Robust folding of a de novo designed ideal protein even with most of the core mutated to valine

Rie Koga, Mami Yamamoto, Takahiro Kosugi, Naohiro Kobayashi, Toshihiko Sugiki, Toshimichi Fujiwara, Nobuyasu Koga, Robust folding of a de novo designed ideal protein even with most of the core mutated to valine. Proceedings of the National Academy of Sciences. 117 (49), 31149-31156 (2020). DOI: 10.1073/pnas.2002120117

Locally applied cilostazol suppresses neointimal hyperplasia by inhibiting tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts

AbstractObjectiveAccumulation of smooth muscle cells and extracellular matrix in the intima of artery bypass grafts induces neointimal hyperplasia, resulting in graft failure. We investigated the inhibitory effect of locally applied cilostazol, an inhibitor of cyclic adenosine monophosphate phosphodiesterase III, on neointimal hyperplasia and the role of tenascin-C synthesis and smooth muscle cell proliferation in free artery grafts.Methods and resultsWe established a distal anastomotic stricture model of free artery graft stenosis using rat abdominal aorta. In this model, neointimal hyperplasia was observed not only in the distal anastomotic site but also in the graft body at postoperative day 14 and was markedly progressed at day 28. Strong expression of tenascin-C was found in the media and neointima of the graft body. When cilostazol was locally administered around the graft using Pluronic gel, neointimal hyperplasia of the graft was significantly suppressed in comparison with gel-treated control graft. The mean neointima/media area ratio was reduced by 86.6% for the graft body and by 75.8% for the distal anastomotic site versus the control. Cilostazol treatment decreased cell proliferation and tenascin-C expression in the neointima. In an in vitro experiment using cultured smooth muscle cells isolated from rat aorta, cilostazol completely suppressed the tenascin-C mRNA expression induced by platelet-derived growth factor-BB.ConclusionA single topical administration of cilostazol may suppress neointimal hyperplasia by inhibiting cell proliferation and tenascin-C synthesis in free artery grafts, presenting the potential for clinical use in vascular surgery

Endobronchial Ultrasound-guided Transbronchial Needle Aspiration for the Diagnosis of Intrathoracic Lesions : Experience of a Single Academic Medical Center

Article信州医学雑誌 60(5): 249-255(2012)journal articl

Ruptured Small Intestinal Stromal Tumor Causing Concurrent Gastrointestinal and Intra-Abdominal Hemorrhage: A Case Report

Gastrointestinal stromal tumors (GISTs) originate from mesenchymal cells throughout the gastrointestinal tract. A common symptom is gastrointestinal hemorrhage; intra-abdominal hemorrhage is relatively rare. There are few reports of GIST presenting with both types of hemorrhage concurrently. A 77-year-old man was admitted to our hospital because of melena and anemia (Hb: 4.7 g/dL). Computed tomography revealed a small bowel tumor and high-density fluid in both the small intestine and the pelvic floor. We diagnosed a small intestinal tumor with concurrent gastrointestinal and intra-abdominal hemorrhage, and performed emergency surgery. The tumor arose from the small intestine and was ruptured. We found hemorrhage in the pelvic cavity and performed partial small intestine resection. Pathological findings revealed that the tumor was positive for c-Kit protein and was diagnosed as GIST. The patient was discharged from the hospital on postoperative day 9 and received imatinib 1 month postoperatively. We experienced a very rare case of ruptured GIST originating from the small intestine associated with both gastrointestinal and intra-abdominal hemorrhage. We also reviewed the relevant literature

Clinical Significance of Serum Antithrombin III Activity After Hepatectomy for Hepatocellular Carcinoma

