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1.
Zhonghua Yan Ke Za Zhi ; 57(1): 56-62, 2021 Jan 11.
Artículo en Zh | MEDLINE | ID: mdl-33412643

RESUMEN

Objective: To analyze the distribution characteristics of the anterior corneal astigmatism in 140 000 cataract patients from 18 hospitals in China. Methods: Retrospective study. A total of 143 889 patients (143 889 right eyes) over the age of 40 years with age-related catarac were admitted to 18 Aier eye hospitals in China from July 2015 to October 2018. The average values of the three measurements of the magnitude of anterior corneal astigmatism, the meridian of corneal astigmatism, anterior chamber depth, corneal refractive power, and axial length measured by IOLMaster 500 were obtained. The data acquisition method of each sub-center was to collect and analyze the electronic case data in accordance with the inclusion and exclusion criteria, and to provide them for the sponsor Wuhan Aier Eye Hospital. Non-normal distribution data are presented as M (P25, P75). Mann-Whitney test, Kruskal-Wallis test, Chi-square test were used to analyze the distribution differences of the magnitude of corneal astigmatism and the meridian of corneal astigmatism in gender, age, anterior chamber depth, corneal refractive power and axial length. Results: Among the 143 889 patients, 84 319 were females and 59 570 were males, the median age was 72 (65, 78) years old, the median corneal astigmatism was 0.84 (0.51, 1.33) D; the corneal astigmatism was ≥0.75 D in 80 895 patients (56.22%) and was ≥1.00 D in 57 304 patients (39.83%). The median corneal astigmatism was 0.87 (0.53, 1.37) D in women and 0.82 (0.50, 1.29) D in men; with statistical difference (U=-14.891; P<0.05). The proportion of with-the-rule (WTR) astigmatism was 33.26% (28 046/84 319) for women and 34.26% (20 408/59 570) for men; The proportion of against-the-rule (ATR) astigmatism was 49.08% (41 385/84 319) for women and 46.91% (27 945/59 570) for men, with statistical difference (χ²=70.913; P<0.05). With the increase of age, the magnitude of corneal astigmatism first decreased from 0.94 (0.57, 1.48) D to 0.75 (0.46, 1.18) D, and then increased to 1.19 (0.74, 1.79) D, with statistical difference (H=1 263.438; P<0.05), and the change was at 61 to 70 years old. With the increase of age, the proportion of WTR astigmatism decreased from 77.50% (396/511) to 12.50% (3/24), the proportion of ATR astigmatism increased from 11.15% (57/511) to 79.07% (34/43), and the proportion of oblique astigmatism changed little from 17.02% (16/94) to 19.92% (245/1 230), the distribution difference was significant (χ²=10 174.496; P<0.05). As the anterior chamber became shallow, the magnitude of corneal astigmatism significantly increased from 0.82 (0.51, 1.31) D to 1.05 (0.61, 1.56) D, and the proportion of ATR astigmatism increased from 47.32% (60 207/127 227) to 51.69% (184/356) (H=409.961, χ²=120.995, both P<0.05). With the corneal refractive power rising, the magnitude of corneal astigmatism increased from 0.80 (0.49, 1.33) D to 0.95 (0.58, 1.53) D, the proportion of ATR astigmatism decreased from 52.84% (4 963/9 392) to 39.97% (9 023/22 577); the difference was significant (H=808.562, χ²=752.147, both P<0.05). When the axial length was>25.00 mm, the magnitude of corneal astigmatism was highest [1.04 (0.62, 1.65) D], and the proportion of ATR astigmatism was also highest [49.00% (10 964/22 376)]; the difference was significant (H=2 071.198, χ²=131.130, all P<0.05). Conclusions: The meridian of corneal astigmatism in middle-aged and elderly cataract patients is mainly ATR astigmatism. With the increasing of age, the magnitude of corneal astigmatism decreases first and then increases. The turning point from the proportion of WTR astigmatism to the proportion of ATR astigmatism is 65 years old. The shallower the anterior chamber is, the more the magnitude of corneal astigmatism and the proportion of ATR astigmatism increase. When the axial length is>25.00 mm, both the magnitude of corneal astigmatism and the proportion of ATR astigmatism reach the peak. (Chin J Ophthalmol, 2021, 57: 56-62).


