A Case of Dual-pathology Hepatocellular Carcinoma (HCC) and Cholangiolocellular Carcinoma (CoCC) after Eradication of Hepatitis C Virus (HCV) Infection

A 75-year-old Japanese man visited our hospital for further examination of liver tumors. He had a history of successful hepatitis C virus (HCV) eradication and therapy for hepatocellular carcinoma (HCC) at another hospital. Magnetic resonance imaging (MRI) revealed two tumors in the liver. He underwent anterior inferior (S5) and posterior inferior (S6) subsegmentectomy of the liver. Microscopic examination found that one tumor was HCC while the other was cholangiolocellular carcinoma (CoCC). We experienced a rare case of liver cancer with two synchronous pathologies, HCC and CoCC

Patched1 Haploinsufficiency Increases Adult Bone Mass and Modulates Gli3 Repressor Activity

SummaryHedgehog (Hh)-Patched1 (Ptch1) signaling plays essential roles in various developmental processes, but little is known about its role in postnatal homeostasis. Here, we demonstrate regulation of postnatal bone homeostasis by Hh-Ptch1 signaling. Ptch1-deficient (Ptch1+/−) mice and patients with nevoid basal cell carcinoma syndrome showed high bone mass in adults. In culture, Ptch1+/− cells showed accelerated osteoblast differentiation, enhanced responsiveness to the runt-related transcription factor 2 (Runx2), and reduced generation of the repressor form of Gli3 (Gli3rep). Gli3rep inhibited DNA binding by Runx2 in vitro, suggesting a mechanism that could contribute to the bone phenotypes seen in the Ptch1 heterozygotes. Moreover, systemic administration of the Hh signaling inhibitor cyclopamine decreased bone mass in adult mice. These data provide evidence that Hh-Ptch1 signaling plays a crucial role in postnatal bone homeostasis and point to Hh-Ptch1 signaling as a potential molecular target for the treatment of osteoporosis

Critical phase of a magnetic hard hexagon model on triangular lattice

We introduce a magnetic hard hexagon model with two-body restrictions for configurations of hard hexagons and investigate its critical behavior by using Monte Carlo simulations and a finite size scaling method for discreate values of activity. It turns out that the restrictions bring about a critical phase which the usual hard hexagon model does not have. An upper and a lower critical value of the discrete activity for the critical phase of the newly proposed model are estimated as 4 and 6, respectively.Comment: 11 pages, 8 Postscript figures, uses revtex.st

SORL1 Is Genetically Associated with Late-Onset Alzheimer’s Disease in Japanese, Koreans and Caucasians

To discover susceptibility genes of late-onset Alzheimer’s disease (LOAD), we conducted a 3-stage genome-wide association study (GWAS) using three populations: Japanese from the Japanese Genetic Consortium for Alzheimer Disease (JGSCAD), Koreans, and Caucasians from the Alzheimer Disease Genetic Consortium (ADGC). In Stage 1, we evaluated data for 5,877,918 genotyped and imputed SNPs in Japanese cases (n = 1,008) and controls (n = 1,016). Genome-wide significance was observed with 12 SNPs in the APOE region. Seven SNPs from other distinct regions with p-values ,261025 were genotyped in a second Japanese sample (885 cases, 985 controls), and evidence of association was confirmed for one SORL1 SNP (rs3781834, P=7.3361027 in the combined sample). Subsequent analysis combining results for several SORL1 SNPs in the Japanese, Korean (339 cases, 1,129 controls) and Caucasians (11,840 AD cases, 10,931 controls) revealed genome wide significance with rs11218343 (P=1.7761029) and rs3781834 (P=1.0461028). SNPs in previously established AD loci in Caucasians showed strong evidence of association in Japanese including rs3851179 near PICALM (P=1.7161025) and rs744373 near BIN1 (P = 1.3961024). The associated allele for each of these SNPs was the same as in Caucasians. These data demonstrate for the first time genome-wide significance of LOAD with SORL1 and confirm the role of other known loci for LOAD in Japanese. Our study highlights the importance of examining associations in multiple ethnic populations