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141.
John J.M. Wiener Alvah T. Wickboldt Danielle K. Wiener Alice Lee-Dutra James P. Edwards Lars Karlsson Steven Nguyen Siquan Sun Todd K. Jones Cheryl A. Grice 《Bioorganic & medicinal chemistry letters》2010,20(7):2375-2378
A novel class of tetrahydropyrido-pyrazole thioether amines that display potency against human Cathepsin S have been previously reported. Here, further SAR investigations of the P3, P4, and P5 regions are described. In particular, 4-fluoropiperidine is identified as a competent P3 binding element when utilized in conjunction with a (S)-2-hydroxypropyl linker-containing P5 moiety and oxamide or sulfonamide P4 substitution. 相似文献
142.
The etiologies of the inflammatory bowel diseases (IBD; Crohn's disease, ulcerative colitis) have not been fully elucidated. However, there is very good evidence implicating T cell and T cell trafficking to the gut and its associated lymphoid tissue as important components in disease pathogenesis. The objective of this review is to provide an overview of the mechanisms involved in naive and effector T cell trafficking to the gut-associated lymphoid tissue (GALT; Peyer's patches, isolated lymphoid follicles), mesenteric lymph nodes and intestine in response to commensal enteric antigens under physiological conditions as well as during the induction of chronic gut inflammation. In addition, recent data suggests that the GALT may not be required for enteric antigen-driven intestinal inflammation in certain mouse models of IBD. These new data suggest a possible paradigm shift in our understanding of how and where naive T cells become activated to yield disease-producing effector cells. 相似文献
143.
144.
Ann-Charlotte Karlsson Stefan Alenius Camilla Björkman Ylva Persson Stina Englund 《Acta veterinaria Scandinavica》2010,52(1):1-4
Background
Reproductive disorders associated with chlamydial infection have been reported worldwide in cattle and there are indications of potential venereal transmission.Methods
Semen samples from 21 dairy bulls and cauda epididymidis tissue samples from 43 beef bulls were analysed for chlamydial agent by real-time polymerase chain reaction (PCR) including an internal amplification control (mimic). Additionally, presence of antibodies against Chlamydophila (Cp.) abortus among the bulls was investigated with the commercial Pourquier® ELISA Cp. abortus serum verification kit.Results
No chlamydial agent was detected by PCR in either the semen samples or in the tissue samples. Additionally, no antibodies against Cp. abortus were detected.Conclusions
The results suggest that Cp. abortus is very rare, or absent in Swedish bulls and thus the risk for venereal transmission of chlamydial infection through their semen is low. However, because Chlamydophila spp. infection rates seem to differ throughout the world, it is essential to clarify the relative importance of transmission of the infection through semen on cattle fertility. 相似文献145.
Williams AR Greeff JC Vercoe PE Dobson RJ Karlsson LJ 《Animal : an international journal of animal bioscience》2010,4(1):122-127
The peri-parturient period is crucial for controlling worms as the acquired immunity of ewes is disrupted, resulting in an increase in faecal worm egg counts. Two hypotheses were tested in this experiment - that ewes bred for worm resistance would have lower faecal worm egg counts than unselected control ewes, during late pregnancy and lactation, under similar but separate grazing areas; and also that numbers of infective nematode larvae would be lower on pastures grazed by resistant ewes than pastures grazed by unselected control ewes. Faecal samples were collected from resistant and unselected ewes in late pregnancy and early lactation, during the winter rainfall season, and analysed for numbers of Trichostrongylus colubriformis and Teladorsagia circumcincta. Pasture samples were taken 1 week before and 7 weeks after lambing started and analysed for infective larvae. In all sheep, worm egg counts rose 2 weeks prior to lambing and continued into lactation. Worm egg counts were significantly lower in the resistant ewes from 1 week before lambing to 2 weeks after lambing. There were no differences in egg counts between single- and twin-bearing ewes in the resistant line. However, twin-bearing control ewes had significantly higher egg counts than single-bearing control ewes. Following lactation, plots grazed by resistant ewes had substantially less contamination with T. colubriformis larvae, but there were no differences in numbers of T. circumcincta larvae. Our results demonstrate that sheep bred for worm resistance has lower worm burdens during the peri-parturient phase and that lambs born to resistant ewes face a lower larval challenge during their introduction to grazing. In our environment, selection for low worm egg counts has produced sheep highly resistant to T. colubriformis, but has had less impact on resistance towards T. circumcincta. 相似文献
146.
Eva Falck Sandra Karlsson Jessica Carlsson Gisela Helenius Mats Karlsson Karin Klinga-Levan 《Cancer cell international》2010,10(1):46
Glutathione peroxidase 3 (GPX3) is one of the key enzymes in the cellular defense against oxidative stress and the hepatocyte
growth factor receptor, (MET) has been suggested to be influenced by the GPX3 gene expression. In a previous microarray study performed by our group, Gpx3 was identified as a potential biomarker for rat endometrial adenocarcinoma (EAC), since the expression was highly downregulated
in rat EAC tumors. Herein, we have investigated the mRNA expression and Gpx3 and Met in rat EAC by real time quantitative PCR (qPCR), and the methylation status of Gpx3. In addition we have examined the expression of GPX3 and MET in 30 human EACs of different FIGO grades and 20 benign endometrial tissues. We found that the expression of GPX3 was uniformly down regulated in both rat and human EAC, regardless of tumor grade or histopathological subtype, implying
that the down-regulation is an early event in EAC. The rate of Gpx3 promoter methylation reaches 91%, where biallelic methylation was present in 90% of the methylated tumors. The expression
of the Met oncogene was slightly upregulated in EACs that showed loss of expression of Gpx3, but no tumor suppressor activity of Gpx3/GPX3 was detected. Preliminary results also suggest that the production of H2O2 is higher in rat endometrial tumors with down-regulated Gpx3 expression. A likely consequence of loss of GPX3 protein function would be a higher amount of ROS in the cancer cell environment.
Thus, the results suggest important clinical implications of the GPX3 expression in EAC, both as a molecular biomarker for EAC and as a potential target for therapeutic interventions. 相似文献
147.
The effect of pertussis toxin (PT) on the aggregation of pigment granules in melanophores from cuckoo wrasse (Labrus ossifagus L.) was studied. The results indicate the presence of a PT resistant alpha 2-adrenoceptor signal transduction mechanism. 相似文献
148.
This article describes a stock-based methodology designed to analyze the redistribution of substance stocks to environmental compartments. The methodology is then applied to investigate the requirements and possibilities for avoiding undesired future accumulation of cadmium in Swedish arable soils. A prospective decomposition analysis of human cadmium mobilization is thus performed to estimate the potential amounts that can end up in arable soils through different flows from the cadmium stocks identified. The requirements for cadmium abatement to achieve prescribed goals for accumulation limits are determined and compared with past and current achievements and with the varying qualities of possible abatement methods.
A stock-based methodology adds some important information to traditional scenario techniques based on substance flow analysis. The most obvious is that the fact that stocks are limited actually matters for long-term accumulation of cadmium in arable land. The methodology may also contribute certain indicators, for instance, on abatement requirements, which could serve as a complement to regulation and local quality measures on specific flows at an aggregated policy level. The stock perspective also sheds new light on actions such as increased recycling.
Concerning the specific example used in the study, it is possible to achieve a future addition of cadmium in Swedish agricultural soils that is significantly lower than in the past, although the amount depends to a large degree on activities and policies outside Sweden. Considerable uncertainty exists regarding future depositions from air, especially that from distributed small-scale emissions from fuel burning and reemission of already deposited cadmium from natural media. Measures must also be taken to guarantee a continued low addition in the form of mineral phosphorus fertilizers. 相似文献
A stock-based methodology adds some important information to traditional scenario techniques based on substance flow analysis. The most obvious is that the fact that stocks are limited actually matters for long-term accumulation of cadmium in arable land. The methodology may also contribute certain indicators, for instance, on abatement requirements, which could serve as a complement to regulation and local quality measures on specific flows at an aggregated policy level. The stock perspective also sheds new light on actions such as increased recycling.
Concerning the specific example used in the study, it is possible to achieve a future addition of cadmium in Swedish agricultural soils that is significantly lower than in the past, although the amount depends to a large degree on activities and policies outside Sweden. Considerable uncertainty exists regarding future depositions from air, especially that from distributed small-scale emissions from fuel burning and reemission of already deposited cadmium from natural media. Measures must also be taken to guarantee a continued low addition in the form of mineral phosphorus fertilizers. 相似文献
149.
We present a model for the activity of protein clusters based on a simultaneous desorption of an activator (agonist, substrate molecule, etc.) and an inactivator (antagonist, inhibitor, etc.) caused by the collision or interaction between two effector molecules (e.g. receptors, enzymes). This model gives rise to switch-like dose-response curves, which are difficult to explain by ordinary co-operativity. It fits with recent experimental results obtained on single cells. Some other interesting aspects of the model are also pointed out. The model is similar to the model used to explain steep 'dose-response curves' in heterogeneous catalysis, caused by the reaction between two different molecules or atoms on the surface of the catalyst. 相似文献
150.
Arsenic trioxide and neuroblastoma cytotoxicity 总被引:2,自引:0,他引:2
Pettersson HM Karlsson J Pietras A Øra I Påhlman S 《Journal of bioenergetics and biomembranes》2007,39(1):35-41
The majority of aggressive forms of the childhood tumor neuroblastoma can with current treatment protocols not be cured and
possess a major challenge in pediatric oncology. After initial rounds of chemotherapy, surgery and irradiation, which in most
cases result in tumor regression, these aggressive neuroblastomas relapse and frequently develop drug resistance. As approximately
50% of the children with neuroblastoma have an aggressive form, there is a compelling demand for new treatment strategies.
Arsenic trioxide has the capacity to kill multidrug-resistant neuro-blastoma cells in vitro and in vivo and the drug is currently being evaluated in clinical trials. In this report we discuss the background to the use of arsenic
trioxide in cancer therapy and the currently known mechanisms by which arsenic trioxide kills human neuroblastoma cells. 相似文献