Asunto(s)
Astigmatismo , Catarata , Anciano , Astigmatismo/epidemiología , Biometría , Catarata/epidemiología , China/epidemiología , Córnea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
2.
Proc Natl Acad Sci U S A ; 105(33): 11857-62, 2008 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-18697930

RESUMEN

Understanding the pathways that control epithelial carcinogenesis is vital to the development of effective treatments. The Polycomb group family member Bmi1 is overexpressed in numerous epithelial tumors, but its role in their development has not been established. We now show a key role for Bmi1 in lung adenocarcinoma. Whereas lung development occurs normally in Bmi1-deficient mice, loss of Bmi1 decreases the number and progression of lung tumors at a very early point in an oncogenic K-ras-initiated mouse model of lung cancer. This correlates with a defect in the ability of Bmi1-deficient putative bronchiolalveolar stem cells (BASCs) to proliferate in response to the oncogenic stimulus. Notably, in the absence of oncogenic K-ras, Bmi1-deficient BASCs show impaired proliferation and self-renewal capacity in culture and after lung injury in vivo. Abrogated lung cancer development and BASC self-renewal occur partially in a p19(ARF)-dependent manner. Our data suggest that Bmi1 deficiency suppresses tumor development by limiting the expansion potential of BASCs, the apparent lung cancer cells of origin. Because Bmi1 is elevated in additional tumor types, this suggests that Bmi1 plays a key role in regulating proliferation of both stem cells and tumor cells in diverse adult epithelial tissues.


Asunto(s)
Bronquios/citología , Transformación Celular Neoplásica/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Alveolos Pulmonares/citología , Proteínas Represoras/metabolismo , Células Madre/metabolismo , Animales , Bronquios/metabolismo , Proliferación Celular , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Células Cultivadas , Neoplasias Pulmonares/genética , Ratones , Ratones Noqueados , Proteínas Nucleares/deficiencia , Proteínas Nucleares/genética , Complejo Represivo Polycomb 1 , Proteínas Proto-Oncogénicas/deficiencia , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas p21(ras)/deficiencia , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Alveolos Pulmonares/metabolismo , Proteínas Represoras/genética , Células Madre/citología
3.
Clin Cancer Res ; 27(22): 6174-6183, 2021 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-34518312

RESUMEN

PURPOSE: To evaluate the tissue distribution and clinical significance of OX40 and OX40L in human non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Using multiplexed quantitative immunofluorescence, we conducted simultaneous and localized measurements of OX40 and OX40L proteins, major T-cell subsets, and conventional type 1 dendritic cells (cDC1) in 614 primary NSCLCs from three independent cohorts represented in tissue microarrays. We also measured OX40L protein in samples from a phase I clinical trial of intratumor administration of a lipid nanoparticle encapsulated mRNA encoding OX40L (mRNA-2416) in human solid tumors. Finally, we studied the OX40 pathway in 212 uterine/ovarian serous carcinomas. RESULTS: OX40 protein was expressed in approximately 90% of NSCLCs, and OX40L was detected in approximately 10% of cases. Increased expression of OX40 was associated with higher CD4+ and CD8+ T lymphocytes, as well as cDC1s. Elevated expression of OX40L was consistently associated with increased CD4+ tumor-infiltrating lymphocytes and longer overall survival. No association was found between OX40 or OX40L levels and oncogenic driver mutations in EGFR and KRAS in lung adenocarcinomas. Delivering OX40L mRNA using intratumor mRNA-2416 injection mediated increased local OX40L protein levels that was most prominent in a patient with ovarian serous carcinoma. Detectable OX40L protein levels were observed in 15% of primary uterine/ovarian serous malignancies and associated with longer survival. CONCLUSIONS: The OX40 pathway is expressed in a fraction of NSCLCs and is associated with a favorable immune contexture. Although OX40L is uncommonly expressed in NSCLC and serous malignancies, it is associated with better prognosis and can be introduced using exogenous mRNA.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma de Pulmón de Células no Pequeñas/genética , Humanos , Liposomas , Neoplasias Pulmonares/genética , Nanopartículas , Ligando OX40/genética
4.
Oecologia ; 164(4): 871-80, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20652592

RESUMEN

Expression of crassulacean acid metabolism (CAM) is characterized by extreme variability within and between taxa and its sensitivity to environmental variation. In this study, we determined seasonal fluctuations in CAM photosynthesis with measurements of nocturnal tissue acidification and carbon isotopic composition (δ(13)C) of bulk tissue and extracted sugars in three plant communities along a precipitation gradient (500, 700, and 1,000 mm year(-1)) on the Yucatan Peninsula. We also related the degree of CAM to light habitat and relative abundance of species in the three sites. For all species, the greatest tissue acid accumulation occurred during the rainy season. In the 500 mm site, tissue acidification was greater for the species growing at 30% of daily total photon flux density (PFD) than species growing at 80% PFD. Whereas in the two wetter sites, the species growing at 80% total PFD had greater tissue acidification. All species had values of bulk tissue δ(13)C less negative than -20‰, indicating strong CAM activity. The bulk tissue δ(13)C values in plants from the 500 mm site were 2‰ less negative than in plants from the wetter sites, and the only species growing in the three communities, Acanthocereus tetragonus (Cactaceae), showed a significant negative relationship between both bulk tissue and sugar δ(13)C values and annual rainfall, consistent with greater CO(2) assimilation through the CAM pathway with decreasing water availability. Overall, variation in the use of CAM photosynthesis was related to water and light availability and CAM appeared to be more ecologically important in the tropical dry forests than in the coastal dune.


