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)

To investigate left ventricular size and performance during graded submaximal exercise, 14 normal subjects with a mean age of 21 years exercised in a supine position to achieve the target heart rate. Using two-dimensional echocardiography, we recorded and analysed the left ventricular (LV) cross-sectional area and internal dimension at the level of the tips of the mitral valve at rest and during mild, moderate and severe exercise. The heart rate and systolic blood pressure increased substantially from rest to peak exercise (71 +/- 11 to 162 +/- 10 beats/min, 122 +/- 10 to 204 +/- 22 mmHg). The end-diastolic cross-sectional area and internal dimension (EDA & EDD) increased by 1.1-2.2 cm2 (7-13%) and 0.2-0.3 cm (4-7%), respectively, from mild to moderate exercise, (p less than 0.05-0.001). At peak exercise, however, these decreased and showed no statistically significant difference from the values at rest. The end-systolic cross-sectional area and internal dimension (ESA & ESD) decreased by 1.1 to 1.6 cm2 (14-20%) and 0.2-0.3 cm (7-10%), respectively, from moderate to severe exercise (p less than 0.01-0.001). However, the end-systolic values during mild exercise were not significantly different from those at rest. The stroke area (EDA-ESA) and dimension (EDD-ESD) increased by 1.6-2.6 cm2 (19-31%) and 0.2-0.6 cm (25-38%), respectively, during all levels of graded exercise (p less than 0.05-0.001). The percent change of LV cross-sectional area and internal dimension during systole increased gradually from rest to moderate exercise (51.0 +/- 7.1 to 61.9 +/- 4.4%, 35.4 +/- 3.9 to 45.0 +/- 3.7%), respectively, and showed no further increase during peak exercise. The mean circumferential fiber shortening velocity increased sharply from rest to peak exercise (1.27 +/- 0.14 to 2.25 +/- 0.21 circ/sec). These results suggest that the Frank-Starling mechanism operates during mild to moderate exercise, and contractility increases markedly at moderate to severe exercise levels as cardiac performance is augmented during graded submaximal exercise.
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PMID:Left ventricular size and performance during graded supine exercise in normal subjects. 664 45

This study describes local immune responses in cerebral ischemia induced by permanent occlusion of the middle cerebral artery (MCAO) in the rat. The temporal and spatial pattern of leukocyte infiltration was characterized immunocytochemically using monoclonal antibodies against CD5, a pan T cell marker, against CD4 and CD8 for subtyping of T lymphocytes, and ED1, a marker for macrophages. CD5+ T cells were present in some animals on the pial surface at day 1 and with increasing numbers mainly at the edges of the infarcts at days 3 and 7. By day 14 their number had significantly decreased. Subtyping of T lymphocytes revealed that CD4+ helper/inducer T cells were rare, while CD8+ lymphocytes were abundant. Moreover, CD8+ lymphocytes outnumbered CD5+ T cells indicating the presence of CD5-/CD8+ natural killer (NK) cells. ED1+ macrophages primarily infiltrated the core of the infarct starting on day 1. Infiltrating leukocytes expressed leukocyte function associated antigen-1 and MHC class I and II antigens. Early after infarction, increased expression of the intercellular adhesion molecule-1 was found on vessels and leukocytes. In conclusion, this study shows that lymphocytes enter the nervous system not only in autoimmune diseases, but also in response to primarily 'non-immune' neuronal damage such as stroke.
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PMID:Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion. 753 Feb 60

