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1.
Kardiologiia ; 62(9): 37-43, 2022 Sep 30.
Artículo en Ruso, Inglés | MEDLINE | ID: mdl-36206136

RESUMEN

Aim      To compare long-term outcomes of x-ray endovascular (percutaneous coronary intervention, PCI, and lower limb angioplasty with stent placement, LLA; group 1) and combination treatments (PCI and open LLA surgery; group 2) in patients with chronic lower limb ischemia (CLLI) associated with ischemic heart disease (IHD).Material and methods  This retrospective study has been conducted in the Vishnevsky National Medical Research Center of Surgery since 2019. The study includes 92 patients with stage 2B CLLI associated with IHD who were managed from January 1, 2017 through December 31, 2020. Long-term outcomes were evaluated in 76 (82.6 %) patients. The endpoint was severe cardiovascular complications (CVC), including death, myocardial infarction, and acute cerebrovascular disease (ACVD).Results In group 1 during the long-term period, 1 (2.7%) fatal outcome due to pneumonia was observed. In group 2, 4 (10 %) patients died: 1 (2.5 %) patient due to ACVD, 1 (2.5 %) patient due to progression of oncological process, and 2 2 (5 %) patients due to COVID-19. Also, 2 (5.5 %) and 1 (2.5 %) cases of acute coronary syndrome (ACS) were observed in groups 1 and 2, respectively (p=0.61).Conclusion      In the x-ray endovascular (group1) and the combination (group 2) intervention groups, lethal outcomes due to myocardial infarction were absent. This fact confirms the importance of PCI in patients with CLLI for prevention of possible ACS in the long-term. Both therapeutic tactics in managing CLLI patients with IHD demonstrated high safety and clinical efficacy during the hospital and long-term periods and can be extensively used in routine clinical practice.


Asunto(s)
Síndrome Coronario Agudo , COVID-19 , Infarto del Miocardio , Isquemia Miocárdica , Intervención Coronaria Percutánea , Humanos , Extremidad Inferior , Isquemia Miocárdica/complicaciones , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/terapia , Intervención Coronaria Percutánea/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento
2.
Lupus ; 27(13): 2057-2068, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30336752

RESUMEN

OBJECTIVE: The increment of CD4+CD25-Foxp3+T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4+CD25-Foxp3+T cells and Treg cells (CD4+CD25+Foxp3+ T cells) in a large sample of Chinese SLE patients in different disease states. METHODS: A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4+CD25-Foxp3+ T cells and Treg cells were performed by flow cytometry. The correlation of CD4+CD25-Foxp3+T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. RESULTS: CD4+CD25-Foxp3+ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4+CD25-Foxp3+ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4+CD25-Foxp3+ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4+CD25-Foxp3+ T cells expressed more IFN-γ and less CTLA-4 than CD4+CD25+Foxp3+ T cells, which were similar to CD4+CD25+Foxp3- T cells, and expressed similar IL-17, ICOS and Helios to CD4+CD25+Foxp3+ T cells. The synthesis capacity of IL-10 of CD4+CD25-Foxp3+ T cells and the expression of GITR on CD4+CD25-Foxp3+ T cells were between CD4+CD25+Foxp3+ and CD4+CD25+Foxp3- T cells. CONCLUSIONS: Our results indicate that increased CD4+CD25-Foxp3+ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Lupus Eritematoso Sistémico/inmunología , Linfocitos T Reguladores/inmunología , Adolescente , Adulto , Anciano , Estudios de Casos y Controles , Niño , China , Femenino , Citometría de Flujo , Factores de Transcripción Forkhead/metabolismo , Humanos , Inmunofenotipificación , Lupus Eritematoso Sistémico/fisiopatología , Masculino , Persona de Mediana Edad , Subgrupos de Linfocitos T/inmunología , Adulto Joven
3.
Cell Mol Biol (Noisy-le-grand) ; 61(3): 12-6, 2015 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-26068913

RESUMEN

Resistance to chemotherapeutic drugs is a major obstacle in hepatocellular carcinoma (HCC) therapy. MicroRNA—145 (miR—145) has been shown to be down—regulated in several cancers and may be involved in the process of carcinogenesis. The present study aimed to evaluate the effects of miR—145 in adriamycin (ADM)—resistant human HCC cells. We found that miR—145 was significantly reduced in HepG2/ADM and HuH7/ADM cells compared with the chemosensitive parental cells. Up—regulation of miR—145 increased the ADM cytotoxicity in chemoresistant tumor cells. In addition, Smad3 was identified as the target of miR—145 and miR—145 overexpression inhibited Smad3 expression both at the mRNA and protein levels. The luciferase reporter assay confirmed that Smad3 was a direct target of miR—145. Moreover, up—regulation of miR—145 suppressed Smad3 related EMT features as shown by increased expression of E—cadherin and reduced vimentin level in HepG2/ADM and HuH7/ADM cells. Our study demonstrated that miR—145 modulated both chemoresistance and EMT in HCC cells, and up—regulation of miR—145 might be a potential therapeutic strategy for treatment of chemoresistant HCC.


