Diffuse Leptomeningeal Glioneuronal Tumors: A Case Series of Five Patients with Parenchymal Forms and an Analysis of the Diagnostic Challenges, Treatment Options and Outcomes.

BACKGROUND: Diffuse leptomeningeal glioneuronal tumors (DL-GNT) are rare glioneuronal neoplasms with oligodendroglioma-like cells. These tumors can present as a dominant intracranial mass or as a solitary spinal cord mass without leptomeningeal involvement. In this study, we aimed to determine the magnetic resonance imaging and histopathological features, treatment modalities, and clinical outcomes of the parenchymal forms of DL-GNTs. METHODS: This is a retrospective three-center case series study of 5 patients with a confirmed parenchymal form of DLGTs, out of which 4 patients were adults. Brain and spinal cord MR imaging were performed in all patients at either 1.5 or 3T. The patients' age ranged from 5 years to 50 years with a mean age of 27.6 years at presentation. RESULTS: Four of the tumors were located in the frontal lobe, and one in the tectum. They were usually solid-cystic enhancing tumors as the other mixed neuronal-glial tumors. All of the tumors had an extension to the superficial surface of a cerebral hemisphere. One had systemic bone metastases. The clinical signs and symptoms of the parenchymal form varied based on the location of the mass, in contrast to the leptomeningeal form associated with hydrocephalus. In one case, the tumor's initial grade was defined as intermediate. The initial histopathology of the two cases was low-grade and no upgrade occurred in the follow-up period. In two cases, although the tumors were low grade initially, they progressed to an anaplastic form in the follow-up period. CONCLUSION: The parenchymal form of DL-GNTs is common in adults. Extension to the superficial surface of a cerebral hemisphere is a distinctive imaging feature. Systemic osseous metastasis may occur. Due to the presence of common histopathological features, including the biphasic composition of glial and neuronal cell elements and oligodendroglioma-like cells, a proposed classification approach might be more beneficial for the histopathological and imaging description, and management of the glioneuronal tumors with oligodendroglioma-like features.

The potential utility of real-time PCR of the 16S-rRNA gene in the diagnosis of neonatal sepsis.

Istanbullu K, Köksal N, Çetinkaya M, Özkan H, Yakut T, Karkucak M, Dogan H. The potential utility of real-time PCR of the 16S-rRNA gene in the diagnosis of neonatal sepsis. Turk J Pediatr 2019; 61: 493-499. The purpose of this study was to evaluate the efficacy of real-time polymerase chain reaction (PCR) of the 16S rRNA gene in diagnosis of neonatal sepsis and compare it with conventional blood culture. A total of 150 infants were enrolled in this prospective study. The infants were classified into two groups: sepsis group (n=100) and control group (n=50). Blood samples for complete blood count, C-reactive protein, procalcitonin, serum-amyloid A, blood culture and PCR were obtained before initiating antibiotic treatment. Eight specific probes were used to perform PCR analysis for detection of 8 different microorganisms. The positivity rates of blood culture and PCR were found as 11% and 3%, respectively. The diagnosis of neonatal sepsis by PCR revealed a 16.6 % sensitivity, 97.8 % specificity, 33.3% positive predictive value and 94.8% negative predictive value compared with the blood culture. This study showed a low sensitivity of PCR of the 16S rRNA gene in the diagnosis of neonatal sepsis. This may be associated with the identification of rare microorganisms in the blood culture that were not included to PCR analysis. Implementation of all suspectible microorganisms into PCR assay may increase the sensitivity of 16S rRNA gene PCR in diagnosis of neonatal sepsis.

Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial Mediterranean fever / Investigação de polimorfismos no gene MEFV (G138G e A165A) em pacientes adultos com febre mediterrânica familiar

Abstract Aim: Various mutations have been identified in the Mediterranean fever (MEFV) gene which is reported to be responsible from Familial Mediterranean fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. Methods: One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. Results: As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p < 0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p > 0.05). Conclusions: To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed.