Asunto(s)
Dióxido de Carbono/metabolismo , Crassulaceae/metabolismo , Crassulaceae/efectos de la radiación , Ecosistema , Luz , Ácidos/metabolismo , Ácidos/efectos de la radiación , Cactaceae/química , Cactaceae/metabolismo , Cactaceae/efectos de la radiación , Isótopos de Carbono/metabolismo , Crassulaceae/química , México , Lluvia , Estaciones del Año
5.
Sci Transl Med ; 11(477)2019 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-30700577

RESUMEN

Many solid cancers contain dysfunctional immune microenvironments. Immune system modulators that initiate responses to foreign pathogens could be promising candidates for reigniting productive responses toward tumors. Interleukin-1 (IL-1) and IL-12 cytokine family members cooperate at barrier tissues after microbial invasion, in human inflammatory diseases, and in antitumoral immunity. IL-36γ, in classic alarmin fashion, acts in damaged tissues, whereas IL-23 centrally coordinates immune responses to danger signals. In this study, direct intratumoral delivery of messenger RNAs (mRNAs) encoding these cytokines produced robust anticancer responses in a broad range of tumor microenvironments. The addition of mRNA encoding the T cell costimulator OX40L increased complete response rates in treated and untreated distal tumors compared to the cytokine mRNAs alone. Mice exhibiting complete responses were subsequently protected from tumor rechallenge. Treatments with these mRNA mixtures induced downstream cytokine and chemokine expression, and also activated multiple dendritic cell (DC) and T cell types. Consistent with this, efficacy was dependent on Batf3-dependent cross-presenting DCs and cytotoxic CD8+ T cells. IL-23/IL-36γ/OX40L triplet mRNA mixture triggered substantial immune cell recruitment into tumors, enabling effective tumor destruction irrespective of previous tumoral immune infiltrates. Last, combining triplet mRNA with checkpoint blockade led to efficacy in models otherwise resistant to systemic immune checkpoint inhibition. Human cell studies showed similar cytokine responses to the individual components of this mRNA mixture, suggesting translatability of immunomodulatory activity to human patients.


Asunto(s)
Inmunidad , Interleucina-1/genética , Interleucina-23/genética , Neoplasias/inmunología , Ligando OX40/genética , ARN Mensajero/administración & dosificación , Animales , Proliferación Celular , Modelos Animales de Enfermedad , Humanos , Inflamación/patología , Interleucina-1/metabolismo , Interleucina-23/metabolismo , Ganglios Linfáticos/patología , Activación de Linfocitos/inmunología , Ratones , Ligando OX40/metabolismo , Distribución Tisular , Microambiente Tumoral/inmunología
6.
Cancer Immunol Res ; 7(9): 1457-1471, 2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31331945

RESUMEN

The success of targeted or immune therapies is often hampered by the emergence of resistance and/or clinical benefit in only a subset of patients. We hypothesized that combining targeted therapy with immune modulation would show enhanced antitumor responses. Here, we explored the combination potential of erdafitinib, a fibroblast growth factor receptor (FGFR) inhibitor under clinical development, with PD-1 blockade in an autochthonous FGFR2K660N/p53mut lung cancer mouse model. Erdafitinib monotherapy treatment resulted in substantial tumor control but no significant survival benefit. Although anti-PD-1 alone was ineffective, the erdafitinib and anti-PD-1 combination induced significant tumor regression and improved survival. For both erdafitinib monotherapy and combination treatments, tumor control was accompanied by tumor-intrinsic, FGFR pathway inhibition, increased T-cell infiltration, decreased regulatory T cells, and downregulation of PD-L1 expression on tumor cells. These effects were not observed in a KRASG12C-mutant genetically engineered mouse model, which is insensitive to FGFR inhibition, indicating that the immune changes mediated by erdafitinib may be initiated as a consequence of tumor cell killing. A decreased fraction of tumor-associated macrophages also occurred but only in combination-treated tumors. Treatment with erdafitinib decreased T-cell receptor (TCR) clonality, reflecting a broadening of the TCR repertoire induced by tumor cell death, whereas combination with anti-PD-1 led to increased TCR clonality, suggesting a more focused antitumor T-cell response. Our results showed that the combination of erdafitinib and anti-PD-1 drives expansion of T-cell clones and immunologic changes in the tumor microenvironment to support enhanced antitumor immunity and survival.


