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1.
Ultrasound Obstet Gynecol ; 55(2): 157-169, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31479546

RESUMEN

OBJECTIVE: To perform a meta-analysis and meta-regression of randomized controlled trials (RCTs) to evaluate the impact of low-dose aspirin (LDA) on perinatal outcome, independent of its effect on pre-eclampsia (PE), preterm birth and low birth weight. METHODS: An electronic search of EMBASE, PubMed, CENTRAL, PROSPERO and Google Scholar databases was performed to identify RCTs assessing the impact of LDA in pregnancy, published in English prior to May 2019, which reported perinatal outcomes of interest (placental abruption, delivery mode, low 5-min Apgar score, neonatal acidosis, neonatal intensive care unit admission, periventricular hemorrhage and perinatal death). Risk ratios (RR) and 95% CI were calculated and pooled for analysis. Analysis was stratified according to gestational age at commencement of treatment (≤ 16 weeks vs > 16 weeks) and subgroup analysis was performed to assess the impact of aspirin dose (< 100 mg vs ≥ 100 mg). Meta-regression was used to assess the impact of LDA on perinatal outcome, independent of the reduction in PE, preterm birth and low birth weight. RESULTS: Forty studies involving 34 807 participants were included. When LDA was commenced ≤ 16 weeks' gestation, it was associated with a significant reduction in the risk of perinatal death (RR, 0.47; 95% CI, 0.25-0.88; P = 0.02; number needed to treat, 92); however, this risk reduction was only seen when a daily dose of ≥ 100 mg was administered. If commenced > 16 weeks' gestation, LDA was associated with a significant reduction in 5-min Apgar score < 7 (RR, 0.75; 95% CI, 0.58-0.96; P = 0.02) and periventricular hemorrhage (RR, 0.68; 95% CI, 0.47-0.99; P = 0.04), but a trend towards an increase in the risk of placental abruption (RR, 1.20; 95% CI, 1.00-1.46; P = 0.06) was also noted. LDA was not associated with any significant increase in adverse events if commenced ≤ 16 weeks gestation. LDA had no effect on delivery mode, irrespective of the gestational age at which it was started. Meta-regression confirmed that the effect of LDA on perinatal death, when treatment was started ≤ 16 weeks' gestation, was independent of any reduction in the rate of PE and preterm birth. CONCLUSION: LDA improves some important perinatal outcomes, without increasing adverse events such as placental abruption or periventricular hemorrhage, and its utility, if commenced prior to 16 weeks' gestation, may be considered in a wider context beyond the prevention of PE or fetal growth restriction. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Impacto de la aspirina en dosis bajas en los resultados perinatales adversos: metaanálisis y metaregresión OBJETIVO: Realizar un metaanálisis y una metaregresión de ensayos controlados aleatorizados (ECA) para evaluar el impacto de la aspirina en dosis bajas (LDA, por sus siglas en inglés) en el resultado perinatal, independientemente de su efecto en la preeclampsia (PE), el parto pretérmino y el peso bajo al nacer. MÉTODOS: Se realizó una búsqueda electrónica en las bases de datos EMBASE, PubMed, CENTRAL, PROSPERO y Google Scholar para identificar ECA que hubieran evaluado el impacto de la LDA en el embarazo, publicados en inglés antes de mayo de 2019, que informaran sobre resultados perinatales de interés (desprendimiento de la placenta, modo de parto, baja puntuación de Apgar a los 5 minutos, acidosis neonatal, ingreso en la unidad de cuidados intensivos neonatales, hemorragia periventricular y muerte perinatal). Se calcularon los cocientes de riesgo (CR) y el IC del 95% y se combinaron para el análisis. El análisis se estratificó según la edad gestacional al comienzo del tratamiento (≤16 semanas vs. >16 semanas) y se realizaron análisis de subgrupos para evaluar el impacto de la dosis de aspirina (<100 mg vs ≥100 mg). Se utilizó la metarregresión para evaluar el impacto de LDA en el resultado perinatal, independientemente de la reducción de la PE, el parto pretérmino y el bajo peso al nacer. RESULTADOS: Se incluyeron 40 estudios con 34 807 participantes. Cuando se inició el tratamiento con LDA a ≤ 16 semanas de gestación, se asoció con una reducción significativa del riesgo de muerte perinatal (CR, 0,47; IC 95%, 0,25-0,88; P=0,02; número necesario a tratar, 92); sin embargo, esta reducción del riesgo sólo se observó cuando se administró una dosis diaria de ≥ 100 mg. Si se inició con una gestación de > 16 semanas, el tratamiento con LDA se asoció con una reducción significativa en la puntuación de Apgar a los 5 minutos < 7 (CR, 0,75; 95% CI, 0,58-0,96; P = 0,02) y la hemorragia periventricular (CR, 0,68; 95% CI, 0,47-0,99; P = 0,04), pero también se notó una tendencia al aumento en el riesgo de desprendimiento prematuro de la placenta (CR, 1,20; 95% CI, 1,00-1,46; P = 0.06). El tratamiento con LDA no se asoció con ningún aumento significativo de los eventos adversos si se inició a ≤ 16 semanas de gestación. El tratamiento con LDA no tuvo ningún efecto sobre el modo de parto, independientemente de la edad gestacional en la que se inició. La metaregresión confirmó que el efecto de la LDA en la muerte perinatal, cuando se inició el tratamiento a ≤ 16 semanas de gestación, fue independiente de cualquier reducción en la tasa de PE y de nacimientos prematuros. CONCLUSIÓN: El tratamiento con LDA mejora algunos resultados perinatales importantes, sin aumentar los eventos adversos como el desprendimiento de la placenta o la hemorragia periventricular, y su utilidad, si se inicia antes de las 16 semanas de gestación, puede considerarse en un contexto más amplio, más allá de la prevención de la PE o la restricción del crecimiento fetal. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.


