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1.
Encephale ; 41(4 Suppl 1): S50-5, 2015 Sep.
Artículo en Francés | MEDLINE | ID: mdl-26746323

RESUMEN

OBJECTIVE: Group debriefing has been a topic of controversy regarding its temporal dimension. What is the opportune time for using this communication device and when is it the most effective? In practice, group debriefing is generally used after the fact, in post-event interventions. What is the rationale for delaying the debriefing process? Debriefing follows a logical progression that goes from evocation of the event to the expression of a possible future. How should one view this progression in relation to the subject's logical temporality? Finally, are the temporalities of the subjects and the group compatible? The objective of this paper is to show that one of the particularities of group debriefing is that it associates group temporality and subjective logical time. METHODOLOGY: This study describes the temporal modalities of group debriefing practiced at the Emergency Medical-Psychological Unit of the Ille-et-Vilaine Department of France, based on the analysis of a clinical case. The debriefing situation presented here took place in a firm following a suicide. Four female employees of the firm saw the body of a person committing suicide as it fell from the higher floors of the building. The psychoanalytic research on subjective time, used as a basis for this study, points out two dimensions of time, prograde and retrograde. Retrograde time produces a feedback effect via which the subject reorganizes his/her past. Psychoanalysis also describes a logical time specific to each subject, which can be broken down into three time frames: seeing, understanding, and concluding. In group debriefing, the time course is group-specific. RESULTS: We show that the subjects' temporality is interconnected with the temporal progression of the group during debriefing. We present some elements showing how subjective and group positioning evolved in relation to the shared temporal unfolding of the debriefing. The debriefing consisted of three time frames. The first involved evoking the tragic experience of the event; it brought out the common points in the women's experience of the event, and a solution of "withdrawal" as a protection mechanism. Individual experiences, such as the desire to avoid or see the scene, or the ability or inability to call for help, were also present. The second time frame pertained to the symptomatology and subsequent experience of the event; here, we observed evocation of similar symptoms among some of the participants but also after the event, depending on individual subjectivity. The relationship to the event was also addressed in terms of the ability or inability of each individual to cope with the event and overcome it. The third time frame involved projection into the future; a sense of relief became manifest as the debriefing progressed. This third time frame permitted evocation of a possible way of "breaking away" from the event, linked to each person's history and connected in particular to the relationship with death evoked during the second time frame. The debriefing also helped in acknowledging the pain brought about by the traumatic event, a beneficial factor in psychic processing. CONCLUSION: Group debriefing articulates subjective time and group time. In practice, debriefing follows chronological time, at the same time as it mobilizes logical time. It brings to bear a double temporality that must be taken into account during both the implementation and unfolding phases of the debriefing process, but also in the objectives set for this device. The clinician-debriefer must consider this double temporality in order to direct the debriefing in a way suited to the clinical implications that justify its use, and must do so with tact and moderation, without imposition on the subjects'individual temporalities and defenses.


Asunto(s)
Intervención en la Crisis (Psiquiatría)/métodos , Servicios Médicos de Urgencia , Servicio de Urgencia en Hospital , Humanos , Factores de Tiempo
2.
Ann Chir Plast Esthet ; 57(4): 350-5, 2012 Aug.
Artículo en Francés | MEDLINE | ID: mdl-21945510

RESUMEN

UNLABELLED: In 10 cases of abdominoplasty where an important rectus diastasis had to be corrected, we completed the plication of the rectus sheath included in a classical abdominoplasty with the laparoscopic positioning of an intraperitoneal prosthesis. PURPOSE: To assess the middle-term results of this technique and present its advantages and drawbacks. PATIENTS AND METHOD: Fifteen patients have been operated from 2007 to 2011 by two surgeon teams. Ten of them have accepted to be included in our survey. RESULTS: All the patients said they were satisfied with their surgery. Four of them reported mild pain during the first postoperative weeks, and two of them mentioned very moderate pain at the time of the survey. The surgeons were not satisfied with the results obtained in two cases. Only one of these two patients accepted revision abdominoplasty with a good result. CONCLUSION: Laparoscopic positioning of an intraperitoneal prosthesis, coupled with a classical plication of the rectus sheath, gives excellent results in difficult cases of rectus diastasis.


