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1.
Int J Ophthalmol ; 17(5): 940-950, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38766336

RESUMEN

AIM: To gain insights into the global research hotspots and trends of myopia. METHODS: Articles were downloaded from January 1, 2013 to December 31, 2022 from the Science Core Database website and were mainly statistically analyzed by bibliometrics software. RESULTS: A total of 444 institutions in 87 countries published 4124 articles. Between 2013 and 2022, China had the highest number of publications (n=1865) and the highest H-index (61). Sun Yat-sen University had the highest number of publications (n=229) and the highest H-index (33). Ophthalmology is the main category in related journals. Citations from 2020 to 2022 highlight keywords of options and reference, child health (pediatrics), myopic traction mechanism, public health, and machine learning, which represent research frontiers. CONCLUSION: Myopia has become a hot research field. China and Chinese institutions have the strongest academic influence in the field from 2013 to 2022. The main driver of myopic research is still medical or ophthalmologists. This study highlights the importance of public health in addressing the global rise in myopia, especially its impact on children's health. At present, a unified theoretical system is still needed. Accurate surgical and therapeutic solutions must be proposed for people with different characteristics to manage and intervene refractive errors. In addition, the benefits of artificial intelligence (AI) models are also reflected in disease monitoring and prediction.

2.
Int J Ophthalmol ; 17(1): 1-6, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38239946

RESUMEN

AIM: To develop an artificial intelligence (AI) diagnosis model based on deep learning (DL) algorithm to diagnose different types of retinal vein occlusion (RVO) by recognizing color fundus photographs (CFPs). METHODS: Totally 914 CFPs of healthy people and patients with RVO were collected as experimental data sets, and used to train, verify and test the diagnostic model of RVO. All the images were divided into four categories [normal, central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), and macular retinal vein occlusion (MRVO)] by three fundus disease experts. Swin Transformer was used to build the RVO diagnosis model, and different types of RVO diagnosis experiments were conducted. The model's performance was compared to that of the experts. RESULTS: The accuracy of the model in the diagnosis of normal, CRVO, BRVO, and MRVO reached 1.000, 0.978, 0.957, and 0.978; the specificity reached 1.000, 0.986, 0.982, and 0.976; the sensitivity reached 1.000, 0.955, 0.917, and 1.000; the F1-Sore reached 1.000, 0.955 0.943, and 0.887 respectively. In addition, the area under curve of normal, CRVO, BRVO, and MRVO diagnosed by the diagnostic model were 1.000, 0.900, 0.959 and 0.970, respectively. The diagnostic results were highly consistent with those of fundus disease experts, and the diagnostic performance was superior. CONCLUSION: The diagnostic model developed in this study can well diagnose different types of RVO, effectively relieve the work pressure of clinicians, and provide help for the follow-up clinical diagnosis and treatment of RVO patients.

3.
Int J Ophthalmol ; 16(9): 1431-1440, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37724282

RESUMEN

AIM: To explore the latest application of artificial intelligence (AI) in optical coherence tomography (OCT) images, and to analyze the current research status of AI in OCT, and discuss the future research trend. METHODS: On June 1, 2023, a bibliometric analysis of the Web of Science Core Collection was performed in order to explore the utilization of AI in OCT imagery. Key parameters such as papers, countries/regions, citations, databases, organizations, keywords, journal names, and research hotspots were extracted and then visualized employing the VOSviewer and CiteSpace V bibliometric platforms. RESULTS: Fifty-five nations reported studies on AI biotechnology and its application in analyzing OCT images. The United States was the country with the largest number of published papers. Furthermore, 197 institutions worldwide provided published articles, where University of London had more publications than the rest. The reference clusters from the study could be divided into four categories: thickness and eyes, diabetic retinopathy (DR), images and segmentation, and OCT classification. CONCLUSION: The latest hot topics and future directions in this field are identified, and the dynamic evolution of AI-based OCT imaging are outlined. AI-based OCT imaging holds great potential for revolutionizing clinical care.

