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1.
Immunol Invest ; 45(3): 223-34, 2016.
Article in English | MEDLINE | ID: mdl-27018548

ABSTRACT

AIM OF STUDY: This work was performed to evaluate the level of IL-4, and to clarify the role of IL-4 gene polymorphism at position cytosine -590-to-thyamine (C-590T), IL-4Rα gene polymorphism at position adenine +4679-to-guanine (A+4679G) [isoleucine-50-valine (I50V)] and STAT6 gene polymorphism at position guanine 2964-to-adenine (G2964A) in Saudi children with non-atopic dermatitis (non-AD) and atopic dermatitis (AD) to identify their role in the pathogenesis of these diseases. SUBJECTS AND METHODS: This study included 150 children: 50 healthy children as controls, 50 with non-AD, and 50 with AD. They were subjected to full clinical examination, complete blood picture, skin prick test, and determination of serum interleukin-4 (IL-4) and total immunoglobulin-E (IgE) levels. Detection of interleukin-4 gene (C-590T), interleukin-4 receptor alpha gene (A+4679G) (I50V), and STAT6 gene (G2964A) polymorphisms were performed by PCR-based restriction fragment length polymorphism (PCR-RFLP). RESULTS: There was a significant (P < 0.01) association between genotype and allele frequencies of IL-4Rα (A+4679G) (I50V) polymorphism in the AD group (but not non-AD group). Moreover, there was a significant association between genotype and allele frequencies of the STAT6 (G2946A) polymorphism in the non-AD (P < 0.05) and AD (P < 0.01) groups. On the other hand, there was no significant association between genotype and allele frequencies of the (C-590T) polymorphism in the non-AD group and AD group. There was a significant (P < 0.001) higher total IgE level in patients compared to the controls. Moreover, the mean values of total IgE were significantly different among the different allelic variants of (C-590T), (I50V), (G2964A) polymorphisms of IL-4, IL-4Rα, and STAT6 genes, respectively, in all the studied groups. On the other hand, there was no significant difference of serum IL-4 levels among all the studied patients, or among the different allelic variants of (C-590T), (I50V), (G2964A) polymorphisms of IL-4, IL-4Rα, and STAT6 genes, respectively. CONCLUSION: IL-4Rα gene (I50V) and STAT6 gene (G2964) polymorphisms may play a role in development of eczema; however, the IL-4 gene polymorphism (C-590T) had no relationship with susceptibility to the disease among Saudi children.


Subject(s)
Dermatitis, Atopic/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Interleukin-4/genetics , Polymorphism, Single Nucleotide , Receptors, Interleukin-4/genetics , STAT6 Transcription Factor/genetics , Alleles , Case-Control Studies , Child , Child, Preschool , Dermatitis, Atopic/immunology , Female , Gene Frequency , Genotype , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Interleukin-4/blood , Male , Saudi Arabia
2.
Cytotherapy ; 17(11): 1646-54, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26253898

ABSTRACT

BACKGROUND AIMS: Because of reproductive toxic effects of chemotherapy, researchers have taken some techniques to preserve fertility potential. The present study was designed to point out the potential role of spermatogonial stem cell (SSC) therapy in reversing cisplatin (CP)-induced testicular toxicity and restore the spermatogenesis. METHODS: Sixty rats were randomly divided into three groups: group 1, control group; group 2, rats received CP in a dose of 7 mg/kg/day for 5 consecutive days; group 3, CP was injected at 7 mg/kg per day for 5 consecutive days, and, on the 6th day of the experiment, rats were treated with SSC. Forty days after receiving the last dose of CP, rats were euthanized under anesthesia; testes were collected, and gene expression using real-time polymerase chain reaction for P53, Bax, caspase 9 and cytochrome c, testicular histological findings and oxidative status were determined. RESULTS: Administration of cisplatin caused significant increases in malondialdehyde levels, Bax and caspase 9 genes expression levels concomitant with significant decreases in anti-oxidant enzyme activities, p53 and cytochrome c gene expression levels, along with some histopathological lesions in testicular tissue. SCC attenuated the disturbance in oxidant/anti-oxidant status and testicular apoptosis; this is associated with improvements in the histopathological view of the testicular tissue. CONCLUSIONS: The current study highlights evidence that the SCC has anti-oxidative and anti-apoptotic properties that could reverse CP-induced testicular toxicity, in addition to their role in spermatogenesis.


