Investigation of Immunovascular Polymorphisms and Intersections in Psoriasis.

BACKGROUND: Psoriasis is a chronic, inflammatory skin disease. The etiology of the disease is unknown. It is a polygenic and multifactorial disease, which interacts with genetic and environmental factors. Genetic factors (polymorphism/mutation) can alter the immune system and normal physiologically functioning keratinocytes to pathological or predisposition levels. AIMS: We aimed to investigate psoriasis at a different and novel window by searching for vascular and immunological variations and intersections in psoriasis. We investigated the main vascular and hypoxic controlling factors, which are vascular endothelial growth factor (VEGF) and hypoxia inducible factor 1 alpha (HIF-1α), as well as immunological and serotonergic factors, such as TNF-α, IL-10, and 5HT2A, which could connect each other to the pathogenesis of psoriasis. SUBJECTS AND METHODS: Nine single nucleotide polymorphisms (SNPs) in five genes were genotyped by mini-array format in 300 subjects: VEGF (rs2010963, rs833061, and rs1570360), HIF-1α (rs11549465), TNF-α (rs361525, rs1799964, and rs1800629), IL-10 (rs1800896), and 5HT2A (rs6311). RESULTS: An association was found between rs1800629 (TNF-α) and Type I psoriasis, and rs833061 (VEGF) and Type II psoriasis. Haplotype analysis suggests that the coexistence of the polymorphisms rs1799964 (TNF-α), rs2010963 (VEGF), rs833061 (VEGF), and rs6311 (5HT2A) may be a protective factor for psoriasis. CONCLUSION: Our results suggest that the vascular component of the studied vasculo-immunologic variation is more relevant in the pathogenesis of psoriasis.

Tumour suppressor PTEN enhanced enzyme activity of GPx, SOD and catalase by suppression of PI3K/AKT pathway in non-small cell lung cancer cell lines.

Phosphates and tensin homologue deleted on chromosome 10 (PTEN) is a tumour suppressor gene which dephosphorilates phosphoinositol 3,4,5 triphosphates. Therefore PTEN can regulate PI3K/AKT pathway in cells. Because of promoter methylation or gene deletion, PTEN expression is commonly decreased or lost in non-small cell lung cancer (NSCLC) cell lines. Therefore, we hypothesized that PTEN could regulate the activity of superoxide dismutase (CuZnSOD), glutathione peroxidase (GPx) and catalase. We first recreated PTENwt, G129R and G129E expressions in lung cell lines, in which endogenous PTEN expression was not detected. Then, we showed that PTEN could suppress AKT activity by its lipid phosphatase domain. We then examined the effect of recreated PTEN expressions in NSCLC cells. While PTENwt expression caused enhanced activity of SOD, GPx and catalase in transfected cells lines, neither G129R nor G129E expression effected enzyme activities. These results suggest that PTEN can up-regulate SOD, GPx and catalase activity by inhibition of PI3K/AKT pathway in NSCLC cell lines.

Vitamin D receptor gene polymorphisms and haplotypes (Apa I, Bsm I, Fok I, Taq I) in Turkish psoriasis patients.

BACKGROUND: Psoriasis is an inflammatory disease characterized by increased squamous cell proliferation and impaired differentiation. Vitamin D, Calcitriol, and its analogues are successfully used for psoriasis therapy. However, it is unknown why some psoriasis patients are resistant to Vitamin D therapy. Vitamin D mediates its activity by a nuclear receptor. It is suggested that polymorphisms and haplotypes in the VDR gene may explain the differences in response to vitamin D therapy. MATERIAL/METHODS: In this study, 102 psoriasis patients and 102 healthy controls were studied for VDR gene polymorphisms. The Fok I, Bsm I, Apa I and Taq I polymorphisms were examined by PCR-RFLP, and 50 subjects received vitamin D therapy to evaluate the association between VDR gene polymorphisms and response to vitamin D therapy. Existence of cutting site is shown by capital letters, and lack was shown by lower case. The haplotypes were analysed by CHAPLIN. RESULTS: There was significant difference in allele frequency of T and genotype frequency of Tt between cases and controls (p values 0.038 and 0.04, respectively). The Aa and bb genotypes were significantly higher in early onset than late onset psoriasis (p values 0.008 and 0.04, respectively). The genotypes Ff, ff and TT are significantly different between vitamin D3 therapy responders and non-responders (p values 0.04, 0.0001, 0.009, respectively). To the best of our knowledge, this is the first report showing importance of VDR gene haplotypes in psoriasis, the significance of the Wald and LR (Likelihood Ratio) statistics (p=0,0042) suggest that FfBbAatt is a disease-susceptibility haplotype. CONCLUSIONS: Haplotype analysis is a recent and commonly used method in genetic association studies. Our results reveal a previously unidentified susceptibility haplotype and indicate that certain haplotypes are important in the resistance to vitamin D3 therapy and the onset of psoriasis. The haplotypes can give valuable data where genotypes unable to do.

