNP) along the CDKN2A/B/ANRIL locus in 1505 individuals. The participants were divided in three groups: centenarians, septuagenarians and young controls. Centenarians were 593 participants (age range 100-116 years, mean 105.9 years), septuagenarians were 434 volunteers aged between 69 and 71 years (mean 70.1 ± 0.9 years) and the 478 young controls were under the age of 50 years (range 14-50 years, mean 41.8 years). We genotyped the SNP rs1333049 in an additional sample of 231 coronary artery disease patients to confirm the 9p21 association.The leading coronary artery disease-associated SNP rs1333049 was associated with coronary artery disease; however, none of the 9p21 SNP evaluated in the present study were associated with extreme longevity.Our findings suggest that the 9p21 disease-associated polymorphisms do not contribute to the life-long protection from cardiovascular and other age-related diseases observed in centenarians. It is likely that this protection is mediated by mechanisms different from the ones underlying the 9p21 association.

The adsorption of dimethylsilicone (DMS) from its emulsion onto hair-surface models was investigated. The model surfaces were prepared on silicon wafers by utilizing a micro-phase separation in mixed Langmuir monolayers with a chemically adsorptive organosilane, n-octadecyltriethoxysilane (ODTES), as one component. The resulting surfaces consisted of hydrophobic micro-domains of polymerized ODTES and a surrounding hydrophilic surface silanol (SiOH) region of the silicon wafer, corresponding to the healthy and damaged regions of the hair surface, respectively, in terms of surface wettability. DMS preferentially adsorbed onto the high surface energy hydrophilic region of the model surface when the hydrophobic micro-domains were composed of fully condensed alkyl chains. The surface energy of the micro-domains could be controlled by using palmitic acid (PA) as the second component to form the micro-domains in the phase-separated Langmuir monolayers. The increase in the surface energy of the micro-domains induced the adsorption of DMS onto the intrinsically hydrophobic domain surface.

Recent genetic association studies have identified 55 genetic loci associated with obesity or body mass index (BMI). The vast majority, 51 loci, however, were identified in European-ancestry populations. We conducted a meta-analysis of associations between BMI and ∼2.5 million genotyped or imputed single nucleotide polymorphisms among 86 757 individuals of Asian ancestry, followed by in silico and de novo replication among 7488-47 352 additional Asian-ancestry individuals. We identified four novel BMI-associated loci near the KCNQ1 (rs2237892, P = 9.29 × 10(-13)), ALDH2/MYL2 (rs671, P = 3.40 × 10(-11); rs12229654, P = 4.56 × 10(-9)), ITIH4 (rs2535633, P = 1.77 × 10(-10)) and NT5C2 (rs11191580, P = 3.83 × 10(-8)) genes. The association of BMI with rs2237892, rs671 and rs12229654 was significantly stronger among men than among women. Of the 51 BMI-associated loci initially identified in European-ancestry populations, we confirmed eight loci at the genome-wide significance level (P < 5.0 × 10(-8)) and an additional 14 at P < 1.0 × 10(-3) with the same direction of effect as reported previously. Findings from this analysis expand our knowledge of the genetic basis of obesity.

The kinetic parameters of deswelling and the change of a lower critical solution temperature (LCST) for poly(N-isopropylacrylamide) gel, poly(NIPAAm) gel, were investigated in the presence of glucose and other sugars as hydrophilic probes. The enthalpy of activation (ΔH≠) and the entropy of activation (ΔS≠) for deswelling were influenced by the concentration of additive sugars. Plots of ΔH≠ against TΔS≠ fell on a straight line, of which the slope was approximately 0.91–0.94. This result shows a compensation effect of the free energy of activation (ΔG≠) concerning the relationship between ΔH≠ and ΔS≠ for deswelling of poly(NIPAAm) gel. The molecular interaction between sugar and water clusters involved with the polymer is responsible for the compensation effect between ΔH≠ and ΔS≠. The equatorial hydroxy groups of sugar molecules interact easily with water clusters around the hydrophobic isopropyl groups (the iceberg) to form hydrogen bonds, which give rise to change the situation of polymer hydration. A d...

Thermally sensitive poly( N -isopropylacrylamide/acrylamide) gel, which exhibits a thermal property of a lower critical solution temperature (LCST), was applied as a carrier immobilizing amyloglucosidase (AG) in order to form a glycosidic bond. Isomaltose and maltose were produced from glucose in a process of reverse reaction of hydrolysis using immobilized AG. Isomaltose was accumulated predominantly in the enzymatic reaction with 2 mol dm −3 glucose solution, while AG hydrolyzed maltose to glucose in the process. The yield of isomaltose was 13 times as much as that of maltose catalyzed by the immobilized AG under the swelling state of the gel at 20 °C. The role of polymer gel for isomaltose synthesis was discussed in connection with the LCST.

