Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 14 de 14
Filtrar
1.
Sci Rep ; 14(1): 5489, 2024 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-38448478

RESUMEN

Ecological compensation has emerged as a crucial institutional framework for managing the interplay between ecological preservation and economic development in China. This study focuses on the specific case of grassland ecological compensation to investigate the protection of rights and interests of non-governmental subjects. By utilizing data derived from questionnaire responses, this study examines the legal rights, obligations, and responsibilities associated with grassland ecological compensation. Statistical techniques such as Z-distribution, chi-square test, and non-parametric measures of correlation are employed to analyze the collected data, which are presented using tables and graphs. Furthermore, this research evaluates the current state of rights and interests of compensation subjects engaged in ecological compensation practices, aiming to enhance our comprehension and assessment of the extent to which the ecological compensation system safeguards the rights and interests of individuals. The findings show that a substantial number of respondents see current grassland ecological compensation methods in China as reasonable but insufficient, indicating a need for method diversification. There's a clear preference for a shared responsibility model over government-only funding, especially in regions with large grassland areas. This highlights the necessity for adaptable laws and a legal framework that accommodates diverse stakeholder needs. Additionally, the importance of clear property rights is emphasized for sustainable land use. The study suggests legislative reform towards a more equitable and effective approach to grassland conservation, providing valuable recommendations for refining and advancing the ecological compensation system.Author name 1 (Ziqi Liu) mismatch between ms and metadata. We have foolowed metadata. Kindly check and confirm.The metadata is right. Thank you.


Asunto(s)
Desarrollo Económico , Pradera , Humanos , China , Recolección de Datos , Ecosistema
2.
BMC Public Health ; 24(1): 280, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-38263032

RESUMEN

BACKGROUND: The overall level of negative affect (NeA) has been linked to impaired health. However, whether the diurnal timing of NeA matters and whether the NeA-health relationship is mediated by sleep quality remain unclear. METHODS: Using a longitudinal dataset (2006, 2009 and 2014 waves) consisting of 1959 participants, we examined the within-person impact of both bedtime NeA and non-bedtime NeA measured by Day Reconstruction Method (DRM) on subjective health measured by Visual Analogue Scale (VAS), and the mediating effect of sleep quality on the NeA-health relationships by fixed effect models. RESULTS: Bedtime NeA predicted poorer health, while non-bedtime NeA was unrelated to health. The deleterious impact of bedtime NeA reduced and became non-significant after sleep quality was controlled for. Bedtime NeA also significantly predicted impaired sleep quality. CONCLUSIONS: Bedtime NeA is a stronger predictor of poorer health than non-bedtime NeA, and the deleterious influence of bedtime NeA on health seems to operate through poor sleep quality. Therefore, interventions to reduce bedtime NeA could potentially improve subsequent sleep quality, thereby protecting people to some extent from impaired health status.


Asunto(s)
Autoevaluación Diagnóstica , Calidad del Sueño , Humanos , China , Estado de Salud , Dimensión del Dolor
3.
Healthcare (Basel) ; 11(3)2023 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-36766973

RESUMEN

BACKGROUND: General practitioners (GPs) play a vital role in primary health care services and promoting the health equity of residents, but there is a paucity of evidence on equity in the allocation of GP resources in mainland China. This study explores equity in the allocation of GP resources from 2012 to 2019 in mainland China. METHODS: We used GP data from 31 provinces, autonomous regions, and municipalities in mainland China. Lorenz curves, Gini coefficients, Theil indices, and agglomeration degree were used to analyze the data. RESULTS: The total number of GPs in China was 365,082 in 2019, which corresponded to 2.61 GPs per 10,000 residents and accounted for 9.44% of the total number of practicing doctors in 2019. From 2012 to 2019, the Gini coefficient of GP allocation based on population decreased from 0.3123 to 0.1872. However, the Gini coefficient based on geographical area was maintained at 0.7108-0.7424. The Theil index of GP allocation based on population decreased from 0.0742 to 0.0270, but GP allocation based on geographical area was maintained at 0.5765-0.6898. The intra-regional contribution rates were higher than the inter-regional rates. The agglomeration degree based on geographical area and population decreased in the eastern region but increased in the central and western regions. CONCLUSIONS: The number of Chinese GPs has increased rapidly in recent years, but the distribution of GPs across China is uneven. In the western and middle regions, there is a relative shortage. Equity in the allocation of GP resources based on population was far greater than that based on geographical area. In the future, the tough issue of inequitable GP resource allocation should be resolved by comprehensive measures from a multidisciplinary perspective.

4.
Artículo en Inglés | MEDLINE | ID: mdl-33919789

RESUMEN

Although the diurnal rhythms of affect influence people's health and behavior, there is a lack of evidence from rural China, where the types and timing of social activities may differ from Western contexts. In this study, a total of 2847 Chinese rural residents from three provinces of China are interviewed using the abbreviated Day Reconstruction Method (DRM) questionnaire. Diurnal rhythms of three affective subjective wellbeing (SWB) indicators-positive affect (PoA), negative affect (NeA), and net affect are analyzed by multilevel models. Our results show PoA and net affect generally increase in magnitude throughout the day with two peaks around noon and in the evening, respectively; whereas, there is an overall decline in NeA as the day passes with two troughs occurring at lunchtime and in the evening. These patterns, however, flatten considerably, with the lunchtime peaks in PoA and net affect (and trough in NeA) disappearing entirely, after further controlling for two social environmental factors-activity type and the quality of social interaction. This study, set in rural China, corroborates the diurnal rhythms of affect from prior Western research to some extent, and highlights that social environmental factors have a significant effect on diurnal rhythms of affect in the rural Chinese context. It is possible that the diurnal rhythms of affect could change in response to stimulation from the environment. Improving some social environmental factors, such as organizing pleasant activities and creating a friendly interactive environment, could contribute to the increase in positive affect and decline in negative affect, thereby enhancing the quality of life.


Asunto(s)
Ritmo Circadiano , Calidad de Vida , China , Humanos , Población Rural , Medio Social
5.
Anal Chim Acta ; 1123: 28-35, 2020 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-32507237

RESUMEN

One of the major challenges facing the early diagnosis of chronic myelogenous leukemia (CML) patients today is enhancing the simplicity, rapidness, sensitivity and specificity of detection assay for easy clinical implementation. RNA-cleaving fluorogenic DNAzymes (RFDs) are single-stranded DNA molecules with catalytic activity and can produce fluorescent signals when combined with specific targets. As K562 cells were the first established human immortalized myelogenous leukemia line, we try to screen several RFDs using the crude extracellular mixture of K562 cells through the SELEX process. We obtained an RFD probe A1-3 that is able to distinguish K562 cells from other tumor cell lines. 10 nM of A1-3 can induce an increase of detectable fluorescence signal. Moreover, the RFD assay system can work well for target detection in complex serum matrix. The optimized RFD assay system with low cost also has a desirable ability to exactly distinguish K562 cells after truncation of 20 bases in the 5'end of A1-3. This study is the first report to investigate the RFD system for detection of K562 cells using cell culture supernatants as the complex target. This RFD assay system could potentially be applied for the diagnosis of CML.


Asunto(s)
ADN Catalítico/química , Colorantes Fluorescentes/química , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico por imagen , ADN Catalítico/sangre , ADN Catalítico/metabolismo , Colorantes Fluorescentes/metabolismo , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/sangre , Leucemia Mielógena Crónica BCR-ABL Positiva/metabolismo , Células Tumorales Cultivadas
6.
Front Physiol ; 11: 208, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32256382

RESUMEN

Chinese giant salamander Andrias davidianus has strong tolerance to starvation. Fasting triggers a complex array of adaptive metabolic responses, a process in which the liver plays a central role. Here, a high-throughput proteomic analysis was carried out on liver samples obtained from adult A. davidianus after 3, 7, and 11 months of fasting. As a result, the expression levels of 364 proteins were significantly changed in the fasted liver. Functional analysis demonstrated that the expression levels of key proteins involved in fatty acid oxidation, tricarboxylic acid cycle, gluconeogenesis, ketogenesis, amino acid oxidation, urea cycle, and antioxidant systems were increased in the fasted liver, especially at 7 and 11 months after fasting. In contrast, the expression levels of vital proteins involved in pentose phosphate pathway and protein synthesis were decreased after fasting. We also found that fasting not only activated fatty acid oxidation and ketogenesis-related transcription factors PPARA and PPARGC1A, but also activated gluconeogenesis-related transcription factors FOXO1, HNF4A, and KLF15. This study confirms the central role of lipid and acetyl-CoA metabolism in A. davidianus liver in response to fasting at the protein level and provides insights into the molecular mechanisms underlying the metabolic response of A. davidianus liver to fasting.

7.
Artículo en Inglés | MEDLINE | ID: mdl-31311072

RESUMEN

Background: Village doctors, as gatekeepers for the health of rural residents in China, are confronted with adversity in providing the basic public health services (BPHS), which has significantly impeded them from providing high quality BPHS. This study aimed to explore the obstacles and difficulties faced by village doctors in order to improve the quality and efficiency of BPHS provision and increase the health level of the population. Methods: In-depth interviews were employed to conduct this qualitative study. A total of 51 village doctors in four cities of Shandong Province were interviewed. The interviews were transcribed, anonymized, and imported into NVivo11.0 to facilitate management. Thematic framework analysis employing the constant comparison method was applied to the data analysis. Results: The main challenges faced by village doctors comprised the shortage, gender imbalance, and poor education of village doctors; older village doctors in some villages; low income; lack of social security; inappropriate performance assessment; inadequate professional BPHS training; heavy workload; and insufficient cooperation from rural residents, which have exacerbated the quality, efficiency, and accessibility of BPHS to some extent. Conclusions: Village doctors, as the important BPHS providers in rural Shandong, are facing a wide range of challenges. It is urgent for government officials and policy makers to consider these challenges and concentrate on improving the quality of BPHS provision by developing relevant and practical strategies.


Asunto(s)
Actitud del Personal de Salud , Atención a la Salud/organización & administración , Médicos de Atención Primaria , Administración en Salud Pública , Calidad de la Atención de Salud/organización & administración , Servicios de Salud Rural/organización & administración , China , Femenino , Humanos , Masculino , Salud Pública , Investigación Cualitativa , Salud Rural
8.
Artículo en Inglés | MEDLINE | ID: mdl-28621760

RESUMEN

Objective: This study aimed to assess the quantitative effects of short-term exposure of ambient nitrogen dioxide (NO2) on respiratory disease (RD) mortality and RD hospital admission in China through systematic review and meta-analysis. Methods: A total of 29 publications were finally selected from searches in PubMed, Web of Science, CNKI and Wanfang databases. Generic inverse variance method was used to pool effect estimates. Pooled estimates were used to represent the increased risk of RD mortality and RD hospital admission per 10 µg/m³ increase in NO2 concentration. Results: Positive correlations were found between short-term NO2 exposure and RD in China. RD mortality and RD hospital admission respectively increased by 1.4% (95% CI: 1.1%, 1.7%) and 1.0% (95% CI: 0.5%, 1.5%) per 10 µg/m³ increase in NO2 concentration. Differences were observed across geographic regions of China. The risk of RD mortality due to NO2 was higher in the southern region (1.7%) than in the north (0.7%). Conclusions: Evidence was found that short-term exposure to NO2 was associated with an increased risk of RD mortality and RD hospital admission in China and these risks were more pronounced in the southern regions of the country, due in part to a larger proportion of elderly persons with increased susceptibility to NO2 in the population compared with the north.


Asunto(s)
Contaminantes Atmosféricos/análisis , Hospitalización/estadística & datos numéricos , Dióxido de Nitrógeno/análisis , Enfermedades Respiratorias/mortalidad , China/epidemiología , Humanos , Enfermedades Respiratorias/inducido químicamente
9.
PLoS One ; 5(8): e12381, 2010 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-20865034

RESUMEN

BACKGROUND: KIR2DS5 gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation. METHODOLOGY/PRINCIPAL FINDINGS: In our studies on KIR2DS5 gene associations with human diseases, we compared the frequencies of this gene in patients and relevant controls. Typing for KIR2DS5 gene was performed by either individual or multiplex polymerase chain reactions which, when compared in the same samples, gave concordant results. We noted an apparently protective effect of KIR2DS5 gene presence in several clinical conditions, but not in others. Namely, this effect was observed in ankylosing spondylitis (p=0.003, odds ratio [OR]=0.47, confidence interval [CI]=0.28-0.79), endometriosis (p=0.03, OR=0.25, CI = 0.07-0.82) and acute rejection of kidney graft (p=0.0056, OR=0.44, CI=0.24-0.80), but not in non-small-cell lung carcinoma, rheumatoid arthritis, spontaneous abortion, or leukemia (all p>0.05). In addition, the simultaneous presence of KIR2DS5 gene and HLA-C C1 allotype exhibited an even stronger protective effect on ankylosing spondylitis (p=0.0003, OR=0.35, CI=0.19-0.65), whereas a lack of KIR2DS5 and the presence of the HLA-C C2 allotype was associated with ankylosing spondylitis (p=0.0017, OR=1.92, CI=1.28-2.89), whereas a lack of KIR2DS5 and presence of C1 allotype was associated with rheumatoid arthritis (p=0.005, OR=1.47, CI=1.13-1.92). The presence of both KIR2DS5 and C1 seemed to protect from acute kidney graft rejection (p=0.017, OR=0.47, CI=0.25-0.89), whereas lack of KIR2DS5 and presence of C2 seemed to favor rejection (p=0.0015, OR=2.13, CI=1.34-3.37). CONCLUSIONS/SIGNIFICANCE: Our results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.


Asunto(s)
Enfermedad/genética , Receptores KIR/genética , Adulto , Anciano , Anciano de 80 o más Años , Endometriosis/genética , Femenino , Frecuencia de los Genes , Rechazo de Injerto/genética , Humanos , Masculino , Persona de Mediana Edad , Receptores KIR/metabolismo , Espondilitis Anquilosante/genética , Adulto Joven
10.
Ann Neurol ; 65(6): 658-66, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19630074

RESUMEN

OBJECTIVE: Multiple sclerosis (MS) is a chronic inflammatory disease affecting the central nervous system. A human leukocyte antigen (HLA) class II association is well established (DRB1*1501-DQB1*0602), but more recently HLA class II-independent associations with HLA class I variants have also been reported. The HLA class I (HLA-A, -B, -C) molecules serve as ligands for both T-cell receptors and killer immunoglobulin-like receptors (KIRs). We investigated the HLA class I alleles defined by their KIR binding motifs and the KIR genes to evaluate whether these genes could influence MS susceptibility or severity, alone or in combination. METHODS: We typed Norwegian MS patients (n = 631) and controls (n = 555) for HLA-A, -B, -C and -DRB1 alleles as well as the presence or absence of genes encoding inhibitory (KIR2DL1, KIR2DL2, KIR2DL3, KIR2DL5, KIR3DL1, KIR3DL2, KIR3DL3) and activating (KIR2DS1, KIR2DS2, KIR2DS3, KIR2DL4, KIR2DS4, KIR2DS5, KIR3DS1) KIRs. RESULTS: The frequency of the HLA-Bw4 specificity, which is the ligand for the inhibitory KIR3DL1, was significantly reduced in MS patients as compared with controls (41.4% vs 55.1%, p(uncorrected (uc)) = 4.6 x 10(-6)). Also after stratifying for known HLA class II associations, the HLA-Bw4 association was seen (p(uc) = 0.002). No significant differences in gene carrier frequencies of inhibitory and activating KIRs were observed. However, our data indicate that MS patients who carry the activating KIR2DS2 and the inhibitory KIR2DL2 genes have more severe disease than patients not carrying these genes. INTERPRETATION: Carriage of the ligand of the inhibitory KIR3DL1 receptor, HLA-Bw4, was found to protect against MS in an HLA-DRB1 independent manner.


Asunto(s)
Antígenos HLA-B/fisiología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/prevención & control , Receptores KIR/metabolismo , Adolescente , Adulto , Niño , Femenino , Tamización de Portadores Genéticos , Antígenos HLA-B/genética , Antígenos HLA-B/metabolismo , Antígenos HLA-DR/fisiología , Cadenas HLA-DRB1 , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/metabolismo , Unión Proteica/inmunología , Receptores KIR/genética , Receptores KIR/fisiología , Adulto Joven
11.
J Hepatol ; 46(5): 899-906, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17383044

