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Trichorhinophalangeal syndrome is a rare autosomal dominant disorder characterized by distinctive craniofacial and skeletal abnormalities. This study aimed to delineate the trichorhinophalangeal syndrome phenotype and to compare the clinical and molecular findings between trichorhinophalangeal syndrome types I and II.A total of 22 trichorhinophalangeal syndrome patients aged 0.9-45 years from 17 families were enrolled. Nineteen patients were diagnosed with trichorhin ophalangeal syndrome I and 3 with trichorhinophalangeal syndrome II. Genetic analyses were made by TRPS1 sequencing and/or chromosomal microarray analyses.A novel frameshift variant (c.531_532del), a known missense variant, and whole-gene deletions were the pathogenic TRPS1 variants detected in trichorhinophalangeal syndrome I. Three trichorhinophalangeal syndrome II patients had large deletions with variable breakpoints involving the TRPS1-EXT1 interval. All patients had the typical craniofacial findings of trichorhinophalangeal syndrome such as a pear-shaped nose, long philtrum, and thin upper lip, as well as cone-shaped epiphyses. Sparse hair and eyebrows (20/22), short metacarpals and metatarsals (20/22), and small hands (19/22) were common. While craniofacial and limb abnormalities were similar in trichorhinophalangeal syndrome I and II, 3 of 19 trichorhinophal angeal syndrome I patients had mild, and 2 of 3 trichorhinophalangeal syndrome II patients had severe intellectual disability. Three trichorhinophalangeal syndrome II patients including the patient with the EXT1 deletion beginning from exon 2 had exostoses. In trichorhinophal angeal syndrome II, although microdeletion sizes and facial or skeletal features were not correlated, patients with larger deletions had severe intellectual disability.This study has expanded the existing knowledge on the phenotype-genotype spectrum in trichorhinophalangeal syndrome. We suggest including the EXT1 gene partially in the minimal critical region for trichorhinophalangeal syndrome II.

Protoporphyrin IX (PpIX), which is an efficient photosensitive agent, cannot be used directly in photodynamic therapy due to its aggregation in physiological environment. If PpIX is made water-soluble without losing its photosensitive properties, it can be used in many medical fields, including cancer treatment. Here we report synthesis of PpIX homologue with mPEG550 (Porfipeg) and its photodynamic effects on both in-vitro and in-vivo environment. Porfipeg is synthesized to give PpIX the ability to dissolve in water. Spectrometric (FT-IR, NMR, MS, UV-vis and Fluorescence) measurements were performed. Porfipeg can penetrate into the cells and indicates no cytotoxicity in the dark whereas cell viability significantly reduced with light irradiation. The cells can be visualized by fluorescence microscope. In-vivo experiment revealed that intravenous injection of Porfipeg is more efficient than intraperitoneal injection for the acute photodynamic effects within 30 min. Moreover it is excreted by the kidneys. In conclusion, Porfipeg has remarkable potentials to be used in both fluorescence guidance in surgeries and photodynamic therapy for cancer treatment.

Colorectal cancer is one of the most common types of cancer. Drug resistance and drug-induced damage of healthy tissues are major obstacles in cancer treatment. Therefore, to develop efficient anticancer therapy, it is necessary to find compounds that affect tumor cells, but do not exhibit toxicity to healthy cells. Caffeic acid phenethyl ester (CAPE) has been demonstrated to have anticancer properties in many types of cancer. In this study, the cytotoxic and apoptotic effects of CAPE on the RKO colorectal cancer cell line and CCD 841-CoN normal colorectal cell line was investigated. In addition, changes in the survivin expression were determined. According to the results, CAPE decreased cell viability in the RKO cell line in a dose-dependent manner. Likewise, CAPE induced apoptotic cell death in approximately 40% of the RKO cells. Furthermore, CAPE treatment increased the Serine 15 (Ser15) and Serine 46 (Ser46) phosphorylation of p53, while decreased the survivin expression. The results suggested that CAPE induced apoptosis by regulating p53 phosphorylation, leading to inhibition of the survivin expression. In accordance with the results, it is suggested that CAPE might be evaluated as an alternative drug in cancer therapy and further investigation is needed within this scope.

