Lancet neurology
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A large and complex gene on the X chromosome encodes dystrophin. Many mutations have been described in this gene, most of which affect the expression of the muscle isoform, the best-known protein product of this locus. These mutations result in the Duchenne and Becker muscular dystrophies (DMD and BMD). ⋯ Rare mutations also account for the allelic disorder X-linked dilated cardiomyopathy, in which dystrophin expression or function is affected mostly or exclusively in the heart. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has provided insights into several regulatory mechanisms governing the gene expression profile. Here, we focus on current understanding of the genotype-phenotype relation for mutations in the dystrophin gene and their implications for gene functions.
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Between 6.5% and 15.0% of all strokes occur in patients already in hospital, many of whom are there for surgical procedures or cardiac disorders. This important group of patients could potentially be assessed more rapidly than others and could be candidates for interventional therapies. However, delays in recognition and assessment are common, possibly related to comorbidities and the complexities of hospital practice. ⋯ In the postoperative setting, intra-arterial thrombolysis is feasible and reasonably safe in carefully selected patients. Experimental agents and the manipulation of physiological variables are other treatment possibilities that could be applied early in this group of patients. Increasing the awareness by hospital physicians of such interventions may be an important factor that reduces delays in assessment of patients who have stokes while in hospital.
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Review
Functional roles and therapeutic targeting of gelatinase B and chemokines in multiple sclerosis.
Multiple sclerosis (MS) is a demyelinating disease of the CNS of unknown cause. Pathogenetic mechanisms, such as chemotaxis, subsequent activation of autoreactive lymphocytes, and skewing of the extracellular proteinase balance, are targets for new therapies. ⋯ Blockage of chemotaxis or cell adhesion molecule engagement, and inhibition of hydroxymethyl-glutaryl-coenzyme-A reductase to lower expression of gelatinase B, may become effective treatments of MS, alone or in combination with interferon beta. This may allow interferon beta to be used at lower doses and prevent side-effects.