RESUMEN
Drosophila larvae and adults exhibit a naturally occurring genetically based behavioural polymorphism in locomotor activity while foraging. Larvae of the rover morph exhibit longer foraging trails than sitters and forage between food patches, while sitters have shorter foraging trails and forage within patches. This behaviour is influenced by levels of cGMP-dependent protein kinase (PGK) encoded by the foraging (for) gene. Rover larvae have higher expression levels and higher PGK activities than do sitters. Here we discuss the importance of the for gene for studies of the mechanistic and evolutionary significance of individual differences in behaviour. We also show how structure-function analysis can be used to investigate a role for mushroom bodies in larval behaviour both in the presence and in the absence of food. Hydroxyurea fed to newly hatched larvae prevents the development of all post-embryonically derived mushroom body (MB) neuropil. This method was used to ablate MBs in rover and sitter genetic variants of foraging to test whether these structures mediate expression of the foraging behavioural polymorphism. We found that locomotor activity levels during foraging of both the rover and sitter larval morphs were not significantly influenced by MB ablation. Alternative hypotheses that may explain how variation in foraging behaviour is generated are discussed.
Asunto(s)
Conducta Animal/fisiología , Encéfalo/fisiología , Drosophila melanogaster/fisiología , Animales , Clonación Molecular , GMP Cíclico/fisiología , Proteínas Quinasas Dependientes de GMP Cíclico/genética , Proteínas Quinasas Dependientes de GMP Cíclico/fisiología , Drosophila melanogaster/genética , Conducta Alimentaria/fisiología , Genes de Insecto , Larva/fisiología , Modelos Neurológicos , Actividad Motora/genética , Actividad Motora/fisiología , Transducción de SeñalRESUMEN
BACKGROUND: The purpose of this study was to prospectively assess the effects of azathioprine on the humoral immune response to HLA alloantigens and allograft function in children receiving cryopreserved valved allografts. METHODS: We randomized 13 children to receive azathioprine or not to receive azathioprine (controls) after receiving a cryopreserved valved allograft. Azathioprine patients received intraoperatively 4 mg/kg of azathioprine and 2.0 +/- 0.5 mg/kg once daily for 3 months after operation. Panel reactive antibodies against HLA class I and class II alloantigens were measured before, 1 month, and 3 months after operation. RESULTS: Panel reactive antibodies were not significantly different between the azathioprine and control groups before (0.0% +/- 0% versus 1.6% +/- 1%), 1 month (59% +/- 17% versus 71% +/- 12%), or 3 months (84% +/- 15% versus 96% +/- 1.3%) after operation. There were no differences in degree of allograft valve stenosis between azathioprine (31.5 +/- 26 mm Hg, 13.4 +/- 7 months postoperatively) and control groups (25.4 +/- 11 mm Hg, 17.2 +/- 10 months postoperatively) or allograft valve insufficiency. CONCLUSIONS: Azathioprine does not significantly decrease the immune response to HLA alloantigens or affect the function of cryopreserved valved allografts used in children to repair congenital heart defects.
Asunto(s)
Azatioprina/uso terapéutico , Inmunosupresores/uso terapéutico , Adolescente , Formación de Anticuerpos/efectos de los fármacos , Válvula Aórtica/trasplante , Azatioprina/farmacología , Niño , Preescolar , Criopreservación , Femenino , Cardiopatías Congénitas/cirugía , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase II/inmunología , Humanos , Inmunosupresores/farmacología , Masculino , Estudios Prospectivos , Válvula Pulmonar/trasplante , Trasplante HomólogoRESUMEN
OBJECTIVE: To determine whether recombinant human granulocyte colony-stimulating factor (G-CSF) administration: 1) accelerates production of neutrophils; 2) increases bone marrow stored and precursor neutrophils; and 3) is safe in newborn infants with neutropenia and clinical signs of early-onset sepsis. STUDY DESIGN: We randomized 20 infants with neutropenia and clinical signs of early-onset sepsis in the first 3 days of life to receive G-CSF (10 microg/kg/d) or placebo for 3 days. Entry criteria included neutropenia as defined by Manroe criteria, an elevated immature to total neutrophil ratio [(I/T) >/=0.25], and a requirement for ventilatory support. Cultures were obtained and antibiotics initiated on all study infants. Circulating absolute neutrophil count (ANC), I/T ratio, bone marrow neutrophil storage pool (NSP) and neutrophil proliferative pool (NPP), and plasma G-CSF concentrations were evaluated. Also, severity of illness as determined using the Score for Neonatal Acute Physiology (SNAP), morbidity, and mortality were recorded. RESULTS: Circulating ANC increased in both G-CSF and placebo recipients by day 1. Also, the I/T neutrophil ratio decreased in both G-CSF and placebo recipients. There were no significant differences in the ANC or I/T ratio between the two groups during the study period. Similarly, bone marrow NSP and NPP did not differ between G-CSF and placebo recipients at study entry or day 2. No differences were observed in the secondary outcome measures including severity of illness, morbidity, and mortality. CONCLUSIONS: Administration of recombinant G-CSF to infants with neutropenia and clinical signs of early-onset sepsis did not increase circulating ANC, or bone marrow NSP and NPP compared with placebo. No differences were observed between G-CSF and placebo recipients in severity of illness, morbidity, or mortality. No adverse effects of G-CSF administrations were noted.
Asunto(s)
Bacteriemia/terapia , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Enfermedades del Prematuro/terapia , Neutropenia/terapia , Bacteriemia/inmunología , Bacteriemia/mortalidad , Médula Ósea/efectos de los fármacos , Médula Ósea/inmunología , Método Doble Ciego , Factor Estimulante de Colonias de Granulocitos/sangre , Humanos , Recién Nacido , Enfermedades del Prematuro/inmunología , Enfermedades del Prematuro/mortalidad , Recuento de Leucocitos/efectos de los fármacos , Neutropenia/inmunología , Neutropenia/mortalidad , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Proteínas Recombinantes , Tasa de SupervivenciaRESUMEN
This study shows that the broad anti-HLA antibody response against cryopreserved valved allografts used for surgical repair of congenital heart disease persists beyond 1 year after implantation. In 3 patients, there were clearly defined HLA antibody specificities consistent with the HLA phenotypes of the patients, i.e., the panel-reactive antibody was directed against major alloantigen groups that were not expressed by the antibody responders.
Asunto(s)
Válvula Aórtica/trasplante , Epítopos , Cardiopatías Congénitas/cirugía , Antígenos de Histocompatibilidad Clase I/inmunología , Isoanticuerpos/sangre , Válvula Pulmonar/trasplante , Adolescente , Niño , Preescolar , Criopreservación , Humanos , Lactante , Recién Nacido , Estudios Prospectivos , Factores de Tiempo , Trasplante HomólogoRESUMEN
Naturally occuring polymorphisms in behavior are difficult to map genetically and thus are refractory to molecular characterization. An exception is the foraging gene (for), a gene that has two naturally occurring variants in Drosophila melanogaster food-search behavior: rover and sitter. Molecular mapping placed for mutations in the dg2 gene, which encodes a cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG). Rovers had higher PKG activity than sitters, and transgenic sitters expressing a dg2 complementary DNA from rover showed transformation of behavior to rover. Thus, PKG levels affected food-search behavior, and natural variation in PKG activity accounted for a behavioral polymorphism.
Asunto(s)
Proteínas Quinasas Dependientes de GMP Cíclico/genética , Drosophila melanogaster/genética , Drosophila melanogaster/fisiología , Conducta Alimentaria , Genes de Insecto , Animales , Animales Modificados Genéticamente , GMP Cíclico/metabolismo , Proteínas Quinasas Dependientes de GMP Cíclico/metabolismo , Larva/genética , Larva/fisiología , Fenotipo , Polimorfismo Genético , Transducción de SeñalRESUMEN
OBJECTIVE: We hypothesized that using a higher dose of erythropoietin (Epo) and starting treatment on the first day of life would reduce the transfusion requirements of ventilator-dependent and non-ventilator-dependent very low birth weight (VLBW) infants. Moreover, we hypothesized that this treatment would be cost-effective. METHODS: We randomly assigned 20 ill newborn VLBW infants to receive either Epo (200 units/kg per day) or placebo during their first 2 weeks of life. The caregivers were unaware of the treatment assignments, and erythrocyte transfusions were administered according to hematocrit and signs of anemia. RESULTS: On day 1, reticulocyte counts and hematocrits were similar in the two groups. During the subsequent 2 weeks, reticulocyte counts of the placebo recipients fell significantly below those of the Epo recipients, but hematocrits in the two groups did not differ. More transfusions were received by the placebo recipients (mean = 1.4 per patient) than by the Epo recipients (mean = 0.2 per patient; p < 0.01). No adverse effects of Epo were noted, and the costs in the placebo group exceeded those in the Epo group. CONCLUSIONS: We conclude that administration of Epo to VLBW infants during the first 2 weeks of life results in fewer transfusions and is cost-effective.
Asunto(s)
Transfusión de Eritrocitos/estadística & datos numéricos , Eritropoyetina/economía , Eritropoyetina/uso terapéutico , Recién Nacido de Bajo Peso , Enfermedades del Recién Nacido/terapia , Análisis Costo-Beneficio , Costos y Análisis de Costo , Método Doble Ciego , Transfusión de Eritrocitos/economía , Humanos , Recién Nacido , Enfermedades del Recién Nacido/economíaRESUMEN
A method for the volumetric assessment of early cerebral infarction, together with its statistical and biological validation, is described. In halothane anaesthetised rats the stem of the right middle cerebral artery was occluded and 3 hours later (with full monitoring of respiratory and cardiovascular status) the animals were killed by perfusion fixation. In normotensive normocapnic animals the volume of infarction was 52 +/- 4 mm3 in the cerebral cortex and 21 +/- 1 mm3 in the corpus striatum. The reproducibility of the volumetric assessment was found to be excellent (coefficient of correlation 0.995 on 18 replicate measurements). The minimum number of stereotactic levels which must be assessed to yield accurate volumetric measurements of infarction is 8. The method is sensitive at detecting alterations in the amount of infarction. For example, it can readily detect the increase in amount of structural damage in cerebral cortex following a transient episode of hypotension. This approach allows an objective assessment of drug therapy and management strategies in the treatment of cerebral infarction.
Asunto(s)
Ataque Isquémico Transitorio/patología , Telencéfalo/patología , Animales , Presión Sanguínea , Arterias Cerebrales , Infarto Cerebral/patología , Modelos Animales de Enfermedad , Hipotensión/patología , Masculino , Ratas , Ratas EndogámicasRESUMEN
We used the [14C]iodoantipyrine autoradiography technique to study the effect of pretreatment with the calcium antagonist nimodipine on local cerebral blood flow (lCBF) in rats that underwent middle cerebral artery (MCA) occlusion. In untreated control animals there were profound localized reductions in 1CBF 30 minutes after MCA occlusion. These were most pronounced in neocortical areas and in the caudate nucleus ipsilateral to the MCA occlusion. In animals pretreated with nimodipine (1 microgram X kg-1 X min-1 for 30 minutes before and 30 minutes after MCA occlusion), the ipsilateral decrease in 1CBF in cortical regions was significantly less than that in control animals. The drug did not appear to alter 1CBF in the ipsilateral caudate nucleus. Neuropathological quantification of the ischemic damage present 3 hours after occlusion showed that nimodipine pretreatment reduced the volume and extent of cellular damage in the periphery but not in the core of the lesion.