A new silicon phthalocyanine with piperazine-furan ring and its quaternized form were synthesized. All compounds were analyzed by spectroscopic techniques (FT-IR, H-1-NMR, MS, and UV-vis), and the absorbance characteristics of silicon phthalocyanines were evaluated with the expected strong typical absorption bands in the far-red spectrum. The cytotoxic effects of these phthalocyanines induced by photodynamic therapy (PDT) were determined in a dose-dependent manner. Following cytotoxicity analysis, flow cytometric research of cell death was performed. The formation of reactive oxygen species (ROS) was determined by confocal microscopy. High levels of cytotoxicity and decreased viable cell population have been detected in cancer cells after treatment. In addition, ROS formation was observed in PDT treated cancer cells. However, low levels of cell death and ROS formation were observed in non-tumorigenic cells. According to western blot data, PDT-mediated treatment was found to provide different expression patterns of the cleaved PARP1 protein. The presented study demonstrates that PDT-mediated treatment of newly synthesized phthalocyanines has significant anti-cancer effects on breast cancer cells and may induce different cell death pathways.

Pontocerebellar hypoplasia consists of a rare heterogeneous group of congenital neurodevelopmental disorders characterized by hypoplasia and atrophy of the cerebellar cortex, dentate and pontine nuclei, and inferior olives. The very low density lipoprotein receptor protein is an integral part of the reelin signaling pathway, which guides neuroblast migration in the cerebral cortex and cerebellum. Mutations in this receptor cause nonprogressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia. In this report, we present 3 patients from 2 different families displaying very low density lipoprotein receptor–associated pontocerebellar hypoplasia, cortical dysplasia, mental retardation, and bipedal gait. One of the siblings has also displayed dysmorphic features, as we previously reported before the identification of the genetic defect in this family.

Purpose: Fluorescence in situ hybridization (FISH) is a powerful tool for quantitative analysis of chromosomes and genes and can be applied in a variety of specimens, including cell cultures, isolated nuclei from fresh and fixed tissues, and histological tissue sections. For detection of numerical chromosome aberrations, we examined prostatic cancer samples at our department. In addition, we also observed primary and secondary aberrations taking part in the initiation and progression of tumours. Materials and Methods: FISH using chromosome-specific α-satellite DNA probes for chromosomes 7, 8, 9, 10, 17, X and Y was performed on 19 prostatic cancer and 19 benign prostatic hyperplasia (BPH) samples obtained from transurethral resection (TUR) and archival paraffin-embedded blocks. Results: Numerical aberrations were observed in 41% of the tumours studied. A range of aberrant copy numbers of chromosome 9 (68%), 7 (63%), 8 (58%), 17 (37%), Y (32%) and 10 (26%) was observed. We did not observe significant aberrations in BPH samples. In prostate cancer patients, chromosomes 7 (47%), 8 (58%) and 9 (63%) were monosomic by FISH. Monosomy 8 and 9 were significant differences ( p >0.05) between prostate cancer and BPH patients. Conclusions: FISH analysis could be observed an one of strongest methods of analysis in detecting numerical aberrations of individual chromosomes with application to paraffin-block samples, metaphase and, interphase nuclei. To our knowledge, this analysis is firstly studied in Turkish patients. Therefore, results of this analysis may be important for Turkish patients.

Purine biosynthesis and metabolism, conserved in all living organisms, is essential for cellular energy homeostasis and nucleic acids synthesis. The de novo synthesis of purine precursors is under tight negative feedback regulation mediated by adenosine and guanine nucleotides. We describe a new distinct early-onset neurodegenerative condition resulting from mutations in the adenosine monophosphate deaminase 2 gene (AMPD2). Patients have characteristic brain imaging features of pontocerebellar hypoplasia (PCH), due to loss of brainstem and cerebellar parenchyma. We found that AMPD2 plays an evolutionary conserved role in the maintenance of cellular guanine nucleotide pools by regulating the feedback inhibition of adenosine derivatives on de novo purine synthesis. AMPD2 deficiency results in defective GTP-dependent initiation of protein translation, which can be rescued by administration of purine precursors. These data suggest AMPD2-related PCH as a new, potentially treatable early-onset neurodegenerative disease.

Item does not contain fulltext The translation of "next-generation" sequencing directly to the clinic is still being assessed but has the potential for genetic diseases to reduce costs, advance accuracy, and point to unsuspected yet treatable conditions. To study its capability in the clinic, we performed whole-exome sequencing in 118 probands with a diagnosis of a pediatric-onset neurodevelopmental disease in which most known causes had been excluded. Twenty-two genes not previously identified as disease-causing were identified in this study (19% of cohort), further establishing exome sequencing as a useful tool for gene discovery. New genes identified included EXOC8 in Joubert syndrome and GFM2 in a patient with microcephaly, simplified gyral pattern, and insulin-dependent diabetes. Exome sequencing uncovered 10 probands (8% of cohort) with mutations in genes known to cause a disease different from the initial diagnosis. Upon further medical evaluation, these mutations were found to account for each proband's disease, leading to a change in diagnosis, some of which led to changes in patient management. Our data provide proof of principle that genomic strategies are useful in clarifying diagnosis in a proportion of patients with neurodevelopmental disorders.

