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Dupilumab Leads to Clinical Improvements including the Acquisition of Tolerance to Causative Foods in Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Disorders.
Arakawa, N, Yagi, H, Shimizu, M, Shigeta, D, Shimizu, A, Nomura, S, Takizawa, T, Yamada, Y
Biomolecules. 2023;(1)
Abstract
A recent report showed that most pediatric cases of non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal disorders (EGIDs) (non-EoE EGIDs) are persistent and severe compared with those of EoE, thus requiring further effective therapeutic approaches. In this study, we present the first case based on a systematic search of non-EoE EGID for which tolerance to causative foods and histological and symptomatic improvements were achieved following dupilumab administration, after elimination diets and omalizumab and mepolizumab treatments. Driven by this case, we investigated the efficacies of biological treatments in non-EoE EGID cases based on the patient studied herein, and other patients identified in the conducted systematic review. Seven articles, including five different biologics, were reviewed. Both clinical efficacies and impact differences among the targeted molecules are demonstrated in this study. Our findings show that dupilumab may affect mechanisms that can suppress symptoms induced by offending foods that are different from those induced by other biologics as identified in the conducted systematic review. Additional studies are required to address the unmet needs of non-EoE EGID treatments.
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Peritoneal dissemination of pancreatic cancer caused by endoscopic ultrasound-guided fine needle aspiration: A case report and literature review.
Kojima, H, Kitago, M, Iwasaki, E, Masugi, Y, Matsusaka, Y, Yagi, H, Abe, Y, Hasegawa, Y, Hori, S, Tanaka, M, et al
World journal of gastroenterology. 2021;(3):294-304
Abstract
BACKGROUND Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a biopsy technique widely used to diagnose pancreatic tumors because of its high sensitivity and specificity. Although needle-tract seeding caused by EUS-FNA has been recently reported, dissemination of pancreatic cancer cells is generally considered to be a rare complication that does not affect patient prognosis. However, the frequency of dissemination and needle-tract seeding appears to have been underestimated. We present a case of peritoneal dissemination of pancreatic cancer due to preoperative EUS-FNA. CASE SUMMARY An 81-year-old man was referred to the Department of Surgery of our hospital in Japan owing to the detection of a pancreatic mass on computed tomography during medical screening. Trans-gastric EUS-FNA revealed that the mass was an adenocarcinoma; hence laparoscopic distal pancreatectomy with lympha-denectomy was performed. No intraoperative peritoneal dissemination and liver metastasis were visually detected, and pelvic lavage cytology was negative for carcinoma cells. The postoperative surgical specimen was negative for carcinoma cells at the dissected margin and the cut end margin; however, pathological findings revealed adenocarcinoma cells on the peritoneal surface proximal to the needle puncture site, and the cells were suspected to be disseminated via EUS- FNA. Hence, the patient received adjuvant therapy with S-1 (tegafur, gimeracil, and oteracil potassium); however, computed tomography performed 5 mo after surgery revealed liver metastasis and cancerous peritonitis. The patient received palliative therapy and died 8 mo after the operation. CONCLUSION The indications of EUS-FNA should be carefully considered to avoid iatrogenic dissemination, especially for cancers in the pancreatic body or tail.
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Comparison of olanexidine versus povidone-iodine for preventing surgical site infection in gastrointestinal surgery: study protocol for a multicentre, single-blind, randomised controlled clinical trial.
Takeuchi, M, Obara, H, Kawakubo, H, Shinoda, M, Okabayashi, K, Mayanagi, S, Irino, T, Fukuda, K, Nakamura, R, Wada, N, et al
BMJ open. 2019;(5):e028269
Abstract
INTRODUCTION The prevalence of surgical site infection (SSI) remains higher in gastrointestinal surgery than in other surgeries. Although several guidelines have indicated the efficacy of chlorhexidine and povidone-iodine in reducing the SSI rate, the optimal recommendation has still not been established. Therefore, it is necessary to determine the more effective antiseptic for surgical site preparation. Olanexidine (1.5% olanedine, Otsuka Pharmaceutical Factory, Tokushima, Japan), which is a new antiseptic in Japan, has antimicrobial activity against a wide range of bacteria, including Gram-positive and Gram-negative bacteria. Our study will contribute to determining a new antiseptic for use in gastrointestinal and other surgeries. METHODS AND ANALYSIS We propose a multicentre, randomised controlled clinical trial for comparing two treatments, that is, 1.5% olanexidine or 10% povidone-iodine, for surgical skin preparation to prevent SSI in clean-contaminated gastrointestinal surgeries with surgical wounds. Patients aged ≥20 years at the time of consent will be included. The primary outcome measure is the 30-day postoperative SSI rate. For the primary analysis, which is aimed at comparing the treatment effects, the adjusted risk ratio and its 95% CI will be estimated using the Mantel-Haenszel method. ETHICS AND DISSEMINATION The protocol was first approved by the Institutional Review Board of Keio University School of Medicine, followed by the institutional review board of each participating site. Participant recruitment began in June 2018. The final results will be published in international peer-reviewed medical journals. TRIAL REGISTRATION NUMBER UMIN 000031560; Pre-results.
