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Item Open Access Assessment of diagnostic enzyme-linked immunosorbent assay kit and serological markers in human brucellosis(2008) Cakan G.; Bezirci F.B.; Kacka, A.; Cesur, S.; Aksaray, S.; Tezeren, D.; Saka, D.; Ahmed, K.This study was performed to evaluate commercial brucella immunoglobulin G and M-enzymelinked immunosorbent assay (IgG and IgM ELISA) kits for the diagnosis of human brucellosis and to suggest a candidate prognostic marker for human brucellosis. We determined the serum levels of brucella IgG, IgM, C-reactive protein (CRP), soluble CD14 (sCD 14), and neopterin in patients with brucellosis and compared them with those of normal healthy persons, patients with tuberculosis, and patients with other diseases. It was found that the sensitivity of ELISA to diagnose brucellosis was high when both IgG and IgM ELISA were used together. This study showed that serum CRP, sCD14, or neopterin levels were significantly high during the course of human brucellosis. The above markers, alone or in combination, might have the potential to evaluate treatment outcomes in human brucellosis. The markers that can predict the variability of agglutination titer was also determined. It was found that the titer value alone does not fully represent disease status.Item Open Access Asymmetric dimethylarginine concentrations are elevated in women with gestational diabetes(2010) Akturk, M.; Altinova, A.; Mert I.; Dincel, A.; Sargin, A.; Buyukkagnici, U.; Arslan, M.; Danisman, N.As shown in the previous studies, asymmetric dimethylarginine (ADMA) is related to endothelial dysfunction, whereas high-sensitive C-reactive protein (hCRP) is the marker of inflammation. In our study, we investigated ADMA, hCRP, and homocysteine concentrations in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) during late pregnancy. Fifty-four women with GDM and 69 women with NGT between 32 and 39 weeks of gestation were included in this study. ADMA, hCRP, homocysteine, lipid parameters, glycated hemoglobin (HbA1c) levels, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. The plasma ADMA concentrations were significantly higher in GDM patients than in NGT subjects (P = 0.03) and the hCRP levels were also significantly increased in GDM group when compared with those in the NGT group (P = 0.008). However, plasma homocysteine levels did not differ between the groups (P = 0.4), while HOMA-IR, insulin, and triglyceride levels were higher in the GDM group than in the NGT group (P = 0.001, 0.002, and 0.02, respectively). The ADMA concentrations in the third trimester were positively correlated with the glucose levels the 50-g glucose challenge test (GCT) during 24-28 weeks in the whole group (r = 0.21, P = 0.02). Our results demonstrate that ADMA and hCRP are elevated in women with GDM during late pregnancy. Further studies are needed to clarify the significance and the underlying mechanisms of the elevated ADMA and hCRP levels in women with GDM. © 2010 Springer Science+Business Media, LLC.Item Open Access Audiovisual associations alter the perception of low-level visual motion(Frontiers Research Foundation, 2015) Kafaligonul H.; Oluk, C.Motion perception is a pervasive nature of vision and is affected by both immediate pattern of sensory inputs and prior experiences acquired through associations. Recently, several studies reported that an association can be established quickly between directions of visual motion and static sounds of distinct frequencies. After the association is formed, sounds are able to change the perceived direction of visual motion. To determine whether such rapidly acquired audiovisual associations and their subsequent influences on visual motion perception are dependent on the involvement of higherorder attentive tracking mechanisms, we designed psychophysical experiments using regular and reverse-phi random dot motions isolating low-level pre-attentive motion processing. Our results show that an association between the directions of low-level visual motion and static sounds can be formed and this audiovisual association alters the subsequent perception of low-level visual motion. These findings support the view that audiovisual associations are not restricted to high-level attention based motion system and early-level visual motion processing has some potential role. © 2015 Kafaligonul and Oluk.Item Open Access Common telomerase reverse transcriptase promoter mutations in hepatocellular carcinomas from different geographical locations(WJG