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1.
Colorectal Dis ; 21(8): 932-942, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31062521

RESUMEN

AIM: The aim was to evaluate the influence of operative approach for low anterior resection (LAR) on oncological and postoperative outcomes. Minimally invasive surgical approaches are increasingly used for the treatment of rectal cancer with mixed outcomes. METHOD: We compared patients undergoing LAR in the National Cancer Database between 2010 and 2015 by surgical approach. Multivariable regression was used to identify risk factors associated with conversion rate, prolonged length of stay (LOS) and 30-day unplanned readmission. RESULTS: During the study period, 41 282 patients underwent LAR: 6035 robotic-assisted (RLAR) (14.6%), 13 826 laparoscopic (LLAR) (33.5%) and 21 421 open (OLAR) (51.9%). In propensity score matched analysis, RLAR compared to LLAR was associated with shorter LOS (6.3 vs 6.8 days, P < 0.0001), lower risk of prolonged LOS (22.1% vs 25.6%, P < 0.0001) and lower rate of conversion to open (7.5% vs 14.95%, P < 0.0001). Compared to OLAR, RLAR had shorter LOS (6.3 vs 7.8 days, P < 0.0001) and less prolonged LOS (14.1% vs. 20.9%, P < 0.0001). In multivariable analysis, for conversion to open, the laparoscopic approach was one of the risk factors; for prolonged LOS, conversion to open and non-robotic approaches (i.e. LLAR and OLAR) were risk factors; and for unplanned 30-day readmission, conversions and prolonged LOS were risk factors. CONCLUSIONS: For patients with rectal cancer, RLAR shows recovery benefits over both open and laparoscopic LAR with reduced conversion to open compared with LLAR and less prolonged LOS compared with LLAR and OLAR. RLAR is associated with short-term oncological outcomes comparable to OLAR, supporting its use in minimally invasive surgery for rectal cancer.


Asunto(s)
Conversión a Cirugía Abierta/estadística & datos numéricos , Laparoscopía/estadística & datos numéricos , Proctectomía/métodos , Neoplasias del Recto/cirugía , Procedimientos Quirúrgicos Robotizados/estadística & datos numéricos , Bases de Datos Factuales , Femenino , Humanos , Laparoscopía/métodos , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Readmisión del Paciente/estadística & datos numéricos , Periodo Posoperatorio , Puntaje de Propensión , Factores de Riesgo , Procedimientos Quirúrgicos Robotizados/métodos , Factores de Tiempo , Resultado del Tratamiento
2.
J Anim Sci ; 95(11): 4718-4727, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29293732

RESUMEN

Genetic parameters are required to evaluate carcass merit using correlated real-time ultrasound (RTU) measurements. Many registered bulls and heifers are measured using RTU before consideration for selection as parents, whereas few animals are recorded for carcass traits and those are often crossbred steers. The objective of this study was to estimate genetic parameters required for evaluating carcass merit in the American Hereford Association (AHA) and the American Simmental Association (ASA) using multivariate models and to assess accuracy of carcass trait estimated breeding values (EBV) for selection candidates. All available carcass data including carcass weight (CWT), fat thickness (FAT), longissimus muscle area (LMA), and marbling score (MRB) were provided by the AHA and the ASA along with RTU data including fat thickness (UFAT), longissimus muscle area (ULMA), and percentage of intramuscular fat (UIMF). Carcass data comprised 6,054 AHA and 9,056 ASA cattle, while RTU data in comparable numbers from close relatives comprised 6,074 AHA and 7,753 ASA cattle. Pedigrees included 33,226 AHA and 37,665 ASA animals. Fixed effects for carcass and RTU data included contemporary group, age at scan/slaughter, and major breed percentages. Restricted maximum likelihood procedures were applied to all the carcass and RTU measurements, along with birth weight to account for selection, fitting 8-trait multivariate models separately for each breed association. Heritability estimates for AHA and ASA carcass traits were 0.41 ± 0.04 and 0.25 ± 0.03 for FAT, 0.47 ± 0.04 and 0.32 ± 0.03 for LMA, 0.48 ± 0.04 and 0.43 ± 0.04 for MRB, 0.51 ± 0.04 and 0.34 ± 0.03 for CWT, and for RTU traits were 0.29 ± 0.04 and 0.37 ± 0.03 for UFAT, 0.31 ± 0.04 and 0.44 ± 0.03 for ULMA, and 0.45 ± 0.04 and 0.42 ± 0.03 for UIMF. Genetic correlations for AHA and ASA analyses between FAT and UFAT were 0.74 ± 0.08 and 0.28 ± 0.13, between LMA and ULMA were 0.81 ± 0.07 and 0.57 ± 0.10, and between MRB and UIMF were 0.54 ± 0.08 and 0.73 ± 0.07. Predictions of carcass merit using RTU measurements in Hereford cattle would be more reliable for FAT and LMA than MRB, but the reverse would be true for admixed Simmental cattle. Genetic correlations for MRB in AHA and for FAT and LMA in ASA are less than currently assumed in their national evaluations. Collection of greater numbers of carcass measurements would improve the accuracy of genetic evaluations for carcass traits in both breeds.


