28 results on '"Castejon, R."'
Search Results
2. (683) - Assessment of the Degree of Immunosuppression Measured by Residual Expression of Genes Regulated by T-Cell Nuclear Factor (NFAT-RGE) in Lung Transplant Recipients
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Ruiz, V., Erro, M., Ussetti, P., Rosado, S., Castejón, R., Aguilar, M., Revilla, E., Bravo Masgoret, C., Saez Gimenez, B., Zapata, M., Berastegui Garcia, C., Lopez Meseguer, M., Villena, Y., Vima Bofarull, J., Monforte, V., and Gomez, S.
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- 2024
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3. Decrease of regulatory T cells in patients with systemic lupus erythematosus
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Mellor-Pita, S, Citores, M J, Castejon, R, Tutor-Ureta, P, Yebra-Bango, M, Andreu, J L, and Vargas, J A
- Published
- 2006
4. Aminoguanidine reduces apoptosis of circulating V Beta 8.2 T lymphocytes in Lewis rats with actively induced experimental autoimmune encephalomyelitis. Association with persistent inflammation of the central nervous system and lack of recovery
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Puerta, C., Martı́nez, I., Baranda, P., Blasco, M.R., Castejón, R., Vargas, J.A., and Garcı́a-Merino, A.
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- 2000
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5. Short-term atorvastatin therapy improves arterial stiffness of middle-aged systemic lupus erythematosus patients with pathological pulse wave velocity
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Castejon, R, primary, Castañeda, A, additional, Sollet, A, additional, Mellor-Pita, S, additional, Tutor-Ureta, P, additional, Jimenez-Ortiz, C, additional, and Yebra-Bango, M, additional
- Published
- 2016
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6. Metabolic syndrome is associated with decreased circulating endothelial progenitor cells and increased arterial stiffness in systemic lupus erythematosus
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Castejon, R, primary, Jimenez-Ortiz, C, additional, Rosado, S, additional, Tutor-Ureta, P, additional, Mellor-Pita, S, additional, and Yebra-Bango, M, additional
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- 2015
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7. Short-term atorvastatin therapy improves arterial stiffness of middle-aged systemic lupus erythematosus patients with pathological pulse wave velocity.
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Castejon, R., Castañeda, A., Sollet, A., Mellor-Pita, S., Tutor-Ureta, P., Jimenez-Ortiz, C., and Yebra-Bango, M.
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SYSTEMIC lupus erythematosus treatment , *STATINS (Cardiovascular agents) , *ATHEROSCLEROSIS , *ATORVASTATIN , *PROGENITOR cells - Abstract
Objectives Statins have been proposed as a potential treatment for systemic lupus erythematosus (SLE) due to their immunomodulatory properties, their role restoring endothelial function and preventing atherosclerosis. We evaluate the effect of a short period treatment with a low dose of atorvastatin and its withdrawal on early stage subclinical atherosclerosis. Methods Thirty-seven SLE females received 20 mg/day atorvastatin during eight weeks. At baseline, at the end of treatment and six months after atorvastatin withdrawal, disease activity, subclinical atherosclerosis –assessed by measuring carotid-femoral pulse wave velocity (PWV) – and quantification of circulating endothelial progenitor cells (EPC) – as a surrogate biological marker of subclinical atherosclerosis – were carried out. Results The group of SLE patients with baseline pathological arterial stiffness showed a significant decrease of PWV after atorvastatin therapy (8.43 ± 1.45 m/s vs 7.42 ± 1.06 m/s; p = 0.002) that is maintained six months after treatment finished. Only patients of the middle-aged group showed a nearly significant decrease in the PWV measured along the study (7.16 ± 1.23 m/s vs 6.76 ± 0.82 m/s; p = 0.05). Atorvastatin induced a significant decrease in the circulating EPC percentage (0.65 ± 0.67 vs 0.40 ± 0.31; p = 0.023) as well as a downward trend of disease activity that it is observed by a decrease in SLE disease activity index simultaneously with an increase in C3 complement and significant decrease in serum concentration of vascular endothelial grow factor (VEGF) and sVCAM-1. Conclusions Short-term atorvastatin therapy reduces arterial stiffness of SLE patients with baseline pathological PWV, who are mainly in the group of middle-aged patients. Further studies are needed to determine whether these patients would benefit from statin therapy in preventing cardiovascular events. [ABSTRACT FROM AUTHOR]
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- 2017
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8. Authors' reply
- Author
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Valero-Gonzalez, S, primary, Castejon, R, additional, Jimenez-Ortiz, C, additional, Rosado, S, additional, Tutor-Ureta, P, additional, Vargas, J-A, additional, and Yebra-Bango, M, additional
- Published
- 2014
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9. Decreased circulating endothelial progenitor cells as an early risk factor of subclinical atherosclerosis in systemic lupus erythematosus
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Castejon, R., primary, Jimenez-Ortiz, C., additional, Valero-Gonzalez, S., additional, Rosado, S., additional, Mellor, S., additional, and Yebra-Bango, M., additional
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- 2013
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10. Increased arterial stiffness is independently associated with metabolic syndrome and damage index in systemic lupus erythematosus patients
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Valero-Gonzalez, S, primary, Castejon, R, additional, Jimenez-Ortiz, C, additional, Rosado, S, additional, Tutor-Ureta, P, additional, Vargas, J-A, additional, and Yebra-Bango, M, additional
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- 2013
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11. Metabolic syndrome is associated with decreased circulating endothelial progenitor cells and increased arterial stiffness in systemic lupus erythematosus.
