Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway

The efficient induction of cardiomyocyte differentiation from embryonic stem (ES) cells is crucial for cardiac regenerative medicine. Although Wnts play important roles in cardiac development, complex questions remain as to when, how and what types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up-regulated during cardiomyocyte differentiation from ES cells. Therefore, we investigated when and how Wnt2 acts in cardiogenesis during ES cell differentiation. Wnt2 was strongly expressed in the early developing murine heart. We applied this embryonic Wnt2 expression pattern to ES cell differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation. Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased cardiomyocyte differentiation from ES cells. Interestingly, the effects on cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2 didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is required for cardiomyocyte differentiation from ES cells. Therefore we conclude that Wnt2 plays strong positive stage-specific role in cardiogenesis through non-canonical Wnt pathway in murine ES cells.     

Pathological complete response of synchronous multiple liver metastases associated with advanced gastric cancer to gastrectomy and prompt S-1 treatment in combination with fractional cisplatin: report of a case

Systemic chemotherapy is the treatment recommended for prolonged survival in cases of metastatic gastric cancer. There have been a number of clinical reports of surgical resection of liver metastasis in selected patients with gastric cancer. Here, we report on a case of treatment of far advanced gastric cancer with synchronous multiple liver metastases with prompt S-1 in combination with fractional cisplatin sandwiched between twostage surgery. Metastases including peritoneal dissemination and extensive lymph node involvement were absent so it was feasible to completely remove all of the macroscopic liver metastases. Each step of the chemotherapy progressed satisfactorily and histological examination after the hepatectomy yielded a pathologically complete response of liver metastases from the gastric cancer. This strategy provides a promising treatment for far advanced gastric cancer with a limited number of synchronous liver metastases. The referral to surgical oncology is a crucial step for the documentation of pathological complete response.     

Clinical features and varieties of non-motor fluctuations in Parkinson's disease: A Japanese multicenter study

ObjectiveThis multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD).MethodsTo identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis.ResultsThe patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation.ConclusionForty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.     

Ethnic differences in genetic predisposition to hypertension

Recently, large-scale meta-analyses of genome-wide association (GWA) studies have identified a number of loci significantly associated with systolic and/or diastolic blood pressure (BP). Most of the GWA studies reported to date were conducted in populations of European descent. Given the appreciable ethnic differences in clinical presentation of hypertension, studies in non-European populations allow us to assess the relevance of the findings in Europeans to other ethnic groups and to potentially discover novel variants. Before the GWA scan era, the presence of racial or ethnic differences has been widely recognized for response to antihypertensive therapies, salt sensitivity and impact of obesity on developing hypertension. Despite a limited number of genetic loci that have been proven to show substantial ethnic differences, we can assume four possible genetic mechanisms--(1) absence of target variants in other ethnic groups; (2) presence of allelic heterogeneity; (3) difference in linkage disequilibrium structure; and (4) gene-gene and gene-environment interactions. Considering such a number of potential sources of heterogeneity, we should be cautious about claiming the presence of genuine ethnic differences in genetic susceptibility to BP-related traits or hypertension. Approximately a quarter of BP-associated loci that have been reported in four meta-analyses of GWA studies (i.e., 8 out of 34 loci) appear to be common across three ethnic groups--Europeans, east Asians and south Asians. 'Transethnic' BP meta-analysis will be useful not only for revealing novel susceptibility loci and pathophysiological pathways but also for facilitating the fine mapping of common causal variants.