RESUMEN

BACKGROUND/AIMS: Combinations of killer immunoglobulin-like receptors (KIRs) and HLA class I ligands that reduce natural killer (NK) cell inhibition have been shown to increase risk for autoimmune diseases. We aimed to clarify to what extent such combinations influence susceptibility to primary sclerosing cholangitis (PSC). METHODS: Three hundred and sixty-five Scandinavian PSC patients and 368 healthy controls were genotyped for the presence or absence of genes encoding all KIRs using a PCR-SSP approach. KIR binding site variation of HLA-A, -B and -C was also determined. RESULTS: The KIR gene frequencies were similar among patients and controls. However, the frequency of HLA-Bw4 and -C2, which are ligands for the inhibitory KIRs 3DL1 and 2DL1, respectively, was significantly reduced in PSC patients as compared with controls (38.2% vs. 54.7%, P(corrected)[P(c)]=0.0006 and 42.7% vs. 56.9%, P(c)=0.009, respectively). Two HLA risk haplotypes in PSC (carrying DRB1*0301 or DRB1*1501, respectively) were devoid of both of these alleles, and carried the 5.1 variant of the major histocompatibility complex class I chain-related A (MICA) gene previously reported to influence PSC susceptibility. CONCLUSIONS: Particular variants of ligands for NK cell receptors encoded at three neighbouring genes in the HLA complex may contribute to PSC associations observed in this genetic region.


Asunto(s)
Colangitis Esclerosante/genética , Frecuencia de los Genes , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Células Asesinas Naturales/metabolismo , Polimorfismo Genético , Receptores Inmunológicos/genética , Adolescente , Adulto , Anciano , Enfermedades Autoinmunes , Niño , Colangitis Esclerosante/diagnóstico por imagen , Colangitis Esclerosante/inmunología , Predisposición Genética a la Enfermedad , Antígeno HLA-B7/genética , Antígeno HLA-B8/genética , Antígenos HLA-C/genética , Antígeno HLA-DR3/genética , Antígeno HLA-DR6/genética , Cadenas HLA-DRB1 , Haplotipos/genética , Humanos , Ligandos , Desequilibrio de Ligamiento , Persona de Mediana Edad , Noruega , Radiografía , Receptores KIR , Receptores KIR2DL1 , Receptores KIR3DL1
12.
Leuk Res ; 31(2): 261-5, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16876862

RESUMEN

In systemic mastocytosis with associated clonal, hematological non-mast cell lineage disease (SM-AHNMD), mast cell infiltration of the bone marrow coexists with a hematologic neoplasm, usually of myeloid origin. Activating KIT gene mutations are universally present in these neoplastic mast cells. When SM is associated with AML, the leukemic cells commonly carry the t(8;21)(q22;q22) core binding factor translocation. The precise relationship between neoplastic mast cells and the leukemic clone has remained unclear. By target FISH analysis, we demonstrate t(8;21) in the bone marrow mast cells of a patient with systemic mastocytosis associated with t(8;21) AML, thus, proving the origin of these neoplastic mast cells from the leukemic clone. We also show that after successful allogeneic hematopoietic stem cell transplantation, these neoplastic bone marrow mast cells can persist without adverse consequences and gradually decline with time.


Asunto(s)
Cromosomas Humanos Par 8/genética , Leucemia Mieloide/genética , Mastocitos/patología , Mastocitosis Sistémica/genética , Neoplasias Primarias Secundarias/genética , Enfermedad Aguda , Cromosomas Humanos Par 21/genética , Análisis Citogenético/métodos , Exones , Femenino , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ/métodos , Leucemia Mieloide/diagnóstico , Leucemia Mieloide/terapia , Mastocitosis Sistémica/diagnóstico , Mastocitosis Sistémica/terapia , Persona de Mediana Edad , Neoplasias Primarias Secundarias/diagnóstico , Neoplasias Primarias Secundarias/terapia , Mutación Puntual , Reacción en Cadena de la Polimerasa/métodos , Proteínas Proto-Oncogénicas c-kit/genética
13.
Cancer Immunol Immunother ; 52(12): 761-70, 2003 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-14564482

RESUMEN

Chronic myelogenous leukemia (CML) is characterized by a t(9;22) translocation resulting in expression of BCR-ABL fusion oncoproteins which are unique to the leukemic cells, necessary for oncogenesis, and potentially immunogenic. We have previously shown that human dendritic cells transduced with an adeno-associated virus vector encoding the fusion region of the b3a2 splice variant (p210(b3a2)) of the BCR-ABL oncoprotein elicit specific T-cell responses in vitro. Two cytotoxic T lymphocyte (CTL) clones generated in this fashion displayed restriction with previously unreported HLA alleles. The first, T1/B9, was CD4(+) and restricted by DRB5*0101 (autologous) or DRB1*1101 (allogeneic). The minimum cytotoxic epitope (MCE) binding to DRB5*0101 for this clone was identified as FKQSSKALQ, overlapping the p210(b3a2) fusion point (boldface). The MCE of DRB1*1101 for this clone differed from DRB5*0101, but also included the fusion point. The clonality of CTL T1/B9 was verified by analyses of TCRalpha/beta chain usage and DNA sequence analyses. To our knowledge, this is the first description of a single clone recognizing both DRB5*0101 and DRB1*1101. The other CTL clone, T1/33, was CD8+ and recognized HLA-B*3501 or B*3503 complexed with an MCE, RPVASDFEP, derived from the c-abl sequence in proximity to the p210(b3a2) fusion point. K562 cells transfected with plasmids encoding HLA-DRA + B5*0101, B*3501, or B*3503 but not controls expressing DRA + DRB1*1501 were lysed by cognate CTL clones, confirming that DRB5*0101 and B*3501/3 could present p210(b3a2) joining region epitopes via endogenous processing. The identification of three additional HLA alleles (DRB5*0101, B*3501, and B*3503) presenting the p210(b3a2) fusion-region antigen will broaden the application of vaccine strategies for targeting CML cells. The findings of single CTL clones cross-recognizing autologous (DRB5*0101 or B*3501) and allogeneic (DRB1*1101 or B*3503) HLA alleles presenting BCR-ABL fusion-region epitopes implies the potential separation of graft-versus-leukemia from graft-versus-host effects.


Asunto(s)
Presentación de Antígeno , Células Dendríticas/inmunología , Proteínas de Fusión bcr-abl/inmunología , Antígenos HLA-DR/inmunología , Linfocitos T Citotóxicos/inmunología , Adenoviridae/genética , Secuencia de Aminoácidos , Secuencia de Bases , Citotoxicidad Inmunológica/genética , Vectores Genéticos/genética , Cadenas HLA-DRB1 , Cadenas HLA-DRB5 , Humanos , Células K562 , Datos de Secuencia Molecular , Fragmentos de Péptidos/inmunología , Receptores de Antígenos de Linfocitos T alfa-beta/metabolismo , Transducción Genética
14.
Cancer Res ; 62(11): 3175-83, 2002 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-12036931

RESUMEN

Chronic myelogenous leukemia (CML) is characterized by a t(9;22) translocation, which results in the expression of chimeric BCR-ABL fusion oncoproteins that are necessary for oncogenesis, unique to the leukemic clones, and represent enticing targets for immunotherapy. As a strategy for the immunotherapy of CML, we constructed a recombinant adeno-associated virus vector encoding the p210(BCR-ABL) b3a2 variant fusion region with flanking sequences (CWRBA) and used it to express the BCR-ABL fusion region within primary human dendritic cells (DCs), the most potent antigen-presenting cells currently known. Peripheral blood mononuclear cells from healthy donors were primed and restimulated in vitro with autologous DCs transduced with purified CWRBA, CWRAP (negative control), or pulsed with a peptide corresponding to the fusion domain (positive control). No specific responses were generated using DCs transduced with CWRAP. In contrast, CWRBA-transduced DCs primed autologous T cells in an antigen-specific, MHC-restricted fashion to levels comparable with the positive control. CWRBA-transduced DCs elicited both cytotoxic CD4+/Th1 and CD8+ responses, although the former were more readily detected in this system. Cytotoxicity against a tumor cell line endogenously expressing the p210(BCR-ABL) b3a2 variant fusion region was also demonstrable. In addition, HLA-DRB5(*)0101+DRA (DR2a) was identified as a new restriction element capable of presenting the b3a2 BCR-ABL fusion region epitope. Thus, the construct developed herein may serve as a candidate vaccine for gene-based antigen-specific immunotherapy of CML and may serve as a paradigm for the use of DCs transduced with recombinant adeno-associated virus vectors encoding multiepitope immunogens for vaccine development.


Asunto(s)
Células Dendríticas/inmunología , Proteínas de Fusión bcr-abl/inmunología , Vacunas de ADN/inmunología , Secuencia de Aminoácidos , Línea Celular , Dependovirus/genética , Epítopos de Linfocito T , Proteínas de Fusión bcr-abl/genética , Vectores Genéticos/genética , Humanos , Células K562 , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/inmunología , Datos de Secuencia Molecular , Estructura Terciaria de Proteína , Linfocitos T Citotóxicos/inmunología , Transducción Genética , Vacunas de ADN/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...