Huseyin Bagci

No Strong Association Between HER-2/neu Protein Overexpression and Gene Amplification in High-grade Invasive Urothelial Carcinomas

The generation of urothelial carcinoma is caused by the accumulation of various molecular changes, as in most malignancies. There are conflicting data about the status of HER-2/neu oncogene in urothelial carcinomas. The aim of this study was to determine the status of HER-2/neu oncogene in high-grade invasive urothelial carcinoma of urinary bladder both in protein and DNA level. We evaluated HER-2/neu protein overexpression by immunohistochemistry (IHC) and gene amplification by fluorescent in situ hybridization (FISH) and real-time quantitative PCR in paraffin-embedded samples of high-grade invasive urothelial carcinoma obtained from 36 patients. Polysomy 17 was also assessed by FISH. Immunohistochemically, HER-2/neu protein overexpression was observed in 22 (61.1%) tumors (ten tumors with score 3+ and 12 with score 2+). Fourteen of 36 tumors (38.9%) were evaluated as negative (score 0 or 1+). Complete concordance between FISH and the PCR was seen in all of the samples scored as 0 and 1+ by IHC. HER-2/neu gene amplification was observed in three of 27 (11.1%) tumors by FISH (nine samples were non-informative) and in eight of 36 (22.2%) tumors by the PCR. The complete concordance between HER2-2/neu protein overexpression and gene amplification was seen only in three of 27 tumors. Polysomy 17 was seen in nine tumors (33.3%). The results indicated that, in contrast to breast cancer, there was no strong association between HER-2/neu overexpression and gene amplification in invasive urothelial carcinomas, and polysomy 17 was higher in tumors showing HER-2/neu overexpression.

The Role of RELN in Lissencephaly and Neuropsychiatric Disease

Reelin is an extracellular matrix‐associated protein important in the regulation of neuronal migration during cerebral cortical development. Point mutations in the RELN gene have been shown to cause an autosomal recessive human brain malformation termed lissencephaly with cerebellar hypoplasia (LCH). Recent work has raised the possibility that reelin may also play a pathogenic role in other neuropsychiatric disorders. We sought, therefore, to define more precisely the phenotype of RELN gene disruption. To do this, we performed a clinical, radiological, and molecular study of a family in whom multiple individuals carry a chromosomal inversion that disrupts the RELN locus. A 6‐year‐old girl homozygous for the pericentric inversion 46,XX,inv7(p11.2q22) demonstrated the same clinical features that have been previously described in association with RELN point mutations. The girls brain magnetic resonance imaging (MRI) findings, including pachygyria and severe cerebellar hypoplasia, were identical to those seen with RELN point mutations. Fluorescence in situ hybridization confirmed that one of the breakpoints of this inversion mapped to within the RELN gene, and Western blotting revealed an absence of detectable serum reelin protein. Several relatives who were heterozygous for this inversion were neurologically normal and had no signs of psychotic illness. Our findings demonstrate the distinctive phenotype of LCH, which is easily distinguishable from other forms of lissencephaly. Although RELN appears to be critical for normal cerebral and cerebellar development, its role, if any, in the pathogenesis of psychiatric disorders remains unclear.

Familial influence on parkinsonism in a rural area of Turkey (Kızılcaboluk–Denizli): A community-based case-control study

This population‐based study on parkinsonism in a genetically isolated community from a rural area of Turkey aimed to provide a selective evaluation of environmental and heritable risk factors. An increased prevalence of parkinsonism (4.1%) was detected in the village of Kızılcaboluk for people 65 years of age and older. This study included 36 patients with parkinsonism living in Kızılcaboluk and three times that number of age‐ and sex‐matched people serving as controls. A questionnaire including demographic data, family history, education, occupation, data on exposures to pesticides, smoking, alcohol intake, and head trauma was administered. We found a significant association of parkinsonism cases with a positive family history in first‐degree relatives (odds ratio [OR], 7.48; 95% confidence interval [CI], 2.52–22.17; P < 0.0001) and with pesticide exposure (OR, 2.96; 95% CI, 1.31–6.69; P = 0.015) compared to the control subjects. The value of genetically isolated populations for the identification of genetic risk factors for common and complex disorders has gained much attention recently because the genetic make‐up of these populations is likely to be less complex than that of the general population and our findings should prompt investigations to the nature of a familial aggregation of parkinsonism in this population.

Progressive autosomal dominant optic atrophy and sensorineural hearing loss in a Turkish family

Purpose: To describe the clinical features, mode of inheritance, and linkage analysis of ten affected members of a three-generation family with progressive optic atrophy and progressive hearing loss. Materials and methods: The proband, a 10-year-old boy, presented with progressive visual failure. Ten other members in his family, including his mother, half-sister, aunt, two uncles, grandfather, and some of the cousins, also had progressive visual loss and hearing loss. Six affected and four unaffected cases were examined in detail. Blood samples were drawn from 16 members for DNA extraction. Two loci previously described for optic atrophy were tested for linkage in the present family. Results: The mode of inheritance was clearly autosomal dominant. Six members of the family were found to have progressive optic atrophy and hearing loss, both starting in the first decade of life. Total or red-green color blindness was detected in some patients. None of the members of this family showed evidence of other systemic disorders; however, four had blepharochalasis. No other cause could be found for the hearing or the visual loss. Linkage analysis excluded OPA1 and OPA2. Conclusion: The present Turkish family belongs to the group of individuals with autosomal dominantly inherited optic atrophies with hearing loss. Linkage analysis excluded OPA1 and OPA2, indicating that a novel gene defect underlies the disease in this family. Further genome-wide linkage analysis and identification of the disease-associated gene will help define the pathophysiology of this syndrome.

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

Summary 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.

HLA-B51 gene and its expression in association with Behçet’s Disease in Denizli Province of Turkey

Behçet’s Disease (BD) is a multisystemic inflammatory disorder as a triad of symptoms including recurrent oral and genital aphthous ulceration, and uveitis with unknown pathogenesis. Many researchers have tried to investigate the association of HLA-B51 gene with the BD. We aimed to investigate the association of the HLA-B51 gene and its expression, also polymorphic structure by PCR, RT-PCR and sequence specific oligonucleotide primers and probes in BD patients (n: 35) and control group (n: 50). According to our results, we did not observe any association in between HLA-B51 gene, its polymorphism, expression and BD patients.

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 Gramstain. Thirty-three cervices from women who underwent total hysterectomy for noninvasive noncervical 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.