Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a novel transthyretin mutation at codon 18 where Asp is replaced by Gly (D18G) in a Hungarian kindred. This mutation is associated with meningocerebrovascular amyloidosis, producing dementia, ataxia, and spasticity. Fifty different transthyretin mutations are related to amyloid deposition, typically producing a peripheral neuropathy or cardiac dysfunction. These symptoms are absent in this family. Up to now, amyloid-beta (A beta), cystatin C, and prion proteins have been known to be deposited as amyloid in the brain, leading to stroke or dementia. With this report we establish that transthyretin amyloid deposition can also produce central nervous system dysfunction as the major clinical symptom.
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PMID:Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G) 857 96

In the acute phase of the stroke, it must be prudent to reduce blood pressure (BP) because the rapid reduction might cause the exacerbation of the perfusion pressure to the brain. The target BP level should be higher than the level of primary prevention as the blood pressure regulatory function is disturbed in acute phase. In chronic phase, BP should be reduced so slowly through the several months so as not to cause the ischemia of the brain by rapid reduction of BP. However, the optimal target BP level should be the same degree as the primary prevention level as far as the speed of reduction is taken into consideration. The several large scale trials, are now in progress to determine the optimal BP level for the secondary prevention in the patients with prion stroke.
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PMID:[Antihypertensive therapy of patients with cerebrovascular disease]. 928 31

Creutzfeldt-Jakob disease (CJD) is a degenerative process of the brain, induced by novel infectious agent or prion, and is usually characterized by a rapidly progressive dementia in association with myoclonus. However different patterns of disease presentation have been identified. The authors describe three probable cases of CJD. None of them had positive family history or any known modes of iatrogenic transmission. Interestingly, all the cases presented like a stroke. This is the first series of CJD cases from this part of country.
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PMID:Stroke like presentation of Creutzfeldt Jakob disease: an unusual variant. 1127 58

Murine prion disease is accompanied by a modified inflammatory response characterized by early but prolonged microglial activation and T-lymphocyte recruitment. In this model, we look at the profile of cytokine production, particularly IL-1beta. Mice inoculated with prion-infected brain homogenate show typical signs of prion disease. We were unable to detect any IL-1beta using immunohistochemistry, with various fixation protocols, or ELISA between 8 and 24 wk post-inoculation. Also, there was no increase in mRNA for IL-1beta, IL-6, IFNgamma, and iNOS as measured by quantitative RT-PCR. Using the same procedures and examining tissues at the same time, IL-1beta immunostaining was detected in infiltrating inflammatory cells in mouse brains injected with LPS or in a delayed-type hypersensitivity response in the brain. Soluble IL-1beta was also increased, as measured by ELISA, and there was an increase in mRNA species for IL-1beta, IL-6, TNFalpha but not IFNgamma or iNOS in these brains. These data reveal that chronic neurodegeneration seen in prion disease does not induce production of a range of proinflammatory mediators despite showing marked microglial activation and raise the question as to whether IL-1beta would exacerbate the neurodegeneration as it does in acute neurodegeneration following head injury and stroke.
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PMID:Absence of detectable IL-1beta production in murine prion disease: a model of chronic neurodegeneration. 1127 5

The expression of cyclooxygenase-2 (COX-2) and the synthesis of prostaglandin E2 (PGE2) as well as of cytokines such as interleukin-6 (IL-6) have all been suggested to propagate neuropathology in different brain disorders such as HIV-dementia, prion diseases, stroke and Alzheimer's disease. In this report, we show that PGE2-stimulated IL-6 release in U373 MG human astroglioma cells and primary rat astrocytes. PGE2-induced intracellular cAMP formation was mediated via prostaglandin E receptor 2 (EP2), but inhibition of cAMP formation and protein kinase A or blockade of EP1/EP2 receptors did not affect PGE2-induced IL-6 synthesis. This indicates that the cAMP pathway is not part of PGE2-induced signal transduction cascade leading to IL-6 release. The EP3/EP1-receptor agonist sulprostone failed to induce IL-6 release, suggesting an involvement of EP4-like receptors. PGE2-activated p38 mitogen-activated kinase (p38 MAPK) and protein kinase C (PKC). PGE2-induced IL-6 synthesis was inhibited by specific inhibitors of p38 MAPK (SB202190) and PKC (GF203190X). Although, up to now, EP receptors have only rarely been linked to p38 MAPK or PKC activation, these results suggest that PGE2 induces IL-6 via an EP4-like receptor by the activation of PKC and p38 MAPK via an EP4-like receptor independently of cAMP.
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PMID:Mechanisms of prostaglandin E2-induced interleukin-6 release in astrocytes: possible involvement of EP4-like receptors, p38 mitogen-activated protein kinase and protein kinase C. 1173 6

chlamdAs with other organ systems, the vulnerability of the nervous system to infectious agents increases with aging. Several different infectious agents can cause neurodegenerative conditions, with prominent examples being human immunodeficiency virus (HIV-1) dementia and prion disorders. Such infections of the central nervous system (CNS) typically have a relatively long incubation period and a chronic progressive course, and are therefore increasing in frequency as more people live longer. Infectious agents may enter the central nervous system in infected migratory macrophages, by transcytosis across blood-brain barrier cells or by intraneuronal transfer from peripheral nerves. Synapses and lipid rafts are important sites at which infectious agents may enter neurons and/or exert their cytotoxic effects. Recent findings suggest the possibility that infectious agents may increase the risk of common age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and stroke. While scenarios can be envisioned whereby viruses such as Chlamydia pneumoniae, herpes simplex and influenza promote damage to neurons during aging, there is no conclusive evidence for a major role of these pathogens in neurodegenerative disorders. In the case of stroke, blood vessels may be adversely affected by bacteria or viruses resulting in atherosclerosis.
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PMID:Infectious agents and age-related neurodegenerative disorders. 1516 5

