UMLS:C0038454 - FACTA Search

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Query: UMLS:C0038454 (stroke)
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The APP was employed in our 21st TAH calf and has now been implanted in a total of 11 animals. The APP has a dynamic stroke volume of 105 ml, an ejection fraction of 75%, and a peak flow of 14 L/min. The TAH features 2 APPs which have polysulfone cases and contain smooth, seam-free polyurethane sacs. Concavoconvex Bjork-Shiley valves are used. The pumps are pneumatically driven but may be easily converted to pusher-plate drive. A pneumatic drive console and an automatic control unit complete the system. The automatic control unit permits independent control of the right and left hearts as a function of left atrial and aortic pressure respectively. The average survival of the APP TAH calves has been 65 days. Hematologic study has revealed basically normal results with minimal elevation of serum hemoglobin and lactic acid dehydrogenase (LDH), indicative of a low level of hemolysis. Elelvation of central venous pressure (CVP) and total blood volume continue to be a problem with some TAH calves but not all. The APP has led to a dramatic increase in duration of survival and decrease in thromboembolism.
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PMID:Total artificial heart implantation in calves with pump on an angled port design. 52 90

We here introduce an office or bedside method of evaluating both the motor and sensory components of swallowing, called fiberoptic endoscopic evaluation of swallowing with sensory testing (FEESST). FEESST combines the established endoscopic evaluation of swallowing with a technique that determines laryngopharyngeal (LP) sensory discrimination thresholds by endoscopically delivering air pulse stimuli to the mucosa innervated by the superior laryngeal nerve. Endoscopic assessment of LP sensory capacity followed by endoscopic visualization of deglutition was prospectively performed 148 times on 133 patients with dysphagia over an 8-month period. The patients had a variety of underlying diagnoses, with stroke and chronic neurologic disease predominating (n = 94). Subsequent to LP sensory testing, a complete dysphagia evaluation was conducted. Various food and liquid consistencies were dyed green, and attention was paid to their management throughout the pharyngeal stage of swallowing. Evidence of latent swallow initiation, pharyngeal pooling and/or residue, laryngeal penetration, laryngeal aspiration, and/or reflux was noted. Recommendations for therapeutic intervention were based on information obtained during the FEESST and often involved the employment of compensatory swallowing strategies, modification of the diet or its presentation, placement on non-oral feeding status, and/or referral to other related specialists. All patients successfully completed the examination. In 111 of the evaluations (75%), severe (>6.0 mm Hg air pulse pressure [APP]) unilateral or bilateral LP sensory deficits were found. With puree consistencies, 31% of evaluations with severe deficits, compared to 5% of evaluations with either normal sensitivity or moderate (4.0 to 6.0 mm Hg APP) LP sensory deficits, displayed aspiration (p < .001, chi2 test). With puree consistencies, 69% of evaluations with severe deficits, compared to 24% with normal or moderate deficits, displayed laryngeal penetration (p < .001, chi2 test). FEESST allows the clinician to obtain a comprehensive bedside assessment of swallowing that is performed as the initial swallowing evaluation for the patient with dysphagia.
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PMID:FEESST: a new bedside endoscopic test of the motor and sensory components of swallowing. 959 14

A high risk factor for spontaneous and often fatal lobar hemorrhage is cerebral amyloid angiopathy (CAA). We now report that CAA in an amyloid precursor protein transgenic mouse model (APP23 mice) leads to a loss of vascular smooth muscle cells, aneurysmal vasodilatation, and in rare cases, vessel obliteration and severe vasculitis. This weakening of the vessel wall is followed by rupture and bleedings that range from multiple, recurrent microhemorrhages to large hematomas. Our results demonstrate that, in APP transgenic mice, the extracellular deposition of neuron-derived beta-amyloid in the vessel wall is the cause of vessel wall disruption, which eventually leads to parenchymal hemorrhage. This first mouse model of CAA-associated hemorrhagic stroke will now allow development of diagnostic and therapeutic strategies.
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PMID:Spontaneous hemorrhagic stroke in a mouse model of cerebral amyloid angiopathy. 1122 52

