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    ADAMTS4, 5, 9, and 15 Expressions in the Autopsied Brain of Patients with Alzheimer's Disease: A Preliminary Immunohistochemistry Study
    (Kure Iletisim Grubu A S, 2016) Pehlivan, Sultan; Fedakar, Recep; Eren, Bulent; Akyol, Sumeyya; Eren, Filiz; Inanir, Nursel Turkmen; Gurses, Murat Serdar
    Objective: Recent studies performed in the central nervous system highlight the pathophysiological relevance of A disintegrin-like and metalloproteinase with thrombospondin motifs (ADAMTS) genes and their protein products. The determination of alterations in expression profiles of ADAMTS family genes in Alzheimer's disease (AD) patients may contribute to the explanation of tissue pathology and also new ideas for remedial approaches for this incurable but preventable disease. Therefore, the goal of this study was to describe and identify the distribution, characteristics, and any changes in the expression, in other words, immunoreactivity, for aggrecanases (ADAMTS4, 5, 9, and 15) proteins in AD brain. Methods: Nine cases that were autopsied in the Council of Forensic Medicine, Bursa Morgue Department in 2013, were selected. All of the cases were sent for autopsy to the institution within 8 hours after death. At autopsy, tissue samples were obtained for histopathological examination of organs for determining the cause of death. Out of these, two cases were diagnosed with AD by neurologists when they were alive. Immunohistochemical staining was performed on the brain slides by using relevant primary and secondary antibodies against aggrecanase proteins. All images were acquired using a X200 objective of a microscope (Olympus BX53) and evaluated by the staining intensity using a semi-quantitative scoring system. Results: ADAMTS4 and 5 were slightly under-expressed in the brains from autopsied AD cases compared to those of control brains and suggested that extracellular matrix (ECM) degradation was not endorsed in AD brain. On the other hand, ADAMTS9 and 15 aggrecanases were not found to be expressed in correspondent brain sections of AD and control cases. Conclusion: The current study demonstrated that some aggrecanases were found to be under-expressed in AD brains. Additional studies in which all ADAMTS enzymes will be studied in terms of mRNA and protein levels are needed to understand the relative contributions of ADAMTS genes and proteins in AD brains.
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    Immunohistochemical Determination of HIF, TSP-1, ADAMTS1, and ADAMTS8 Expressions in the Brains of Alzheimer's Disease Patients: A Preliminary Autopsy Study
    (Erciyes Univ Sch Medicine, 2016) Inanir, Nursel Turkmen; Eren, Filiz; Fedakar, Recep; Eren, Bulent; Demircan, Kadir; Gurses, Murat Serdar; Ural, Mustafa
    Objective: Alzheimer's disease (AD) is a progressive neurodegenerative disease that mostly affects the elderly population. Recent studies performed in AD highlight the pathophysiological relevance of disintegrin and metalloproteinase with thrombospondin type 1-like motifs (ADAMTS) genes and their products, namely hypoxia inducible factor-1 (HIF-1) and thrombospondin-1 (TSP-1). Thus, the aim of this study was to describe and identify the distribution, characteristics, and any changes in the expression and immunoreactivity for HIF-1, TSP-1, and ADAMTS1 and 8 in AD brains. Materials and Methods: Nine patients who were autopsied in the Council of Forensic Medicine, Bursa Morgue Department in 2013, were selected. All patients were sent for autopsy to the Morgue Department within 8 h after death. At the autopsy, tissue samples of the organs were obtained for histopathological examination for determining the cause of death. Among these, two patients were clinically diagnosed with AD. Results: Immunohistochemical staining was performed, and the staining intensity/extensity was evaluated using a semi-quantitative scoring system. Median distribution (extensity) scores of the immunohistochemical staining were estimated as 2 for HIF-1, 0.67 for TSP-1, 3.11 for ADAMTS1, and 2.78 for ADAMTS8. Intensity scores were estimated as 1.22 for HIF-1, 0.56 for TSP-1, 3 for ADAMTS1, and 2.11 for ADAMTS8. Conclusion: Our study suggests that ADAMTS1 and ADAMTS8 expressions are not specific for AD. To understand and provide definitive data on all aspects of metalloproteinases, extracellular matrix proteins, and transcriptional factor effects to AD, further studies are needed, where other metalloproteinases and related molecules/enzymes should be studied.
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    The Role of ADAMTS1 and Versican in Human Myocardial Infarction: A Postmortem Study
    (Oxford Univ Press, 2016) Pehlivan, Sultan; Gurses, Murat Serdar; Ural, Mustafa Numan; Akyol, Sumeyya; Eren, Filiz; Inanir, Nursel Turkmen; Gulec, Mehmet Akif
    Objective: To determine the role of a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) and fragmented versican in the myocardial infarction (MI) process in humans and to evaluate the diagnostic efficacy of ADAMTS1 for postmortem diagnosis of MI. Methods: Thirty autopsied individuals were allocated into 2 groups, namely, a study group of individuals who died of myocardial infarction (n = 20), and a control group who died of trauma (n = 10). We performed standard immunohistochemical staining on myocardial tissue specimens, studying anti-ADAMTS1, anti-versican, and anti-versican C terminal peptide sequence (DPEAAE) fragments. Results: Strong, diffuse staining was observed throughout myocardial tissue for ADAMTS1 in the 2 groups. However, in the study group, we observed no expression for ADAMTS1 around fibrotic areas but detected slight staining in coagulative and necrotic zones. Conclusion: Similar localizations of ADAMTS and fragmented versican in human heart tissue indicate that versican presumably is cleaved by ADAMTS1. Hence, ADAMTS1 can be regarded as a new marker for postmortem differential diagnosis of MI.