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1.
Br J Surg ; 104(13): 1775-1784, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-29091283

RESUMEN

BACKGROUND: Hepatic resection and radiofrequency ablation (RFA) are treatment options for early-stage hepatocellular carcinoma (HCC). Whether tumour recurrence and long-term survival favour either treatment has not been established. This randomized trial aimed to test the hypothesis that RFA is superior to hepatic resection in terms of lower tumour recurrence rate and better long-term survival. METHODS: Patients with early-stage HCC (solitary tumour no larger than 5 cm; or no more than 3 tumours, each 3 cm or smaller) were randomized into hepatic resection and RFA groups. Demographic and clinical characteristics, and short- and long-term outcome measures were compared between groups. Primary and secondary outcome measures were overall tumour recurrence and survival respectively. RESULTS: Clinicopathological data were similar in the two groups, which each contained 109 patients. The RFA group had a shorter treatment duration, less blood loss and shorter hospital stay than the resection group. Mortality and morbidity rates were similar in the two groups. The overall tumour recurrence rate was similar in the resection and RFA groups (71·3 versus 81·7 per cent respectively). The 1-, 3-, 5- and 10-year overall survival rates were 94·5, 80·6, 66·5 and 47·6 per cent respectively in the resection group, compared with 95·4, 82·3, 66·4 and 41·8 per cent in the RFA group (P = 0·531). Corresponding disease-free survival rates were 74·1, 50·9, 41·5 and 31·9 per cent in the resection group, and 70·6, 46·6, 33·6 and 18·6 per cent in the RFA group (P = 0·072). CONCLUSION: RFA for early-stage HCC is not superior to hepatic resection, in terms of tumour recurrence, overall survival and disease-free survival. Registration number: HKUCTR-10 (http://www.hkuctr.com).


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Hepatectomía , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia , Adulto , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica , Carcinoma Hepatocelular/patología , Colorantes , Supervivencia sin Enfermedad , Femenino , Hepatitis C/complicaciones , Hong Kong/epidemiología , Humanos , Verde de Indocianina , Tiempo de Internación , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Adulto Joven
2.
Eur J Clin Microbiol Infect Dis ; 34(7): 1381-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25800414

RESUMEN

Clostridium difficile ribotype 002 with hypersporulating capacity has been increasingly identified in Hong Kong. Proactive infection control measures are important to prevent the establishment of endemicity of C. difficile ribotype 002. A total of 329 patients with healthcare-associated C. difficile infection (CDI) were recruited in our healthcare network between 1 January 2008 and 30 June 2012 in this study. The incidence rates of healthcare-associated CDI per 10,000 admissions and 10,000 patient-days increased significantly by 15.3 and 17.0%, respectively, per quarter (p < 0.001) from 2008 1Q to 2010 1Q by segmented Poisson regression. With the full implementation of enhanced infection control interventions, there was an immediate significant reduction in both healthcare-associated CDI rates per 10,000 admissions and per 10,000 patient-days by 47% (p < 0.001) in 2010 2Q, followed by a further decline of CDI per 10,000 admissions and CDI per 10,000 patient-days by -19.4 and -19.8% from 2010 2Q to 2012 2Q, respectively (p < 0.001), despite a replacement of hand washing with soap and water by alcohol-based hand rub in the healthcare network. The proportion of C. difficile ribotype 002 was not statistically different (34/177, 19.2% vs. 25/152, 16.4%, p = 0.515), and the consumption of broad-spectrum antibiotics presented as divided daily dose per 1,000 acute bed-day occupancy per quarter remained unchanged (140.9 vs. 152.3) before and after infection control interventions. Our results suggested that the reduction of healthcare-associated CDI was attributable to infection control interventions instead of replacement of ribotypes or reduction in antimicrobial selective pressure.


