Evaluation of the role of FTO (rs9939609) and MC4R (rs17782313) gene polymorphisms in type 1 diabetes and their relation to obesity.

OBJECTIVES: This study aims to explore the effects of fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) gene polymorphisms in children with type 1 diabetes (T1D) and their relation to obesity. METHODS: Fat mass obesity-associated (FTO) (rs9939609) and melanocortin 4 receptor (MC4R) (rs17782313) gene polymorphisms were evaluated in 164 patients and 100 controls, and genotypes, alleles, and haplotype frequencies were compared between cases and controls. RESULTS: A significant association with T1D development was found with the TC, CC, and TC+CC genotypes and the C allele of MC4R rs17782313. In addition, TA, AA, and TA+AA genotypes and the A allele of FTO rs9939609 may also be risky for T1D development. While the TC and TC+CC genotypes of MC4R rs17782313 may be protective against obesity development, the AA genotype and A allele of FTO rs9939609 may also be protective against obesity development. Regarding obese subjects, comparing diabetics vs. non-diabetic studied subjects, FTO rs9939609, TA, AA, and TA+AA genotypes and the A allele had significantly higher frequencies in T1D with a higher risk of developing T1D. However, conducting multivariable analysis using significant covariates in univariable analysis revealed that only earlier age of T1D onset, lower C-peptide, and the MC4R dominant model were considered independent predictors of obesity within T1D. CONCLUSIONS: The role of both genes' polymorphisms on the pathogenesis and the outcome of T1D and obesity can help in understanding the pathogenesis of both diseases and their associations with each other's and may be used as novel therapeutic targets for both diseases.

CD44, CD90 and CD96 expression in immune thrombocytopenia purpura (ITP) patients.

Studying the expression of hematopoietic stem cell markers from different sources might be useful in understanding stem cell biology in different niche conditions. The study aimed to assess the difference in cell surface markers (CD44, CD90, CD96) on hematopoietic stem cells in three different niche conditions; umbilical cord blood (UCB), normal bone marrow (NBM) and bone marrow samples from idiopathic (immune) thrombocytopenic purpura (IBM). This study was conducted on 300 cases divided into three study groups; 100 umbilical cord blood units collected from mothers undergoing cesarian section in gynecology and obstetrics department, 100 bone marrow samples from idiopathic (immune) thrombocytopenic purpura patients collected from university children hospital and 100 normal bone marrow samples with no evidence of disease in bone marrow tissue. CD44 was significantly elevated in UCB and NBM groups compared to IBM group (<0.001). There was also a significant elevation of CD90 and CD96 in IBM group compared to NBM group and UCB (<0.001). CD90 and CD96 play a role in the pathogenesis of ITP disorder and could be applied as a targeted therapy to improve the outcome of this disease.

The Mechanical Autophagy as a Part of Cellular Immunity; Facts and Features in Treating the Medical Disorders.

Autophagy is a cellular housekeeping process that incorporates lysosomal-degradation to maintain cell survival and energy sources. In recent decades, the role of autophagy has implicated in the initiation and development of many diseases that affect humanity. Among these diseases are autoimmune diseases and neurodegenerative diseases, which connected with the lacking autophagy. Other diseases are connected with the increasing levels of autophagy such as cancers and infectious diseases. Therefore, controlling autophagy with sufficient regulators could represent an effective strategy to overcome such diseases. Interestingly, targeting autophagy can also provide a sufficient method to combat the current epidemic caused by the ongoing coronavirus. In this review, we aim to highlight the physiological function of the autophagic process to understand the circumstances surrounding its role in the cellular immunity associated with the development of human diseases.

The Potentiality of Human Umbilical Cord Isolated Mesenchymal Stem/Stromal Cells for Cardiomyocyte Generation.

