Matrix Metalloproteinases 2 and 9 Polymorphism in Patients With Myeloproliferative Diseases: A STROBE-Compliant Observational Study

Chronic myeloproliferative disorders such as polycythemia vera (PV), essential thrombocytosis (ET), and idiopathic myelofibrosis arise from clonal proliferation of neoplastic stem cells in the bone marrow. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases that have potential to degrade all types of extracellular matrix (ECM) and also play a role in remodeling of the ECM. It is known that MMPs play a role in bone marrow remodeling.The primary goal of our study is to explore the relationship between chronic myeloproliferative diseases and some of MMP gene polymorphisms. The demonstration of a relationship will help to understand whether these polymorphisms may be a potential early diagnosis marker of the diseases.Patients were selected from outpatient clinics of Turgut Ozal University Hospital, Ankara, Turkey, between December 2010 and May 2011. Twenty-eight patients that previously diagnosed and followed-up with PV, 17 with secondary polycythemia (SP), and 12 with ET were enrolled in the study, along with a control group of 22 healthy people.DNA was isolated from peripheral blood. Using polymerase chain reaction–restriction fragment length polymorphism method, MMP2 and MMP9 gene polymorphisms were analyzed with agarose gel electrophoresis. There was a statistically significant difference between the study groups and the control group in terms of Gln279Arg polymorphisms rates of MMP9. The highest MMP9 Gln279Arg polymorphism rate was observed in the ET group. But nobody from the control group had polymorphic MMP9. There was no statistically significant difference between the groups in terms of MMP2-735 C > T polymorphism rates.In conclusion, MMP9 gene Gln279Arg polymorphism was associated with ET, SP, and PV diseases. Hence, we believe that these gene polymorphisms may play a role in the mechanism of bone marrow fibrosis and may be a factor that increases the risk of thrombosis. Illumination of the molecular basis of the relationship between MMP-thrombosis and MMP-fibrosis provides a better understanding of the pathophysiology of PV and ET diseases and will allow new approaches to diagnosis and treatment.     

High-resolution HLA-DRB1 and DQB1 genotyping in Japanese patients with testicular germ cell carcinoma.

We report for the first time the frequency distributions of HLA-DRB1 and -DQB1 genes in 55 patients with testicular germ cell carcinoma (TGC) using the modified PCR-RFLP method and compare the results with those for 1216 healthy Japanese control subjects. The modified PCR-RFLP method produced accurate, reproducible cleavage patterns that are easily discriminated. HLA-DRB1*0410 was the susceptibility allele (RR = 3.26, P = 0.006) and DQB1*0602 appears to be a candidate protective allele (RR = 0.26, P = 0.02) for TGC in the Japanese. None of the HLA-DRB1 and -DQB1 alleles showed a specific tendency for histological type or clinical stage of the tumours. Previous studies based on serotyping methods failed to show these allelic associations. High-resolution genotyping is essential because the peptide-binding domain of MHC class II molecules is determined more precisely by their genotypes than by their serotypes. In addition, inherent technical difficulties and typing errors of up to 25% make serotyping inefficient. Our results suggest that high-resolution genotyping is a useful genetic marker to determine risk for TGC.     

The Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease.

Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in recognition of, and subsequent immune response activation against, mycobacteria. The genetic polymorphism of TLR2 (arginine to glutamine substitution at residue 753 (Arg753Gln)) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to mycobacteria. The aim of the present study was to investigate the Arg753Gln single nucleotide polymorphism of the TLR2 gene in tuberculosis (TB) patients compared to healthy controls. A retrospective case/control study was carried out. The Arg753Gln polymorphism of the TLR2 gene was studied in 151 TB patients compared to 116 ethnically and age-matched healthy control subjects. The TLR2 polymorphism (adenine (A) allele) was observed in 17.9 and 7.7% of TB patients and controls, respectively. When the ratios of the three genotypes were compared between the two groups, the AA genotype was found to be more significantly associated with TB. Allele frequencies for guanine (G) and A were found to be 0.95 and 0.05 in the control group and 0.86 and 0.14 in the TB patient group, respectively. The risk of developing TB disease was increased 6.04- and 1.60-fold for carriers of the AA and GA genotypes, respectively. In conclusion, the present data suggest that the arginine to glutamine substitution at residue 753 polymorphism of the Toll-like receptor 2 gene influences the risk of developing tuberculosis.     

Synthesis of 3-[2-(2,3-dihydro-5-phenyl-4-substituted-3H-1,2,4- triazole-3-thione-2-yl)-acetylamino]-2-methyl-4(3H)-quinazolinones and their pharmacological activities

Some 2-methyl-3-triazole-substituted-4(3H)-quinazolinones 3a-f were prepared and tested for their H1- and H2-antihistaminic activities. In addition these compounds are central nervous system depressants and anticonvulsants. 3e shows highly significant decrease of locomotor activity.     

Effects of simplifying choice tasks on estimates of taste heterogeneity in stated-choice surveys

Researchers usually employ orthogonal arrays or D-optimal designs with little or no attribute overlap in stated-choice surveys. The challenge is to balance statistical efficiency and respondent burden to minimize the overall error in the survey responses. This study examined whether simplifying the choice task, by using a design with more overlap, provides advantages over standard minimum-overlap methods. We administered two designs for eliciting HIV test preferences to split samples. Surveys were undertaken at four HIV testing locations in San Francisco, California. Personal characteristics had different effects on willingness to pay for the two treatments, and gains in statistical efficiency in the minimal-overlap version more than compensated for possible imprecision from increased measurement error.     

Effect of dietary selenium and vitamin E on the biomechanical properties of rabbit bones

Summary It is generally agreed that combined deficiency of selenium and vitamin E leads to several abnormalities including Kashin-Beck disease which is an endemic and chronic degenerative osteoarthrosis. The abnormalities can be reversed by the administration of various forms of selenium and vitamin E.The present study was designed to investigate the effects of dietary selenium and vitamin E on bone tissue and on the biomechanical properties of bone. Young rabbits of both sexes were fed with either a selenium- and vitamin E-adequate diet (control group), or a selenium- and vitamin E-deficient diet or a selenium-excess diet. The selenium-deficient diet resulted in a significant decrease in plasma selenium level and the selenium-excess diet resulted in a significant increase in the plasma selenium level with respect to the corresponding control values (p<0.05). The diets did not affect the blood cell counts considerably but erythrocyte glutathione peroxidase activity increased (decreased) relatively when the plasma selenium level increased (decreased) (p<0.05). The light microscopic investigations of the bone tissues of the two experimental groups indicate that the findings of the present work are compatible with osteomalacia. The biomechanical properties of the bones from the three groups were determined experimentally with bending tests. Both the Se-and vitamin E-deficient diet and the Se-excess diet decreased the biomechanical strength of the bones significantly while the bones belonging to the control group always had the largest modulus of elasticity (p<0.05).     

A clinico-pathological study of laryngeal and hypopharyngeal carcinoma: correlation of cord-arytenoid mobility with histopathologic involvement.

OBJECTIVE: This study evaluates the vocal cord and arytenoid mobility in relation to the tumoral involvement of the cricoarytenoid joint (CAJ), thyroarytenoid (TA) muscle, and posterior cricoarytenoid (PCA) muscle in whole-organ sections of total laryngectomy specimens. STUDY DESIGN AND SETTING: The study was prospectively carried out between 1998 and 2003 and involved 133 primary squamous cell carcinoma cases of larynx or pyriform sinus that were treated with total laryngectomy. Preoperative mobility of vocal cords and arytenoids were evaluated separately and correlated with histopathologic findings. RESULTS: In cases with fixed vocal cord CAJ, TA muscle, and PCA muscle were involved in 42.4%, 72.9%, and 27.1% of the cases, respectively, while in cases with fixed arytenoid these structures were affected in 40%, 66.3%, and 25.3% of the cases. Weight effect seemed to play a role in 60% and 50% of the cases of supraglottic and pyriform sinus carcinoma, respectively. CONCLUSION: Careful evaluation of the mobility of the cord arytenoid unit separately helps the surgeon to better understand the patterns of tumoral extension guiding for the appropriate surgery which should be undertaken.