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Castejon, R., Jimenez-Ortiz, C., Rosado, S., Tutor-Ureta, P., Mellor-Pita, S., and Yebra-Bango, M.
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METABOLIC syndrome risk factors , *PROGENITOR cells , *ENDOTHELIUM physiology , *ARTERIAL diseases , *SYSTEMIC lupus erythematosus - Abstract
Objectives Metabolic syndrome (MetS) is highly prevalent in patients with systemic lupus erythematosus (SLE) and it has been associated with increased cardiovascular risk. We examined the contribution of MetS to inflammatory markers, arterial stiffness and circulating endothelial progenitor cells (EPCs) as surrogates of subclinical atherosclerosis. Methods Cardiovascular risk factors, SLE-specific factors and peripheral blood EPCs were assessed in 50 female SLE patients. MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III. Simultaneously, atherosclerosis was assessed by measuring the carotid–femoral pulse wave velocity (PWV) by doppler velocimetry. Results Beyond the factors included in the definition, SLE patients with MetS have a significantly higher serum level of uric acid (6.88 ± 2.20 vs 4.45 ± 1.17, p < 0.001) and some inflammatory biomarkers such as homocysteine, IL-8, sICAM-1 or complement molecules. The presence of MetS in our patients was closely linked with a significantly increased patient organ damage score (3.20 ± 1.97 vs 1.60 ± 1.67, p = 0.008), a decreased percentage of circulating EPCs (0.53 ± 0.24 vs 0.85 ± 0.57, p = 0.007) and an increased arterial stiffness (9.89 ± 2.40 vs 7.13 ± 1.51, p < 0.001). Conclusions MetS may contribute to the development of atherosclerosis by significantly increasing inflammation levels and arterial stiffness and decreasing circulating EPCs. This finding would justify close monitoring of these patients. [ABSTRACT FROM AUTHOR]
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- 2016
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12. Toll-like Receptor 3 L412F Polymorphism May Protect Against Acute Graft Rejection in Adult Patients Undergoing Liver Transplantation for Hepatitis C-Related Cirrhosis
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Citores, M.J., primary, Baños, I., additional, Noblejas, A., additional, Rosado, S., additional, Castejon, R., additional, and Cuervas-Mons, V., additional
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- 2011
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13. Increased arterial stiffness is independently associated with metabolic syndrome and damage index in systemic lupus erythematosus patients.
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Valero-Gonzalez, S, Castejon, R, Jimenez-Ortiz, C, Rosado, S, Tutor-Ureta, P, Vargas, J-A, and Yebra-Bango, M
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SYSTEMIC lupus erythematosus , *ARTERIAL diseases , *METABOLIC syndrome , *CARDIOVASCULAR diseases risk factors , *AGE factors in disease , *DISEASES in women - Abstract
Objectives: We evaluated whether traditional or non-traditional cardiovascular (CV) risk factors and systemic lupus erythematosus (SLE)-related risk factors were associated with pathological arterial stiffness measured by pulse wave velocity (PWV) adjusted for patients' age and blood pressure. Method: CV risk factors were measured in the 46 SLE female patients studied. Activity and organ damage were assessed by the SLE Disease Activity Index (SLEDAI) and the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index, respectively. Other lupus-related parameters and information concerning treatment were recorded. Subclinical atherosclerosis was assessed by PWV calculated from pulse wave recording by Doppler, a non-invasive method to measure arterial stiffness. Multivariate logistic regression analysis was used to identify independent determinants of increased PWV. Results: PWV was categorized as normal or pathological arterial stiffness following the reference values adjusted by age and blood pressure recently published by the European Society of Cardiology. Pathological PWV was associated with CV risk factors including homocysteine (p = 0.01), high-sensitivity C-reactive protein (hs-CRP; p = 0.03), uric acid (p = 0.01), and metabolic syndrome (p = 0.007). With regard to SLE-specific risk factors, a significant association was found between PWV and SLICC/ACR score (p = 0.006). Multivariate analysis showed that increased PWV was independently associated with metabolic syndrome [odds ratio (OR) 6.6, 95% confidence interval (CI) 1.2-38, p = 0.03] and SLICC/ACR score (OR 1.5, 95% CI 1-2.32, p = 0.05). Conclusions: We have found a close link between metabolic syndrome and SLICC/ACR score with increased aortic stiffness. These variables might be an indicator of subclinical atherosclerosis in SLE women without clinical evidence of atherosclerotic cardiovascular disease (CVD). [ABSTRACT FROM AUTHOR]
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- 2014
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14. Prognostic significance of natural killer cell activity in patients with laryngeal carcinoma.