Subject(s)
Adult Stem Cells/drug effects , Cell- and Tissue-Based Therapy/methods , Cisplatin/adverse effects , Stem Cell Transplantation/methods , Testis/drug effects , Testis/pathology , Adult Stem Cells/metabolism , Adult Stem Cells/physiology , Animals , Antioxidants/metabolism , Apoptosis/drug effects , Gene Expression Regulation/drug effects , Male , Malondialdehyde/metabolism , Rats, Wistar , Spermatozoa/drug effects
3.
J Infect Dev Ctries ; 9(4): 388-93, 2015 Mar 15.
Article in English | MEDLINE | ID: mdl-25881528

ABSTRACT

INTRODUCTION: Hospital-acquired infections continue to be a major public health problem, especially among neonates. Large proportions of infants are admitted to neonatal intensive care units (NICUs) and receive potent systemic antibiotics while the diagnostic work-up is still in progress. This study aimed to evaluate the recent methods for diagnosing neonatal sepsis (NS) and compare them to conventional diagnostic work-up. METHODOLOGY: The study included 100 neonates divided into three groups: proven early-onset NS, clinical early-onset NS, and negative infectious status. Bacterial DNA was detected in the blood by broad-range 16S rDNA polymerase chain reaction (PCR). Markers for diagnosis of bacterial infection, which includedprocalcitonin (PCT), interleukin-6 (IL-6), and highly sensitive C-reactive protein (hs-CRP), were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Blood culture was positive in 25 cases, while PCR for 16S rDNA was positive in 32 cases. Hs-CRP was significantly elevated in 30 patients in group 1, 35 patients in group 2, and 8 patients in group 3. IL-6 was significantly elevated in 28 patients in group 1, 24 patients in group 2, and 9 patients in group 3. PCT was found to be significantly elevated in 29 patients in group 1, 31 patients in group 2, and 2 patients in group 3. CONCLUSIONS: The16S rDNA PCR assay was more sensitive than blood culture. The combination of markers (hs-CRP, PCT, and IL-6) is better than single markers to diagnose sepsis. PCT had greater diagnostic value than did hs-CRP and IL-6, while IL-6 was better for diagnosis of neonatal infection.


Subject(s)
Bacteria/isolation & purification , Bacteriological Techniques/methods , Cross Infection/diagnosis , Diagnostic Tests, Routine/methods , Molecular Diagnostic Techniques/methods , Sepsis/diagnosis , C-Reactive Protein/analysis , Calcitonin/blood , DNA, Bacterial/blood , DNA, Ribosomal/chemistry , DNA, Ribosomal/genetics , Enzyme-Linked Immunosorbent Assay , Female , Humans , Infant, Newborn , Interleukin-6/blood , Male , Polymerase Chain Reaction , Protein Precursors/blood , RNA, Ribosomal, 16S/genetics , Sensitivity and Specificity
4.
Arch Med Res ; 46(2): 127-32, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25616839

ABSTRACT

BACKGROUND AND AIMS: We undertook this study to detect if there is a relationship between lactate production in the myocardium and the presence or absence of chest pain in patients with coronary artery disease (CAD). METHODS: Forty six patients with significant CAD including left anterior descending artery underwent echocardiography study, coronary angiography and pacing-induced ischemia. Serum lactate levels were determined in four blood samples, from mid-LV cavity and from coronary sinus before and after pacing-induced ischemia. Twenty eight patients comprised angina group and 18 patients comprised silent myocardial ischemia (SMI) group during pacing-induced ischemia. RESULTS: Eighteen patients (64.3%) of angina group had lactate production during ischemia. Eighteen patients of SMI group (100%) had diminished lactate extraction, and none had lactate production. CONCLUSION: The novel finding of this study is that the major difference in metabolism during SMI and angina pectoris is in the state of lactate production, which is absent during SMI and present during angina. We assume that lactate is the stimulus of cardiac ischemic pain and when its level increases, it stimulates pain receptors leading to chest pain.


