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Biomedical subjects

F Aboul-Enein

Publications and source records attributed to F Aboul-Enein.

4 recordsLinked to original sources
PubMed2006

Late-onset metachromatic leukodystrophy: genotype strongly influences phenotype.

BACKGROUND: P426L and I179S are the two most frequent mutations in juvenile and adult metachromatic leukodystrophy (late-onset MLD), which, in contrast to infantile MLD, show marked phenotypic heterogeneity. OBJECTIVE: To search for genotype-phenotype correlations in late-onset MLD. METHODS: The authors reviewed the clinical course of 22 patients homozygous for mutation P426L vs 20 patients heterozygous for mutation I179S, in which the second arylsulfatase A (ASA) mutation had also been determined. RESULTS: P426L homozygotes principally presented with progressive gait disturbance caused by spastic paraparesis or cerebellar ataxia; mental disturbance was absent or insignificant at the onset of disease but became more apparent as the disease evolved. In contrast, compound heterozygotes for I179S presented with schizophrenia-like behavioral abnormalities, social dysfunction, and mental decline, but motor deficits were scarce. Reduced peripheral nerve conduction velocities and less residual ASA activity were present in P426L homozygotes vs I179S heterozygotes. CONCLUSION: The characteristic clinical differences between homozygous P426L and compound heterozygous I179S patients establish a distinct genotype-phenotype correlation in late-onset metachromatic leukodystrophy.

Adolescent↗
PubMed2005

Mitochondrial damage and histotoxic hypoxia: a pathway of tissue injury in inflammatory brain disease?

The immunological mechanisms leading to tissue damage in inflammatory brain diseases are heterogeneous and complex. They may involve direct cytotoxicity of T lymphocytes, specific antibodies and activated effector cells, such as macrophages and microglia. Here we describe that in certain inflammatory brain lesions a pattern of tissue injury is present, which closely reflects that found in hypoxic conditions of the central nervous system. Certain inflammatory mediators, in particular reactive oxygen and nitrogen species, are able to mediate mitochondrial dysfunction, and we suggest that these inflammatory mediators, when excessively liberated, can result in a state of histotoxic hypoxia. This mechanism may play a major role in multiple sclerosis, not only explaining the lesions formed in a subtype of patients with acute and relapsing course, but also being involved in the formation of diffuse "neurodegenerative" lesions in chronic progressive forms of the disease.

Brain Diseases↗
PubMed2004

Expression of major histocompatibility complex class I molecules on the different cell types in multiple sclerosis lesions.

Multiple sclerosis is considered to be an immune-mediated disease of the central nervous system, characterized by chronic inflammation, primary demyelination and axonal damage. The mechanisms of demyelination and axonal injury are heterogeneous and complex. One possible mechanism is direct damage of oligodendrocytes and neurons by Class I MHC restricted cytotoxic T-cells. In this study we analyzed the expression of functional MHC class I molecule complex, consisting of alpha-chain and beta2-microglobulin, in a large sample of human autopsy material, containing 10 cases of acute MS, 10 cases of chronic active MS, 10 cases of chronic inactive MS and 21 controls. To examine the expression of MHC class I and II molecules on the different cell-types in brain, we used quantitative immunohistochemical techniques, double staining and confocal laser microscopy scans on paraffin embedded sections. We found constitutive expression of MHC class I molecule on microglia and endothelial cells. A hierarchical up-regulation of MHC class I was present on astrocytes, oligodendrocytes, neurons and axons, depending upon the severity of the disease and the activity of the lesions. MHC class II molecules were expressed on microglia and macrophages, but not on astrocytes. These data indicate that in MS lesions all cells of the central nervous system are potential targets for Class I MHC restricted cytotoxic T-cells.

Adult↗