ラビット下肢虚血モデルに対する自家骨髄間葉系幹細胞移植は血管内皮機能を改善する

Background: The purpose of this study was to determine whether autologous mesenchymal stem cells (MSCs) implantation improves endothelial dysfunction in a rabbit ischemic limb model. Methods: We evaluated the effect of MSC implantation on limb blood flow (LBF) responses to acetylcholine (ACh), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP), an endothelium-independent vasodilator, in rabbits with limb ischemia in which cultured MSCs were implanted (n=20) or saline was injected as a control group (n=20). LBF was measured using an electromagnetic flowmeter. A total of 106 MSCs were implanted into each ischemic limb. Results: Histological sections of ischemic muscle showed that capillary index (capillary/muscle fiber) was greater in the MSC implantation group than in the control group. Laser Doppler blood perfusion index was significantly increased in the MSC implantation group compared with that in the control group. LBF response to ACh was greater in the MSC group than in the control group. After administration of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, LBF response to ACh was similar in the MSC implantation group and control group. Vasodilatory effects of SNP in the two groups were similar. Conclusions: These findings suggest that MSC implantation induces angiogenesis and augments endothelium-dependent vasodilation in a rabbit ischemic model through an increase in nitric oxide production.広島大学(Hiroshima University)博士(医学)Philosophy in Medical Sciencedoctora

Endothelial Dysfunction, Increased Arterial Stiffness, and Cardiovascular Risk Prediction in Patients With Coronary Artery Disease: FMD‐J (Flow‐Mediated Dilation Japan) Study A

BackgroundThe usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known.Methods and ResultsWe measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed.ConclusionsIn patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification

FMD, PWV, and Cardiovascular Events

Background The usefulness of vascular function tests for management of patients with a history of coronary artery disease is not fully known. Methods and Results We measured flow‐mediated vasodilation (FMD) and brachial–ankle pulse wave velocity (baPWV) in 462 patients with coronary artery disease for assessment of the predictive value of FMD and baPWV for future cardiovascular events in a prospective multicenter observational study. The first primary outcome was coronary events, and the second primary outcome was a composite of coronary events, stroke, heart failure, and sudden death. During a median follow‐up period of 49.2 months, the first primary outcome occurred in 56 patients and the second primary outcome occurred in 66 patients. FMD above the cutoff value of 7.1%, derived from receiver‐operator curve analyses for the first and second primary outcomes, was significantly associated with lower risk of the first (hazard ratio, 0.27; 95% confidence interval, 0.06–0.74; P=0.008) and second (hazard ratio, 0.32; 95% confidence interval, 0.09–0.79; P=0.01) primary outcomes. baPWV above the cutoff value of 1731 cm/s was significantly associated with higher risk of the first (hazard ratio, 1.86; 95% confidence interval, 1.01–3.44; P=0.04) and second (hazard ratio, 2.19; 95% confidence interval, 1.23–3.90; P=0.008) primary outcomes. Among 4 groups stratified according to the combination of cutoff values of FMD and baPWV, stepwise increases in the calculated risk ratio for the first and second primary outcomes were observed. Conclusions In patients with coronary artery disease, both FMD and baPWV were significant predictors of cardiovascular events. The combination of FMD and baPWV provided further cardiovascular risk stratification

Meso-γ-scale convective systems observed by a 443-MHz wind-profiling radar with RASS in the Okinawa subtropical region

We observed a meso-γ-scale convective system in July 2007 using a 443-MHz wind profiler radar (WPR) with a radio acoustic sounding system (RASS) at the NICT Ogimi observatory in Okinawa, Japan. We analyzed the virtual temperature, Tv, the Brunt–Vaisala frequency squared, N2, and three components of wind velocity profiles from the WPR-RASS data. We also employed a non-hydrostatic meso-scale (NHM) numerical model. Although the island of Okinawa was covered with a Pacific high-pressure system from 21–26 July, the atmospheric condition was convectively unstable below about 5 km. A number of convective clouds generally appeared from 11:00–18:00 in local time (i.e., Japan Standard Time; JST) with a typical horizontal scale of 10 km and temporal scale of 40–60 min. We focused on the convective system that passed over the Ogimi radar site on 23rd and 25th July. Just before rain occurred on these days, a low N2 region extended upward to 2.0 km, and this characteristics is also commonly seen around a convective cloud in the NHM model. The cloud water content from the NHM model indicated that the cloud top height correlates with the low N2 structure. Before the convective system was generated, N2 decreased below an altitude of about 1 km, because air with low Tv intruded at 1–3 km, and the surface temperature increased due to solar radiation. The sea-breeze from both the east and west coasts of Okinawa collided to force the convergence below 1 km. Thus, the synergetic effects of the low static stability and convergence seemed to trigger the generation of a convective system, which eventually grew to 11 km over the radar site

Outcomes of curative nephrectomy against renal cell carcinoma based on a central pathological review of 914 specimens from the era of cytokine treatment.

[Background]The purpose of this study was to determine the state of modern practice with regard to renal cell carcinoma (RCC) outcomes and to assess the effects on survival of such clinical and pathological factors such as histological subtype (HS) and nuclear grade by conducting a central pathological review based on the current World Health Organization classification and the staging system of the American Joint Committee on Cancer/Union for International Cancer Control. [Methods]We collected glass slides and clinical data sets for 914 cases of RCC treated with curative nephrectomy from 1995 to 2000. Overall (OS), cancer-specific (CSS), and relapse-free (RFS) survival were compared for HS and nuclear grades determined by a central pathology review board comprising 5 board-certified pathologists, pathological staging, and a variety of clinical factors. [Results]The 5 and 7-year CSS in this study were 96 and 93 %, respectively, values superior to those reported in Western countries. Concordance between the original and reviewed HS and nuclear grades were 90.9 and 21.1 %, respectively. HS correlated with OS (P = 0.043) but was not an independent prognostic factor in the multivariate analysis (P = 0.820). Tumor size, Fuhrman grade, and infiltration type were common independent prognostic factors for OS, CSS, and RFS. [Conclusions]This study revealed RCC outcomes in the era of cytokine treatment for metastasis. Central pathological review is an essential component of a multicenter study with long-term follow-up. Tumor size, Fuhrman grade, and infiltration type had much greater effects than HS on survival after curative nephrectomy