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      Nonproliferative and Proliferative Lesions of the Rat and Mouse Endocrine System

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          Abstract

          The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is a joint initiative among the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the endocrine organs (pituitary gland, pineal gland, thyroid gland, parathyroid glands, adrenal glands and pancreatic islets) of laboratory rats and mice, with color photomicrographs illustrating examples of the lesions. The standardized nomenclature presented in this document is also available electronically on the internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and aging lesions as well as lesions induced by exposure to test materials. A widely accepted and utilized international harmonization of nomenclature for endocrine lesions in laboratory animals will decrease confusion among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists.

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          Most cited references166

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          Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009.

          Different types of cell death are often defined by morphological criteria, without a clear reference to precise biochemical mechanisms. The Nomenclature Committee on Cell Death (NCCD) proposes unified criteria for the definition of cell death and of its different morphologies, while formulating several caveats against the misuse of words and concepts that slow down progress in the area of cell death research. Authors, reviewers and editors of scientific periodicals are invited to abandon expressions like 'percentage apoptosis' and to replace them with more accurate descriptions of the biochemical and cellular parameters that are actually measured. Moreover, at the present stage, it should be accepted that caspase-independent mechanisms can cooperate with (or substitute for) caspases in the execution of lethal signaling pathways and that 'autophagic cell death' is a type of cell death occurring together with (but not necessarily by) autophagic vacuolization. This study details the 2009 recommendations of the NCCD on the use of cell death-related terminology including 'entosis', 'mitotic catastrophe', 'necrosis', 'necroptosis' and 'pyroptosis'.
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            Increased number of islet-associated macrophages in type 2 diabetes.

            Activation of the innate immune system in obesity is a risk factor for the development of type 2 diabetes. The aim of the current study was to investigate the notion that increased numbers of macrophages exist in the islets of type 2 diabetes patients and that this may be explained by a dysregulation of islet-derived inflammatory factors. Increased islet-associated immune cells were observed in human type 2 diabetic patients, high-fat-fed C57BL/6J mice, the GK rat, and the db/db mouse. When cultured islets were exposed to a type 2 diabetic milieu or when islets were isolated from high-fat-fed mice, increased islet-derived inflammatory factors were produced and released, including interleukin (IL)-6, IL-8, chemokine KC, granulocyte colony-stimulating factor, and macrophage inflammatory protein 1alpha. The specificity of this response was investigated by direct comparison to nonislet pancreatic tissue and beta-cell lines and was not mimicked by the induction of islet cell death. Further, this inflammatory response was found to be biologically functional, as conditioned medium from human islets exposed to a type 2 diabetic milieu could induce increased migration of monocytes and neutrophils. This migration was blocked by IL-8 neutralization, and IL-8 was localized to the human pancreatic alpha-cell. Therefore, islet-derived inflammatory factors are regulated by a type 2 diabetic milieu and may contribute to the macrophage infiltration of pancreatic islets that we observe in type 2 diabetes.
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              Very slow turnover of beta-cells in aged adult mice.

              Although many signaling pathways have been shown to promote beta-cell growth, surprisingly little is known about the normal life cycle of preexisting beta-cells or the signaling pathways required for beta-cell survival. Adult beta-cells have been speculated to have a finite life span, with ongoing adult beta-cell replication throughout life to replace lost cells. However, little solid evidence supports this idea. To more accurately measure adult beta-cell turnover, we performed continuous long-term labeling of proliferating cells with the DNA precursor analog 5-bromo-2-deoxyuridine (BrdU) in 1-year-old mice. We show that beta-cells of aged adult mice have extremely low rates of replication, with minimal evidence of turnover. Although some pancreatic components acquired BrdU label in a linear fashion, only 1 in approximately 1,400 adult beta-cells were found to undergo replication per day. We conclude that adult beta-cells are very long lived.
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                Author and article information

                Journal
                J Toxicol Pathol
                J Toxicol Pathol
                TOX
                Journal of Toxicologic Pathology
                Japanese Society of Toxicologic Pathology
                0914-9198
                1881-915X
                28 July 2018
                2018
                : 31
                : 3 Suppl
                : 1S-95S
                Affiliations
                [1 ]Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center, Basel, Switzerland
                [2 ]Boehringer Ingelheim Pharma, Biberach an der Riss, Germany
                [3 ]Compugen, Inc., Nonclinical Safety, South San Francisco, California, USA
                [4 ]BioMarin Pharmaceuticals Inc., San Rafael, California, USA
                [5 ]Merck KGaA, D64293 Darmstadt, Germany
                [6 ]In Vivo Animal Core, Unit for Laboratory Animal Medicine, University of Michigan Medical School, Ann Arbor, Michigan USA
                [7 ]AbbVie, Preclinical Safety, North Chicago, Illinois, USA
                [8 ]Covance, Chantilly, Virginia, USA
                [9 ]Fraunhofer ITEM, Department of Pathology, Hannover, Germany
                [10 ]Iwate University, Faculty of Agriculture, Iwate, Japan
                [11 ]Bayer CropScience, Sophia-Antipolis, Cedex, France
                [12 ]AstraZeneca Pathology, Drug Safety and Metabolism, IMED Biotech Unit, Gothenburg, Sweden
                [13 ]Tohkai Cytopathology Institute, Cancer Research and Prevention, Gifu, Japan
                [14 ]LSI Medience Corporation, Nonclinical Research Center, Ibaraki, Japan
                [15 ]Toxicology & Pathology Consulting, LLC, Ann Arbor, Michigan, USA
                [16 ]Ohio University, Department of Biomedical Sciences, Athens, Ohio, USA
                Author notes
                *Address correspondence to: Thomas J. Rosol, DVM, PhD, MBA, Department of Biomedical Sciences, Ohio University, 1 Ohio University, Athens, Ohio, 45701, USA. e-mail: rosolt@ 123456ohio.edu
                Article
                2017-I001
                10.1293/tox.31.1S
                6108091
                30158740
                ff3d1a69-71c0-44af-9485-83770dd1b2b9
                ©2018 The Japanese Society of Toxicologic Pathology

                This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.

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                Pathology
                diagnostic pathology,nomenclature,pituitary,pituicytes,hypophysis,pineal,pinealocytes,thyroid,follicular cells,c cells,parathyroid,chief cells,adrenal,cortical cells,medullary cells,pancreas,islets,islets of langerhans

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