肝線維化におけるコラーゲン分泌機構の解析

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 堅田 利明, 東京大学教授 一條 秀憲, 東京大学教授 関水 和久, 東京大学准教授 千原 崇裕, 東京大学講師 前田 和哉University of Tokyo(東京大学

Arterial embolization in patients with grade-4 blunt renal trauma: evaluation of the glomerular filtration rates by dynamic scintigraphy with 99mTechnetium-diethylene triamine pentacetic acid

<p>Abstract</p> <p>Background</p> <p>High-grade blunt renal trauma has been treated by arterial embolization (AE). However, it is unknown whether AE preserves renal function, because conventional renal function tests reflect total renal function and not the function of the injured kidney alone. Dynamic scintigraphy can assess differential renal function.</p> <p>Methods</p> <p>We performed AE in 17 patients with grade-4 blunt renal trauma and determined their serum creatinine (sCr) level and glomerular filtration rate (GFR; estimated by dynamic scintigraphy) after 3 months. In 4 patients with low GFR of the injured kidney (<20 ml·min^-1·1.73 m^-2), the GFR and sCr were measured again at 6 months. Data are presented as median and interquartile range (25th, 75th percentile).</p> <p>Results</p> <p>The median GFR of the injured kidney, total GFR, and median sCr at 3 months were 29.3 (23.7, 35.3) and 96.8 (79.1, 102.6) ml·min^-1·1.73 m^-2and 0.6 (0.5, 0.7) mg/dl, respectively. In the patients with low GFR (ml·min^-1·1.73 m^-2), the median GFR of the injured kidney, total GFR, and median sCr (mg/dl) were 16.2 (15.7, 16.3), 68.7 (61.1, 71.6), and 0.7 (0.7, 0.9), respectively, at 3 months and 34.5 (29.2, 37.0), 90.9 (79.1, 98.8), and 0.7 (0.7, 0.8), respectively, at 6 months.</p> <p>Conclusions</p> <p>The function of the injured kidney was preserved in all patients, indicating the efficacy of AE for the treatment of grade-4 blunt renal trauma.</p

Presence of corrective saccades in patients with normal vestibulo-ocular reflex gain in video head impulse test

BackgroundThe video head impulse test (vHIT) is a valuable clinical tool that can help identify dysfunction of the semicircular canals. While in cases with semicircular canal dysfunction, both decreased vestibulo-ocular reflex (VOR) gain and corrective saccades (CS) are usually observed, there are cases which show CS despite normal VOR gain in vHIT.ObjectiveThis study aimed to investigate the clinical characteristics of patients who showed CS with normal VOR gain in vHIT.Materials and methodsAmong 390 patients who underwent vHIT, 51 patients (20 males and 31 females, age 31–87 years, average 61.3 years old) who showed CS with normal VOR gain unilaterally during horizontal vHIT were included. All patients had normal vHIT (normal VOR gain and absent CS) on the contralateral side.The VOR gain of vHIT, the maximum slow phase velocity in the caloric test, and the amplitude of cervical and ocular vestibular evoked myogenic potentials (cVEMPs and oVEMPs) were analyzed.ResultsThe VOR gain on the affected side (0.95 ± 0.08) was significantly smaller than that on the contralateral side (1.03 ± 0.13) in horizontal vHIT (p &lt; 0.001). The maximum slow phase velocity in the caloric test on the affected side (17.9 ± 17.8 degrees/s) was significantly smaller than that on the contralateral side (21.3 ± 16.6 degrees/s, p = 0.020). There were no significant differences in the amplitude of cVEMPs or oVEMPs between the affected side and the contralateral side (p = 0.096 for cVEMP; p = 0.770 for oVEMP).ConclusionThe side that showed CS with normal VOR gain in horizontal vHIT showed significantly smaller VOR gain as well as smaller caloric responses compared to the contralateral side. Having CS with normal VOR gain could be a sensitive indicator of mild dysfunction of the semicircular canals

A case of well-differentiated cholangiolocellular carcinoma visualized with contrast-enhanced ultrasonography using Sonazo

