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We performed flume experiments to examine tsunami flow conditions, sedimentary processes, and the distribution of tsunami deposits on a narrow coastal lowland backed by a cliff. The experiments directed tsunamis of eight magnitudes onto a terrestrial model of a narrow coastal plain backed by a cliff, and the results were compared with those of similar, previously conducted experiments without a cliff. In the experimental series with the cliff, the tsunami flow was blocked and pooled, and, as a consequence, the flow changed from supercritical to subcritical with a hydraulic jump. The flow transformation forced the suspended sediment in the subsequent flow to stall and deposit. As a result, the distribution of deposits show a local maximum at a short distance from the cliff, in particular in the case of larger tsunami flows. This result suggests that an impeder such as a cliff can cause transformation of a tsunami flow and locally thick deposits.

Using the 160-m-long flume at Tsukuba University we undertook an experiment to provide a first estimate of the virtual velocity of sand in the size range 0.5 – 2.0 mm. For the flow velocity used in our experiment this sediment-size range would conventionally be regarded as suspended sediment. The virtual velocity is found to be 37-41 % of the flow velocity. Paradoxically, virtual velocity decreases as particle size decreases. Such a lower virtual velocity of finer sediment is not inconceivable. First, trapping of the sediment appears to be a function of bed roughness, and there is a probable relationship between bed roughness and trapping efficiency for particles of different sizes. Secondly, finer particles are more likely to find sheltered positions on a rough bed and thus experience lower mobility, relative to the more exposed coarser grains, as observed for bedload transport. Thirdly, the virtual velocity of particles undergoing bedload transport has been found, in some instances, to be lower for finer clasts. We combine our data with previous studies of virtual velocity of bedload to develop, for the first time, an hypothesis for an holistic analysis of sediment movement in rivers.

Aim: Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this st\udy was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients. Methods Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan® just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined. Results CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28 kg/m2 (r = 0.579, P

We developed a portable device made of poly(dimethylsiloxane) (PDMS)/polymethylmethacrylate (PMMA) for long-term 3D cell culture of vascular endothelial cells for the development of a vascular network and evaluated the device under different transitions between normoxia and hypoxia with good optical accessibility. The combination of a nested reservoir device and a bicarbonate/ascorbate buffer system accomplished on-chip incubation with 4.91 &plusmn, 0.86% pO2 and 5.19 &plusmn, 1.70% pCO2 for up to 10 days. Seventy-two hours of normoxic incubation preceding hypoxic culture increased the cell viability, network formation, and size and stability of the resulting lumens compared with those completely maintained in normoxia for the same total duration. We employed different parameters of the network (e.g., total mesh area, total length, number of branches, among others) for the comparison of different oxygen treatments in the device. The differential effect of hypoxic conditions based on the maturity of the vessels may be used as an external factor to improve vascular development in vitro.

To identify and interpret tsunami deposits correctly, a better understanding of the effects of both tsunami magnitude and topographic setting are required. In the present study, laboratory experiments were performed to model these effects on sedimentary processes and the distribution of tsunami deposits on coastal lowlands. The experiments directed tsunamis of eight different magnitudes on to three different models of terrestrial topography: one with flat topography, one with a shallow water-filled pool, and one with a deep water-filled pool. The results suggested a relationship between the distribution of tsunami deposits and the hydraulic condition of the tsunami flow onto the terrestrial topography. In particular, the tsunami deposits in the pools were spatially more variable than those on land because of the variation in flow intensity associated with transformation of the flow from supercritical to subcritical with a hydraulic jump. We observed a gap between the landward extent of deposits and the tsunami inundation distance, particularly in the experiments with a pool. The total amount of sediment in tsunami deposits on the terrestrial area was found to depend on the magnitude of the tsunami, but the thickness of the deposits at any one given spot did not always depend on the tsunami magnitude, even in the same topographic. These results show that terrestrial topography has significant effects on the spatial distribution of tsunami deposits that must be taken into consideration when interpreting the history and magnitude of paleotsunami events from tsunami deposits.