4.
Int J Ophthalmol ; 16(7): 995-1004, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465510

RESUMEN

AIM: To conduct a classification study of high myopic maculopathy (HMM) using limited datasets, including tessellated fundus, diffuse chorioretinal atrophy, patchy chorioretinal atrophy, and macular atrophy, and minimize annotation costs, and to optimize the ALFA-Mix active learning algorithm and apply it to HMM classification. METHODS: The optimized ALFA-Mix algorithm (ALFA-Mix+) was compared with five algorithms, including ALFA-Mix. Four models, including ResNet18, were established. Each algorithm was combined with four models for experiments on the HMM dataset. Each experiment consisted of 20 active learning rounds, with 100 images selected per round. The algorithm was evaluated by comparing the number of rounds in which ALFA-Mix+ outperformed other algorithms. Finally, this study employed six models, including EfficientFormer, to classify HMM. The best-performing model among these models was selected as the baseline model and combined with the ALFA-Mix+ algorithm to achieve satisfactory classification results with a small dataset. RESULTS: ALFA-Mix+ outperforms other algorithms with an average superiority of 16.6, 14.75, 16.8, and 16.7 rounds in terms of accuracy, sensitivity, specificity, and Kappa value, respectively. This study conducted experiments on classifying HMM using several advanced deep learning models with a complete training set of 4252 images. The EfficientFormer achieved the best results with an accuracy, sensitivity, specificity, and Kappa value of 0.8821, 0.8334, 0.9693, and 0.8339, respectively. Therefore, by combining ALFA-Mix+ with EfficientFormer, this study achieved results with an accuracy, sensitivity, specificity, and Kappa value of 0.8964, 0.8643, 0.9721, and 0.8537, respectively. CONCLUSION: The ALFA-Mix+ algorithm reduces the required samples without compromising accuracy. Compared to other algorithms, ALFA-Mix+ outperforms in more rounds of experiments. It effectively selects valuable samples compared to other algorithms. In HMM classification, combining ALFA-Mix+ with EfficientFormer enhances model performance, further demonstrating the effectiveness of ALFA-Mix+.

5.
Int J Ophthalmol ; 15(3): 446-452, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35310056

RESUMEN

AIM: To delineate the different imaging characteristics of uveal schwannoma from melanoma and discuss the optimal treatment strategy for intraocular schwannoma. METHODS: Case series of three patients diagnosed with intraocular schwannoma was collected at Zhongshan Ophthalmic Center, Guangzhou, China from July 2014 to December 2020. All the study patients underwent ultrasonography and magnetic resonance imaging (MRI). The clinical features, therapeutic strategies, and prognoses of all patients were reviewed. RESULTS: Ultrasonography of all three patients (all females, mean age, 39y, age range, 23-54y) showed low to medium reflectivity with a homogeneous internal structure. MRI of all three patients demonstrated isointensity on T1-weighted imaging spin-echo (T1WI SE) images and hypointense on fast spin-echo T2-weighted images (FSE T2WI) images with respect to the brain. Minimally invasive pars plana vitrectomy (PPV) and local resection of the tumor was performed for all patients, and the diagnosis of schwannoma was confirmed by histopathological examination. CONCLUSION: The present study indicates that ultrasonography and MRI features of uveal schwannoma may contribute to the differentiation of uveal schwannoma from melanoma, and the optimal therapy for intraocular schwannoma is minimally invasive PPV and local resection.

