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132 results on '"Akihiro Katayama"'

1. Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3)

Author

Satoshi Yamaguchi, Koki Mise, Jun Wada, Kenichi Shikata, Takashi Matsuoka, Haruhito A Uchida, Asami Ueno, Yasuhiro Onishi, Ayaka Kanno, Ichiro Nojima, Chigusa Higuchi, Satoshi Miyamoto, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Akihiro Katayama, Mayu Watanabe, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhito Miyashita, Shinichiro Ando, and Tomokazu Nunoue

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Introduction ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1–7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not.Research design and methods Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year.Results The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR.Conclusions Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD.Trial registration number UMIN000011525.

Published
2024
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2. Glycoprotein nonmetastatic melanoma protein B regulates lysosomal integrity and lifespan of senescent cells

Author

Masayoshi Suda, Ippei Shimizu, Goro Katsuumi, Chieh Lun Hsiao, Yohko Yoshida, Naomi Matsumoto, Yutaka Yoshida, Akihiro Katayama, Jun Wada, Masahide Seki, Yutaka Suzuki, Shujiro Okuda, Kazuyuki Ozaki, Mayumi Nakanishi-Matsui, and Tohru Minamino

Subjects
Medicine, Science
Abstract

Abstract Accumulation of senescent cells in various tissues has been reported to have a pathological role in age-associated diseases. Elimination of senescent cells (senolysis) was recently reported to reversibly improve pathological aging phenotypes without increasing rates of cancer. We previously identified glycoprotein nonmetastatic melanoma protein B (GPNMB) as a seno-antigen specifically expressed by senescent human vascular endothelial cells and demonstrated that vaccination against Gpnmb eliminated Gpnmb-positive senescent cells, leading to an improvement of age-associated pathologies in mice. The aim of this study was to elucidate whether GPNMB plays a role in senescent cells. We examined the potential role of GPNMB in senescent cells by testing the effects of GPNMB depletion and overexpression in vitro and in vivo. Depletion of GPNMB from human vascular endothelial cells shortened their replicative lifespan and increased the expression of negative cell cycle regulators. Conversely, GPNMB overexpression protected these cells against stress-induced premature senescence. Depletion of Gpnmb led to impairment of vascular function and enhanced atherogenesis in mice, whereas overexpression attenuated dietary vascular dysfunction and atherogenesis. GPNMB was upregulated by lysosomal stress associated with cellular senescence and was a crucial protective factor in maintaining lysosomal integrity. GPNMB is a seno-antigen that acts as a survival factor in senescent cells, suggesting that targeting seno-antigens such as GPNMB may be a novel strategy for senolytic treatments.

Published
2022
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3. Case of subcutaneous insulin resistance syndrome treated with ultra‐rapid insulin lispro

Author

Takahiro Ishii, Akihiro Katayama, Mihiro Sue, Remi Kuribayashi, Masafumi Tenta, Yuichi Matsushita, Masaya Takeda, Izumi Iseda, Satomi Tani, and Kazuyuki Hida

Subjects
Subcutaneous insulin resistance syndrome, Type 2 diabetes mellitus, Ultra‐rapid insulin lispro, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Abstract Subcutaneous insulin resistance syndrome is a rare condition that causes difficulty in glycemic control due to severe resistance to subcutaneous insulin injections. We herein present a case of a 40‐year‐old woman with type 2 diabetes mellitus who had been diagnosed with subcutaneous insulin resistance syndrome since the age of 29 years, and had been persistently treated with continuous subcutaneous insulin infusion using a mixture of insulin lispro and heparin. The patient was switched from insulin lispro plus heparin to ultra‐rapid insulin lispro; given that it contains treprostinil and citrate, it is expected to have similar effects as heparin, and shows similar glucose‐lowering effects and insulin absorption. Our results suggest that treatment with ultra‐rapid insulin lispro is effective for subcutaneous insulin resistance syndrome.

Published
2022
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4. Euglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus 3 days after initiating sodium‐glucose cotransporter 2 inhibitor while on an extremely low carbohydrate diet: A case report

Author

Ayumi Inoue, Akihiro Katayama, Mihiro Sue, Momoka Hasegawa, Megumi Maeda, Masaki Matoba, Takahiro Ishii, Remi Kuribayashi, Masafumi Tenta, Yuichi Matsushita, Masaya Takeda, Izumi Iseda, Toshiyuki Wakatsuki, and Kazuyuki Hida

Subjects
euglycemic diabetes ketoacidosis, low‐carbohydrate diet, sodium‐glucose cotransporter 2 inhibitor, type 2 diabetes mellitus, Medicine, Medicine (General), R5-920
Abstract

Abstract This paper presents a case with type 2 diabetes mellitus on a very‐low‐carbohydrate diet who developed euglycemic diabetic ketoacidosis (EDKA) 3 days after starting sodium‐glucose cotransporter 2 inhibitors (SGLT2i). When initiating SGLT2i, healthcare providers should confirm the implementation of a low‐carbohydrate diet and provide intensive guidance to prevent EDKA.

Published
2022
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5. Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2

Author

Tomokazu Nunoue, Satoshi Yamaguchi, Sanae Teshigawara, Akihiro Katayama, Atsuko Nakatsuka, Jun Eguchi, Toshiro Niki, and Jun Wada

Subjects
Medicine, Science
Abstract

Abstract The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.

Published
2021
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7. Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4

Author

Satoshi Yamaguchi, Dongxiao Zhang, Akihiro Katayama, Naoko Kurooka, Ryosuke Sugawara, Haya Hamed Hassan Albuayjan, Atsuko Nakatsuka, Jun Eguchi, and Jun Wada

Subjects
non-coding RNAs, microRNA, adipose tissues, Adipogenesis, mTORC1, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

MicroRNAs expressed in adipocytes are involved in transcriptional regulation of target mRNAs in obesity, but miRNAs critically involved in this process is not well characterized. Here, we identified upregulation of miR-221-3p and miR-222-3p in the white adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir221 and Mir222 are paralogous genes and share the common seed sequence and Mir221/222AdipoKO mice fed with HFHS chow demonstrated resistance to the development of obesity compared with Mir221/222flox/y. Ddit4 is a direct target of Mir221 and Mir222, and the upregulation of Ddit4 in Mir221/222AdipoKO was associated with the suppression of TSC2 (tuberous sclerosis complex 2)/mammalian target of rapamycin complex 1 (mTORC1)/S6K (ribosomal protein S6 kinase) pathway. The overexpression of miR-222-3p linked to enhanced adipogenesis, and it may be a potential candidate for miRNA-based therapy.

Published
2022
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8. Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor‐induced diabetes mellitus: A report of two cases

Author

Noriko Fujiwara, Mayu Watanabe, Akihiro Katayama, Yohei Noda, Jun Eguchi, Hitomi Kataoka, Shunsuke Kagawa, and Jun Wada

Subjects
C‐peptide, diabetes mellitus, immune checkpoint inhibitor, insulin secretion, Medicine, Medicine (General), R5-920
Abstract

Abstract Immune checkpoint inhibitor‐induced diabetes mellitus is a rare immune‐related adverse event. This report illustrates clinical data and insulin secretory ability before and after the onset of immune checkpoint inhibitor‐induced diabetes.

Published
2021
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9. Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)

Author

Koki Mise, Mariko Imamura, Satoshi Yamaguchi, Mayu Watanabe, Chigusa Higuchi, Akihiro Katayama, Satoshi Miyamoto, Haruhito A. Uchida, Atsuko Nakatsuka, Jun Eguchi, Kazuyuki Hida, Tatsuaki Nakato, Atsuhito Tone, Sanae Teshigawara, Takashi Matsuoka, Shinji Kamei, Kazutoshi Murakami, Ikki Shimizu, Katsuhiro Miyashita, Shinichiro Ando, Tomokazu Nunoue, Michihiro Yoshida, Masao Yamada, Kenichi Shikata, and Jun Wada

Subjects
cardiovascular event, diabetes, lectins, N-glycans, urinary biomarkers, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease.Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, P = 0.002) and Calsepa [High-Man (Man2–6)]: 1.56 (1.19–2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001–0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045–0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively].Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE.Trial Registration: This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).

Published
2021
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10. Risk Factors for the Requirement of Antenatal Insulin Treatment in Gestational Diabetes Mellitus

Author

Mayu Watanabe, Akihiro Katayama, Hidetoshi Kagawa, Daisuke Ogawa, and Jun Wada

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Poor maternal glycemic control increases maternal and fetal risk for adverse outcomes, and strict management of gestational diabetes mellitus (GDM) is recommended to prevent neonatal and maternal complications. However, risk factors for the requirement of antenatal insulin treatment (AIT) are not well-investigated in the pregnant women with GDM. We enrolled 37 pregnant women with GDM and investigated the risk for AIT by comparing the patients with AIT (AIT group; n=10) and without insulin therapy (Diet group; n=27). The 1-h and 2-h plasma glucose levels and the number of abnormal values in 75 g OGTT were significantly higher in AIT group compared with Diet group. By logistic regression analysis, plasma glucose level at 1-h was significant predictor for AIT and the odds ratios were 1.115 (1.004–1.239) using forward selection method and 1.192 (1.006–1.413) using backward elimination method. There were no significant differences in obstetrical outcomes and neonatal complications. 1-h plasma glucose levels in 75 g OGTT are useful parameters in predicting the requirement for AIT in GDM. Both maternal and neonatal complications are comparable in GDM patients with and without insulin therapy.

Published
2016
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11. Pemt deficiency ameliorates endoplasmic reticulum stress in diabetic nephropathy.

Author

Mayu Watanabe, Atsuko Nakatsuka, Kazutoshi Murakami, Kentaro Inoue, Takahiro Terami, Chigusa Higuchi, Akihiro Katayama, Sanae Teshigawara, Jun Eguchi, Daisuke Ogawa, Eijiro Watanabe, Jun Wada, and Hirofumi Makino

Subjects
Medicine, Science
Abstract

Phosphatidylethanolamine N-methyltransferase (Pemt) catalyzes the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) mainly in the liver. Under an obese state, the upregulation of Pemt induces endoplasmic reticulum (ER) stress by increasing the PC/PE ratio in the liver. We targeted the Pemt gene in mice to explore the therapeutic impact of Pemt on the progression of diabetic nephropathy and diabetes, which was induced by the injection of streptozotocin (STZ). Although the blood glucose levels were similar in STZ-induced diabetic Pemt+/+ and Pemt-/-mice, the glomerular hypertrophy and albuminuria in Pemt-/- mice were significantly reduced. Pemt deficiency reduced the intraglomerular F4/80-positive macrophages, hydroethidine fluorescence, tubulointerstitial fibrosis and tubular atrophy. The expression of glucose-regulated protein-78 (GRP78) was enriched in the renal tubular cells in STZ-induced diabetic mice, and this was ameliorated by Pemt deficiency. In mProx24 renal proximal tubular cells, the treatment with ER-stress inducers, tunicamycin and thapsigargin, increased the expression of GRP78, which was reduced by transfection of a shRNA lentivirus for Pemt (shRNA-Pemt). The number of apoptotic cells in the renal tubules was significantly reduced in Pemt-/- diabetic mice, and shRNA-Pemt upregulated the phosphorylation of Akt and decreased the cleavage of caspase 3 and 7 in mProx24 cells. Taken together, these findings indicate that the inhibition of Pemt activity ameliorates the ER stress associated with diabetic nephropathy in a model of type 1 diabetes and corrects the functions of the three major pathways downstream of ER stress, i.e. oxidative stress, inflammation and apoptosis.

Published
2014
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12. Urinary fetuin-A is a novel marker for diabetic nephropathy in type 2 diabetes identified by lectin microarray.

