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1.
Kjetil Taskn Rigmor Solberg Ying Zhao Vidar Hansson Tore Jahnsen Michael J. Siciliano 《Genomics》1996,36(3):535
We have determined the chromosomal localization of the gene for the catalytic subunit Cα of cAMP-dependent protein kinase (locus PRKACA) to human chromosome 19 using polymerase chain reaction (PCR) and Southern blot analysis of two different somatic cell hybrid mapping panels. In addition, PCR analysis of a chromosome 19 mapping panel revealed the presence of a human Cα-specific amplification product only in cell lines containing the region 19p13.1 to 19q12. Finally, two-color fluorescencein situhybridization to metaphase chromosomes using the human Cα cDNA and human chromosome 19 inter-Alu-PCR product as probes localized the human Cα gene to chromosome region 19p13.1. 相似文献
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Nociceptin-immunoreactive cellbodies were detected in the human trigeminal ganglion, while no such fibers were identified in the temporal artery or in dermal tissue from the neck region. In four healthy subjects receiving nociceptin into the temporal muscle in an open labeled design no pain was detected. In 10 healthy subjects who received 200pmol of nociceptin into tender non-dominant trapezius muscles in a placebo-controlled, randomized, balanced, and double-blinded design local tenderness increased (P=0.025) while no pain was noted. Thus, the action of nociceptin should be searched for in the trigeminal ganglion and/or in the central nervous system (CNS). 相似文献
3.
Rahman S Magalhaes I Rahman J Ahmed RK Sizemore DR Scanga CA Weichold F Verreck F Kondova I Sadoff J Thorstensson R Spångberg M Svensson M Andersson J Maeurer M Brighenti S 《Molecular medicine (Cambridge, Mass.)》2012,18(1):647-658
To prevent the global spread of tuberculosis (TB) infection, a novel vaccine that triggers potent and long-lived immunity is urgently required. A plasmid-based vaccine has been developed to enhance activation of major histocompatibility complex (MHC) class I–restricted CD8+ cytolytic T cells using a recombinant Bacille Calmette-Guérin (rBCG) expressing a pore-forming toxin and the Mycobacterium tuberculosis (Mtb) antigens Ag85A, 85B and TB10.4 followed by a booster with a nonreplicating adenovirus 35 (rAd35) vaccine vector encoding the same Mtb antigens. Here, the capacity of the rBCG/rAd35 vaccine to induce protective and biologically relevant CD8+ T-cell responses in a nonhuman primate model of TB was investigated. After prime/boost immunizations and challenge with virulent Mtb in rhesus macaques, quantification of immune responses at the single-cell level in cryopreserved tissue specimen from infected organs was performed using in situ computerized image analysis as a technological platform. Significantly elevated levels of CD3+ and CD8+ T cells as well as cells expressing interleukin (IL)-7, perforin and granulysin were found in TB lung lesions and spleen from rBCG/rAd35-vaccinated animals compared with BCG/rAd35-vaccinated or unvaccinated animals. The local increase in CD8+ cytolytic T cells correlated with reduced expression of the Mtb antigen MPT64 and also with prolonged survival after the challenge. Our observations suggest that a protective immune response in rBCG/rAd35-vaccinated nonhuman primates was associated with enhanced MHC class I antigen presentation and activation of CD8+ effector T-cell responses at the local site of infection in Mtb-challenged animals. 相似文献
4.
Robert Smith Harald T. Johansen Hilde Nilsen Mads H. Haugen Solveig J. Pettersen Gunhild M. Mælandsmo Magnus Abrahamson Rigmor Solberg 《Biochimie》2012
Legumain, an asparaginyl endopeptidase, is up-regulated in tumour and tumour-associated cells, and is linked to the processing of cathepsin B, L, and proMMP-2. Although legumain is mainly localized to the endosomal/lysosomal compartments, legumain has been reported to be localized extracellularly in the tumour microenvironment and associated with extracellular matrix and cell surfaces. The most potent endogenous inhibitor of legumain is cystatin E/M, which is a secreted protein synthesised with an export signal. Therefore, we investigated the cellular interplay between legumain and cystatin E/M. As a cell model, HEK293 cells were transfected with legumain cDNA, cystatin E/M cDNA, or both, and over-expressing monoclonal cell lines were selected (termed M38L, M4C, and M3CL, respectively). Secretion of prolegumain from M38L cells was inhibited by treatment with brefeldin A, whereas bafilomycin A1 enhanced the secretion. Cellular processing of prolegumain to the 46 and 36 kDa enzymatically active forms was reduced by treatment with either substance alone. M38L cells showed increased, but M4C cells decreased, cathepsin L processing suggesting a crucial involvement of legumain activity. Furthermore, we observed internalization of cystatin E/M and subsequently decreased intracellular legumain activity. Also, prolegumain was shown to internalize followed by increased intracellular legumain processing and activation. In addition, in M4C cells incomplete processing of the internalized prolegumain was observed, as well as nuclear localized cystatin E/M. Furthermore, auto-activation of secreted prolegumain was inhibited by cystatin E/M, which for the first time shows a regulatory role of cystatin E/M in controlling both intra- and extracellular legumain activity. 相似文献
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6.
In this paper we examine the hypothesis that diapause induction in the polyvoltine pod midge Dasyneura brassicae Winn. (Diptera: Cecidomyiidae) is controlled by cumulative global solar radiation during the larval stage. The correlation
between field observations of relative diapause for 3 years and four environmental factors (daylength, temperature, cumulative
daylight time, and cumulative global solar radiation) was investigated. The cumulative global solar radiation during the larval
stage clearly showed the strongest correlation with the observed relative diapause. It was estimated that larvae which cumulated
less than 71.1 kWh m−2 entered diapause. Compared to former theories on diapause induction in insects, this hypothesis explains how temperature
and light can function together and, furthermore, it removes the requirement for biological clock involvement in diapause
induction in insects.
Received: 21 December 1996 / Accepted: 26 February 1997 相似文献
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Rigmor Malmgren Marie Åsberg Per Olsson Göran Tornling Gunnar Unge 《Life sciences》1981,29(25):2649-2658
The 5-HT uptake kinetics in platelets from ten depressed patients were studied with a highly reproducible method which detects specific changes in the platelet 5-HT transport. The six patients with endogenous depression had a disturbed 5-HT-uptake. A passive diffusion of 5-HT predominated over the active 5-HT-transport. This disturbance was not found in the four non-endogenously depressed patients or in the fifty normal controls. These findings suggest that platelets from endogenously depressed patients may have abnormal physical membrane characteristics. 相似文献
9.
Human Immunodeficiency Virus Type 1 Env Trimer Immunization of Macaques and Impact of Priming with Viral Vector or Stabilized Core Protein 总被引:1,自引:0,他引:1
Andreas Mrner Iyadh Douagi Mattias N. E. Forsell Christopher Sundling Pia Dosenovic Sijy O'Dell Barna Dey Peter D. Kwong Gerald Voss Rigmor Thorstensson John R. Mascola Richard T. Wyatt Gunilla B. Karlsson Hedestam 《Journal of virology》2009,83(2):540-551
Currently there is limited information about the quality of immune responses elicited by candidate human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env)-based immunogens in primates. Here we describe a comprehensive analysis of neutralizing antibody and T-cell responses obtained in cynomolgus macaques by three selected immunization regimens. We used the previously described YU2-based gp140 protein trimers administered in an adjuvant, preceded by two distinct priming strategies: either alphavirus replicon particles expressing matched gp140 trimers or gp120 core proteins stabilized in the CD4-bound conformation. The rationale for priming with replicon particles was to evaluate the impact of the expression platform on trimer immunogenicity. The stable core proteins were chosen in an attempt to expand selectively lymphocytes recognizing common determinants between the core and trimers to broaden the immune response. The results presented here demonstrate that the platform by which Env trimers were delivered in the priming (either protein or replicon vector) had little impact on the overall immune response. In contrast, priming with stable core proteins followed by a trimer boost strikingly focused the T-cell response on the core sequences of HIV-1 Env. The specificity of the T-cell response was distinctly different from that of the responses obtained in animals immunized with trimers alone and was shown to be mediated by CD4+ T cells. However, this regimen showed limited or no improvement in the neutralizing antibody responses, suggesting that further immunogen design efforts are required to successfully focus the B-cell response on conserved neutralizing determinants of HIV-1 Env. 相似文献
10.
Matthew P. Johnson Linda T. Roten Thomas D. Dyer Christine E. East Siri Forsmo John Blangero Shaun P. Brennecke Rigmor Austgulen Eric K. Moses 《Human genetics》2009,126(5):655-666
Preeclampsia is a heritable pregnancy disorder that presents new onset hypertension and proteinuria. We have previously reported
genetic linkage to preeclampsia on chromosomes 2q, 5q and 13q in an Australian/New Zealand (Aust/NZ) familial cohort. This
current study centered on identifying the susceptibility gene(s) at the 5q locus. We first prioritized candidate genes using
a bioinformatic tool designed for this purpose. We then selected a panel of known SNPs within ten prioritized genes and genotyped
them in an extended set of the Aust/NZ families and in a very large, independent Norwegian case/control cohort (1,139 cases,
2,269 controls). In the Aust/NZ cohort we identified evidence of a genetic association for the endoplasmic reticulum aminopeptidase
1 (ERAP1) gene (rs3734016, P
uncorr = 0.009) and for the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene (rs2549782, P
uncorr = 0.004). In the Norwegian cohort we identified evidence of a genetic association for ERAP1 (rs34750, P
uncorr = 0.011) and for ERAP2 (rs17408150, P
uncorr = 0.009). The ERAP2 SNPs in both cohorts remained statistically significant (rs2549782, P
corr = 0.018; rs17408150, P
corr = 0.039) after corrections at an experiment-wide level. The ERAP1 and ERAP2 genes encode enzymes that are reported to play a role in blood pressure regulation and essential hypertension in addition
to innate immune and inflammatory responses. Perturbations within vascular, immunological and inflammatory pathways constitute
important physiological mechanisms in preeclampsia pathogenesis. We herein report a novel preeclampsia risk locus, ERAP2, in a region of known genetic linkage to this pregnancy-specific disorder. 相似文献