Assessment of CTLA-4 Gene Expression Levels on CD8+ T Cells in Renal Transplant Patients and Relation with Serum sCTLA-4 Levels.

CTLA-4 (Cytotoxic T Lymphocyte Antigen-4) is an immune regulator molecule that is expressed on a variety of immune cells, including CD4+ and CD8+ T cells. After realizing the significance of this regulator molecule, researchers began to concentrate on its activation or inhibition in cancer. Even though there have been some studies on organ transplantation and autoimmunity, the role of the CTLA-4 molecule in renal transplantation has not been demonstrated. The goal of this study was to see how CTLA-4 gene expression and serum sCTLA-4 levels affected renal transplant patients. Peripheral blood samples were collected before and 1-3 months after renal transplantation from 29 recipients. CD8+ T lymphocytes were separated using magnetic beads and purity of the cells controlled by Flow cytometry. CTLA-4 mRNA levels were determined by Real-Time PCR while serum sCTLA-4 levels were assessed by ELISA. 55% of the patient had decreased level of CTLA-4 mRNA after transplantation when compared to pre-transplantation levels. Moreover 61% of the patient had lower serum sCTLA-4 levels after transplantation. sCTLA-4 levels were decreased 11% of the patients with rejection episode after transplantation when compared to stabile patients (5%). Kidney rejection is a complicated process influenced by numerous unknown factors. Several parameters should be evaluated together to precise rejection episodes or graft dysfunctions. Further research focused on the other immune checkpoint regulator molecules could give an opportunity to have an idea about the effect of these molecules on renal transplantation.

Boric Acid Affects Cell Proliferation, Apoptosis, and Oxidative Stress in ALL Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is a type of acute lymphoblastic leukemia from early T-cell progenitors. Interest grows in creating less toxic agents and therapies for chemo-resistant T-ALL cancer. Recently, elemental boron has special properties useful in the creation of new drugs. Studies have revealed the cytotoxic properties of boric acid (BA) on cancer, but not fully understood. We aimed to investigate the effect of BA on cell proliferation, apoptosis, and oxidative stress in the Jurkat cells. The effects of BA on cell viability were determined by 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assay for 24-48-72 h. The impact of BA on apoptosis was analyzed by acridine orange/ethidium bromide. Expression of apoptosis regulatory genes (Bcl-2, Bax, Caspase-3-8-9) and apoptotic miRNA (miR-21) was used by real-time quantitative polymerase chain reaction (RT-qPCR). The total oxidant status (TOS), total antioxidant status (TAS), and the oxidative stress index (OSI) value were calculated for oxidative stress. We determined the cytotoxic activity of BA on Jurkat cells by using XTT and defined the IC50 concentration (802.7 µg/mL) of BA. The findings clearly show that BA inhibited Jurkat cell proliferation dose-dependently. BA induced apoptosis through downregulated anti-apoptotic genes, and upregulated pro-apoptotic genes. Additionally, we found that BA significantly reduced the expression of miR-21 (p<0.001). Our findings demonstrated that different doses of BA increased TAS levels while decreasing TOS levels in Jurkat cells. Our study suggests that BA might be potential anti-cancer agent candidate in ALL via inhibition of cell proliferation, induced apoptosis, and reducing the amounts of anti-oxidants in cells.

Association between mannose binding lectin gene polymorphisms and clinical severity of COVID-19 in children.