Asunto(s)
Abdominoplastia/métodos , Laparoscopía/métodos , Enfermedades Musculares/cirugía , Recto del Abdomen , Adulto , Femenino , Humanos , Persona de Mediana Edad
3.
Prog Urol ; 21(12): 859-65, 2011 Nov.
Artículo en Francés | MEDLINE | ID: mdl-22035912

RESUMEN

PURPOSE: Cell therapy for urinary incontinence management has been experienced in animals with encouraging results, but studies in human beings are lacking. Our primary objective was to assess the safety of intrasphincteric injections of autologous muscular cells in patients with postprostatectomy incontinence (PPI). Secondary objectives focused on complications efficacy. METHODS: We conducted an open, prospective study in a single center on 12 patients presenting PPI. Patients underwent intrasphincteric injections of autologous muscular cells isolated from a biopsy of deltoid muscle. The primary endpoint was the Q(max) variation at the three month visit in order to assess potential bladder outlet obstruction. Secondary endpoints assessed side effects and efficacy parameters based on symptoms, quality of life score, voiding diary, pad-test, and urethral pressure profile at one, two, three, six and 12 months after injection. RESULTS: No immediate complication occurred and no significant variation was noted on Q(max). The only side effects possibly product-related were three cases of urinary tract infection treated by antibiotics. An acceptable safety and tolerability of the procedure whatever the injected dose of muscular cells was demonstrated. Results on efficacy after one year were heterogeneous, with 4/12 patients describing reduced urine leakage episodes, 1/12 patient presenting increased maximal closure pressure, and 8/12 patients showing improvement on pad-test. CONCLUSIONS: Cell therapy consisting of intrasphincteric injections of autologous muscular cells in patients with PPI was a feasible and safe procedure. The results point out that some subjects may positively respond to this procedure, but clinical efficacy remains to be confirmed.


Asunto(s)
Células Musculares/trasplante , Prostatectomía/efectos adversos , Uretra , Incontinencia Urinaria de Esfuerzo/etiología , Incontinencia Urinaria de Esfuerzo/cirugía , Anciano , Músculo Deltoides , Estudios de Factibilidad , Estudios de Seguimiento , Humanos , Inyecciones Intralesiones , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Medición de Riesgo , Trasplante Autólogo , Resultado del Tratamiento
4.
Ann Chir Plast Esthet ; 55(5): 354-62, 2010 Oct.
Artículo en Francés | MEDLINE | ID: mdl-20869154

RESUMEN

Radiation burn is a determinist effect of localized irradiation. The lesion is in good correlation with absorbed dose. Radiation burn is different from thermal burn. The evolution is spatiotemporal unpredictable with successive inflammatory waves and recurrence of necrosis. The conventional surgical treatment is rarely efficient because each surgical operative act seems to stimulate the inflammatory waves and fibro-necrosis process. The lesion can escape to this conventional surgical treatment. The new therapeutic approach combines surgery and cellular therapy with local administration of autologous mesenchymal stem cells. From 5 years, cell therapy have been an adjuvant treatment of surgery. This association is a therapeutic innovation, it's now the recommendation for conservative surgery of this very serious radiation burn.


Asunto(s)
Quemaduras/terapia , Traumatismos por Radiación/terapia , Adulto , Quemaduras/etiología , Quemaduras/cirugía , Terapia Combinada , Humanos , Masculino , Trasplante de Células Madre Mesenquimatosas , Traumatismos por Radiación/complicaciones , Traumatismos por Radiación/cirugía
5.
Diagn Interv Imaging ; 99(10): 615-624, 2018 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29773346

RESUMEN

PURPOSE: To compare changes in inferior vena cava (IVC) filter positional parameters from insertion to removal and examine how they affect retrievability amongst various filter types. MATERIALS AND METHODS: A total of 447 patients (260 men, 187 women) with a mean age of 55 years (range: 13-91 years) who underwent IVC filter retrieval between 2007-2014 were retrospectively included. Post-insertion and pre-retrieval angiographic studies were assessed for filter tilt, migration, strut wall penetration and retrieval outcomes. ANCOVA and multiple logistic regression models were used to analyze factors affecting retrieval success. Pairwise comparisons between filter types were performed. RESULTS: Of 488 IVC filter retrieval attempts, 94.1% were ultimately successful. The ALN filter had the highest mean absolute value of tilt (5.6 degrees), the Optease filter demonstrated the largest mean migration (-8.0mm) and the Bard G2 filter showed highest mean penetration (5.2mm). Dwell time of 0-90 days (OR, 11.1; P=0.01) or 90-180 days (OR, 2.6; P=0.02), net tilt of 10-15 degrees (OR 8.9; P=0.05), caudal migration of -10 to 0mm (OR, 3.46; P=0.03) and penetration less than 3mm (OR, 2.6; P=0.01) were positive predictors of successful retrievability. Higher odds of successful retrieval were obtained for the Bard G2X, Bard G2 and Cook Celect when compared to the ALN and Cordis Optease filters. CONCLUSION: Shorter dwell time, lower mean tilt, caudal migration and less caval wall penetration are positive predictors of successful IVC filter retrieval.


