[show abstract][hide abstract] ABSTRACT: Tumor draining lymph nodes form the first line of defense against tumor dissemination. Lymphocyte subpopulations activated during anti-tumor response determine the outcome of host-tumor interaction. In the present study we explored the percentages of different subtypes of CD4+ lymphocytes, including regulatory cells (TFR, CD25-, and CD25+ Treg cells), helper subsets (Th1, Th2, Th17, and Tfh cells), and the expression level of their cognate cytokines (IFNγ, IL4, and IL17) in tumor draining lymph nodes of patients with breast cancer, and compared the results between node negative (LN-) and node positive (LN+) patients. Forty seven sentinel and auxiliary lymph nodes with or without tumor involvement were collected from untreated breast cancer patients undergoing surgical resection. Mononuclear cells obtained from fresh homogenized lymph nodes were subjected to surface and intracellular staining by flow cytometry. The results revealed the presence of a newly identified subtype of regulatory T cells, TFR, as well as CD25- Treg cells in TDLNs of the breast cancer patients. In addition, evaluation of different helper and regulatory subgroups of CD4+ T lymphocytes showed that upon metastasis of tumor cells to lymph nodes together with the progression of the disease stage, the immune responses changed from an inflammatory to an inhibitory state, as evidenced by a reduction in pro-inflammatory and anti-tumor cytokines, IL17 and IFNγ, as well as an increase in pro-tumorigenic phenotypes, Th2 and Treg cells. This situation may provide a favorable condition for tumor growth and spread.
[show abstract][hide abstract] ABSTRACT: Haptoglobin is an acute phase protein with antioxidant and immunomodulatory properties. Gene polymorphism may be a risk factor for diabetic vascular disease in Iranian population.
The study investigates the existence or not of an association between haptoglobin genotypes and prevalence of diabetic microangiopathy in individuals with type 2 diabetic microangiopathy.
We included 206 type 2 diabetic patients (<5 years duration) categorized into two groups according to the presence or absence of diabetic microvascular complications. The cases of interest were diabetic neuropathy, retinopathy, and nephropathy identified during clinical and or laboratory examination. In addition, 114 age- and sex-matched individuals were selected to serve as a control group. Haptoglobin genotyping was done using an amplification gel electrophoresis.
The frequency of haptoglobin phenotype 2-1 in diabetic patients was 70/206 (33.9%) as compared with 54/114 (47.3%) in nondiabetics (P = 0.01). However, the frequency of haptoglobin phenotype 2-2 was greater in diabetics (126/114, 61.1%) than in those without diabetes (56/114, 49.1%; P = 0.02). Patients with diabetic microangiopathy; however, did not differ significantly between haptoglobin phenotype groups.
Haptoglobin phenotype 2-2 is considered to be a major susceptibility gene for type 2 diabetic patients. Moreover, haptoglobin phenotype 2-1may be good prognostic factors for the development of diabetes mellitus.
North American journal of medical sciences. 09/2013; 5(9):529-35.
[show abstract][hide abstract] ABSTRACT: Three organotin(IV) complexes, Ph2Sn(mstsc) (1), Me2Sn(mstsc) (2) and Bu2Sn(mstsc) (3), have been synthesized from reaction of R2SnCl2 (R = Ph, Me and Bu) with 3-methoxysalicylaldehyde thiosemicarbazone (H2mstsc). The synthesized complexes have been characterized by elemental analysis and FT-IR, 1H, 13C and 119Sn NMR spectroscopy. The structures of 2 and 3 have been also confirmed by X-ray crystallography. On the basis of spectral and structural data thiosemicarbazone acts as a tridentate dianionic ligand and coordinates to tin through phenolic oxygen, the azomethine nitrogen and thiolate sulfur atoms. The metal coordination geometry for 2 and 3 is described as distorted square pyramid and the crystal lattices are stabilized by intermolecular hydrogen bands. On the basis of 119Sn NMR data, coordination number of tin retains five in solution. The in vitro antibacterial activity of ligand and its complexes has been evaluated against one Gram-positive and three Gram-negative bacteria. Complex 2 exhibited good activity along with the standard antibacterial drugs. The in vitro cytotoxicities of the synthesized compounds against Jurkat cells were evaluated by the standard WST-1 assay. The activity decreases in the order 3 > 1 > 2 = H2mstsc.
