14 results on '"S. Grancha"'
Search Results
2. PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects
- Author
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Francisco España, S. Grancha, Fernando Ferrando, Amparo Vayá, Amparo Estellés, Rafael Seguí, Cristina Falcó, Piedad Villa, Yolanda Mira, and Justo Aznar
- Subjects
Venous thrombosis ,medicine.medical_specialty ,business.industry ,Internal medicine ,Genotype ,medicine ,Hematology ,medicine.disease ,business ,Gastroenterology - Published
- 2000
3. Lipoprotein(a) Levels and Isoforms and Fibrinolytic Activity in Postmenopause – Influence of Hormone Replacement Therapy
- Author
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S. Grancha, Justo Aznar, Juan Gilabert, Antonio Cano, Francisco España, Amparo Estellés, and Cristina Falcó
- Subjects
medicine.medical_specialty ,biology ,business.industry ,medicine.drug_class ,Plasmin ,medicine.medical_treatment ,Hematology ,Lipoprotein(a) ,Steroid hormone ,Endocrinology ,Estrogen ,Internal medicine ,Fibrinolysis ,Euglobulin lysis time ,biology.protein ,Medicine ,business ,Plasminogen activator ,Lipoprotein ,medicine.drug - Abstract
SummaryEpidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in postmenopausal women via several mechanisms, including modifications in the fibrinolytic system and lipoprotein(a) [Lp(a)] levels. The aim of this study was to examine the influence of the levels and isoforms of Lp(a) on fibrinolytic activity in 91 postmenopausal women in comparison with premenopause and analyze the effect of HRT on those parameters. In postmenopause, an increase in plasma Lp(a) and plasminogen activator inhibitor-1 (PAI-1) levels was found. A significant inverse correlation was observed between Lp(a) or PAI-1 levels and plasmin generation. Plasma samples with low molecular weight (MW) apo(a) isoforms showed higher plasmin inhibition than plasmas with high MW apo(a) isoforms and similar levels of total Lp(a) and PAI-1. HRT induced a significant decrease in Lp(a) and PAI-1 levels and an increase in estradiol levels, as well as an increase in fibrinolytic activity. A significant correlation was found between the percentages of variation in Lp(a) levels and in plasmin generation and between the percentages of variation in PAI-1 levels and in the euglobulin lysis time under HRT. In conclusion, the increase in fibrinolytic activity observed in women under HRT could be explained by two independent mechanisms: (a) the decrease in PAI-1 and (b) the decrease in the inhibition of plasmin generation due to the decrease in Lp(a) levels.
- Published
- 1999
4. Altered expression of plasminogen activator inhibitor type 1 in placentas from pregnant women with preeclampsia and/or intrauterine fetal growth retardation
- Author
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Raymond R. Schleef, M. Keeton, Juan Gilabert, Justo Aznar, Amparo Estellés, F Espna, David J. Loskutoff, S. Grancha, and Yutaka Eguchi
- Subjects
medicine.medical_specialty ,Immunology ,Syncytiotrophoblasts ,In situ hybridization ,Cell Biology ,Hematology ,Biology ,medicine.disease ,Biochemistry ,Preeclampsia ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Placenta ,embryonic structures ,medicine ,Immunohistochemistry ,Northern blot ,Plasminogen activator ,Immunostaining ,reproductive and urinary physiology - Abstract
Elevated plasma levels of type 1 plasminogen activator inhibitor (PAI- 1) have been implicated in mediating the fibrin deposition and occlusive lesions that occur within the placental vasculature in preeclampsia (PE) and intrauterine growth retardation (IUGR). In this report we identify the cells within the normal-appearing villous tissue that are responsible for the local production of PAI-1 in women with PE and IUGR. Levels for another fibrinolytic inhibitor (ie, type 2 plasminogen activator inhibitor [PAI-2]) were determined for comparative purposes. Elevated levels of PAI-1 were detected in placenta extracts from PE/IUGR patients (121 +/- 38 ng/mg, n = 8) when compared with the levels in placenta extracts from normal women (43 +/- 17 ng/mg, n = 10) or women with IUGR but not PE (51 +/- 22 ng/mg, n = 11). Immunohistochemical analysis of paraffin sections showed an increased immunoreactivity for