Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 107
Filtrar
1.
Nat Mater ; 17(3): 231-236, 2018 03.
Artículo en Inglés | MEDLINE | ID: mdl-29403056

RESUMEN

The discovery of a two-dimensional electron gas (2DEG) at the LaAlO3/SrTiO3 interface 1 has resulted in the observation of many properties2-5 not present in conventional semiconductor heterostructures, and so become a focal point for device applications6-8. Its counterpart, the two-dimensional hole gas (2DHG), is expected to complement the 2DEG. However, although the 2DEG has been widely observed 9 , the 2DHG has proved elusive. Herein we demonstrate a highly mobile 2DHG in epitaxially grown SrTiO3/LaAlO3/SrTiO3 heterostructures. Using electrical transport measurements and in-line electron holography, we provide direct evidence of a 2DHG that coexists with a 2DEG at complementary heterointerfaces in the same structure. First-principles calculations, coherent Bragg rod analysis and depth-resolved cathodoluminescence spectroscopy consistently support our finding that to eliminate ionic point defects is key to realizing a 2DHG. The coexistence of a 2DEG and a 2DHG in a single oxide heterostructure provides a platform for the exciting physics of confined electron-hole systems and for developing applications.

2.
Leukemia ; 32(2): 273-284, 2018 02.
Artículo en Inglés | MEDLINE | ID: mdl-28701730

RESUMEN

Chromosomal rearrangements of the human MLL/KMT2A gene are associated with infant, pediatric, adult and therapy-induced acute leukemias. Here we present the data obtained from 2345 acute leukemia patients. Genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and 11 novel TPGs were identified. Thus, a total of 135 different MLL rearrangements have been identified so far, of which 94 TPGs are now characterized at the molecular level. In all, 35 out of these 94 TPGs occur recurrently, but only 9 specific gene fusions account for more than 90% of all illegitimate recombinations of the MLL gene. We observed an age-dependent breakpoint shift with breakpoints localizing within MLL intron 11 associated with acute lymphoblastic leukemia and younger patients, while breakpoints in MLL intron 9 predominate in AML or older patients. The molecular characterization of MLL breakpoints suggests different etiologies in the different age groups and allows the correlation of functional domains of the MLL gene with clinical outcome. This study provides a comprehensive analysis of the MLL recombinome in acute leukemia and demonstrates that the establishment of patient-specific chromosomal fusion sites allows the design of specific PCR primers for minimal residual disease analyses for all patients.


Asunto(s)
N-Metiltransferasa de Histona-Lisina/genética , Leucemia Mieloide Aguda/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Adulto , Niño , Aberraciones Cromosómicas , Rotura Cromosómica , Femenino , Reordenamiento Génico/genética , Humanos , Lactante , Masculino , Proteínas de Fusión Oncogénica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Translocación Genética/genética
3.
Am J Transplant ; 17(2): 365-376, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27376767

RESUMEN

We investigated whether serum deprivation induces islet amyloid polypeptide (IAPP) oligomer accumulation and/or a proinflammatory response and, if so, whether the addition of interleukin (IL)-1 receptor antagonist to the culture medium can relieve the proinflammatory response during serum-deprived culture of nonhuman primate (NHP) islets. After culture in medium with and without Ana under serum-deprived culture conditions, IAPP oligomer/amyloid accumulation, in vitro viability, islet function, cytokine secretion, and posttransplantation outcome in streptozotocin-induced diabetic nude mice were determined in islets isolated from heterozygote human IAPP transgenic (hIAPP+/- ) mice and/or NHP islets. Serum deprivation induced accumulation of IAPP oligomer, but not amyloid, in NHP islets. Anakinra (Ana) protected islets from the serum deprivation-induced impairment of in vitro viability and glucose-stimulated insulin secretion and attenuated serum deprivation-induced caspase-1 activation, transcription, and secretion of IL-1ß, IL-6, and tumor necrosis factor-α in hIAPP+/- mice and NHP islets. Supplementation of medium with Ana during serum-deprived culture also improved posttransplantation in vivo outcomes of NHP islets. In conclusion, serum deprivation induced accumulation of IAPP oligomers and proinflammatory responses in cultured isolated islets. Supplementation of the culture medium with Ana attenuated the functional impairment and proinflammatory responses induced by serum deprivation in ex vivo culture of NHP islets.


