Blood Protein

Source: www.ncbi.nlm.nih.gov --- 1 day ago
Endothelial Protein C receptor-assisted transport of activated Protein C across the mouse Blood-brain barrier. J Cereb Blood Flow Metab. 2008 Oct 8; Authors: Deane R, Larue B, Sagare AP, Castellino FJ, Zhong Z, Zlokovic BV Activated Protein C (APC), a serine-protease with anticoagulant, anti-inflammatory, and cytoprotective activities, is neuroprotective and holds potential to treat different neurologic disorders. It is unknown whether APC crosses the Blood-brain barrier (BBB) to reach its therapeutic targets in the brain. By using a brain vascular perfusion technique, we show that (125)I-labeled plasma-derived mouse APC enters the brain from cerebrovascular circulation by a concentration-dependent mechanism. The permeability surface area product of (125)I-APC (0.1 nmol/L) in different forebrain regions ranged from 3.11 to 4.13 muL/min/g brain. This was approximately 80- to 110-fold greater than for (14)C-inulin, a simultaneously infused reference tracer. The K(m) value for APC BBB cortical transport was 1.6+/-0.2 nmol/L. Recombinant APC variants with reduced anticoagulant activity, 5A-APC and 3K3A-APC, but not Protein C, exhibited high affinity for the APC BBB transport system. Blockade of APC-binding site on endothelial Protein C receptor (EPCR), but not blockade of its protease-activated receptor-1 (PAR1) catalytic site, inhibited by >85% APC entry into the brain. APC brain uptake was reduced by 64% in severely deficient EPCR mice, ...

Source: www.ncbi.nlm.nih.gov --- 6 days ago
Related Articles Functional alteration of red Blood cells by a Mega-Dalton Protein of Plasmodium falciparum. Blood. 2008 Oct 2; Authors: Glenister FK, Fernandez KM, Kats LM, Hanssen E, Mohandas N, Coppel RL, Cooke BM Proteins exported from Plasmodium falciparum parasites into red Blood cells (RBCs) interact with the membrane skeleton and contribute to the pathogenesis of malaria. Specifically, exported proteins increase RBC membrane rigidity, decrease deformability and increase adhesiveness, culminating in intravascular sequestration of infected RBCs (iRBCs). Pf332 is the largest (> 1 MDa) known malaria Protein exported to the RBC membrane but its function has not previously been determined. To determine the role of Pf332 in iRBCs, we have engineered and analysed transgenic parasites with Pf332 either deleted or truncated. When compared to RBCs infected with wild-type parasites, mutants lacking Pf332 were consistently more rigid, significantly less adhesive to CD36 and showed decreased expression of the major cytoadherence ligand, PfEMP1, on the iRBC surface. These abnormalities were associated with quantitative and dramatic morphological changes in Maurer's clefts (MCs); membrane structures that transport malaria proteins to the RBC membrane. In contrast, RBCs infected with parasites expressing truncated forms of Pf332, while still hyper-rigid, showed a normal adhesion profile and morphologically-normal MCs. Our results suggest that ...

Source: www.ncbi.nlm.nih.gov --- 16 days ago
Related Articles Blood substrates and hormonal responses to increased egg white Protein intake prior to a 12,000 m run in heat. J Nutr Sci Vitaminol (Tokyo). 2008 Apr;54(2):154-62 Authors: Mekata Y, Hayashi N, Masuda Y, Kashimura O, Arai S, Kawano Y This study was undertaken to investigate the effects of isoenergetic and increased amounts of egg white Protein one hour before a run on the changes in the post-exercise Blood biochemistry and the rating of the perceived exertion (RPE). Twenty-four male distance runners were divided into four groups. Venous Blood samples were collected at three time points: just before the experiment (Pre), just after a 12,000 m run (Post 0 h) and one hour after the run (Post 1 h). After the first Blood sampling, each participant consumed one of the four isoenergetic supplements (86 kcal); 0 g, 5 g, 10 g, or 20 g of egg white Protein. The Blood glucose, free amino acid, and branched chain amino acid (BCAA) levels in the 0 g, 5 g, and 10 g Protein groups were higher at Post 0 h than at Pre. The pre-exercise intake of the 20 g Protein group showed the smallest changes in the Blood biochemicals. The RPE scores were significantly higher at Post 0 h, and did not vary among the four Protein groups. Accordingly, the pre-exercise carbohydrate intakes significantly altered the post-exercise Blood biochemisty findings, but the pre-exercise Protein intake did not. Furthermore, the changes in the RPE scores in our pre ...