PAI-1 in the placental villous syncytiotrophoblasts from PE/IUGR women compared with the immunostaining of placental samples from the normal or IUGR group. In contrast, antigen levels and immunostaining for PAI-2 were reduced in the placentas harvested from not only the PE/IUGR women (209 +/- 144 ng/mg) but also the IUGR group (169 +/- 106 ng/mg) in comparison with the PAI-2 levels in normal placentas (535 +/- 98 ng/mg). To document that the increased immunoreactivity for PAI-1 in PE/IUGR syncytiotrophoblasts was mediated by an increased production of PAI-1 within these cells, in situ hybridization analysis was performed. A strong positive signal for PAI-1 mRNA in villous syncytiotrophoblasts from PE patients (n = 5) was obtained after 2 weeks of exposure to the NTB2 emulsion in comparison with the weak signal for PAI-1 mRNA that required a 10-week exposure of the normal placenta sections (n = 10). Northern blotting for PAI-1 mRNA showed that both transcripts (ie, 3.2 and 2.3 kb) were elevated in samples of two PE patients in comparison with the PAI-1 mRNA transcripts present in a normal placenta and an IUGR placental sample. These results show increased PAI-1 and mRNA levels in placentas from PE patients and raise the possibility that localized elevated levels of PAI-1 may play a role in the initiation of placental damage, as well as in the thrombotic complications associated with this disease.
- Published
- 1994
5. PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects
- Author
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Fernando Ferrando, Rafael Seguí, Francisco España, S. Grancha, Piedad Villa, Amparo Vayá, Justo Aznar, Amparo Estellés, Yolanda Mira, and Cristina Falcó
- Subjects
Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Pathology ,Genotype ,medicine.medical_treatment ,Thrombophilia ,Gastroenterology ,Statistics, Nonparametric ,chemistry.chemical_compound ,Risk Factors ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Fibrinolysis ,medicine ,Humans ,Genetic Predisposition to Disease ,Antigens ,Risk factor ,Allele ,Promoter Regions, Genetic ,Triglycerides ,Venous Thrombosis ,Chi-Square Distribution ,business.industry ,Thrombin ,Hematology ,Middle Aged ,medicine.disease ,Thrombosis ,Venous thrombosis ,chemistry ,Case-Control Studies ,Tissue Plasminogen Activator ,Plasminogen activator inhibitor-1 ,Female ,business ,Protein C - Abstract
Impaired fibrinolysis as a result of increased plasminogen activator inhibitor-1 (PAI-1) levels in plasma is a common finding in patients with deep vein thrombosis (DVT). A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to influence the levels of PAI-1. The 4G allele was found to be associated with higher plasma PAI-1 activity (act), but contradictory results on the incidence of the 4G allele in DVT patients have been reported. The aim of this study was to analyse whether the PAI-1 promoter 4G/5G genotype increases the risk of venous thrombosis in subjects with thrombophilic defects, and to determine the distribution of the PAI-1 4G/5G genotype and its relation to plasma PAI-1 levels in 190 unrelated patients with DVT in comparison with a control group of 152 healthy subjects. No differences between the 4G/5G allele distribution in the DVT group (0.43/0.57) and in the control group (0.42/0.58) were observed. However, the presence of the 4G allele significantly increased the risk of thrombosis in patients with other thrombophilic defects. Significantly higher PAI-1 levels were observed in DVT patients than in the controls. Our results also showed significant differences in the plasma levels of PAI-1 antigen (ag) and PAI-1 act among the 4G/5G genotypes in DVT patients. A multivariate analysis revealed that, in the DVT group, PAI-1 ag levels were influenced by the 4G allele dosage, triglyceride levels and body mass index (BMI). The influence of the 4G allele dosage on PAI-1 levels was independent of the triglyceride levels and BMI. In the control group, no significant correlation between PAI-1 levels and 4G allele dosage was observed. In conclusion, the PAI-1 promoter polymorphism was found to have an influence on PAI-1 levels in DVT patients and on the risk of venous thrombosis in subjects with other genetic thrombophilic defects.
- Published
- 2000
6. Plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G genotype and increased PAI-1 circulating levels in postmenopausal women with coronary artery disease - Influence of hormone replacement therapy
- Author
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Amparo Estellés, Francisco España, G. Tormo, Cristina Falcó, R. Segui, Justo Aznar, S. Grancha, Juan Gilabert, and Antonio Cano
- Subjects
medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,Hormone replacement therapy (menopause) ,Hematology ,Biology ,medicine.disease ,Coronary artery disease ,chemistry.chemical_compound ,Endocrinology ,Antigen ,chemistry ,Estrogen ,Polymorphism (computer science) ,Internal medicine ,Plasminogen activator inhibitor-1 ,Genotype ,medicine ,Allele - Abstract
SummaryIncreased circulating levels of type 1 plasminogen activator inhibitor (PAI-1) have been associated with coronary artery disease (CAD). However, genetic and environmental determinants of PAI-1 expression are only partially understood. The levels of PAI-1 have been found to relate to 4/5 guanosine (4G/5G) polymorphism in the promoter region of the PAI-1 gene. The 4G allele in this polymorphism has been associated with higher levels of plasma PAI-1 activity, but despite the strong correlation between PAI-1 activity and antigen, no association has been found between PAI-1 antigen levels and the PAI-1 promoter 4G/5G genotype. The aim of the present study was to analyze the influence of the PAI-1 promoter 4G/5G genotype on PAI-1 levels in post-menopause women with coronary disease in comparison with healthy women in pre and postmenopausal status, and the influence of this genotype on variations in PAI-1 levels after hormone replacement therapy (HRT). No differences between 4G/5G allele distribution in the groups studied were observed. The group of postmenopausal women with CAD showed significantly increased PAI-1 antigen and activity levels in comparison with the control groups, and the levels of PAI-1 correlated with the 4G/5G genotype. A multivariate analysis revealed that in the CAD group there was a high correlation between 4G allele dosage and PAI-1 antigen levels, which were also influenced by the triglyceride levels but not by estrogen or glucose levels. After hormone replacement therapy the decrease in PAI-1 levels was correlated with the 4G allele dosage. We conclude that in the group of postmenopausal women with CAD the influence of the PAI-1 promoter 4G/5G genotype on PAI-1 levels is more evident than in the control groups, and that the decrease in PAI-1 levels after HRT in CAD women correlates with the 4G allele dosage.
- Published
- 1999
7. Abnormal expression of type 1 plasminogen activator inhibitor and tissue factor in severe preeclampsia
- Author
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Terri Thinnes, Koji Yamamoto, Juan Gilabert, Francisco España, Justo Aznar, Amparo Estellés, David J. Loskutoff, and S. Grancha
- Subjects
medicine.medical_specialty ,Placenta ,Pregnancy Complications, Cardiovascular ,Fibrin ,Preeclampsia ,Thromboplastin ,Tissue factor ,chemistry.chemical_compound ,Syncytiotrophoblast ,Pre-Eclampsia ,Pregnancy ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Medicine ,Humans ,RNA, Messenger ,Vitronectin ,reproductive and urinary physiology ,In Situ Hybridization ,biology ,business.industry ,Tumor Necrosis Factor-alpha ,Hematology ,medicine.disease ,Immunohistochemistry ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Plasminogen activator inhibitor-1 ,embryonic structures ,Immunology ,biology.protein ,Tumor necrosis factor alpha ,Female ,business ,Interleukin-1 - Abstract
SummaryPreeclampsia is a multisystemic obstetric disease of unknown etiology that is commonly associated with fibrin deposition, occlusive lesions in placental vasculature, and intrauterine fetal growth retardation. We previously reported that type 1 plasminogen activator inhibitor (PAI-1) levels are significantly increased in plasma and placenta from pregnant women with preeclampsia compared to normal pregnant women. In the present report we localize the expression of placental PAI-1 in greater detail and compare it with that of tissue factor (TF), a procoagulant molecule, and vitronectin (Vn), a PAI-1 cofactor. We also examine the expression of two cytokines, tumor necrosis factor α (TNFα) and interleukin-1 (IL-1), in order to begin to define the underlying mechanisms responsible for the elevated levels of PAI-1 and fibrin deposits observed in placenta from preeclampsia. We demonstrate a significant increase in PAI-1, TF and TNFα antigen and PAI-1 and TF mRNA in placentas from preeclamptic patients. PAI-1 mRNA was increased not only in syncytiotrophoblast and infarction areas, but also in fibroblasts and in some endothelial cells of fetal vessels in placentas from preeclamptic patients. However, there was no colocalization between PAI-1, TF, Vn and TNFα in placental villi. The elevated TNFα in the placenta may induce PAI-1 and TF, and thus promote the thrombotic alterations associated with preeclampsia.
- Published
- 1998
8. Activated protein C resistance phenotype in patients with antiphospholipid antibodies
- Author
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Francisco España, Piedad Villa, Amparo Estellés, Cristina Falcó, S. Grancha, and Justo Aznar
- Subjects
Adult ,Blood Platelets ,Male ,medicine.medical_specialty ,Abortion, Habitual ,Adolescent ,Asymptomatic ,Gastroenterology ,Pathology and Forensic Medicine ,Pregnancy ,Internal medicine ,medicine ,Humans ,Child ,Blood Coagulation ,Phospholipids ,Aged ,Lupus anticoagulant ,medicine.diagnostic_test ,business.industry ,General Medicine ,Middle Aged ,Thrombophlebitis ,medicine.disease ,Thrombosis ,Pulmonary embolism ,Venous thrombosis ,Cerebrovascular Disorders ,Phenotype ,Antibodies, Anticardiolipin ,Child, Preschool ,Lupus Coagulation Inhibitor ,Immunology ,Antibodies, Antiphospholipid ,Female ,Partial Thromboplastin Time ,medicine.symptom ,Activated protein C resistance ,business ,Protein C ,circulatory and respiratory physiology ,medicine.drug ,Partial thromboplastin time - Abstract
The effect of antiphospholipid antibodies (aPL) on the action of activated protein C (APC) was examined in 32 patients: 19 with lupus anticoagulant (LA), 6 with anticardiolipin antibodies (aCL), and 7 with LA and aCL. Eighteen patients had a ratio of activated partial thromboplastin time (APTT) with APC to APTT without APC (APTT ratio)
- Published
- 1997
9. Decreased expression of PAI-2 mRNA and protein in pregnancies complicated with intrauterine fetal growth retardation
- Author
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Francisco España, Justo Aznar, Juan Gilabert, S. Grancha, Melitina Chirivella, and Amparo Estellés
- Subjects
Adult ,medicine.medical_specialty ,Placenta ,Syncytiotrophoblasts ,In situ hybridization ,Biology ,Pre-Eclampsia ,Pregnancy ,Internal medicine ,Gene expression ,medicine ,Plasminogen Activator Inhibitor 2 ,Humans ,RNA, Messenger ,reproductive and urinary physiology ,In Situ Hybridization ,Messenger RNA ,Fetus ,Fetal Growth Retardation ,Infant, Newborn ,Hematology ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,In utero ,embryonic structures ,Plasminogen activator inhibitor-2 ,Female - Abstract
SummaryAn increase in plasma plasminogen activator inhibitors (PAIs), fundamentally PAI type 2 (PAI-2), has been described in normal pregnancy probably because the placenta is the main source of the high plasma levels of this protein. Although we have previously described plasmatic alterations of these inhibitors in pregnancies complicated with intrauterine fetal growth retardation (IUGR), no reports have been published about placental PAI-2 mRNA expression. In the present study, the placental PAI-2 expression determined in pregnancies complicated with IUGR and in severe preeclamptic patients was compared with that of normal pregnancies in order to identify the placental cell types expressing PAI-2 and to determine whether the production of PAI-2 is altered in placentas from IUGR. In situ hybridization analyses show that the syncytiotrophoblasts are the cells with the greatest PAI-2 expression in placenta. We report that the significant decrease in plasma and placental PAI-2 levels in IUGR groups is fundamentally due to a diminished expression of PAI-2 mRNA in placenta.
- Published
- 1996
10. Fibrinolytic system and reproductive process with special reference to fibrinolytic failure in pre-eclampsia
- Author
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Amparo Estellés, Juan Gilabert, Justo Aznar, Francisco España, and S. Grancha
- Subjects
Male ,Ovulation ,medicine.medical_specialty ,medicine.medical_treatment ,Biology ,chemistry.chemical_compound ,Pre-Eclampsia ,Cell Movement ,Pregnancy ,Internal medicine ,Placenta ,Fibrinolysis ,medicine ,Humans ,Spermatogenesis ,reproductive and urinary physiology ,T-plasminogen activator ,Reproduction ,Rehabilitation ,Obstetrics and Gynecology ,Trophoblast ,Spermatozoa ,medicine.anatomical_structure ,Endocrinology ,Reproductive Medicine ,chemistry ,Plasminogen activator inhibitor-1 ,Fertilization ,embryonic structures ,Plasminogen activator inhibitor-2 ,Female ,Plasminogen activator ,Fibrinolytic agent - Abstract
Here we summarize the recent progress in research on the role of the fibrinolytic system in reproduction, with a special emphasis on the role of the plasminogen activator inhibitors in fetal development. Trophoblasts produce fibrinolytic proteins that can promote normal implantation and regulate blood flow to the fetus and placenta throughout pregnancy. Normal pregnancy is associated with a hypofibrinolytic state that is fundamentally caused by an increase in plasminogen activator inhibitors types 1 and 2. In pre-eclampsia, a fibrinolytic failure, resulting from an increase in plasma and placental concentrations of plasminogen activator inhibitor-1, was observed. The localized elevated concentrations of placenta plasminogen activator inhibitor-1 protein and mRNA observed in pre-eclamptic patients would be expected to foster the deposition of fibrin and thus play a role in the complications associated with this disease. The decreased plasminogen activator inhibitor-2 concentrations in placenta and plasma from intrauterine fetal growth retardation pregnancies and the positive correlation between plasma/placenta plasminogen activator inhibitor-2 concentration and birthweight suggest that this inhibitor could be considered an adequate marker of placental function.
- Published
- 1995
11. The effect of estrogen replacement therapy with or without progestogen on the fibrinolytic system and coagulation inhibitors in postmenopausal status
- Author
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Miguel Tortajada, Francisco España, S. Grancha, Rosa Barrachina, Antonio Cano, Juan Gilabert, Justo Aznar, and Amparo Estellés
- Subjects
Adult ,medicine.medical_specialty ,Medroxyprogesterone ,Time Factors ,medicine.drug_class ,medicine.medical_treatment ,Administration, Oral ,Administration, Cutaneous ,Protein S ,Internal medicine ,Fibrinolysis ,Plasminogen Activator Inhibitor 1 ,medicine ,Humans ,Hormone replacement therapy ,Aged ,Urokinase ,biology ,Estradiol ,Progesterone Congeners ,business.industry ,Antithrombin ,Estrogen Replacement Therapy ,Obstetrics and Gynecology ,Lipoprotein(a) ,Middle Aged ,Postmenopause ,Endocrinology ,Estrogen ,Tissue Plasminogen Activator ,biology.protein ,Female ,Hormone therapy ,business ,Plasminogen activator ,medicine.drug ,Protein C - Abstract
OBJECTIVE: The aim of this study was to analyze several fibrinolytic components and coagulation inhibitors in postmenopausal women and to evaluate the effect of hormone replacement therapy. STUDY DESIGN: Several hemostatic parameters were evaluated in 75 postmenopausal women before and after 3 to 4 and 12 months of hormone therapy. RESULTS: An increase in plasma fibrinolytic activity primarily related to a significant increase in tissue-type plasminogen activator and a decrease in plasminogen activator inhibitor type 1 was observed in women receiving hormone replacement therapy. A significant decrease in protein S and lipoprotein(a) was detected under therapy. No modifications in tissue-type plasminogen activator/plasminogen activator inhibitor-1 and activated protein C/α 1 -antitrypsin complexes, urokinase activity, plasminogen, and antithrombin III were detected. CONCLUSIONS: The increase in fibrinolytic activity and the decrease in lipoprotein(a) levels observed in women receiving hormone replacement therapy could help decrease the risk of coronary disease associated with the postmenopausal state.
- Published
- 1995
12. Evaluation of plasminogen activators and plasminogen activator inhibitors in plasma and amniotic fluid in pregnancies complicated with intrauterine fetal growth retardation
- Author
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Francisco España, S. Grancha, Micó Jm, Justo Aznar, Ayuso Mj, Amparo Estellés, M. Chirivella, and Juan Gilabert
- Subjects
Adult ,medicine.medical_specialty ,Amniotic fluid ,Birth weight ,medicine.medical_treatment ,Preeclampsia ,Plasminogen Activators ,Pregnancy ,Internal medicine ,Fibrinolysis ,medicine ,Fetal growth ,Plasminogen Activator Inhibitor 2 ,Humans ,Urokinase ,Fetal Growth Retardation ,business.industry ,Obstetrics and Gynecology ,medicine.disease ,Amniotic Fluid ,Plasminogen Inactivators ,Endocrinology ,Reproductive Medicine ,Female ,business ,Plasminogen activator ,medicine.drug - Abstract
Several fibrinolytic parameters were determined in plasma and amniotic fluid from normotensive pregnancies complicated by intrauterine fetal growth retardation (IUGR) and severe preeclamptic (PE) patients with IUGR and compared with data from normal pregnancies. A significant decrease in plasminogen activator type 2 (PAI-2) and urokinase levels in plasma and amniotic fluid was observed in IUGR groups in comparison with normal pregnancy. No significant differences were observed between the control and IUGR groups in relation to the other fibrinolytic parameters, except for plasma PAI type 1 and tissue-type plasminogen activator levels, which were significantly increased in the PE group. A significant positive correlation was observed between birth weight and PAI-2 levels in both plasma and amniotic fluid, but the plasma PAI-2 levels showed a higher correlation. In conclusion, these results suggest that the PAI-2 level measured in plasma is a more adequate marker of placental function than the PAI-2 level measured in amniotic fluid.
- Published
- 1994
13. 108 Relationship between PAI-1 promoter polymorphism and PAI-1 circulating levels in postmenopausal women with coronary artery disease (CAD)
- Author
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J. Gilabert, Francisco España, Amparo Estellés, S. Grancha, G. Tormo, Justo Aznar, and Cristina Falcó
- Subjects
Coronary artery disease ,medicine.medical_specialty ,Postmenopausal women ,business.industry ,Internal medicine ,medicine ,Promoter polymorphism ,CAD ,medicine.disease ,business ,Gastroenterology - Published
- 1997
14. Modifications in the fibrinolytic system by hormone-replacement therapy (HRT)
- Author
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A. Cano, S. Grancha, J. Gilabert, Francisco España, Justo Aznar, Amparo Estellés, and M. Tortajada
- Subjects
medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,medicine ,Hematology ,Hormone replacement therapy ,business - Published
- 1994
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