Author

Kentaro Inoue, Jun Wada, Jun Eguchi, Atsuko Nakatsuka, Sanae Teshigawara, Kazutoshi Murakami, Daisuke Ogawa, Takahiro Terami, Akihiro Katayama, Atsuhito Tone, Izumi Iseda, Kazuyuki Hida, Masao Yamada, Tomohisa Ogawa, and Hirofumi Makino

Subjects
Medicine, Science
Abstract

We analyzed the urine samples of patients with type 2 diabetes at various stages of diabetic nephropathy by lectin microarray to identify a biomarker to predict the progression of diabetic nephropathy. Japanese patients with type 2 diabetes at various stages of nephropathy were enrolled and we performed lectin microarray analyses (n = 17) and measured urinary excretion of fetuin-A (n = 85). The increased signals of urine samples were observed in Siaα2-6Gal/GalNAc-binding lectins (SNA, SSA, TJA-I) during the progression of diabetic nephropathy. We next isolated sialylated glycoproteins by using SSA-lectin affinity chromatography and identified fetuin-A by liquid chromatography-tandem mass spectrometer. Urinary excretion of fetuin-A significantly increased during the progression of albuminuria (A1, 0.40 ± 0.43; A2, 0.60 ± 0.53; A3 1.57 ± 1.13 ng/gCr; p = 7.29 × 10(-8)) and of GFR stages (G1, 0.39 ± 0.39; G2, 0.49 ± 0.45; G3, 1.25 ± 1.18; G4, 1.34 ± 0.80 ng/gCr; p = 3.89 × 10(-4)). Multivariate logistic regression analysis was employed to assess fetuin-A as a risk for diabetic nephropathy with microalbuminuria or GFR

Published
2013
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15. Correction: Time course change of the insulin requirements during the perioperative period in hepatectomy and pancreatectomy by using an artificial pancreas STG-55

Author

Sanae Teshigawara, Atsuhito Tone, Akihiro Katayama, Yusuke Imai, Toshihisa Tahara, Mayumi Senoo, Satoko Watanabe, Mitsuhiro Kaneto, Yasuyuki Shimomura, Chiaki Yagi, Hiroki Kajioka, Toru Kojima, Takefumi Niguma, and Tatsuaki Nakatou

Subjects
Endocrinology, Diabetes and Metabolism, Internal Medicine, Correction
Published
2023

