The Role of Parkin in Rat Pancreatic Beta Cells Fate.

Parkin is a member of the mitochondrial quality control system that plays a major role in mitophagy. Although the loss of function mutations in the Parkin gene has been associated with the Familial Parkinson's phenotype, research in recent years points out that Parkin's function is not limited to neurodegenerative diseases. Parkin's function impressing key cellular quality control mechanisms, including the ubiquitin-proteasome and autophagy-lysosome systems, makes it an important player in the maintenance of cellular homeostasis. In this study, we investigated whether Parkin affects cell viability and ER stress responses under lipotoxic conditions in INS-1E cells. Our results may suggest that silencing Parkin may affect autophagy in addition to apoptosis.  We also showed that Parkin may have a protective effect against lipo-toxic effects in INS-1E cells. Consistent with previous studies, we observed that stress responses were different for high and low palmitic acid doses. The Parkin being inhibited under high-dose PA treatment and active under low-dose PA treatment indicate that regulation of stress responses is controlled by environmental conditions. Our preliminary findings may suggest that in low lipotoxic conditions, Parkin affects the ER stress response by modulating Chop activity and Ca2+ release from the ER to the cytoplasm.

Beta-Cell Golgi Stress Response to Lipotoxicity and Glucolipotoxicity: A Preliminary Study of a Potential Mechanism of Beta-Cell Failure in Posttransplant Diabetes and Intraportal Islet Transplant.

OBJECTIVES: Lipotoxicity and glucolipotoxicity are among the mostimportanttriggers of beta-cell failure in patients with type 2 and posttransplant diabetes. Because the Golgi apparatus is a vital organelle in secretory cells like beta cells, its behavior under stress conditions determines the cell's functional capacity. MATERIALS AND METHODS: To mimic lipotoxicity and glucolipotoxicity as metabolic stresses for beta-cell failure, rat insulinoma INS-1E cells were treated with palmitic acid, glucose, or both. Cells were cultured in the presence of 5.0, 16.7, or 33 mM glucose with or without 0.5 mM palmitic acid for 8, 16, 24, and 48 hours. Incubation in the presence of any of the 3 concentrations of glucose with 0.5 mM palmitic acid provided glucolipotoxicity. In addition to the endoplasmic reticulum stress marker (Hspa5), we evaluated changes in Golgi function under experimental metabolic stresses. In doing this, we measured expression levels of the genes coding Golgi structural proteins (Acbd3,Golga2, and Arf1), Golgi glycosylation enzymes sialyltransferaz10 and sialyltransferase 1 (St3gal1), and Golgi stress mediators (Creb3 and Arf4). RESULTS: Golgi responded to lipotoxicity and glucolipotoxicity by increasing the expression of St3gal1 (P = .05 in both conditions) and Creb3 (P = .022 and P = .01, respectively). The Arf4 gene transcript also increased in glucolipotoxic media (P = .03). Glucotoxicity alone did not induce a change in the transcript levels of Creb3 and Arf4. Lipotoxicity and glucolipotoxicity induced Creb3 and Arf4 expression, which are important Golgi stress response mediators leading to apoptosis. CONCLUSIONS: This preliminary study showed that the Golgi stress response is important in lipotoxic and glucolipotoxic conditions in terms of beta-cell failure. Solving the mystery of intracellular molecular mechanisms leading to beta-cell dysfunction is crucial to understanding the pathophysiology of posttransplant diabetes and most probably the failure of intraportal islet transplants in the long term.

Lack of association between MMP13 (rs3819089), ADAM12 (rs3740199-rs1871054) and ADAMTS14 (rs4747096) genotypes and advanced-stage knee osteoarthritis.

