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J. M. Conlon
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L. Grimelius
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G. Wallin
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L. Thim
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ABSTRACT

An extract of a tumour metastases from a human medullary thyroid carcinoma contained a high concentration (at least 2·9 nmol/g wet weight) of the immunoregulatory peptide, thymosin-β4. The peptide was isolated as a mixture of two components with free and blocked NH2-terminal amino acid residues, the latter form predominating (approximately 98% of the total). The primary structure of the peptide was established by automated Edman degradation after cleavage with cyanogen bromide. The amino acid sequence of human thymosin-β4 was identical to thymosin-β4 previously isolated from calf thymus. Further studies are warranted to determine whether thymosin-β4 production is a useful marker for thyroid and other tumours.

J. Endocr. (1988) 118, 155–159

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G. Millington
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J. C. Buckingham
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Introduction

Communication between the neuroendocrine and immune systems is crucial to host defence in both health and disease for it provides a humoral means whereby the central nervous system may fine tune the immune system and thereby bring to bear the influence of a variety of physical, emotional and environmental factors. In the past decade, several lines of communication between the two systems have been identified. These include direct autonomic innervation of lymphoid tissues and humoral factors derived from immune cells (e.g. cytokines, eicosanoids, peptides) and peripheral endocrine glands (e.g. peptides, steroids). Central to this complex interplay are the thymic hormones, a heterogeneous family of polypeptides produced by the thymic epithelium whose members include thymosin α1, thymosin β4, thymopoietin, thymulin, MB-35 and a number of less well-characterized peptides (Table 1). These peptides possess a spectrum of immunoregulatory properties. In addition, they provide the basis of a significant humoral

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C Giuliani Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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M Saji Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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I Bucci Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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G Fiore Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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M Liberatore Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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D S Singer Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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F Monaco Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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L D Kohn Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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G Napolitano Unit of Endocrinology, Department of Medicine and Sciences of Aging, University ‘G D’Annunzio’ and Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Campus Universitario, via Colle dell’Ara, 66013 Chieti, Italy
Arthur G Janes Cancer Center and Richard J Solove Research Institute, Ohio State University, Columbus, Ohio 43210, USA
Unit of Immuno-oncology Aging Research Center, Ce.S.I., ‘Gabriele D’Annunzio’ University Foundation, Chieti-Pescara, Italy
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Edison Biotechnology Institute and Department of Biomedical Sciences, College of Osteopathic Medicine, Ohio University, Athens, Ohio 45701, USA

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, thymosin α1 and α,γ-interferons, also regulate MHC class I expressions in thyroid cells ( Saji et al. 1992 b , Giuliani et al. 2000 , Napolitano et al. 2000 , Grassadonia et al. 2004 ). We have previously defined the 5′ flanking region of

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Wenxia He Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan, Hubei 430072, People's Republic of China
Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan, Hubei 430072, People's Republic of China

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Xiangyan Dai Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan, Hubei 430072, People's Republic of China
Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan, Hubei 430072, People's Republic of China

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Xiaowen Chen Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan, Hubei 430072, People's Republic of China
Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan, Hubei 430072, People's Republic of China

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Jiangyan He Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan, Hubei 430072, People's Republic of China

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Zhan Yin Key Laboratory of Aquatic Biodiversity and Conservation of Chinese Academy of Sciences, University of Chinese Academy of Sciences, Institute of Hydrobiology, Chinese Academy of Sciences, 7 Donghu South Road, Wuhan, Hubei 430072, People's Republic of China

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90 sample) are summarized in Table 3 . Among the major secreted molecules and the molecules involved in the processing of protein secretion, only secretogranin III ( scg3 ), thymosin-β 15a ( tmsb15a ), neuromedin S ( nms ), ependymin ( epd

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Cesidio Giuliani
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Ines Bucci
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Valeria Montani
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Dinah S Singer Unit of Endocrinology, Experimental Immunology Branch, Department of Biomedical Sciences, Department of Medicine and Sciences of Aging, University ‘G. D'Annunzio’ and Aging Research Center (Ce.S.I.), ‘Gabriele D'Annunzio’ University Foundation, via Colle dell'Ara, Chieti-Pescara, 66013 Chieti, Italy

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Fabrizio Monaco
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Leonard D Kohn Unit of Endocrinology, Experimental Immunology Branch, Department of Biomedical Sciences, Department of Medicine and Sciences of Aging, University ‘G. D'Annunzio’ and Aging Research Center (Ce.S.I.), ‘Gabriele D'Annunzio’ University Foundation, via Colle dell'Ara, Chieti-Pescara, 66013 Chieti, Italy

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Giorgio Napolitano
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Vincenzo S D'Agostini C Grelli S Bucci I Singer DS Kohn LD Monaco F 2000 Thymosin-α1 regulates MHC class-I expression in FRTL-5 cells at a transcriptional level . European Journal of Immunology 30 778 – 786 . Giuliani C Noguchi Y

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A Hourvitz Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

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E Gershon Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

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J D Hennebold Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

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S Elizur Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

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E Maman Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

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C Brendle Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

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E Y Adashi Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

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N Dekel Division of Reproductive Sciences, Department of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake City, Utah 84132, USA
Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel

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X16053 Mouse mRNA for thymosin beta-4 98% 0 2-B9 NM_008218 Mus musculus

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