日本DMAT（Disaster Medical Assistance ...Team：災害医療派遣チーム）隊員養成研修を開始後4年以上が経過した。その間に実災害を経験したことにより得られた，さまざまな教訓や改善された仕組みがある。これを生かすために，研修内容の改訂が必要になった。そこで研修講師に対して現行プログラムの改良点に関するアンケートを実施した。そして，その結果を基に厚生労働科学研究「健康危機・大規模災害に対する初動期医療体制のあり方に関する研究」の研究会議において，プログラム見直しに関する議論を行った。これにより得られた結論は，以下の3点にまとめられる。①新しいプログラム内容や研修方法に関する改訂案の提示，②隊員の知識や技能レベルを標準化し，効率的な研修を実施するために，事前のJPTECTM，JATECTM受講が望ましいことの提示，③ DMAT研修受講後の隊員が知識と技能を維持，更新するために標準化された継続研修案の提示。
A new beam-forming technique for an ultrasonic transmitting array using multidimensional sigma-delta (/spl Sigma//spl Delta/) modulation is described. Waveforms required for driving the array are ...converted to binary streams which are oversampled spatially and temporally. The ultrasonic wavefront generated by the binary streams is approximately equal to the one generated by the original driving waveforms. The shapes and the levels of the transmitted beams are controlled precisely with simple electrical circuits since the large dynamic range waveforms are replaced with binary ones. In this paper, various array geometries are presented. Computer simulation and experimental results using a linear array made of VDF-TrFe copolymer are presented for evaluation and demonstration of the applicability of the proposed method.
The integrin family is a transmembrane receptor that plays critical roles in the cell-cell and cell-extracellular matrix adhesion, signal transduction such as cell cycle regulation, organization of ...the intracellular cytoskeleton, and immune responses. Consequently, dysfunction of integrins is associated with a wide range of human diseases, including cancer and immune diseases, which makes integrins therapeutic targets for drug discovery. Here we report the cryo-EM structure of the human α-I domain-containing full-length integrin αEβ7, which is expressed in the leukocytes of the immune system and a drug target for inflammatory bowel disease (IBD). The structure reveals the half-bent conformation, an intermediate between the close and the open conformation, while the α-I domain responsible for the ligand binding covers the headpiece domain by a unique spatial arrangement. Our results provide the structural information for the drug design targeting IBD.
•The Cryo-electron microscopy structure of integrin αEβ7 was determined.•The inactive integrin αEβ7 is a half-bent structure that is difficult to predict.•The α-I domain is positionally stable through interactions with the head domain.•The apo structure strongly reflects the physiological condition.•The cryo-EM structures will accelerate a next-generation integrin drug discovery.
Abstract Pyroglutamylated RF-amide peptide (QRFP) is a peptide hormone with a C-terminal RF-amide motif. QRFP selectively activates a class A G-protein-coupled receptor (GPCR) GPR103 to exert various ...physiological functions such as energy metabolism and appetite regulation. Here, we report the cryo-electron microscopy structure of the QRFP26-GPR103-G q complex at 3.19 Å resolution. QRFP26 adopts an extended structure bearing no secondary structure, with its N-terminal and C-terminal sides recognized by extracellular and transmembrane domains of GPR103 respectively. This movement, reminiscent of class B1 GPCRs except for orientation and structure of the ligand, is critical for the high-affinity binding and receptor specificity of QRFP26. Mutagenesis experiments validate the functional importance of the binding mode of QRFP26 by GPR103. Structural comparisons with closely related receptors, including RY-amide peptide-recognizing GPCRs, revealed conserved and diversified peptide recognition mechanisms, providing profound insights into the biological significance of RF-amide peptides. Collectively, this study not only advances our understanding of GPCR-ligand interactions, but also paves the way for the development of novel therapeutics targeting metabolic and appetite disorders and emergency medical care.
Abstract
Lysophosphatidic acid receptor 1 (LPA
1
) is one of the six G protein-coupled receptors activated by the bioactive lipid, lysophosphatidic acid (LPA). LPA
1
is a drug target for various ...diseases, including cancer, inflammation, and neuropathic pain. Notably, LPA
1
agonists have potential therapeutic value for obesity and urinary incontinence. Here, we report a cryo-electron microscopy structure of the active human LPA
1
-G
i
complex bound to ONO-0740556, an LPA analog with more potent activity against LPA
1
. Our structure elucidated the details of the agonist binding mode and receptor activation mechanism mediated by rearrangements of transmembrane segment 7 and the central hydrophobic core. A structural comparison of LPA
1
and other phylogenetically-related lipid-sensing GPCRs identified the structural determinants for lipid preference of LPA
1
. Moreover, we characterized the structural polymorphisms at the receptor-G-protein interface, which potentially reflect the G-protein dissociation process. Our study provides insights into the detailed mechanism of LPA
1
binding to agonists and paves the way toward the design of drug-like agonists targeting LPA
1
.
The endothelin ET
B
receptor is a promiscuous G-protein coupled receptor that is activated by vasoactive peptide endothelins. ET
B
signaling induces reactive astrocytes in the brain and ...vasorelaxation in vascular smooth muscle. Consequently, ET
B
agonists are expected to be drugs for neuroprotection and improved anti-tumor drug delivery. Here, we report the cryo-electron microscopy structure of the endothelin-1-ET
B
-G
i
complex at 2.8 Å resolution, with complex assembly stabilized by a newly established method. Comparisons with the inactive ET
B
receptor structures revealed how endothelin-1 activates the ET
B
receptor. The NPxxY motif, essential for G-protein activation, is not conserved in ET
B
, resulting in a unique structural change upon G-protein activation. Compared with other GPCR-G-protein complexes, ET
B
binds G
i
in the shallowest position, further expanding the diversity of G-protein binding modes. This structural information will facilitate the elucidation of G-protein activation and the rational design of ET
B
agonists.
Background: Endoscopic submucosal dissection (ESD) was developed for en bloc removal of large and flat gastrointestinal tract neoplasms. In Japan, ESD is performed under conscious sedation. The ...risks for sedation‐related complications of ESD, such as postoperative pneumonia, have not been evaluated. The aim of this study was to evaluate the incidence of postoperative pneumonia after ESD in a multicenter survey.
Patients and Methods: A total of 1188 patients with upper gastric neoplasms treated with ESD in nine hospitals were enrolled from May 2003 to September 2008. The en bloc resection rates and complications (bleeding, perforation, and postoperative pneumonia) were assessed. The correlations between the clinical variables and complications were investigated using logistic regression models.
Results: The en bloc resection rate was 95.3%. Bleeding, perforation, and pneumonia occurred in 37 (3.1%), 49 (4.1%), and 19 (1.6%) patients, respectively. Univariate analysis indicated that procedure time, but not specimen size, or patient age, or sex, was significantly related to bleeding and perforation. The incidence of pneumonia was higher in patients with ulceration, older patients (≥75 years), and those with a long procedure duration (≥5 h).
Conclusion: The incidence of pneumonia, but not perforation and bleeding, after ESD, is high in older patients (≥75 years). Special care should be taken with older patients undergoing ESD to minimize the risk of postoperative pneumonia.