In hypertensive vascular lesions, various pathologic changes are exhibited. To clarify the mechanisms responsible for this diversity of vascular lesions, we immunohistochemically examined hypertensive vascular lesions in stroke-prone spontaneously hypertensive rats with reference to the distribution of macrophage subsets. The brain, kidney, heart, and aorta were dissected from stroke-prone spontaneously hypertensive rats and Wistar-Kyoto rats at 8, 12, 16, and 20 weeks of age. Immunohistochemistry was performed with antibodies against the macrophage markers ED1, ED2, and OX42, the MHC class II antigen marker OX6, the T-lymphocyte markers CD4, CD5, and CD8, and other markers, such as alpha-smooth muscle actin, proliferating cell nuclear antigen, and von Willebrand factor. Fibrinoid necrosis was dominant in the brain, and fibrocellular proliferative lesions were dominant in the kidney. Immunohistochemically, the decreased intensity of alpha-smooth muscle actin immunostaining preceded the formation of vascular lesions. Although preexisting ED2-positive perivascular resident macrophages completely disappeared in fibrinoid necrosis, MHC class II-negative and ED1-positive macrophages were scattered around the lesion and showed phagocytosis in the brain, which indicates that macrophages in fibrinoid necrosis had extravasated and acted only as scavengers. In the kidney, there was extensive accumulation of MHC class II-positive and ED1-positive macrophages with T lymphocytes along the affected arteries. These inflammatory cells seemed to be supplied through the perivascular interstitial space, not through the endothelium, and the accumulation of these cells preceded the development of fibrocellular proliferative lesions. In the heart and aorta, macrophage accumulation was either absent or slight, and vascular lesions were rarely observed. These findings suggest that heterogeneity in the time course of macrophage infiltration and in the distribution of macrophage subsets among the vascular trees of various organs seems to be correlated with the diversity of hypertensive vascular lesions. Differences in the routes that supply macrophages and their functions may determine the pathologic changes in the vascular lesions.
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PMID:Heterogeneity in the appearance and distribution of macrophage subsets and their possible involvement in hypertensive vascular lesions in rats. 876 13

The potentially neurotrophic cytokine transforming growth factor-beta1 (TGF-beta1) is locally expressed following human stroke and experimental ischemic lesions, but the cellular source(s) and profile of induction have so far not been established in experimental focal cerebral ischemia. This study presents the time course and a cellular localization of TGF-beta1 mRNA, visualized by in situ hybridization combined with immunohistochemical staining for microglia, macrophages, or astrocytes, on brain sections from adult spontaneously hypertensive rats subjected to transient proximal occlusion of their middle cerebral artery. Six hours after ischemia, an early and transient neuronal and microglial expression of TGF-beta1 mRNA was observed in the extraischemic cingulate and frontal cortices. Both early and protracted expression of TGF-beta1 mRNA in the caudate-putamen and neocortical infarcts and in the caudate-putamen penumbra colocalized with OX42/ED1-immunoreactive microglia and macrophages, whereas TGF-beta1 mRNA in the neocortical penumbra colocalized with OX42/ED1-immunoreactive cells of a microglial morphology. No astrocytes were double-labeled. The number of TGF-beta1 mRNA-expressing microglia and macrophages increased strongly during the first week. Thereafter, TGF-beta1 mRNA became increasingly restricted to the neocortical penumbra (3 weeks), and after 3 months it was confined to activated microglia in the anterior commissure. Our data establish activated microglia and macrophages as the major source of TGF-beta1 mRNA following experimental focal cerebral ischemia. Consequently, TGF-beta1-mediated functions may be exerted by microglia both in the early degenerative phase, and later in combination with blood-borne macrophages, in the remodeling and healing phase after focal cerebral ischemia.
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PMID:Microglia and macrophages are major sources of locally produced transforming growth factor-beta1 after transient middle cerebral artery occlusion in rats. 981 24

Afterload corrected fractional area change (FACac) is a simple measurement of contractility which can be acquired during surgery without the need to acutely alter volume. We have validated it against the load-independent measurement, stroke force / end-diastolic area relationship (SF/EDA) in patients undergoing cardiac surgery. SF/EDA regressions were analysed before and after cardiopulmonary bypass in 39 patients and compared with simultaneously acquired FACac data. End-systolic and end-diastolic areas (ESA and EDA) were measured by transesophageal echocardiography and substituted for ventricular volumes. Pulmonary capillary wedge pressure was substituted for end-diastolic pressure and peak-systolic pressure for end-systolic pressure. Stroke force is the integral of the pressure-area loop and a square shape was assumed for calculation. FACac = FAC x log 10(SVRI) x 100%, where SVRI is calculated without multiplication by 80. Comparison of the methods was done by ordinary least products regression analysis where SF/EDA = a+b (FACac). a = 0.004 (95% CI -5.46 to 5.46). b = 0.857 (95% CI 0.777 to 0.936). Agreement between SF/EDA and FACac was identified by the absence of fixed bias. Both SF/EDA and FACac identified a reduction in contractility following cardiopulmonary bypass of similar magnitude suggesting load-independence of FACac. In contrast, the load-dependent indexes, cardiac index and FAC, increased in value but in the presence of reduced afterload. FACac may be used as a simplified index to reflect a relatively load-independent index of left ventricular contractility. Its simplicity offers promise of clinical utility.
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PMID:Afterload corrected fractional area change (FACac): a simple, relatively load-independent measurement of left ventricular contractility in humans. 1117 46