Asunto(s)
Antiinfecciosos/uso terapéutico , Clostridioides difficile , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Antiinfecciosos/farmacología , Clostridioides difficile/clasificación , Clostridioides difficile/genética , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/prevención & control , Infección Hospitalaria , Femenino , Hong Kong/epidemiología , Hospitales Universitarios , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estaciones del Año
3.
Eur J Clin Microbiol Infect Dis ; 34(4): 713-8, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25413926

RESUMEN

An increasing endemicity of multiple-drug-resistant Acinetobacter baumannii (MRAB) ST457 was noted in Hong Kong. The epidemiology, risk factors, and infection control measures to prevent nosocomial transmission of this epidemic clone were analyzed. A total of 5,058 patients cultured positive with A. baumannii between 1 January 2004 and 30 June 2014 were included, of which 297 (5.9 %) had bacteremia. The first case of MRAB bacteremia emerged in 2009, with an incidence that increased from 0.27 (one case) in 2009 to 1.86 (14 cases) per 100,000 patient-days in 2013 (p < 0.001). With the implementation of strict contact precautions and directly observed hand hygiene in conscious patients immediately before receiving meals and medications in July 2013, the incidence of MRAB bacteremia reduced from its peak to 0.77 (one case) per 100,000 patient-days in the first 6 months of 2014 (p < 0.001). Patients from long-term care facilities for the elderly [odds ratio (OR) 18.6, confidence interval (CI) 2.1-162.4, p = 0.008] and history of carbapenem (OR 7.0, CI 1.7-28.0, p = 0.006) and beta-lactam/beta-lactamase use (OR 5.6, CI 1.1-28.7, p = 0.038) 90 days prior to admission were independent risk factors for MRAB bacteremia by logistic regression when compared with carbapenem-susceptible A. baumannii bacteremia.


Asunto(s)
Infecciones por Acinetobacter/prevención & control , Acinetobacter baumannii/efectos de los fármacos , Bacteriemia/prevención & control , Farmacorresistencia Bacteriana Múltiple , Enfermedades Endémicas/prevención & control , Higiene de las Manos/métodos , Control de Infecciones/métodos , Infecciones por Acinetobacter/epidemiología , Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/epidemiología , Bacteriemia/microbiología , Niño , Preescolar , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/prevención & control , Femenino , Hong Kong/epidemiología , Hospitales , Humanos , Incidencia , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven
4.
Infect Immun ; 81(7): 2405-14, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23630957

RESUMEN

Clostridium perfringens type D causes disease in sheep, goats, and other ruminants. Type D isolates produce, at minimum, alpha and epsilon (ETX) toxins, but some express up to five different toxins, raising questions about which toxins are necessary for the virulence of these bacteria. We evaluated the contribution of ETX to C. perfringens type D pathogenicity in an intraduodenal challenge model in sheep, goats, and mice using a virulent C. perfringens type D wild-type strain (WT), an isogenic ETX null mutant (etx mutant), and a strain where the etx mutation has been reversed (etx complemented). All sheep and goats, and most mice, challenged with the WT isolate developed acute clinical disease followed by death in most cases. Sheep developed various gross and/or histological changes that included edema of brain, lungs, and heart as well as hydropericardium. Goats developed various effects, including necrotizing colitis, pulmonary edema, and hydropericardium. No significant gross or histological abnormalities were observed in any mice infected with the WT strain. All sheep, goats, and mice challenged with the isogenic etx mutant remained clinically healthy for ≥24 h, and no gross or histological abnormalities were observed in those animals. Complementation of etx knockout restored virulence; most goats, sheep, and mice receiving this complemented mutant developed clinical and pathological changes similar to those observed in WT-infected animals. These results indicate that ETX is necessary for type D isolates to induce disease, supporting a key role for this toxin in type D disease pathogenesis.


Asunto(s)
Toxinas Bacterianas/metabolismo , Infecciones por Clostridium/patología , Clostridium perfringens/patogenicidad , Cabras/microbiología , Ovinos/microbiología , Animales , Toxinas Bacterianas/genética , Clostridium perfringens/genética , Clostridium perfringens/metabolismo , Femenino , Técnicas de Inactivación de Genes , Genes Bacterianos , Prueba de Complementación Genética , Intestinos/microbiología , Estimación de Kaplan-Meier , Masculino , Ratones , Viabilidad Microbiana , Mutación , Plásmidos/genética , Plásmidos/metabolismo , Virulencia
5.
Br J Cancer ; 104(9): 1452-8, 2011 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-21468052