Asunto(s)
Antirreumáticos/farmacología , Medio de Cultivo Libre de Suero/toxicidad , Inflamación/prevención & control , Proteína Antagonista del Receptor de Interleucina 1/farmacología , Islotes Pancreáticos/efectos de los fármacos , Animales , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Humanos , Inflamación/inducido químicamente , Islotes Pancreáticos/patología , Macaca fascicularis , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos
4.
J Eur Acad Dermatol Venereol ; 31(5): 894-897, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27549434

RESUMEN

BACKGROUND: Phototherapy is the preferred treatment modality for active and generalized vitiligo. One of the widely accepted consensus on starting dose of phototherapy is using a uniform dose of 280 mJ/cm2 regardless of patients' Fitzpatrick skin phototype (SPT). However, in many clinical experiences with Asian vitiligo patients, the protocol seems suboptimal. OBJECTIVE: To gather more evidence on establishing a higher starting dosage for Asian vitiligo patients undergoing phototherapy. METHODS: We enrolled generalized vitiligo patients with lesions sized adequate enough for phototest. Minimal erythema dose (MED) of vitiligo lesion and non-lesion was measured along with melanin index (MI). RESULTS: Relatively, a wide range of MED and MI was observed even among patients with similar SPT. The range of MED for lesional skin was 300-700 mJ/cm2 and the MED for non-lesion was 500-800 mJ/cm2 . Correlation was noted between lesional MED and non-lesional MI (Spearman correlation, ρ = 0.664 [P < 0.036]) and mean lesional MED was approximately 65% of mean non-lesional MED. CONCLUSION: Results from phototest and tolerability of patients to doses higher than 280 mJ/cm2 may indicate that higher starting doses might be appropriate for Asian vitiligo patients.


Asunto(s)
Fototerapia , Rayos Ultravioleta , Vitíligo/terapia , Anciano , Pueblo Asiatico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto
5.
Niger J Clin Pract ; 19(4): 502-7, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27251968

RESUMEN

BACKGROUND: Imaging methods that use ionizing radiation in emergency departments (EDs) have increased with advances in radiological diagnostic methods. Physician and nurse awareness of the radiation dose in the ED and the associated cancer risks to which the patients are exposed were surveyed with a questionnaire. METHODS: A total of 191 subjects in six EDs participated in this study. ED physicians and ED nurses were asked about the risks and the radiation doses of imaging methods ordered in the ED. The differences between the two groups were compared using Student's t-test for continuous variables. A Fisher's exact and Chi-squared tests were used for categorical variables. RESULTS: A total of 82 ED physicians and 109 ED nurses completed the questionnaire; 38 (46.3%) physicians and 8 (7.3%) nurses correctly answered the question about the chest X-ray radiation dose. A question about the number of chest X-rays that is equivalent to the dose of a pelvic X-ray was answered correctly by 5 (6.1%) physicians and 9 (8.3%) nurses (P = 0.571). Questions regarding abdominal computed tomography (CT), chest CT, brain CT, abdominal ultrasonography, and brain magnetic resonance imaging were answered correctly more frequently by the physician group than the nurse group (P < 0.05). The risk of developing cancer over a lifetime due to a brain CT was correctly answered by 21 (25.6%) physicians and 30 (27.5%) nurses (P = 0.170). A similar question regarding abdominal CT was correctly answered by 21 (25.6%) physicians and 42 (38.5%) nurses (P = 0.127). CONCLUSIONS: Knowledge of the radiation exposure of radiology examinations was lower in nurses than physicians, but knowledge was poor in both groups. ED physicians and nurses should be educated about radiation exposure and cancer risks associated with various diagnostic radiological methods.


Asunto(s)
Servicio de Urgencia en Hospital , Conocimientos, Actitudes y Práctica en Salud , Cuerpo Médico de Hospitales , Neoplasias Inducidas por Radiación , Personal de Enfermería en Hospital , Exposición a la Radiación/efectos adversos , Adulto , Distribución de Chi-Cuadrado , Femenino , Humanos , Imagen por Resonancia Magnética/efectos adversos , Masculino , Radiografía Torácica/efectos adversos , República de Corea , Factores de Riesgo , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos X/efectos adversos , Ultrasonografía/efectos adversos
6.
J Dent Res ; 94(8): 1135-42, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25940145

