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1.
Nat Commun ; 14(1): 1970, 2023 04 08.
Article in English | MEDLINE | ID: mdl-37031257

ABSTRACT

Adeno-associated virus (AAV)-based gene therapy could be facilitated by the development of molecular switches to control the magnitude and timing of expression of therapeutic transgenes. RNA interference (RNAi)-based approaches hold unique potential as a clinically proven modality to pharmacologically regulate AAV gene dosage in a sequence-specific manner. We present a generalizable RNAi-based rheostat wherein hepatocyte-directed AAV transgene expression is silenced using the clinically validated modality of chemically modified small interfering RNA (siRNA) conjugates or vectorized co-expression of short hairpin RNA (shRNA). For transgene induction, we employ REVERSIR technology, a synthetic high-affinity oligonucleotide complementary to the siRNA or shRNA guide strand to reverse RNAi activity and rapidly recover transgene expression. For potential clinical development, we report potent and specific siRNA sequences that may allow selective regulation of transgenes while minimizing unintended off-target effects. Our results establish a conceptual framework for RNAi-based regulatory switches with potential for infrequent dosing in clinical settings to dynamically modulate expression of virally-delivered gene therapies.


Subject(s)
Dependovirus , Genetic Therapy , RNA Interference , Dependovirus/genetics , Dependovirus/metabolism , RNA, Small Interfering/metabolism , Transgenes , RNA, Double-Stranded , Genetic Vectors/genetics
2.
Biofouling ; 33(4): 336-351, 2017 04.
Article in English | MEDLINE | ID: mdl-28403635

ABSTRACT

The one-domain approach (ODA) was used as an alternative to solve fluid-biofilm interfacial behavior in a 2-D model for diffusion-reaction-convection coupled with prediction of irregular growth of biofilms via a cellular automaton strategy. The simulations exhibited errors of <7% compared with the porosity of a previously reported capillary experimental system. Additionally, biofilm surface geometrical aspects were satisfactorily compared with reports of experimental and similar rigorously simulated benchmark systems. The method developed was applied to simulate typical biofilm systems predicting recirculation flow patterns, interface concentration profiles, and clogging of the inlet section of the capillary tube, which are phenomena that affect the efficiency of diverse biotechnological applications, including membrane bioreactors and biofilters. The ODA method applied to the governing equations of momentum and mass transfer combined with a cellular automaton algorithm is a suitable and straightforward approach for modeling solid-state fermentation at different sophistication levels.


Subject(s)
Biofilms/growth & development , Models, Theoretical , Algorithms , Bioreactors/microbiology , Biotechnology/methods , Diffusion , Porosity , Surface Properties
3.
Support Care Cancer ; 23(1): 169-75, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25035064

ABSTRACT

PURPOSE: The objectives of this study were to electromyographically (EMG) describe and analyze factors associated with long thoracic nerve injuries in breast cancer patients after axillary lymph node dissection. METHODS: This was a prospective longitudinal observational study. Two hundred sixty-four women with primary invasive breast cancer were included between 2008 and 2011. All of them were treated by axillary lymph node dissection. Patients were evaluated at 1, 6, and 12 months following surgery. The presence of winged scapula was systematically tested at each follow-up and an EMG performed whenever it was observed. Affected and unaffected groups were compared for demographic, tumour, and treatment variables. Student t test, Mann-Whitney U test, chi-squared or Fisher test were computed as appropriate. RESULTS: Among the 36 (13.6%) winged scapula observed, the EMG confirmed long thoracic nerve injury in 30 (11.3%) of them, 27 were partial axonotmesis and three were severe axonotmesis. At 12 months, the EMG showed that injury persisted in six (2.27%) patients. Patients with long thoracic nerve injury had a lower body mass index than unaffected patients (26.2 vs. 28.2, p = 0.045). Age, tumour stage, type of breast surgery, nodes excised, surgical complications, previous chemotherapy and previous hormonotherapy were not factors associated with winged scapula. CONCLUSIONS: A lower body mass index was the only factor associated to long thoracic nerve injury. In most of the patients, the EMG showed partial axonotmesis. At 12 months, 2.27% of studied patients remained with an unsolved long thoracic nerve injury.