Resumo Objetivo: Identificaram-se mutações no gene da febre mediterrânica (MEFV) relatadas como responsáveis pela febre mediterrânica familiar (FMF). Este estudo teve como objetivo determinar a frequência de mutações no MEFV na região sul do mar de Mármara e investigar o impacto dos polimorfismos genéticos G138G (rs224224, c.414A > G) e A165A (rs224223, c.495C > A) nos achados clínicos da doença. Métodos: Foram incluídos neste estudo 116 pacientes com diagnóstico de FMF e 95 indivíduos no grupo controle. Usou-se o método de análise da sequência de DNA para identificar as 10 mutações mais prevalentes localizadas nos éxons 2 e 10 do gene MEFV. Resultados: Como resultado da análise da mutação MEFV, a mutação mais comum foi a mutação alélica M694 V, com uma taxa de frequência de 41,8%. Quando os grupos de pacientes e controles foram comparados em termos de frequência de ambos os alelos polimórficos (alelo polimórfico G, observado no G138G e o alelo polimórfico A, observado no A165A), a variação observada foi estatisticamente significativa (p < 0,001). Verificou-se que os tipos de mutação no MEFV não tinham relação com os achados clínicos nem com a amiloidose (p > 0,05). Conclusões: Que se tem conhecimento, este estudo é o primeiro feito na região sul do mar de Mármara que relata a frequência de mutações no MEFV. Os achados indicam que os polimorfismos G138G e A165A podem ter um impacto sobre o progresso da doença. Acredita-se que são necessários mais estudos que abranjam um maior número de casos e investiguem os polimorfismos do gene MEFV.

Investigation of MEFV gene polymorphisms (G138G and A165A) in adult patients with familial Mediterranean fever.

AIM: Various mutations have been identified in the Mediterranean fever (MEFV) gene which is reported to be responsible from Familial Mediterranean fever (FMF). In our study, we aimed to determine the frequency of the MEFV mutations in our region and to investigate the impact of G138G (rs224224, c.414A>G) and A165A (rs224223, c.495C>A) gene polymorphisms on the clinical findings of the disease. METHODS: One hundred and sixteen patients diagnosed with FMF and 95 control subjects were included in this study. We used the DNA sequence analysis method to identify the most prevailing 10 mutations located in exon 2 and 10 of MEFV gene. RESULTS: As a result of the MEFV mutation analysis, the most common mutation was the M694V mutation allele with a frequency rate of 41.8%. When the patients group and control group were compared in terms of frequency of both polymorphic alleles (G polymorphic allele, observed in G138G and the A polymorphic allele, observed in A165A), the variation was observed to be statistically significant (p<0.001). It was found that the MEFV mutation types have no relation with clinical findings and amyloidosis (p>0.05). CONCLUSIONS: To our knowledge, our study is the first study in the Southern Marmara region that reports the frequency of MEFV mutations. Our findings imply that the polymorphisms of G138G and A165A may have an impact on progress of the disease. We think that more studies, having higher number of cases and investigating the polymorphisms of MEFV gene, are needed.

Delayed Puberty and Gonadal Failure in Patients with HAX1 Mutation.

PURPOSE: Homozygous mutations in the HAX1 gene cause an autosomal recessive form of severe congenital neutropenia (SCN). There are limited data on cases of gonadal insufficiency that involve the HAX1 gene mutation. We aimed to evaluate the pubertal development and gonadal functions of our patients with a p.Trp44X mutation in the HAX1 gene. METHOD: Pubertal development, physical and laboratory findings of one male and seven female patients with HAX1 deficiency were evaluated. RESULTS: The age of the patients was between 13 and 25 years. All female patients were diagnosed with primary ovarian insufficiency (POI) based on amenorrhea and elevated gonadotropins. The ovary volumes in female patients were determined to be smaller than normal for their age through sonographic studies. Short stature associated with gonadal insufficiency was also observed in three patients. CONCLUSION: The HAX1 gene is important for ovarian development, in which a p.Trp44X mutation may cause POI in female patients. It is crucial to follow up and evaluate the gonadal functions of female patients in such cases.