Source: www.sciencedaily.com --- 18 days ago
Using atomic force microscopy -- a microscope with very high resolution -- and isolating Blood vessels outside the body, researchers have identified a Protein that plays an important role in the control of tissue Blood flow and vascular resistance. This new knowledge brings researchers one step closer to understanding vascular diseases, such as high Blood pressure, diabetes and other vascular problems. ...

Source: pubs.acs.org --- 17 days ago
Hana Vaisocherová, Wei Yang, Zheng Zhang, Zhiqiang Cao, Gang Cheng, Marek Piliarik, Jiřı́ Homola, and Shaoyi Jiang Web Release Date: Tue, 23 Sep 2008 00:00:00 EDT (Small Correspondence) DOI: 10.1021/ac8015888 ...

Source: www.virtualmedicalcentre.com --- 37 days ago
Researchers have identified a Protein called Flil that is required for the development of Blood and Blood vessels. Using frog and zebrafish embryos to study the effect of the Protein on developing cel ...

Source: www.labnews.com --- 30 days ago
The U.S. Patent and Trademark Office granted Banyan Biomarkers Inc. a patent for "Neural Proteins as Biomarkers for Traumatic Brain Injury," which were licensed from the University of Florida.Specifically, the patent covers the detection of certain neuronal Protein markers found in the ... ...

Source: www.nih.gov --- 2 hours ago
National Institutes of Health (NIH) scientists have identified a Protein that plays matchmaker between two key types of white Blood cells, T and B cells, enabling them to interact in a way that is crucial to establishing long-lasting immunity after an infection. ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles Effects of ginkgo biloba extract EGb761 on expression of RAGE and LRP-1 in cerebral microvascular endothelial cells under chronic hypoxia and hypoglycemia. Acta Neuropathol. 2008 Oct 1; Authors: Yan FL, Zheng Y, Zhao FD Alzheimer's disease (AD), characterized by accumulation of amyloid-beta Protein (Abeta) in brain parenchyma, is closely associated with brain ischemia. Decreased clearance of Abeta from brain is the main cause of Abeta accumulation in sporadic AD. However, the mechanisms underlying ischemia-mediated AD pathogenesis remain unclear. The receptor for advanced end glycation products (RAGE) and low-density lipoprotein receptor-related Protein-1 (LRP-1) expressed at Blood brain barrier (BBB) are actively involved in Abeta clearance. RAGE is thought to be a primary transporter of Abeta across BBB into the brain from the systemic circulation, while LRP-1 mediates the transport of Abeta out of the brain. Ginkgo biloba extract EGb761, a traditional Chinese medicine, has been widely used in the treatment of AD. To investigate the effects of EGb761 on the expression of RAGE and LRP-1 in endothelial cells in response to ischemic injury, we cultured bEnd.3 cells, an immortalized mouse cerebral microvessel endothelial cell line, under a chronic hypoxic and hypoglycemic condition (CHH) to mimic ischemic injury of BBB, and then treated with EGb 761. We found that EGb 761 markedly ameliorated the damage (evaluated by MT ...