Is Helicobacter pylori a pathogenic agent of the cervix uteri?

BACKGROUND: Helicobacter pylori is a gram-negative, microaerophilic rod-shaped bacterium that lives beneath the gastric mucosal layers, on the surface of epithelial cells. Gastric infection with this organism causes inflammation of the gastric mucosa, which can lead to gastritis, duodenal or gastric ulcers and even in rare cases to gastric carcinoma or MALT lymphoma. Approximately 50% of the population of the entire world is believed to be infected with H. pylori, but the exact route of transmission is still uncertain. It has been speculated that the cervix, with its endocervical columnar epithelium and acidic mucous layer, might provide a suitable environment for H. pylori. H. pylori might be a pathogenic agent for cervical infection. In order to address this issue we studied H. pylori in the endocervical tissue. METHODS: To investigate our hypothesis, we examined cervical tissue using PCR, culture, and Gram-stain. Thirty-three cervices from women who underwent total hysterectomy for noninvasive non-cervical benign uterine diseases were analyzed in this study. Twenty-one patients had cervicitis and 12 patients were included as controls. RESULTS: Of the 29 patients studied, none showed evidence of H. pylori infection. H. pylori was not detected by PCR, histology, or culture. CONCLUSIONS: We could not detect H. pylori in the cervix of patients with cervicitis. H. pylori-infected patients' cervices remain to be investigated, and a larger study is needed to draw firm conclusions.

Existence of acute lymphoblastic leukemia and osteosarcoma in a child.

The existence of acute lymphoblastic leukemia (ALL) and osteosarcoma is described. An 8-year-old girl had osteosarcoma diagnosed on radiologic and pathologic examination during ALL maintenance treatment. Cytogenetic analyses in primary cell culture of osteosarcoma tissue from the patient showed complex chromosomal abnormalities including t(1;19), usually seen in B precursor cell ALL, and del 13, found in a great majority of primary osteosarcomas. To show the possibility of the existence of the genetic susceptibility caused by gene rearrangements, we used molecular technique. But we could not determine any association between gene and genetic susceptibility.

Incidence and molecular analysis of glucose-6-phosphate dehydrogenase deficiency in the province of Denizli, Turkey.

BACKGROUND: G6PD deficiency is a widespread abnormality of glucose-6-phosphate dehydrogenase, a red cell enzyme, which gives rise to hemolysis under oxidative stress. In Turkey, G6PD deficiency has a variable frequency in different regions. The prevalence and genotypes of G6PD deficiency are not known in Denizli province of the Aegean region of Turkey. Accordingly, this study was designed to investigate the prevalence of enzyme deficiency and the distribution of the Mediterranean mutation of G6PD in this region. MATERIAL/METHODS: A total of 1950 students (918 females, 1032 males, ages between 14 and 17) were screened by the Fluorescent Spot Test, and the G6PD deficiency was confirmed by quantitative spectrophotometric assay. The G6PD deficient subjects were further analyzed by the PCR/RFLP technique to identify the presence of the 563 T Mediterranean mutation. RESULTS: 24 of the subjects were found to be deficient in this enzyme, a frequency of 1.23%. Of 24 deficient subjects, 19 (79%) had the 563 T Mediterranean mutation. CONCLUSIONS: The frequency of G6PD enzyme deficiency appears to be low compared with those found in the malaria-endemic Mediterranean region of Turkey. The molecular pathology of G6PD deficiency is related to the G6PD-563 T mutation in the Denizli region.