Asunto(s)
Composición Corporal , Bovinos/genética , Tejido Adiposo/diagnóstico por imagen , Animales , Peso al Nacer , Bovinos/fisiología , Femenino , Masculino , Músculos Paraespinales/diagnóstico por imagen , Linaje , Fenotipo , Ultrasonografía/veterinaria
3.
Mol Psychiatry ; 18(3): 288-99, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-22614291

RESUMEN

Neurogenetics research has begun to advance our understanding of how genetic variation gives rise to individual differences in brain function, which, in turn, shapes behavior and risk for psychopathology. Despite these advancements, neurogenetics research is currently confronted by three major challenges: (1) conducting research on individual variables with small effects, (2) absence of detailed mechanisms, and (3) a need to translate findings toward greater clinical relevance. In this review, we showcase techniques and developments that address these challenges and highlight the benefits of a neurogenetics approach to understanding brain, behavior and psychopathology. To address the challenge of small effects, we explore approaches including incorporating the environment, modeling epistatic relationships and using multilocus profiles. To address the challenge of mechanism, we explore how non-human animal research, epigenetics research and genome-wide association studies can inform our mechanistic understanding of behaviorally relevant brain function. Finally, to address the challenge of clinical relevance, we examine how neurogenetics research can identify novel therapeutic targets and for whom treatments work best. By addressing these challenges, neurogenetics research is poised to exponentially increase our understanding of how genetic variation interacts with the environment to shape the brain, behavior and risk for psychopathology.


Asunto(s)
Encéfalo/fisiopatología , Individualidad , Trastornos Mentales/genética , Trastornos Mentales/fisiopatología , Animales , Epigenómica , Estudio de Asociación del Genoma Completo , Humanos , Modelos Biológicos , Terapia Molecular Dirigida/psicología
4.
Neuropharmacology ; 61(4): 665-76, 2011 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-21619887

RESUMEN

Inhibition of phosphodiesterase 9 (PDE9) has been reported to enhance rodent cognitive function and may represent a potential novel approach to improving cognitive dysfunction in Alzheimer's disease. PF-04447943, (6-[(3S,4S)-4-methyl-1-(pyrimidin-2-ylmethyl)pyrrolidin-3-yl]-1-(tetrahydro-2H-pyran-4-yl)-1,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one), a recently described PDE9 inhibitor, was found to have high affinity (Ki of 2.8, 4.5 and 18 nM) for human, rhesus and rat recombinant PDE9 respectively and high selectivity for PDE9 versus PDEs1-8 and 10-11. PF-04447943 significantly increased neurite outgrowth and synapse formation (as indicated by increased synapsin 1 expression) in cultured hippocampal neurons at low (30-100 nM) but not high (300-1000 nM) concentrations. PF-04447943 significantly facilitated hippocampal slice LTP evoked by a weak tetanic stimulus at a concentration of 100 nM but failed to affect response to the weak tetanus at either 30 or 300 nM, or the LTP produced by a theta burst stimulus. Systemic administration of PF-04447943 (1-30 mg/kg p.o.) dose-dependently increased cGMP in the cerebrospinal fluid 30 min after administration indicating target engagement in the CNS of rats. PF-04447943 (1-3 mg/kg p.o.) significantly improved cognitive performance in three rodent cognition assays (mouse Y maze spatial recognition memory model of natural forgetting, mouse social recognition memory model of natural forgetting and rat novel object recognition with a scopolamine deficit). When administered at a dose of 3 mg/kg p.o., which improved performance in novel object recognition, PF-04447943 significantly increased phosphorylated but not total GluR1 expression in rat hippocampal membranes. Collectively these data indicate that PF-04447943 is a potent, selective brain penetrant PDE9 inhibitor that increased indicators of hippocampal synaptic plasticity and improved cognitive function in a variety of cognition models in both rats and mice. Results with PF-04447943 are consistent with previously published findings using a structurally diverse PDE9 inhibitor, BAY73-6199, and further support the suggestion that PDE9 inhibition may represent a novel approach to the palliative remediation of cognitive dysfunction.


