RESUMEN

Objective: To systematically compare the differences in the detection rate of prostate cancer with fusion targeting biopsy and systemic biopsy. Methods: A computer-based search of PubMed, Medline, China Biomedical Literature Database and Wanfang database (from the beginning of establishment of library to October 2016) on the detection rate of prostate cancer by fusion targeting biopsy and systemic biopsy was performed manually.The inclusion and exclusion criteria were formulated by 2 reviewers, and the data were extracted and evaluated respectively. RevMan5.3 software was used to analyze the detection rate of prostate cancer by two biopsy methods. Results: A total of 15 related clinical studies were included, 5 337 cases were enrolled in the study, including 2 667 cases of targeted fusion biopsy and 2 670 cases of routine systemic biopsy. The results showed that the overall detection rate of prostate cancer in targeting fusion biopsy was significantly higher than that of conventional systemic biopsy (OR=1.16, 95% CI 1.04-1.30, P=0.007). The detection rates of prostate cancer with different risk grades by two biopsy methods were conducted. We found that targeted fusion biopsy had a significant advantage compared with conventional system biopsy (OR=1.37, 95% CI 1.19-1.58, P<0.05) in middle and high risk prostate cancer with Gleason ≥ 7 points. In low-risk prostate cancer patients with Gleason score <7, the detection rate of prostate cancer by targeted fusion biopsy was lower (OR=0.76, 95% CI 0.65-0.89, P<0.05) than that of conventional systemic biopsy. Conclusions: Targeted fusion biopsy was significantly better than systemic biopsy in the overall detection rate of prostate cancer and the detection rate of the middle and high risk prostate cancer with Gleason ≥7 points. However, systemic biopsy performed better in patients with Gleason<7 points of low-risk prostate cancer.

Asunto(s)

Biopsia Guiada por Imagen , Neoplasias de la Próstata/diagnóstico , China , Humanos , Masculino , Imagen Multimodal

RESUMEN

Several different mutations collaborate with the fusion proteins in core-binding factor acute myeloid leukemia (CBF-AML) to induce leukemogenesis, but their prognostic significance remains unclear. We screened 354 predominantly younger (<60 years) adults with t(8;21) (n=199) or inv(16) (n=155) entered into UK MRC trials for KIT, FLT3 tyrosine kinase domain (FLT3(TKD)), N-RAS, K-RAS and c-CBL mutations and FLT3 internal tandem duplications (FLT3(ITD)) and assessed the impact of relative mutant level on outcome. Overall, 28% had KIT, 6% FLT3(ITD), 10% FLT3(TKD), 27% RAS and 6% CBL mutations. Mutant levels for all genes/loci were highly variable. KIT mutations were associated with a higher cumulative incidence of relapse but in multivariate analysis this was only significant for cases with a higher mutant level of 25% or greater (95% confidence interval (CI)=1.01-1.52, P=0.04). Similarly, only FLT3(ITD-HIGH) was a significant adverse factor for overall survival (OS; CI=1.27-5.39, P=0.004). Conversely, FLT3(TKD-HIGH) and CBL(HIGH) were both favorable factors for OS (CI= 0.31-0.89, P=0.01 and CI=0.05-0.85, P=0.02, respectively). KIT mutations were frequently lost at relapse, which is relevant to minimal residual disease detection and the clinical use of KIT inhibitors. These results indicate that relative mutant level should be taken into account when evaluating the impact of mutations in CBF-AML.

Asunto(s)

Factores de Unión al Sitio Principal/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Mutación , Proteínas Proto-Oncogénicas c-cbl/genética , Proteínas Proto-Oncogénicas c-kit/genética , Tirosina Quinasa 3 Similar a fms/genética , Adolescente , Adulto , Anciano , Aberraciones Cromosómicas , Estudios de Cohortes , Exones , Femenino , Genotipo , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Recurrencia , Inducción de Remisión , Resultado del Tratamiento , Adulto Joven