Evaluation of TNF-alpha gene (G308A) and MBL2 gene codon 54 polymorphisms in Turkish patients with tuberculosis.

OBJECTIVE: MBL acts as a binding protein that enables uptake of mycobacteria into macrophages. And, TNF-alpha is an important cytokine that is involved in control of mycobacterial infections both in-vivo and in-vitro. A large number of genetic factors exerting susceptibility to tuberculosis has been identified, among which mannose-binding lectin and tumor necrosis factor-alpha call attention. The objective of this study is to compare the frequency of TNF-alpha and MBL gene polymorphisms between patients diagnosed with tuberculosis and healthy volunteers in Turkey, and determine the association between tuberculosis and TNF-alpha gene (G308A) and MBL2 gene codon 54 polymorphisms. MATERIAL AND METHODS: The study included 69 patients who were diagnosed with tuberculosis and 70 control subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to detect TNF-alpha (G308A) gene and MBL2 gene codon 54 polymorphisms. For statistical analysis, the significance level was determined as p<0.05. RESULTS: A comparison between patient and control groups in TNF-alpha (G308A) gene and MBL2 gene codon 54 polymorphisms showed no statistically significant difference (p>0.05). However, a comparison of mean body mass index (BMI) and smoking status showed a statistically significant difference between the tuberculosis and control groups (p=0.01 and p=0.009, respectively). CONCLUSION: Our results suggest that the MBL2 gene Codon 54 and TNF-alpha gene G308A polymorphisms are not associated with an increased risk for development of tuberculosis in our patients. Further studies are required including more cases of tuberculosis patients and other potentially relevant gene polymorphisms.

GSTT1 and GSTM1 gene polymorphisims in sarcoidosis.

INTRODUCTION: Sarcoidosis is a granulomatous disease of unknown cause, which affects all systems, especially the lungs and the lymphatic system. Genetic and environmental factors are held accountable for the etiology. Based on the general opinion, sarcoidosis develops after exposure to a specific environmental agent by genetically susceptible individuals.  The present study aimed to evaluate the disease susceptibility of the GSTT1 and GSTM1 gene polymorphisms in the patients with sarcoidosis. METHOD: The present study included 78 patients; 38 patients with histopathologically verified sarcoidosis and 40 control subjects. Multiplex PCR method was used to determine the GSTT1 and GSTM1 gene polymorphisms. The genotype was determined based on the bands formed in the agarose gel electrophoresis. The statistical analysis was done using the chi-square test. RESULTS: The positive/negative genotype rates were 79%/21% and 53%/47%, respectively in the case group for the GSTT1 and GSTM1 gene polymorphisms, whereas the positive/negative genotype rates were 77%/23% and 55%/45% in the control group. There was no statistically significant difference in the positive and negative genotypes compared with the case group and the control group for the GSTT1 and GSTM1 gene polymorphisms (p > 0.05). DISCUSSION: The results from the present study suggest that there is not any association with the control group for the disease susceptibility of the GSTT1 and GSTM1 gene polymorphisms in patients with sarcoidosis, and this result should be supported by large-scale studies because of the limited number of cases in the present study.

An Unusual Case of LCHAD Deficiency Presenting With a Clinical Picture of Hemophagocytic Lymphohistiocytosis: Secondary HLH or Coincidence?

There are published reports stating that some of the congenital metabolic diseases, such as lysinuric protein intolerance, multiple sulphatase deficiency, galactosemia, Gaucher disease, Pearson syndrome, and galactosialidosis, might lead to secondary hemophagocytic lymphohistiocytosis (HLH). However, to date, to our knowledge, the long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency has never been investigated among patients with HLH. Here, we report on a patient who was referred to our institution for a differential diagnosis of pancytopenia, liver failure, and rhabdomyolysis. The patient was diagnosed with HLH. Further investigation revealed an underlying diagnosis of the LCHAD deficiency. Our case was reported to contribute to the literature, as well as the HLH clinic, emphasizing the consideration of LCHAD deficiency, especially in 1 to 6 months' old infants with laboratory findings of hypoglycemia, metabolic acidosis, and elevated creatine kinase.