Source: www.ncbi.nlm.nih.gov --- 6 days ago
Related Articles Endothelial progenitor cell homing: prominent role of the IGF2-IGF2R-PLC{beta}2 axis. Blood. 2008 Oct 2; Authors: Maeng YS, Choi HJ, Kwon JY, Park YW, Choi KS, Min JK, Kim YH, Suh PG, Kang KS, Won MH, Kim YM, Kwon YG Homing of endothelial progenitor cells (EPCs) to the neovascular zone is now considered to be an essential step in the formation of vascular networks during embryonic development and also for neovascularization in postnatal life. We report here the prominent role of the insulin-like growth factor 2 (IGF2)/IGF2 receptor (IGF2R) system in promoting EPC homing. With high-level expression of IGF2R in EPCs, IGF2-induced hypoxic conditions stimulated multiple steps of EPC homing in vitro and promoted both EPC recruitment and incorporation into the neovascular area, resulting in enhanced angiogenesis in vivo. Remarkably, all IGF2 actions were exerted predominantly through IGF2R-linked G(i) Protein signaling and required intracellular Ca(2+) mobilization induced by the beta2 isoform of phospholipase C. Together, these findings indicate that locally generated IGF2 at either ischemic or tumor sites may contribute to postnatal vasculogenesis by augmenting the recruitment of EPCs. The utilization of the IGF2/IGF2R system may therefore be useful for the development of novel means to treat angiogenesis-dependent diseases. PMID: 18832656 [PubMed - as supplied by publisher] ...

Source: www.ncbi.nlm.nih.gov --- 8 days ago
Related Articles Induction of the Wnt antagonist, Dickkopf-1, contributes to the development of neuronal death in models of brain focal ischemia. J Cereb Blood Flow Metab. 2008 Oct 1; Authors: Mastroiacovo F, Busceti CL, Biagioni F, Moyanova SG, Meisler MH, Battaglia G, Caricasole A, Bruno V, Nicoletti F Inhibition of the canonical Wnt pathway has been implicated in the pathophysiology of neuronal death. Here, we report that the secreted Wnt antagonist, Dickkopf-1 (Dkk-1) is rapidly induced in neurons after induction of focal brain ischemia. In rats undergoing transient focal ischemia in response to brain infusion of endothelin-1, Dkk-1 was induced in neurons of the ischemic core and the penumbra region. Induction of Dkk-1 was associated with a reduced expression of beta-catenin (a downstream signaling molecule of the canonical Wnt pathway), and was not observed in neurons expressing the protective Protein, heat shock Protein-70. Treatment with lithium ions, which, inter alia, rescue the canonical Wnt pathway, was highly protective against ischemic damage. Dkk-1 was also induced in cortical neurons of mice undergoing permanent middle cerebral artery (MCA) occlusion. This model allowed us to compare wild-type mice with doubleridge mice, which are characterized by a reduced expression of Dkk-1. Doubleridge mice showed an attenuated reduction of beta-catenin and a reduced infarct volume in response to MCA occlusion, providing a direct de ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles Blood-brain barrier changes and cell invasion differ between therapeutic immune clearance of neurotrophic virus and CNS autoimmunity. Proc Natl Acad Sci U S A. 2008 Sep 30; Authors: Fabis MJ, Phares TW, Kean RB, Koprowski H, Hooper DC CNS tissues are protected from circulating cells and factors by the Blood-brain barrier (BBB), a specialization of the neurovasculature. Outcomes of the loss of BBB integrity and cell infiltration into CNS tissues can differ vastly. For example, elevated BBB permeability is closely associated with the development of neurological disease in experimental allergic encephalomyelitis (EAE) but not during clearance of the attenuated rabies virus CVS-F3 from the CNS tissues. To probe whether differences in the nature of BBB permeability changes may contribute to the pathogenesis of acute neuroinflammatory disease, we compared the characteristics of BBB permeability changes in mice with EAE and in mice clearing CVS-F3. BBB permeability changes are largely restricted to the cerebellum and spinal cord in both models but differ in the extent of leakage of markers of different size and in the nature of cell accumulation in the CNS tissues. The accumulation in the CNS tissues of CD4 T cells expressing mRNAs specific for IFN-gamma and IL-17 is common to both, but iNOS-positive cells invade into the CNS parenchyma only in EAE. Mice that have been immunized with myelin basic Protein (MBP) and infected e ...