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GH30 Glucuronoxylan-Specific Xylanase from Streptomyces turgidiscabies C56.
Maehara, T, Yagi, H, Sato, T, Ohnishi-Kameyama, M, Fujimoto, Z, Kamino, K, Kitamura, Y, St John, F, Yaoi, K, Kaneko, S
Applied and environmental microbiology. 2018;(4)
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Abstract
Endoxylanases are important enzymes in bioenergy research because they specifically hydrolyze xylan, the predominant polysaccharide in the hemicellulose fraction of lignocellulosic biomass. For effective biomass utilization, it is important to understand the mechanism of substrate recognition by these enzymes. Recent studies have shown that the substrate specificities of bacterial and fungal endoxylanases classified into glycoside hydrolase family 30 (GH30) were quite different. While the functional differences have been described, the mechanism of substrate recognition is still unknown. Therefore, a gene encoding a putative GH30 endoxylanase was cloned from Streptomyces turgidiscabies C56, and the recombinant enzyme was purified and characterized. GH30 glucuronoxylan-specific xylanase A of Streptomyces turgidiscabies (StXyn30A) showed hydrolytic activity with xylans containing both glucuronic acid and the more common 4-O-methyl-glucuronic acid side-chain substitutions but not on linear xylooligosaccharides, suggesting that this enzyme requires the recognition of glucuronic acid side chains for hydrolysis. The StXyn30A limit product structure was analyzed following a secondary β-xylosidase treatment by thin-layer chromatography and mass spectrometry analysis. The hydrolysis products from both glucuronoxylan and 4-O-methylglucuronoxylan by StXyn30A have these main-chain substitutions on the second xylopyranosyl residue from the reducing end. Because previous structural studies of bacterial GH30 enzymes and molecular modeling of StXyn30A suggested that a conserved arginine residue (Arg296) interacts with the glucuronic acid side-chain carboxyl group, we focused on this residue, which is conserved at subsite -2 of bacterial but not fungal GH30 endoxylanases. To help gain an understanding of the mechanism of how StXyn30A recognizes glucuronic acid substitutions, Arg296 mutant enzymes were studied. The glucuronoxylan hydrolytic activities of Arg296 mutants were significantly reduced in comparison to those of the wild-type enzyme. Furthermore, limit products other than aldotriouronic acid were observed for these Arg296 mutants upon secondary β-xylosidase treatment. These results indicate that a disruption of the highly conserved Arg296 interaction leads to a decrease of functional specificity in StXyn30A, as indicated by the detection of alternative hydrolysis products. Our studies allow a better understanding of the mechanism of glucuronoxylan recognition and enzyme specificity by bacterial GH30 endoxylanases and provide further definition of these unique enzymes for their potential application in industry.IMPORTANCE Hemicellulases are important enzymes that hydrolyze hemicellulosic polysaccharides to smaller sugars for eventual microbial assimilation and metabolism. These hemicellulases include endoxylanases that cleave the β-1,4-xylose main chain of xylan, the predominant form of hemicellulose in lignocellulosic biomass. Endoxylanases play an important role in the utilization of plant biomass because in addition to their general utility in xylan degradation, they can also be used to create defined compositions of xylooligosaccharides. For this, it is important to understand the mechanism of substrate recognition. Recent studies have shown that the substrate specificities of bacterial and fungal endoxylanases that are classified into glycoside hydrolase family 30 (GH30) were distinct, but the difference in the mechanisms of substrate recognition is still unknown. We performed characterization and mutagenesis analyses of a new bacterial GH30 endoxylanase for comparison with previously reported fungal GH30 endoxylanases. Our study results in a better understanding of the mechanism of substrate specificity and recognition for bacterial GH30 endoxylanases. The experimental approach and resulting data support the conclusions and provide further definition of the structure and function of GH30 endoxylanases for their application in bioenergy research.
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Long-term complete response of advanced hepatocellular carcinoma treated with multidisciplinary therapy including reduced dose of sorafenib: case report and review of the literature.