BACKGROUND: Mannose-binding lectin (MBL) is a member of innate immunity and acts with MASP (MBL-associated serine protease) to activate the lectin pathway of the complement system. MBL gene polymorphisms are associated with susceptibility to infectious diseases. This study investigated whether MBL2 genotype, serum MBL levels, and serum MASP-2 levels affect the course of SARS-CoV-2 infection. METHODS AND RESULTS: Pediatric patients diagnosed with COVID-19 by positive real-time polymerase chain reaction (PCR) were included in the study. Single nucleotide polymorphisms in the promoter and exon 1 in the MBL2 gene (rs11003125, rs7096206, rs1800450, rs1800451, rs5030737) were identified by a PCR and restriction fragment length polymorphisms analysis. Serum MBL and MASP-2 levels were measured by ELISA. COVID-19 patients were divided into asymptomatic and symptomatic. Variables were compared between these two groups. A total of 100 children were included in the study. The mean age of the patients was 130 ± 67.2 months. Of the patients, 68 (68%) were symptomatic, and 32 (32%) were asymptomatic. The polymorphisms in the - 221nt and - 550nt promoter regions did not differ between groups (p > 0.05). All codon 52 and codon 57 genotypes were determined as wild-type AA. AB genotypes were found 45.6% in symptomatic patients while 23.5% in asymptomatics. Moreover, BB genotype was detected 9.4% in symptomatic and 6.3% in asymptomatic patients (p < 0.001). B allele was more frequent in symptomatic patients (46.3%) compared to asymptomatic patients (10.9%). (p < 0.001). Serum MBL and MASP-2 levels did not differ statistically between the groups (p = 0.295, p = 0.073). CONCLUSION: These findings suggest that codon 54 polymorphism in the MBL2 gene exon-1 region can be associated with the symptomatic course of COVID-19.

Determination of High-Resolution HLA-DQB1 Suballeles and IL-17 Polymorphisms in Turkish Pediatric Patients.

Celiac disease (CD) is an autoimmune enteropathy in the small intestine caused by gluten intolerance of the patients. The most important genetic disease-related factor is human leukocyte antigen (HLA)-DQ polymorphism. Association between interleukin (IL)-17A expression of CD4 + T cells and various autoimmune diseases has been reported. The aim of this study was to investigate the relationship between single nucleotide polymorphism (rs2275913) IL-17A and HLA-DQ polymorphisms in Turkish pediatric celiac patients. Study group included 125 pediatric celiac patients with CD and 100 healthy pediatric controls. Deoxyribonucleic acid was isolated from peripheral blood samples. IL-17A polymorphism (rs2275913) was analyzed by polymerase chain reaction-restriction fragment polymorphism method. IL-17A polymorphism and low-/high-resolution HLA-DQ results of patients were evaluated. GG and GA genotype frequencies of IL-17A (rs2275913) polymorphism were significantly higher ( p < 0.05) in the CD patients than the control group. HLA-DQB1*02 and HLA-DQA1*05 alleles were detected in patients, while HLA-DQB1*03 and HLA-DQA1*01 alleles in the control group. Also, when we compared the patient and control groups in terms of HLA-DQ-DR haplotypes, HLA-DQB1*02-DQA1*05-DRB1*03 was found with the relative risk of 42.5 ( p < 0.05). As a result of high-resolution HLA-DQB1 typing, DQB1*02:01 and DQB1*03:02 were at high frequency ( p < 0.05; in 25 patient group). IL-17A (rs2275913) polymorphism genotype frequency was found to be significant in the patient group compared with the control group. The most common HLA-DQB1 suballele was observed as DQB1*02:01.

Could presepsin be an alternative marker in the early diagnosis of sepsis in COVID-19?

In critical patients with Coronavirus Disease (COVID-19), we investigated the diagnostic value of presepsin in the early diagnosis of superinfection with sepsis, and the effect of antibiotic treatment (AT) in the levels of presepsin and procalcitonin and C-reactive protein. A total of 68 critical patients with sepsis and septic shock in the intensive care unit and 20 outpatients (control group) with COVID-19 were taken. ICU patients (n = 68) were further divided into three groups. C(-)AT(-) had negative blood or tracheal aspirate cultures (C) and not AT on admission to ICU (n = 18), C(-)AT(+) had negative C and AT on admission to intensive care unit (n = 31) and C(+) had positive C (n = 19). Presepsin, procalcitonin, C-reactive protein results were compared between the groups. There were no significant relationships between presepsin levels with sepsis, septic shock, mortality, or length of stay in ICU in patients with COVID-19. For procalcitonin and C-reactive protein levels in C(-)AT(+) and C(+) groups were significantly higher than in control and C(-)AT(-) groups (p < .001). C-reactive protein levels in C(-)AT(-) group were significantly higher than in the control group (p < .001). PCT and CRP, there was no difference between C(-)AT(+) and C(+) groups, and procalcitonin there was no difference between control and C(-)AT(-) groups. Presepsin was not found as a useful biomarker for the prediction of sepsis in COVID-19 patients. These study findings indicate that procalcitonin and C-reactive protein may be an indicator of an early diagnostic marker for superinfection in critical COVID-19 patients.