The surface property of vessels (matrices) for gelation affected the deswelling process of thermosensitive poly(N-isopropylacrylamide) (NIPAAm) gels. Cracks were frequently observed on the gel surface in the process of deswelling. The outbreak of cracks caused a change of the deswelling rates. The deswelling rate was accelerated in the case of the gel prepared in a matrix made of hydrophobic polytetrafluoroethylene (PTFE) or silicone, while no acceleration for deswelling was observed in the case of the gel prepared on hydrophilic glass. The probability of cracking and the deswelling rate increased with increasing hydrophobicity of the matrix surface. The storage moduli (E′) of the swollen gels (22°C) prepared on glass and PTFE as the matrices were 50 and 18 kPa, respectively. The deswelling time for gels prepared in PTFE matrix decreased from 400 (gels prepared on glass) to 50 min without cracking. The hydrophobic matrix was suitable for preparation of the fast-responsive poly(NIPAAm) gel.

Significant evidence has been provided for the pathophysiological involvement of the β 2 -adrenergic receptor ( ADRB2 ) in hypertension. Among ADRB2 polymorphisms identified to date, 2 amino acid substitutions, Arg16Gly and Gln27Glu, and a promoter variant, T-47C, are considered functionally important. In particular, Arg16Gly was shown to be associated with hypertension in black and white subjects. To investigate the relevance of ADRB2 polymorphisms to hypertension, we undertook an extensive association study in a Japanese population. An association was tested in 2 ways. First, a case-control study was conducted in 842 hypertensive and 633 normotensive subjects. In addition to the overall comparison between case and control groups, each was stratified by body mass index and compared with an independent panel of 525 diabetic subjects. Second, ANOVA and multivariate analyses were performed to test the significance of an association between ADRB2 genotype and the level of blood pressure within the entire population except for 395 subjects who had been under treatment for hypertension. Although no significant association was observed for Arg16Gly and T-47C, 2 analytical methods indicated a marginal association ( P =0.01 to 0.04) between the Glu27 variant and lower blood pressure levels. Given such a normotensive propensity, the odds ratio for Glu27 versus Gln27 allele frequencies was estimated to be 0.74, with a wide confidence interval (95% CI, 0.55 to 0.99) reflecting the low Glu27-allele frequency (6% to 8%) in Japanese. There were no apparent confounding influences of obesity and diabetes on the postulated association. Our data suggest that 3 ADRB2 polymorphisms tested are unlikely to confer principal genetic susceptibility for hypertension in the Japanese population. However, further investigation is warranted to clarify the relevance of ADRB2 polymorphisms to blood pressure regulation.

ヤギ毛への酸性色素オレンジIIの吸着に関して，毛に浸透し色素を毛に吸着しやすくすると考えられているベンジルアルコールの影響，色素吸着に及ぼすpHや温度，グリシンや各種ヒドロキシ酸の存在などの影響を定量的に検討した． ベンジルアルコール無添加の場合，ΔSの値はすべて負になり，またΔHは−25 – −100 kJ mol−1の範囲にあるので，ヤギ毛のタンパク質に対して色素は主に水素結合あるいはイオン結合していると推察する．グリコール酸，乳酸などヒドロキシ酸の場合は，リン酸よりもΔHがより負側にシフトした．グリシンでは，低pHになるとH3N+–CH2–COO−よりH3N+–CH2–COOHが多くなり，色素は毛に吸着しやすい． グリコール酸とともにベンジルアルコールを添加すると，ΔH，ΔSは共に正になった．ベンジルアルコールは毛に浸透し色素吸着面を広げるので，色素の吸着速度は速くなり，また色素飽和吸着量もベンジルアルコール無添加に比べると大きい．一方，平衡定数は小さくなり，色素のヤギ毛タンパク質への結合を阻害するようである．ベンジルアルコールがヤギ毛の内部へ浸透することは，色素吸着がLangmuir吸着等温式で扱うような簡単な吸着平衡では説明できないことを示している．