22. Empagliflozin in Patients with Chronic Kidney Disease

Author

Herrington, William G, Staplin, Natalie, Wanner, Christoph, Green, Jennifer B, Hauske, Sibylle J, Emberson, Jonathan R, Preiss, David, Judge, Parminder, Mayne, Kaitlin J, Ng, Sarah Y A, Sammons, Emily, Zhu, Doreen, Hill, Michael, Stevens, Will, Wallendszus, Karl, Brenner, Susanne, Cheung, Alfred K, Liu, Zhi-Hong, Li, Jing, Hooi, Lai Seong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Maggioni, Aldo P, Pontremoli, Roberto, Deo, Rajat, Goto, Shinya, Rossello, Xavier, Tuttle, Katherine R, Steubl, Dominik, Petrini, Michaela, Massey, Dan, Eilbracht, Jens, Brueckmann, Martina, Landray, Martin J, Baigent, Colin, Haynes, Richard, The EMPA-KIDNEY Collaborative Group: Colin Baigent, Martin J Landray, Christoph Wanner, William G Herrington, Richard Haynes, Jennifer B Green, Sibylle J Hauske, Martina Brueckmann, Mark Hopley, Maximillian von-Eynatten, Jyothis George, Susanne Brenner, Alfred K Cheung, David Preiss, Zhi-Hong Liu, Jing Li, Laiseong Hooi, Wen Liu, Takashi Kadowaki, Masaomi Nangaku, Adeera Levin, David Cherney, Roberto Pontremoli, Aldo P Maggioni, Natalie Staplin, Jonathan Emberson, Stefan Hantel, Shinya Goto, Rajat Deo, Katherine R Tuttle, Michael Hill, Parminder Judge, Kaitlin J Mayne, Sarah Y A Ng, Xavier Rossello, Emily Sammons, Doreen Zhu, Peter Sandercock, Rudolf Bilous, Charles Herzog, Paul Whelton, Janet Wittes, Derrick Bennett, Patricia Achiri, Chrissie Ambrose, Cristina Badin, Jill Barton, Richard Brown, Andy Burke, Sebastian Butler, Rejive Dayanandan, Pia Donaldson, Robert Dykas, Lucy Fletcher, Kate Frederick, Hannah Kingston, Mo Gray, Emily Harding, Akiko Hashimoto, Lyn Howie, Susan Hurley, Ryonfa Lee, Nik Luker, Kevin Murphy, Mariko Nakahara, John Nolan, Michelle Nunn, Sorcha Mulligan, Akiko Omata, Sandra Pickworth, YanRu Qiao, Shraddha Shah, Karen Taylor, Alison Timadjer, Monique Willett, Liz Wincott, Qin Yan, Hui Yu, Louise Bowman, Fang Chen, Robert Clarke, Michelle Goonasekera, Waseem Karsan, Marion Mafham, Christina Reith, Mohammed Zayed, Ritva Ellison, Rowan Moys, Will Stevens, Kevin Verdel, Karl Wallendszus, Chris Bowler, Anna Brewer, Andy Measor, Guanguo Cui, Charles Daniels, Angela Field, Bob Goodenough, Ashley Lawson, Youcef Mostefai, Dheeptha Radhakrishnan, Samee Syed, Shuang Xia, Ruth Adewuyi-Dalton, Thomas Arnold, Anne-Marie Beneat, Anoushka Bhatt, Chloe Bird, Andrew Breach, Laura Brown, Mark Caple, Tatyana Chavagnon, Karen Chung, Sarah Clark, Luminita Condurache, Katarzyna Eichstadt, Marta Espino Obrero, Scarlett Forest, Helen French, Nick Goodwin, Andrew Gordon, Joanne Gordon, Cat Guest, Tina Harding, Michal Hozak, Matthew Lacey, David MacLean, Louise Messinger, Stewart Moffat, Martin Radley, Claire Shenton, Sarah Tipper, Jon Tyler, Lesley Weaving, James Wheeler, Elissa Williams, Tim Williams, Hamish Woodhouse, Angela Chamberlain, Jo Chambers, Joanne Davies, Denise Donaldson, Pati Faria-Shayler, Denise Fleming-Brown, Jennifer Ingell, Carol Knott, Anna Liew, Helen Lochhead, Juliette Meek, Isabel Rodriguez-Bachiller, Andrea Wilson, Patrick Zettergren, Rach AitSadi, Ian Barton, Alex Baxter, Yonghong Bu, Lukasz Danel, Sonja Grotjahn, Rijo Kurien, Michael Lay, Archie Maskill, Aleksandra Murawska, Rachel Raff, Allen Young, Rebecca Sardell, Vladimir Cejka, Marcela Fajardo-Moser, Christian Hartner, Doris Poehler, Janina Renner, Franziska Scheidemantel, Miya Bryant, Anita Hepditch, Cassandra Johnson, Erin Latore, Yolanda Miller, Lauren Price, Merilee Whalen, Ashleigh Wheeler, Jenny Ingell, Yu An, Yinghua Chen, Peiling Chen, Hao Dai, Hong Du, Fang Feng, Qing Guo, Libo Hou, Wuhanbilige Hundei, Binbin Jin, Yan Li, Jiamin Liu, Xia Song, Yanping Wang, Yanwu Yu, Ning Zhang, Lingshan Zhao, Hui Zhong, Cheng Beng Goh, Ye Mun Low, Soon Yi Sor, Farah Hanis Zulkipli, Sarojini Sivanandam, Natsuki Arai, Ai Fukasawa, Mizue Furukawa, Keisuke Habuki, Shoko Hayashi, Wakako Isari, Saki Kanegae, Maria Kawai, Reiki Kobayashi, Takako Kuramae, Chika Kuribayashi, Sawako Maeno, Satoshi Masumoto, Tomoko Morisaki, Minoru Oda, Kazue Sawada, Kenta Sugamori, Ayana Tatsuzawa, Aiko Tomita, Kazuyuki Yuasa, Hiroko Inazawa, Amanda Axler, Kerri Gallo, Ester Baldini, Barbara Bartolomei Mecatti, Francesca Bianchini, Martina Ceseri, Laura Cipressa, Gianna Fabbri, Andrea Lorimer, Donata Lucci, Sharang Ghavampour, Anja Knoppe, Hans Schmidt-Gurtler, Hubert Dumann, Sybille Merscher, Margret Patecki, Georg Rainer Schlieper, Anke Torp, Bianca Weber, Maja Zietz, Bernd Hohenstein, Urs Benck, Diliana Draganova, Thomas Weinreich, Lothar Wolf, Jasmine Gaidu, Hanna Reiner, Mandy Visnjic, Daniel Steffl, Marie Breitenfeldt, Annette Kraemer-Guth, Christine Braun, Simone Hagge, Michael Schomig, Stephan Matthias, Dominik Stoffler, Beate Schumacher, Thomas Sitter, Louise Fuessl, Julia Krappe, Jerome Loutan, Volker Vielhauer, Luciano Andriaccio, Magdalena Maurer, Bernhard Winkelmann, Martin Dursch, Linda Seifert, Linda Tenbusch, Julia Weinmann-Menke, Simone Boedecker, Wiebke Kaluza-Schilling, Daniel Kraus, Carina Krieger, Margit Schmude, Anne Schreiber, Ewelina Eckrich, Diethelm Tschope, Abdulwahab Arbi, Young Lee-Barkey, Bernd Stratmann, Natalie Prib, Sina Rolfsmeier, Irina Schneider, Lars Rump, Johannes Stegbauer, Christine Pötz, Mara Schemmelmann, Claudia Schmidt, Michael Koch, Sendogan Aker, Annika Küpper, Manuela Martin, Thiemo Pfab, Christian Albert, Michael Haase, Barbara Zander, Claudia Schneider-Danwitz, Wolfgang Seeger, Wolf-Adam Seeger, Britta Zemann, Christoph Stellbrink, Kristin Marx, Ekaterina Stellbrink, Britta Brettschneider, Stephanie Watson, Marion Iselt, Gerhard Klausmann, Inga-Nadine Kummer, Auguste Kutschat, Simone Streitenberger, Matthias Girndt, Silke Markau, Ina Girakossyan, Claudia Hanf, Joachim Beige, Ralph Wendt, Ulrike Schmidt, Andreas Schneider, Roland Veelken, Claudia Donhauser, Luis Becker, Nexhat Miftari, Ricarda Wolfling, Sarah Morlok, Christian Hugo, Alexander Paliege, Jens Passauer, Julian Stumpf, Annegret Fleischer, Kerstin Haaser, Bernhard Kraemer, Jan Jochims, Bernd Kruger, Claudia Foellinger, Anastassiya Reisler, Frank Strutz, Stefan Haack, Ursula Hohenstatt, Martin Busch, Konstantin Herfurth, Gunter Wolf, Rainer Paul, Hermann Haller, Jessica Kaufeld, Jan Menne, Elisabeth Bahlmann-Kroll, Angela Bergner, Horst Weihprecht, Aydin Er, Florian Sonntag, Elif Turan, Michael Wittmann, Franziska Klauser, Eva Voigt, Volker Schettler, Egbert Schulz, Madlen Rohnstock, Elke Schettler, Bernd Schroppel, Rene van Erp, Martin Kachele, Ulla Ludwig, Lena Schulte-Kemna, Waltraud Kmietschak, Elke Preiss, Martina Ruocco, Gunnar Heine, Martin Brzoska, Sebastian Gabel, Christina Büttner, Asma Sabarai, Bernhard Banas, Tobias Bergler, Yvonne Ehrl, Franz Putz, Antonia Schuster, Stefanie Kuhn, Torsten Schramm, Stefan Degenhardt, Gerhard Schmidt, Lea Weiland, Ulrike Giebeln-Hudnell, Jan Kielstein, Gabriele Eden, Brigitte Fuchs, Gina Morig, Manuela Winkler, Harald Darius, Charalampos Kriatselis, Carl-Philipp Roesch, Astrid Maselli, Dominik Alscher, Markus Ketteler, Moritz Schanz, Severin Schricker, Bianka Rettenmaier, Andrea Schwab, Pablo Pergola, Irene Leal, Melissa Cagle, Anna Romo, Anthony Torres, Sucharit Joshi, Kulli Barrett, Alexis Africano, Vicki Dodds, Dorleena Gowen, Ashlee Morris, Juan Fernandez, Guillermo Jimenez, Ricardo Viera, Kendaling Bruce, Ryan Barrios, Maylin Garcia, Kerelyn Garcia, Iradis Leal, David Tietjen, David Bains, Carlo Castillo, Genielle Brewer, Justin Davis, Natalie Freking, Brittany Golson, Sally Ham, Jesslyn Roesch, Pusadee Suchinda, Shameem Beigh, Usah Lilavivat, Joyce Bilton, Kim Bocchicchia, Jeffrey Turner, Neera Dahl, Aldo Peixoto, Yasemin Kavak, Lauren Liberti, Hari Nair, Nicolas Page, Stephanie Rosenberg, Kathryn Simmons, Tamara Isakova, Rebecca Frazier, Rupal Mehta, Anand Srivastava, Patrick Fox, Jonathan Hecktman, Alexander Hodakowski, Carlos Martinez, Rachel Phillips, Alexis Stevenson, Reem Mustafa, Kyle Jansson, Cassandra Kimber, Jason Stubbs, Ahmad Tuffaha, Sri Yarlagadda, Debbie Griffin, Elisabeth Laundy, Zhuo Tang, Radica Alicic, Ann Cooper, Lisa Davis, Ashwini Gore, Rebecca Goldfaden, Leslie Harvill, Lisa Hichkad, Barry Johns, Thomas Jones, Kayla Merritt, Jennifer Sheldon, Jennifer Stanfield, Lindsay Alexander, Kaitlyn Preston, Lindsey Wood, Rajesh Pradhan, Roger DeRaad, Kelli McIntosh, Louis Raymond, Michael Shepperd, Susan McLaughlin, Mary Seifert, Andrew Shepherd, Joseph Aiello, William Durham, Laurie Loudermilk, John Manley, Sabrina Burnette, Stephanie Evans, Tara Johnson, Lance Sloan, Judy Ann Acosta, Stacy Gillham, Katia Sloan, SueAnn Squyres, Michael Rocco, Amret Hawfield, Ben Bagwell, Lauren Richmond, Joseph Soufer, Subha Clarke, Amanda Aliu, Kristine Calabrese, Amanda Davis, Veronica Poma, Tracy Spinola, James Magee, Ricardo Silva, Rushab Choksi, Lorraine Dajani, John Evans, Anil George, Prasanth Krish, Gerard Martins, Mae Sheikh-Ali, David Sutton, Freda Driver, Abraham Hanburry, Laura Hume, Amber Hurst, Matthew Taddeo, Marla Turner, Veronica Yousif, 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Hartner, Christian, Poehler, Dori, Renner, Janina, Scheidemantel, Franziska, Bryant, Miya, Hepditch, Anita, Johnson, Cassandra, Latore, Erin, Miller, Yolanda, Price, Lauren, Whalen, Merilee, Wheeler, Ashleigh, Ingell, Jenny, An, Yu, Chen, Yinghua, Chen, Peiling, Dai, Hao, Du, Hong, Feng, Fang, Guo, Qing, Hou, Libo, Hundei, Wuhanbilige, Jin, Binbin, Li, Yan, Liu, Jiamin, Song, Xia, Wang, Yanping, Yu, Yanwu, Zhang, Ning, Zhao, Lingshan, Zhong, Hui, Beng Goh, Cheng, Mun Low, Ye, Yi Sor, Soon, Hanis Zulkipli, Farah, Sivanandam, Sarojini, Arai, Natsuki, Fukasawa, Ai, Furukawa, Mizue, Habuki, Keisuke, Hayashi, Shoko, Isari, Wakako, Kanegae, Saki, Kawai, Maria, Kobayashi, Reiki, Kuramae, Takako, Kuribayashi, Chika, Maeno, Sawako, Masumoto, Satoshi, Morisaki, Tomoko, Oda, Minoru, Sawada, Kazue, Sugamori, Kenta, Tatsuzawa, Ayana, Tomita, Aiko, Yuasa, Kazuyuki, Inazawa, Hiroko, Axler, Amanda, Gallo, Kerri, Baldini, Ester, Bartolomei Mecatti, Barbara, Bianchini, Francesca, Ceseri, Martina, Cipressa, Laura, Fabbri, Gianna, Lorimer, Andrea, Lucci, Donata, Ghavampour, Sharang, Knoppe, Anja, Schmidt-Gurtler, Han, Dumann, Hubert, Merscher, Sybille, Patecki, Margret, Rainer