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Venus has no significant internal magnetic field, which allows the solar wind to interact directly with its atmosphere. A field is induced in this interaction, which partially shields the atmosphere, but we have no knowledge of how effective that shield is at solar minimum. (Our current knowledge of the solar wind interaction with Venus is derived from measurements at solar maximum.) The bow shock is close to the planet, meaning that it is possible that some solar wind could be absorbed by the atmosphere and contribute to the evolution of the atmosphere. Here we report magnetic field measurements from the Venus Express spacecraft in the plasma environment surrounding Venus. The bow shock under low solar activity conditions seems to be in the position that would be expected from a complete deflection by a magnetized ionosphere. Therefore little solar wind enters the Venus ionosphere even at solar minimum.
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OBJECTIVES: To study voice prosthesis survival, complications, efficacy and impact on quality of life. METHODS: A single-center observational study was performed in patients treated for squamous cell carcinoma of the larynx or hypopharynx by total (pharyngo)-laryngectomy between 2010 and 2015. Study data comprised: maximum phonation time (sec), number of and reasons for prosthesis exchanges (leakage through or around the prosthesis, expulsion or inclusion of the prosthesis), plus 2 quality of life questionnaires (QLQ-C30, QLQ-H&N35) and the Voice Handicap Inventory (VHI 30). RESULTS: Forty-nine patients were included. The most common causes of prosthesis exchange were leakage through (73.2%) or around the prosthesis (18.5%). The median time between exchanges was 4 months. Global quality of life status on the QLQ-C30 was 63.5. Mean maximum phonation time was 7.4sec. Mean VHI was 46/120; 10 patients had a mild voice handicap, 12 moderate and 10 severe. No relation emerged between the number of prosthesis exchanges per year and quality of life. Voice handicap significantly decreased quality of life, with QLQ-C30 72.3 for the 22 patients with mild to moderate voice handicap and 44.2 for the 10 patients with severe voice handicap (P=0.001). CONCLUSION: Voice restoration by tracheoesophageal prosthesis after total (pharyngo)-laryngectomy is a reliable technique that decreases voice handicap and, despite potentially serious complications, has little negative impact on quality of life.
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Neoplasias Laríngeas , Laringe Artificial , Carcinoma de Células Escamosas de Cabeza y Cuello , Voz , Humanos , Neoplasias Laríngeas/cirugía , Laringectomía/efectos adversos , Laringectomía/métodos , Calidad de Vida , Habla , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugíaRESUMEN
This study aims to determine the frequency and causes of cochlear explants with re-implantation (ERI) after 5 years' follow up of the patients included in the French national EPIIC (étude post-inscription des implants cochléaires) registry tracking patients with cochlear implantation. This multicenter, descriptive prospective study was conducted on 5051 patients enrolled in the EPIIC database between January 2012 and December 2016. Ninety-five patients (1.9%) received a primary implant and an ERI during the study. Of these, four benefitted from two ERIs. The number of ERIs was significantly higher in the pediatric population than among adults. The explantation and reimplantation were performed simultaneously in 86% of cases. The reasons for explantation were: in 46.4% of cases linked to a malfunction of the implant, and in 39.3% of cases for medical or surgical reasons. The number of electrodes inserted was significantly higher after the ERI than after the first implantation. There was just one post-ERI infection for these 95 explanted and re-implanted patients. As well as explantation with reimplantation rarely being necessary, it generally presents no major surgical difficulty and in most cases it allows a better integration than in the first implantation.