The brain's response to ischemia, which helps determine clinical outcome after stroke, is regulated partly by competing genetic programs that respectively promote cell survival and delayed cell death. Many genes involved in this response have been identified individually or systematically, providing insights into the molecular basis of ischemic injury and potential targets for therapy. The development of microarray systems for gene expression profiling permits screening of large numbers of genes for possible involvement in biological or pathological processes. Therefore, we used an oligodeoxynucleotide-based microarray consisting of 374 human genes, most implicated previously in apoptosis or related events, to detect alterations in gene expression in the hippocampus of rats subjected to 15 minutes of global cerebral ischemia followed by up to 72 hours of reperfusion. We found 1.7-fold or greater increases in the expression of 57 genes and 1.7-fold or greater decreases in the expression of 34 genes at 4, 24, or 72 hours after ischemia. The number of induced genes increased from 4 to 72 hours, whereas the number of repressed genes decreased. The induced genes included genes involved in protein synthesis, genes mutated in hereditary human diseases, proapoptotic genes, antiapoptotic genes, injury-response genes, receptors, ion channels, and enzymes. We detected transcriptional induction of several genes implicated previously in cerebral ischemia, including ALG2, APP, CASP3, CLU, ERCC3, GADD34, GADD153, IGFBP2, TIAR, VEGF, and VIM, as well as other genes not so implicated. We also found coinduction of several groups of related genes that might represent functional modules within the ischemic neuronal transcriptome, including VEGF and its receptor, NRP1; the IGF1 receptor and the IGF1-binding protein IGFBP2; Rb, the Rb-binding protein E2F1, and the E2F-related transcription factor, TFDP1; the CACNB3 and CACNB4 beta-subunits of the voltage-gated calcium channel; and caspase-3 and its substrates, ACINUS, FEM1, and GSN. To test the hypothesis that genes identified through this approach might have roles in the pathophysiology of cerebral ischemia, we measured expression of the products of two induced genes not heretofore implicated in cerebral ischemia-GRB2, an adapter protein involved in growth-factor signaling pathways, and SMN1, which participates in RNA processing and is deleted in most cases of spinal muscular atrophy. Western analysis showed enhanced expression of both proteins in hippocampus at 24 to 72 hours after ischemia, and SMN1 was localized by immunohistochemistry to hippocampal neurons. These results suggest that microarray analysis of gene expression may be useful for elucidating novel molecular mediators of cell death and survival in the ischemic brain.
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PMID:Microarray analysis of hippocampal gene expression in global cerebral ischemia. 1145 15

Normal ageing and Alzheimer's disease (AD) have many features in common and, in many respects, both conditions only differ by quantitative criteria. A variety of genetic, medical and environmental factors modulate the ageing-related processes leading the brain into the devastation of AD. In accordance with the concept that AD is a metabolic disease, these risk factors deteriorate the homeostasis of the Ca(2+)-energy-redox triangle and disrupt the cerebral reserve capacity under metabolic stress. The major genetic risk factors (APP and presenilin mutations, Down's syndrome, apolipoprotein E4) are associated with a compromise of the homeostatic triangle. The pathophysiological processes leading to this vulnerability remain elusive at present, while mitochondrial mutations can be plausibly integrated into the metabolic scenario. The metabolic leitmotif is particularly evident with medical risk factors which are associated with an impaired cerebral perfusion, such as cerebrovascular diseases including stroke, cardiovascular diseases, hypo- and hypertension. Traumatic brain injury represents another example due to the persistent metabolic stress following the acute event. Thyroid diseases have detrimental sequela for cerebral metabolism as well. Furthermore, major depression and presumably chronic stress endanger susceptible brain areas mediated by a host of hormonal imbalances, particularly the HPA-axis dysregulation. Sociocultural and lifestyle factors like education, physical activity, diet and smoking may also modulate the individual risk affecting both reserve capacity and vulnerability. The pathophysiological relevance of trace metals, including aluminum and iron, is highly controversial; at any rate, they may adversely affect cellular defences, antioxidant competence in particular. The relative contribution of these factors, however, is as individual as the pattern of the factors. In familial AD, the genetic factors clearly drive the sequence of events. A strong interaction of fat metabolism and apoE polymorphism is suggested by intercultural epidemiological findings. In cultures, less plagued by the 'blessings' of the 'cafeteria diet-sedentary' Western lifestyle, apoE4 appears to be not a risk factor for AD. This intriguing evidence suggests that, analogous to cardiovascular diseases, apoE4 requires a hyperlipidaemic lifestyle to manifest as AD risk factor. Overall, the etiology of AD is a key paradigm for a gene-environment interaction. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:A unifying hypothesis of Alzheimer's disease. III. Risk factors. 1240 43

