Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 9 de 9
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
J Obstet Gynaecol Can ; 36(7): 598-604, 2014 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25184978

RESUMEN

OBJECTIVE: To determine the effectiveness of portable lactate analyzers in identifying fetal acidosis by correlating arterial and venous lactate values from umbilical cord blood with lactate, pH, and base excess measurements from central laboratory analyzers. METHODS: We performed a prospective study using arterial and venous cord blood from 52 women with a singleton fetus delivered at term. We evaluated the correlation between the cord blood lactate concentration measured using two of the same portable devices (Lactate Plus, Nova Biomedical) with the result from a central laboratory analyzer. Analyses of the correlation between arterial lactate concentration measured on the portable device with arterial pH and base excess were then performed. RESULTS: We observed a median arterial pH of 7.24 (range 7.05 to 7.35) and a median arterial lactate concentration of 3.7 mmol/L (range 1.7 to 8.8 mmol/L). An excellent correlation was observed between lactate concentrations measured by the two portable devices (arterial R² = 0.98 and venous R² = 0.98), and between the portable device and the central laboratory analyzer (arterial R² = 0.94 and venous R² = 0.95). In our population, the optimal cut-offs to predict a pH < 7.20 or a base excess > -8.0 mmol/L were a lactate concentration of 4.9 mmol/L and 5.3 mmol/L, respectively, according to receiver operator characteristic analysis. With a lactate concentration > 4.9 mmol/L, the portable device had a sensitivity of 82% and a specificity of 90% to identify samples with an arterial pH < 7.20. CONCLUSION: Cord blood lactate concentration measured with a portable device is a good predictor of cord blood base excess and pH. Future studies should be designed to correlate scalp blood lactate measurements with clinical outcomes.


Objectif : Déterminer l'efficacité des analyseurs de lactate portatifs, pour ce qui est de l'identification de l'acidose fœtale, en mettant en corrélation les valeurs artérielle et veineuse du lactate constatées dans le sang de cordon ombilical et les mesures du lactate, du pH et de l'excès de bases révélées par les analyseurs du laboratoire central. Méthodes : Nous avons mené une étude prospective en utilisant le sang de cordon artériel et veineux prélevé chez 52 femmes qui ont connu une grossesse monofœtale s'étant soldée en un accouchement à terme. Nous avons évalué la corrélation entre la concentration en lactate du sang de cordon mesurée au moyen de deux exemplaires du même appareil portatif (Lactate Plus, Nova Biomedical) et le résultat obtenu au moyen d'un analyseur du laboratoire central. Nous avons par la suite procédé à des analyses de la corrélation entre la concentration artérielle en lactate mesurée au moyen de l'appareil portatif et les valeurs artérielles du pH et de l'excès de bases. Résultats : Nous avons constaté un pH artériel médian de 7,24 (plage : 7,05 - 7,35) et une concentration artérielle en lactate médiane de 3,7 mmol/l (plage : 1,7 - 8,8 mmol/l). Une excellente corrélation a été constatée entre les concentrations en lactate mesurées par les deux appareils portatifs (R2 artériel = 0,98 et R2 veineux = 0,98) et entre les concentrations mesurées par l'appareil portatif et par l'analyseur du laboratoire central (R2 artériel = 0,94 et R2 veineux = 0,95). Au sein de notre population, les seuils optimaux permettant de prédire un pH < 7,20 ou un excès de bases > −8,0 mmol/l ont été des concentrations en lactate de 4,9 mmol/l et de 5,3 mmol/l, respectivement, selon l'analyse de la fonction d'efficacité du récepteur. En présence d'une concentration en lactate > 4,9 mmol/l, l'appareil portatif comptait une sensibilité de 82 % et une spécificité de 90 % pour ce qui est de l'identification des prélèvements présentant un pH artériel < 7,20. Conclusion : La concentration en lactate du sang de cordon qui est mesurée au moyen d'un appareil portatif constitue un bon facteur prédictif pour ce qui est du pH et de l'excès de bases du sang de cordon. De futures études devraient être conçues de façon à pouvoir mettre en corrélation les concentrations en lactate dans le sang prélevé sur le cuir chevelu et les résultats cliniques.