RESUMEN

BACKGROUND: Aggressive fibromatosis (desmoid tumour) is a locally invasive tumour caused by mutations resulting in ß-catenin protein stabilisation. Apc1638N mice are predisposed to developing aggressive fibromatosis tumours, and male mice develop greater numbers of tumours than female mice, suggesting a role for androgens in this tumour type. METHODS: Human aggressive fibromatosis tumours were examined for the expression of the androgen receptor, and primary human tumour cell cultures were treated with testosterone. Orchidectomised Apc1638N mice were investigated for the development of tumours, and were treated with testosterone to study the effect of tumour formation and the level of ß-catenin. RESULTS: Androgen receptors are universally expressed in human aggressive fibromatosis tumours. Testosterone increased the proliferation rate and ß-catenin protein level in a dose-dependent manner in human aggressive fibromatosis tumours. Orchiectomy reduced the number and size of tumours that formed in male Apc1638N mice to a similar level as observed in female mice. Testosterone treatment increased the number of tumours that formed in orchidectomised male mice, and resulted in a marked increase in ß-catenin protein levels. CONCLUSION: Testosterone regulates ß-catenin protein level and proliferation rate in this mesenchymal tumour. This work identifies the therapeutic use of testosterone blockade in aggressive fibromatosis as an area for further investigation.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Fibromatosis Agresiva/metabolismo , Fibromatosis Agresiva/patología , Testosterona/efectos adversos , Testosterona/metabolismo , beta Catenina/metabolismo , Animales , Femenino , Regulación Neoplásica de la Expresión Génica , Genes APC , Predisposición Genética a la Enfermedad , Humanos , Masculino , Ratones , Ratones Endogámicos , Mutación , Orquiectomía , ARN/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , beta Catenina/efectos de los fármacos , beta Catenina/genética
6.
Br J Surg ; 98(9): 1292-300, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21656513

RESUMEN

BACKGROUND: There is a trend to offer liver transplantation to patients with hepatocellular carcinoma (HCC) with tumour status within the Milan criteria but with preserved liver function. This study aimed to evaluate the outcome of such patients following partial hepatectomy as primary treatment. METHODS: A retrospective analysis was performed on all adult patients with HCC and tumour status within the Milan criteria undergoing partial hepatectomy at a single centre from 1995 to 2008. Their outcomes were compared with those of similar patients having right-lobe living donor liver transplantation (LDLT) as primary treatment. RESULTS: A total of 408 patients with HCC were enrolled. Some 384 patients with a solitary tumour 5 cm or less in diameter had a better 5-year survival rate than 24 patients with oligonodular tumours (2-3 nodules, each 3 cm or less in size) (70·7 versus 46 per cent; P = 0·025). Multivariable analysis identified younger age (65 years or less), lack of postoperative complications, negative resection margin, absent microvascular invasion and non-cirrhotic liver as predictors of favourable overall survival. The 5-year survival rate of 287 younger patients with chronic liver disease and R0 hepatectomy was 72·8 per cent, comparable to that of 81 per cent in 50 similar patients treated by LDLT (P = 0·093). CONCLUSION: Partial hepatectomy for patients with HCC and tumour status within the Milan criteria achieved a satisfactory 5-year survival rate, particularly in younger patients with solitary tumours and R0 hepatectomy. Patients with oligonodular tumours have a worse survival and might benefit from liver transplantation.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Enfermedad Crónica , Supervivencia sin Enfermedad , Femenino , Hepatectomía/mortalidad , Hepatitis/mortalidad , Hepatitis/cirugía , Humanos , Cirrosis Hepática/mortalidad , Cirrosis Hepática/cirugía , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
7.
Arch Toxicol ; 85(11): 1419-27, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21445588