AIM To properly assess the guidance for perioperative management, we undertook a clinical epidemiology study with the primary aim of evaluating the incidence of perioperative vascular complications and their associated factors in a cohort of Japanese patients who underwent non-cardiac surgery in a tertiary medical care center. METHODS This observational study comprised two parts. In the first part, thrombotic and bleeding events and their risk factors in the perioperative period were evaluated in a total of 2,654 consecutive patients. In the second part, perioperative changes in coagulation-related factors, including the thrombin-antithrombin complex(TAT) and platelet aggregation activity, were serially characterized in 82 individuals randomly chosen from the consecutive patients. RESULTS The incidence of perioperative vascular complications was as follows: 1.0% for major bleeding, 0.21% for stroke and 0.21% for venous thromboembolism. No episodes of symptomatic myocardial infarction were identified in the studied population. Perioperative changes in coagulation-related factors were found to be complex and correlated in the mixed direction of pro- and anticoagulation. The TAT values showed prolonged(across postoperative days 1-5) and prominent(>116% increase) perioperative activation of coagulation, whereas global coagulation parameters, such as the prothrombin time, showed a tendency of anticoagulation in the immediate postoperative period. CONCLUSIONS Our data confirm the relatively low incidence of perioperative vascular complications in the general Japanese non-cardiac surgical population. Given the delicate balance between thrombotic and bleeding events, it is important to comprehensively understand the associations between the patient's baseline risk factors and vascular complications for effective clinical management.

Our patient was a 58-year-old woman with internal bleeding hemorrhoids who was undergoing FOLFOX6 treatment for unresectable multiple hepatic metastases of colorectal cancer. Response evaluation after 6 courses showed stable disease (SD), but side effects necessitated a change in regimen. Hemorrhoidal bleeding had also increased, and hemorrhoid-sclerosing therapy with ALTA(ZION)injections was administered. Because no bleeding was evident after treatment and the clinical course was uneventful, chemotherapy with bevacizumab was restarted. No hemorrhoidal bleeding occurred after bevacizumab administration, and the patient is currently continuing chemotherapy. In patients with advanced cancer who have bleeding internal hemorrhoids that cannot be controlled with conservative treatment, hemorrhoid-sclerosing therapy using ALTA appears to offer an effective treatment variation that enables the use of bevacizumab in cases with limited available therapeutic regimen options.

Several lines of evidence have suggested altered functions of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). In the search for polymorphisms in the 5'-flanking and 5'-noncoding regions of the BDNF gene, we found a novel nucleotide substitution (C270T) in the noncoding region. We performed an association study between this polymorphism and AD in a Japanese sample of 170 patients with sporadic AD (51 early-onset and 119 late-onset) and 498 controls. The frequency of individuals who carried the mutated type (T270) was significantly more common in patients with late-onset AD than in controls (P = 0.00004, odds ratio: 3.8, 95% CI 1.9-7.4). However, there was no significant difference in the genotype distribution between the patients with early-onset AD and the controls, although this might be due to the small sample size of the early-onset group. Our results suggest that the C270T polymorphism of the BDNF gene or other unknown polymorphisms, which are in linkage disequilibrium, give susceptibility to late-onset AD. We obtained no evidence for the possible interactions between the BDNF and apolipoprotein E (APOE) genes, suggesting that the possible effect of the BDNF gene on the development of late-onset AD might be independent of the APOE genotype.

The peptide syntheses were performed with α-chymotrypsin immobilized in the thermosensitive poly( N -isopropylacrylamide/acrylamide) (NIPAAm/AAm) gels. In the reaction between N -acetylphenylalanine ethyl ester (Ac-Phe-OEt) and alaninamide (Ala-NH 2 ), the product ratio of Ac-Phe–Ala-NH 2 /Ac-Phe-OH increased with lowering temperature. The highest ratio was 3.3 in the reaction with immobilized enzyme at −10°C, while that was around 1.4 with free enzyme at 34°C. On the contrary, CBZ-Phe–Leu-NH 2 obtained from N -carbobenzoxyphenylalanine (CBZ-Phe) and leucinamide (Leu-NH 2 ) increased with increasing temperature (conversion: 13% at 10°C, 34% at 35°C) in Tris buffer without the organic solvent. The gel of NIPAAm copolymerized with AAm (NIPAAm/AAm=80/20) was effective as compared with the poly(NIPAAm) gel for the peptide production catalyzed by α-chymotrypsin using the ester substrate as the acyl donor. The reaction mechanism was discussed in connection with the hydrophobic surroundings inside the deswollen thermosensitive polymer gel.

