RESUMEN
Objective: To evaluate the diagnostic efficacy and practicality of the Jaundice color card (JCard) as a screening tool for neonatal jaundice. Methods: Following the standards for reporting of diagnostic accuracy studies (STARD) statement, a multicenter prospective study was conducted in 9 hospitals in China from October 2019 to September 2021. A total of 845 newborns who were admitted to the hospital or outpatient department for liver function testing due to their own diseases. The inclusion criteria were a gestational age of ≥35 weeks, a birth weight of ≥2 000 g, and an age of ≤28 days. The neonate's parents used the JCard to measure jaundice at the neonate's cheek. Within 2 hours of the JCard measurement, transcutaneous bilirubin (TcB) was measured with a JH20-1B device and total serum bilirubin (TSB) was detected. The Pearson's correlation analysis, Bland-Altman plots and the receiver operating characteristic (ROC) curve were used for statistic analysis. Results: Out of the 854 newborns, 445 were male and 409 were female; 46 were born at 35-36 weeks of gestational age and 808 were born at ≥37 weeks of gestational age. Additionally, 432 cases were aged 0-3 days, 236 cases were aged 4-7 days, and 186 cases were aged 8-28 days. The TSB level was (227.4±89.6) µmol/L, with a range of 23.7-717.0 µmol/L. The JCard level was (221.4±77.0) µmol/L and the TcB level was (252.5±76.0) µmol/L. Both the JCard and TcB values showed good correlation (r=0.77 and 0.80, respectively) and agreements (96.0% (820/854) and 95.2% (813/854) of samples fell within the 95% limits of agreement, respectively) with TSB. The JCard value of 12 had a sensitivity of 0.93 and specificity of 0.75 for identifying a TSB ≥205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.35 for identifying a TSB ≥342.0 µmol/L. The TcB value of 205.2 µmol/L had a sensitivity of 0.97 and specificity of 0.60 for identifying TSB levels of 205.2 µmol/L, and a sensitivity of 1.00 and specificity of 0.26 for identifying TSB levels of 342.0 µmol/L. The areas under the ROC curve (AUC) of JCard for identifying TSB levels of 153.9, 205.2, 256.5, and 342.0 µmol/L were 0.96, 0.92, 0.83, and 0.83, respectively. The AUC of TcB were 0.94, 0.91, 0.86, and 0.87, respectively. There were both no significant differences between the AUC of JCard and TcB in identifying TSB levels of 153.9 and 205.2 µmol/L (both P>0.05). However, the AUC of JCard were both lower than those of TcB in identifying TSB levels of 256.5 and 342.0 µmol/L (both P<0.05). Conclusions: JCard can be used to classify different levels of bilirubin, but its diagnostic efficacy decreases with increasing bilirubin levels. When TSB level are ≤205.2 µmol/L, its diagnostic efficacy is equivalent to that of the JH20-1B. To prevent the misdiagnosis of severe jaundice, it is recommended that parents use a low JCard score, such as 12, to identify severe hyperbilirubinemia (TSB ≥342.0 µmol/L).
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Bilirrubina , Hiperbilirrubinemia Neonatal , Ictericia Neonatal , Sensibilidad y Especificidad , Humanos , Recién Nacido , Bilirrubina/sangre , Estudios Prospectivos , Femenino , Masculino , Hiperbilirrubinemia Neonatal/diagnóstico , Hiperbilirrubinemia Neonatal/sangre , Ictericia Neonatal/diagnóstico , Ictericia Neonatal/sangre , Curva ROC , Tamizaje Neonatal/métodos , Edad Gestacional , PadresRESUMEN
OBJECTIVE: To investigate the predictive value of SYNTAX (Synergy between Percutaneous Coronary Intervention with Taxus and Cardiac Surgery) score (SS) combined with reactive hyperemia index (RHI) in predicting 2-year major adverse cardiovascular events (MACE) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). BACKGROUND: Both SS and RHI are good predictors of MACE; however, it is unknown whether combining SS and RHI could improve predictability of MACE in patients with ACS undergoing PCI. METHODS: We undertook a prospective study in 401 ACS patients that underwent PCI. The RHI-SYNTAX score (RSS) was calculated by categorizing and summing up the RHI and SS of individual patients. Patients with RHI < 1.67 are given 1 point, RHI ≥ 1.67 given 0 points, and those with SS ≤ 22 scored as 0 and SS > 22 as 1 point. Patients were classified into three groups: low RSS (group 0), moderate RSS (group 1), and high RSS (group 2). RESULTS: Among patients in the low, moderate, and high groups, the 2-year rates of MACE were 5.50, 10.66, and 23.33%, respectively (p < .0001). Total revascularization rates were 1.83, 2.54, and 8.89%, respectively (p = .015). Ischemic stroke rates were 0.00, 3.67, and 5.56%, respectively (p = .031). By multivariate analysis, the RSS was an independent predictor of 2-year MACE (hazard ratio: 2.09, 95% CI: 1.36-3.21, p = .001). Receiver-operator characteristic analysis indicated that the area under the curve significantly improved from 0.63 to 0.69, when RHI was added to SS (p < .0001). CONCLUSIONS: RSS is correlated with 2-year MACE in patients presenting with ACS undergoing PCI.