RESUMEN

Biocides are added to biodiesels to inhibit and remove microbial growth. The effects of 5-chloro-2-methyl-4-isothiazolin-3-one (CMIT), a candidate biodiesel biocide, were studied using freshly isolated rat alveolar macrophages (AM) and NR8383 cell line. CMIT markedly inhibited phagocytic oxidative burst as measured by zymosan-induced chemiluminescence, and cellular cytokine secretion as measured by zymosan-induced TNF-α secretion. The 50% inhibition concentration (LC(50)) for CMIT was 0.002-0.004 mM for both cellular functions. AM exposed to CMIT for as little as 2 min showed markedly inhibited functions that persisted for at least 5 h. Sodium metabisulfite was able to partially neutralize the inhibitory activity of CMIT. Cysteine and glutathione, when present at a molar ratio of 2-1 or higher against CMIT, were effective neutralizers, while serine, histidine, alanine, and albumin were without effect. When the AM testing system was used to compare the toxicity of CMIT against three other candidate biodiesel biocides, methylene dithiocyanate (MDC) was found to be of comparable toxicity to CMIT, 2-methyl-4-isothiazolin-3-one (MIT) was much less toxic, and dimethyl acetylenedicarboxylate (DMAD) was non-toxic. Because AM is among the first cell-type exposed to inhaled biodiesel aerosols, the result suggested that CMIT present in biodiesel may produce respiratory effects, and further investigations including animal studies are warranted.


Asunto(s)
Biocombustibles/toxicidad , Desinfectantes/toxicidad , Macrófagos Alveolares/efectos de los fármacos , Tiazoles/farmacología , Alquinos/toxicidad , Animales , Línea Celular , Cisteína/metabolismo , Citocinas/metabolismo , Glutatión/metabolismo , Luminiscencia , Macrófagos Alveolares/citología , Masculino , Ratas , Ratas Sprague-Dawley , Estallido Respiratorio/efectos de los fármacos , Tiazoles/toxicidad , Factor de Necrosis Tumoral alfa/metabolismo , Zimosan/metabolismo
8.
Am J Transplant ; 10(5): 1178-88, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20420630

RESUMEN

In this study, we aimed to investigate the significance of hepatic stellate cells (HSCs) activation in small-for-size fatty liver graft injury and to explore the underlying molecular mechanism in a rat liver transplantation model. A rat orthotopic liver transplantation model using fatty grafts (40% of fatty changes) and cirrhotic recipients was applied. Intragraft gene expression profiles, ultrastructure features and HSCs activation were compared among the rats received different types of grafts (whole vs. small-for-size, normal vs. fatty). The distinct molecular signature of small-for-size fatty graft injury was identified by cDNA microarray screening and confirmed by RT-PCR detection. In vitro functional studies were further conducted to investigate the direct effect of specific molecular signature on HSCs activation. HSCs activation was predominantly present in small-for-size fatty grafts during the first 2 weeks after transplantation, and was strongly correlated with progressive hepatic sinusoidal damage and significant upregulation of intragraft Wnt4 signaling pathway. In vitro suppression of Wnt4 expression could inhibit HSC activation directly. In conclusion, upregulation of Wnt4 signaling led to direct HSC activation and subsequently induced small-for-size fatty liver grafts injury. Discovery of this distinct mechanism may lay the foundation for prophylactic treatment for marginal graft injury in living donor liver transplantation.


Asunto(s)
Transducción de Señal/genética , Animales , Hígado Graso/patología , Perfilación de la Expresión Génica , Células Estrelladas Hepáticas , Trasplante de Hígado/fisiología , Donadores Vivos , Masculino , Análisis de Secuencia por Matrices de Oligonucleótidos , Ratas , Ratas Sprague-Dawley , Procedimientos de Cirugía Plástica , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba , Proteínas Wnt , Proteína Wnt4
9.
Br J Surg ; 96(1): 81-7, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19065644

RESUMEN

BACKGROUND: The aim of this retrospective study was to determine the impact of postoperative complications on the long-term outcome of curative liver resection for hepatocellular carcinoma (HCC). METHODS: A total of 863 patients who had curative resection of HCC from December 1989 to December 2004 were included in the analysis. Median follow-up was 35.6 months. RESULTS: Some 288 patients (33.4 per cent) developed postoperative complications. The hospital mortality rate was 5.3 per cent (46 patients). Multiple logistic regression analysis showed that older age and massive intraoperative blood loss were related to a significantly higher complication rate. Demographics of patients with and without postoperative complications were comparable. The former had significantly more blood loss (median 1.1 versus 0.7 litres; P < 0.001) and required more transfused blood (P < 0.001). The overall survival rates of patients without complications at 1, 3, 5 and 10 years were 83.6, 62.8, 51.5 and 32.1 per cent respectively. Corresponding rates for those with complications were 67.8, 52.4, 41.5 and 26.6 per cent (P = 0.004). Cox proportional hazard model analysis revealed that the presence of postoperative complications was independently associated with poor overall survival. CONCLUSION: Postoperative complications can affect overall long-term survival after resection of HCC.


Asunto(s)
Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Complicaciones Posoperatorias/etiología , Carcinoma Hepatocelular/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Tiempo de Internación , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento
10.
Trends Cell Biol ; 7(4): 157-61, 1997 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-17708934

RESUMEN

The activity of most protein kinases is highly regulated, typically via phosphorylation and/or subunit association. However, the folding of protein kinases into an active state or a form capable of activation is now emerging as another important step through which they can be regulated. The 50-kDa protein Cdc37 and the associated heat-shock protein Hsp90 have been found to bind to, and be required for the activity of, diverse protein kinases, including Cdk4, v-Src, Raf and SEVENLESS. Together, Cdc37 and Hsp90 may act as a general chaperone for protein kinases, in particular those involved in signal-transduction pathways and cell-cycle control.

11.
J Cell Biol ; 114(4): 755-65, 1991 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1831203

RESUMEN

We have measured the levels of cyclin mRNAs and polypeptides during oogenesis, progesterone-induced oocyte maturation, and immediately after egg activation in the frog, Xenopus laevis. The mRNA for each cyclin is present at a constant level of approximately 5 x 10(7) molecules per oocyte from the earliest stages of oogenesis until after fertilization. The levels of polypeptides show more complex patterns of accumulation. The B-type cyclins are first detectable in stage IV and V oocytes. Cyclin B2 polypeptide is present at approximately 2 x 10(9) molecules (150 pg) per oocyte by stage VI. The amount increases after progesterone treatment, but returns to its previous level after GVBD and undergoes no further change until it is destroyed at fertilization. Cyclin B1 is present at 4 x 10(8) molecules per oocyte in stage VI oocytes, and rises steadily during maturation, ultimately reaching similar levels to cyclin B2 in unfertilized eggs. Unlike the B-type cyclins, cyclin A is barely detectable in stage VI oocytes, and only starts to be made in significant amounts after oocytes are exposed to progesterone. A portion of all the cyclins are destroyed after germinal vesicle breakdown (GVBD), and cyclins B1 and B2 also experience posttranslational modifications during oocyte maturation. Progesterone strongly stimulates both cyclin and p34cdc2 synthesis in these oocytes, but whereas cyclin synthesis continues in eggs and after fertilization, synthesis of p34cdc2 declines strongly after GVBD. The significance of these results is discussed in terms of the activation and inactivation of maturation-promoting factor.


Asunto(s)
Ciclinas/genética , Oocitos/fisiología , Oogénesis , Animales , Proteína Quinasa CDC2/metabolismo , Células Cultivadas , Ciclinas/biosíntesis , Ciclinas/metabolismo , Femenino , Meiosis , Metafase , Oocitos/citología , Oocitos/efectos de los fármacos , Fosfoproteínas/aislamiento & purificación , Progesterona/farmacología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Tiempo , Xenopus laevis
12.
J Cell Biol ; 149(2): 281-92, 2000 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-10769022

RESUMEN

During differentiation, skeletal muscle cells withdraw from the cell cycle and fuse into multinucleated myotubes. Unlike quiescent cells, however, these cells cannot be induced to reenter S phase by means of growth factor stimulation. The studies reported here document that both the retinoblastoma protein (Rb) and the cyclin-dependent kinase (cdk) inhibitor p21 contribute to this unresponsiveness. We show that the inactivation of Rb and p21 through the binding of the adenovirus E1A protein leads to the induction of DNA replication in differentiated muscle cells. Moreover, inactivation of p21 by E1A results in the restoration of cyclin E-cdk2 activity, a kinase made nonfunctional by the binding of p21 and whose protein levels in differentiated muscle cells is relatively low in amount. We also show that restoration of kinase activity leads to the phosphorylation of Rb but that this in itself is not sufficient for allowing differentiated muscle cells to reenter the cell cycle. All the results obtained are consistent with the fact that Rb is functioning downstream of p21 and that the activities of these two proteins may be linked in sustaining the postmitotic state.