In Japan, light water reactors are built on the seacoast because they use seawater as the final heatsink. Leakage of seawater from the condenser section of the reactor could lead to contamination of the reactor coolant, and stainless steels can be susceptible to crevice corrosion in chloride-contaminated water. Therefore, it is necessary to develop counter measures for suppressing the initiation of crevice corrosion and for repassivating the corroding crevice to maintain structural reliability. To accomplish this, first the effect of molybdate anion on suppressing the initiation of crevice corrosion on 316L stainless steel in chloride-contaminated water was evaluated by potentiostatic immersion tests. Next, the effect of molybdate anion addition on the repassivation of corroding crevices was also evaluated through potentiostatic immersion tests as a function of the concentration of chloride anion. Based on the results of these examinations, the beneficial effects of the presence of molybdate anion on the suppression of initiation and propagation of crevice corrosion were quantitatively evaluated in terms of critical potentials.

Aim Although hyponatremia is associated with a poor prognosis in liver cirrhosis, little is known about the clinical significance of serum sodium concentration in cirrhosis in Japan. This study investigated associations of mortality in Japanese cirrhosis patients taking conventional diuretics with serum sodium concentration and other clinical characteristics. Methods A total of 171 consecutive patients with cirrhosis who were taking diuretic medication were enrolled retrospectively. We determined the prevalence of low serum sodium concentration and searched for associations with age, sex, etiology, complications of cirrhosis, liver function tests and Model for End-Stage Liver Disease (MELD) and MELD-Na scores. The predictive ability of sodium level on mortality was also investigated. Results Median serum sodium concentration was 139 mEq/L (interquartile range, 137-141). Only eight of 171 (4.7%) patients had low serum sodium ( Conclusion Serum sodium concentration below 139 mEq/L and MELD-Na score above 10.5 may be predictive markers for mortality in patients with cirrhosis despite being within normal ranges. These markers may help to better assess and manage the prognosis of patients with cirrhosis in Japan.

The development of bedforms under unidirectional, oscillatory and combined-flows results from temporal changes in sediment transport, flow and morphological response. In such flows, the bedform characteristics (for example, height, wavelength and shape) change over time, from their initiation to equilibrium with the imposed conditions, even if the flow conditions remain unchanged. These variations in bedform morphology during development are reflected in the sedimentary structures preserved in the rock record. Hence, understanding the time and morphological development in which bedforms evolve to an equilibrium stage is critical for informed reconstruction of the ancient sedimentary record. This article presents results from a laboratory flume study on bedform development and equilibrium development time conducted under purely unidirectional, purely oscillatory and combined-flow conditions, which aimed to test and extend an empirical model developed in past work solely for unidirectional ripples. The present results yield a unified model for bedform development and equilibrium under unidirectional, oscillatory and combined-flows. The experimental results show that the processes of bedform genesis and growth are common to all types of flows, and can be characterized into four stages: (i) incipient bedforms; (ii) growing bedforms; (iii) stabilizing bedforms; and (iv) fully developed bedforms. Furthermore, the development path of bedform; growth exhibits the same general trend for different flow types (for example, unidirectional, oscillatory and combined-flows), bedform size (for example, small versus large ripples), bedform shape (for example, symmetrical or rounded), bedform planform geometry (for example, two-dimensional versus three-dimensional), flow velocities and sediment grain sizes. The equilibrium time for a wide range of bed configurations was determined and found to be inversely proportional to the sediment transport flux occurring for that flow condition.