Asunto(s)
Acidosis/diagnóstico , Sangre Fetal/metabolismo , Enfermedades Fetales/diagnóstico , Ácido Láctico/sangre , Diagnóstico Prenatal/instrumentación , Diagnóstico Prenatal/métodos , Humanos , Concentración de Iones de Hidrógeno , Estudios Prospectivos , Sensibilidad y Especificidad
2.
Mol Vis ; 17: 1850-61, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21850159

RESUMEN

PURPOSE: Nanophthalmos is a rare genetic ocular disorder in which the eyes of affected individuals are abnormally small. Patients suffer from severe hyperopia as a result of their markedly reduced axial lengths, but otherwise are capable of seeing well unlike other more general forms of microphthalmia. To date one gene for nanophthalmos has been identified, encoding the membrane-type frizzled related protein MFRP. Identification of additional genes for nanophthalmos will improve our understanding of normal developmental regulation of eye growth. METHODS: We ascertained a cohort of families from eastern Canada and Mexico with familial nanophthalmos. We performed high density microsatellite and high density single nucleotide polymorphism (SNP) genotyping to identify potential chromosomal regions of linkage. We sequenced coding regions of genes in the linked interval by traditional PCR-based Sanger capillary electrophoresis methods. We cloned and sequenced a novel cDNA from a putative causal gene to verify gene structure. RESULTS: We identified a linked locus on chromosome 2q37 with a peak logarithm (base 10) of odds (LOD) score of 4.7. Sequencing of coding exons of all genes in the region identified multiple segregating variants in one gene, recently annotated as serine protease gene (PRSS56), coding for a predicted trypsin serine protease-like protein. One of our families was homozygous for a predicted pathogenic missense mutation, one family was compound heterozygous for two predicted pathogenic missense mutations, and one family was compound heterozygous for a predicted pathogenic missense mutation plus a frameshift leading to obligatory truncation of the predicted protein. The PRSS56 gene structure in public databases is based on a virtual transcript assembled from overlapping incomplete cDNA clones; we have now validated the structure of a full-length transcript from embryonic mouse brain RNA. CONCLUSIONS: PRSS56 is a good candidate for the causal gene for nanophthalmos in our families.


Asunto(s)
Ojo/fisiopatología , Hiperopía/genética , Microftalmía/genética , Serina Proteasas , Animales , Secuencia de Bases , Canadá , Clonación Molecular , Estudios de Cohortes , Análisis Mutacional de ADN , Exones , Ojo/patología , Ligamiento Genético , Genotipo , Técnicas de Genotipaje , Heterocigoto , Homocigoto , Humanos , Hiperopía/etiología , Hiperopía/patología , Escala de Lod , Proteínas de la Membrana/genética , México , Ratones , Microftalmía/complicaciones , Microftalmía/patología , Datos de Secuencia Molecular , Mutación , Linaje , Serina Proteasas/genética
3.
Hum Mutat ; 32(10): 1114-7, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21681853

RESUMEN

Hajdu-Cheney syndrome (HCS) is a rare genetic disorder whose hallmark is acro-osteolysis, shortening of terminal phalanges, and generalized osteoporosis. We assembled a cohort of seven families with the condition and performed whole exome resequencing on a selected set of affected patients. One protein-coding gene, NOTCH2, carried heterozygous truncating variants in all patients and their affected family members. Our results replicate recently published studies of HCS and further support this as the causal gene for the disorder. In total, we identified five novel and one previously reported mutation, all clustered near the carboxyl terminus of the gene, suggesting an allele specific genotype-phenotype effect since other mutations in NOTCH2 have been reported to cause a form of Alagille syndrome. Notch-mediated signaling is known to play a role in bone metabolism. Our results support a potential therapeutic role for Notch pathways in treatment of osteoporosis.


