シュウジュツキ ノ ケッカン キノウ ホゴ センリャク

Potassium channels play an essential role in the membrane potential of arterial smooth muscle, and also in regulating contractile tone. Especially, in vascular smooth muscle, the opening of adenosine triphosphate（ATP）-sensitive potassium（KATP）channels leads to membrane hyperpolarization, resulting in muscle relaxation and vasodilation. This activation also plays a role in tissues during pathophysiologic events such as ischemia, hypoxia, and vasodilatory shock. In this review, we will describe the physiological and pathophysiological roles of vascular smooth muscle KATP channels in relation to the effects of anesthetics and perioperative managements. Although accumulated evidence suggests that many anesthetics and perioperative managements（especially, diabetes and hyperglycemia）modify the above function of K+ channels as a metabolic sensor. Use of effective volatile anesthetics and the strict glycemic control may contribute to protect perioperative vascular function

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.As a result, 79 GRADE-based recommendations, 5 Good Practice Statements (GPS), 18 expert consensuses, 27 answers to background questions (BQs), and summaries of definitions and diagnosis of sepsis were created as responses to 118 CQs. We also incorporated visual information for each CQ according to the time course of treatment, and we will also distribute this as an app. The J-SSCG 2020 is expected to be widely used as a useful bedside guideline in the field of sepsis treatment both in Japan and overseas involving multiple disciplines.other authors: Satoru Hashimoto,Daisuke Hasegawa,Junji Hatakeyama,Naoki Hara,Naoki Higashibeppu,Nana Furushima,Hirotaka Furusono,Yujiro Matsuishi,Tasuku Matsuyama,Yusuke Minematsu,Ryoichi Miyashita,Yuji Miyatake,Megumi Moriyasu,Toru Yamada,Hiroyuki Yamada,Ryo Yamamoto,Takeshi Yoshida,Yuhei Yoshida,Jumpei Yoshimura,Ryuichi Yotsumoto,Hiroshi Yonekura,Takeshi Wada,Eizo Watanabe,Makoto Aoki,Hideki Asai,Takakuni Abe,Yutaka Igarashi,Naoya Iguchi,Masami Ishikawa,Go Ishimaru,Shutaro Isokawa,Ryuta Itakura,Hisashi Imahase,Haruki Imura,Takashi Irinoda,Kenji Uehara,Noritaka Ushio,Takeshi Umegaki,Yuko Egawa,Yuki Enomoto,Kohei Ota,Yoshifumi Ohchi,Takanori Ohno,Hiroyuki Ohbe,Kazuyuki Oka,Nobunaga Okada,Yohei Okada,Hiromu Okano,Jun Okamoto,Hiroshi Okuda,Takayuki Ogura,Yu Onodera,Yuhta Oyama,Motoshi Kainuma,Eisuke Kako,Masahiro Kashiura,Hiromi Kato,Akihiro Kanaya,Tadashi Kaneko,Keita Kanehata,Ken-ichi Kano,Hiroyuki Kawano,Kazuya Kikutani,Hitoshi Kikuchi,Takahiro Kido,Sho Kimura,Hiroyuki Koami,Daisuke Kobashi,Iwao Saiki,Masahito Sakai,Ayaka Sakamoto,Tetsuya Sato,Yasuhiro Shiga,Manabu Shimoto,Shinya Shimoyama,Tomohisa Shoko,Yoh Sugawara,Atsunori Sugita,Satoshi Suzuki,Yuji Suzuki,Tomohiro Suhara,Kenji Sonota,Shuhei Takauji,Kohei Takashima,Sho Takahashi,Yoko Takahashi,Jun Takeshita,Yuuki Tanaka,Akihito Tampo,Taichiro Tsunoyama,Kenichi Tetsuhara,Kentaro Tokunaga,Yoshihiro Tomioka,Kentaro Tomita,Naoki Tominaga,Mitsunobu Toyosaki,Yukitoshi Toyoda,Hiromichi Naito,Isao Nagata,Tadashi Nagato,Yoshimi Nakamura,Yuki Nakamori,Isao Nahara,Hiromu Naraba,Chihiro Narita,Norihiro Nishioka,Tomoya Nishimura,Kei Nishiyama,Tomohisa Nomura,Taiki Haga,Yoshihiro Hagiwara,Katsuhiko Hashimoto,Takeshi Hatachi,Toshiaki Hamasaki,Takuya Hayashi,Minoru Hayashi,Atsuki Hayamizu,Go Haraguchi,Yohei Hirano,Ryo Fujii,Motoki Fujita,Naoyuki Fujimura,Hiraku Funakoshi,Masahito Horiguchi,Jun Maki,Naohisa Masunaga,Yosuke Matsumura,Takuya Mayumi,Keisuke Minami,Yuya Miyazaki,Kazuyuki Miyamoto,Teppei Murata,Machi Yanai,Takao Yano,Kohei Yamada,Naoki Yamada,Tomonori Yamamoto,Shodai Yoshihiro,Hiroshi Tanaka,Osamu NishidaGuideline