Subject(s)
Angina Pectoris/blood , Coronary Artery Disease/blood , Lactates/metabolism , Myocardial Ischemia/blood , Myocardium/metabolism , Adult , Aged , Angina Pectoris/diagnostic imaging , Coronary Angiography , Coronary Artery Disease/diagnostic imaging , Echocardiography , Female , Heart/physiopathology , Humans , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging
5.
Gene ; 545(2): 276-81, 2014 Jul 25.
Article in English | MEDLINE | ID: mdl-24742632

ABSTRACT

OBJECTIVE: To determine whether IL-4, IL-4Rα and STAT6 polymorphisms are associated with susceptibility to dermatitis in Egyptian children. METHODS: We genotyped three groups of children, consisting of 106 atopic dermatitis (AD) children, 95 non-AD children, and 100 of healthy controls, for IL-4 (-590 C/T), (-33 C/T), IL-4Rα (I50V), (Q576R) and STAT6 (2964 G/A), (2892 C/T) gene polymorphisms using PCR-RFLP assay. Total serum IgE and serum IL-4 levels were detected by ELISA. RESULTS: There was a non-significant association of IL-4 -590 C/T, -33 C/T polymorphisms in the children with non-AD or those with AD when compared with the controls. We identified a significant association between IL-4Rα I50V, Q576R polymorphisms and dermatitis susceptibility in AD (p=0.002, <0.001 respectively), whereas no such association was observed in non-AD group (p=0.52, 0.99 respectively). A significant association between STAT6 polymorphisms and both types of dermatitis was found. Patients who were carriers of IL4 -590C, IL-4Rα I50V G, STAT6 2964 A and STAT6 2892 T had an increased risk of AD [OR and 95% CI: 3.2 (2.5-4.2), p=0.005]. Furthermore, there was no relation between each polymorphism and serum IL-4 level (p>0.05 for each) while homozygosity for the risk alleles of IL-4, IL-4Rα and STAT6 SNPs were significantly associated with increased total IgE levels in all subjects. CONCLUSION: In Egyptian children, the IL-4Rα and the STAT6 polymorphism may play a role in susceptibility to AD. In addition, gene-gene interaction between the IL-4, the IL-4Rα and the STAT6 significantly increases an individual's susceptibility to AD.


Subject(s)
Dermatitis/genetics , Interleukin-4/genetics , Receptors, Interleukin-4/genetics , Alleles , Child , Child, Preschool , Dermatitis/immunology , Dermatitis/metabolism , Dermatitis, Atopic/genetics , Dermatitis, Atopic/immunology , Dermatitis, Atopic/metabolism , Egypt , Epistasis, Genetic , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Interleukin-4/metabolism , Interleukin-4 Receptor alpha Subunit/genetics , Interleukin-4 Receptor alpha Subunit/metabolism , Polymorphism, Genetic , Receptors, Interleukin-4/blood , Receptors, Interleukin-4/metabolism , STAT6 Transcription Factor/genetics , Signal Transduction
6.
Gene ; 536(2): 393-7, 2014 Feb 25.
Article in English | MEDLINE | ID: mdl-24315820

ABSTRACT

OBJECTIVES: Rheumatoid arthritis (RA) is a chronic inflammatory disease. Transforming growth factor-ß1 (TGF-ß1) may be a promising candidate gene for susceptibility and severity in RA. We aimed to determine whether TGF-ß1 polymorphism is associated with susceptibility to RA and progression of joint destruction, as well as to identify the interaction between TGF-ß1 polymorphism and biochemical risk factor. METHODS: A total of 160 RA patients and 168 healthy unrelated controls were tested for the TGF-ß1 (869C/T) polymorphism using polymerase chain reaction. RESULTS: The TGF-ß1 T allele was associated with susceptibility to RA. Within the RA group, TGF-ß1 T allele carriers had a significant increased risk to develop osteoporosis (OR=4.4, 95% CI=-2. 4-8.1, P<0.001), as well as more likely to develop bone erosion (OR=1.7, 95% CI=0. 99-2.7, P=0. 034). Better prediction was achieved when the TGF-ß1 TT genotype was used in combination with either elevated, rheumatoid factor (RF) or C-reactive protein (CRP) (OR=6.8, 3.7 respectively). Also, they increased the risk to develop bone erosion in patients with rheumatoid arthritis (OR=3.3, 9.8, P=0.017, 0.001 respectively). CONCLUSION: Our results suggest that TGF-ß1 TT genotype may determine the development of osteoporosis and bone erosion in RA. Also, our results points to a synergism between TGF-ß1 TT genotype and elevated serum RF or elevated CRP that lead to the development of osteoporosis and bone erosion in patients with rheumatoid arthritis.


Subject(s)
Arthritis, Rheumatoid/genetics , Genetic Predisposition to Disease/genetics , Polymorphism, Single Nucleotide/genetics , Transforming Growth Factor beta1/genetics , Alleles , C-Reactive Protein/genetics , Disease Progression , Genotype , Humans , Middle Aged , Osteoporosis/genetics , Risk Factors
7.
Cell Immunol ; 285(1-2): 31-7, 2013.
Article in English | MEDLINE | ID: mdl-24044964

ABSTRACT

Studying gene-environment interactions may elucidate the complex origins of atopic diseases. The aim of this study was to evaluate the association of CD14 polymorphisms and atopy in Egyptian children and to study whether atopy is influenced by CD14 interaction with tobacco smoke exposure. CD14 -159 C/T and CD14 -550 C/T were genotyped in 500 asthmaic children, 150 allergic rhinitis children and 150 controls. We found that CD14 -159T allele, CD14 -550T allele and CD14 -159T/-550T haplotype were significantly associated with atopic asthma and allergic rhinitis groups. CD14 -159 TT and CD14 -550 TT genotypes associated with elevated IgE levels in children exposed to tobacco smoke. The TT genotype of CD14 -159 C/T and CD14 -550 C/T was associated with higher serum levels of sCD14. The present study indicated that CD14 gene polymorphisms may contribute to susceptibility to atopy in Egyptian children and influenced with tobacco smoke exposure.


Subject(s)
Asthma/genetics , Gene-Environment Interaction , Lipopolysaccharide Receptors/genetics , Rhinitis, Allergic, Perennial/genetics , Tobacco Smoke Pollution , Asthma/immunology , Child , Egypt , Environmental Exposure , Female , Genetic Predisposition to Disease , Genotype , Haplotypes , Humans , Immunoglobulin E/blood , Male , Polymorphism, Single Nucleotide , Rhinitis, Allergic , Rhinitis, Allergic, Perennial/immunology , Surveys and Questionnaires , Nicotiana
8.
Cytokine ; 61(3): 849-55, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23394902

ABSTRACT

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which interleukin-4 (IL-4) plays an important role. This study aimed to investigate the influence of IL-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms on RA susceptibility, activity and severity in Egyptian population. MATERIALS AND METHODS: One hundred and seventy-two RA patients and 172 controls were enrolled in this study. IL-4 VNTR and IL-4-590 promoter polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IL-4 and anti-cyclic citrullinated peptides (anti-CCPs) antibody concentrations were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Subjects with IL-4-590 TT genotype were significantly more likely to develop RA. IL-4 VNTR 1/1 genotype, IL-4-590 TT and CT genotypes were significantly more associated with erosive RA and positive anti-CCP antibody. RA severity parameters were significantly increased, while, IL-4 level was significantly decreased in RA patients with IL-4 VNTR 1/1 and IL-4-590 TT genotypes. Only patients with IL-4-590 TT genotype showed a significant increase of all RA activity parameters. CONCLUSION: IL-4 VNTR and IL-4-590 promoter polymorphisms may be helpful for assessing RA severity in Egyptian population. Moreover, IL-4-590 promoter polymorphism may be associated with increased risk and activity of RA.


Subject(s)
Arthritis, Rheumatoid/blood , Arthritis, Rheumatoid/genetics , Genetic Predisposition to Disease , Interleukin-4/blood , Interleukin-4/genetics , Polymorphism, Genetic , Severity of Illness Index , Alleles , Arthritis, Rheumatoid/pathology , Case-Control Studies , Egypt , Humans , Joints/pathology , Middle Aged , Minisatellite Repeats/genetics , Peptides, Cyclic/immunology , Polymorphism, Single Nucleotide/genetics , Promoter Regions, Genetic/genetics
9.
Med Oncol ; 29(5): 3055-62, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22653756