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Gonzalez FM, Vargas JA, Lopez-Cortijo C, Castejon R, Gorriz C, Ramirez-Camacho R, Millan I, and Durantez A
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- 1998
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15. Apoptosis and cancer | Apoptosis y cancer
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Vargas, J. A., Sanchez-Prieto, R., Castejon, R., and Cajal, S. R.
16. IgA Anti-β2-Glycoprotein I Antibodies as Markers of Thrombosis and Severity in COVID-19 Patients.
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Mellor-Pita S, Tutor-Ureta P, Velasco P, Plaza A, Diego I, Vázquez-Comendador J, Vionnet AP, Durán-Del Campo P, Moreno-Torres V, Vargas JA, and Castejon R
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- Humans, Male, Female, Middle Aged, Retrospective Studies, Adult, Aged, Aged, 80 and over, COVID-19 immunology, COVID-19 complications, COVID-19 blood, beta 2-Glycoprotein I immunology, Immunoglobulin A blood, Thrombosis immunology, Antibodies, Antiphospholipid blood, Biomarkers blood, SARS-CoV-2 immunology, Severity of Illness Index
- Abstract
Patients with COVID-19 may develop a hypercoagulable state due to tissue and endothelial injury, produced by an unbalanced immune response. Therefore, an increased number of thromboembolic events has been reported in these patients. The aim of this study is to investigate the presence of antiphospholipid antibodies (aPL) in COVID-19 patients, their role in the development of thrombosis and their relationship with the severity of the disease. In this retrospective study, serum samples from 159 COVID-19 patients and 80 healthy donors were analysed for the presence of aPL. A total of 29 patients (18.2%) and 14 healthy donors (17.5%) were positive for aPL. Nineteen COVID-19 patients (12%) but no healthy donor presented a positive percentage of the IgA isotype aPL. IgA anti-β2-glycoprotein I antibodies (anti-β2GPI) were the most frequent type (6.3%) in patients but was not detected in any healthy donor. The positivity of this antibody was found to be significantly elevated in patients with thromboembolic events (25% vs. 5%, p = 0.029); in fact, patients with positive IgA anti-β2GPI had an incidence of thrombosis over six times higher than those who had normal antibody concentrations [OR (CI 95%) of 6.67 (1.5-30.2), p = 0.014]. Additionally, patients with moderate-severe disease presented a higher aPL positivity than patients with mild disease according to the Brescia ( p = 0.029) and CURB-65 ( p = 0.011) severity scales. A multivariate analysis showed that positivity for IgA anti-β2GPI is significantly associated with disease severity measured by CURB-65 [OR (CI 95%) 17.8 (1.7-187), p = 0.0016]. In conclusion, COVID-19 patients have a significantly higher positive percentage of the IgA isotype aPL than healthy donors. IgA anti-β2GPI antibodies were the most frequently detected aPL in COVID-19 patients and were associated with thrombosis and severe COVID-19 and are thus proposed as a possible marker to identify high-risk patients.
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- 2024
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17. Calcium and vitamin D supplement intake may increase arterial stiffness in systemic lupus erythematosus patients.
