Apoptosis-dependent externalization and involvement in apoptotic cell clearance of DmCaBP1, an endoplasmic reticulum protein of Drosophila

To elucidate the actions of Draper, a receptor responsible for the phagocytic clearance of apoptotic cells in Drosophila, we isolated proteins that bind to the extracellular region of Draper using affinity chromatography. One of those proteins has been identified to be an uncharacterized protein called Drosophila melanogaster calcium-binding protein 1 (DmCaBP1). This protein containing the thioredoxin-like domain resided in the endoplasmic reticulum and seemed to be expressed ubiquitously throughout the development of Drosophila. DmCaBP1 was externalized without truncation after the induction of apoptosis somewhat prior to chromatin condensation and DNA cleavage in a manner dependent on the activity of caspases. A recombinant DmCaBP1 protein bound to both apoptotic cells and a hemocyte-derived cell line expressing Draper. Forced expression of DmCaBP1 at the cell surface made non-apoptotic cells susceptible to phagocytosis. Flies deficient in DmCaBP1 expression developed normally and showed Draper-mediated pruning of larval axons, but a defect in the phagocytosis of apoptotic cells in embryos was observed. Loss of Pretaporter, a previously identified ligand for Draper, did not cause a further decrease in the level of phagocytosis in DmCaBP1-lacking embryos. These results collectively suggest that the endoplasmic reticulum protein DmCaBP1 is externalized upon the induction of apoptosis and serves as a tethering molecule to connect apoptotic cells and phagocytes for effective phagocytosis to occur. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc

LINE-1 hypomethylation status of circulating cell-free DNA in plasma as a biomarker for colorectal cancer.

Colorectal cancer (CRC) is a serious public health problem and non-invasive biomarkers improving diagnosis or therapy are strongly required. Circulating cell-free DNA (cfDNA) has been a promising target for this purpose. In this study, we evaluated the potential of long interspersed nuclear element-1 (LINE-1) hypomethylation as a blood biomarker for CRC. LINE-1 hypomethylation level in plasma cfDNA in 114 CRC patients was retrospectively examined by absolute quantitative analysis of methylated alleles real-time PCR, and was expressed using LINE-1 hypomethylation index (LHI) [unmethylated copy number/ (methylated copy number + unmethylated copy number)]. Greater LHI values indicated enhanced hypomethylation. In our clinicopathological analysis, CRC patients with large tumors (≥6.0 cm), advanced N stage (≥2), and distant metastasis (M1) had statistically significantly higher cfDNA LHI than other CRC patients, suggesting cfDNA LHI as a disease progression biomarker for CRC. Furthermore, early stage I/II (n = 57) as well as advanced stage III/IV (n =57) CRC patients had significantly higher cfDNA LHI than healthy donors (n=53) [stage I/II: median 0.369 (95% confidence interval, 0.360-0.380) vs. 0.332 (0.325-0.339), P \u3c 0.0001; stage III/IV: 0.372 (0.365-0.388) vs. 0.332 (0.325-0.339), P \u3c 0.0001]. The receiver operating characteristic analysis showed that cfDNA LHI had the detection capacity of CRC with area under the curve(AUC) of 0.79 and 0.83 in stage I/II and stage III/IV CRC patients, respectively. The present study demonstrated for the first time the potential of plasma cfDNA LHI as a novel biomarker for CRC, particularly for early stage detection

Factor of increased propofol dosage during dental treatment under intravenous anesthesia.

Introduction　Dental treatment using propofol (trade name Diprivan) was carried out for people with disabilities who have difficulties with dental treatment so that dental treatment could be carried out safely and smoothly. This time, we investigated for the purpose of clarifying the factors of those who need 3.5 µg/ml or more when sedated with propofol.　Object and method　Methods　　The subjects were 34 persons, who required the intravenous anesthesia method at the time of dental treatment, among patients who visited Matsumoto Dental University Hos-pital special specialist department from May 1st to September 30 th , 2015. Gender, age, presence or absence of regular medications were noted, weight and height were measured, and BMI was calculated. Disease, treatment, type of disability, and intellectual level from the　medical record were entered on the survey form. As an evaluation of adaptability to dental treatment, they were classified into 4 stages: “Can sit on the medical table”; “Can sleep the 　treatment table”; “Can do an oral examination”; and “Can do PTC”.　The diffuser TCI function was used to initiate intravenous administration at the target 　blood concentration of 3.0 µg/ml. Dental treatment was started with blood concentration in the brain when the opening device was smoothly inserted. If this target was not possible,　0.2 µg/ml each was listed. Blood concentrations and intracerebral concentrations of propofol during treatment were recorded. The intracerebral concentration where the opening device was smoothly inserted, the lowest brain concentration and the maximum brain concentration at the time of treatment were also recorded.Result　34 subjects (28 males, 6 females) had an average age of 37.6±12.4 years. The items asso-　ciated with brain concentration of propofol were subjects aged 50 years or older (P = 0.01), 　BMI (P = 0.15), dental phobia (P = 0.001), and autistic spectrum disease (P = 0.07). The factor that required propofol brain concentration of over 3.5 µg/ml was dental phobia (odds ratio: 28.5: confidence interval 1.₉–421) by the logistic regression analysis.　Conclusion　A factor that requires propofol of 3.5 µg/ml or more at the time of dental treatment, for those who can assume a supine position without making refusing actions at the medical table, was dental phobia. There was no relevance to the content of treatment or to the adaptability to dental treatment.

Formative Factors of Membranous Substances on Dorsum of Tongue, Teeth, Buccal Mucosa in Elderly Persons Requiring Nursing Care

要介護者の口腔粘膜にみられる付着物は，痰，痂皮，剥離上皮と呼ばれているが，上皮成分を主体とした付着物を剥離上皮膜と定義づけ，本研究にて，要介護高齢者の口腔内に形成された剥離上皮膜を部位別に形成要因を検討した。調査対象者は，入院中の患者のうち65 歳以上の要介護高齢者70 名であった（81.1±7.7 歳）。入院記録より年齢，疾患，常用薬，寝たきり度を調査し，意識レベル，発語の可否，介助磨きの頻度は担当看護師から聴取した。歯科医師が口腔内診査を行い，膜状物質の形成の有無，Gingival Index などを評価した。形成された膜状物質は，歯科医師がピンセットで採取した。粘膜保湿度（舌背部，舌下粘膜）は，粘膜湿潤度試験紙（キソウエット®）により10秒法で評価した。採取された膜状物質は，通法に従ってパラフィン切片を作製し，HE 染色とサイトケラチン1 による免疫染色で重層扁平上皮か否かについて確認し，重層扁平上皮由来の角質変性物が認められたものを剥離上皮膜と判断した。剥離上皮膜形成の有無を従属変数として，患者背景・口腔内の14 項目，疾患の15 項目，常用薬の32項目，合計61項目を独立変数として部位ごとで決定木分析を行った。すべての部位で剥離上皮膜の形成に最優先される要因は「摂食状況」であり，経口摂取者には，剥離上皮膜がみられなかった。第2 位は舌背部で舌背湿潤度，頰部で開口，歯面の第3 位が開口であり，口腔粘膜の乾燥を示唆する結果であった。以上，剥離上皮膜の形成要因には口腔乾燥があり，保湿の維持が剥離上皮膜の予防につながると考えられた

Semantic Characterizations for Reachability and Trace Equivalence in a Linear Logic-Based Process Calculus (Preliminary Report)

We give semantic characterizations for the notions of reachability and trace equivalence in a linear-logic based framework of asyncronous concurrent process calculus. Usually the reachability relation in linear logic-based concurrent process calculi is characterized by the logical notion of provability, which is in turn characterized by model-theoretic semantics such as the phase semantics. The standard phase semantics is, however, too abstract to give concrete meanings to processes due to the presence of the closure operation. To remedy this, we introduce a simplification of the phase semantics, which we call the naive phase semantics, and show that the reachability relation is also characterized by the completeness with respect to the naive phase semantics. On the other hand, the logical provability does not provide any satisfactory notion of equivalence over processes. We consider the trace equivalence (Hoare[Hoa80]) for our process calculus and introduce certain algebraic models, which we call the trace semantics. Then the trace equivalence is characterized by the completeness with respect to the trace semantics