A5069848340- Crystal Structures and Properties
- Geological and Geochemical Analysis
- Blood Coagulation and Thrombosis Mechanisms
- Clay minerals and soil interactions
- High-pressure geophysics and materials
- X-ray Diffraction in Crystallography
- Mineralogy and Gemology Studies
- Nuclear materials and radiation effects
- Neuroendocrine regulation and behavior
- Chemical Synthesis and Characterization
- Neurotransmitter Receptor Influence on Behavior
- Protease and Inhibitor Mechanisms
- Geochemistry and Geologic Mapping
- Blood properties and coagulation
- Zeolite Catalysis and Synthesis
- Advanced Condensed Matter Physics
- Stress Responses and Cortisol
- earthquake and tectonic studies
- Hypothalamic control of reproductive hormones
- Glass properties and applications
- Advanced Glycation End Products research
- Primate Behavior and Ecology
- Geochemistry and Elemental Analysis
- Atrial Fibrillation Management and Outcomes
- Venomous Animal Envenomation and Studies
Yamaguchi University
2015-2024
Universität Hamburg
2023
Tohoku University
2021
Fukuoka University
1988-2020
Saitama Prefecture
2018
Komatsu (Japan)
2018
Institut des Géosciences de l'Environnement
2018
École Nationale Supérieure des Mines de Paris
2018
Géosciences Montpellier
2018
ParisTech
2018
S100/calgranulin polypeptides are present at sites of inflammation, likely released by inflammatory cells targeted to such loci a range environmental cues. We report here that receptor for AGE (RAGE) is central cell surface EN-RAGE (extracellular newly identified RAGE-binding protein) and related members the superfamily. Interaction EN-RAGEs with cellular RAGE on endothelium, mononuclear phagocytes, lymphocytes triggers activation, generation key proinflammatory mediators. Blockade...
The receptor for advanced glycation end products (RAGE), a newly-identified member of the immunoglobulin superfamily, mediates interactions product (AGE)-modified proteins with endothelium and other cell types. Survey normal tissues demonstrated RAGE expression in situations which accumulation AGEs would be unexpected, leading to hypothesis that under physiologic circumstances, might mediate interaction ligands distinct from AGEs. Sequential chromatography bovine lung extract identified...
The pattern recognition receptor, RAGE (receptor for advanced glycation endproducts), propagates cellular dysfunction in several inflammatory disorders and diabetes. Here we show that functions as an endothelial adhesion receptor promoting leukocyte recruitment. In animal model of thioglycollate-induced acute peritonitis, recruitment was significantly impaired RAGE-deficient mice opposed to wild-type mice. diabetic observed enhanced the inflamed peritoneum compared with nondiabetic mice;...
The thrombin thrombomodulin dependent activation of the plasma protein TAFI (Thrombin Activatable Fibrinolysis Inhibitor) and Subsequent Inhibition by TAFIa is described. Work to date indicates that a carboxypeptidase B enzyme suppress fibrinolysis most likely down regulating cofactor functions partially degraded fibrin. existence provides explanation for apparent profibrinolytic effect activated C. implies an explicit molecular connection between blood coagulation fibrinolytic cascades...
The latent plasma carboxypeptidase thrombin-activable fibrinolysis inhibitor (TAFI) is activated by thrombin/thrombomodulin on the endothelial cell surface, and functions in dampening fibrinolysis. In this study, we examined effect of TAFI (TAFIa) modulating proinflammatory bradykinin, complement C5a, thrombin-cleaved osteopontin. Hydrolysis bradykinin C5a osteopontin peptides TAFIa was as efficient that plasmin-cleaved fibrin peptides, indicating these are also good substrates for TAFIa....
The effect of acute inflammation on the synthesis plasma proteins by liver was studied in rats.The rates incorporation ~-[I-'~C]leucine into bloodstream changed 24 h after injection turpentine following factors: total serum protein, 1.6; al-acid glycoprotein and major phase al-protein, 20; fibrinogen, 4.8; transferrin, 1.3; albumin, 0.4.The changes preceded concentrations above plasma.The body pools, measured whole rat homogenates 3 days inducing inflammation, increased 18-fold for...
To investigate the consequence of deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI), we generated homozygous TAFI-deficient mice by targeted gene disruption. Intercrossing heterozygous TAFI produced offspring expected Mendelian ratio, indicating that transmission mutant allele did not lead to embryonic lethality. developed normally, reached adulthood, and were fertile. No gross physical abnormalities observed up 24 months age. Hematological analysis show any major differences...
To investigate the consequence of deficiency in thrombin-activatable fibrinolysis inhibitor (TAFI), we generated homozygous TAFI-deficient mice by targeted gene disruption. Intercrossing heterozygous TAFI produced offspring expected Mendelian ratio, indicating that transmission mutant allele did not lead to embryonic lethality. developed normally, reached adulthood, and were fertile. No gross physical abnormalities observed up 24 months age. Hematological analysis show any major differences...