Press, 2015) Cevik, D.; Yildiz G.; Ozturk, M.AIM: To determine the mutation status of human telomerase reverse transcriptase gene (TERT ) promoter region in hepatocellular carcinoma (HCC) from different geographical regions. METHODS: We analyzed the genomic DNA sequences of 59 HCC samples comprising 15 cell lines and 44 primary tumors, collected from patients living in Asia, Europe and Africa. We amplified a 474 bp DNA fragment of the promoter region of TERT gene including the 1295228 and 1295250 sequence of chromosome 5 by using PCR. Amplicons were then sequenced by Sanger technique and the sequence data were analyzed with by using DNADynamo software in comparison with wild type TERT gene sequence as a reference. RESULTS: The TERT mutations were found highly frequent in HCC. Eight of the fifteen tested cell lines displayed C228T mutation, and one had C250T mutation with a mutation frequency up to 60%. All of the mutations were heterozygous and mutually exclusive. Ten out of forty-four tumors displayed C228T mutation, and additional five tumors had C250T mutation providing evidence for mutation frequency of 34% in primary tumors. Considering the geographic origins of HCC tumors tested, TERT promoter mutation frequencies were higher in African (53%), when compared to non-African (24%) tumors (P = 0.056). There was also a weak inverse correlation between TERT promoter mutations and murine double minute 2 single nucleotide polymorphism 309 TG polymorphism (P = 0.058). Mutation frequency was nearly two times higher in established HCC cell lines (60%) compared to the primary tumors (34%). CONCLUSION: TERT promoter is one of most frequent mutational targets in liver cancer, and hepatocellular carcinogenesis is highly associated with the loss of telomere-dependent cellular senescence control. © The Author(s) 2015.Item Open Access Effect of patient sex on white matter alterations in unilateral medial temporal lobe epilepsy with hippocampal sclerosis assessed by diffusion tensor imaging(2013) Oguz, K.K.; Tezer I.; Sanverdi, E.; Has, A.C.; Bilginer, B.; Dolgun, A.; Saygi, S.BACKGROUND AND PURPOSE: Studies shows ictal behavior and symptoms are affected by patient sex in temporal lobe epilepsy. The purpose of our study was to determine whether alterations in the WM as assessed by DTI display different patterns in male and female patients with unilateral HS. MATERIALS AND METHODS: Patients with unilateral HS were categorized as women with right HS ( n=12), men with right HS ( n=10), women with left HS ( n=12), and men with left HS ( n=10). DTI of the brain along 64 noncollinear directions was obtained from 44 patients and 37 sex-matched control participants. We used TBSS to analyze whole-brain WM. Regions with significant changes of FA and MD, and their mean FA, MD, total number of significant voxels, and asymmetry indices were determined for each group. RESULTS: All groups showed bilateral and extensive reductions of FA and elevated MD in the WM, more prominent ipsilateral to the affected hippocampus. The total number of voxels with decreased FA in patients compared with that of control participants was higher in women with right HS (24,727 vs 5,459) and in men with left HS (27,332 vs 14,013) than in their counterparts. Changes in MD associated with right HS were more extensive in both men and women (right vs left HS, women: 16,926 vs 5,458; men: 5,389 vs 4,764) than in those with left HS. In patients with right HS, the ipsilateral cingulum, uncinate fasciculus, internal and external capsules, and right acoustic radiation were involved extensively in women. CONCLUSIONS: Women and men showed different patterns in extent of WM alterations associated with HS.Item Open Access Expression of CK-19 and CEA mRNA in peripheral blood of gastric cancer patients(2010) Kutun, S.; Celik, A.; Cem Kockar, M.; Erkorkmaz, U.; Eroǧlu, A.; Cetin, A.; Erkosar, B.; Yakicier, C.Aim: To investigate the clinical and pathological relevance of detection of circulating tumor cells (CTC) in the peripheral blood of gastric carcinoma patients before operation. Patients and Methods: Fifty patients with gastric adenocarcinoma were analysed prospectively. Patients were divided into two groups according to the extent of the tumor. Group I (unresectable) consisted of 22, and group II (resectable) consisted of 28 patients. Peripheral blood samples were collected pre-operatively from all 50 patients as well as from ten healthy controls and analyzed for carcinoembryonic antigen (CEA) and cytokeratin-19 (CK-19) messenger