Asunto(s)
Resistencia a Antineoplásicos , Transición Epitelial-Mesenquimal , MicroARNs/metabolismo , Regiones no Traducidas 3' , Cadherinas/metabolismo , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Células Hep G2 , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , MicroARNs/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Proteína smad3/genética , Proteína smad3/metabolismo , Regulación hacia Arriba , Vimentina/metabolismo
4.
Urologiia ; (1): 58-61, 2015.
Artículo en Ruso | MEDLINE | ID: mdl-26094389

RESUMEN

From a surgeon's perspective, intraureteral jj-stent is an optimal tool to ensure upper urinary tract drainage. This paper presents preliminary results of our study investigating the use of ureteral stents with nanostructured coating in renal transplant recipients. The use of nanostructured coating based on amorphous carbon and silver nanocrystallites eliminated bacteriuria by week 4 after stenting in the treatment group with significant decrease of urine sediments while in the control group bacteriuria was found in 83,3% cases. Symptoms of bladder irritability depended on stent construction rather than presence of coating.


Asunto(s)
Materiales Biocompatibles Revestidos , Trasplante de Riñón , Nanopartículas , Stents , Uréter , Carbono/química , Femenino , Humanos , Masculino , Plata/química
5.
Biomed Khim ; 66(5): 401-405, 2020 Sep.
Artículo en Ruso | MEDLINE | ID: mdl-33140734

RESUMEN

The study of interaction between surface viral proteins and model phospholipids is important for learning more details about the mechanisms of viral penetration into cells during infection. In this context, liposomes represent suitable systems for modeling a cell membrane. The binding of hemagglutinin (HA) of influenza virus with phosphatidylcholine liposomes was studied by equilibrium adsorption. It was interesting elucidate changes occurring in the structure of a protein during its translocation from the surface into the interior part of the membrane. In this work, we have studied characteristics of the protein-lipid interaction during HA complex formation with phospholipids including adsorption of HA on a phospholipid bilayer. Using the Scatchard equation and the Gibbs-Helmholtz equation at pH 4.0 and pH 6.0 thermodynamic parameters were determined. The results concluded the hydrophobic type of interaction between viral protein and liposomes. The additional confirmation of hydrophobic protein-lipid interaction presence was determination of HA distribution constants in two-phase systems: dextran-polyethylene glycol (K1) and dextran-polyethylene glycol esterified with palmitic acid (K2). The presence of hydrophobic interaction between HA and the liposome membrane was also confirmed using the quenching method of intrinsic protein fluorescence by a neutral quencher with acrylamide. At pH 4.0, an increase in the Stern-Volmer quenching constant was observed for the HA+liposome from phosphatidylcholine system, which is caused by structural changes in HA upon incorporation into the liposome bilayer. The fluorescence quenching rate constants calculated using the Stern-Volmer equation indicate a static quenching mechanism in which the quencher interacts with fluophors of a stationary protein molecule. The obtained results are interesting for not only studying virus and cell fusion theoretically, but also have practical applications. Using values of the protein-bilayer binding constant and free energy constant, it is possible to select the optimal phospholipid composition of liposomes or virosomes to obtain a stronger complex with various viral proteins. With two-phase systems, it is possible to determine the presence of hydrophobic sites on the viral protein surface, which can be used for evaluation both protein-lipid and protein-protein interaction.


Asunto(s)
Liposomas , Orthomyxoviridae , Hemaglutininas , Concentración de Iones de Hidrógeno , Fosfatidilcolinas , Tailandia , Termodinámica
6.
Sci Rep ; 8(1): 4851, 2018 Mar 19.
Artículo en Inglés | MEDLINE | ID: mdl-29555981

