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Kondo, Naoyuki,Ueda, Yoshihiro,Kita, Toshiyuki,Ozawa, Madoka,Tomiyama, Takashi,Yasuda, Kaneki,Lim, Dae-Sik,Kinashi, Tatsuo American Society for Microbiology 2017 Molecular and cellular biology Vol.37 No.8
<P><B>ABSTRACT</B></P><P>Antigen-specific adhesion between T cells and antigen-presenting cells (APC) during the formation of the immunological synapse (IS) is mediated by LFA-1 and ICAM-1. Here, LFA-1–ICAM-1 interactions were measured at the single-molecule level on supported lipid bilayers. High-affinity binding was detected at low frequencies in the inner peripheral supramolecular activation cluster (SMAC) zone that contained high levels of activated Rap1 and kindlin-3. Rap1 was essential for T cell attachment, whereas deficiencies of ste20-like kinases, Mst1/Mst2, diminished high-affinity binding and abrogated central SMAC (cSMAC) formation with mislocalized kindlin-3 and vesicle transport regulators involved in T cell receptor recycling/releasing machineries, resulting in impaired T cell-APC interactions. We found that NDR1 kinase, activated by the Rap1 signaling cascade through RAPL and Mst1/Mst2, associated with and recruited kindlin-3 to the IS, which was required for high-affinity LFA-1/ICAM-1 binding and cSMAC formation. Our findings reveal crucial roles for Rap1 signaling via NDR1 for recruitment of kindlin-3 and IS organization.</P>
Naotaka Ogasawara,Mari Mizuno,Ryuta Masui,Yoshihiro Kondo,Yoshiharu Yamaguchi,Kenichiro Yanamoto,Hisatsugu Noda,Noriko Okaniwa,Makoto Sasaki,Kunio Kasugai 대한소화기내시경학회 2014 Clinical Endoscopy Vol.47 No.2
Background/Aims: Despite improvements in endoscopic hemostasis and pharmacological therapies, upper gastrointestinal (UGI) ulcersrepeatedly bleed in 10% to 20% of patients, and those without early endoscopic reintervention or definitive surgery might be at ahigh risk for mortality. This study aimed to identify the risk factors for intractability to initial endoscopic hemostasis. Methods: We analyzed intractability among 428 patients who underwent emergency endoscopy for bleeding UGI ulcers within 24hours of arrival at the hospital. Results: Durable hemostasis was achieved in 354 patients by using initial endoscopic procedures. Sixty-nine patients with Forrest typesIa, Ib, IIa, and IIb at the second-look endoscopy were considered intractable to the initial endoscopic hemostasis. Multivariate analysisindicated that age ≥70 years (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.07 to 4.03), shock on admission (OR, 5.26; 95% CI,2.43 to 11.6), hemoglobin <8.0 mg/dL (OR, 2.80; 95% CI, 1.39 to 5.91), serum albumin <3.3 g/dL (OR, 2.23; 95% CI, 1.07 to 4.89), exposedvessels with a diameter of ≥2 mm on the bottom of ulcers (OR, 4.38; 95% CI, 1.25 to 7.01), and Forrest type Ia and Ib (OR, 2.21;95% CI, 1.33 to 3.00) predicted intractable endoscopic hemostasis. Conclusions: Various factors contribute to intractable endoscopic hemostasis. Careful observation after endoscopic hemostasis is importantfor patients at a high risk for incomplete hemostasis.