Deletion and point mutants of soluble thrombomodulin were used to compare contrast elements primary structure required for the activation thrombin-activable fibrinolysis inhibitor (TAFI) protein C. The smallest mutant capable efficiently promoting TAFI contained residues including c-loop epidermal growth factor-3 (EGF3) through EGF6. This is 13 longer than that functioned well with C; latter consisted from interdomain loop connecting EGF3 EGF4 Alanine showed no loss function in C mutations...
Abstract Background: Mitochondrial gene mutations play a role in the development of diabetes mellitus. We have assessed frequency A3243G and other mitochondrial Japan relationship to clinical features diabetes. Methods: DNA was obtained from peripheral leukocytes 240 patients with mellitus (39 type 1; 188 2; 13 gestational diabetes) 125 control subjects. used PCR-restriction fragment length polymorphism analysis (ApaI) for PCR-single-strand conformation determine including nucleotide...
Vascular dysfunction in patients with diabetes mellitus is related to advanced glycation end product (AGE) formation. We previously showed that AGEs produce an increase vascular permeability and generated oxidant stress after binding the receptor (RAGE) present on endothelium. RAGE, a 35-kDa protein belongs immunoglobulin superfamily, has been cloned from rat lung cDNA library, recombinant soluble RAGE (rR-RAGE) produced insect cells. The sequence of highly conserved between human rat....
Thrombomodulin (TM) is an endothelial cell surface-bound cofactor in thrombin-dependent formation of activated protein C, a potent anticoagulant. Cofactor activity has been localized to the carboxyl-terminal half six epidermal growth factor-like (EGF) domains TM (TME). To identify residues TME that are critical for activity, 77 alanine point mutants were made between Cys-333 and Cys-462 by site-directed mutagenesis (all except Ala, Cys, Gly, Pro). Mutants expressed Escherichia coli measured...
AbattractThe amino acid sequence of rabbit cholesteryl ester transfer protein (CETP) has been obtained from cloned cDNA and genomic sequences.The 496 CETP an overall homology 81% compared to the 476 human CETP, with two-thirds substitutions being conservative.Like is ex- tremely hydrophobic, which consistent its function in neutral lipids.The data implies extensive structural similarity between CETP.Rabbit mRNA estimated be 2.2 kilobases size, 300 nucleotides longer than corresponding mRNA,...
The biosynthesis and secretion of α2‐macroglobulin, transferrin, α1‐acid glycoprotein α1‐proteinase inhibitor were studied in rat hepatocyte primary cultures. After labelling with [ 35 S]methionine, two forms, which can be separated electrophoretically differing by molecular weight, found for each the four glycoproteins. following weights estimated intracellular precursors secreted forms: 176 000 182 000; 84 86 glycoprotein, 39 43 000–60 inhibitor, 49 54 000. Carbohydrate moieties could...
Abstract Objective Osteopontin (OPN) is a proinflammatory cytokine that plays an important role in the pathogenesis of rheumatoid arthritis (RA). OPN can be cleaved by thrombin, resulting OPN‐R and exposing cryptic C‐terminal α4β1 α9β1 integrin–binding motif (SVVYGLR). Thrombin‐activatable carboxypeptidase B (CPB), also called thrombin‐activatable fibrinolysis inhibitor, removes arginine from OPN‐R, generating OPN‐L abrogating its enhanced cell binding. We undertook this study to investigate...
Summary Thrombin-activatable fibrinolysis inhibitor (TAFI) is synthesized by the liver and thought to circulate in plasma as a plasminogen-bound zymogen. When it activated thrombin/thrombomodulin complex, TAFI exhibits carboxypeptidase B-like activity. To study structure-function relationship of TAFI, we expressed recombinant human insect cells. During cloning cDNA from several libraries, identified second which differed published sequence at 2 positions. One these sequences resulted...
Poly(A) + RNA isolated from the livers of normal rats and suffering an acute inflammation was translated in a cell‐free translation system rabbit reticulocytes. The products were immunoprecipitated with specific antisera against α1‐acid glycoprotein, α2‐macroglobulin, transferrin, α1‐proteinase inhibitor albumin. 15 to 21 h after intramuscular injection turpentine 73‐, 66‐, 2.8‐, 2‐fold increases translatable mRNAs for transferrin inhibitor, respectively, observed. For albumin decrease mRNA...
Thrombomodulin (TM) is a cofactor for activation of protein C by thrombin.We showed that SO-90% this activity lost oxidation Metsss, located within the short interdomain loop between epidermal growth factor-like domains 4 and 5 (Glaser, C. B.,
We have discovered a novel small-molecule TAFIa inhibitor, BX 528, which is potent, highly selective against other carboxypeptidases and safe. The present study was to determine if 528 can enhance exogenous endogenous thrombolysis in four different animal models. In the first three models, thrombus induced by FeCl (2) (dogs) or laser (rats) injury of femoral artery, formed ex vivo implanted jugular vein rabbits. A low dose t-PA given induce low-level on an established thrombus. Co-treatment...