Subject(s)
Breast Neoplasms/pathology , Lymph Node Excision/adverse effects , Lymph Nodes/surgery , Thoracic Nerves/injuries , Aged , Axilla , Body Mass Index , Electromyography , Female , Humans , Longitudinal Studies , Lymphatic Metastasis , Mastectomy , Middle Aged , Prospective Studies , Scapula/abnormalities
4.
Arch Gerontol Geriatr ; 59(1): 39-43, 2014.
Article in English | MEDLINE | ID: mdl-24726179

ABSTRACT

Sarcopenia is the loss of muscle mass and strength, which in the elderly can result in disability and affect functional outcomes after hospitalization. The aim of this study was to evaluate the functional outcomes and mortality during hospitalization and at three months post-discharge, according to the presence of sarcopenia. Prospective study of 99 patients (38.4% men, aged 84.6) admitted in a subacute geriatric care unit who underwent a rehabilitation intervention. Main outcomes were mortality and functional improvement at discharge and at three-month follow-up. Sarcopenia was assessed by handgrip strength (hydraulic dynamometer) and by body composition bioimpedance. Forty-six (46.5%) patients met diagnostic criteria of sarcopenia. Patients with sarcopenia had a worse prior functional status than those without the condition (Barthel Index: 64.2±22.8 vs 73.3±21.8; p=0.04) but both groups had similar functional decline at admission (Barthel Index: 24±15.1 vs 28.5±15.2; p=0.1) and achieved similar functional improvement at discharge (20.4±18.3 vs 27.4±21; p=0.08). Barthel Index at discharge remained comparatively worse in patients with sarcopenia (44.2±26.6 vs 55.9±26.7; p=0.03). After completing a 3-month at-home rehabilitation program, no changes in functional capacity were observed in patients with sarcopenia; their peers improved their Barthel Index scores (45.5±24.8 vs 61.6±26.6; p=0.007). Mortality rates at 3-month follow-up did not differ between groups. In conclusion, patients with sarcopenia had a worse functional status, similar functional improvement during hospitalization and a lack of recovery after returning home. Further studies are needed to establish long-terms effects on mortality.


Subject(s)
Geriatric Assessment , Recovery of Function , Sarcopenia/physiopathology , Subacute Care , Aged , Aged, 80 and over , Comorbidity , Female , Follow-Up Studies , Hand Strength/physiology , Humans , Length of Stay/statistics & numerical data , Male , Patient Compliance , Prospective Studies , Sarcopenia/mortality , Sarcopenia/rehabilitation , Spain
5.
Int Urol Nephrol ; 44(5): 1369-74, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22648292

ABSTRACT

PURPOSE: Areas of lower enhancement on computed tomography are frequently seen in renal-cell carcinoma. We investigated whether tumor enhancement on the most prominent hypodense areas correlates with the nuclear grade and other pathologic variables. METHODS: From 2004 to 2009, all consecutive patients with a preoperative tomography who underwent radical or partial nephrectomy for renal-cell carcinoma at our tertiary referral center were retrospectively analyzed. Enhancement of the entire tumor on the slice with most prominent areas of lower enhancement was determined. RESULTS: Forty-eight patients were included. Clear-cell carcinoma comprised 91.6 %. Mean areas of lower enhancement for nuclear grade tumors 1-4 were 67.4, 38.7, 27.9, and 15.1 HU, respectively. Areas of lower enhancement negatively correlated with size, nuclear grade, T stage, and pathological stage. Tumors with extension beyond Gerota's fascia (10.5 vs. 35.9 HU, p < 0.001) and positive surgical margins (21.2 vs. 34.8 HU, p = 0.04) had more prominent areas of lower enhancement than organ-confined tumors. When comparing nuclear grade 1-3 to nuclear grade 4 tumors, these areas were significantly lower in the later (36.5 vs. 15.1 HU, p < 0.001). Receiver-operating characteristics curves for detecting nuclear grade 4 showed an area under the curve of 0.808 (95 % CI 0.659-0.957). CONCLUSIONS: Lower enhancement of the entire tumor at the point where hypodense tumor areas are more predominant on tomography is associated with higher nuclear grade and more advanced stage.


Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Tomography, X-Ray Computed , Area Under Curve , Carcinoma, Renal Cell/surgery , Contrast Media , Female , Humans , Kidney Neoplasms/surgery , Male , Neoplasm Grading , Neoplasm Staging , Nephrectomy , Population Surveillance , ROC Curve , Radiographic Image Enhancement , Retrospective Studies , Statistics, Nonparametric
6.
Urol Int ; 85(1): 23-9, 2010.
Article in English | MEDLINE | ID: mdl-20693824

ABSTRACT

INTRODUCTION: The application of current prognosticators in locally advanced nonmetastatic renal cell carcinoma (RCC) is controversial. We analyzed the impact of clinical and pathological variables on the survival of this subset of patients. PATIENTS AND METHODS: We studied patients with RCC in stages III and IV without metastases, treated surgically between 1980 and 2009. We calculated disease-free (DFS) and cancer-specific survival (CSS), and the relation of clinical and pathological variables with these end-points. RESULTS: We identified 126 patients with locally advanced RCC; 8.7% had sarcomatoid differentiation. Tumor stage was pT3a in 48% and pT3b in 42%; 11.9% had lymph node invasion (N+). Patients with N- and N+ had a 10-year DFS of 49.0 and 23.4%, respectively (p = 0.0001). In multivariate analysis N+ (p = 0.0002) was the strongest predictor of DFS. The 10-year CSS of patients without sarcomatoid differentiation was 53.1% while those with sarcomatoid differentiation did not reach the median time to death (p < 0.0001). In multivariate analysis, sarcomatoid differentiation (p = 0.01) was the strongest predictor of CSS. CONCLUSIONS: Locally advanced RCC portends poor prognosis. Preoperatively, weight loss and Eastern Cooperative Oncology Group performance status are predictors of recurrence and mortality, respectively. However, the most powerful predictors of DFS and CSS in our cohort were lymph node status and sarcomatoid differentiation.


Subject(s)
Carcinoma, Renal Cell/mortality , Carcinoma, Renal Cell/pathology , Cell Differentiation , Kidney Neoplasms/mortality , Kidney Neoplasms/pathology , Lymph Nodes/pathology , Adult , Aged , Aged, 80 and over , Carcinoma, Renal Cell/surgery , Chemotherapy, Adjuvant , Chi-Square Distribution , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Kidney Neoplasms/surgery , Lymphatic Metastasis , Male , Mexico , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Nephrectomy , Proportional Hazards Models , Risk Assessment , Risk Factors , Survival Rate , Time Factors , Treatment Outcome
7.
Univ. sci ; 15(2): 130-138, mayo-ago. 2010. tab
Article in Spanish | LILACS-Express | LILACS | ID: lil-637342

ABSTRACT

Objetivo. Establecer si existe relación entre el tipo y la cantidad de carbohidratos dietarios consumidos habitualmente con los niveles plasmáticos de lípidos, lipoproteínas y apolipoproteína B100 (ApoB100) Materiales y métodos. La muestra estuvo conformada por la base de datos de 144 de profesores de la Universidad Javeriana que previamente hicieron parte de otra investigación y de la cual se empleo la información sobre su alimentación, niveles plasmáticos de lípidos, lipoproteínas y ApoB100. Para determinar la relación entre las variables dependientes e independientes se realizó análisis de correlación simple y múltiple, en los casos de no correlación, se aplicó la prueba Chi² de independencia para relacionar el consumo de carbohidratos totales, azúcares y fibra total. Adicionalmente el análisis de varianza de un factor comparó los niveles de lípidos, lipoproteínas y ApoB100 con el consumo de carbohidratos totales, azúcares y fibra. Resultados. 76 hombres y 68 mujeres. La mayor parte de la población consume por encima de la recomendación diaria de carbohidratos totales, los hombres presentaron mayor consumo de carbohidratos tipo azúcares y más elevados los niveles plasmáticos de triglicéridos y lipoproteínas de muy baja densidad (VLDL), mientras que mujeres presentaron niveles más elevados en sus lipoproteínas de alta densidad (HDL). Al relacionar gramos de cada tipo de carbohidratos, con los niveles de lípidos, lipoproteínas y ApoB100 no se encontró correlación significativa para ninguno de los casos (p>0,05). Conclusión. No se encontró relación significativa entre el tipo y la cantidad de carbohidratos consumidos con los niveles plasmáticos de lípidos, lipoproteínas y ApoB100.