Asunto(s)
Antineoplásicos Inmunológicos/farmacología , Inmunidad/efectos de los fármacos , Neoplasias/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptores de Factores de Crecimiento de Fibroblastos/antagonistas & inhibidores , Animales , Biomarcadores , Línea Celular Tumoral , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Humanos , Inmunofenotipificación , Linfocitos Infiltrantes de Tumor/efectos de los fármacos , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Ratones , Ratones Transgénicos , Mutación , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/metabolismo , Pronóstico , Receptor de Muerte Celular Programada 1/genética , Pirazoles/farmacología , Quinoxalinas/farmacología , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Factores de Crecimiento de Fibroblastos/genética , Receptores de Factores de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal/efectos de los fármacos , Subgrupos de Linfocitos T/efectos de los fármacos , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Resultado del Tratamiento , Microambiente Tumoral
7.
Cancer Res ; 65(24): 11354-60, 2005 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-16357142

RESUMEN

The metazoan cell cycle is driven by the timely and composite activities of cyclin-dependent kinases (CDKs). Among these, cyclin D- and cyclin E-dependent kinases phosphorylate the pRb family proteins during G(1) phase of the cell cycle and thereby advance cells beyond the restriction point. Increasing evidence suggests that cyclin D-dependent kinases might affect events other than Rb pathway-mediated entry into S phase, such as accumulation of cell mass. However, little is known about cyclin D activity toward Rb-independent pathway(s) or non-pRb substrates. In this article, we show that the tumor suppressor TSC2 is a cyclin D binding protein. Coexpression of cyclin D1-CDK4/6 in cultured cells leads to increased phosphorylation and decreased detection of both TSC2 and TSC1, and promotes the phosphorylation of the mTOR substrates, 4E-BP1 and S6K1, two key effectors of cell growth that are negatively regulated by the TSC1-TSC2 complex. At the cellular level, ectopic expression of cyclin D1 restores the cell size decrease caused by TSC1-TSC2 expression. Intriguingly, down-regulation of TSC proteins was also observed by the expression of a mutant cyclin D1 that is unable to bind to CDK4/6, or by the coexpression of cyclin D1 with either an INK4 inhibitor or with catalytically inactive CDK6, indicating that cyclin D may regulate TSC1-TSC2 independently of CDK4/6. Together, these observations suggest that mammalian D-type cyclins participate in cell growth control through negative regulation of TSC1-TSC2 function.


Asunto(s)
Ciclina D1/metabolismo , Fase G1 , Regulación de la Expresión Génica , Proteína de Retinoblastoma/metabolismo , Proteínas Supresoras de Tumor/metabolismo , Proteínas Adaptadoras Transductoras de Señales , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Proteínas Portadoras/metabolismo , Proteínas de Ciclo Celular , Células Cultivadas , Quinasa 4 Dependiente de la Ciclina/metabolismo , Quinasa 6 Dependiente de la Ciclina/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Humanos , Riñón/metabolismo , Osteosarcoma/metabolismo , Osteosarcoma/patología , Fosfoproteínas/metabolismo , Fosforilación , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo , Proteína 1 del Complejo de la Esclerosis Tuberosa , Proteína 2 del Complejo de la Esclerosis Tuberosa
8.
Biotechnol Adv ; 35(6): 726-750, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28739505

RESUMEN

Softwood bark is an important source for producing chemicals and materials as well as bioenergy. Extraction is regarded as a key technology for obtaining chemicals in general, and valorizing bark as a source of such chemicals in particular. In this paper, properties of 237 compounds identified in various studies dealing with extraction of softwood bark were described. Finally, some challenges and perspectives on the production of chemicals from bark are discussed.


Asunto(s)
Antioxidantes/química , Corteza de la Planta/química , Extractos Vegetales/química , Antioxidantes/aislamiento & purificación
9.
Neural Comput ; 12(12): 2965-89, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11112262

RESUMEN

We investigate the computational properties of finite binary- and analog-state discrete-time symmetric Hopfield nets. For binary networks, we obtain a simulation of convergent asymmetric networks by symmetric networks with only a linear increase in network size and computation time. Then we analyze the convergence time of Hopfield nets in terms of the length of their bit representations. Here we construct an analog symmetric network whose convergence time exceeds the convergence time of any binary Hopfield net with the same representation length. Further, we prove that the MIN ENERGY problem for analog Hopfield nets is NP-hard and provide a polynomial time approximation algorithm for this problem in the case of binary nets. Finally, we show that symmetric analog nets with an external clock are computationally Turing universal.