RESUMEN

We propose the unique structure of highly dispersible single-walled carbon nanotubes (SWCNTs) in various solvents and polymers using the ZnO nano particle template. Buckled nanospring-shaped carbon nanotubes (NS-CNTs) were synthesized by a chemical reaction of ZnO nanoparticles with acid-treated SWCNTs and then dissolving ZnO through chemical etching. The unique structure of distorted hexagonal NS-CNTs encircled around ZnO nanoparticles was formed by the bending of SWCNTs caused by the agglomeration of chemically adsorbed Zn(OH)2, which is further crystallized as the polycrystalline ZnO inner core. The highly dispersible NS-CNTs could be incorporated in the poly[(vinylidenefluoride-co-trifluoroethylene] [P(VDF-TrFE)] copolymer, one of widely studied ferro- and piezo-electric polymer, up to the value of 15 wt% as nanofillers. The relative dielectric constant (K) of polymer nanocomposite, at 1 kHz, was greatly enhanced from 12.7 to the value of 62.5 at 11 wt% of NS-CNTs, corresponding to a 492% increase compared to that of pristine P(VDF-TrFE) with only a small dielectric loss tangent (D) of 0.1.

7.
Zhonghua Yi Shi Za Zhi ; 47(5): 262-272, 2017 Sep 28.
Artículo en Zh | MEDLINE | ID: mdl-29874717

RESUMEN

In the Huang di nei jing(Huangdi's Internal Classic), jin ye (fluid and humor) is described in two senses, broad and narrow, though not so strictly.Sometimes, jin ye is explained ambiguously as "sweat" and "urine" , as in the phrase "the bladder, being a house of jin ye" , here "jin ye" refers to the urine. In the Qi jue lun pian of Su wen (Chapter on Qi-Syncope of Plain Questions) , the "bao" in the sentence "heat of bao moved to bladder" refersto the uterus. In the Shi cong rong lun pian (Chapter of Readily Inspecting) of Plain Questions, the "bladder" in the phrase "gallbladder, stomach, large intestine, small intestine, spleen, bao and bladder" , which, being an annotation of "bao" originally, is mistakenly incorporated into the text of the Classic. In the Wu wei lun of Ling shu (On Five Tastes in Miraculous Pivot) , the "bao" in "bao of bladder" refers to the external hou (external manifestation) of the bladder, that is the scrotum. In the Bei ji qian jin yao fang (Essential Prescriptions Worth a Thousand Gold for Emergencies) , the short sentence "pang guang zou bao" is an error in itself. In the sentence of "settled in the bao and zhi causing to dream of defecation and urination" in the Yin xie fa meng (Dreams due to Evils) of Miraculous Pivot, "bao" refers to uterus, and "zhi" to anus. In Bi lun pian(Chapter on Impediment) of Plain Questions, "the man suffered bao bimight feel internal pain when the lesser abdomen and bladder are pressed" , here, "bao" refers to the bladder. In the Wu yin wu wei(Chapter on Five Sound and Five Tastes) of Miraculous Pivot, the "bao" in the sentence "thoroughfare vessel and conception vessel all starts from bao" , again, "bao" here refers to the bladder, rather than to the uterus. From the above descriptions of "bladder" and "bao" in the Huangdi's Internal Classic, the "bladder" in ancient medical books refers to the substantial bladder, an anatomical organ, and "bao" refers to cystiform organs, including the bladder, uterus, scrotum etc.


Asunto(s)
Medicina Tradicional China , Vejiga Urinaria/fisiología , Libros , Humanos , Orina
8.
Oncogene ; 36(20): 2857-2867, 2017 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-27941887

RESUMEN

Recently single-cell whole-exome sequencing (scWES) has deeply expanded and sharpened our knowledge of cancer evolution and subclonality. Herein, with scWES and matched bulk whole-exome sequencing (bulk WES) on two colorectal cancer (CRC) patients with normal or adenomatous polyps, we found that both the adenoma and cancer were of monoclonal origin, and both shared partial mutations in the same signaling pathways, but each showed a specific spectrum of heterogeneous somatic mutations. In addition, the adenoma and cancer further developed intratumor heterogeneity with the accumulation of nonrandom somatic mutations specifically in GPCR, PI3K-Akt and FGFR signaling pathways. We identified novel driver mutations that developed during adenoma and cancer evolution, particularly in OR1B1 (GPCR signaling pathway) for adenoma evolution, and LAMA1 (PI3K-Akt signaling pathway) and ADCY3 (FGFR signaling pathway) for CRC evolution. In summary, we demonstrated that both colorectal adenoma and CRC are monoclonal in origin, and the CRCs further diversified into different subclones with heterogeneous mutation profiles accumulating in GPCR, PI3K-Akt and FGFR signaling pathways. ScWES provides evidence for the importance of mutations in certain pathways that would not be as apparent from bulk sequencing of tumors, and can potentially establish whether specific mutations are mutually exclusive or occur sequentially in the same subclone of cells.


