984 resultados para epsilon toxin


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At head of title: The University of Michigan, College of Engineering, Dept. of Chemical and Metallurgical Engineering. Final report.

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Mode of access: Internet.

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"Paper written under Contract Nonr. 58304."

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The use of botulinum neurotoxins for the treatment of muscle hyperactivity and spasticity disorders has been remarkably successful, owing to the abilities of the toxins to elicit prolonged localized paralysis and the rarity of serious adverse effects. However, botulinum toxins are the most deadly protein toxins known, and existing antidotes possess limited effectiveness. Paradoxically, in situ, the intoxicated motoneuron does not die. It reacts by emanating a sprouting network known to implement new functional synapses, leading to resumption of neurotransmission. Recent studies have highlighted ways of accelerating this natural recovery process to overcome paralysis successfully. Developing new therapeutic strategies and treatments for botulism will require more research into the molecular understanding of this 'naturally occurring' recovery process.

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Stx2d is a recently described Shiga toxin whose cytotoxicity is activated 10- to 1,000-fold by the elastase present in mouse or human intestinal mucus. We examined Shiga toxigenic Escherichia coli (STEC) strains isolated from food and livestock sources for the presence of activatable stx(2d). The stx(2) operons of STEC were first analyzed by PCR-restriction fragment length polymorphism (RFLP) analysis and categorized as stx(2), stx(2c) (vha), stx(2c) (vhb), or stx(2d) (EH250). Subsequently, the stx(2c) (vha) and stx(2c) (vhb) operons were screened for the absence of a PstI site in the stx(2a) subunit gene, a restriction site polymorphism which is a predictive indicator for the stx(2d) (activatable) genotype. Twelve STEC isolates carrying putative stx(2d) operons were identified, and nucleotide sequencing was used to confirm the identification of these operons as stx(2d). The complete nucleotide sequences of seven representative stx(2d) operons were determined. Shiga toxin expression in stx(2d) isolates was confirmed by immunoblotting. stx(2d) isolates were induced for the production of bacteriophages carrying stx. Two isolates were able to produce bacteriophages phi1662a and phi1720a carrying the stx(2d) operons. RFLP analysis of bacteriophage genomic DNA revealed that phi1662a and phi1720a were highly related to each other; however, the DNA sequences of these two stx(2d) operons were distinct. The STEC strains carrying these operons were isolated from retail ground beef. Surveillance for STEC strains expressing activatable stx(2d) Shiga toxin among clinical cases may indicate the significance of this toxin subtype to human health.

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Neuropsychiatric complications are common in patients with chronic hepatitis C undergoing treatment with interferon alpha. These side effects include alterations of mood, cognition, and neuroendocrine function and are unpredictable. In a number of neurological disorders characterized by neuropsychiatric symptoms and cognitive dysfunction, inheritance of an apolipoprotein E (APOE) epsilon4 allele is associated with adverse neuropsychiatric outcomes. The authors present evidence that the APOE genotype may influence a patient's neuropsychiatric response to interferon alpha treatment. The inheritance of APOE genotypes was examined in 110 patients with chronic hepatitis C treated with interferon alpha. A retrospective investigation was conducted by assessing the rates of psychiatric referral and neuropsychiatric symptoms experienced during treatment along with other complaints indicating psychological distress. A highly statistically significant association was seen between APOE genotypes and interferon-induced neuropsychiatric symptoms. Patients with an epsilon4 allele were more likely to be referred to a psychiatrist and had more neuropsychiatric symptoms during antiviral treatment than those without an epsilon4 allele. Additionally, patients with an epsilon4 allele were more likely to experience irritability or anger and anxiety or other mood symptoms. These data demonstrate that an individual's APOE genotype may influence the neuropsychiatric response to antiviral therapy with interferon alpha. Prospective studies evaluating the importance of APOE in susceptibility to interferon alpha-induced neuropsychiatric complications are needed. Moreover, pathways involving APOE should be considered in understanding the pathophysiology of interferon alpha-induced neuropsychiatric complications.