Schlieper, Georg, Torp, Anke, Weber, Bianca, Zietz, Maja, Hohenstein, Bernd, Benck, Ur, Draganova, Diliana, Weinreich, Thoma, Wolf, Lothar, Gaidu, Jasmine, Reiner, Hanna, Visnjic, Mandy, Steffl, Daniel, Breitenfeldt, Marie, Kraemer-Guth, Annette, Braun, Christine, Hagge, Simone, Schomig, Michael, Matthias, Stephan, Stoffler, Dominik, Schumacher, Beate, Sitter, Thoma, Fuessl, Louise, Krappe, Julia, Loutan, Jerome, Vielhauer, Volker, Andriaccio, Luciano, Maurer, Magdalena, Winkelmann, Bernhard, Dursch, Martin, Seifert, Linda, Tenbusch, Linda, Weinmann-Menke, Julia, Boedecker, Simone, Kaluza-Schilling, Wiebke, Kraus, Daniel, Krieger, Carina, Schmude, Margit, Schreiber, Anne, Eckrich, Ewelina, Tschope, Diethelm, Arbi, Abdulwahab, Lee-Barkey, Young, Stratmann, Bernd, Prib, Natalie, Rolfsmeier, Sina, Schneider, Irina, Rump, Lar, Stegbauer, Johanne, Pötz, Christine, Schemmelmann, Mara, Schmidt, Claudia, Koch, Michael, Aker, Sendogan, Küpper, Annika, Martin, Manuela, Pfab, Thiemo, Albert, Christian, Haase, Michael, Zander, Barbara, Schneider-Danwitz, Claudia, Seeger, Wolfgang, Seeger, Wolf-Adam, Zemann, Britta, Stellbrink, Christoph, Marx, Kristin, Stellbrink, Ekaterina, Brettschneider, Britta, Watson, Stephanie, Iselt, Marion, Klausmann, Gerhard, Kummer, Inga-Nadine, Kutschat, Auguste, Streitenberger, Simone, Girndt, Matthia, Markau, Silke, Girakossyan, Ina, Hanf, Claudia, Beige, Joachim, Wendt, Ralph, Schmidt, Ulrike, Schneider, Andrea, Veelken, Roland, Donhauser, Claudia, Becker, Lui, Miftari, Nexhat, Wolfling, Ricarda, Morlok, Sarah, Hugo, Christian, Paliege, Alexander, Passauer, Jen, Stumpf, Julian, Fleischer, Annegret, Haaser, Kerstin, Kraemer, Bernhard, Jochims, Jan, Kruger, Bernd, Foellinger, Claudia, Reisler, Anastassiya, Strutz, Frank, Haack, Stefan, Hohenstatt, Ursula, Busch, Martin, Herfurth, Konstantin, Wolf, Gunter, Paul, Rainer, Haller, Hermann, Kaufeld, Jessica, Menne, Jan, Bahlmann-Kroll, Elisabeth, Bergner, Angela, Weihprecht, Horst, Er, Aydin, Sonntag, Florian, Turan, Elif, Wittmann, Michael, Klauser, Franziska, Voigt, Eva, Schettler, Volker, Schulz, Egbert, Rohnstock, Madlen, Schettler, Elke, Schroppel, Bernd, van Erp, Rene, Kachele, Martin, Ludwig, Ulla, Schulte-Kemna, Lena, Kmietschak, Waltraud, Preiss, Elke, Ruocco, Martina, Heine, Gunnar, Brzoska, Martin, Gabel, Sebastian, Büttner, Christina, Sabarai, Asma, Banas, Bernhard, Bergler, Tobia, Ehrl, Yvonne, Putz, Franz, Schuster, Antonia, Kuhn, Stefanie, Schramm, Torsten, Degenhardt, Stefan, Schmidt, Gerhard, Weiland, Lea, Giebeln-Hudnell, Ulrike, Kielstein, Jan, Eden, Gabriele, Fuchs, Brigitte, Morig, Gina, Winkler, Manuela, Darius, Harald, Kriatselis, Charalampo, Roesch, Carl-Philipp, Maselli, Astrid, Alscher, Dominik, Ketteler, Marku, Schanz, Moritz, Schricker, Severin, Rettenmaier, Bianka, Schwab, Andrea, Pergola, Pablo, Leal, Irene, Cagle, Melissa, Romo, Anna, Torres, Anthony, Joshi, Sucharit, Barrett, Kulli, Africano, Alexi, Dodds, Vicki, Gowen, Dorleena, Morris, Ashlee, Fernandez, Juan, Jimenez, Guillermo, Viera, Ricardo, Bruce, Kendaling, Barrios, Ryan, Garcia, Maylin, Garcia, Kerelyn, Leal, Iradi, Tietjen, David, Bains, David, Castillo, Carlo, Brewer, Genielle, Davis, Justin, Freking, Natalie, Golson, Brittany, Ham, Sally, Roesch, Jesslyn, Suchinda, Pusadee, Beigh, Shameem, Lilavivat, Usah, Bilton, Joyce, Bocchicchia, Kim, Turner, Jeffrey, Dahl, Neera, Peixoto, Aldo, Kavak, Yasemin, Liberti, Lauren, Nair, Hari, Page, Nicola, Rosenberg, Stephanie, Simmons, Kathryn, Isakova, Tamara, Frazier, Rebecca, Mehta, Rupal, Srivastava, Anand, Fox, Patrick, Hecktman, Jonathan, Hodakowski, Alexander, Martinez, Carlo, Phillips, Rachel, Stevenson, Alexi, Mustafa, Reem, Jansson, Kyle, Kimber, Cassandra, Stubbs, Jason, Tuffaha, Ahmad, Yarlagadda, Sri, Griffin, Debbie, Laundy, Elisabeth, Tang, Zhuo, Alicic, Radica, Cooper, Ann, Davis, Lisa, Gore, Ashwini, Goldfaden, Rebecca, Harvill, Leslie, Hichkad, Lisa, Johns, Barry, Jones, Thoma, Merritt, Kayla, Sheldon, Jennifer, Stanfield, Jennifer, Alexander, Lindsay, Preston, Kaitlyn, Wood, Lindsey, Pradhan, Rajesh, Deraad, Roger, Mcintosh, Kelli, Raymond, Loui, Shepperd, Michael, Mclaughlin, Susan, Seifert, Mary, Shepherd, Andrew, Aiello, Joseph, Durham, William, Loudermilk, Laurie, Manley, John, Burnette, Sabrina, Evans, Stephanie, Johnson, Tara, Sloan, Lance, Ann Acosta, Judy, Gillham, Stacy, Sloan, Katia, Squyres, Sueann, Rocco, Michael, Hawfield, Amret, Bagwell, Ben, Richmond, Lauren, Soufer, Joseph, Clarke, Subha, Aliu, Amanda, Calabrese, Kristine, Davis, Amanda, Poma, Veronica, Spinola, Tracy, Magee, Jame, Silva, Ricardo, Choksi, Rushab, Dajani, Lorraine, Evans, John, George, Anil, Krish, Prasanth, Martins, Gerard, Sheikh-Ali, Mae, Sutton, David, Driver, Freda, Hanburry, Abraham, Hume, Laura, Hurst, Amber, Taddeo, Matthew, Turner, Marla, Yousif, Veronica, Beddhu, Srinivasan, Al-Rabadi, Laith, Abraham, Nikita, Caamano, Amalia, Carle, Judy, Gonce, Victoria, Staylor, Kaitlyn, Zhou, Na, Bansal, Shweta, Bhattarai, Manoj, Sharma, Kumar, Debnath, Subrata, Garza, Aliseiya, Velagapudi, Chakradhar, Rovner, Sergio, Almeida, Javier, Casares, Pablo, Stewart-Ray, Verlaine, Almaraz, Rene, Dayrell, Renata, Moncada, Ana, Pulido, Ricardo, Rodriquez, Roxana, Deeb, Wasim, Degoursey, Kathryn, Gloria, Rodel, Greene, Trevor, Miller, Robert, Pereira, Edward, Roura, Miguel, Domingo, Debbie, Dorestin, Sasha, Hodge, William, Jackson, Cathy, Lund, Deborah, Taylor, Katrina, Boren, Kenneth, Cleveland, Brittany, Gaiser, Sandra, Sahani, Mandeep, Aldrich, Logan, Edmerson, Exodu, Limon, Edmond, Valletta, Cole, Vasquez, Patricia, Provenzano, Christopher, Brar, Navkiranjot, Henderson, Heather, Keith, Bellovich, Khai, Qur, Khairullah, Quresh, Makos, Gail, Topf, Joel, Gasko, Sherry, Henschel, Rosemarie, Knapp, Kaitlin, Kozlowski, Teresa, Lafleur, Paula, Varughese, Ashwathy, Xue, Hui, Wu, Patricia, Arechiga, Olga, Darbeau, Shan, Fechter, Michael, Martinez, Stephanie, Hanson, Lenita, Cooper, Nyla, Madera, Areli, Cadorna, Jay, Sheridan, Rita, Sparks, Helen, Eilerman, Bradley, Bodine, Susanne, Eid, Wael, Flora, Rebecca, Avery, Amber, Hardy, Cashmere, Biscoveanu, Mihaela, Nagelberg, Steven, Cummins, Tracey, Rahbari-Oskoui, Frederic, Oommen, Anju, Forghani, Zohreh, Hitchcock, Stacie, Hosein, Darya, Watkins, Diane, Patel, Minesh, Lambert, Anthony, Newman, Elizabeth, Wood, Autumn, Ross, Tammy, Topping, Stephany, Mulhern, Jeffrey, Murphy, Lorna, Vasseur, Ann, Greenwood, Gregory, Hadley, Alexander, Laurienti, Denise, Marshall, Christopher, Mclean, Nichola, Satko, Scott, Caudill, Brandy, Maris, Jacob, Rogers, Janice, Vanhoy, Cindy, Thomas, George, Nakhoul, George, O'Toole, John, Taliercio, Jonathan, Cooperman, Leslie, Markovic, Marina, Tucky, Barbara, Dev, Devasmita, Hasan, Alia, Yalamanchili, Hima, Jain, Namita, Mcneil, Lesley, Wines, Eric, Park, Jean, Ghazi, Adline, Hamm, Mia, Patel, Teja, Mottl, Amy, Chang, Emily, Derebail, Vimal, Cole, Emmie, Froment, Anne, Kelley, Sara, Osmond Foster, Jordan, Mahabadi, Vahid, Jafari, Golriz, Kamarzarian, Anita, Arriaga, Wendy, Arteaga, Daisy, Machicado, Rosario, Naverrete, Genesi, Kumar, Prashant, Nazeer, Imran, Urquia, Karina, Glider, Tammi, Jones, Vickie, Rucker, Savannah, Wiley, Jennifer, Pandey, Rahul, Arroyo, Jesu, Pariani, Harish, Ahmad, Mohammad, Mozaffari, Shahin, Perez, Erika, Budoff, Matthew, Roy, Sion, Birudaraju, Divya, Ghanem, Ahmed, Hamal, Sajad, Aronoff, Stephen, Joye Petr, Elisa, Sachson, Richard, Wiebel, Jaime, Akram, Sana, Jones, Laurie, Knight, Curti, Tarlac, Maurie, Ahmed, Shahbaz, Szerlip, Harold, Akinfolarin, Akinwande, Mehta, Ankit, Camp, Shana, Castro, Cindy, Cooper, Zanaida, Terry, Jessica, Awad, Ahmed, Kothapalli, Bhavya, Lustig, Ryan, Alfaress, Serine, Jasim, Hyder, Parrigon, Mary, Karounos, Denni, Ahmed, Sadiq, Berry, Maggie, Oremus, Ruth, Hernandez-Cassis, Carlo, Ugwu, Elia, Junejo, Nazia, Suazo, Nancy, Segal, Mark, Kazory, Amir, Brown, Sherry, Daniels, Tristan, Dayi, Sofia, Hogan, Renee, Mccray, Kathy, Stickley, Jennifer, Rahman, Mahboob, Dobre, Mirela, Negrea, Lavinia, Padiyar, Aparna, Pradhan, Nishigandha, Rashidi, Arash, Sarabu, Nagaraju, Donley, Vicki, Young, Tricia, Oguchi, Godson, Onyema, Judepatrick, Damianik, Kahla, Dienes, Jack, Plummer-Morgan, Judith, Roman, Marilyn, Skipper, Mauver, Villaruel, Stacey-Ann, Williams, Krystle, Sugimoto, Danny, Dugas, Jeffrey, Ahmed, Ismeal, Bhairoo, Jamie, Rijos, Dolore, Salim, Huzaifa, Gavrila, Madita, Lafferty, Kathryn, Rabara, Ria, Ruse, Sally, Weetman, Maria, Bushnell, Jame, Power, Albert, Jenkins, Alison, Jones, Stefanie, Scott, Amanda, Byrne, Cath, Jesky, Mark, Cowley, Alison, Mchaffie, Emma, Waterfall, Holly, Taylor, Jo, Bough, Laura, Phillips, Thoma, Winter-Goodwin, Barbara, Phin Kon, Sui, Macdougall, Iain, Lioudaki, Eirini, Shah, Sapna, Sharpe, Claire, Aguilar, Francisco, Hernandez Pena, Abegail, Pugay, Conception, Te, Amelia, Finn, Hugh, Hanif, Wasim, Mostafa, Samiul, Aitken, Alice, Draxlbauer, Katharine, Grobovaite, Evelina, Kearney, Jennifer, Mccarthy, Theresa, Gentile, Giorgio, Browne, Duncan, Chellamuthu, Palanichamy, Dugal, Tabinda, Chant, Terri, Jones, Laura, Laity, Emily, Miners, Megan, Muir, Jame, Swanson, Elizabeth, Frankel, Andrew, Tomlinson, Jame, Alegata, Marlon, Almasarwah, Rashid, Apostolidi, Anthoula, Vourvou, Maria, Walters, Thoma, Taal, Maarten, Dukka, Hari, Kolhe, Nitin, Mcdonald, Carly, White, Kelly, Ugni, Shiva, Gunda, Smita, Oluyombo, Rotimi, Brindle, Vicki, Coutts, Ping, Fuller, Tracy, Nadar, Evelyn, Ramadoss, Suresh, Motherwell, Nichola, Pajak, Susannah, Tonks, Louise, Bhandari, Sunil, Bodington, Richard, Hazara, Adil, Fellowes, Dominic, Wong, Christopher, Goldsmith, Christopher, Barnes, Sherald, Bennett, Ann, Burston, Claire, Hope, Samantha, Hunt, Nicola, Kurian, Lini, Fish, Richard, Farrugia, Daniela, Lee, Judy, Sadler, Emma, Turner, Hannah, Hill, Christopher, Brown, Henry, Masengu, Agne, Maxwell, Peter, Bleakley, Nina, Murtagh, Hugh, Petchey, William, Yiu, Vivian, Kellett, Joanne, Williams, Angharad, Clarke, Helen, Carnall, Victoria, Benyon, Sarah, Blake, Caroline, Estcourt, Stephanie, Piper, Jane, Morgan, Neal, Hutchinson, Carolyn, Mckinley, Teresa, Woodman, Alastair, Graham, Judi, Leonard, Niall, Smyth, John, Adell, Vicki, Hagan, Samantha, Caplin, Ben, Oomatia, Amin, Damian, Eleanor, Sobande, Toluleyi, Doulton, Tim, Delaney, Michael, Montasser, Mahmoud, Hansen, Jenny, Loader, David, Moon, Angela, Morris, France, Sinha, Smeeta, Chukwu, Chukwuma, Hudson, Amy, Campbell, Diane, Kershaw, Melanie, Whittaker, Stephanie, Irtiza-Ali, Ayesha, Ghalli, Farid, Nosseir, Heba, Leslie, Allison, Trivedi, Kate, Fraser, Donald, Alhadj Ali, Mohammad, Griffin, Sian, Latif, Farah, Witczak, Justyna, Wonnacott, Alexa, Jeffers, Lynda, Webley, Yvette, Phelan, Paul, Miller-Hodges, Eve, Geddes, Ailsa, Glenwright, Margaret, Hunter, Amy, Pickett, Thoma, Moriarty, Jim, Hill, Linda, Tyler, Amanda, Ayub, Waqar, Evans, Gail, Hewins, Sue, Hewitt, Davina, Read, Kerry, Bell, Samira, Cosgrove, Leanne, Craik, Rachel, Murray, Shona, Bhandary, Nitin, Coles, Holly, Easow, Rashmi, Joseph, Maya, Khwaja, Arif, Jackson, Yvonne, Mbuyisa, Angeline, Sellars, Rachel, Chitalia, Nihil, Mohandas, Cynthia, Gherman, Anca, Kamundi, Charlotte, Olufuwa, Olumide, Mccafferty, Kieran, Adeleke, Adedolapo, Healy, Cara, Jeyarajah, Damini, Kinsella-Perks, Edward, Smith, Richard, Camilleri, Brian, Buckman, Carol, Finch, Jenny, Rivers, Vanessa, Connor, Andrew, Carr, Sheila, Shainberg, Lisa, Lewington, Andrew, Baker, Richard, Dorey, Suzannah, Tobin, Kay, Wheatley, Rosalyn, Banerjee, Debasish, Hull, Richard, Abat, Sharirose, Paul, Riny, Karim, Mahzuz, Htet, Zay, Tufail, Saad, Varma, Ravi, Convery, Karen, Fottrell-Gould, Deirdre, Hudig, Lisa, Tropman, Emily, Abdul-Samad, Thahir, Grace, Anne, Phipps, Marie, Suckling, Rebecca, Somalanka, Subash, Sood, Bhrigu, Swift, Pauline, Acheampong, Sarah, Ansu, Kwame, Augustin, Martia, Sampson, Anna, Vinall, Lynn, Wren, Kim, Wanninayake, Shamila, Wooding, Nichola, Edwards, Heather, Owen, Lydia, Bolton, Stephanie, Carson, Marion, Matthews, Michael, Brunskill, Nigel, Jesus-Silva, Jorge, Howson, Alex, Quashie-Akponeware, Mary, Tindall, Hilary, Nethaji, Chidambaram, Eldon, Helen, Patel, Rajan, Mark, Patrick, Rankin, Alastair, Sullivan, Michael, Forsyth, Kirsty, Mcdougall, Rowan, Dasgupta, Tanaji, Davies, Louisa, Ryder, Maggie, Grimmer, Philip, Macdonald, Clare, Webster, Mary, Newcastle, Newcastle, Ellam, Timothy, Wong, Edwin, Meshykhi, Christine, Webster, Andrea, Wilson, Peter, Vilar, Enric, Berdeprado, Jocelyn, Doctolero, Eunice, Wilkinson, Lily, Mccarroll, Frank, Ammar, Hesham, Kuan, Ying, Moran, Conor, Shivashankar, Girish, Campbell, Ryan, Glowski, Deborah, Mcdermott, Paula, Ali, Amar, Patel, Zuber, Bond, Christine, Whalley, Gillian, Zhang, Haitao, Yang, Liu, Zhang, Lihua, Kan, Tingting, Zhu, Ling, Zhao, Jinghong, Hou, Weiping, Wu, Jing, Cheng, Hong, Bian, Weijing, Zhao, Zhirui, Shao, Fengmin, Cao, Huixia, Jiao, Xiaojing, Niu, Peiyuan, Niu, Jianying, Chen, Yu, Zhang, Lihong, Zhu, Shenglang, Lin, Haiyan, Yao, Shaopeng, Chen, Jiehui, Jiang, Ying, Hu, Ying, Xiao, Huaying, Yang, Fuye, Zhang, Xinzhou, Guo, Baochun, Jin, Qiu, Liu, Lixia, Xiao, Xiangcheng, Xie, Yanyun, Meng, Ting, Xu, Chuanwen, Huang, Jie, Xu, Yanmei, Kong, Weixin, Wang, Xiaoliang, Liu, Qianpan, Wang, Xueying, Gao, Ming, Hu, Xiumei, Lu, Ying, Wang, Li, Peng, Kun, Wang, Wei, Gong, Qiuhong, Cai, Jianfang, Li, Xiaojue, Liu, Xuejiao, Zhou, Shuhan, Liu, Hong, Weng, Yao, Tang, Shuai, Yao, Yao, Zhao, Shi, Cheng, Chen, Wei, Wei, Li, Na, Aqashiah