The ability of contemporary cardiologists to judge the ischemic impact of a coronary lesion visually

Background: Landmark trials showed that invasive pressure measurement (Fractional Flow Reserve, FFR) was a better guide to coronary stenting than visual assessment. However, present-day interventionists have benefited from extensive research and personal experience of mapping anatomy to hemodynamics. Aims: To determine if visual assessment of the angiogram performs as well as invasive measurement of coronary physiology. Methods: 25 interventional cardiologists independently visually assessed the single vessel coronary disease of 200 randomized participants in The Objective Randomized Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina trial (ORBITA). They gave a visual prediction of the FFR and Instantaneous Wave-free Ratio (iFR), denoted vFFR and viFR respectively. Each judged each lesion on 2 occasions, so that every lesion had 50 vFFR, and 50 viFR assessments. The group consensus visual estimates (vFFR-group and viFR-group) and individual cardiologists' visual estimates (vFFR-individual and viFR-individual) were tested alongside invasively measured FFR and iFR for their ability to predict the placebo-controlled reduction in stress echo ischemia with stenting. Results: Placebo-controlled ischemia improvement with stenting was predicted by vFFR-group (p < 0.0001) and viFR-group (p < 0.0001), vFFR-individual (p < 0.0001) and viFR-individual (p < 0.0001). There were no significant differences between the predictive performance of the group visual estimates and their invasive counterparts: p = 0.53 for vFFR vs FFR and p = 0.56 for viFR vs iFR. Conclusion: Visual assessment of the angiogram by contemporary experts, provides significant additional information on the amount of ischaemia which can be relieved by placebo-controlled stenting in single vessel coronary artery disease

フェリチンの鉄酸化・ミネラル化に関する研究

Ferritin keeps cells from being damaged by reactive oxygen species produced by Fe2+ and storages the oxidized iron in its cavity as iron cores. The iron core contains a various amount of inorganic phosphate (Pi). In bacteria, the amount of phosphate is comparable to that of iron. In contrast, ferritins from mammals contain only a tenth phosphate. It is not clear how the phosphate works in the iron oxidation and mineralization process. In this research, I investigated the effect of the phosphate on the structural feature of iron cores formed in the cavity of Escherichia coli ferritin (EcFtnA) and on its function. First, the structure of iron cores was characterized using analytical ultracentrifugation, transmission electron microscopy and small-angle X-ray scattering. These experiments revealed that the iron core was a cluster of small particles of which diameter were 2-4 nm in the absence of phosphate whereas it had a hollow spherical structure of which the inner and outer diameters were 6 and 8 nm, respectively. The effects of phosphate on the oxidation/mineralization kinetics were also investigated spectrophotometrically. The oxidation reaction showed at least two kinetic phases when iron atoms beyond 72 Fe/protein shell were added. The initial phase corresponds to the binding of three irons to a ferroxidase center and subsequent oxidation, whereas the second one reflects the turnover, that is, the movement of oxidized iron from the ferroxidase center to the cavity. By comparing the kinetic curves with and without phosphates, it was revealed that the phosphate accelerated only the second phase, suggesting that the phosphate increases the turnover rate of the iron oxidation and/or mineralization process by EcFtnA.Neuroferritinopathy is a rare disease caused by mutations to human ferritin light chain gene (ftl1). While 9 of ten mutations reported to date produce ferritin mutants extended from 4 to 16 amino acid residues in the C-terminal region, A96T is a point mutant associated with neuroferritinopathy. The functional information of A96T has not been obtained in contrast to frameshift mutants. The iron incorporation activity of A96T mutant was investigated by native-PAGE using Prussian blue staining and change in absorbance intensity at 310nm. The result revealed that the iron incorporation activity of A96T is similar to that of human ferritin light chain wild type, and suggested that the pathogenic mechanism caused by A96T is different from the model proposed for frameshift mutants.創価大

フェリチンの鉄酸化・ミネラル化に関する研究

Ferritin keeps cells from being damaged by reactive oxygen species produced by Fe2+ and storages the oxidized iron in its cavity as iron cores. The iron core contains a various amount of inorganic phosphate (Pi). In bacteria, the amount of phosphate is comparable to that of iron. In contrast, ferritins from mammals contain only a tenth phosphate. It is not clear how the phosphate works in the iron oxidation and mineralization process. In this research, I investigated the effect of the phosphate on the structural feature of iron cores formed in the cavity of Escherichia coli ferritin (EcFtnA) and on its function. First, the structure of iron cores was characterized using analytical ultracentrifugation, transmission electron microscopy and small-angle X-ray scattering. These experiments revealed that the iron core was a cluster of small particles of which diameter were 2-4 nm in the absence of phosphate whereas it had a hollow spherical structure of which the inner and outer diameters were 6 and 8 nm, respectively. The effects of phosphate on the oxidation/mineralization kinetics were also investigated spectrophotometrically. The oxidation reaction showed at least two kinetic phases when iron atoms beyond 72 Fe/protein shell were added. The initial phase corresponds to the binding of three irons to a ferroxidase center and subsequent oxidation, whereas the second one reflects the turnover, that is, the movement of oxidized iron from the ferroxidase center to the cavity. By comparing the kinetic curves with and without phosphates, it was revealed that the phosphate accelerated only the second phase, suggesting that the phosphate increases the turnover rate of the iron oxidation and/or mineralization process by EcFtnA.Neuroferritinopathy is a rare disease caused by mutations to human ferritin light chain gene (ftl1). While 9 of ten mutations reported to date produce ferritin mutants extended from 4 to 16 amino acid residues in the C-terminal region, A96T is a point mutant associated with neuroferritinopathy. The functional information of A96T has not been obtained in contrast to frameshift mutants. The iron incorporation activity of A96T mutant was investigated by native-PAGE using Prussian blue staining and change in absorbance intensity at 310nm. The result revealed that the iron incorporation activity of A96T is similar to that of human ferritin light chain wild type, and suggested that the pathogenic mechanism caused by A96T is different from the model proposed for frameshift mutants.創価大