Asunto(s)
Transformación Celular Neoplásica/genética , Neoplasias Colorrectales/genética , Exoma , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Anciano , Anciano de 80 o más Años , Biomarcadores , Transformación Celular Neoplásica/metabolismo , Pólipos del Colon/diagnóstico , Pólipos del Colon/genética , Pólipos del Colon/patología , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Análisis de Secuencia de ADN , Análisis de la Célula Individual
9.
Bone Joint Res ; 5(9): 412-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27669712

RESUMEN

OBJECTIVES: Interleukin 18 (IL-18) is a regulatory cytokine that degrades the disc matrix. Bone morphogenetic protein-2 (BMP-2) stimulates synthesis of the disc extracellular matrix. However, the combined effects of BMP-2 and IL-18 on human intervertebral disc degeneration have not previously been reported. The aim of this study was to investigate the effects of the anabolic cytokine BMP-2 and the catabolic cytokine IL-18 on human nucleus pulposus (NP) and annulus fibrosus (AF) cells and, therefore, to identify potential therapeutic and clinical benefits of recombinant human (rh)BMP-2 in intervertebral disc degeneration. METHODS: Levels of IL-18 were measured in the blood of patients with intervertebral disc degenerative disease and in control patients. Human NP and AF cells were cultured in a NP cell medium and treated with IL-18 or IL-18 plus BMP-2. mRNA levels of target genes were measured by real-time polymerase chain reaction, and protein levels of aggrecan, type II collagen, SOX6, and matrix metalloproteinase 13 (MMP13) were assessed by western blot analysis. RESULTS: The serum level of patients (IL-18) increased significantly with the grade of IVD degeneration. There was a dramatic alteration in IL-18 level between the advanced degeneration (Grade III to V) group and the normal group (p = 0.008) Furthermore, IL-18 induced upregulation of the catabolic regulator MMP13 and downregulation of the anabolic regulators aggrecan, type II collagen, and SOX6 at 24 hours, contributing to degradation of disc matrix enzymes. However, BMP-2 antagonised the IL-18 induced upregulation of aggrecan, type II collagen, and SOX6, resulting in reversal of IL-18 mediated disc degeneration. CONCLUSIONS: BMP-2 is anti-catabolic in human NP and AF cells, and its effects are partially mediated through provocation of the catabolic effect of IL-18. These findings indicate that BMP-2 may be a unique therapeutic option for prevention and reversal of disc degeneration.Cite this article: S. Ye, B. Ju, H. Wang, K-B. Lee. Bone morphogenetic protein-2 provokes interleukin-18-induced human intervertebral disc degeneration. Bone Joint Res 2016;5:412-418. DOI: 10.1302/2046-3758.59.BJR-2016-0032.R1.

10.
Leukemia ; 13(7): 1062-70, 1999 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10400422

RESUMEN

The aberrant expression of tissue factor (TF) in acute promyelocytic leukemia (APL) cells has been implicated in the pathogenesis of the APL coagulopathy. In this study, we found that in APL patients receiving ATRA or As2O3 treatment, the improvement in hypercoagulobility and hyperfibrinolysis paralleled the correction of plasma fibrinogen level and amelioration of bleeding symptoms. Notably, clinical improvement was also correlated to ATRA/As2O3-induced rapid decrease of membrane procoagulant activity (PCA) and TF contents of APL blasts. Consistent with the in vivo findings, the membrane PCA, TF antigen and its mRNA level within NB4 cells were rapidly down-regulated by 1 microM ATRA or As2O3, while 0.2 microg/ml DNR increased these TF parameters prior to its effect upon apoptosis induction. The down-regulation of TF mRNA by ATRA was partially de novo protein synthesis-dependent and at least partially attributed to a mechanism of destabilizing TF mRNA. On the other hand, in addition to its modulation on mRNA, As2O3 could also induce an accelerated TF protein turnover. These distinct effects were corroborated with the properties of these agents in causing the degradation of PML-RARalpha protein. All three therapeutic agents, however, enhanced the potential of NB4 cells to stimulate the expression of TF and PCA in endothelium. Taken together, our data suggest that the rapid and distinct regulation of TF on APL cells by these therapeutic agents might at least partially contribute to their effects on APL coagulopathy.


