Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21
Filtrar
1.
Resusc Plus ; 15: 100407, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37363123

RESUMEN

Introduction: Bystanders' interventions improve chances of survival from out-of-hospital cardiac arrest (OHCA) before Emergency Medical Services arrive. Some areas in England are of concern. These high-risk areas have a higher incidence of cardiac arrest combined with lower-than-average bystander CPR rates and are characterised by higher proportions of minority ethnic group residents and deprivation.Collaborating with people from the Black African and Caribbean and South Asian minority communities in deprived areas of England, we aim to develop and evaluate the implementation of theoretically informed intervention(s) to address factors contributing to lower bystander intervention rates. Methods: The study is a collaborative realist enquiry, informed by the Theoretical Domains Framework and associated Behaviour Change Wheel. It consists of 1) a realist evidence synthesis to produce initial program theories developed from primary workshop data and published evidence. It will include identifying factors contributing to the issue and potential interventions to address them; 2) theoretically informed intervention development, using the initial program theories and behaviour change theory and 3) a realist mixed methods implementation evaluation with embedded feasibility.Public involvement (PPI) as study team and public advisory group members is key to this study.We will conduct realist evidence synthesis, qualitative and statistical analyses appropriate to the various methods used. Dissemination: We will develop a dissemination plan and materials targeted to members of the public in high-risk areas as well as academic outputs. We will hold an event for participating community groups and stakeholders to share findings and seek advice on next steps. Study registration: ISRCTN90350842. Registration date 28.03.2023. The study was registered after its start date.

2.
Artículo en Inglés | MEDLINE | ID: mdl-36834122

RESUMEN

Asians believe discussing death-related topics is inauspicious and may bring bad luck. It is critical to explore the end-of-life care preferences of the Asian elderly with less-threatening tools. The study examined older adults' preferences regarding end-of-life treatments by applying a cartoon version of the Life Support Preferences Questionnaire (LSPQ). A cross-sectional survey was conducted to understand older adults' preferences for end-of-life treatments. A total of 342 older adults participated in the study, comprising 268 elderly patients from a veterans hospital located in northern Taiwan and 74 elderly family members of the patients. Regardless of scenario, cardiopulmonary resuscitation (CPR) had the lowest score, indicating that older adults considered it a less desirable medical treatment. By contrast, antibiotics and intravenous infusions had the highest scores, indicating that older adults tended to prefer them. End-of-life care preferences were significantly different in genders. CPR and surgical preferences of older adults differed significantly with education level. Different demographic characteristics had different end-of-life treatment preferences, and future research may develop advance care planning programs for different attributes. This cartoon version of the LSPQ can help healthcare professionals to understand older adults' preferences for end-of-life care and warrants further empirical research.


Asunto(s)
Antibacterianos , Toma de Decisiones , Humanos , Masculino , Femenino , Anciano , Infusiones Intravenosas , Estudios Transversales , Encuestas y Cuestionarios
3.
J Hosp Palliat Nurs ; 2022 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-36155387

RESUMEN

This study aimed to explore the factors affecting the behavioral intentions of older adults toward advance care planning (ACP). A questionnaire survey was conducted at 2 medical wards and a senior activity center in northern Taiwan. Four hundred one participants were older adults aged over 65 years, comprising hospitalized patients, their caregivers, and members of a senior activity center. The regression model revealed that participant type (patient, caregiver, or community resident); financial support; discussion of ACP with family; and knowledge, attitudes, and subjective norms accounted for 46.3% of the variance in behavioral intentions. The behavioral intention of caregivers was higher than that of patients. The behavioral intention of participants who were financially dependent on the family was lower than that of pensioners. Regarding discussing ACP with family, older adults in the contemplation and preparation stages score higher on behavioral intention than those in the precontemplation stage. This study supports the theory of reasoned action. Older adults' ACP knowledge and attitudes need to be enhanced through education. Caregivers' behavioral intentions tend to perform ACP. Sharing their caring experiences may be a strategy for promoting ACP. Older adults' financial status affects their behavioral intentions. Therefore, financial planning should be performed early and should incorporate ACP.