Mazlan, Sadanah, Zubaidah Bahtar, Alia, Katiman, Elliyyin, Othman, Noraini, Mushahar, Lily, Mazlan, Nurdiana, Sharafina Safiee, Nur, Ramasamy, Sarasa, Seng Wong, Hin, Ahmad Rosdi, Hajar, Zhao Zhi Tan, Esther, Fan Tay, Ju, Seng Teng, Kok, Yahaya, Hasnah, Jiun Liu, Wen, Wee Ee, Lik, Kay Leong Khoo, Kenneth, Mohd Yusoff, Yuana, Safhan Mohamad Nor, Fariz, Kamil Ahmad, Mohd, Ramli Seman, Mohd, Hui Hong Tan, Clare, Lui Sian Ngu, Laura, Yoke May Chan, Jaime, Peji, Javelin, Loong Loh, Chek, Yan Lee, Yee, Ramanaidu, Sridhar, Mean Thong, Kah, Hong Wong, Yik, Junus, Suria, Hua Ching, Chen, Faisal Asmee, Mohammad, Ruziana Ku Md Razi, Ku, Leong Low, Chun, Sze Bing Sim, Christopher, Duan Tham, Zhang, Kamila Abdullah, Noor, Meng Chen, Tai, Chieh Chan, Yong, Chang, Eason, Yean Kang, Huan, Quan Lee, Kai, Ann Lee, Sue, Kheng Lee, Aik, Vinathan, Jeevika, Abdul Cader, Rizna, Mustafar, Ruslinda, Kamaruzaman, Lydia, Mohd, Rozita, Ismail, Rahimah, Men Leong, Chong, Koon Low, Chee, Wei Wong, Liang, Adnan, Norlezah, Ibrahim, Sabariah, Zaimi Abdul Wahab, Mohamad, Bavanandan, Sunita, Shen Lim, Yik, Hazlina Wan Mohamad, Wan, Munirah Jaafar, Siti, Ashykeen Mohd Fauzi, Nur, Sudin, Aziee, Kun Lim, Soo, Chung Gan, Chye, Hing, Albert, Ahmad Faizal Alaidin Razali, Wan, Fong Liew, Yew, Bao Tyng Chan, Chelsia, Chih Cheng, Mei, Chen Ong, Yu, Meng Ong, Loke, Amalina Mohamed Affandi, Farah, Rahmat, Korina, Chai Peng, Ban, Amat, Masayu, Hadafi Ahmad, Nuzaimin, Yee Mah, Doo, Loon Tye, Yi, Azhari, Zaid, Nabilah Mohamad Zaini, Siti, Aidil Musa, Mohd, Ahmad Miswan, Norazinizah, Ramli, Rafizanur, Aziah Ahmad, Nor, Leong Goh, Bak, Izah Ahmad, Nurul, Huda Ibrahim, Fairol, Jian Ng, Tze, Shanmuganathan, Malini, Lian Tay, Li, Harun, Zaiha, Ramli, Salmi, 'Ain Yusof, Nurul, Abd Rahman, Rossenizal, Iqbal Abdul Hafidz, Muhammad, Hidayati Mohd Sharif, Nur, Yasmoon Awang, Irda, Nakashima, Eitaro, Imamine, Rui, Minatoguchi, Makiko, Miura, Yukari, Nakaoka, Miduki, Suzuki, Yoshiki, Yoshikawa, Hitomi, Shin, Koki, Fujita, Kanae, Iwasa, Misuzu, Sasajima, Haruka, Sato, Airi, Hamamoto, Yoshiyuki, Fujita, Yuki, Haraguchi, Takuya, Hyo, Takanori, Izumi, Kiyohiro, Komiya, Toshiyuki, Kubota, Sodai, Kurose, Takeshi, Kuwata, Hitoshi, Nakatani, Susumu, Oishi, Kaori, Okamoto, Saki, Okamura, Kaori, Takeoka, Jun, Tanaka, Nagaaki, Tanigaki, Katsuya, Toda, Naohiro, Watanabe, Koin, Komori, Hiromi, Kumuji, Rika, Takesada, Asako, Tanaka, Aya, Maruyama, Shoichi, Hasegawa, Tomonori, Ishiguro, Akiko, Ishimoto, Takuji, Ito, Kazuhiro, Kamimura, Yutaka, Kato, Noritoshi, Kato, Sawako, Kojima, Hiroshi, Kosugi, Tomoki, Maeda, Kayaho, Mizuno, Masasi, Saito, Shoji, Sato, Hitomi, Sato, Yuka, Suzuki, Yasuhiro, Tanaka, Akihito, Yasuda, Yoshinari, Hasegawa, Fujiko, Hayashi, Maiko, Higashi, Shizuka, Shimamura, Kaho, Sumi, Momoko, Tajima, Kazuki, Unekawa, Chimaki, Wakayama, Kana, Wakita, Yukiko, Otani, Takatoshi, Imai, Ayako, Kawashima, Sayaka, Kogure, Eri, Sato, Tomoe, Takezawa, Misato, Yoshida, Shinya, Araki, Hideo, Katsuda, Yuko, Konishi, Masahiro, Matsunaga, Takahiro, Oe, Masashi, Ogane, Kunihiro, Sakai, Masato, Takahashi, Tomoko, Yamano, Takahiro, Yokoyama, Takuya, Ito, Hitomi, Katayama, Masayo, Kuroda, Emi, Ikeda, Toru, Kojo, Takuma, Yoshidome, Etsuo, Mizumachi, Rieko, Yamamoto, Akane, Yamasaki, Narihisa, Yamasaki, Yoshihiko, Wada, Jun, Eguchi, Jun, Higuchi, Chigusa, Katayama, Akihiro, Kinomura, Masaru, Kitagawa, Masashi, Kitamura, Shinji, Miyamoto, Satoshi, Morinaga, Hiroshi, Nakatsuka, Atsuko, Nojima, Ichiro, Shikata, Kenichi, Sugiyama, Hitoshi, Tanabe, Katsuyuki, Tsuji, Kenji, Uchida, Haruhito, Watanabe, Mayu, Hashimoto, Chie, Kato, Takahiro, Yamamoto, Sayaka, Wada, Takehiko, Fukagawa, Masafumi, Hamano, Naoto, Koizumi, Masahiro, Komaba, Hirotaka, Nakagawa, Yosuke, Iwamoto, Michiyo, Masutani, Kosuke, Katanosaka, Akane, Kiyota, Mayu, Uchi, Hikari, Ueda, Yuka, Yamamoto, Sonoka, Nagasu, Hajime, Itano, Seiji, Iwakura, Tsukasa, Kadoya, Hiroyuki, Kanda, Eiichiro, Kashihara, Naoki, Kidokoro, Kengo, Kondo, Megumi, Sasaki, Tamaki, Satoh, Minoru, Tokuyama, Atsuyuki, Umeno, Reina, Wada, Yoshihisa, Yamamoto, Toshiya, Yamanouchi, Yu, Abe, Masumi, Inukai, Yoko, Ogawa, Wataru, Asahara, Shunichiro, Fujii, Hideki, Goto, Shunsuke, Hirota, Yushi, Hosooka, Tetsuya, Kono, Keiji, Nishi, Shinichi, Okada, Yuko, Sakaguchi, Kazuhiko, Sugawara, Kenji, Takahashi, Michiko, Takai, Tomoko, Tamori, Yoshikazu, Watanabe, Kentaro, Kitajima, Miyu, Nishi, Misaki, Wada, Junko, Ito, Yasuhiko, Kamiya, Hideki, Asai, Akimasa, Asai, Nao, Asano, Saeko, Banno, Shogo, Ejima, Yohei, Hase, Hanako, Hayami, Tomohide, Himeno, Tatsuhito, Ishikawa, Takahiro, Ito, Mayumi, Iwagaitsu, Shiho, Kasagi, Rina, Kato, Yoshiro, Kato, Makoto, Kato, Koichi, Katsuno, Takayuki, Kawai, Miyuka, Kinashi, Hiroshi, Kondo, Masaki, Koshino, Masako, Matsuoka, Naoya, Morishita, Yoshiaki, Motegi, Mikio, Nakamura, Jiro, Shimoda, Hiromi, Sugiyama, Hirokazu, Tsunekawa, Shin, Yamaguchi, Makoto, Takahashi, Kazuyo, Watada, Hirotaka, Funayama, Takashi, Furukawa, Yasuhiko, Gohda, Tomohito, Goto, Hiromasa, Kaga, Hideyoshi, Kanaguchi, Yasuhiko, Kanazawa, Akio, Kaneko, Kayo, Kano, Toshiki, Kihara, Masao, Kimura, Shogo, Kobayashi, Takashi, Maiguma, Masayuki, Makita, Yuko, Mano, Satoshi, Mita, Tomoya, Miyatsuka, Takeshi, Murakoshi, Maki, Muto, Masahiro, Nakata, Masami, Nakata, Junichiro, Nishida, Yuya, Nohara, Nao, Ogihara, Takeshi, Sato, Daisuke, Sato, Junko, Sato, Hiroaki, Suzuki, Yusuke, Suzuki, Ruka, Suzuki, Hitoshi, Takagi, Miyuki, Tamura, Yoshifumi, Uchida, Toyoyoshi, Ueda, Seiji, Asawa, Miki, Miyaji, Minako, Nagashima, Eri, Shibata, Yoshie, Yanagisawa, Eri, Yamauchi, Toshimasa, Hirakawa, Yosuke, Nishi, Hiroshi, Shojima, Nobuhiro, Horikawa, Satoko, Nakayama, Yukiko, Yamada, Naoko, Omori, Yuki, Yano, Shintaro, Ioka, Miyabi, Kuwabara, Nahoko, Nagano, Remi, Nozawa, Megumi, Osawa, Yumi, Maegawa, Hiroshi, Kume, Shinji, Araki, Shinichi, Miyazawa, Itsuko, Morino, Katsutaro, Kawai, Ikuko, Sobata, Masumi, Takaoka, Motoko, Iwaita, Yasushi, Udagawa, Takashi, Inamori, Ami, Kawase, Aya, Yamanaka, Aya, Shimano, Hitoshi, Fujita, Akiko, Iwasaki, Hitoshi, Kai, Hirayasu, Osaki, Yoshinori, Saito, Chie, Sekiya, Motohiro, Tsunoda, Ryoya, Yamagata, Kunihiro, Nakamura, Rikako, Yamada, Aiko, Ohsugi, Mitsuru, Awazawa, Motoharu, Bouchi, Ryotaro, Hashimoto, Shota, Hashimoto, Makiko, Hisatake, Tomoko, Ihana, Noriko, Ishizuka, Koko, Izumi, Kazuo, Kajio, Hiroshi, Kobayashi, Michi, Kodani, Noriko, Maruyama, Koji, Matsumoto, Michihiro, Matsushita, Maya, Nakamura, Tomoka, Sugiyama, Takehiro, Tanabe, Akiyo, Terakawa, Aiko, Ueki, Kojiro, Orimo, Yuko, Ozawa, Takako, Takahira, Eriko, Yamasaki, Yoshimitsu, Haneda, Masakazu, Tomita, Tadahiro, Akimoto, Saori, Fujimoto, Akihiro, Ishihara, Kenji, Murakami, Chiho, Nishiyama, Akiyo, Toyonaga, Yukiko, Uozumi, Kana, Yamaji, Yukihiro, Shigehara, Tetsuya, Okajyo, Jun, Shimizu, Yukihiro, Iwasaki, Shingo, Fukao, Yuki, Furusho, Megumi, Nunokawa, Shintaro, Katagiri, Hideki, Izumi, Tomohito, Kaneko, Keizo, Kodama, Shinjiro, Miyazaki, Mariko, Munakata, Yuichiro, Nagasawa, Tasuku, Oe, Yuji, Sugawara, Hiroto, Takahashi, Kei, Hirata, Kazushige, Inomata, Keiko, Otomo, Shoko, Uchida, Taeko, Yamashita, Chigusa, Kiyosue, Arihiro, Tamura, Ryota, Dube, Francoi, Bolduc, Marilene, Talbot, Marie-Christine, Cham, Leslie, Lai, Vesta, Tse, Josephine, Jolly, Shivinder, Duck, Tabbatha, Lyle, Scott, Epp, Rachel, Galloway, Camille, Haskett, Susan, Matvienko, Elizabeta, Paulsen, Liam, Moist, Louise, Lozon, Zabrina, Ramsey, Tina, Whitmore, Brittany, Al-Zeer, Bader, Macleod, Paula, O'Sullivan, Aoife, Sheriff, Zainab, Tholl, Sam, Pandey, Amritanshu, Armstrong, Samantha, Gebeyehu, Bethelihem, Toth, Patrick, Goldenberg, Ronald, Jahangiriesmaili, Mahsa, Sanguila, Shariff, Suresh, Neethi, Talsania, Tanvi, Zalunardo, Nadia, Agharazii, Mohsen, Roussel, Marie-Pier, Saillant, Annie, Samson, France, Bajaj, Harpreet, Bhavsar, Miken, Dhall, Parul, Dhillon, Gagandeep, Grewal, Bhupinder, Nimbkar, Taniya, Madore, Francoi, Marcotte, Guylaine, Steen, Oren, Bullen, Mathura, Raguwaran, Shayani, Valleteau, Andre, Langlois, Marie-France, Brown, Christine, Steele, Andrew, Garrity, Melissa, Ghate, Taneera, Robinson, Holly, Tolibas, Michael, Tailor, Chetna, Elliott, Lauren, McClary-Wright, Christine, Boreky, Fadia, Fikry, Sameh, Ali, Ayesha, Barot, Chintankumar, Basily, Wagdy, Saram, Thisun, Varad, Vinay, Khandwala, Hasnain, Aguilera, Alex, Alvarez, Patricia, Gill, Balwinder, Huda, Nazihah, Navivala, Aamir, Pinto, Daniel, Bevilacqua, Micheli, Fung, Elaine, Hernandez, Geraldine, Mann, Puneet, Saini, Jaskiran, Rabasa-Lhoret, Remi, Bovan, Danijela, Devaux, Marie, Barnini, Cecilia, Leoncini, Giovanna, Manco, Luca, Nobili, Giulia, Piemontese, Matteo, Aucella, Filippo, Grifa, Rachele, Totaro, Francesco, La Manna, Gaetano, Capelli, Irene, Cianciolo, Giuseppe, Lerario, Sarah, Zappulo, Fulvia, Rosati, Alberto, Fani, Filippo, Spatoliatore, Giuseppe, Gesualdo, Loreto, Pesce, Francesco, Russo, Maria, Zippo, Maria, Cafiero, Cesira, Motta, Daria, Bianco, Simona, Bilucaglia, Donatella, Messa, Piergiorgio, Pavone, Laura, Tripodi, Federica, Vettoretti, Simone, Fioretto, Paola, Carraro, Gianni, Farnia, Filippo, Postal, Anna, D'Amelio, Alessandro, Cardone, Antonio, Piccinni, Giovanni, Aloisi, Annalisa, Scolari, Francesco, Alberici, Federico, Guerini, Alice, Saccà, Chiara, Salviani, Chiara, Zani, Roberta, DE NICOLA, Luca, Garofalo, Carlo, Elena Liberti, Maria, Minutolo, Roberto, Pennino, Luigi, Polese, Lucio, Mené, Paolo, Barberi, Simona, Falcone, Clorinda, Russo, Francesco, Caroppo, Maurizio, Santorelli, Gennaro, Rivera, Rodolfo, Santoro, Domenico, Giuffrida, Alfio, Zirino, Fortunata, Calvi, Cristina, Estienne, Luca, Gambaro, Giovanni, Gangemi, Concetta, Ortalda, Vittorio, Pessolano, Giuseppina, Grandaliano, Giuseppe, Baccaro, Rocco, Ferraro, Pietro, Mangiacapra, Roberto, Melandri, Marco, Foligno, Nadia, Quartagno, Rita, Vezzoli, Giuseppe, Brioni, Elena, and Group, EMPA-KIDNEY Collaborative