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Síndrome Coronario Agudo/terapia , Cateterismo Cardíaco , Angiografía Coronaria , Vasos Coronarios/diagnóstico por imagen , Hiperemia/fisiopatología , Intervención Coronaria Percutánea , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/mortalidad , Síndrome Coronario Agudo/fisiopatología , Anciano , Vasos Coronarios/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/instrumentación , Intervención Coronaria Percutánea/mortalidad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
The aim of this study is to investigate the expression of mTOR in breast cancer and observe the effect of CCI-779 on proliferation and apoptosis of MDA-MB-231 cells. Immunohistochemical staining was used to detect the expression of mTOR protein in breast cancer tissues and MDA-MB-231 cells. MTT assay was used to assess the effect of CCI-779 on proliferation of MDA-MB-231 cells. Annex-inV-FITC/ PI assay was utilized to evaluate the effect of CCI-779 on apoptosis of MDA-MB-231 cells. Among the 71 cases of breast cancer tissues, 54.9% were mTOR-positive that exhibited significantly higher expression than the 32 cases of normal tissues (21.9%); mTOR protein was also found to be expressed in MDA-MB-231 cells. The mTOR inhibitor CCI-779 significantly inhibited the proliferation of MDA-MB-231 cells that was dose- and time-dependent. However, CCI-779 was unable to induce apoptosis of MDA-MB-231 cells as demonstrated with AnnexinV-FITC/PI assay. mTOR plays a key role in the initiation and development of breast cancer, and its inhibitor CCI-779 exerts a strong suppressive activity against MDA-MB-231 cells, suggesting its therapeutic potential to treat breast cancer.
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Apoptosis , Neoplasias de la Mama/patología , Serina-Treonina Quinasas TOR/fisiología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/etiología , Línea Celular Tumoral , Proliferación Celular , Femenino , Humanos , Sirolimus/análogos & derivados , Sirolimus/farmacología , Sirolimus/uso terapéutico , Serina-Treonina Quinasas TOR/análisis , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
The effect of thermal and thermosonic treatments on the inactivation kinetics of polyphenol oxidase (PPO) in mushroom (Agaricus bisporus) was studied in 55-75°C temperature range. In both the processes, the inactivation kinetics of PPO followed a first-order kinetics (R(2)=0.941-0.989). The D values during thermal inactivation varied from 112±8.4min to 1.2±0.07min while they varied from 57.8±6.1min to 0.88±0.05min during thermosonic inactivation at the same temperature range. The activation energy during thermal inactivation was found to be 214±17kJ/mol, while it was 183±32kJ/mol during thermosonic inactivation. The inactivating effect of combined ultrasound and heat was found to synergistically enhance the inactivation kinetics of PPO. The D values of PPO decreased by 1.3-3 times during thermosonic inactivation compared to the D values of PPO during thermal inactivation at the temperature range. Therefore, thermosonication can be further developed as an alternative to "hot break" process of mushroom.
