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)

CD105 (endoglin) is a receptor for transforming growth factor beta (TGFbeta). Although methods to measure soluble forms of TGFbeta and CD105 have been published, no assay is available to quantify the receptor-ligand complexes. We describe both an indirect enzyme-linked immunosorbent assay for the quantitation of soluble CD105-TGFbeta1 and the characterization of the complexes by immunoprecipitation and immunoblotting. Mab E9, specifically reactive with CD105, was utilised as the capture reagent in the ELISA system. Detection of complexes was achieved using chicken antibody against TGFbeta1 and the subsequent detection of bound antibody demonstrated by the addition of anti-species antiserum conjugated to horseradish peroxidase (HRP). By using enhanced chemiluminescence and optimised antibodies, the assay was made sufficiently sensitive and reproducible to detect low levels of circulating complexes. Whether the assay had any practical applications was evaluated in breast cancer patients. Plasma levels of CD105-TGFbeta1 were significantly elevated in 59 patients with breast cancer compared to 52 age matched normal women (p < 0.001). Immunoprecipitation using a rabbit anti-CD105 antibody, which reacts with both dimeric and monomeric CD105, and immunoblotting showed that three molecular forms of CD105-TGFbeta1 complexes > 200, 195, and 125 kDa existed in the plasma. We believe these represent the oligomer, dimer and probably the protease degraded form of CD105 complexed to TGFbeta1. The resistance to hypertonic solution, SDS and heat treatment suggested that the soluble CD105-TGFbeta1 complex may be linked by covalent bonds. The measurement of CD105-TGFbeta complexes in the circulation may have important clinical applications not only in cancer but also in patients with other angiogenic diseases such as rheumatoid arthritis, myocardial infarction and stroke.
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PMID:Immunodetection and characterisation of soluble CD105-TGFbeta complexes. 981 25

In order to maintain and improve mental health of elderly people living in the community, a cross sectional survey was conducted to elucidate their happiness and background factors. The subjects were elderly persons living in the community who were able to fill in the questionnaire themselves. The study employed the self-recording questionnaire forms used in Kahoku Longitudinal Aging Study by Matsubayashi et al. Happiness was assessed using a visual analogue scale. Out of 2,379 elderly persons who were able to fill in the questionnaire by themselves in 2,361 (99.2%) returned the questionnaire sheets. After removing inadequate responses, analysis was possible for 1,873 (78.7%) (860 men (average age 72.7 years) and 1,013 women (average age 72.8 years). Among those with greater happiness, the ratio of those living with others (p = 0.0051) was high as well as those with spouses (p = 0.0240), without a history of hypertension (p = 0.0096) and apoplexy (p = 0.0039), not receiving medication regularly (p = 0.0039), with regular habit of walking (p < 0.001), or with work (p < 0.001). As for the relationship between happiness and various scores, the higher the happiness scale became, the scores for ADL, information-related function, functional and emotional support network, healthy condition, appetite condition, sleep condition, memory condition, family relationships, friendship, economic condition became significantly higher (p < 0.001, respectively). On multiple regression analysis using the background factors for happiness as explanatory variables, factors such as functional support network (p < 0.001), emotional support network (p = 0.0254), healthy condition (p < 0.001), good memory condition (p = 0.0027), friendship (p < 0.001), good economic condition (p < 0.001) were significant independent contributing factors. As for the relation between SDS and happiness, the more serious the SDS score (higher score) became, the scores for the feeling of happiness became significantly smaller (p < 0.001). For amelioration of the happiness of elderly persons living in the community, attempts should be made to improve the background factors clarified by the present study by efficiently utilizing health, medical and welfare services.
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PMID:[Happiness and background factors in community-dwelling older persons]. 1068 97

Information is lacking regarding dynamic platelet accumulation at the site of the occluded middle cerebral artery (MCA) and the relationship between platelet aggregation in downstream cerebral microvessels and loss of perfusion and vascular integrity of these microvessels. In the present study, we employed a model of embolic MCA occlusion in the rat to simultaneously measure temporal and spatial profiles of platelet accumulation at the site of the embolus occluding the MCA and within downstream cerebral microvessels. We also measured the integrity of microvessels and matrix metalloproteinase (MMP) activity in ischemic brain. Rats (n=36) were subjected to embolic MCA occlusion. Immunohistochemistry was used to detect microvascular integrity, plasminogen activator inhibitor 1 (PAI-1) and the deposition of fibrin. SDS-PAGE zymography was used to measure MMP2 and MMP9 activities. Accumulation of platelets and increases in PAI-1 immunoreactivity at the site of the embolus occluding the MCA were detected 1 h (n=7) and 4 h (n=7) after ischemia, respectively, and numbers of GPIIb/IIIa immunoreactive downstream cerebral microvessels increased significantly (209+/-59; n=7; P<0.05) 4 h after ischemia, suggesting dynamic platelet aggregation. A significant (n=7; P<0.01) diffuse loss of type IV collagen immunoreactivity in microvessels was temporally associated with platelet GPIIb/IIIa immunoreactivity within the vessels. Triple immunostaining revealed that microvessels containing platelet aggregates exhibited loss of type IV collagen immunoreactivity and both intra- and extra-vascular fibrin deposition, suggesting that intravascular platelet aggregation is associated with decreases in the integrity of the microvascular basal lamina and blood-brain barrier leakage. A significant increase (P<0.05) in MMP9 was detected at 4 h (n=3) and 24 h (n=3) after ischemia but levels of MMP2 were not significantly changed in ischemic brain. Our data suggest that dynamic platelet aggregation in ischemic brain may contribute to time-dependent resistance to fibrinolysis. In addition, platelet deposition and increased MMP9 coincided with degradation of type IV collagen and loss of vascular integrity. These data suggest an important role for post-occlusive distal platelet deposition in the pathophysiology of stroke.
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PMID:Dynamic platelet accumulation at the site of the occluded middle cerebral artery and in downstream microvessels is associated with loss of microvascular integrity after embolic middle cerebral artery occlusion. 1153 35

To determine the activity of matrix metalloproteinases (MMP), especially MMP-2 and MMP-9, which play an important role in ischemic stroke and intracerebral hemorrhage, we adapted a simple and rapid method for localizing gelatinase activity to a gelatin film in situ-overlay technique previously used in cancer research. Ten micrometer cryosections of rat brain from controls and animals subjected to 3 h of ischemia and 48 h of reperfusion (suture model for transient cerebral ischemia) were used. After thawing, a gelatin film with a polyester base was put on the slide, incubated for 24 h at 37 degrees C, stained with Ponceau S, and then discolored in bi-distilled water. Non-staining areas on the film corresponded to lysis zones, caused by activated MMPs. This was proven by MMP incubation at various concentrations on the plain gelatin film and pretreatment with EDTA (an MMP inhibitor), which prevents lysis zones in normal and ischemic brains. As confirmatory tests, SDS-PAGE zymography was used to define MMP activity, and also MMP-2 immunohistochemistry to detect the possibly cellular origin of MMPs. Normal rat brain exhibited a low background activity, which was visible as a light halo-like lysis zone over and around the brain. Areas in normal brain with medium MMP activity were within the white matter (corpus callosum, anterior commissure, and cerebellum). Ischemic brain exhibited high activity lysis zones within the infarcted area (detected by microtubuli associated protein-2 staining). These zones consisted of microscopically small lysis holes with a diameter of about 10-20 microm. Immunohistochemistry showed that especially microvessels expressed MMP antigen. SDS-PAGE zymography differentiated between a high level of activated MMPs in the ischemic area and a low level in the non-ischemic basal ganglia. The gelatin film in situ-overlay technique is able to localize MMP activity in ischemic rat brain tissue on a microscopic level.
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PMID:A gelatin in situ-overlay technique localizes brain matrix metalloproteinase activity in experimental focal cerebral ischemia. 1204 62

Inherited amino acid substitutions at position 21, 22, or 23 of amyloid beta (Abeta) lead to presenile dementia or stroke. Insulin-degrading enzyme (IDE) can hydrolyze Abeta wild type, yet whether IDE is capable of degrading Abeta bearing pathogenic substitutions is not known. We studied the degradation of all of the published Abeta genetic variants by recombinant rat IDE (rIDE). Monomeric Abeta wild type, Flemish (A21G), Italian (E22K), and Iowa (D23N) variants were readily degraded by rIDE with a similar efficiency. However, proteolysis of Abeta Dutch (E22Q) and Arctic (E22G) was significantly lower as compared with Abeta wild type and the rest of the mutant peptides. In the case of Abeta Dutch, inefficient proteolysis was related to a high content of beta structure as assessed by circular dichroism. All of the Abeta variants were cleaved at Glu3-Phe4 and Phe4-Arg5 in addition to the previously described major sites within positions 13-15 and 18-21. SDS-stable Abeta dimers were highly resistant to proteolysis by rIDE regardless of the variant, suggesting that IDE recognizes a conformation that is available for interaction only in monomeric Abeta. These results raise the possibility that upregulation of IDE may promote the clearance of soluble Abeta in hereditary forms of Abeta diseases.
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PMID:Differential degradation of amyloid beta genetic variants associated with hereditary dementia or stroke by insulin-degrading enzyme. 1269 13

We evaluated the expression of two extra-cellular protease systems in a model of spontaneous cerebrovascular pathology: spontaneously hypertensive stroke-prone rats (SHRSP). The appearance of brain damage in individual animals was imaged and followed by means of magnetic resonance imaging (MRI). In situ zymography of brain slices obtained 3 days after the appearance of brain damage showed an increase in plasminogen activator (PA)/plasmin activity that co-localised with the cerebral damage detected by MRI; there was also concomitant accumulation/activation of inflammatory cells in the damaged area. Proteolytic activity was inhibited by the urokinase-specific inhibitor amiloride but not by an antibody against tissue-type plasminogen activator (t-PA). SDS-PAGE zymography of brain extracts revealed the presence of 58 kDa plasminogen-dependent lysis areas in the ischemic and non-ischemic tissues, and a 33 kDa lysis area in ischemic tissue only. An antibody against t-PA inhibited the former, whereas the latter was inhibited by amiloride. The specific induction of urokinase-type plasminogen activator (u-PA) in the damaged tissue was further confirmed by the fact that both u-PA protein mass and mRNA were markedly increased in the damaged cerebral areas. Concomitant metalloproteinase-2 (MMP-2) activation was only observed in the damaged area. These data suggest that u-PA is expressed and selectively catalyses proteolysis in the injured area of spontaneous brain damage in SHRSP.
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PMID:Endogenous proteolytic activity in a rat model of spontaneous cerebral stroke. 1274 36

(3S)-(+)-(5-Chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indole-2-one) (MaxiPost, BMS-204352) is a potent and specific opener for maxi-K channels and has potential to prevent and treat ischemic stroke. Following single intravenous doses of [14C]BMS-204352 to rats, only 10 to 12% of radioactivity was extractable from plasma with organic solvents. The unextractable radioactivity remained associated with the proteins (mostly albumin) after SDS-polyacrylamide gel electrophoresis or dialysis. Following acid hydrolysis in 6 M HCl for 24 h at 110 degrees C from plasma proteins collected from nine rats dosed with [14C]BMS-204352, one major radioactive product was isolated and identified as a lysine-adduct of des-fluoro des-O-methyl BMS-204352 by liquid chromatography/mass spectrometry and NMR analyses as well as by comparison with the synthetic analog, lysine-adduct of des-fluoro BMS-204352 (BMS-349821). The covalent binding of BMS-204352 results from the displacement of the ring-fluorine atom of des-O-methyl BMS-204352 with the epsilon-amino group of a lysine residue. Microsomal incubations of [14C]BMS-204352 resulted in low levels of covalent binding of radioactivity to proteins. This in vitro covalent binding required cytochrome P450-reductase cofactor NADPH and was attenuated by glutathione. P4503A inhibitors ketoconazole and troleadomycin selectively prevented the covalent binding in vitro. Based on these observations, a two-step bioactivation process for the protein covalent binding of BMS-204352 was postulated: 1) P4503A-mediated O-demethylation leading to spontaneous release of HF and the formation of an ortho-quinone methide reactive metabolite and 2) nucleophilic addition of the epsilon-amino group of protein lysine residue(s) in protein to form des-fluoro des-O-methyl BMS-204352 lysine adduct.
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PMID:Protein covalent binding of maxipost through a cytochrome P450-mediated ortho-quinone methide intermediate in rats. 1281 59

The study aimed at determination of circulating immune complexes (CIC) levels in a serum of patients with ischemic and hemorrhagic strokes, isolation of the complexes and their antigen composition identification. Spectrophotometric assay, polyethylene glycol precipitation and SDS PAG electrophoresis were used. Comparing to controls, significantly elevated levels of both small and big CIC were detected in the serum of the patients with ischemic stroke, while in the patients with hemorrhage stroke only the level of small CIC was elevated. The antigen CIC composition was specific for each stroke form and for control group either. Being compared to literature data, the results obtained revealed a specificity of the antigen CIC composition in ischemic and hemorrhagic strokes.
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PMID:[Circulating immune complexes in ischemic and hemorrhagic strokes]. 1283 May 18

The blood-feeding behaviour of nymphs and adults of Triatoma brasiliensis fed on the forearm of human volunteers was studied by electronic monitoring of the cibarial pump. Parameters of total contact time (TT), initial weight (IW), weight gain (WG), ingestion rate (IR), pump frequency (F), quantity of liquid ingested per cibarial pump stroke (QLC) and non-ingestive time (NIT) (cumulative probing time and pumping interruptions during blood feeding) were measured. Protein profile (SDS-PAGE) and quantity of proteins of salivary gland extracts (QP) were also determined for each stage. The TT reflects the feeding performance of the insects and differed between instars, varying between 18.3+/-2.5 min for the first instar and 33.9+/-2.3 min for the fifth instar. The observed increase in the IR when comparing different instars was related to the increase in the cibarial pump volume inferred from the QLC data. During development, the volume of the cibarial pump grew asymmetrically determining the different contact times observed among the instars. Males and females presented a remarkable sexual dimorphism in respect to the volume of the cibarial pump, females showing a better performance compared to males. Despite the differences, the results show that each of the development stages of T. brasiliensis was able to obtain a relatively fast bloodmeal, with few interruptions and without causing pain, providing further evidence of the capacity of this species to adapt to domestic environments.
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PMID:Blood-feeding performance of nymphs and adults of Triatoma brasiliensis on human hosts. 1287 30

Concentrations of stimulating (glutamate, aspartate) and inhibitory (GAMK, glycin) amino acids were measured in cerebrospinal liquid of 67 patients with ischemic stroke. The condition of stress-realising and stress-limiting systems (SRS and SLS) was assessed by dynamics of stimulating and inhibitory amino acids. High and rapidly increasing concentration of glutamate within the first 24 h of the disease predicts a poor prognosis. Early rise of GAMK concentration is a favourable and reliable prognostic sign. Hyperactivation of glutamatergic system and deficiency of inhibitory GAMK-ergic system cause imbalance between mediators and metabolites of SRS and SLS. The severity and duration of this imbalance determine severity of clinical symptoms and outcome of the disease.
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PMID:[Correlation between some stress-realizing and stress-limiting systems in an acute period of ischemic stroke]. 1556 96


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