Journal of Molecular Structure 04/2013; 1037:136–143. · 1.40 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background and purpose: Influenza is a respiratory infection that annually affects 5-15% of the global population. Influenza A/H1N1 is the most virulent human pathogens that results in a more severe disease and was first reported in 2009. The aim of this study was to investIgAte the epidemiology of influenza A/H1N1 in patients referring to several hospitals in North of Iran during 2009-2011. Materials and methods: This descriptive cross-sectional study was done on patients with symptoms of influenza using Real-Time PCR analysis. Results: The patients included 572 (41.97%) male and 791 (58.03%) female. The prevalence of influenza A/H1N1 was seen more in patients aged 21-30 (25%) years. In this study, 205 patients (15.4%) were diagnosed with influenza A/H1N1 including 94 (54.85%) male and 111 (54.15%) female. Influenza A/H1N1-associated death was seen in five patients (2.44%). Conclusion: Influenza A viruses are constantly evolving by mutation or by reassortment. The influenza virus evolves rapidly, and new strains quickly replace the older once, therefore, new vaccines should be developed for immunization against new strains of influenza.
Journal of Mazandaran University of Medical Sciences. 01/2013;
[show abstract][hide abstract] ABSTRACT: Background and purpose: Hepatitis B virus (HBV) is a major global health problem. The
prevalence of HBV infection varies throughout regions of the world. More than 350 million people live
with chronic HBV infection and many different clinical symptoms are associated with it. Long-term
complications of HBV infection lead to cirrhosis of the liver and hepatocellular carcinoma. Consequently,
0.5-1.2 million death occurs every year. However, early diagnosis and appropriate treatment could reduce
such complications. This study intended to investigate the correlation of serum concentrations of HBVDNA
and HBeAg with liver enzymes.
Materials and methods: In this cross-sectional study, serum samples of 146 chronic hepatitis B
patients were studied. They referred to RaziTeaching Hospital, Qaemshahr, from 2007 to 2009. The
subjects were assessed regarding HBV-DNA, HBeAg and ALT enzymes. The patients’ serum was
extracted and Real Time PCR test was performed using HBV RG Kit (Nov in Gene). Afterwards, the
patients’ medical records were studied and the data was analyzed using Pearson correlation coefficient
and t-test in SPSS.
Results: From the total of 146 patients, 94 were found negative HBeAg and 52 were HBeAg
positive. No correlation was seen between HBV-DNA level and AST enzyme, while there was a
significant relationship between HBV-DNA level and ALT enzyme.
Conclusion: ALT enzyme is a reliable indicator for severity of liver involvement even in
negative HBeAg stages and hidden period of the disease. Hence, the serum levels of HBV-DNA and ALT
should be measured in such individuals before developing liver cirrhosis and thereby starting immediate
[show abstract][hide abstract] ABSTRACT: Asthma and allergies in addition to demanding social costs-the economic community, one of the major causes of morbidity and mortality in the world is considered. In the last decade in Iran despite the positive developments in many areas of health records into categories based asthma and allergy international standards, less attention has been paid. Improving the quality of care system, identifying groups at risk of asthma and allergies, control plan, prevention and assessment of asthma and allergies due to possible that when allergy and asthma information registration system and create the complete and timely data to be collected. Considering now an efficient national system of registration allergy and asthma that can meet the health needs can no need for this study was felt.
This study, study-the comparison was done in the years 2010-2011. In this research, using library resources, information networks and consultations with experts inside the country gathered on the main axis and branches of national registration system, asthma and allergies in American countries-Australia and England were examined and given economic conditions, cultural and geographical themes for our records system, the axes were proposed objectives, structure, data elements, standard registration process? Data and classification systems are given.
The proposed model for national registration system, asthma and allergies in the country is shown in a table. In this table the proposed system based on six main "targets", "structure", "data elements", "data collection process," "registration criteria" and "classification system" is designed.
The results and recommendations to the International Institute for asthma and allergies, reduction in low registers, and can increase the quality of the proposed model, including advantages in comparison with the existing system of the country noted.
[show abstract][hide abstract] ABSTRACT: The association between HER2 Ile655Val single nucleotide polymorphism and cancer is controversial.
The aim of our study was to investigate this polymorphism in patients with ovarian cancer.