OBJECTIVES: The aim of this study was to investigate the relationship between MMP13 rs3819089, ADAM12 rs3740199 and rs1871054, and ADAMTS14 rs4747096 genotypes in patients with radiologically diagnosed knee osteoarthritis (OA). PATIENTS AND METHODS: A total of 300 patients (68 males, 232 females; mean age: 61.6 years; range, 25 to 89 years) who were admitted to the orthopedics and traumatology clinic and diagnosed with knee OA according to the 2000 American College of Rheumatology (ACR) criteria between October 2018 and March 2019 were prospectively analyzed. Patients with Grades III-IV OA according to the Kellgren-Lawrence (K-L) grading system were included in the patient group (n=150) and those without radiological features of knee OA (K-L Grades I-II) were included in the control group (n=150) voluntarily. The presence of single nucleotide polymorphisms (SNPs) in the targeted genes in both groups was assessed by real-time polymerase chain reaction in the peripheral blood sample. RESULTS: The most common nucleotides in both the control and patient groups were CG for rs3740199 and CT for rs1871054 in the ADAM12 gene, and the most common nucleotides in alleles were GG for MMP13 rs3819089 and AA for ADAMTS14 rs4747096. No statistically significant relationship was detected between the gene polymorphisms and advanced OA. CONCLUSION: The study results suggest that ADAM12 rs3740199 and rs1871054, MMP13 rs3819089, and ADAMTS14 rs4747096 polymorphisms have no relationship with knee OA susceptibility in the Turkish population. However, as this is the first study to investigate the relationship between the SNPs of ADAM12, ADAMTS14, and MMP13 genes and the development of OA in the Turkish population, it would contribute to our understanding of the molecular bases of OA.

Endothelial nitric oxide synthase gene polymorphisms in patients with slow coronary flow.

BACKGROUND AND AIMS: The aim of this study was to explore potential associations of the intron 4 variable number of tandem repeats (VNTR) and E298A polymorphisms of the endothelial nitric oxide synthase (eNOS) gene with slow coronary flow (SCF). The association between plasma nitrate and nitrite (NO x ) concentrations and eNOS gene polymorphisms was also assessed. MATERIALS AND METHODS: The intron 4 VNTR and E298A polymorphisms of the eNOS gene were evaluated in the isolated DNA blood samples obtained from the SCF patient group (n = 30) and healthy group consisted of age- and sex-matched controls (n = 61). RESULTS: Plasma NO x level was significantly lower in patients with SCF than in controls. In addition, patients with SCF have significantly lower nitric oxide levels than control subjects within each genotype variants. The allele and genotyped frequencies of the eNOS intron 4 VNTR and E298A polymorphisms were similar between patients with SCF and the controls. Plasma NO x concentrations with respect to the relevant genotypes were found insignificant. DISCUSSION AND CONCLUSION: Plasma NO x is lower in patients with SCF than in healthy subjects. Our findings may suggest the lack of association between intron 4 VNTR and E298A polymorphisms of the eNOS gene and SCF.

The relationship of recurrent aphthous stomatitis and Helicobacter pylori, cytokine gene polymorphism and cobalamin.

BACKGROUND/AIMS: The aim of the present study was to investigate whether Helicobacter pylori causes or triggers recurrent aphthous stomatitis (RAS) through cytokine gene polymorphism and/or cobalamin deficiency. MATERIALS AND METHODS: Thirty-six patients with RAS and 130 patients without RAS were genotyped for IL-1ß (-511C/T) and IL-6 (-174G/C) and evaluated for H. pylori infection and serum cobalamin level. RESULTS: The patient groups according to RAS had similar rates of H. pylori gastritis and interleukin genotypes/alleles, and there was a non-significant difference between serum cobalamin levels (p>0.05). RAS patients with H. pylori gastritis showed a higher frequency (51.9%) of GC IL-6 genotype than RAS patients without H. pylori gastritis (11.1%) (p=0.036). Non-GG genotype and C allele were increased in patients without RAS and with H. pylori gastritis (p<0.05). Patients with H. pylori gastritis showed a lower value of serum cobalamin without statistical significance, although this difference was more prominent in RAS patients (p=0.07). CONCLUSION: The carriage of the C allele of IL-6 may lead a susceptibility to chronic gastric inflammation after contamination with H. pylori. If H. pylori infection is justified as a predisposing factor for RAS and its severity by further studies, we can speculate that subjects with genetic susceptibility to this infection may benefit from H. pylori eradication treatment with respect to RAS.

