EFFICACY OF INTERFERON THERAPY FOR CHRONIC HEPATITIS C ： A COOPERATIVE STUDY IN ELEVEN HOSPITALS

We investigated the influences of liver histology，serum levels of hepatitis C virus (HCV) and HCV genotypes on responsiveness to interferon (IFN) therapy in 342 patients with chronic hepatitis C. Either 9 million units (MU) of lymphoblastoid alpha IFN or 3 MU of recombinant IFN-alpha was administered daily for 2 weeks and then three times a week for 22 weeks. IFN responses were divided into three groups on the basis of the results of polymerase chain reaction (PCR) assay detecting HCV-RNA in serum. Complete response (CR) was defined as sustained elimination of HCV for at least 6 months after treatment，partial response (PR) as HCV elimination for a limited period，non-response (NR) as continuously positive for HCV-RNA in serum. Quantitation of pre-treament HCV-RNA amount in serum was determined by competitive PCR assay in 47 patients. HCV genotyping was performed in 114 patients by PCR with genotype-specific primers. CR was obtained in 97 patients (28.4%)，PR in 104 (30.4%) and NR in 141 (41.2%). IFN responses，represented by CR/PR/NR，were 15/18/11 in 44 patients with chronic persistent hepatitis (CPH)，72/65/73 in 210 patients with chronic aggressive hepatitis (CAH) 2a，and 10/21/57 in 88 patients with CAH2b. CR rate was lower in patients with CAH2b (11.4%) compared to those with CPH (34.1%) or CAH2a (34.3%). Averages of pre-treatment serum HCV-RNA amount (copies/50μl) were 10³·⁵⁵ in 13 CRs，10⁴·⁵⁶ in 17 PRs，and 10⁵·⁹⁵ in 17 NRs. There was a positive correlation between pre-treatment HCV-RNA levels and IFN unresponsiveness. HCV genotyping in 114 patients revealed that HCV type Ⅰ infection was observed in one，type Ⅱ in 94，type Ⅲ in 11，type Ⅳ in 6 and mixed (types Ⅱ and Ⅳ) in 2 patients，and their IFN responses (CR/PR/NR) were 0/0/1，28/26/40，3/5/3，1/3/2 and 0/1/1，respectively

Antimicrobial Activity of Peracetic Acid Preparation in the Presence of Various Compounds

It is known that peracetic acid (PAA) is one of the few powerful antimicrobial agents available for use as a sporicidal agent. In this study, the antimicrobial action of a commercial preparation of PAA is characterized and the effects of chemicals on the action are investigated using Escherichia coli cells. The antimicrobial activity of the PAA preparation used in this study was markedly higher under high temperatures and low pHs. However, such a high activity of PAA preparation was strictly inhibited in the presence of a chemical, such as some amino acids, metal salts, and metal chelating agents. By the quantitative analysis of PAA and H_2O_2, it was also observed that these inhibitory chemicals had a strong influence on decomposition of PAA. Although manganese sulfate, and O, O\u27-bis(2-aminoethyl) ethyleneglycol-N, N, N\u27, N\u27-tetraacetic acid (EGTA) had a slight inhibitory effect on the PAA antimicrobial action, these chemicals decomposed PAA, suggesting that these chemicals might reduce cell activity to the PAA resistance. Furthermore, our results indicate that the H_2O_2 contained in the PAA preparation has a slight effect on the antimicrobial action of the PAA preparation

Structure–function studies of ultrahigh molecular weight isoprenes provide key insights into their biosynthesis

Some plant trans-1,4-prenyltransferases (TPTs) produce ultrahigh molecular weight trans-1,4-polyisoprene (TPI) with a molecular weight of over 1.0 million. Although plant-derived TPI has been utilized in various industries, its biosynthesis and physiological function(s) are unclear. Here, we identified three novel Eucommia ulmoides TPT isoforms—EuTPT1, 3, and 5, which synthesized TPI in vitro without other components. Crystal structure analysis of EuTPT3 revealed a dimeric architecture with a central hydrophobic tunnel. Mutation of Cys94 and Ala95 on the central hydrophobic tunnel no longer synthesizd TPI, indicating that Cys94 and Ala95 were essential for forming the dimeric architecture of ultralong-chain TPTs and TPI biosynthesis. A spatiotemporal analysis of the physiological function of TPI in E. ulmoides suggested that it is involved in seed development and maturation. Thus, our analysis provides functional and mechanistic insights into TPI biosynthesis and uncovers biological roles of TPI in plants