Glutathione S-transferase T1, M1 and P1 Genetic Polymorphisms and Susceptibility to Colorectal Cancer in Turkey.

Colorectal cancer (CRC) is reported to be the third most common cancer worldwide and the fourth most common cause of cancer related deaths. CRC is considered to be a multifactorial disease whose risk varies due to the complex interaction between individual genetic basis and exposure to multiple endogenous factors. Glutathione S-transferases are pro-carcinogenic in CRC and are required for the conjugation between chemotherapeutics and broad spectrum xenobiotics. One hundred and eleven patients with CRC and 128 control subjects without any cancer history were enrolled in this study. Multiplex PCR was applied to determine polymorphisms for the GSTT1 and M1 genes, and PCR-RFLP was applied for the GSTP1 (Ile105Val) gene polymorphism. Values <0.05 were defined as statistically significant. We detected a significant high correlation between predisposition for CRC and presence of the Ile/Ile genotype of the GSTP1 (IIe105Val) gene polymorphism, but we did not find a significant relationship between predisposition for CRC and GSTT1 and M1 deletion polymorphisms. In addition, we did not determine a relationship between GSTT1, M1 and P1 gene polymorphisms and any clinicopathological features of CRC. GSTT1 null/GSTM1 positive and GSTT1 null/GSTM1 positive/GSTP1 Ile/ Ile genotypes were significantly higher in the patient group. Our results revealed that there is no relationship among CRC, its clinicopathologic features, and GSTT1 M1 gene polymorphisms. However, there was a significant correlation between CRC and the GSTP1 Ile/Ile genotype. Further studies with larger patient groups are required to delineate the relationships between GST gene polymorphisms and the clinicopathologic features of CRC in Turkey.

Reanalysis of human blastocysts with different molecular genetic screening platforms reveals significant discordance in ploidy status.

OBJECTIVE: The objective of this study is to determine mosaicism and its effect on blastocysts; abnormal blastocysts determined by molecular testing were sequentially biopsied and retested. MATERIAL AND METHOD: We re-biopsied 37 blastocyst-stage abnormal embryos from eight patients, which were reanalyzed to determine the level of concordance between biopsies and inter-laboratory congruence between reputable commercial PGS laboratories. RESULTS: The main outcome measures were intra-embryo variation between sequential embryo biopsies and inter-laboratory variation between two PGS laboratories. The compatibility between both aCGH and NGS was found to be 11 % (3/27). Importantly, 9/27 (33 %) of embryos originally reported to be aneuploid, upon repeat assessment, were found to be euploid. The concurrence for SNP array and NGS was 50 % (3/6), and 17 % (1/6) of these abnormal embryos tested normal upon re-evaluation with NGS. NGS resulted 41 % (11/27) normal results when 27 of CGH abnormal embryos were retested. Concordance between aCGH and NGS was 4 % (1/27) whereas in three instances, gender discrepancy was observed with NGS when aCGH abnormal embryos were reanalyzed. CONCLUSIONS: The results of these studies reinforce the prevalence of inconsistencies during PGS evaluation of trophectoderm biopsies possibly due to variations in platform sensitivity and heightening concerns over the clinical tractability of such technology in human ARTs..

Spectrum of EGFR gene mutations and ALK rearrangements in lung cancer patients in Turkey.