Superoxide Dismutase and Catalase Genotypes in Pediatric Migraine Patients.

This study compared superoxide dismutase (SOD) and catalase (CAT) alleles in 97 consecutive children and adolescents with migraine to 96 healthy children and adolescents. Isolated genomic DNA was used as a template for SOD1 (35 A/C), SOD2 16 C/T, and CAT2 [(-262 C/T) and (-21 A/T)] allele genotyping. The SOD2 16 C/T genotype and C allele frequency differed significantly between controls and migraine (P = .047; P = .038). CAT -21 AA genotype and A allele frequency were significantly higher in both migraine with aura patients (P = .013; P = .004) and migraine without aura patients (P = .003; P = .001) compared to controls. To our knowledge, this is the first demonstration of differences in SOD and CAT genotypes between pediatric migraine patients and age-matched controls. Further studies on the functional implications of these genetic variants on neural antioxidant capacity and the use of antioxidant modulators for migraine treatment are warranted.

TGF-ß1 genotype in pediatric migraine patients.

There is no information about the role of transforming growth factor-beta 1 (TGF-ß1) in the pathogenesis of pediatric migraine. This study included 100 consecutive children and adolescents in whom migraine was diagnosed and 88 healthy children and adolescents. The isolated genomic DNA was used as a template for TGFß-1 (-800G/A, -509C/T, 869T/C [codon 10] and 915G/C [codon 25]) genotyping. The allelic frequency of 509C/T was significantly different between control and migraine without aura patients (P = .04). Codon 10 C/T genotypic and C10 C allelic frequency of TGF-ß1 polymorphisms were significantly higher in migraine and migraine without aura patients versus healthy controls (P = .00; P = .00). To our knowledge, this is the first report dealing with the relationship between TGF-ß1 genotype and migraine in the pediatric age group. Further studies related to this subject are needed, along with a search for new therapeutic agents with anti-inflammatory properties.

Involvement of Toll-like receptors in cervical cancer susceptibility among Tunisian women.

Previous studies underscored the importance of genetic factors in the pathogenesis of certain cancers, including cervical cancer. Epidemiological evidence supports an association between specific polymorphisms of Toll-like receptors (TLR) with several human pathological states, including cervical cancer. The aim of this study was to investigate the link between specific gene variants in TLR2 (-196 to -174 del), TLR3 (c.1377 C>T), TLR4 (Asp299Gly), and TLR9 (2848 G>A) and susceptibility to cervical cancer in Tunisian women. Study subjects comprised 122 women with histopathologically-confirmed cervical cancer, and 260 unrelated age- and ethnically-matched healthy females, who served as controls. TLR genotyping was done using PCR-restriction fragment length polymorphism. The C/C genotype of TLR3 (c.1377 C>T) is associated with cervical cancer susceptibility (OR: 1.71, CI: 1.08-2.70). For TLR4 (Asp299Gly), the Asp/Asp genotype and the Asp allele were associated with higher risk of developing cervical cancer (OR: 4.95, CI: 1.97-13.22) and (OR: 5.17, CI: 2.11-13.50) respectively. We demonstrated no association between the TLR2 (-196 to -174 del) and the TLR 9 (2848 G>A) polymorphisms and the susceptibility of cervical cancer among Tunisian women. However, the C/C genotype for the TLR3 (c.1377 C>T) polymorphism and the Asp/Asp genotype and the Asp allele for (Asp299Gly) TLR4 polymorphism were found to be associated with a higher risk of cervical cancer.

Multidrug resistance 1 (MDR1) 3435C/T genotyping in childhood drug-resistant epilepsy.

