Clinical features of hepatocellular carcinoma (HCC) with normal serum alpha-fetoprotein (AFP) levels were compared with those of AFP-positive cases. A total of 606 patients were divided into four groups based on their serum AFP levels at the time of diagnosis: group 1 (less than or equal to 20 ng/ml, N = 125), group 2 (20-1000 g/ml, N = 256), group 3 (1000-10000 ng/ml, N = 149), and group 4 (greater than 10000 ng/ml, N = 76). Increasing prevalence of group 1 patients and decreasing prevalence of group 4 were noted during the last 9 years. The proportion of hepatitis B virus-positive cases was significantly lower in group 1 than in group 4. The serum glutamic oxaloacetic transaminase/serum glutamic pyruvic transaminase ratio was found to be significantly higher in group 4 than in group 1 regardless of the size of the tumors. The survival rates were compared among the four groups in size matched cases since the size of the tumor significantly influenced their prognosis. The median survival in relatively small HCC patients (less than or equal to 5 cm in diameter, N = 199) were 24.6 months for group 1, 20.6 months for group 2, and 13.7 months for group 3 patients; and those in large HCC (greater than 50% in the proportion of the tumor area, N = 200) were 15.1 months for group 1, 6.3 months for group 2, 5.8 months for group 3, and 5.2 months for group 4. Thus, serum AFP values at the time of presentation are not only of diagnostic value, but also of prognostic significance in patients with HCC.

on behalf of the Japanese Coronary Spasm Association Background-Coronary artery spasm plays an important role in the pathogenesis of ischemic heart disease; however, its role in sudden cardiac death remains to be fully elucidated. We examined the clinical characteristics and outcomes of patients with vasospastic angina (VSA) in our nationwide multicenter registry by the Japanese Coronary Spasm Association. September 2007 and December 2008, 1429 patients with VSA (male/female, 1090/339; median, 66 years) were identified. They were characterized by a high prevalence of smoking and included 35 patients who survived out-of-hospital cardiac arrest (OHCA). The OHCA survivors, as compared with the remaining 1394 non-OHCA patients, were characterized by younger age (median, 58 versus 66 years; PϽ0.001) and higher incidence of left anterior descending coronary artery spasm (72% versus 53%, PϽ0.05). In the OHCA survivors, 14 patients underwent implantable cardioverter-defibrillator (ICD) implantation while intensively treated with calcium channel blockers. Survival rate free from major adverse cardiac events was significantly lower in the OHCA survivors compared with the non-OHCA patients (72% versus 92% at 5 years, PϽ0.001), including appropriate ICD shocks for ventricular fibrillation in 2 patients. Multivariable analysis revealed that OHCA events were significantly correlated with major adverse cardiac events (hazard ratio, 3.25; 95% confidence interval, 1.39 to 7.61; PϽ0.01). Conclusions-These results from the largest vasospastic angina cohort indicate that vasospasm patients who survived OHCA are high-risk population. Further studies are needed to determine whether implantable cardioverter-defibrillator therapy improves patient prognosis. (Circ Arrhythm Electrophysiol. 2011;4:295-302.) Methods and Results-BetweenKey Words: acetylcholine Ⅲ angina pectoris Ⅲ arrhythmia, cardiac Ⅲ prognosis Ⅲ coronary vasospasm O ut-of-hospital cardiac arrest (OHCA) is a major public health problem. Its estimated number is 300 000 to 400 000 per year in the United States. 1 A prospective study showed an incidence of 53 in 100 000 per year, with 25% of victims being younger than 65 years. 2 Causes of OHCA are strongly associated with coronary artery disease as evidenced at autopsy, and the survival rate from OHCA still remains to be substantially improved. 1 Importantly, a significant number of OHCA cases remained unexplained if victims have no structural abnormalities (eg, organic coronary stenosis) in the postmortem analysis. 3 This finding strongly suggests that functional abnormalities of the coronary artery are also involved in the pathogenesis of OHCA. 4 Clinical Perspective on p 302Recently, the prevalence of early access to emergency medical service, early bystander cardiopulmonary resuscitation, and early defibrillation has been increasing, with a resultant improvement of the survival rate from OHCA. [5][6][7] The progress of the chain of survival now opens the window to elucidate the underlying mechanisms of patients who surviv...

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In the late stages of the global dispersal of dogs, dingoes appear in the Australian archaeological record 3500 years BP, and dogs were one of three domesticates brought with the colonization of Polynesia, but the introduction routes to this region remain unknown. This also relates to questions about human history, such as to what extent the Polynesian culture was introduced with the Austronesian expansion from Taiwan or adopted en route, and whether pre-Neolithic Australia was culturally influenced by the surrounding Neolithic world. We investigate these questions by mapping the distribution of the mtDNA founder haplotypes for dingoes (A29) and ancient Polynesian dogs (Arc1 and Arc2) in samples across Southern East Asia (n = 424) and Island Southeast Asia (n = 219). All three haplotypes were found in South China, Mainland Southeast Asia and Indonesia but absent in Taiwan and the Philippines, and the mtDNA diversity among dingoes indicates an introduction to Australia 4600–18 300 years BP. These results suggest that Australian dingoes and Polynesian dogs originate from dogs introduced to Indonesia via Mainland Southeast Asia before the Neolithic, and not from Taiwan together with the Austronesian expansion. This underscores the complex origins of Polynesian culture and the isolation from Neolithic influence of the pre-Neolithic Australian culture.

Imaging plays an important role in the evaluation and management of acute pulmonary embolism (PE). Computed tomography (CT) pulmonary angiography (CTPA) is the current standard of care and provides accurate diagnosis with rapid turnaround time. CT also provides information on other potential causes of acute chest pain. With dual-energy CT, lung perfusion abnormalities can also be detected and quantified. Chest radiograph has limited utility, occasionally showing findings of PE or infarction, but is useful in evaluating other potential causes of chest pain. Ventilation-perfusion (VQ) scan demonstrates ventilation-perfusion mismatches in these patients, with several classification schemes, typically ranging from normal to high. Magnetic resonance imaging (MRI) also provides accurate diagnosis, but is available in only specialized centers and requires higher levels of expertise. Catheter pulmonary angiography is no longer used for diagnosis and is used only for interventional management. Echocardiography is used for risk stratification of these patients. In this article, we review the role of imaging in the evaluation of acute PE.

Furthermore, the differentiation inhibited by the stretching was also restored by synthetic PPARγ ligand. Collectively, these results suggest that the inhibition of adipocyte differentiation in response to stretching is mainly attributable to the reduced expression of PPARγ2, which is mediated by activation of the ERK/MAPK system.

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The development of obesity involves multiple mechanisms. Here, we identify adipocyte signaling through the guanosine triphosphatase Rho and its effector Rho-kinase as one such mechanism. Mice fed a high-fat diet (HFD) showed increased Rho-kinase activity in adipose tissue compared to mice fed a low-fat diet. Treatment with the Rho-kinase inhibitor fasudil attenuated weight gain and insulin resistance in mice on a HFD. Transgenic mice overexpressing an adipocyte-specific, dominant-negative form of RhoA (DN-RhoA TG mice) showed decreased Rho-kinase activity in adipocytes, decreased HFD-induced weight gain, and improved glucose metabolism compared to wild-type littermates. Furthermore, compared to HFD-fed wild-type littermates, DN-RhoA TG mice on a HFD showed decreased adipocyte hypertrophy, reduced macrophage recruitment to adipose tissue, and lower expression of mRNAs encoding various adipocytokines. Lipid accumulation in cultured adipocytes was associated with increased Rho-kinase activity and increased abundance of adipocytokine transcripts, which was reversed by a Rho-kinase inhibitor. Direct application of mechanical stretch to mature adipocytes increased Rho-kinase activity and stress fiber formation. Stress fiber formation, which was also observed in adipocytes from HFD-fed mice, was prevented by Rho-kinase inhibition and in DN-RhoA TG mice. Our findings indicate that lipid accumulation in adipocytes activates Rho to Rho-kinase (Rho-Rho-kinase) signaling at least in part through mechanical stretch and implicate Rho-Rho-kinase signaling in inflammatory changes in adipose tissue in obesity. Thus, inhibition of Rho-Rho-kinase signaling may provide a therapeutic strategy for disrupting a vicious cycle of adipocyte stretch, Rho-Rho-kinase signaling, and inflammation of adipose tissue that contributes to and aggravates obesity.