Genomic DNA was extracted from peripheral blood leukocytes of 107 patients and 130 healthy women. HER2 gene polymorphism was assessed by PCR-RFLP.
No significant difference was observed in genotype and allele frequency between patient and control groups according to HER2 Ile655Val polymorphism. The disease stage, age, and histological type were also not associated with the polymorphism.
Our data showed that HER2 Ile655Val single nucleotide polymorphism was not significantly associated with onset, histological type, age, and stage of ovarian cancer in Iranian patients.
Iranian Red Crescent medical journal. 01/2013; 15(1):1-3.
[show abstract][hide abstract] ABSTRACT: To explore if the increased percentages of Regulatory T (Treg) cells, as well as, overexpression of Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) are involved in laryngeal-squamous cell carcinoma (SCC), 45 patients with laryngeal-SCC and 27 healthy controls were enrolled. Flow cytometry was performed to investigate, in the peripheral blood, the prevalence of CD4+CD25+FoxP3+ Treg cells, as well as, surface and intracellular expression of CTLA-4 by the main lymphocyte subsets (CD4+, CD8+ and CD19+). The results indicated intracellular (In)CTLA4 with considerable higher expression in the CD8+ lymphocytes among patients with laryngeal-SCC compared with the control group (8.2 ± 8.7 versus 2.3 ± 3.5, P = 0.001). The mean percentage of InCTLA4+CD4+ and InCTLA4+CD19+ lymphocytes was also significantly higher in patients (8.7 ± 7.8 versus 4.4 ± 4.2, P = 0.018 and 0.6 ± 0.8 versus 0.2 ± 0.2, P = 0.024, respectively). With respect to surface (Sur)CTLA4, the difference between patients and controls was, however, significant only in the case of CD8+ lymphocytes (0.7 ± 0.6 versus 0.3 ± 0.3, P = 0.003, respectively). The percentage of Treg cells was observed to be significantly higher in patients (7.5 ± 6.3 and 3.2 ± 1.9, P < 0.0001). Furthermore, association analysis revealed the association of Treg cell increase with the higher tumor-size and lymphnode stage (P < 0.005). These data collectively suggest that patients with laryngeal-SCC may benefit from immunotherapy targeting CTLA4 and Treg cells.
[show abstract][hide abstract] ABSTRACT: Background: CCL22/MDC is a CC chemokine with a critical role in regulation of the immune balance in physiological condition. CCL22/CCR-4 ligation has been documented to participate in the migration of regulatory T (Treg) cells and Th2 lymphocytes to the site of breast tumors; circumstances that are known to be associated with poor prognosis. Objective: To investigate the association of a single nucleotide polymorphism (SNP) in CCL22 gene; 16C/A (rs4359426; Asp2Ala), with susceptibility to breast cancer in a sample of Iranian population. Methods: 161 patients with pathologically confirmed breast carcinoma (mean age 49.3 ± 11.5 yrs) and 178 age-matched healthy women (mean age: 49.3 ± 12.9 yrs) were studied. CCL22 genotypes were investigated by the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Data was verified by direct automated sequencing. Arlequin analysis showed no deviation from Hardy-Weinberg equilibrium. Results: The most frequent genotype in both patient and control groups was wild type CC genotype with frequency of 146 out of 161 (90.7%) among patients and 153 out of 178 (86.0%) in control group (p=0.24). The frequency of CA genotype was 15 (9.3%) and 23 (12.9%) in patients and controls, respectively (p=0.38). No AA genotype was observed among patients but this genotype was observed with the frequency of 2 out of 178 (1.1%) in control subjects. The minor allele frequency (MAF) was 0.07 in the population. Conclusion: No correlation was found between the investigated genotypes and clinicopathological characteristics of the patients. Conclusively, results of this investigation do not support the association of 16C/A SNP (rs4359426; Asp2Ala) in CCL22 gene with susceptibility to, and progression of, breast cancer in Iranian population.
Iranian journal of immunology: IJI 12/2012; 9(4):226-33.
