Frequency of CYP1A1*2C polymorphism in patients with leukemia in the Iranian population

Background: CYP1A1, a member of the cytochrome P450 (CYP) enzymes, plays a very important role in metabolizing carcinogens. The aim of this case-control study was to detect the frequency of CYP1A1*2C polymorphism in Iranian leukemic patients and determine the role of this allele's variants, if any, as a risk factor for developing leukemia. Methods: Thirty-nine patients with chronic myeloid leukemia (CML), 105 with acute myeloid leukemia (AML), 95 healthy volunteers as the adult control group, 85 children with acute lymphoblastic leukemia (ALL), and 94 healthy children as the children control group were studied. Genomic DNA was assayed for restriction fragment length polymorphism (RFLP) in the CYP1A1*2C loci by amplification followed by digestion with BsrDI. Results: The frequencies of AA genotype (wild) were 82.05, 62.85, 84.70, 85.10, and 80 in CML, AML, ALL, the children control group, and the adult control group, respectively. The frequencies of AG genotype (heterogeneous) were 17.95, 36.20, 15.30, 14.90, and 18.95 in CML, AML, ALL, the children control group, and the adult control group, respectively. The frequencies of GG genotype (mutant) were 0.95 and 1.05 in AML and the adult control groups respectively; whereas, it was not observed in CML, ALL, or the children control group. Logistic regression analysis showed a significant correlation between the CYP1A1*2C polymorphism AG and AML patients (OR=2.4, 95 CI=1.3-4.7, P>0.05). Conclusion: A higher frequency of CYP1A1*2C, observed in AML patients, compared with the adult control group indicates an increased risk for AML in individuals carrying the heterozygote allele CYP1A1*2C. However, the results did not show any association between CYP1A1*2C genotypes and risk of ALL or CML. © 2011 by The American Society for Clinical Pathology

Association of FXII 5�UTR 46C>T polymorphism with FXII activity and risk of thrombotic disease

Objective: Thrombotic diseases are caused by genetic and environmental factors. There are a number of well-characterized genetic defects that lead to increased risk of thrombosis. Results from previous studies have indicated that FXII is involved in the pathogenesis of thrombophilic diseases. However, the results in this regard are highly controversial. One of the most important determinants of Plasma FXII level is 46CgT polymorphism in the FXII gene. In the present study, the risk of thrombophilic diseases related to this polymorphism was investigated in a case-control study. Material and Methods: One hundred and sixty subjects were studied: 120 patients diagnosed with thrombophilia (96 venous thromboembolism, 24 arterial thrombosis), and 40 age-gender-matched controls. For each subject, FXII activity level was measured by a one-step clotting assay with FXII-deficient plasma, and 46CγT polymorphism was genotyped using a restriction fragment length polymorphism (RFLP) method. Results: In this study, the previous observation that individuals with different genotypes for the 46 CγT polymorphism show significant differences in FXII activity levels was confirmed. Most importantly, FXII activity �68 was associated with an increased risk of venous thrombosis with an adjusted odds ratio (OR) of 4.7 (95 confidence interval CI: 1.03-21.1, p=0.04). However, it was not a risk factor for arterial thrombosis with adjusted OR of 5 (95% CI: 0.91-27.1, p=0.09). In CT and TT genotype, the adjusted ORs were 2 (95% CI: 0.9-4.4, p=0.11) and 2.3 (95% CI: 0.45-11, p=0.48), respectively, for patients with venous thrombosis compared with the controls. Similarly, the adjusted ORs in arterial thrombosis were 1.2 (95% CI: 0.4-3.6, p=0.76) for CT and 1.8 (95% CI: 0.2-14.9, p=0.59) for TT genotype. Thus, we did not find any association of the mutated T allele in the heterozygous or homozygous state with an increased risk of venous or arterial thrombosis. Conclusion: Lower FXII activity is not a risk factor; rather, it simply represents a risk marker for thrombosis

On the relationship between the reversed hazard rate and elasticity

Despite hazard and reversed hazard rates sharing a number of similar aspects, reversed hazard functions are far less frequently used. Understanding their meaning is not a simple task. The aim of this paper is to expand the usefulness of the reversed hazard function by relating it to other well-known concepts broadly used in economics: (linear or cumulative) rates of increase and elasticity. This will make it possible (i) to improve our understanding of the consequences of using a particular distribution and, in certain cases, (ii) to introduce our hypotheses and knowledge about the random process in a more meaningful and intuitive way, thus providing a means to achieving distributions that would otherwise be hardly imaginable or justifiable

Immunosuppressive potential of human amnion epithelial cells in the treatment of experimental autoimmune encephalomyelitis

BACKGROUND: Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). In recent years, it has been found that cells such as human amnion epithelial cells (hAECs) have the ability to modulate immune responses in vitro and in vivo and can differentiate into multiple cell lineages. Accordingly, we investigated the immunoregulatory effects of hAECs as a potential therapy in an MS-like disease, EAE (experimental autoimmune encephalomyelitis), in mice. METHODS: Using flow cytometry, the phenotypic profile of hAECs from different donors was assessed. The immunomodulatory properties of hAECs were examined in vitro using antigen-specific and one-way mixed lymphocyte proliferation assays. The therapeutic efficacy of hAECs was examined using a relapsing-remitting model of EAE in NOD/Lt mice. T cell responsiveness, cytokine secretion, T regulatory, and T helper cell phenotype were determined in the peripheral lymphoid organs and CNS of these animals. RESULTS: In vitro, hAECs suppressed both specific and non-specific T cell proliferation, decreased pro-inflammatory cytokine production, and inhibited the activation of stimulated T cells. Furthermore, T cells retained their naïve phenotype when co-cultured with hAECs. In vivo studies revealed that hAECs not only suppressed the development of EAE but also prevented disease relapse in these mice. T cell responses and production of the pro-inflammatory cytokine interleukin (IL)-17A were reduced in hAEC-treated mice, and this was coupled with a significant increase in the number of peripheral T regulatory cells and naïve CD4+ T cells. Furthermore, increased proportions of Th2 cells in the peripheral lymphoid organs and within the CNS were observed. CONCLUSION: The therapeutic effect of hAECs is in part mediated by inducing an anti-inflammatory response within the CNS, demonstrating that hAECs hold promise for the treatment of autoimmune diseases like MS

Current k-records and their use in distribution-free confidence intervals

In a sequence of independent and identically distributed (iid) random variables, the kth largest (smallest) observation in a partial sample is well-known as the upper (lower) k-record value, when its value is greater (smaller) than the corresponding observation in the previous partial sample. In this paper, we consider the k-record statistics at the time when the nth k-record of any kind (either an upper or lower) is observed, termed as current k-records. We derive a general expression for the joint probability density function (pdf) of these current k-records and use it to construct distribution-free confidence intervals for population quantiles. It is shown that the expected width of these confidence intervals is decreasing in k and increasing in n. We also discuss the construction of tolerance intervals and limits in terms of current k-records. Finally, a numerical example is presented to illustrate all the methods of inference developed here.

Altered Expression of CD44, SIRT1, CXCR4, miR-21, miR-34a, and miR-451 Genes in MKN-45 Cell Line After Docetaxel Treatment.

PURPOSE: Today it is known that the gene expression profile of cancer stem cells differs from other cancer cells, which may lead to the resistance to routine treatments. The aim of this study was to investigate the effect of docetaxel (DOC) treatment on CD44+ cell frequency in human gastric cancer (GC) MKN-45 cell line and its effect on expression levels of SIRT1, CXCR4, microRNA (miR)-21, miR-451, and miR-34a that are closely correlated with the chemoresistance or self-renewal of cancer stem cells (CSCs). METHODS: The cytotoxic effect of DOC on MKN-45 cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT)-assay. The frequency of CD44+ cells was measured by flow cytometry in the treated and control groups. The expression level of SIRT1, CXCR4, miR-21, miR-451, and miR-34a was assessed in DOC-treated and non-treated cells using quantitative real-time PCR. Data were analyzed using Statistical Package for the Social Sciences (SPSS) software. RESULTS: The half-maximal inhibitory concentration (IC50) of DOC was 10 μg/ml after 48 h. Flow cytometry showed a significant increase in CD44+ cells after treatment with DOC (94.3%) when compared with non-treated cells (84.6%) (P < 0.01). The expression of SIRT1, CXCR4, and miR-21 was up-regulated (1.4-fold, 6.7-fold, and 1.22-fold, respectively, P < 0.05) in DOC-treated cells relative to non-treated cells, while miR-451 and miR-34a were down-regulated (0.14-fold and 0.36-fold, respectively, P < 0.05). CONCLUSION: DOC treatment affected CD44+ cell frequency in MKN-45 cell line and induced significant changes in the expression of SIRT1, CXCR4, miR-21, miR-451, and miR-34a that are implicated in stemness and chemo-radioresistance, which might offer new insights for future GC therapies

SOLID WASTE MANAGEMENT IN TABRIZPETROCHEMICAL COMPLEX

Tabriz petrochemical complex is located in the northwest of Iran. Major products of this industry include raw plastics like, polyethylene, polystyrene, acrylonitrile, butadiene, styrene, etc. Sources of waste generation include service units, health and cure units, water, power, steam and industrial processes units. In this study, different types of solid waste including hazardous and non hazardous solid wastes were investigated separately. The aim of the study was to focus on the management of the industrial wastes in order to minimize the adverse environmental impacts. In the first stage, locating map and dispersion limits were prepared. Then, the types and amounts of industrial waste generated in were evaluated by an inventory and inspection. Wastes were classified according to Environmental Protection Agency and Basel Standards and subsequently hazards of different types were investigated. The waste management of TPC is quite complex because of the different types of waste and their pollution. In some cases recycling/reuse of waste is the best option, but treatment and disposal are also necessary tools. In this study, using different sources and references, generally petrochemical sources, various solid waste management practices were investigated and the best options were selected. Some wastes should be treated before land filling and some of them should be reused or recycled. In the case of solid waste optimization, source reduction ways were recommended as well as prior incineration system was modified