Subjects
chronic renal disease, empagliflozin, empa-kidney, General Medicine
Abstract

Background The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients. Methods We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m2 of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m2 with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to Results A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; PConclusions Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110. opens in new tab; EudraCT number, 2017-002971-24. opens in new tab.)

Published
2023

23. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice

Author

Masayoshi Suda, Ippei Shimizu, Goro Katsuumi, Yohko Yoshida, Yuka Hayashi, Ryutaro Ikegami, Naomi Matsumoto, Yutaka Yoshida, Ryuta Mikawa, Akihiro Katayama, Jun Wada, Masahide Seki, Yutaka Suzuki, Atsushi Iwama, Hironori Nakagami, Ayako Nagasawa, Ryuichi Morishita, Masataka Sugimoto, Shujiro Okuda, Masanori Tsuchida, Kazuyuki Ozaki, Mayumi Nakanishi-Matsui, and Tohru Minamino

Subjects
Aging, Neuroscience (miscellaneous), Geriatrics and Gerontology
Published
2021

24. Case of subcutaneous insulin resistance syndrome treated with ultra‐rapid insulin lispro

Author

Yuichi Matsushita, Kazuyuki Hida, Takahiro Ishii, Satomi Tani, Mihiro Sue, Akihiro Katayama, Remi Kuribayashi, Izumi Iseda, Masaya Takeda, and Masafumi Tenta

Subjects
medicine.medical_specialty, endocrine system diseases, business.industry, Endocrinology, Diabetes and Metabolism, Type 2 Diabetes Mellitus, General Medicine, Heparin, medicine.disease, Subcutaneous insulin, Endocrinology, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Insulin lispro, Insulin absorption, business, Treprostinil, medicine.drug, Glycemic
Abstract

Subcutaneous insulin resistance syndrome is a rare condition that causes difficulty in glycemic control due to severe resistance to subcutaneous insulin injections. We herein present a case of a 40-year-old woman with type 2 diabetes mellitus who had been diagnosed with subcutaneous insulin resistance syndrome since the age of 29 years, and had been persistently treated with continuous subcutaneous insulin infusion using a mixture of insulin lispro and heparin. The patient was switched from insulin lispro plus heparin to ultra-rapid insulin lispro; given that it contains treprostinil and citrate, it is expected to have similar effects as heparin, and shows similar glucose-lowering effects and insulin absorption. Our results suggest that treatment with ultra-rapid insulin lispro is effective for subcutaneous insulin resistance syndrome.

Published
2021

27. A case of type 2 diabetes mellitus leading to euglycemic diabetic ketoacidosis in 3 days after starting sodium-glucose cotransporter 2 inhibitor while on a very-low-carbohydrate diet

Author

Ayumi Inoue, Akihiro Katayama, Mihiro Sue, Momoka Hasegawa, Megumi Maeda, Masaki Matoba, Takahiro Ishii, Remi Kuribayashi, Masafumi Tenta, Yuichi Matsushita, Masaya Takeda, Izumi Iseda, Toshiyuki Wakatsuki, and Kazuyuki Hida

Abstract

This paper presents a case with type 2 diabetes mellitus on a very low-carbohydrate diet who developed euglycemic diabetic ketoacidosis (EDKA) 3 days after starting sodium-glucose cotransporter 2 inhibitors (SGLT2i). When initiating SGLT2i, healthcare providers should confirm the implementation of a low-carbohydrate diet and provide intensive guidance to prevent EDKA.

Published
2022

28. Analysis of inflammatory cytokines and estimated glomerular filtration rate decline in Japanese patients with diabetic kidney disease: a pilot study

Author

Yuka Sugawara, Yosuke Hirakawa, Koki Mise, Kosuke Kashiwabara, Ko Hanai, Satoshi Yamaguchi, Akihiro Katayama, Yasuhiro Onishi, Yui Yoshida, Naoki Kashihara, Yutaka Matsuyama, Tetsuya Babazono, Masaomi Nangaku, and Jun Wada

Subjects
Japan, Biochemistry (medical), Clinical Biochemistry, Drug Discovery, Diabetes Mellitus, Disease Progression, Cytokines, Humans, Diabetic Nephropathies, Pilot Projects, Kidney, Glomerular Filtration Rate
Abstract

Background: It is important to identify additional prognostic factors for diabetic kidney disease. Materials & methods: Baseline levels of ten cytokines (APRIL/TNFSF13, BAFF/TNFSF13B, chitinase 3-like 1, LIGHT/TNFSF14, TWEAK/TNFSF12, gp130/sIL-6Rβ, sCD163, sIL-6Rα, sTNF-R1, sTNF-R2) were measured in two cohorts of diabetic patients. In one cohort (n = 777), 156 individuals were randomly sampled after stratification and their plasma samples were analyzed; in the other cohort (n = 69), serum samples were analyzed in all the individuals. The levels of cytokines between rapid (estimated glomerular filtration rate decline >5 ml/min/1.73 m2/year) and non-rapid decliners were compared. Results: Multivariate analysis demonstrated significantly high levels of LIGHT/TNFSF14, TWEAK/TNFSF12 and sTNF-R2 in rapid decliners. Conclusion: These three cytokines can be potential biomarkers for the progression of diabetic kidney disease.

Published
2022

32. Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study

Author

Naoko Kurooka, Jun Eguchi, Kazutoshi Murakami, Shinji Kamei, Toru Kikutsuji, Sakiko Sasaki, Akiho Seki, Satoshi Yamaguchi, Ichiro Nojima, Mayu Watanabe, Chigusa Higuchi, Akihiro Katayama, Haruhito A. Uchida, Atsuko Nakatsuka, Kenichi Shikata, and Jun Wada

Subjects
Hypertriglyceridemia, Male, Nutrition and Dietetics, Cross-Sectional Studies, Diabetic Retinopathy, Diabetes Mellitus, Type 2, Endocrinology, Diabetes and Metabolism, Internal Medicine, Humans, Diabetic Nephropathies, Female, Cardiology and Cardiovascular Medicine, Receptors, Lipoprotein
Abstract

Glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) plays a crucial role in lipolytic processing. Previous studies have shown that GPIHBP1 mutations cause severe hypertriglyceridemia and that serum GPIHBP1 levels are marginally higher in patients with coronary heart disease; however, the role of GPIHBP1 in type 2 diabetes mellitus (T2DM) remains unknown.We investigated the association between circulating GPIHBP1 levels and the prevalence of microvascular complications in T2DM.A total of 237 subjects with T2DM and 235 non-diabetic control subjects were enrolled in this study. Their serum GPIHBP1 levels were evaluated using ELISA assays.Circulating GPIHBP1 levels were higher in patients with T2DM (952.7 pg/mL [761.3-1234.6], p0.0001) than in non-diabetic subjects (700.6 [570.8-829.6]), but did not differ in T2DM patients with or without hypertriglyceridemia. Serum GPIHBP1 levels were significantly higher in patients with T2DM with diabetic retinopathy (DR), diabetic nephropathy (DN), and microvascular complications than in those without these complications. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses revealed that the presence of microvascular complications, but not macrovascular complications, was independently associated with serum GPIHBP1 levels, which could predict the presence of diabetic microvascular complications.Elevated GPIHBP1 levels are associated with microvascular complications in T2DM and may help to predict their progression.

Published
2021

33. Author Correction: Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2

Author

Akihiro Katayama, Tomokazu Nunoue, Atsuko Nakatsuka, Toshiro Niki, Jun Eguchi, Sanae Teshigawara, Satoshi Yamaguchi, and Jun Wada

Subjects
medicine.medical_specialty, Science, Galectins, Redox, Mice, Internal medicine, medicine, Animals, Obesity, RNA, Small Interfering, Author Correction, Mice, Knockout, Multidisciplinary, Chemistry, Body Weight, Peroxiredoxins, medicine.disease, Lipid Metabolism, Disease Models, Animal, Endocrinology, Glucose, Adipose Tissue, Liver, Medicine, Disease Susceptibility, Oxidation-Reduction, Biomarkers, Protein Binding
Abstract

The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9

Published
2021

34. Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor‐induced diabetes mellitus: A report of two cases

Author

Hitomi Kataoka, Jun Eguchi, Shunsuke Kagawa, Yohei Noda, Noriko Fujiwara, Mayu Watanabe, Akihiro Katayama, and Jun Wada

Subjects
Medicine (General), insulin secretion, medicine.medical_treatment, Immune checkpoint inhibitors, animal diseases, immune checkpoint inhibitor, chemical and pharmacologic phenomena, Case Report, Longitudinal observation, chemistry.chemical_compound, R5-920, Diabetes mellitus, medicine, Insulin secretion, Adverse effect, C-peptide, business.industry, C‐peptide, Insulin, General Medicine, biochemical phenomena, metabolism, and nutrition, medicine.disease, Immune checkpoint, chemistry, Immunology, diabetes mellitus, Medicine, bacteria, biological phenomena, cell phenomena, and immunity, business
Abstract

Immune checkpoint inhibitor‐induced diabetes mellitus is a rare immune‐related adverse event. This report illustrates clinical data and insulin secretory ability before and after the onset of immune checkpoint inhibitor‐induced diabetes.