DNA Sequencing Methods: From Past to Present.

Next-generation sequencing (NGS) is a highly effective genetic diagnostic test used in disease diagnosis. Although the Sanger method is used as the traditional method in genome studies, the use of NGS methods has been increasing with the development of technology. The foundation of next-generation sequencing was laid with the methods developed by Allan Maxam-Walter Gilbert and 2 Nobel laureates, Frederick Sanger. Initially, first-generation sequencing methods completed a certain part of the DNA with great efforts in a few days, while in today's technology, the entire DNA of even the most complex organisms is sequenced in 1 day. Second- and third-generation sequencing methods have been developed with improvements in cost, time, and accuracy of sequencing. The data obtained from these methods are interpreted with bioinformatics and contributed to the development of next-generation sequencing technology. These developments have increased the interest in studies on the relationship between next-generation sequencing and DNA or RNA depending on diseases. In this review, past and present methods of next-generation sequencing technologies are mentioned in detail and the difficulties and conveniences of these methods are reviewed.

The changes in the expression levels of ß-catenin gene in pre- and post- Kidney Transplants.

PURPOSE: Wnt signaling is an important pathway in kidney development and disease. We aimed to establish the levels of ß-catenin expression in CD4+ T cells before and after renal transplantation and to associate it with the form of transplant type, rejection, and graft dysfunction. METHODS: CD4+ T cells were isolated from patients before and after kidney transplantation and their purity was confirmed by flow cytometer. RNA isolation and cDNA synthesis were carried out from these cells. The expression changes of the ß-catenin were investigated by real-time polymerase chain reaction (RT-PCR). Changes in the ß-catenin protein levels were determined by the western blot analysis. RESULTS: The increasing expression levels of ß-catenin were detected in 60.8% of the patients 6 months after transplantation when compared to patients before transplantation result. 12 of these 14 patients had no graft rejection. It was observed that 11 of 14 patients with increased ß-catenin expression had not graft dysfunction after the transplantation. CONCLUSION: According to our results, the increased levels of ß-catenin expression after transplantation may have a protective function for kidney survival. To understand this protective mechanism, further analysis of this signaling pathway is necessary.

Human Leucocyte Antigen B50 Is Associated with Conversion to Generalized Myasthenia Gravis in Patients with Pure Ocular Onset.

OBJECTIVES: The aim of this study was to investigate the associations between major histocompatibility complex (MHC) class I and II alleles and disease characteristics in Turkish patients with myasthenia gravis (MG). SUBJECTS AND METHODS: The MHC class I and II alleles of 108 unrelated MG patients were genotyped. The human leucocyte antigen (HLA) distribution of all MG patients and subgroups of MG patients (grouped according to disease characteristics) was compared to that of 250 healthy controls. RESULTS: Overall distributions of HLA-B*61 and C*05 were more frequent in MG patients (7.4 vs. 2.0% and 14.8 vs. 6.8%, respectively) than in non-MG patients. Subgroup analyses revealed that HLA-DRB1*14 and DQB1*02 alleles were more frequent in early-onset MG [n = 10 (20.8%) vs. n = 25 (10.0%) and n = 21 (43.8%) vs. n = 59 (23.6%)]. In patients seropositive for anti-AchR antibodies, the frequencies of HLA-B*50 and C*05 were higher. HLA-C*05, DRB1*01, and DRB1*11 were higher in patients with ocular MG. In addition, HLA-A*01, A*31, B*08, and DRB1*14 were higher among patients with thymic hyperplasia, whereas DQB1*03 was lower. However, all of these differences lost significance after correction of the p value for multiple comparisons. No allele association was found among patients with thymoma. Strikingly, patients with generalized MG who had pure ocular symptoms at disease onset had significantly increased HLA-B*50 compared to the controls (corrected p < 0.001, OR = 9.92; 95% CI 3.05-32.22). CONCLUSION: The HLA-B*50 allele was associated with conversion to generalized disease in patients with pure ocular symptoms at disease onset. This finding could extend our understanding of the complex interactions between the pathogenesis of MG and genetic heritage.

Pediatric small bowel transplantation: A single-center experience from Turkey.