ABSTRACT

Progression from chronic hepatitis C virus infection to cirrhosis then to hepatocellular carcinoma usually results in some protein changes in peripheral blood. We evaluated MAGE-4 mRNA, TGFß1 and AFP in peripheral blood as potential biochemical markers for diagnosis and prognosis of some complications of HCV infection. MAGE-4 mRNA in blood by reverse transcription polymerase chain reaction, serum TGF-Β1 and AFP by ELISA was assayed in seventy-five individuals who were classified into five groups: group I (control) comprised fifteen apparently healthy volunteers, group II involved fifteen HCV-infected patients without cirrhosis, group III involved fifteen HCV fifteen HCV-infected patients with cirrhosis, group IV included fifteen HCV-infected patients with cirrhosis and early stage HCC, and group V included fifteen HCV cirrhotic patients and late-stage HCC. We found that the frequency of positivity of MAGE-4 among the late hepatoma group was 40 %, while in the early hepatoma group the positivity was 6.7 %. The results for TGF-Β1 revealed a significant increase in serum TGF-Β1 in groups IV and V as compared to control, II, III groups. The obtained results of AFP showed a significant positive increase in serum AFP in groups IV and V when compared to groups II and III. Detection of MAGE-4 transcripts in blood, especially with follow-up survey, may help to predict the prognosis and monitoring of the response to the therapy, and serum TGF-Β1 level in HCC patients is directly correlated with metastasis and recurrence of tumors and increases gradually with the progression of HCC.


Subject(s)
Antigens, Neoplasm/blood , Biomarkers, Tumor/analysis , Carcinoma, Hepatocellular/blood , Hepatitis C/complications , Liver Neoplasms/blood , Neoplasm Proteins/blood , Transforming Growth Factor beta1/blood , Antigens, Neoplasm/genetics , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/virology , Disease Progression , Enzyme-Linked Immunosorbent Assay , Hepatitis C/blood , Hepatitis C/genetics , Humans , Liver Cirrhosis/blood , Liver Cirrhosis/virology , Liver Neoplasms/genetics , Liver Neoplasms/virology , Neoplasm Proteins/genetics , RNA, Messenger/blood , Reverse Transcriptase Polymerase Chain Reaction , Transforming Growth Factor beta1/analysis
10.
Cell Immunol ; 274(1-2): 34-8, 2012.
Article in English | MEDLINE | ID: mdl-22402138

ABSTRACT

The aim of the study was to investigate whether polymorphisms in genes encoding Toll-like receptors (TLR2 and TLR4) may modify relative risk for development of asthma or allergic rhinitis. The results showed that the genotype and allele frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not significantly different between asthmatic children or allergic rhinitis when compared to controls (p>0.05 for each) or even when compared further with IgE level. However, it was shown that the mutant allele of TLR2 or TLR4 polymorphisms were significantly associated with the moderate-severe group compared to the mild group in both atopic asthmatics and allergic rhinitis group (p>0.001 for each). In conclusion, our study demonstrates a lack of association of TLR2 and TLR4 polymorphisms with asthma and allergic rhinitis but suggests significant association between these genetic variants and the disease severity.


Subject(s)
Asthma/genetics , Rhinitis, Allergic, Seasonal/genetics , Toll-Like Receptor 2/genetics , Toll-Like Receptor 4/genetics , Adolescent , Case-Control Studies , Child , Child, Preschool , Female , Genetic Predisposition to Disease , Genetic Variation , Genotype , Humans , Immunoglobulin E/blood , Male , Polymorphism, Single Nucleotide
11.
Gene ; 498(2): 270-5, 2012 May 01.
Article in English | MEDLINE | ID: mdl-22387727

ABSTRACT

Genetics polymorphism of the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and associated with coronary artery disease (CAD). We aimed to investigate the association between the RAS genes and premature CAD (PCAD) in Egyptians. 116 patients with PCAD, 114 patients with late onset CAD and 119 controls were included in the study. Angiotensin converting enzyme (ACE), angiotensin II receptor type 1 (ATR1) and angiotensinogen (AGT) genes polymorphisms were analyzed by polymerase chain reaction (PCR). We found that ACE DD, AGT TT and ATR1 CC increased the risk of PCAD by 2.7, 2.8 and 2.86 respectively). Smoking, hypertension, diabetes, total cholesterol, triglycerides and LDL cholesterol were independent risk factors for the development of PCAD. We conclude that the ACE DD, AGT TT and ATR1 CC genotypes may increase the susceptibility of an individual to have PCAD. The coexistence of CAD risk factors with these risky RAS genotypes may lead to the development of PCAD in Egyptian patients.


Subject(s)
Coronary Artery Disease/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Renin-Angiotensin System/genetics , Adult , Aged , Angiotensinogen/genetics , Cholesterol/blood , Coronary Artery Disease/blood , Coronary Artery Disease/etiology , Egypt , Female , Humans , Hypertension/complications , Lipoproteins, LDL/blood , Male , Middle Aged , Peptidyl-Dipeptidase A/genetics , Receptor, Angiotensin, Type 1/genetics , Risk Factors , Smoking , Triglycerides/blood
12.
Rheumatol Int ; 32(8): 2325-30, 2012 Aug.
Article in English | MEDLINE | ID: mdl-21626027

ABSTRACT

CD4 is a candidate gene in autoimmune diseases, including rheumatoid arthritis (RA). Because the CD4 receptor is crucial for appropriate antigen responses of CD4+ T cells, changes in CD4 expression and CD4+ T-cell activity may influence tolerance or tissue destruction in autoimmune diseases and contribute to their risk. We analyzed two polymorphisms of the CD4 in 172 female Egyptian patients with RA and in 112 matched healthy control. Genotyping of CD4-11743 and CD4-10845 was determined by restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). Subjects with the CC genotype of CD4-11743 were significantly more likely to develop RA (OR = 2.7, P = 0.03) and more likely to have sever RA (OR = 2.7, P = 0.024). Carrier of A allele of CD4-10845 was significantly more likely to develop sever RA (OR = 3.7, P = 0.000). CD4-11743 genetic polymorphisms are associated with the susceptibility and severity of RA, and CD4-10845 genetic polymorphisms are associated with the severity of RA.


Subject(s)
Arthritis, Rheumatoid/genetics , CD4 Antigens/genetics , Enhancer Elements, Genetic , Polymorphism, Genetic , Adult , Analysis of Variance , Arthritis, Rheumatoid/diagnosis , Arthritis, Rheumatoid/epidemiology , Arthritis, Rheumatoid/immunology , Case-Control Studies , Chi-Square Distribution , Egypt/epidemiology , Female , Gene Frequency , Genetic Predisposition to Disease , Humans , Incidence , Middle Aged , Odds Ratio , Phenotype , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length , Risk Assessment , Risk Factors , Severity of Illness Index , Sex Factors
13.
Med Oncol ; 29(2): 994-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-21452042

ABSTRACT

The dissemination of hepatocellular carcinoma (HCC) cells into the circulation plays a critical role in post-operative recurrence and metastasis. Early detection of metastatic tumor cells is critical to identify HCC patients at high risk of relapse. MAGE-3 and -4 genes were evaluated by reverse transcription polymerase chain reaction for the possibility of using them as new markers for early detection of metastases in 160 chronic HCV Egyptian patients, 115 of them were complicated with HCC. The expressions of MAGE-3 and MAGE-4 mRNA in peripheral blood of patients with metastatic HCC were 36 and 52%, respectively. While the expressions of MAGE-3 and MAGE-4 mRNA in peripheral blood of patients with localized HCC were 12.5 and 15%, respectively. Moreover, at least one type of mRNA was found in the peripheral blood of 68% of the metastatic HCC patients and in 20% of the localized HCC patients. While neither the controls nor the cirrhotic patients show expression of MAGE-4 mRNA in their peripheral blood. MAGE-3 and MAGE-4 may be a promising diagnostic tool for monitoring the prognosis of HCC patients and early detection of occult hematogenous metastasis of HCC.


Subject(s)
Antigens, Neoplasm/genetics , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/secondary , Hepacivirus/pathogenicity , Hepatitis C/complications , Liver Neoplasms/etiology , Liver Neoplasms/pathology , Neoplasm Proteins/genetics , Case-Control Studies , Cohort Studies , Early Detection of Cancer , Egypt , Female , Follow-Up Studies , Hepatitis C/genetics , Hepatitis C/virology , Humans , Liver/metabolism , Liver Cirrhosis/genetics , Liver Cirrhosis/pathology , Liver Cirrhosis/virology , Male , Middle Aged , Neoplasm Metastasis , Prognosis , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction
14.
Cell Immunol ; 271(1): 192-6, 2011.
Article in English | MEDLINE | ID: mdl-21777909

ABSTRACT

Rheumatoid arthritis (RA) is a chronic autoimmune disorder associated with altered expression of pro-inflammatory cytokines. We aim to elucidate the association between the -308G/A polymorphism of the TNF-α gene and 196M/R polymorphism in TNFRII gene and susceptibility and severity of RA. One hundred and seventy-two RA patients and one hundred and sixty controls were enrolled in the study. Polymorphisms (SNPs) at position -308 of TNF and -196 of TNFRII genes were determined using restriction fragment length polymorphism-polymerase chain reaction (PCR-RFLP). TNF AA genotype was more prevalent among the patients. GG genotype was significantly more likely to have erosive arthropathy. TNFRII RR genotype was more prevalent among the patients. Our findings suggest that the 308AA genotype of TNF-α and TNFRII 196M/R polymorphism are associated with RA susceptibility. While only the 308GG genotype of TNF-α is associated with RA severity.


Subject(s)
Arthritis, Rheumatoid/genetics , Polymorphism, Single Nucleotide , Receptors, Tumor Necrosis Factor, Type II/genetics , Tumor Necrosis Factor-alpha/genetics , Adult , Alleles , Analysis of Variance , Arthritis, Rheumatoid/pathology , Female , Gene Frequency , Genetic Predisposition to Disease/genetics , Genotype , Humans , Middle Aged , Polymerase Chain Reaction , Polymorphism, Restriction Fragment Length
15.
Ann Allergy Asthma Immunol ; 106(6): 474-80, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21624746

ABSTRACT

BACKGROUND: Asthma is a chronic inflammation of the airways associated with recurrent symptoms that range from mild to debilitating. Interleukin-10 (IL-10) is a cytokine that displays pleiotropic effects in asthma and allergy. OBJECTIVE: To determine whether polymorphisms of IL-10/IL-10R pathway contribute to asthma susceptibility in Egyptian children. METHODS: The IL-10 (-1082G/A), IL-10R1 (G330R), and signal transducer and activator of transcription 3 (STAT3) rs2293452 single-nucleotide polymorphism (SNP) were genotyped in 110 atopic children with asthma, 110 non-atopic children with asthma, and 110 healthy children. Serum IL-10 and immunoglobulin E (IgE) levels were determined by enzyme-linked immunosorbent assay. RESULTS: A significant association was observed between the IL-10 polymorphism and asthma in both atopic (P = .03) and non-atopic asthma groups (P = .04). The genotype frequencies of IL-10R1 polymorphisms did not differ between all groups. We identified a significant association between STAT3 polymorphism and asthma susceptibility in atopic asthma (P < .001), whereas no such association was observed in the non-atopic asthma group (P = .9). No evidence of gene interactions was found. CONCLUSION: Polymorphisms of IL-10 and STAT3 may be useful as a new DNA-based diagnostic biomarker for identifying high-risk children susceptible to asthma.


Subject(s)
Asthma/genetics , Asthma/immunology , Interleukin-10/genetics , Receptors, Interleukin-10/genetics , STAT3 Transcription Factor/genetics , Base Sequence , Child , Enzyme-Linked Immunosorbent Assay , Genotype , Humans , Immunoglobulin E/blood , Immunoglobulin E/genetics , Inflammation , Interleukin-10/blood , Polymerase Chain Reaction , Polymorphism, Single Nucleotide , Risk Factors , Sequence Analysis, DNA , Signal Transduction
16.
Immunol Invest ; 40(5): 523-34, 2011.
Article in English | MEDLINE | ID: mdl-21425907

ABSTRACT

OBJECTIVES: To assess serum interleukin (IL) 13 levels in atopic diseases and to determine the role of IL-13R A(1) gene polymorphism (+1398 A/G) in pathogenesis of these diseases. METHODS: Serum total immunoglobulin (Ig) E and IL-13 levels were measured by ELISA and the IL-13R A(1) gene (+1398 A/G) was screened by PCR-restriction fragment length polymorphism (RFLP) in 240 asthmatic children (120 atopic and 120 nonatopic) and 120 allergic rhinitis patients compared with 120 age-matched controls. RESULTS: No significant association was observed between genotype frequencies of the IL-13R A(1) +1398 A/G polymorphism in patients groups compared to in controls. There was a significant increase in serum levels of total IgE & IL-13 towards heterozygous AG and homozygous GG than homozygous AA in atopic asthma, non-atopic asthma and allergic rhinitis groups (P < 0.001 for each). A highly significant increase of serum IL-13 in atopic asthma as compared with controls (P < 0.001) and with nonatopic asthmatics (P < 0.001) was shown. CONCLUSION: The IL-13R A(1) +1398 A/G polymorphism does not contribute to asthma or allergic rhinitis susceptibility, yet serum IL-13 can be used as a marker in atopic diseases and to differentiate between atopic and non-atopic asthma.