10.
J Cataract Refract Surg ; 30(3): 620-5, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-15050258

RESUMEN

PURPOSE: To investigate the effect of hyperthermia for the treatment of long-standing corneal flap striae after laser in situ keratomileusis (LASIK). SETTING: TLC Laser Eye Center, Garden City, New York, USA. METHODS: Patients with visually significant flap striae at least 3 weeks post-LASIK were offered hyperthermic treatment. The central 6.0 mm of epithelium was removed from affected corneas, and the flaps were elevated. A striae removal spatula was heated to 65 degrees C in sterile water, and both sides of the flaps were mechanically massaged with the spatula for 5 to 10 minutes until the striae were visually reduced. RESULTS: Thirty-six eyes of 34 patients were treated with hyperthermia to remove corneal striae. All patients had a clinical reduction in striae. The mean pretreatment best corrected visual acuity (BCVA) was 20/44, improving to 20/25 on follow-up (mean follow-up 16.4 months). Patients subjectively noted reduced haze and glare and no loss of BCVA. There were no serious flap complications. CONCLUSION: Hyperthermic treatment is a safe, effective treatment option for corneal striae after LASIK.


Asunto(s)
Enfermedades de la Córnea/terapia , Sustancia Propia , Hipertermia Inducida , Queratomileusis por Láser In Situ , Complicaciones Posoperatorias/terapia , Colgajos Quirúrgicos , Adulto , Enfermedades de la Córnea/etiología , Femenino , Humanos , Masculino , Seguridad , Resultado del Tratamiento , Agudeza Visual
11.
Cornea ; 23(3): 314-7, 2004 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15084869

RESUMEN

OBJECTIVE: To describe a case of keratomycosis caused by Arthrographis kalrae, mimicking Acanthamoeba keratitis. METHODS: Case report. RESULTS: A 23-year-old female contact lens wearer developed dendritic keratitis in her amblyopic eye (OD). Baseline vision was 20/50. Treatment with trifluridine 1% resulted in resolution of the dendrite, but an area of stromal haze developed, spreading to a discontinuous ring shape, and the vision dropped to 20/200. Photophobia was intense, and pain was out of proportion to the examination. Cultures were sent, and empiric treatment of Acanthamoeba was begun, without subsequent improvement. After 4 weeks, cultures were positive for a fungal species. Amphotericin 0.5% drops were begun, with moderately rapid resolution of the active keratitis. At last follow-up, best-corrected vision was 20/100. Review of the culture showed the organism to be Arthrographis kalrae. CONCLUSION: Arthrographis kalrae has been reported only once before as an ocular pathogen. As in the previously reported case of Arthrographis, our patient's presentation was strongly suggestive of Acanthamoeba keratitis.


Asunto(s)
Infecciones Fúngicas del Ojo/diagnóstico , Queratitis/diagnóstico , Hongos Mitospóricos/aislamiento & purificación , Micosis/diagnóstico , Queratitis por Acanthamoeba/diagnóstico , Adulto , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Diagnóstico Diferencial , Infecciones Fúngicas del Ojo/tratamiento farmacológico , Infecciones Fúngicas del Ojo/microbiología , Femenino , Humanos , Queratitis/tratamiento farmacológico , Queratitis/microbiología , Queratitis Dendrítica/complicaciones , Queratitis Dendrítica/tratamiento farmacológico , Micosis/tratamiento farmacológico , Micosis/microbiología , Soluciones Oftálmicas
12.
Cornea ; 21(2): 161-3, 2002 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11862086

RESUMEN

PURPOSE: To investigate the efficacy of topical cyclosporine A 0.5% as a substitute for corticosteroids in the management of therapeutic keratoplasties for mycotic keratitis. METHODS: Prospective, nonrandomized interventional case series. Three patients with culture-proven mycotic keratitis underwent therapeutic keratoplasties. All were treated with topical cyclosporine A 0.5% postoperatively as a primary or an adjunctive therapy for prevention of allograft rejection. The patients were followed up from 15 to 42 months for maintenance of graft clarity and best-corrected visual acuity. RESULTS: Two of three patients maintained clear grafts while using topical cyclosporine A 0.5% twice daily with best-corrected visual acuity of 20/40 and 20/50. One patient developed an opacified graft secondary to preexisting ocular surface disease. CONCLUSIONS: Topical cyclosporine A 0.5% may be a useful adjunct in the management of therapeutic keratoplasties for mycotic keratitis.


Asunto(s)
Ciclosporina/uso terapéutico , Infecciones Fúngicas del Ojo/cirugía , Rechazo de Injerto/prevención & control , Inmunosupresores/uso terapéutico , Queratitis/microbiología , Queratitis/cirugía , Queratoplastia Penetrante , Micosis/cirugía , Administración Tópica , Anciano , Candida albicans/aislamiento & purificación , Cryptococcus/aislamiento & purificación , Ciclosporina/administración & dosificación , Infecciones Fúngicas del Ojo/microbiología , Femenino , Humanos , Inmunosupresores/administración & dosificación , Masculino , Persona de Mediana Edad , Micosis/microbiología , Estudios Prospectivos , Pseudallescheria/aislamiento & purificación , Resultado del Tratamiento , Agudeza Visual
13.
Cell Stem Cell ; 9(3): 272-81, 2011 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-21885022