Asunto(s)
Proteínas E1A de Adenovirus/metabolismo , Quinasas CDC2-CDC28 , Diferenciación Celular/fisiología , Quinasas Ciclina-Dependientes/metabolismo , Ciclinas/metabolismo , Replicación del ADN/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteína de Retinoblastoma/metabolismo , Animales , Línea Celular , Sistema Libre de Células , Ciclina E/metabolismo , Quinasa 2 Dependiente de la Ciclina , Inhibidor p21 de las Quinasas Dependientes de la Ciclina , Quinasas Ciclina-Dependientes/antagonistas & inhibidores , Ratones , Músculo Esquelético/citología , Músculo Esquelético/fisiología , Mutagénesis , Proteínas Recombinantes/metabolismo , Transfección
13.
Science ; 270(5233): 90-3, 1995 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-7569954

RESUMEN

The activation of cyclin-dependent kinases (CDKs) requires the phosphorylation of a conserved threonine (Thr160 in Cdk2) by CDK-activating kinase (CAK). Human KAP (also called Cdi1), a CDK-associated phosphatase, was shown to dephosphorylate Thr160 in human Cdk2. KAP was unable to dephosphorylate Tyr15 and only dephosphorylated Thr160 in native monomeric Cdk2. The binding of cyclin A to Cdk2 inhibited the dephosphorylation of Thr160 by KAP but did not preclude the binding of KAP to the cyclin A-Cdk2 complex. Moreover, the dephosphorylation of Thr160 by KAP prevented Cdk2 kinase activity upon subsequent association with cyclin A. These results suggest that KAP binds to Cdk2 and dephosphorylates Thr160 when the associated cyclin subunit is degraded or dissociates.


Asunto(s)
Quinasas CDC2-CDC28 , Proteínas de Ciclo Celular , Quinasas Ciclina-Dependientes/metabolismo , Fosfoproteínas Fosfatasas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Tirosina Fosfatasas , Secuencia de Aminoácidos , Secuencia de Bases , Línea Celular , Quinasa 2 Dependiente de la Ciclina , Proteínas Inhibidoras de las Quinasas Dependientes de la Ciclina , Ciclinas/metabolismo , Fosfatasas de Especificidad Dual , Células HeLa , Humanos , Datos de Secuencia Molecular , Fosforilación , Proteínas Recombinantes de Fusión/metabolismo , Treonina/metabolismo , Quinasa Activadora de Quinasas Ciclina-Dependientes
15.
Gut ; 57(1): 98-102, 2008 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-17483190

RESUMEN

BACKGROUND/AIM: To examine the risks for hepatocellular carcinoma (HCC) with respect to hepatitis B virus (HBV) genotypes, specific viral mutations (MT), serum HBV DNA levels, and cirrhosis. METHODS: HBV genotypes, 1653/1753/core promoter (CP)/precore MT and HBV DNA levels were determined in 248 HBV patients with HCC and 248 HBV controls. RESULTS: Genotype C, CP-MT, T1653, HBV DNA levels >or=4 log(10) copies/ml and cirrhosis had a higher risk for HCC compared to patients with genotype B (p = 0.001, OR 1.9), CP wild-type (WT) (p<0.001, OR 4.1), C1653 (p = 0.028, OR 2.4), HBV DNA <4 log(10) copies/ml (p = 0.003, OR 2.1) and without cirrhosis (p<0.001, OR 4.0) respectively. Multivariate analysis showed that CP-MT, T1653, HBV DNA >or=4 log(10) copies/ml and cirrhosis were independent factors for HCC (all p<0.05). A receiver operating characteristics curve showed no cut-off HBV DNA level associated with minimal chance of HCC. Patients with CP-MT and cirrhosis had a 22.2-fold increased risk of HCC compared to patients with CP-WT and without cirrhosis. Patients with CP-MT and HBV DNA levels >or=4 log(10) copies/ml had a 7.2-fold increased risk of HCC compared to patients with CP-WT and HBV DNA levels <4 log(10) copies/ml. Patients with CP-MT and T1653 had a 9.9-fold increased risk of HCC compared to patients with wild-type for both regions. CONCLUSIONS: CP-MT, T1653, HBV DNA levels >or=4 log(10) copies/ml and cirrhosis are independent factors for development of HCC. The risks increased substantially in patients having these factors in combination.