4.
Clin Diabetes ; 40(2): 196-203, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35669300

RESUMEN

Adolescents with type 1 diabetes face barriers that can have a negative influence on self-management behaviors. This study was an analysis of semi-structured interviews with adolescents, parents, and health care providers to better understand these barriers among adolescents in Jordan. Adolescents with type 1 diabetes reported individual-level barriers including feeling labeled, pitied, and stigmatized for having type 1 diabetes. They also discussed the system-level barrier of an education system that does not adapt to meet their needs. Individual- and system-level barriers are interrelated and could influence adolescents' decisions regarding whether to disclose their condition to others.

5.
Curr Diabetes Rev ; 18(9): e140222201109, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35156585

RESUMEN

BACKGROUND: Type 1 diabetes is the most common endocrine condition among adolescents. Diabetes self-management can be challenging during adolescence. OBJECTIVE: The objective of this study is to understand how adolescents and their parents manage type 1 diabetes in Jordan. METHODS: Constructivist grounded theory methodology principles were used to achieve the study aim. A total of 48 participants were recruited using purposive and theoretical sampling techniques, including adolescents and their parents. Data were collected (October 2016 - April 2017) using 38 semi-structured, audio-recorded interviews (one-to-one or joint interviews based on participants' preferences). Data were collected and analyzed concurrently using different levels of coding, constant comparative analysis, and memo writing. This study was approved by relevant ethics committees from the University of Manchester and Jordan University Hospital. RESULTS: The theme of living with diabetes is presented and discussed in this article. Culture emerged as the central theme; two aspects of culture are presented in this article: collectivism and cultural beliefs. CONCLUSION: This study identified that diabetes self-management could be influenced by the culture in which Jordanian adolescents live in as well as being shaped by their religious beliefs. These findings are potentially transferable to other Arab and non-Arab countries that share similar cultural aspects and religious beliefs.


Asunto(s)
Diabetes Mellitus Tipo 1 , Automanejo , Adolescente , Diabetes Mellitus Tipo 1/terapia , Conductas Relacionadas con la Salud , Humanos , Jordania , Padres
6.
BMJ Open ; 11(4): e049290, 2021 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-33827851

RESUMEN

INTRODUCTION: The craniofacial abnormalities found in infants with cleft palate (CP) decrease their airway patency and increase their risk of obstructive sleep apnoea (OSA). We hypothesise that optimising sleep position in infants with CP may improve airway patency and offer a 'low-cost, high-impact' intervention to prevent the negative impacts of OSA. Because cleft centres give inconsistent advice about sleep position: some recommend back-lying and others side-lying, we will compare these in a randomised controlled trial. METHODS AND ANALYSIS: The aim is to determine the clinical effectiveness of side-lying as compared with back-lying sleep positioning in terms of reducing oxygen desaturation resulting from OSA in 244 infants aged 3-5 weeks of age, diagnosed with an isolated CP in/by UK cleft centres. Primary outcome is the 4% Oxygen Desaturation Index measured using pulse oximetry during sleep. RESEARCH PLAN: 1. Multicentre randomised controlled trial of side-lying compared with back-lying sleep positioning in reducing oxygen desaturation resulting from OSA in infants with CP at one month of age. 2. Internal pilot questionnaire-based study to support parents and clinicians regarding study participation, seeking to identify and address any barriers to recruitment. Monitoring data from the internal pilot will be used in the final analysis. 3. Co-development of new UK recommendations with Cleft Lip and Palate Association (CLAPA) regarding sleep position for infants with CP. ETHICS AND DISSEMINATION: The study protocol has received the favourable opinion of the West Midlands-South Birmingham Research Ethics Committee. Study results will be published on affiliated webpages and in peer-reviewed publications and conference contributions. TRIAL REGISTRATION NUMBER: NCT04478201.