Author Posting.This is the author's version of the work.It is posted here by permission of The Japan Society of Hepatology for personal use，not for redistribution.The definitive version was published in Hepatology Research, Voume39, Issue 2, pages 207-212. https://doi.org/10.1111/j.1872-034X.2008.00446.xWe here report the first case of cholangiolocellular carcinoma (CoCC) visualized with contrast-enhanced ultrasonography (CEUS) using a second-generation contrast agent, Sonazoid. A 76-year-old man was admitted to our hospital for evaluation of a hepatic tumor. The tumor was described as having hyper-enhancement in the early phase and persistent enhancement in the late phase by contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), as well as hypervascularity by angiography. CEUS assessment of the nodule showed diffuse and homogeneous enhancement in the pure arterial phase, which became progressively hypoechoic relative to the adjacent liver parenchyma during the portal vein and late phases (mixed vascular phase), and showed a contrast defect with an unclear border in the Kupffer phase. Histologically we diagnosed this hepatic tumor as CoCC. In light of the above findings and the rarity of CoCC, it is helpful to incorporate the results of several imagings, such as CT, MRI, angiography and CEUS with a second-generation contrast agent when clinically diagnosing CoCC.ArticleHEPATOLOGY RESEARCH. 39(2):207-212 (2009)journal articl

Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy

Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy

A Report on Hydrographic Activities Following the Great East Japan Earthquake

The Great East Japan Earthquake (Mw9.0) on 11 March 2011 accompanied with a huge tsunami of more than 10 meters in height devastated many cities and ports along the Pacific coast of northeastern Japan, and claimed nearly 20,000 lives with many of them still missing. This report reviews actions taken by the Japan Hydrographic and Oceanographic Department (JHOD) after this unprecedented disaster. Immediately after the earthquake, the JHOD carried out hydrographic surveys for the urgent need to help clear the passage in ports due to sunken debris swept away by the tsunami. These surveys have enabled the vessels with relief supplies on board for the affected areas to enter the ports. The JHOD revisited the affected ports for the next stage of hydrographic surveys. These surveys will contribute to revised nautical charts based on new data collected after the earthquake, and includes the ongoing restoration and reconstruction work of quays and port facilities. This stage includes the re-determination of the datum level of the affected ports, which is necessary because of large subsidence being reported in the areas. All of these efforts by the JHOD clearly demonstrate the significance of the hydrographic activities in case of the post-quake emergency situation, not only for the safety of navigation but also for economic recovery

Mucin-hypersecreting bile duct neoplasm characterized by clinicopathological resemblance to intraductal papillary mucinous neoplasm (IPMN) of the pancreas

<p>Abstract</p> <p>Background</p> <p>Although intraductal papillary mucinous neoplasm (IPMN) of the pancreas is acceptable as a distinct disease entity, the concept of mucin-secreting biliary tumors has not been fully established.</p> <p>Case presentation</p> <p>We describe herein a case of mucin secreting biliary neoplasm. Imaging revealed a cystic lesion 2 cm in diameter at the left lateral segment of the liver. Duodenal endoscopy revealed mucin secretion through an enlarged papilla of Vater. On the cholangiogram, the cystic lesion communicated with bile duct, and large filling defects caused by mucin were observed in the dilated common bile duct. This lesion was diagnosed as a mucin-secreting bile duct tumor. Left and caudate lobectomy of the liver with extrahepatic bile duct resection and reconstruction was performed according to the possibility of the tumor's malignant behavior. Histological examination of the specimen revealed biliary cystic wall was covered by micropapillary neoplastic epithelium with mucin secretion lacking stromal invasion nor ovarian-like stroma. The patient has remained well with no evidence of recurrence for 38 months since her operation.</p> <p>Conclusion</p> <p>It is only recently that the term "intraductal papillary mucinous neoplasm (IPMN)," which is accepted as a distinct disease entity of the pancreas, has begun to be used for mucin-secreting bile duct tumor. This case also seemed to be intraductal papillary neoplasm with prominent cystic dilatation of the bile duct.</p

RINL, Guanine Nucleotide Exchange Factor Rab5-Subfamily, Is Involved in the EphA8-Degradation Pathway with Odin

The Rab family of small guanosine triphosphatases (GTPases) plays a vital role in membrane trafficking. Its active GTP-bound state is driven by guanine nucleotide-exchange factors (GEFs). Ras and Rab interactor (or Ras interaction/interference)-like (RINL), which contains a conserved VPS9 domain critical for GEF action, was recently identified as a new Rab5 subfamily GEF in vitro. However, its detailed function and interacting molecules have not yet been fully elucidated. Here we found that RINL has GEF activity for the Rab5 subfamily proteins by measuring their GTP-bound forms in cultured cells. We also found that RINL interacts with odin, a member of the ankyrin-repeat and sterile-alpha motif (SAM) domain-containing (Anks) protein family. In addition, the Eph tyrosine kinase receptor EphA8 formed a ternary complex with both RINL and odin. Interestingly, RINL expression in cultured cells reduced EphA8 levels in a manner dependent on both its GEF activity and interaction with odin. In addition, knockdown of RINL increased EphA8 level in HeLa cells. Our findings suggest that RINL, as a GEF for Rab5 subfamily, is implicated in the EphA8-degradation pathway via its interaction with odin