Asunto(s)
Remoción de Dispositivos , Filtros de Vena Cava , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Angiografía , Femenino , Migración de Cuerpo Extraño/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Diseño de Prótesis , Estudios Retrospectivos , Resultado del Tratamiento , Vena Cava Inferior/diagnóstico por imagen , Adulto Joven
6.
J Clin Invest ; 101(10): 2129-39, 1998 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-9593769

RESUMEN

Airway hyperresponsiveness leading to subepithelial fibrosis is mediated by inflammatory cells activated by T helper (Th) 2-derived cytokines such as IL-4 and IL-5. By analyzing the phenotype and response of human lung fibroblasts derived from either fetal (ICIG7) or adult (CCL202) tissue as well as from a Th2-type stromal reaction (FPA) to IL-4 and IL-13, we provide evidence that human lung fibroblasts may behave as inflammatory cells upon activation by IL-4 and IL-13. We show that the three types of fibroblasts constitute different populations that display a distinct pattern in cell surface molecule expression and proinflammatory cytokine and chemokine release. All fibroblasts express functional but different IL-4/IL-13 receptors. Thus, while IL-4 receptor (R) alpha and IL-13Ralpha1 chains are present in all the cells, CCL202 and FPA fibroblasts coexpress the IL-13Ralpha2 and the IL-2Rgamma chain, respectively, suggesting the existence of a heterotrimeric receptor (IL-4Ralpha/IL-13Ralpha/IL-2Rgamma) able to bind IL-4 and IL-13. Stimulation with IL-4 or IL-13 triggers in the fibroblasts a differential signal transduction and upregulation in the expression of beta1 integrin and vascular cell adhesion molecule 1 and in the production of IL-6 and monocyte chemoattractant protein 1, two inflammatory cytokines important in the pathogenesis of allergic inflammation. Our results suggest that when activated by IL-4 and IL-13, different subsets of lung fibroblasts may act as effector cells not only in the pathogenesis of asthma but also in lung remodeling processes. They may also differentially contribute to trigger and maintain the recruitment, homing, and activation of inflammatory cells.


Asunto(s)
Interleucina-13/farmacología , Interleucina-4/farmacología , Antígenos de Superficie/inmunología , Asma/fisiopatología , Moléculas de Adhesión Celular/análisis , Línea Celular , Quimiocinas/metabolismo , Reactivos de Enlaces Cruzados/metabolismo , Citocinas/metabolismo , Citometría de Flujo , Regulación de la Expresión Génica/genética , Humanos , Hipersensibilidad/fisiopatología , Inflamación/fisiopatología , Subunidad alfa1 del Receptor de Interleucina-13 , Pulmón , Fenotipo , Fosfotirosina/análisis , ARN Mensajero/análisis , Receptores de Interleucina/metabolismo , Receptores de Interleucina-13 , Receptores de Interleucina-4/metabolismo
7.
Oncogene ; 19(51): 5898-905, 2000 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-11127821

RESUMEN

IL-4 and IL-13 act on human lung fibroblasts through specific receptors differing in their composition. Indeed, the gammac chain is constitutively expressed in tumor lung myofibroblast but not in normal cells. Here, we have analysed the signal transduction induced by IL-4 and IL-13 in both cell types, in order to better understand the molecular mechanisms underlying tumor stromal development. The IL-4Ralpha chain is constitutively phosphorylated and pre-associated with the JAK1 protein in both cell types. In normal cells, we detected the activation of the classic IRS-2 or JAK1/STAT6 pathways, the phosphorylation of JAK2, while Tyk2 was constitutively phosphorylated and not modified by both cytokines. In addition to these pathways, in lung tumor myofibroblasts, IL-4 and IL-13 induced the phosphorylation of JAK3 and increased the phosphorylation of Tyk2. Interestingly, in both cell types IL-4 and IL-13 triggered an unusual pattern of STAT1 and STAT3 activation. These events probably correspond to a tissue-specific signaling important for the immunoregulatory functions of airways fibroblasts. Indeed, the inflammatory-like pattern of STATs signaling triggered by IL-4 and IL-13 in these cells may favor the homing of inflammatory and/or metastatic cells. In lung myofibroblasts, these properties could be modified through the different pattern of JAK activation.


Asunto(s)
Interleucina-13/farmacología , Interleucina-4/farmacología , Neoplasias Pulmonares/metabolismo , Pulmón/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas de Unión al ADN/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Fibroblastos/metabolismo , Humanos , Proteínas Sustrato del Receptor de Insulina , Péptidos y Proteínas de Señalización Intracelular , Janus Quinasa 1 , Pulmón/citología , Pulmón/efectos de los fármacos , Neoplasias Pulmonares/enzimología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/fisiología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Fosfoproteínas/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Tirosina Quinasas/metabolismo , Receptores de Interleucina-4/metabolismo , Factor de Transcripción STAT1 , Factor de Transcripción STAT3 , Factor de Transcripción STAT6 , Transducción de Señal/fisiología , Transactivadores/metabolismo
8.
Oncogene ; 12(5): 1015-23, 1996 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-8649792

