Yoshihiko Izumida - Academia.edu (original) (raw)

Papers by Yoshihiko Izumida

Background: Government policies in the U.S. and E.U. promote standardization and value creation i... more Background: Government policies in the U.S. and E.U. promote standardization and value creation in the use of FAIR (Findability, Accessibility, Interoperability and Reusability) data. Objective: In this global trend, the interoperable interface called Sync for Science-J (S4S-J) for linking Electronic Medical Record (EMR) and Personal Health Record (PHR) was launched on the Basic Policy for Economic and Fiscal Management and Reform in Japan. Methods: S4S-J controls data distribution consisting of EMR and Patient-Generated Health Data (PGHD) and converts this information into QR codes that can be scanned by mobile applications. This system facilitates data sharing based on personal information beliefs and unlocks siloed IoT systems with Privacy Preference Manager (PPM). In line with Japanese information handling practices, the development of a mobile-cloud network will lower barriers to entry and enable accelerated data sharing. To ensure cross-compatibility and compliance with future international data standardization, S4S-J conforms to the HL7-FHIR standard and uses the international standardized LOINC to redefine medical terms used in different terminology standards in different medical fields. It is developed as an applied standard in the medical information intended for industry, healthcare services and research through secondary use of data. Results: A multicenter collaborative study was initiated to investigate the effectiveness of this system as a registry clinical trial and a multicenter randomized controlled trial, the EMBRACE study of the mobile health (mHealth) application M?Link for hyperglycemic disorders in pregnancy, which implements EMR-PHR interoperable interface S4S-J. Conclusions: The patient-centric data flow of the S4S-J in Japan is expected to guarantee the right to data portability, which promotes the maximum benefit of use by patients themselves, which in turn contributes to the promotion of open science. Clinical Trial: 1) Efficacy of MLink based telemedicine on GDM in a randomized controlled trial (EMBRACE), jRCT1032230258, https://jrct.niph.go.jp/en-latest-detail/jRCT1032230258 2) Study on Registry of Pregnancy with Abnormal Glucose Metabolism, jRCT1030220452, https://jrct.niph.go.jp/en-latest

The FEBS Journal

During periods of fasting, the body undergoes a metabolic shift from carbohydrate utilization to ... more During periods of fasting, the body undergoes a metabolic shift from carbohydrate utilization to the use of fats and ketones as an energy source, as well as the inhibition of de novo lipogenesis and the initiation of gluconeogenesis in the liver. The transcription factor sterol regulatory element‐binding protein‐1 (SREBP‐1), which plays a critical role in the regulation of lipogenesis, is suppressed during fasting, resulting in the suppression of hepatic lipogenesis. We previously demonstrated that the interaction of fasting‐induced Kruppel‐like factor 15 (KLF15) with liver X receptor (LXR) serves as the essential mechanism for the nutritional regulation of SREBP‐1 expression. However, the underlying mechanisms of KLF15 induction during fasting remain unclear. In this study, we show that the glucocorticoid receptor (GR) regulates the hepatic expression of KLF15 and, subsequently, lipogenesis through the KLF15‐SREBP‐1 pathway during fasting. KLF15 is necessary for the suppression of ...

Journal of Investigative Dermatology, May 1, 2018

Desmoglein 3 (Dsg3), encoded by DSG3 gene, is the major component of desmosomes which contribute ... more Desmoglein 3 (Dsg3), encoded by DSG3 gene, is the major component of desmosomes which contribute to cell-cell adhesion in epidermis. Dsg3-deficient mice show erosions in the mucosa and hypotrichosis, caused by loss of cell-cell adhesion. Autoantibodies against human Dsg3, called as mucosal pemphigus vulgaris, lead to suprabasal acantholysis histologically and blister formation limited to the mucosa clinically. A patient with Dsg3 deficiency, however, has never been reported. A 1 year-old female baby presented with recurrent erosions in the oral and laryngeal mucosa after birth. Her conjunctival and genital mucosa is spared and her hair was normally growing. Histological examination of skin biopsy showed suprabasal acantholytic blisters, but direct and indirect immunofluorescences were negative. Whole genome sequencing from her DNA identified a novel homozygous nonsense mutation in desmoglein 3. Using direct sequencing and restriction fragment length polymorphism assays, we found that her parents harbor the heterozygous mutations in DSG3. Immunofluorescence and immunoblotting showed that Dsg3 was not observed in keratinocytes from her skin as well as oral mucosa. Electron microscopy of her skin biopsy shows mature desmosomes in the basal layer. In conclusion, we describe a new hereditary disease featuring recurrent mucosal erosions caused by homozygous mutation in DSG3. 740 Chromosomal microarray analysis for the molecular diagnosis of nevoid basal cell carcinoma syndrome and X-linked ichthyosis