The left and right neocortex of the brain has been shown to exert asymmetrical effects on the immune system. In the present study, we used a middle cerebral artery (MCA) occlusion model in Wistar rats to analyze the influence of unilateral CNS ischemia on spleen cell number and function. The occlusion time was 1 h, followed by reperfusion with survival for 0, 2, 7, 14, and 28 days. Changes in plasma norepinephrine levels were used as an index of peripheral sympathetic activity. Results showed that the total number of spleen cells significantly decreased after 2-28 days of survival in animals with cerebral ischemia compared to sham-operated controls. There was no change in the percentage of CD5(+)-CD4(+) T cells, MHC class II(+) cells, or ED1(+) macrophages. However, the percentage of CD5(+)-CD8(+) T cells decreased at 2 days, resulting in an increased CD4/CD8 ratio, and both parameters returned to control levels after 7 days. Mitogen-induced T and B lymphocyte proliferation increased after 0-28 days post-ischemia independently of the mitogen used. There was no difference in immune response or norepinephrine levels between left and right MCA occlusions. These results are consistent with the notion that cerebral ischemia induces mobilization of certain immune cells from the periphery to the brain, where they may contribute to the local inflammatory response. Additionally, the data indicate that cerebral ischemia is followed by a systemic activation of T and B lymphocytes. Absence of asymmetric effects of left versus right stroke, and failure to demonstrate any suppressive effects of left-sided lesions on lymphocyte proliferation, probably reflects the fact that these large cerebral ischemic lesions affect both cortical and subcortical areas.
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PMID:Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats. 1241 24

Death receptors (DRs) are a growing family of transmembrane proteins that can detect the presence of specific extracellular death signals and rapidly trigger cellular destruction by apoptosis. Eight human DRs (Fas, TNF-R1, TRAMP, TRAIL-R1, TRAIL-R2, DR-6, EDA-R and NGF-R) have been identified. The best studied to date is Fas (CD95). Expression and signaling by Fas and its ligand (FasL, CD95L) is a tightly regulated process essential for key physiological functions in a variety of organs, including the maintenance of immune homeostasis. Recently, strong evidence has shown that dysregulation of Fas expression and/or signaling contributes to the pathogenesis of tissue destructive diseases such as graft-versus-host disease, toxic epidermal necrolysis, multiple sclerosis and stroke. With these new developments, strategies for modulating the function of Fas signaling have emerged and provided novel protein-based therapeutic possibilities that will be discussed herein. Selective triggering of DR-mediated apoptosis in cancer cells is an emerging approach that is being intensely investigated as a mode of cancer therapy. Local administration of Fas agonists, and more promisingly, systemic use of soluble recombinant forms of TRAIL have shown efficacy in preclinical models of the disease. Developments in this field that may have important clinical implications for the treatment of cancer are reviewed.
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PMID:Protein-based therapeutic approaches targeting death receptors. 1265