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Mellor-Pita S, Tutor-Ureta P, Rosado S, Alkadi K, Granado F, Jimenez-Ortiz C, and Castejon R
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- Adult, Aged, Atherosclerosis blood, Atherosclerosis complications, Biomarkers blood, Calcium administration & dosage, Cross-Sectional Studies, Female, Humans, Lupus Erythematosus, Systemic blood, Lupus Erythematosus, Systemic complications, Middle Aged, Risk Factors, Vitamin D administration & dosage, Vitamin D Deficiency blood, Vitamin D Deficiency complications, Young Adult, Atherosclerosis chemically induced, Calcium adverse effects, Dietary Supplements adverse effects, Lupus Erythematosus, Systemic physiopathology, Vascular Stiffness drug effects, Vitamin D adverse effects, Vitamin D Deficiency drug therapy
- Abstract
Objectives: Low serum levels of 25-hydroxyvitamin D (25(OH)D) have been associated with a higher frequency of risk factors and cardiovascular disease. The aim of this study is to evaluate the association of 25(OH)D, cardiovascular risk factors, and subclinical atherosclerosis in systemic lupus erythematosus (SLE) patients., Method: Forty-seven female SLE patients were studied. Data collected included demographics, SLE activity, disease damage, cardiovascular risk factors, and markers of subclinical atherosclerosis. Patient treatments and vitamin D and calcium supplementation (VitD-Ca) were recorded. Vitamin D deficiency was defined as serum 25(OH)D < 50 nmol/l measured by ultra-high-performance liquid chromatography. Atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry and intima-media thickness (IMT) by B-mode ultrasound scanning., Results: 61.7% of patients were vitamin D deficient with a mean level of 31.91 ± 10.21 nmol/l. Serum vitamin D concentration was significantly higher in the 23 patients taking VitD-Ca supplements than that in patients not supplemented (p = 0.004). No significant association was found between 25(OH)D serum levels and cardiovascular risk factors, disease activity, or different treatments for SLE. A significant positive correlation was found between 25(OH)D levels, PWV (p = 0.02), and IMT (p = 0.01); moreover, patients taking VitD-Ca supplements presented an increased arterial stiffness., Conclusion: Patients with arterial stiffness showed higher levels of serum vitamin D and most of them were on VitD-Ca supplements. Although prospective studies with a larger number of patients and follow-up are needed, our findings suggest that VitD-Ca supplementation may have effects on SLE patients' arterial stiffness.
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- 2019
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18. Serum cystatin C is associated with kidney function but not with cardiovascular risk factors or subclinical atherosclerosis in patients with Systemic Lupus Erythematosus.
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Garcia-Garcia P, Castejon R, Tutor-Ureta P, Silvestre RA, Mellor-Pita S, Jimenez-Ortiz C, and Yebra-Bango M
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- Adult, Aged, Aged, 80 and over, Atherosclerosis etiology, Atherosclerosis physiopathology, Biomarkers blood, Cardiovascular Diseases etiology, Cardiovascular Diseases physiopathology, Creatinine blood, Cross-Sectional Studies, Cytokines blood, Female, Humans, Kidney Function Tests, Lupus Erythematosus, Systemic complications, Lupus Erythematosus, Systemic physiopathology, Middle Aged, Risk Factors, Young Adult, Atherosclerosis blood, Cardiovascular Diseases blood, Cystatin C blood, Glomerular Filtration Rate physiology, Kidney physiopathology, Lupus Erythematosus, Systemic blood
- Abstract
Cystatin C (CysC) is a protein considered as an excellent marker of renal function, and it has been suggested as an independent predictor of cardiovascular (CV) risk. We evaluated the association of serum CysC with renal function, CV risk factors, inflammation, and subclinical atherosclerosis in Systemic Lupus Erythematosus (SLE) patients. Sixty-one SLE female patients were selected according to estimated glomerular filtration rate (GFR) > 60 ml/min/1.73m
2 . Renal function parameters, SLE specific factors, CV risk factors, and inflammatory markers were assessed. Subclinical atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry. Serum CysC concentration was measured using a particle-enhanced immunonephelometric assay that established 0.59-1.01 mg/l as reference values. Patients with high CysC showed significantly altered creatinine, microalbuminuria, and GFR in addition to a significant higher presence of traditional CV risk factors such as arterial hypertension (p < 0.001), metabolic syndrome (p < 0.001), hypertrigliceridemia (p < 0.001), tobacco habit (p < 0.05), and a strong association with arterial stiffness (p = 0.017). Positive correlation between CysC, homocysteine (r = 0.511; p < 0.001) and fibrinogen levels (r = 0.304; p < 0.02) were also observed. A significantly higher SLICC/ACR score was related to high CysC level (p = 0.011), together with higher endothelin-1 and lower TNF serum concentration (p < 0.005). Considering only patients without any renal impairment (microalbumin/creatinine <30 mg/g), no association between CysC level and CV risk factors, arterial stiffness, or SLE-related factors was found. Serum CysC is a good marker of renal function in SLE patients, but it is not independently associated with cardiovascular risk factor or subclinical atherosclerosis.- Published
- 2017
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19. Synergistic Activity of Deguelin and Fludarabine in Cells from Chronic Lymphocytic Leukemia Patients and in the New Zealand Black Murine Model.
