Browsing by Author "Ural, Mustafa Numan"
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Item ADAMTS4, 5, 9, and 15 expressions in the autopsied brain of patients with Alzheimer’s disease: A preliminary immunohistochemistry study(Küre İletişim Grubu, 2015-07-06) Pehlivan, Sultan; Eren, Bülent; Akyol, Sümeyya; Eren, Filiz; Tagil, Süleyman Murat; Demircan, Kadir; Fedakar, Recep; İnanır, Nursel Türkmen; Gürses, Murat Serdar; Ural, Mustafa Numan; Uludağ Üniversitesi/Tıp Fakültesi/Adli Tıp Anabilim Dalı.; 0000-0002-9982-0476; AAC-8913-2020; AAH-6287-2021; 8725968900; 56712925300; 55979536300; 57163358100Objective: 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.Item Adli otopsilerde hipokampüs doku örneklerinde skleroz ve demir birikiminin değerlendirilmesi(Uludağ Üniversitesi, 2016) Ural, Mustafa Numan; Durak, Dilek; Uludağ Üniversitesi/Tıp Fakültesi/Adli Tıp Anabilim Dalı.Genellikle şiddetli hafıza kaybı veya kognitif fonksiyonlarında gerileme şikayeti olan yaşlı bireylerde nadiren otopsilerde tespit edilen hipokampal skleroz hipokampusun subikulum ve cornu ammoniste selektif nöronal hücre kaybı ve astro/fibriler gliozis ile karakterizedir. Demir birikimi ise reaktif oksijen türlerinin aşırı üretilmesine, protein agregasyonuna, DNA ve fosfolipid oksidasyonuna neden olarak etkilenen beyin bölgelerinde hücre hasarı ve nöron dejenerasyonuna sebep olmaktadır. Çalışmamızda hipokampal skleroz ve demir birikimi ile adli otopsilerdeki ölüm nedenleri, yaşlanma, nörodejeneratif ve psikiyatrik hastalıklar arasındaki ilişkinin tespit edilmesi amaçlandı. Bu çalışmaya Adli Tıp Kurumu Bursa Grup Başkanlığı Morg İhtisas Dairesi'nde 2015 yılında yapılan 1650 adli otopsi olgusu içerisinden 109 olgu dahil edildi. Histopatolojik değerlendirme için hazırlanan parafin bloklardan alınan kesitler skleroz için hemotoksilen eozin ile boyandıktan sonra aynı bloklardan alınan yeni kesitlere Perls' metodu ile demir boyama uygulandı. Olgularımızın 19'unda (%17,4) hipokampal skleroz, 8'inde (%7,3) demir boyanma saptandı. Skleroz ve demir boyanma saptanan olguların yaş ortalaması sırasıyla 51,57 ± 20,45 ve 54,87 ± 14,31 yıl idi. Ayrıca, skleroz saptanan olguların 4'ünde demir boyanma mevcuttu. Çalışmamızdaki 10 olguda depresyon öyküsü bulunmakta olup 3'ünde (%30) hipokampal bölgede demir boyanma saptandı. Sonuç olarak, çalışmamızda hipokampüste skleroz ve demir birikimi saptanan adli olguların daha yaşlı olduğu ancak ölüm nedenleri ve nörodejeneratif hastalıklar ile skleroz ve demir birikimi arasında anlamlı bir ilişki olmadığı görüldü. Bununla birlikte, depresyon öyküsü bulunan olgularda hipokampal demir birikimi anlamlı olarak yüksek bulundu. Hipokampal skleroz ve demir birikiminin ölüm nedenleri, yaşlanma, nörodejeneratif ve psikiyatrik hastalıklar ile ilişkili olup olmadığının tespiti için daha geniş olgu serileri ve daha kapsamlı faktörlerin sorgulanması gerektiği kanısındayız.Item Pathophysiological function of ADAMTS enzymes on molecular mechanism of Alzheimer's disease(Int Soc Aging & Disease, 2016-01-11) Güleç, Mehmet Akif; Akyol, Ömer; Akyol, Sümeyya; Gürses, Murat Serdar; Ural, Mustafa Numan; Uludağ Üniversitesi/Tıp Fakültesi/Adli Tıp Anabilim Dalı.; 0000-0002-9982-0476; AAC-8913-2020; 55979536300; 57163358100The extracellular matrix (ECM) is an environment that has various enzymes attended in regeneration and restoration processes which is very important to sustain physiological and biological functions of central nervous system (CNS). One of the participating enzyme systems in ECM turnover is matrix metalloproteinases. A disintegrin-like and metalloproteinase with thrombospondin type 1 motifs (ADAMTS) is a unique family of ECM proteases found in mammals. Components of this family may be distinguished from the ADAM (A Disintegrin and Metalloproteinase) family based on the multiple copies of thrombospondin 1-like repeats. The considerable role of the ADAMTS in the CNS continues to develop. Evidences indicate that ADAMTS play an important role in neuroplasticity as well as nervous system pathologies such as Alzheimer's disease (AD). It is hopeful and possible that ADAMTS family members may be utilized to develop therapies for CNS pathologies, ischemic injuries, neurodegenerative and neurological diseases. To understand and provide definitive data on ADAMTS to improve structural and functional recovery in CNS injury and diseases, this review aimed to enlighten the subject extensively to reach certain information on metalloproteinases and related molecules/enzymes. It will be interesting to examine how ADAMTS expression and action would affect the initiation/progression of above-mentioned clinical situations, especially AD.Item The role of ADAMTS1 and versican in human myocardial infarction: A postmortem study(Oxford University, 2016-08) Pehlivan, Sultan; Akyol, Sümeyya; Eren, Filiz; Güleç, Mehmet Akif; Eren, Bülent; Demircan, Kadir; Akyol, Ömer; Gürses, Murat Serdar; Ural, Mustafa Numan; İnanır, Nursel Türkmen; Fedakar, Recep; Uludağ Üniversitesi/Tıp Fakültesi/Adli Tıp Anabilim Dalı.; 0000-0002-9982-0476; 0000-0002-4047-6455; AAH-6287-2021; AAC-8913-2020; 55979536300; 57163358100; 57188706721; 8725968900Objective: 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.