Asunto(s)
Labio Leporino , Fisura del Paladar , Apnea Obstructiva del Sueño , Labio Leporino/complicaciones , Fisura del Paladar/complicaciones , Humanos , Lactante , Recién Nacido , Oxígeno , Ensayos Clínicos Controlados Aleatorios como Asunto , Sueño
7.
Cleft Palate Craniofac J ; 56(2): 222-230, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-29665338

RESUMEN

OBJECTIVE: To identify outcomes relating to sleep-disordered breathing (SDB) that are relevant to parents, during the early weeks of caring for infants with cleft palate (CP), and compare these with clinical outcomes identified in a systematic search of research literature. DESIGN: A qualitative study using telephone/face-to-face interviews with parents explored their understanding of breathing and respiratory effort in infants with CP. SETTING: Care provided by 3 specialist cleft centers in the United Kingdom, with study conducted in parents' homes. PARTICIPANTS: Criteria for participation were parents of infants with isolated CP aged 12 to 16 weeks. Thirty-one parents of infants with CP (over 12 weeks) were invited to participate in the interview. Interviews were completed with 27 parents; 4 parents could not be contacted after completing the sleep monitoring. RESULTS: Parents' description of infants' sleep suggests that breathing is not considered as a separate priority from their principal concerns of feeding and sleeping. They observe indicators of infants' breathing, but these are not perceived as signs of SDB. Parents' decision to use lateral or supine sleep positioning reflects their response to advice from specialists, observation of their infants' comfort, ease of breathing, and personal experience. Outcomes, identified in published research of SDB, coincide with parents' concerns but are expressed in medical language and fit into distinct domains of "snoring," "sleep," "gas exchange," and "apnea." CONCLUSIONS: Parents' description of sleeping and respiration in infants with CP reflect their everyday experience, offering insight into their understanding, priorities, and language used to describe respiration. Understanding parents' individual priorities and how these are expressed could be fundamental to selecting meaningful outcomes for future studies of airway interventions.


Asunto(s)
Fisura del Paladar , Síndromes de la Apnea del Sueño , Humanos , Lactante , Padres , Ronquido , Reino Unido
8.
Artículo en Inglés | MEDLINE | ID: mdl-28725453

RESUMEN

BACKGROUND: Implementation intentions enable individuals to translate good intentions into action. Parents and children can find maintaining oral health difficult, as evidenced by the presence of tooth decay. This is a common condition in children in spite of being preventable through the use of regular tooth brushing, fluoride protection and avoiding sugar intake. Even when parents and children are positive about looking after the teeth, they can face challenges in maintaining consistent habits. The aim of this paper is to describe the design of a video animation to teach parents and children how to use implementation intentions to establish new habits to improve oral health, applied in this case, to parents and children with cleft lip and/or palate (CLP). METHODS: Evidence from a qualitative study of parents' and children's knowledge, beliefs and behaviour informed the design of an animation forming part of an intervention for children and parents using implementation intentions. The user views generated a set of guiding principles to determine the style and content of a teaching video, whilst an animation designer translated the key messages of implementation intention into images and characters appealing and meaningful to the target audience of children and parents. RESULTS: A team of researchers, an animation designer and a script writer designed a 2-min video as a teaching tool for children and parents. The team drafted and iteratively refined the content and visuals, with guidance from an advisory group and informal discussions with children in the target age group and their parents. Planning, consulting, designing and production of the animation spanned a total of 20 weeks. The video explains how to formulate 'if-then' plans using the voices of a boy and his mother in a conversation, with examples from oral health to illustrate how to enact intentions. It is available via digital media and designed to be delivered by dental care practitioners. The effectiveness of the intervention will be evaluated as part of a feasibility study. CONCLUSION: The current study describes the development of an intervention mediated through an animation tutorial that enables children and parents to devise 'if-then' plans to improve oral health as a collaborative endeavour between parents and children. The animation uses examples from oral health, but we believe there is scope for exploring application of the intervention to other areas of behaviour.

