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21.
Phosphodiesterase-4 (PDE4) is one of the main enzymes that specifically terminate the action of cAMP, thereby contributing to intracellular signaling following stimulation of various G protein-coupled receptors. PDE4 expression and activity are modulated by agents affecting cAMP levels. The selective PDE4 inhibitor (R)-rolipram labeled with C-11 was tested in vivo in rats to analyze changes in PDE4 levels following drug treatments that increase synaptic noradrenaline (NA), serotonin (5HT), histamine (HA) and dopamine (DA) levels. We hypothesized that increasing synaptic neurotransmitter levels and subsequent cAMP-mediated signaling would significantly enhance (R)-[(11)C]rolipram retention and specific binding to PDE4 in vivo. Pre-treatments were performed 3 h prior to tracer injection, and rats were sacrificed 45 min later. Biodistribution studies revealed a dose-dependent increase in (R)-[(11)C]rolipram uptake following administration of the monoamine oxidase (MAO) inhibitor tranylcypromine, NA and 5HT reuptake inhibitors (desipramine [DMI], maprotiline; and fluoxetine, sertraline, respectively), and the HA H(3) receptor antagonist (thioperamide), but not with DA transporter blockers GBR 12909, cocaine or DA D(1) agonist SKF81297. Significant increases in rat brain and heart reflect changes in PDE4 specific binding (total-non-specific binding [coinjection with saturating dose of (R)-rolipram]). These results demonstrate that acute treatments elevating synaptic NA, 5HT and HA, but not DA levels, significantly enhance (R)-[(11)C]rolipram binding. Use of (R)-[(11)C]rolipram and positron emission tomography as an index of PDE4 activity could provide insight into understanding disease states with altered NA, 5HT and HA concentrations. 相似文献
22.
Songhua Zhang Joseph Desrosiers Jose R. Aponte-Pieras Kristen DaSilva Loren D. Fast Frances Terry William D. Martin Anne S. De Groot Leonard Moise Steven F. Moss 《PloS one》2014,9(4)
H. pylori persists in the human stomach over decades and promotes several adverse clinical sequelae including gastritis, peptic ulcers and gastric cancer that are linked to the induction and subsequent evasion of chronic gastric inflammation. Emerging evidence indicates that H. pylori infection may also protect against asthma and some other immune-mediated conditions through regulatory T cell effects outside the stomach. To characterize the complexity of the CD4+ T cell response generated during H. pylori infection, computational methods were previously used to generate a panel of 90 predicted epitopes conserved among H. pylori genomes that broadly cover HLA Class II diversity for maximum population coverage. Here, these sequences were tested individually for their ability to induce in vitro responses in peripheral blood mononuclear cells by interferon-γ ELISpot assay. The average number of spot-forming cells/million PBMCs was significantly elevated in H. pylori-infected subjects over uninfected persons. Ten of the 90 peptides stimulated IFN-γ secretion in the H. pylori-infected group only, whereas two out of the 90 peptides elicited a detectable IFN-γ response in the H. pylori-uninfected subjects but no response in the H. pylori-infected group. Cytokine ELISA measurements performed using in vitro PBMC culture supernatants demonstrated significantly higher levels of TNF-α, IL-2, IL-4, IL-6, IL-10, and TGF-β1 in the H. pylori-infected subjects, whereas IL-17A expression was not related to the subjects H. pylori-infection status. Our results indicate that the human T cell responses to these 90 peptides are generally increased in actively H. pylori-infected, compared with H. pylori-naïve, subjects. This information will improve understanding of the complex immune response to H. pylori, aiding rational epitope-driven vaccine design as well as helping identify other H. pylori epitopes with potentially immunoregulatory effects. 相似文献
23.
Although, in general, twins have higher perinatal mortality rates than singletons, preterm twins have lower perinatal mortality rates than singletons of the same birth weight or gestational age. This study investigated the hypotheses that this paradoxical twin advantage: 1) is due to gestational age distribution differences between the singleton and twin populations, and 2) is due to increased likelihood of birth having occurred in a tertiary perinatal center. A pre-existing, time-limited data set of all births in the province of Ontario in odd years between 1979 and 1985 was chosen for this study because of the large sample size (n = 618,579). Multivariable logistic regression of the relationship between perinatal mortality and twin status was controlled for mother's age, hospital level and gestational age. Findings confirm the lower mortality of preterm twins. After controlling for level of hospital of birth this difference remained, suggesting that level of hospital of birth was not a major factor responsible for the twin advantage. Analyses in which gestational age was standardized indicate that, for those whose gestational age was less than 2 SD below the mean for their particular group (twin or singleton), twins were actually at higher risk than singletons. These results support hypothesis 1 and do not strongly support hypothesis 2. The results also support earlier authors' suggestions that the definition of term birth should be different for twins and singletons 相似文献
24.
Cardiomyogenic differentiation of human adipose‐derived mesenchymal stem cells transduced with Tbx20‐encoding lentiviral vectors 下载免费PDF全文
25.
Michael K. Dame Narasimharao Bhagavathula Cohra Mankey Marissa DaSilva Tejaswi Paruchuri Muhammad Nadeem Aslam James Varani 《In vitro cellular & developmental biology. Animal》2010,46(2):114-122
Normal and neoplastic human colon tissue obtained at surgery was used to establish conditions for organ culture. Optimal conditions
included an atmosphere of 5% CO2 and 95% O2; tissue partially submerged with mucosa at the gas interface; and serum-free medium with 1.5 mM Ca2+ and a number of growth supplements. Histological, histochemical, and immunohistochemical features that distinguish normal
and neoplastic tissue were preserved over a 2-d period. With normal tissue, this included the presence of elongated crypts
with small, densely packed cells at the crypt base and mucin-containing goblet cells in the upper portion. Ki67 staining,
for proliferating cells, was confined to the lower third of the crypt, while expression of extracellular calcium-sensing receptor
was seen in the upper third and surface epithelium. E-cadherin and β-catenin were expressed throughout the epithelium and
confined to the cell surface. In tumor tissue, the same disorganized, abnormal glandular structures seen at time zero were
present after 2 d. The majority of cells in these structures were mucin-poor, but occasional goblet cells were seen and mucin
staining was present. Ki67 staining was seen throughout the abnormal epithelium and calcium-sensing receptor expression was
weak and variable. E-cadherin was seen at the cell surface (similar to normal tissue), but in some places, there was diffuse
cytoplasmic staining. Finally, intense cytoplasmic and nuclear β-catenin staining was observed in cultured neoplastic tissue. 相似文献
26.
27.
R.L. Konger S.D. Billings N.C. Prall T.M. Katona S.C. DaSilva C.R.J. Kennedy S. Badve S.M. Perkins P.T. LaCelle 《Prostaglandins, leukotrienes, and essential fatty acids》2009,81(4):279-290
We have previously demonstrated that the EP1 subtype of PGE2 receptor is expressed in the differentiated compartment of normal human epidermis and is coupled to intracellular calcium mobilization. We therefore hypothesized that the EP1 receptor is coupled to keratinocyte differentiation. In in vitro studies, radioligand binding, RT-PCR, immunoblot and receptor agonist-induced second messenger studies demonstrate that the EP1 receptor is up-regulated by high cell density in human keratinocytes and this up-regulation precedes corneocyte formation. Moreover, two different EP1 receptor antagonists, SC51322 and AH6809, both inhibited corneocyte formation. SC51322 also inhibited the induction of differentiation-specific proteins, cytokeratin K10 and epidermal transglutaminase. We next examined the immunolocalization of the EP1 receptor in non-melanoma skin cancer in humans. Well-differentiated SCCs exhibited significantly greater membrane staining, while spindle cell carcinomas and BCCs had significantly decreased membrane staining compared with normal epidermis. This data supports a role for the EP1 receptor in regulating keratinocyte differentiation. 相似文献
28.
29.
Protein acetylation affects acetate metabolism,motility and acid stress response in
Escherichia coli 下载免费PDF全文
30.
Eric AF Sim?es Xavier Carbonell-Estrany John R Fullarton Johannes G Liese Jose Figueras-Aloy Gunther Doering Juana Guzman European RSV Risk Factor Study Group 《Respiratory research》2008,9(1):78