Shinoda, M, Kishida, N, Itano, O, Ei, S, Ueno, A, Kitago, M, Abe, Y, Hibi, T, Yagi, H, Masugi, Y, et al
World journal of surgical oncology. 2015;:144
Abstract
An 83-year-old man underwent computed tomography during a routine check-up due to a history of surgical treatment for pancreatic cancer. Two tumors were detected in the anterior segment of the liver. A needle biopsy of the larger tumor was performed, and pathological examination showed that the tumor was a poorly differentiated hepatocellular carcinoma. Resection was not performed considering the patient's poor physical condition. Thus, transcatheter arterial chemoembolization and radiofrequency ablation of the tumors were performed. Three months later, residual tumor of the larger lesion and multiple pulmonary metastases were detected. This time, continuous hepatic arterial infusion chemotherapy was performed. Although the pulmonary metastases markedly reduced, tumor thrombi appeared in the right portal vein on computed tomography. Finally, sorafenib was administered, which led to disappearance of the tumor thrombi and no other signs of recurrence 8 months after initiation of sorafenib on computed tomography. Although sorafenib administration has continued at reduced doses of 200 mg per day or less due to hypertension, complete response has persisted for the past 34 months. It is noteworthy that sorafenib has been given at reduced doses, but a long-term complete response is maintained in a patient who had portal tumor thrombi and distant metastasis. Herein, we present this rare case of advanced hepatocellular carcinoma controlled with reduced doses of sorafenib following multidisciplinary therapy, describe our single center experience with sorafenib use in patients with hepatocellular carcinoma, and review previous reports that focused on dose reduction of sorafenib.
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Effects of nicorandil on cardiovascular events in patients with coronary artery disease in the Japanese Coronary Artery Disease (JCAD) study.
Horinaka, S, Yabe, A, Yagi, H, Ishimitsu, T, Yamazaki, T, Suzuki, S, Kohro, T, Nagai, R, ,
Circulation journal : official journal of the Japanese Circulation Society. 2010;(3):503-9
Abstract
BACKGROUND Nicorandil has cardioprotective effects in the ischemic myocardium, mimicking ischemic preconditioning, and is thus expected to improve the prognosis of ischemic heart disease (IHD). As part of the Japanese Coronary Artery Disease (JCAD) Study, a multicenter collaborative prospective observational study of a large cohort of coronary artery disease patients, the effect of nicorandil on outcome was examined. METHODS AND RESULTS In total, 2,558 patients with nicorandil treatment and controls subjected to propensity score matching were eligible among 13,812 patients registered in the JCAD study. The mean follow-up interval was 2.7 years. The primary endpoint, death from all causes, was significantly lower, by 35% (hazard ratio 0.65, P=0.0008), in the nicorandil group than in the control group. There were also significant reductions in secondary endpoints, including cardiac death (56%), fatal myocardial infarction (56%), cerebral or vascular death (71%), and congestive heart failure (33%) in the nicorandil group, with no excess of deaths from other non-cardiovascular causes. Treatment with nicorandil reduced the number of deaths from all causes to a similar extent with or without treatment with sulfonylureas. CONCLUSIONS The reduction in cardiovascular death with nicorandil was large in patients with IHD, which has important implications for treatment.
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Renal insufficiency is related to painless myocardial infarction.
Komukai, K, Ogawa, T, Yagi, H, Date, T, Suzuki, K, Sakamoto, H, Miyazaki, H, Takatsuka, H, Shibayama, K, Ogawa, K, et al
Circulation journal : official journal of the Japanese Circulation Society. 2007;(9):1366-9
Abstract
BACKGROUND Acute myocardial infarction (MI) sometimes occurs without painful symptoms and in such cases, prognosis is worsened by delays in diagnosis and revascularization. Renal insufficiency induces many types of neuropathy, but the relation between renal insufficiency and painless MI remains unclear. METHODS AND RESULTS Patients with MI and elevated creatine kinase levels were retrospectively analyzed. Renal insufficiency (serum creatinine concentration > or =1.5 mg/dl) and other characteristics (age, sex, body mass index, hypertension, smoking, diabetes mellitus, dyslipidemia, history of stroke, previous MI, hemodialysis, and atrial fibrillation) were compared between patients who had MI with painful symptoms (painful MI, n=131) and patients who had MI without painful symptoms (painless MI, n=18). Other variables compared were the time from symptom onset to admission, peak creatine kinase concentration, Killip class, site of MI, emergency coronary angiography, postprocedural Thrombolysis In Myocardial Infarction grade III flow, and in-hospital death. Univariate analysis identified older age, renal insufficiency, and previous MI as predictors of painless MI. Patients with painless MI showed higher rates of Killip class > or =II and in-hospital death and a longer time from symptom onset to admission. However, multivariate analysis identified only renal insufficiency as an independent predictor of painless MI. CONCLUSIONS MI without painful symptoms frequently develops in patients who have renal insufficiency, so the possibility of painless MI should be evaluated in such patients to ensure early diagnosis and treatment.
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[Suppressive effect of nicorandil in ventricular arrhythmias after reperfusion therapy in patients with acute myocardial infarction].
Hara, H, Horinaka, S, Yabe, A, Yagi, H, Tsuboko, Y, Yoshida, K, Iemura, T, Matsuoka, H
Journal of cardiology. 2007;(3):135-41
Abstract
BACKGROUND Nicorandil is reported to inhibit reperfusion arrhythmias in patients with acute myocardial infarction (AMI), but few studies have counted ventricular arrhythmias with Holter electrocardiograms in patients treated with nicorandil following AMI reperfusion. OBJECTIVES In the present study, we examined the effects of nicorandil by investigating the occurrence of ventricular arrhythmia with Holter electrocardiogram monitoring after percutaneous coronary intervention with acute myocardial infarction. METHODS Forty patients with AMI who underwent successful percutaneous coronary intervention (PCI) were enrolled and randomly assigned to nicorandil or placebo groups. Following PCI, nicorandil was infused intravenously at 6 mg/hr for 24 hr, with Holter electrocardiogram monitoring. Patients with 100 or more premature ventricular contractions (PVCs) over the 24-hour period were studied. The total number of PVCs, frequency of occurrence of ventricular tachycardia, and clinical characteristics were compared between the two groups. RESULTS Fourteen patients in the nicorandil group and 12 patients in the placebo group exhibited 100 or more PVCs over the 24-hour period. Lesion characteristics and procedural factors did not differ between the two groups. Fewer PVCs were counted in the nicorandil group than in the placebo group(144.6 +/- 106.5 vs 286.8 +/- 159.1 beats/day, p = 0.012). The frequency of coupled PVCs was lower in the nicorandil group (6.9 +/- 6.9 vs 16.3 +/- 12.8 beats/day, p = 0.025). Although the frequency of ventricular tachycardia did not differ between the two groups, ventricular tachycardia duration was significantly shorter in the nicorandil group (3.73 +/- 2.30 vs 8.34 +/- 7.45 sec, p = 0.03). CONCLUSIONS Our study indicates nicorandil inhibits ventricular arrhythmias following PCI for patients with AMI. Nicorandil treatment following PCI for AMI is convenient and may reduce the rate of cardiac events by inhibiting ventricular arrhythmias, thereby potentially improving the prognosis.
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Von Willebrand factor-cleaving protease and Upshaw-Schulman syndrome.
Fujimura, Y, Matsumoto, M, Yagi, H, Yoshioka, A, Matsui, T, Titani, K
International journal of hematology. 2002;(1):25-34
Abstract
Vascular endothelial cell (EC)-produced plasma von Willebrand factor (vWF) plays a critical role in primary hemostasis through its action of anchoring platelets onto the injured denuded subendothelial matrices under high shear stress. Unusually large vWF multimers (UL-vWFMs), present in plasma immediately after release from ECs, are most biologically active, but they are soon cleaved and degraded into smaller vWFMs by a specific plasma protease, termed vWF-cleaving protease (vWF-CPase), in normal circulation. Recent studies on the relationship between UL-vWFMs and vWF-CPase, together with its autoantibody (inhibitor) have brought about a clear discrimination between thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Furthermore, a congenital deficiency of this enzyme activity has been shown to cause Upshaw-Schulman syndrome, a complex constitutional bleeding diathesis. Successful purification of vWF-CPase revealed that this enzyme is composed of a single polypeptide with a molecular mass of approximately 190 kd, and its complementary DNA cloning unambiguously indicated that it is uniquely produced in the liver and its gene is located on chromosome 9q34. The messenger RNA of vWF-CPase had a span of 4.6 kb, and its enzyme was designated ADAMTS 13. The predicted complete amino acid sequence of this enzyme consisted of 1427 residues, including a signal peptide, a short propeptide terminating in the sequence RQRR, a reprolysin-like metalloprotease domain, a disintegrin-like domain, a thrombospondin-1 repeat (TSP1), a cysteine-rich domain, an ADAMTS spacer, 7 additional TSP1 repeats, and 2 CUB domains.