Recently a significant association of a missense mutation (Glu298Asp) of the endothelial nitric oxide synthase (NOS3) gene with late-onset Alzheimer's disease (LOAD) was reported. We tried to replicate this finding in a Japanese sample of 121 patients with LOAD, 51 with early-onset AD (EOAD), and 165 medical controls. However, the genotype and allelic distributions for the Glu298Asp polymorphism were similar for these three groups, suggesting that the Glu298Asp polymorphism of the NOS3 gene has no relevance to the development of AD in Japanese.

Fast-responsive deswelling of poly(N-isopropylacrylamide) gel after a freeze-dry (FD) treatment was investigated by means of SEM images and a kinetic method using a N-isopropylacrylamide (NIPAAm) monomer from the viewpoint of the mesoscopic structure comprising a partitioned polymer-network. It was deduced from SEM images that an elastic frame comprising a partitioned polymer-network is formed by a hydrophobic interaction between polymer chains in the FD-treated gel. Fast-deswelling of the FD-treated gel results from the elasticity of a partitioned polymer-network caused water to release. The kinetic parameters on deswelling of both the conventional gel and the FD-treated gel were determined in the presence of an NIPAAm monomer. This monomer in solution is considered to play two directly-opposed roles in making a skin on the surface of the conventional gel: One is for disturbing the formation of hydrogen bonding between amide groups in the polymer; the other is for accelerating the separation of hydrated ...

Paraoxonase 1 (PON1) is proposed to have an anti-atherogenic action. Two polymorphisms at the PON1 (M/L55 and Q/R192) have been shown to be associated with coronary artery disease (CAD). This conclusion is not drawn universally, however, and specific ethnic characteristics may be important determinants in this association. Recently two homologues of PON1 — PON2 and PON3 — were identified and Sanghera et al. demonstrated C/S311 polymorphism at PON2 was associated with the risk of CAD. Within that context, we investigated the association between the aforementioned three polymorphisms and CAD and ischemic stroke in a Japanese population. The study population included 431 control subjects, 210 CAD patients, and 235 ischemic stroke patients. Genotype distributions and allele frequencies of M/L55 and C/S311 were similar among the control and patient groups, whereas the R192 allele frequency was significantly higher (P

Nitric oxide (NO) and its reactant product, peroxynitrite, have been implied to mediate neuronal damage following cerebral ischemia. However, the cellular targets of these compounds remain unclear. Studies using poly(ADP-ribose) polymerase (PARP) inhibitors and PARP knock-out mice have recently demonstrated that excessive activation of this nuclear enzyme plays an important role in NO-induced neurotoxicity. To evaluate the relevance of this plausible candidate gene to human stroke, we undertook a case-control study in Japanese. Participants comprised 213 cerebral infarction cases and 374 age- and sex-matched controls. As a primary investigation, we screened polymorphic sites of the PARP gene, and newly identified a total of four polymorphisms in 1230-bp 5'-flanking sequence. None of them were, however, located on the known promoter components of the gene. Two bi-allelic polymorphisms selected and a CA-repeat polymorphism were subsequently characterized in the case-control study, but none were significantly associated with cerebral infarction in the present study. Our data thus suggest that the tested PARP polymorphisms do not principally contribute to cerebral infarction, although extensive searches would be required to clarify whether the PARP gene plays an important role in the pathogenesis of human stroke.

To evaluate the effects of nongenetic factors, aging, and salt-loading on the quantitative trait loci (QTLs) for blood pressure (BP), we conducted a genome-wide linkage analysis using multiple sets of BP measurements in 125 male F2 generation cross derived from stroke-prone spontaneously hypertensive rats and normotensive Wistar-Kyoto rats. The experiment was arranged in two stages. In the first stage, corresponding to the developing period of the rats, BP was measured repeatedly without loading of salt; this continued until the rats were 5 months of age. In the second stage, after the baseline BP leveled off, 1% salt water was given to the rats and BP was monitored for the subsequent 7 months. Genome scanning was performed using 201 markers. In the developing period, three QTLs were identified on chromosomes 1, 3, and 4 (logarithmic odds [LOD] scores of 5.6, 3.1, and 3.2, respectively), which had peaks at 8 or 10 weeks of age. In the latter salt-loading stage, QTLs for BP were detected on chromosomes 1 and 10 (LOD scores 4.6 and 4.5, respectively). When the BP increase during salt-loading was analyzed as a phenotype, however, only the region on chromosome 10 showed linkage at a suggestive level (LOD score 3.2). The present study provides experimental evidence that QTLs for BP could be modulated by nongenetic factors, such as aging and salt-loading.