INTRODUCTION: A mutation at nucleotide position 3435 in exon 26 of the multidrug resistance 1 (MDR1) gene is the most frequently studied polymorphism in relation to multidrug resistance. However, there are conflicting data as to whether the CC or TT genotype of the 3435C>T polymorphism is associated with drug resistance. METHODS AND RESULTS: We investigated the association between this polymorphism in drug-resistant childhood epilepsy by comparison with drug-responsive patients. In total, 59 patients with drug-resistant epilepsy, defined as having four or more seizures within a 12-month period while using three or more AEDs, 60 children with drug-responsive epilepsy who had remained seizure-free for 12months on their current AED regimen and 76 healthy children were involved in this study. Genotype frequencies in drug-resistant patients were as follows: 32.2% CC, 44.1% CT, 23.7% TT; in the drug-responsive group: 20.0% CC, 50.0% CT, 30.0% TT; in the control group: 24.3% CC, 50.0% CT, 25.7% TT. Comparison of drug-resistant and drug-responsive patients revealed no significant difference in genotype frequency. The findings of the epilepsy patients were not significantly different from those of the healthy control subjects. CONCLUSIONS: Our study does not support any significant association between the MDR1 polymorphism and drug-resistant childhood epilepsy.

Endothelial nitric oxide synthase polymorphism influences renal allograft outcome.

BACKGROUND: Atherosclerotic lesions within the graft are considered to be a major cause of interstitial fibrosis/tubular atrophy (IF/TA). We evaluated the factors that influence the development of IF/TA and three- and five-yr graft survival including nitric oxide synthase (eNOS) and angiotensin II type 1 and type 2 receptor gene polymorphism. METHODS: Seventy-one male and 35 female patients (age: 34.9 ± 11.2 yr) who underwent living-related renal transplantation were included. Angiotensin type 1 and type 2 receptor gene polymorphisms and eNOS intron 4 gene polymorphism were analyzed. The pre- and post-transplant laboratory data, patient characteristics, acute rejection episodes, and presence of IF/TA were evaluated. RESULTS: Patients with the bb allele of eNOS gene had a lower prevalence of post-transplant third year (12.6% and 38.5%, p = 0.005) and fifth year IF/TA (46.6% and 82.3%, p = 0.02) and a lower incidence of five-yr graft failure (35.4% and 55.6%, p < 0.005). The eNOS gene polymorphism was independent and was the most prominent factor associated with third and fifth year IF/TA (p = 0.01, RR: 29.72, and p = 0.03, RR: 4.1, respectively). No significant relationship existed when angiotensin II gene polymorphisms were considered. CONCLUSIONS: We concluded that recipient eNOS gene polymorphism can predict IF/TA, and the presence of the bb allele is associated with better graft outcome.

Associations between endothelial nitric oxide synthase A/B, angiotensin converting enzyme I/D and serotonin transporter L/S gene polymorphisms with pulmonary hypertension in COPD patients.

Different biochemical pathways and cellular mechanisms play role in the pathogenesis of pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). Alveolar hypoxia is not the only determinant of vascular remodeling, genetic factors are thought to have additive effects. We aimed to investigate the effects of endothelial nitric oxide synthase (eNOS A/B), angiotensin converting enzyme (ACE I/D) and serotonin transporter (5-HTT L/S) gene polymorphisms on development and severity of PH in COPD patients. 50 COPD patients without PH (group 1); 30 COPD patients with PH confirmed with echocardiography (group 2) and 49 healthy subjects (group 3) as control group were included to the study. eNOS A/B, ACE I/D and 5-HTT L/S gene polymorphisms and allele frequencies of COPD patients with and without PH and healthy subjects were determined. Functional parameters and echocardiographic measurements were recorded. Patients with PH were also assessed in two subgroups according to the severity of pulmonary arterial pressure (PAP). Significant differences among three groups in the distribution of 5-HTT genotype and allele frequency were present (respectively p = 0.002; p = 0.021). In group 2, LL and LS genotype rate was 93.3 % with a frequency of 71.2 % L allele and 28.3 % of S allele. 5-HTT LL genotype was present in 88.9 % of patients with PAP ≥50 mmHg significantly (p = 0.012). Other genotype distributions were not significantly different between two subgroups. The results of this study can suggest that COPD patients with L allele of 5-HTT may have higher risk for the development of PH and patients with LL genotype of 5-HTT may present higher PAP. We also demonstrated that eNOS and ACE gene polymorphisms were not associated with the development and severity of PH in our study population. Further studies with larger numbers of patients are needed to explore these relationships.