BACKGROUND: The new therapeutic strategy of managing cardiac diseases is based on cell therapy; it highly suggests the use of multipotent mesenchymal stem/stromal cells (MSCs). MSCs widely used in researches are known to be isolated from bone marrow. However, this research seeks to use a human umbilical cord (HUC) as an alternative source of MSCs. Since HUC Wharton's jelly (WJ)-isolated MSCs originate as fetal tissue they are highly preferable for their potential advantages over other adult tissues. METHODS: The researchers used enzymatic digestion to establish a primary HUC-WJ-isolated MSC line. Then, flow cytometry was used to characterize MSCs and hematopoietic stem cells (HSCs) markers' expression. In addition, the cardiac differentiation capacity of HUC-WJ-isolated MSCs in vitro was investigated by two protocols. Protocol-1 necessitates the dependence on merely 5-azacytidine (5-Aza), whereas in protocol-2, 5-Aza was supported by basic fibroblast growth factor (BFGF). The comparative study between the two protocols was applied by inspecting the ultrastructure of differentiated cells, measuring RT-PCR mRNA cardiac markers and the quantitative detection of cardiac proteins. RESULTS: HUC-WJ isolated MSCs were expressed by CD90+ve, CD105+ve, CD106+ve, CD45-ve, and CD146-ve. Remarkable TNNT1, NKX2.5, and Desmin mRNA expression and higher quantitative LDH and cTnI were detected by applying protocol-2. This same protocol-2 induced cardiac morphological features that were revealed by identifying cardiomyocyte-like cells and typical sarcomeres. CONCLUSION: HUC-WJ is proved to be an ethical and effective source of MSCs induced cardiac differentiation, whereas BFGF supports 5-Aza in MSCs-cardiomyocytes differentiation.

Age dependent association of inbreeding with risk for schizophrenia in Egypt.

BACKGROUND: Self-reported consanguinity is associated with risk for schizophrenia (SZ) in several inbred populations, but estimates using DNA-based coefficients of inbreeding are unavailable. Further, it is not known whether recessively inherited risk mutations can be identified through homozygosity by descent (HBD) mapping. METHODS: We studied self-reported and DNA-based estimates of inbreeding among Egyptian patients with SZ (n = 421, DSM IV criteria) and adult controls without psychosis (n = 301), who were evaluated using semi-structured diagnostic interview schedules and genotyped using the Illumina Infinium PsychArray. Following quality control checks, coefficients of inbreeding (F) and regions of homozygosity (ROH) were estimated using PLINK software for HBD analysis. Exome sequencing was conducted in selected cases. RESULTS: Inbreeding was associated with schizophrenia based on self-reported consanguinity (χ2 = 4.506, 1 df, p = 0.034) and DNA-based estimates for inbreeding (F); the latter with a significant F × age interaction (ß = 32.34, p = 0.0047). The association was most notable among patients older than age 40 years. Eleven ROH were over-represented in cases on chromosomes 1, 3, 6, 11, and 14; all but one region is novel for schizophrenia risk. Exome sequencing identified six recessively-acting genes in ROH with loss-of-function variants; one of which causes primary hereditary microcephaly. CONCLUSIONS: We propose consanguinity as an age-dependent risk factor for SZ in Egypt. HBD mapping is feasible for SZ in adequately powered samples.

Randomized controlled trial of adjunctive Valproate for cognitive remediation in early course schizophrenia.

BACKGROUND: Schizophrenia (SZ) is associated with cognitive impairment that contributes to disability, but the cognitive dysfunction is relatively refractory to pharmacologic intervention. Though Valproate augmentation is reported to improve psychopathology among patients with SZ, its effects on cognitive functions have not been investigated systematically. METHODS: Using a randomized double blind placebo controlled design, the effects of Valproate or placebo as adjuncts to risperidone (RISP) treatment were evaluated among patients with early course SZ (N = 109). Domains of cognitive function, estimated using the Arabic version of the Penn Computerized Neurocognitive Battery, were the prime outcomes. Clinical severity and social function were secondary outcomes. We also explored the effects of valproate treatment on serological responses to Toxoplama Gondii (TOXO), a putative risk factor for cognitive dysfunction in SZ. RESULTS: There were no significant differences between Valproate and placebo (PLA) treated groups with respect to changes in cognitive functions, positive or negative symptom scores or daily function scores at the beginning and end of the study. No significant Valproate/PLA differences were noted on TOXO serostatus or TOXO-related cognitive dysfunction. CONCLUSION: Valproate treatment may not be beneficial for cognitive dysfunction in SZ or for TOXO infection.

Rapidly mutating Y-STRs in rapidly expanding populations: Discrimination power of the Yfiler Plus multiplex in northern Africa.