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Implantación Coclear/estadística & datos numéricos , Implantes Cocleares/estadística & datos numéricos , Remoción de Dispositivos/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Implantes Cocleares/efectos adversos , Francia , Humanos , Lactante , Persona de Mediana Edad , Estudios Prospectivos , Falla de Prótesis , Reimplantación/estadística & datos numéricos , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVES: The aim of this study was to evaluate peri- and post-operative complications related to cochlear implantations. We searched for risk factors predicting these complications and analyzed the complications in the youngest and most elderly. STUDY DESIGN: Retrospective analysis of cochlear implant patients. MATERIALS AND METHODS: All patients who underwent cochlear implantation in France between January 2012 and December 2016 were anonymized and registered in the EPIIC database. This population included 3483 adults and 2245 children. Their demographic and surgical data and their incidence of peri- or post-operative complications, including their severity, whether major or minor, were all indicated. RESULTS: The global complication rate was 6.84%. The risk of complication was higher in initial implantation versus reimplantation (P<0.0001). The risk was also higher for bilateral implantation versus unilateral (P<0.0001). Complications were more frequent for patients with cochlear malformation (P=0.002). There was no difference in complication rates across age groups; babies under 1 year old, and the elderly over 80 and even over 90, did not have more complications than the rest of the population. Patients treated in the daily care unit had no more complications than those who were hospitalized for one night or more (P=0.64). CONCLUSION: Cochlear implantation is a safe technique with a low incidence of complications. The absence of increased risk in patients at the extremes of the age spectrum justifies offering this solution to all, without age limitation.
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Implantación Coclear/efectos adversos , Pérdida Auditiva/rehabilitación , Complicaciones Intraoperatorias/epidemiología , Complicaciones Posoperatorias/epidemiología , Sistema de Registros/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Cóclea/anomalías , Implantación Coclear/métodos , Centros de Día/estadística & datos numéricos , Francia/epidemiología , Pérdida Auditiva/etiología , Hospitalización/estadística & datos numéricos , Humanos , Incidencia , Lactante , Persona de Mediana Edad , Reoperación/efectos adversos , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Adulto JovenRESUMEN
OBJECTIVE: Multi-centre study of the National French Registry (EPIIC) of patients with cochlear implants, focusing on infants who were operated-on under the age of 24 months between 2012 and 2016. PATIENTS AND METHODS: A total of 615 profoundly deaf infants, who received cochlear implants (CIs) before their second birthday, were included in the registry by different CI centers. Epidemiological, surgical, speech therapy and school, follow-up data were included in the registry, 12, 24, 36 and 48 months thereafter. The following parameters were studied: type of implantation (uni- or bilateral), complications, cause of deafness, category of auditory perception (CAP), Open-set word recognition score (OSW), speech intelligibility rating, lexical comprehension with EVIP (Peabody), communication mode and type of schooling. Bilateral simultaneous CI (BiCI) and unilateral CI (UniCI) groups were compared. RESULTS: There were 744 implantations. The explantation-reimplantation rate, within the four-year follow-up, was just 3.6%. Mean implantation age was 16.0 months, and similar in the two groups (BiCI/UniCI). A total of 51% of children had their first implant between 12 and 18 months, and 15% before 12 months. Implantation was unilateral in 52% of cases. Fifty-six percent of the bilateral procedures were sequential, with a mean delay of 16.8 months for the second implantation. The cause of deafness was unknown in 52% of cases. Of the 48% (297/615) of attributed cases, 32% had clear genetic causes. The remaining deafness was due to cytomegalovirus (CMV, 8%), inner-ear malformation (5%) and meningitis (3%). The main complications were from infections (47%) and internal device failure (25%). Four years post-operation, 84% of the UniCI and 75% of BiCl groups had a CAP≥5, and 83% of UniCl and 100% BiCI had OSW≥80%. Furthermore 74% of UniCI and 77% of BiCI communicated orally and 85% of UniCI and 90% of BiCI integrated into mainstream schooling. CONCLUSION: The French Registry of cochlear implants (EPIIC) is the only such national registry in the world. Our analysis illustrates the immediate benefits of, either single or double, cochlear implantation for language, perception skills and schooling.