Asunto(s)
Desprendimiento Prematuro de la Placenta/inducido químicamente , Aspirina/efectos adversos , Parto Obstétrico/estadística & datos numéricos , Enfermedades del Recién Nacido/inducido químicamente , Atención Prenatal/métodos , Puntaje de Apgar , Aspirina/administración & dosificación , Femenino , Retardo del Crecimiento Fetal/prevención & control , Humanos , Recién Nacido de Bajo Peso , Recién Nacido , Unidades de Cuidado Intensivo Neonatal/estadística & datos numéricos , Muerte Perinatal/etiología , Preeclampsia/prevención & control , Embarazo , Resultado del Embarazo , Nacimiento Prematuro/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de Regresión
2.
Eur J Clin Nutr ; 72(4): 623-626, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29391593

RESUMEN

Suboptimal vitamin D (vitD) status and reduced lean body mass are highly prevalent in pediatric inflammatory bowel diseases (IBD). The study objective was to determine sarcopenia prevalence and associations with vitD status in newly diagnosed pediatric IBD. Children with Crohn's disease (CD; n = 58) and ulcerative colitis (UC; n = 27) were included. Primary outcomes included body composition (total/regional/percent fat mass (FM), fat-free mass (FFM), skeletal muscle mass (SMM)), and vitD status (serum 25(OH)D). Sarcopenia was defined as SMM-z < -2. Additional variables measured included serum CRP, ESR, anthropometric, Pediatric Crohn's Disease Activity Index (PCDAI), and the Pediatric Ulcerative Colitis Disease Activity index (PUCAI). Sarcopenia and suboptimal 25(OH)D levels (< 50 nmol/l) were found in 23.5% (n = 20) and 52% (n = 44) of children, respectively. Younger children (< 13 years) with CD with suboptimal 25(OH)vitD (< 50 nmol/l) had the greatest frequency of sarcopenia (57.1%) (p = 0.004). Sarcopenia was prevalent in newly diagnosed, young children with CD with vitD deficiency.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Sarcopenia , Deficiencia de Vitamina D , Vitamina D/sangre , Adolescente , Niño , Preescolar , Estudios de Cohortes , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/epidemiología , Estado Nutricional , Factores de Riesgo , Sarcopenia/complicaciones , Sarcopenia/epidemiología , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/epidemiología
3.
Can J Gastroenterol ; 23(12): 811-5, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20011733