The male-specific northern African genetic pool is characterised by a high frequency of the E-M81 haplogroup, which expanded in very recent times (2-3 kiloyears ago). As a consequence of their recent coalescence, E-M81 chromosomes often cannot be completely distinguished on the basis of their Y-STR profiles, unless rapidly-mutating Y-STRs (RM Y-STRs) are analysed. In this study, we used the Yfiler® Plus kit, which includes 7 RM Y-STRs and 20 standard Y-STR, to analyse 477 unrelated males coming from 11 northern African populations sampled from Morocco, Algeria, Libya and Egypt. The Y chromosomes were assigned to monophyletic lineages after the analysis of 72 stable biallelic polymorphisms and, as expected, we found a high proportion of E-M81 subjects (about 46%), with frequencies decreasing from west to east. We found low intra-population diversity indexes, in particular in the populations that experienced long-term isolation. The AMOVA analysis showed significant differences between the countries and between most of the 11 populations, with a rough differentiation between northwestern Africa and northeastern Africa, where the Egyptians Berbers from Siwa represented an outlier population. The comparison between the Yfiler® and the Yfiler® Plus network of the E-M81 Y chromosomes confirmed the high power of discrimination of the latter kit, thanks to higher variability of the RM Y-STRs: indeed, the number of chromosomes sharing the same haplotype was drastically reduced from 201 to 81 and limited, in the latter case, to subjects from the same population.

Comparison of the percentages of CD4+ CD25high FOXP3+ , CD4+ CD25low FOXP3+ , and CD4+ FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia.

PROBLEM: Little is known about how preeclampsia affects regulatory T-cell count and functions in umbilical cord blood of babies born to preeclamptic mothers. Here, we analyze the percentage of CD4+  CD25high  FOXP3+ , CD4+  CD25low  FOXP3+ , and CD4+  FOXP3+ Tregs, in the umbilical cord blood of babies born to mothers with and without preeclampsia. METHOD OF STUDY: The percentage of umbilical cord blood CD4+  CD25high  FOXP3+ , CD4+  CD25low  FOXP3+ , and CD4+  FOXP3+ Tregs were analyzed by flow cytometry. RESULTS: CD4+  CD25high  FOXP3+ Treg (%) and CD4+  FOXP3+ Treg (%) were significantly lower, while CD4+  CD25low (%) was significantly higher in umbilical cord blood of babies born to preeclamptic mothers. CONCLUSION: Preeclampsia is associated with immune dysregulation which leads to a deficiency in Treg (CD4+  CD25high  FOXP3+ ) in the umbilical cord blood of babies born to preeclamptic mothers.

IRF5, PTPN22, CD28, IL2RA, KIF5A, BLK and TNFAIP3 genes polymorphisms and lupus susceptibility in a cohort from the Egypt Delta; relation to other ethnic groups.

OBJECTIVE: To replicate a single nucleotide polymorphism (SNP) of known genes for lupus (IRF5 rs10488631, PTPN22 rs2476601, BLK rs2736340 and TNFAIP3 rs5029939) and other autoimmune diseases (CD28 rs1980422, IL2RA rs2104286 and KIF5A rs1678542) on a newly studied Egyptian cohort to investigate the genetic disparity with different studied ethnic groups in relation to lupus susceptibility. METHODS: 170 Egyptian patients from Egypt Delta with SLE and 241 matched healthy controls were genotyped by Taqman real time PCR for the selected SNPs. RESULTS: The results revealed significant association with IRF5 (p<0.0001) and PTPN22 (p=0.008) and insignificant association with KIF5A, CD28, IL2RA, BLK and TNFAIP3 genes. CONCLUSIONS: This study may provide an additional evidence for the association between IRF5 and PTPN22 and lupus susceptibility and may exclude it for CD28, IL2RA, and KIF5A.

HLA-DQB1* alleles and genetic susceptibility to type 1 diabetes mellitus.