Evidence is presented which supports the conclusion that the hormetic dose-response model is the most common and fundamental in the biological and biomedical sciences, being highly generalizable across biological model, endpoint measured and chemical class and physical agent. The paper provides a broad spectrum of applications of the hormesis concept for clinical medicine including anxiety, seizure, memory, stroke, cancer chemotherapy, dermatological processes such as hair growth, osteoporosis, ocular diseases, including retinal detachment, statin effects on cardiovascular function and tumour development, benign prostate enlargement, male sexual behaviours/dysfunctions, and prion diseases.
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PMID:Hormesis and medicine. 1866 93

Recent advances indicate that maintaining a balanced level of autophagy is critically important for neuronal health and function. Pathologic dysregulation of macroautophagy has been implicated in synaptic dysfunction, cellular stress, and neuronal cell death. Autophagosomes and autolysosomes are induced in acute and chronic neurological disorders including stroke, brain trauma, neurotoxin injury, Parkinson's, Alzheimer's, Huntington's, motor neuron, prion, lysosomal storage, and other neurodegenerative diseases. Compared to other cell types, neuronal autophagy research presents particular challenges that may be addressed through still evolving techniques. Neuronal function depends upon maintenance of axons and dendrites (collectively known as neurites) that extend for great distances from the cell body. Both autophagy and mitochondrial content have been implicated in regulation of neurite length and function in physiological (plasticity) and pathological remodeling. Here, we highlight several molecular cell biological and imaging methods to study autophagy and mitophagy in neuritic and somatic compartments of differentiated neuronal cell lines and primary neuron cultures, using protocols developed in toxic and genetic models of parkinsonian neurodegeneration. In addition, mature neurons can be studied using in vivo protocols for modeling ischemic and traumatic injuries. Future challenges include application of automated computer-assisted image analysis to the axodendritic tree of individual neurons and improving methods for measuring neuronal autophagic flux.
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PMID:Autophagy in neurite injury and neurodegeneration: in vitro and in vivo models. 1921 9

Although it has been known for more than twenty years that an aberrant conformation of the prion protein (PrP) is the causative agent in prion diseases, the role of PrP in normal biology is undetermined. Numerous studies have suggested a protective function for PrP, including protection from ischemic and excitotoxic lesions and several apoptotic insults. On the other hand, many observations have suggested the contrary, linking changes in PrP localization or domain structure--independent of infectious prion conformation--to severe neuronal damage. Surprisingly, a recent report suggests that PrP is a receptor for toxic oligomeric species of a-beta, a pathogenic fragment of the amyloid precursor protein, and likely contributes to disease pathogenesis of Alzheimer disease. We sought to access the role of PrP in diverse neurological disorders. First, we confirmed that PrP confers protection against ischemic damage using an acute stroke model, a well characterized association. After ischemic insult, PrP knockouts had dramatically increased infarct volumes and decreased behavioral performance compared to controls. To examine the potential of PrP's neuroprotective or neurotoxic properties in the context of other pathologies, we deleted PrP from several transgenic models of neurodegenerative disease. Deletion of PrP did not substantially alter the disease phenotypes of mouse models of Parkinson disease or tauopathy. Deletion of PrP in one of two Huntington disease models tested, R6/2, modestly slowed motor deterioration as measured on an accelerating rotarod but otherwise did not alter other major features of the disease. Finally, transgenic overexpression of PrP did not exacerbate the Huntington motor phenotype. These results suggest that PrP has a context-dependent neuroprotective function and does not broadly contribute to the disease models tested herein.
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PMID:Context dependent neuroprotective properties of prion protein (PrP). 1990 59

Genetic transmissible spongiform encephalopathies (TSEs) account for approximately 10-15% of overall human prion diseases worldwide, but genotype-phenotype correlations remain incomplete. Here we report the case of an 80-year-old man who developed rapidly progressive behavioral abnormalities and myoclonus following a stroke. Repeated electroencephalography (EEG) revealed a general slowing of the basic activity, as well as several episodes of triphasic waves, with neither periodic activity nor recorded seizure. 14.3.3 protein was detected in cerebral cerebrospinal fluid, and direct sequencing of the PRNP gene showed an E196K mutation associated with homozygosity for methionine at codon 129. The patient was diagnosed with probable genetic prion disease with a Creutzfeldt-Jakob disease-like phenotype. The PRNP E196K mutation has only rarely been described in the literature, and generally patients exhibited an atypical initial phenotype, mainly involving abnormal behavioral features. Further observations are needed to confirm this particular clinical pattern associated with the mutation.
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PMID:Rare E196K mutation in the PRNP gene of a patient exhibiting behavioral abnormalities. 2000 32


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