Source: www.ncbi.nlm.nih.gov --- 2 days ago
Related Articles Correlates of C-reactive Protein levels in young adults: a population-based cohort study of 3827 subjects in Brazil. Braz J Med Biol Res. 2008 May;41(5):357-67 Authors: Nazmi A, Oliveira IO, Victora CG The socio-demographic, behavioral and anthropometric correlates of C-reactive Protein levels were examined in a representative young adult Brazilian population. The 1982 Pelotas Birth Cohort Study (Brazil) recruited over 99% of births in the city of Pelotas that year (N = 5914). Individuals belonging to the cohort have been prospectively followed up. In 2004-2005, 77.4% of the cohort was traced, members were interviewed and 3827 individuals donated Blood. Analyses of the outcome were based on a conceptual model that differentiated confounders from potential mediators. The following independent variables were studied in relation to levels of C-reactive Protein in sex-stratified analyses: skin color, age, family income, education, parity, body mass index, waist circumference, smoking, fat/fiber/alcohol intake, physical activity, and minor psychiatric disorder. Geometric mean (95% confidence interval) C-reactive Protein levels for the 1919 males and 1908 females were 0.89 (0.84-0.94) and 1.96 mg/L (1.85-2.09), respectively. Pregnant women and those using oral contraceptive therapies presented the highest C-reactive Protein levels and all sub-groups of women had higher levels than men (P < 0.001). Significant associations be ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles Tryptophan free diet delays healing of chronic gastric ulcers in rat. J Physiol Pharmacol. 2008 Aug;59 Suppl 2:53-65 Authors: Konturek PC, Burnat G, Brzozowski T, Zopf Y, Konturek SJ Melatonin (MT) is an ubiquitous molecule, representing one of the phylogenetically oldest signaling mechanisms. Our previous studies demonstrated that MT and its precursor L-tryptophan (L-Trp) show strong protective effect on gastric mucosa. The aim of the present study was: 1) to assess the effect of MT and L-Trp on healing of chronic gastric ulcer and accompanying changes in gastric mucosal Blood flow (GBF); 2) to study the effect of MT and L-Trp on expression of iNOS. cNOS and HSP70 in ulcerated mucosa; 3) to compare the effect of L-Trp free and L-Trp rich diet on ulcer healing and gene expression of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), superoxide dismutase (SOD), cyclooxygenase-2 (COX-2) and NFkappaB-p65 Protein expression in ulcer area and intact non-ulcerated. Chronic ulcers were induced in Wistar rats by Okabe's modification of acetic acid method. Rats with chronic gastric ulcers were divided in following treatment groups: 1) vehicle (saline); 2) MT (20mg/kg-d i.p.) and 3) L-Trp (100 mg/kg i.p.). The expression of iNOS, cNOS and HSP70 Protein was measured by Western blot. In separate experiments, the influence of commercially available (Bio-Serv, USA) L-Trp free diet (TFD) was compared to the L ...

Source: www.ncbi.nlm.nih.gov --- 8 days ago
Related Articles cIAP1-dependent TRAF2 degradation regulates the differentiation of monocytes into macrophages and their response to CD40-ligand. Blood. 2008 Sep 30; Authors: Dupoux A, Cartier J, Cathelin S, Filomenko R, Solary E, Dubrez-Daloz L Peripheral Blood monocytes are plastic cells that migrate to tissues and differentiate into various cell types including macrophages, dendritic cells and osteoclasts. We have described the migration of cIAP1 (Inhibitor of Apoptosis Protein 1), a member of IAP family of proteins, from the nucleus to the Golgi apparatus in monocytes undergoing differentiation into macrophages. Here, we show that, once in the cytoplasm, cIAP1 is involved in the degradation of the adaptor Protein TRAF2 by the proteosomal machinery. Inhibition of cIAP1 prevents the decrease in TRAF2 expression that characterizes macrophage formation. We demonstrate that TRAF2 is initially required for macrophage differentiation as its silencing prevents Ikappa-Balpha degradation, NFB-kappaB p65 nuclear translocation and the differentiation process. Then, we show that cIAP1 mediated degradation of TRAF2 allows the differentiation process to progress. This degradation is required for the macrophages to be fully functional as TRAF2 overexpression in differentiated cells decreases the c-Jun N-terminal kinase-mediated synthesis and the secretion of pro-inflammatory cytokines such as interleukin-8 and MCP-1 in response to CD40 ligand. We ...