RESUMEN

This study was conducted to identify proteins associated with the endogenous synthesis of conjugated linoleic acid (CLA) from trans-vaccenic acid (TVA; trans-11 C18:1, a precursor for CLA endogenous synthesis) in mammary tissues. Six lactating goats were divided into 2 groups. One group was given an intravenous bolus injection of TVA (150mg) twice daily over 4 d; the other group received saline injections. Treatment with TVA increased the concentration of cis-9,trans-11 CLA and TVA in goat milk. Additionally, TVA treatment increased the expression of stearoyl-CoA desaturase (SCD) in mammary tissue. Using 2-dimensional gel electrophoresis and electrospray ionization quadrupole time-of-flight mass spectrometry, 3 proteins affected by infusions of TVA were identified. Proteasome (prosome, macropain) subunit α type 5 (PSMA5) was upregulated, whereas peroxiredoxin-1 and translationally controlled tumor protein 1 were downregulated in TVA-treated animals compared with the vehicle-injected controls. Only the effect of TVA on PSMA5 could be confirmed by Western blot analysis. To further explore the regulation of PSMA5 in mammary epithelial cells when TVA is converted into CLA, we used a differentiated bovine mammary epithelial cell line treated with TVA for 6h. Changes in cis-9,trans-11 CLA concentrations and mRNA expression patterns of both SCD and PSMA5 were monitored. The concentration of cis-9,trans-11 CLA increased after TVA treatment. The mRNA expression level of PSMA5 was significantly elevated to 6h, but SCD mRNA expression only increased in 2h after TVA treatment. These results indicate that PSMA5 is highly expressed in goat mammary tissue and bovine mammary epithelial cells when TVA is converted into CLA. Our data suggest that PSMA5 protein is associated with CLA biosynthesis in mammary tissue.

Asunto(s)

Cabras/metabolismo , Ácidos Linoleicos Conjugados/metabolismo , Glándulas Mamarias Animales/metabolismo , Leche/química , Ácidos Oléicos/farmacología , Animales , Western Blotting , Bovinos , Línea Celular , Electroforesis en Gel Bidimensional/veterinaria , Femenino , Ácidos Linoleicos Conjugados/análisis , Ácidos Linoleicos Conjugados/genética , ARN/química , ARN/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Espectrometría de Masa por Ionización de Electrospray/veterinaria

RESUMEN

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is one of the most widespread and destructive wheat diseases worldwide. Growing resistant cultivars is the preferred means of control of the disease. The winter wheat cultivar Xiaoyan 54 has high-temperature resistance to stripe rust. To identify genes for stripe rust resistance, Xiaoyan 54 was crossed with Mingxian 169, a winter wheat genotype susceptible to all Chinese races of the pathogen. Seedlings and adult plants of the parents and F(1), F(2), F(3) and F(4) progeny were tested with Chinese race CYR32 under controlled greenhouse conditions and in the field. Xiaoyan 54 has two recessive resistance genes, designated as Yrxy1 and Yrxy2, conferring high-temperature resistance. Simple sequence repeat (SSR) primers were used to identify molecular markers flanking Yrxy2 using 181 plants from one segregating F(3) line. A total of nine markers, two of which flanked the locus at genetic distances of 4.0 and 6.4 cM on the long arm of chromosome 2A were identified. Resistance gene analog polymorphism (RGAP) and SSR techniques were used to identify molecular markers linked to Yrxy1. A linkage group of nine RGAP and two SSR markers was constructed for Yrxy1 using 177 plants of another segregating F(3) line. Two RGAP markers were closely linked to the locus with genetic distances of 2.3 and 3.5 cM. Amplification of a set of nulli-tetrasomic Chinese Spring lines with RGAP markers M8 and M9 and the two SSR markers located Yrxy1 on the short arm of chromosome 7A. The SSR markers Xbarc49 and Xwmc422 were 15.8 and 26.1 cM, respectively, from the gene. The closely linked molecular markers should be useful for incorporating the resistance genes into commercial cultivars and combining them with other genes for stripe rust resistance.

Asunto(s)

Basidiomycota/patogenicidad , Mapeo Cromosómico , Genes de Plantas , Enfermedades de las Plantas/genética , Triticum/genética , Basidiomycota/inmunología , Cromosomas de las Plantas , Cruzamientos Genéticos , ADN de Plantas/genética , ADN de Plantas/aislamiento & purificación , Resistencia a la Enfermedad , Genes Recesivos , Ligamiento Genético , Marcadores Genéticos , Genotipo , Enfermedades de las Plantas/inmunología , Inmunidad de la Planta , Reacción en Cadena de la Polimerasa , Polimorfismo Genético , Plantones/genética , Plantones/inmunología , Triticum/microbiología

RESUMEN

PbTe nanocrystals were prepared by a modified molten composite-hydroxides method at 180 degrees C for different times, using Pb(NO3)2 and TeO2 as starting materials and KBH4 as a reductant. The nanocrystal structure and morphologies of the synthesized products were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and high resolution TEM (HRTEM), respectively. The results showed that the reaction time has a significant influence on the size and shape of the as-prepared PbTe nanocrystals. As the reaction time increased, the as-prepared products were eventually transformed from nanomaterials (nanocubes, nanorods, and nanosheets) to microcrystals with different morphologies (microcubes, mciroprisms, and microplates). The formation mechanism of the PbTe was proposed, and a one-dimensional oriented attachment growth process combined with two-dimensional oriented attachment growth process was suggested for the growth of nanorods and nanosheets.

RESUMEN

The present study was conducted to examine the effects of different plant oils or plant oil mixtures and high-temperature, microtime processing (HTMT) on the CLA content in Hanwoo steers. Experiment 1, consisting of 3 in vitro trials, was conducted to determine how the biohydrogenation of C18 fatty acids and CLA production were affected by fat sources (tallow, soybean oil, linseed oil, or mixtures of soybean oil and linseed oil) or HTMT treatment in the rumen fluid. The results showed that HTMT was capable of protecting unsaturated fatty acids from biohydrogenation by ruminal bacteria. The HTMT-treated diet containing 4% linseed oil (LU) and a supplement containing 2% linseed oil and 1% soybean oil treated with HTMT + 1% soybean oil (L(2)S(1)U+S(1)) produced an increased quantity of trans-11 C18:1 and cis-9, trans-11 CLA, and a reduced quantity of trans-10, cis-12 CLA. Based on these results, in vivo studies (Exp. 2) were conducted with LU and L(2)S(1)U+S(1). These 2 treatments increased the content of cis-9, trans-11 CLA in LM compared with the control diet. The content of trans-10, cis-12 CLA in subcutaneous fat was also increased in the L(2)S(1)U+S(1) treatment compared with other treatments. The subcutaneous fat thickness in the LU treatment was decreased compared with the L(2)S(1)U+S(1) treatment. The LU treatment significantly decreased fatty acid synthase expression but simultaneously increased leptin expression. In this report, we showed that diets containing LU and L(2)S(1)U+S(1) were capable of increasing CLA in the intramuscular fat of beef.

Asunto(s)

Bovinos/metabolismo , Dieta/veterinaria , Grasas de la Dieta/administración & dosificación , Manipulación de Alimentos/métodos , Calor , Ácidos Linoleicos Conjugados/biosíntesis , Aceites de Plantas/administración & dosificación , Tejido Adiposo/metabolismo , Animales , Composición Corporal , Ácidos Grasos/análisis , Ácidos Grasos/sangre , Ácidos Grasos/química , Contenido Digestivo/química , Regulación Enzimológica de la Expresión Génica , Ácidos Linoleicos Conjugados/análisis , Ácidos Linoleicos Conjugados/sangre , Metabolismo de los Lípidos/fisiología , Masculino , Rumen/química

RESUMEN

SiCN nanowires are synthesized by pyrolysis of hexamethyldisilazane (HMDSN) using ferrocene as a catalyst precursor at 1200 degrees C in a flowing argon atmosphere on the surface of mullite substrate, polycrystalline alumina wafer and quartz tube. In oxygen-contained argon atmosphere, SiCN/SiO2 nanocables are synthesized. The as-synthesized products are characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy and high-resolution electron microscopy equipped with energy dispersive X-ray spectroscopy. The lengths of the nanowires and nanocables are in the millimeter range. The diameter of the SiCN nanowires grown on mullite substrate and alumina wafer ranges from about 10-70 nm, while that of the nanowires grown on quartz tube surface is in the range of around 7-10 nm. The diameters of the SiCN/SiO2 nanocables are relatively large. A vapor-liquid-solid growth mechanism of the nanostructures is proposed. The electrical resistivity of a single SiCN/SiO2 nanocable is reported for the first time.

Asunto(s)

Antígenos HLA-DR , Trasplante de Células Madre Hematopoyéticas , Adolescente , Adulto , Anciano , Niño , Preescolar , Estudios de Cohortes , Subtipos Serológicos HLA-DR , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Lactante , Estimación de Kaplan-Meier , Persona de Mediana Edad , Estudios Retrospectivos , Prevención Secundaria , Hermanos , Trasplante Isogénico

RESUMEN

Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II-IV) and transplant-related mortality were significantly decreased (P=0.01 and P<10(-4), respectively) and relapse incidence was significantly higher (P=0.003) after RIC transplantation. Leukaemia-free survival was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML.

Asunto(s)

Trasplante de Células Madre Hematopoyéticas/métodos , Leucemia Mieloide Aguda/terapia , Acondicionamiento Pretrasplante/métodos , Anciano , Causas de Muerte , Relación Dosis-Respuesta a Droga , Relación Dosis-Respuesta en la Radiación , Femenino , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/mortalidad , Prueba de Histocompatibilidad , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia , Sistema de Registros , Estudios Retrospectivos , Hermanos , Análisis de Supervivencia , Trasplante Homólogo , Resultado del Tratamiento

RESUMEN

One hundred and nineteen undergraduate students (62 men and 57 women) of Chinese origin at the National University of Singapore answered three self-report humor questionnaires. Students were also asked to supply their favorite joke (M. A. Johnson, 1991) and a description of a person with an outstanding sense of humor (M. Crawford & D. Gressley, 1991). These responses were compared with results obtained using the same questionnaires and methods in previous studies in Israel and the United States. In general, means and reliabilities of results obtained from the Singapore study replicated those found in other countries. However, Singaporean participants reported significantly less use of humor for coping. Content analysis of jokes supplied by Singaporean students reflected conservative values: Compared with American students, they reported a significantly greater number of jokes with aggressive content and relatively fewer jokes with sexual content. Contrary to expectations, very few gender differences were found. Regardless of gender, a majority of participants nominated a man as an example of a person with an outstanding sense of humor.

Asunto(s)

Cultura , Ingenio y Humor como Asunto , Adulto , Comparación Transcultural , Femenino , Humanos , Masculino , Distribución Aleatoria , Factores Sexuales , Singapur , Encuestas y Cuestionarios

RESUMEN

Real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) is the method of choice for rapid and reproducible measurements of cytokine or growth factor expression in small samples. Fluorescence detection methods for monitoring real-time PCR include fluorogenic probes labelled with reporter and quencher dyes, such as Taqman probes or Molecular Beacons and the dsDNA-binding dye SYBR Green I. Fluorogenic (Taqman) probes for a range of human and rat cytokines and growth factors were tested for sensitivity and compared with an assay for SYBR Green I quantification using real-time fluorescence monitoring (PE Applied Biosystems Model 7700 sequence detector). SYBR Green I detection involved analysis of the melting temperature of the PCR product and measurement of fluorescence at the optimum temperature. Fluorogenic probes provided sensitive and reproducible detection of targets that ranged from low (<10 copies/reaction) to high (>107 copies/ reaction) expression. SYBR Green I gave reproducible quantification when the target gene was expressed at moderate to high levels (> or =1000 copies/reaction), but did not give consistently reproducible quantification when the target gene was expressed at low levels. Although optimization of melting temperature improved the specificity of SYBR Green I detection, in our hands it did not equal the reproducible sensitivity and specificity of fluorogenic probes. The latter method is the first choice for measurement of low-level gene expression, although SYBR Green I is a simple and reproducible means to quantify genes that are expressed at moderate to high levels.

Asunto(s)

Citocinas/genética , Colorantes Fluorescentes/metabolismo , Péptidos y Proteínas de Señalización Intercelular , Compuestos Orgánicos , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Animales , Benzotiazoles , Tampones (Química) , Citocinas/metabolismo , Diaminas , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Humanos , Interferón gamma/genética , Interferón gamma/metabolismo , Proteínas/genética , Proteínas/metabolismo , Quinolinas , ARN Mensajero/genética , Ratas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

Cells that are apoptotic and comprise less than 2% of the total cellular population are difficult to detect by conventional methods (i.e., DNA ladder). We discuss a new methodological technique, PCR-amplified DNA ladder, to detect very low levels of DNA fragmentation (indicative of apoptosis) in a myocardial infarct heart failure model. Results and methodology are contrasted with the traditional DNA ladder technique.

Asunto(s)

Apoptosis/genética , Fragmentación del ADN , Insuficiencia Cardíaca/patología , Reacción en Cadena de la Polimerasa/métodos , Animales , Modelos Animales de Enfermedad , Insuficiencia Cardíaca/genética , Conejos

RESUMEN

The redistribution of purinergic P2X receptor subunits (P2X(1) to P2X(7)) within the rabbit aorta wall three weeks after endothelial balloon injury/cholesterol feeding was examined. P2X(1) receptor cluster density was elevated in the media following balloon injury/cholesterol feeding by about 30% and these clusters appeared on smooth muscle cells throughout the greatly expanded neointima but they did not change significantly on the endothelial cells following balloon injury. P2X(4) clusters were found in high density throughout the media and in very high density in the enlarged neointima following balloon injury, particularly on the endothelial cells where the density increased about 10-fold after balloon injury. P2X(5) clusters were found in high density in the media of normal aorta but with little change following balloon injury. P2X(3), P2X(6) and P2X(7) cluster density was low in normal aorta and remained unchanged following balloon injury. All receptor subunits were found on endothelial cells. It is suggested that the release of ATP from damaged endothelial cells and from smooth muscle cells sufficient to activate P2X(4) receptors may contribute to neointimal proliferation.

Asunto(s)

Aorta/metabolismo , Arteriosclerosis/metabolismo , Colesterol en la Dieta/farmacología , Endotelio Vascular/metabolismo , Alimentos Formulados/efectos adversos , Músculo Liso Vascular/metabolismo , Receptores Purinérgicos P2/metabolismo , Animales , Aorta/lesiones , Aorta/fisiopatología , Arteriosclerosis/patología , Arteriosclerosis/fisiopatología , Cateterismo/efectos adversos , Modelos Animales de Enfermedad , Endotelio Vascular/lesiones , Endotelio Vascular/fisiopatología , Inmunohistoquímica , Inflamación/metabolismo , Inflamación/patología , Inflamación/fisiopatología , Músculo Liso Vascular/patología , Músculo Liso Vascular/fisiopatología , Conejos , Receptores Purinérgicos P2X , Receptores Purinérgicos P2X3 , Receptores Purinérgicos P2X4 , Receptores Purinérgicos P2X5 , Receptores Purinérgicos P2X7 , Regulación hacia Arriba/fisiología

RESUMEN

Expression of recombinant proteins is an important method for the characterisation of the structure and function of proteins. However, many expression methods can be difficult, time-consuming and lead to low protein yields. The Promega Pinpoint Xal-T vector system is a unique, one-step cloning method that allows the direct insertion of polymerase chain reaction (PCR) fragments into the expression vector. We describe our experience of the use of this system to clone and express three proteins (8-12 kDa) directly from their PCR products. The proteins are expressed as fusion proteins with a 13 kDa biotinylated tag that can be used for detection of the expressed protein and affinity purification. In our case, the yield was greater than 20 mg per litre of culture. Expressed proteins were purified by Q-Sepharose anion-exchange chromatography and reverse-phase high-performance liquid chromatography (HPLC) instead of the conventional method of avidin-biotin affinity chromatography. The Pinpoint vector proved to be a relatively simple and fast protein expression technique suitable for wide application for expressing recombinant proteins.

Asunto(s)

Clonación Molecular/métodos , Vectores Genéticos , Péptidos y Proteínas de Señalización Intercelular , Reacción en Cadena de la Polimerasa/métodos , Animales , Biotina , Proteínas Portadoras/genética , Pollos , Expresión Génica , Humanos , Cadenas Ligeras de Miosina/genética , Plásmidos , Proteínas/genética , Conejos , Proteínas Recombinantes de Fusión

RESUMEN

alpha-Interferon (IFN) has been used to induce cytogenetic remission in chronic myeloid leukaemia (CML), but there are few indicators to predict IFN response. The role of the chimaeric BCR/ABL gene in the malignant process is undisputed. There are, however, conflicting views as to whether the breakpoint site within the BCR gene, and the type of mRNA produced determine disease prognosis and progression. The function and clinical significance of the newly discovered ABL/BCR mRNA has not been investigated for a correlation with CML prognosis or response to therapy. We have used a two-step reverse transcriptase polymerase chain reaction (RT-PCR) to detect the transcripts of the chimaeric genes BCR/ABL, ABL/BCR, as well as the normal ABL and BCR genes in 24 CML patients treated with IFN. Because of the variable expression of the four transcripts at presentation, a correlation between gene expression, prognosis and clinical progression was examined. No correlation between prognosis and gene expression was seen. Also, no correlation was found between expression of BCR, ABL or BCR/ABL mRNA and response to treatment with IFN. However, 7/10 ABL/BCR mRNA positive patients achieved a major cytogenetic response to IFN; but of the 13 ABL/BCR mRNA negative patients, only two achieved a major cytogenetic response (P = 0.013). Further studies are required to confirm these findings.

Asunto(s)

Proteínas de Fusión bcr-abl/biosíntesis , Interferón-alfa/uso terapéutico , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mielógena Crónica BCR-ABL Positiva/terapia , Adolescente , Adulto , Secuencia de Bases , Niño , Femenino , Proteínas de Fusión bcr-abl/genética , Expresión Génica , Genes abl , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa/métodos , Pronóstico , ARN Mensajero/genética , ARN Neoplásico/genética , Resultado del Tratamiento

Asunto(s)

Trasplante de Médula Ósea/inmunología , Antígenos de Histocompatibilidad Clase I/genética , Antígenos de Histocompatibilidad Clase I/inmunología , Ácidos Nucleicos Heterodúplex/análisis , Donantes de Tejidos , Alelos , Secuencia de Bases , Exones , Femenino , Genotipo , Humanos , Masculino , Datos de Secuencia Molecular , Ácidos Nucleicos Heterodúplex/genética , Reacción en Cadena de la Polimerasa/métodos

RESUMEN

This report describes a patient presenting with acute myeloid leukaemia (AML-FAB classification M2). Phenotypic markers were positive for cells of the myeloid lineage, but negative for monocyte/macrophage, megakaryocyte, and T-cell lineages. The occasional blast was positive for CALLA. All blasts carried the Philadelphia chromosome (Ph+), with 20% also harbouring a monosomy 7 (a cytogenetic marker for AML). Reverse transcriptase polymerase chain reaction (RT-PCR) analysis revealed the presence of two BCR/Abl mRNA transcripts; b2a2, the CML-type and E1a2, the ALL-type. Immunoglobulin (Ig) gene analysis demonstrated the presence of a small population of cells containing rearranged Ig genes. After a short remission, the patient relapsed. At relapse the leukaemia had undergone a major phenotypic switch from AML to ALL, with blasts bearing B-cell markers. Ig gene analysis confirmed a monoclonal population of B-cells. The Ph+ persisted, but the monosomy 7 had disappeared. The same two BCR/Abl mRNA transcripts were found at relapse as at presentation. To our knowledge, this is the first report of an AML simultaneously expressing BCR/Abl transcripts from both the minor and major BCR. The possible mechanisms of this dual expression are discussed.

Asunto(s)

Proteínas de Fusión bcr-abl/genética , Genes abl , Leucemia Mielógena Crónica BCR-ABL Positiva/genética , Leucemia Mieloide Aguda/genética , ARN Mensajero/genética , Transcripción Genética , Secuencia de Bases , Femenino , Expresión Génica , Reordenamiento Génico , Humanos , Persona de Mediana Edad , Datos de Secuencia Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Empalme del ARN

RESUMEN

Twenty-seven patients with renal failure (16 on CAPD and 11 predialysis) were treated with erythropoietin. At 12 weeks, the mean haemoglobin concentration (+/- SEM) in the CAPD patients had increased from 7.07 +/- 0.20 to 10.88 +/- 0.45 g/dl (two-tailed paired t test, P < 0.0001) and in the predialysis patients from 6.90 +/- 0.35 to 10.05 +/- 0.47 g/dl (P < 0.0001). Predialysis patients were taking more antihypertensive medication at baseline. No increase was required in either group after erythropoietin; there was no change in blood pressure in the CAPD patients, though in the predialysis patients the systolic blood pressure rose slightly from 132 to 146 mmHg (P = 0.029) and the mean blood pressure from 95 to 103 mmHg (P = 0.028). In 12 patients (6 on CAPD and 6 predialysis) the red cell volume, plasma volume, and total blood volume were measured before and after treatment. In the CAPD patients there was a marked expansion of the red cell volume from 912 +/- 127 to 1471 +/- 222 ml (P = 0.004) and a concomitant contraction of the plasma volume from 3932 +/- 250 to 3178 +/- 326 ml (P = 0.005), leaving the blood volume unchanged from 4843 +/- 352 to 4649 +/- 503 ml. Predialysis patients had a similar expansion of the red cell volume from 733 +/- 59 to 1304 +/- 161 ml (P = 0.017) but no contraction of the plasma volume (from 3417 +/- 354 to 3314 +/- 260 ml), so that the blood volume tended to expand from 4149 +/- 347 to 4618 +/- 414 ml (P = 0.053).(ABSTRACT TRUNCATED AT 250 WORDS)

Asunto(s)

Volumen Sanguíneo/efectos de los fármacos , Eritropoyetina/efectos adversos , Hipertensión/inducido químicamente , Diálisis Peritoneal Ambulatoria Continua , Presión Sanguínea/efectos de los fármacos , Humanos , Hipertensión/prevención & control , Proteínas Recombinantes/efectos adversos

RESUMEN

The demethylation and hydroxylation of amitriptyline were calculated from the ratios between the area under concentration--time curve (AUC) of amitriptyline and its three metabolites in eight healthy Chinese volunteers after a single oral dose of 100 mg amitriptyline. Great interindividual differences in AUCs of amitriptyline and its metabolites were observed. HPLC method was used to determine the debrisoquine hydroxylation phenotype in seven out of the eight volunteers. Six subjects were found to be rapid and one slow debrisoquine hydroxylators. The ratio between debrisoquine and 4-hydroxydebrisoquine in urine correlated significantly with the rate of amitriptyline hydroxylation and the AUCs of amitriptyline and 10-hydroxyamitriptyline, but not with that of amitriptyline demethylation. There also was a weak correlation between total plasma clearance and the hydroxylation of debrisoquine. These data suggest that the hydroxylation of amitriptyline and debrisoquine may be regulated by similar enzymatic processes and the demethylation and hydroxylation processes in amitriptyline metabolism appear to undergo two separate pathways.

Asunto(s)

Amitriptilina/metabolismo , Adulto , Amitriptilina/análogos & derivados , Amitriptilina/sangre , Amitriptilina/farmacocinética , Pueblo Asiatico , Debrisoquina/metabolismo , Debrisoquina/farmacocinética , Humanos , Hidroxilación , Masculino , Tasa de Depuración Metabólica/genética , Nortriptilina/análogos & derivados , Nortriptilina/sangre , Fenotipo , Polimorfismo Genético , Especificidad de la Especie

RESUMEN

It is reported that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), a physiological factor, has an inductive effect on the differentiation of a novel human megakaryoblastic leukemia cell line (HIMeg) in vitro. At the concentrations ranging from 10(-9) to 10(-6) mol/L, 1,25(OH)2D3 showed inhibition of proliferation on HIMeg cells which was demonstrated by count of survival cells and cloning efficiency. Meanwhile, using light/electron microscopy, stain of cytochemistry (including immunoenzymatic technique) and flow cytometry, we found that HIMeg cells could be further induced into more mature cells in megakaryocytic lineage confirmed by a series of evidence, including the changes of cell morphology/structure and cytochemistry, increased expression of differentiation antigens on the cell surface, and polyploidization. So, it is possible for 1,25(OH)2D3 to promote the differentiation of the cells in megakaryocytic lineage in vivo and to be used to treat acute megakaryoblastic leukemia and other diseases with malignant megakaryocytosis.

Asunto(s)

Calcitriol/farmacología , Leucemia Megacarioblástica Aguda/patología , Diferenciación Celular/efectos de los fármacos , División Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Humanos , Poliploidía , Células Tumorales Cultivadas/efectos de los fármacos , Células Tumorales Cultivadas/patología