This study tested the hypothesis that the preload-adjusted maximal power index (PA-PWRmax) is a load-independent index of human myocardial contractility. Based on the ventricular pressure-volume relationship and derived from stroke work, the index is the product of instantaneous ventricular pressure and volume changes, divided by a correction term of end-diastolic volume (EDV2) or end-diastolic area (EDA3/2) to adjust for preload effects. Echocardiographic measures of instantaneous ventricular area change may be used to obtain PA-PWRmax noninvasively. We prospectively evaluated 28 human subjects undergoing cardiac evacuation before cardiopulmonary bypass procedures. Continuous peripheral arterial pressure, pulmonary arterial pressure, and echocardiographic views of the left ventricle in the transgastric short-axis view were recorded. Simultaneously gated instantaneous fractional shortening (FS) and PA-PWRmax indices were calculated, with FS = (EDA - ESA)/EDA and PA-PWRmax = [MAP (EDA - ESA)]/ EDA3/2, where ESA = end-systolic area and MAP = instantaneous mean arterial pressure. FS decreased uniformly with cardiac evacuation and decreasing pulmonary artery diastolic pressure (t = -5.4; 95% confidence interval, -10 to -0.046; p < 0.001), as did PA-PWRmax (t = -5.8; 95% confidence interval, -2.25 to -1.08; p < 0.001). FS and PA-PWRmax showed a strong downward correlation (r = 0.81). Unlike previous studies of autonomically denervated animals, our study did not find PA-PWRmax to be preload independent, perhaps because of the instantaneous homeostatic mechanisms of the human autonomic nervous system linking contractility to loading conditions.
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PMID:Is PA-PWRmax truly a preload-independent index of myocardial contractility in anesthetized humans? 1510 76

Free radicals and inflammatory mediators are involved in transient focal cerebral ischemia (FCI). Preadministration of N-acetylcysteine (NAC) has been found to attenuate the cerebral ischemia-reperfusion injury in a rat model of experimental stroke. This study was undertaken to investigate the neuroprotective potential of NAC administered after ischemic events in experimental stroke. FCI was induced for 30 min by occluding the middle cerebral artery (MCA). NAC (150 mg/kg) was administered intraperitoneally at the time of reperfusion followed by another dose 6 hr later. Animals were sacrificed after 24 hr of reperfusion. The cerebral infarct consistently involved the cortex and striatum. Infarction was assessed by staining the brain sections with 2,3,5-triphenyltetrazolium chloride. Animals treated with NAC showed a significant reduction in infarct area and infarct volume and an improvement in neurologic scores and glutathione level. Reduction in infarction was significant even when a single dose of NAC was administered at 6 hr of reperfusion. Immunohistochemical and quantitative real-time PCR studies demonstrated a reduction in the expression of proinflammatory cytokines such as tumor necrosis factor alpha (TNFalpha) and interleukin 1beta (IL-1beta) and inducible nitric oxide synthase (iNOS) in NAC compared to that in vehicle-treated animals. The expression of activated macrophage/microglia (ED1) and apoptotic cell death in ischemic brain was also reduced by NAC treatment. These results indicate that in a rat model of experimental stroke, administration of NAC even after ischemia onset protected the brain from free radical injury, apoptosis, and inflammation, with a wide treatment window.
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PMID:Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. 1511 24

Immunophilin ligands, such as cyclosporin A and FK506, have neuroprotective effects in experimental stroke models, although the precise mechanism is unclear. Cyclophilin C-associated protein (CyCAP) is a natural cellular ligand for the immunophilin, cyclophilin C, and has a protective effect against endotoxins by downmodulating the proinflammatory response. Expressions of CyCAP and cyclophilin C mRNA in a rat middle cerebral artery (MCA) occlusion ischemia model were investigated by Northern blotting and in situ hybridization. Both CyCAP and cyclophilin C mRNAs were ubiquitously distributed in the neurons of the normal brain. Expression increased in neurons of the periinfarct zone up to 7 days after MCA occlusion. The neuronal distribution was confirmed by counterimmunostaining of NeuN. Both mRNAs were predominantly expressed in microglia of the ischemic core at 7 days, confirmed by immunostaining with the microglial marker, ED1. The quantification of CyCAP and cyclophilin C mRNAs at 7 days by Northern blot analysis showed the 8.5-fold increase (P<0.005, n=6) and 6.8-fold increase (P<0.005, n=6), respectively, in ischemic core compared with control. The coincidence of CyCAP and cyclophilin C expression in neurons and microglia suggests distinct roles in each cellular population. In particular, the early increase in penumbral neurons might be related to protection in periinfarct neurons.
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PMID:Cyclophilin C-associated protein and cyclophilin C mRNA are upregulated in penumbral neurons and microglia after focal cerebral ischemia. 1564 40


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