RESUMEN

BACKGROUND: Patients with inflammatory bowel disease (IBD) often do not take their medications as prescribed. OBJECTIVE: To examine self-reported adherence rates in IBD patients at the Stollery Children's Hospital (Edmonton, Alberta) and to determine predictors of medication adherence. METHODS: A survey was mailed to 212 pediatric IBD patients of the Stollery Children's Hospital. A chart review was completed for those who returned the survey. RESULTS: A total of 119 patients completed the survey. The nonresponders were significantly older than responders (14.5 years versus 13.2 years; P=0.032). The overall adherence rate was 80%. Nonadherence was associated with older age (14.6 years versus 13.0 years; P=0.04), longer disease duration (5.0 years versus 3.1 years; P=0.004) and reported use of herbal medications (40.0% versus 13.6%; P=0.029). The most common reasons reported for missing medications were forgetfulness, feeling better and too many medications. In addition, patients reported being more likely to take anti-inflammatory medications and less likely to take herbal medicines. CONCLUSION: Identified predictors of nonadherence such as age, disease duration and use of herbal treatments may enable the development of specific strategies to improve adherence in adolescents with IBD.


Asunto(s)
Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Cumplimiento de la Medicación , Fitoterapia , Adolescente , Factores de Edad , Alberta , Antiinflamatorios/uso terapéutico , Niño , Estudios Transversales , Recolección de Datos , Femenino , Hospitales Pediátricos , Humanos , Masculino , Factores de Tiempo
4.
Minerva Pediatr ; 61(3): 253-62, 2009 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19461569

RESUMEN

Intestinal failure (IF) is a complex, chronic illness, of increasing importance in the pediatric critical care setting. We can expect an increase in pediatric IF given an increase in the survivors of extreme prematurity and complex congenital heart disease. Overall priorities for management of this condition include surgical and medical strategies to promote intestinal adaptation and to reduce complications, particularly related to malnutrition, liver disease and sepsis. In this review the authors propose that the optimal care for children with IF are multidisciplinary teams abreast of the newest strategies for intestinal rehabilitation. Early listing for intestinal transplantation for children at greatest risk of long-term parenteral nutrition dependency and its life threatening complications is appropriate.


Asunto(s)
Cuidados Críticos , Síndromes de Malabsorción , Niño , Tratamiento de Urgencia/métodos , Humanos , Intestinos/trasplante , Hepatopatías/prevención & control , Síndromes de Malabsorción/complicaciones , Síndromes de Malabsorción/etiología , Síndromes de Malabsorción/mortalidad , Síndromes de Malabsorción/terapia , Desnutrición/prevención & control , Grupo de Atención al Paciente , Factores de Riesgo , Sepsis/prevención & control , Resultado del Tratamiento
5.
Palliat Med ; 22(4): 336-42, 2008 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-18541637

RESUMEN

The aspiration to design and conduct high-quality research in palliative care has been an important but elusive goal. The article evaluates the nature of research methodologies presented in published research within the broad remit of palliative care. A systematic search of the Medline database between 1997 and 2006, using the keywords 'palliative care' or 'end-of-life care' and 'research methodology', identified over 318 publications. A bibliometric analysis indicates an incremental increase in published outputs per year, from 27 countries, with articles widely distributed across 108 journals. The heterogeneity of the research methodologies and the journals publishing them, present challenges in defining what constitutes 'high quality'. We argue that although this diversity leads to a lack of coherence for a single disciplinary paradigm for palliative care, there is a greater acknowledgement of the differing epistemological and theoretical frameworks used by researchers. This could be regarded as enriching our understanding of what it means to be dying in contemporary society.


Asunto(s)
Bibliometría , Cuidados Paliativos , Proyectos de Investigación/normas , Humanos
6.
Sex Transm Infect ; 82(4): 298-300, 2006 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-16877578

RESUMEN

OBJECTIVE: To explore the associations between self reported high risk sexual behaviours and subsequent diagnosis with hepatitis C virus (HCV) infection. METHODS: The Sex, Health and Anti-Retrovirals Project (SHARP) was a cross sectional study of sexual behaviour in HIV positive, men who have sex with men (MSM) attending a London outpatient clinic. From July 1999 to August 2000 participants completed a computer assisted self interview questionnaire (CASI) on recent sexual behaviour, recreational drug use, and detailed reporting of the last two sexual episodes involving different partners. Results were combined with routine clinic data and subsequent testing for HCV up to 21 April 2005. A new HCV diagnosis was defined as anti-HCV antibody seroconversion or positive HCV RNA following a previous negative. Incident rate ratios (IRR) were calculated using Poisson regression in Stata (version 9). Men contributed time at risk from interview until either their diagnosis or their last negative test result. RESULTS: Of the 422 men who completed questionnaires, 308 (73%) had sufficient clinical and HCV testing data available for analysis. Incident HCV infection was identified in 11 men. Unprotected anal intercourse, more than 30 sex partners in the past year, higher numbers of new anal sex partners, rimming (oro-anal sex), fisting, use of sex toys, and intranasal recreational drug use were associated with HCV. In multivariate analysis only fisting remained associated with HCV (adjusted IRR 6.27, p = 0.005). CONCLUSIONS: In this study of HIV positive MSM, fisting is strongly associated with HCV infection. Where individuals report high risk sexual behaviours, clinicians should offer appropriate testing for HCV infection.


Asunto(s)
Seropositividad para VIH/psicología , Hepatitis C Crónica/psicología , Homosexualidad Masculina/psicología , Sexo Inseguro , Adulto , Estudios Transversales , Humanos , Masculino , Persona de Mediana Edad , Autorrevelación , Parejas Sexuales , Encuestas y Cuestionarios
7.
Eur Respir J ; 23(6): 813-7, 2004 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15218991

RESUMEN

Endobronchial ultrasound (EBUS) allows identification of airway wall structures and could potentially be utilised for in vivo studies of airway thickening in asthma. The present study investigated whether inflation of the fluid-filled balloon sheath over the transducer (necessary to provide sonic coupling with the airway wall) influenced in vitro measurements. In vivo comparability of EBUS with high resolution computed tomography scanning (HRCT), an established method for measuring wall thickness, was determined in control subjects. The airway diameter and wall thickness were studied using EBUS in 24 cartilaginous airways obtained from four sheep, before and after balloon sheath inflation during immersion in saline. To assess EBUS versus HRCT comparability of airway measures in vivo, 12 control subjects underwent imaging of the posterior basal bronchus of the right lower lobe by both techniques. Intra- and interobserver agreement were also assessed. Results with and without the balloon sheath gave comparable measures of airway internal diameter and wall thickness in vitro. Statistical analysis showed agreement between EBUS and HRCT, and intra- and interobserver variability in vivo. The current study concludes that endobronchial ultrasound, which does not present a radiation risk, could be utilised in the in vivo study of cartilaginous airway wall remodelling in respiratory diseases, such as asthma.


Asunto(s)
Bronquios/diagnóstico por imagen , Bronquios/patología , Adulto , Animales , Broncografía , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Técnicas In Vitro , Masculino , Ovinos , Tomografía Computarizada por Rayos X , Ultrasonografía
8.
Reproduction ; 126(5): 589-97, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-14611631

RESUMEN

The autosomal gene DAZL is a member of a family of genes (DAZL, DAZ, BOULE), all of which contain a consensus RNA binding domain and are expressed in germ cells. Adult male and female mice null for Dazl lack gametes. In order to define more precisely the developmental stages in germ cells that require Dazl expression, the patterns of germ cell loss in immature male and female wild-type (+/+, WT) and Dazl -/- (DazlKO) mice were analysed. In females, loss of germ cells occurred during fetal life and was coincident with progression of cells through meiotic prophase. In males, testes were recovered from WT and DazlKO males obtained before and during the first wave of spermatogenesis (days 2-19). Mitotically active germ cells were present up to and including day 19. Functional differentiation of spermatogonia associated with detection of c-kit positive cells did not depend upon expression of Dazl. RBMY-positive cells (A, intermediate, B spermatogonia, zygotene and preleptotene spermatocytes) were reduced in DazlKO compared with WT testes. Staining of cell squashes from day 19 testes with anti-gamma-H2AX and anti-SCP3 antibodies showed that germ cells from DazlKO males were unable to progress beyond the leptotene stage of meiotic prophase I. It was concluded that in the absence of Dazl, germ cells can complete mitosis, and embark on functional differentiation but that, in both sexes, progression through meiotic prophase requires this RNA binding protein.