The EGFR gene and ALK rearrangements are two genetic drivers of non-small cell lung cancer (NSCLC). The frequency of EGFR mutations and ALK rearrangement varies according to not only ethnicity but also gender, smoking status and the histological type of NSCLC. In the present study, we demonstrated the distribution of EGFR mutations in 132 NSCLC patients by using a pyrosequencing technique and the distribution of ALK rearrangements in 51 NSCLC patients by using fluorescent in situ hybridization technique in Turkey. Additionally, we compared the clinicopathological data of NSCLC patients with the mutation status of EGFR in their cancerous tissues. Both EGFR mutations and ALK rearrangements were identified in 19 (14.39 %) and 1 (1.96 %) patients, respectively. We found EGFR mutations in codon 861, 719 and 858 with the ratios of 10.52 % (2/19), 10.52 % (2/19) and 31.58 % (6/19), respectively, and deletion of exon 19 in 47.37 % (9/19) of the patients. We found the frequency of EGFR mutations to be significantly higher in female patients and nonsmokers (p = 0.043, p = 0.027, respectively). Consequently, we found EGFR mutations to be more frequent in female patients and nonsmokers. Future studies on larger patient groups would provide more accurate data to exhibit the relationship between EGFR mutations and ALK rearrangements and the clinicopathological status.

Distribution of KRAS and BRAF Mutations in Metastatic Colorectal Cancers in Turkish Patients.

The results of this study demonstrate the potential prognostic and predictive values of KRAS and BRAF gene mutations in patients with colorectal cancer (CRC). It has been proven that KRAS and BRAF mutations are predictive biomarkers for resistance to anti-EGFR monoclonal antibody treatment in patients with metastatic CRC (mCRC). We demonstrated the distribution of KRAS (codons 12, 13 and 61) and BRAF (codon 600) gene mutations in 50 mCRCs using direct sequencing and compared the results with clinicopathological data. KRAS and BRAF mutations were identified in 15 (30%) and 1 (2%) patients, respectively. We identified KRAS mutations in codon 12, 13 and 61 in 73.3% (11/15), 20% (3/15) and 6.67% (1/15) of the positive patients, respectively. The KRAS mutation frequency was significantly higher in tumors located in the ascending colon (p=0.043). Thus, we found that approximately 1/3 of the patients with mCRC had KRAS mutations and the only clinicopathological factor related to this mutation was tumor location. Future studies with larger patient groups should yield more accurate data regarding the molecular mechanism of CRC and the association between KRAS and BRAF mutations and clinicopathological features.

Associations analysis of GSTM1, T1 and P1 Ile105Val polymorphisms with carpal tunnel syndrome.

Oxidative stress was related with carpal tunnel syndrome (CTS). We aimed to clarify the associations between glutathione S-transferase (GST)M1, GSTT1 and GSTP1-Ile105Val polymorphisms and CTS. One hundred-forty patients with CTS and 97 healthy controls were enrolled in this study. Tinel and Phalen signs were noted as positive or negative. Functional and clinical status of patients was evaluated by the Boston Questionnaire. The intensity of hand and/or wrist pain was evaluated on 10 cm visual analog scale (VAS). We applied the polymerase chain reaction (PCR) to determine the polymorphisms of the GSTM1 and GSTT1 and the PCR-restriction fragment length polymorphism method for detecting the GSTP1-Ile105Val polymorphism. The M1 null genotype was significantly higher in patients with CTS compared to healthy controls, and the M1 null genotype seemed to increase the risk of CTS approximately two-fold (P = 0.011; odds ratio (OR) = 1.98; 95 % confidence interval (CI) 1.17-3.36). The M1 null, T1 present combined genotype was significantly higher in patients with CTS compared to healthy controls (P = 0.043); however, it seemed not to increase the risk of CTS (P = 0.14; OR = 0.62; 95 % CI 0.33-1.76). We found significantly higher levels of the VAS, Boston Symptom Severity Scale and Phalen sign in patients with the Ile/Val or the Val/Val genotypes compared to those in patients with the Ile/Ile genotype (P = 0.003, 0.004 and 0.044, respectively). We proposed that genes involved in the protection from oxidative stress may influence the susceptibility, clinical and functional status of CTS. The GSTM1 null genotype may be related with the development of CTS, whereas the Val allele of GSTP1-Ile105Val polymorphism may be associated with worse functional and clinical status in CTS.

Glutathione S-Transferase M1 and T1 Gene Polymorphisms in Patients with Chronic Plaque-Type Psoriasis: A Case-Control Study.