AIM: To determine human leukocyte antigen (HLA)-DQB1 allele association with susceptibility to type 1 diabetes (T1D) and to clinical and laboratory findings. METHODS: This study was conducted on 85 unrelated Egyptian children with T1D recruited consecutively from the Pediatric Diabetes Endocrinology outpatients Clinic; Mansoura University Children's Hospital, Egypt. Patient mean follow up period was 2.5 years. Patients were subdivided according to level of HbA1c (optimal/suboptimal control < 8.5% and poor control ≥ 8.5%). The control group consisted of 113 unrelated age- and sex-matched healthy subjects without T1D or other autoimmune diseases. Genomic DNA extraction was done for all subjects using a DNA isolation kit. HLA-Class II-DQB1 allele typing was carried out with a polymerase chain reaction-sequence-specific oligonucleotide probe using a INNO-LiPA HLA-DQB1 update kit. RESULTS: Significant differences were detected between Egyptian patients with T1D and control groups in the frequencies of DQB1*02 [44.4% vs 18.6%, corrected P value (Pc) < 0.001] and DQB1*03 (41.2% vs 24.4%, Pc < 0.001). Significant differences were also observed between control groups and T1D patients in the frequencies of DQB1*05 (14.6% vs 7.2%, P = 0.029) and DQB1*06 (34.1% vs 7.2%, P < 0.001). However, after correction for multiple comparisons, the significance was retained for HLA-DQB1*06 (Pc < 0.001) but lost for HLA-DQB1*05. HLA-DQB1*0201, *0202, *030201 were positively associated with T1D (Pc = 0.014, Pc < 0.001, and Pc < 0.001 respectively), while HLA-DQB1*060101 was negatively associated (Pc < 0.001) with the condition. Although the HLA-DQB1 alleles 030101 and 050101 were significantly higher in controls (P = 0.016, P = 0.025 respectively), both of them lost statistical significance after correction of P value. The frequency of the HLA-DQB1 genotypes 02/02, 02/03, and 03/03 was higher in T1D patients, and the frequency of the genotypes 03/06, 05/06, and 06/06 was higher in controls, these differences being statistically significant before correction. After correction, the genotypes 02/02, 02/03 in T1D, and the genotypes 03/06, 06/06 in controls were still significant (Pc = 0.01, Pc < 0.001, Pc < 0.001, and Pc = 0.04, respectively). Non-significant associations were found between the frequency HLA-DQB1 alleles and genotypes in T1D in relation to the grade of diabetic control, Microalbuminuria, age, gender, age of presentation, weight, height, frequency of diabetic ketoacidosis (P = 0.42), serum cholesterol, and fasting and post-prandial level of C-peptide (P = 0.83, P = 0.9, respectively). CONCLUSION: The Current work suggests that HLA-DQB1 alleles *030201, *0202, *0201, and genotypes 02/03, 02/02 may be susceptibility risk factors for development of T1D in Egyptian children, while the HLA-DQB1*060101 allele, and 03/06, 06/06 genotypes may be protective factors. HLA-DQB1 alleles and genotypes do not contribute to microalbuminuria or grade of diabetic control.

Does telomere length mediate associations between inbreeding and increased risk for bipolar I disorder and schizophrenia?

We have recently found that consanguinity is a risk factor for bipolar I disorder (BP1) and schizophrenia (SZ) in Egypt. Inbreeding has been associated with increased cellular stress and impaired physiological function in plants and animals. Previous studies have reported that telomere length (TL), an index of oxidative stress and cellular senescence is significantly reduced among patients with SZ or mood disorders compared with control individuals. Hence we evaluated TL as a possible mediator of the observed association between consanguinity and BP1/SZ risk. Patients with BP1 (n=108), or SZ (n=60) were compared with screened adult controls in separate experiments. TL was estimated using a quantitative PCR (qPCR) based assay. The inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA polymorphisms ('DNA-based' rate); and from family history data ('self report'). Significant correlation between TL and DNA based inbreeding was not observed overall, though suggestive trends were present among the SZ cases. No significant case-control differences in TL were found after controlling for demographic variables. In conclusion, reduced TL may not explain a significant proportion of observed associations between consanguinity and risk for BP1/SZ.

Interleukin-12 and peripheral blood invariant natural killer T cells as an axis in childhood asthma pathogenesis.