Background and Aims An association of homozygous MTHFR 677T genotypes with elevated plasma homocysteine level has been documented, but results are still controversial. We aimed to investigate prevalence of the C677T polymorphism in patients with acute myocardial infarction (MI) in the Eastern Black Sea region of Turkey. Methods We studied genomic DNA of 231 unrelated patients (aged 59 ± 13 years; 175 male, 56 female) with first anterior acute MI and 242 healthy controls (aged 54 ± 19 years; 182 male, 60 female) using real-time polymerase chain reaction kits for the MTHFR C677T mutation. Results Prevalence of MTHFR C677T mutant genotype was 49.1% (CT: 45.8%, TT: 3.3%) in controls and 48.45% (CT: 38.5%, TT: 9.95%) in patients with acute MI. The TT mutation was more frequent in patients with acute MI than in controls (9.95 vs. 3.3%) (OR; 3.23, 95% CI; [1.34–8.05], p = 0.003). Conclusions The MTHFR gene homozygote TT mutation is a risk factor for patients with MI in the eastern Black Sea Turkish Population.

A newborn, who had the congenital anomalies including protuberance on the right lower leg, bilateral equinovarus deformity of the feet, genu valgum with knee flexion deformity, syndactyly between the first and the second digit on the right, in addition with the absence of the fifth digit. Echocardiography revealed a secundum type atrial septal defect. The combination of these congenital defects associated with developmental anomalies of lower extremities. We discuss the clinical, radiological findings and pathogenesis of this lower extremity malformation.

We report six patients with Cockayne syndrome type B without photosensitivity. The patients are from the same inbred family and exhibit variable clinical features. The main clinical manifestations were progressive encephalopathy including intracranial calcification and white-matter lesions, dwarfism without growth hormone deficiency, senile appearance, mental and motor retardation, atrophy of subcutaneous fat tissue, severe pectus carinatus, and spasticity. Clinical photosensitivity was not observed in any patient. Other clinical findings were cataract, pigmentary retinopathy, and peripheral neuropathy. The onset of the disease was between 3 and 6 months of age. Molecular genetic analyses in the family established linkage to ERCC6, the gene responsible for Cockayne syndrome type B, confirming the clinical diagnosis. ( J Child Neurol 2006;21:333—337; DOI 10.2310/7010.2006.00082).

The evaluation of multiple congenital abnormalities and/or mental retardation (MCA/MR) is always a challenge to clinicians. The recognition of specific physical or behavioral characteristics can vastly improve diagnostic yield. Chromosomal abnormalities account for a high percentage in the etiology of MCA/MR. In this study, frequency of chromosomal abnormalities was 4.81% of 457 patients. Chromosomal abnormalities and polymorphisms were detected in 65 (14.21%) (structural and numerical chromosomal abnormalities in 22 patients and polymorphisms in 43) of 457 MR and/or MCA patients. Our results show that chromosomal abnormalities contribute much to the causation of multiple malformations and/or MR. It is essential that fluorescence in situ hybridization (FISH) be used in conjunction with standard methods in order to maximize obtainable information for better management of patients with MR and/or MCA.

An increased incidence of sister chromatid exchanges (SCEs) in peripheral lymphocytes of operating room personnel exposed to waste anesthetic gases has been reported. We investigated whether the increase of SCEs in anesthesiologists was reversible. Twenty-five anesthesiologists exposed to waste anesthetic gases such as sevoflurane and nitrous oxide were compared with nonexposed internists working in the same hospital. The concentrations of sevoflurane and nitrous oxide in the operating rooms were measured. The incidence of SCE was measured in lymphocytes cultures of anesthesiologists before and after a 2-mo leave from the operating room. These values of SCE were compared with those of nonexposed physicians. Occupational exposure to sevoflurane and nitrous oxide in the operating rooms were above the threshold values. There was a significant difference in SCE values of the anesthesiologists compared with the nonexposed physicians (11.9 +/- 4.4 versus 4.2 +/- 1.1, P0.001). After a 2-mo leave from the operating room, the SCE values of the anesthesiologists were significantly lower compared with those taken before the leave (4.8 +/- 1.8 and 11.9 +/- 4.4, respectively, P0.001). We conclude that the increase of SCE in anesthesiologists exposed to increased environmental concentrations of waste anesthetics gases, such as sevoflurane and nitrous oxide, are reversible if they work free from exposure for 2 mo.