RESUMEN

Human melanomas may express both in vivo and in vitro functional IL-Rs and may be expected to directly respond to injected IL2. This may generate biological situations which may be favourable for the patient, but also for tumor progression. Here, we analyse the latter hypothesis. MELP is a melanoma cell line derived from a patient whose metastasis increased in size during IL2/IFN alpha biotherapy [correction of biotheraphy]. These cells have been characterized in vitro for their phenotype and for their sensitivity to IL2. In vitro MELP cells express an IL2-R alpha(+) beta(+) gamma(-) phenotype and IL2 treatment induces the acquisition of new functional characteristics represented (i) by the increased surface expression of two markers of metastatic evolution (ICAM-1 and CD44); (ii) by the stable induction of the IL2-R gamma with the appearance of functional IL2-R beta complex, which are also recognized by GM-CSF; (iii) by the inhibition of transcription of a regulatory cytokine such as IL6; (iv) by a differential effect of IL6 on CD44 surface expression in MELP cells treated or not with IL2 (MILG cells); (v) by the acquisition of faster growth rates and appearance of piling up and multilayer cellular organization; (vi) by the development of rapidly growing tumors in nude mice. IL2 induces in MELP cells a tumor progression process that could mimic the metastatic evolution observed in vivo during biotherapy. Therefore, MELP phenotype may help to define a subset of patients in which IL2 therapy may trigger unfavourable evolution.


Asunto(s)
Interleucina-2/farmacología , Melanoma/patología , Adulto , Animales , Antígenos de Neoplasias/análisis , División Celular/efectos de los fármacos , Citocinas/metabolismo , Progresión de la Enfermedad , Humanos , Receptores de Hialuranos/análisis , Molécula 1 de Adhesión Intercelular/análisis , Interleucina-2/uso terapéutico , Interleucina-6/metabolismo , Masculino , Melanoma/química , Melanoma/metabolismo , Melanoma/secundario , Melanoma/terapia , Ratones , Ratones Desnudos , Receptores de Interleucina-2/análisis , Receptores de Interleucina-2/química , Transcripción Genética , Células Tumorales Cultivadas
9.
Oncogene ; 16(19): 2503-12, 1998 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-9627116

RESUMEN

IL-15 is a novel cytokine active through the IL-2R/betagamma. Since several human melanoma cell lines display functional IL-2Rs, we studied the IL-15/melanoma cells interactions. Ten out of 17 melanoma cell lines express the IL-15 transcript and four of them express levels of IL-15 mRNA similar to those detected in control activated monocytes. Nine out of ten cell lines also express two transcripts for the IL-15R alpha originated by the alternative splicing of exon'3'. Two melanoma cell lines, MELP and MELREO, derived from patients with rapidly progressive primary melanomas, co-express the two IL-15 transcripts, originated by alternative splicing of exon 'A'. Intracellular IL-15 protein was only detected in these two cells lines and it is mainly retained in the Endoplasmic Reticulum (ER). However, a small amount of IL-15 is also found in the Golgi apparatus and in the early endosomes, suggesting production and intercellular trafficking of endogenous IL-15 protein. Nevertheless, no biologically active IL-15 could be detected in the supernatant of all melanoma cells. The anti IL-15 blocking mAb M111 causes the up regulation of HLA Class I in dense MELP and MELREO cultures. These data suggest that IL-15 is probably active through juxtacrine loops negatively controlling HLA Class I molecules expression. These data offer, for the first time, a likely explanation to the controversial issue of IL-15 secretion and constitute a natural model for understanding IL-15 routing. Moreover, we identify a subset of melanoma cells producing IL-15, possibly involved in tumor escape mechanisms.


Asunto(s)
Interleucina-15/metabolismo , Melanoma/metabolismo , Biomarcadores de Tumor , Medios de Cultivo , Progresión de la Enfermedad , Citometría de Flujo , Antígenos de Histocompatibilidad Clase I/biosíntesis , Humanos , Interleucina-15/genética , Melanoma/genética , Melanoma/fisiopatología , Microscopía Confocal , Reacción en Cadena de la Polimerasa/métodos , ARN , Receptores de Interleucina-15 , Receptores de Interleucina-2/genética , Células Tumorales Cultivadas
10.
Stem Cells Dev ; 14(2): 204-12, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15910247

RESUMEN

Bone marrow-derived mesenchymal stem cells (MSCs) are known to interact with hematopoietic stem cells (HSCs) and immune cells, and are of potential interest to be used as therapeutic agents for enhancing allogenic hematopoietic engraftment and preventing graft-versus-host disease (GVHD). Galectin 1 (Gal1) belongs to a family of structurally related molecules expressed in many vertebrate tissues that exert their functions both by binding to glycoconjugates, and by interaction with protein partners. In this work using a proteomic approach, we looked for the presence and the localization of Gal1 in short- and long-term culture of human (h) hMSC. We first determined, that Gal1 is one of the major proteins expressed in hMSC. We futher demonstrated that its expression is maintained when hMSC are expanded through a subculturing process up to five passages. Moreover, Gal1 is secreted and found at the cell surface of MSC, participating in extra cellular matrix (ECM)-cell interactions. Given the immunomodulatory properties of Gal1, its potential involvement in immunological functions of hMSC could be suggested.