BACKGROUND/AIMS: Small bowel transplantation (SBTx) is a treatment option for patients with serious parenteral nutrition-related problems in intestinal failure. Izmir Tepecik Training Research Hospital Organ Transplantation Center is still the only pediatric intestinal transplant center in Turkey. MATERIAL AND METHODS: This study was approved by the local ethics committee. Patients' data were analyzed from the medical charts and the hospital digital database. Seven isolated SBTxs were performed in six children between 2010 and 2016. RESULTS: One jejunal segment and six partial jejuno-ileal segments were used for seven transplants. All grafts were retrieved from deceased donors (one child and six adult donors). The six recipients had a mean age of 8.8±6.9 years (9 months to 17 years; M: 4, F: 2). The mean follow-up period of patients was 727±848 (34 to 1950) days. Acute cellular rejection (ACR) rates were 57% (n: 4) in the first 2 months. Graft loss due to severe ACR was seen in one patient. Central line-associated fungal (n: 3, 42%) and bacterial infections (n: 3, 42%) were seen in the first 2 months. Two Epstein-Barr virus (EBV) infections were recorded between 3 and 8 months in two patients. Our 1-year patient and graft survival rates were 71% and 71%, respectively. CONCLUSION: SBTx has become a treatment modality for patients with intestinal failures. Management of ACR and infections are still challenging problems in SBTx. Appropriate-sized cadaveric donors are very limited in Turkey for pediatric intestinal transplantation candidates. Although the number of SBTxs performed was small, this study shows promising results.

Single antigen flow beads for identification of human leukocyte antigen antibody specificities in hypersensitized patients with chronic renal failure.

AIMS OF THIS STUDY: Aims of this study were to identify class I and class II antibodies in highly sensitized patients by flow cytometry single antigen bead (FC-SAB) assay and to evaluate according to donor HLA type in order to increase their kidney transplantation chance. MATERIAL AND METHODS: We analyzed 60 hypersensitive patients of 351 individuals, who applied to our laboratory for PRA test in November 2013-December 2014. Flow cytometric PRA screening and single antigen bead commercial kits were used for these analyses. RESULTS: In our study group, 19 (31.7%) of these patients were male while 41 (68.3%) patients were female. The most common acceptable antigens were A*02 (10.11%), HLA-A*23 (10.11%), HLA-B*38 (8.79%) and HLA-DRB1*03 (7.83%) in hypersensitive patients. The highest antibody reactivity on SAB was observed against HLA-A*25, HLA-B*45, HLA-DRB1*04 and HLA-DRB1*08 antigens. CONCLUSIONS: The determination of these acceptable and unacceptable antigens may increase their transplantation chance. Pre-transplant HLA antibody identifications provide prognostic information with respect to the determination of patients who are at increased risk of graft loss.

Familial Mediterranean fever gene mutations in north-eastern part of Anatolia with special respect to rare mutations.

We aimed to determine the frequency of mutations, carrier rates and the association of rare mutations with Familial Mediterranean Fever (FMF) symptoms. There is a need to evaluate as many different populations as possible in order to determine either specific rare mutations or a range of disease-associated mutations. The demographic data and FMF symptoms related to MEFV gene mutations were collected from 731 participants. Exon 2 and exon 10 of the MEFV gene were tested by DNA sequencing. The rare mutations were identified as: M694I (1.1%, n=12), E148V (0.6%, n=6), T267I (0.5%, n=5), L110P (0.2%, n=2), E167D (0.2%, n=2), K695R (0.1%, n=1) and an insertion G (Guanine) mutation (0.4%, n=4) at the 777th codon of exon 10. We used routine comprehensive detection systems such as Sanger sequence that can catch rare mutations, for definite diagnosis and treatment of FMF disease.

De novo produced anti-human leukocyte antigen antibodies relation to alloimmunity in patients with chronic renal failure.