ribonucleic acids (mRNAs). Tumor localisation, stage, presence of signet cell formation, nodal metastases, serousal and lymphovascular invasion were recorded for all patients. Results: Expression of CK-19 was detected in 24 (48%), and CEA in 10 (20%) cases. Nine patients (40%) in group I and 15 (53.6%) in group II were positive for CK-19 expression. CEA expression was more frequent among group I patients (6 vs. 4 cases). There was no significant difference between the groups in the expression of CK-19 and CEA mRNA, tumor localisation, presence of signet formation, and presence and extent of nodal metastases. Patients with major vascular invasion (MVI) expressed significantly higher levels of CTC mRNA compared to those without MVI (p = 0.023 for CEA, and p = 0.009 for CK-19). The median 1 and 2-year survival was 9.5 and 10.5 months for group I, and 20 and 28.5 months for group II, respectively (p = 0.001). The mean survival was 6.7 months for patients with MVI, and 30.2 months for those without MVI (p = 0.0001). Conclusions: High levels of CTCs were observed in patients with MVI invasion, rather than other causes of unresectability. It can be suggested that expression of both CEA and CK-19 in the peripheral blood of gastric cancer patients are strong predictors of MVI and significantly worse survival rates. Copyright © Experimental Oncology, 2010.Item Open Access Extreme clonality in lymphoblastoid cell lines with implications for allele specific expression analyses(2008) Plagnol V.; Uz, E.; Wallace, C.; Stevens H.; Clayton, D.; Ozcelik, T.; Todd J.A.Lymphoblastoid cell lines (LCL) are being actively and extensively used to examine the expression of specific genes and (genome-wide expression profiles, including allele specific expression assays. However, it has recently been shown that approximately 10% of human genes exhibit random patterns of monoallelic expression within single clones of LCLs. Consequently allelic imbalance studies could be significantly compromised if bulk populations of donor cells are clonal, or near clonal. Here, using X chromosome inactivation as a readout, we confirm and quantify widespread near monoclonality in two independent sets of cell lines. Consequently, we recommend where possible the use of bulk, non cell line, ex vivo cells for allele specific expression assays. © 2008 Plagnol et al.Item Open Access Gadolinium leakage into subarachnoid space and cystic metastases(2013) Elçin Yildiz, A.; Atli, E.; Karli Oǧuz, K.Subarachnoid space (SAS) and cystic metastatic lesions of brain parenchyma appear hypointense on fluid-attenuated inversion-recovery (FLAIR) and T1-weighted magnetic resonance imaging (MRI) unless there is a hemorrhage or elevated protein content. Otherwise, delayed enhancement and accumulation of contrast media in SAS or cyst of metastases should be considered. We present hyperintense SAS and cystic brain metastases of lung cancer on FLAIR and T1-weighted MRI, respectively, in a patient who had been previously given contrast media for imaging of spinal metastases and had mildly impaired renal functions, and discuss the relevant literature. © Turkish Society of Radiology 2013.Item Open Access Iatrogenic superficial external pudendal artery pseudoaneurysm: Treatment with doppler us-guided compression(Tehran University of Medical Sciences (TUMS), 2014) Algin O.; Mustafayev, A.; Ozmen, E.Pseudoaneurysms rarely occur as a serious complication following incomplete hemostasis of an arterial puncture site. As a result of the increase in diagnostic and therapeutic angiography, the frequency of iatrogenic pseudoaneurysm has increased as well. Iatrogenic pseudoaneurysms associated with angiographic catheterization occur most commonly in the common femoral artery. Here we report a case of iatrogenic superficial external pudendal artery (SEPA) pseudoaneurysm following cardiac catheterization, which was diagnosed with Doppler ultrasound (US) and multidetector computed tomographic angiography (MDCTA) before Doppler US-guided compression therapy. To the best of our knowledge, iatrogenic SEPA pseudoaneurysm, which is an unusual vessel location for pseudoaneurysm occurrence, has not been reported in the literature. In patients in whom anticoagulant-thrombolytic therapy or therapeutic catheterization with larger sized sheath is planned, determination of the precise localization of arterial puncture site is important for the prevention of iatrogenic pseudoaneurysm development. Arterial puncture guided with Doppler US might reduce complications. When