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Agaricales/enzimología , Catecol Oxidasa/antagonistas & inhibidores , Calor , Ultrasonido , Catecol Oxidasa/metabolismo , Estabilidad de Enzimas , Cinética , TermodinámicaRESUMEN
Selective blockade of CD28 is a promising therapy to inhibit pathogenic alloimmunity. However, evaluation of this approach in transplantation has been very limited. Using a novel nonactivating single-chain Fv-based reagent (α28scFv), we have investigated the role of CD28 and cytotoxic T lymphocyte antigen 4 (CTLA-4) in a murine cardiac transplant model. Blockade of CD28 for 2 weeks after engraftment promoted allograft survival, and significantly attenuated chronic rejection when combined with transient CD154-blockade or calcineurin inhibition. Graft acceptance was associated with decreased alloantibody production, increased proportion of early graft infiltration by regulatory T cells and increased expression of regulatory dendritic cell genes. Blockade of CTLA-4 during α28scFv-based treatments led to prompt rejection in all animals and inhibited expression of forkhead box P3 (Foxp3), programmed death (PD)-1 and 2,3-indoleamine dioxygenase (IDO) in the graft. These results show that CD28 signaling during the first weeks after transplant is a pivotal mediator of pathogenic alloimmunity, and that selective CD28 blockade prolongs graft acceptance by at least two immunomodulatory mechanisms. Selective CD28 inhibition while sparing CTLA-4 is thus a promising approach to inhibit pathogenic alloimmunity.
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Antígenos CD28/antagonistas & inhibidores , Antígeno CTLA-4/inmunología , Trasplante de Corazón/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática , Citometría de Flujo , Prueba de Cultivo Mixto de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Trasplante HomólogoRESUMEN
WO(3) and Zn-doped WO(3) thin films were prepared on indium-tin oxide glass by a dip-coating. The composite films were characterized by UV-Vis absorption spectra, X-ray diffraction and scanning electron microscope. The effect of preparation conditions (concentration of Zn, annealing temperature, number of layers) on the photocurrent was studied. It was found that the photocurrent under visible light displayed the highest value for 2% Zn-WO(3) films annealed at 400 degrees C. The photocatalytic activity of the Zn-doped WO(3) was evaluated in terms of decay rate of nitrite ions under visible light. The influence of applied potential, initial pH and nitrite concentration on the reaction rate was studied. The experiments demonstrated that NO(2)(-) could be efficiently degraded on the doped photoanode that showed a higher activity than the undoped WO(3) especially under high anodic potential (>0.7 V). The rate of degradation was enhanced in aqueous NaCl solutions. Furthermore, it was demonstrated that the photodegradation mechanism of NO(2)(-) proceeded mainly indirectly via OH radicals. The possible reason of enhancement of reaction rate was also discussed.
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Luz , Nitritos/química , Óxidos/química , Fotoquímica/métodos , Tungsteno/química , Zinc/química , Catálisis , Electrodos , Difracción de Rayos XRESUMEN
Cinnamyl alcohol dehydrogenase (CAD; EC 1.1.1.195) has been thought to mediate the reduction of both coniferaldehyde and sinapaldehyde into guaiacyl and syringyl monolignols in angiosperms. Here, we report the isolation of a novel aspen gene (PtSAD) encoding sinapyl alcohol dehydrogenase (SAD), which is phylogenetically distinct from aspen CAD (PtCAD). Liquid chromatography-mass spectrometry-based enzyme functional analysis and substrate level-controlled enzyme kinetics consistently demonstrated that PtSAD is sinapaldehyde specific and that PtCAD is coniferaldehyde specific. The enzymatic efficiency of PtSAD for sinapaldehyde was approximately 60 times greater than that of PtCAD. These data suggest that in addition to CAD, discrete SAD function is essential to the biosynthesis of syringyl monolignol in angiosperms. In aspen stem primary tissues, PtCAD was immunolocalized exclusively to xylem elements in which only guaiacyl lignin was deposited, whereas PtSAD was abundant in syringyl lignin-enriched phloem fiber cells. In the developing secondary stem xylem, PtCAD was most conspicuous in guaiacyl lignin-enriched vessels, but PtSAD was nearly absent from these elements and was conspicuous in fiber cells. In the context of additional protein immunolocalization and lignin histochemistry, these results suggest that the distinct CAD and SAD functions are linked spatiotemporally to the differential biosynthesis of guaiacyl and syringyl lignins in different cell types. SAD is required for the biosynthesis of syringyl lignin in angiosperms.
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Acroleína/análogos & derivados , Alcohol Deshidrogenasa/genética , Oxidorreductasas de Alcohol/genética , Magnoliopsida/enzimología , Proteínas de Plantas/genética , Acroleína/metabolismo , Alcohol Deshidrogenasa/metabolismo , Oxidorreductasas de Alcohol/metabolismo , Oxidorreductasas de Alcohol/fisiología , Secuencia de Aminoácidos , Pared Celular/química , Clonación Molecular , ADN Complementario , Inhibidores Enzimáticos/metabolismo , Inmunohistoquímica , Cinética , Lignina/biosíntesis , Lignina/química , Lignina/clasificación , Lignina/genética , Lignina/metabolismo , Magnoliopsida/genética , Magnoliopsida/metabolismo , Datos de Secuencia Molecular , Fenoles/química , Fenoles/metabolismo , Filogenia , Proteínas de Plantas/metabolismo , Tallos de la Planta/citología , Especificidad de la Especie , Especificidad por SustratoRESUMEN
From the leaves of Mallotus apelta, seven benzopyran compounds were obtained and their structures were determined using spectroscopic methods. One showed moderate antibiotic activity against Micrococcus lutens.