Interleukin-12 (IL-12) is a key cytokine involved in regulating the balance between TH1 and TH2 cells by promoting TH1 response. A reduced capacity to produce this cytokine could lead to aberrant TH2 development. On the same aspect significant impact of IL-12 on invariant natural killer T (iNKT) cells was reported. Therefore, we examined the serum levels of IL-12 and the absolute number of peripheral blood iNKT cells from 37 children with controlled asthma and 11 normal controls (age-matched) and correlating these two parameters with clinical asthma severity and Pulmonary function tests (PFTs). A significant decrease of serum levels of IL-12 and peripheral iNKT cells was found in total asthmatic cases compared with normal controls. This significant decrease of IL-12 levels was observed in severe asthmatic patients compared with mild and moderate cases. Serum levels of IL-12 and the numbers of peripheral iNKT cells were positively correlated with PFTs in both total asthmatic groups and in children with severe persistent asthma. Inverse correlation was found between serum level of IL-12 and different degrees of asthma. Whereas the numbers of peripheral blood iNKT cells showed no significant difference between clinical asthma severities. Impaired IL-12 production in asthmatic children beside decreasing the number of peripheral blood iNKT cells could be considered as a key component in asthma pathogenesis and hence their therapeutic manipulation may be of help in asthma management.

Consanguinity and increased risk for schizophrenia in Egypt.

BACKGROUND: Consanguinity has been suggested as a risk factor for psychoses in some Middle Eastern countries, but adequate control data are unavailable. Our recent studies in Egypt have shown elevated parental consanguinity rates among patients with bipolar I disorder (BP1), compared with controls. We have now extended our analyses to schizophrenia (SZ) in the same population. METHODS: A case-control study was conducted at Mansoura University Hospital, Mansoura, Egypt (SZ, n=75; controls, n=126, and their available parents). The prevalence of consanguinity was estimated from family history data ('self report'), followed by DNA analysis using short tandem repeat polymorphisms (STRPs, n=63) ('DNA-based' rates). RESULTS: Self-reported consanguinity was significantly elevated among the patients (SZ: 46.6%, controls: 19.8%, OR 3.53, 95% CI 1.88, 6.64; p=0.000058, 1 d.f.). These differences were confirmed using DNA-based estimates for coefficients of inbreeding (inbreeding coefficients as means+/-standard error, cases: 0.058+/-0.007, controls: 0.022+/-0.003). CONCLUSIONS: Consanguinity rates are significantly elevated among Egyptian SZ patients in the Nile delta region. The associations are similar to those observed with BP1 in our earlier study. If replicated, the substantial risk associated with consanguinity raises public health concerns. They may also pave the way for gene mapping studies.

HLA class I and class II HLA DRB profiles in Egyptian children with rheumatic valvular disease.

Poststreptococcal sequelae, especially acute rheumatic fever/rheumatic heart disease continues to occur in significant proportions in many parts of the world, especially in less developed countries. An important factor in the study of rheumatic heart disease is the human genetic susceptibility to the disease. The aim of the present study was to detect the most prevalent HLA class I and class II types associated with risk of rheumatic heart disease in Egyptian children. Our study was performed on 100 patients with rheumatic valvular heart diseases and 71 control subjects. Patients were recruited from the Heart Institute, Embaba, Egypt. HLA typing for HLA class I was performed by serotyping and HLDR allele genotyping was performed using INNO-LiPA kits. In the study of HLA class I, there was a statistically significant increase in the B5 allele (P = 0.03; odds ratio, 3.46 [1.12-10.72]) in patients compared to controls, while B49 and B52 alleles (P = 0.004 and P = 0.02) were found in controls only. There was a statistically significant increase in HLA DR* 04-02, 3.46 (1.12-10.72) and HLA DR *10-0101 5.75 (1.27-25.98) in patients. Meanwhile HLA DR*1309120 was found only in controls (P = 0.02). Our study provides further information on the genetic predisposition for rheumatic valvular disease and the protective genotypes in rheumatic heart disease. Further insight into the molecular mechanisms of the disease will be a useful tool for predicting clinical outcome in those patients and, thus, potentially offer new means and approaches to treatment and prophylaxis, including a potential vaccine.

Comparative study of antinuclear antibody detection by indirect immunofluorescence and enzyme immunoassay in lupus patients.