RESUMEN

Chicken ovalbumin upstream promoter transcription factor 2 (COUP-TFII), an orphan nuclear receptor belonging to the steroid-thyroid hormone receptor superfamily, plays an important role in cell fate determination of various tissues. However, the specific role of COUP-TFII in tooth development has not yet been elucidated. In the present study, we aimed to explore the role of COUP-TFII in dentin sialophosphoprotein (DSPP) expression and matrix mineralization in odontoblast-lineage cells. In primary human dental pulp cells (HDPCs) and murine dental papilla-derived cells (MDPC-23) cultured in a mineralizing medium, the expression of COUP-TFII was induced along with the increased odontoblast-specific dentin matrix protein-1 (DMP-1) and DSPP expression. Endogenous expression of COUP-TFII in maxillary second molar germs of rats showed an increasing tendency as development of the tooth progressed. Also, COUP-TFII protein was detected in greater quantity in the odontoblastic layer of second molar germs than in that of third molar germs of rats. Overexpression of COUP-TFII using an adenoviral system upregulated the expression of odontoblast-specific genes with increased alkaline phosphatase activity and matrix mineralization in odontoblast-lineage cells. In contrast, knockdown of COUP-TFII using small interfering RNA decreased the expression of odontoblast-specific genes, which reduced matrix mineralization. Mechanistic studies revealed that COUP-TFII increased DSPP transcription by direct binding on the DSPP promoter. In addition, COUP-TFII physically interacted with the homeodomain transcription factor Msx2 and antagonistically regulated the Msx2 effect on DSPP promoter activity. Taken together, these results suggest that COUP-TFII has a stimulatory role in DSPP expression and matrix mineralization in odontoblast-lineage cells.


Asunto(s)
Factor de Transcripción COUP II/metabolismo , Dentinogénesis , Proteínas de la Matriz Extracelular/metabolismo , Odontoblastos/metabolismo , Fosfoproteínas/metabolismo , Sialoglicoproteínas/metabolismo , Animales , Western Blotting , Diferenciación Celular , Células Cultivadas , Proteínas de Homeodominio/metabolismo , Humanos , Inmunoprecipitación , Ratones , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Coloración y Etiquetado , Transfección
7.
Am J Transplant ; 15(6): 1543-54, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25865268

RESUMEN

The spheroid culture method is an effective strategy for ex vivo expansion of an autologous therapeutic cell population. We investigated if cotransplantation of bone marrow-derived spheroids (BM-spheroid) formed using 3D culture of BM-derived mononuclear cells (BM-MNCs) could improve the posttransplant outcome of islet grafts using a mouse syngeneic marginal mass renal subcapsular islet transplantation model. Using green fluorescent protein transgenic (GFP-Tg) mice, the role of the BM-spheroids and the contribution of vessels derived from donors and recipients in grafted areas were assessed by immunohistochemistry. Compared to fresh BM-MNCs and nonspheroid remnant cells (BM-nonspheroid), the BM-spheroids, mainly composed of CXCR4(+) CD14(+) myeloid cells, showed higher angiogenic capacity, such as in vitro self-formed vessel structures; increased expression of angiogenic and chemoattractive factors; and incorporation into new vessel formation in basement membrane matrix plugs. BM-spheroid cotransplantation with islets improved the posttransplant outcomes in terms of glucose tolerance, serum insulin level, and diabetes reversal rate when compared with cotransplantation of BM-nonspheroids. Immunohistochemistry revealed that cotransplantation of the BM-spheroids increased vessel density, area of grafted endocrine and non-endocrine tissue, and ß cell proliferation. In conclusion, cotransplantation of islets and BM-spheroids improved islet function through facilitation of revascularization and an increase in cell proliferation and islet cell mass.


Asunto(s)
Células de la Médula Ósea/citología , Células de la Médula Ósea/fisiología , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Trasplante de Islotes Pancreáticos/métodos , Islotes Pancreáticos/irrigación sanguínea , Células Mieloides/citología , Células Mieloides/fisiología , Animales , Glucemia/metabolismo , Comunicación Celular/fisiología , Proliferación Celular/fisiología , Trasplante de Células/métodos , Células Cultivadas , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/cirugía , Modelos Animales de Enfermedad , Supervivencia de Injerto/fisiología , Técnicas In Vitro , Islotes Pancreáticos/fisiología , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neovascularización Fisiológica/fisiología , Estreptozocina/efectos adversos
8.
Cell Death Differ ; 21(7): 1150-9, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-24658401

