Multiple sclerosis (MS) is a chronic neurological disease of unknown etiology, but a genetic basis for the disease is undisputed. We have reported that CD24 is required for the pathogenicity of autoreactive T cells in experimental autoimmune encephalomyelitis, the mouse model of MS. Here we investigate the contribution of CD24 to MS by studying single-nucleotide polymorphism in the ORF among 242 MS patients and 207 population controls. This single-nucleotide polymorphism results in replacement of alanine (CD24 a ) with valine (CD24 v ) in the mature protein. We found that the CD24 v/v renders a >2-fold increase in the relative risk of MS in the general population (P ‫؍‬ 0.023). Among familial MS, the CD24 v allele is preferentially transmitted into affected individuals (P ‫؍‬ 0.017). Furthermore, 50% of CD24 v/v patients with expanded disability status scale 6.0 reached the milestone in 5 years, whereas the CD24 a/v (P ‫؍‬ 0.00037) and CD24 a/a (P ‫؍‬ 0.0016) patients did so in 16 and 13 years, respectively. Moreover, our data suggest that the CD24 v/v patients expressed higher levels of CD24 on peripheral blood T cells than did the CD24 a/a patients. Transfection with CD24 a and CD24 v cDNA demonstrated that the CD24 v allele can be expressed at higher efficiency than the CD24 a alleles. Thus, CD24 polymorphism is a genetic modifier for susceptibility and progression of MS in the central Ohio cohort that we studied, perhaps by affecting the efficiency of CD24 expression on the cell surface.single-nucleotide polymorphism ͉ disease susceptibility ͉ autoimmunity ͉ costimulatory molecules ͉ T lymphocytes M ultiple sclerosis (MS) is a chronic disorder in the CNS that affects Ϸ0.1% of Caucasians of northern European origin (1). The incidence of MS is increased among family members of affected individuals. The concordance rate of the identical twins can be as high as 30% (1-3). The HLA loci is perhaps the most important genetic element for MS susceptibility, because the HLA-DR2 allele has been identified as the most important susceptibility gene among Caucasians (4-10). Several additional loci have also been proposed (8-12).One of the whole-genome scans suggested a linkage disequilibrium in distal 6q (8) whose identity has not been revealed. An interesting candidate in the region is CD24 (13), which we showed to be essential for the induction of experimental autoimmune encephalomyelitis (EAE) in mice (13). CD24 is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein with expression in a variety of cell types that can participate in the pathogenesis of MS, including activated T cells (14, 15), B cells (16), macrophages (17), dendritic cells (18), and local antigen-presenting cells in the CNS, such as vascular endothelial cells, astrocytes, and microglia (our unpublished observation). It is well established that in the mouse CD24 mediates a CD28-independent costimulatory pathway that promotes activation of CD4 and CD8 T cells (16)(17)(18)(19)(20)(21). In addition, CD24 has been shown to modulate the very l...

Electrical activation during VF is organized. The degree of linking of EA directions during VF is not affected by the presence of MI, the site of recording, or repeated inductions of VF. During the first 5 seconds of VF, the degree of linking decreases.

Frequency characteristics of repeated episodes of VF induced in the same subjects show fair-to-good but not excellent reproducibility. Bipolar recordings were far more reproducible than unipolar recordings, but both bipolar configurations had similar reproducibility. These findings have implications for both the pathophysiology of induced VF and the design of VF detection algorithms.

(1) Some VF characteristics are altered in ischemic regions including a longer VFCL and greater percentage of functional block. (2) VF characteristics are unchanged in immediately adjacent nonischemic myocardium. (3) Although the ischemic zone may be involved in the initiation of VF and has unique activation characteristics during VF, it does not affect VF characteristics in the adjacent nonischemic zone, suggesting that it may not play a major role in VF maintenance.

During VF, in animals with subacute or chronic healing MI, (1) the size of activation wave fronts is larger, (2) the cycle length of VF is longer, (3) the conduction velocities are slower, and (4) the degree of organization is greater than in control animals. Thus, the characteristics of VF throughout the heart are altered by the presence of regional myocardial infarction. The implications of these findings for the initiation and maintenance of VF in the presence of different underlying myocardial substrates require further study.