Objective To investigate the ratio of chromosomal abnormalities in recurrent fetal wastage. Study design We conducted a study of the cytogenetic data of 645 couples (1290 patients) with recurrent fetal wastage examined at the Department of Medical Biology and Genetics, Trabzon, Turkey. Couples who had first trimester miscarriages/abortion, preceded or followed by a second or third trimester fetal death/fetal abnormalities were recruited from Obstetrics and Gynecology Clinics for cytogenetics analysis. Results Chromosome abnormalities were found in 25 (3.86%) patients. The chromosomal abnormalities were structural (3.71%) and numerical (0.15%). Polymorphisms of heterochromatin blocks and inv(9) were shown in 115 (17.51%) patients. Conclusions Chromosome analyses are an important and necessary part of the etiological research in couples with recurrent fetal wastage.

We describe a 2-year-old female patient who had megaloblastic anaemia caused by selective vitamin B 12 malabsorption (Imerslund-Grasbeck syndrome) and del (21)(q22). To our knowledge, this is the first observation of Imerslund-Grasbeck syndrome associated with del(21)(q22) in the literature.

İnce bağırsak epiteli, basit yapısı ve sürekli yenilenme yeteneği sayesinde memeli yetişkin kök hücre çalışmalarında kullanılabilecek en uygun dokulardan biridir. İnce bağırsağın epitel yapısını kript ve villus yapıları oluşturmaktadır. Villuslar, alt mukozada bulunan kript adı verilen yapıda yerleşik kök hücre popülasyonundan sürekli olarak yenilenmektedir. Bu tez kapsamında, kök hücrelerin sürekli çoğalıp farklılaşma özelliğinden dolayı ince bağırsak epiteli şeçilmiştir. Kriptin yapısında bulunan kök hücreler etraflarındaki niş (mikroçevre) hücrelerinin desteğiyle fonksiyonlarını yerine getirmektedir. Bu nedenle, doku kültürü çalışmalarında, tek bir hücre tipi yerine doku oluşumunda rol alan farklı hücre gruplarıyla çalışılması gerekmektedir. Bilim adamları bu gibi durumlarda canlı model organizmalara yönelmektedirler. Canlı organizmalar üzerinde çalışma zorluklarının aşılmasına yönelik arayışlar, 3-boyutlu (3D) kültürler ile elde edilebilen organoid sistemlerinin oluşturulmasına yol açmıştır. Hedef organdan köken alan ve stroma oluşturma yeteneğine sahip kök hücrelere, gerekli koşulların sağlanmasıyla oluşturulan, minyatür organ benzeri yapılar, organoid olarak adlandırılır. Organoid sistemi ile çalışılacak dokunun yapısını oluşturan tüm hücrelerin aynı kültür ortamında üretilmesi sağlanmaktadır. Bu çalışmayla, 3-boyutlu kültür sisteminin kurulması ve organoid oluşturulması amaçlanmıştır. Organoid sisteminin kurulması ileride yapılacak, kript biyolojisi, kök hücre çalışmaları, markır gen arama ve anti kanser tedavilerinin geliştirilmesi gibi çalışmalar için, in vitro ortamda organın fizyolojik ortamının taklit edilebilmesi ve genetik dengesizlik oluşmadan uzun süre çoğaltılabilmesi gibi önemli avantajlar sağlayacağını düşünmekteyiz. Bu çalışmada, fare ince bağırsak kript yapısından izole edilen hücrelerden 3-boyutlu kültür ile in vitro ortamda organın minyatür hali olan, ince bağırsak organoidi oluşturulmuştur. Organoidlerin oluşturulması ve yeni çalışmaların planlanması, ülkemize ve üniversitemize dünyada son zamanlarda üzerinde çokça çalışmaların başlatıldığı ve gelişme gösteren bir konuya dahil olma şansı verecektir. Small intestinal epithelium is one of the most convenient tissue for mammalian adult stem cell studies thanks to its simple structure and rapidly regeneration ability. The intestinal epithelium consists of crypt and villus. Villus is enriched by several contiguous, proliferative 'crypt' compartments within the underlying submucosa. In this study, small intestine is chosen due to its property of rapidly proliferation and differentiation ability of stem cells. Tissue stem cells function with the support of niche (microenvironment) cells. Therefore, in tissue culture studies various cell types should be used rather than a single type of cells. Scientists trend to living organisms when they need this kind of situations. Challenges of studying with living organisms have led to the establishment of organoids which are obtained by three-dimensional cultures. Mini-organ like structures generated by providing necessary conditions for stem cells which are originated from target organs and able to form stroma, are called organoids. Organoid systems allow different cell types originated from same tissue to grow in the same culture dish.In this study it is aim to establish 3-dimensional culture system and organoid. To form the organoid system will provide significant benefits, such as modelling the physiological environment of an organ and long term replication without genetic instability for future studies including crypt biology, stem cell research and marker gene search, development of anti-cancer treatment, etc. In this study, we have been formed organoids from the cells isolated from mice intestine crypt structures using 3-dimensional culture techniques. We strongly suggest that establishment of organoids will contribute to our university, country and the studies which have been shown great progress and attracts growing interest in the world, recently. 71