9.
Trials ; 18(1): 564, 2017 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-29178932

RESUMEN

BACKGROUND: The Herbst appliance is an orthodontic appliance that is used for the correction of class II malocclusion with skeletal discrepancies. Research has shown that this is effective. However, a potential harm is excessive protrusion of the lower front teeth. This is associated with gingival recession, loss of tooth support, and root resorption. This trial evaluates a method of reducing this problem. METHODS/DESIGN: The study is a single-center, randomised, assessor-blinded, superiority clinical trial with parallel 1:1 allocation. Male and female young people (10-14 years old) with prominent front teeth (class II, division 1) will be treated in one orthodontic clinic. Group 1 will be treated with the conventional Herbst appliance with dental anchorage and group 2 with the Herbst appliance with indirect skeletal anchorage for 12 months. The primary objective will be to compare the proclination of the lower incisors between the Herbst appliance with dental anchorage and skeletal anchorage. Secondary objectives will be to evaluate the changes occurring between the groups in the mandible, maxilla, lower and upper molars, and in gingival recession and root resorption at the end of the treatment. Additionally, the young patient's experience using the appliances will be assessed. The primary outcome measure will be the amount of lower incisor proclination at the end of treatment. This will be assessed by cone-beam computed tomography (CBCT) superimposition. Secondary outcome measures will be the changes in the mandible, maxilla, lower and upper molars at the end of treatment assessed by tomography superimposition and the young patient's experience using the appliances assessed by self-reported questionnaires and semi-structured interviews. The randomisation method will be blocked randomisation, using software to generate a randomised list. The allocation concealment will be done in opaque envelopes numbered from 1 to 40 containing the treatment modality. The randomisation will be implemented by the secretary of the Department of Orthodontics of Rio de Janeiro State University before the beginning of the study. The patients and the orthodontists who will treat the patients cannot be blinded, as they will know the type of appliance used. The technician who will take the CBCT image and the data analyst will be blinded to patients' group allocation. DISCUSSION: If this new intervention is effective, the findings can change orthodontic practice and may also be relevant to other forms of treatment in which appliances are fixed to the bones of the jaws. However, if the bone anchoring is not effective, the trial will provide much needed information on the use of this comparatively new development. TRIAL REGISTRATION: ClinicalTrials.gov, protocol ID: NCT0241812 . Registered on 26 March 2015.


Asunto(s)
Maloclusión Clase II de Angle/terapia , Métodos de Anclaje en Ortodoncia/instrumentación , Aparatos Ortodóncicos Funcionales , Ortodoncia Correctiva/instrumentación , Adolescente , Brasil , Niño , Tomografía Computarizada de Haz Cónico , Femenino , Humanos , Masculino , Maloclusión Clase II de Angle/diagnóstico por imagen , Métodos de Anclaje en Ortodoncia/efectos adversos , Diseño de Aparato Ortodóncico , Ortodoncia Correctiva/efectos adversos , Satisfacción del Paciente , Radiografía Dental/métodos , Proyectos de Investigación , Factores de Tiempo , Resultado del Tratamiento
10.
BMC Oral Health ; 17(1): 120, 2017 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-28836989

RESUMEN

BACKGROUND: Children with a Cleft Lip and/or Palate (CL/P) have been reported to have poorer oral health than those without the condition. The consequences for these children can be particularly problematic due to implications for future treatments. Tooth brushing is an important behaviour contributing to children's oral health, but is under researched in the CL/P population. The aim of the study is to explore the experience of maintaining tooth brushing among children in the United Kingdom (UK) with a CL/P and their parents. METHODS: Semi-structured interviews were carried out with twenty-two parents and sixteen children with a CL/P (5-11 years), recruited at a cleft centre in the UK. Thematic analysis was used for data analysis. RESULTS: Three key themes were drawn from the qualitative data: first, parents of children with a CL/P generally had strong motivation to look after their children's teeth but children's motivation was inconsistent. Second, parents were primary enablers of children's tooth brushing behaviour, often employing approaches adapted to their child's characteristics to encourage tooth brushing. Third, a range of obstacles were encountered by parents and children in maintaining regular tooth brushing behaviours. They reported obstacles such as issues related to CL/P, 'forgetting' and childhood illness. CONCLUSIONS: The paper suggests that parents of children with a CL/P need support to enact their intention to maintain regular tooth brushing and prioritise tooth brushing within the context of demanding and dynamic family life.


Asunto(s)
Labio Leporino/psicología , Fisura del Paladar/psicología , Motivación , Padres/psicología , Cepillado Dental , Niño , Conducta Infantil , Preescolar , Femenino , Humanos , Intención , Masculino , Salud Bucal , Investigación Cualitativa
11.
Int J Paediatr Dent ; 27(4): 264-272, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27532347