Asunto(s)
Antineoplásicos/uso terapéutico , Arsenicales/uso terapéutico , Endotelio Vascular/efectos de los fármacos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Óxidos/uso terapéutico , Tromboplastina/biosíntesis , Tretinoina/uso terapéutico , Adolescente , Adulto , Trióxido de Arsénico , Coagulación Sanguínea/efectos de los fármacos , Daunorrubicina/uso terapéutico , Ensayos de Selección de Medicamentos Antitumorales , Endotelio Vascular/citología , Endotelio Vascular/metabolismo , Femenino , Fibrinólisis/efectos de los fármacos , Humanos , Leucemia Promielocítica Aguda/metabolismo , Masculino , Persona de Mediana Edad
11.
Oncogene ; 34(13): 1736-42, 2015 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-24747973

RESUMEN

High-throughput screens (HTS) of compound toxicity against cancer cells can identify thousands of potential new drug-leads. But only limited numbers of these compounds can progress to expensive and labor-intensive efficacy studies in mice, creating a 'bottle neck' in the drug development pipeline. Approaches that triage drug-leads for further study are greatly needed. Here we provide an intermediary platform between HTS and mice by adapting mouse models of pediatric brain tumors to grow as orthotopic xenografts in the brains of zebrafish. Freshly isolated mouse ependymoma, glioma and choroid plexus carcinoma cells expressing red fluorescence protein were conditioned to grow at 34 °C. Conditioned tumor cells were then transplanted orthotopically into the brains of zebrafish acclimatized to ambient temperatures of 34 °C. Live in vivo fluorescence imaging identified robust, quantifiable and reproducible brain tumor growth as well as spinal metastasis in zebrafish. All tumor xenografts in zebrafish retained the histological characteristics of the corresponding parent mouse tumor and efficiently recruited fish endothelial cells to form a tumor vasculature. Finally, by treating zebrafish harboring ERBB2-driven gliomas with an appropriate cytotoxic chemotherapy (5-fluorouracil) or tyrosine kinase inhibitor (erlotinib), we show that these models can effectively assess drug efficacy. Our data demonstrate, for the first time, that mouse brain tumors can grow orthotopically in fish and serve as a platform to study drug efficacy. As large cohorts of brain tumor-bearing zebrafish can be generated rapidly and inexpensively, these models may serve as a powerful tool to triage drug-leads from HTS for formal efficacy testing in mice.


Asunto(s)
Neoplasias Encefálicas/patología , Modelos Animales de Enfermedad , Glioma/patología , Animales , Niño , Descubrimiento de Drogas , Ensayos Analíticos de Alto Rendimiento , Humanos , Ratones , Trasplante de Neoplasias , Transcriptoma , Trasplante Heterólogo , Pez Cebra
12.
DNA Seq ; 11(1-2): 21-8, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10902906

RESUMEN

Cathepsin D is a major lysosomal aspartic proteinase participating in the degradation or modification of intra- and extracellular matrix molecules, and its activity is known to increase in the process of tissue reorganization during the early phase of salamander limb regeneration. Here, we report the cloning of a salamander cathepsin D cDNA from Hynobius leechii and its expression profile in normal and retinoic acid (RA) treated limb regenerates. The gene expression of cathepsin D increased notably during the dedifferentiation stage and decreased gradually thereafter. Furthermore, RA that enhances dedifferentiation of regenerating salamander limb caused the elevation of cathepsin D expression both in terms of level and duration. These results suggest that cathepsin D plays important role(s) in the dedifferentiation process, and enhancement of cathepsin D expression might be closely related to RA-evoked pattern duplication.


Asunto(s)
Catepsina D/genética , Regeneración/fisiología , Urodelos/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , ADN Complementario , Extremidades/fisiología , Perfilación de la Expresión Génica , Humanos , Ratones , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido , Tretinoina/farmacología , Regulación hacia Arriba/efectos de los fármacos , Urodelos/fisiología
13.
Chin Med J (Engl) ; 114(1): 30-4, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11779431

RESUMEN

OBJECTIVE: To study the effect of all-trans retinoic acid (ATRA) and arsenic troxide (As2O3) on tissue factor (TF) expression and procoagulant activity (PCA) of acute promyelocytic leukemia (APL) cells in vivo and in vitro. METHODS: PCA from freshly isolated APL blasts from APL patients treated with ATRA or As2O3 was detected using a one-stage clotting assay. TF antigen was detected by ELISA and TF mRNA by RT-PCR. The maturation sensitive (NB4) or resistant subclones (NB4-R1) of the promyelocytic NB4 cell line, as well as U937 cells infected with pMSCV-PML-RARa treated with or without ATRA or As2O3, were also examined. RESULTS: Both ATRA and As2O3 can down-regulate the TF antigen, its mRNA transcription and membrane PCA of APL cells in vivo and in vitro, in a time-dependent manner. The TF antigen level in PML-RARa + U937 cells was significantly higher than that in U937 cells infected with retrovirus vector. Both ATRA and As2O3 can also down-regulate the TF antigen in U937 cells transfected with or without PML-RARa. CONCLUSION: Tissue factor expression and PCA in APL cells may be down-regulated by ATRA and As2O3. By down-regulating TF expression, As2O3 might also be used to improve the DIC-related hemorrhage in APL. Our data indicate that elevated TF antigen in PML-RARa + U937 may be related to the fusion protein PML-RARa. The down-regulating effect of ATRA and As2O3 on TF expression in U937 cells might not involve this fusion protein.