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020)

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2020 (J-SSCG 2020), a Japanese-specific set of clinical practice guidelines for sepsis and septic shock created as revised from J-SSCG 2016 jointly by the Japanese Society of Intensive Care Medicine and the Japanese Association for Acute Medicine, was first released in September 2020 and published in February 2021. An English-language version of these guidelines was created based on the contents of the original Japanese-language version. The purpose of this guideline is to assist medical staff in making appropriate decisions to improve the prognosis of patients undergoing treatment for sepsis and septic shock. We aimed to provide high-quality guidelines that are easy to use and understand for specialists, general clinicians, and multidisciplinary medical professionals. J-SSCG 2016 took up new subjects that were not present in SSCG 2016 (e.g., ICU-acquired weakness [ICU-AW], post-intensive care syndrome [PICS], and body temperature management). The J-SSCG 2020 covered a total of 22 areas with four additional new areas (patient- and family-centered care, sepsis treatment system, neuro-intensive treatment, and stress ulcers). A total of 118 important clinical issues (clinical questions, CQs) were extracted regardless of the presence or absence of evidence. These CQs also include those that have been given particular focus within Japan. This is a large-scale guideline covering multiple fields; thus, in addition to the 25 committee members, we had the participation and support of a total of 226 members who are professionals (physicians, nurses, physiotherapists, clinical engineers, and pharmacists) and medical workers with a history of sepsis or critical illness. The GRADE method was adopted for making recommendations, and the modified Delphi method was used to determine recommendations by voting from all committee members.other authors: Yasuhiro Norisue, Satoru Hashimoto, Daisuke Hasegawa, Junji Hatakeyama, Naoki Hara, Naoki Higashibeppu, Nana Furushima, Hirotaka Furusono, Yujiro Matsuishi, Tasuku Matsuyama, Yusuke Minematsu, Ryoichi Miyashita, Yuji Miyatake, Megumi Moriyasu, Toru Yamada, Hiroyuki Yamada, Ryo Yamamoto, Takeshi Yoshida, Yuhei Yoshida, Jumpei Yoshimura, Ryuichi Yotsumoto, Hiroshi Yonekura, Takeshi Wada, Eizo Watanabe, Makoto Aoki, Hideki Asai, Takakuni Abe, Yutaka Igarashi, Naoya Iguchi, Masami Ishikawa, Go Ishimaru, Shutaro Isokawa, Ryuta Itakura, Hisashi Imahase, Haruki Imura, Takashi Irinoda, Kenji Uehara, Noritaka Ushio, Takeshi Umegaki, Yuko Egawa, Yuki Enomoto, Kohei Ota, Yoshifumi Ohchi, Takanori Ohno, Hiroyuki Ohbe, Kazuyuki Oka, Nobunaga Okada, Yohei Okada, Hiromu Okano, Jun Okamoto, Hiroshi Okuda, Takayuki Ogura, Yu Onodera, Yuhta Oyama, Motoshi Kainuma, Eisuke Kako, Masahiro Kashiura, Hiromi Kato, Akihiro Kanaya, Tadashi Kaneko, Keita Kanehata, Ken-ichi Kano, Hiroyuki Kawano, Kazuya Kikutani, Hitoshi Kikuchi, Takahiro Kido, Sho Kimura, Hiroyuki Koami, Daisuke Kobashi, Iwao Saiki, Masahito Sakai, Ayaka Sakamoto, Tetsuya Sato, Yasuhiro Shiga, Manabu Shimoto, Shinya Shimoyama, Tomohisa Shoko, Yoh Sugawara, Atsunori Sugita, Satoshi Suzuki, Yuji Suzuki, Tomohiro Suhara, Kenji Sonota, Shuhei Takauji, Kohei Takashima, Sho Takahashi, Yoko Takahashi, Jun Takeshita, Yuuki Tanaka, Akihito Tampo, Taichiro Tsunoyama, Kenichi Tetsuhara, Kentaro Tokunaga, Yoshihiro Tomioka, Kentaro Tomita, Naoki Tominaga, Mitsunobu Toyosaki, Yukitoshi Toyoda, Hiromichi Naito, Isao Nagata, Tadashi Nagato, Yoshimi Nakamura, Yuki Nakamori, Isao Nahara, Hiromu Naraba, Chihiro Narita, Norihiro Nishioka, Tomoya Nishimura, Kei Nishiyama, Tomohisa Nomura, Taiki Haga, Yoshihiro Hagiwara, Katsuhiko Hashimoto, Takeshi Hatachi, Toshiaki Hamasaki, Takuya Hayashi, Minoru Hayashi, Atsuki Hayamizu, Go Haraguchi, Yohei Hirano, Ryo Fujii, Motoki Fujita, Naoyuki Fujimura, Hiraku Funakoshi, Masahito Horiguchi, Jun Maki, Naohisa Masunaga, Yosuke Matsumura, Takuya Mayumi, Keisuke Minami, Yuya Miyazaki, Kazuyuki Miyamoto, Teppei Murata, Machi Yanai, Takao Yano, Kohei Yamada, Naoki Yamada, Tomonori Yamamoto, Shodai Yoshihiro, Hiroshi Tanaka & Osamu Nishid