RESUMEN

BACKGROUND: Children with cleft lip and/or palate (CLP) are prone to poorer oral health outcomes than their peers, with serious implications for treatment. Little is known of the knowledge and practice of children with CLP in caring for teeth and how these contribute to oral health. AIM: To investigate (i) parents' and children's knowledge of oral health, (ii) how knowledge is acquired, and (iii) how knowledge is implemented. DESIGN: A qualitative design was used to investigate knowledge, beliefs, and practices reported by parents and children, age 5-11 years with CLP. Data were collected from 22 parents and 16 children and analysed using thematic analysis. RESULTS: Four themes were derived as follows: (i) implicit knowledge: children express simple knowledge underpinned by basic rationales, (ii) situated knowledge: children gain skills as part of everyday childhood routines, (iii) maintaining good practice in oral health: parents take a lead role in motivating, monitoring, and maintaining children's toothbrushing, and (iv) learning opportunities: pivotal moments provide opportunities for children to extend their knowledge. CONCLUSION: Developers of oral health education interventions should take account of children's implicit knowledge and the transmission of beliefs between generations that influence toothbrushing behaviours. This could enhance interventions to support parents and children's practice.


Asunto(s)
Fisura del Paladar , Conocimientos, Actitudes y Práctica en Salud , Higiene Bucal , Padres , Niño , Preescolar , Humanos , Investigación Cualitativa
12.
Immunology ; 143(4): 679-91, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24990409

RESUMEN

CD1d-mediated lipid antigen presentation activates a subset of innate immune lymphocytes called invariant natural killer T (NKT) cells that, by virtue of their potent cytokine production, bridge the innate and adaptive immune systems. Transforming growth factor (TGF-ß) is a known immune modulator that can activate the mitogen-activated protein kinase p38; we have previously shown that p38 is a negative regulator of CD1d-mediated antigen presentation. Several studies implicate a role for TGF-ß in the activation of p38. Therefore, we hypothesized that TGF-ß would impair antigen presentation by CD1d. Indeed, a dose-dependent decrease in CD1d-mediated antigen presentation and impairment of lipid antigen processing was observed in response to TGF-ß treatment. However, it was found that this inhibition was not through p38 activation. Instead, Smads 2, 3 and 4, downstream elements of the TGF-ß canonical signalling pathway, contributed to the observed effects. In marked contrast to that observed with CD1d, TGF-ß was found to enhance MHC class II-mediated antigen presentation. Overall, these results suggest that the canonical TGF-ß/Smad pathway negatively regulates an important arm of the host's innate immune responses - CD1d-mediated lipid antigen presentation to NKT cells.


Asunto(s)
Presentación de Antígeno/inmunología , Antígenos CD1d/metabolismo , Transducción de Señal , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Animales , Presentación de Antígeno/efectos de los fármacos , Línea Celular , Femenino , Antígenos de Histocompatibilidad Clase II/inmunología , Lípidos/inmunología , Lisosomas/metabolismo , Ratones , Modelos Inmunológicos , Transporte de Proteínas , Factor de Crecimiento Transformador beta/farmacología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
13.
J Virol ; 82(15): 7492-503, 2008 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-18508900

RESUMEN

Broad, multispecific CD4(+) and CD8(+) T-cell responses to the hepatitis C virus (HCV), as well as virus-cross-neutralizing antibodies, are associated with recovery from acute infection and may also be associated in chronic HCV patients with a favorable response to antiviral treatment. In order to recapitulate all of these responses in an ideal vaccine regimen, we have explored the use of recombinant HCV polypeptides combined with various Th1-type adjuvants and replication-defective alphaviral particles encoding HCV proteins in various prime/boost modalities in BALB/c mice. Defective chimeric alphaviral particles derived from the Sindbis and Venezuelan equine encephalitis viruses encoding either the HCV envelope glycoprotein gpE1/gpE2 heterodimer (E1E2) or nonstructural proteins 3, 4, and 5 (NS345) elicited strong CD8(+) T-cell responses but low CD4(+) T helper responses to these HCV gene products. In contrast, recombinant E1E2 glycoproteins adjuvanted with MF59 containing a CpG oligonucleotide elicited strong CD4(+) T helper responses but no CD8(+) T-cell responses. A recombinant NS345 polyprotein also stimulated strong CD4(+) T helper responses but no CD8(+) T-cell responses when adjuvanted with Iscomatrix containing CpG. Optimal elicitation of broad CD4(+) and CD8(+) T-cell responses to E1E2 and NS345 was obtained by first priming with Th1-adjuvanted proteins and then boosting with chimeric, defective alphaviruses expressing these HCV genes. In addition, this prime/boost regimen resulted in the induction of anti-E1E2 antibodies capable of cross-neutralizing heterologous HCV isolates in vitro. This vaccine formulation and regimen may therefore be optimal in humans for protection against this highly heterogeneous global pathogen.