Objective. To establish if there is any relationship between the type and amount of dietary carbohydrates commonly consumed and the plasmatic levels of lipids, lipoproteins and apolipoprotein B100 (ApoB100). Materials and methods. The final sample was conformed by the database of 144 lecturers of the Pontificia Universidad Javeriana who had previously participated in another survey and from which we used information on their food habits, plasmatic lipid levels, lipoproteins and ApoB100. To determine the relationship between the dependent and independent variables, simple and multiple correlation analyses were done. In the cases of no correlation we applied the independence Chi² test to find the relationship with the consumption of total carbohydrates, sugars and total fiber. Additionally, with a one-factor analysis of variance we compared plasmatic levels of lipids, lipoproteins and ApoB100 with the consumption of total carbohydrates, sugars and fiber. Results. Most of the population consumes above the daily total carbohydrate recommendation, men presented greater carbohydrate consumption of the type of sugars and more elevated plasmatic levels of triglycerides and lipoproteins of investivery low density (VLDL), whereas women presented higher levels of their high density lipoproteins (HDL). When relating grams of each type of carbohydrates with the levels of lipids, lipoproteins and ApoB100, no significant correlation was found for any of the cases (p>0,05). Conclusion. There was no significant relationship between the type and amount of carbohydrates consumed with the plasmatic levels of lipids, lipoproteins and Apo B100.


Objetivo. Estabelecer a possível relação entre o tipo e a quantidade de carboidratos na dieta normalmente consumida com os níveis plasmáticos de lipídios, lipoproteínas e apolipoproteína B100 (ApoB100). Materiais e métodos. A amostra consistiu de um banco de dados de 144 professores da "Universidad Javeriana" que anteriormente fizeram parte de outra pesquisa, e da qual foi utilizada a informação sobre sua alimentação, os níveis plasmáticos de lipídios, lipoproteínas e ApoB100. Para determinar a relação entre as variáveis dependentes e independentes foi realizada uma análise de correlação simples e múltipla, em casos de ausência de correlação foi usado o teste do Chi² de independência para relacionar o consumo dos carboidratos totais, açúcares e fibra total. Além disso, a análise de variância de um fator comparou os níveis de lipídios, lipoproteínas e ApoB100 com o consumo de carboidratos totais, açúcares e fibras. Resultados. 76 homens e 68 mulheres. A maior parte da população consome acima da dose diária recomendada de carboidratos totais, os homens apresentaram maior consumo de carboidratos tipo açúcares, e mais elevados os níveis plasmáticos de triglicérides e lipoproteínas de muito baixa densidade (VLDL), enquanto que as mulheres apresentaram níveis mais elevados em lipoproteína de alta densidade (HDL). Ao relacionar gramas de cada tipo de carboidratos com os níveis de lipídios, lipoproteínas e ApoB100, nenhuma correlação significativa foi encontrada para qualquer um dos casos (p> 0,05). Conclusão. Nenhuma relação significativa foi encontrada entre o tipo e a quantidade de carboidratos consumida com os níveis plasmáticos de lipídios, lipoproteínas e ApoB100.

8.
Transfusion ; 48(12): 2540-8, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18680546

ABSTRACT

BACKGROUND: False-positive results for hepatitis C virus antibody (anti-HCV) occur with unacceptable frequency in low-prevalence populations. The purpose of the study was to determine whether signal-to-cutoff (S/CO) ratios of anti-HCV assay-reactive samples could be used to discriminate false-positive from true-positive anti-HCV results and avoid the need for supplemental testing. STUDY DESIGN AND METHODS: Using receiver-operating characteristic curve, the cutoff point that identifies the major proportion (>/=95%) of false-positive results, with a minor proportion (<5%) of true-positive anti-HCV results, was determined. An anti-HCV assay (VITROS, Ortho Clinical Diagnostics) was used to detect the antibodies. The third-generation recombinant immunoblot assay and HCV RNA tests were performed on all included donors. Third-generation RIBA is the gold standard for identifying false-positive antibody results. RESULTS: A total of 649 anti-HCV-positive blood donors were identified. A S/CO ratio of less than 4.5, defining very low levels in this value, was the optimal cutoff point to identify false-positive results; 315 of 322 samples with very low levels were false-positive anti-HCV results (97.8%; 95% confidence interval [CI], 95.8%-99.0%) and 7 were true-positive (2.2%; 95% CI, 1.0%-4.3%). Viremia was detected in none of them. A direct relationship was observed between positive supplemental testing and increased antibody levels in the other 327 samples. CONCLUSION: The high prediction rate of false-positive anti-HCV results using very low levels by the Ortho VITROS anti-HCV assay safely avoids the need for supplemental testing.