RESUMEN

BMI1 is required for the self-renewal of stem cells in many tissues including the lung epithelial stem cells, Bronchioalveolar Stem Cells (BASCs). Imprinted genes, which exhibit expression from only the maternally or paternally inherited allele, are known to regulate developmental processes, but what their role is in adult cells remains a fundamental question. Many imprinted genes were derepressed in Bmi1 knockout mice, and knockdown of Cdkn1c (p57) and other imprinted genes partially rescued the self-renewal defect of Bmi1 mutant lung cells. Expression of p57 and other imprinted genes was required for lung cell self-renewal in culture and correlated with repair of lung epithelial cell injury in vivo. Our data suggest that BMI1-dependent regulation of expressed alleles at imprinted loci, distinct from imprinting per se, is required for control of lung stem cells. We anticipate that the regulation and function of imprinted genes is crucial for self-renewal in diverse adult tissue-specific stem cells.


Asunto(s)
Células Madre Adultas/metabolismo , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Represoras/metabolismo , Proteínas Quinasas Asociadas a Fase-S/metabolismo , Células Madre Adultas/patología , Animales , Supervivencia Celular/genética , Células Cultivadas , Inhibidor p16 de la Quinasa Dependiente de Ciclina/genética , Perfilación de la Expresión Génica , Genes p16/fisiología , Sitios Genéticos , Impresión Genómica/genética , Pulmón/patología , Ratones , Ratones Mutantes , Proteínas Nucleares/genética , Complejo Represivo Polycomb 1 , Proteínas Proto-Oncogénicas/genética , ARN Interferente Pequeño/genética , Regeneración/genética , Proteínas Represoras/genética , Proteínas Quinasas Asociadas a Fase-S/genética
14.
Mol Biol Cell ; 21(21): 3639-53, 2010 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-20826610

RESUMEN

DNA synthesis-coupled proteolysis of the prereplicative complex component Cdt1 by the CRL4(Cdt2) E3 ubiquitin ligase is thought to help prevent rereplication of the genome during S phase. To directly test whether CRL4(Cdt2)-triggered destruction of Cdt1 is required for normal cell cycle progression in vivo, we expressed a mutant version of Drosophila Cdt1 (Dup), which lacks the PCNA-binding PIP box (Dup(ΔPIP)) and which cannot be regulated by CRL4(Cdt2). Dup(ΔPIP) is inappropriately stabilized during S phase and causes developmental defects when ectopically expressed. Dup(ΔPIP) restores DNA synthesis to dup null mutant embryonic epidermal cells, but S phase is abnormal, and these cells do not progress into mitosis. In contrast, Dup(ΔPIP) accumulation during S phase did not adversely affect progression through follicle cell endocycles in the ovary. In this tissue the combination of Dup(ΔPIP) expression and a 50% reduction in Geminin gene dose resulted in egg chamber degeneration. We could not detect Dup hyperaccumulation using mutations in the CRL4(Cdt2) components Cul4 and Ddb1, likely because these cause pleiotropic effects that block cell proliferation. These data indicate that PIP box-mediated destruction of Dup is necessary for the cell division cycle and suggest that Geminin inhibition can restrain Dup(ΔPIP) activity in some endocycling cell types.


Asunto(s)
Proteínas de Ciclo Celular/genética , Proteínas de Unión al ADN/genética , Proteínas de Drosophila/genética , Fase S/genética , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Ubiquitina-Proteína Ligasas/metabolismo , Secuencia de Aminoácidos , Animales , Animales Modificados Genéticamente , Ciclo Celular/genética , Ciclo Celular/fisiología , Proteínas de Ciclo Celular/metabolismo , Procesos de Crecimiento Celular/fisiología , Proteínas Cullin/genética , Proteínas Cullin/metabolismo , Replicación del ADN , Proteínas de Unión al ADN/metabolismo , Drosophila/citología , Drosophila/enzimología , Drosophila/genética , Drosophila/metabolismo , Proteínas de Drosophila/antagonistas & inhibidores , Proteínas de Drosophila/metabolismo , Endodesoxirribonucleasas/genética , Endodesoxirribonucleasas/metabolismo , Femenino , Geminina , Regulación de la Expresión Génica , Masculino , Datos de Secuencia Molecular , Mutación , Folículo Ovárico/metabolismo , Antígeno Nuclear de Célula en Proliferación/metabolismo , Dominios y Motivos de Interacción de Proteínas , Fase S/fisiología , Complejos de Ubiquitina-Proteína Ligasa
16.
Yan Ke Xue Bao ; 16(2): 149-52, 2000 Jun.
Artículo en Zh | MEDLINE | ID: mdl-12579928