Asunto(s)
Anticuerpos Antivirales/inmunología , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Hepacivirus/inmunología , Vacunas contra Hepatitis Viral/inmunología , Proteínas Virales/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Alphavirus/genética , Animales , Colesterol/administración & dosificación , Colesterol/farmacología , Reacciones Cruzadas , Citocinas/biosíntesis , Combinación de Medicamentos , Femenino , Vectores Genéticos , Inmunización Secundaria , Leucocitos Mononucleares/inmunología , Ratones , Ratones Endogámicos BALB C , Pruebas de Neutralización , Fosfolípidos/administración & dosificación , Fosfolípidos/farmacología , Polisorbatos/administración & dosificación , Polisorbatos/farmacología , Saponinas/administración & dosificación , Saponinas/farmacología , Bazo/inmunología , Escualeno/administración & dosificación , Escualeno/farmacología , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Vacunas contra Hepatitis Viral/genética , Proteínas Virales/genética
14.
J Gen Virol ; 87(Pt 8): 2253-2262, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16847121

RESUMEN

Although approximately 3 % of the world's population is infected with Hepatitis C virus (HCV), there is no prophylactic vaccine available. This study reports the design, cloning and purification of a single polyprotein comprising the HCV core protein and non-structural proteins NS3, NS4a, NS4b, NS5a and NS5b. The immunogenicity of this polyprotein, which was formulated in alum, oil-in-water emulsion MF59 or poly(dl-lactide co-glycolide) in the presence or absence of CpG adjuvant, was then determined in a murine model for induction of B- and T-cell responses. The addition of adjuvants or a delivery system to the HCV polyprotein enhanced serum antibody and T-cell proliferative responses, as well as IFN-gamma responses, by CD4+ T cells. The antibody responses were mainly against the NS3 and NS5 components of the polyprotein and relatively poor responses were elicited against NS4 and the core components. IFN-gamma responses, however, were induced against all of the individual components of the polyprotein. These data suggest that the HCV polyprotein delivered with adjuvants induces broad B- and T-cell responses and could be a vaccine candidate against HCV.


Asunto(s)
Anticuerpos Antivirales/sangre , Linfocitos T CD4-Positivos/inmunología , Hepacivirus/inmunología , Poliproteínas/inmunología , Vacunas contra Hepatitis Viral/inmunología , Proteínas Virales/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Compuestos de Alumbre/administración & dosificación , Compuestos de Alumbre/farmacología , Animales , Proliferación Celular , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Interferón gamma/biosíntesis , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Modelos Animales , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/farmacología , Poliglactina 910/administración & dosificación , Poliproteínas/genética , Polisorbatos/administración & dosificación , Escualeno/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunología , Proteínas del Núcleo Viral/genética , Proteínas del Núcleo Viral/inmunología , Vacunas contra Hepatitis Viral/genética , Proteínas no Estructurales Virales/genética , Proteínas no Estructurales Virales/inmunología , Proteínas Virales/genética
15.
Immunity ; 22(5): 571-81, 2005 May.
Artículo en Inglés | MEDLINE | ID: mdl-15894275

RESUMEN

Extracellular antigens are internalized and processed before binding MHC class II molecules within endosomal and lysosomal compartments of professional antigen presenting cells (APC) for subsequent presentation to T cells. Yet select cytoplasmic peptides derived from autoantigens also intersect and bind class II molecules via an unknown mechanism. In human B lymphoblasts, inhibition of the peptide transporter associated with antigen processing (TAP) failed to alter class II-restricted cytoplasmic epitope presentation. By contrast, decreased display of cytoplasmic epitopes via class II molecules was observed in cells with diminished expression of the lysosome-associated membrane protein-2 (Lamp-2). Overexpression of Lamp-2 isoform A (Lamp-2a), an established component of chaperone-mediated autophagy, enhanced cytoplasmic autoantigen presentation. Manipulating APC expression of heat shock cognate protein 70 (hsc70), a cofactor for Lamp-2a, also altered cytoplasmic class II peptide presentation. These results demonstrate a novel role for the lysosomal Lamp-2a-hsc70 complex in promoting immunological recognition and antigen presentation.


Asunto(s)
Presentación de Antígeno , Antígenos CD/metabolismo , Antígenos de Histocompatibilidad Clase II/metabolismo , Transportadoras de Casetes de Unión a ATP , Antígenos CD/genética , Línea Celular , Citoplasma/inmunología , Electroporación , Endosomas/inmunología , Glutamato Descarboxilasa/inmunología , Proteínas del Choque Térmico HSC70 , Proteínas HSP70 de Choque Térmico/genética , Proteínas HSP70 de Choque Térmico/metabolismo , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Técnicas In Vitro , Proteínas de Membrana de los Lisosomas , Lisosomas/inmunología , Fragmentos de Péptidos/inmunología , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Transfección
16.
Eur J Immunol ; 35(3): 879-89, 2005 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15724241

RESUMEN

NKT cell activation plays an important role in regulating innate and adaptive immunity during infection. We have previously found that there is a dramatic reduction in the NKT cell population on day 3 after an acute lymphocytic choriomeningitis virus (LCMV) infection. In this study, we report that this loss continued for at least 3 months and was not simply due to internalization of the TCR. Concomitant with the decrease in NKT cells was an increase in the percentage of Annexin V(+) NKT cells that remained in vivo, suggesting that the reduction in NKT cells at these late stages post-infection occurred by activation-induced cell death. Interestingly, APC from LCMV-infected mice could activate NKT cells in vitro at higher levels than those from uninfected mice and was concomitant with an increase in apoptosis in NKT cells. However, this could not be blocked by mAb to murine CD1d, and APC from LCMV-infected (but not uninfected) CD1d1-deficient mice could also stimulate NKT cells. Collectively, our data suggest that the activation and subsequent long-term loss of NKT cells is a normal component of the host's antiviral immune response, and this occurs in a CD1d-independent manner.


Asunto(s)
Infecciones por Arenaviridae/inmunología , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/virología , Activación de Linfocitos/inmunología , Animales , Antígenos CD1/inmunología , Antígenos CD1d , Apoptosis/inmunología , Femenino , Virus de la Coriomeningitis Linfocítica/inmunología , Masculino , Ratones , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Tiempo
17.
J Leukoc Biol ; 77(2): 151-8, 2005 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15548574

RESUMEN

Mice were infected with lymphocytic choriomeningitis virus (LCMV) to determine if changes in CD1d expression occurred during an acute virus infection. It is interesting that a decrease in CD1d expression on splenic dendritic cells (DC) and macrophages (MPhi) was observed for at least 3 months post-LCMV infection, and vaccinia virus and vesicular stomatitis virus induced similar changes in CD1d upon infection with those viruses. The reduction of CD1d cell-surface expression on DC and MPhi was independent of interferon-gamma and interleukin-12 expression but partially recovered in transporter associated with antigen processing-1-deficient mice, suggesting that CD8+ T cells may play a role. Thus, one consequence of the induction of a cellular immune response is a change in CD1d expression, which may constitute a key element in regulating antiviral immunity.


Asunto(s)
Antígenos CD1/genética , Células Dendríticas/inmunología , Coriomeningitis Linfocítica/virología , Virus de la Coriomeningitis Linfocítica/inmunología , Macrófagos/inmunología , Enfermedad Aguda , Animales , Antígenos CD1/inmunología , Antígenos CD1d , Células Dendríticas/citología , Regulación hacia Abajo , Femenino , Regulación de la Expresión Génica , Células Asesinas Naturales/inmunología , Coriomeningitis Linfocítica/inmunología , Macrófagos/citología , Masculino , Ratones , Ratones Endogámicos C57BL , ARN/genética , Bazo/citología , Bazo/inmunología
18.
J Immunol ; 172(6): 3454-61, 2004 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-15004145