6.
Int J Ophthalmol ; 12(5): 802-808, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31131240

RESUMEN

AIM: To investigate microvascular changes in eyes with central retinal vein occlusion (CRVO) complicated by macular edema before and after intravitreal conbercept injection and evaluate correlations between these changes and best-corrected visual acuity (BCVA) and retinal thickness. METHODS: Twenty-eight eyes of 28 patients with macular edema caused by CRVO were included in this retrospective study. All patients received a single intravitreal conbercept injection to treat macular edema. BCVA and the results of optical coherence tomography angiography (OCTA) automatic measurements of the vessel density in the superficial (SCP) and deep retinal capillary plexus (DCP), the foveal avascular zone (FAZ) area, the FAZ perimeter (PERIM), the vessel density within a 300-µm wide ring surrounding the FAZ (FD-300), the acircularity index (AI), the choriocapillaris flow area, and retinal thickness were recorded before and at one month after treatment and compared with the results observed in age- and sex-matched healthy subjects. RESULTS: The vessel density in the SCP and DCP, the FD-300, and the flow area of the choriocapillaris were all significantly lower in CRVO eyes than in healthy eyes, while the AI and retinal thickness were significantly higher (all P<0.05). After treatment, retinal thickness was significantly decreased, and the mean BCVA had markedly improved from 20/167 to 20/65 (P=0.0092). The flow area of the choriocapillaris was also significantly improved, which may result from the reduction of shadowing effect caused by the attenuation of macular edema. However, there were no significant changes in SCP and DCP vessel density after treatment. The flow area of the choriocapillaris at baseline was negatively correlated with retinal thickness. CONCLUSION: OCTA enables the non-invasive, layer-specific and quantitative assessment of microvascular changes both before and after treatment, and can therefore be used as a valuable imaging tool for the evaluation of the follow-up in CRVO patients.

7.
Int J Ophthalmol ; 11(8): 1390-1395, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30140646

RESUMEN

AIM: To determine the prevalence and characteristics of peripheral myopic retinopathy among a sample of Guangzhou office workers. METHODS: A cross-sectional study of Guangzhou Chinese office works in different departments and units of the Guangzhou Power Supply Bureau, China, in 2016. Myopic retinopathy was recorded and analyzed with a scanning laser ophthalmoscope and by slit-lamp microscopy combined with a three-mirror contact lens. RESULTS: In total, 1910 eyes of 955 subjects (508 females and 447 males) aged 21-59y were included; 69.6% of these eyes were myopic. The myopia group had a younger age and worse uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA) when compared with hyperopia and emmetropia groups (P<0.001). The axial length (AL) was significantly longer, the spherical equivalent (SE) was more serious, and the optic nerve crescent was significantly larger in subjects with myopia than with hyperopia and emmetropia. Subjects with myopia, and especially high myopia, had the highest frequency of myopic retinal 18 changes (49.4%, P<0.001) [white-without-pressure (43.8%, P<0.001), lattice degeneration (4.5%, P=0.044)] among the three groups. Logistic regression confirmed that any myopia (OR: 3.41, P<0.001) [mild myopia (OR: 1.93, P=0.001), moderate myopia (OR:3.64, P<0.001), and high myopia (OR:10.58, P<0.001)], a greater AL (OR: 1.55, P<0.001) and a much higher SE (OR: 0.77, P<0.001) increased the risk for peripheral retinal changes. CONCLUSION: Myopia-related retinal changes are positively associated with greater AL, higher SE, and myopia.

8.
PLoS Pathog ; 11(3): e1004725, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25781895

RESUMEN

Dendritic cells (DCs) and macrophages (Møs) internalize and process exogenous HIV-derived antigens for cross-presentation by MHC-I to cytotoxic CD8⁺ T cells (CTL). However, how degradation patterns of HIV antigens in the cross-presentation pathways affect immunodominance and immune escape is poorly defined. Here, we studied the processing and cross-presentation of dominant and subdominant HIV-1 Gag-derived epitopes and HLA-restricted mutants by monocyte-derived DCs and Møs. The cross-presentation of HIV proteins by both DCs and Møs led to higher CTL responses specific for immunodominant epitopes. The low CTL responses to subdominant epitopes were increased by pretreatment of target cells with peptidase inhibitors, suggestive of higher intracellular degradation of the corresponding peptides. Using DC and Mø cell extracts as a source of cytosolic, endosomal or lysosomal proteases to degrade long HIV peptides, we identified by mass spectrometry cell-specific and compartment-specific degradation patterns, which favored the production of peptides containing immunodominant epitopes in all compartments. The intracellular stability of optimal HIV-1 epitopes prior to loading onto MHC was highly variable and sequence-dependent in all compartments, and followed CTL hierarchy with immunodominant epitopes presenting higher stability rates. Common HLA-associated mutations in a dominant epitope appearing during acute HIV infection modified the degradation patterns of long HIV peptides, reduced intracellular stability and epitope production in cross-presentation-competent cell compartments, showing that impaired epitope production in the cross-presentation pathway contributes to immune escape. These findings highlight the contribution of degradation patterns in the cross-presentation pathway to HIV immunodominance and provide the first demonstration of immune escape affecting epitope cross-presentation.