Maternal-fetal proinflammatory cytokine gene polymorphism and preterm birth.

Association between maternal-fetal proinflammatory cytokine genotype and preterm birth was studied. Isolated genomic DNA from maternal and cord blood samples of 100 preterm and 101 term labors were used for TNFα (-238G/A, -308G/A), IL-1α (4845G/T), and IL-1ß (-511C/T) genotyping. TNFα -238 GA genotype in term neonates was significantly higher than the premature neonates (p<0.05). Maternal-fetal TNFα -238 heterozygosity was associated with term labor (p<0.05). TNFα -308 GA and AA genotypes were associated with term labor (mothers and neonates, respectively; p<0.05 and p<0.001). The incidence of term labor was significantly increased in TNFα -308 GA genotype. If a -308GA carrier has a fetus with GG genotype, the incidence of preterm labor increases (p<0.01). The 4845 T allele was significantly higher in preterm mothers and neonates (p<0.001 and p<0.001). The effect of maternal-fetal genotype for the pregnancy outcome reveals that maternal 4845GG and GT genotypes increase term labor incidence, whereas fetal 4845 TT genotype was a significant independent risk factor for preterm birth (p<0.01). IL-1ß -511 TT genotype was significantly higher in preterm neonates. The preterm labor risk was significantly increased in maternal -511 TT genotype and fetal CT genotypes, whereas with maternal -511 CT or TT genotypes or a -511 TT fetus, the incidence of term pregnancy increases (p<0.01).

Genetic mutations in Turkish population with pulmonary embolism and deep venous thrombosis.

Venous thromboembolism (VTE) is a universal health hazard. Inherited and acquired risk factors increase the risk of VTE. We evaluated the relationship between factor V (G1691A, A1090G, and A1299G), prothrombin (PT G20210A), methylenetetrahydrofolate reductase (MTHFR C677T) mutations, plasminogen activator inhibitor 1 (PAI-1 -675) polymorphism, and VTE in Turkish population. In all, 80 patients with VTE and 104 controls were included. Heterozygous factor V Leiden (FVL) mutation was significantly higher among patients (P = .04) with allele frequency of 6.3% (P = .01). Heterozygous PT G20210A mutation was also significantly higher among patients (P = .001) with allele frequency of 6.9% (P = .003). MTHFR 677TT genotype was significantly higher in patients (P = .009) with allele frequency of 23.8% (P = .005). No significant difference was found in FV A1090G and FV A1299G mutation rate as well as PAI-1 genotypes and their allele frequencies (P > .05). Thus, frequencies of FV G1691A, PT G20210A, and MTHFR C677T mutations are higher in patients with VTE. FV A1090G, FV A1299G mutations, and PAI-1 gene polymorphisms may not be a risk factor for VTE in Turkish population.

The role of plasminogen activator inhibitor-1 and angiotensin-converting enzyme gene polymorphisms in bronchopulmonary dysplasia.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a multifactorial disease of preterm infants that is characterized by airway injury, inflammation, and parencymal remodeling. Activation of the coagulation cascade leads to intraalveolar fibrin deposition in many inflammatory pulmonary disorders. Increased fibrin formation or decreased fibrinolysis may cause extravascular fibrin deposition. Extravascular fibrin deposits in septae and alveoli due to the altered fibrin turnover are the pathological hallmarks of BPD, which strongly indicate the importance of the imbalance in the competing activities of coagulation and fibrinolysis. OBJECTIVE: We investigated the predictive value of variations in plasminogen activator inhibitor-1 (PAI-1) and angiotensin-converting enzyme (ACE) genes as molecular determinants for BPD in neonates. METHODS: The study group comprised 98 preterm infants with BPD and a control group including 94 preterm infants without BPD. Restriction fragment size analyses were performed by visualizing digested polymerase chain reaction products for ACE and PAI-1 genotypes. RESULTS: No significant associations were found between ACE, PAI-1 gene polymorphisms, and BPD phenotype in our population. CONCLUSIONS: The two gene polymorphisms (PAI-1 and ACE) had no role in the development of BPD in our study. Further studies with other genes are required for the identification of molecular predisposing factors for BPD that may help in the development of new treatments.