Asunto(s)
3',5'-AMP Cíclico Fosfodiesterasas/antagonistas & inhibidores , Cognición/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Inhibidores de Fosfodiesterasa/farmacología , Pirazoles/farmacología , Pirimidinonas/farmacología , Sinapsis/efectos de los fármacos , Sinapsis/enzimología , 3',5'-AMP Cíclico Fosfodiesterasas/metabolismo , Animales , Células CHO , Cognición/fisiología , Cricetinae , Cricetulus , Relación Dosis-Respuesta a Droga , Femenino , Células HEK293 , Hipocampo/efectos de los fármacos , Hipocampo/enzimología , Humanos , Macaca mulatta , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Plasticidad Neuronal/fisiología , Inhibidores de Fosfodiesterasa/metabolismo , Pirazoles/metabolismo , Pirimidinonas/metabolismo , Ratas , Ratas Sprague-Dawley , Ratas Wistar
5.
Diabetologia ; 53(5): 914-23, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20146051

RESUMEN

AIMS/HYPOTHESIS: Skin and soft tissue infections (SSTIs) cause substantial morbidity in persons with diabetes. There are few data on pathogens or risk factors associated with important outcomes in diabetic patients hospitalised with SSTIs. METHODS: Using a clinical research database from CareFusion, we identified 3,030 hospitalised diabetic patients with positive culture isolates and a diagnosis of SSTI in 97 US hospitals between 2003 and 2007. We classified the culture isolates and analysed their association with the anatomic location of infection, mortality, length of stay and hospital costs. RESULTS: The only culture isolate with a significantly increased prevalence was methicillin-resistant Staphylococcus aureus (MRSA); prevalence for infection of the foot was increased from 11.6 to 21.9% (p < 0.0001) and for non-foot locations from 14.0% to 24.6% (p = 0.006). Patients with non-foot (vs foot) infections were more severely ill at presentation and had higher mortality rates (2.2% vs 1.0%, p < 0.05). Significant independent risk factors associated with higher mortality rates included having a polymicrobial culture with Pseudomonas aeruginosa (OR 3.1), a monomicrobial culture with other gram-negatives (OR 8.9), greater illness severity (OR 1.9) and being transferred from another hospital (OR 5.1). These factors and need for major surgery were also independently associated with longer length of stay and higher costs. CONCLUSIONS/INTERPRETATION: Among diabetic patients hospitalised with SSTI from 2003 to 2007, only MRSA increased in prevalence. Patients with non-foot (vs foot) infections were more severely ill. Independent risk factors for increased mortality rates, length of stay and costs included more severe illness, transfer from another hospital and wound cultures with Pseudomonas or other gram-negatives.


Asunto(s)
Complicaciones de la Diabetes/epidemiología , Enfermedad Iatrogénica/epidemiología , Tiempo de Internación/economía , Infecciones por Pseudomonas/epidemiología , Infecciones de los Tejidos Blandos/epidemiología , Infecciones Cutáneas Estafilocócicas/epidemiología , Complicaciones de la Diabetes/economía , Complicaciones de la Diabetes/microbiología , Diabetes Mellitus/economía , Diabetes Mellitus/microbiología , Costos de la Atención en Salud , Humanos , Enfermedad Iatrogénica/economía , Pacientes Internos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Prevalencia , Pseudomonas/aislamiento & purificación , Infecciones por Pseudomonas/economía , Infecciones por Pseudomonas/etiología , Factores de Riesgo , Infecciones de los Tejidos Blandos/economía , Infecciones de los Tejidos Blandos/etiología , Infecciones Cutáneas Estafilocócicas/economía , Infecciones Cutáneas Estafilocócicas/etiología
6.
Psychopharmacology (Berl) ; 182(1): 132-43, 2005 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-16025321