Asunto(s)
Antineoplásicos/farmacología , Arsenicales/farmacología , Regulación Leucémica de la Expresión Génica/efectos de los fármacos , Leucemia Promielocítica Aguda/tratamiento farmacológico , Óxidos/farmacología , ARN Mensajero/análisis , Tromboplastina/genética , Tretinoina/farmacología , Adolescente , Adulto , Trióxido de Arsénico , Femenino , Humanos , Leucemia Promielocítica Aguda/metabolismo , Leucemia Promielocítica Aguda/patología , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/fisiología , Proteínas de Fusión Oncogénica/fisiología , Células Tumorales Cultivadas
14.
Oncogenesis ; 3: e96, 2014 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-24686726

RESUMEN

Dysregulation of Sonic hedgehog (Shh) signaling has been implicated in glioma pathogenesis. Yet, the role of this pathway in gliomagenesis remains controversial because of the lack of relevant animal models. Using the cytokeratin 5 promoter, we ectopically expressed a constitutively active zebrafish Smoothened (Smoa1) in neural progenitor cells and analyzed tumorigenic capacity of activated Shh signaling in both transient and stable transgenic fish. Transient transgenic fish overexpressing Smoa1 developed retinal and brain tumors, suggesting smoa1 is oncogenic in the zebrafish central nervous system (CNS). We further established stable transgenic lines that simultaneously developed optic pathway glioma (OPG) and various retinal tumors. In one of these lines, up to 80% of F1 and F2 fish developed tumors within 1 year of age. Microarray analysis of tumor samples showed upregulated expression of genes involved in the cell cycle, cancer signaling and Shh downstream targets ptc1, gli1 and gli2a. Tumors also exhibited specific gene signatures characteristic of radial glia and progenitor cells as transcriptions of radial glia genes cyp19a1b, s100ß, blbp, gfap and the stem/progenitor genes nestin and sox2 were significantly upregulated. Overexpression of GFAP, S100ß, BLBP and Sox2 was confirmed by immunofluorescence. We also detected overexpression of Mdm2 throughout the optic pathway in fish with OPG, therefore implicating the Mdm2-Tp53 pathway in glioma pathogenesis. In conclusion, we demonstrate that activated Shh signaling initiates tumorigenesis in the zebrafish CNS and provide the first OPG model not associated with neurofibromatosis 1.

15.
Transplant Proc ; 43(5): 1751-3, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21693271

RESUMEN

AIM: The aim was to deduce suitable calcineurin inhibitor concentrations for the Chinese liver transplantation population. METHODS: We retrospectively studied 97 liver transplant recipients who displayed stable liver and renal function. No grafts were obtained from prisoners, procurements were performed with donor consent conforming to international ethics regulations. At 3, 6, and 12 months, we increased the concentrations and doses of calcineurin inhibitors as well as the values of alanine transaminase and serum creatinine. RESULTS: Twenty-eight recipients received cyclosporine and 69 tacrolimus. The mean cyclosporine daily dosages were 203 ± 62 mg at 3, 188 ± 55 mg at 6, and 173 ± 52 mg at 12 months, the tacrolimus daily dosages were 3.08 ± 0.98, 2.82 ± 0.98, and 2.58 ± 0.93 mg, respectively. The corresponding mean cyclosporine peak concentrations (C(2)) were 806 ± 322 ng/mL, 681 ± 206 ng/mL, and 644 ± 190 ng/mL and the mean tacrolimus trought concentrations (C(0)) 6.61 ± 3.02 ng/mL, 5.85 ± 2.44 ng/mL, and 5.22 ± 2.33 ng/mL, respectively. In both groups, transaminases and serum creatinine were stable over time. CONCLUSIONS: An individualized immunosuppressive regimen for the local population is necessary. We delayed calcineurin inhibitors with subsequent low-dose mycophenolate mofetil plus minimized calcineurin inhibitors, which seemed to be nephroprotective and safe for Chinese liver transplantation patients.