Asunto(s)
Eliminación de Gen , Oogénesis/genética , Profase/genética , Proteínas de Unión al ARN/genética , Espermatogénesis/genética , Animales , Femenino , Inmunohistoquímica/métodos , Masculino , Ratones , Ratones Noqueados , Oocitos/citología , Proteínas de Unión al ARN/análisis , Espermatozoides/citología
9.
Cytogenet Genome Res ; 103(3-4): 330-6, 2003.
Artículo en Inglés | MEDLINE | ID: mdl-15051956

RESUMEN

The Y(d1) deletion in mice removes most of the multi-copy Rbmy gene cluster that is located adjacent to the centromere on the Y short arm (Yp). XY(d1) mice develop as females because Sry is inactivated, probably because it is now juxtaposed to centromeric heterochromatin. We have previously produced XY(d1)Sry transgenic males and found that they have a substantially increased frequency of abnormal sperm. Staining of testis sections with a polyclonal anti-RBMY antibody appeared to show a marked decrease of RBMY protein in the spermatids of XY(d1)Sry males compared to control males, which led us to suggest that this may be responsible for the increase in sperm anomalies. In the current study we sought to determine whether augmenting Rbmy expression specifically in the spermatids of XY(d1)Sry males would ameliorate the sperm defects. An expressing Rbmy transgene driven by the spermatid-specific mouse protamine 1 promotor (mP1Rbmy) was therefore introduced into XY(d1)Sry males. This failed to reduce the frequency of abnormal sperm. In the course of this study, a new RBMY antibody was generated that, in contrast to the original antibody, failed to detect RBMY in spermatid stages by immunostaining. The lack of RBMY was confirmed by western blotting of lysates from purified round spermatids and elongating spermatids. The implications of these results for the proposed role for RBMY in sperm development are discussed.


Asunto(s)
Proteínas de Unión al ARN/fisiología , Espermatogénesis , Espermatozoides/citología , Animales , Eliminación de Gen , Masculino , Ratones , Ratones Transgénicos , Proteínas Nucleares , Proteínas de Unión al ARN/genética , Cabeza del Espermatozoide/ultraestructura , Espermátides/citología , Espermátides/metabolismo
10.
Cytogenet Genome Res ; 99(1-4): 252-6, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12900572

RESUMEN

XO Turner women, irrespective of the parental source of the X chromosome, are of short stature, and this is now thought to be largely a consequence of haploinsufficiency for the pseudoautosomal region (PAR) gene SHOX. X(p)O mice (with a paternal X) are developmentally retarded in fetal life, are underweight at birth, and show reduced weight gain in the first few weeks after birth. X(m)O mice, on the other hand, are more developmentally advanced than their XX siblings in fetal life; their postnatal growth has not hitherto been assessed. Here we show that X(m)O mice are not underweight at birth, but they nevertheless show reduced weight gain postnatally. The fact that postnatal growth is affected in X(p)O and X(m)O mice, means that this must be due to X dosage deficiency. In order to see if haploinsufficiency for a PAR gene was responsible for this growth deficit (cf SHOX deficiency in Turner women), X(m)Y*(X) females, in which the Y*(X) chromosome provides a second copy of the PAR, were compared with XX females. These X(m)Y*(X) females were also growth-retarded relative to their XX sibs, suggesting that it may be haploinsufficiency for a non-dosage-compensated X gene or genes outside the PAR that is responsible for the postnatal growth deficit in XO mice. The X genes known to escape X inactivation in the mouse have closely similar Y homologues. X(m)YSRY-negative females were therefore compared with XX females to see if the presence of the SRY-negative Y chromosome corrected the growth deficit; this proved to be the case. The postnatal growth deficit of XO mice is therefore probably due to haploinsufficiency for a non-dosage-compensated X gene that has a Y homologue that provides an equivalent function in the somatic tissues of males.