RESUMEN

MicroRNAs have crucial roles in lung cancer cell development. They regulate cell growth, proliferation and migration by mediating the expression of tumor suppressor genes and oncogenes. We identified and characterized the novel miR-9500 in human lung cancer cells. The miR-9500 forms a stem-loop structure and is conserved in other mammals. The expression levels of miR-9500 were reduced in lung cancer cells and lung cancer tissues compared with normal tissues, as verified by TaqMan miRNA assays. It was confirmed that the putative target gene, Akt1, was directly suppressed by miR-9500, as demonstrated by a luciferase reporter assay. The miR-9500 significantly repressed the protein expression levels of Akt1, as demonstrated via western blot, but did not affect the corresponding mRNA levels. Akt1 has an important role in lung carcinogenesis, and depletion of Akt1 has been shown to have antiproliferative and anti-migratory effects in previous studies. In the current study, the overexpression of miR-9500 inhibited cell proliferation and the expression of cell cycle-related proteins. Likewise, the overexpression of miR-9500 impeded cell migration in human lung cancer cells. In an in vivo assay, miR-9500 significantly suppressed Fluc expression compared with NC and ASO-miR-9500, suggesting that cell proliferation was inhibited in nude mice. Likewise, miR-9500 repressed tumorigenesis and metastasis by targeting Akt1. These data indicate that miR-9500 might be applicable for lung cancer therapy.


Asunto(s)
Movimiento Celular , Proliferación Celular , Neoplasias Pulmonares/genética , MicroARNs/fisiología , Proteínas Proto-Oncogénicas c-akt/genética , Interferencia de ARN , Regiones no Traducidas 3' , Animales , Secuencia de Bases , Sitios de Unión , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/enzimología , Neoplasias Pulmonares/patología , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Metástasis de la Neoplasia , Trasplante de Neoplasias , Proteínas Proto-Oncogénicas c-akt/metabolismo
9.
Oncogene ; 33(38): 4675-84, 2014 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-24662814

RESUMEN

We provide detailed mechanisms of Ahnak-mediated potentiation of transforming growth factor ß (TGFß) signaling, which leads to a negative regulation of cell growth. We show that Smad3 interacts with Ahnak through MH2 domain and that Ahnak stimulates Smad3 localization into nucleus leading to potentiating TGFß-induced transcriptional activity of R-Smad. Moreover, overexpression of Ahnak resulted in growth retardation and cell cycle arrest through downregulation of c-Myc and cyclin D1/D2. We describe results from analyses of Ahnak(-/-) mouse model expressing middle T antigen in a mammary gland-specific manner (MMTV(Tg/+)Ahnak(-/-)), which showed significantly progressed hyperplasia of mammary glands compared with MMTV(Tg/+)Ahnak(+/+). Finally, we screened multiple human breast cancer tissues and showed that the expression of Ahnak in cancer tissues is lower than that in control tissues by 50%. Taken together, these data indicate that Ahnak mediates a negative regulation of cell growth and acts as novel tumor suppressor through potentiation of TGFß signaling.


Asunto(s)
Proteínas de la Membrana/fisiología , Proteínas de Neoplasias/fisiología , Proteínas Smad/metabolismo , Animales , Células COS , Puntos de Control del Ciclo Celular , Proliferación Celular , Chlorocebus aethiops , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Desnudos , Células 3T3 NIH , Trasplante de Neoplasias , Proteínas Serina-Treonina Quinasas/metabolismo , Receptor Tipo I de Factor de Crecimiento Transformador beta , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/fisiología , Proteínas Supresoras de Tumor/fisiología
10.
J Dent Res ; 93(5): 483-9, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24570149

RESUMEN

ATF6 is an endoplasmic reticulum (ER) membrane-bound transcription factor that regulates various cellular functions. The purpose of this study was to investigate the role of ATF6 in odontoblast differentiation. Rat tooth germs were isolated, changes in gene expression were evaluated over time, and localization of ATF6 was determined by immunohistochemistry. Human dental pulp cells (HDPCs) were cultured with 50 µg/mL ascorbic acid and 5 mmol/L ß-glycerophosphate or 100 ng/mL bone morphogenetic protein 2 to induce differentiation. Translocation of ATF6 was observed by immunofluorescence and confocal microscopy. Overexpression of ATF6 was performed with an adenoviral vector. Matrix mineralization was evaluated by alizarin red staining. Immunoreactivity to anti-ATF6 was observed in the odontoblastic layer of the molar tooth germ, and expressions of ATF6, dentin sialophosphoprotein (DSPP) and dentin matrix protein 1 (DMP1) increased gradually during tooth germ development. When HDPCs were cultured in differentiation media, ATF6, DSPP, and DMP1 expression increased with the expression of unfolded protein response (UPR) markers, BiP and CHOP. Immunofluorescence results showed that ATF6 protein moved from cytoplasm to nucleus when cells were exposed to differentiation media. Notably, overexpression of ATF6 increased DSPP and DMP1 expression, alkaline phosphatase (ALP) activity, and matrix mineralization in HDPC cultures. Inhibition of ATF6 decreased ALP activity and mineralization. These results suggest that ER membrane-bound transcriptional factor ATF6 may be involved in odontoblastic differentiation.


