Indirect Fist Percussion of the Liver Is a More Sensitive Technique for Detecting Hepatobiliary Infections than Murphy’s Sign

Background. Murphy’s sign and Charcot’s triad are established clinical findings of acute cholecystitis and cholangitis, respectively, but both show low sensitivity and limited clinical application. We evaluated if indirect fist percussion of the liver improves the efficiency of diagnosing cholecystitis and cholangitis when used as a diagnostic adjunct. Methods. The presence/absence of right upper quadrant (RUQ) tenderness, Murphy’s sign, and pain induced by indirect fist percussion of the liver was assessed, and the results were compared with the definite diagnosis based on ultrasound and additional examinations in patients aged over 18 who visited our outpatient clinic with suspected hepatobiliary diseases. Results. Four hundred and eight patients were investigated, and 40 had hepatobiliary infection (acute cholecystitis: 10, acute cholangitis: 28, liver abscess: 1, and hepatic cyst infection: 1). The sensitivity of indirect fist percussion of the liver for diagnosing hepatobiliary infection was 60%, being significantly higher than that of RUQ tenderness (33%) and Murphy’s sign (30%), and its specificity was 85%. There was no significant improvement in sensitivity or diagnostic accuracy when Murphy’s sign was combined with indirect fist percussion of the liver. Conclusion. Indirect fist percussion-induced liver pain is a useful clinical finding to diagnose hepatobiliary infection, with high-level sensitivity

On Wittgenstein's Understanding of Ethical Value : From the Perspective of Tractatus Logico-Philosophicus and A Lecture on Ethics

departmental bulletin pape

The uncoating of EV71 in mature late endosomes requires CD-M6PR

Enterovirus 71 (EV71) is one of the causative agents of hand-foot-and-mouth disease, which in some circumstances could lead to severe neurological diseases. Despite of its importance for human health, little is known about the early stages of EV71 infection. EV71 starts uncoating with its receptor, human scavenger receptor B2 (hSCARB2), at low pH. We show that EV71 was not targeted to lysosomes in human rhabdomyosarcoma cells overexpressing hSCARB2 and that the autophagic pathway is not essential for EV71 productive uncoating. Instead, EV71 was efficiently uncoated 30 minutes after infection in late endosomes (LEs) containing hSCARB2, mannose-6-phosphate receptor (M6PR), RAB9, bis(monoacylglycero)phosphate and lysosomal associated membrane protein 2 (LAMP2). Furthering the notion that mature LEs are crucial for EV71 uncoating, cation-dependent (CD)-M6PR knockdown impairs EV71 infection. Since hSCARB2 interacts with cation-independent (CI)-M6PR through M6P-binding sites and CD-M6PR also harbor a M6P-binding site, CD-M6PR is likely to play important roles in EV71 uncoating in LEs

Anti-Tumor Effect against Human Cancer Xenografts by a Fully Human Monoclonal Antibody to a Variant 8-Epitope of CD44R1 Expressed on Cancer Stem Cells

BACKGROUND: CD44 is a major cellular receptor for hyaluronic acids. The stem structure of CD44 encoded by ten normal exons can be enlarged by ten variant exons (v1-v10) by alternative splicing. We have succeeded in preparing MV5 fully human IgM and its class-switched GV5 IgG monoclonal antibody (mAb) recognizing the extracellular domain of a CD44R1 isoform that contains the inserted region coded by variant (v8, v9 and v10) exons and is expressed on the surface of various human epithelial cancer cells. METHODS AND PRINCIPAL FINDINGS: We demonstrated the growth inhibition of human cancer xenografts by a GV5 IgG mAb reshaped from an MV5 IgM. The epitope recognized by MV5 and GV5 was identified to a v8-coding region by the analysis of mAb binding to various recombinant CD44 proteins by enzyme-linked immunosorbent assay. GV5 showed preferential reactivity against various malignant human cells versus normal human cells assessed by flow cytometry and immunohistological analysis. When ME180 human uterine cervix carcinoma cells were subcutaneously inoculated to athymic mice with GV5, significant inhibition of tumor formation was observed. Furthermore, intraperitoneal injections of GV5markedly inhibited the growth of visible established tumors from HSC-3 human larynx carcinoma cells that had been subcutaneously transplanted one week before the first treatment with GV5. From in vitro experiments, antibody-dependent cellular cytotoxicity and internalization of CD44R1 seemed to be possible mechanisms for in vivo anti-tumor activity by GV5. CONCLUSIONS: CD44R1 is an excellent molecular target for mAb therapy of cancer, possibly superior to molecules targeted by existing therapeutic mAb, such as Trastuzumab and Cetuximab recognizing human epidermal growth factor receptor family

スチームコンベクションオーブン調理と真空調理による水溶性ビタミンの調理損失の比較：かぼちゃおよび大根の煮物について

The purpose of this study is to compare and study water-soluble vitamin losses before and after cooking pumpkin and Japanese radish (daikon) with a steam convection oven (SC cooking) and a vacuum-packed pouch (V-P P cooking). Pumpkin was cut into 2.5 cm cubes and daikon into 2.0 cm cubes. For SC cooking, pumpkin was heated for 15 minutes and daikon for 60 minutes with liquid seasoning. For V-P P cooking, pumpkin and daikon were vacuum-packed with liquid seasoning and heated under the same conditions as SC cooking. For pumpkin, percentages of niacin, folic acid and pantothenic acid in uncooked samples, as well as those cooked by SC cooking and V-P P cooking were compared. For daikon, percentages of vitamins B1, B2, B6 and C, niacin, folic acid and pantothenic acid in uncooked samples, as well as those cooked by SC cooking and V-P P cooking were compared. Setting the percentages of vitamins remained in uncooked samples as 100 %, those in SC and V-P P cooked samples of pumpkin were calculated as follows: niacin 93.1 %, 85.4 %; folic acid 84.0 %, 74.4 %; and pantothenic acid 97.9 %, 89.1 %, respectively. Percentages of vitamins in SCand V-P P cooked samples of daikon were as follows: vitamin B1 97.4 %, 94.0 %; vitamin B2 not detected, not detected; vitamin B6 66.6 %, 65.2 %; vitamin C 43.3 %, 52.2 %; niacin 80.0 %, 66.7 %; folic acid 37.7 %, 37.7 %; and pantothenic acid 72.0 %, 65.4 %, respectively.These results indicated that vitamin losses measured in this study were attributable to the cooking process, suggesting that the degree of vitamin losses due to the cooking process varied according to the characteristics of vitamins and cooking methods.論

Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

母親のPorphyromonas gingivalis歯性感染が仔の脳組織に与える影響

内容の要約広島大学(Hiroshima University)博士(歯学)Doctor of Philosophy in Dental Sciencedoctora

閉塞性睡眠時無呼吸症候群（OSAS）に対する下顎前方位型口腔内装置（MAD）による咬合機能および歯列・顎顔面形態への影響

内容の要約広島大学(Hiroshima University)博士(歯学)Doctor of Philosophy in Dental Sciencedoctora