AIMS: Chronic renal failure causes patients to become dialysis dependent, which is exhausting for them both financially and psychologically. However, the definitive treatment of chronic renal failure is transplantation. One of the crucial factors affecting success in transplantation is the presence of anti-human leukocyte antigen (HLA) antibodies in patients. HLA alloimmunization is caused by various sensitization events such as blood transfusion, pregnancy, and transplantation. In this study, different sensitization events were compared to determine the effectiveness on the panel-reactive antibody status in female solid organ transplantation candidates based upon pregnancy. RESULTS: When results were evaluated in terms of alloimmunization rates, 62.8%, 73.4%, and 14.9% of the patients were found to have blood transfusion, pregnancy, and rejection history, respectively. Three hundred twenty-six of the 444 women had had at least one pregnancy. Panel-reactive antibody (PRA) (class I and/or II)-positive rates were significantly higher among patients with pregnancy and blood transfusion history (43.7%) than patients with only pregnancy history (27.5%) and pregnancy and transplantation history (40%). While transplantation history significantly affects class II anti-HLA levels, blood transfusion raises class I levels. CONCLUSIONS: Solid organ transplantation appears to have the strongest HLA alloimmunization effect followed by pregnancy and blood transfusion, especially for class II HLA antigens. Patients who were sensitized by more than one sensitization event have a lower chance to have a solid organ transplantation. In this case, identification of donor-specific antibodies and the results of the cross-match tests play an important role both before and postrenal transplantation.

The association of human leukocyte antigen polymorphisms with disease severity and latency period in patients with silicosis.

BACKGROUND: Denim sandblasting may cause silicosis as a result of free crystalline silica inhalation. Its pathogenesis remains unclear, but autoimmunity may play a role in the development of silicosis. The present study aimed to investigate the relationships between human leukocyte antigen (HLA) and the severity and latency period of silicosis. METHODS: 48 silicotic patients in the Eastern part of Turkey were classified according to their latency period and disease severity. The distribution of HLAs according to disease severity and latency period was assessed. RESULTS: A23 (7.5%), B49 (7.5%), and B51 (25%) were more common in the mild group than in the severe group, and B55 (8.9%) and DR4 (17.9%) were more common in the severe group than in the mild one. Only B51 was significantly more common in the mild group than in the severe one (25%, n = 10 vs. 7.1%, n = 4; p = 0.016). CONCLUSIONS: This study suggests that HLA antigens may play a particular role in the severity of silica-induced lung disease, but there was no association between HLA and progression time of the disease.

Investigation of ErbB-2 overexpression on patients with gastric cancer in Eastern Anatolia of Turkey.

BACKGROUND/AIMS: In the present study, the frequency of ErbB-2 overexpression and its relationship with pathologic parameters on patients with gastric cancer in Eastern Anatolia of Turkey was studied. MATERIALS AND METHODS: A total of 32 newly diagnosed patients were enrolled in the study. DNA isolation was performed on paraffinized tumor tissues obtained from patients by endoscopy or surgical resection. ErbB-2 overexpression was investigated from the isolated DNA by "Real Time Polymerase Chain Reaction". RESULTS: ErbB-2 positivity was detected in five (15.6%) of 32 gastric cancer patients. The correlation between distant metastases and ErbB-2 positivity was found to be statistically significant (p=0.04). Additionally, no statistically significant correlation was noted between ErbB-2 positivity and parameters such as level of differentiation (p=0.7), the depth of tumor invasion (p=0.08), lymph node metastases (p=0.6), Lauren's classification (p=0.4), World Health Organization classification (p=0.3), tumor, node, metastasis staging (p=0.3) and tumor localization (p=0.2). Lymph node involvement was present in all ErbB-2 positive patients, the depth of tumor invasion was T3 (one case) and T4 (four cases) with the cardia being the most common location, which was remarkable, though not statistically significant (p>0.05). All ErbB-2 positive patients were detected with intestinal-type gastric cancer according to Lauren's classification and with the tubular-type according to World Health Organization classification. CONCLUSION: According to our findings, given the rates of ErbB-2 overexpression (15.6%) in gastric cancer, the investigation of ErbB-2 overexpression as an important biomarker in humanized monoclonal-antibody treatment in patients with gastric cancer was considered appropriate.

HLA B27 subtype distribution among patients with ankylosing spondylitis in eastern Turkey.