Asunto(s)
Reactividad Cruzada/inmunología , Células Dendríticas/inmunología , VIH-1/inmunología , Evasión Inmune/inmunología , Macrófagos/inmunología , Linfocitos T Citotóxicos/inmunología , Epítopos de Linfocito T/inmunología , Infecciones por VIH/inmunología , Humanos , Epítopos Inmunodominantes/inmunología , Espectrometría de Masas
9.
Biomed Res Int ; 2014: 364961, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24790997

RESUMEN

Purpose. To observe the long-term effectiveness of scleral buckling and transscleral cryopexy conducted under a surgical microscope in the treatment of uncomplicated rhegmatogenous retinal detachment. Methods. This was a retrospective analysis in a total of 227 consecutive patients (244 eyes) with uncomplicated rhegmatogenous retinal detachment (proliferative vitreoretinopathy ≤ C2). All patients underwent scleral buckling and transscleral cryopexy under a surgical microscope without using a binocular indirect ophthalmoscope or a contact lens. Results. After initial surgery, complete retinal reattachment was achieved in 226 eyes (92.6%), and retinal redetachment developed in 18 eyes (7.4%). The causes of retinal redetachment included presence of new breaks in eight eyes (44%), failure to completely seal the breaks in five eyes (28%), missed retinal breaks in four eyes (22%), and iatrogenic retinal breaks in one eye (6%). Scleral buckling surgery was performed again in 12 eyes (66%). Four eyes (22%) developed proliferative vitreoretinopathy and then were treated by vitrectomy. The sealing of retinal breaks and complete retinal reattachment were achieved in 241 eyes (98.8%). Conclusion. Probably because of clear visualization of retinal breaks and being controllable under a surgical microscope, the microsurgery of scleral buckling and transscleral cryopexy for uncomplicated retinal detachment exhibits advisable effectiveness.


Asunto(s)
Crioterapia/métodos , Enfermedades Hereditarias del Ojo/diagnóstico , Enfermedades Hereditarias del Ojo/cirugía , Microcirugia/métodos , Desprendimiento de Retina/diagnóstico , Desprendimiento de Retina/cirugía , Curvatura de la Esclerótica/métodos , Cirugía Asistida por Computador/métodos , Adolescente , Adulto , Anciano , Niño , Preescolar , Terapia Combinada/métodos , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
10.
J Telemed Telecare ; 19(1): 55-9, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23434538

RESUMEN

We evaluated the accuracy of an app for the iPad tablet computer (Eye Chart Pro) as a portable method of visual acuity (VA) testing. A total of 120 consecutive patients (240 eyes) underwent visual acuity test with an iPad 2 and a conventional light-box chart. The logMAR VA results from the iPad were significantly higher than those from the light-box (P < 0.001). Bland-Altman analysis revealed a mean difference (bias) of 0.02 logMAR units between the VA results from the iPad chart and the light-box chart, with 95% limits of agreement of -0.14 to 0.19. Two groups of patients were defined: in Group 1 there were 182 eyes with VA better than 0.1 according to the light-box VA test. The median logMAR VA by the iPad was 0.54 and by the light-box chart it was 0.52; there was no significant difference between them (P = 0.69). In Group 2 there were 58 eyes with VA equal to or worse than 0.1 according to the light-box VA test. The median logMAR VA by the iPad was 1.26 and was 1.10 by the light box; the result from the iPad was significantly lower (P < 0.001). The Eye Chart Pro app installed on the iPad is reliable for VA testing only when the Snellen VA is better than 0.1 (20/200).