Published
2021

35. The hypoglycemia-prevention effect of sensor-augmented pump therapy with predictive low glucose management in Japanese patients with type 1 diabetes mellitus: a short-term study

Author

Kenichi Shikata, Akihiro Katayama, Sanae Teshigawara, Jun Wada, Jun Eguchi, Atsuko Nakatsuka, Atsuhito Tone, Satoshi Miyamoto, and Mayu Watanabe

Subjects
Pediatrics, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Hypoglycemia, 03 medical and health sciences, Low glucose, 0302 clinical medicine, Type 1 diabetes mellitus (T1DM), Diabetes mellitus, Internal Medicine, medicine, Sensor-augmented pump therapy (SAP), Glycemic, Type 1 diabetes, Continuous glucose monitoring, business.industry, Area under the curve, nutritional and metabolic diseases, Predictive low glucose management (PLGM), medicine.disease, Severe hypoglycemia, Original Article, business
Abstract

Aims/introduction The predictive low glucose management (PLGM) system was introduced in March 2018 in Japan. Although there are some reports demonstrating the benefit of PLGM in preventing hypoglycemia, no data are currently available in Japanese patients with type 1 diabetes mellitus (T1DM). The aim of the present study is to evaluate the effect of PLGM with sensor-augmented pump therapy in the prevention of hypoglycemia in Japanese patients. Materials and methods We included 16 patients with T1DM who used the MiniMed®640G system after switching from the MiniMed®620G system. We retrospectively analysed the data of the continuous glucose monitoring system in 1 month after switching to MiniMed®640G. Results The area under the curve (AUC) of hypoglycemia of 180 mg/dL and the duration of hyperglycemia did not change. With the PLGM function, 79.3% of the predicted hypoglycemic events were avoided. Conclusions The hypoglycemia avoidance rate was comparable to those in previous reports. In addition, we demonstrated that PLGM can markedly suppress severe hypoglycemia without deteriorating glycemic control in Japanese T1DM patients. It is necessary to further investigate the effective use of the PLGM feature such as establishing a lower limit and the timing of resumption.

Published
2019

36. Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2)

Author

Atsuhito Tone, Shinichiro Ando, Takashi Matsuoka, Tatsuaki Nakato, Kazutoshi Murakami, Akihiro Katayama, Chigusa Higuchi, Haruhito A. Uchida, Atsuko Nakatsuka, Tomokazu Nunoue, Mayu Watanabe, Koki Mise, Sanae Teshigawara, Kenichi Shikata, Satoshi Miyamoto, Jun Eguchi, Satoshi Yamaguchi, Michihiro Yoshida, Katsuhiro Miyashita, Kazuyuki Hida, Masao Yamada, Jun Wada, Shinji Kamei, Mariko Imamura, and Ikki Shimizu

Subjects
medicine.medical_specialty, Glycan, Urinary system, 030209 endocrinology & metabolism, N-glycans, Type 2 diabetes, 030204 cardiovascular system & hematology, Cardiovascular Medicine, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, medicine, Diseases of the circulatory (Cardiovascular) system, urinary biomarkers, Prospective cohort study, Original Research, biology, diabetes, business.industry, Proportional hazards model, Hazard ratio, medicine.disease, cardiovascular event, lectins, RC666-701, biology.protein, Biomarker (medicine), business, Cardiology and Cardiovascular Medicine
Abstract

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear.Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease.Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24–2.55, P = 0.002) and Calsepa [High-Man (Man2–6)]: 1.56 (1.19–2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001–0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045–0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively].Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE.Trial Registration: This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).

Published
2021
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37. Video-assisted thyroidectomy (VANS method) for benign thyroid nodule: summary of 182 cases in a single institution

Author

Yasuaki Harabuchi, Kenichiro Nomura, Akihiro Katada, Tatsuya Hayashi, Seigo Ueda, Toshihiro Nagato, Kan Kishibe, Miki Takahara, and Akihiro Katayama

Subjects
03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, 030220 oncology & carcinogenesis, Family medicine, Medicine, 030211 gastroenterology & hepatology, business
Published
2017

38. Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2

Author

Jun Eguchi, Jun Wada, Satoshi Yamaguchi, Toshiro Niki, Atsuko Nakatsuka, Akihiro Katayama, Sanae Teshigawara, and Tomokazu Nunoue

Subjects
medicine.medical_specialty, Immunoprecipitation, Molecular biology, Science, Metabolic disorders, Adipose tissue, Adipokine, Inflammation, Diseases, medicine.disease_cause, Article, Medical research, Internal medicine, medicine, Protein disulfide-isomerase, Gene knockdown, Multidisciplinary, Chemistry, Health care, Experimental models of disease, Endocrinology, Apoptosis, Medicine, medicine.symptom, Oxidative stress
Abstract

The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity.

Published
2021

39. Video-assisted total thyroidectomy for Graves' disease

Author

Kenichiro Nomura, Akihiro Katayama, Akihiro Katada, Toshihiro Nagato, Miki Takahara, Kan Kishibe, Yasuaki Harabuchi, Tatsuya Hayashi, and Seigo Ueda

Subjects
Total thyroidectomy, medicine.medical_specialty, business.industry, Graves' disease, Medicine, Video assisted, business, medicine.disease, Surgery
Published
2016

40. Risk Factors for the Requirement of Antenatal Insulin Treatment in Gestational Diabetes Mellitus

Author

Akihiro Katayama, Hidetoshi Kagawa, Mayu Watanabe, Jun Wada, and Daisuke Ogawa

Subjects
Adult, Blood Glucose, medicine.medical_specialty, Article Subject, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Logistic regression, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Pregnancy, Risk Factors, Internal medicine, Diabetes mellitus, Humans, Hypoglycemic Agents, Insulin, Medicine, 030212 general & internal medicine, Glycemic, Glucose tolerance test, lcsh:RC648-665, medicine.diagnostic_test, business.industry, Obstetrics, nutritional and metabolic diseases, Odds ratio, Glucose Tolerance Test, medicine.disease, Gestational diabetes, Diabetes, Gestational, Female, business, Research Article
Abstract

Poor maternal glycemic control increases maternal and fetal risk for adverse outcomes, and strict management of gestational diabetes mellitus (GDM) is recommended to prevent neonatal and maternal complications. However, risk factors for the requirement of antenatal insulin treatment (AIT) are not well-investigated in the pregnant women with GDM. We enrolled 37 pregnant women with GDM and investigated the risk for AIT by comparing the patients with AIT (AIT group;n=10) and without insulin therapy (Diet group;n=27). The 1-h and 2-h plasma glucose levels and the number of abnormal values in 75 g OGTT were significantly higher in AIT group compared with Diet group. By logistic regression analysis, plasma glucose level at 1-h was significant predictor for AIT and the odds ratios were 1.115 (1.004–1.239) using forward selection method and 1.192 (1.006–1.413) using backward elimination method. There were no significant differences in obstetrical outcomes and neonatal complications. 1-h plasma glucose levels in 75 g OGTT are useful parameters in predicting the requirement for AIT in GDM. Both maternal and neonatal complications are comparable in GDM patients with and without insulin therapy.

Published
2016

41. Two Cases of Optic Nerve Neuropathy from Graves’ Ophthalmopathy Treated by Endoscopic Orbital Decompression

Author

Noriko Nishikawa, Kenichiro Nomura, Harumasa Yokota, Kan Kishibe, Akihiro Katada, Akihiro Katayama, Toshihiro Nagato, Tatsuya Hayashi, Yasuaki Harabuchi, and Yuki Komabayashi

Subjects
Graves' ophthalmopathy, 03 medical and health sciences, medicine.medical_specialty, 0302 clinical medicine, business.industry, Orbital decompression, 030221 ophthalmology & optometry, Optic nerve, medicine, 030209 endocrinology & metabolism, medicine.disease, business, Surgery
Published
2016

43. Identification of Circulating miR-101, miR-375 and miR-802 as Biomarkers for Type 2 Diabetes

Author

Hirofumi Makino, Satoshi Yamaguchi, Jun Wada, Sakiko Sasaki, Jun Eguchi, Atsuko Nakatsuka, Akihiro Katayama, Naoto Takahashi, Sanae Teshigawara, Chigusa Higuchi, Daisuke Ogawa, Motoko Kanzaki, and Kazutoshi Murakami

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Renal function, Adipose tissue, Type 2 diabetes, White adipose tissue, Biology, Mice, chemistry.chemical_compound, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Animals, Humans, Aged, Triglyceride, nutritional and metabolic diseases, Glucose Tolerance Test, Middle Aged, medicine.disease, Mice, Inbred C57BL, MicroRNAs, Circulating MicroRNA, Cross-Sectional Studies, Diabetes Mellitus, Type 2, chemistry, Female, Body mass index, Biomarkers
Abstract

Purpose The unique circulating microRNAs (miRNAs) observed in patients with type 2 diabetes (T2D) are candidates as new biomarkers and therapeutic targets. In order to identify circulating miRNAs relevant to the disease process in case of type 2 diabetes, we performed the Illumina sequencing of miRNAs derived from the serum, liver and epididymal white adipose tissue (WAT) of diet-induced obese male C57BL/6J mice. Basic Procedures We selected four miRNAs, miR-101, miR-335, miR-375, and miR-802, which are increased in the sera and tissues of obese mice, and measured the serum levels of miRNAs in T2D and subjects with normal glucose tolerance (NGT). Main Findings The serum concentrations of miRNAs, log 10 miR-101, log 10 miR-375, and log 10 miR-802, were significantly increased in the T2D patients compared with NGT subjects (1.41 ± 2.01 v.s . − 0.57 ± 1.05 (P = 1.36 × 10 − 5 ), 0.20 ± 0.58 v.s. 0.038 ± 1.00 (P = 3.06 × 10 − 6 ), and 2.45 ± 1.27 v.s . 0.97 ± 0.98 (P = 0.014), respectively). The log 10 miR-335 values did not demonstrate any significant differences between the T2D and NGT groups (− 1.08 ± 1.35 v.s . − 0.38 ± 1.21 (P = 0.25)). According to the stepwise regression analysis, the HbA1c was an independent predictor of miR-101. Regarding the serum miR-802 levels, eGFR, HbA1c and HDL-C values were identified as significant determinants. Principal Conclusions The present findings demonstrated that the circulating miR-101, miR-375 and miR-802 levels are significantly increased in T2D patients versus NGT subjects and they may become the new biomarkers for type 2 diabetes.

Published
2015

44. Adipocyte-Specific Inhibition of Mir221/222 Ameliorates Diet-Induced Obesity Through Targeting Ddit4.

Author

Satoshi Yamaguchi, Dongxiao Zhang, Akihiro Katayama, Naoko Kurooka, Ryosuke Sugawara, Albuayjan, Haya Hamed Hassan, Atsuko Nakatsuka, Jun Eguchi, and Jun Wada

Subjects
TUBEROUS sclerosis, GENETIC transcription regulation, RNA sequencing, LABORATORY mice, OBESITY
Abstract

MicroRNAs expressed in adipocytes are involved in transcriptional regulation of target mRNAs in obesity, but miRNAs critically involved in this process is not well characterized. Here, we identified upregulation of miR-221-3p and miR-222-3p in the white adipose tissues in C57BL/6 mice fed with high fat-high sucrose (HFHS) chow by RNA sequencing. Mir221 and Mir222 are paralogous genes and share the common seed sequence and Mir221/222AdipoKO mice fed with HFHS chow demonstrated resistance to the development of obesity compared with Mir221/222flox/y. Ddit4 is a direct target of Mir221 and Mir222, and the upregulation of Ddit4 in Mir221/222AdipoKO was associated with the suppression of TSC2 (tuberous sclerosis complex 2)/mammalian target of rapamycin complex 1 (mTORC1)/S6K (ribosomal protein S6 kinase) pathway. The overexpression of miR-222-3p linked to enhanced adipogenesis, and it may be a potential candidate for miRNA-based therapy. [ABSTRACT FROM AUTHOR]

Published
2021
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45. Comparison of New Preservation Solutions, HN-1 and University of Wisconsin Solution, in Pancreas Preservation for Porcine Islet Isolation

Author

Issei Saitoh, Hirofumi Noguchi, Takashi Kuise, Kentaro Inoue, Yasufumi Noguchi, Atsuko Nakatsuka, Akihiro Katayama, Daisho Hirota, Takashi Kawai, Noriko Imagawa, Hitomi Kataoka, Jun Wada, Toshiyoshi Fujiwara, and Masami Watanabe

Subjects
endocrine system, geography, medicine.medical_specialty, geography.geographical_feature_category, endocrine system diseases, business.industry, Porcine islets, Islet, Article, Surgery, Andrology, Transplantation, medicine.anatomical_structure, Preservation solutions, General Earth and Planetary Sciences, Medicine, Viaspan, Pancreatic islet transplantation, business, Pancreas, General Environmental Science, Collagenase activity
Abstract

For pancreatic islet transplantation, maintaining organ viability after pancreas procurement is critical and a major determinant for better graft function and survival. University of Wisconsin (UW) solution is currently the gold standard for abdominal organ preservation and the pancreas in particular. However, in the use of UW preservation solution for islet transplantation, there are disadvantages to be overcome, such as the inhibition of collagenase activity during pancreatic digestion. In this study, we compared UW solution with HN-1 solution in pancreas preservation for islet isolation. Islet yield was significantly greater in the HN-1 group than the UW group both before and after purification. In the in vitro assay, the adenosine triphosphate content in cultured islets was significantly higher in the HN-1 group than in the UW group. Furthermore, in streptozotocin-induced diabetic nude mice, the islet graft function of the HN-1 group was superior to that of the UW group. We concluded that the use of HN-1 solution is a promising approach for optimal pancreas preservation in islet transplantation.