[show abstract][hide abstract] ABSTRACT: Background: Variations in Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) affect the expression and function of this protein. Objective: We aimed to investigate the association of +49 A/G (rs231775), +1822 C/T (rs231779) and +6230 A/G (CT60, rs3087243) genetic variations, as well as the merged haplotypes in CTLA-4 gene with susceptibility to, or progression of head and neck cancer. Methods: Eighty patients with confirmed head and neck (HN) cancer (age 54.9 ± 16.1 years) and 85 healthy age/sex-matched controls (age 56.3 ± 12.4 years) were enrolled in the study. Genotypes were investigated by the PCR-RFLP method. Arlequin software package was used to check for Hardy-Weinberg equilibration, and to estimate the haplotypes. Results: At position +6230 A/G (CT60), AA genotype, as well as A allele was significantly decreased in patients with HN cancers than controls (18.8% vs. 40.7%, p=0.004; odds ratio=0.34, and 46.3% vs. 61.7, p=0.007; odds ratio=0.53%, respectively). Nearly the same results were obtained when we compared the subgroup of patients with squamous cell carcinoma of the HN (SCC-HN) with control subjects. The frequencies of genotypes and alleles at other positions were not significantly different between patients and controls, however ACG, GTA and GCA haplotypes emerged from three investigated loci occurred with significantly more frequencies in patients (p<0.0001), while ACA and GTG haplotypes were more frequent among controls (p<0.0001). Significant differences of haplotypes, genotypes and alleles frequencies resisted the Bonferroni correction. Conclusion: Our results suggest that CT60 A allele, as well as ACA and GTG haplotypes in CTLA-4 gene may have protective roles against HN cancer in Iranian population, while ACG, GTA and specially GCA haplotypes may render susceptibility.
Iranian journal of immunology: IJI 09/2012; 9(3):188-98.
[show abstract][hide abstract] ABSTRACT: We hypothesized that the increased percentages of Regulatory T (Treg) cells, as well as over expression of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) by lymphocyte subsets might be associated with lung cancer. Accordingly, peripheral blood of 23 new cases with non-small cell lung cancer (NSCLC) and 16 healthy volunteers were investigated, by follow cytometry, for the prevalence of CD4+CD25+FoxP3+ Treg cells as well as surface (sur-) and intracellular (In-) expression of CTLA-4 by the main lymphocyte subsets (CD4+, CD8+ and CD19+). Results indicated that NSCLC patients had an increased percentage of Treg cells than controls (7.9±4.1 versus 3.8±1.8, P=0.001). The proportion of Treg cells was observed to be increased by stage increase in patients (stage II=5.2±2.4, stage III=7.9±4.4, stage IV=12.0±2.2), and also significantly higher in metastatic than non-metastatic stages (12.0±2.2 versus 6.8±3.9, P=0.023). Increase of SurCTLA-4- as well as InCTLA-4-expressing lymphocytes in patients were observed in nearly all investigated subsets, but significant differences between patients and controls were observed about InCTLA-4+CD4+ lymphocytes (8.6±7.1 and 3.8±5.3 respectively, P=0.006) as well as SurCTLA-4+CD8+ lymphocytes (0.3±0.2 and 0.2±0.1 respectively, P=0.047). In conclusion, the results suggest that immunotherapy regimen targeting CTLA-4 and Treg cells might be beneficial in lung cancer patients.
Lung cancer (Amsterdam, Netherlands) 05/2012; 77(2):306-11. · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: Eight genotypes of HBV (A-H) are recognized. A simple, rapid, and more specific genotyping system for HBV involving PCR using type-specific primers is described. The complete genomes of 234 human HBV strains for all the genotypes submitted to GenBank were aligned. The type-specific primers were designed based on the differences in the sizes of bands for eight genotypes in two sets. This genotyping system was tested with 24 positive HBV DNA controls. PCR was performed using two sets of type-specific primers for each sample in two tube. All 24 samples were PCR positive and possessed type-specific bands. PCR mix containing set 1 primers revealed specific bands of genotypes B, C, F and G, whereas PCR mix containing set 2 primers revealed specific bands of genotypes A, D, E and H. Type-specific PCR products were identified accurately by their sizes in agarose gels. The simplicity and rapidity of this PCR assay may reduce the cost and complexity of recognizing these genotypes. This method may be useful for HBV genotyping in large-scale clinical and epidemiologic studies.