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Percepción Auditiva , Lenguaje Infantil , Implantación Coclear/estadística & datos numéricos , Implantes Cocleares/estadística & datos numéricos , Sordera/rehabilitación , Sistema de Registros/estadística & datos numéricos , Factores de Edad , Implantación Coclear/efectos adversos , Implantación Coclear/métodos , Implantes Cocleares/efectos adversos , Comunicación , Corrección de Deficiencia Auditiva/instrumentación , Corrección de Deficiencia Auditiva/estadística & datos numéricos , Sordera/etiología , Remoción de Dispositivos/estadística & datos numéricos , Educación de Personas con Discapacidad Auditiva/métodos , Educación de Personas con Discapacidad Auditiva/estadística & datos numéricos , Estudios de Seguimiento , Francia , Humanos , Lactante , Recién Nacido , Integración Escolar/estadística & datos numéricos , Reoperación/estadística & datos numéricos , Instituciones Académicas , Inteligibilidad del Habla , Logopedia/estadística & datos numéricos , Factores de TiempoRESUMEN
OBJECTIVE: Evaluate in France the outcomes of cochlear implantation outside the selection criteria, off-label. MATERIAL AND METHODS: This is a prospective cohort study including adults and children having received a cochlear implant (CI) in an off-label indication, that is outside the criteria established by the "Haute Autorité de santé (HAS)" in 2012. The data was collected from the "EPIIC" registry on recipients who received CIs in France between 2011 and 2014. Speech audiometry was performed at 60dB preimplantation and after one year of CI use, as well as an evaluation of the scores of the quality of life with the APHAB questionnaire, the scores for CAP and the professional/academic status in pre- and post-implantation conditions. Major and minor complications at surgery have been recorded. RESULTS: In total, 590 patients (447 adults and 143 children) with an off-label indication for CIs were included in this study from the EPIIC registry (11.7% of the whole cohort of EPIIC). For adults, the median percentage of comprehension using monosyllabic word lists was 41% in preimplantation condition versus 53% after one year of CI use (P<0.001) and 60% versus 71% in dissyllabic word lists (P<0.001). The CAP scores were 5 versus 6 in pre- and post-implantation conditions respectively (P<0.001) and the APHAB scores were statistically lower after implantation (P<0.001). In the children cohort, the median percentage of comprehension using monosyllabic word lists was 51% in preimplantation condition and 65% after CI (P<0.001), and 48% versus 82% (P<0.001) for dissyllabic word lists. The CAP scores were 5 versus 7 respectively in pre- and post-CI conditions (P<0.001). Thirty-two minor complications (5.4%) and 17 major complications (2.8%) were reported in our panel of off-label indication patients. CONCLUSION: These results suggest that a revision of the cochlear implantation candidacy criteria is necessary to allow more patients with severe or asymmetric hearing loss to benefit from a CI when there is an impact on quality of life despite the use of an optimal hearing aid.
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Implantación Auditiva en el Tronco Encefálico/estadística & datos numéricos , Implantación Coclear/estadística & datos numéricos , Implantes Cocleares/estadística & datos numéricos , Pérdida Auditiva/rehabilitación , Selección de Paciente , Sistema de Registros/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Audiometría del Habla/métodos , Niño , Preescolar , Implantación Coclear/efectos adversos , Implantes Cocleares/efectos adversos , Femenino , Francia/epidemiología , Encuestas Epidemiológicas , Humanos , Masculino , Persona de Mediana Edad , Uso Fuera de lo Indicado/estadística & datos numéricos , Complicaciones Posoperatorias/epidemiología , Periodo Posoperatorio , Cuidados Preoperatorios , Estudios Prospectivos , Calidad de Vida , Adulto JovenRESUMEN
OBJECTIVES: To analyze the performance of cochlear implants in French patients aged 65 and over, implanted between 2012 and 2016, using data from the French national registry for cochlear implants (EPIIC). MATERIALS AND METHODS: The French national registry incorporates patient data from before implantation and for three years after implantation, stratified in different age groups (18-39, 40-64years, 65-74years and>75years). Here, we assessed the latter two categories. Hearing was assessed using mono- and disyllabic words in a silent background. The Category of Auditory Performance (CAP) scale was also implemented and subjects took the Abbreviated Profile of Hearing Aid Benefit (Aphab) questionnaire. RESULTS: The population aged over 65 accounted for 38% (n=1193) of the 3178 adult implanted patients. The performance for mono- and disyllabic words in silence, the CAP scores and the APHAB questionnaire answers for ease of communication, background noise and reverberation were dramatically improved at one year post-implantation (P<0.0001 for each score) and remained stable between one and three years thereafter. The percentage improvement was similar across all age groups. The scores for loud-noise intolerance did not change after cochlear implantation in any age group. CONCLUSION: Cochlear implants improve hearing and communication in subjects aged 65 and over, with comparable efficiency to that achieved in younger subjects. Cochlear implantation should thus be proposed whenever hearing aids provide only limited benefit. However, between 2012 and 2016, cochlear implantation was given to less than 1% of the French population aged 65 and over with profound deafness.