Glycoprotein IIIa gene polymorphism and coronary artery disease.

OBJECTIVE: Prevalence of glycoprotein IIIa gene polymorphisms (PIA2) has been reported to be elevated in persons who die of sudden death. PIA2 has been suggested as contributing to the development of atherosclerosis via coronary plaque rupture and thrombus formation. In this prospective study, we investigated the correlation between the PIA2 polymorphism, atherosclerotic plaque burden, and its prognostic significance. METHODS AND RESULTS: One hundred and seventy-eight patients (mean age 51 +/- 9.6 years) suspected to have atherosclerotic coronary artery disease underwent a coronary angiography and were evaluated for gene polymorphisms. Patients were followed up for 4 years for major adverse cardiac events (MACE). Thirty-eight patients (21%) had the PIA2 polymorphism.There was no statistically significant correlation between presence of atherosclerotic plaque burden, severity of coronary artery stenosis, and glycoprotein genotype. During the follow-up there were no significant differences between the 2 groups with regard to MACE. Any cause of death and cardiovascular death were higher in patients with PIA2 polymorphism but these differences were not significant. On univariate analysis, smoking, presence of severe coronary artery disease, and presence of myocardial infarction were correlated with elevated risk of MACE; presence of atypical angina was correlated with fewer MACE. On multivariate analysis, smoking was an independent risk factor for a MACE. On univariate or multivariate analysis, there was no relation between the PIA2 polymorphism and a MACE. CONCLUSIONS: The glycoprotein IIb/IIIa genotype was not shown to indicate the presence of atherosclerotic plaque. There was no correlation between the genotype and plaque vulnerability.

Lack of association between FXIII-Val34Leu, FVII-323 del/ins, and transforming growth factor beta1 (915G/T) gene polymorphisms and bronchopulmonary dysplasia: a single-center study.

Bronchopulmonary dysplasia (BPD) is a multifactorial disease of preterm infants that is characterized by airway injury, inflammation, and parenchymal remodeling. Extravascular fibrin deposits in septae and alveoli due to the altered fibrin turnover are the pathological hallmarks of BPD that strongly indicates the importance of the imbalance in the competing activities of coagulation and fibrinolysis. Activation of the coagulation cascade leads to intraalveolar fibrin deposition in many inflammatory pulmonary disorders. Increased fibrin formation or decreased fibrinolysis may cause extravascular fibrin deposition. We evaluated the association between FXIII-Val34Leu, FVII-323 del/ins, and transforming growth factor beta1 (TGF-beta(1)) (915G/T) gene polymorphisms in patients with BPD. The study group consisted of 98 preterm infants with BPD. Ninety-four of the 192 preterm neonates were without BPD and sampled for the control group. Restriction fragment size analyses were performed by examining digested PCR products for FXIII-Val34Leu, FVII-323 del/ins, and TGF-beta(1) (915G/C) genotypes. No significant associations were found between FXIII-Val34Leu, FVII-323 del/ins, TGF-beta(1) (915G/C) gene polymorphisms and BPD phenotype in our population. Further studies with other genes are required for the identification of molecular predisposing factors for BPD that may help in the development of new treatments and hence might allow for targeting of this treatment to a "high-risk" subgroup, reducing unnecessary exposure to potentially harmful therapies.

Incidence of and risk factors for childhood thrombosis: a single-center experience in Ankara, Turkey.