Asunto(s)
Carcinoma Hepatocelular/virología , Elementos de Facilitación Genéticos/genética , Virus de la Hepatitis B/genética , Neoplasias Hepáticas/virología , Mutación/genética , Regiones Promotoras Genéticas/genética , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , ADN Viral/sangre , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Curva ROC
16.
Curr Oncol ; 26(4): e458-e465, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-31548813

RESUMEN

Objective: Paraneoplastic neurologic syndrome (pns) is a rare condition indirectly caused by an underlying malignancy. In many cases, the malignancy is occult at the time of the pns diagnosis, and the optimal diagnostic modality to detect the underlying tumour is unclear. In the present study, we aimed to assess the utility of 18F-fluorodeoxyglucose positron-emission tomography (fdg-pet) or pet integrated with computed tomography (pet/ct) in the investigation of these patients. Methods: We retrospectively analyzed data from the PET Access Program (pap) database in the province of Ontario to identify patients who underwent fdg-pet/ct imaging as part of a workup for pns. In all patients, prior conventional imaging was negative or indeterminate. To determine the diagnostic accuracy of fdg-pet/ct, data about demographics, presenting symptoms, and biochemical and radiologic workup, including fdg-pet/ct imaging results, were compared with data collected by the Ontario Cancer Registry (ocr). A systematic review of the literature and meta-analysis using our study inclusion criteria were performed for studies of fdg-pet accuracy. Results: Of 29 patients identified in the pap database, 9 had fdg-pet/ct results suspicious for malignancy. When correlated with data from the ocr, 5 fdg-pet/ct results were informative, resulting in a detection rate of 17%. Local sensitivity and specificity were 0.83 and 0.83 respectively. Two studies meeting our criteria were identified in the literature. The pooled sensitivity and specificity from the literature and local data were 0.88 and 0.90 respectively. Conclusions: When investigating for underlying malignancy in patients with suspected pns and negative conventional imaging, pet has high sensitivity and specificity.


Asunto(s)
Fluorodesoxiglucosa F18/administración & dosificación , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ontario , Síndromes Paraneoplásicos del Sistema Nervioso/metabolismo , Estudios Retrospectivos , Sensibilidad y Especificidad , Adulto Joven
17.
Clin Microbiol Infect ; 25(3): 372-378, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-29906597

RESUMEN

OBJECTIVES: Automated point-of-care molecular assays have greatly shortened the turnaround time of respiratory virus testing. One of the major bottlenecks now lies at the specimen collection step, especially in a busy clinical setting. Saliva is a convenient specimen type that can be provided easily by adult patients. This study assessed the diagnostic validity, specimen collection time and cost associated with the use of saliva. METHODS: This was a prospective diagnostic validity study comparing the detection rate of respiratory viruses between saliva and nasopharyngeal aspirate (NPA) among adult hospitalized patients using Xpert® Xpress Flu/RSV. The cost and time associated with the collection of saliva and nasopharyngeal specimens were also estimated. RESULTS: Between July and October 2017, 214 patients were recruited. The overall agreement between saliva and NPA was 93.3% (196/210, κ 0.851, 95% CI 0.776-0.926). There was no significant difference in the detection rate of respiratory viruses between saliva and NPA (32.9% (69/210) versus 35.7% (75/210); p 0.146). The overall sensitivity and specificity were 90.8% (81.9%-96.2%) and 100% (97.3%-100%), respectively, for saliva, and were 96.1% (88.9%-99.2%) and 98.5% (94.7%-99.8%), respectively, for NPA. The time and cost associated with the collection of saliva were 2.26-fold and 2.59-fold lower, respectively, than those of NPA. CONCLUSIONS: Saliva specimens have high sensitivity and specificity in the detection of respiratory viruses by an automated multiplex Clinical Laboratory Improvement Amendments-waived point-of-care molecular assay when compared with those of NPA. The use of saliva also reduces the time and cost associated with specimen collection.