Published
2013

46. Visceral Adipose Tissue-derived Serine Proteinase Inhibitor Inhibits Apoptosis of Endothelial Cells as a Ligand for the Cell-Surface GRP78/Voltage-dependent Anion Channel Complex

Author

Shigeru Kakuta, Jun Eguchi, Kazuyuki Hida, Akihiro Katayama, Daisuke Ogawa, Yoichiro Iwakura, Hideo Yagita, Yasushi Matsuki, Kanji Higashio, Atsuko Nakatsuka, Motoko Kanzaki, Izumi Iseda, Hirofumi Makino, Kazutoshi Murakami, Ryuji Hiramatsu, Sanae Teshigawara, Takahiro Terami, Kentaro Inoue, and Jun Wada

Subjects
Male, medicine.medical_specialty, Voltage-dependent anion channel, Thapsigargin, Endothelium, Physiology, Adipose tissue, Apoptosis, Mice, Transgenic, Ligands, Streptozocin, Adenoviridae, Diabetes Mellitus, Experimental, Mice, chemistry.chemical_compound, Adipokines, Internal medicine, medicine, Animals, Humans, Voltage-Dependent Anion Channels, Rats, Wistar, Endoplasmic Reticulum Chaperone BiP, Protein kinase B, Cells, Cultured, Heat-Shock Proteins, Serpins, Cell Proliferation, biology, Endoplasmic reticulum, Cell Membrane, Rats, Mice, Inbred C57BL, Disease Models, Animal, medicine.anatomical_structure, Endocrinology, chemistry, biology.protein, Phosphorylation, Endothelium, Vascular, Cardiology and Cardiovascular Medicine
Abstract

Rationale: Visceral adipose tissue-derived serine proteinase inhibitor (vaspin) is an adipokine identified from visceral adipose tissues of genetically obese rats. Objective: The role of vaspin in the diabetic vascular complications remains elusive, and we investigated the effects of vaspin on the vascular function under the diabetic milieu. Methods and Results: Adenovirus carrying the full length of the vaspin gene (Vaspin-Ad) ameliorated intimal proliferation of balloon-injured carotid arteries in diabetic Wistar rats. The expression of Ccl2, Pdgfb, and Pdgfrb genes was significantly reduced by the treatment of Vaspin-Ad. In cuff-injured femoral arteries, the intimal proliferation was ameliorated in vaspin transgenic (Vaspin Tg) mice. The application of recombinant vaspin and Vaspin-Ad promoted the proliferation and inhibited the apoptosis of human aortic endothelial cells. Adenovirus expressing vaspin with calmodulin and streptavidin-binding peptides was applied to human aortic endothelial cells, subjected to tandem tag purification and liquid chromatography-tandem mass spectrometry, and we identified GRP78 (78-kDa glucose-regulated protein) as an interacting molecule. The complex formation of vaspin, GRP78, and voltage-dependent anion channel on the plasma membrane was confirmed by the immunoprecipitation studies using aortas of Vaspin Tg mice. The binding assay using 125 I-vaspin in human aortic endothelial cells revealed high-affinity binding (dissociation constant = 0.565×10 –9 m) by the treatment of 5 μM thapsigargin, which recruited GRP78 from the endoplasmic reticulum to plasma membrane by inducing endoplasmic reticulum stress. In human aortic endothelial cells, vaspin induced phosphorylation of Akt and inhibited the kringle 5-induced Ca 2+ influx and subsequent apoptosis. Conclusions: Vaspin is a novel ligand for the cell-surface GRP78/voltage-dependent anion channel complex in endothelial cells and promotes proliferation, inhibits apoptosis, and protects vascular injuries in diabetes mellitus.

Published
2013

47. Intra-arterial cisplatin with concomitant radiation for advanced hypopharyngeal cancer

Author

Akihiro Katayama, Kan Kishibe, Yasuaki Harabuchi, Akihiro Katada, Isamu Kunibe, Miki Takahara, Kenichiro Nomura, and Tatsuya Hayashi

Subjects
Cisplatin, medicine.medical_specialty, business.industry, medicine.medical_treatment, Urology, Cancer, Hypopharyngeal cancer, medicine.disease, Surgery, Laryngectomy, Otorhinolaryngology, Concomitant, Toxicity, medicine, External beam radiotherapy, business, Chemoradiotherapy, medicine.drug
Abstract

Objectives/Hypothesis: The current study evaluated the efficacy of radiation and concomitant high-dose superselective intra-arterial cisplatin infusion (RADPLAT) for patients with advanced hypopharyngeal cancer. Study Design: Retrospective, single-institutional study. Methods: Between February 2004 and October 2010, 43 patients with T2N0 or worse cancer were given superselective intra-arterial infusions of cisplatin (100-mg/m2 or 75-mg flat dose per week) with simultaneous intravenous infusions of thiosulfate to neutralize cisplatin toxicity and conventional external beam radiotherapy (60–66 Gy). Results: In total, three, seven, 21, and 12 patients were diagnosed with stage II, III, IVA, and IVB cancer, respectively. During the median follow-up period of 34 months, the 3-year overall survival, disease-specific survival, and progression-free survival rates for all patients were 52.2%, 68.2%, and 56.1%, respectively. The 3-year local control and laryngoesophageal dysfunction-free survival rates were 81.6% and 49.4%, respectively. No patient died because of treatment toxicity. Among grade IV toxicity, cerebral infarction (n = 1) and laryngeal necrosis (n = 1) resulting in laryngectomy were observed. Conclusions: Despite being a single-institution experience, the results of the current study suggest that RADPLAT can achieve favorable survival rates and high rates of laryngeal preservation for patients with advanced hypopharyngeal cancers. Laryngoscope, 2012

Published
2012

48. Comparison of Incubation Solutions Prior to the Purification of Porcine Islet Cells

Author

Yasufumi Noguchi, Masami Watanabe, Takashi Kawai, Noriko Imagawa, Issei Saitoh, Akihiro Katayama, Atsuko Nakatsuka, Toshiyoshi Fujiwara, Hitomi Kataoka, Hirofumi Noguchi, and Takashi Kuise

Subjects
Differential centrifugation, medicine.medical_specialty, geography, endocrine system, Chromatography, geography.geographical_feature_category, endocrine system diseases, Porcine islets, Common method, Biology, Islet, Article, Incubation period, Endocrinology, Internal medicine, medicine, General Earth and Planetary Sciences, Pancreatic islet transplantation, Viaspan, Incubation, General Environmental Science
Abstract

For pancreatic islet transplantation, one of the most important steps of islet isolation is islet purification. The most common method of islet purification is density gradient centrifugation because there are differences in density between islets and acinar tissue. However, the density of islets/acinar tissue depends on several conditions, such as the incubation time before purification and the osmolality of the preincubation solution. In this study, we evaluated the impact of using two different preincubation solutions before purification. We used the University of Wisconsin (UW) solution and a new preservation solution (HN-1), which we recently developed. There were no significant differences between the two solutions in terms of the islet yield, rate of viability, and purity or stimulation index after purification. There were also no differences in the attainability and suitability of posttransplantation normoglycemia. Our study shows that the HN-1 solution is equivalent to the UW solution for preincubation before islet purification.

Published
2016

49. Vaspin Is an Adipokine Ameliorating ER Stress in Obesity as a Ligand for Cell-Surface GRP78/MTJ-1 Complex

Author

Kentaro Inoue, Kazuyuki Hida, Kanji Higashio, Takahiro Terami, Jun Wada, Jun Eguchi, Yoichiro Iwakura, Motoko Kanzaki, Daisuke Ogawa, Akihiro Katayama, Sanae Teshigawara, Hideo Yagita, Yasushi Matsuki, Atsuko Nakatsuka, Chikage Sato Horiguchi, Hirofumi Makino, Kazutoshi Murakami, Shigeru Kakuta, Izumi Iseda, and Ryuji Hiramatsu

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Adipose tissue, Adipokine, Mice, Transgenic, Biology, Intra-Abdominal Fat, Ligands, Mice, Downregulation and upregulation, Adipokines, Internal medicine, Cell Line, Tumor, Internal Medicine, medicine, Animals, Humans, Obesity, Protein kinase A, Protein kinase B, Endoplasmic Reticulum Chaperone BiP, Heat-Shock Proteins, Serpins, Mice, Knockout, Endoplasmic reticulum, Cell Membrane, HSP40 Heat-Shock Proteins, Endoplasmic Reticulum Stress, Recombinant Proteins, Neoplasm Proteins, Rats, Up-Regulation, Protein Transport, Endocrinology, Unfolded protein response, Hepatocytes, Phosphorylation, Obesity Studies, Signal Transduction
Abstract

It is unknown whether adipokines derived from adipose tissues modulate endoplasmic reticulum (ER) stress induced in obesity. Here, we show that visceral adipose tissue-derived serine protease inhibitor (vaspin) binds to cell-surface 78-kDa glucose-regulated protein (GRP78), which is recruited from ER to plasma membrane under ER stress. Vaspin transgenic mice were protected from diet-induced obesity, glucose intolerance, and hepatic steatosis, while vaspin-deficient mice developed glucose intolerance associated with upregulation of ER stress markers. With tandem affinity tag purification using HepG2 cells, we identified GRP78 as an interacting molecule. The complex formation of vaspin, GRP78, and murine tumor cell DnaJ-like protein 1 (MTJ-1) (DnaJ homolog, subfamily C, member 1) on plasma membrane was confirmed by cell-surface labeling with biotin and immunoprecipitation in liver tissues and H-4-II-E-C3 cells. The addition of recombinant human vaspin in the cultured H-4-II-E-C3 cells also increased the phosphorylation of Akt and AMP-activated protein kinase (AMPK) in a dose-dependent manner, and anti-GRP78 antibodies completely abrogated the vaspin-induced upregulation of pAkt and pAMPK Vaspin is a novel ligand for cell-surface GRP78/MTJ-1 complex, and its subsequent signals exert beneficial effects on ER stress-induced metabolic dysfunctions. Diabetes 61:2823-2832, 2012

Published
2012

50. Four Cases of Mumps with Laryngeal Edema

Author

Naoki Hatayama, Takumi Kumai, Saeko Yoshida, Akihiro Katayama, Toshihiro Nagato, Tatsuya Hayashi, Kan Kishibe, and Yasuaki Harabuchi

Subjects
medicine.medical_specialty, biology, Respiratory airway, business.industry, medicine.medical_treatment, Mumps virus, medicine.disease, Laryngeal Edema, medicine.disease_cause, Surgery, Tracheotomy, Otorhinolaryngology, Immunoglobulin M, Edema, medicine, biology.protein, medicine.symptom, Intravenous steroids, business, Meningitis
Abstract

Mumps virus infections primarily involve the parotid glands and most frequently affect school-aged children. Mumps has many complications, such as meningitis, but laryngeal edema is not a common one. We present four cases of mumps with laryngeal edema. The patients were a 39-year-old male, 23-year-old female, 29-year-old female and 31-year-old female. They came to our hospital complaining of submandibular and subaural regional swelling and dyspnea. In every case, fiberscopic findings revealed edema of the arytenoid. Laboratory examination showed normal WBC, slightly high CRP and high serum amylase. Their mumps titers were positive for immunoglobulin M and G. The patients were admitted to our hospital and were started on intravenous steroids. In one case, because of progressive dyspnea, a tracheotomy was needed. All symptoms of laryngeal edema improved within 3 days. In previous reports in the literature, there were four cases of mumps with laryngeal edema which required a tracheotomy because of aggravation of dyspnea. If a patient with mumps complains of dyspnea, examination of the respiratory airway is important.

Published
2012

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