Focal cerebral ischemia activates the nuclear protein poly(ADP-ribose) polymerase (PARP). Apoptosis-inducing factor (AIF) is a flavoprotein that is normally confined to the mitochondria, but translocates to the nucleus, as shown by in vitro models of neuronal injury. Using INO-1001, a novel potent inhibitor of PARP, we determined the role of PARP activation in the process of AIF translocation in a rat model of focal cerebral ischemia. The potency of INO-1001 as a PARP inhibitor and its cytoprotective potential in oxidant-challenged human neuronal SK-N-MC cells was first confirmed in vitro. PARP inhibition markedly reduced infarct size and improved neurological status in both transient and permanent models of MCA occlusion in Sprague-Dawley rats, with a therapeutic window of 6 h and 2 h in the transient and permanent ischemia models, respectively. The PARP inhibitor reduced the accumulation of poly(ADP-ribose) in the ischemic/reperfused hemisphere and reduced the accumulation of APP in the white matter of the affected hemisphere, consistently with protection against neuronal necrosis and axonal damage, respectively. Immunohistochemical analysis showed the appearance of AIF labeling in neuronal nuclei of the border zone ischemic area in the striatum after stroke. Cytoplasmatic (axonal) AIF staining was significantly diminished in the necrotic core of the striatum, while it was somewhat enhanced at the borderline ischemic territories of the white matter. Inhibition of PARP with INO-1001 reshifted the location of the apoptotic marker to the axons in the ipsilateral striatum. Thus, PARP inhibition is neuroprotective and regulates the ischemic nuclear translocation of AIF in stroke.
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PMID:Poly(ADP-ribose) polymerase inhibition protect neurons and the white matter and regulates the translocation of apoptosis-inducing factor in stroke. 1476 66

Neurobehavioral deficits in higher cortical systems have not been described previously in a large animal model of diffuse brain injury. Anesthetized 3-5 day old piglets were subjected to either mild (142 rad/s) or moderate (188 rad/s) rapid non-impact axial rotations of the head. Multiple domains of cortical function were evaluated 5 times during the 12 day post-injury period using tests of neurobehavioral function devised for piglets. There were no observed differences in neurobehavioral outcomes between mild injury pigs (N=8) and instrumented shams (N=4). Moderately injured piglets (N=7) had significantly lower interest in exploring their environment and had higher failure rates in visual-based problem solving compared to instrumented shams (N=5) on days 1 and 4 after injury. Neurobehavioral functional deficits correlated with neuropathologic damage in the neonatal pigs after inertial head injury. Injured axons detected by immunohistochemistry (beta-APP) were absent in mild injury and sham piglets, but were observed in moderately injured piglet brains. In summary, we have developed a quantitative battery of neurobehavioral functional assessments for large animals that correlate with neuropathologic axonal damage and may have wide applications in the fields of cardiac resuscitation, stroke, and hypoxic-ischemic brain injury.
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PMID:Neurobehavioral functional deficits following closed head injury in the neonatal pig. 1717 4