suspected, MDCTA is useful in the diagnosis and demonstration of iatrogenic pseudoaneurysms. Treatment of US-guided compression should be the first choice for iatrogenic pseudoaneurysms. Interventional radiologists and cardiologists should have enough experience about the catheterization complications and their treatment in order to decrease the morbidity and mortality related to the intervention.Item Open Access Identification of endogenous reference genes for qRT-PCR analysis in normal matched breast tumor tissues(Cognizant Communication Corporation, 2009) Gur-Dedeoglu, B.; Konu, O.; Bozkurt, B.; Ergul, G.; Seckin, S.; Yulug, I. G.Quantitative gene expression measurements from tumor tissue are frequently compared with matched normal and/or adjacent tumor tissue expression for diagnostic marker gene selection as well as assessment of the degree of transcriptional deregulation in cancer. Selection of an appropriate reference gene (RG) or an RG panel, which varies depending on cancer type, molecular subtypes, and the normal tissues used for interindividual calibration, is crucial for the accurate quantification of gene expression. Several RG panels have been suggested in breast cancer for making comparisons among tumor subtypes, cell lines, and benign/malignant tumors. In this study, expression patterns of 15 widely used endogenous RGs (ACTB, TBP, GAPDH, SDHA, HPRT, HMBS, B2M, PPIA, GUSB, YWHAZ2, PGK1, RPLP0, PUM1, MRPL19, and RPL41), and three candidate genes that were selected through analysis of two independent microarray datasets (IL22RA1, TTC22, ZNF224) were determined in 23 primary breast tumors and their matched normal tissues using qRTPCR. Additionally, 18S rRNA, ACTB, and SDHA were tested using randomly primed cDNAs from 13 breast tumor pairs to assess the rRNA/mRNA ratio. The tumors exhibited significantly lower rRNA/mRNA ratio when compared to their normals, on average. The expression of the studied RGs in breast tumors did not exhibit differences in terms of grade, ER, or PR status. The stability of RGs was examined based on two different statistical models, namely GeNorm and NormFinder. Among the 18 tested endogenous reference genes, ACTB and SDHA were identified as the most suitable reference genes for the normalization of qRTPCR data in the analysis of normal matched tumor breast tissue pairs by both programs. In addition, the expression of the gelsolin (GSN) gene, a well-known downregulated target in breast tumors, was analyzed using the two most suitable genes and different RG combinations to validate their effectiveness as a normalization factor (NF). The GSN expression of the tumors used in this study was significantly lower than that of normals showing the effectivity of using ACTB and SDHA as suitable RGs in this set of tumor–normal tissue panel. The combinational use of the best performing two RGs (ACTB and SDHA) as a normalization factor can be recommended to minimize sample variability and to increase the accuracy and resolution of gene expression normalization in tumor–normal paired breast cancer qRT-PCR studies.Item Open Access Malignant-lesion segmentation using 4D co-occurrence texture analysis applied to dynamic contrast-enhanced magnetic resonance breast image data(2007) Woods, B.J.; Clymer, B.D.; Kurc, T.; Heverhagen J.T.; Stevens, R.; Orsdemir, A.; Bulan O.; Knopp, M.V.Purpose: To investigate the use of four-dimensional (4D) co-occurrence-based texture analysis to distinguish between nonmalignant and malignant tissues in dynamic contrast-enhanced (DCE) MR images. Materials and Methods: 4D texture analysis was performedon DCE-MRI data sets of breast lesions. A model-free neural network-based classification system assigned each voxel a "nonmalignant" or "malignant" label based on the textural features. The classification results were compared via receiver operating characteristic (ROC) curve analysis with the manual lesion segmentation produced by two radiologists (observers 1 and 2). Results: The mean sensitivity and specificity of the classifier agreed with the mean observer 2 performance when compared with segmentations by observer 1 for a 95% confidence interval, using a two-sided t-test with α = 0.05. The results show that an area under the ROC curve (Az) of 0.99948, 0.99867, and 0.99957 can be achieved by comparing the classifier vs. observer 1, classifier vs. union of both observers, and classifier vs. intersection of both observers, respectively. Conclusion: This study shows that a neural network classifier based on 4D texture analysis inputs can achieve a performance comparable to that achieved by human observers, and that further research in this area is warranted. © 2007 Wiley-Liss, Inc.Item Open Access Mutation in TOR1AIP1 encoding LAP1B in a form of muscular dystrophy: A novel gene related to nuclear envelopathies(Elsevier Ltd, 2014) Kayman-Kurekci G.; Talim, B.; Korkusuz P.; Sayar, N.; Sarioglu, T.; Oncel I.; Sharafi P.; Gundesli H.; Balci-Hayta, B.; Purali, N.; Serdaroglu-Oflazer P.; Topaloglu H.; Dincer P.We performed genome-wide homozygosity mapping and mapped a novel myopathic phenotype to chromosomal region 1q25 in a consanguineous family with three affected individuals manifesting proximal and distal weakness and atrophy, rigid spine and contractures of the proximal and distal interphalangeal hand joints. Additionally, cardiomyopathy and respiratory involvement were noted. DNA sequencing of torsinA-interacting protein 1 (TOR1AIP1) gene encoding lamina-associated polypeptide 1B (LAP1B), showed a homozygous c.186delG mutation that causes a frameshift resulting in a premature stop codon (p.E62fsTer25). We observed that expression of LAP1B was absent in the patient skeletal muscle fibres. Ultrastructural examination showed intact sarcomeric organization but alterations of the nuclear envelope including nuclear fragmentation, chromatin bleb formation and naked chromatin. LAP1B is a type-2 integral membrane protein localized in the inner nuclear membrane that binds to both A- and B-type lamins, and is involved in the regulation of torsinA ATPase. Interestingly, luminal domain-like LAP1 (LULL1)-an endoplasmic reticulum-localized partner of torsinA-was overexpressed in the patient's muscle in the absence of LAP1B. Therefore, the findings suggest that LAP1 and LULL1 might have a compensatory effect on each other. This study expands the spectrum of genes associated with nuclear envelopathies and highlights the critical function for LAP1B in striated muscle. © 2014 Elsevier B.V.Item Open Access Mutations in the very low-density lipoprotein receptor VLDLR cause cerebellar hypoplasia and quadrupedal locomotion in humans(National Academy of Sciences, 2008) Ozcelik, T.; Akarsu, N.; Uz, E.; Caglayan, S.; Gulsuner, S.; Onat, O. E.; Tan, M.; Tan, U.Quadrupedal gait in humans, also known as Unertan syndrome, is a rare phenotype associated with dysarthric speech, mental retardation, and varying degrees of cerebrocerebellar hypoplasia. Four large consanguineous kindreds from Turkey manifest this phenotype. In two families (A and D), shared homozygosity among affected relatives mapped the trait to a 1.3-Mb region of chromosome 9p24. This genomic region includes the VLDLR gene, which encodes the very low-density lipoprotein receptor, a component of the reelin signaling pathway involved in neuroblast migration in the cerebral cortex and cerebellum. Sequence analysis of VLDLR revealed nonsense mutation R257X in family A and single-nucleotide deletion c2339delT in family D. Both these mutations are predicted to lead to truncated proteins lacking transmembrane and signaling domains. In two other families (B and C), the phenotype is not linked to chromosome 9p. Our data indicate that mutations in VLDLR impair cerebrocerebellar function, conferring in these families a dramatic influence on gait, and that hereditary disorders associated with quadrupedal gait in humans are genetically heterogeneous.Item Open Access Na+/I-symporter and type 3 iodothyronine deiodinase gene expression in amniotic membrane and placenta and its relationship to maternal thyroid hormones(2013) Akturk, M.; Oruc, A.S.; Danisman, N.; Erkek, S.; Buyukkagnici, U.; Unlu, E.; Tazebay, U.H.Placental type 3 iodothyronine deiodinase (D3) potentially protects the fetus from the elevated maternal thyroid hormones. Na+/I- symporter (NIS) is a plasma membrane glycoprotein, which mediates active iodide uptake. Our objectives were to establish the distribution of NIS and D3 gene expressions in the placenta and the amniotic membrane and to investigate the relationship between placental D3 and NIS gene expressions and maternal iodine, selenium, and thyroid hormone status. Thyroid hormones, urinary iodine concentration (UIC), and selenium levels were measured in 49 healthy term pregnant women. NIS and D3 gene expressions were studied with the total mRNA RT-PCR method in tissues from maternal placenta (n = 49), fetal placenta (n = 9), and amniotic membrane (n = 9). NIS and D3 gene expressions were shown in the fetal and maternal sides of the placenta