International Journal of Medical Sciences

Objectives: There are currently no appropriate markers and target for prophylaxis against COVID-1... more Objectives: There are currently no appropriate markers and target for prophylaxis against COVID-19-related thrombosis, especially in the not-severe cases. We tested the hypothesis that inflammation is a suitable marker and target for prophylaxis against COVID-19-related thrombosis. Methods: Data of all 32 COVID-19 patients admitted to Saitama Medical Center between January 1 and March 30, 2021, were analyzed. Patients were divided into severe (requiring oxygen, n=12) and non-severe (no requirement for oxygen, n=20), and also those with high C-reactive protein (CRP) level (cutoff value: 30 mg/L, n=21) and low-CRP (n=11). We also compared the clinical and laboratory data of a 46-year-old post-liver transplant male patient, who was treated with a combination of immunosuppressants (methylprednisolone, fludrocortisone, cyclosporine, and everolimus) with those of other COVID-19 patients, using the Smirnoff-Grubbs and Box plots tests. Results: The levels of CRP, ferritin, lactate dehydrogenase, aspartate aminotransferase, and thrombinantithrombin complex (TAT) were significantly higher in the high-severity group than the low-severity group; while other coagulation parameters were comparable. The time between onset of illness and blood levels of lactate dehydrogenase, fibrinogen, D-dimer, TAT, and plasmin alpha2-plasmin inhibitor complex (PIC) were significantly higher whereas lymphocyte count was significantly lower in the high-CRP group. Extremely low levels of TAT, PIC, and plasminogen activator inhibitor-1 (PAI-1) were recorded in the liver transplant patient treated with immunosuppressants. The TAT, PIC, and PAI-1 levels were deemed outliers. Conclusions: Inflammation is a potentially suitable marker and target for prophylaxis against COVID-19-related thrombosis.

Diabetic medicine : a journal of the British Diabetic Association, Jan 20, 2015

Insulin allergy, one of insulin's adverse effects, is rare, especially in patients with Type ... more Insulin allergy, one of insulin's adverse effects, is rare, especially in patients with Type 2 diabetes, but management is difficult and no effective strategy has yet been established. We experienced an insulin allergy case successfully managed with a novel combination of insulins. A 38-year-old woman started insulin therapy when diabetes was diagnosed at age 19 years. Despite poorly controlled diabetes because of poor adherence, she hoped to conceive a child and continuous subcutaneous insulin infusion was introduced using insulin aspart at age 32 years. One month thereafter, she developed skin reactions at the subcutaneous insulin infusion catheter insertion site. The patient was then tested for all rapid-acting insulin formulations, all of which triggered local reactions. She decided to continue the continuous subcutaneous infusion of human regular insulin, accompanied by oral cetirizine hydrochloride and betamethasone valerate ointment. The patient was admitted to our hospit...

European Surgical Research, 2005

We investigated the feasibility of correcting the congenital absence of albumin in Nagase analbum... more We investigated the feasibility of correcting the congenital absence of albumin in Nagase analbuminemic rats (NARs) by allogeneic bone marrow cell transplantation (BMT). Seven-week-old male NARs were used as recipients, and 6- to 8-week-old male Sprague-Dawley (SD) rats were used as allograft donors. NARs were divided into three groups: a BMT group (n = 10) in which bone marrow cells were infused into the liver; a hepatocyte transplantation (HCT) group (n = 8) in which hepatocytes were transplanted into the liver, and a control group (n = 8) in which PBS was injected into the portal vein. Serum albumin levels were measured as an indicator of the function of the grafted cells, and the phenotypic characteristics of the engrafted cells in the recipient’s liver were assessed with immunohistochemical and immunofluorescence techniques. At 8 weeks after cell transplantation, the serum albumin levels of the BMT group and HCT group were significantly higher than in the control group. The hep...

Cell Transplantation, 2005

Pancreatic islet transplantation is limited by shortage of donor organs. Although β-cell lines co... more Pancreatic islet transplantation is limited by shortage of donor organs. Although β-cell lines could be used, their secretion of insulin is characteristically glucose independent and immunoisolation is required. Here we show that intrasplenic transplantation of encapsulated glucose-responsive mouse insulinoma cells reversed streptozotocin (STZ)-induced diabetes in rats. MIN-6 cells derived from a transgenic mouse expressing SV 40 large T antigen in pancreatic β-cells were transfected with minigene encoding for human glucagon-like-peptide-1 under the control of rat insulin promoter. The cells were encapsulated in alginate/poly-L-lysine and used for cell transplantation in STZ-diabetic rats. Rats with nonfasting blood glucose (n-FBG) greater than 350 mg/dl were used. In group I rats (n = 6) 20 million encapsulated cells were injected into the spleen. Group II rats (n = 6) received empty capsules. n-FBG was measured biweekly. After 4 and 8 weeks, an intraperitoneal glucose tolerance te...

Objective Persons with type 2 diabetes are often stigmatised for having what is considered a life... more Objective Persons with type 2 diabetes are often stigmatised for having what is considered a lifestyle-related disease. Accordingly, some blame themselves for their condition, resulting in feelings of low self-worth that ultimately impact their self-management behaviours. However, there are no studies examining why some do not blame themselves for their condition and manage to maintain their self-worth in relation to their illness. This study aimed to explore an understanding of how such persons experience the maintenance of self-worth in relation to their illness over the lifelong course of treatment. Design A cross-sectional qualitative study. Face-to-face semistructured interviews were conducted with a purposive sampling strategy. The data was analysed using a qualitative descriptive method that involved concurrent data collection and constant comparative analysis. Setting Two tertiary-level hospitals in Japan. Participants Thirty-three outpatients with type 2 diabetes who curren...

iScience, 2021

Summary KLF15 is a transcription factor that plays an important role in the activation of glucone... more Summary KLF15 is a transcription factor that plays an important role in the activation of gluconeogenesis from amino acids as well as the suppression of lipogenesis from glucose. Here we identified the transcription start site of liver-specific KLF15 transcript and showed that FoxO1/3 transcriptionally regulates Klf15 gene expression by directly binding to the liver-specific Klf15 promoter. To achieve this, we performed a precise in vivo promoter analysis combined with the genome-wide transcription-factor-screening method “TFEL scan”, using our original Transcription Factor Expression Library (TFEL), which covers nearly all the transcription factors in the mouse genome. Hepatic Klf15 expression is significantly increased via FoxOs by attenuating insulin signaling. Furthermore, FoxOs elevate the expression levels of amino acid catabolic enzymes and suppress SREBP-1c via KLF15, resulting in accelerated amino acid breakdown and suppressed lipogenesis during fasting. Thus, the FoxO-KLF15 pathway contributes to switching the macronutrient flow in the liver under the control of insulin.

Biochemical and Biophysical Research Communications, 2009

It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis... more It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic b-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lep ob/ob /HSL À/À) and explored the role of HSL in pancreatic b-cells in the setting of obesity. Lep ob/ob /HSL À/À developed elevated blood glucose levels and reduced plasma insulin levels compared with Lep ob/ob /HSL +/+ in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep +/+ background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lep ob/ob islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lep ob/ob mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.

SSRN Electronic Journal, 2021

KLF15 is a transcription factor that plays an important role in the activation of gluconeogenesis... more KLF15 is a transcription factor that plays an important role in the activation of gluconeogenesis from amino acids as well as the suppression of lipogenesis from glucose. Although it is well known that hepatic Klf15 expression is elevated during fasting, its regulatory mechanisms have not been elucidated. Here we identified the transcription start site of liver-specific KLF15 transcript and showed that FoxO1 and FoxO3 (FoxOs) transcriptionally regulate Klf15 gene expression by directly binding to the liver-specific Klf15 promoter. To achieve this, we performed a precise in vivo promoter analysis using “in vivo Ad-luc” analytical system, combined with the genome-wide screening method “TFEL scan”, using our original cDNA library named Transcription Factor Expression Library (TFEL), which covers nearly all the transcription factors in the mouse genome. Hepatic Klf15 expression is significantly increased by the attenuation of the insulin signaling in STZ-induced insulin deficiency and insulin receptor knockdown models. In addition, we have found that FoxOs elevate the expression levels of amino acid catabolic enzymes via KLF15, resulting in accelerated amino acid metabolism during fasting. Based on these findings, we conclude that the FoxO-KLF15 pathway switches the macronutrient flow in the liver under the control of insulin.

Biochemical and biophysical research communications, 2005

Recent studies have demonstrated that the transplantation of bone marrow cells following diabetes... more Recent studies have demonstrated that the transplantation of bone marrow cells following diabetes induced by streptozotocin can support the recovery of pancreatic b-cell mass and a partial reversal of hyperglycemia. To address this issue, we examined whether the c-Met/hepatocyte growth factor (HGF) signaling pathway was involved in the recovery of b-cell injury after bone marrow transplantation (BMT). In this model, donor-derived bone marrow cells were positive for HGF immunoreactivity in the recipient spleen, liver, lung, and pancreas as well as in the host hepatocytes. Indeed, plasma HGF levels were maintained at a high value.The frequency of c-Met expression and its proliferative activity and differentiative response in the pancreatic ductal cells in the BMT group were greater than those in the PBS-treated group, resulting in an elevated number of endogenous insulin-producing cells. The induction of the c-Met/HGF signaling pathway following BMT promotes pancreatic regeneration in...

Biochemical and Biophysical Research Communications

SAGE Open Medicine

Objectives: The aim of this study is to empirically examine a full pathway model of health litera... more Objectives: The aim of this study is to empirically examine a full pathway model of health literacy, and health and well-being outcomes among patients with type 2 diabetes. Methods: A three-wave longitudinal survey was administered to 148 patients with diabetes. Covariance structure analysis was conducted to create a path diagram, with health literacy and burden of medical expenses included as independent variables and with psychosocial factors, behaviors, and health and well-being outcomes included as dependent variables. Results: The model fit indices showed a comparative fit index of 0.985 at baseline, 0.959 after 3 months, and 0.948 after 6 months, with a root mean square error of approximation of 0.040 at baseline, 0.079 after 3 months, and 0.085 after 6 months. There were 14 significant paths across the three time points between health literacy and understanding of diabetes care, self-efficacy, communication with doctors, and medication adherence. Conclusion: The model fitness...

FEBS Letters

Glucocorticoids have various medical uses but are accompanied by side effects. The glucocorticoid... more Glucocorticoids have various medical uses but are accompanied by side effects. The glucocorticoid receptor (GR) has been reported to regulate the clock genes, but the underlying mechanisms are incompletely understood. In this study, we focused on the suppressive effect of the GR on the expression of Rev-erba (Nr1d1), an important component of the clock regulatory circuits. Here we show that the GR suppresses Rev-erba expression via the formation of a complex with CLOCK and BMAL1, which binds to the E-boxes in the Nr1d1 promoter. In this GR-CLOCK-BMAL1 complex, the GR does not directly bind to DNA, which is referred to as tethering. These findings provide new insights into the role of the GR in the control of circadian rhythm.

Orphanet Journal of Rare Diseases

Background: There is now an international partnership to establish global programs for patients w... more Background: There is now an international partnership to establish global programs for patients with rare and undiagnosed diseases, involving interdisciplinary expert panels and phenotype-driven genetic analyses utilizing next-generation sequencing and analytics. Whereas it is crucial to have data such as the actual number of undiagnosed patients, to help inform the implementation plan with such programs, there have been no systematic studies to quantitate the numbers of patients principally because of the inherent difficulty in most health systems to identify patients whose condition has not yet been diagnosed and coded. Our national experience with a rare disease program, Nan-Byo which was established in 1972, and the more recently expanded Initiative on Rare and Undiagnosed Diseases (IRUD), provided a unique opportunity to design a cross-sectional study to ascertain the undiagnosed patients in Japan based on the IRUD referral criteria. Results: Two rounds of online surveys were performed: one survey targeting physicians affiliated with general hospitals (GH) and family clinics (FC) (the response rate: 30.6% (242/792)) and one nationwide survey targeting university hospitals (UH) in Japan (47.1% (839/1781)). A high percentage of doctors needing IRUD was seen in pediatrics at GH, FC, while there was a clear demand for IRUD in most departments at UH. We calculated the number of undiagnosed patients in Japan, as the "percentage of doctors needing IRUD" × "number of patients who would be referred to IRUD per doctor needing IRUD (cases/person)" × "total number of doctors in the relevant facilities in Japan (persons)", resulting in 3681 cases in pediatrics/pediatric surgery and 33,703 cases in other departments, for a total of 37,384 cases. Conclusions: Our study revealed the extant demand for IRUD in most departments and 37,000+ potential patients with undiagnosed diseases in the Japanese health system. These data inform the establishment of an equitable, sustainable, efficient and effective outpatient-based IRUD. These findings would serve as a valuable reference for undiagnosed diseases programs in different international jurisdictions and for countries and regions who also share vision(s) for societal implementation that help to advance international efforts to support patients with rare diseases who are direly waiting for diagnosis, subsequent treatment and care.

FEBS letters, 2018

The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the stron... more The SNP rs7903146 at the transcription factor 7-like 2 (TCF7L2) locus is established as the strongest known genetic marker for type 2 diabetes via genome-wide association studies. However, the functional SNPs regulating TCF7L2 expression remain unclear. Here, we show that the SNP rs7074440 is a candidate functional SNP highly linked with rs7903146. A reporter plasmid with rs7074440 normal allele sequence exhibited 15-fold higher luciferase activity compared with risk allele sequence in hepatocytes, demonstrating a strong enhancer activity at rs7074440. Additionally, we identified C-FOS as an activator binding to the rs7074440 enhancer using a TFEL genome-wide screen method. Consistently, knockdown of C-FOS significantly reduced TCF7L2 expression in hepatocytes. Collectively, a novel enhancer regulating TCF7L2 expression was revealed through searching for functional SNPs.