RESUMEN

PURPOSE: To evaluate the effectiveness of orthokeratology (Ortho-K) for treatment of myopia in youngths. METHODS: 110 eyes of 56 young peoples with myopia received Ortho-K were studied. The patients were divided into 3 groups according to preoperative diopters. No. I: -1.00(-)-3.00 D, No. II: -3.25(-)-6.00 D, NO. III: -6.25(-)-7.50 D. The uncorrected visual acuities, residual diopters and corneal refractive powers at various time of three months after the operation were statistically analyzed and compared with that of preoperation. Correlation analysis and linear regression analysis were performed between the corneal refractive reduction (X) and clinical refractive reduction (Y) after 3 months of the operation. RESULTS: In 110 eyes, the uncorrected visual acuities in the first day, first week, first month, second month and third month after operation were significantly improved than that of the preoperation (P < 0.01). The mean residual diopters were significantly reduced than that of preoperation (P < 0.01). The mean refractive powers of cornea were significantly decreased than that of the preoperative (P < 0.01). There was significant correlation between the corneal refractive reduction and clinical refractive reduction. (r = 0.3181, P < 0.001). CONCLUSION: Orthokeratology is a safe and effective therapeutic method for treatment of myopia in youngths. The long term effect of Orthokeratology need further observation.


Asunto(s)
Lentes de Contacto de Uso Prolongado , Miopía/terapia , Adolescente , Adulto , Niño , Topografía de la Córnea , Femenino , Humanos , Masculino , Refracción Ocular , Resultado del Tratamiento , Agudeza Visual
17.
Z Alternsforsch ; 40(4): 261-8, 1985.
Artículo en Alemán | MEDLINE | ID: mdl-4049929

RESUMEN

An analysis of the operation records for the years from 1910 to 1980 shows a considerable increase in the indication for surgical treatment. While the average age of the groups of patients does not increase in general, an increase in the number of patients operated on in higher age can be proved. This paper gives an outline of problems of preparation for operations, the application of narcosis techniques and postoperational care for these groups of patients.


Asunto(s)
Departamentos de Hospitales/tendencias , Servicio de Cirugía en Hospital/tendencias , Procedimientos Quirúrgicos Operativos/tendencias , Adolescente , Adulto , Factores de Edad , Anciano , Niño , Femenino , Alemania Oriental , Humanos , Masculino , Persona de Mediana Edad , Factores Sexuales
18.
Diabetologia ; 47(1): 124-31, 2004 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-14666366

RESUMEN

AIMS/HYPOTHESIS: Retinal vascular leakage is an early pathological feature in diabetic retinopathy and can lead to macular oedema and loss of vision. Previously we have shown that plasminogen kringle 5 (K5), an angiogenic inhibitor, inhibits retinal neovascularisation in the rat model of oxygen-induced retinopathy (OIR). The purpose of this study was to examine the effect of K5 on vascular leakage in the retina. METHODS: Neonatal rats were exposed to hyperoxia to induce OIR. Diabetes was induced in adult rats by injecting streptozotocin. Vascular permeability was measured by Evans blue method. Expression of vascular endothelial growth factor (VEGF) was evaluated using immunohistochemistry and western blot analysis. RESULTS: Rats with OIR and diabetes showed abnormal vascular hyperpermeability in the retina and iris. Intravitreal injection of K5, reduced vascular permeability in both animal models, but did not affect permeability in normal rats. K5 reduced vascular permeability at doses substantially lower than that required for inhibition of retinal neovascularisation. The K5-induced reduction in vascular permeability correlated with its down-regulation of VEGF expression in the retina. Moreover, K5 inhibited IGF-1-induced hyperpermeability, which is known to arise through up-regulation of endogenous VEGF expression. However, K5 had no effect on the hyperpermeability induced by injection of exogenous VEGF. CONCLUSIONS/INTERPRETATION: Very low doses of K5 reduce pathological vascular leakage in the retina. K5 thus has therapeutic potential in the treatment of diabetic macular oedema. This effect can be ascribed, at least in part, to the down-regulation of endogenous VEGF expression.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Diabetes Mellitus Experimental/fisiopatología , Retinopatía Diabética/prevención & control , Fragmentos de Péptidos/uso terapéutico , Plasminógeno/uso terapéutico , Animales , Diabetes Mellitus Experimental/patología , Retinopatía Diabética/patología , Inmunohistoquímica , Factor I del Crecimiento Similar a la Insulina/farmacología , Ratas , Ratas Endogámicas BN , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/farmacología
19.
CLAO J ; 28(2): 69-71, 2002 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12054372