Asunto(s)
Trastornos del Crecimiento/genética , Aberraciones Cromosómicas Sexuales , Cromosoma X/genética , Animales , Peso al Nacer , Cruzamientos Genéticos , Femenino , Genotipo , Trastornos del Crecimiento/patología , Masculino , Ratones , Ratones Endogámicos C3H , Ratones Endogámicos , Ratones Mutantes , Factores de Tiempo
11.
Int J Eat Disord ; 30(3): 245-51, 2001 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11746283

RESUMEN

OBJECTIVE: To compare the bone density of adolescent patients with anorexia nervosa with adolescent patients with other dieting disorders and to evaluate risk factors for low bone density in these patients. METHOD: Sixty-nine consecutive female patients referred to an adolescent eating disorders clinic were studied by interview, blood sampling, body composition, and lumbar spine bone density measurement using dual energy X-ray absorptiometry. RESULTS: Although patients with anorexia nervosa were more malnourished, their bone density was similar to other dieting patients. Patients were divided into a low and normal bone density group irrespective of psychiatric diagnosis. Patients with low bone density had dieted for longer, had lower lean body mass, more often had not achieved menarche, and had longer duration of secondary amenorrhea and lower estrogen levels. DISCUSSION: Irrespective of clinical diagnosis, adolescents with dieting disorders have increased risk of low bone density when malnutrition commences early in puberty and is associated with reduced lean body mass and impaired ovarian function.


Asunto(s)
Anorexia Nerviosa/complicaciones , Densidad Ósea , Trastornos de Alimentación y de la Ingestión de Alimentos/complicaciones , Adolescente , Amenorrea/complicaciones , Amenorrea/etiología , Índice de Masa Corporal , Dieta Reductora , Estrógenos/deficiencia , Femenino , Humanos , Menarquia , Trastornos Nutricionales/complicaciones , Pubertad , Factores de Riesgo
12.
J Cell Sci ; 114(Pt 18): 3367-75, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11591824

RESUMEN

Progression through meiotic prophase is associated with dramatic changes in chromosome condensation. Two proteins that have been implicated in effecting these changes are the mammalian HP1-like protein M31 (HP1beta or MOD1) and the unusual core histone macroH2A1.2. Previous analyses of M31 and macroH2A1.2 localisation in mouse testis sections have indicated that both proteins are components of meiotic centromeric heterochromatin and of the sex body, the transcriptionally inactive domain of the X and Y chromosomes. This second observation has raised the possibility that these proteins co-operate in meiotic sex chromosome inactivation. In order to investigate the roles of M31 and macroH2A1.2 in meiosis in greater detail, we have examined their localisation patterns in surface-spread meiocytes from male and female mice. Using this approach, we report that, in addition to their previous described staining patterns, both proteins localise to a focus within the portion of the pseudoautosomal region (PAR) that contains the steroid sulphatase (Sts) gene. In light of the timing of its appearance and of its behaviour in sex-chromosomally variant mice, we suggest a role for this heterochromatin focus in preventing complete desynapsis of the terminally associated X and Y chromosomes prior to anaphase I.


Asunto(s)
Proteínas Cromosómicas no Histona/metabolismo , Heterocromatina/metabolismo , Histonas/metabolismo , Oocitos/citología , Espermatozoides/citología , Animales , Arilsulfatasas/genética , Proteínas Cromosómicas no Histona/química , Proteínas Cromosómicas no Histona/genética , Emparejamiento Cromosómico/genética , Emparejamiento Cromosómico/fisiología , Femenino , Heterocromatina/química , Histonas/química , Histonas/genética , Masculino , Meiosis/fisiología , Ratones , Mapeo Físico de Cromosoma , Profase/genética , Profase/fisiología , Cromosomas Sexuales/fisiología , Esteril-Sulfatasa
13.
Org Lett ; 3(8): 1201-3, 2001 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-11348194

RESUMEN

[structure: see text]. Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to those of many naturally occurring DNA binding proteins. A machine-assisted Fmoc solid phase synthesis of polyamides has been optimized to afford high stepwise coupling yields (>99%). Two monomer building blocks, Fmoc-Py acid and Fmoc-Im acid, were prepared in multigram scale. Cleavage by aminolysis followed by HPLC purification affords up to 200 mg quantities of polyamide with purities and yields greater than or equal to those reported using Boc chemistry. A broader set of reaction conditions will increase the number and complexity of minor groove binding polyamides which may be prepared and help ensure compatibility with many commercially available peptide synthesizers.


