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971.
The long-acting antibiotic tulathromycin is on the marked for treatment of pulmonary infection of cattle, swine and horses. To measure disposition and distribution of tulathromycin in foals, a high throughput method was developed for horse plasma (calibration range: 0.006-0.8 microg/mL) and broncho-alveolar cells (calibration range: 0.1-4.0 microg/10(9)cells) using tandem mass spectrometry. Tulathromycin was extracted from plasma and broncho-alveolar fluid using cation exchange cartridges with acetonitrile/ammonia (95:5, v/v). The chromatography was performed isocratically with a mobile phase consisting of 5 mM ammonium formiate buffer/acetonitrile (30:70, v/v). The mass spectrometer operated in selected ion mode with atmospheric pressure chemical ionization to monitor the respective MH+ ions m/z 577.3 for tulathromycin and m/z 679.3 for the internal standard roxithromycin. All quality parameters fulfilled the international criteria for bioanalytical method validation and were successfully applied to the determination of tulathromycin in plasma of foals and broncho-alveolar cells. In foals, tulathromycin after intramuscular administration was rapidly absorbed, widely distributed and slowly eliminated. It cumulated manifold in broncho-alveolar cells.  相似文献   
972.
The colonic epithelium continuously regenerates with transitions through various cellular phases including proliferation, differentiation and cell death via apoptosis. Human colonic adenocarcinoma (Caco-2) cells in culture undergo spontaneous differentiation into mature enterocytes in association with progressive increases in expression of glutathione S-transferase alpha-1 (GSTA1). We hypothesize that GSTA1 plays a functional role in controlling proliferation, differentiation and apoptosis in Caco-2 cells. We demonstrate increased GSTA1 levels associated with decreased proliferation and increased expression of differentiation markers alkaline phosphatase, villin, dipeptidyl peptidase-4 and E-cadherin in postconfluent Caco-2 cells. Results of MTS assays, BrdU incorporation and flow cytometry indicate that forced expression of GSTA1 significantly reduces cellular proliferation and siRNA-mediated down-regulation of GSTA1 significantly increases cells in S-phase and associated cell proliferation. Sodium butyrate (NaB) at a concentration of 1 mM reduces Caco-2 cell proliferation, increases differentiation and increases GSTA1 activity 4-fold by 72 hours. In contrast, 10 mM NaB causes significant toxicity in preconfluent cells via apoptosis through caspase-3 activation with reduced GSTA1 activity. However, GSTA1 down-regulation by siRNA does not alter NaB-induced differentiation or apoptosis in Caco-2 cells. While 10 mM NaB causes GSTA1-JNK complex dissociation, phosphorylation of JNK is not altered. These findings suggest that GSTA1 levels may play a role in modulating enterocyte proliferation but do not influence differentiation or apoptosis.  相似文献   
973.
Severe familial amyloid cardiomyopathy (FAC) in a Danish kindred is associated with a specific mutation (Met for Leu 111) in the transthyretin (TTR) gene. The mutation causes the loss of a DdeI restriction site in the gene, allowing molecular diagnostic studies. We studied formalin-fixed, paraffin-embedded tissues, up to 39 years old, from 29 family members of this kindred. DNA was partially purified from deparaffinized tissue sections and a DNA sequence of the TTR gene flanking the mutation site was amplified by the polymerase chain reaction (PCR), followed by restriction enzyme analysis. Amplified DNA was obtained from tissues representing 23 of the 29 persons. Ten out of the 23 family members were found to carry the TTR Met 111 mutation, whereas 13 were not affected. The results were consistent with known clinical data and with corresponding serum TTR examinations. This retrospective study shows that archival tissues can be used to confirm the diagnosis and disease pattern in members of families affected by hereditary diseases.  相似文献   
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Here, we used an obstacle treadmill experiment to investigate the neuromuscular control of locomotion in uneven terrain. We measured in vivo function of two distal muscles of the guinea fowl, lateral gastrocnemius (LG) and digital flexor-IV (DF), during level running, and two uneven terrains, with 5 and 7 cm obstacles. Uneven terrain required one step onto an obstacle every four to five strides. We compared both perturbed and unperturbed strides in uneven terrain to level terrain. When the bird stepped onto an obstacle, the leg became crouched, both muscles acted at longer lengths and produced greater work, and body height increased. Muscle activation increased on obstacle strides in the LG, but not the DF, suggesting a greater reflex contribution to LG. In unperturbed strides in uneven terrain, swing pre-activation of DF increased by 5 per cent compared with level terrain, suggesting feed-forward tuning of leg impedance. Across conditions, the neuromechanical factors in work output differed between the two muscles, probably due to differences in muscle-tendon architecture. LG work depended primarily on fascicle length, whereas DF work depended on both length and velocity during loading. These distal muscles appear to play a critical role in stability by rapidly sensing and responding to altered leg-ground interaction.  相似文献   
978.

Background

We evaluated if exposure to RF-EMF was associated with reported quality of sleep in 2,361 children, aged 7 years.

Methods

This study was embedded in the Amsterdam Born Children and their Development (ABCD) birth cohort study. When children were about five years old, school and residential exposure to RF-EMF from base stations was assessed with a geospatial model (NISMap) and from indoor sources (cordless phone/WiFi) using parental self-reports. Parents also reported their children’s use of mobile or cordless phones. When children were seven years old, we evaluated sleep quality as measured with the Child Sleep Habits Questionnaire (CSHQ) filled in by parents. Of eight CSHQ subscales, we evaluated sleep onset delay, sleep duration, night wakenings, parasomnias and daytime sleepiness with logistic or negative binomial regression models, adjusting for child’s age and sex and indicators of socio-economic position of the parents. We evaluated the remaining three subscales (bedtime resistance, sleep anxiety, sleep disordered breathing) as unrelated outcomes (negative control) because these were a priori hypothesised not to be associated with RF-EMF.

Results

Sleep onset delay, night wakenings, parasomnias and daytime sleepiness were not associated with residential exposure to RF-EMF from base stations. Sleep duration scores were associated with RF-EMF levels from base stations. Higher use mobile phones was associated with less favourable sleep duration, night wakenings and parasomnias, and also with bedtime resistance. Cordless phone use was not related to any of the sleeping scores.

Conclusion

Given the different results across the evaluated RF-EMF exposure sources and the observed association between mobile phone use and the negative control sleep scale, our study does not support the hypothesis that it is the exposure to RF-EMF that is detrimental to sleep quality in 7-year old children, but potentially other factors that are related to mobile phone usage.  相似文献   
979.
For nearly 40 years functional studies of the mouse quaking gene (qkI) have focused on its role in the postnatal central nervous system during myelination. However, the homozygous lethality of a number of ENU-induced alleles reveals that quaking has a critical role in embryonic development prior to the start of myelination. In this article, we show that quaking has a previously unsuspected and essential role in blood vessel development. Interestingly, we found that quaking, a nonsecreted protein, is expressed in the yolk sac endoderm, adjacent to the mesodermal site of developing blood islands, where the differentiation of blood and endothelial cells first occurs. Antibodies against PE-CAM-1, TIE-2 and SM-alpha-actin reveal that embryos homozygous for the qk(k2) allele have defective yolk sac vascular remodeling and abnormal vessels in the embryo proper at midgestation, coinciding with the timing of embryonic death. However, these mutants exhibit normal expression of Nkx2.5 and alpha-sarcomeric actin, indicating that cardiac muscle differentiation was normal. Further, they had normal embryonic heart rates in culture, suggesting that cardiac function was not compromised at this stage of embryonic development. Together, these results suggest that quaking plays an essential role in vascular development and that the blood vessel defects are the cause of embryonic death.  相似文献   
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