Asunto(s)
Inhibidores de la Calcineurina , Ciclosporina/administración & dosificación , Inmunosupresores/administración & dosificación , Trasplante de Hígado , Tacrolimus/administración & dosificación , Adulto , China , Ciclosporina/sangre , Monitoreo de Drogas , Femenino , Humanos , Inmunosupresores/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tacrolimus/sangre
16.
Dev Dyn ; 199(4): 253-67, 1994 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-8075430

RESUMEN

In the regenerating limbs of Korean salamanders, Hynobius leechii, retinoic acid (RA) induces duplication of skeletal structures in the proximodistal (PD) axis and often in the transverse axes. In the present study, the stage-dependent effects of RA for the duplication of limb skeletal structures at two amputation levels, the distal stylopodium and the distal zeugopodium, were studied using larval limbs of Korean salamanders. The results showed that the mean level of proximalization (MLP) by RA treatment increased during the stages of dedifferentiation and early bud formation while the MLP declined thereafter in both amputation levels. The decline of the MLP at the later stages of regeneration was due to the high frequency of hypomorphic regeneration or blocked regeneration. When the effects of RA treatment at two amputation levels were compared, the overall trends were similar but the actual timing was delayed for 2-4 days in the proximal level of amputation. Furthermore, the peak level of proximalization was achieved earlier and the peak level remained longer in the distal stylopodial level of amputation compared to the distal zeugopodial level of amputation. Since the histological observations revealed that the dedifferentiation period was also extended up to 2-4 days in the proximal level of amputation, the acid phosphatase activity during the course of regeneration was measured to look for a quantitative relationship between the enzyme activity and the states of dedifferentiation. The results show that the level and the duration of acid phosphatase activity in the upper arm regenerates are both higher and longer than those in the lower arm regenerates. Furthermore, RA treatment caused an increase in acid phosphatase activity. Thus our results suggest that the state of dedifferentiation might be closely linked to the extent of proximalization of regenerating limbs by RA treatment.


Asunto(s)
Miembro Anterior/fisiología , Regeneración/efectos de los fármacos , Tretinoina/farmacología , Urodelos/fisiología , Fosfatasa Ácida/análisis , Animales , Regeneración Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Miembro Anterior/efectos de los fármacos , Miembro Anterior/enzimología , Miembro Anterior/lesiones , Húmero/efectos de los fármacos , Húmero/lesiones , Húmero/patología , Húmero/fisiología , Larva , Radio (Anatomía)/efectos de los fármacos , Radio (Anatomía)/lesiones , Radio (Anatomía)/patología , Radio (Anatomía)/fisiología , Tretinoina/toxicidad , Cúbito/efectos de los fármacos , Cúbito/lesiones , Cúbito/patología , Cúbito/fisiología , Urodelos/crecimiento & desarrollo
17.
Prog Clin Biol Res ; 383B: 749-58, 1993.
Artículo en Inglés | MEDLINE | ID: mdl-8115390

RESUMEN

The morphological and biochemical data obtained in this series of experiments clearly confirm the previous finding about the relationship between the stage of limb regeneration and the effects of RA on duplication, i.e., the most sensitive stage for RA-induced duplication is the stage of dedifferentiation, regardless of the level of amputation. However, when the RA effects were expressed as a function of time after amputation, the upper arm regenerates clearly showed a prolonged and delayed response to RA treatment compared to the lower arm regenerates. These findings were further supported by the data on acid phosphatase activity, which may reflect the level of dedifferentiation. Furthermore, the slow increase of this enzyme activity above the control level until 8 days after RA-injection corresponds to the late appearance of limb regenerates after RA treatment. At present, we do not have any clear explanation why upper arm regenerates and lower arm regenerates show differences in the MLP's and different temporal profiles for the RA-evoked limb pattern duplications. However, the difference in the level of dedifferentiation after simple amputation and after RA-treatment suggests that RA-induced changes in the positional identity of blastema cells may require a prolonged and augmented state of dedifferentiation. In this scheme, the level and type of CRABP may play a critical role as suggested in the case of regenerating axolotl limbs (McCormick et al., 1988).