Source: www.ncbi.nlm.nih.gov --- 6 days ago
Related Articles Human C/EBP{epsilon} activator and repressor isoforms differentially reprogram myeloid lineage commitment and differentiation. Blood. 2008 Oct 2; Authors: Bedi R, Du J, Sharma AK, Gomes I, Ackerman SJ CCAAT enhancer binding Protein epsilon (C/EBPepsilon) is required for the terminal differentiation of neutrophils and eosinophils. Human C/EBPepsilon is expressed as four isoforms (32, 30, 27 and 14kD) through differential RNA splicing, and alternative promoters and translational start sites. The C/EBPepsilon(32/30) isoforms are transcriptional activators, whereas C/EBPepsilon(27) interacts with and represses GATA-1 transactivation of eosinophil promoters. C/EBPepsilon(14) contains only DNA binding and dimerization domains, and may function as a dominant negative regulator. To define functional activities for these C/EBPepsilon isoforms in myelopoiesis, human CD34+ progenitors were transduced with IRES-eGFP retroviral vectors encoding the 32/30, 27 and 14kD isoforms, purified by FACS, and analyzed in colony-forming assays and suspension cultures. Progenitors transduced with C/EBPepsilon(32/30) default exclusively to eosinophil differentiation and gene expression, independent of IL-5, and regardless of inclusion of cytokines to induce other lineages. In contrast, the putative repressor C/EBPepsilon(27) isoform strongly inhibits eosinophil differentiation and gene expression, including GATA-1, promoting granulocyte (neutro ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles Regulating the angiogenic balance in tissues. Cell Cycle. 2008 Jul;7(13):2056-70 Authors: Pollina EA, Legesse-Miller A, Haley EM, Goodpaster T, Randolph-Habecker J, Coller HA A balance between angiogenesis inducers and inhibitors in the microenvironment controls the rate of new Blood vessel formation. We hypothesized that fibroblasts, an important cellular constituent of the tissue stroma, secrete molecules that contribute to this balance. We further hypothesized that fibroblasts secrete molecules that promote angiogenesis when they are in a proliferative state and molecules that inhibit angiogenesis when they are not actively cycling (quiescent). Microarray analysis revealed that angiogenesis inducers and inhibitors are regulated as fibroblasts transition into a quiescent state and reenter the cell cycle in response to changes in serum. To assess whether changes in transcript levels result in changes in the levels of secreted proteins, we collected conditioned medium from proliferating and quiescent fibroblasts and performed immunoblotting for selected proteins. Secreted Protein levels of the angiogenesis inhibitor pigment epithelium derived factor (PEDF) were higher in quiescent than proliferating fibroblasts. Conversely, proliferating fibroblasts secreted increased levels of the angiogenesis inducer vascular endothelial growth factor-C (VEGF-C). For the angiogenesis inhibitor thrombospondin-2, quiescent cells secre ...

Source: www.ncbi.nlm.nih.gov --- 9 days ago
Related Articles Recombinant tissue plasminogen activator in the treatment of pleural infections in adults. Respir Med. 2008 Sep 26; Authors: Froudarakis ME, Kouliatsis G, Steiropoulos P, Anevlavis S, Pataka A, Popidou M, Mikroulis D, Pneumatikos I, Bouros D BACKGROUND: Intrapleural recombinant tissue plasminogen activator (r-TPA) has been successfully evaluated in pediatric patients with complicated parapneumonic pleural effusion (CPE) and pleural empyema (PE). Yet, there is no data concerning r-TPA in adults with CPE/PE. The aim of our study was to investigate the efficacy and complications of r-TPA in adult patients with CPE/PE. METHODS: Twenty consecutive patients (mean age 50+/-18.9 years) with pleural infection (14 CPE and 6 PE) were included. Chest tube was inserted under guidance of chest ultrasound and/or computed tomography. After failure of pleural fluid drainage, 25mg of r-TPA was administered intrapleurally in a single daily dose. The evaluation was made according to imaging and clinical status. RESULTS: The mean volume of fluid increased significantly after r-TPA administration (p<0.0001). White Blood cells count (WBC) and C-reactive Protein (CRP) were significantly improved after r-TPA instillations (both p<0.0001). Significant clinical and imaging improvement was noted in all but one patient after r-TPA administration (overall p<0.0001). Complications observed were mild: pain in 4 (25%) and local bleeding in 3 (15%) pa ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles Elevated plasma adiponectin and decreased plasma homocysteine and asymmetric dimethylarginine in children with type 1 diabetes. Scand J Clin Lab Invest. 2008 Sep 30;:1-7 Authors: Heilman K, Zilmer M, Zilmer K, Kool P, Tillmann V Objective. Type 1 diabetes has a bad prognosis concerning the pathogenesis of cardiovascular diseases (CVD). The purpose of this study was to evaluate different possible new risk indices for CVD in children with type 1 diabetes. Material and methods . The present study included 30 children with diabetes (mean HbA1C 9.8%), aged between 4.7 and 18.6 years and with no clinical evidence of vascular complications, and 30 healthy subjects matched by sex, age and body mass index. Blood pressure was measured and Blood samples were obtained for lipid profile, creatinine, glucose, high sensitive C-reactive Protein (hsCRP), intercellular adhesion molecule-1 (ICAM-1), asymmetric dimethylarginine (ADMA), adiponectin and homocysteine. Results. Children with diabetes had significantly higher Blood pressure, plasma hsCRP, ICAM-1, adiponectin levels and lower homocysteine, ADMA concentrations than their control subjects. In multivariate regression analysis, the best predictors for systolic Blood pressure were diabetes group, plasma homocysteine concentration and BMI (Adj R(2) = 0.38, p<0.0001), and for diastolic Blood pressure diabetes group and triglycerides level (Adj R(2) = 0.27, p<0.0001). Conclusions . Chi ...

Source: www.ncbi.nlm.nih.gov --- 7 days ago
Related Articles AA-amyloidosis can be transferred by peripheral Blood monocytes. PLoS ONE. 2008;3(10):e3308 Authors: Sponarova J, Nyström SN, Westermark GT Spongiform encephalopathies have been reported to be transmitted by Blood transfusion even prior to the clinical onset. Experimental AA-amyloidosis shows similarities with prion disease and amyloid-containing organ-extracts can prime a recipient for the disease. In this systemic form of amyloidosis N-terminal fragments of the acute-phase reactant apolipoprotein serum amyloid A are the main amyloid Protein. Initial amyloid deposits appear in the perifollicular region of the spleen, followed by deposits in the liver. We used the established murine model and induced AA-amyloidosis in NMRI mice by intravenous injections of purified amyloid fibrils ('amyloid enhancing factor') combined with inflammatory challenge (silver nitrate subcutaneously). Blood plasma and peripheral Blood monocytes were isolated, sonicated and re-injected into new recipients followed by an inflammatory challenge during a three week period. When the animals were sacrificed presence of amyloid was analyzed in spleen sections after Congo red staining. Our result shows that some of the peripheral Blood monocytes, isolated from animals with detectable amyloid, contained amyloid-seed that primed for AA-amyloid. The seeding material seems to have been phagocytosed by the cells since the AA-precursor (SAA1) was found not ...