Asunto(s)
Computadoras de Mano , Trastornos de la Visión/diagnóstico , Pruebas de Visión/instrumentación , Agudeza Visual , Adulto , Anciano , Anciano de 80 o más Años , Diagnóstico por Computador/instrumentación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Programas Informáticos , Pruebas de Visión/métodos
11.
Clin Exp Ophthalmol ; 41(8): 779-87, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23331298

RESUMEN

BACKGROUND: The vitreous has been shown to induce epithelial-mesenchymal transdifferentiation because it induces fibroblast-like morphology, enhanced migration and invasion in retinal pigment epithelial cells in proliferative vitreoretinopathy. Rac1 is the principal mediator of cell migration. In the current study, the relationship between Rac1 and cell migration, and invasion in vitreous-transformed retinal pigment epithelial cells was investigated using NSC23766, a specific inhibitor of Rac guanosine-5'-triphosphatase activity, and the involvement of a Rac1 guanosine-5'-triphosphatase-dependent pathway was detected. DESIGN: One-way design with multiple levels and repeated measurement design. PARTICIPANTS AND SAMPLES: The vitreous humor was collected from 20 healthy donor eyes and the retinal pigment epithelial cells were obtained from 9 healthy donor eyes. METHODS: Human low-passage retinal pigment epithelial cells were treated with normal medium or 25% vitreous medium. Rac1 activity was measured using a pull-down assay. The cytotoxicity of NSC23766 was measured using the trypan blue dye exclusion test. Cell migration was measured using a wound healing assay. Cell invasion was determined using a transwell invasion assay. Protein expression of Rac1 and phosphorylation of LIM kinase 1 and cofilin were detected by Western blot analysis. MAIN OUTCOME MEASURES: Cell migration, invasion, Rac1 activity and phosphorylation of LIM kinase 1 and cofilin. RESULTS: Rac1guanosine-5'-triphosphatase was activated in vitreous-transformed retinal pigment epithelial cells. A Rac inhibitor suppressed vitreous-induced migration and invasion in retinal pigment epithelial cells. Cofilin phosphorylation was activated by vitreous treatment but blocked by NSC23766. CONCLUSIONS: Rac1 mediates vitreous-transformed retinal pigment epithelial cells' plasticity of mesenchymal movement via Rac1 guanosine-5'-triphosphatase-dependent pathways that modulate LIM kinase 1 and cofilin activity. Rac inhibition may be considered a novel treatment for proliferative vitreoretinopathy.


Asunto(s)
Movimiento Celular/fisiología , Células Madre Mesenquimatosas/citología , Epitelio Pigmentado de la Retina/citología , Vitreorretinopatía Proliferativa/patología , Cuerpo Vítreo/fisiología , Proteína de Unión al GTP rac1/fisiología , Adolescente , Adulto , Anciano , Aminoquinolinas/farmacología , Western Blotting , Línea Celular Transformada , Supervivencia Celular , Transdiferenciación Celular , Células Cultivadas , Inhibidores Enzimáticos/farmacología , Humanos , Quinasas Lim/metabolismo , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Fosforilación , Pirimidinas/farmacología , Epitelio Pigmentado de la Retina/metabolismo , Adulto Joven , Proteína de Unión al GTP rac1/antagonistas & inhibidores
12.
J Immunol ; 188(12): 5924-34, 2012 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-22586036

RESUMEN

Viruses evade immune detection partly through immune-associated mutations. Analyses of HIV sequences derived from infected individuals have identified numerous examples of HLA-associated mutations within or adjacent to T cell epitopes, but the potential impact of most mutations on epitope production and presentation remains unclear. The multistep breakdown of proteins into epitopes includes trimming of N-extended peptides into epitopes by aminopeptidases before loading onto MHC class I molecules. Definition of sequence signatures that modulate epitope production would lead to a better understanding of factors driving viral evolution and immune escape at the population level. In this study, we identified cytosolic aminopeptidases cleavage preferences in primary cells and its impact on HIV Ag degradation into epitopes in primary human cell extracts by mass spectrometry and on epitope presentation to CTL. We observed a hierarchy of preferred amino acid cleavage by cytosolic aminopeptidases. We demonstrated that flanking mutations producing more or less cleavable motifs can increase or decrease epitope production and presentation by up to 14-fold. We found that the efficiency of epitope production correlates with cleavability of flanking residues. These in vitro findings were supported by in vivo population-level analyses of clinically derived viral sequences from 1134 antiretroviral-naive HIV-infected individuals: HLA-associated mutations immune pressures drove the selection of residues that are less cleavable by aminopeptidases predominantly at N-flanking sites, leading to reduced epitope production and immune recognition. These results underscore an important and widespread role of Ag processing mutations in HIV immune escape and identify molecular mechanisms underlying impaired epitope presentation.


Asunto(s)
Aminopeptidasas/inmunología , Presentación de Antígeno/inmunología , Epítopos de Linfocito T/inmunología , Infecciones por VIH/inmunología , Proteínas del Virus de la Inmunodeficiencia Humana/inmunología , Evasión Inmune/inmunología , Aminopeptidasas/genética , Aminopeptidasas/metabolismo , Presentación de Antígeno/genética , Separación Celular , Epítopos de Linfocito T/metabolismo , Citometría de Flujo , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Antígenos de Histocompatibilidad Clase I/inmunología , Proteínas del Virus de la Inmunodeficiencia Humana/metabolismo , Humanos , Evasión Inmune/genética , Activación de Linfocitos/genética , Activación de Linfocitos/inmunología , Mutación
13.
J Clin Invest ; 121(6): 2480-92, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21555856

RESUMEN

Induction of virus-specific CD8⁺ T cell responses is critical for the success of vaccines against chronic viral infections. Despite the large number of potential MHC-I-restricted epitopes located in viral proteins, MHC-I-restricted epitope generation is inefficient, and factors defining the production and presentation of MHC-I-restricted viral epitopes are poorly understood. Here, we have demonstrated that the half-lives of HIV-derived peptides in cytosol from primary human cells were highly variable and sequence dependent, and significantly affected the efficiency of cell recognition by CD8⁺ T cells. Furthermore, multiple clinical isolates of HLA-associated HIV epitope variants displayed reduced half-lives relative to consensus sequence. This decreased cytosolic peptide stability diminished epitope presentation and CTL recognition, illustrating a mechanism of immune escape. Chaperone complexes including Hsp90 and histone deacetylase HDAC6 enhanced peptide stability by transient protection from peptidase degradation. Based on empirical results with 166 peptides, we developed a computational approach utilizing a sequence-based algorithm to estimate the cytosolic stability of antigenic peptides. Our results identify sequence motifs able to alter the amount of peptide available for loading onto MHC-I, suggesting potential new strategies to modulate epitope production from vaccine immunogens.


Asunto(s)
Presentación de Antígeno , Epítopos/inmunología , Antígenos VIH/inmunología , Proteína p24 del Núcleo del VIH/inmunología , Transcriptasa Inversa del VIH/inmunología , VIH-1/inmunología , Especificidad del Receptor de Antígeno de Linfocitos T , Linfocitos T Citotóxicos/inmunología , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/inmunología , Vacunas contra el SIDA , Algoritmos , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Biología Computacional , Secuencia de Consenso , Citosol/inmunología , Antígenos VIH/química , Proteína p24 del Núcleo del VIH/química , Transcriptasa Inversa del VIH/química , Antígenos HLA-A/inmunología , Antígeno HLA-A3 , Antígenos HLA-B/inmunología , Proteínas HSP90 de Choque Térmico/fisiología , Semivida , Histona Desacetilasa 6 , Histona Desacetilasas/fisiología , Humanos , Técnicas In Vitro , Datos de Secuencia Molecular , Fragmentos de Péptidos/inmunología , Fragmentos de Péptidos/metabolismo , Estabilidad Proteica , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/química
14.
Annu Rev Cell Dev Biol ; 25: 539-66, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19575637

RESUMEN

Bilayer synthesis during membrane biogenesis involves the concerted assembly of multiple lipid species, requiring coordination of the level of lipid synthesis, uptake, turnover, and subcellular distribution. In this review, we discuss some of the salient conclusions regarding the coordination of lipid synthesis that have emerged from work in mammalian and yeast cells. The principal instruments of global control are a small number of transcription factors that target a wide range of genes encoding enzymes that operate in a given metabolic pathway. Critical in mammalian cells are sterol regulatory element binding proteins (SREBPs) that stimulate expression of genes for the uptake and synthesis of cholesterol and fatty acids. From work with Saccharomyces cerevisiae, much has been learned about glycerophospholipid and ergosterol regulation through Ino2p/Ino4p and Upc2p transcription factors, respectively. Lipid supply is fine-tuned through a multitude of negative feedback circuits initiated by both end products and intermediates of lipid synthesis pathways. Moreover, there is evidence that the diversity of membrane lipids is maintained through cross-regulatory effects, whereby classes of lipids activate the activity of enzymes operating in another metabolic branch.


Asunto(s)
Membrana Celular/metabolismo , Metabolismo de los Lípidos , Lípidos de la Membrana/metabolismo , Animales , Colesterol/metabolismo , Humanos , Proteínas de Unión a los Elementos Reguladores de Esteroles/metabolismo
15.
PLoS Pathog ; 5(4): e1000365, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19343217

RESUMEN

Human lymphocyte antigen (HLA)-restricted CD8(+) cytotoxic T lymphocytes (CTL) target and kill HIV-infected cells expressing cognate viral epitopes. This response selects for escape mutations within CTL epitopes that can diminish viral replication fitness. Here, we assess the fitness impact of escape mutations emerging in seven CTL epitopes in the gp120 Env and p24 Gag coding regions of an individual followed longitudinally from the time of acute HIV-1 infection, as well as some of these same epitopes recognized in other HIV-1-infected individuals. Nine dominant mutations appeared in five gp120 epitopes within the first year of infection, whereas all four mutations found in two p24 epitopes emerged after nearly two years of infection. These mutations were introduced individually into the autologous gene found in acute infection and then placed into a full-length, infectious viral genome. When competed against virus expressing the parental protein, fitness loss was observed with only one of the nine gp120 mutations, whereas four had no effect and three conferred a slight increase in fitness. In contrast, mutations conferring CTL escape in the p24 epitopes significantly decreased viral fitness. One particular escape mutation within a p24 epitope was associated with reduced peptide recognition and high viral fitness costs but was replaced by a fitness-neutral mutation. This mutation appeared to alter epitope processing concomitant with a reduced CTL response. In conclusion, CTL escape mutations in HIV-1 Gag p24 were associated with significant fitness costs, whereas most escape mutations in the Env gene were fitness neutral, suggesting a balance between immunologic escape and replicative fitness costs.


Asunto(s)
VIH-1/inmunología , Mutación , Linfocitos T Citotóxicos/inmunología , Replicación Viral , Secuencia de Aminoácidos , Epítopos de Linfocito T/inmunología , Evolución Molecular , Proteína gp120 de Envoltorio del VIH/genética , Proteína gp120 de Envoltorio del VIH/metabolismo , VIH-1/genética , VIH-1/fisiología , Proteínas del Virus de la Inmunodeficiencia Humana/genética , Proteínas del Virus de la Inmunodeficiencia Humana/metabolismo , Humanos , Modelos Moleculares , Datos de Secuencia Molecular , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/metabolismo
16.
Sci STKE ; 2007(392): pl3, 2007 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-17595222

RESUMEN

Phagocytes, such as macrophages, neutrophils, and dendritic cells, play important roles in the innate immune system through their ability to engulf, kill, and digest invading microbes. In cooperation with the humoral adaptive immune system, coating of substrates with immunoglobulin G (IgG) antibodies enhances several aspects of phagocytosis, including the recognition of substrates by cell surface IgG (Fcgamma) receptors, particle internalization, generation of microbicidal oxygen species, and targeting of lysosomes to phagosomes. We describe a cell-free scintillation proximity assay developed to study the mechanisms of lysosome targeting to phagosomes and the regulation of this process by IgG. The approach involves the use of isolated phagosomes containing scintillant latex beads and lysosomes labeled with a tritiated marker. Scintillation results only when lysosomes and phagosomes come into immediate contact and requires supplementation of reactions with adenosine triphosphate and cytosol; addition of cytosol from IgG-conditioned cells enhances this signal. The method is useful for investigating the biochemistry and regulation of the early tethering and docking steps of lysosome and phagosome interactions.


Asunto(s)
Inmunoglobulina G/inmunología , Lisosomas/metabolismo , Fagocitosis/inmunología , Fagosomas/metabolismo , Adenosina Trifosfato/metabolismo , Colesterol/análogos & derivados , Citosol , Inmunoglobulina G/metabolismo , Microesferas , Conteo por Cintilación/métodos , Tritio
17.
Zhonghua Yan Ke Za Zhi ; 41(3): 216-20, 2005 Mar.
Artículo en Chino | MEDLINE | ID: mdl-15840361

RESUMEN

OBJECTIVE: To evaluate the conversion of macular function in diabetic macular edema (DME) after vitreous surgery. METHODS: Seventeen eyes of 16 patients were assessed after pars plana vitrectomy for DME. Multifocal electroretinogram (mfERG) techniques were used to evaluate the effects of treatment on macular visual function, and retinal foveal thickness was determined by optical coherence tomography before and after vitrectomy. Patients were followed up continually for 7 months. The correlation between the change of tomographic features and visual functions were analyzed. RESULTS: During the follow-up period, the retinal function in macular areas recovered and the foveal thickness decreased gradually. While compared with preoperative values, the response of positive wave (P1) have shown decreases in implicit time and increases in amplitude since the forth and fifth postoperative month respectively (P < 0.05). While compared between each postoperative period, the P1 responses have increased significantly since the forth postoperative month. The correlation between the increase of P1 amplitude in macular area and the decrease of retinal foveal thickness was significant (r = 0.954, P < 0.001). CONCLUSIONS: Macular function get improvement gradually in DME after vitreous surgery; The restoration of macular function is coincident with the reduction of macular edema.


Asunto(s)
Retinopatía Diabética/cirugía , Mácula Lútea/fisiopatología , Edema Macular/cirugía , Vitrectomía , Adulto , Anciano , Retinopatía Diabética/patología , Electrorretinografía , Femenino , Estudios de Seguimiento , Humanos , Mácula Lútea/patología , Masculino , Persona de Mediana Edad
19.
Zhonghua Yan Ke Za Zhi ; 39(12): 740-2, 2003 Dec.
Artículo en Chino | MEDLINE | ID: mdl-14769226

RESUMEN

OBJECTIVE: To investigate the effect of vitrectomy combined with full endocular panretinal photocoagulation in patients with late stage of proliferative diabetic retinopathy (PDR). METHODS: Pars plana vitrectomy combined with full panretinal photocoagulation were undergone in 56 eyes (56 cases) with late stage of PDR, including 32 eyes with tractive retinal detachment. Preoperative and postoperative visual acuity, anterior segment by slit lamp and fundus examination by indirect ophthalmoscopy, as well as fluorescein angiography (FFA) were analyzed. RESULTS: Retina were reattached in 52 eyes. Vitreous hemorrhage, retinal bleeding, exudation and neovascular changes were not observed in these eyes. Non-irrigated areas were not found in 28/32 eyes in which FFA examination has been performed. Final visual acuity was improved in 52 eyes. CONCLUSION: Full endocular panretinal photocoagulation with low energy is an effective and safe procedure with low rate of complications for the late stage of PDR.


Asunto(s)
Retinopatía Diabética/terapia , Fotocoagulación , Vitrectomía , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Agudeza Visual
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