RESUMEN

RATIONALE: Previous studies have demonstrated behaviors indicative of anxiolysis in rats pretreated with the nociceptin receptor (opioid receptor like-1, ORL-1) agonist, Ro64-6198. OBJECTIVES: The aim of this study was to examine the effects of Ro64-6198 in anxiety models across three species: rat, guinea pig, and mouse. In addition, the receptor specificity of Ro64-6198 was studied, using the ORL-1 receptor antagonist, J-113397, and ORL-1 receptor knockout (KO) mice. Finally, neurological studies examined potential side effects of Ro64-6198 in the rat and mouse. RESULTS: Ro64-6198 (3-10 mg/kg) increased punished responding in a rat conditioned lick suppression test similarly to chlordiazepoxide (6 mg/kg). This effect of Ro64-6198 was attenuated by J-113397 (10 mg/kg), but not the mu opioid antagonist, naltrexone (3 mg/kg). In addition, Ro64-6198 (1-3 mg/kg) reduced isolation-induced vocalizations in rat and guinea pig pups. Ro64-6198 (3 mg/kg) increased the proportion of punished responding in a mouse Geller-Seifter test in wild-type (WT) but not ORL-1 KO mice, whereas diazepam (1-5.6 mg/kg) was effective in both genotypes. In rats, Ro64-6198 reduced locomotor activity (LMA) and body temperature and impaired rotarod, beam walking, and fixed-ratio (FR) performance at doses of 10-30 mg/kg, i.e., three to ten times higher than an anxiolytic dose. In WT mice, Ro64-6198 (3-10 mg/kg) reduced LMA and rotarod performance, body temperature, and FR responding, but these same measures were unaffected in ORL-1 KO mice. Haloperidol (0.3-3 mg/kg) reduced these measures to a similar extent in both genotypes. These studies confirm the potent, ORL-1 receptor-mediated, anxiolytic-like effects of Ro64-6198, extending the findings across three species. Ro64-6198 has target-based side effects, although the magnitude of these effects varies across species.


Asunto(s)
Ansiolíticos/farmacología , Nivel de Alerta/efectos de los fármacos , Imidazoles/farmacología , Receptores Opioides/agonistas , Compuestos de Espiro/farmacología , Animales , Ansiolíticos/toxicidad , Bencimidazoles/farmacología , Clordiazepóxido/farmacología , Condicionamiento Clásico/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Cobayas , Imidazoles/toxicidad , Masculino , Ratones , Ratones Noqueados , Actividad Motora/efectos de los fármacos , Antagonistas de Narcóticos , Piperidinas/farmacología , Ratas , Especificidad de la Especie , Compuestos de Espiro/toxicidad , Vocalización Animal/efectos de los fármacos , Receptor de Nociceptina
7.
J Endocrinol ; 185(1): 151-64, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15817836

RESUMEN

Recent work has shown that neuromedin U (NmU), a peptide initially identified as a smooth muscle contractor, may play a role in regulating food intake and energy homeostasis. To further evaluate this putative function, we measured food intake, body weight, energy expenditure and glucose homeostasis in transgenic mice that ubiquitously overexpress murine proNmU. NmU transgenic mice were lighter and had less somatic and liver fat, were hypophagic, and had improved insulin sensitivity as judged by an intraperitoneal insulin tolerance test. Transgenic mice had higher levels of hypothalamic NPY, POMC and MCH mRNA. There was no difference in O2 consumption between genotypes; however, NmU transgenic mice displayed a modest increase in respiratory quotient during food deprivation and refeeding. There were no behavioral disturbances in the NmU transgenic mice that could account for the results (e.g. changes in locomotor activity). When placed on a high-fat diet, transgenic mice remained lighter than wild-type mice and ate less, but gained weight at a rate similar to wild-type mice. Despite the increased weight gain with high-fat feeding, glucose tolerance was significantly improved in the transgenic mice. These findings support the hypothesized role of NmU as an endogenous anorexigenic peptide.


Asunto(s)
Anorexia/genética , Peso Corporal , Encéfalo/metabolismo , Neuropéptidos/genética , Animales , Composición Corporal , Calorimetría Indirecta , Ingestión de Alimentos , Metabolismo Energético , Ingeniería Genética , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Homeostasis , Hibridación in Situ/métodos , Insulina/sangre , Leptina/sangre , Masculino , Ratones , Ratones Transgénicos , Neuropéptidos/metabolismo , Reacción en Cadena de la Polimerasa/métodos
8.
Gut ; 52(6): 827-33, 2003 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-12740338