Subject(s)
Hepatitis C Antibodies/blood , Adult , False Positive Reactions , Female , Hepatitis C Antibodies/immunology , Humans , Male
9.
Life Sci ; 78(3): 279-83, 2005 Dec 05.
Article in English | MEDLINE | ID: mdl-16183081

ABSTRACT

Autologous transplant of bone marrow stem cells (BMSC), although extremely useful after acute myocardial events, has not been evaluated in patients with old (>one-year-old) myocardial infarction. Our aim was to determine if CD34(+)-enriched peripheral-blood cells, obtained by apheresis, injected directly into the severely damaged myocardium of five patients with old myocardial infarction could restore depressed myocardial function. We found that 28 weeks after revascularization and peri-infarction injection of the enriched CD34(+) peripheral mononuclear cells, ventricular hemodynamic parameters that included left ventricular ejection fraction, left ventricular diastolic volume, ventricular systolic volume and left ventricular diastolic diameter approximated normal values and there was no restenosis; two patients have been followed for >52 weeks and their parameters are within normal values. In conclusion, intramyocardial injection of easily obtained CD34(+) enriched peripheral blood cells represent an encouraging procedure for patients with severely scarred and dysfunctional myocardium.


Subject(s)
Bone Marrow Cells/cytology , Granulocyte Colony-Stimulating Factor/therapeutic use , Hematopoietic Stem Cell Transplantation , Myocardial Infarction/surgery , Adult , Antigens, CD34/metabolism , Bone Marrow Cells/drug effects , Bone Marrow Cells/metabolism , Filgrastim , Granulocyte Colony-Stimulating Factor/administration & dosage , Heart/diagnostic imaging , Hematopoietic Stem Cell Mobilization , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Myocardial Infarction/diagnostic imaging , Myocardial Infarction/physiopathology , Myocardial Revascularization , Radionuclide Imaging , Recombinant Proteins , Time Factors , Transplantation, Autologous , Treatment Outcome , Ventricular Function, Left
10.
NOVA publ. cient ; 3(3): 31-36, ene.-jun. 2005. ilus, tab, graf
Article in Spanish | LILACS | ID: lil-438603

ABSTRACT

El objetivo del presente trabajo fue estudiar el efecto del polimorfismo genético de la Apolipoproteína E ApoE) sobre los niveles plasmáticos de lípidos y lipoproteínas en una cohorte de 200 individuos adultos sanos (20-65 años) residentes en Bogotá D.C. La frecuencia de los alelos de la Apo E fue 0.05 para el alelo e2; 0.87 para el e3 y 0.08 para el alelo e4. Los individuos se clasificaron de acuerdo al genotipo de la ApoE en:E3/2, E3/3, E4/3, E4/4 y E4/2, el genotipo de mayor frecuencia fue el E3/3 (77.1)porciento Al comparar lacolesterolemia entre los sujetos E3/2, E3/3 y E4/3 se observaron niveles incrementados significativamente(p<0.05) en el grupo E4/3 (172.1±16.9) comparados con los del grupo E3/2 (148.7±32.1). Los niveles detriglicéridos presentaron una tendencia hacia niveles más altos en los individuos con genotipo Apo E4/3 alcómpralos con E3/3 y E3/2. En la población estudiada, el polimorfismo de la ApoE es un importante determinante genético de los niveles plasmáticos de lípidos y lipoproteínas, es así como la presencia del alelo e4 dela Apo E puede influir en el incremento de los niveles de colesterol total, colesterol-LDL y triglicéridos siendo un factor de riesgo de enfermedad cardiovascular


Subject(s)
Humans , Adult , Polymorphism, Genetic/genetics , Polymorphism, Genetic/immunology , Lipids/analysis
11.
Rev. invest. clín ; 57(2): 156-162, mar.-abr. 2005. ilus, tab
Article in Spanish | LILACS | ID: lil-632500

ABSTRACT

Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, differents cellular lines such as cardiomyocites, sheletal myoblast, embryonic stem cells and adult mesenchymal stem cells has been used, resulting in an improvement in ventricular function and decrease in amount of infarted tissue. The first three cells line have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, prior to stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation metods in infarted myocardial tissue.