RESUMEN

CD1d1-restricted NK T (NKT) cells rapidly secrete both Th1 and Th2 cytokines upon activation and are therefore thought to play a regulatory role during an immune response. In this study we examined the role of CD1d1 molecules and NKT cells in regulating virus-induced cytokine production. CD1d1-deficient (CD1KO) mice, which lack NKT cells, were infected with lymphocytic choriomeningitis virus, and spontaneous cytokine release from splenocytes was measured. We found that CD1KO mice produce significantly higher amounts of IL-2, IL-4, and IFN-gamma compared with wild-type controls postinfection. Depletion studies of individual lymphocyte subpopulations suggested that CD4+ T cells are required; however, isolation of specific lymphocyte populations indicated that CD4+ T cells alone are not sufficient for the increase in cytokine production in CD1KO mice. Splenocytes from lymphocytic choriomeningitis virus-infected CD1KO mice continued to produce enhanced cytokine levels long after viral clearance and cleared viral RNA faster than wild-type mice. There was no difference in the number of splenocytes between uninfected wild-type and CD1KO mice, whereas the latter knockout mice had an increased number of splenocytes after infection. Collectively, these data provide clear evidence that the expression of CD1d1 molecules controls the magnitude of the cell-mediated immune response to an acute viral infection.


Asunto(s)
Antígenos CD1/fisiología , Coriomeningitis Linfocítica/inmunología , Coriomeningitis Linfocítica/prevención & control , Enfermedad Aguda , Animales , Antígenos CD1/biosíntesis , Antígenos CD1/genética , Antígenos CD1d , Relación Dosis-Respuesta Inmunológica , Femenino , Interferón gamma/biosíntesis , Interleucina-2/biosíntesis , Interleucina-4/biosíntesis , Cinética , Coriomeningitis Linfocítica/genética , Coriomeningitis Linfocítica/virología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Bazo/citología , Bazo/inmunología , Bazo/virología , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Subgrupos de Linfocitos T/virología
19.
Eur J Immunol ; 33(10): 2736-43, 2003 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-14515257

RESUMEN

CD11b, CD11c, and F4/80 are normally used to define dendritic cell and/or macrophage populations. In this study, the expression of all three markers was observed on CD8(+) T cells following infection of mice with several distinct viruses. Using lymphocytic choriomeningitis virus as a model virus, it was found that relatively more CD11b(+)CD8(+) and CD11c(+)CD8(+) T cells were present in the periphery than in primary lymphoid organs; in contrast, the F4/80(+)CD8(+) T cell population was more prevalent in the spleen. All three myeloid markers were detected on virus-specific CTL. The expression of CD11b and CD11c on CD8(+) T cells correlated with their level of CTL activity, whereas the F4/80(+)CD8(+) T cell population increased after the peak of the CTL response but did not have higher CTL activity. These data suggest that there is a differential induction of CD11b, CD11c, and F4/80 on virus-specific CD8(+) T cells following an acute virus infection.


Asunto(s)
Antígenos de Diferenciación/análisis , Antígeno CD11b/análisis , Antígeno CD11c/análisis , Linfocitos T CD8-positivos/química , Coriomeningitis Linfocítica/inmunología , Enfermedad Aguda , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Linfocitos T Citotóxicos/química
20.
Crit Rev Immunol ; 23(5-6): 403-19, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-15030309

RESUMEN

CD1d molecules are lipid antigen-presenting molecules. They are involved in presenting these antigens to a unique subpopulation of T cells called natural killer T (NKT) cells, which have the capacity to produce both T helper (Th) 1 and Th2 cytokines. Thus, it is possible that the antigens presented by CD1d and/or the level at which they are presented could have profound effects on the immunoregulation of autoimmune and infectious diseases, as well as cancer. Because of the ability of CD1d-binding ligands to modulate NKT cell responses, targeting CD1d-mediated antigen presentation as a novel approach for new therapies in these and other diseases holds great promise.


Asunto(s)
Presentación de Antígeno , Antígenos CD1/metabolismo , Células Asesinas Naturales/inmunología , Subgrupos de Linfocitos T/inmunología , Secuencia de Aminoácidos , Animales , Antígenos CD1/química , Antígenos CD1/genética , Antígenos CD1d , Enfermedades Autoinmunes/tratamiento farmacológico , Infecciones Bacterianas/inmunología , Citocinas/biosíntesis , Glucolípidos/inmunología , Glucolípidos/uso terapéutico , Humanos , Infecciones/tratamiento farmacológico , Ratones , Modelos Inmunológicos , Datos de Secuencia Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Tirosina/química , Virosis/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...