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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interpretation of results for CA 15.3, carcinoembryonic antigen (CEA), and tissue polypeptide antigen (TPA) during breast cancer monitoring requires data on intra- (CVP) and inter- (CVG) individual biological variation, analytical imprecision (CVA), and indices of individuality. The average CVP and CVG obtained from 22 healthy women were, respectively, 6.2% and 62.9% (CA 15.3), 9.3% and 86.8% (CEA), and 28.3% and 133% (TPA). The indices of individuality were all < 0.6: 0.2 (CA 15.3), 0.15 (CEA), and 0.2 (TPA). CVA depended on the concentration of the analytes. CVP and CVA determine what constitutes a significant difference between sequential results. Assuming a CVA of 11.2% (CA 15.3), 9.5% (CEA), or 11.9% (TPA), results must differ by 30%, 31%, or 72%, respectively, for P < or = 0.05. We found that CVP and CVA contribute considerably to the variation during breast cancer monitoring. Consequently, both CVP and CVA should be considered in criteria for marker evaluation. Because of low indices of individuality, conventional cutoff limits are inappropriate both for initial identification and for follow-up of breast cancer.
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PMID:Interpretation of results for tumor markers on the basis of analytical imprecision and biological variation. 840 93

The prototypical integrin receptor, alpha IIb beta 3, isolated from the membrane fraction of human blood platelets by solubilization in Triton X-100 (reduced) and affinity chromatography on lentil lectin-agarose, has been further purified by gel filtration chromatography in octyl glucoside to obtain the intact receptor complex in a form suitable for hydrodynamic measurements. The molecular weight [(6.0 +/- 0.2) x 10(3)] and Stokes radius (2.3 +/- 0.1 nm) of detergent micelles formed in 0.03 M octyl glucoside have been determined by classical light scattering intensity and dynamic light scattering measurements, respectively. An algorithm has been developed which explicitly considers the contribution of detergent micelles to the intensity autocorrelation function of particles suspended in detergent. This procedure has been validated with polystyrene particles of known radius, as well as with the soluble protein fibrinogen. Application of these procedures to dynamic light scattering data obtained with alpha IIb beta 3 resulted in a translational diffusion coefficient (Dto(20,w)) of (2.78 +/- 0.31) x 10(-7) cm2 s-1, corresponding to a Strokes radius (Rs) of 7.67 +/- 0.85 nm for the integrin/octyl glucoside complex. Light scattering intensity measurements gave a molecular weight of (2.26 +/- 0.22) x 10(5) for the polypeptide moiety of the complex, in excellent agreement with the 2.28 x 10(5) value calculated from primary structure data. As a spherical, hydrated alpha IIb beta 3 complex, with bound detergent, would exhibit a Stokes radius of approximately 5 nm, these data indicate considerable asymmetry in the solution conformation of alpha IIb beta 3.
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PMID:Dynamic light scattering studies of alpha IIb beta 3 solution conformation. 847 5

1. This study was undertaken to determine whether the AT1 receptor directly contributes to hypertension-induced cardiac hypertrophy and gene expressions. 2. Stroke-prone spontaneously hypertensive rats (SHRSP) were given orally an AT1, receptor antagonist (losartan, 30 mg kg-1 day-1), an angiotensin converting enzyme inhibitor (enalapril 10 mg kg-1 day-1), a dihydropyridine calcium channel antagonist (amlodipine, 5 mg kg-1 day-1), or vehicle (control), for 8 weeks (from 16 to 24 weeks of age). The effects of each drug were compared on ventricular weight and mRNA levels for myocardial phenotype- and fibrosis-related genes. 3. Left ventricular hypertrophy of SHRSP was accompanied by the increase in mRNA levels for two foetal phenotypes of contractile proteins (skeletal alpha-actin and beta-myosin heavy chain (beta-MHC)), atrial natriuretic polypeptide (ANP), transforming growth factor-beta-1 (TGF-beta 1) and collagen, and a decrease in mRNA levels for an adult phenotype of contractile protein (alpha-MHC). Thus, the left ventricle of SHRSP was characterized by myocardial transition from an adult to a foetal phenotype and interstitial fibrosis at the molecular level. 4. Although losartan, enalapril and amlodipine lowered blood pressure of SHRSP to a comparable degree throughout the treatment, losartan caused regression of left ventricular hypertrophy of SHRSP to a greater extent than amlodipine (P < 0.01). 5. Losartan significantly decreased mRNA levels for skeletal alpha-actin, ANP, TGF-beta 1 and collagen types I, III and IV and increased alpha-MHC mRNA in the left ventricle of SHRSP. Amlodipine did not alter left ventricular ANP, alpha-MHC and collagen types I and IV mRNA levels of SHRSP. 6. The effects of enalapril on left ventricular hypertrophy and gene expressions of SHRSP were similar to those of losartan, except for the lack of inhibition of collagen type I expression by enalapril. 7. Unlike the hypertrophied left ventricle, there was no significant difference between losartan and amlodipine in the effects on non-hypertrophied right ventricular gene expressions of SHRSP. 8. Our results show that hypertension causes not only left ventricular hypertrophy but also molecular transition of myocardium to a foetal phenotype and interstitial fibrosis-related molecular changes. These hypertension-induced left ventricular molecular changes may be at least in part mediated by the direct action of local angiotensin II via the AT1, receptor.
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PMID:Effects of an AT1 receptor antagonist, an ACE inhibitor and a calcium channel antagonist on cardiac gene expressions in hypertensive rats. 876 77