Background & Aims Primary biliary cholangitis (PBC) is an autoimmune liver disease characterized by portal inflammation and immune-mediated destruction of intrahepatic bile ducts that often leads to liver decompensation, and liver failure. Although the biochemical response to ursodeoxycholic acid (UDCA) can predict disease outcome in PBC, few biomarkers have been identified as prognostic tools applicable prior to UDCA treatment. We therefore sought to identify such indicators of long-term outcome in PBC in the Japanese population. Methods The pre-biopsy serum samples and subsequent clinical data of 136 patients with PBC treated with UDCA were analyzed over a median follow-up period of 8.8 years. Serum levels of biomarkers related to microbial translocation (sCD14, EndoCAb, and I-FABP) were measured along with those of 33 cytokines and chemokines and additional autoantibodies. Associations between the tested parameters and the clinical outcomes of liver decompensation and liver-related death/liver transplantation were evaluated using the Cox proportional hazards model with stepwise methods and Kaplan-Meier analysis. Results Elevated levels of serum IL-8, and sCD14 before UDCA therapy were significantly associated with both liver decompensation and liver-related death/liver transplantation. In multivariate analyses, IL-8 ≥ 46.5 pg/mL or sCD14 ≥ 2.0 μg/mL at enrollment demonstrated the same results. Kaplan-Meier analysis also revealed IL-8 and sCD14 to be significantly associated with a poor outcome. sCD14 was significantly correlated with IL-8. EndoCAb and I-FABP were not related to disease outcome. Conclusions Serum IL-8 and sCD14 levels before UDCA therapy represent noninvasive surrogate markers of prognosis in patients with PBC. This article is protected by copyright. All rights reserved.

A 77-year-old male with a long history of alcohol consumption and smoking was admitted for hoarseness and dysphagia. Computed tomography revealed thickening of the middle intrathoracic esophageal wall and multiple mediastinal lymph node swellings. Esophagogastroduodenoscopic examination disclosed an advanced-stage squamous cell carcinoma lesion in the middle intrathoracic esophagus with synchronous early stage Barrett's adenocarcinoma. The patient underwent endoscopic submucosal dissection for the adenocarcinoma followed by chemoradiation therapy for the squamous cell carcinoma. In spite of their common risk factors, the simultaneous manifestation of esophageal squamous cell carcinoma and Barrett's adenocarcinoma is extremely rare and requires further study.

We report the experimental discovery of autogenic cyclicity in delta foreset bedding that arises simply from steady water and sediment input under particular hydraulic characteristics. This autogenesis is intrinsic to Froude-supercritical flow associated with a train of upstream-migrating hydraulic jumps that delineate cyclic steps. Upstream migration of hydraulic jumps is associated with discrete packages of sediment accumulation on the foreset slope. This synchronism originates from the periodic alternation between supercritical and subcritical flow states on the delta topset just upstream of the shoreline, i.e., the topset–foreset break of the delta. The alternation in turn depends on the distance from the topset–foreset break to the nearest hydraulic jump immediately upstream. When the hydraulic jump is still in close proximity to the river mouth (delta shore), it reworks existing topset deposits (and perhaps upper foreset deposits as well) as it migrates upstream. Reworked sediment is then entrained into the subcritical flow between the shore and the hydraulic jump, which then emplaces this fine suspended sediment onto the foreset slope. As the hydraulic jump moves sufficiently far upstream of the mouth, the topset flow becomes supercritical, with a flow velocity sufficient to transport fine sediment offshore beyond the foreset. Under these conditions, the sediment emplaced on the foreset tends to be coarser material deposited via avalanching or proximal deposition from suspension. The details of this selective sedimentation vary according to the material in the topset bed near the mouth that is available for entrainment into the subcritical flow. Regardless of the details, however, distinct cyclic sedimentation of the delta foreset can be sustained as long as the inflow conditions of water and sediment dictate the formation of cyclic steps on the alluvial bed of the topset. Such hydraulic autogenesis accounts for a set of stratigraphic features that are common in ancient Gilbert deltas.

