Lymphocyte apoptosis and proliferation related gene products in childhood acute lymphoblastic leukemia

The aim of the study is to characterize markers of apoptosis in children with ALL in relation to treatment outcome of the disease. The study was performed on 34 children with ALL and 60 healthy children as a control group. Apoptosis was assessed by cell morphology; DNA fragmentation; ELISA and RT-PCR for CD95, CD95L, BcL2 and NF-KB; and flowcytometry for CD95, CD40, CD49d, and CD11a. Apoptosis was significantly lower in cases than controls. Apoptosis detected by CD95 ligand was significantly lower in cases with no remission after treatment than those with remission. Antiapoptotic factors: CD40, BcL2, and NF-KB were all found to be higher in cases than controls and in cases with no remission than those with remission, CD49d was significantly lower in cases than controls, and significantly lower in cases with no remission. CD11a levels were not different among various groups. Delayed apoptosis of ALL cells is genetically controlled either directly or indirectly by a network of oncogenes and tumor suppressor genes. CD40 appeared to stimulate both T and lineage and is considered the most potent influencer and predictor to resistance to therapy. Inhibitors for the activity of CD40, 8c/2 and NF-kB as well as stimulants to CD95 could have a potential therapeutic benefit

Plasma homocysteine as an indicator of folate and vitamin B[12] status in children with acute lymphoblastic leukemia

Folate and vitamin B[12] are important in ensuring proper DNA replication and normal cell division. Their depletion might enhance carcinogenesis. The sulphur containing amino acid homocysteine gained considerable interest as a useful marker of impaired function of folate and vitamin B[12]. The present work aimed to evaluate plasma homocysteine level as a more sensitive indicator of folate and vitamin B[12] status in children with acute lymphoblastic leukemia. This study included fifteen children with newly diagnosed acute lymphoblastic leukemia attending pediatric department of Shatby Hospital, Alexandria University. The control group included fifteen normal healthy volunteers matched for age and sex. In patients, blood samples were collected at the time of diagnosis before any treatment. RBC's folate, plasma folate and vitamin B[12] were estimated using RIA kit. Plasma homocysteine was determined using EIA kit. RBC's folate, plasma folate and vitamin B[12] were significantly lower while plasma homocysteine was significantly elevated in the patient group when compared to the control group. Plasma homocysteine correlated negatively with RBC's folate in both studied groups. This study showed a strong association between folate deficiency, hyperhomocysteinemia and ALL in children. Prospective studies are necessary to further define whether alterations in plasma tHcy and RBC's folate levels can be considered as risk markers or are a consequence of progression of acute lymphoblastic leukemia

Study of some autoantibodies in cases of lymphoproliferatve disease

lymphoproliferative disorders are usually complicated by autoimmune disorders, the aim of this work is to study the autoimmune profile in some cases of lymphoproliferative disease. Material and Sixty cases of B-lymphoproliferative disorders, forty-five cases of non-Hodgkin lymphoma [NHL] and fifteen chronic lymphocytic leukemia [CLL] were included in this study. The autoimmune profile including; anti-nuclear antibodies, anti-ds-DNA anti-cardiolipin antibodies, both IgG and IgM were evaluated. 42% percent of studied cases displayed one or more autoimmune marker positivity. A total thirteen out of sixty [22%] were postive for anti-nuclear antibodies; three out fifteen CLL cases [20%] and ten out of forty-five non-Hodgkin lymphoma cases [22%]. Two out of fifteen [13%] CLL cases and eight out of forty-five [18%] NHL cases were positive for anti-ds-DNA antibodies. Only thirty-eight cases were tested for anti-cardiolipin antibodies; three case were acL IgG positive and nine were acL IgM positive. Although there was a high percent of positive autoimmune marker, SLE was diagnosed clinically in only of the NHL cases [2.2%]. HCV seropositivity was tested to exclude HCV as a contributing factor for autoantibodies development. Causes of autoimmune phenomena in lymphoproliferative conditions are heterogeneous and the association may not necessarily causal; certain individuals may be genetically predisposed to develop both disorders i.e. that genetic factors disturbing the regulation of the immune system may predispose both to lymphoid neoplasms and to autoimmune disease

Study of apoptosis inducing Fas receptors on T and B lymphocytes, soluble Fas and caspase 3 in type 1 diabetes mellitus

Aim: The aim of this work was designed to assess the expression of Fas receptors on T and B lymphocytes from patients with type 1 diabetes mellitus at different stages of the disease and to analyse the role of the soluble isoform of Fas and caspase-3 in Fas mediated apoptosis of T and B lymphocytes. Subjects and this study was carried on 21 type 1 diabetic patients divided into two groups: newly diagnosed [ND] and longstanding [LS], and 10 normal subjects as control group. All patients were subjected to thorough history taking, clinical examination, and laboratory investigations [fasting blood glucose and glycated haemoglobin], Immunofluorescence staining and flow cytometry analysis for Fas receptors on T and B -lymphocytes was done. Soluble isoform of Fas [S-Fas] was measured in the plasma by Elisa, and caspase-3 activity was assessed by colorimetric chemical method. Fas receptors: expression on T lymphocytes was significantly decreased among ND diabatic patients than LS and normal controls [P<0.001 and P < 0.049] and the percentage of T cells expressing Fas receptors was significantly increased in ND diabetics versus LS and controls [P = 0.000 and P= 0.000]. The soluble isoform of Fas was significantly increased in ND diabetic patients as compared to LS and control groups [P =0.000 and P< 0.015]. There was a positive correlation [r=0.750, P= 0.000] between Fas receptor expression as mean fluorescence intensity ratio of T cells and that of B cells and a negative correlation with s-Fas [r= 0.750, P= 0.000 and r= -0.540, P=0.004 and r= -0.573, P=0.002, respectively] in diabetic patients. Conclusions: Defective apoptosis of peripheral lymphocytes is well documented and clearly expressed both at the cell membrane Fas receptors and plasma s-Fas levels in ND type 1 diabetic patients. So, it is likely that defective Fas-mediated apoptosis of peripheral lymphocytes may contribute partly to loss of tolerance seen in type 1 diabetes mellitus

Influence of cancer on the enzyme performance of DNA-ALKYL transferase, lactic dehydrogen, acid and alkaline phosphatase in human blood

Since it was reported that cancer exhibits a greater rate of aerobic glycolysis than normal tissue, there have been numerous efforts to identify enzymatic defects in cancer tissue. Attempts have been made to use enzyme assays as a diagnostic tool in cancer and cancer follow up. Abnormal enzyme activity patterns of human plasma frequently reflect those of tissues in disease conditions. In our study, human serum acid phosphatase [AcP], lactic dehydrogenase [LDH], and alkaline phosphatase [AIP] were studied biochemically to evaluate the total enzyme activity among fifty cancer patients in comparison to twenty healthy individuals. Cancer cases involved cases of breast, liver, bone, prostate, lung and oral cancers. The results showed that 46% of cancer patients had elevated levels of AcP, 68% had elevated levels of LDH and 36% had elevated levels of AIP. Since cancer reflect to a greater extent the environmental exposure background, the intensity of human serum O [6]-alkyl guanine DNA-alkyl transferase [ATase] was detected by western blotting immuno-assay in sera of cancer patients in comparison to healthy individuals. The levels of ATase were higher among cancerous patients. The results suggest that the assay of enzymes in serum of cancer patients may serve as a useful tool in the diagnosis and follow-up of cancer and to study the degree of cancer progression or the feasibility of cancer treatment