Asunto(s)
Aminoácidos/síntesis química , Fluorenos/síntesis química , Imidazoles/química , Biosíntesis de Péptidos , Péptidos/síntesis química , Pirroles/química , Cromatografía Líquida de Alta Presión , ADN/metabolismo , Ligandos , Modelos Químicos , Resinas de Plantas/química
14.
Nat Genet ; 27(3): 271-6, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11242108

RESUMEN

In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis. Here we use an antibody specific for a phosphorylated histone (gamma-H2AX, which marks the sites of DSBs) to investigate the timing, distribution and Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast, recombination in the mouse is initiated by Spo11-dependent DSBs that form during leptotene. Loss of gamma-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'.


Asunto(s)
ADN/genética , Integrasas , Meiosis/genética , Recombinación Genética , Animales , Anticuerpos , Proteínas de Ciclo Celular , ADN/metabolismo , ADN Nucleotidiltransferasas/metabolismo , Proteínas de Unión al ADN , Endodesoxirribonucleasas , Esterasas/genética , Esterasas/metabolismo , Femenino , Histonas/inmunología , Histonas/metabolismo , Masculino , Meiosis/fisiología , Ratones , Ratones Noqueados , Microscopía Fluorescente , Proteínas/genética , Proteínas/metabolismo , Recombinasas , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
15.
Q J Exp Psychol A ; 53(4): 1105-16, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11131815

RESUMEN

Hanley, Smith, and Hadfield (1998) showed that when participants were asked to recognize famous people from hearing their voice, there was a relatively large number of trials in which the celebrity's voice was felt to be familiar but biographical information about the person could not be retrieved. When a face was found familiar, however, the celebrity's occupation was significantly more likely to be recalled. This finding is consistent with the view that it is much more difficult to associate biographical information with voices than with faces. Nevertheless, recognition level was much lower for voices than for faces in Hanley et al.'s study, and participants made significantly more false alarms in the voice condition. In the present study, recognition performance in the face condition was brought down to the same level as recognition in the voice condition by presenting the faces out of focus. Under these circumstances, it proved just as difficult to recall the occupations of faces found familiar as it was to recall the occupations of voices found familiar. In other words, there was an equally large number of familiar-only responses when faces were presented out of focus as in the voice condition. It is argued that these results provide no support for the view that it is relatively difficult to associate biographical information with a person's voice. It is suggested instead that associative connections between processing units at different levels in the voice-processing system are much weaker than is the case with the corresponding units in the face-processing system. This will reduce the recall of occupations from voices even when the voice has been found familiar. A simulation was performed using the latest version of the IAC model of person recognition (Burton, Bruce, & Hancock, 1999) which demonstrated that the model can readily accommodate the pattern of results obtained in this study.


Asunto(s)
Cara , Recuerdo Mental , Voz , Adolescente , Adulto , Aprendizaje por Asociación , Atención , Aprendizaje Discriminativo , Femenino , Humanos , Masculino , Distorsión de la Percepción
16.
Gene Expr ; 9(1-2): 77-91, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11097426

RESUMEN

A current goal in molecular medicine is the development of new strategies to interfere with gene expression in living cells in the hope that novel therapies for human disease will result from these efforts. This review focuses on small-molecule or chemical approaches to manipulate gene expression by modulating either transcription of messenger RNA-coding genes or protein translation. The molecules under study include natural products, designed ligands, and compounds identified through functional screens of combinatorial libraries. The cellular targets for these molecules include DNA, messenger RNA, and the protein components of the transcription, RNA processing, and translational machinery. Studies with model systems have shown promise in the inhibition of both cellular and viral gene transcription and mRNA utilization. Moreover, strategies for both repression and activation of gene transcription have been described. These studies offer promise for treatment of diseases of pathogenic (viral, bacterial, etc.) and cellular origin (cancer, genetic diseases, etc.).


Asunto(s)
Regulación de la Expresión Génica , Animales , ADN/química , ADN/efectos de los fármacos , Diseño de Fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Terapia Genética/métodos , Humanos , Sustancias Intercalantes/química , Sustancias Intercalantes/farmacología , Sustancias Intercalantes/uso terapéutico , Conformación de Ácido Nucleico , Biosíntesis de Proteínas/efectos de los fármacos , Transcripción Genética/efectos de los fármacos
17.
Chromosoma ; 109(6): 426-32, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11072798

RESUMEN

During male meiosis in mammals the X and Y chromosomes become condensed to form the sex body (XY body), which is the morphological manifestation of the process of meiotic sex chromosome inactivation (MSCI). An increasing number of sex body located proteins are being identified, but their functions in relation to MSCI are unclear. Here we demonstrate that assaying male sex body located proteins during XY female mouse meiosis, where MSCI does not take place, is one way in which to begin to discriminate between potential functions. We show that a newly identified protein, "Asynaptin" (ASY), detected in male meiosis exclusively in association with the X and Y chromatin of the sex body, is also expressed in pachytene oocytes of XY females where it coats the chromatin of the asynapsed X in the absence of MSCI. Furthermore, in pachytene oocytes of females carrying a reciprocal autosomal translocation, ASY associates with asynapsed autosomal chromatin. Thus the location of ASY to the sex body during male meiosis is likely to be a response to the asynapsis of the non-homologous regions [outside the pseudoautosomal region (PAR)] of the heteromorphic X-Y bivalent, rather than being related to MSCI. In contrast to ASY, the previously described sex body protein XY77 proved to be male sex body specific. Potential functions for MSCI and the sex body are discussed together with the possible roles of these two proteins.


Asunto(s)
Cromatina/metabolismo , Meiosis , Proteínas Nucleares , Proteínas/metabolismo , Factores de Transcripción , Cromosoma X , Cromosoma Y , Animales , Proteínas de Unión al ADN/genética , Femenino , Masculino , Ratones , Ratones Endogámicos , Ratones Mutantes , Proteínas/inmunología , Proteína de la Región Y Determinante del Sexo , Testículo/inmunología , Testículo/metabolismo
19.
J AOAC Int ; 83(4): 837-46, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10995110

RESUMEN

A method was developed and validated for determination and quantitation of tilmicosin residues in swine, cattle, and sheep edible tissues, as well as chicken fat, skin, and muscle over a concentration range of 0.025 microg/g-20 microg/g. For chicken kidney and liver, the method was validated over a range of 0.060 microg/g-20 microg/g. The tissue sample was extracted with methanol and a C18 cartridge was used for solid-phase extraction cleanup. A reversed-phase gradient liquid chromatographic method with detection at 280 nm was used to separate the tilmicosin from matrix components in 30 min run time. The limit of quantitation (LOQ) of the method was 0.025 microg/g for all tested tissues except chicken kidney and liver, for which the LOQ was 0.06 microg/g. Average recoveries for tissue samples ranged from 73 to 98%. Relative standard deviation values ranged from 0.6 to 14.7%.


Asunto(s)
Antibacterianos/análisis , Pollos , Cromatografía Líquida de Alta Presión/métodos , Macrólidos , Carne/análisis , Ovinos , Porcinos , Tilosina/análogos & derivados , Tilosina/análisis , Tejido Adiposo/química , Animales , Bovinos , Residuos de Medicamentos/análisis , Contaminación de Alimentos , Riñón/química , Hígado/química , Músculo Esquelético/química , Control de Calidad , Sensibilidad y Especificidad , Piel/química
20.
Chemistry ; 6(15): 2772-4, 2000 Aug 04.
Artículo en Inglés | MEDLINE | ID: mdl-10985725

RESUMEN

The preparative scale kinetic resolution of racemic aldols 1-4 using aldolase antibodies 38C2 (Aldrich no. 47995-0) and 84G3 (Aldrich no. 52785-8) is described. These reactions use a biphasic aqueous/organic solvent system that allows the catalyst to be reused. Reaction scales range from miligrams to grams, with 0.0086 to 0.12 mol% of antibody binding sites. Because antibodies 38C2 and 84G3 have opposite enantioselectivities, both aldol product enantiomers are accessible by kinetic resolution.


Asunto(s)
Aldehídos/aislamiento & purificación , Anticuerpos Catalíticos , Fructosa-Bifosfato Aldolasa , Fragmentos Fab de Inmunoglobulinas , Aldehídos/química , Indicadores y Reactivos , Cinética , Estereoisomerismo
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