This study was conducted to analyze the incidence of and risk for thrombosis in thrombotic children monitored in the Department of Pediatric Hematology of our hospital at the time of diagnosis, in addition to the clinical characteristics of those patients. The clinical and laboratory findings of 122 patients diagnosed with thrombosis from 1997 to 2006 were retrospectively analyzed. The incidence of thrombosis was 88.6/10,000 hospital admissions. The authors found that 31.1% of the patients studied had a thrombosis in more than 1 region. The incidence of thrombosis by anatomic site was as follows: 42 thromboses in the peripheral arterial system, 39 in an intracardiac region, 38 in the abdominal venous system, 36 in the deep peripheral venous system, and 28 in the cerebral vascular system. The mean age of the patients at the time of diagnosis was 4.9 years. Of the patients studied, 10.7% were neonates, 35.3% were infants younger than 1 year, and 48.4% were younger than 2 years. Most of the patients had a congenital cardiac disease and spontaneous thrombosis, and 66.1% had at least 1 acquired risk factor, the most common of which were having undergone surgery (42%) or wearing a central venous catheter (39%). A hereditary factor for the development of thrombosis was present in 54% of the patients. The most frequently observed hereditary risk factor was the MTHFR 677C-T mutation, and the second most common was the factor V Leiden mutation. Thrombosis should be considered a systemic disorder, and thrombotic patients should be evaluated with appropriate methods. Acquired and hereditary risk factors should be analyzed systematically in thrombotic patients.

Prevalence of thrombophilic mutations and ACE I/D polymorphism in Turkish ischemic stroke patients.

The aim of this study was to evaluate the prevalence of factor V Leiden (FVL), prothrombin G20210A, methylenetetrahydrofolate reductase (MTHFR) C677T gene mutations, and angiotensin-converting enzyme (ACE) I/D polymorphism in ischemic stroke (IS) patients. A total of 162 Turkish IS patients were included and analyzed according to stroke subtype by the TOAST classification. Their genotype data were compared with those of the control group, representing the healthy population, using the chi(2) test. The frequency of FVL heterozygocity was 12.3% in this series-higher than that in the normal population (9.8%; statistically insignificant, P = .478). The frequency of the ACE D/D genotype in all stroke patients and those with stroke of undetermined etiology was higher than that in our population (52.5% and 59.2%, respectively, vs 39.3%; statistically significant, P = .034, P = .020). Our results may suggest that ACE D/D genotype is a risk factor for IS, particularly in those with stroke of undetermined etiology in the Turkish population.

Clinical findings and HER-2/neu gene amplification status of breast carcinoma patients.

The study group was derived from the archival materials of 48 invasive intraductal breast cancer patients who had undergone partial mastectomy/ axillary dissection. All patients included in the study had clinically T1-2N0M0 invasive ductal carcinoma. To detect HER-2/neu status, fluorescent in situ hybridization was performed using a HER-2/neu locus-specific probe. Signals were counted and patients were classified in three groups according to signal ratios: signal ratio <2, group 1 (n=31); signal ratio 2-4, group 2 (n=11); signal ratio >4, group 3 (n=6). Ratios of axillary metastatic lymph nodes to dissected total lymph nodes were 17%, 23% and 83% in groups 1, 2 and 3 respectively (P=0.003). The number of metastatic axillary lymph nodes, and the ratio of microscopic metastatic lymph nodes were highest in group 3 (P=0.001 and P=0.008, respectively). No significant difference was observed between groups for distant metastasis in a 5-year follow-up period. Signal ratios decreased with estrogen receptor expression (P=0.03). Histopathologically, an irregular growth pattern of the tumor was observed in 100% of the patients in group 3, and in 54% and 60% in groups 1 and 2, respectively (P=0.04). Lymphovascular invasion of the tumor was significantly higher in group 3 compared to the other two groups (P=0.01). The extensive intraductal component ratio was the highest in group 3 (P=0.04). The appearance of desmoplastic reaction and lymphocyte infiltration did not show significant difference between the groups. Our results show that HER-2/neu signal ratio increases with lymphovascular invasion, an extensive intraductal component, irregular growth pattern and axillary metastasis in clinically T1-2N0M0 invasive ductal carcinoma of the breast.