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1.
The mechanism for oxytocin's (OT) stimulation of PGF(2alpha) secretion from porcine endometrium is not clear, but is thought to involve mobilization of intracellular Ca(2+) and subsequent activation of protein kinase C (PKC). This study determined: (1) if mobilization of inositol trisphosphate-sensitive Ca(2+) by thapsigargin or activation of PKC by phorbol 12-myristate 13-acetate (PMA) could stimulate PGF(2alpha) release from luminal epithelial, glandular epithelial and stromal cells of porcine endometrium and (2) if inhibitors of various PKC isotypes could attenuate the ability of OT, thapsigargin and PMA to stimulate PGF(2alpha) secretion from these cells. Thapsigargin and PMA each stimulated (P < 0.01) PGF(2alpha) secretion from all three endometrial cell types examined. However, the effects of thapsigargin and PMA were synergistic (P < 0.05) only in stromal cells. Three protein kinase C inhibitors (i.e. G?6976, G?6983 and Ro-31-8220) differentially attenuated (P < 0.05) the ability of OT, thapsigargin and PMA to stimulate PGF(2alpha) release. These results are consistent with the hypothesis that OT mobilizes Ca(2+) to activate a Ca(2+)-dependent PKC pathway to promote PGF(2alpha) secretion from porcine endometrial cells. The differing pattern of response to isotype-specific inhibitors of PKC among cell types suggests that distinct PKC isoforms are differentially expressed in luminal epithelial, glandular epithelial and stromal cells. 相似文献
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JG Hansen W Gao J Dupuis GT O’Connor W Tang M Kowgier A Sood SA Gharib LJ Palmer M Fornage SR Heckbert BM Psaty SL Booth SUNLIGHT Consortium Patricia A Cassano 《Respiratory research》2015,16(1)
Background
Vitamin D is associated with lung function in cross-sectional studies, and vitamin D inadequacy is hypothesized to play a role in the pathogenesis of chronic obstructive pulmonary disease. Further data are needed to clarify the relation between vitamin D status, genetic variation in vitamin D metabolic genes, and cross-sectional and longitudinal changes in lung function in healthy adults.Methods
We estimated the association between serum 25-hydroxyvitamin D [25(OH)D] and cross-sectional forced expiratory volume in the first second (FEV1) in Framingham Heart Study (FHS) Offspring and Third Generation participants and the association between serum 25(OH)D and longitudinal change in FEV1 in Third Generation participants using linear mixed-effects models. Using a gene-based approach, we investigated the association between 241 SNPs in 6 select vitamin D metabolic genes in relation to longitudinal change in FEV1 in Offspring participants and pursued replication of these findings in a meta-analyzed set of 4 independent cohorts.Results
We found a positive cross-sectional association between 25(OH)D and FEV1 in FHS Offspring and Third Generation participants (P = 0.004). There was little or no association between 25(OH)D and longitudinal change in FEV1 in Third Generation participants (P = 0.97). In Offspring participants, the CYP2R1 gene, hypothesized to influence usual serum 25(OH)D status, was associated with longitudinal change in FEV1 (gene-based P < 0.05). The most significantly associated SNP from CYP2R1 had a consistent direction of association with FEV1 in the meta-analyzed set of replication cohorts, but the association did not reach statistical significance thresholds (P = 0.09).Conclusions
Serum 25(OH)D status was associated with cross-sectional FEV1, but not longitudinal change in FEV1. The inconsistent associations may be driven by differences in the groups studied. CYP2R1 demonstrated a gene-based association with longitudinal change in FEV1 and is a promising candidate gene for further studies.Electronic supplementary material
The online version of this article (doi:10.1186/s12931-015-0238-y) contains supplementary material, which is available to authorized users. 相似文献3.
Utility of the white gene in estimating phylogenetic relationships among mosquitoes (Diptera: Culicidae) 总被引:2,自引:0,他引:2
The utility of a nuclear protein-coding gene for reconstructing
phylogenetic relationships within the family Culicidae was explored.
Relationships among 13 species representing three subfamilies and nine
genera of Culicidae were analyzed using a 762-bp fragment of coding
sequence from the eye color gene, white. Outgroups for the study were two
species from the sister group Chaoboridae. Sequences were determined from
clone PCR products amplified from genomic DNA, and aligned following
conceptual intron splicing and amino acid translation. Third codon
positions were characterized by high levels of divergence and biased
nucleotide composition, the intensity and direction of which varied among
taxa. Equal weighting of all characters resulted in parsimony and
neighboring-joining trees at odds with the generally accepted phylogenetic
hypothesis based on morphology and rDNA sequences. The application of
differential weighting schemes recovered the traditional hypothesis, in
which the subfamily Anophelinae formed the basal clade. The subfamily
Toxorhynchitinae occupied an intermediate position, and was a sister group
to the subfamily Culicinae. Within Culicinae, the genera Sabethes and
Tripteroides formed an ancestral clade, while the Culex-Deinocerites and
Aedes- Haemagogus clades occupied increasingly derived positions in the
molecular phylogeny. An intron present in the Culicinae- Toxorhynchitinae
lineage and one outgroup taxon was absent in the basal Anophelinae lineage
and the second outgroup taxon, suggesting that intron insertions or
deletions may not always be reliable systematic characters.
相似文献
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Anton GT Terwisscha van Scheltinga Marjolijn N Lub-de Hooge Keelara Abiraj Carolien P Schr?der Linda Pot Birgit Bossenmaier Marlene Thomas Gabriele H?lzlwimmer Thomas Friess Jos GW Kosterink Elisabeth GE de Vries 《MABS-AUSTIN》2014,6(4):1051-1058
The humanized monoclonal antibody with high affinity for the human epidermal growth factor receptor (HER) 3, RG7116, is a glycoengineered, IgG1 class antibody. By labeling RG7116 with zirconium-89 (89Zr) we aimed to visualize in vivo HER3 expression and study the biodistribution of this antibody in human tumor-bearing mice. Biodistribution of 89Zr-RG7116 was studied in subcutaneously xenografted FaDu tumor cells (HER3-positive). Dose-dependency of 89Zr-RG7116 organ distribution and specific tumor uptake was assessed by administering doses ranging from 0.05 to 10 mg/kg RG7116 to SCID/Beige mice. Biodistribution was analyzed at 24 and 144 h after injection. MicroPET imaging was performed at 1, 3, and 6 days after injection of 1.0 mg/kg 89Zr-RG7116 in the FaDu, H441, QG-56 and Calu-1 xenografts with varying HER3 expression. The excised tumors were analyzed for HER3 expression. Biodistribution analyses showed a dose- and time-dependent 89Zr-RG7116 tumor uptake in FaDu tumors. The highest tumor uptake of 89Zr-RG7116 was observed in the 0.05 mg/kg dose group with 27.5%ID/g at 144 h after tracer injection. MicroPET imaging revealed specific tumor uptake of 89Zr-RG7116 in FaDu and H441 models with an increase in tumor uptake over time. Biodistribution data was consistent with the microPET findings in FaDu, H441, QG56 and Calu-1 xenografts, which correlated with HER3 expression levels. In conclusion, 89Zr-RG7116 specifically accumulates in HER3 expressing tumors. PET imaging with this tracer provides real-time non-invasive information about RG7116 distribution, tumor targeting and tumor HER3 expression levels. 相似文献
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During the past 2 decades, commercial preparations of FSH have been extensively used to superovulate cattle. The problems that have been encountered in superovulation of cattle include high variability in the ovulation rate and subsequent yield of viable embryos. The lack of predictability in superovulatory trials has been attributed to difficulties in standardizing the potency of commercial FSH preparations. Traditionally, FSH potency has been tested in bioassays that utilize specific responses in whole animals or primary cell cultures. Whole animal bioassays lack sensitivity, while primary cell culture bioassays, which use fresh cells, have inherent variability within each preparation. An FSH bioassay that employed a stable chimeric cell line expressing the human FSH-R was used to provide an accurate measurement of FSH bioactivity. The hormonal potency of 2 commercial preparations of FSH used to superovulate cattle was determined using FSH immuno- and bioassays. Commercial FSH preparations differed in potency. One commercial product, prepared in 4 different years, showed no difference in the immunoactive levels of FSH. In the same product stored under identical conditions, FSH bioactivity varied from year to year. There was variability in FSH bioactivity both between and within commercial products. The lack of correlation between bioactivity and immunoactivity of commercial FSH preparations may explain, in part, the variability observed in superovulation of cattle. 相似文献
9.
The purpose of this study was to investigate the need for and choice of stratification factors, and the effects of blinding
and placebo in a clinical experiment. Eighty dogs with canine hip dysplasia (CHD) were included in a randomized, placebo-controlled
and double blind clinical trial with stratified parallel group design, in which body weight and degree of CHD were used as
stratification factors. Thirty-eight dogs were allocated to gold bead implantation and 42 to placebo. After six months, 33
of the 42 placebo-treated dogs received gold bead implantation in an open study lasting a further 18 months. The main outcome
variable in the study was change in pain signs of CHD as assessed by the owner. No significant difference in the main outcome
variable, regardless of the treatment given, could be detected in the two chosen stratification factors. The only factor to
influence the main outcome variable significantly was age. The blinding procedure used in the study, in which 60% of the owners
correctly guessed the treatment given, was found sufficient. Of those who guessed the treatment erroneously, 88% believed
the treatment given was gold bead implantation. The treatment efficacy after six months in the blinded treatment group was
found to be significantly larger compared to the efficacy obtained in the open study. A significant placebo effect was therefore
detected. Conclusion and Clinical Relevance: The age of the dogs influenced the outcome of the CHD treatment, and is recommended
as a stratification factor. A significant placebo effect has to be expected and an optimal blinding procedure is necessary
in similar clinical studies. 相似文献
10.
In swine, endometrial prostaglandin F(2alpha) (PGF(2alpha)) is the luteolysin. The capacity of luminal epithelial cells isolated from the endometrium of day 16 cyclic pigs, to secrete PGF(2alpha)500 Omega/cm(2)), they were treated on the apical, basal or both surfaces with 0 or 100 nM oxytocin (OT) in Experiment 1 or phorbol 12-myristate 13-acetate (PMA) in Experiment 2. In the absence of OT or PMA, PGF(2alpha) secretion occurred primarily from the basal surface and was approximately 12-fold greater (P < 0.001) than from the apical surface. Treatment with OT did not stimulate PGF(2alpha) secretion from either surface regardless of which surface was treated. In contrast, PMA increased PGF(2alpha) secretion from both surfaces. Treatment of the apical surface or both surfaces with PMA increased (P < 0.001) PGF(2alpha) secretion similarly from both surfaces. Treatment of only the basal surface with PMA increased (P < 0.01) PGF(2alpha) secretion from both surfaces, but tended (P = 0. 06) to increase its secretion from the basal surface more than from the apical surface. These results indicated that PGF(2alpha) secretion by luminal epithelial cells obtained from cyclic pigs occurs primarily toward a basal direction and is not stimulated by oxytocin. Activation of protein kinase C stimulates directional secretion of PGF(2alpha) from both surfaces of the epithelial cells. 相似文献