Cytotoxic T-lymphocyte antigen 4 gene polymorphisms and susceptibility to chronic hepatitis B

AIM:To assess the three polymorphism regions withincytotoxic T-lymphocyte antigen 4(CTLA-4)gene,a C/Tbase exchange in the promoter region-318(CTLA-4-318C/T),an A/G substitution in the exon 1 position49(CTLA-4 49A/G),a T/C substitution in 1172(CTLA-4-1172T/C)in patients with chronic hepatitis B.METHODS:Fifty-one patients with chronic hepatitis Bvirus infection and 150 healthy subjects were recruitedsequentially as they presented to the hepatic clinic.Clas-sification of chronic hepatitis B virus(HBV)-infected pa-tients was as asymptomatic carrier state(26 patients)and chronic hepatitis B(25 patients).Genomic DNA wasisolated from anti-coagulated peripheral blood Buffy coatusing Miller's salting-out method.The presence of theCTLA-4 gene polymorphisms was determined using poly-merase chain reaction amplification refractory mutationsystem(ARMS).RESULTS:We observed a significant association be-tween-318 genotypes frequency(T C-,T C ,T-C )and susceptibility to chronic hepatitis B(P=0.012,OR=0.49,95%CI:0.206-1.162).However,we did notobserve a significant association for 49 genotype fre-quency(T C ,T C- T-C )and -1172 genotype fre-quency(C T ,T C- C T-)and state of disease.CONCLUSION:Our results suggest that CTLA-4 genepolymorphisms may partially be involved in the suscepti-bility to chronic hepatitis B.     

Nonvirally engineered porcine adipose tissue-derived stem cells: use in posterior spinal fusion

Multiple factors alter intervertebral disc volume, structure, shape, composition, and biomechanical properties, often leading to low back pain. Spinal fusion is frequently performed to treat this problem. We recently published results of our investigation of a novel system of in vivo bone formation, in which we used nonvirally nucleofected human mesenchymal stem cells that overexpress a bone morphogenetic protein gene. We hypothesized that primary porcine adipose tissue-derived stem cells (ASCs) nucleofected with plasmid containing recombinant human bone morphogenetic protein-6 (rhBMP-6) could induce bone formation and achieve spinal fusion in vivo. Primary ASCs were isolated from freshly harvested porcine adipose tissue. Overexpression of rhBMP-6 was achieved ex vivo by using a nucleofection technique. Transfection efficiency was monitored by assessing a parallel transfection involving an enhanced green fluorescent protein reporter gene and flow cytometry analysis. rhBMP-6 protein secreted by the cells was measured by performing an enzyme-linked immunosorbent assay. Genetically engineered cells were injected into the lumbar paravertebral muscle in immunodeficient mice. In vivo bone formation was monitored by a quantitative microcomputed tomography (muCT). The animals were euthanized 5 weeks postinjection, and spinal fusion was evaluated using in vitro muCT and histological analysis. We found formation of a large bone mass adjacent to the lumbar area, which produced posterior spinal fusion of two to four vertebrae. Our data demonstrate that efficient bone formation and spinal fusion can be achieved using ex vivo, nonvirally transfected primary ASCs. These results could pave the way to a novel biological solution for spine treatment.     

Identification of disease-causing variants in the EXOSC gene family underlying autosomal recessive intellectual disability in Iranian families

Neurodevelopmental delay and intellectual disability (ID) can arise from numerous genetic defects. To date, variants in the EXOSC gene family have been associated with such disorders. Using next-generation sequencing (NGS), known and novel variants in this gene family causing autosomal recessive ID (ARID) have been identified in five Iranian families. By collecting clinical information on these families and comparing their phenotypes with previously reported patients, we further describe the clinical variability of ARID resulting from alterations in the EXOSC gene family, and emphasize the role of RNA processing dysregulation in ARID.     

Barriers and facilitators of implementing child injury surveillance system

Purpose: Child injuries are a global public health problem and injury surveillance systems (ISS) can be beneficial by providing timely data. However, ISS implementation has challenges. Opinions of stakeholders of ISS implementation barriers and facilitators are a good source to understand this phenomenon. The aim of this study is to investigate barriers and facilitators of implementing ISS in Iran. Methods: This is a qualitative study. Data were gathered through interviews with 14 experts in the field of child injury and prevention from Iranian Ministry of Health and Medical Education (MOHME), medical universities, pediatrics hospitals, general hospitals and health houses during January 2017 to September 2017. Data collection and analysis continued until data saturation. Data were analyzed using content analysis through identifying meaning units. Results: Barriers were classified in three main categories and nine subcategories including management barriers (including performance, coordination and cooperation, supervision and attitude), weakness in data capture and usage (including data collection, data recording and data dissemination) and resource limitation (including human and financial resources). Facilitators identified in three areas of policy making (including empowerment and attitude), management (including organization, function and cooperation and coordination) and data recording and usage (including data collection/distribution and data recording). Conclusion: The most important barrier is lack of national policy in child injury prevention. The most important facilitator is improving MOHME function through passing supportive regulations. Effective data usage and dissemination of information to those requiring data for policy making can help reduce child injuries. Coalition of stakeholders helps overcome existing barriers.     

Increased copy number at 17q22-q24 by CGH in breast cancer is due to high-level amplification of two separate regions

Studies by comparative genomic hybridization (CGH) have defined a chromosomal site at 17q22-q24 that is often overrepresented in breast cancer, neuroblastoma, and several other tumor types. Due to the limited resolution and dynamic range of CGH, it remains unclear whether this gain reflects high-level amplification of small subregion(s) or low-level gain of most of the distal 17q. We used 32 physically mapped 17q probes to construct more accurate copy number profiles for 14 breast cancer cell lines by interphase fluorescence in situ hybridization (FISH). Six cell lines (43%) showed an increased copy number of the 17q22-q24 region by CGH, and seven (50%) by FISH. FISH copy number profiles had a substantially higher dynamic range than did CGH profiles. FISH revealed two independent, highly amplified regions (A and B) at 17q23, separated by about 5 Mb of non-amplified DNA. These regions were distinctly telomeric from the ERBB2 gene locus. However, region A was often co-amplified with ERBB2, whereas B was amplified in cell lines that showed no ERBB2 amplification. We conclude that distal 17q gains recently discovered in breast cancer by CGH are due to high-level amplifications of two different regions at 17q23. This chromosomal region has previously been reported to undergo allelic loss and therefore was thought to harbor a tumor suppressor gene. The present FISH data provide support for the presence, and a starting point for the positional isolation, of 17q23 genes whose upregulation by amplification may play a role in the progression of breast cancer and many other tumor types. Genes Chromosomes Cancer 20:372–376, 1997. © 1997 Wiley-Liss, Inc.     

The Investigation of Risk Factors Impacting Breast Cancer in Guilan Province

Introduction: Breast cancer is multifactorial therefore more recognition of risk factors is important in its prevention. Objective: This study was conducted in order to determine the factors influencing breast cancer in women referred to health centers in Guilan province in 2015-2016. Method: In a case- control study, 225 women with breast cancer were investigated. The control group consisted of 225 healthy women of the relatives (third-rank) whose phone numbers were obtained from the patients. Data were collected through telephone interviews. Results: The risk of breast cancer raised in women who have a family history of other cancers (OR= 3.5; 95% CI= 1.96-6.6) ,exposure to X-Ray (OR= 2.5; 95% CI=1.1-5.5), having more than 4 children (OR= 2.695% CI=1.2-4.8), age more than 36 years at first pregnancy(OR=2.3; 95% CI=0.7-5.1),primary levelof education (OR= 5.4;95% CI=2.8-11.2) and inadequate intake of fruit (OR=1.5; 95% CI=1-2.2). Also, presence of the following factors reduced breast cancer risk: regular menstruation (OR= 0.66; CI=0.4- 0.9), duration of breastfeeding more than 12 months, less than 6 months and 7-12 months (OR=0.23; 95% CI=0.09-0.59 , OR=0.29; 95% CI=0.17-0.49 and OR=0.03; 95% CI=0.01-0.08) and parity (OR=0.4; 95% CI=0.27-0.83) In multiple linear regression analysis of higher education (OR=0.16; 95% CI=0.03-0.77), using contraceptives for more than 16 years (OR=2.3; 95% CI=1.4-3.9), family history of other cancers (OR=6.1; 95% CI=1.9-19.3) and a history of X-Ray exposure (OR=4.4; 95% CI=1.07-18.1) were considered as predictive factors. Conclusion: The results of this study emphasize the importance of informing women about breast cancer risk factors. So, identification of these risk factors is required as important means of prevention and treatment of breast cancer.