Weather watch/warning systems have been established for human health outcomes. Our study aims to develop and demonstrate a weather watch/warning system for asthma and stroke within the whole of South Korea, using a stratified regression approach. We converted claim-based health insurance data covering almost all medical claims for the only health insurance system in Korea for asthma and stroke from 1996-2003 into personalized disease episode data, and combined them with meteorological data. We utilized a step-wise regression method using factors extracted from the meteorological data to develop stratified models for six (stroke) and nine (asthma) regional and day-of-week strata. Validation studies showed that the actual number of hospitalizations in 2003 increased according to the three-leveled predictions (levels I, II, and III) from the model based on the 1996-2002 data. This system is accessible via the internet (http://industry.kma.go.kr/APP/sub_APP15_H01.htm) at the Korean Meteorological Administration website.
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PMID:The weather watch/warning system for stroke and asthma in South Korea. 1836 1

In this study, we tested if caspase-3 inhibition decreased ischemia-induced Abeta elevation by reducing beta-secretase (BACE1) activity. Changes in caspase-3, Abeta and BACE1 levels were detected in rat striatum on different days after middle cerebral artery occlusion using immunostaining. We found that the positive labeled cells of activated caspase-3, Abeta, and BACE1 were significantly and time-dependently increased in the ipsilateral striatum. The results of Western blotting and RT-PCR showed that caspase-3 inhibitor Z-DEVD-FMK reduced BACE1 mRNA and protein levels, and inhibited its protease activity, thereby decreasing the amount of APP C99 and Abeta in ischemic brains. Moreover, Z-DEVD-FMK reduced BACE1 and GFAP double-labeled cells, but not GFAP protein levels or GFAP-labeled cells, in the ipsilateral striatum. Thus, we demonstrated that caspase-3 inhibition attenuated ischemia-induced Abeta formation by reducing BACE1 production and activity. This finding provides a therapeutic strategy for preventing Abeta accumulation and reducing the risk of neurodegeneration after stroke.
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PMID:Caspase inhibition attenuates accumulation of beta-amyloid by reducing beta-secretase production and activity in rat brains after stroke. 1880 88

The essential metals iron, zinc and copper deposit near the Abeta (amyloid beta-peptide) plaques in the brain cortex of AD (Alzheimer's disease) patients. Plaque-associated iron and zinc are in neurotoxic excess at 1 mM concentrations. APP (amyloid precursor protein) is a single transmembrane metalloprotein cleaved to generate the 40-42-amino-acid Abetas, which exhibit metal-catalysed neurotoxicity. In health, ubiquitous APP is cleaved in a non-amyloidogenic pathway within its Abeta domain to release the neuroprotective APP ectodomain, APP(s). To adapt and counteract metal-catalysed oxidative stress, as during reperfusion from stroke, iron and cytokines induce the translation of both APP and ferritin (an iron storage protein) by similar mechanisms. We reported that APP was regulated at the translational level by active IL (interleukin)-1 (IL-1-responsive acute box) and IRE (iron-responsive element) RNA stem-loops in the 5' untranslated region of APP mRNA. The APP IRE is homologous with the canonical IRE RNA stem-loop that binds the iron regulatory proteins (IRP1 and IRP2) to control intracellular iron homoeostasis by modulating ferritin mRNA translation and transferrin receptor mRNA stability. The APP IRE interacts with IRP1 (cytoplasmic cis-aconitase), whereas the canonical H-ferritin IRE RNA stem-loop binds to IRP2 in neural cell lines, and in human brain cortex tissue and in human blood lysates. The same constellation of RNA-binding proteins [IRP1/IRP2/poly(C) binding protein] control ferritin and APP translation with implications for the biology of metals in AD.
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PMID:Iron and the translation of the amyloid precursor protein (APP) and ferritin mRNAs: riboregulation against neural oxidative damage in Alzheimer's disease. 1902 41

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