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Chun Zeng Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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Xin Yi Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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Danny Zipris Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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Hongli Liu Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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Lin Zhang Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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Qiaoyun Zheng Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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Krishnamurthy Malathi Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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Ge Jin Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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Aimin Zhou Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA
Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA
Clinical Chemistry Program, Center for Gene Regulation in Health and Diseases, Department of Cancer Biology, Barbara Davis Center of Childhood Diabetes, Central Laboratory, Department of Biological Sciences, Department of Biological Sciences, Department of Chemistry, Cleveland State University, SI 424, Cleveland, Ohio 44115, USA

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interferon-γ and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice . Journal of Clinical Investigation 87 739 – 742 . ( doi:10.1172/JCI115055 ) di Cesare E Previti M Russo F Brancatelli S Ingemi MC Scoglio R Mazzù N

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M R Kraus Department of Gastroenterology and Hepatology, Medizinische Poliklinik, University of Würzburg, Klinikstrasse 6-8, D-97070 Würzburg, Germany
Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany

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A Schäfer Department of Gastroenterology and Hepatology, Medizinische Poliklinik, University of Würzburg, Klinikstrasse 6-8, D-97070 Würzburg, Germany
Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany

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T Bentink Department of Gastroenterology and Hepatology, Medizinische Poliklinik, University of Würzburg, Klinikstrasse 6-8, D-97070 Würzburg, Germany
Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany

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M Scheurlen Department of Gastroenterology and Hepatology, Medizinische Poliklinik, University of Würzburg, Klinikstrasse 6-8, D-97070 Würzburg, Germany
Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany

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B Weissbrich Department of Gastroenterology and Hepatology, Medizinische Poliklinik, University of Würzburg, Klinikstrasse 6-8, D-97070 Würzburg, Germany
Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany

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O Al-Taie Department of Gastroenterology and Hepatology, Medizinische Poliklinik, University of Würzburg, Klinikstrasse 6-8, D-97070 Würzburg, Germany
Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany

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J Seufert Department of Gastroenterology and Hepatology, Medizinische Poliklinik, University of Würzburg, Klinikstrasse 6-8, D-97070 Würzburg, Germany
Division of Metabolism, Endocrinology and Molecular Medicine, Medizinische Poliklinik, University of Würzburg, Würzburg, Germany
Institute for Virology and Immunobiology, University of Würzburg, Versbacher Strasse 7, D-97078 Würzburg, Germany

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Introduction Interferon alfa is therapeutically used, e.g. in malignant diseases and chronic viral hepatitis. Recombinant human interferon alfa has proven its antiviral effect in several licensing trials ( McHutchison et al. 1998

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Marcella Salzano Department of Medicine and Surgery, Clinical and Molecular Endocrinology and Oncology, University of Salerno, Via Allende, 84081 Baronissi, Salerno, Italy Departments of

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Eleonora Russo Department of Medicine and Surgery, Clinical and Molecular Endocrinology and Oncology, University of Salerno, Via Allende, 84081 Baronissi, Salerno, Italy Departments of

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Loredana Postiglione Department of Medicine and Surgery, Clinical and Molecular Endocrinology and Oncology, University of Salerno, Via Allende, 84081 Baronissi, Salerno, Italy Departments of

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Anna Guerra
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Vincenzo Marotta Department of Medicine and Surgery, Clinical and Molecular Endocrinology and Oncology, University of Salerno, Via Allende, 84081 Baronissi, Salerno, Italy Departments of

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Silvano Esposito
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Mario Vitale
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present in HT and has a crucial role in the pathogenesis of the disease by secreting inflammatory cytokines such as interferon-γ (IFN-γ; Salgame et al . 1991 , Romagnani 1994 , Carter & Dutton 1996 , Pala et al . 2000 , Mazziotti et al . 2003

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Janne Jensen Department of Medical Biochemistry and Genetics, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark

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Elisabeth D Galsgaard Department of Medical Biochemistry and Genetics, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark

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Allan E Karlsen Department of Medical Biochemistry and Genetics, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark

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Ying C Lee Department of Medical Biochemistry and Genetics, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark

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Jens H Nielsen Department of Medical Biochemistry and Genetics, University of Copenhagen, Panum Institute, Blegdamsvej 3, DK 2200 Copenhagen N, Denmark
Pharmacology Research 4, Novo Nordisk A/S, Novo Nordisk Park F6.2.13, DK 2760 Måløv, Denmark
Steno Diabetes Center, Niels Steensensvej 2, DK 2820 Gentofte, Denmark

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Introduction The proinflammatory cytokines interleukin-1β (IL-1β), interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) are toxic to pancreatic β-cells and have been implicated in the pathogenesis of type 1 diabetes ( Eizirik

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Marta Labeur Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Damian Refojo Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Barbara Wölfel Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Johanna Stalla Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Vivian Vargas Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Marily Theodoropoulou Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Michael Buchfelder Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Marcelo Paez-Pereda Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Eduardo Arzt Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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Günter K Stalla Department of Neuroendocrinology, Department of Inflammatory Disorders of the CNS at the Max Planck Institute of Psychiatry, Department of Neurosurgery, Affectis Pharmaceuticals, Laboratorio de Fisiología y Biología Molecular, Department of Molecular Neurogenetics

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, Arzt 2001 , Nudi et al . 2005 ). Previous reports showed that interferon-γ (IFNG), a potent immunostimulatory cytokine, also plays a regulatory role in the adenohypophysis. Vankelecom et al . (1990 , 1992 ) described that IFNG inhibits agonist