Abstract —Significant association between a Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene and essential hypertension was recently reported in Japanese populations, with the 298Asp variant showing a higher prevalence in hypertensive patients (10.3% to 12.0%) than in normotensive subjects (5.0% to 5.8%). In contrast, another study demonstrated that the 298Glu variant was significantly associated with hypertension in a Caucasian population. We therefore undertook an extensive association study in Japanese to resolve these contradictory claims. A total of 1165 individuals were selected from clinic outpatients and hospital staff in a single institution. The relevance of the Glu298Asp polymorphism to hypertension in this population was tested in 2 ways. First, a case-control study was conducted in 549 hypertensive and 513 normotensive subjects within the study population, with the χ 2 statistic used to test the significance of an association between eNOS genotype and the presence of hypertension. Second, an ANOVA was used to test the significance of an association between eNOS genotype and the level of blood pressure within the entire population except for 167 hypertensive subjects who had been under treatment for hypertension. No significant association was observed in either of the statistics tested. Allele frequencies of 298Asp were concordant across the panels: 8.4% in hypertensive subjects, 8.2% in normotensive subjects, and 7.9% and 9.5% in 2 additional sample populations used as reference panels. Taken together, our results do not support the previous observation that the molecular variant of the eNOS gene may confer principal susceptibility for essential hypertension but rather suggest the existence of sampling variation.

The kinetic parameters of deswelling for conventional and macroporous poly(N-isopropylacrylamide) gels were determined in order to point out the rate-determining step on the deswelling process in a NaCl or KCl solution. The apparent activation energy for the deswelling of the conventional gel in water (130 kJ mol−1) was larger than that of the macroporous gel in water (25 kJ mol−1). The split process of the skin layer, which was formed on the surface of the gel by heating from outside of gel, was considered concerning the rate-determining step in the case of the conventional gel. The activation entropy changes at 313 K (ΔS313’s) of the macroporous gel were determined to be −65 J K−1 mol−1 in 0.1 M NaCl (1 M = 1 mol dm−3), of which the cation exhibits a structure-forming property, and 180 J K−1 mol−1 in 0.1 M KCl, of which the cation exhibits a structure-breaking property. The sign of ΔS313 for the macroporous gel was negative at higher than 0.3 M NaCl or KCl. In order to point out the rate-determining ste...

Control of the immobilized enzyme reaction was investigated by using a magnetic heating. β-Galactosidase and 24% γ-Fe2O3 were entrapped in a copolymer gel of N-isopropylacrylamide and acrylamide. The heat was generated inside the gel due to the hysteresis loss of γ-Fe2O3 under exposure in an alternating magnetic field (effective value 840 Oe, 2.3 kHz), and the temperature elevated above the lower critical solution temperature of the gel. The intermittent exposure of the magnetic field (0.5 min on, 15 min off) could control the temperature cycle between 20.2 and 31.4°C. The process of deswelling–swelling of the gels was repeated by the thermal cycling operation. The product concentration increased no more than 5% in the enzyme reaction. This was smaller than the result reported in the isothermal operation (heating from outside of the gel). It was considered that the hydraulic pump effect was not observed by heating from inside the gel: As compared with the isothermal operation at 31.4°C (around 4.2 kJ/h for heating the solution in the column), the thermal cycling operation was found to need less energy for intermittent heating (1.2 kJ/h) in order to keep the same conversion in the enzyme reaction.

AIM: Mutations of the 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) gene cause the syndrome of apparent mineralocorticoid excess, a rare autosomal recessive form of hypertension. We therefore investigated the question of whether variants of the 11beta-HSD2 gene can contribute to genetic susceptibility to essential hypertension. SUBJECTS AND METHODS: We performed a linkage study in 162 French hypertensive sibships using the affected sib-pair method on 347 sibling pairs and a polymorphic microsatellite marker that we identified in a 30 kb cosmid clone containing the 11beta-HSD2 gene. The coding sequence, introns 2-4 and 350 bp of the 5'-flanking region of the 11beta-HSD2 gene were screened for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism, and a single polymorphism, Glu178/Glu (G534A), was identified in exon 3, which did not change the encoded amino acid sequence. A case-control study was conducted on 370 hypertensive subjects with a positive family history of hypertension and 783 French subjects with hypertension with or without a family history of hypertension, compared with 313 normotensive control subjects, all of whom were analyzed for the newly identified bi-allelic polymorphism. RESULTS: Statistical analyses using the affected sib-pair method did not show significant linkage between the 11beta-HSD2 microsatellite marker and hypertension. Furthermore, no positive association with hypertension was found with the Glu178/Glu (G534A) polymorphism. CONCLUSION: Our data do not suggest that variants of the 11beta-HSD2 gene contribute substantially to essential hypertension in Caucasians.