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Rebolleda N, Losada-Fernandez I, Perez-Chacon G, Castejon R, Rosado S, Morado M, Vallejo-Cremades MT, Martinez A, Vargas-Nuñez JA, and Perez-Aciego P
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- Age Factors, Animals, Apoptosis drug effects, Apoptosis Regulatory Proteins metabolism, Cells, Cultured, Drug Synergism, Female, Humans, Immunoblotting, Immunohistochemistry, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Leukemia, Lymphocytic, Chronic, B-Cell pathology, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Mice, Inbred NZB, NF-kappa B metabolism, Neoplasms, Experimental metabolism, Neoplasms, Experimental pathology, Proto-Oncogene Proteins c-akt metabolism, Rotenone administration & dosage, Rotenone pharmacology, Signal Transduction drug effects, Tumor Cells, Cultured, Vidarabine administration & dosage, Vidarabine pharmacology, Antineoplastic Combined Chemotherapy Protocols pharmacology, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Neoplasms, Experimental drug therapy, Rotenone analogs & derivatives, Vidarabine analogs & derivatives
- Abstract
B-cell chronic lymphocytic leukemia (CLL) remains an incurable disease, and despite the improvement achieved by therapeutic regimes developed over the last years still a subset of patients face a rather poor prognosis and will eventually relapse and become refractory to therapy. The natural rotenoid deguelin has been shown to induce apoptosis in several cancer cells and cell lines, including primary human CLL cells, and to act as a chemopreventive agent in animal models of induced carcinogenesis. In this work, we show that deguelin induces apoptosis in vitro in primary human CLL cells and in CLL-like cells from the New Zealand Black (NZB) mouse strain. In both of them, deguelin dowregulates AKT, NFκB and several downstream antiapoptotic proteins (XIAP, cIAP, BCL2, BCL-XL and survivin), activating the mitochondrial pathway of apoptosis. Moreover, deguelin inhibits stromal cell-mediated c-Myc upregulation and resistance to fludarabine, increasing fludarabine induced DNA damage. We further show that deguelin has activity in vivo against NZB CLL-like cells in an experimental model of CLL in young NZB mice transplanted with spleen cells from aged NZB mice with lymphoproliferation. Moreover, the combination of deguelin and fludarabine in this model prolonged the survival of transplanted mice at doses of both compounds that were ineffective when administered individually. These results suggest deguelin could have potential for the treatment of human CLL.
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- 2016
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20. Decreased circulating endothelial progenitor cells as an early risk factor of subclinical atherosclerosis in systemic lupus erythematosus.
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Castejon R, Jimenez-Ortiz C, Valero-Gonzalez S, Rosado S, Mellor S, and Yebra-Bango M
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- Adult, Asymptomatic Diseases, Atherosclerosis blood, Atherosclerosis etiology, Carotid Artery Diseases blood, Carotid Artery Diseases etiology, Carotid Intima-Media Thickness, Cross-Sectional Studies, Female, Flow Cytometry, Humans, Lupus Erythematosus, Systemic blood, Lupus Erythematosus, Systemic complications, Middle Aged, Pulse Wave Analysis, Risk Factors, Vascular Stiffness, Young Adult, Atherosclerosis diagnostic imaging, Carotid Artery Diseases diagnostic imaging, Endothelial Cells cytology, Lupus Erythematosus, Systemic physiopathology, Stem Cells cytology
- Abstract
Objective: Endothelial progenitor cells (EPCs) play an important role in vascular damage repair and it has been suggested that a decreased number of these cells is associated with increased subclinical atherosclerosis. Our study aim was to evaluate whether the number of circulating EPCs in patients with SLE is associated with subclinical atherosclerosis, the presence of cardiovascular (CV) risk factors and SLE-specific factors., Methods: Forty-six female SLE patients were included. At the time of each patient's appointment, CV risk factors, SLE-specific factors and EPCs were assessed in peripheral blood by flow cytometry. Simultaneously, atherosclerosis was assessed by measuring the carotid-femoral pulse wave velocity (PWV) by Doppler velocimetry, intima media thickness (IMT) and carotid plaque by B-mode US scanning., Results: Patients were classificated according to PWV following the reference values adjusted by age and blood pressure published by the European Society of Cardiology. Patients with pathological values of PWV showed a significant decrease of circulating EPC percentage compared with normal PWV patients. Decreased EPC counts were also associated with certain risk factors, including hypertension, tobacco use, impaired glucose metabolism, and metabolic syndrome, and correlate with high levels of high-sensitivity CRP (hsCRP) or fibrinogen. The presence of carotid plaque and IMT measurement were unrelated with EPC quantification., Conclusion: Patients with a reduced percentage of EPCs showed pathological arterial stiffness and association with certain CV risk factors, suggesting that the measurement of circulating EPCs can be used as a biological marker to determine subclinical atherosclerosis in SLE.