Synthetic human brain natriuretic peptide (sBNP) is a polypeptide with the same amino acid sequence as the naturally occurring hormone. Preclinical studies have demonstrated that BNP has potent hemodynamic, diuretic, and natriuretic effects that might be beneficial in treating patients with heart failure. This study was a randomized, double-blind, placebo-controlled, ascending-dose trial of sBNP administered as a single intravenous bolus in 27 heart failure patients. Six groups of patients received sequentially increasing doses of sBNP (0.3, 1, 3, 10, 15, and 20 micrograms/kg, respectively) as a single intravenous injection, and hemodynamics were assessed by pulmonary artery monitoring catheter. The 10 and 15 micrograms/kg doses of sBNP resulted in significant reductions in pulmonary capillary wedge pressure (-73%, p < 0.001), mean pulmonary artery pressure (-41%, p < 0.001), mean arterial blood pressure (-28%, p = 0.001), and systemic vascular resistance (-53%, p = 0.004). Significant increases occurred in cardiac index (68%, p < 0.001) and stroke volume index (72%, p < 0.001). The magnitude and duration of hemodynamic changes were dose dependent. There were no adverse effects. sBNP injected as a single intravenous bolus in heart failure patients improves hemodynamics in a dose-related fashion. Further clinical investigations to determine the use of sBNP in decompensated heart failure are clearly warranted.
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PMID:Hemodynamic effects of a single intravenous injection of synthetic human brain natriuretic peptide in patients with heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. 888 62

Basic fibroblast growth factor is a biologically active polypeptide with mitogenic, angiogenic and neurotrophic properties. In the present study, the temporal and spatial expressions of basic fibroblast growth factor in stroke-prone spontaneously hypertensive rats were compared to two related strains of rat: spontaneously hypertensive rats and normotensive Wistar Kyoto rats. Higher levels of total RNA concentration were found in cerebral cortex of four-week-old stroke-prone rats compared to spontaneously hypertensive rats and Wistar Kyoto rats. Northern blot analysis showed no changes in levels of basic fibroblast growth factor messenger RNA with increasing age in cerebral cortex of Wistar Kyoto and spontaneously hypertensive rats. However, significant increases were found in 26- and 38-week-old stroke-prone rats compared to four-week-old stroke-prone rats. Although messenger RNA increases were also found in subcortical and cerebellar regions, a significant difference in levels of basic fibroblast growth factor messenger RNA was observed only in cerebral cortices among these three strains. This age-related increase in basic fibroblast growth factor messenger RNA correlated with the increase incidence of stroke in stroke-prone rats. Immunohistochemical study further revealed a dramatic increase in levels of basic fibroblast growth factor immunoreactivity in cerebral cortex of 30-week-old stroke-prone rats as compared to young stroke-prone rats, as well as age-matched Wistar Kyoto and spontaneously hypertensive rats. This increase in basic fibroblast growth factor immunoreactivity therefore appears very specific to aged stroke-prone rats. However, immunoreactivity decreased once severe tissue damages were observed in the cerebral cortex. Basic fibroblast growth factor-positive cells were diffusely expressed in cerebral cortex; double staining with glial fibrillary acidic protein showed the majority of these basic fibroblast growth factor-positive cells to be astrocytes. In summary, although young stroke-prone spontaneously hypertensive rats showed significantly higher RNA concentration, significant increases in levels of basic fibroblast growth factor, including both messenger RNA and protein expression, were observed in aged stroke-prone rats with a high incidence of stroke. These findings suggest the possibility that basic fibroblast growth factor may play a role in the developmental sequelae of cerebral lesions in stroke-prone spontaneously hypertensive rats.
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PMID:Elevated basic fibroblast growth factor levels in stroke-prone spontaneously hypertensive rats. 901 38

Basic fibroblast growth factor (bFGF) is a heparin-binding polypeptide with potent trophic and protective effects on brain neurons, glia and endothelia. In previous studies, we showed that intravenously administered bFGF reduced the volume of cerebral infarcts following permanent occlusion of the middle cerebral artery in rats. In the current study, we examined the time dependence of bFGF infusion on infarct reduction, and the effect of co-infusion of bFGF with heparin. We found a significant reduction in infarct volume when the bFGF infusion (50 microg/kg per h for 3 h) was begun up to 3 h, but not 4 h after the onset of ischemia. The infarct reducing effects of bFGF were not altered by co-infusion of heparin. These results are potentially important in light of the ongoing clinical trials of intravenous bFGF in acute stroke.
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PMID:Time window of infarct reduction by intravenous basic fibroblast growth factor in focal cerebral ischemia. 918 30

Focal cerebral infarction (stroke) due to unilateral occlusion of the middle cerebral artery in mature rats produces deficits in sensorimotor function of the contralateral limbs that recover partially over time. We found that biweekly intracisternal injection of basic fibroblast growth factor (bFGF; 0.5 microg/injection), a potent neurotrophic polypeptide, markedly enhanced recovery of sensorimotor function of the contralateral limbs during the first month after stroke without apparent adverse side effects. Immunostaining for growth-associated protein 43 (GAP-43), a molecular marker of axonal sprouting, showed a selective increase in GAP-43 immunoreactivity in the intact sensorimotor cortex contralateral to cerebral infarcts following bFGF treatment. These results show that bFGF treatment can enhance functional recovery after stroke, and that the mechanism may include stimulation of neuronal sprouting in the intact brain.
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PMID:Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction. 922 35

We report a novel G13513A mutation in the mitochondrial ND5 gene in a patient who had morphologically and biochemically abnormal muscle mitochondria and died at age 45 with a diagnosis of MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). The mutation affects an evolutionarily conserved nucleotide and was heteroplasmic in muscle, leukocytes, and several autopsy tissues, including brain. The mutation was less abundant (<5%) in leukocytes from an asymptomatic sister and was not found in over 100 controls, thus satisfying accepted criteria for pathogenicity. Our report reinforces the concept of genetic heterogeneity in MELAS and confirms that MELAS can be due to mutations in polypeptide-coding mtDNA genes.
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PMID:Identification of a novel mutation in the mtDNA ND5 gene associated with MELAS. 929 5

The pharmacologic management of hemostasis in patients undergoing cardiopulmonary bypass may be accompanied by adverse responses. Evaluating the safety profile of hemostatic agents (eg, lysine analogs, aprotinin, protamine, or even donor blood) should be done objectively. Subsequent to early anecdotal reports, the safety profile of aprotinin, a broad-spectrum serine protease inhibitor, has been thoroughly evaluated in multiple double-blind, placebo-controlled, multicenter studies. Although associated with decreased fibrinolysis, aprotinin has not been associated with an increased risk of post-cardiopulmonary bypass myocardial infarction, graft closure, stroke, or increased risk of renal dysfunction from US studies. As with any polypeptide, there is a risk of anaphylaxis, which is influenced not only by prior exposure but also by time since prior exposure. In a similar fashion, after early anecdotal reports, evaluations involving large numbers of patients have helped define adverse reactions to protamine. Adverse reactions to blood products also must be considered in any safety comparisons involving hemostatic agents.
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PMID:Hemostatic agents and their safety. 1046 43

Fibroblast growth factors (FGFs) are being investigated in human clinical trials as treatments for angina, claudication, and stroke. We designed a molecule structurally unrelated to all FGFs, which potently mimicked basic FGF activity, by combining domains that (1) bind FGF receptors (2) bind heparin, and (3) mediate dimerization. A 26-residue peptide identified by phage display specifically bound FGF receptor (FGFR) 1c extracellular domain but had no homology with FGFs. When fused with the c-jun leucine zipper domain, which binds heparin and forms homodimers, the polypeptide specifically reproduced the mitogenic and morphogenic activities of basic FGF with similar potency (EC50 = 240 pM). The polypeptide required interaction with heparin for activity, demonstrating the importance of heparin for FGFR activation even with designed ligands structurally unrelated to FGF. Our results demonstrate the feasibility of engineering potent artificial agonists for the receptor tyrosine kinases, and have important implications for the design of nonpeptidic ligands for FGF receptors. Furthermore, artificial FGFR agonists may be useful alternatives to FGF in the treatment of ischemic vascular disease.
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PMID:Semirational design of a potent, artificial agonist of fibroblast growth factor receptors. 1058 18


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