Dual function of Sec16B: Endoplasmic reticulum-derived protein secretion and peroxisome biogenesis in mammalian cells

The origin of peroxisomes has long been disputed. However, recent evidence suggests that peroxisomes can be formed de novo from the endoplasmic reticulum (ER) in yeast and higher eukaryotes. Sec16A and Sec16B, mammalian orthologs of yeast Sec16, are scaffold proteins that organize ER exit sites by interacting with COPII components. We recently demonstrated that Sec16B, but not Sec16A, regulates the transport of peroxisomal biogenesis factors from the ER to peroxisomes in mammalian cells. The C-terminal region of Sec16B, which is not conserved in Sec16A, is required for this function. The data suggest that Sec16B in ER areas other than ER exit sites plays this role. Our findings provide an unexpected connection between at least part of the COPII machinery and the formation of preperoxisomal vesicles at the ER, and offer an explanation of how secretory and peroxisomal trafficking from the ER are distinguished

Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar morphogenesis

BRIP1 is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1 and plays an important role in BRCA1-dependent DNA repair and DNA damage-induced checkpoint control. Recent studies implicate BRIP1 as a moderate/low-penetrance breast cancer susceptibility gene. However, the phenotypic effects of BRIP1 dysfunction and its role in breast cancer tumorigenesis remain unclear. To explore the function of BRIP1 in acinar morphogenesis of mammary epithelial cells, we generated BRIP1-knockdown MCF-10A cells by shRNA-mediated RNA interference and examined its effect in a three-dimensional culture model. Genome-wide gene expression profiling by microarray and quantitative RT-PCR were performed to identify alterations in gene expression in BRIP1-knockdown cells compared with control cells. The microarray data were further investigated using the pathway analysis and Gene Set Enrichment Analysis (GSEA) for pathway identification. BRIP1 knockdown in non-malignant MCF-10A mammary epithelial cells by RNA interference induced neoplastic-like changes such as abnormal cell adhesion, increased cell proliferation, large and irregular-shaped acini, invasive growth, and defective lumen formation. Differentially expressed genes, including MCAM, COL8A1, WIPF1, RICH2, PCSK5, GAS1, SATB1, and ELF3, in BRIP1-knockdown cells compared with control cells were categorized into several functional groups, such as cell adhesion, polarity, growth, signal transduction, and developmental process. Signaling-pathway analyses showed dysregulation of multiple cellular signaling pathways, involving LPA receptor, Myc, Wnt, PI3K, PTEN as well as DNA damage response, in BRIP1-knockdown cells. Loss of BRIP1 thus disrupts normal mammary morphogenesis and causes neoplastic-like changes, possibly via dysregulating multiple cellular signaling pathways functioning in the normal development of mammary glands

Cancer prevention by adult-onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice.

Children are especially sensitive to ionizing radiation and chemical carcinogens, and limiting their cancer risk is of great public concern. Calorie restriction (CR) is a potent intervention for suppressing cancer. However, CR is generally not appropriate for children. This study, therefore, examined to see if adult-onset CR influences the lifetime cancer risk in mice after early-life exposure to ionizing radiation. Infant male mice (1-week-old) were exposed to 3.8 Gy X-rays, fed a control 95 kcal/week or CR 65 kcal/week diet from 7 weeks of age (adult stage), and their lifespan and tumor development were assessed. Irrespective of CR, X-rays shortened lifespan by 38%, and irrespective of irradiation CR extended lifespan by 20%. Thymic lymphoma (TL) and early-occurring non-TL were induced by radiation. The liver and Harderian gland were more susceptible to radiation-induced tumors than the lungs and non-thymic lymphoid tissues (late occurring). CR reduced the risk of hepatocellular carcinoma, late-occurring non-TL, lung tumor, Harderian tumor, and hemangioma but had less impact on TL and early-occurring non-TL. Most notably, the effects of X-rays on induction of lung tumors, late-occurring non-TL and hemangioma were essentially canceled by CR. The ability of CR to prevent late-occurring tumors was the same for non-irradiated and irradiated mice, indicating that the mechanism by which CR influences cancer is independent of irradiation. Our results indicate that adult-onset CR significantly inhibits late-occurring tumors in a tissue-dependent manner regardless of infant radiation exposure