Macroporous poly( N -isopropylacrylamide) gel, swollen in NaCl solution, showed electric conductivity inside the gel. Swollen gel could be heated electrically by the application of AC voltage (100 V, 50 Hz) through the inserted electrodes within both ends of the gel rod. Joule's heat generated inside the gel was effective in bringing about a phase transition of gel. The gel swollen in 0.5 M NaCl solution at 22°C could generate the contractile stress with increasing temperature of gel after applying AC voltage. The deswelling rate and the maximum stress generated were 1.3 kPa s −1 and 8.0 kPa, respectively. The device of a bundle of 5 gel rods ( = 1.5 mm) could lift the weight (10 kPa as tensile strength) within 20 s, and work mechanically faster than the device of magnetic heating reported in our previous paper. The electric heating device gel could save more energy by reducing heat loss due to radiation.

Many rat strains have been employed in the genetic study of quantitative traits such as blood pressure. In such genetic studies, it is essential to prepare rat genetic maps fine enough to identify the genes regulating quantitative traits. However, it is not an easy task to isolate a sufficient number of genetic markers polymorphic between a particular pair of rat strains. In this study, we applied the randomly amplified microsatellite polymorphism (RAMP) method, a simple method to identify co-dominant markers (Wu et al. Nucleic Acids Res 22, 3257, 1994), to isolate markers polymorphic between the stroke-prone spontaneously hypertensive rat and the Wistar-Kyoto rat, a genetically hypertensive strain and its normotensive control strain, which share a common genetic background. We successfully identified 111 RAMP markers distributed throughout the rat genome after screening 3046 sets of primers. We also showed that we could isolate ordinary simple-sequence-length-polymorphism markers by cloning RAMP markers. The RAMP method is a simple and efficient way to identify co-dominant genetic markers on mammalian genomes.

The deswelling kinetics of a macroporous poly(N-isopropylacrylamide) gel in a NaCl solution was investigated. NaCl was used as the probe in order to trace out any hydration from the hydrated polymer chains. In the case of macroporous gel immersed in a NaCl solution, the minimum of the initial deswelling rate (v = 0.06 s−1) appeared at around 0.2—0.3 M (1 M = 1 mol dm−3) when the equilibrated gels (at 22 °C) were heated to 40 °C. The maxima of the apparent activation energy (Ea = 110 kJ mol−1) and the change in the activation entropy (ΔS313 = 80 J K−1 mol−1) were at 0.2—0.3 M NaCl. These results indicate that deswelling of the gel in a NaCl solution advanced on the condition of the following two factors. One is an electrostatic repulsion between Cl− ions below 0.2—0.3 M. Another is a salting-out effect due to NaCl above 0.2—0.3 M. The deswelling kinetics and the lower critical solution temperatures of the gels in other alkalimetal halide solutions were also measured in order to clarify the effect of the sp...

Abstract —Significant linkage and association of α-adducin, a cytoskeleton protein involved in transmembrane ion transport, with essential hypertension were recently shown in Caucasian populations, especially in relation to salt sensitivity. The present study investigated the relevance of this candidate gene to hypertension in a well-characterized Japanese population. A total number of 507 individuals were selected from clinic outpatients. Hypertensive subjects were defined on the basis of the individual’s blood pressure readings before starting medications; the criteria included systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥95 mm Hg. Patients with diabetes mellitus, renal failure, and secondary forms of hypertension had been excluded. Control subjects had blood pressure values 2 statistics; in addition, the association was tested with blood pressure as a continuous variable. No significant association was found in either of the statistics tested. The 460Trp variant appeared to be relatively common in the Japanese (54% to 60%) compared with a reported prevalence of 13% to 23% in Caucasians. The present study brought up an important issue concerning the pathophysiological role of α-adducin in non-Caucasian populations, given the likely ethnic variation in the nature of genetic susceptibility loci. The 460Trp variant of the α-adducin gene is unlikely to have a major effect on susceptibility to hypertension in the Japanese population studied, although the present study does not exclude the involvement of α-adducin in the pathogenesis of hypertension.