[Background] As antithrombin III (AT-III) is produced in the hepatocytes, its serum activity decreases at the time of liver failure, in addition to ischemia reperfusion injury, vascular endothelial dysfunction, and disseminated intravascular coagulation (DIC). Here, we examined whether the serum AT-III value after hepatectomy could be a prognostic factor for hepatocellular carcinoma (HCC). [Methods] Of 141 patients who underwent hepatectomy for HCC, data for 101 patients in whom serum AT-III activity was measured on the first postoperative day were extracted. Patients with serum AT-III activity > 50% and ? 50% were assigned to high value (72 cases) and low value (29 cases) groups, respectively. We examined the clinical and prognostic differences between these two groups. [Results] The average age of enrolled patients (83 men and 18 women) was 68.0 years. The 5-year overall survival rate was 88% and 60% in the high and low value groups, respectively (P < 0.01). Furthermore, the 2-year relapse-free survival rate was 71% and 54% in the high and low value groups, respectively (P = 0.03). [Conclusion] This is the first study to demonstrate that serum AT-III levels on the first postoperative day may serve as a prognostic factor in HCC patients

Platelet-to-Lymphocyte Ratio Multiplied by the Cytokeratin-19 Fragment Level as a Predictor of Pathological Response to Neoadjuvant Chemotherapy in Esophageal Squamous Cell Carcinoma

[Background] The standard treatment for resectable advanced esophageal squamous cell carcinoma in Japan is surgery followed by neoadjuvant chemotherapy, and it is important to predict the effect of neoadjuvant chemotherapy before treatment. Therefore, this study aims to extract conventional blood examination data, such as tumor markers and/or inflammatory/nutritional index levels, that can predict the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy. [Methods] We retrospectively analyzed the medical records of 66 patients with thoracic esophageal squamous cell carcinoma who received neoadjuvant chemotherapy, followed by curative esophagectomy at Tottori University Hospital between June 2009 and December 2019. [Results] We demonstrated that the product of the platelet-to-lymphocyte ratio (PLR) multiplied by the cytokeratin-19 fragment (CYFRA) level, which was termed “PLR-CYFRA,” is the most accurate indicator that predicts the pathological response to neoadjuvant chemotherapy, with the highest area under the curve [0.795 (95% confidence interval: 0.665–0.925), P < 0.001] in receiver operating characteristic analyses. Therefore, we divided patients into the PLR-CYFRALow (< 237.6, n = 21) and PLR-CYFRAHigh (≥ 237.6, n = 45) groups and found that the percentage of PLR-CYFRALow was significantly higher in patients with a better pathological response (P < 0.001). Furthermore, patients with good pathological response had significantly better prognoses in terms of disease-specific survival (P = 0.014), recurrence-free survival (P = 0.014), and overall survival (P = 0.032). In the multivariate analysis, PLR-CYFRA was an independent predictor of the pathological response of patients with esophageal squamous cell carcinoma to neoadjuvant chemotherapy (P = 0.002). [Conclusion] Pretreatment PLR-CYFRA might be a useful and simple tool that predicts the pathological effect of neoadjuvant chemotherapy in esophageal squamous cell carcinoma

Cooking Vessels, Volumes, and Venues: Evidence from LM IIIC Kavousi Vronda and Karphi

Glowacki, K.T., and L.P. Day. “Cooking Vessels, Volumes, and Venues: Evidence from LM IIIC Kavousi Vronda and Karphi.” Abstract of paper read at Διατροφικές συνήθειες και πρακτικές στην Κρήτη διαχρονικά [Dietary Habits and Practices in Crete over Time], Museum of Cretan Ethnology, Voroi, Crete, Greece, September 9–10, 2017.Our understanding of diet and culinary practices at the Late Minoan IIIC settlement sites of Kavousi Vronda and Karphi is based upon several different types of physical evidence that have been recovered through excavation. These include the botanical and faunal remains of plants and animals available to and consumed by the inhabitants; ceramic vessels used for the cooking and consumption of food and drink; built and fixed cooking installations, such as hearths and ovens; and the architectural spaces within the settlements where food preparation and consumption most likely took place. Each type of evidence is, by itself, incomplete and dependent upon differential preservation resulting from site formation processes specific to each archaeological context. Taken together, however, they allow us to gain important insights into key aspects of food cultivation, provisioning, processing, preparation, and convivial practices on Crete in the 12th and 11th centuries BC. In this paper, we will compare and contrast the evidence for food preparation and dining at each site, paying special attention to the forms and sizes of ceramic vessels used for cooking and consumption