Asunto(s)
Factor de Transcripción Activador 6/fisiología , Odontoblastos/fisiología , Factor de Transcripción Activador 6/análisis , Adenoviridae/genética , Fosfatasa Alcalina/análisis , Animales , Proteína Morfogenética Ósea 2/farmacología , Calcificación Fisiológica/fisiología , Técnicas de Cultivo de Célula , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Línea Celular , Núcleo Celular/ultraestructura , Citoplasma/ultraestructura , Pulpa Dental/citología , Proteínas de la Matriz Extracelular/análisis , Regulación de la Expresión Génica/genética , Vectores Genéticos/genética , Humanos , Odontoblastos/efectos de los fármacos , Fosfoproteínas/análisis , Ratas , Ratas Sprague-Dawley , Sialoglicoproteínas/análisis , Germen Dentario/citología , Germen Dentario/crecimiento & desarrollo , Factor de Transcripción CHOP/análisis , Respuesta de Proteína Desplegada/fisiología
11.
Transplant Proc ; 45(8): 3097-101, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24157043

RESUMEN

INTRODUCTION: We investigated the optimal method for transportation of isolated porcine islets from an isolation facility to a transplant hospital or research center in terms of temperature, oxygen supply, and shaking effect. METHODS: Commercially available insulator boxes with thermoregulators exposed for 5 hours under two external temperatures (4°C and 37°C) were monitored using HOBO temperature loggers. To find the optimal transport device, we compared islet counts, viability, quality, and function in conical tubes, gas-permeable bags (GPB) and gas-permeable flasks (GPF) after 1, 3 and 5 hours. To evaluate the effects of shaking on islets, we also analyzed the difference between a control and a shaking group in each device with time. RESULTS: Commercially available Styrofoam insulators with thermoregulators maintained the internal temperature near the target. Islet recovery rate for GPF, which was higher than other devices, was maintained, while those decreased with time for conical tube and GPB containers adenosine diphosphate/adenosine triphosphate (ADP/ATP) ratio for GPF was lower than other devices, albeit not significantly fluoroscein acrimide/propidium iodide (AO/PI) ratio for GPF was higher than other devices after 5 hours. Glucose stimulated index was not different among the devices. In comparison with the control group, shaking yielded comparable islet survival, viability and function. CONCLUSION: Our study demonstrated that the use of commercially available insulator boxes with thermoregulators maintained internal temperature close to the target value and that GPF was more favorable for islet oxygenation during transportation. This study also suggested negligible impact of shaking on isolated porcine islets during transportation.


Asunto(s)
Islotes Pancreáticos/citología , Animales , Femenino , Islotes Pancreáticos/fisiología , Porcinos
12.
Leukemia ; 27(11): 2165-76, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23628958

RESUMEN

Chromosomal rearrangements of the human MLL (mixed lineage leukemia) gene are associated with high-risk infant, pediatric, adult and therapy-induced acute leukemias. We used long-distance inverse-polymerase chain reaction to characterize the chromosomal rearrangement of individual acute leukemia patients. We present data of the molecular characterization of 1590 MLL-rearranged biopsy samples obtained from acute leukemia patients. The precise localization of genomic breakpoints within the MLL gene and the involved translocation partner genes (TPGs) were determined and novel TPGs identified. All patients were classified according to their gender (852 females and 745 males), age at diagnosis (558 infant, 416 pediatric and 616 adult leukemia patients) and other clinical criteria. Combined data of our study and recently published data revealed a total of 121 different MLL rearrangements, of which 79 TPGs are now characterized at the molecular level. However, only seven rearrangements seem to be predominantly associated with illegitimate recombinations of the MLL gene (≈ 90%): AFF1/AF4, MLLT3/AF9, MLLT1/ENL, MLLT10/AF10, ELL, partial tandem duplications (MLL PTDs) and MLLT4/AF6, respectively. The MLL breakpoint distributions for all clinical relevant subtypes (gender, disease type, age at diagnosis, reciprocal, complex and therapy-induced translocations) are presented. Finally, we present the extending network of reciprocal MLL fusions deriving from complex rearrangements.