ウェーブリップルは，与えられた振動流条件と堆積物特性の下で，安定的に持続する特定の形状，サイズ，波峰線オリエンテーションを有する．振動流条件が変わるとウェーブリップルはその条件下での定常状態の獲得をめざして遷移する．新たな振動流方向が初期リップルの波峰線と直交する場合，遷移過程は（1）初期リップルと定常リップルの波長の大小関係，（2）振動流の非対称性，（3）堆積物粒径に依存する．とくに，初期リップルの波長が定常リップルのそれよりも大きいと，初期リップルの形状の一部をとどめる遷移リップルが一時的に現れる．地層に見られる遷移リップルは，地層形成時の振動流条件を推測する重要な手がかりとなりうる．

In this paper, nanobubble shrunk from microbubble generated by electrolysis was observed by optical microscope in order to distinguish a bubble from impurities or contamination in the water. To keep microbubbles in focus, it is necessary to generate microbubble whose diameter is less than 5μm in focal position directly since its rising velocity is negligibly small and shrink rapidly. Therefore, diameter distribution of bubble generated by electrolysis was firstly investigated under the different configurations of electrode diameter, concentration of solution and voltage. In the result, when diameter of electrode was less than 1μm, distribution of bubble diameter was decreased to generate smaller bubble. Observation of Brownian motion of nanobubble was succeeded. Root mean square of displacement and diameter of nanobubble were simultaneously measured and compared with a behavior of the ZnO solid particle. As a consequence, root mean square of displacement of bubble is smaller than that of ZnO particle due to different structure of interface.

A 33-year-old man presented with pain and palsy of the leg in 2008 for treatment of hepatocellular carcinoma with huge distant metastases. The patient's tumors had slowly enlarged despite several treatments. Oral administration of sorafenib at 800 mg/day with careful observation was commenced in 2009. Laboratory investigations on day 7 showed massive tumor lysis. An abdominal CT showed multiple low density areas and tumor markers decreased, indicating extended tumor necrosis. In conclusion, clinicians should bear in mind not only the published adverse effects, but also massive tumor lysis, when treating patients with large tumor burden by sorafenib., Article, INTERNAL MEDICINE. 49(11):991-994 (2010)

Wave-flume experiments on the process of deformation of pre-existing two-dimensional ripples revealed that one of two distinct types of three-dimensional patterned ripple, the rhombic or the barrel type, emerged in the early stages of the experimental runs. Rhombic-type ripples were characterized by a staggered pattern of similar-sized mounds, whereas the barrel-type ripples had a barrel-like plan shape arranged in echelons. The former ripples were formed under strongly asymmetrical flow conditions with large excursion distances of water particle motion near the pre-existing rippled bed, whereas the latter were formed under relatively symmetrical flow conditions with small excursion distances. The emergence of both types of ripples was also highly dependent on sediment grain size. Copyright © 2009 John Wiley & Sons, Ltd.

Setting the experimental condition under partially standing wave, which little attention has been given to in spite of being found in nature, a series of wave-flume experiments of development of ripples were performed, using four kinds of sand with different diameters (0.15 mm≤D≤1.23 mm). Ripples developed under partially standing waves showed the cross-shore variations in ripple spacing, asymmetry and crest-line pattern, depending on the positions to ‘nodes’ and ‘anti-nodes’, and on grain size. Ripple spacing was the largest under nodes and the smallest under anti-nodes and was associated with the variation in the orbital diameter. Ripples with rounded crests and bifurcated crest-lines tended to form under anti-nodes.

Non-invasive steatosis-quantifying methods are required for non-alcoholic fatty liver disease (NAFLD) patients in order to monitor disease severity and assess therapeutic efficacy. Controlled attenuation parameter (CAP) evaluated with vibration-controlled transient elastography can predict the presence of steatosis, but its application to absolute hepatic fat quantitation remains unclear. The aim of this st\udy was to examine whether CAP is correlated with real hepatic fat content in NAFLD patients.Eighty-two NAFLD patients who had undergone percutaneous liver biopsy were enrolled. CAP was measured using FibroScan(®) just before liver biopsy. The percentage of fat droplet area to hepatocyte area in biopsied specimen was determined morphometrically using computerized optical image analyzing system. The correlation between CAP and liver histology was examined.CAP showed an excellent correlation with actual liver fat percentage in the NAFLD patients with body mass index (BMI) of less than 28 kg/m(2) (r = 0.579, P 0.0001), especially less than 25 kg/m(2) (r = 0.708, P 0.01), but the meaningful correlation disappeared in the patients with BMI of 28 kg/m(2) or more. In the patients with BMI of less than 28 kg/m(2) , CAP quantitativeness was affected by the presence of stage 2-4 fibrosis, but not the presence of hepatocyte ballooning and severity of lobular inflammation.CAP may be a promising tool for quantifying hepatic fat content in NAFLD patients with none-to-mild obesity and liver fibrosis. Further improvement of CAP performance is needed for the NAFLD patients with BMI of more than 28 kg/m(2) or significant hepatic fibrosis.

OBJECTIVES:Noninvasive markers of liver fibrosis in patients with primary biliary cirrhosis (PBC) are needed for predicting disease progression. As the Wisteria floribunda agglutinin-positive Mac-2-binding protein (WFA+-M2BP) was recently established as a liver fibrosis glycobiomarker in chronic hepatitis C, we assessed its efficacy in evaluating liver fibrosis stage and disease progression in PBC.METHODS:A total of 137 patients with PBC who underwent liver biopsy and serological tests for WFA+-M2BP were enrolled. All patients were treated with ursodeoxycholic acid. Clinical data were compared with those for other noninvasive markers (aspartate aminotransferase-to-platelet ratio, FIB-4 index, aspartate aminotransferase/alanine aminotransferase ratio, Forn’s index, and Mayo score) for estimating liver fibrosis using receiver operating characteristic analysis. The association between WFA+-M2BP and clinical outcome (liver decompensation, liver transplantation, or death) was evaluated using the Cox proportional hazards model with stepwise method.RESULTS:WFA+-M2BP was independently associated with liver fibrosis stage as determined by liver biopsy. The cutoff values of WFA+-M2BP for fibrosis stages ≥F1, ≥F2, ≥F3, and F4 were 0.7, 1.0, 1.4, and 2.0, respectively. The area under the receiver operating characteristic curve values for significant fibrosis, severe fibrosis, and cirrhosis were 0.979, 0.933, and 0.965, respectively. WFA+-M2BP was significantly superior to the other indices for the determination of significant and severe fibrosis stages. Furthermore, the WFA+-M2BP level at enrollment was strongly and independently associated with clinical outcome (hazard ratio 18.59, P=0.021).CONCLUSIONS:Baseline measurements of WFA+-M2BP represent a simple and reliable noninvasive surrogate marker of liver fibrosis and prognosis in patients with PBC., Article, AMERICAN JOURNAL OF GASTROENTEROLOGY.110(6):857-864(2015)

There are many sand banks in Seto Inland Sea, making patchy shallow zones less than 10 m deep. Due to the shallow environment, the surface sediment on the sand banks in the Hojo area, in the southern part of Aki Nada, Shikoku Island, Japan, often has a larger amount of benthic microalgae than other areas. We hypothesized that benthic microalgae contributed to the secondary production of coastal waters around sand bank areas, and investigated the food-web structure of the Hojo area using stable isotopes in early summer, mid summer and fall. Mean carbon isotopic signatures of several consumers in early summer ( 16.9 to 15.1‰ for polychaeta; 17.3 to 13.9‰ for brachyuran crabs; 17.2 to 15.3 for fish) and fall ( 16.2 to 14.3‰ for shrimps; 14.0 to 11.2‰ for brachyuran crabs) were more enriched than that of the particulate organic materials of the surface water around sand banks (mainly phytoplankton) ( 20.5 0.0‰ in early summer and 18.3 0.1‰ in fall). Organic materials attached to cobbles, representative of benthic microalgae, showed similar or more enriched signatures than consumers ( 14.7 0.0‰ in early summer and 10.3 0.0‰ in fall). These results suggest that benthic microalgae on the sand bank contribute greatly to the secondary or higher production of coastal waters in Hojo area.

The lack of systematic studies of the influence of bottom irregularities on ripple initiation led to a series of wave-flume experiments with the purpose of exploring a general relationship. Three types of sand beds with different degrees of roughness were prepared for the experiments: flat, notched, notch-mounded beds. Three kinds of well-sorted sands with different diameters were used for the bed material: fine, medium, and coarse sands. With combinations of waves, water depth, sand, and bed roughness, 248 experimental runs were carried out. Data were analyzed considering (1) the mobility of sediment, expressed in terms of the mobility number, M, (2) the degree of bed roughness, represented by the Reynolds number, Re, and (3) the asymmetry of flow field due to nonlinearity of waves, represented by the relative water depth, kh (= 2πh/L; h = water depth and L = wavelength). The result showed that the threshold for rippling is described by M = 2 + A exp B, where A = 5.7 (3.79/(kh + 0.65) − 1) and B...

Laboratory experiments using a wave flume were designed to examine the threshold condition for ripple formation under asymmetrical oscillatory flows on an artificially roughened bed. Three types of sand beds were prepared in the experiments: they were flat, notched, and notch-mounded beds with bed roughness increasing in this order. The beds were constructed with three kinds of well-sorted sand with similar density, but different diameters. Data analyses were made using the two dimensionless parameters: the mobility number, M, a simplified form of the Shields number, and the Ursell number, U, a surrogate for asymmetry of flow field. The result confirmed that the threshold for ripple initiation is decreased with increasing bed perturbation and that as the bed perturbation increases, the dependency of this threshold on the flow asymmetry becomes less and finally null for the notch-mounded bed. This relationship is quantified by the following equations: M=17−14.5e−0.03U on the flat bed, M=5.0−2.5e−0.1U for the notched bed, and M=2.5 for the notch-mounded bed. A comparison between the previous field data and the present laboratory findings indicates that the threshold in the notch-mounded bed experiment, M=2.5, seems to provide a critical condition for rippling in the natural environment.

A wave-flume experiment was conducted to examine the formative condition for three types of distinctive bedforms that emerged through deformation of existing ripples due to waning wave power. They were ripple marks with: (1) a single secondary crest, (2) double secondary crests, and (3) a rounded crest. Data were analysed using two parameters, kh and d0/λ*, where k is the wave number, h is the water depth, d0 is the near-bottom orbital diameter, and λ* is the spacing of existing ripples. The former quantity, kh, was employed as a surrogate for the degree of flow asymmetry. The result showed that ripples with secondary crests developed under a rather symmetrical flow field with kh ≳ 0·7, if d0/λ* ≲ 1·2, whereas rounded-crest ripples emerged under asymmetrical flow field with kh ≲ 0·7, if d0/λ* ≲ −2·9 kh + 3·2. The number of secondary crests, which initially occurred in each trough, was single if d0/λ* ≳ 0·8, or double if d0/λ* ≲ 0·8. Copyright © 2004 John Wiley & Sons, Ltd.

Although hyponatremia is associated with a poor prognosis in liver cirrhosis, little is known about the clinical significance of serum sodium concentration in cirrhosis in Japan. This study investigated associations of mortality in Japanese cirrhosis patients taking conventional diuretics with serum sodium concentration and other clinical characteristics.A total of 171 consecutive patients with cirrhosis who were taking diuretic medication were enrolled retrospectively. We determined the prevalence of low serum sodium concentration and searched for associations with age, sex, etiology, complications of cirrhosis, liver function tests and Model for End-Stage Liver Disease (MELD) and MELD-Na scores. The predictive ability of sodium level on mortality was also investigated.Median serum sodium concentration was 139 mEq/L (interquartile range, 137-141). Only eight of 171 (4.7%) patients had low serum sodium (130 mEq/L). Median MELD-Na score was 10.5 (interquartile range, 8.0-14.3). Cumulative survival rates were significantly lower in patients with Na of less than 139 mEq/L or MELD-Na score of 10.5 or more (log-rank test, P = 0.017 and P = 0.0002, respectively). Several liver function tests, MELD and MELD-Na scores, and the incidence of ascites were all significantly associated with patients having Na of less than 139 mEq/L.Serum sodium concentration below 139 mEq/L and MELD-Na score above 10.5 may be predictive markers for mortality in patients with cirrhosis despite being within normal ranges. These markers may help to better assess and manage the prognosis of patients with cirrhosis in Japan.

In this paper we investigated ζ potential of microbubbles by electrophoresis method. The individual bubble diameter measured by means of interferometric laser imaging technique. The experimental results showed that different methods for producing microbubbles which were pressurizing dissolution method, swiveling gas-liquid two-phase flow method and electrolysis method did not make difference in the resultant values of ζ potential. In order to understand the mechanism of charging characteristic of microbubbles, we changed the pH of the deionized water and added alcohols or a surfactant to the deionized water. The results showed that the absolute value of the ζ potential increased when the pH increased. ζ potential was drastically changed by alcohols and surfactant which easily absorbed on the air-water interface. Moreover, simultaneous measurement of ζ potential and diameter of shriking microbubble resulted that bubbles shose diameter is less than 3 μm were observed by using Mie theory.

The development of simple, noninvasive markers of liver fibrosis is urgently needed for primary biliary cirrhosis (PBC). This study examined the ability of several serum biomarkers of cell death to estimate fibrosis and prognosis in PBC. A cohort of 130 patients with biopsy-proven PBC and 90 healthy subjects were enrolled. We assessed the utility of the M30 ELISA, which detects caspase-cleaved cytokeratin-18 (CK-18) fragments and is representative of apoptotic cell death, as well as the M65 and newly developed M65 Epideath (M65ED) ELISAs, which detect total CK-18 as indicators of overall cell death, in predicting clinically relevant fibrosis stage. All 3 cell death biomarkers were significantly higher in patients with PBC than in healthy controls and were significantly correlated with fibrosis stage. The areas under the receiver operating characteristic curve for the M65 and M65ED assays for differentiation among significant fibrosis, severe fibrosis, and cirrhosis were 0.66 and 0.76, 0.66 and 0.73, and 0.74 and 0.82, respectively. In multivariate analysis, high M65ED (hazard ratio 6.13; 95% confidence interval 1.18-31.69; P = 0.031) and severe fibrosis (hazard ratio 7.45; 95% confidence interval 1.82-30.51; P = 0.005) were independently associated with liver-related death, transplantation, or decompensation. High serum M65ED was also significantly associated with poor outcome in PBC (log-rank test; P = 0.001). Noninvasive cell death biomarkers appear to be clinically useful in predicting fibrosis in PBC. Moreover, the M65ED assay may represent a new surrogate marker of adverse disease outcome.

At least two different protease pathways have been implicated in the degradation that is required to control the eukaryotic cell cycle; these two pathways center on the activities of ubiquitin/proteasome and cysteine protease. The proteasome inhibitors, lactacystin and AcLLnL and the cysteine protease inhibitor E-64-d were tested for their ability to inhibit the cell cycles of Xenopus embryos. Lactacystin, AcLLnL and E-64-d all caused the complete arrest of the cell cycle. To define the specific cell cycle processes that were affected by the two inhibitors, we performed a cytological analysis. Inhibition of the cell cycle by lactacystin and E-64-d occurred during prophase and metaphase. The number of cells that arrested in prophase was 1.4-times higher in the E-64-d-treated group than in the control group and the number of arrested cells in the lactacystin-treated group was 1.4-times higher than in the E-64-d-treated group. The number of cells that arrested in metaphase was 3-to-4-times higher in the E-64-d and lactacystin groups than in the control group. These results indicate that both cysteine protease(s) and proteasomes are involved in the prophase and metaphase stages of cell division.

Certain clinical aspects of vivax malaria are no longer defined as benign. We present a case of vivax malaria with three relapses in a pregnant Japanese woman who had returned to Japan from the Comoros Islands in East Africa. Data on the successful delivery, examination of Duffy-blood group antigen, and microscopic findings of growing stages of Plasmodium vivax are thought to be of considerable interest.