and amniotic membrane. Mean blood selenium level was 66 ± 26.5 μg/l, and median UIC was 143 μg/l. We could not demonstrate any statistically significant relationship of spot UIC and blood selenium with NIS and D3 expression (p > 0.05). Positive correlations were found between NIS and thyroxine-binding globulin (TBG) (r = 0.3, p = 0.042) and between D3 and preoperative glucose levels (r = 0.4, p = 0.006). D3 and NIS genes are expressed in term placenta and amniotic membrane; thus, in addition to placenta, amniotic membrane contributes to regulation of maternofetal iodine and thyroid hormone transmission. Further studies are needed to clarify the relationship between maternal glucose levels and placental D3 expression and between TBG and placental NIS expression. © 2013 Springer Science+Business Media New York.Item Open Access Neural correlates of acquired color category effects(2012) Clifford, A.; Franklin, A.; Holmes, A.; Drivonikou V.G.; Özgen, E.; Davies I.R.L.Category training can induce category effects, whereby color discrimination of stimuli spanning a newly learned category boundary is enhanced relative to equivalently spaced stimuli from within the newly learned category (e.g., categorical perception). However, the underlying mechanisms of these acquired category effects are not fully understood. In the current study, Event-Related Potentials (ERPs) were recorded during a visual oddball task where standard and deviant colored stimuli from the same or different novel categories were presented. ERPs were recorded for a test group who were trained on these novel categories, and for an untrained control group. Category effects were only found for the test group on the trained region of color space, and only occurred during post-perceptual stages of processing. These findings provide new evidence for the involvement of cognitive mechanisms in acquired category effects and suggest that category effects of this kind can exist independent of early perceptual processes. © 2012.Item Open Access Neuro-ophthalmologic findings in humans with quadrupedal locomotion(2012) Sarac O.; Gulsuner, S.; Yildiz-Tasci, Y.; Ozcelik, T.; Kansu, T.Purpose: To report the neuro-ophthalmologic findings in four patients from the same family with cerebellar ataxia, mental retardation, and dysequilibrium syndrome (CAMRQ)2 associated with quadrupedal locomotion. Method: A case series. Results: All four patients carry the private missense mutation, WDR81 p.P856L. The brain Magnetic Resonance Imaging (MRI) of these patients revealed morphological abnormalities including mild hypoplasia of the corpus callosum, and atrophy of superior, middle, and inferior peduncles of the cerebellum. All patients had down-beat nystagmus, while two male patients additionally had bilateral temporal disc pallor along with ring-shaped macular atrophy. Conclusions: The neuro-ophthalmic examination in CAMRQ2 revealed downbeat nystagmus in all patients, and temporal disc pallor and macular atrophy in two patients. It remains to be determined whether these findings are consistent in other forms of CAMRQ with mutations in VLDLR or CA8. © 2012 Informa Healthcare USA, Inc.Item Open Access De novo balanced (X;14) translocation in a patient with recurrent miscarriages: Case report(2011) Alpaslan Pinarli F.; Ökten G.; ÖzçelIk, T.; Kara, N.; Güneş, S.; Koçak I.We report a 23-year-old phenotypically normal female patient who had previously suffered from recurrent spontaneous abortion (RSA) who found to have an X;14 trans location and a Methylene- Tetrahdrofolate-Reductase (MTHFR) C677T heterozygote mutation. G-banding cytogenetic analysis was cultured from the peripheral blood lymphocy tes. MTHFR, factor V Leiden and prothrombin gene mutations were studied from DNA obtained from peripheral blood lym- phocytes with stripassay. DNA for X inactivation pattern study was also obtained with the method described above. G-banding cytogentic analysis from cultured peripheral blood lymphocytes of the patient revealed 46,XderX,t(X;14)(q13;q32) and found to be heterozygous for C677T MTHFR mutation. An X inactivation pattern study revealed a complete inactivated nor mal X chromosome, asexpected. The possible causes of recurrent miscarriages in our patient were unbalanced gametes, skewed X inactivation and MTHFR C677T heterozygote mutation. © 2011 by Türkiye Klinikleri.Item Open Access Perisylvian GABA levels in schizophrenia and bipolar disorder(Elsevier Ireland Ltd, 2017) Atagün, M. İ.; Şıkoglu, M. E.; Soykan, Ç.; Can, S. S.; Ulusoy-Kaymak