Support system for pathologists and researchers

Aims: In Japan, cancer is the most prevalent cause of death; the number of patients suffering from cancer is increasing. Hence, there is an increased burden on pathologists to make diagnoses. To reduce pathologists′ burden, researchers have developed methods of auto-pathological diagnosis. However, virtual slides, which are created when glass slides are digitally scanned, saved in a unique format, and it is difficult for researchers to work on the virtual slides for developing their own image processing method. This paper presents the support system for pathologists and researchers who use auto-pathological diagnosis (P-SSD). Main purpose of P-SSD was to support both of pathologists and researchers. P-SSD consists of several sub-functions that make it easy not only for pathologists to screen pathological images, double-check their diagnoses, and reduce unimportant image data but also for researchers to develop and apply their original image-processing techniques to pathological images. Methods: We originally developed P-SSD to support both pathologists and researchers developing auto-pathological diagnoses systems. Current version of P-SSD consists of five main functions as follows: (i) Loading virtual slides, (ii) making a supervised database, (iii) learning image features, (iv) detecting cancerous areas, (v) displaying results of detection. Results: P-SSD reduces computer memory size random access memory utilization and the processing time required to divide the virtual slides into the smaller-size images compared with other similar software. The maximum observed reduction in computer memory size and reduction in processing time is 97% and 99.94%, respectively. Conclusions: Unlike other vendor-developed software, P-SSD has interoperability and is capable of handling virtual slides in several formats. Therefore, P-SSD can support both of pathologists and researchers, and has many potential applications in both pathological diagnosis and research area

Safety of Sofosbuvir and Ribavirin Combination Therapy in a Patient Who Developed Anemia due to Ribavirin

Interferon (IFN) and ribavirin (RBV) combination therapy was previously the standard of care for treatment of hepatitis C virus (HCV) genotype 2 infection. But, it often induced hemolytic anemia. In 2014, sofosbuvir (SOF) was approved for the treatment of chronic HCV genotype 2 in Japan. SOF/RBV therapy is more effective against genotype 2 than IFN/RBV therapy. We report a case of a 74-year-old woman with chronic HCV genotype 2b infection. She received five treatments including RBV and IFN therapy before SOF was approved and all of them were ineffective. Therapies that included RBV induced severe anemia and led to discontinuation of treatment. With pegylated IFN/RBV therapy, the maximum change in hemoglobin (Hb) from baseline was −3.7 g/dL. However, SOF/RBV therapy was effective and she achieved sustained virologic response (SVR) with a maximum change in Hb from baseline of only −1.2 g/dL. We also found reticulocyte count was very low during treatment in this case and speculate it was one of the reasons that she developed hemolytic anemia with RBV. In conclusion, SOF/RBV therapy is effective and allowed the patient to achieve SVR. An SOF/RBV regimen is safe and effective for patients who have or are at risk of anemia induced by RBV

Association of dipeptidyl peptidase‐4 inhibitor use and risk of pancreatic cancer in individuals with diabetes in Japan

ABSTRACT Aims/Introduction This study was designed and carried out to investigate the association of dipeptidyl peptidase‐4 inhibitor (DPP‐4i) use with pancreatic cancer (PC) in individuals with diabetes in Japan. Materials and Methods The JMDC Claims Database, which contains the medical and prescription information of Japanese employment‐based health insurance programs, was used. The primary outcome was duration to the first occurrence of PC (International Classification of Diseases 10th Revision code C25), both all and hospitalized, from prescription of DPP‐4is or other oral glucose‐lowering agents (GLAs). Results Individuals with diabetes who received DPP‐4is (n = 61,430) or other oral GLAs (n = 83,304) were analyzed. Follow‐up periods (median [interquartile range]) were 17 months (8–33) for DPP‐4is and 14 months (7–28) for other oral GLAs. Kaplan–Meier curve analysis to determine the duration of first use of DPP4i or other oral GLA to diagnosis of PC disclosed no differences between the two groups in duration to all or hospitalized PC (log‐rank test: all, P = 0.7140; hospitalized, P = 0.3446). Cox proportional hazards models showed that use of DPP‐4is did not affect the PC risk adjusted for medications, age, sex and risk comorbidities (all, hazard ratio 1.1, 95% confidence interval 0.8–1.3, P = 0.6518; hospitalized, hazard ratio 1.1, 95% confidence interval 0.8–1.4, P = 0.6662). Similar results were obtained when individuals with ≥2 years oral GLA treatment and those with medical checkup data (e.g., smoking or drinking habit) available were analyzed. Conclusion This database study shows that there is not a significant PC risk due to DPP‐4i treatment in individuals with diabetes in Japan, but larger studies with longer follow up are required to confirm these findings