Refugia in glacial ages led to the current discontinuous distribution patterns of the dark red-backed vole Myodes rex on Hokkaido, Japan.

The terrestrial mammalian fauna of the North Japanese island, Hokkaido, is more similar to that of Southern Siberia than to the main island of Japan, Honshu. Three species of the genus Myodes (Muridae, Rodentia) are found on Hokkaido, but not on Honshu. While Myodes rufocanus and M. rutilus are widely distributed across Hokkaido as well as the Eurasian continent, M. rex, which is endemic to Hokkaido and its adjacent islands, shows a discontinuous distribution pattern. We analyzed the phylogeographic history of M. rex using the mitochondrial DNA control region in order to interpret their discontinuous distribution pattern. Phylogenetic relationships among 54 distinct haplotypes showed that M. rex can be divided into four clades that occur on the northern, central, and southern regions of the Hokkaido mainland and on Rishiri Island, respectively. The phylogroups in the northern and central regions were largely separated in space, although several areas of sympatry were found. The phylogroup in the southern region, which was clearly separated from other phylogroups, showed markedly low genetic variability. All analyzed individuals from the population on Rishiri belonged to a separate lineage. Across a range of divergence rate estimates, we dated the basal divergence of all phylogroups to the mid to late Pleistocene, with subsequent signals of population expansion within lineages. We conclude that current phylogeographic structure in M. rex likely reflects Pleistocene survival in several separate refugia in situ. Past glacial ages have thus played an important role in shaping the current distribution patterns of mammalian species on Hokkaido.

Intra-individual comparison of liver stiffness measurements by magnetic resonance elastography and two-dimensional shear-wave elastography in 888 patients.

PURPOSE: Quantitative elastography methods, such as ultrasound two-dimensional shear-wave elastography (2D-SWE) and magnetic resonance elastography (MRE), are used to diagnose liver fibrosis. The present study compared liver stiffness determined by 2D-SWE and MRE within individuals and analyzed the degree of agreement between the two techniques. METHODS: In total, 888 patients who underwent 2D-SWE and MRE were analyzed. Bland-Altman analysis was performed after both types of measurements were log-transformed to a normal distribution and converted to a common set of units using linear regression analysis for differing scales. The expected limit of agreement (LoA) was defined as the square root of the sum of the squares of 2D-SWE and MRE precision. The percentage difference was expressed as (2D-SWEMRE)/ mean of the two methods×100. RESULTS: A Bland-Altman plot showed that the bias and upper and lower LoAs (ULoA and LLoA) were 0.0002 (95% confidence interval [CI], -0.0057 to 0.0061), 0.1747 (95% CI, 0.1646 to 0.1847), and -0.1743 (95% CI, -0.1843 to -0.1642), respectively. In terms of percentage difference, the mean, ULoA, and LLoA were -0.5944%, 19.8950%, and -21.0838%, respectively. The calculated expected LoA was 17.1178% (95% CI, 16.6353% to 17.6002%), and 789 of 888 patients (88.9%) had a percentage difference within the expected LoA. The intraclass correlation coefficient of the two methods indicated an almost perfect correlation (0.8231; 95% CI, 0.8006 to 0.8432; P<0.001). CONCLUSION: Bland-Altman analysis demonstrated that 2D-SWE and MRE were interchangeable within a clinically acceptable range.

Osteological and genetic analysis of the extinct Ezo wolf (Canis lupus hattai) from Hokkaido Island, Japan.

The Ezo wolf (Canis lupus hattai Kishida, 1931 ) is an extinct subspecies that inhabited Hokkaido in Japan until the middle of the Meiji Period. Because there are very few preserved skeletons, no osteological and/or genetic analyses of the Ezo wolf have been conducted. In this study, 20 cranial and eight mandibular characters were measured on Ezo wolf skeletons, and mitochondrial DNA (mtDNA) was analyzed to assess genetic relationships between the Ezo wolf and other wolf lineages, including the Japanese wolf on Honshu. The morphological study showed that the Ezo wolf is larger than the Japanese wolf and similar in size to the grey wolf of the Asian and American Continents. MtDNA control sequences (751 bp) from two Ezo wolves were identical to those from the Canadian grey wolf. The morphological and genetic characters indicate that the ancestor of the Ezo wolf was genetically related to that of the grey wolf in Canada.