Asunto(s)
Galectina 1/biosíntesis , Células Madre Mesenquimatosas/citología , Proteómica/métodos , Secuencia de Aminoácidos , Anticuerpos Monoclonales/química , Western Blotting , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Diferenciación Celular , Membrana Celular/metabolismo , Proliferación Celular , Células Cultivadas , Electroforesis en Gel Bidimensional , Matriz Extracelular/metabolismo , Citometría de Flujo , Células Madre Hematopoyéticas/citología , Humanos , Procesamiento de Imagen Asistido por Computador , Inmunofenotipificación , Datos de Secuencia Molecular , Unión Proteica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Factores de Tiempo
11.
Arterioscler Thromb Vasc Biol ; 21(8): 1353-8, 2001 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-11498465

RESUMEN

Hypercholesterolemia is frequently associated with elevated Lp(a) levels, an independent risk factor for coronary, cerebrovascular, and peripheral vascular disease. A portion of apolipoprotein(a) [apo(a)] circulates as a series of fragments derived from the N-terminal region of apo(a). The relationship of elevated lipoprotein(a) [Lp(a)] levels to those of circulating apo(a) fragments in polygenic hypercholesterolemia is indeterminate. Therefore, plasma Lp(a) and plasma and urinary apo(a) fragment levels were measured by ELISA in 82 patients with polygenic type IIa hypercholesterolemia (low density lipoprotein cholesterol >/=4.13 mmol/L and triglycerides <2.24 mmol/L) and in 90 normolipidemic subjects. Lp(a) levels were significantly elevated in patients compared with control subjects (0.35+/-0.4 and 0.24+/-0.31 mg/mL, respectively; median 0.13 and 0.11 mg/mL, respectively; P=0.039), although apo(a) isoform distribution did not differ. Patients displayed significantly higher plasma and urinary apo(a) fragment levels than did control subjects (respective values were as follows: 4.97+/-5.51 and 2.15+/-2.57 [median 2.85 and 1.17] microg/mL in plasma, P<0.0001; 75+/-86 and 40+/-57 [median 38 and 17] ng/mg urinary creatinine in urine, P<0.0001). The ratio of plasma apo(a) fragments to Lp(a) levels was also significantly higher in patients than in control subjects (1.93+/-1.5% and 1.75+/-2.36%, respectively; P<0.0001). We conclude that increased plasma Lp(a) levels in polygenic hypercholesterolemia are associated with elevated circulating levels of apo(a) fragments but that this increase is not due to decreased renal clearance of apo(a) fragments. Furthermore, we identified a new pattern of apo(a) fragmentation characterized by the predominance of a fragment band whose size was related to that of the parent apo(a) isoform and that was superimposed on the series of fragments described previously by Mooser et al (J Clin Invest. 1996; 98:2414-2424). This new pattern was associated with small apo(a) isoforms and did not discriminate between hypercholesterolemic and normal subjects. However, this new apo(a) fragment pattern may constitute a novel marker for cardiovascular risk.


Asunto(s)
Apolipoproteínas A/química , Hipercolesterolemia/metabolismo , Adolescente , Adulto , Anciano , Apolipoproteínas A/sangre , Apolipoproteínas A/orina , Femenino , Humanos , Lípidos/sangre , Lipoproteína(a)/sangre , Masculino , Persona de Mediana Edad , Isoformas de Proteínas
12.
Atherosclerosis ; 34(3): 233-41, 1979 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-574769

RESUMEN

Four groups of rats were fed, for 45 days, one of the following semipurified diets containing sucrose 55% (w/w) and (a) casein 25%, (b) casein 24%, saponins (from Saponaria officinalis) 1%, (c) isolated soy protein 25%, (d) soy protein 24%, saponins 1%. The soy protein diet, compared to the casein one, produced an increase in the fecal excretion of neutral sterols on the 29th and 42nd days, without any modification in the liver, aorta and serum cholesterol concentrations. The effect of soy protein cannot be attributed to its saponin content but other substances associated to soy protein may interfere. With the casein diet, added saponins increased the fecal excretion of neutral sterols and bile acids and decreased liver and aorta cholesterol levels. Serum cholesterol was found unchanged. The effects of saponins were suppressed or greatly reduced with the soy protein diet. These results could be explained by binding of the sterols in insoluble forms.