Asunto(s)
Rotura Cromosómica , Reordenamiento Génico , Leucemia/genética , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteínas de Fusión Oncogénica/genética , Translocación Genética/genética , Enfermedad Aguda , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Animales , Niño , Preescolar , Femenino , N-Metiltransferasa de Histona-Lisina , Humanos , Lactante , Recién Nacido , Leucemia/clasificación , Masculino , Ratones , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Pronóstico , Adulto Joven
13.
Am J Transplant ; 13(6): 1429-40, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23601171

RESUMEN

Bone marrow-derived early endothelial progenitor cells (BM-EPCs) are a clinical tool for enhancing revascularization. However, the therapeutic efficacy of co-transplantation of BM-EPC with islets has not been investigated. In this study, marginal mass islets were co-transplanted with or without BM-EPCs under the kidney capsules of syngeneic streptozotocin-induced diabetic mice. Using green fluorescent protein transgenic (GFP-Tg) mice as BM-EPC and islet donors or recipients, the role of EPCs in revascularization was assessed for graft morphology, vascular density and fate of EPCs by immunohistochemistry. Islet-EPC co-transplantation improved the outcome of islet transplantation as measured by glucose tolerance, serum insulin level and diabetes reversal rate, compared with transplantation of islets alone. Between groups, the morphology of islet grafts showed significant differences in size and composition of grafted endocrine tissues. Significantly more vessel density derived from donors and recipients was detected with islet-EPC co-transplantation. Abundant GFP-Tg mice-derived BM-EPCs (GFP-EPCs) were observed in or around islet grafts and incorporated into CD31-positive capillaries. Remaining GFP-EPCs expressed VEGF. In conclusion, co-transplantation of islets with BM-EPCs could improve the outcome of marginal mass islet transplantation by promoting revascularization and preserving islet morphology.


Asunto(s)
Células de la Médula Ósea/citología , Endotelio Vascular/citología , Supervivencia de Injerto/fisiología , Trasplante de Islotes Pancreáticos , Islotes Pancreáticos/irrigación sanguínea , Trasplante de Células Madre/métodos , Células Madre/citología , Animales , Modelos Animales de Enfermedad , Células Endoteliales , Masculino , Ratones , Ratones Endogámicos C57BL
14.
J Eur Acad Dermatol Venereol ; 27(2): e243-6, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-22646755

RESUMEN

BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a commonly acquired leucoderma that is characterized by discrete, round or oval porcelain-white macules ∼2-5 mm in diameter that increases in number with age. A variety of therapies with variable success rates, including cryotherapy, superficial abrasion and topical retinoids are currently being used. OBJECTIVES: The effects of fractional CO(2) laser therapy on IGH were investigated in this pilot study. PATIENTS AND METHODS: A total of 40 patients with IGH were enrolled. The hypopigmented lesions were treated using a 10 600-nm carbon dioxide fractional laser (CO(2) FL). Two months after a single treatment, physicians' clinical assessments were performed and the patients' overall satisfaction was evaluated. RESULTS: The mean age of enrolled patients was 57.5 ± 10.9 years and the gender ratio was 7 : 33. The face was the most commonly treated area, although the extremities are epidemiologically the most frequently affected areas. Two months after treatment, objective assessments performed by two independent dermatologists indicated more than 50% improvement in 36 patients (90%), compared with baseline. In addition, 33 patients (82.5%) were very satisfied or satisfied with just one session of CO(2) FL treatment. Although a few patients complained of long-standing erythema and postinflammatory hyperpigmentation, these problems spontaneously resolved within 2 months after the assessments. No other noticeable side effects were observed. CONCLUSION: CO(2) FL might be a very convenient and effective modality for treating IGH without significant side effects.


Asunto(s)
Dióxido de Carbono , Terapia por Láser , Láseres de Gas , Trastornos de la Pigmentación/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad
15.
Transplant Proc ; 44(2): 583-4, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22506295

RESUMEN

Factor X (FX) deficiency is a rare, autosomal-recessive coagulation disorder. Diagnosis can be confirmed by a factor X assay. Although fresh frozen plasma and prothrombin complex concentrates have been used as a temporary treatment of bleeding symptoms and preparation for surgery, frequent transfusion has its risk and prothrombin complex is not available in Korea. We report the first pediatric case of successful liver transplantation for the correction of a severe congenital FX deficiency in a child with recurrent life-threatening hemorrhagic episodes.