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- 2014
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21. CD154 expression triggered by purine analogues in vitro: Correlation with treatment response and autoimmune events in chronic lymphocytic leukemia.
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Citores MJ, Castejon R, Villarreal M, Rosado S, Garcia-Marco JA, and Vargas JA
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- Aged, Aged, 80 and over, Antineoplastic Agents pharmacology, Autoimmunity drug effects, Cells, Cultured, Female, Flow Cytometry, Humans, Immunophenotyping, Leukemia, Lymphocytic, Chronic, B-Cell drug therapy, Leukemia, Lymphocytic, Chronic, B-Cell immunology, Leukemia, Lymphocytic, Chronic, B-Cell metabolism, Male, Middle Aged, Outcome Assessment, Health Care methods, Prognosis, Vidarabine pharmacology, CD40 Ligand biosynthesis, Cladribine pharmacology, Vidarabine analogs & derivatives
- Abstract
Objective: Despite a fludarabine-based treatment is the first choice of therapy in chronic lymphocytic leukemia (CLL), not all patients achieve a partial or complete response and some of them develop autoimmune manifestations. The aim of this study was to evaluate the influence of CD154 on these adverse effects because CD154 is involved in both B-cell survival and autoimmunity., Materials and Methods: Peripheral blood mononuclear cells (PBMC) from 36 patients with CLL were cultured in vitro with fludarabine or 2-chlorodeoxyadenosine for 24, 48, and 72 hours., Results: Seven patients (19.4%) presented CD154 expression in PBMC cultured with purine analogues in vitro for 24 and/or 48 hours, while no expression was found when cultured in media alone. These seven patients showed a decreased apoptotic rate in vitro after purine analogues compared with those patients who did not express CD154 (p = 0.01 for fludarabine; p < 0.001 for 2-chlorodeoxyadenosine). CD154 expression was found to have prognostic value for response to fludarabine in vivo and was associated with the development of autoimmune manifestations (odds ratio = 25; 95% confidence interval = 3.5-166.7; p < 0.001)., Conclusion: Our preliminary results suggest that CD154 expression in CLL patients, which may be induced by purine analogues, is associated with resistance to fludarabine and with development of autoimmune manifestations., (Copyright 2010 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc. All rights reserved.)
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- 2010
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22. Monocytes and T lymphocytes contribute to a predominance of interleukin 6 and interleukin 10 in systemic lupus erythematosus.
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Mellor-Pita S, Citores MJ, Castejon R, Yebra-Bango M, Tutor-Ureta P, Rosado S, Andreu JL, and Vargas JA
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- Adolescent, Adult, Case-Control Studies, Cells, Cultured, Female, Humans, Interferon-gamma blood, Interferon-gamma metabolism, Interleukin-10 blood, Interleukin-6 blood, Lupus Erythematosus, Systemic blood, Lupus Erythematosus, Systemic metabolism, Lupus Erythematosus, Systemic therapy, Male, Middle Aged, Monocytes metabolism, T-Lymphocytes metabolism, Tumor Necrosis Factor-alpha blood, Tumor Necrosis Factor-alpha metabolism, Young Adult, Interleukin-10 metabolism, Interleukin-6 metabolism, Lupus Erythematosus, Systemic immunology, Monocytes pathology, T-Lymphocytes pathology
- Abstract
Objective: To investigate the contribution of T lymphocytes and monocytes to cytokine production in systemic lupus erythematosus (SLE)., Methods: Forty-five SLE patients and 19 healthy volunteers were included. Serum levels of tumor necrosis factor alpha (TNFalpha), interferon gamma (IFN gamma), interleukin (IL)-6, and IL10 were quantified by ELISA. The cytokine production capacities of peripheral blood mononuclear cells were assessed by culturing in vitro with PMA+Ionomycin or LPS. The intracellular cytokine expression was measured by flow cytometry in T lymphocytes and monocytes, respectively. The influence of the disease activity (measured as the SLE-disease activity index; SLEDAI) and the treatment the patients were receiving was evaluated., Results: Serum IL10, IL6, and TNFalpha levels were increased in patients (P
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- 2009
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23. Induction of foxP3+ regulatory T cells in the periphery of T cell receptor transgenic mice tolerized to transplants.
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Cobbold SP, Castejon R, Adams E, Zelenika D, Graca L, Humm S, and Waldmann H
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- Amino Acid Sequence, Animals, Antibodies, Monoclonal administration & dosage, Antibodies, Monoclonal pharmacology, CD4 Antigens immunology, Cell Division genetics, Cell Division immunology, Clonal Deletion genetics, Clone Cells, DEAD-box RNA Helicases, Female, Glucocorticoid-Induced TNFR-Related Protein, Growth Inhibitors pharmacology, Lymphocyte Activation genetics, Male, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mice, Knockout, Mice, Transgenic, Minor Histocompatibility Antigens, Molecular Sequence Data, Proteins immunology, Receptors, Nerve Growth Factor biosynthesis, Receptors, Tumor Necrosis Factor biosynthesis, Skin Transplantation immunology, T-Lymphocyte Subsets cytology, Transforming Growth Factor beta physiology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, Receptors, Antigen, T-Cell genetics, T-Lymphocyte Subsets immunology, T-Lymphocyte Subsets metabolism, Transplantation Tolerance genetics
- Abstract
Transplantation tolerance can be induced in mice by grafting under the cover of nondepleting CD4 plus CD8 or CD154 mAbs. This tolerance is donor Ag specific and depends on a population of CD4(+) regulatory T cells that, as yet, remain poorly defined in terms of their specificity, origin, and phenotype. Blocking of the Ag-specific response in vitro with an anti-CD4 mAb allowed T cells from monospecific female TCR-transgenic mice against the male Ag Dby, presented by H-2E(k), to express high levels of foxP3 mRNA. foxP3 induction was dependent on TGF-beta. The nondepleting anti-CD4 mAb was also able to induce tolerance in vivo in such monospecific TCR-transgenic mice, and this too was dependent on TGF-beta. As in conventional mice, acquired tolerance was dominant, such that naive monospecific T cells were not able to override tolerance. Splenic T cells from tolerant mice proliferated normally in response to Ag, and secreted IFN-gamma and some IL-4, similar to control mice undergoing primary or secondary graft rejection. High levels of foxP3 mRNA, and glucocorticoid-induced TNFR superfamily member 18 (GITR)(+) CD25(+) T cells were found within the tolerated skin grafts of long-term tolerant recipients. These data suggest that regulatory T cells maintaining transplantation tolerance after CD4 Ab blockade can be induced de novo through a TGF-beta-dependent mechanism, and come to accumulate in tolerated grafts.
- Published
- 2004
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24. Regulatory T cells and dendritic cells in transplantation tolerance: molecular markers and mechanisms.
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Cobbold SP, Nolan KF, Graca L, Castejon R, Le Moine A, Frewin M, Humm S, Adams E, Thompson S, Zelenika D, Paterson A, Yates S, Fairchild PJ, and Waldmann H
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- Animals, Antigens, CD immunology, Gene Expression Profiling, Humans, Dendritic Cells immunology, Dendritic Cells metabolism, T-Lymphocytes immunology, T-Lymphocytes metabolism, Transplantation Tolerance immunology
- Abstract
Transplantation tolerance can be induced in adult rodents using monoclonal antibodies against coreceptor or costimulation molecules on the surface of T cells. There are currently two well-characterized populations of T cells, demonstrating regulatory capacity: the "natural" CD4+CD25+ T cells and the interleukin (IL)-10-producing Tr1 cells. Although both types of regulatory T cells can induce transplantation tolerance under appropriate conditions, it is not clear whether either one plays any role in drug-induced dominant tolerance, primarily due to a lack of clear-cut molecular or functional markers. Similarly, although dendritic cells (DCs) can be pharmacologically manipulated to promote tolerance, the phenotype of such populations remains poorly defined. We have used serial analysis of gene expression (SAGE) with 29 different T-cell and antigen-presenting cell libraries to identify gene-expression signatures associated with immune regulation. We found that independently derived, regulatory Tr1-like clones were highly concordant in their patterns of gene expression but were quite distinct from CD4+CD25+ regulatory T cells from the spleen. DCs that were treated with the tolerance-enhancing agents IL-10 or vitamin D3 expressed a gene signature reflecting a functional specification in common with the most immature DCs derived from embryonic stem cells.
- Published
- 2003
- Full Text
- View/download PDF
25. Does a critical hemodynamic situation develop from right ventriculotomy and free wall infarct or from small changes in dysfunctional right ventricle afterload?
- Author
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Fantidis P, Castejon R, Fernández Ruiz A, Madero-Jarabo R, Cordovilla G, and Sanz Galeote E
- Subjects
- Animals, Constriction, Dogs, Models, Cardiovascular, Myocardial Infarction complications, Pulmonary Artery physiopathology, Tricuspid Valve Insufficiency complications, Ventricular Function, Right, Heart Failure etiology, Heart Ventricles surgery, Hemodynamics, Myocardial Infarction physiopathology, Tricuspid Valve Insufficiency physiopathology
- Abstract
An experimental model for right ventricle free wall infarct associated with double ventriculotomy and tricuspid insufficiency was created to evaluate whether right ventricle failure can cause profound refractory heart failure or whether modifications in right ventricular afterload are more influential in this regard. In our model, the left ventricle, interventricular septum and right atrial wall were maintained intact and pulmonary banding made it possible to modify right ventricular afterload during the experiment. The results of our study showed that pure right ventricular failure does affect the hemodynamic state negatively, but it is not itself, a cause of death in dogs. A slight increase in the dysfunctional right ventricular afterload produced a profound deterioration in the hemodynamic state that required pulmonary artery debanding within no more than 10 minutes.
- Published
- 1992
26. Electrophysiologic changes during acute rejection of heterotopically transplanted rat hearts.
- Author
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Castejon R, Gamallo C, Cabo J, Diez-Pardo JA, Ruiz MR, and Cordovilla G
- Subjects
- Abdomen, Animals, Electrodes, Implanted, Electrophysiology, Female, Male, Myocardial Contraction physiology, Rats, Rats, Inbred Strains, Electrocardiography methods, Graft Rejection physiology, Heart Conduction System physiology, Heart Transplantation physiology, Signal Processing, Computer-Assisted, Transplantation, Heterotopic physiology
- Abstract
Noninvasive monitoring of heart allograft rejection was performed by electrophysiologic techniques using an implanted electrode located on the epicardial surface of the heterotopic transplanted heart of rats. R wave and slew rate determinations were performed daily in 30 syngeneic and 66 allogeneic transplants. These determinations were later compared with histopathologic studies of the transplanted hearts. R wave and slew rate values of allogeneic or rejecting hearts were found to decrease significantly compared with syngeneic or nonrejecting hearts on the days studied. This noninvasive electrophysiologic method may be a promising method for monitoring heart allograft rejection.
- Published
- 1991
27. An experimental study of lymphatic vessel autotransplantation in the dog.
- Author
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Castejon R, Gamallo C, and Jimenez-Cossio J
- Subjects
- Animals, Dogs, Lymphatic System surgery, Lymphedema surgery, Transplantation, Autologous, Lymphatic System physiology
- Abstract
To provide greater insight into microsurgical treatment of lymphedema, 7 mongrel dogs underwent autotransplantation of a lymphatic collector into the contralateral lower limb. Two months later, lymphatic vessels were studied using patent blue dye, light microscopy, and histomorphometry. Patency of the transplanted lymphatics was uniformly observed although there was a notable increase in the width of the intima and a corresponding reduction in the size of the lymphatic lumen. Of note, there was a striking absence of inflammatory infiltrate at the recipient site.
- Published
- 1990
28. Electrophysiological and anatomical findings in heart transplantation: experimental study.
- Author
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Castejon R, Cabo J, Gamallo C, Diez-Pardo JA, and Cordovilla G
- Subjects
- Abdomen, Animals, Cardiac Pacing, Artificial, Cell Count, Organ Size, Rats, Rats, Inbred F344, Rats, Inbred Lew, Rats, Inbred Strains, Sensitivity and Specificity, Electrocardiography, Graft Rejection physiology, Heart physiopathology, Heart Transplantation physiology, Myocardium pathology, Transplantation, Heterotopic
- Abstract
The diagnosis of acute rejection by electrophysiological methods is based on the fact that signs of rejection such as inflammatory infiltrate, interstitial edema, and mostly myocyte necrosis lead to obligated alterations in electrophysiological properties of the myocardium. In a total of 276 heterotopic abdominal transplants in rats, a noninvasive monitoring of heart allograft rejection by conventional ECG and electrophysiological techniques was performed. The correlation of these findings with pathological studies, including histologic determination of the degree of acute rejection, analysis of weight and cardiac perimeter, and volumetric cell density were also evaluated in 96 of them, 66 were allogeneic and 30 syngeneic. Sensitivity and specificity of the R wave and slew rate was also determined with respect to the Billingham classification. Results of the correlation analysis showed that electrophysiological variations in R wave and slew rate correlated more intensely with changes in volumetric cell density. The greatest sensitivity and specificity was observed in R wave changes in relation to the Billingham classification.
- Published
- 1990
- Full Text
- View/download PDF
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