Journal of virological methods 02/2012; 181(1):114-6. · 2.13 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lentivirus-derived vectors are among the most promising viral vectors for gene therapy which is currently available, but their use in clinical practice is limited due to associated risk of insertional mutagenesis. Gene targeting is an ideal method for gene therapy, but it has low efficiency in comparison to viral vector methods. In this study, we are going to design and construct an integrase-minus lentiviral vector. This vector is suitable for transient expression of gene and gene targeting with viral vector.
In this experimental study, three missense mutations were induced in the catalytic domain of Integrase gene in the pLP1 plasmid and resulted D64V, D116A and E152G changes in the amino acid sequence through site directed mutagenesis. The pLenti6.2-GW/EmGFP transfer vector, associated with native and mutated packaging mix, was transfected into 293T cell line. In order to titer the lentivirus stock, the viruses were harvested. Finally, the viruses transduced into COS-7 cell line to assess green fluorescent protein (GFP) gene expression by a fluorescence microscopy.
Recombinant and wild lentiviruses titer was about 5~8×10(6) transducing units/ml in COS-7 cell line. The number of GFP-positive cells transduced with native viruses was decreased slightly during two weeks after viral transduction. In contrast, in the case of integrase-minus viruses, a dramatic decrease in the number of GFP positive cells was observed.
This study was conducted to overcome the integration of lentiviral genome into a host genome. Nonintegrating lentiviral vectors can be used for transient gene expression and gene targeting if a Target gene cassette is placed in the lentivirus gene structure. This combination method decreases disadvantages of both processes, such as random integration of lentiviruses and low efficiency of gene targeting.
[show abstract][hide abstract] ABSTRACT: Background and purpose: Host genetic and environmental factors and factors associated with
hepatitis C virus (HCV) play critical roles in development of the hepatitis. This study was performed to
investigate the association between Interleukin-28B (IL-28B) genetic variants and chronic hepatitis C.
Materials and methods: This case-control study was conducted in 133 HCV-RNA positive
patients attending two methadone treatment clinics, a hemophilia center, a thalassemia center and three
dialysis center in Mazandaran province, Iran, 2010-2011. In addition, 173 HCV negative subjects were
recruited as the controls. The two groups were matched for age, sex and geographic region. The IL-28B
genotype at polymorphic site rs12979860 was determined by Tetra-ARMS-PCR method. Quantitative
and qualitative data were analyzed using Student t and Chi square tests, respectively.
Results: The mean age of patients with HCV (96 male, 27 female) was 36.38 ± 12.49 years. The
control group comprised 107 male and 66 female with the mean age of 38.27 ± 11.27 years. The
distribution of IL-28B genotypes did not differ between the two groups (P= 0.008). On the other hand, the
frequency of C/C, C/T and T/T genotypes were 41.4, 41.6 and 17.3% in experimental group and 42.5,
40.6, and 16.9% in the control group, respectively. The frequency of C and T alleles was not significantly
different between the two groups (P= 0.84).
Conclusion: No significant difference was observed in the frequency of the rs12979860
polymorphism in upstream of IL-28B among HCV patients and control groups. According to the proven
role of C allele in association with HCV treatment response it is assumed that genetic differences in
IL-28B or IFN-λ could predict treatment outcome.
Keywords: IL-28B, polymorphism, hepatitis C infection
J Mazand Univ Med Sci 2012; 22(95): 19-27. 01/2012; 22(95):19-27.
[show abstract][hide abstract] ABSTRACT: Myasthenia gravis (MG) is the most common disorder of neuromuscular junction in which autoantibodies develop against nicotinic acetylcholine receptor for unknown reasons. The association of immunomodulator genes with different autoimmune disease has been studied in recent years.
The aim of this study was to investigate correlation between a genetic variation in Stromal Cell Derived Factor-1 (SDF1) and susceptibility to MG in an Iranian population.
Genotyping of SDF1 at position 801 G/A was performed by Polymerase Chain Reaction-Restriction Length Polymorphism (PCR-RFLP) in 87 patients with confirmed myasthenia gravis and 261 normal control subjects.
No statistically significant differences were observed in the frequencies of genotypes and alleles between patients and controls (p>0.05). Furthermore, no significant differences in the genotype distribution were found between the cases with different stages (p>0.05).
Our data suggest that the SDF1 gene polymorphism at position 801 G/A is not associated with myasthenia gravis.
Iranian journal of immunology: IJI 06/2011; 8(2):90-5.