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Implantación Coclear/estadística & datos numéricos , Implantes Cocleares/estadística & datos numéricos , Pérdida Auditiva/rehabilitación , Sistema de Registros/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Percepción Auditiva , Implantación Coclear/métodos , Comunicación , Femenino , Francia , Encuestas Epidemiológicas , Pérdida Auditiva/etiología , Pruebas Auditivas/métodos , Humanos , Masculino , Persona de Mediana Edad , Ruido/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVES: Assessment of the incidence and results of bilateral cochlear implantation in adults and children in France. MATERIALS AND METHODS: Multicenter retrospective study of data in the French national registry of cochlear implantations from January 1st 2012 to December 31st 2016. Functional results from CAP (Category of Auditory Performance) questionnaires and speech audiometry tests, with mono- and di-syllabic word-lists, were compared before and after implantation. Speech audiometry tests were carried out against a noisy background, except before simultaneous implantations. RESULTS: Nine hundred and forty two bilateral cochlear implantations were performed during this period, that is, 16.4% of all cochlear implantations. Five hundred and eighty eight bilateral implantations were performed sequentially. 59% of the bilateral implantations were performed in children. Bilateral implants significantly improved CAP scores in all cases (P<0.001). Auditory performance, with the two types of word-list, were significantly improved after simultaneous implantation (P<0.01). After sequential implantation, the speech discrimination score, already very good with the first implant, reached 63±26% [0-100] with monosyllabic word lists, and 72±28% [0-100] with dissyllabic words. There were more complications due to surgery in bilateral cases than in the entire population of cochlear recipients (9.1% vs 6.4%, P<0.02). CONCLUSION: Hearing is significantly improved by simultaneous cochlear implantation. For sequential implantation, at one year, when auditory results were already excellent from the first implant, in the bimodal condition CAP scores were significantly improved, although there was no further change in speech audiometry in noise.
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Implantación Coclear/métodos , Implantes Cocleares/estadística & datos numéricos , Sordera/rehabilitación , Sistema de Registros/estadística & datos numéricos , Adulto , Audiometría del Habla/métodos , Percepción Auditiva , Niño , Implantación Coclear/efectos adversos , Implantación Coclear/estadística & datos numéricos , Sordera/etiología , Femenino , Francia , Humanos , Masculino , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Pruebas de Discriminación del Habla/estadística & datos numéricosRESUMEN
This study concerns the results of cochlear implantation in children and adults from French cochlear implantation centers, monitored at one, two and three years by the Cochlear Implant French Registry EPIIC. This multicenter study enrolled 2603 subjects (1667 adults and 936 children) implanted in one ear. The following parameters were studied: hearing overall performances, monosyllabic or dissyllabic word perception, speech intelligibility, self-assessment questionnaire of Cochlear Implant (CI) benefits (Abbreviated profile of Hearing aid Benefit); professional activity and schooling. This study confirms the ceiling effect in adults' performances after the 1st year and the progressive growth in children's performances. It also shows that the contralateral hearing aid enhances performances compared to the CI alone condition, in all follow-up sessions. The French register of CIs is the only worldwide register of systematic follow-up on a period of three years and more of all adults and children implanted in a country.
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Implantación Coclear/estadística & datos numéricos , Implantes Cocleares/estadística & datos numéricos , Sordera/rehabilitación , Calidad de Vida , Sistema de Registros/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Percepción Auditiva , Niño , Preescolar , Educación , Empleo , Estudios de Seguimiento , Francia , Humanos , Lactante , Recién Nacido , Autoevaluación (Psicología) , Inteligibilidad del Habla , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cochlear and brainstem implants have been included on the list of reimbursable products (LPPR) in France since March of 2009. The implants were initially inscribed for 5 years, after which an application for renewal with the French National Commission for the Evaluation of Medical Devices and Health Technologies (Commission Nationale d'évaluation des dispositifs médicaux et des technologies de santé - CNEDiMTS) was required [Haute Autorité de santé, 2009]. Upon registration to the list of reimbursable products, the companies and the reference centers for cochlear and brainstem implants were asked to set up a post-registration registry called EPIIC. This article reports the evolution in the EPIIC registry of the general indicators for 5051 patients over the five years from 2012-2016.
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Implantes Auditivos de Tronco Encefálico/estadística & datos numéricos , Implantes Cocleares/estadística & datos numéricos , Sistema de Registros/estadística & datos numéricos , Comités Consultivos/organización & administración , Factores de Edad , Anciano , Anciano de 80 o más Años , Implantes Auditivos de Tronco Encefálico/economía , Implantación Coclear/estadística & datos numéricos , Implantes Cocleares/economía , Seguridad Computacional , Bases de Datos como Asunto , Aprobación de Recursos/legislación & jurisprudencia , Remoción de Dispositivos/estadística & datos numéricos , Francia , Guías como Asunto/normas , Sector de Atención de Salud/economía , Sector de Atención de Salud/legislación & jurisprudencia , Humanos , Lactante , Recién Nacido , Reembolso de Seguro de Salud , Control de Calidad , Estándares de Referencia , Factores de TiempoRESUMEN
The effects of electron beam emissions from Spacelab were recorded with onboard diagnostic instruments. The variation of the Spacelab-shuttle potential with respect to the ambient plasma near the scientific air lock was investigated. Data on the waves and instabilities triggered by the electron beams are discussed. Within the electron gyrofrequency and electron plasma frequency range, strong signals were detected by both electric and magnetic antennas during the beam emissions. The frequencies of the emitted waves were compared to the characteristic plasma frequencies to enable mode identification.
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BACKGROUND: Nasal Polyposis (NP) is defined as a chronic inflammatory disease of sinonasal mucosa leading to diffuse formation of benign polyps. Although family histories are frequently suggested in medical literature, no specific study focused on this point has been reported. The purpose of this study is to determine whether a hereditary factor could be implied for NP in a family where several members were affected. We included 99 members of this family. METHODS: All patients were assessed for conditions known to be associated with the development or presence of NP. Concerning NP, patients were screened with a validated questionnaire and selected patients had a medical examination by an Ear, Nose and Throat practitioner. RESULTS: Thirteen patients had a personal history of NP without asthma, aspirin intolerance, Churg Strauss syndrome, cystic fibrosis, Young's syndrome, bare lymphocyte syndrome, or primary ciliary dyskinesia. Within this family, 19.7% of those older than 17 years were affected by NP, as compared with the national French prevalence of 2.1%. CONCLUSIONS: Regarding the pedigree, we discuss different modes of inheritance. The presence of consanguineous unions in this family suggests the possibility of a common ancestor and thus a recessive autosomal mode of inheritance.
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Consanguinidad , Patrón de Herencia/genética , Pólipos Nasales/genética , Enfermedades de los Senos Paranasales/genética , Adolescente , Adulto , Niño , Femenino , Francia , Ligamiento Genético/genética , Humanos , Masculino , Persona de Mediana Edad , Pólipos Nasales/mortalidad , Pólipos Nasales/patología , Enfermedades de los Senos Paranasales/mortalidad , Enfermedades de los Senos Paranasales/patología , LinajeRESUMEN
A nonspecific opsonin function has been ascribed to human alpha 2 HS glycoprotein. Its serum level has been shown to be decreased in trauma patients. Recent studies from this laboratory revealed a heterogeneity among the products obtained in the course of the preparation of the protein. To date, no definitive agreement existed with regard to a molecular homogeneous entity of alpha 2 HS glycoprotein (Ba-alpha 2 glycoproteins). The purpose of the current work was to study the variations in serum level of alpha 2 HS in patients suffering from an acute inflammatory process of bacterial etiology and to determine whether a decrease in alpha 2 HS was accompanied by the appearance of fragments of this protein in the serum. A method of preparing alpha 2 HS was thus developed, using an immune absorbent as a final purification step. In an intermediary step of the preparation, alpha 2 HS was found to bind zinc when metal chelate affinity chromatography was employed. Immunologically and physico-chemically pure alpha 2 HS was obtained. The protein consists of a unique polypeptide chain of about 50,000 daltons and has a unique amino-terminal residue, alanine. However, the protein maintained its molecular integrity with difficulty, and spontaneous fragments ranging from 30,000 to less than 10,000 daltons were produced in some of the preparations. No major modification in the molecular structure of the protein was noted in the sera of subjects suffering from an acute inflammatory process. Serum level of alpha 2 HS and alpha 1 antitrypsin (AT)was determined in 23 patients. When the acute-phase (AP-)reactant alpha 1 AT was increased (difference with normal mean greater than +2 or +3 SD), the sera showed a large decrease in alpha 2 HS (difference with normal mean less than -2 or -3 SD). The serum level of alpha 2 HS, albumin, alpha 2 macroglobulin, and of positive AP-reactants, orosomucoidinal study of seven patients. The results were submitted to a principal components analysis. Alpha 2 HS showed a negative correlation with the AP-reactants alpha 1 AT, orosomucoid, and haptoglobin (P less than 0.05) and a positive correlation with albumin (P less than 0.05); these findings indicate that alpha 2 HS is a negative AP-reactant. In addition, analysis of the principal components confirms thestrong analogy between alpha 2 HS and albumin and indicates that serum level behavior of the AP-reactants during the course of the disease closely depends on the protein studied.
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Proteínas Sanguíneas/aislamiento & purificación , alfa-Macroglobulinas/metabolismo , Cromatografía de Afinidad , Cromatografía por Intercambio Iónico , Electroforesis en Gel de Poliacrilamida , Femenino , Humanos , Inmunodifusión , Inmunoelectroforesis , Masculino , Peso Molecular , alfa-Macroglobulinas/aislamiento & purificaciónRESUMEN
The conventional hearing aid has benefited from the progress made in electronic miniaturization and digital signal processing. The prescriber should be familiar with these improvements, the anatomic and acoustic limitations related to hearing aids, the possibilities of surgical rehabilitation, as well as the indications for other auditive rehabilitation techniques (bone conduction hearing, middle ear implant, and cochlear implant). A hearing aid should be prescribed within a precise context taking into account patient history, clinical examination, audiometric testing, and choice of the device. Optimal management of a hearing device for a child should be conducted within an adapted network including a specialized ENT physician, audiophonology, a qualified hearing prosthetist, a speech therapist, etc.).
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Audífonos , Adaptación Fisiológica , Audiometría , Conducción Ósea , Trastornos de la Audición/terapia , Humanos , Miniaturización , Procesamiento de Señales Asistido por Computador , Localización de SonidosRESUMEN
Isoelectric focusing in polyacrylamide gel was used to reveal the two alpha 1-acid glycoprotein populations separated by affinity chromatography on Con A-Sepharose from human purified alpha 1-acid glycoprotein, whole normal serum and sera from patients undergoing an acute inflammatory process. The concanavalin A non-reactive peak had a lower isoelectric point than did the concanavalin A reactive peak. Moreover, crossed immunoaffinity electrophoresis with free concanavalin A revealed three alpha 1-acid glycoprotein populations (concanavalin A reactive, weakly and non-reactive). A significant difference was observed between the patterns of normal and of inflammatory sera, since the concanavalin A reactive fraction was enhanced during the inflammatory process. These results suggest a variation in relative ratios of the different types of peripheral oligosaccharide branches in the alpha 1-acid glycoprotein populations.