Asunto(s)
Colesterol/metabolismo , Proteínas en la Dieta/farmacología , Saponinas/farmacología , Esteroles/metabolismo , Animales , Aorta/metabolismo , Ácidos y Sales Biliares/metabolismo , Caseínas/farmacología , Colesterol/sangre , Dieta , Heces/análisis , Hígado/metabolismo , Masculino , Ratas , Glycine max
13.
Atherosclerosis ; 118(1): 135-43, 1995 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-8579623

RESUMEN

Nonenzymatic glycation of lipoprotein may contribute to the premature atherogenesis of patients with diabetes mellitus by diverting lipoprotein catabolism from non-atherogenic to atherogenic pathways. It has been demonstrated that the proportion of apolipoprotein B-100 (apo B-100) in glycated form is significantly higher in diabetic patients than in non-diabetic controls, and equally that plasma lipoprotein(a) Lp(a) levels may be increased in diabetic patients. Consequently, we have evaluated the glycation of Lp(a) in vitro and in vivo, by use of a combination of m-aminophenylboronate affinity chromatography and enzyme-linked immunosorbent assay (ELISA) for apo B-100 and Lp(a). In vitro studies were performed on normolipodemic plasma samples containing elevated concentrations of Lp(a). These studies establish that Lp(a) can be glycated in vitro in the presence of high concentrations of glucose, although to a lesser extent than low density lipoprotein (LDL) (15.8% +/- 4.4% and 30.2% +/- 5.4% (P = 0.0001) after a 48 h incubation at 37 degrees C, respectively). We have also shown that apo B-100 was more glycated than apo(a) in the Lp(a) particle. In vivo studies have shown that the percentage of glycated Lp(a) in diabetic patients was significantly higher than in the control population (2.8% +/- 1.07% versus 2.0% +/- 0.43%, P = 0.017). The level of glycated Lp(a) is also positively correlated with that of HbA1c in diabetic patients (r=0.6, P=0.002). Since our results show that Lp(a) is less susceptible to glycation than LDL, we speculate that glycation of LDL may be more relevant to the cardiovascular risk associated with this particle than with Lp(a).


Asunto(s)
Lipoproteína(a)/metabolismo , Apolipoproteína B-100 , Apolipoproteínas B/metabolismo , Diabetes Mellitus/metabolismo , Ensayo de Inmunoadsorción Enzimática , Glicosilación , Humanos , Técnicas In Vitro , Lipoproteínas LDL/metabolismo
14.
Atherosclerosis ; 136(2): 389-94, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9543111

RESUMEN

Epidemiological studies have shown lipoprotein(a) (Lp(a)) to be an independent risk factor for cardiovascular disease. Lp(a) is a cholesterol-rich, low-density lipoprotein (LDL)-like particle to which a large glycoprotein, apolipoprotein(a) (apo(a)) is attached. Plasma Lp(a) levels are highly genetically determined and influenced to a minor degree by environmental factors. In an effort to determine whether Lp(a) might be associated with longevity, we have evaluated Lp(a) levels and apo(a) isoform sizes in a population of French centenarians (n = 109) compared to a control group (n = 227). The mean age of centenarians was 101.5 +/- 2.4 years while the control group was 39.4 +/- 7.2 years. Plasma levels of total cholesterol and triglyceride were within the normal range in both centenarian and control subjects. Lp(a) levels were higher in centenarians (both male and female) than in the normolipidemic control group (mean Lp(a) level = 0.33 +/- 0.42 and 0.22 +/- 0.27 mg/ml, respectively, P < 0.005). The distribution of apo(a) isoforms was significantly shifted towards small isoform size in the centenarian population as compared to the controls (54.4 and 41.4% of isoforms < or = 27 kringles (kr), respectively, P = 0.04). Nonetheless, the apo(a) size distribution in centenarians did not entirely explain the high Lp(a) levels observed in this population. Factors other than apo(a) size, and which may be either genetic or environmental in nature, appear to contribute to the elevated plasma Lp(a) levels of our centenarian population. We conclude therefore that high plasma Lp(a) levels are compatible with longevity.


Asunto(s)
Apolipoproteínas A/sangre , Lipoproteína(a)/sangre , Longevidad , Adulto , Anciano , Anciano de 80 o más Años , Colesterol/sangre , Femenino , Francia , Humanos , Masculino , Triglicéridos/sangre
15.
J Med Chem ; 42(20): 4161-71, 1999 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-10514286

RESUMEN

Pyridyl esters of 6-substituted 2-oxo-2H-1-benzopyran-3-carboxylic acid were designed as mechanism-based inhibitors of human leukocyte elastase. Compounds of series 4 specifically inhibited this enzyme. Several of the tested compounds (series 2 and 3) acted as powerful time-dependent inhibitors of both human leukocyte elastase and alpha-chymotrypsin; some compounds of these series inhibited thrombin. Trypsin was not inhibited. A transient inactivation was observed for human leukocyte elastase (k(i)/K(I) = 107 000 M(-1). s(-1) for 4c) and thrombin (k(i)/K(I) = 7 200 M(-1).s(-1) for 3b) as demonstrated by spontaneous or hydroxylamine-accelerated reactivation, irrespective of the nature of the substituent at the 6-position. Conversely, alpha-chymotrypsin was irreversibly inhibited by 6-chloromethyl derivatives (k(i)/K(I) = 107 400 M(-1). s(-1) for 3b). The presence of a latent alkylating function at the 6-position (chloromethyl group) was required for leading to this inactivation. In the absence of such an alkylating function (series 4), human leukocyte elastase was specifically inhibited suggesting that this new series of human leukocyte elastase inhibitors may be of potential therapeutic interest in degradative and degenerative processes involving this enzyme.