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Benzopiranos/aislamiento & purificación , Rosales/química , Benzopiranos/química , Benzopiranos/farmacología , Escherichia coli/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Pruebas de Sensibilidad Microbiana , Micrococcus luteus/efectos de los fármacos , Estructura Molecular , Pseudomonas aeruginosa/efectos de los fármacos , Espectrometría de Masa por Ionización de Electrospray , Staphylococcus aureus/efectos de los fármacosRESUMEN
Three coumarino-lignoids, aquillochin (1), cleomiscosin A and 5'-demethylaquillochin have been isolated from Mallotus apelta. The structure of the new compound 3 was determined by spectroscopic techniques.
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Euphorbiaceae , Plantas Medicinales , Cumarinas/química , Medicamentos Herbarios Chinos/química , HumanosRESUMEN
AIM: To examine the effects of bilobalide on nitric oxide-induced neurotoxicity in pheochromocytoma-derived PC12 cells (PC12 cells). METHODS: PC12 cell survival was monitored by LDH release and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Superoxide dismutases (SOD) and catalase (CAT) activities were measured based on their abilities to inhibit the oxidation of epinephrine by the xanthine-xanthine oxidase system or to decompose H2O2 respectively. The content of malondialdehyde (MDA) was measured by a fluorometric assay to indicate the lipid peroxidation. RESULTS: 3-Morpholinosydnonimine (SIN-1, 50-300 mumol.L-1) induced PC12 cell damage. After the cells had been pretreated with 10 mumol.L-1 bilobalide for 24 h, the cell viability was increased to 91% +/- 30% from 52% +/- 14% in SIN-1 alone group. Moreover, the activities of SOD and CAT were increased after cells were treated with bilobalide. CONCLUSION: The NO-induced neurotoxicity can be protected by bilobalide in PC12 cells. The bilobalide-induced increase in SOD and CAT activities may serve as one of the mechanisms underlying the neuroprotective effect of bilobalide.
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Ciclopentanos/farmacología , Diterpenos , Furanos/farmacología , Fármacos Neuroprotectores/farmacología , Animales , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Ginkgólidos , L-Lactato Deshidrogenasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Malondialdehído/metabolismo , Óxido Nítrico , Células PC12 , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
AIM: To study the effect of bilobalide, a terpene extracted from the leaves of Ginkgo biloba, on beta-amyloid peptide fragment 25-35 (A beta 25-35)-induced PC12 cell cytotoxicity. METHODS: 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assay were used to measure the viability of PC12 cells. Thiobarbituric acid-reactive substances were measured to determine lipid peroxidation of cells. Antioxidant enzymes in PC12 cells were detected. RESULTS: Treatment of PC12 cells with A beta 25-35 (100 mumol.L-1) for 24 h caused a great decrease in cell viability (P < 0.01 compared with control). Bilobalide 25-100 mumol.L-1 dose-dependently attenuated the cytotoxic effect of A beta 25-35. Bilobalide also inhibited A beta 25-35 (100 mumol.L-1)-induced elevation of lipid peroxidation and decline of antioxidant enzyme activities. CONCLUSION: Bilobalide protected PC12 cells from A beta 25-35-induced cytotoxicity.
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Péptidos beta-Amiloides/antagonistas & inhibidores , Ciclopentanos/farmacología , Diterpenos , Furanos/farmacología , L-Lactato Deshidrogenasa/metabolismo , Fármacos Neuroprotectores/farmacología , Fragmentos de Péptidos/antagonistas & inhibidores , Animales , Catalasa/metabolismo , Supervivencia Celular/efectos de los fármacos , Ginkgólidos , Glutatión Peroxidasa/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Células PC12 , Ratas , Superóxido Dismutasa/metabolismoRESUMEN
Two new diterpenoids, malloapeltene (6,8-dihydroxy-cembrene-5-one) and malloapeltin (4alpha,15,16-trihydroxy-dolabradane) were isolated and characterized from the petroleum ether fraction of the alcoholic extract of Mallotus apelta Muell.Arg. Their structures were determined by spectral methods.