Dünya sağlık örgütü (WHO) tarafından IV. derece (greyd) olarak sınıflandırılan Glioblastoma multiforme (GBM), glial kökenli, en sık ve malign tümörlerden biri olup tüm primer beyin tümörlerinin dörtte birini oluşturur. Görülme sıklığı 45-70 yaşları arasında ve hastaların sağ kalım süresi 12-15 aydır.Çalışmamız, GBM olgularında sıklıkla rastlanan IDH1 geninin 4. ekzon mutasyonlarının DNA dizi analizi ile taranması ve 10q23/PTEN lokus kayıplarının FISH analizi ile belirlenmesi ve olguların yaş/sağ kalım ilişkilerinin değerlendirilmesi amacıyla yapılmıştır. Bu amaçla, Karadeniz Teknik Üniversitesi Tıp Fakültesi Tıbbi Patoloji Anabilim Dalı' nda GBM tanısı almış 54 olguya ait parafine gömülü arşiv materyallerinden elde edilen DNA' lara dizi analizi yapıldı. Ayrıca IDH1 geninde mutasyon taşıyan 5 olgu ve taşımayan 15 olgu olmak üzere toplam 20 GBM olgusu ve kontrol amacıyla 10 normal beyin dokusu FISH analizinde incelenmek üzere çalışmaya alındı.Literatürde GBM' lerde IDH1 mutasyonları genellikle p.R132H şeklinde olup mutasyon oranının %6-30 arasında olduğu bildirilmiştir. Çalışmamızda olguların primer ve sekonder ayrımları yapılmamış olup IDH1 p.R132H mutasyon frekansı %9.3 olarak bulundu. IDH1 p.R132H mutasyonu taşıyan olguların yaş ortalaması 46, mutasyon taşımayanların ortalaması ise; 56 olarak saptandı. IDH1 p.R132H mutasyonu ile olguların yaşı arasında istatistiksel olarak anlamlı bir fark bulunamadı. Mutasyon taşıyanların ortalama sağ kalım süresi 12 ay iken taşımayanların sağ kalım süresi 8 ay olarak saptanmış olup aralarında istatistiksel olarak anlamlı bir fark bulunamadı.Doğu Karadeniz bölgesinde daha önce GBM genetiği konusunda araştırmalar yapılmamış olduğundan bu araştırma bölgemize has ilk çalışma olması yönünden önemlidir. Çalışmamızın bu açıdan yapılacak yeni çalışmalara ışık tutacağı düşünülmektedir. Glioblastoma Multiforme (GBM) derived from glial cells is one of the most frequent and malignant brain tumors classified as grade IV by WHO (World Health Organization) accounts for one in four of all primary brain tumors. Incidence is between 45 and 70 years and overall survival time of patients is 12-15 months.In our study, screening of exon 4 of IDH1 gene by sequencing which is frequently encountered in GBMs, detection of deletion of 10q23/PTEN locus by FISH analysis and evaluation of the correlation between age of patients and survival were aimed. For this purpose, DNAs obtained from paraffin embedded archival materials belong to 54 cases diagnosed as GBM in of Karadeniz Technical University, Faculty of Medicine, Department of Medical Pathology were sequenced. Additionally overall 20 cases; (5 of them which harbored a IDH1 mutation) and 10 non-neoplastik brain tissues that were used as controls included in FISH analysis study.The most detected IDH1 mutation is p.R132H in GBMs which frequency reported as 6-30% in GBMs in the literature. In this study, the classification of the GBM cases was not done and the IDH1 p.R132H mutation frequency was detected as 9.3%. The average age of the cases harboring the p.R132H mutation was calculated 46 while the average age of patients without this mutation was 56. There is not statistical significance between average age of the cases and IDH1 p.R132H mutation. The survival rate of the patients with this mutation was calculated 12 months while it was 8 months for the patients with no mutation; however, this finding was not statistically significant.As there is not any conducted study on genetic of the GBM in the Black Sea Region, this study is important and it is very unique to our region. It is believed that this study will shed light on this issue for future studies. 85