Asunto(s)
Cumarinas/síntesis química , Inhibidores Enzimáticos/síntesis química , Elastasa de Leucocito/antagonistas & inhibidores , Cromatografía Líquida de Alta Presión , Cumarinas/química , Inhibidores Enzimáticos/química , Humanos , Cinética , Relación Estructura-Actividad
16.
J Med Chem ; 39(13): 2579-85, 1996 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-8691456

RESUMEN

A series of esters and amides of 6-(chloromethyl)-2-oxo-2H-1-benzopyran-3-carboxylic acid were synthesized and evaluated in vitro for their inhibitory activity toward bovine alpha-chymotrypsin and human leukocyte elastase. Both series behaved as time-dependent inhibitors of alpha-chymotrypsin, but ester-type coumarins were clearly more efficient than the corresponding amides in inactivating the serine proteinase. The best inactivations were observed with "aromatic" esters, in particular with meta-substituted phenyl esters such as m-chlorophenyl 6-(chloromethyl)-2-oxo-2H-1-benzopyran-3-carboxylate, which appears to be one of the most powerful inactivators of alpha-chymotrypsin yet reported (kinact/KI = 760,000 M-1 S-1 at pH 7.5 and 25 degrees C). Usually, the coumarin derivatives failed to inhibit significantly human leukocyte elastase. As a result, the reported series of aromatic coumarinic esters behaves as a new chemical family of selective alpha-chymotrypsin inhibitors.


Asunto(s)
Benzopiranos/síntesis química , Benzopiranos/farmacología , Quimotripsina/antagonistas & inhibidores , Inhibidores de Serina Proteinasa/síntesis química , Inhibidores de Serina Proteinasa/farmacología , Animales , Benzopiranos/química , Bovinos , Humanos , Cinética , Elastasa de Leucocito , Espectroscopía de Resonancia Magnética , Estructura Molecular , Elastasa Pancreática/antagonistas & inhibidores , Inhibidores de Serina Proteinasa/química , Relación Estructura-Actividad
17.
Melanoma Res ; 7 Suppl 2: S7-17, 1997 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9578412

RESUMEN

MELP is an interleukin (IL)-2 receptor (IL-2R; alpha+ beta+ gamma-) melanoma cell line that was derived, before the beginning of the immunotherapy, from a patient whose metastasis increased in size during treatment with IL-2/interferon-alpha. In these cells, continuous culture in the presence IL-2 (1000 UI/ml) causes the selection of a cell sub-line (termed MILG) expressing the gamma-chain which is tumorigenic in nude mice. Here, we further analysed the characteristics of MELP and MILG cells as well as clones selected at limiting dilution in the presence of high concentrations of IL-2 or IL-15, or those selected after transfection for the expression of a human IL-2 transgene (MELP-CL1). MELP cells, but not six other melanomas cell lines, shed two soluble immunosuppressive molecules, CD25 and intercellular adhesion molecule-1, whose levels also strongly increase in vivo during immunotherapy. In vitro MELP cells express transcripts for IL-6, transforming growth factor, basic fibroblast growth factor and vascular-endothelial growth factor. Cloning at limiting dilution was obtained in culture fed with IL-2 or IL-15. All these clones, as MILG cells, express the transcript for the IL-2R gamma chain. This could favour improved interactions with cytokines using this chain. By contrast, MELP-CL1 cells, which secrete low amounts of biologically active IL-2 (200 UI/10(6) cells) exhibit a phenotype and growth characteristics similar to those of the parental MELP cells. Indeed, a crosslinking experiment with 125I-IL-2, has showed that MELP and MELP-CL1 cells display a scant IL-2 binding ability that is strongly increased in MELP cells fed for 1 week with 1000 UI/ml IL-2. These cells, as well as MILG cells express a betagamma-complex which can also bind IL-15. IL-2 induces a rapid tyrosine phoshorylation in MILG cells, which is followed by a prolonged induction of c-fos and c-jun genes. By contrast, in MELP cells IL-2 only causes a delayed induction of c-myc gene. All MELP derivatives, but not MILG cells, express the transcripts for IL-15, which is not secreted but is present as an intracellular protein. All MELP cells express the transcript for the IL-15R alpha chain. MELP-CL1 cells are not tumorigenic in nude mice, whereas MILG cells form rapidly growing tumours in 75% of the mice. Coinjection at the same site of MILG and MELP-CL1 cells causes the rapid regression of MILG tumours in 80% of the mice, whereas their bilateral injection causes the rapid development of MILG tumours in 100% of the nude mice. Finally, treatment in nude mice of MILG cells with low amounts of IL-2 (1000 UI per mouse) and IL-15 (50 ng per mouse) induces the development of much more aggressive tumours.The expression of functional IL-2Rs in a subset of human melanomas could be responsible for tumour progression.


