Endothelial nitric oxide synthase Glu 298 Asp (G894T) and Apolipoprotein E gene polymorphism as possible risk factors for coronary heart disease among Egyptians.

In Egypt, The prevalence of chronic heart disease (CHD) is 8.3%. It is the principal cause of death and is responsible for 22% of total mortality. The age-adjusted mortality rate is 174 per 100,000 of population. There are many studies on traditional risk factors and CHD in Egypt but the study of novel risk factors is deficient. OBJECTIVES: The aim of the present case control study was to investigate the relation between CHD susceptibility and Endothelial Nitric Oxide Synthase (eNOS) Glu 298 Asp (G894T) and Apolipoprotein E (ApoE) gene polymorphism in a cohort of Egyptian individuals. METHODS: Genotyping of eNOS (Glu298Asp) and Apo E genes polymorphisms were done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method for 100 CHD cases and 100 age and sex matched healthy controls. RESULTS: A statistically significant association was observed between GT and TT genotypes of endothelial nitric oxide synthase gene with CHD with OR = 2.03 and 3.5; respectively. Also, carriers of E4 allele and especially E3/E4 genotype were at higher risk of CHD with OR = 3.3 for both. Significant association was also observed between the presence of combined GTE3E4 genotype and CHD with OR = 6.6. CONCLUSION: GT and TT genotypes of endothelial nitric oxide synthase gene, E3/E4 genotype of Apo E gene polymorphism and combined GTE3E4 genotype can be considered risk factors for the development of CHD among Egyptians.

Hematopoietic stem cells: an overview.

Considerable efforts have been made in recent years in understanding the mechanisms that govern hematopoietic stem cell (HSC) origin, development, differentiation, self-renewal, aging, trafficking, plasticity and transdifferentiation. Hematopoiesis occurs in sequential waves in distinct anatomical locations during development and these shifts in location are accompanied by changes in the functional status of the stem cells and reflect the changing needs of the developing organism. HSCs make a choice of either self-renewal or committing to differentiation. The balance between self-renewal and differentiation is considered to be critical to the maintenance of stem cell numbers. It is still under debate if HSC can rejuvenate infinitely or if they do not possess ''true" self-renewal and undergo replicative senescence such as any other somatic cell. Gene therapy applications that target HSCs offer a great potential for the treatment of hematologic and immunologic diseases. However, the clinical success has been limited by many factors. This review is intended to summarize the recent advances made in the human HSC field, and will review the hematopoietic stem cell from definition through development to clinical applications.

Immunology of hematopoietic stem cell transplant.

Hematopoietic stem cell transplantation (HSCT) is a procedure in which infusion of hematopoietic stem cells is used to reestablish hematopoietic function in patients with damaged or defective bone marrow or immune systems. Early and late complications following allogeneic HSCT include acute and chronic graft-versus-host disease (GVHD), donor rejection, graft failure, relapse of primary malignancy, conditioning-related toxicity, immunodeficiency and infections. Immunology has a central role in allogeneic hematopoietic cell transplantation. Any appreciation of the immunological mechanism involved in engraftment, GVHD, the development of tolerance, immune reconstitution, and the control of malignancy requires some understanding of the immunologic basis for immune reactions provoked by grafting tissue from one individual to another. In the future it should be possible to learn what gene(s) must be activated and which must be repressed to force stem cells into division without maturation; to engineer a mechanism into the cells that stops proliferation and sets the stage for amplification; to search if there could be a universal donor cell line, neatly packaged and stabilized in sealed vials and distributed by the pharmaceutical industry; to modify the transplanted cells in such a way that they have a proliferative advantage over those of the host and to deliver the lethal blow against the neoplasm, perhaps the cells that are infused will be engineered in such a way as to be able to distinguish between normal host cells and tumor.