El infarto del miocardio es la principal causa de falla cardiaca y muerte en países industrializados. A la fecha, la cardiomioplastia celular ha emergido como una alternativa en la regeneración de infartos miocárdicos. En modelos animales se han utilizado diferentes líneas celulares como cardiomiocitos fetales, mioblastos de músculo esquelético, células tallo embrionarias y células tallo mesenquimales del adulto, con mejoría en la función ventricular y disminución del área de tejido infartado. Las tres primeras líneas celulares tienen desventajas porque son alogénicas y difíciles de obtener. Las células tallo mesenquimales del adulto son autólogas y se pueden obtener de aspirados de médula ósea o de la circulación periférica previa estimulación con citocinas (G-CSF). La implantación de estas células en seres humanos con infartos del miocardio recientes y antiguos han mostrado mejorías similares a los reportes con modelos animales. Estos hallazgos alientan a continuar la investigación clínica y básica en busca de los mecanismos de diferenciación celular y selección de vías de implantación, en tejido miocárdico infartado.


Subject(s)
Animals , Humans , Mesenchymal Stem Cell Transplantation , Myocardial Infarction/surgery , Cell Differentiation , Clinical Trials as Topic , Granulocyte Colony-Stimulating Factor/pharmacology , Growth Substances/pharmacology , Hematopoietic Stem Cell Mobilization , Models, Cardiovascular , Myocardial Infarction/pathology , Myocytes, Cardiac/cytology , Stem Cells/classification , Transplantation, Autologous
12.
Rev Invest Clin ; 57(2): 156-62, 2005.
Article in Spanish | MEDLINE | ID: mdl-16524054

ABSTRACT

Myocardial infarction is the leading cause of congestive heart failure and death in industrializated countries. The cellular cardiomyoplasty has emerged as an alternative treatment in the regeneration of infarted myocardial tissue. In animals' models, different cellular lines such as cardiomyocites, skeletal myoblasts, embryonic stem cells and adult mesenchymal stem cells have been used, resulting in an improvement in ventricular function and decrease in amount of infarcted tissue. The first three cells lines have disvantages as they are allogenics and are difficult to obtain. The adult mesenchymal stem cells are autologous and can be obtained throught the aspiration of bone marrow or from peripherical circulation, after stimulating with cytokines (G-CSF). The implantation in humans with recent and old myocardial infarction have shown improvements similar to those shown in animal models. These findings encourage the continued investigation in the mechanism of cellular differentiation and implantation methods in infarcted myocardial tissue.


Subject(s)
Mesenchymal Stem Cell Transplantation , Myocardial Infarction/surgery , Animals , Cell Differentiation , Clinical Trials as Topic , Granulocyte Colony-Stimulating Factor/pharmacology , Growth Substances/pharmacology , Hematopoietic Stem Cell Mobilization , Humans , Models, Cardiovascular , Myocardial Infarction/pathology , Myocytes, Cardiac/cytology , Stem Cells/classification , Transplantation, Autologous
13.
Haematologica ; 89(3): 365-6, 2004 Mar.
Article in English | MEDLINE | ID: mdl-15020281

ABSTRACT

We evaluated the impact of adding dexamethasone before chemotherapy in 95 children with de novo standard-risk acute lymphoblastic leukemia (ALL). The children were randomly divided into 2 groups: one group was given dexamethasone, the other was not. The initial characteristics and mean follow-up of both groups were similar. Day +14 blast percentage was significantly lower in the dexamethasone group. Disease-free survival at 40-months follow-up was better (almost significantly so) in the dexamethasone group.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Dexamethasone/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Child , Drug Administration Schedule , Female , Humans , Male , Remission Induction
14.
Plant Physiol ; 134(1): 18-27, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14730060

ABSTRACT

To monitor the expression of T-DNA-tagged plant genes in vivo, a collection of 20,261 transgenic lines of Arabidopsis (Columbia-0) were generated with the promoter trap vector pTluc, which carries a promoterless firefly luc (luciferase) reporter gene linked to the right T-DNA border. By detection of bioluminescence in 3-week-old seedlings, 753 lines were identified showing constitutive, organ-specific, and stress-responsive luciferase expression patterns. To facilitate the identification of well-defined luciferase expression patterns, a pooled seed stock was established. Several lines showed sugar, salt, and abscisic acid (ABA)-inducible luciferase activity. Segregation analysis of 215 promoter trap lines indicated that about 50% of plants contained single insertions, whereas 40% carried two and 10% carried three or more T-DNA tags. Sequencing the T-DNA insert junctions isolated from 17 luciferase-expressing lines identified T-DNA tags in 5'- and 3'-transcribed domains and translational gene fusions generated by T-DNA insertions in exons and introns of Arabidopsis genes. Tissue specific expression of eight wild-type Arabidopsis genes was confirmed to be similar to the luminescence patterns observed in the corresponding luciferase-tagged lines. Here, we describe the characterization of a transcriptional luc reporter gene fusion with the WBC-type ABC transporter gene At1g17840. Expression of wild-type and luciferase-tagged At1g17840 alleles revealed similar induction by salt, glucose, and ABA treatments and gibberellin-mediated down-regulation of ABA-induced expression. These results illustrate that luciferase gene traps are well suited for monitoring the expression of stress-responsive Arabidopsis genes in vivo.