Human leukocyte antigen (HLA) B27 has a strong association with ankylosing spondylitis (AS) and other spondyloarthropathies. More than 70 subtypes of HLA B27 have been described. The present study investigated B27 subtype distribution among B27-positive patients with AS classified according to the modified New York criteria and healthy controls. Sequence-specific primer polymerase chain reaction technique was used for B27 subtyping of 43 unrelated patients with AS and 39 volunteer bone marrow donors. Among patients with AS, the male-female ratio was 6.2 and the mean age was 30 years. No relationship was found between the B27 subtypes and clinical and laboratory findings in patients with AS (p>0.05). Similarly, the frequencies of B27 subtypes did not significantly differ between patients and controls. In this study, B*2746, B*2749, and B*2767 subtypes were detected for the first time. Among B27 subtypes, the most common B27 alleles found in the patients and the controls were B*2702 and B*2705. In addition, B*2702 subtype was found predominantly in both patients (48.8%) and controls (46.2%). In conclusion, in addition to commonly encountered B*2702 and B*2705 HLA subtypes, a B*2749 subtype in a patient with AS and B*2746 as well as B*2767 subtypes in controls were determined for the first time.

Role of HLA allele polymorphism in chronic hepatitis B virus infection and HBV vaccine sensitivity in patients from eastern Turkey.

Human leukocyte antigen (HLA) alleles have been associated with the clinical outcomes of hepatitis B virus (HBV) infection, which range from spontaneous recovery to hepatocellular carcinoma. In this study involving subjects from eastern Turkey, the frequencies of HLA-B35, HLA-CW4, HLA-DQ2, and HLA-DQ8 were markedly higher in the chronic HBV group than those in the spontaneously recovered group; the frequencies of HLA-A11 and HLA-A24 in the nonresponsive HBV vaccine group were markedly higher than those in the responsive HBV vaccine group; and the frequency of HLA-CW6 in the nonresponsive HBV vaccine group was significantly lower than in the responsive group. A complete understanding of HLA types associated with the progression to chronic HBV infection and their effects within the cell at the molecular level will be an important contribution in the development of new HBV vaccines and new treatment strategies for chronic HBV infection.

Genotype-phenotype correlation in patients with familial Mediterranean fever in East Anatolia (Turkey).

AIMS: Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease. Clinical symptoms and findings (phenotypes) seen in this disease are generally fever, abdominal pain, and arthritis. Amyloidosis is also a significant complication. Phenotype-genotype correlations in FMF have not been conclusively resolved. The aims of this study were to find the most frequent mutation/genotype of FMF, as well as to investigate the role of genetic factors on the phenotype and on the development of amyloidosis in a population living in East Anatolia (Turkey). This study included 105 adult patients with FMF. DNA samples were obtained from peripheral blood lymphocytes of the patients. Mutations of the Mediterranean fever (MEFV) gene were analyzed with an FMF Strip Assay test kit (ViennaLab Labordiagnostika GmbH, Vienna, Austria). Patients were separated according to genotypes, and phenotypes were compared statistically by the chi-square test. RESULTS: The most frequent mutation was M694V (53%) and the most frequent genotype was M694V/M694V (26%). In total, 81% of the patients experienced abdominal pain, 76% had fever, and 22% had arthritis. Fever and arthritis were determined in similar ratios to other genotypes (76% and 19%, respectively) in the M694V/M694V genotype (74% and 29%, respectively) (p > 0.50 and p > 0.20, respectively). However, the patients without the M694V/M694V genotype (86%) had a higher abdominal pain ratio than did the patients with the M694V/M694V genotype (67%) (p <0.05). Renal amyloidosis was determined in 33% of both M694V/M694V and M680I(G/C)/M680I(G/C) homozygous groups and in 12% of the heterozygous groups (p < 0.02 and p < 0.00002, respectively). In other words, homozygous groups had higher ratios of renal amyloidosis. CONCLUSIONS: The most frequent mutation in FMF was M694V and the most frequent genotype was M694V/M694V. Fever, abdominal pain, arthritis, and renal amyloidosis were determined not only in patients with M694V/M694V genotype but also in other genotypes. Therefore, genotypes may not predict phenotypes in FMF. Renal amyloidosis was seen more frequently in homozygous genotypes.

Distribution of HLA Tissue Groups in Patients with Gastric Cancer.

OBJECTIVE: Gastric cancer is an important disease that is seen all over the world and that threats public health. At the same time, gastric cancer is a heterogeneous disorder with multifactorial etiologies. Recent studies have shown a significant association between HLA antigens and gastric adenocarcinoma. The aim of the present study was to determine the distribution of HLA class I (HLA-A, B and C) and class II (HLA-DR, DQ and DP) antigens in Turkish patients with gastric adenocarcinoma. MATERIALS AND METHODS: HLA alleles or HLA haplotypes associated with gastric cancer were established in the Turkish population using PSR-SSP analysis in 71 unrelated patients with gastric cancer and in 82 unrelated healthy controls. The statistical significance of differences in allele frequencies between patients and controls was measured by the Chi-square test with Yates's correction. RESULTS: The study revealed that the HLA-Cw5 antigen is more prevalent in patients with gastric cancer (p=0.042) and that the HLA-DRB1*15 antigen is more prevelent in the control group (p=0.021). CONCLUSION: It is probable that HLA-Cw5 is a risk factor for gastric cancer whereas HLA-DRB1*15 plays a protective role for this disease. The results show that different loci on HLA may control resistance to or tendency for any disease in different societies; each society should determine its own tissue group.

The frequency of familial mediterranean Fever related amyloidosis in renal waiting list for transplantation.

OBJECTIVE: Our goal is to investigate the distribution of MEFV mutations in patients with renal amyloidosis who are in renal transplant waiting list which is prepared for transplantation. MATERIALS AND METHODS: FMF was diagnosed in 25 of the 297 patients between the years 2004 and 2008, who were involved in the study (15 male, 10 female; age 34±7.8). 5 out of 25 patients were transplanted, remaining were waiting for Tx. Biopsy results were amyloidosis and taken from renal (n:16), rectal (n:8) and duodenal (1).All of them were carrier of mutations in both pyrin alleles.The primer cause of chronic renal failure in our group was secondary AA amyloidosis. DNA was isolated from 25 whole blood samples. The NanoChip Molecular Biology Workstation (Nanogen) uses electronic microarrays for mutation detection. Exon 2,3,5 and 10 of pyrin gene genotypes were identified in the NanoChip. RESULTS: Genetic analysis of the patients demonstrated that each subject carries either homozygote or compound heterozygote mutations of the gene. The most common mutations were M694V, V726A, E148Q and M680I. CONCLUSIONS: The clinic manifestation and complain of our patients were febrile and painful attacks such as in the abdomen, chest and joints due to inflammation of the peritoneum, pleura and synovial membrane. The major problem in FMF is the occurrence of amyloidosis that primarily affects the kidneys causing proteinuria and renal failure. Dialysis and renal transplantation can be treatment, but it is important to diagnose FMF at earliest stages. The percentage of FMF patients in our waiting list was 8.4%. Moreover, in our region FMF incidence is highly frequent, so FMF should be chased by genetically so as to prevent chronic renal failure due to amyloidosis.

Exposure to bitumen fumes and genotoxic effects on Turkish asphalt workers.

OBJECTIVE: Bitumen fumes consist essentially of polycyclic aromatic hydrocarbons (PAHs) and their derivatives, some of which are known to be carcinogenic or cocarcinogenic in humans. The aim of this study was to investigate exposure to asphalt fumes among Turkish asphalt workers and determine whether any effects could be detected with genotoxic tests. STUDY DESIGN: The study included 26 asphalt workers and 24 control subjects. Sister chromatid exchange (SCE) and micronucleus (MN) were determined in peripheral lymphocytes. Urinary 1-hydroxypyrene (1-OHP) excretion was used as a biomarker of occupational exposure to PAHs. RESULTS: The asphalt workers had a significant increase in SCEs and MN (for each, p < 0.001). A positive correlation existed between the duration of exposure and rates of SCE or MN frequencies (r = 0.49, p < 0.05; r = 0.53, p < 0.05, respectively). The concentration of 1-OHP in urine was higher for the asphalt workers than for the controls (p < 0.001). However, we found that there was no statistically significant correlation between the urinary 1-OHP concentration and SCEs or MN frequencies (r = 0.25, p > 0.5; r = 0.17, p > 0.5, respectively). CONCLUSIONS: This study shows that Turkish asphalt workers have an increased exposure to PAHs from bitumen fumes, and genotoxic effects could be detected by SCEs and MN tests.