Asunto(s)
Coagulación Sanguínea/genética , Deficiencia del Factor X/cirugía , Hemorragia/prevención & control , Trasplante de Hígado , Pruebas de Coagulación Sanguínea , Análisis Mutacional de ADN , Deficiencia del Factor X/sangre , Deficiencia del Factor X/complicaciones , Deficiencia del Factor X/diagnóstico , Deficiencia del Factor X/genética , Femenino , Hemorragia/sangre , Hemorragia/genética , Humanos , Lactante , Masculino , Índice de Severidad de la Enfermedad , Resultado del Tratamiento
16.
Transplant Proc ; 44(2): 484-6, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22410052

RESUMEN

The aim of this study was to present our experience with more than 200 cases of orthotopic liver transplantation (OLT) at a single center. We conducted a retrospective, single-center assessment of the demographic and clinical factors in children who underwent OLT from 1994 to 2010. Two hundred children younger than 18 years of age underwent 200 primary and 9 liver re-transplantations. The overall patient survival rates before 2003 at 1, 5, and 10 years were 86.4%, 79.5%, and 78.4%, respectively; whereas after 2003 they were 95.4% and 95.4% at 1 and 5 years, respectively (P<.05). Our center's results showed durable, improved outcomes in recent years.


Asunto(s)
Trasplante de Hígado , Factores de Edad , Distribución de Chi-Cuadrado , Femenino , Humanos , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/mortalidad , Masculino , Reoperación , República de Corea , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
17.
Oncogene ; 31(17): 2187-98, 2012 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-21927028

RESUMEN

Although the hyper-glycosylated transmembrane protein Mucin 1 (MUC1) is aberrantly overexpressed in human breast carcinoma, the biological significance of MUC1 overexpression is unclear. This study showed that MUC1 expression promoted the synthesis and secretion of vascular endothelial growth factor (VEGF) through the AKT signaling pathway. Increase VEGF production through MUC1 expression had a number of effect. First, MUC1 transfection increased expression of VEGF in breast cancer cells. Second, MUC1-mediated VEGF induction was attenuated by a chemical inhibitor of AKT or MUC1 knock-down by MUC1 siRNA. Third, MUC1 expression led to the activation of insulin-like growth factor-1 receptor, which correlated with VEGF expression. In addition, when MDA-MB-231 human breast cancer cells were directly injected into NOD/SCID mice, MUC1 expression accelerated xenograft tumor growth in vivo. Finally, MUC1 expression enhanced tumor growth and angiogenesis in a PyMT-MMTV/hMUC1 transgenic mouse model. Concurrent with these results, analysis of a human tissue microarray identified a high correlation between MUC1 and VEGF expression in human breast carcinoma. The current report is the first to demonstrate that MUC1 expression promotes angiogenesis in human breast cancer in vivo and in vitro.


Asunto(s)
Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/metabolismo , Mucina-1/metabolismo , Neovascularización Patológica , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Ratones , Ratones SCID , Mucina-1/genética , Trasplante de Neoplasias , Fosfatidilinositol 3-Quinasas/metabolismo , Receptores de Somatomedina/metabolismo , Transducción de Señal , Transfección , Trasplante Heterólogo , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular/metabolismo
18.
J Eur Acad Dermatol Venereol ; 26(1): 54-8, 2012 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21366711

RESUMEN

BACKGROUND: Flushing is defined clinically as a transient reddening of the face and other areas. Due to the transient nature of flushing, a patient may not show signs of flushing during laser treatment. OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of 595-nm pulsed-dye laser treatment of flushing or erythema after provocation of flushing by topical niacin cream. METHODS: We retrospectively reviewed a total of 25 Korean patients with facial flushing who were treated with three sessions of 595-nm pulsed-dye laser after the application of topical niacin cream. RESULTS: Follow-up results revealed that 12 of the 25 patients demonstrated marked (51-75%) clinical improvement of baseline facial erythema. Eight patients had moderate (26-50%) improvement and three demonstrated near total (≥ 75%) improvement. Two patients showed minimal to no (0-25%) improvement. We observed that the reactivity to topical niacin cream was markedly reduced in 64% of our patients after 595-nm pulsed-dye laser treatments. Minimal post-therapy facial oedema was noted in most of the patients, which usually resolved spontaneously within 2 days. Pronounced facial swelling was observed in four patients. CONCLUSION: We suggest that 595-nm pulsed-dye laser treatment after provocation of flushing by topical niacin cream may provide a new treatment algorithm for facial flushing in Asians.


