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  • 1
    Keywords: MICE ; SUPPRESSION ; COLORECTAL-CANCER ; GRANZYME-B ; inflammation ; INTERLEUKIN-10 ; MAST-CELLS ; HELPER-CELLS ; TH17 CELLS ; LINEAGE DIFFERENTIATION
    Abstract: The role of regulatory T cells (T(regs)) in human colon cancer (CC) remains controversial: high densities of tumor-infiltrating T(regs) can correlate with better or worse clinical outcomes depending on the study. In mouse models of cancer, T(regs) have been reported to suppress inflammation and protect the host, suppress T cells and protect the tumor, or even have direct cancer-promoting attributes. These different effects may result from the presence of different T(reg) subsets. We report the preferential expansion of a T(reg) subset in human CC with potent T cell-suppressive, but compromised anti-inflammatory, properties; these cells are distinguished from T(regs) present in healthy donors by their coexpression of Foxp3 and RORgammat. T(regs) with similar attributes were found to be expanded in mouse models of hereditary polyposis. Indeed, ablation of the RORgammat gene in Foxp3(+) cells in polyp-prone mice stabilized T(reg) anti-inflammatory functions, suppressed inflammation, improved polyp-specific immune surveillance, and severely attenuated polyposis. Ablation of interleukin-6 (IL-6), IL-23, IL-17, or tumor necrosis factor-alpha in polyp-prone mice reduced polyp number but not to the same extent as loss of RORgammat. Surprisingly, loss of IL-17A had a dual effect: IL-17A-deficient mice had fewer polyps but continued to have RORgammat(+) T(regs) and developed invasive cancer. Thus, we conclude that RORgammat has a central role in determining the balance between protective and pathogenic T(regs) in CC and that T(reg) subtype regulates inflammation, potency of immune surveillance, and severity of disease outcome.
    Type of Publication: Journal article published
    PubMed ID: 23241743
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  • 2
    ISSN: 0888-7543
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 175 (1993), S. 261-264 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Physics Letters A 162 (1992), S. 91-95 
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary 10 patients with acute lymphoblastic leukaemia were tissue-typed for 21 HL-A specificities. Of these, genotypes of 9 pateints were determined by family analyses. Haplotype HL-A1,8 occurred in 5 out of 18 instances. On phenotype basis, a slight increase was observed in the incidence of antigens HL-A1 and HL-A8. No loss of HL-A specificities could be detected on lymphocytes through family analyses.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1211
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract The HLA class II antigens of the human major histocompatibility complex play an important role in immune response. The quality of the immune response is determined not only by polymorphisms in their coding region, but also by the level of their cell-surface expression which affects, for example, the extent of T-cell activation. We have previously described allelic polymorphisms in the upstream regulatory regions of HLA-DRB genes, which affected DNA-protein interactions and resulted in significantly different promoter strengths. In the present study, we investigated the effect of polymorphisms in the X and Y box motifs on the transcriptional activity of DRB1 geme promoters in the DR1, DR51, and DR53 haplotype groups. We used normal, chimeric, and mutated DRB promoters and compared their relative abilities to initiate transcription of the CAT reporter gene in human B-cell lines. The results show that polymorphisms in both the X1 and Y box motifs play a dominant role in the promoter strength. In the gel mobility shift assay, we observed differential ability of nuclear proteins that bind to the polymorphic X1 and Y box elements. The results in the present study confirm earlier data in that the nucleotide variation in the X1 box affects the level of expression of DRB1 genes. In addition, the present data demonstrate that polymorphism in the Y box, which affects the inverted CCAAT sequence, also plays a dominant role in the transcriptional activity of DRB1 promoters.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Applied physics 57 (1993), S. 65-82 
    ISSN: 1432-0649
    Keywords: 92.60.Ek ; 43.85.+f ; 92.60.Sz
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract Hazardous situations in air pollution can many a times be avoided in case short term local weather forecasting of the boundary layer meteorology becomes available. Amongst the various remote sensing techniques, it has been seen that acoustic remote sensing (SODAR) of the lower atmosphere can be employed to determine and predict the atmospheric boundary layer meteorological parameters. In specific, information can be obtained about thermal stratification, mixing height, low level disturbances, depth of the planetary boundary layer, stability classification, wind velocity, wind variances, turbulence parameters, and diffusion characteristics etc. when SODAR is used in conjunction with surface level measurements of the usual meteorological parameters. In the paper a brief description of the acoustic remote sensing technique and a review of the work done during the last two decades to determine the various air quality related meteorological parameters has been given. The methodology to determine mixing height, stability classification and diffusion and dispersion characteristics using mostly the information from the SODAR echograms has also been described. The SODAR echograms obtained at Delhi for the period May 1977 to April 1982 have been processed and analyzed using pattern recognition to determine these parameters. Doppler SODAR information of wind speed and direction have not been treated for the above purpose. Using the Gaussian dispersion model, pollution concentration downwind of a emission source (in the present case it is a cement factory at Nimbahera, Chittorgarh, India) has also been computed with the help of SODAR determined data. It has been found that measured values with the help of high volume sampler conform to the estimated pollution concentration. A peak in the value of the estimated pollution concentration during the fumigation period has also been seen.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Aims  To evaluate the advantages of using a sweat patch (PharmCheck™) for detecting cocaine abuse in cocaine-dependent patients participating in a clinical trial. The utility of the sweat patch was assessed from the following perspectives: the reliability and validity of quantitative sweat patch results, the possible degradation of cocaine to benzoylecgonine (BE) as a function of the length of time that a patch is worn, the completeness of the dataset yielded by thrice-weekly urine toxicology compared with thrice-weekly and weekly sweat patches, and the relative costs associated with sweat patch versus urine measures.Design  Data were collected during a 10-week out-patient clinical trial in which participants wore two sweat patches, one applied every visit and one applied weekly. Urine samples were collected thrice weekly, as were self-reports of substance use.Setting  A multi-site clinical trial conducted in Boston, Cincinnati and New York, USA.Participants  Twenty-seven participants with comorbid diagnoses of cocaine dependence and adult attention deficit disorder completed the study.Measurements  Sweat patch and urine samples were analyzed by standard methods for cocaine and cocaine metabolites.Findings  Quantitative sweat patch measures had good reliability in that the correlation between the weekly and per-visit patches was 0.96 (P 〈 0.0001). The concurrent validity, as judged by the correlation between quantitative urine BE levels and either weekly (0.76, P 〈 0.0001) or per-visit (0.73, P 〈 0.0001) cocaine sweat patch levels was reasonable. The correlation between the self-report of cocaine use and these same two patches, however, was lower (0.40, P 〈 0.05 and 0.30, P 〈 0.05, respectively). The results revealed no significant degradation of cocaine to BE associated with wearing the patch for a longer time. Finally, the per-visit patch provided cocaine use data on 80.5% of all study days (a total of 70), while urine toxicology and the weekly patch provided 77.4% and 76.1%, respectively.Conclusions  The present findings suggest that the PharmCheck™ patch might be an attractive alternative to urine toxicology for use as an outcome measure in cocaine clinical trials.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1360-0443
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine , Psychology
    Notes: Aims  To conduct a preliminary evaluation of the safety and efficacy of reserpine, gabapentin or lamotrigine versus an unmatched placebo control as a treatment for cocaine dependence.Design  A 10-week out-patient study using the Cocaine Rapid Efficacy and Safety Trial (CREST) study design.Setting  The study was conducted at the Cincinnati Medication Development Research Unit (MDRU).Participants  Participants met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence. Sixty participants were enrolled, with 50 participants completing the final study measures.Intervention  The targeted daily doses of medication were reserpine 0.5 mg, gabapentin 1800 mg and lamotrigine 150 mg. All participants received 1 hour of manualized individual cognitive behavioral therapy on a weekly basis.Measurements  Primary outcome measures of efficacy included urine benzoylecgonine (BE) level, Cocaine Clinical Global Impression scale—observer and self-report of cocaine use. Safety measures included adverse events, electrocardiograms (ECGs), vital signs and laboratory tests.Findings  Subjective measures of cocaine dependence indicated significant improvement for all study groups. Urine BE results indicated a significant improvement for the reserpine group (P 〈 0.05) and non-significant changes for the other study groups. No pattern of physical or laboratory abnormalities attributable to treatment with any of the medications was identified. There were three serious adverse events reported, none of which were related to study procedures. The medications appeared to be tolerated well.Conclusions  The present findings suggest that reserpine may be worthy of further study as a cocaine dependence treatment.
    Type of Medium: Electronic Resource
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