OBJECTIVE: To determine the role of glutathione S-transferase (GST) isoenzyme polymorphisms as susceptibility factors in patients with psoriasis in a Turkish cohort. SUBJECTS AND METHODS: In this case-control study, 105 patients with plaque-type psoriasis and 102 healthy controls were recruited from the dermatology outpatient clinics of two university hospitals. Genomic DNA was extracted from whole blood using a DZ DNA isolation kit. Multiplex PCR was used to determine GSTM1 and GSTT1 polymorphisms in the isolated DNAs. RESULTS: Of the 150 patients with psoriasis, 83 (79%) were identified with the GSTT1 genotype and 22 (21%) with the null genotype. Of the 102 patients in the control group, 69 (67.6%) subjects were identified with the GSTT1 genotype and 33 (32.4%) with the null genotype. There was no significant difference between the patient and control groups (p = 0.063). Regarding the GSTM1 polymorphism, 54 (51.4%) patients were identified with this genotype and 51 (48.6%) with the null genotype; in the control group, 50 (49%) were identified with this genotype and 52 (51%) with the null genotype. Again there was no statistically significant difference between the groups (p = 0.957). CONCLUSION: In this Turkish cohort of patients with psoriasis, neither GSTT1 nor GSTM1 polymorphisms were associated with disease susceptibility. Larger studies with a wider range of GST isoenzyme are needed.

Association of GSTM1, GSTT1, GSTP1-ILE105VAL and ACE I/D polymorphisms with ankylosing spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin. The aim of this study is to clarify the relationships between susceptibility and severity of AS and GST-mu1 (GSTM1), GST-theta1 (GSTT1), GST-pi1 (GSTP1)-Ile105Val and angiotensin-converting enzyme (ACE) I/D polymorphisms in AS patients. One hundred thirty-eight AS patients and seventy-one healthy controls were enrolled in this study. Erythrocyte sedimentation rate and C-reactive protein (CRP) levels of the AS patients were recorded. The scores of the numeric rating scale (NRS) pain, the Bath Ankylosing Spondylitis Activity Index, the Bath Ankylosing Spondylitis Metrology Index and the Bath Ankylosing Spondylitis Functional Index were calculated. The genotypes distributions and allele frequencies of GSTM1, GSTT1, GSTP1-Ile105Val and ACE I/D polymorphisms were compared between patients and healthy controls. The Multiplex polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism methods were used to detect the polymorphisms of ACE I/D, the GSTT1 and GSTM1 genes and the GSTP1-Ile105Val polymorphism, respectively. There were significantly higher levels of the GSTT1 null and the ACE II genotypes in AS patients compared to those in healthy controls (p = 0.002 and 0.005, respectively). We found significantly higher levels of CRP and the NRS pain scores in the patients with ACE ID or DD genotypes compared to those in the patients with ACE II genotypes (p = 0.005 and 0.035, respectively). The present results showed that genes involved in protection from oxidative stress and ACE gene may influence disease development and course in AS.

A Turkish Patient With Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Mimicking Diabetic Ketoacidosis

Abstract Succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency is an autosomal recessive disorder of ketone body utilization that is clinically characterized with intermittent ketoacidosis crises. We report here the second Turkish case with SCOT deficiency. She experienced 3 ketoacidotic episodes: The first ketoacidotic crisis mimicked diabetic ketoacidosis because of the associated hyperglycemia. Among patients with SCOT deficiency, the blood glucose levels at the first crises were variable, and this case had the highest ever reported blood glucose level. She is a compound heterozygote with 2 novel mutations, c.517A>G (K173E) and c.1543A>G (M515V), in exons 5 and 17 of the OXCT1 gene, respectively. In patient's fibroblasts, SCOT activity was deficient and, by immunoblot analysis, SCOT protein was much reduced. The patient attained normal development and had no permanent ketosis. The accurate diagnosis of SCOT deficiency in this case had a vital impact on the management strategy and outcome.

Qualitative and quantitative evaluation of the BCR-ABL fusion gene in chronic myelogenous leukemia by flourescence in situ hybridization and molecular genetic methods.

AIMS: Fluorescence in situ hybridization (FISH) and quantitative real-time polymerase chain reaction (QRT-PCR) were used to diagnose or screen for minimal residual disease (MRD) in Philadelphia (Ph) chromosome-positive leukemia. We compared the diagnostic utility of FISH and QRT-PCR at various time points in the course of chronic myelogenous leukemia (CML) and to determine the mean initial values for patients whose QRT-PCR results were not known at the time of diagnosis. RESULTS: We analyzed 135 results for 78 CML patients tested by FISH and QRT-PCR for the Ph chromosomal translocation. All newly diagnosed cases were positive by both methods. On follow-up following treatment, 1 case was FISH positive and QRT-PCR negative; 61 cases were FISH negative and QRT-PCR positive. Overall concordance was 54.1%. There was good concordance between QRT-PCR results and cytogenetic response categories. CONCLUSIONS: We confirmed that QRT-PCR allows precise measurement of low levels of BCR-ABL transcripts and can serve as a sensitive indicator of MRD. We also demonstrated 100% correlation between QRT-PCR and FISH in newly diagnosed CML.

Association and Prognostic Significance of the Functional -1562C/T Polymorphism in the Promoter Region of MMP-9 in Turkish Patients with Gastric Cancer.

Matrix metalloproteinases (MMPs) are a group of zinc-dependent peptidases that participate in matrix turnover in solid malignancies. The aim of this study was twofold. First, we sought to investigate under a case-control design the association between the functional -1562C/T polymorphism in the promoter region of MMP-9 and gastric cancer (GC) in a Turkish sample. Second, we examined its prognostic significance in GC patients. A total of 144 subjects were enrolled in the case-control study (79 GC cases and 65 controls). Overall survival (OS) and progression-free survival (PFS) served as the main outcome measures in the longitudinal study. The MMP-9 -1562C/T polymorphism was genotyped using a polymerase chain reaction-restriction fragment length polymorphism method. The odds ratio (OR) of GC for the CC genotype relative to the CT+TT genotypes was not significant (OR = 0.89, 95 % confidence interval [CI] = 0.44-1.82, P = 0.75). These results did not change after allowance for age and sex in multivariable regression analysis (OR = 0.81, 95 % CI = 0.40-1.94, P = 0.84). When the MMP-9 -1562C/T polymorphism was analyzed among GC patients in relation to OS and PFS, we found no significant differences between subjects with the CC and CT+TT genotypes. In conclusion, the results of our study did not point toward a major role of the MMP-9 -1562C/T polymorphism in the pathogenesis and clinical course of GC in Turkish subjects.

Oxytocin system social function impacts in children with attention-deficit/hyperactivity disorder.

To investigate relationships between the polymorphisms and social functioning of children with Attention Deficit/Hyperactivity Disorder (ADHD), according to the polymorphism of three oxytocin receptor (OXTR) genes (rs53576, rs13316193, and and rs2268493). A total of 198 children-studying in the same primary and secondary school and matched in terms of age and gender (99 ADHD, 99 control)-were included in this study. The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version was administered to establish the clinical diagnosis. The Social Reciprocity Scale (SRS) was applied to evaluate social functioning. The total genomic DNA was isolated from buccal mucosa samples. No significant differences were determined between the ADHD and control groups in terms of rs2268493, rs13316193, and rs53576 genotype distribution (P = 0.078, P = 0.330, and P = 0.149, respectively). However, the control group T allele frequency in the OXTR Single Nucleotide Polymorphism (SNP) rs2268493 was significantly higher than the ADHD group (P = 0.024). Compared to the control group, the ADHD group had a higher score on the SRS scale (SRS total; Z = -21,135, P < 0.001). No significant difference existed in the SRS scale scores between the children with the T/T genotype and the C allele in the ADHD group (SRS total; Z = -0.543, P = 0.587). The allele distribution of the OXTR gene SNP rs2268493 was significantly different in the ADHD group, compared to the control group. This observation is important in understanding the underlying biological infrastructure in ADHD and developing treatment modalities.