Araştırma Çıktıları

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    Loss-of-Function Mutations in ELMO2 Cause Intraosseous Vascular Malformation by Impeding RAC1 Signaling
    (CELL PRESS, 2016-01-01) Cetinkaya, Arda; Xiong, Jingwei Rachel; Vargel, Ibrahim; Kosemehmetoglu, Kemal; Canter, Halil Ibrahim; Gerdan, Omer Faruk; Longo, Nicola; Alzahrani, Ahmad; Camps, Mireia Perez; Taskiran, Ekim Zihni; Laupheimer, Simone; Botto, Lorenzo D.; Paramalingam, Eeswari; Gormez, Zeliha; Uz, Elif; Yuksel, Bayram; Ruacan, Sevket; Sagiroglu, Mahmut Samil; Takahashi, Tokiharu; Reversade, Bruno; Akarsu, Nurten Ayse
    Vascular malformations are non-neoplastic expansions of blood vessels that arise due to errors during angiogenesis. They are a heterogeneous group of sporadic or inherited vascular disorders characterized by localized lesions of arteriovenous, capillary, or lymphatic origin. Vascular malformations that occur inside bone tissue are rare. Herein, we report loss-of-function mutations in ELMO2 (which translates extracellular signals into cellular movements) that are causative for autosomal-recessive intraosseous vascular malformation (VMOS) in five different families. Individuals with VMOS suffer from life-threatening progressive expansion of the jaw, craniofacial, and other intramembranous bones caused by malformed blood vessels that lack a mature vascular smooth muscle layer. Analysis of primary fibroblasts from an affected individual showed that absence of ELMO2 correlated with a significant downregulation of binding partner DOCK1, resulting in deficient RAC1-dependent cell migration. Unexpectedly, elmo2-knockout zebrafish appeared phenotypically normal, suggesting that there might be human-specific ELMO2 requirements in bone vasculature homeostasis or genetic compensation by related genes. Comparative phylogenetic analysis indicated that elmo2 originated upon the appearance of intramembranous bones and the jaw in ancestral vertebrates, implying that elmo2 might have been involved in the evolution of these novel traits. The present findings highlight the necessity of ELMO2 for maintaining vascular integrity, specifically in intramembranous bones.
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    Generation of Bone Tissue Using Adipose Tissue-derived Stem Cells
    (BEZMIALEM VAKIF UNIV, 2021-01-01) Baygol, Emre Gonenc; Guneren, Ethem; Karaaltin, Mehmet Veli; Canter, Halil Ibrahim; Ozturk, Kahraman; Ovali, Ercument; Ozpur, Mustafa Aykut; Yildiz, Kemalettin; Eyuboglu, Fatma
    Objective: Bone grafts and even bone substitutes do not meet all of the requirements of bony reconstructions. The aim of this study was to generate bone tissue from autologous adipose tissue-derived mesenchymal stem cells (ATDMSCs) and decellularised bone allografts. Methods: A 1.5 cm bone defect developed in the middle third of the rabbit's ulna. Reconstructions were carried out using miniplate and screws and interpositional autogenous bone grafts according to the designs of the groups: (1) No touch, (2) cryopreserved, (3) decellularised and (4) ATDMSCs-implanted decellularised bones. Before implantation, ATDMSCs in the last group were labelled with Q-dot and identified microscopically. Results: Graft recovery and irregular callus formation were observed in the first, second and forth groups. In the first group, the organisation of Haversian systems, the structure of the lacunae and the presence of canaliculi ossiums were observed
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    Reliability of Measurements on Plaster and Digital Models of Patients with a Cleft Lip and Palate
    (AVES, 2019-01-01) Yilmaz, R. Burcu Nur; Cakan, Derya Germec; Altay, Merve; Canter, Halil Ibrahim
    Objective: The purpose of this study was to determine (1) the more and less reliable measurements/methods and (2) the influence of knowledge and skill on the inter-examiner, intra-examiner, and inter-method reliability of nasolabial measurements on plaster casts and three dimensional (3D) stereophotogrammetric images of casts in infants with an unrepaired unilateral cleft lip and palate (UUCLP). Methods: Preoperative extraoral plaster casts from 42 patients with UUCLP were measured with a digital caliper, and the image acquisition of casts was performed with the 3dMDface stereophotogrammetry system (3dMD, Atlanta, GA). Two examiners (one post-graduate student, one lecturer) evaluated 19 nasolabial measurements in two separate sessions. Results: Intra-rater, inter-rater, and inter-method reliability was lower in measurements of nasal, philtral, and nasal floor width. Almost all of the interclass correlation coefficients (ICC) for measurements performed by the lecturer were above 0.75, whereas the intra-examiner reliability of some measurements performed by the postgraduate student showed low ICC (< 0.75). Conclusion: Measurements of curving slopes, such as nasal width, of small dimensions, such as nostril floor width, and deformity-affected anatomic parts, such as philtrum width, presented a low reliability. Measurements on 3D images showed a higher reliability compared to plaster model measurements performed by the postgraduate student. Therefore, it may be recommended to use 3D digital images of infants with CLP for nasolabial measurements especially if performed in postgraduate settings.