Evaluation of pathological features of hepatocellular carcinoma by contrast-enhanced ultrasonography: comparison with pathology on resected specimen.

Features of hepatocellular carcinoma (HCC) observed by contrast-enhanced ultrasonography (CEUS) were compared to pathological features of corresponding resected HCC specimens, to evaluate the ability of CEUS to depict the pathological features of HCC. We investigated 50 HCC nodules that were treated by surgical resection. All nodules had been examined by CEUS with intravenous contrast agent (Levovist) before surgery. CEUS findings were divided into three phases for evaluation and classification of enhancement patterns: two vascular phases (arterial phase and portal venous phase) and the delayed phase. Pathological examination focused on differentiation and on the presence or absence of a tumor capsule, intratumoral septum, and intratumoral necrosis. All 21 nodules that showed a linear or annular vessel around the tumor margin in the arterial phase had capsular formation. Of the 27 nodules that showed heterogeneous perfusion in the portal venous phase, 21 (77.8%) had an intratumoral septum and 23 (85.2%) showed intratumoral necrosis. All nodules that were depicted as a defect with an unclear margin in the delayed phase were well-differentiated HCCs, whereas all nodules that were depicted as a defect with a clear margin were moderately or poorly differentiated HCCs. From our observations, the arterial, portal venous, and delayed phases of CEUS could reflect different pathological aspects of HCC. Some pathological characteristics of HCC might be evaluated preoperatively and non-invasively, by means of combined analysis of three phases of CEUS findings.

Clinical utility of doppler ultrasonography in evaluation of early therapeutic efficacy after transcatheter arterial embolization in patients with hepatocellular carcinoma.

This study was undertaken to determine the value of Doppler ultrasonography in the early evaluation of therapeutic efficacy of hepatocellular carcinoma after transcatheter arterial embolization (TAE). Fifty-two nodules in which tumor vascularity had been detected by Doppler ultrasonography before TAE were examined in 41 patients. Doppler signals were evaluated 1 week after TAE, and the results were compared with tumor vascularity as determined by dynamic magnetic resonance imaging (dynamic MRI), which was used as the gold standard. The sonographic signal disappeared in 41 (79%) of the 52 nodules and remained in 11 (21%). All nodules in which intratumor vascularity had been detected showed positive stain to dynamic MRI. Four of 41 nodules in which the sonographic signal disappeard showed positive stain on dynamic MRI. The Sensitivity of Doppler ultrasonography was 73%; specificity, 100%; and accuracy, 92%. Flow signal in deeply (≥5 cm) located small (<3 cm) nodules tended to be more difficult to detect. We conclude that Doppler ultrasonography warrants use after TAE in the early evaluation as a specific and noninvasive imaging technique.

Comparison of IV contrast-enhanced sonography and histopathology of pancreatic cancer.

OBJECTIVE: We compared contrast-enhanced sonography findings with pathologic findings in pancreatic cancer to evaluate the ability of contrast-enhanced sonography to depict the pathologic changes associated with pancreatic cancer. SUBJECTS AND METHODS: Thirty-four patients with pancreatic cancer who underwent surgery were investigated. Sonography was performed with contrast material (Levovist) for all patients before surgery. Pathologic findings were evaluated on the basis of the resected cancer specimens. We compared contrast-enhanced sonography findings with pathologic findings. RESULTS: All tumors that were hyperechoic on contrast-enhanced sonography were papillary adenocarcinoma, and all tumors that were hypoechoic on contrast-enhanced sonography were ductal adenocarcinoma. Among ductal adenocarcinomas, five (71.4%) of seven tumors for which the size of the hypoechoic area was unchanged on contrast-enhanced sonography had clear tumor margins with no infiltration or inflammation in the margin. In contrast, all tumors for which the size of the hypoechoic area was reduced on contrast-enhanced sonography had unclear tumor margins with infiltration of cancerous cells and inflammation. Nine (90%) of 10 tumors that showed partial contrast enhancement or a vascular shadow in a hypoechoic area had large or medium-sized vessels within a tumor at pathology. In contrast, only one (4.8%) of 21 tumors that did not show the vascular shadow in a hypoechoic area had no large or medium-sized vessels in a tumor. CONCLUSION: Contrast-enhanced sonography well reflects the pathologic changes of pancreatic cancer and will provide useful information in a pretreatment evaluation. Further studies with a large number of patients will be required to confirm this finding.