Asunto(s)
Técnicas de Diagnóstico Molecular/métodos , Pruebas en el Punto de Atención , Infecciones del Sistema Respiratorio/diagnóstico , Manejo de Especímenes/métodos , Anciano , Anciano de 80 o más Años , Costos y Análisis de Costo , Femenino , Humanos , Virus de la Influenza A/aislamiento & purificación , Virus de la Influenza B/aislamiento & purificación , Masculino , Persona de Mediana Edad , Técnicas de Diagnóstico Molecular/normas , Nasofaringe/virología , Estudios Prospectivos , Reproducibilidad de los Resultados , Virus Sincitiales Respiratorios/aislamiento & purificación , Infecciones del Sistema Respiratorio/virología , Saliva/virología , Sensibilidad y Especificidad , Manejo de Especímenes/economía , Factores de Tiempo
18.
Ann Surg Oncol ; 15(4): 993-1000, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18236111

RESUMEN

Liver transplantation (LT) which is currently an established therapy for sma1l, early stage hepatocellular carcinoma (HCC) in patients with cirrhosis requires in most cases long waiting period. Tumor development during the waiting period may be associated with vascular invasion which is a strong factor of postoperative recurrence. Therefore, local treatment of the tumor including trans-arterial chemoembolization (TACE), percutaneous radiofrequency (RF) or partial liver resection can be used before transplantation. In the present paper we reviewed the efficacy of these treatments prior to LT. Although, TACE induced complete tumor necrosis in some patients there is no convincing arguments showing that this treatment reduces the rate of drop out before LT, nor improves the survival after LT. Although, RF can induce complete necrosis in the majority of small tumors (<2.5 cm), there is no data demonstrating that this treatment reduce the rate of drop out before LT, nor improves the survival after LT. It has been showed that both short and long term survival after LT was not compromised by previous partial liver resection of HCC. However, there is no data demonstrating that liver resection before LT, which can be used either as a bridge treatment or as a primary treatment, improves the survival after LT. The current data suggest that there is no role for pre-transplant therapy for HCC within Milano criteria transplanted within six months. On the opposite, if the waiting time is predicted to be prolonged, the risk of tumor progression and either drop-off from the list or interval dissemination with post-transplant tumor recurrence is recognized. In this setting, bridge therapy can reduce that risk but its efficacy has to be determined.


Asunto(s)
Carcinoma Hepatocelular/terapia , Ablación por Catéter , Quimioembolización Terapéutica , Hepatectomía , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Ablación por Catéter/estadística & datos numéricos , Quimioembolización Terapéutica/estadística & datos numéricos , Progresión de la Enfermedad , Hepatectomía/estadística & datos numéricos , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Trasplante de Hígado , Morbilidad , Estadificación de Neoplasias , Cuidados Preoperatorios , Análisis de Supervivencia , Resultado del Tratamiento , Listas de Espera
20.
Adv Colloid Interface Sci ; 261: 15-27, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-30293697

RESUMEN

This review describes new methods for the particle extraction through liquid-liquid interface (PELLI). The discovery of new surface modification techniques, advanced extractors and new adsorption mechanisms enabled novel applications of PELLI in nanotechnology of metals, quantum dots, oxides and hydroxides. Colloidal and interface chemistry of PELLI is emerging as a new area of technological and scientific interest. The progress achieved in the understanding of particle behavior and interactions at the liquid-liquid interface, phase transfer and interface reactions allowed for the development of new extraction mechanisms. An important breakthrough was the development of surface modification techniques for extraction of functional oxides. Especially important is the possibility of particle transfer from the synthesis medium to the device processing medium, which facilitates agglomerate-free processing of functional nanoparticles. Multifunctional extractor molecules were discovered and used as capping and reducing agents for particle synthesis or dispersing and charging agents for colloidal processing. The progress achieved in the development of extractors and extraction mechanisms has driven the advances in the surface modification and functionalization of materials. New PELLI techniques were used for the development of advanced materials and devices for optical, photovoltaic, energy storage, electronic, biomedical, sensor and other applications.

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