Subject(s)
Asthma/blood , Asthma/genetics , Interleukin-13 Receptor alpha1 Subunit/genetics , Interleukin-13/blood , Polymorphism, Genetic , Rhinitis, Allergic, Seasonal/blood , Rhinitis, Allergic, Seasonal/genetics , Asthma/immunology , Case-Control Studies , Child , Child, Preschool , Egypt , Female , Gene Frequency/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Male
17.
Mol Cell Biochem ; 351(1-2): 261-8, 2011 May.
Article in English | MEDLINE | ID: mdl-21264495

ABSTRACT

This study aimed to evaluate the clinical reliability and accuracy of two MAGE transcripts (MAGE-A3, MAGE-A4 mRNA) in the peripheral blood (PB) of patients with breast cancer (BC), and to evaluate their potential limits and utility to detect BC. We aimed also to analyze their relation to clinicopathological characteristics of the tumor. This study is a prospective, controlled, double-blinded study conducted on 100 BC women and 100 age-matched control women. There were 52 patients with localized breast mass with no evidence of nodal affection or distant metastases and 48 patients suffering from metastatic BC. MAGE-A3 and MAGE-A4 mRNA in the PB were assayed using reverse transcriptase-polymerase chain reaction (RT-PCR). None of the control women was positive for either MAGE-A3, MAGE-A4. In BC women, positivity for MAGE-A3 in PB was observed in 37 patients (37%), and MAGE-A4 positivity was observed in 11 patients (11%); with 100% specificity for both transcripts. The presence of MAGE-A3 was significantly associated with nodal status (P = 0.009), tumor size (P = 0.009), and American Joint Committee on Cancer stage (P = 0.009), whereas MAGE-A4 positivity was significantly associated with histological grade (P = 0.020). RT-PCR assays of MAGE-A3 and MAGE-A4 in the PB of BC patients may have prognostic and predictive implications, and they are promising specific tumor markers of BC.


Subject(s)
Antigens, Neoplasm/genetics , Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Genetic Predisposition to Disease , Neoplasm Proteins/genetics , Base Sequence , Breast Neoplasms/immunology , Breast Neoplasms/pathology , DNA Primers , Female , Humans , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction
18.
Mol Cell Biochem ; 351(1-2): 117-23, 2011 May.
Article in English | MEDLINE | ID: mdl-21229382

ABSTRACT

The HDL-associated paraoxonase (PON) activities play a role in decreasing oxidative stress, which is known to contribute to cancer development. The aim of this study was to examine the relation between the PON1 L55M and Q192R polymorphisms and breast cancer (BC) risk in Egyptian females and to analyze their relation to clinicopathological parameters of BC. Both polymorphisms were characterized in 100 BC Egyptian females and 100 healthy women who had no history of any malignancy by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, using DNA from peripheral blood in a case control study. With respect to PON1 L55M, the mutated allele (M) frequency was found in 70.5% in BC patients and in 53.5% in controls; the M allele was significantly associated with an increased risk of BC (adjusted odds ratio (OR(adj)) 2.07, 95% confidence interval (95% CI) 1.37-3.13; P = 0.011). The homozygous mutant genotype (MM) significantly increased the risk of BC (OR(adj) 2.07, 95% CI 1.17-3.64, P = 0.011). However, as regard PON1 Q192R, the R mutated allele frequency was found in 28.5% in BC patients and in 33% in controls, the women who were QR heterozygotes (OR(adj) 0.96, 95% CI 0.55-1.68) or RR homozygotes (OR(adj) 0.64, 95% CI 0.25-1.63), and R allele (OR(adj) 0.81, 95% CI 0.53-1.42) did not show any risk for BC. Both PON1 L55M and Q192R polymorphisms genotype frequencies were not related to patient's age (P = 0.94 and 0.72, respectively). M allele genotypes (LM/MM) carriers showed significant association only with nodal metastases (P = 0.02) but not with other clinicopathologic parameters. However, R allele genotype (QR/RR) carriers showed insignificant correlation with clinicopathological parameters. In conclusion, our results suggest that the M allele of L55M polymorphism could be a suitable marker for BC susceptibility and tumor prognosis in Egyptian women.


Subject(s)
Aryldialkylphosphatase/genetics , Breast Neoplasms/genetics , Genetic Predisposition to Disease , Polymorphism, Genetic , Adult , Breast Neoplasms/pathology , Case-Control Studies , Egypt , Female , Humans , Middle Aged
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