Asunto(s)
Miembro Anterior/efectos de los fármacos , Miembro Anterior/fisiología , Regeneración/efectos de los fármacos , Tretinoina/farmacología , Fosfatasa Ácida/metabolismo , Amputación Quirúrgica , Animales , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Miembro Anterior/patología , Larva/efectos de los fármacos , Larva/fisiología , Regeneración/fisiología , Factores de Tiempo , Tretinoina/administración & dosificación , Urodelos
18.
Wound Repair Regen ; 6(4): 349-57, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9824553

RESUMEN

In the regenerating urodele limb, catheptic activity has been known to be present in the stump tissue undergoing histolysis, and it has been implicated in the modification of some intracellular and extracellular matrix molecules. In this study, we compared spatial and temporal gene expression profiles of cathepsin D in normal, retinoic acid-treated, or denervated larval limb regenerates of Hynobius leechii and compared cathepsin D activities between normal and retinoic acid-treated limb regenerates. The results showed that the expression of cathepsin D increased markedly in the vicinity of an amputation site under the wound epidermis at dedifferentiation stage, whereas the expression level of cathepsin D was low in the denervated limb. With retinoic acid treatment, the expression of cathepsin D was elevated in terms of both level and duration. In addition, the profile of cathepsin D activity coincided well with the expression profile of cathepsin D in normal and retinoic acid-treated limb regenerates. These results suggest that the increase of cathepsin D activity during the dedifferentiation period is due to the upregulation of cathepsin D transcription, and nerve factors are involved in this process. Furthermore, retinoic acid appears to upregulate cathepsin D expression, which might be linked to the enhanced dedifferentiation in the retinoic acid-treated limb regenerates.


Asunto(s)
Catepsina D/efectos de los fármacos , Miembro Posterior/embriología , Regeneración/efectos de los fármacos , Tretinoina/farmacología , Amputación Quirúrgica , Animales , Catepsina D/genética , Modelos Animales de Enfermedad , Expresión Génica , Miembro Posterior/efectos de los fármacos , Hibridación in Situ , Larva , Valores de Referencia , Regeneración/genética , Regulación hacia Arriba , Urodelos
19.
Genetica ; 111(1-3): 213-25, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11841167

RESUMEN

The coupling of the GFP reporter system with the optical clarity of embryogenesis in model fish such as zebrafish and medaka is beginning to change the picture of transgenic fish study. Since the advent of first GFP transgenic fish in 1995, GFP transgenic fish technology have been quickly employed in many areas such as analyses of gene expression patterns and tissue/organ development, dissection of promoters/enhancers, cell lineage and axonal pathfinding, cellular localization of protein products, chimeric embryo and nuclear transplantation, cell sorting, etc. The GFP transgenic fish also have the potentials in analysis of upstream regulatory factors, mutagenesis screening and characterization, and promoter/enhancer trap. Our own studies indicate that GFP transgenic fish may become a new source of novel variety of ornamental fish. Efforts are also being made in our laboratory to turn GFP transgenic fish into biomonitoring organisms for surveillance of environmental pollution.


Asunto(s)
Peces/genética , Proteínas Luminiscentes/genética , Animales , Animales Modificados Genéticamente/embriología , Animales Modificados Genéticamente/genética , Linaje de la Célula , Movimiento Celular , Quimera , Elementos de Facilitación Genéticos , Peces/embriología , Proteínas Fluorescentes Verdes , Mutagénesis , Regiones Promotoras Genéticas
20.
Nature ; 405(6783): 191-5, 2000 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-10821276

RESUMEN

The Fringe protein of Drosophila and its vertebrate homologues function in boundary determination during pattern formation. Fringe has been proposed to inhibit Serrate-Notch signalling but to potentiate Delta-Notch signalling. Here we show that Fringe and Notch form a complex through both the Lin-Notch repeats and the epidermal growth factor repeats 22-36 (EGF22-36) of Notch when they are co-expressed. The Abruptex59b (Ax59b) and AxM1 mutations, which are caused by missense mutations in EGF repeats 24 and 25, respectively, abolish the Fringe-Notch interaction through EGF22-36, whereas the l(1)N(B) mutation in the third Lin-Notch repeat of Notch abolishes the interaction through Lin-Notch repeats. Ax mutations also greatly affect the Notch response to ectopic Fringe in vivo. Results from in vitro protein mixing experiments and subcellular colocalization experiments indicate that the Fringe-Notch complex may form before their secretion. These findings explain how Fringe acts cell-autonomously to modulate the ligand preference of Notch and why the Fringe-Notch relationship is conserved between phyla and in the development of very diverse structures.


Asunto(s)
Proteínas de Insectos/metabolismo , Proteínas de la Membrana/metabolismo , N-Acetilglucosaminiltransferasas , Animales , Línea Celular , Drosophila , Proteínas de Drosophila , Proteínas de Insectos/genética , Proteínas de la Membrana/genética , Mutación , Unión Proteica , Receptores Notch , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Secuencias Repetitivas de Aminoácido
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