To evaluate the value of immunofluorescent and ELISA techniques in early diagnosis of systemic lupus erythematosus (SLE) and to find out whether there is a correlation between Antinuclear antibodies (ANA) pattern and prognosis by observing clinical score changes using British Isles Lupus Assessment Group score. The study included 75 SLE patients, 11 disease control group, and 18 healthy control group. ANA and ds-DNA antibodies detection were done by ELISA and Immunofluorescence for all groups. Immunofluorescence technique is more sensitive for ANA and ds-DNA detection than ELISA technique (100% versus 90.7%,and 93% versus 89.3% respectively); ELISA showed 89.7 % specificity for ANA detection compared to 86.2% for Immunofluorescence, and both have 100% specificity for ds-DNA detection ;homogenous ANA pattern, showed statistically significant higher BILAG score compared to speckled pattern either at the start of the study or after the follow up period (p = 0.000); and ds-DNA titer showed statistically significant decrease in titer after therapy (p = 0.01). ANA detection by Immunofluorescence is more sensitive and effective screening assay in patients with clinical features of SLE and both ds-DNA titer by ELISA and BILAG score for severity index are considered the best markers for follow-up.

Consanguinity associated with increased risk for bipolar I disorder in Egypt.

We aimed to contrast rates of consanguinity among patients with bipolar I disorder (BP1) and controls in a population with customary consanguineous marriages (i.e., marriage between related individuals). Consanguinity increases risk for numerous monogenic and polygenic diseases. Whether the risk for BP1 increases with consanguinity has not been investigated systematically. Two independent studies were conducted in Egypt: (1) Case-control study 93 patients with BP1, 90 screened adult control individuals, and available parents. The inbreeding coefficient/consanguinity rate was estimated in two ways: using 64 DNA polymorphisms ("DNA-based" rate); and from family history data ("self report"); (2) Epidemiological survey: total of 1,584 individuals were screened, from whom self-reported consanguinity data were obtained for identified BP1 cases (n = 35) and 150 randomly selected, unaffected control individuals. DNA-based consanguinity rates showed significant case-control differences (P = 0.0039). Self-reported consanguinity rates were also elevated among BP1 patients in both samples (Study #1 OR = 2.66, 95% confidence intervals, CI: 1.34, 5.29; Study #2: OR = 4.64, 95% CI: 2.01, 10.34). In conclusion, two independent, systematic studies indicate increased consanguinity among Egyptian BP1 patients in the Nile delta region. Self-reported estimates of consanguinity are bolstered by DNA-based estimates, and both show significant case-control differences for BP1.

Vascular endothelial growth factor, p53, and the H-ras oncogene in Egyptian patients with bladder cancer.

AIM: To evaluate the relationship between vascular endothelial growth factor (VEGF), p53, and the H-ras oncogene and different clinicopathological parameters in Egyptian patients with Schistosoma-associated transitional cell carcinoma of the bladder. METHODS: The study included 50 patients with transitional cell carcinoma for whom radical cystectomy and urinary diversions were carried out. VEGF and p53 protein expressions were evaluated with an immunohistochemical staining method, and H-ras oncogene mutations were analyzed with a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. RESULTS: High grade tumors revealed higher p53 immunostaining than low grade tumors (P = 0.016). p53 and VEGF protein expressions, as well as H-ras oncogene mutations, had an insignificant impact on patient outcomes (P = 0.962, P = 0.791, and P = 967, respectively). Cancer extension to regional lymph nodes was associated with poor outcomes (P = 0.008). CONCLUSION: VEGF, p53 and the H-ras oncogene have no relation to patient survival and outcome in Schistosoma-associated transitional cell carcinoma.

Immune reconstitution during maintenance therapy in children with acute lymphoblastic leukemia, relation to co-existing infection.

