Given the recent revision of the Corporate Governance Code and the growing understanding of the Intellectual Property (IP) Landscape, IP activities are expected to contribute to business more than ...they ever have.This paper examines the efficient organizational management and human resource development of the IP department from three perspectives: i) the specialized domain of the IP division, ii) the involvement of management in IP strategy, and iii) the collaboration with internal and external experts.The case studies in this paper suggest that: i) it is rational to enhance expertise on a functional basis, rather than on an individual basis by creating a function-based organization; ii) cooperation between departments under the direction of management is vital since IP strategy is positioned as a part of the business strategy of the company; iii) the active use of external experts would help with adapting to the diversification and deepening of operations more efficiently.
The Japanese hypertension guidelines report that essential hypertension is detected in 1-3% of upper elementary and high school students during blood pressure (BP) screenings. Hypertension in these ...age groups is an emerging public health concern mainly attributed to the rising rate of pediatric obesity. Considering the existence of BP tracking phenomenon, early preventive education and instruction are necessary, especially for male students with moderately elevated BP showing a tendency toward obesity, despite the low prevalence of hypertension in high school students. Students with a positive family history of hypertension and those born with low birth weight need the same measures. Lifestyle habits, such as increased alcohol intake, dramatically change once students begin university; thus, early education and instruction regarding the factors influencing BP are necessary. In particular, for male students with higher BP during high school, caution regarding increased body weight is required irrespective of their level of obesity. Young adults aged <40 years should be educated about the association between body weight and hypertension. Particular caution surrounding lifestyle habits, including drinking and smoking, is warranted in male hypertensive subjects because hypertension at a young age is strongly associated with obesity. BP monitoring and the management of obesity should be considered efficient approaches to the detection and treatment of hypertension. For the lifetime prevention of hypertension, it is essential to be aware of one's health status and learn about healthy lifestyles beginning in childhood. BP measurement may be an appropriate means to achieve this goal.
Aim: The association between aging and insulin resistance has been unclear. We evaluated the effects of aging on visceral fat area (VFA) and subcutaneous fat area (SFA) measured by computed ...tomography, homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) among participants in a comprehensive health checkup. Methods: This study included 1,050 male and 700 female Japanese participants aged 35-84 years in our comprehensive health checkup program during a 2-year period. Participants who were on medication for diabetes mellitus or those who met the pre-determined exclusion criteria were excluded. The participants were divided into five groups according to age. Results: As age increased from Group 1 to Group 5, both VFA and VFA/SFA ratio significantly increased in both male and female participants, whereas logHOMA-IR linearly and significantly decreased (p＜0.0001 for each). Body mass index (BMI), waist circumference (WC), and SFA increased with age in female participants but decreased in male participants. Although age was not or only weakly correlated with logglucose and logHbA1c in both male and female participants, age showed significant negative correlations with loginsulin, logHOMA-IR, and logHOMA-β even after adjusting for BMI and WC (p＜0.0001 for each). Serum high-molecular-weight adiponectin (HMW-ADPN) levels were measured in 114 male and 87 female participants, and logHMW-ADPN was negatively correlated with logHOMA-IR and positively correlated with age in both male and female participants. Conclusions: In the present study, both male and female participants showed increases in VFA and VFA/SFA ratio and decreases in insulin, HOMA-IR, and HOMA-β with age.
Although over 60 loci for type 2 diabetes (T2D) have been identified, there still remains a large genetic component to be clarified. To explore unidentified loci for T2D, we performed a genome-wide ...association study (GWAS) of 6 209 637 single-nucleotide polymorphisms (SNPs), which were directly genotyped or imputed using East Asian references from the 1000 Genomes Project (June 2011 release) in 5976 Japanese patients with T2D and 20 829 nondiabetic individuals. Nineteen unreported loci were selected and taken forward to follow-up analyses. Combined discovery and follow-up analyses (30 392 cases and 34 814 controls) identified three new loci with genome-wide significance, which were MIR129-LEP rs791595; risk allele = A; risk allele frequency (RAF) = 0.080; P = 2.55 × 10(-13); odds ratio (OR) = 1.17, GPSM1 rs11787792; risk allele = A; RAF = 0.874; P = 1.74 × 10(-10); OR = 1.15 and SLC16A13 (rs312457; risk allele = G; RAF = 0.078; P = 7.69 × 10(-13); OR = 1.20). This study demonstrates that GWASs based on the imputation of genotypes using modern reference haplotypes such as that from the 1000 Genomes Project data can assist in identification of new loci for common diseases.
Recently, several genes have been shown to be associated with an increased risk of type 2 diabetes by genome-wide association studies in white populations. To further investigate the involvement of ...these polymorphisms in conferring susceptibility to type 2 diabetes, we examined the association of 14 single nucleotide polymorphisms (SNPs) within 11 candidate loci with type 2 diabetes in a Japanese population.
We analyzed 14 SNPs (rs4402960 in IGF2BP2, rs10811661 in CDKN2A/B, rs1111875 and rs7923837 in HHEX, rs13266634 in SLC30A8, rs1113132 and rs11037909 in EXT2, rs9939609 and rs8050136 in FTO, rs7756992 in CDKAL1, rs1801282 in PPARG Pro12Ara, rs5219 in KCNJ11 Glu23Lys, rs7480010 in LOC387761, and rs9300039 in Ch11) in 1,630 Japanese subjects with type 2 diabetes and in 1,064 control subjects by using an invader assay or a TaqMan assay.
Among the 11 loci examined, 6 were significantly associated with type 2 diabetes in our population by a logistic regression analysis, similar to previously reported results (rs4402960, P = 0.00009; rs10811661, P = 0.0024; rs5219, P = 0.0034; rs1111875, P = 0.0064; rs13266634, P = 0.0073; rs7756992, P = 0.0363). In this population, the remaining five loci were not significantly associated with type 2 diabetes. In addition, we identified significant association of the SNPs in FTO gene with BMI in the control subjects.
We have identified 6 of the 11 loci that were identified by genome-wide association studies in white populations, and these loci are considered strong candidates for type 2 diabetes susceptibility across different ethnicities.
Aim: Early intervention before the progression of chronic kidney disease (CKD) is essential to prevent end-stage renal disease (ESRD) and cardiovascular complications. This study evaluated the ...correlation between metabolic and lifestyle-related factors and the decline of estimated glomerular filtration rate (eGFR) over 1 year in a Japanese population without CKD.Methods: Subjects who received two consecutive annual health checkups from 2013 to 2015 were involved. Factors associated with eGFR decline were identified using multiple regression models.Results: A total of 2531 subjects aged 58.9±11.7 years old were included in this study. Baseline levels of HDL-C and ApoA1 correlated with the eGFR decline over 1 year defined as eGFR reduction rate of 15% or more and/or eGFR at the next year ＜60 ml/min/m2 (odds ratio (OR) 0.87 (per 10 mg/dl); 95% CI, 0.80–0.94; p=0.0012, 0.90 (per 10 mg/dl); 0.86–0.96; p=0.0004, respectively). A U-shaped relationship between the eGFR decline and HDL-C or ApoA1 levels was not observed in non-CKD population of this study. Metabolic syndrome was significantly associated with eGFR decline (OR 1.32; 1.04–1.67; p=0.0205), although obesity-related factors did not show a significant correlation with eGFR decline over 1 year.Conclusion: Low HDL-C and ApoA1 levels significantly correlated with eGFR decline in a short period of 1 year. Metabolic syndrome also showed a significant association with eGFR decline. This study suggests the importance of hypertension and low HDL-C in the metabolic syndrome effect on eGFR decline rather than obesity in non-CKD population.
In 1996, adiponectin was reported to be the most abundant transcript in adipose tissue. Animal studies revealed that administering adiponectin improves insulin resistance and blood glucose levels and ...inhibits atherosclerosis. In the present article, we review the significance of measuring serum high-molecular-weight (HMW) adiponectin levels in human subjects. Our cross-sectional studies revealed that the serum HMW adiponectin concentration was 1.9 times higher in healthy Japanese females than males and had a strong positive correlation with HDL-cholesterol but a negative correlation with BMI and the homeostasis model assessment insulin resistance index (HOMA-IR). They also indicated that the serum HMW adiponectin concentration had a stronger association with HOMA-IR and metabolic syndrome than the total adiponectin concentration. Our longitudinal study, a 6-year follow-up of Japanese men, suggested that a decreased level of HMW adiponectin is a predictor of progression to metabolic syndrome. In another intervention study, lifestyle modification for 3 months induced a decrease in BMI and waist circumference and an increase in serum HMW adiponectin but not the total adiponectin level in 16 Japanese males with metabolic syndrome. Administering thiazolidinediones to diabetic patients increased the serum HMW adiponectin concentration 3 fold and improved glucose and lipid profiles and blood pressure. Some people may inherit a lower serum concentration of adiponectin, and have a higher risk of developing cardiovascular diseases. It is suggested that HMW adiponectin is a useful marker for the evaluation and care of subjects with metabolic syndrome and related disorders.
Abstract Adiponectin is an adipocyte-specific secretory protein that possesses antidiabetic and antiatherosclerotic properties. Recent studies have demonstrated that the high molecular weight (HMW) ...multimer form is the active form of this protein. In patients with type 2 diabetes mellitus, HMW-total adiponectin ratio was reported to be a more useful marker than total adiponectin in the prediction of insulin resistance and metabolic syndrome. In the present study of healthy Japanese male subjects without any medication, we investigated the hypothesis that measuring only HMW adiponectin may be as effective as HMW-total ratio to predict insulin resistance and/or metabolic syndrome. This was a working community–based cross-sectional study of 637 male subjects aged 30 to 65 years. Total and HMW adiponectin concentrations in serum were measured by enzyme-linked immunosorbent assay using commercially available kits. Serum HMW adiponectin level was inversely correlated with homeostasis model assessment of insulin resistance (HOMA-IR) ( r = −0.375, P < .0001) even after adjustment for age and body mass index ( r ′ = −0.245, P < .0001). When we divided the study subjects into quartile groups with equal numbers of subjects, HOMA-IR in the 4 groups based on serum HMW adiponectin level was significantly different ( P < .01). Metabolic syndrome score in the 4 groups based on serum HMW adiponectin level was also significantly different ( P < .01). Area under the curve of receiver operator characteristic curves of HMW adiponectin (0.73) to evaluate the presence of insulin resistance (HOMA-IR >2.5) was larger than that of total adiponectin (0.68) or HMW-total ratio (0.70). Area under the curve of receiver operator characteristic curves of HMW adiponectin (0.70) to evaluate the presence of metabolic syndrome (body mass index–based modified criteria) was also larger than that of total adiponectin (0.65), but equal to that of HMW-total ratio (0.70). These results suggest that simply measuring HMW adiponectin may be as effective as HMW-total ratio to evaluate the presence of insulin resistance and metabolic syndrome, at least in nondiabetic subjects who are not receiving any medication.
Abstract Adiponectin is an adipocyte-specific secretory protein, which possesses antidiabetic and antiatherosclerotic properties. Adiponectin exists as multimers in serum, and high-molecular-weight ...(HMW) adiponectin is particularly considered to be the active form of the protein. The objective of the present study was to examine whether decreased HMW adiponectin is a predictor of progression to metabolic syndrome during a 6-year follow-up period in Japanese men. The study subjects were 416 Japanese men without metabolic syndrome, aged 30 to 59 years at baseline, who had participated in annual health checkups in both 2000 and 2006. Low concentration of HMW adiponectin (≤2.65 μ g/mL) was associated with substantially higher hazard ratio of the progression to metabolic syndrome after adjustment for age and body mass index (hazard ratio, 1.561; 95% confidence interval, 1.051-2.292; P = .028). The number of subjects with the progression to metabolic syndrome in each tertile based on baseline HMW adiponectin concentration was significantly different among the 3 groups (HMW adiponectin: χ2 = 7.473, P = .0238; total adiponectin: χ2 = 4.477, P = .1066; HMW-total adiponectin ratio: χ2 = 1.676, P = .4325). It was suggested that decreased HMW adiponectin is a predictor of the progression to metabolic syndrome in a 6-year follow-up study of Japanese men. Furthermore, it was suggested longitudinally that measuring HMW adiponectin is efficient to predict the progression to metabolic syndrome compared with measuring total adiponectin or HMW-total adiponectin ratio.
Gastric cancer is the third leading cause of cancer mortality in Japan and worldwide. Although previous studies identify various genetic variations associated with gastric cancer, host genetic ...factors are largely unidentified. To identify novel gastric cancer loci in the Japanese population, herein, we carried out a large‐scale genome‐wide association study using 6171 cases and 27 178 controls followed by three replication analyses. Analysis using a total of 11 507 cases and 38 904 controls identified two novel loci on 12q24.11‐12 (rs6490061, P = 3.20 × 10−8 with an odds ratio OR of 0.905) and 20q11.21 (rs2376549, P = 8.11 × 10−10 with an OR of 1.109). rs6490061 is located at intron 19 of the CUX2 gene, and its expression was suppressed by Helicobacter pylori infection. rs2376549 is included within the gene cluster of DEFB families that encode antibacterial peptides. We also found a significant association of rs7849280 in the ABO gene locus on 9q34.2 (P = 2.64 × 10−13 with an OR of 1.148). CUX2 and ABO expression in gastric mucosal tissues was significantly associated with rs6490061 and rs7849280 (P = 0.0153 and 8.00 × 10−11), respectively. Our findings show the crucial roles of genetic variations in the pathogenesis of gastric cancer.
Manhattan plot of gastric cancer GWAS.
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