RESUMEN

BACKGROUND: Mucins are large complex glycoproteins that protect intestinal mucosal surfaces by limiting access of environmental matter to their epithelial cells. Several mucin genes have been described, including MUC3 that is a membrane associated mucin of the small intestine. Increased MUC3 mRNA transcription is induced by incubation of intestinal epithelial cells with a Lactobacillus strain known to be adherent to them. AIMS: To determine whether increased epithelial cell MUC3 mucin expression in response to Lactobacillus strains results in increased extracellular secretion of MUC3 mucins and the importance of epithelial cell adherence in modulation of MUC3 mucin expression. METHODS: HT29 cells grown to enhance expression of MUC3 mucins were incubated with selected Lactobacillus strains. Spent cell culture medium was collected for detection of secreted MUC3 mucins using dot blot immunoassay with a generated MUC3 antibody. Post-incubation HT29 cell RNA was collected for analysis of MUC3 expression by northern blot analysis using a MUC3 cDNA probe. In vitro binding studies using Lactobacillus strains incubated alone or coincubated with enteropathogenic Escherichia coli strain E2348/69 were used for adherence and inhibition of adherence studies, respectively. RESULTS: Lactobacillus strains with minimal ability to adhere to HT29 cells failed to induce upregulation of mucin gene expression. There was a direct correlation between upregulation of MUC3 mucin mRNA expression and extracellular secretion of MUC3 mucin. The same Lactobacillus strains that increased extracellular secretion of MUC3 mucin led to reduced adherence of enteropathogen E coli E2348/69 during coincubation experiments. CONCLUSION: Probiotic microbes induce MUC3 mucin transcription and translation with extracellular secretion of the MUC3 mucins. Epithelial cell adherence enhances the effects of probiotics on eukaryotic mucin expression.


Asunto(s)
Adhesión Bacteriana/fisiología , Mucosa Intestinal/metabolismo , Lactobacillus/fisiología , Mucinas/biosíntesis , Northern Blotting , Células Epiteliales/metabolismo , Células Epiteliales/microbiología , Escherichia coli/patogenicidad , Escherichia coli/fisiología , Técnica del Anticuerpo Fluorescente Indirecta , Células HT29 , Humanos , Sueros Inmunes/inmunología , Mucosa Intestinal/microbiología , Mucina 3 , Mucinas/genética , Mucinas/inmunología , ARN Mensajero/genética , Regulación hacia Arriba
9.
Dev Psychobiol ; 39(4): 286-300, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11745324

RESUMEN

About half of BXSB/MpJ-Yaa mice have ectopias, which are misplaced clusters of neurons located in layer I of cortex. This study replicated several previous findings showing that there are learning differences between mice with ectopias and those without. In addition, we had sufficient numbers of ectopic mice to investigate if ectopics learned differently depending on the cortical location of the ectopia(s). Mice with at least one ectopia located in prefrontal cortex were initially impaired in learning the Morris maze, as well as relearning the Lashley maze when it was inverted, but learned better in the radial-arm maze when compared to ectopic mice with ectopias located in nonprefrontal regions of cortex. Mice with at least one ectopia in motor cortex learned the Lashley maze better than mice with ectopias located outside motor cortex. In sum, the cortical location of the ectopia(s) affected learning performance in certain tasks within the ectopic group, but regardless of the cortical location of the ectopia(s), ectopics still learned differently than nonectopics in several tasks.


Asunto(s)
Corteza Cerebral/patología , Coristoma/patología , Aprendizaje por Laberinto/fisiología , Recuerdo Mental/fisiología , Neuronas , Orientación/fisiología , Animales , Mapeo Encefálico , Femenino , Masculino , Ratones , Ratones Mutantes Neurológicos , Retención en Psicología/fisiología
10.
Nurs Clin North Am ; 36(3): 401-8, vii, 2001 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11532655

RESUMEN

There are many factors that contribute to low bone mass and fracture. A careful health history is essential to identify both sets of risk factors. Identification of risk factors allows appropriate interventions to develop. Once a diagnosis has been established, laboratory and radiographic evaluation is needed to rule out secondary causes of osteoporosis. This article discusses risk factors for osteoporosis and fracture. It also discusses physical, laboratory, and radiographic evaluation.