Immunosuppression is a major side effect of cancer chemotherapy. The process of immune reconstitution can be dissimilar according to the nature of the disease, type and doses of drugs, and age of the patients. Recently, several studies have examined immune reconstitution in children and young adults after intensive chemotherapy for solid tumours or stem cell transplantation. The aim of the present study is to evaluate immune reconstitution (cellular and humoral) in children with acute lymphoblastic leukemia during the maintenance phase of therapy and to correlate between the complicating infections and the abnormalities in immune system during reconstitution. To achieve this goal, 36 children with acute lymphoblastic leukemia (24 females and 12 males) in the maintenance phase of therapy with 12 healthy children of matched age and sex served as a control group were recruited in this study. The patients were taken consecutively from the Hematology/Oncology Outpatient Clinic of Mansoura University Children's Hospital (MUCH). They were subjected to thorough history taking, clinical examination and laboratory investigations in the form of: complete blood count, serum creatinine, liver function tests and evaluation of the immune system by estimation of CD3, CD4, CD8, CD19 and CD56 (cellular immunity) by flow cytometry and immunoglobulins A, M and G (humoral immunity) at the first and the third month of maintenance therapy. The results of the study documented presence and persistence of leucopenia and lymphopenia during maintenance therapy with decreased medians of CD3, CD4 and CD8 from the first to the third month of therapy and in comparison to the control group. The other markers CD19, CD56, IgA, IgM, IgG and CD4/CD8 ratio showed increasing median from the first to the third month of therapy. Also we detect a significant correlation between infection and CD19 and serum IgM at the first month and between infection and CD19, IgM and CD4/CD8 ratio at the third month of therapy. In conclusion, persistent immunosuppression is documented in children with acute lymphoblastic leukemia during maintenance therapy. Reconstitution of B lymphocytes and Natural killer cells occurs early while T cell reconstitution shows delayed recovery of both T helper and T suppressor cells. Immunosupression during maintenance therapy has no major clinical impact in terms of increased incidence or severity of systemic infections.

HLA-class II alleles in Egyptian patients with hepatocellular carcinoma.

UNLABELLED: Hepatocellular carcinoma (HCC) is linked to environmental, dietary, and life style factors. Its incidence and distribution vary widely among ethnic groups, sex, and geographic regions. HBV and HCV Infection, liver cirrhosis, male gender, and old age are important risk factors of HCC. Variability in outcome following exposure, and the clustering of HCC within families raise the possibility that genetic factors are also involved in susceptibility to HCC. The Major Histocompatibility Complex (MHC) plays a key role in anti-virus and tumor defense. HLA polymorphism is implicated in conferring genetic susceptibility to a large number of immune-mediated diseases, including some cancers. The association between HLA class II antigen and HCC in different ethnic populations that has been reported is controversial. Therefore, the aim of this work was to study the association between HLA class II-DRB1 and DQB1 polymorphism and HCC in Egyptian patients and to investigate their role as risk factors for the development of HCC. METHODS: HLA-class II (DRB1 and DQB1) typing was done by SSP for 100 subjects; 50 patients suffering from HCC (45 males and 5 females) with age range 40-64 years (51.16 years (y) +/- 6.16); and 50 normal healthy control subjects. RESULTS: 1. A significantly increased frequency of DRB1*04, and DQB1 *02 in HCC patients versus control group (p = 0.016, and 0.032, respectively) was found; 2. A significantly decreased frequency of DQB1*06 (p = 0.032) was found; 3. A significantly increased frequency of DRB1*07 (odds ratio (OR) = 4.929) was found; and 4. A significantly decreased frequency of DRB1*15 (OR = 0.316) was seen. In conclusion, while some alleles are significantly associated with HCC (DRB1*04, DQB1*02) and others are not associated (DQB1*06); therefore, it can be concluded that the DRB1*04 and DQB1*02 alleles might be risk factors for the occurrence of HCC (OR = 4.373 and 3.807, respectively), and DQB1*06 may be a protective allele (OR = 0.259).

Allele frequencies of 15 short tandem repeats (STRs) in three Egyptian populations of different ethnic groups.

DNA typing of 15 short tandem repeat (STR) loci included in the AmpFlSTR Identifiler PCR amplification kit (Applied Biosystems), was carried out in three Egyptian populations of different ethnic groups: the Berbers from the Siwa oasis (in the North-Western Egyptian desert), the Muslims and the Copts from Adaima (Upper Egypt). A total of 297 individuals were typed. After Bonferroni's correction, no deviations from the Hardy-Weinberg equilibrium were observed for all samples at the 15 STR loci. All loci are highly polymorphic and population differentiation tests showed that 7, 10 and 8 out of 15 loci have significant differences between the Berbers and the Muslim samples, between the Berbers and the Copts, and between the two samples from Adaima, respectively. Comparative analyses between our population data and other geographically related populations gathered from the literature were performed.