Antitumor activity of α-pinene in T-cell tumors

T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeu-tic agents have been developed, their therapeutic effects are suboptimal. α- Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic ma-lignancies. This report provides a comprehensive analysis of the potential benefits of using α- pinene as an antitumor agent for the treatment of T-cell tumors. We found that α- pinene inhibited the proliferation of hematologic malignancies, especially in T- cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and re-active oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α- pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted

Efficacy and safety of micafungin in empiric and D-index-guided early antifungal therapy for febrile neutropenia ; A subgroup analysis of the CEDMIC trial

Objectives: The D-index is defined as the area over the neutrophil curve during neutropenia. The CEDMIC trial confirmed the noninferiority of D-index-guided early antifungal therapy (DET) using micafungin to empirical antifungal therapy (EAT). In this study, we evaluated the efficacy and safety of micafungin in these settings. Methods: From the CEDMIC trial, we extracted 67 and 113 patients who received micafungin in the DET and EAT groups, respectively. Treatment success was defined as the fulfilment of all components of a five-part composite end point. Fever resolution was evaluated at seven days after the completion of therapy. Results: The proportion of high-risk treatments including induction chemotherapy for acute leukemia and allogeneic hematopoietic stem cell transplantation was significantly higher in the DET group than in the EAT group (82.1% vs. 52.2%). The efficacy of micafungin was 68.7% (95%CI: 56.2–79.4) and 79.6% (71.0–86.6) in the DET and EAT groups, respectively. When we focused on high-risk treatments, the efficacy was 69.1% (55.2–80.9%) and 78.0% (65.3–87.7%), respectively (P = 0.30). There was no significant difference in any of the 5 components between the two groups. Conclusions: The efficacy of micafungin in patients undergoing high-risk treatment was not strongly impaired in DET compared to that in EAT

生体制御分子探索と機能解析を基盤とする健康科学

プロジェクト研究報告概要集　　先端科学技術推進機構研究グループ　研究代表者:長岡康夫　研究担当者:下家浩二・松村吉信・福永健

環境アポトジェンを含む環境汚染化学物質の作用動態解析と化学生態学的防除法の開発研究プロジェクト

プロジェクト研究報告概要集　　戦略的研究基盤形成支援事業プロジェクト　研究代表者:土戸哲明　研究担当者:池内俊彦・下家浩二・上里新一・吉田宗弘・福永健治・安原裕紀・長谷川喜衛・岩木宏明・老川典夫・松村吉

Tokyo Guidelines 2018 diagnostic criteria and severity grading of acute cholecystitis (with videos)

The Tokyo Guidelines 2013 (TG13) for acute cholangitis and cholecystitis were globally disseminated and various clinical studies about the management of acute cholecystitis were reported by many researchers and clinicians from all over the world. The 1st edition of the Tokyo Guidelines 2007 (TG07) was revised in 2013. According to that revision, the TG13 diagnostic criteria of acute cholecystitis provided better specificity and higher diagnostic accuracy. Thorough our literature search about diagnostic criteria for acute cholecystitis, new and strong evidence that had been released from 2013 to 2017 was not found with serious and important issues about using TG13 diagnostic criteria of acute cholecystitis. On the other hand, the TG13 severity grading for acute cholecystitis has been validated in numerous studies. As a result of these reviews, the TG13 severity grading for acute cholecystitis was significantly associated with parameters including 30-day overall mortality, length of hospital stay, conversion rates to open surgery, and medical costs. In terms of severity assessment, breakthrough and intensive literature for revising severity grading was not reported. Consequently, TG13 diagnostic criteria and severity grading were judged from numerous validation studies as useful indicators in clinical practice and adopted as TG18/TG13 diagnostic criteria and severity grading of acute cholecystitis without any modification. Free full articles and mobile app of TG18 are available at: http://www.jshbps.jp/modules/en/index.php?content_id=47. Related clinical questions and references are also include