RESUMEN

PURPOSE: To present a case of corneal perforation secondary to herpes simplex reactivation after laser in situ keratomileusis (LASIK) and its subsequent management. METHODSL A case report of a 69-year-old man who underwent LASIK after penetrating keratoplasty for herpes simplex keratitis (HSK) is presented. RESULTS: The patient is a 69-year-old man who had a penetrating keratoplasty of the right eye 6 years prior for corneal scarring secondary to HSK. A spectacle refraction of -13.25 + 6.00 x 45 yielded 20/60 visual acuity in his grafted eye. LASIK was performed, and the patient's visual acuity without correction on postoperative day 1 was 20/60. Ten days after LASIK, the patient developed thinning of the cornea at the temporal edge of the flap, which perforated the following day. The perforation site was glued with cyanoacrylate adhesive and covered with a soft contact lens. After 7 months, a 4-mm lamellar keratoplasty and conjunctivoplasty was performed. Nine months after surgery, the patient's visual acuity without correction is 20/50 and the graft remains intact. CONCLUSION: Herpes simplex keratitis may be a contraindication for LASIK in postkeratoplasty patients. Bandage contact lenses and cyanoacrylate adhesive can be used successfully to manage the rare complication of corneal perforation after LASIK.


Asunto(s)
Lesiones de la Cornea , Queratitis Herpética/complicaciones , Queratomileusis por Láser In Situ/efectos adversos , Simplexvirus/fisiología , Activación Viral , Heridas Penetrantes/virología , Anciano , Conjuntiva/cirugía , Lentes de Contacto Hidrofílicos , Córnea/cirugía , Trasplante de Córnea , Cianoacrilatos/uso terapéutico , Humanos , Queratoplastia Penetrante , Masculino , Registros Médicos , Periodo Posoperatorio , Reoperación , Adhesivos Tisulares/uso terapéutico , Agudeza Visual , Heridas Penetrantes/tratamiento farmacológico , Heridas Penetrantes/cirugía
20.
Ophthalmology ; 110(5): 1023-9; discussion 1029-30, 2003 May.
Artículo en Inglés | MEDLINE | ID: mdl-12750107

RESUMEN

PURPOSE: To investigate the effect of hinge position on corneal sensation and dry eye syndrome after laser in situ keratomileusis (LASIK). DESIGN: Prospective, randomized, self-controlled trial. PARTICIPANTS: Fifty-two patients >/=18 years of age undergoing bilateral LASIK. INTERVENTION: Patients underwent bilateral LASIK with the superior-hinge Hansatome microkeratome in one eye and the nasal-hinge Amadeus microkeratome in the other eye. In all eyes, the flaps were 160 micro m thick, with a diameter of 9.5 mm. MAIN OUTCOME MEASURES: Masked Cochet-Bonnet esthesiometry was performed centrally before surgery and at 1 week, 1 month, 3 months, and 6 months after surgery. Dry eye was evaluated at the same time intervals with lissamine green corneal and conjunctival staining, Schirmer testing with anesthesia, and tear-film breakup time. Subjective evaluation of dry eye sensation was performed at 3 and 6 months after surgery. RESULTS: Corneal sensation was reduced in eyes with either superior- or nasal-hinge corneal flaps at 1 week, 1 month, and 3 months after surgery (P < 0.001). Compared with preoperative values, a significant reduction in corneal sensation remained at 6 months in corneas with superior-hinge flaps (P < 0.001) but not in corneas with nasal-hinge flaps (P = 0.263). Mean corneal sensation was greater in corneas with a nasal-hinge flap compared with corneas with a superior-hinge flap at all postoperative visits (P < 0.001). The loss of sensation was greatest at 1 week and showed improvement at each subsequent time interval up to 6 months. Overall, dry eye signs and symptoms were greatest during the immediate postoperative period and improved at all subsequent time intervals. Dry eye signs and symptoms were generally greatest in the eyes with a superior-hinge flap and milder in eyes with a nasal-hinge flap. CONCLUSIONS: The long posterior corneal nerves, which innervate the cornea, enter the eye at 3- and 9-o'clock. A superior-hinge flap transects both arms of the neuroplexus, whereas a nasal hinge transects only the temporal arm. LASIK results in a significant reduction in corneal sensation. Corneal sensation and dry eye signs and symptoms decreased immediately after LASIK and improved at all time periods between 1 week and 6 months in eyes with both a nasal-hinge flap and a superior-hinge flap. However, the loss of corneal sensation and presence of dry eye syndrome were greater in eyes with a superior-hinge flap than in eyes with a nasal-hinge flap.


Asunto(s)
Córnea/fisiología , Síndromes de Ojo Seco/etiología , Queratomileusis por Láser In Situ/efectos adversos , Trastornos de la Sensación/etiología , Sensación/fisiología , Colgajos Quirúrgicos , Adulto , Sustancia Propia/cirugía , Método Doble Ciego , Síndromes de Ojo Seco/fisiopatología , Femenino , Humanos , Masculino , Estudios Prospectivos , Trastornos de la Sensación/fisiopatología , Factores de Tiempo
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