Subject(s)
Arabidopsis/genetics , Luciferases/genetics , Animals , Artificial Gene Fusion , Base Sequence , Coleoptera/enzymology , Coleoptera/genetics , DNA, Bacterial/genetics , Gene Expression , Genes, Plant , Genes, Reporter , Genetic Vectors , Molecular Sequence Data , Plants, Genetically Modified , Promoter Regions, Genetic , Recombinant Proteins/genetics
15.
Plant J ; 32(2): 233-42, 2002 Oct.
Article in English | MEDLINE | ID: mdl-12383088

ABSTRACT

Induction of knockout mutations by T-DNA insertion mutagenesis is widely used in studies of plant gene functions. To assess the efficiency of this genetic approach, we have sequenced PCR amplified junctions of 1000 T-DNA insertions and analysed their distribution in the Arabidopsis genome. Map positions of 973 tags could be determined unequivocally, indicating that the majority of T-DNA insertions landed in chromosomal domains of high gene density. Only 4.7% of insertions were found in interspersed, centromeric, telomeric and rDNA repeats, whereas 0.6% of sequenced tags identified chromosomally integrated segments of organellar DNAs. 35.4% of T-DNAs were localized in intervals flanked by ATG and stop codons of predicted genes, showing a distribution of 62.2% in exons and 37.8% in introns. The frequency of T-DNA tags in coding and intergenic regions showed a good correlation with the predicted size distribution of these sequences in the genome. However, the frequency of T-DNA insertions in 3'- and 5'-regulatory regions of genes, corresponding to 300 bp intervals 3' downstream of stop and 5' upstream of ATG codons, was 1.7-2.3-fold higher than in any similar interval elsewhere in the genome. The additive frequency of insertions in 5'-regulatory regions and coding domains provided an estimate for the mutation rate, suggesting that 47.8% of mapped T-DNA tags induced knockout mutations in Arabidopsis.


Subject(s)
Arabidopsis/genetics , DNA, Bacterial/genetics , Genome, Plant , Sequence Tagged Sites , Algorithms , Binding Sites/genetics , DNA Mutational Analysis/methods , DNA, Intergenic/genetics , DNA, Plant/chemistry , DNA, Plant/genetics , Models, Genetic , Mutagenesis, Insertional , Mutation , Regulatory Sequences, Nucleic Acid/genetics
16.
Acta méd. colomb ; 27(3): 151-157, mayo-jun. 2002. graf
Article in Spanish | LILACS | ID: lil-358265

ABSTRACT

Objetivo: esta investigación tuvo como objetivo la determinación de los niveles de lipoproteína (a) (Lp(a)) y perfil lipídico en un grupo de individuos sanos. Material y métodos: Doscientos sujetos aparentemente sanos seleccionados al azar (hombres n=78; mujeres n=122) residentes en Bogotá O.C. a los cuales se les determinó colesterol total (Klosses y Shumberger, Lab. Bayer), triglicéridos (Wahlefildwl, Lab. Bayer S.A.), colesterol HDL (Finley, Warnik, Lab. Bayer S.A.), colesterol LDL (Burstein y Samoillee, Lab. Bayer S.A.), apo Al y B (Brustolini D y Maiernam M, por métodos enzimáticos colorimétricos; la Lp(a) por nefelometría y las apoproteínas por turbidimetría. Resultados: los resultados no mostraron una relación directa entre el perfil lipídico y los niveles de Lp(a), observándose que esta es un factor de riesgo independiente que puede inducir enfermedad cardiovascular. Este estudio permitió clasificar los individuos en cuatro grupos según la frecuencia de la distribución de la Lp(a) mostrando que el 85 por ciento exhibían valores < 26 mg/dL. Conclusiones: probabilísticamente se encontró que valores superiores pueden convertirse eventualmente en un factor de riesgo, o por lo menos de alerta, para enfermedad cardiovascular en la población bogotana.