Asunto(s)
Interleucina-15/fisiología , Interleucina-2/fisiología , Melanoma/tratamiento farmacológico , Melanoma/patología , Adulto , Animales , Citocinas/biosíntesis , Progresión de la Enfermedad , Humanos , Molécula 1 de Adhesión Intercelular/biosíntesis , Interleucina-15/biosíntesis , Interleucina-15/farmacología , Interleucina-2/biosíntesis , Interleucina-2/farmacología , Radioisótopos de Yodo , Masculino , Melanoma/metabolismo , Ratones , Ratones Desnudos , Trasplante de Neoplasias , Reacción en Cadena de la Polimerasa , Receptores de Citocinas/biosíntesis , Receptores de Interleucina-2/biosíntesis , Proteínas Recombinantes/farmacología , Transcripción Genética , Transfección , Células Tumorales Cultivadas
18.
J Pers Soc Psychol ; 78(5): 956-64, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10821201

RESUMEN

Individual differences in cognitive processing speed and response execution were examined in relation to extraversion. Event-related potentials (ERPs) were recorded concurrently with reaction time and movement time (MT) measures as participants (N = 67) performed simple reaction time and stimulus-response compatibility tasks. Slower processing speed for extraverts, as indicated by longer latency of a late positive ERP wave, P3, was only evident in conditions in which stimulus information was in conflict with response selection demands. As previously reported, the salient effect in all conditions of both tasks was faster MT for extraverts, an effect that is indicative of differences in fundamental motor processes. On the simple reaction time task, amplitudes of the N1 component, an early negative ERP wave, were smaller for extraverts than for introverts in response to auditory tones, an effect that affirms the enhanced sensory reactivity of introverts to punctate physical stimuli.


Asunto(s)
Cognición , Potenciales Evocados , Extraversión Psicológica , Adolescente , Adulto , Señales (Psicología) , Electroencefalografía , Femenino , Humanos , Masculino , Tiempo de Reacción
19.
Eur J Clin Nutr ; 45(6): 281-6, 1991 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-1915201

RESUMEN

Institutionalized aged subjects, considered free of evolutive disease and whose body weight was stable, were studied. They were divided into two groups depending on their body mass index: controls (BMI greater than or equal to 24) and depleted (BMI less than or equal to 21). The depleted group, as judged by anthropometric measurements, showed dramatically reduced body muscle and adipose masses. Usual blood parameters were normal in both groups. Biochemical markers of the protein and energy status, viz. albumin, transthyretin, transferrin, somatomedin-C, as well as serum levels of osteocalcin and apolipoproteins AI, AII, B, CII, CIII and E, were not affected in the depleted group. However, moderate iron deficiency and marked zinc deficiency were found in this group. It is concluded that in the elderly, biochemical markers of the protein and energy status are not related to the nutritional status assessed by anthropometry.


Asunto(s)
Índice de Masa Corporal , Estado Nutricional/fisiología , Desnutrición Proteico-Calórica/diagnóstico , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Apolipoproteínas/sangre , Peso Corporal , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Masculino , Osteocalcina/sangre , Prealbúmina/metabolismo , Desnutrición Proteico-Calórica/sangre , Desnutrición Proteico-Calórica/fisiopatología , Albúmina Sérica/metabolismo , Transferrina/metabolismo
20.
Behav Res Ther ; 41(5): 587-96, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12711266

RESUMEN

This study evaluated the efficacy of a group cognitive treatment for pathological gambling. Gamblers, meeting DSM-IV criteria for pathological gambling, were randomly assigned to treatment (N=34) or wait-list control (N=24) conditions. Cognitive correction techniques were used first to target gamblers' erroneous perceptions about randomness, and then to address issues of relapse prevention. The dependent measures used were the DSM-IV criteria for pathological gambling, perceived self-efficacy, gamblers' perception of control, desire to gamble, and frequency of gambling. Post-treatment results indicated that 88% of the treated gamblers no longer met the DSM-IV criteria for pathological gambling compared to only 20% in the control group. Similar changes were observed on all outcome measures. Analysis of data from 6-, 12- and 24-month follow-ups revealed maintenance of therapeutic gains. Recommendations for group interventions are discussed, focusing on the cognitive correction of erroneous perceptions toward the notion of randomness.


Asunto(s)
Conducta Adictiva/terapia , Terapia Cognitivo-Conductual/métodos , Juego de Azar/psicología , Psicoterapia de Grupo/métodos , Adulto , Análisis de Varianza , Femenino , Estudios de Seguimiento , Humanos , Masculino , Pruebas Psicológicas , Prevención Secundaria , Resultado del Tratamiento
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