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Inflamación/sangre , Orosomucoide/aislamiento & purificación , Cromatografía de Afinidad , Concanavalina A , Humanos , Focalización Isoeléctrica , Punto IsoeléctricoRESUMEN
The human alpha2-HS glycoprotein (A2HS) and rat phosphoprotein of Mr 63000 (pp63) are homologous plasma proteins and members of the fetuin superfamily. A2HS is involved in important functions such as inhibition of the tyrosine kinase activity of the insulin receptor, regulation of calcium metabolism and osteogenesis as well as protease inhibitory activity. We report an analysis of the 5' transcription control region (4 kb) of the A2HS gene. Its most proximal 300 nt display a very potent transcriptional activity. The latter is likely accounted for by C/EBP and NF1 binding sites that are conserved from the human A2HS gene to the rat pp63 gene. In contrast, these human and rat genes appear to largely diverge beyond their proximal promoter.
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Proteínas Sanguíneas/genética , Regulación Enzimológica de la Expresión Génica , Secuencias Reguladoras de Ácidos Nucleicos , Secuencia de Bases , ADN , Humanos , Datos de Secuencia Molecular , Regiones Promotoras Genéticas , Transcripción Genética , alfa-2-Glicoproteína-HSRESUMEN
The inter H-H cysteinyl peptides and the localization of the J-chain were studied in a human F(c)5mu-like fragment. The latter was found to be built up by non-covalent association of molecular forms of 140 000, 95 000 and 70 000 dalton subunits. The trimeric, dimeric and monomeric forms were obtained from gradual reduction by dithiothreitol of the major component of 140 000 daltons, thus confirming the tetrameric nature of this subunit. The latter was found to result from the association of both components of the 70 000 dalton subunit, with the participation of the inter H-H subunit bridge. Structural analysis of the labelled peptides obtained by partial reduction and alkylation showed the presence of the intersubunit disulfide bridge and of the inter heavy-heavy chain bridge of the C-terminal region, and the absence of the heavy-heavy chain bridge of the hinge region. The sequence of these peptides is identical to the sequences of the corresponding peptides of normal mmu-chains. The J-chain, which was covalently linked to this F(c)5mu-like fragment, was found to be predominantly associated within the 95 000 dalton subunit. The results showed that the J-chain was linked in the protein as a "clasp" within a single subunit and not between two subunits.
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Fragmentos Fc de Inmunoglobulinas , Cadenas J de Inmunoglobulina , Secuencia de Aminoácidos , Aminoácidos/análisis , Animales , Sitios de Unión , Disulfuros/análisis , Electroforesis en Gel de Poliacrilamida , Humanos , Inmunodifusión , Sustancias Macromoleculares , Peso Molecular , Pepsina A , Fragmentos de Péptidos/análisis , Unión Proteica , Púrpura Hiperglobulinémica/inmunología , Conejos/inmunología , TripsinaRESUMEN
BACKGROUND: Preconditioning with brief periods of ischemia protects the coronary endothelium against acute and chronic reperfusion injury, but the mechanisms of this endothelial protection remain unknown. We hypothesized that preconditioning protects endothelial cells through a decreased production of endothelial adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1), leading to a lesser adhesion of neutrophils to the endothelium. METHODS AND RESULTS: Cultured rat aortic endothelial cells were subjected to 6-hour anoxia followed by various durations of reoxygenation. Preconditioning was induced by 1-hour anoxia and 1-hour reoxygenation. ICAM-1 gene expression was measured by polymerase chain reaction, and the percentage of cells expressing ICAM-1 was assessed by confocal laser fluorescence microscopy. Anoxia/reoxygenation increased expression of ICAM-1, with a peak occurring after 6 hours of reoxygenation for mRNA and 9 hours for protein. Preconditioning prevented the increase in ICAM-1. Similar reductions were observed with the free radical scavenger N-2 mercaptopropionyl glycine (MPG). The inhibitory effect of preconditioning on ICAM-1 expression was abolished by an inhibitor of protein kinase C, an inhibitor of nitric oxide synthesis, and by MPG but was not affected by an adenosine receptor antagonist. Finally, both preconditioning and MPG partially prevented the increased adhesion of human neutrophils to reoxygenated endothelial cells. CONCLUSIONS: Preconditioning prevented reoxygenation-induced, free radical-mediated expression of ICAM-1 by a mechanism involving activation of protein kinase C and production of nitric oxide and free radicals, and this is associated with a lesser adhesion of neutrophils to endothelial cells. Such prevention of neutrophil adhesion may contribute to the protective effect of preconditioning against reperfusion-induced endothelial injury.