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GA Johnson
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MM Joyce
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SJ Yankey
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TR Hansen
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TL Ott
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Interferon stimulated gene 17 (ISG17) and Mx are up-regulated in the ruminant uterus in response to interferon-tau (IFNtau) during early pregnancy. Recent evidence strongly indicates that expression of ISGs occur only in stroma (ST) and glandular epithelium (GE) during this time as a result of transcriptional repression by interferon regulatory factor two (IRF-2) expression in the LE. The present report tested this hypothesis by examining mRNA and protein expression of ISG17 and Mx in serial uterine cross-sections obtained from cyclic and early pregnant ewes. In situ and immunocytochemical analysis revealed that ISG17 mRNA and protein were low to undetectable, whereas Mx mRNA was expressed in the lumenal (LE) and superficial GE at all days of the estrous cycle examined. Both ISG17 and Mx mRNA increased in the stratum compactum ST between Days 11 and 13, and expression extended into the deep GE and stratum spongiosum ST on Days 15 through 17 in pregnant ewes. Interestingly the Mx gene continued to be strongly expressed in LE and superficial GE through Day 17 of pregnancy, whereas ISG17 remained low to undetectable in these cells. Collectively, this study highlights the complexity of the uterine environment by unequivocally illustrating differential temporal and spatial expression of the IFN-responsive genes ISG17 and Mx.

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TY Tai
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JY Lu
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CL Chen
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MY Lai
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PJ Chen
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JH Kao
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CZ Lee
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HS Lee
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LM Chuang
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YM Jeng
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This study aimed at elucidating the effects of interferon (IFN)-alpha on glucose metabolism in patients with chronic hepatitis B and C infections. Twenty-eight biopsy-proven patients with chronic hepatitis B (ten cases) and hepatitis C (18 cases) were given IFN-alpha for a total of 24 weeks. The patients received a 75 g oral glucose tolerance test (OGTT), glucagon stimulation test, tests for type 1 diabetes-related autoantibodies and an insulin suppression test before and after IFN-alpha therapy. Ten of the 28 patients responded to IFN-alpha therapy. Steady-state plasma glucose of the insulin suppression test decreased significantly in responders (13.32+/-1.48 (S.E.M.) vs 11.33+/-1.19 mmol/l, P=0.0501) but not in non-responders (12.29+/-1.24 vs 11.11+/-0.99 mmol/l, P=0.2110) immediately after completion of IFN-alpha treatment. In the oral glucose tolerance test, no significant difference was observed in plasma glucose in either responders (10.17+/-0.23 vs 10.03+/-0.22 mmol/l) or non-responders (10.11+/-0.22 vs 9.97+/-0.21 mmol/l) 3 Months after completion of IFN-alpha treatment. However, significant differences were noted in C-peptide in both responders (2.90+/-0.13 vs 2.20+/-0.09 nmol/l, P=0.0040) and non-responders (2.45+/-0.11 vs 2.22+/-0.08 nmol/l, P=0.0287) before vs after treatment. The changes of C-peptide in an OGTT between responders and non-responders were also significantly different (P=0.0028), with responders reporting a greater reduction in C-peptide. No case developed autoantibodies during the treatment. In patients who were successfully treated with IFN-alpha, insulin sensitivity improved and their plasma glucose stayed at the same level without secreting as much insulin from islet beta-cells.

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Madan L Nagpal
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Yue Chen
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Tu Lin
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conserved cysteines, 9–36 and 11–53, that form disulfide bonds ( Booth et al. 2002 ). It has been well documented that interferon (IFN)-γ and tumor necrosis factor (TNF)-α secreted by macrophages induce IP-10 (interferon-γ-inducible protein 10

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Kouki Mori Division of Nephrology, Endocrinology and Vascular Medicine and
Division of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

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Katsumi Yoshida Division of Nephrology, Endocrinology and Vascular Medicine and
Division of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

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Ayumi Komatsu Division of Nephrology, Endocrinology and Vascular Medicine and
Division of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

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Jun-ichi Tani Division of Nephrology, Endocrinology and Vascular Medicine and
Division of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

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Yoshinori Nakagawa Division of Nephrology, Endocrinology and Vascular Medicine and
Division of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

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Saeko Hoshikawa Division of Nephrology, Endocrinology and Vascular Medicine and
Division of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

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Sadayoshi Ito Division of Nephrology, Endocrinology and Vascular Medicine and
Division of Rheumatology and Hematology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan

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augments interferon-γ (IFNγ)-induced class II major histocompatibility complex (MHC) antigen expression ( Weetman & Rees 1988 , Zakarija et al. 1988 ). In FRTL-5 rat thyroid cells, TNFα induces interferon regulatory factor-1 ( Mori et al. 1999 ), which

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Hyungchul Han Department of Animal Science, University of Wyoming, Laramie, Wyoming 82071, USA
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA

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Kathleen J Austin Department of Animal Science, University of Wyoming, Laramie, Wyoming 82071, USA
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA

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Lea A Rempel Department of Animal Science, University of Wyoming, Laramie, Wyoming 82071, USA
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA

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Thomas R Hansen Department of Animal Science, University of Wyoming, Laramie, Wyoming 82071, USA
Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, Colorado 80523, USA

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uterus. Interferon (IFN)-τ is a major paracrine signal that is produced by the bovine conceptus and acts on the endometrium to elicit secondary responses that are necessary to maintain pregnancy ( Roberts et al. 1992 , Thatcher et al. 1995 , Spencer

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