Asunto(s)
Síndrome de Hajdu-Cheney/genética , Mutación , Receptor Notch2/genética , Acroosteólisis/diagnóstico por imagen , Acroosteólisis/genética , Exoma , Cara/anomalías , Salud de la Familia , Femenino , Mano , Deformidades Congénitas de la Mano/diagnóstico por imagen , Humanos , Masculino , Linaje , Radiografía
4.
PLoS Genet ; 6(9): e1001118, 2010 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-20862357

RESUMEN

Tay-Sachs disease is a severe lysosomal disorder caused by mutations in the HexA gene coding for the α-subunit of lysosomal ß-hexosaminidase A, which converts G(M2) to G(M3) ganglioside. Hexa(-/-) mice, depleted of ß-hexosaminidase A, remain asymptomatic to 1 year of age, because they catabolise G(M2) ganglioside via a lysosomal sialidase into glycolipid G(A2), which is further processed by ß-hexosaminidase B to lactosyl-ceramide, thereby bypassing the ß-hexosaminidase A defect. Since this bypass is not effective in humans, infantile Tay-Sachs disease is fatal in the first years of life. Previously, we identified a novel ganglioside metabolizing sialidase, Neu4, abundantly expressed in mouse brain neurons. Now we demonstrate that mice with targeted disruption of both Neu4 and Hexa genes (Neu4(-/-);Hexa(-/-)) show epileptic seizures with 40% penetrance correlating with polyspike discharges on the cortical electrodes of the electroencephalogram. Single knockout Hexa(-/-) or Neu4(-/-) siblings do not show such symptoms. Further, double-knockout but not single-knockout mice have multiple degenerating neurons in the cortex and hippocampus and multiple layers of cortical neurons accumulating G(M2) ganglioside. Together, our data suggest that the Neu4 block exacerbates the disease in Hexa(-/-) mice, indicating that Neu4 is a modifier gene in the mouse model of Tay-Sachs disease, reducing the disease severity through the metabolic bypass. However, while disease severity in the double mutant is increased, it is not profound suggesting that Neu4 is not the only sialidase contributing to the metabolic bypass in Hexa(-/-) mice.


Asunto(s)
Epilepsia/enzimología , Epilepsia/patología , Lisosomas/enzimología , Neuraminidasa/deficiencia , Neuronas/enzimología , Neuronas/patología , Cadena alfa de beta-Hexosaminidasa/metabolismo , Animales , Conducta Animal , Corteza Cerebral/enzimología , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Corteza Cerebral/ultraestructura , Electroencefalografía , Epilepsia/fisiopatología , Gangliósido G(M2)/metabolismo , Técnicas de Inactivación de Genes , Hipocampo/enzimología , Hipocampo/patología , Hipocampo/fisiopatología , Hipocampo/ultraestructura , Aprendizaje/fisiología , Lisosomas/patología , Lisosomas/ultraestructura , Ratones , Actividad Motora/fisiología , Neuraminidasa/metabolismo , Neuronas/ultraestructura
5.
Hum Mol Genet ; 17(11): 1556-68, 2008 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-18270209

RESUMEN

Mammalian sialidase Neu4, ubiquitously expressed in human tissues, is located in the lysosomal and mitochondrial lumen and has broad substrate specificity against sialylated glycoconjugates. To investigate whether Neu4 is involved in ganglioside catabolism, we transfected beta-hexosaminidase-deficient neuroglia cells from a Tay-Sachs patient with a Neu4-expressing plasmid and demonstrated the correction of storage due to the clearance of accumulated GM2 ganglioside. To further clarify the biological role of Neu4, we have generated a stable loss-of-function phenotype in cultured HeLa cells and in mice with targeted disruption of the Neu4 gene. The silenced HeLa cells showed reduced activity against gangliosides and had large heterogeneous lysosomes containing lamellar structures. Neu4(-/-) mice were viable, fertile and lacked gross morphological abnormalities, but showed a marked vacuolization and lysosomal storage in lung and spleen cells. Lysosomal storage bodies were also present in cultured macrophages preloaded with gangliosides. Thin-layer chromatography showed increased relative level of GD1a ganglioside and a markedly decreased level of GM1 ganglioside in brain of Neu4(-/-) mice suggesting that Neu4 may be important for desialylation of brain gangliosides and consistent with the in situ hybridization data. Increased levels of cholesterol, ceramide and polyunsaturated fatty acids were also detected in the lungs and spleen of Neu4(-/-) mice by high-resolution NMR spectroscopy. Together, our data suggest that Neu4 is a functional component of the ganglioside-metabolizing system, contributing to the postnatal development of the brain and other vital organs.


Asunto(s)
Gangliósidos/metabolismo , Lisosomas/metabolismo , Neuraminidasa/genética , Neuraminidasa/fisiología , Animales , Conducta Animal , Encéfalo/enzimología , Encéfalo/fisiología , Encéfalo/ultraestructura , Catálisis , Gangliósido G(M1)/análisis , Gangliósido G(M1)/metabolismo , Gangliósido G(M2)/análisis , Gangliósido G(M2)/metabolismo , Gangliósidos/análisis , Células HeLa , Humanos , Pulmón/enzimología , Pulmón/ultraestructura , Ratones , Ratones Noqueados , Neuraminidasa/metabolismo , Interferencia de ARN , Bazo/enzimología , Bazo/ultraestructura , Distribución Tisular , beta-N-Acetilhexosaminidasas/genética
6.
Dev Biol ; 298(1): 95-106, 2006 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-16860307

RESUMEN

The bHLH-PAS transcription factor SIM1 is required for the development of neurons of the anterior hypothalamus (AH). In order to dissect this developmental program, we compared gene expression in the AH of E12.5 Sim1(+/+) and Sim1(-/-) littermates using an oligonucleotide-based microarray. Our analysis identified 48 genes that were downregulated and 8 genes that were upregulated. We examined the expression pattern of 10 of the identified genes--Cart, Cbln1, Alcam, Unc-13c, Rgs4, Lnx4, Irx3, Sax1, Ldb2 and Neurod6--by in situ hybridization in E12.5 embryos. All of these genes are expressed in domains that are contained within that of Sim1 and their expression is changed in Sim1(-/-) embryos as predicted by the microarray analysis. Classical dating studies have established that the hypothalamus follows an "outside-in" pattern of neurogenesis, with neurons of the lateral hypothalamus being born before the medial ones. Analysis of the genes identified in this microarray study showed that the developing AH is characterized by different layers of gene expression that most likely correspond to distinct waves of neurogenesis. In addition, our analysis suggests that Sim1 function is required for the production or the survival of postmitotic neurons as well as for correct positioning of AH neurons.


Asunto(s)
Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Tipificación del Cuerpo , Hipotálamo Anterior/embriología , Neuronas/fisiología , Proteínas Represoras/metabolismo , Lámina Espiral/embriología , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Diferenciación Celular , Perfilación de la Expresión Génica , Hipotálamo Anterior/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Modelos Biológicos , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Represoras/genética
7.
Development ; 132(24): 5527-37, 2005 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-16291793

RESUMEN

The mammillary body (MB), and its axonal projections to the thalamus (mammillothalamic tract, MTT) and the tegmentum (mammillotegmental tract, MTEG), are components of a circuit involved in spatial learning. The bHLH-PAS transcription factors SIM1 and SIM2 are co-expressed in the developing MB. We have found that MB neurons are generated and that they survive at least until E18.5 in embryos lacking both Sim1 and Sim2 (Sim1(-/-);Sim2(-/-)). However, the MTT and MTEG are histologically absent in Sim1(-/-);Sim2(-/-) embryos, and are reduced in embryos lacking Sim1 but bearing one or two copies of Sim2, indicating a contribution of the latter to the development of MB axons. We have generated, by homologous recombination, a null allele of Sim1 (Sim1(tlz)) in which the tau-lacZ fusion gene was introduced, allowing the staining of MB axons. Consistent with the histological studies, lacZ staining showed that the MTT/MTEG is barely detectable in Sim1(tlz/tlz);Sim2(+/-) and Sim1(tlz/tlz);Sim2(-/-) brains. Instead, MB axons are splayed and grow towards the midline. Slit1 and Slit2, which code for secreted molecules that induce the repulsion of ROBO1-producing axons, are expressed in the midline at the level of the MB, whereas Robo1 is expressed in the developing MB. The expression of Rig-1/Robo3, a negative regulator of Slit signalling, is upregulated in the prospective MB of Sim1/Sim2 double mutants, raising the possibility that the growth of mutant MB axons towards the midline is caused by a decreased sensitivity to SLIT. Finally, we found that Sim1 and Sim2 act along compensatory, but not hierarchical, pathways, suggesting that they play similar roles in vivo.


Asunto(s)
Axones/metabolismo , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Tubérculos Mamilares/embriología , Proteínas Represoras/metabolismo , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Supervivencia Celular , Dosificación de Gen , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Tubérculos Mamilares/citología , Tubérculos Mamilares/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Mutación , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Receptores de Superficie Celular , Receptores Inmunológicos/metabolismo , Proteínas Represoras/genética , Tegmento Mesencefálico/anomalías , Tegmento Mesencefálico/embriología , Tálamo/anomalías , Tálamo/embriología , Proteínas Roundabout
8.
Horm Res ; 64(5): 222-30, 2005.
Artículo en Inglés | MEDLINE | ID: mdl-16227700

RESUMEN

The hypothalamus is a critical integrator of several homeostatic processes that are required for the survival of vertebrates. Disruption of the development of the hypothalamus thus has the potential of perturbing important physiological processes with lifelong consequences. We review current knowledge about how cell types are specified and circuits are formed within the developing hypothalamus. We emphasize the potential clinical impact of the perturbations of these pathways using the regulation of energy balance as a model. We predict that disruption of hypothalamic development is a common, previously unsuspected cause of disorders of homeostatic processes such as obesity and high blood pressure.


Asunto(s)
Enfermedades Hipotalámicas , Hipotálamo/crecimiento & desarrollo , Animales , Núcleo Arqueado del Hipotálamo , Metabolismo Energético , Impresión Genómica , Homeostasis , Humanos , Hipertensión , Enfermedades Hipotalámicas/fisiopatología , Hipotálamo/anomalías , Hipotálamo/fisiopatología , Obesidad/etiología , Núcleo Hipotalámico Paraventricular , Factores de Transcripción/fisiología
9.
Dev Dyn ; 233(2): 652-8, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15844192

RESUMEN

Loss-of-function experiments in mice have shown that the transcription factors Sim1, Otp, Sim2, and Brn2 form a cascade essential for the differentiation of neuroendocrine cells of the anterior hypothalamus that produce vasopressin, oxytocin, somatostatin (SS), thyrotropin-releasing hormone (TRH), and corticotropin-releasing hormone (CRH). Very little is known about how the differentiation of these cell types is regulated in chick. Here, we report the cloning of the chick homolog of Otp. Moreover, we have systematically compared the expression of Sim1, Sim2, Brn2, and Otp with that of the markers of terminal differentiation TRH, SS, CRH, vasotocin, and mesotocin during development of chick embryos. We have found that the cell types studied generally develop in domains expressing these transcriptional regulators but that the pattern of neuronal differentiation and the spatial distribution of some regulators were not the same as in mice. Our results provide a framework useful for the functional analysis of hypothalamus development in chick.


Asunto(s)
Hipotálamo Anterior/citología , Hipotálamo Anterior/embriología , Animales , Biomarcadores , Diferenciación Celular , Núcleo Celular/genética , Embrión de Pollo , Regulación del Desarrollo de la Expresión Génica , Hipotálamo Anterior/metabolismo , Hibridación in Situ , Proteínas del Tejido Nervioso/genética , ARN Mensajero/análisis , ARN Mensajero/genética , Proteínas Represoras/genética , Factores de Transcripción/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...