Asunto(s)
Fracturas Óseas/diagnóstico , Fracturas Óseas/etiología , Anamnesis/métodos , Evaluación en Enfermería/métodos , Osteoporosis/diagnóstico , Osteoporosis/etiología , Examen Físico/métodos , Anciano , Densidad Ósea , Femenino , Fracturas Óseas/sangre , Fracturas Óseas/enfermería , Evaluación Geriátrica , Humanos , Masculino , Persona de Mediana Edad , Osteoporosis/sangre , Osteoporosis/enfermería , Medición de Riesgo , Factores de Riesgo
11.
Neurobiol Learn Mem ; 76(1): 33-45, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11525251

RESUMEN

Approximately 40-60% of BXSB mice have neocortical ectopias, a developmental anomaly characterized by migration of neurons into the neuron-sparse layer I of cortex. Previous studies have shown that ectopic BXSB mice have superior reference, but inferior working, memory on spatial tasks. Female BXSB mice were housed either in an enriched environment or in standard cages at weaning. Subsequently, these animals were tested on four of the Hebb-Williams mazes in a water-based version of this maze. Theoretically, two of the maze configurations placed greater emphasis on reference memory to find the goal, whereas the other two favored working memory. Ectopics reared in standard housing conditions were better than nonectopics on mazes that favored the use of reference memory, but poorer on mazes that favored working memory. In contrast, subjects raised in the enriched environment showed no ectopia differences. A comparison of enriched and standard housing conditions found that the enriched animals had better reference memory but poorer working memory. The latter effect may be because the enriched environment, although more stimulating, did not change in time or space; and other researchers have shown that daily replacement of stimuli in complex environments is correlated with better working memory.


Asunto(s)
Encefalopatías/patología , Coristoma/patología , Ambiente , Aprendizaje por Laberinto/fisiología , Memoria/fisiología , Corteza Somatosensorial/patología , Animales , Conducta Animal/fisiología , Femenino , Ratones , Distribución Aleatoria
12.
Behav Brain Res ; 118(1): 53-60, 2001 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-11163633

RESUMEN

The Ts65Dn mouse is segmentally trisomic for a part of mouse chromosome 16 and is a genetic model for Down syndrome and Alzheimer's disease. Although many studies have examined the learning and memory processes in Ts65Dn mice, it has yet to be determined if Ts65Dn mice are specifically impaired in learning tasks that require an intact hippocampus. Context discrimination learning is dependent on the dorsal hippocampus in mice. In this task, mice learn to discriminate two similar contexts, one of which is associated with foot shock. In the current study, Ts65Dn mice learned almost identically to what has been reported for mice with dorsal hippocampal lesions, while controls behaved similarly to sham lesioned mice. Therefore, Ts65Dn mice have learning deficits in a hippocampal dependent task that may be related to the loss of cholinergic input to the hippocampus, which occurs after 6 months of age.


Asunto(s)
Aprendizaje Discriminativo , Modelos Animales de Enfermedad , Síndrome de Down/psicología , Hipocampo/fisiopatología , Factores de Edad , Animales , Síndrome de Down/patología , Miedo , Genotipo , Hipocampo/fisiología , Masculino , Ratones , Ratones Mutantes Neurológicos
13.
Dev Psychobiol ; 38(1): 33-45, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11150059

RESUMEN

Ts65Dn mice are a genetic model for Down syndrome. Both individuals with Down syndrome and Ts65Dn mice have reduced cerebellar volumes and the cerebellum is involved in motor learning. Conflicting results have been reported on the motor learning abilities of Ts65Dn mice, which may be related to procedural differences between the motor learning tasks used in different laboratories and/or variability in phenotype because of the segregating background on which the mice are maintained. In this study, we examined learning in three types of motor tasks (peg running, accelerating rotorod, and rotating rod) which were initially easy for mice and gradually increased in difficulty. Ts65Dn mice learned the peg running task as well as controls, and learned the accelerating rotorod and rotating rod tasks as well as, and even better than, controls. These data indicate that Ts65Dn mice are not impaired in motor learning.


Asunto(s)
Síndrome de Down/psicología , Aprendizaje , Destreza Motora , Animales , Cerebelo/fisiopatología , Modelos Animales de Enfermedad , Síndrome de Down/fisiopatología , Ratones , Ratones Endogámicos/genética
14.
Behav Neurosci ; 115(6): 1239-46, 2001 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11770055

RESUMEN

All individuals with Down syndrome (DS) eventually develop the neuropathology of Alzheimer's disease (AD), which is characterized by a premature loss of basal forebrain cholinergic neurons. Similarly, between 4 and 6 months of age, Ts65Dn mice, which model DS, lose cholinergic markers in their medial septal neurons. It is not known whether Ts65Dn mice have age-related learning deficits as well. Control and Ts65Dn mice were tested at several ages in context discrimination. Controls at all ages showed no deficits in learning this task. Ts65Dn mice younger than 3 months demonstrated impaired learning, suggesting a possible developmental delay in Ts65Dn mice. Four-month-old Ts65Dn mice showed no deficits, whereas Ts65Dn mice older than 5 months were impaired in learning the task. Therefore, Ts65Dn mice have an age-related learning impairment that coincides with their age-related neuroanatomical abnormalities and, consequently, may be a useful model of AD.


Asunto(s)
Envejecimiento/fisiología , Enfermedad de Alzheimer/fisiopatología , Aprendizaje Discriminativo , Síndrome de Down/fisiopatología , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Prosencéfalo/patología , Prosencéfalo/fisiología , Análisis y Desempeño de Tareas
15.
Physiol Behav ; 70(3-4): 311-7, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11006429

RESUMEN

Male and female mice and rats were tested on a water escape version of the radial-arm maze designed to measure working and reference memory. In both species, females exhibited superior working memory during acquisition, and were better able to handle a higher memory load. However, male mice and rats exhibited better reference memory than females during the asymptotic portion of testing. Our data suggest that females may be better at working memory when both working and reference memory information must be learned simultaneously, and males better at reference memory when it has been differentiated from working memory.


Asunto(s)
Aprendizaje por Laberinto/fisiología , Memoria a Corto Plazo/fisiología , Memoria/fisiología , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos , Ratas , Ratas Wistar , Caracteres Sexuales , Especificidad de la Especie
16.
Physiol Behav ; 70(1-2): 1-5, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-10978470

RESUMEN

Approximately 40-60% of BXSB/MpJ-Yaa mice exhibit neocortical ectopias, which are misplaced clusters of neurons in layer I of cortex. These ectopias are usually located in the prefrontal and/or motor region of cortex in BXSB mice, and are similar in appearance to those found in postmortem analyses of the brains of dyslexic humans. Several within-strain learning differences between mice with ectopias and those without have been reported. In particular, ectopic BXSB mice exhibited superior reference memory learning, but inferior working memory learning in several studies from our laboratory. This study used the Morris water maze delayed matching-to sample task and the water radial-arm maze to asses working memory in female BXSB mice with and without ectopias. In the delayed matching-to sample task, a hidden escape platform remained in a constant position for each four-trial session, but changed position between sessions. Trial 2 was the measure of working memory, i.e., how well did the mouse remember where the platform was located for that session. In the water version of the eight-arm radial maze, hidden escape platforms were located in four of the eight arms, and each platform was removed from the maze once found. This enabled us to assess working and reference memory simultaneously. Ectopic mice demonstrated working memory deficits during the first part of the delayed matching-to sample task compared to nonectopics. Similarly, ectopics made more working memory errors during the latter half of radial-arm maze testing, while not differing from nonectopics in reference memory performance. Additionally, there were significant correlations between measures of working memory in the radial-arm maze and working memory in a delayed matching-to-sample task. These findings are in agreement with other studies demonstrating working memory deficits in ectopic BXSB mice.


Asunto(s)
Trastornos de la Memoria/genética , Trastornos de la Memoria/patología , Memoria a Corto Plazo/fisiología , Neocórtex/anomalías , Neocórtex/patología , Animales , Femenino , Aprendizaje por Laberinto , Trastornos de la Memoria/psicología , Ratones , Ratones Mutantes Neurológicos
17.
Behav Brain Res ; 112(1-2): 135-43, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10862944

RESUMEN

Perinatal gonadal hormones significantly affect subsequent sex differences in reproductive and non-reproductive behaviors in rodents. However, the influence of the sex chromosomes on these behaviors has been largely ignored. To assess the influence of the non-pseudoautosomal region of the Y chromosome, C57BL/JEi male and female mice and mice from the C57BL/6JEi-Y(POS) consomic strain were given behavioral tests known to distinguish males from females. The C57BL/6JEi-Y(POS) strain contains sex-reversed XY-females which, when compared to their XX-female siblings, allow assessment of the influence of the Y chromosome in a female phenotype. XX-females and XY-females did not differ on open-field activity, the Lashley maze, or active avoidance learning, but XY-females were significantly better than XX-females on the Morris hidden platform spatial maze. These findings suggest that males may have both a genetic and a hormonal mechanism to ensure visuospatial superiority.


Asunto(s)
Conducta Animal/fisiología , Trastornos del Desarrollo Sexual , Caracteres Sexuales , Percepción Espacial/fisiología , Cromosoma Y/fisiología , Animales , Cartilla de ADN , Estrógenos/fisiología , Femenino , Masculino , Aprendizaje por Laberinto/fisiología , Ratones , Ratones Endogámicos C57BL , Miogenina/genética , Fenotipo , Reacción en Cadena de la Polimerasa/métodos , Testosterona/fisiología
18.
Mol Cell Biol ; 20(11): 4135-48, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10805755

RESUMEN

The N-end rule relates the in vivo half-life of a protein to the identity of its N-terminal residue. N-terminal asparagine and glutamine are tertiary destabilizing residues, in that they are enzymatically deamidated to yield secondary destabilizing residues aspartate and glutamate, which are conjugated to arginine, a primary destabilizing residue. N-terminal arginine of a substrate protein is bound by the Ubr1-encoded E3alpha, the E3 component of the ubiquitin-proteasome-dependent N-end rule pathway. We describe the construction and analysis of mouse strains lacking the asparagine-specific N-terminal amidase (Nt(N)-amidase), encoded by the Ntan1 gene. In wild-type embryos, Ntan1 was strongly expressed in the branchial arches and in the tail and limb buds. The Ntan1(-/-) mouse strains lacked the Nt(N)-amidase activity but retained glutamine-specific Nt(Q)-amidase, indicating that the two enzymes are encoded by different genes. Among the normally short-lived N-end rule substrates, only those bearing N-terminal asparagine became long-lived in Ntan1(-/-) fibroblasts. The Ntan1(-/-) mice were fertile and outwardly normal but differed from their congenic wild-type counterparts in spontaneous activity, spatial memory, and a socially conditioned exploratory phenotype that has not been previously described with other mouse strains.


Asunto(s)
Amidohidrolasas/fisiología , Asparagina , Conducta Animal , Memoria , Amidohidrolasas/genética , Animales , Reacción de Fuga , Femenino , Expresión Génica , Líquido Intracelular/metabolismo , Aprendizaje , Masculino , Ratones , Ratones Endogámicos C57BL , Desempeño Psicomotor , Conducta Social
19.
J Clin Microbiol ; 38(5): 1866-8, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10790114

RESUMEN

ImmunoCard STAT! E. coli O157:H7 (Meridian Diagnostics, Inc., Cincinnati, Ohio) is a novel rapid (10-min) test for the presence of Escherichia coli O157:H7 in stools. The test may be performed either directly on stool specimens or on an overnight broth culture of stool. In a multicenter prospective study, 14 of 14 specimens positive by culture for E. coli O157:H7 were positive by the ImmunoCard STAT! O157:H7 test, and there were no false positives from 263 culture-negative specimens. In a retrospective study, the test was positive in 339 (81%) of 417 stored culture-positive specimens and the specificity was 95% (98 of 103 specimens). No false positives were associated with alternate stool pathogens. The ImmunoCard STAT! O157:H7 test has high sensitivity and specificity.


Asunto(s)
Escherichia coli O157/aislamiento & purificación , Heces/microbiología , Ensayo de Inmunoadsorción Enzimática/instrumentación , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Estudios Prospectivos , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad
20.
Brain Res ; 863(1-2): 151-9, 2000 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-10773203

RESUMEN

Recently, we published a method for examining working and reference memory in mice using a spatial version of the water radial-arm maze. Here we describe a non-spatial version of the same maze. BXSB mice were able to learn the maze as shown by the decrease in the number of working and reference memory errors over sessions. This maze was used to examine learning differences between males and females and between mice with misplaced clusters of neurons in layer I of cortex (ectopias) and those without. In a prior study using the spatial version of the water radial-arm maze, male BXSB mice had poorer working memory than females during the acquisition phase. Similarly, in this study male BXSB mice demonstrated impaired working memory during the asymptotic phase of non-spatial radial-arm maze learning. Two prior studies showed that mice with neocortical ectopias demonstrated working memory impairments compared to non-ectopic littermates in the spatial version of the water radial-arm maze. Contrary to this, in the non-spatial radial-arm maze used here, ectopic mice were not impaired in working memory and showed better memory when the working memory 'load' was the highest. Overall, both versions of the maze can be useful tools to assess spatial and non-spatial working and reference memory in mice.


Asunto(s)
Aprendizaje por Laberinto/fisiología , Memoria a Corto Plazo/fisiología , Percepción Espacial/fisiología , Animales , Encéfalo/fisiología , Femenino , Masculino , Ratones , Ratones Endogámicos , Caracteres Sexuales
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