Asunto(s)
Cara , Rubor/terapia , Niacina/uso terapéutico , Administración Tópica , Adulto , Terapia Combinada , Femenino , Rubor/tratamiento farmacológico , Humanos , Terapia por Láser , Masculino , Persona de Mediana Edad , Niacina/administración & dosificación , República de Corea , Estudios Retrospectivos
19.
Br J Dermatol ; 166(3): 658-61, 2012 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22050270

RESUMEN

BACKGROUND: Vitiligo is a common acquired depigmentation disorder caused by the loss of melanocytes. Despite the numerous treatment modalities available for vitiligo, responses to treatment are still unsatisfactory. For this reason, new treatment modalities and approaches are needed. OBJECTIVES: To investigate the effects of fractional carbon dioxide (CO(2) ) laser therapy followed by systemic narrowband ultraviolet B (NB-UVB) phototherapy on nonsegmental vitiligo (NSV) as a prospective and randomized left-right comparative study. METHODS: Ten patients with NSV who presented symmetrical vitiligo lesions with no further improvement despite more than 1 year of conventional treatment were enrolled. Two sessions of half-body fractional CO(2) laser therapy were performed at a 2-month interval. NB-UVB phototherapy was then administered to the entire body 5 days after each fractional laser treatment twice a week, increasing the dose incrementally by 15% at each session. Objective clinical assessments were made by two blinded dermatologists using a quartile grading scale, and the patients' overall satisfaction was evaluated using a 10-point visual analogue scale. RESULTS: Two months after the last treatment, mean improvement scores, assessed by physicians, were significantly higher for those treated with half-body fractional CO(2) laser therapy followed by NB-UVB phototherapy, compared with those treated with NB-UVB alone (P=0·034). In addition, according to subjective assessment, the half-body laser treatment followed by NB-UVB showed significantly higher improvements compared with NB-UVB treatment alone (P=0·023). Noticeable adverse events, such as infection, scarring and Koebner phenomenon, were not found in any patient. CONCLUSIONS: This study suggests that fractional CO(2) laser therapy followed by NB-UVB phototherapy could be used effectively and safely as an alternative modality for the treatment of refractory vitiligo.


Asunto(s)
Terapia por Láser/métodos , Terapia Ultravioleta/métodos , Vitíligo/terapia , Adulto , Anciano , Enfermedad Crónica , Terapia Combinada , Femenino , Humanos , Terapia por Láser/instrumentación , Láseres de Gas/uso terapéutico , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Resultado del Tratamiento
20.
Transplant Proc ; 43(6): 2394-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21839275

RESUMEN

INTRODUCTION: De novo autoimmune hepatitis (AIH) after orthotopic liver transplantation (OLT) has been described as a new type of late graft dysfunction in children who have not undergone transplantation for previous autoimmune liver disease. The purpose of this study was to evaluate the clinical aspects of de novo AIH among children following OLT. PATIENTS AND METHODS: Between January 1994 and May 2007, 149 children underwent OLT, including 1 with recurrent AIH who was excluded from this study, whereas 4 others developed de novo AIH (2.7%; n = 4/148). We analyzed the demographics, laboratory characteristics, and response to treatment of the 4 children with de novo AIH following OLT. RESULTS: The 4 patients were all girls with a median interval after OLT to presentation of 6.5 years (range, 0.7-8.8 years). The median age when de novo AIH developed was 12.4 years (range, 8.7-17.3 years). All cases were detected by abnormal liver function tests, namely, increased aspartate aminotransferase (AST; median, 322 IU/L; range, 181-919 IU/L). One patient showed elevated immunoglobulin G. Three patients displayed positive antinuclear antibodies. All were seronegative for smooth muscle antibody and liver-kidney microsomal type 1 antibody. One patient showed anti-mitochondrial antibody. All patients were treated with steroids with or without azathioprine. The liver function tests in these 4 patients, improved by at least 50% during the first month of treatment, responding to steroid treatment with or without azathioprine. CONCLUSION: In preadolescent or adolescent female patients with unexplained graft dysfunction after OLT, it is important to recognize de novo AIH rapidly and to develop an adequate diagnostic strategy, including evaluation of serum autoantibodies, immunoglobulin G, and liver biopsy.


Asunto(s)
Hepatitis Autoinmune/inmunología , Trasplante de Hígado/inmunología , Adolescente , Autoanticuerpos/sangre , Azatioprina/uso terapéutico , Biomarcadores/sangre , Biopsia , Niño , Femenino , Hepatitis Autoinmune/diagnóstico , Hepatitis Autoinmune/tratamiento farmacológico , Humanos , Inmunoglobulina G/sangre , Inmunosupresores/uso terapéutico , Pruebas de Función Hepática , República de Corea , Esteroides/uso terapéutico , Factores de Tiempo , Resultado del Tratamiento
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA