Promoter Polymorphism of RGS2 Gene Is Associated with Change of Blood Pressure in Subjects with Antihypertensive Treatment: The Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study

We performed a prospective study to examine the genetic effect on the response to a calcium (Ca) channel blocker, azelnidipine and an ACE inhibitor, temocapril treatment in patients with hypertension, as a part of the prior clinical trial, the Azelnidipine and Temocapril in Hypertensive Patients with Type 2 Diabetes Study (ATTEST). Methods and Results. All subjects who gave informed consent for genetic research were divided into two groups: the subjects treated with azelnidipine or temocapril, for 52 weeks. We selected 18 susceptible genes for hypertension and determined their genotypes using TaqMan PCR method. RNA samples were extracted from peripheral blood, and quantitative real time PCR for all genes was performed using TaqMan method. One of the polymorphisms of the RGS2 gene was extracted as being able to influence the effect of these treatments to reduce BP. At eight weeks, BP change showed a significant interaction between the A-638G polymorphism of Regulator of G protein signaling-2 (RGS2) gene and treatment with azelnidipine or temocapril. There was no gene whose expression was associated with BP phenotypes or the polymorphisms of each gene. Conclusions. A-638G polymorphism of the RGS-2 gene could be a predictive factor for therapeutic performance of Ca channel blockers

Glycemic Control and Insulin Improve Muscle Mass and Gait Speed in Type 2 Diabetes: The MUSCLES-DM Study

Ken Sugimoto, Hiroshi Ikegami, Yasunori Takata, Tomohiro Katsuya, Masahiro Fukuda, Hiroshi Akasaka, Yasuharu Tabara, Haruhiko Osawa, Yoshihisa Hiromine, Hiromi Rakugi, Glycemic Control and Insulin Improve Muscle Mass and Gait Speed in Type 2 Diabetes: The MUSCLES-DM Study, Journal of the American Medical Directors Association, 2020, https://doi.org/10.1016/j.jamda.2020.11.003

Continuous in-vIvo measurement of the brain tissue and the ischemic muscle gas tension using MEDSPECT, MS-8

I MEDSPECT is a medical mass spectrometer for continuous in-vivo measurement of tissue, blood and respiratory gases. Interfacing catheter for tissue in measurement has Teflon membrane. The permeability and perfusion rate for various gases through its membrane varied with temperature. The temperature coefficient of Teflon catheter in the range of 15℃-40℃ is approximately constant with -2% of correction per degree for oxygen and carbon dioxide. Linear correlation was confirmed experimentally. II The brain tissue gas tensions were measured in ten dogs with intra-venous anesthesia at normothermia and deep hypothermia using perfusion cooling, including circulatory arrest for 30 minutes at 20°C of cerebral temperature. On average, the brain tissue P(O2) was 15mmHg in normothermia when the arterial P(O2) showed 95mmHg and the brain tissue P(CO2) was 49mmHg when the arterial PC02 showed 30mmHg. The brain tissue carbon dioxide tension gradually decreased by cooling and increased during circulatory arrest for 30 minutes; from 45mmHg to 72mmHg. The brain tissue oxygen tension increased during cooling from 15mmHg to 41mmHg and decreased in the circulatory arrest; from 41mmHg to 36mmHg. III The ischemic muscle gas tension was measured in a 22-year-old man, who was suffered from thromboangiitis obliterans bilaterally, and had the popliteal autovein bypass surgery 3 months ago. Control oxygen tensions in the both anterior tibial muscles showed about the same; 35mmHg and 36mmHg respectivelly, and the P(O2) of the non-operated side showed remarkable low level of 18mmHg as compared with the side of arterial reconstruction surgery after 5-minutes ankle exercise

Variantes genéticas en el locus 9p21 contribuyen al desarrollo de arteriosclerosis a través de la modulación de ANRIL y CDKN2A/B

Registro creado en correspondencia al grado de doctora de Ada Congrains Castillo.Los estudios de asociación de todo el genoma (GWAS) han identificado variantes genéticas que contribuyen al riesgo de enfermedad cardiovascular (ECV) en el locus del cromosoma 9p21. La región asociada a CVD es adyacente a los dos inhibidores de quinasas dependientes de ciclina (CDKN) 2A y 2B y los últimos exones del ARN no codificante, ANRIL. Todavía no está claro cuál de estas transcripciones o cómo están involucradas en la patogénesis de la aterosclerosis.Genome-wide association studies (GWAS) have identified genetic variants contributing to the risk of cardiovascular disease (CVD) at the chromosome 9p21 locus. The CVD-associated region is adjacent to the two cyclin dependent kinase inhibitors (CDKN)2A and 2B and the last exons of the non-coding RNA, ANRIL. It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis.Japón. Programa de Promoción de Estudios Fundamentales en el Instituto Nacional de Innovación Biomédica de Japón (HR: 22-2-5), el Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología de Japón (KK: 22510211) y la Fundación NOVARTIS para la Investigación Gerontológica (KK).Tesi

Hyperglycemia in non-obese patients with type 2 diabetes is associated with low muscle mass: The Multicenter Study for Clarifying Evidence for Sarcopenia in Patients with Diabetes Mellitus

AIMS/INTRODUCTION: Hyperglycemia is a risk factor for sarcopenia when comparing individuals with and without diabetes. However, no studies have investigated whether the findings could be extrapolated to patients with diabetes with relatively higher glycemic levels. Here, we aimed to clarify whether glycemic control was associated with sarcopenia in patients with type 2 diabetes. MATERIALS AND METHODS: Study participants consisted of patients with type 2 diabetes (n = 746, the average age was 69.9 years) and an older general population (n = 2, 067, the average age was 68.2 years). Sarcopenia was defined as weak grip strength or slow usual gait speed and low skeletal mass index. RESULTS: Among patients with type 2 diabetes, 52 were diagnosed as having sarcopenia. The frequency of sarcopenia increased linearly with glycated hemoglobin (HbA1c) level, particularly in lean individuals (HbA1c <6.5%, 7.0%, ≥6.5% and <7.0%: 18.5%; HbA1c ≥7.0% and <8.0%: 20.3%; HbA1c ≥8.0%: 26.7%). The linear association was independent of major covariates, including anthropometric factors and duration of diabetes (HbA1c <6.5%: reference; ≥6.5% and <7.0%: odds ratio [OR] 4.38, P = 0.030; HbA1c ≥7.0% and <8.0%: 4.29, P = 0.024; HbA1c ≥8.0%: 7.82, P = 0.003). HbA1c level was specifically associated with low skeletal mass index (HbA1c ≥8.0%: OR 5.42, P < 0.001) rather than weak grip strength (OR 1.89, P = 0.058) or slow gait speed (OR 1.13, P = 0.672). No significant association was observed in the general population with a better glycemic profile. CONCLUSIONS: Poor glycemic control in patients with diabetes was associated with low muscle mass

Impact of Chronic Kidney Disease on the Presence and Severity of Aortic Stenosis in Patients at High Risk for Coronary Artery Disease

<p>Abstract</p> <p>Objective</p> <p>We evaluated the impact of chronic kidney disease (CKD) on the presence and severity of aortic stenosis (AS) in patients at high risk for coronary artery disease (CAD).</p> <p>Methods</p> <p>One hundred and twenty consecutive patients who underwent invasive coronary angiography were enrolled. Aortic valve area (AVA) was calculated by the continuity equation using transthoracic echocardiography, and was normalized by body surface area (AVA index).</p> <p>Results</p> <p>Among all 120 patients, 78% had CAD, 55% had CKD (stage 3: 81%; stage 4: 19%), and 34% had AS (AVA < 2.0cm²). Patients with AS were older, more often female, and had a higher frequency of CKD than those without AS, but the prevalence of CAD and most other coexisting conventional risk factors was similar between patients with and without AS. Multivariate linear regression analysis indicated that only CKD and CAD were independent determinants of AVA index with standardized coefficients of -0.37 and -0.28, respectively. When patients were divided into 3 groups (group 1: absence of CKD and CAD, n = 16; group 2: presence of either CKD or CAD, n = 51; and group 3: presence of both CKD and CAD, n = 53), group 3 had the smallest AVA index (1.19 ± 0.30*# cm²/m², *p < 0.05 vs. group 1: 1.65 ± 0.32 cm²/m², and #p < 0.05 vs. group 2: 1.43 ± 0.29* cm²/m²) and the highest peak velocity across the aortic valve (1.53 ± 0.41*# m/sec; *p < 0.05 vs. group 1: 1.28 ± 0.29 m/sec, and #p < 0.05 vs. group 2: 1.35 ± 0.27 m/sec).</p> <p>Conclusion</p> <p>CKD, even pre-stage 5 CKD, has a more powerful impact on the presence and severity of AS than other conventional risk factors for atherosclerosis in patients at high risk for CAD.</p

アワ メイショ ズエ ニオケル ビザン ノ シゼン ト ケイカン

In this paper the nature and the landscape of the Mt. Bizan are investigated based on “Awa meisho zue” which was a guidebook of Awa (Tokushima) published about 200 years ago. In the picture entitled “Mt. Bizan” a tower at the Jimyoin Temple and two buildings are drawn in the mountain. The mountain is covered with pine trees, and there is a waterfall near the tower. Besides pine trees, three types of trees, Japanese cedar and/or Japanese cypress, trees that presumably cherry, and unknown broadleaf trees are drawn in Mt. Otakiyama that is a part of Mt. Bizan based on the picture entitled “Otakisan Jimyoin”. Other historical records in Edo era coincide with the composition of plant species in Mt. Bizan. Though the vegetation of Mt. Bizan was efended by laws throughout Edo era, it was deforested and the mountain became bald after the Meiji Restoration. Afterwards, it was protected by specifying it as the protection forest and by making it as a park. Now, pine trees and Japanese cedar and/or Japanese cypress have almost been lost, and pasania and live oak are well growing in the mountain. The tower at Jimyoin was burned down by the air raid in the World War II, and the waterfall has thinned. On the other hand, mountain trails and a ropeway were made, and a lot of buildings were built at the top of the mountain. Thus, the nature and the landscape of Mt. Bizan greatly changed in 200 years. However, citizens are still familiar with it as the symbol of Tokushima City

関西大学日本ポピュラー音楽アーカイブ・ミュージアムプロジェクト研究成果報告書

2014年度、2015年度 関西大学研究拠点形成支援経費報告

Genetic Variants of Human Granzyme B Predict Transplant Outcomes after HLA Matched Unrelated Bone Marrow Transplantation for Myeloid Malignancies

Serine protease granzyme B plays important roles in infections, autoimmunity, transplant rejection, and antitumor immunity. A triple-mutated granzyme B variant that encodes three amino substitutions (Q48R, P88A, and Y245H) has been reported to have altered biological functions. In the polymorphism rs8192917 (2364A>G), the A and G alleles represent wild type QPY and RAH mutant variants, respectively. In this study, we analyzed the impact of granzyme B polymorphisms on transplant outcomes in recipients undergoing unrelated HLA-fully matched T-cell-replete bone marrow transplantation (BMT) through the Japan Donor Marrow Program. The granzyme B genotypes were retrospectively analyzed in a cohort of 613 pairs of recipients with hematological malignancies and their unrelated donors. In patients with myeloid malignancies consisting of acute myeloid leukemia and myelodysplastic syndrome, the donor G/G or A/G genotype was associated with improved overall survival (OS; adjusted hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.41–0.89; P = 0.01) as well as transplant related mortality (TRM; adjusted HR, 0.48; 95% CI, 0.27–0.86, P = 0.01). The recipient G/G or A/G genotype was associated with a better OS (adjusted HR, 0.68; 95% CI, 0.47–0.99; P = 0.05) and a trend toward a reduced TRM (adjusted HR, 0.61; 95% CI, 0.35–1.06; P = 0.08). Granzyme B polymorphism did not have any effect on the transplant outcomes in patients with lymphoid malignancies consisting of acute lymphoid leukemia and malignant lymphoma. These data suggest that there is an association between the granzyme B genotype and better clinical outcomes in patients with myeloid malignancies after unrelated BMT