Subject(s)
Heart Diseases , Lipoproteins/analysis , Risk Factors
17.
Acta méd. colomb ; 26(4): 143-148, jul.-ago. 2001. tab, graf
Article in Spanish | LILACS | ID: lil-358372

ABSTRACT

La artritis reumatoidea (AR) es una enfermedad sistémica caracterizada por la inflamación crónica y simétrica de las articulaciones. Los radicales libres son moléculas que podrían intervenir en el proceso inflamatorio articular y sistémico. El sistema antioxidante es un conjunto de sustancias que impiden la formación de radicales libres. Objetivo: determinar la actividad de dos sustancias antioxidantes, la glutatión peroxidasa (GpX) y la superóxido dismutasa (SOD) en pacientes con AR y en controles sanos. Material y métodos: se incluyeron 60 individuos de ambos sexos entre 30 y 60 años, divididos en tres grupos de 20 personas, uno constituido por pacientes con AR activa, otro por pacientes con AR en remisión (según los criterios de remisión de Pinals) y el tercero por controles sanos apareados por sexo y edad con el grupo de pacientes con AR activa. En los dos grupos de pacientes con AR se realizó un recuento de articulaciones inflamadas utilizando el índice articular de Thompson (0= ninguna articulación inflamada; 534= puntaje máximo de inflamación). Se midieron la proteína C reactiva (POR) y la velocidad de sedimentación globular (VSG) en todos los sujetos del estudio. Se realizó la medición en sangre total de SOD (rango normal =164-240 U/ml) y de GpX (rango normal = 4170-10881 U/L) en los tres grupos. Método estadístico: se calcularon los valores p de la prueba t de diferencias de medias poblacionales entre los tres grupos para la SOD, la GpX, la PCR y la VSG. Resultados: el puntaje promedio del índice de Thompson en los pacientes con AR activa fue de 177.5 y en el grupo en remisión fue de 5.5. El nivel promedio de GpX en los individuos sanos (X=6991.5 U/L) y en los pacientes con AR en remisión (X=5703.4 U/L) se encontró dentro de los valores de referencia. En el grupo de AR activa se encontró disminuido de manera significativa (X=2847 U/L) si se compara con el grupo de AR en remisión (p=0.008) y con el de controles sanos (p=4.7 x 105). Para la SOD se encontraron resultados similares en el grupo de sanos (X=212.5 U/ml) y el grupo de pacientes en remisión (205.6 U/ml...


Subject(s)
Antioxidants , Arthritis, Rheumatoid
20.
Rev. colomb. cardiol ; 6(3): 135-40, feb. 1998. tab
Article in Spanish | LILACS | ID: lil-219508

ABSTRACT

El estudio tuvo como propósito evaluar el efecto del consumo frecuente de carne de cerdo tecnificado sobre los niveles de lípidos séricos en adultos sanos. Se seleccionó un grupo de 54 individuos de ambos sexos, entre 18 y 55 años, con índice de masa corporal (IMC) normal y sin antecedentes de enfermedad cardíaca, hepática o renal. Se realizó la valoración nutricional por antropometría, el análisis de consumo de alimentos y el perfil lipídico. Después de consumir 100 gramos de carne de cerdo 3 veces por semana durante un mes, se llevó a cabo una segunda valoración nutricional y determinación del perfil lipídico. Al comparar los datos iniciales con los finales, se encontró que sólo en las mujeres disminuyó en forma estadísticamente significativa el IMC (p=0.0084), y los niveles de colesterol HDL (p<0.0067). Por otro lado en ambos sexos los niveles séricos de colesterol total disminuyeron, mientras que los niveles de triglicéridos aumentaron. Los niveles de colesterol LDL descendieron en los hombres y aumentaron en las mujeres. Estas variaciones no fueron estadísticamente significativas. En conclusión, el consumo de carne de cerdo tecnificado tres veces por semana durante un mes no eleva los niveles séricos de colesterol total, aunque en las mujeres se observó una disminución del colesterol HDL


Subject(s)
Humans , Male , Female , Lipids/blood , Meat , Cholesterol/blood , Swine
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