Asunto(s)
Endotelio Vascular/fisiopatología , Hipoxia/fisiopatología , Molécula 1 de Adhesión Intercelular/biosíntesis , Daño por Reperfusión Miocárdica/fisiopatología , Neutrófilos/fisiología , Animales , Aorta/citología , Adhesión Celular , Células Cultivadas , Cartilla de ADN , Endotelio Vascular/metabolismo , Activación Enzimática , Radicales Libres/metabolismo , Regulación de la Expresión Génica , Hipoxia/metabolismo , Masculino , Daño por Reperfusión Miocárdica/metabolismo , Óxido Nítrico/biosíntesis , Reacción en Cadena de la Polimerasa , Proteína Quinasa C/metabolismo , Ratas , Ratas WistarRESUMEN
Charge shift electrophoresis and crossed hydrophobic interaction immuno-electrophoresis were used to demonstrate the presence of hydrophobic sites in the human C3 molecule. C3b and C3d were true amphiphilic proteins that could bind to hydrophobic surfaces. To the contrary, native C3, that presented the characteristics of amphiphilic proteins upon charge shift electrophoresis, did not bind to hydrophobic surfaces. These results suggested that the hydrophobic sites were located in the internal part of the C3 molecule and they were exposed in the external part when C3 was activated. The action of chaotropes on C3 was studied in detail and showed that the hydrophobic sites protected the thiolester bond (present in the labile site) from hydrolysis by water and thereby preserved the biological properties of native C3.
Asunto(s)
Complemento C3 , Sitios de Unión , Dicroismo Circular , Detergentes , Electroforesis , Hemólisis , Humanos , Fragmentos de Péptidos , Conformación Proteica , Desnaturalización Proteica , Solubilidad , Relación Estructura-Actividad , TemperaturaRESUMEN
The biosynthesis of alternative regulatory complement protein factor H was investigated using both an in vivo rat model and an in vitro rat hepatocyte culture system, and compared to that of C3 component. Subcutaneous injection of a single dose of 20 micrograms of recombinant murine tumor necrosis factor-alpha (rmTNF-alpha) had no effect on factor H liver mRNA levels, while it increased C3 mRNA levels. In correlation with this, serum factor H levels remained unchanged after rmTNF-alpha injection, whereas C3 levels were increased. In contrast in vitro studies showed that rmTNF-alpha had no effect on factor H and C3 expression by rat hepatocytes. Recombinant human interleukin-1 alpha (rhIL-1 alpha) did not alter the expression of factor H, whereas it increased C3 expression, and recombinant human interleukin-6 (rhIL-6) stimulated expression of both proteins. This study shows that TNF-alpha is not directly responsible for the increased levels of factor H observed in vivo during induced inflammation in the rat. Its in vivo effect on C3 secretion might be secondary to the TNF-alpha-induced release of IL-1 and/or IL-6.