S.; Çayköylü, A.; Algın O.; Phillips, M. L.; Öngür, D.; Moore, C. M.The aim of this study is to measure GABA levels of perisylvian cortices in schizophrenia and bipolar disorder patients, using proton magnetic resonance spectroscopy (1H-MRS). Patients with schizophrenia (n = 25), bipolar I disorder (BD-I; n = 28) and bipolar II disorder (BD-II; n = 20) were compared with healthy controls (n = 30).1H-MRS data was acquired using a Siemens 3 T whole body scanner to quantify right and left perisylvian structures’ (including superior temporal lobes) GABA levels. Right perisylvian GABA values differed significantly between groups [χ2= 9.62, df: 3, p = 0.022]. GABA levels were significantly higher in the schizophrenia group compared with the healthy control group (p = 0.002). Furthermore, Chlorpromazine equivalent doses of antipsychotics correlated with right hemisphere GABA levels (r2= 0.68, p = 0.006, n = 33). GABA levels are elevated in the right hemisphere in patients with schizophrenia in comparison to bipolar disorder and healthy controls. The balance between excitatory and inhibitory controls over the cortical circuits may have direct relationship with GABAergic functions in auditory cortices. In addition, GABA levels may be altered by brain regions of interest, psychotropic medications, and clinical stage in schizophrenia and bipolar disorder. � 2016 Elsevier Ireland LtdItem Open Access SIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylation(2011) Acun, T.; Oztas, E.; Yagci, T.; Yakicier, M.C.Background: Smad interacting protein-1 is a transcription factor that is implicated in transforming growth factor-β/bone morphogenetic protein signaling and a repressor of E-cadherin and human telomerase reverse transcriptase. It is also involved in epithelial-mesenchymal transition and tumorigenesis. However, genetic and epigenetic alterations of SIP1 have not been fully elucidated in cancers. In this study, we investigated mutations and promoter hypermethylation of the SIP1 gene in human hepatocellular carcinomas.Methods: SIP1 expression was analyzed in HCC cell lines and primary tumors in comparison to normal and non-tumor liver tissues by using semi-quantitative RT-PCR, quantitative real-time RT-PCR and immunohistochemistry. Mutation and deletion screening of the SIP1 gene were performed by direct sequencing in HCC-derived cells. Restoration of SIP1 expression was sought by treating HCC cell lines with the DNA methyl transferase inhibitor, 5-AzaC, and the histone deacetylase inhibitor, TSA. SIP1 promoter methylation was analyzed by the combined bisulfite restriction analysis assay in in silico-predicted putative promoter and CpG island regions.Results: We found that the expression of SIP1 was completely lost or reduced in five of 14 (36%) HCC cell lines and 17 of 23 (74%) primary HCC tumors. Immunohistochemical analysis confirmed that SIP1 mRNA downregulation was associated with decreased expression of the SIP1 protein in HCC tissues (82.8%). No somatic mutation was observed in SIP1 exons in any of the 14 HCC cell lines. Combined treatment with DNA methyl transferase and histone deacetylase inhibitors synergistically restored SIP1 expression in SIP1-negative cell lines. Analysis of three putative gene regulatory regions revealed tumor-specific methylation in more than half of the HCC cases.Conclusions: Epigenetic mechanisms contribute significantly to the downregulation of SIP1 expression in HCC. This finding adds a new level of complexity to the role of SIP1 in hepatocarcinogenesis. © 2011 Acun et al; licensee BioMed Central Ltd.Item Open Access Variation in the attachment of Streptococcus pneumoniae to human pharyngeal epithelial cells after treatment with S-carboxymethylcysteine(2008) Suer, E.; Sayrac, S.; Sarinay, E.; Ozturk H.E.; Turkoz, M.; Ichinose, A.; Nagatake, T.; Ahmed, K.S-carboxymethylcysteine (S-CMC) is a mucolytic agent that can prevent respiratory infection by decreasing the attachment of respiratory pathogens to human pharyngeal epithelial cells (HPECs). Streptococcus pneumoniae is a major cause of respiratory infections. A previous study revealed that treatment of S. pneumoniae with S-CMC caused a decrease in the attachment of this bacterium to HPECs. In the present study we found that the effect of S-CMC varied according to hosts and strains. S-CMC treatment altered the surface structure of S. pneumoniae, resulting in a decrease of attachment, without affecting the virulence of the bacteria. © 2008 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases.