Rapid estimation of soluble fibrin monomer complexes by high performance liquid chromatography for the purpose of early detection of DIC

Thesis--University of Tsukuba, D.M.S.(B), no. 392, 1987. 6. 30Offprint. Originally published in: Thrombosis research, v. 30, pp. 521-526, 1983Joint author: Yoji IwasakiIncludes supplementary treatise

Destruction of mesoscopic chemically modulated domains in single phase high entropy alloy via plastic deformation

Chemically modulated mesoscopic domains in a fcc single phase CrMnFeCoNi equi-atomic high entropy alloy (HEA) are detected by small angle diffraction performed at a synchrotron radiation facility, whereas the mesoscopic domains cannot be detected by conventional X-ray diffraction and 2D mappings of energy dispersive X-ray spectroscopy by scanning electron microscopy and scanning transmission electron microscopy. The mesoscopic domains are deformed and shrieked, and finally destructed by plastic deformation, which is supported by the comprehensive observations/measurements, such as electrical resistivity, Vickers hardness, electron backscattering diffraction, and hard X-ray photoemission spectroscopy. The destruction of the mesoscopic domains causes the decrease in electrical resistivity via plastic deformation, so called K-effect, which is completely opposite to the normal trend of metals. We confirmed that the presence and the size of local chemical ordering or short-range order domains in the single phased HEA, and furthermore, Cr and Mn are related to form the domains

Impact of HBV Infection on Outcomes of Direct-Acting Antiviral Therapy of Chronic Hepatitis C

Background: Most clinical trials of direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) infection have excluded hepatitis B virus (HBV) coinfection, and little is known about the effects of DAA on chronic hepatitis C patients with HBV coinfection. Recent studies have reported that DAA therapy for HCV can also cause HBV reactivation in patients with HBV and HCV coinfection. The aim of this study was to assess the effects of DAA on sustained virologic response (SVR) and HBV reactivation in patients with chronic hepatitis C. Methods: Participants comprised 199 chronic hepatitis C patients who received DAA therapy (96 men, 103 women; mean age, 66.7 ± 12.0 years). Results: Twelve patients were coinfected with HCV and HBV. Sixty patients were HBV surface antigen negative but positive for hepatitis B core antibody and/or hepatitis B surface antibody, and one hundred and twenty-seven patients had not been exposed to HBV. Rates of SVR in HBV and HCV coinfected patients, HBV prior infection, and no exposure to HBV were 100, 95, and 97%, respectively. Significant differences were seen between each group. No case showed HBV reactivation. Conclusions: DAA treatments were effective in patients with HBV coinfection or HBV prior infection, as well as HCV monoinfection. As the number of cases was small, we still suggest caution regarding HBV reactivation in HCV and HBV coinfected patients undergoing treatment with DAA

Genotype–phenotype correlation for extracolonic aggressive phenotypes in patients with familial adenomatous polyposis

Familial adenomatous polyposis (FAP) patients develop various life-threatening extracolonic comorbidities that appear individually or within a family. This diversity can be explained by the localization of the adenomatous polyposis coli (APC) variant, but few reports provide definitive findings about genotype–phenotype correlations. Therefore, we investigated FAP patients and the association between the severe phenotypes and APC variants. Of 247 FAP patients, 126 patients from 85 families identified to have APC germline variant sites were extracted. These sites were divided into six groups (Regions A to F), and the frequency of severe comorbidities was compared among the patient phenotypes. Of the 126 patients, the proportions of patients with desmoid tumor stage ≥III, number of FGPs ≥1000, multiple gastric neoplasms, gastric neoplasm with high-grade dysplasia, and Spigelman stage ≥III were 3%, 16%, 21%, 12%, and 41%, respectively, while the corresponding rates were 30%, 50%, 70%, 50%, and 80% in patients with Region E (codons 1398–1580) variants. These latter rates were significantly higher than those for patients with variants in other regions. Moreover, the proportion of patients with all three indicators (desmoid tumor stage ≥III, number of FGPs ≥1000, and Spigelman stage ≥III) was 20% for those with variants in Region E and 0% for those with variants in other regions. Variants in Region E indicate aggressive phenotypes, and more intensive management is required

Glucotoxicity Induces Insulin Promoter DNA Methylation in Beta Cells

Recent studies have implicated epigenetics in the pathophysiology of diabetes. Furthermore, DNA methylation, which irreversibly deactivates gene transcription, of the insulin promoter, particularly the cAMP response element, is increased in diabetes patients. However, the underlying mechanism remains unclear. We aimed to investigate insulin promoter DNA methylation in an over-nutrition state. INS-1 cells, the rat pancreatic beta cell line, were cultured under normal-culture-glucose (11.2 mmol/l) or experimental-high-glucose (22.4 mmol/l) conditions for 14 days, with or without 0.4 mmol/l palmitate. DNA methylation of the rat insulin 1 gene (Ins1) promoter was investigated using bisulfite sequencing and pyrosequencing analysis. Experimental-high-glucose conditions significantly suppressed insulin mRNA and increased DNA methylation at all five CpG sites within the Ins1 promoter, including the cAMP response element, in a time-dependent and glucose concentration-dependent manner. DNA methylation under experimental-high-glucose conditions was unique to the Ins1 promoter; however, palmitate did not affect DNA methylation. Artificial methylation of Ins1 promoter significantly suppressed promoter-driven luciferase activity, and a DNA methylation inhibitor significantly improved insulin mRNA suppression by experimental-high-glucose conditions. Experimental-high-glucose conditions significantly increased DNA methyltransferase activity and decreased ten-eleven-translocation methylcytosine dioxygenase activity. Oxidative stress and endoplasmic reticulum stress did not affect DNA methylation of the Ins1 promoter. High glucose but not palmitate increased ectopic triacylglycerol accumulation parallel to DNA methylation. Metformin upregulated insulin gene expression and suppressed DNA methylation and ectopic triacylglycerol accumulation. Finally, DNA methylation of the Ins1 promoter increased in isolated islets from Zucker diabetic fatty rats. This study helps to clarify the effect of an over-nutrition state on DNA methylation of the Ins1 promoter in pancreatic beta cells. It provides new insights into the irreversible pathophysiology of diabetes

Conditioned medium from stem cells derived from human exfoliated deciduous teeth ameliorates NASH via the Gut-Liver axis

Non-alcoholic steatohepatitis (NASH) occurrence has been increasing and is becoming a major cause of liver cirrhosis and liver cancer. However, effective treatments for NASH are still lacking. We examined the benefits of serum-free conditioned medium from stem cells derived from human exfoliated deciduous teeth (SHED-CM) on a murine non-alcoholic steatohepatitis (NASH) model induced by a combination of Western diet (WD) and repeated administration of low doses of carbon tetrachloride intraperitoneally, focusing on the gut-liver axis. We showed that repeated intravenous administration of SHED-CM significantly ameliorated histological liver fibrosis and inflammation in a murine NASH model. SHED-CM inhibited parenchymal cell apoptosis and reduced the activation of inflammatory macrophages. Gene expression of pro-inflammatory and pro-fibrotic mediators (such as Tnf-α, Tgf-β, and Ccl-2) in the liver was reduced in mice treated with SHED-CM. Furthermore, SHED-CM protected intestinal tight junctions and maintained intestinal barrier function, while suppressing gene expression of the receptor for endotoxin, Toll-like receptor 4, in the liver. SHED-CM promoted the recovery of Caco-2 monolayer dysfunction induced by IFN-γ and TNF-α in vitro. Our findings suggest that SHED-CM may inhibit NASH fibrosis via the gut-liver axis, in addition to its protective effect on hepatocytes and the induction of macrophages with unique anti-inflammatory phenotypes

Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III) : a multicenter prospective interventional study

Background Total colectomy is the standard treatment for familial adenomatous polyposis (FAP). Recently, an increasing number of young patients with FAP have requested the postponement of surgery or have refused to undergo surgery. We aimed to evaluate the effectiveness of intensive endoscopic removal for downstaging of polyp burden (IDP) in FAP. Method A single-arm intervention study was conducted at 22 facilities. Participants were patients with FAP, aged ≥ 16 years, who had not undergone colectomy or who had undergone colectomy but had ≥ 10 cm of large intestine remaining. For IDP, colorectal polyps of ≥ 10 mm were removed, followed by polyps of ≥ 5 mm. The primary end point was the presence/absence of colectomy during a 5-year intervention period. Results 222 patients were eligible, of whom 166 had not undergone colectomy, 46 had undergone subtotal colectomy with ileorectal anastomosis, and 10 had undergone partial resection of the large intestine. During the intervention period, five patients (2.3 %, 95 % confidence interval [CI] 0.74 %–5.18 %) underwent colectomy, and three patients died. Completion of the 5-year intervention period without colectomy was confirmed in 150 /166 patients who had not undergone colectomy (90.4 %, 95 %CI 84.8 %–94.4 %) and in 47 /56 patients who had previously undergone colectomy (83.9 %, 95 %CI 71.7 %–92.4 %). Conclusion IDP in patients with mild-to-moderate FAP could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy. However, if the IDP protocol was proposed during a much longer term, it may not preclude the possibility that a large proportion of colectomies may still need to be performed