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Diterpenos/química , Euphorbiaceae/química , Plantas Medicinales/química , Diterpenos/aislamiento & purificación , Resonancia Magnética Nuclear Biomolecular/métodos , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/químicaRESUMEN
Three new diterpenoids, 10-hydroxy-cembrene-5-one, 6-hydroxy-cembrene-5,10-dione and 2alpha,4beta,15,16-tetrahydroxyl-dolabradane were isolated from the petroleum ether fraction of the alcoholic extract of Mallotus apelta Muell.Arg. Their structures were determined by spectral methods.
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Diterpenos , Diterpenos/aislamiento & purificación , Rosales/química , Diterpenos/química , Espectroscopía de Resonancia Magnética , Modelos QuímicosRESUMEN
Much of the controversy surrounding the binding of plasminogen activator inhibitor-1 (PAI-1) to the low density lipoprotein receptor-related protein (LRP) may be due to the labile structure of PAI-1 and the distinct conformations that it can adopt. To examine this possibility and to test the hypothesis that PAI-1 contains a specific high affinity binding site for LRP, a sensitive and quantitative assay for PAI-1 binding to LRP was developed. This assay utilizes a unique PAI-1 mutant that was constructed with a hexapeptide tag at the NH2 terminus, which is recognized by the protein kinase, heart muscle kinase and can be specifically labeled with 32P. Our results show that only 32P-PAI-1 in complex with a proteinase binds LRP with high affinity and is efficiently endocytosed by cells, indicating that a high affinity site for LRP is generated on PAI-1 only when in complex with a proteinase. In addition, PAI-1 in complex with different proteinases is shown to cross-compete for LRP binding, demonstrating that the binding site is independent of the proteinase and therefore must reside on the PAI-1 portion of the complex. Finally, mutagenesis of PAI-1 results in loss of LRP binding, confirming that the high affinity binding site is located on PAI-1 and suggesting that the LRP binding site lays within a region of PAI-1 previously shown to contain the heparin binding domain.
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Endocitosis , Inhibidor 1 de Activador Plasminogénico/metabolismo , Receptores Inmunológicos/metabolismo , Animales , Sitios de Unión , Unión Competitiva , Transporte Biológico , Proteína 1 Relacionada con Receptor de Lipoproteína de Baja Densidad , Ratones , Mutación , Inhibidor 1 de Activador Plasminogénico/genética , Activadores Plasminogénicos/metabolismo , Unión Proteica , Conformación Proteica , Tripsina/metabolismo , Activador de Plasminógeno de Tipo Uroquinasa/metabolismoRESUMEN
Nepsilon-(gamma-glutamyl)lysine cross-links, connecting various peptide chain segments, are frequently the major products in transglutaminase-catalyzed reactions. We have now investigated the effectiveness of these enzymes for hydrolyzing the gamma:epsilon linkage. Branched compounds were synthesized, in which the backbone on the gamma-side of the cross-bridge was labeled with a fluorophor (5-(dimethylamino)-1-naphthalenesulfonyl or 2-aminobenzoyl) attached through an epsilon-aminocaproyl linker in the N-terminal position, and the other branch of the bridge was constructed with Lys methylamide or diaminopentane blocked by 2,4-dinitrophenyl at the Nalpha position. Hydrolysis of the cross-link could be followed in these internally quenched substrates by an increase in fluorescence. In addition to the thrombin and Ca2+-activated human coagulation Factor XIIIa, cytosolic transglutaminases from human red cells and from guinea pig liver were tested. All three enzymes were found to display good isopeptidase activities, with Km values of 10(-4) to 10(-5) M. Inhibitors of transamidation were effective in blocking the hydrolysis by the enzymes, indicating that expression of isopeptidase activity did not require unusual protein conformations. We suggest that transglutaminases may play a dynamic role in biology not only by promoting the formation but also the breaking of Nepsilon-(gamma-glutamyl)lysine isopeptides.
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Péptidos/metabolismo , Transglutaminasas/metabolismo , Animales , Calcio/metabolismo , Citosol/enzimología , Ácido Glutámico , Cobayas , Humanos , Concentración de Iones de Hidrógeno , Hidrólisis , Cinética , Lisina , Péptidos/química , Espectrometría de Fluorescencia , Relación Estructura-ActividadRESUMEN
The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC.