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1.
Encephale ; 48(2): 132-138, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34092379

RESUMEN

BACKGROUND: Cannabis is the most widely used illicit drug in the world. It is responsible for cognitive dysfunction of memory, speed of information processing, attention, and executive functions. Cognitive performance depends on the level of study, tolerance, and duration of abstinence from cannabis use. This study analyses cognitive function in a large population of regular cannabis consumers taking into account level of education. METHODS: A battery of neuropsychological tests using the Cambridge Neuropsychological Test Automated Battery was performed on a population of 58 cannabis users categorized into two groups according to their level of education with a threshold of 12 years of study, and 25 non-users. RESULTS: In Attention Switching Task percent correct trials, significant differences were found between the group of cannabis smokers with less than 12 years of study and the non-smoker group (P=0.022), and between the cannabis users with more than 12 years of study and the non-smoker group (P=0.008). A significantly lower performance in the Rapid Visual Information Processing (Mean latency, Probability of hit, Total hits, Total misses, Correct rejections) was found in the cannabis users with less than 12 years of study compared with the non-user group. CONCLUSION: In our population, chronic cannabis users presented divided and sustained attention and working memory disorders. Rapid Visual Information Processing performance may be influenced by education level in cannabis smokers.


Asunto(s)
Cannabis , Atención , Función Ejecutiva , Humanos , Memoria a Corto Plazo , Pruebas Neuropsicológicas
2.
Int J Clin Pract ; 75(12): e14936, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34605116

RESUMEN

AIM OF THE STUDY: The aim of the study was to investigate whether antenatal corticosteroid therapy (ACST) could impact neurological condition, as assessed through muscular tone, of prematurely born infants. METHODS: All 82 patients at risk of preterm delivery treated and delivered over 12 months were divided into two equal groups regarding the use of ACST. The investigated parameters were pregnancy complications, biophysical profile, Apgar score, gestational age of delivery and all postpartum complications. Neurological development and muscular tone were evaluated at the 1st, 3rd, 6th and 12th months of life using Vojta's method, which classifies muscular tone as good, hypotonic or hypertonic. RESULTS: After therapy, infants from the treated and control groups differed in biophysical profile, Apgar score, length of intensive care, occurrence of respiratory distress syndrome and intraventricular haemorrhage. During the follow-up, significantly more infants from the ACST group had good muscular tone when compared with those from the control group. Regression analysis showed that ASCT can significantly impact an infant's muscular tone. Still, the week of delivery and the complications such as diabetes mellitus, intrauterine growth restriction and respiratory distress syndrome, could change the association of ACST and infants' muscular tone. CONCLUSION: ACST was associated with the positive neurological outcomes of prematurely born infants when assessed through their muscular tone.


Asunto(s)
Complicaciones del Embarazo , Nacimiento Prematuro , Síndrome de Dificultad Respiratoria del Recién Nacido , Corticoesteroides , Femenino , Edad Gestacional , Humanos , Lactante , Recién Nacido , Embarazo , Nacimiento Prematuro/prevención & control , Síndrome de Dificultad Respiratoria del Recién Nacido/tratamiento farmacológico , Síndrome de Dificultad Respiratoria del Recién Nacido/prevención & control
3.
Ann Oncol ; 26(8): 1791-8, 2015 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25908602

RESUMEN

Advances in 'omics' technology and targeted therapeutic molecules are together driving the incorporation of molecular-based diagnostics into the care of patients with cancer. There is an urgent need to assess the efficacy of therapy determined by molecular matching of patients with particular targeted therapies. WINTHER is a clinical trial that uses cutting edge genomic and transcriptomic assays to guide treatment decisions. Through the lens of this ambitious multinational trial (five countries, six sites) coordinated by the Worldwide Innovative Networking Consortium for personalized cancer therapy, we discovered key challenges in initiation and conduct of a prospective, omically driven study. To date, the time from study concept to activation has varied between 19 months at Gustave Roussy Cancer Campus in France to 30 months at the Segal Cancer Center, McGill University (Canada). It took 3+ years to be able to activate US sites due to national regulatory hurdles. Access to medications proposed by the molecular analysis remains a major challenge, since their availability through active clinical trials is highly variable over time within sites and across the network. Rules regarding the off-label use of drugs, or drugs not yet approved at all in some countries, pose a further challenge, and many biopharmaceutical companies lack a simple internal mechanism to supply the drugs even if they wish to do so. These various obstacles should be addressed to test and then implement precision medicine in cancer.


Asunto(s)
Antineoplásicos/uso terapéutico , Ensayos Clínicos como Asunto/métodos , Terapia Molecular Dirigida/métodos , Neoplasias/tratamiento farmacológico , Medicina de Precisión/métodos , Antineoplásicos/economía , Antineoplásicos/provisión & distribución , Canadá , Ensayos Clínicos como Asunto/economía , Ensayos Clínicos como Asunto/legislación & jurisprudencia , Francia , Perfilación de la Expresión Génica , Genómica , Humanos , Israel , Neoplasias/metabolismo , Estudios Prospectivos , España , Estados Unidos
4.
Artículo en Inglés | MEDLINE | ID: mdl-25317114

RESUMEN

BACKGROUND: Competition of probiotic bacteria with other species from the intestinal microbiota involves different mechanisms that occur regardless of probiotics' viability. The objective of this paper was to assess the cytokine serum levels in holoxenic mice after oral administration of non-viable components (NVC) of Enterococcus faecium probiotic culture stimulated with heat-inactivated Escherichia coli and Bacillus cereus in comparison to NVC of unstimulated E. faecium probiotic culture. METHODS: Probiotic E. faecium CMGb 16 culture, grown in the presence of heat-inactivated cultures of E. coli and B. cereus CMGB 102, was subsequently separated into supernatant (SN) and heat-inactivated cellular sediment (CS) fractions by centrifugation. Each NVC was orally administered to holoxenic mice (balb C mouse strain), in three doses, given at 24 hours. Blood samples were collected from the retinal artery, at 7, 14, and 21 days after the first administration of the NVC. The serum concentrations of IL-12 and tumor necrosis factor-alpha (TNF-α) interleukins were assessed by ELISA method. RESULTS: After the oral administration of SN component obtained from the probiotic culture stimulated with heat-inactivated cultures of B. cereus CMGB 102 and E. coli O28, the serum concentrations of IL-12 were maintained higher in the samples collected at 7 and 14 days post-administration. No specific TNF-α profile could be established, depending on stimulated or non-stimulated probiotic culture, NVC fraction, or harvesting time. CONCLUSION: The obtained results demonstrate that non-viable fractions of probiotic bacteria, stimulated by other bacterial species, could induce immunostimulatory effects mediated by cytokines and act, therefore, as immunological adjuvants.

5.
Invest New Drugs ; 31(6): 1530-8, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24077982

RESUMEN

BACKGROUND: The kinesin spindle protein Eg5 is involved in mitosis, and its inhibition promotes mitotic arrest. EMD 534085, a potent, reversible Eg5 inhibitor, demonstrated significant preclinical antitumor activity. METHODS: This first-in-man, single-center, open-label, phase I dose-escalation study (3 + 3 design) investigated EMD 534085 safety, pharmacokinetics and antitumor activity in refractory solid tumors, Hodgkin's lymphoma, or non-Hodgkin's lymphoma. EMD 534085 (starting dose 2 mg/m²/day) was administered intravenously every 3 weeks. Doses were escalated in 100% steps in successive cohorts of 3 patients until grade 2 toxicity occurred, followed by 50% until the first dose-limiting toxicity (DLT) arose. If <2 of 6 patients experienced a DLT, doses were further increased by 25%. Dose-escalation was stopped if a DLT occurred in ≥2 of 6 patients. RESULTS: Forty-four patients received EMD 534085. Median treatment duration was 43 days (range, 21-337). Thirty-eight patients (86%) received ≥2 cycles. DLTs were grade 4 neutropenia (1 patient each at 108 and 135 mg/m²/day), and grade 3 acute coronary syndrome with troponin I elevation (1 patient at 135 mg/m²/day). The maximum tolerated dose (MTD) was 108 mg/m²/day. The most common treatment-related adverse events were asthenia (50%) and neutropenia (32%). EMD 534085 appeared to have linear pharmacokinetics. Increase in phospho-histone H3 positive cells in paired pre- and on-treatment biopsies showed evidence of target modulation. No complete or partial responses were observed. Best response was stable disease in 23 patients (52%). CONCLUSIONS: EMD 534085 appeared to be well tolerated; MTD was 108 mg/m²/day. Preliminary antitumor results suggested limited activity in monotherapy.


Asunto(s)
Antineoplásicos/administración & dosificación , Cinesinas/antagonistas & inhibidores , Neoplasias/tratamiento farmacológico , Quinolinas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/sangre , Antineoplásicos/farmacocinética , Esquema de Medicación , Femenino , Humanos , Masculino , Dosis Máxima Tolerada , Persona de Mediana Edad , Neoplasias/sangre , Neoplasias/patología , Quinolinas/sangre , Quinolinas/farmacocinética , Carga Tumoral/efectos de los fármacos
6.
Br J Cancer ; 106(6): 1107-16, 2012 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-22343619

RESUMEN

BACKGROUND: The rapid collection of diverse genome-scale data raises the urgent need to integrate and utilise these resources for biological discovery or biomedical applications. For example, diverse transcriptomic and gene copy number variation data are currently collected for various cancers, but relatively few current methods are capable to utilise the emerging information. METHODS: We developed and tested a data-integration method to identify gene networks that drive the biology of breast cancer clinical subtypes. The method simultaneously overlays gene expression and gene copy number data on protein-protein interaction, transcriptional-regulatory and signalling networks by identifying coincident genomic and transcriptional disturbances in local network neighborhoods. RESULTS: We identified distinct driver-networks for each of the three common clinical breast cancer subtypes: oestrogen receptor (ER)+, human epidermal growth factor receptor 2 (HER2)+, and triple receptor-negative breast cancers (TNBC) from patient and cell line data sets. Driver-networks inferred from independent datasets were significantly reproducible. We also confirmed the functional relevance of a subset of randomly selected driver-network members for TNBC in gene knockdown experiments in vitro. We found that TNBC driver-network members genes have increased functional specificity to TNBC cell lines and higher functional sensitivity compared with genes selected by differential expression alone. CONCLUSION: Clinical subtype-specific driver-networks identified through data integration are reproducible and functionally important.


Asunto(s)
Neoplasias de la Mama/genética , Simulación por Computador , Redes Reguladoras de Genes , Modelos Biológicos , Mapas de Interacción de Proteínas , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Variaciones en el Número de Copia de ADN , Transición Epitelial-Mesenquimal/genética , Femenino , Expresión Génica , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Genes Relacionados con las Neoplasias , Humanos , Interferencia de ARN , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/genética , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/genética , Receptores de Progesterona/metabolismo
7.
Ann Oncol ; 23(5): 1301-1306, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-21917737

RESUMEN

BACKGROUND: Sequential tumour biopsies are of potential interest for the rational development of molecular targeted therapies. PATIENTS AND METHODS: From June 2004 to July 2009, 186 patients participated in 14 phase I clinical trials in which sequential tumour biopsies (13 trials) and/or sequential normal skin biopsies (6 trials) were optional. All patients had to sign an independent informed consent for the biopsies. RESULTS: Tumour biopsies were proposed to 155 patients and 130 (84%) signed the consent while normal skin biopsies were proposed to 70 patients and 57 (81%) signed the consent. Tumour biopsies could not be carried out in 41 (31%) of the 130 consenting patients. Tumour biopsies were collected at baseline in 33 patients, at baseline and under treatment in 56 patients. Tumour biopsies were obtained using an 18-gauge needle, under ultrasound or computed tomography guidance. Only nine minor complications were recorded. Most tumour biopsy samples collected were intended for ancillary molecular studies including protein or gene expression analysis, comparative genomic hybridization array or DNA sequencing. According to the results available, 70% of the biopsy samples met the quality criteria of each study and were suitable for ancillary studies. CONCLUSIONS: In our experience, the majority of the patients accepted skin biopsies as well as tumour biopsies. Sequential tumour and skin biopsies are feasible and safe during early-phase clinical trials, even when patients are exposed to anti-angiogenic agents. The real scientific value of such biopsies for dose selection in phase I trials has yet to be established.


Asunto(s)
Investigación Biomédica/métodos , Ensayos Clínicos Fase I como Asunto/efectos adversos , Ensayos Clínicos Fase I como Asunto/métodos , Neoplasias/patología , Aceptación de la Atención de Salud , Piel/patología , Adolescente , Adulto , Anciano , Algoritmos , Biopsia/efectos adversos , Biopsia/métodos , Biopsia/psicología , Biopsia/estadística & datos numéricos , Ensayos Clínicos Fase I como Asunto/psicología , Estudios de Factibilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud/psicología , Seguridad del Paciente/estadística & datos numéricos , Adulto Joven
8.
J Neuroeng Rehabil ; 9: 54, 2012 Aug 09.
Artículo en Inglés | MEDLINE | ID: mdl-22876934

RESUMEN

BACKGROUND: The control of movement in humans is hierarchical and distributed and uses feedback. An assistive system could be best integrated into the therapy of a human with a central nervous system lesion if the system is controlled in a similar manner. Here, we present a novel wireless architecture and routing protocol for a distributed functional electrical stimulation system that enables control of movement. METHODS: The new system comprises a set of miniature battery-powered devices with stimulating and sensing functionality mounted on the body of the subject. The devices communicate wirelessly with one coordinator device, which is connected to a host computer. The control algorithm runs on the computer in open- or closed-loop form. A prototype of the system was designed using commercial, off-the-shelf components. The propagation characteristics of electromagnetic waves and the distributed nature of the system were considered during the development of a two-hop routing protocol, which was implemented in the prototype's software. RESULTS: The outcomes of this research include a novel system architecture and routing protocol and a functional prototype based on commercial, off-the-shelf components. A proof-of-concept study was performed on a hemiplegic subject with paresis of the right arm. The subject was tasked with generating a fully functional palmar grasp (closing of the fingers). One node was used to provide this movement, while a second node controlled the activation of extensor muscles to eliminate undesired wrist flexion. The system was tested with the open- and closed-loop control algorithms. CONCLUSIONS: The system fulfilled technical and application requirements. The novel communication protocol enabled reliable real-time use of the system in both closed- and open-loop forms. The testing on a patient showed that the multi-node system could operate effectively to generate functional movement.


Asunto(s)
Terapia por Estimulación Eléctrica/instrumentación , Tecnología Inalámbrica , Algoritmos , Amplificadores Electrónicos , Brazo/fisiología , Biorretroalimentación Psicológica , Sistemas de Computación , Computadores , Estimulación Eléctrica , Electrónica , Diseño de Equipo , Fuerza de la Mano/fisiología , Hemiplejía/rehabilitación , Humanos , Músculo Esquelético/fisiología , Procesamiento de Señales Asistido por Computador , Programas Informáticos
9.
Chirurgia (Bucur) ; 106(2): 177-85, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21696062

RESUMEN

An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.


Asunto(s)
Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Neoplasias del Colon/química , Neoplasias del Colon/genética , Anciano , Transformación Celular Neoplásica/genética , Neoplasias del Colon/enzimología , Neoplasias del Colon/patología , Proteína DEFICIENS/análisis , Proteína DEFICIENS/genética , Progresión de la Enfermedad , Detección Precoz del Cáncer , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Interleucina-8/análisis , Interleucina-8/genética , Masculino , Metaloproteinasa 7 de la Matriz/análisis , Metaloproteinasa 7 de la Matriz/genética , Persona de Mediana Edad , Estadificación de Neoplasias , Osteopontina/análisis , Osteopontina/genética , Reacción en Cadena de la Polimerasa , Valor Predictivo de las Pruebas , Pronóstico , ARN Mensajero/análisis , Sensibilidad y Especificidad
10.
Ann Oncol ; 21(10): 2102-2106, 2010 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20305035

RESUMEN

PURPOSE: To explore whether adjuvant treatment options may impact on the prognosis in localized endometrial stromal sarcomas (ESSs; stages I and II). The historical options usually discussed in addition to hysterectomy and bilateral salpingoophorectomy (BSO) are active surveillance, pelvic radiotherapy, chemotherapy and hormonal therapy, alone or in combination. PATIENTS AND METHODS: Among 84 consecutive patients treated for ESS at a single referral center, 54 with localized stage disease were identified. Recurrence-free survival and overall survival were estimated and patterns of recurrences described. Univariate and multivariate analyses were carried out. RESULTS: With a median follow-up of 58 months, only one patient had died. None of the 23 patients who had received adjuvant therapy relapsed compared with 13 of 31 patients who had not received any adjuvant therapy. Adjuvant treatments were hormonal therapy (n = 10) and brachytherapy with/without pelvic radiotherapy (n = 13). Almost the majority of relapses were local (92%) and extra-pelvic metastasis was observed in nearly half of the patients (46%). In the multivariate analysis, the major determinants of relapse-free survival were adjuvant treatment, myometrial invasion (P = 0.005) and no BSO (P = 0.005). CONCLUSIONS: In this series, adjuvant treatment of localized ESSs was associated with the absence of recurrence.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Braquiterapia , Neoplasias Endometriales/terapia , Histerectomía , Recurrencia Local de Neoplasia/terapia , Neoplasias Pélvicas/terapia , Sarcoma Estromático Endometrial/terapia , Adulto , Anciano , Quimioterapia Adyuvante , Terapia Combinada , Neoplasias Endometriales/patología , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Neoplasias Pélvicas/secundario , Pronóstico , Radioterapia Adyuvante , Estudios Retrospectivos , Sarcoma Estromático Endometrial/patología , Tasa de Supervivencia
11.
Cytogenet Genome Res ; 124(1): 1-11, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19372663

RESUMEN

High-level amplifications observed in tumor cells are usually indicative of genes involved in oncogenesis. We report here a high resolution characterization of a new amplified region in the SW613-S carcinoma cell line. This cell line contains tumorigenic cells displaying high-level MYC amplification in the form of double minutes (DM(+) cells) and non tumorigenic cells exhibiting low-level MYC amplification in the form of homogeneously staining regions (DM(-) cells). Both cell types were studied at genomic and functional levels. The DM(+) cells display a second amplification, corresponding to the 14q24.1 region, in a distinct population of DMs. The 0.43-Mb amplified and overexpressed region contains the PLEK2, PIGH, ARG2, VTI1B, RDH11, and ZFYVE26 genes. Both amplicons were stably maintained upon in vitro and in vivo propagation. However, the 14q24.1 amplicon was not found in cells with high-level MYC amplification in the form of HSRs, either obtained after spontaneous integration of endogenous DM MYC copies or after transfection of DM(-) cells with a MYC gene expression vector. These HSR-bearing cells are highly tumorigenic. The 14q24.1 amplification may not play a role in malignancy per se but might contribute to maintaining the amplification in the form of DMs.


Asunto(s)
Neoplasias de la Mama/genética , Carcinoma/genética , Cromosomas Humanos Par 14 , Cromosomas Humanos Par 8 , Genes myc , Neoplasias de la Mama/patología , Línea Celular Tumoral , Aberraciones Cromosómicas , Cromosomas Artificiales Bacterianos , Células Clonales , Citogenética , ADN de Neoplasias , Femenino , Amplificación de Genes , Humanos , Hibridación Fluorescente in Situ , Hibridación de Ácido Nucleico , Valores de Referencia , Transcripción Genética
12.
Surg Endosc ; 23(2): 356-62, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18461389

RESUMEN

BACKGROUND: This study reviewed a 3-year experience with the implementation of laparoscopic gastrectomy at a community hospital. METHODS: A retrospective chart review identified all patients that underwent laparoscopic gastrectomy between January 2004 and March 2007. Patient demographics, tumor characteristics, length of stay, operative time, and short-term outcomes (postoperative complications and death) were examined. RESULTS: A total of 49 patients were identified; 25 (51%) were male. Median age was 68 years (range 31-90 years). Thirty-five (71%) and seven (14%) patients presented with adenocarcinoma and gastrointestinal stromal tumor (GIST), respectively. Median operative time was 169 min (range 23-387 min). Conversion to open laparotomy was necessary in six cases (12%). Median length of stay was 5 days (range 0-48 days). There were four (8.2%) postoperative deaths, and eight major complications, which included: myocardial infarction, pulmonary embolism, duodenal stump leak, bleeding, dehiscence, anastomotic leak, and obstruction. Of patients undergoing laparoscopic gastrectomy with curative intent, 36/38 (95%) underwent R0 resection. Median number of lymph nodes that were pathologically evaluated was 11 (range 1-27). CONCLUSION: To our knowledge, this is the first study to report on the implementation of laparoscopic gastrectomy in a community hospital setting. Laparoscopic gastrectomy can be performed safely in a community hospital setting with operative times and length of stay that are comparable to open cases. Our short-term outcomes are comparable with existing studies from academic/university centers.


Asunto(s)
Gastrectomía , Tumores del Estroma Gastrointestinal/cirugía , Cirugía General/organización & administración , Hospitales Comunitarios , Laparoscopía , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios de Factibilidad , Femenino , Tumores del Estroma Gastrointestinal/patología , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de Salud , Estudios Retrospectivos , Medición de Riesgo , Neoplasias Gástricas/patología
13.
Roum Arch Microbiol Immunol ; 68(1): 50-4, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19507628

RESUMEN

The purpose of this study was to evaluate the influence of different physico-chemical parameters on Escherichia coli susceptibility to ceftriaxone (CRO), cefotaxime (CTX), imipenem (IMP), and nalidixic acid (as marker for resistance by impermeability). The influence of chemical composition of culture medium was evaluated by the comparative assessment of inhibition growth diameters on different solid media: Mueller Hinton Medium (MH), Plate Count Agar Medium (PCA), MacConkey Medium (MC) and Eosin Methylen Blue Medium (EMB). In order to evaluate the differences in antibiotic susceptibility between the biofilm embedded and planktonic cells, an original, simple experimental model was used, by including the bacterial cells in an agar layer, mimicking the biofilm matrix. Our results demonstrated that the inhibition diameter zone was much larger on PCA, EMB and MC than on MH, considered as general standard medium for the antibiosusceptibility testings (CLSI). When bacterial cells were included in the agar matrix, the growth inhibition diameters obtained for different beta-lactams proved to be different of planktonic cells, i.e.: for CTX, a narrow inhibition diameter was obtained, demonstrating the low efficiency of this antibiotic in the treatment of biofilm associated infections, whereas the CRO proved the same efficiency against planktonic as well as to agar embedded bacteria. The different susceptibility results obtained for the cells embedded in the agar matrix by an adapted disk diffusion method are pleading for the necessity to assess new adapted standard methods and specific parameters in the purpose to determine the antibiotic resistance of bacterial cells isolated from biofilm associated infections.


Asunto(s)
Escherichia coli/efectos de los fármacos , Ácido Nalidíxico/farmacología , beta-Lactamas/farmacología , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Cefotaxima/farmacología , Ceftriaxona/farmacología , Fenómenos Químicos , Medios de Cultivo , Farmacorresistencia Bacteriana , Escherichia coli/fisiología , Imipenem/farmacología , Pruebas de Sensibilidad Microbiana
14.
Leukemia ; 21(5): 917-25, 2007 May.
Artículo en Inglés | MEDLINE | ID: mdl-17315025

RESUMEN

The BCR-ABL oncoprotein exhibits deregulated protein tyrosine kinase activity and is implicated in the pathogenesis of Philadelphia chromosome (Ph)-positive human leukemias. Here, we report that ectopic expression of p210(BCR-ABL) in the megakaryoblastic Mo7e cell line and in primary human CD34(+) progenitors trigger erythroid differentiation at the expense of megakaryocyte (MK) differentiation. Clonal culture of purified CD41(+)CD42(-) cells, a population highly enriched in MK progenitors, combined with the conditional expression of p210(BCR-ABL) tyrosine kinase activity by imatinib identified a true lineage reprogramming. In both Mo7e or CD41(+)CD42(-) cells transduced with p210(BCR-ABL), lineage switching was associated with a downregulation of the friend leukemia Integration 1 (FLI-1) transcription factor. Re-expression of FLI-1 in p210(BCR-ABL)-transduced Mo7e cells rescued the megakaryoblastic phenotype. Altogether, these results demonstrate that alteration of signal transduction via p210(BCR-ABL) reprograms MK cells into erythroid cells by a downregulation of FLI-1. In addition, our findings underscore the role of kinases in lineage choice and infidelity in pathology and suggest that downregulation of FLI-1 may have important implications in CML pathogenesis.


Asunto(s)
Células Eritroides/citología , Proteínas de Fusión bcr-abl/fisiología , Células Madre Hematopoyéticas/citología , Megacariocitos/citología , Receptor 1 de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Diferenciación Celular , Regulación hacia Abajo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Humanos , Transcripción Genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética
15.
Biofabrication ; 9(2): 025029, 2017 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-28462910

RESUMEN

We report on the fabrication of silicon-reinforced carbon (C:Si) structures by combinatorial pulsed laser deposition to search for the best design for a new generation of multi-functional coated implants. The synthesized films were characterized from the morphological, structural, compositional, mechanical and microbiological points of view. Scanning electron microscopy revealed the presence, on top of the deposited layers, of spheroid particulates with sizes in the micron range. No micro-cracks or delaminations were observed. Energy dispersive x-ray spectroscopy and grazing incidence x-ray diffraction pointed to the existence of a C to Si compositional gradient from one end of the film to the other. Raman investigation revealed a relatively high sp3 hybridization of up to 80% at 40-48 mm apart from the edge with higher C content. Si addition was demonstrated to significantly increase C:Si film bonding to the substrate, with values above the ISO threshold for coatings to be used in high-loading biomedical applications. Surface energy studies pointed to an increase in the hydrophilic character of the deposited structures along with Si content up to 52 mN m-1. In certain cases, the Si-reinforced C coatings elicited an antimicrobial biofilm action. The presence of Si was proven to be benign to HEp-2 cells of human origin, without interfering with their cellular cycle. On this basis, reliable C:Si structures with good adherence to the substrate and high efficiency against microbial biofilms can be developed for implant coatings and other advanced medical devices.


Asunto(s)
Tecnología Biomédica/métodos , Carbono/química , Materiales Biocompatibles Revestidos/química , Rayos Láser , Silicio/química , Ciclo Celular , Forma de la Célula , Humanos , Ensayo de Materiales , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Rastreo , Espectrometría por Rayos X , Espectrometría Raman , Propiedades de Superficie , Agua/química , Difracción de Rayos X
16.
Cancer Res ; 55(17): 3735-8, 1995 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-7543817

RESUMEN

Increased serum levels of human chorionic gonadotropin beta subunit (hCG beta) were described previously in patients with bladder cancer. To obtain insight into such production of hCG beta, the expression of hCG beta 7, 8, 5, and 3 genes in bladder carcinomas and normal urothelia was investigated by reverse transcription PCR. Surprisingly, hCG beta mRNAs were detected in both normal urothelial and carcinomatous cells. However, tumor progression was characterized by different patterns of transcription of the hCG beta genes; the beta 7 gene was the only gene transcribed in normal urothelia and Ta tumors included in this study, whereas in addition to beta 7, genes beta 5, 8, and 3 were transcribed in T1 to T4 tumors. Moreover, transcription levels of the latter three genes increased with the stage of the disease. These observations showed that dramatic modifications in the expression of hCG beta genes accompany progression of bladder carcinomas.


Asunto(s)
Biomarcadores de Tumor/análisis , Gonadotropina Coriónica/análisis , Fragmentos de Péptidos/análisis , ARN Mensajero/análisis , ARN Neoplásico/análisis , Neoplasias de la Vejiga Urinaria/genética , Secuencia de Bases , Biomarcadores de Tumor/genética , Gonadotropina Coriónica/genética , Gonadotropina Coriónica Humana de Subunidad beta , Humanos , Datos de Secuencia Molecular , Fragmentos de Péptidos/genética
17.
Cancer Res ; 57(3): 516-23, 1997 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-9012484

RESUMEN

The beta subunit of human chorionic gonadotropin (hCGbeta) is encoded by four nonallelic CGbeta genes. An assay was developed for distinguishing type I CGbeta allelic genes beta7 and beta6, which possess a GCC codon corresponding to an alanine at position 117 of hCGbeta, from type II CGbeta genes beta8, beta5, and beta3 and its allele beta9, which possess a GAC codon corresponding to an aspartic acid at the same position. In normal trophoblast, hCGbeta is encoded by type II CGbeta genes, whereas normal nontrophoblastic tissues of differing histological origin (breast, prostate, skeletal muscle, bladder, adrenal glands, thyroid, colon, and uterus) express only type I CGbeta genes. We studied the expression of CGbeta genes in 86 tumor specimens collected from patients with breast, bladder, prostate, and thyroid cancer and found that up to 61% of these nontrophoblastic tumors expressed type II CGbeta genes. Experiments performed on tumor tissues and their normal counterparts confirmed that the malignant transformation of nontrophoblastic cells is associated with the expression of type II CGbeta genes. These findings provide the basis for a simple test (the CG117 assay) that may be useful for the diagnosis of the most frequent malignancies.


Asunto(s)
Transformación Celular Neoplásica/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/genética , Trofoblastos/metabolismo , Línea Celular , Femenino , Expresión Génica , Humanos , Hormona Luteinizante/genética , Masculino , Biosíntesis de Proteínas , Transcripción Genética
18.
Chirurgia (Bucur) ; 101(5): 471-5, 2006.
Artículo en Inglés | MEDLINE | ID: mdl-17278637

RESUMEN

Cancer is a complex polygenic and multifactorial disease, resulting from successive dynamic changes in the genome of somatic cells and from the accumulation of molecular alterations in both tumour cells and host cells. For the majority of cancers, including many malignancies of the gastrointestinal tract, our current means of diagnosis and treatment of the tumors are grossly insufficient. In recent years the development of several gene expression profiling methods such as comparative genomic hybridization (CGH), differential display, serial analysis of gene expression (SAGE) and DNA arrays, together with the sequencing of the human genome, has provided an opportunity to monitor and investigate the complete cascade of molecular events leading to tumor development and progression. Given the central role played by surgeons in the current management of patients with solid cancers, it is of paramount importance for them to know the principles characterizing this laboratory tools to critically assess the results originating from this biotechnology. We describe in this article the scientific partnership between Fundeni Clinical Institute Bucharest, Romania and RNtech Company, Paris, France for the development of a center of biological resources (Biobank) as well as the standardized protocol of working with the biological samples, the ongoing projects and the future perspectives.


Asunto(s)
Neoplasias Gastrointestinales/genética , Bancos de Tejidos , Investigación Biomédica , Francia , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Hibridación de Ácido Nucleico , Análisis de Secuencia por Matrices de Oligonucleótidos , Rumanía
19.
Sci Rep ; 6: 38971, 2016 12 16.
Artículo en Inglés | MEDLINE | ID: mdl-27982114

RESUMEN

Stream ecosystems show gradual variation of various selection factors, which can result in a zonation of species distributions and gradient evolution of morphological and life-history traits within species. Identifying the selective agents underlying such phenotypic evolution is challenging as different species could show shared and/or unique (species-specific) responses to components of the river gradient. We studied a stream gradient inhabited by two mosquitofishes (genus Gambusia) in the Río Grijalva basin in southern Mexico and found a patchy distribution pattern of both congeners along a stretch of 100 km, whereby one species was usually dominant at a given site. We uncovered both shared and unique patterns of diversification: some components of the stream gradient, including differences in piscine predation pressure, drove shared patterns of phenotypic divergence, especially in females. Other components of the gradient, particularly abiotic factors (max. annual temperature and temperature range) resulted in unique patterns of divergence, especially in males. Our study highlights the complexity of selective regimes in stream ecosystems. It exemplifies that even closely related, congeneric species can respond in unique ways to the same components of the river gradient and shows how both sexes can exhibit quite different patterns of divergence in multivariate phenotypic character suites.


Asunto(s)
Ciprinodontiformes/fisiología , Fenotipo , Animales , Femenino , Masculino , Especificidad de la Especie
20.
New Microbes New Infect ; 13: 87-8, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27547405

RESUMEN

This is the first report of an OXA-72-producing Acinetobacter baumannii strain in Romania, isolated from chronic leg ulcer samples. Identification of the strain was performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Presence of carbapenem resistance genes was investigated by PCR and sequencing. Our data support the spread of the bla OXA-72 gene in Eastern Europe.

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