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11.
12.
Adenoviral vectors expressing siRNAs for discovery and validation of gene function 总被引:5,自引:0,他引:5
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Arts GJ Langemeijer E Tissingh R Ma L Pavliska H Dokic K Dooijes R Mesić E Clasen R Michiels F van der Schueren J Lambrecht M Herman S Brys R Thys K Hoffmann M Tomme P van Es H 《Genome research》2003,13(10):2325-2332
RNA interference is a powerful tool for studying gene function and for drug target discovery in diverse organisms and cell types. In mammalian systems, small interfering RNAs (siRNAs), or DNA plasmids expressing these siRNAs, have been used to down-modulate gene expression. However, inefficient transfection protocols, in particular, for primary cell types, have hampered the use of these tools in disease-relevant cellular assays. To be able to use this technology for genome-wide function screening, a more robust transduction protocol, resulting in a longer duration of the knock-down effect, is required. Here, we describe the validation of adenoviral vectors that express hairpin RNAs that are further processed to siRNAs. Infection of cell lines, or primary human cells, with these viruses leads to an efficient, sequence-specific, and prolonged reduction of the corresponding target mRNA, resulting in a reduction of the encoded protein level in the cell. For knock-down of one of the targets, GalphaS, we have measured inhibition of ligand-dependent, G-protein-coupled signaling. It is expected that this technology will prove to be of great value in target validation and target discovery efforts. 相似文献
13.
T-cell receptor usage of interleukin-2-responsive peripheral gamma delta T cells. 总被引:1,自引:0,他引:1
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D L Orsini Y M Kooy M A Van der Tol L Struyk P Van den Elsen F Koning 《Immunology》1995,86(3):385-391
The majority of human peripheral gamma delta T cells express the V gamma 9 gene in combination with the V delta 2 gene. The diversity of this subset of gamma delta T cells is limited by a preferential usage of the J gamma P gene segment and a highly distinctive junctional motif of the T-cell receptor (TCR) delta chain. We and others have observed that peripheral blood derived V gamma 9+V delta 2+ gamma delta T cells of healthy individuals are activated after stimulation with interleukin-2 (IL-2) in vitro, but only a small percentage of gamma delta T cells subsequently proliferates. To assess whether the proliferating, IL-2-responsive gamma delta T cells represent a selective group of T cells, we have analysed TCR junctional features of IL-2-responsive gamma delta T cells. Out of 30 individuals studied, nine were identified as IL-2-responders and three as IL-2-hyperresponders. The TCR V(D)J gene usage from IL-2 stimulated peripheral blood lymphocytes of these IL-2-(hyper)responsive individuals was analysed. The results showed that in most individuals gamma delta T cells polyclonally expanded after stimulation with IL-2. In two IL-2-hyperresponder individuals, however, a monoclonal expansion of a particular V gamma 9+V delta 2+ gamma delta T cell was found. In one of these individuals, this V gamma 9+V delta 2+ T-cell clone expressed a very rare gamma delta TCR type because of the presence of an Ala within the junctional region at a conserved position relative to V delta framework residues (delta 97), which is very infrequently used by peripheral blood V gamma 9+V delta 2+ cells. This particular clonotype could also be detected in unstimulated PBL samples taken from that individual, and made up for 30% of the total peripheral gamma delta T-cell pool. These data indicate that in general IL-2-responsive V gamma 9+V delta 2+ gamma delta T cells represent a polyclonal population, reflecting in vivo stimulation with multiple antigens or superantigens. In contrast, monoclonal expansions of gamma delta T cells after stimulation with IL-2 can also occur, which may be related to an in vivo stimulation by one particular antigen, rendering this gamma delta T-cell type dominant in the peripheral blood. 相似文献
14.
Frits Ørskov Ida Ørskov Doyle J. Evans Jr. R. Bradley Sack David A. Sack Torkel Wadström 《Medical microbiology and immunology》1976,162(2):73-80
106 enterotoxigenicEscherichia coli strains from children and adults from many parts of the world were serotyped for O and H antigens. Some OH types,i.e. O6H16, O8H9, O15H11, O25H42, O78H11 and O78H12, were found repeatedly from different geographical locations. Some of these OH serotypes were only found rarely among more than 20000E. coli strains collected over many years from different locations and sources. It is suggested that these special OH serotypes represent clones which have been selected to the special conditions in the small intestine and selected to carry the plasmids necessary to provoke diarrhoea. 相似文献
15.
Gerhard Zingler Gabriele Blum Ursula Falkenhagen Ida Orskov Frits Orskov Jörg Hacker Manfred Ott 《Medical microbiology and immunology》1993,182(1):13-24
Escherichia coli isolates of serotype O6:K5 are the most common causative agents of cystitis and pyelonephritis in adults. To answer the question, as to whether strains of this particular serotype represent one special clonal group, out of a collection of 34 serotype O6:K5 isolates [Zingler et al. (1990) Zentralbl. Bakteriol Mikrobiol Hyg [A] 274:372–381] 15 strains were selected and analyzed in detail. The flagellar (H) antigen and the outer membrane protein (OMP) pattern were determined. Further serum resistance properties and the genetic presence and expression of other virulence factors, including hemolysin, aerobactin, P fimbriae, S/F1C fimbriae and type 1 fimbriae was evaluated. In addition the Xba-Imacrorestriction pattern of ten representative isolates was elaborated and the fimbrial (F) antigen type of the P fimbriae was determined, to obtain the complete O:K:H:F pattern. These analyses could clearly show that the O6:K5 isolates do not represent one clonal group. The XbaI-macrorestriction profiles were heterogeneous and marked differences in the hybridization patterns, using virulence-associated gene probes in Southern hybridization of long-range-separated genomic DNA, were observed among the strains. However, some of strains showed similarities in the genomic profiles, arguing for clonal groupings among the O6:K5 isolates. Interstingly the strains grouped together exhibited the same fimbrial F type that many indicate a coincidence of this phenotypic trait with clonality.In memoriam of Prof. G. Naumann 相似文献
16.
Agnes M. Willemen Frits A. Goossens Hans M. Koot Carlo Schuengel 《Clinical psychology & psychotherapy》2008,15(5):340-351
An Alarm Stress Task was developed to study affect regulation in the context of parent–child interactions in adolescents (mean age = 12.72, standard deviation = 2.06) with (n = 20) and without (n = 20) mental health problems. Changes in heart rate (HR), preejection period (PEP) and respiratory sinus arrhythmia (RSA) were used as indicators of affect regulation. HR increased, and PEP and RSA decreased significantly in reaction to a suggested failure on a simple task, indicating that this procedure induced affective arousal in adolescents. During reunion with the parent, RSA increased significantly. Support seeking on reunion was associated with stronger parasympathetic reactivity during stress and reunion, consistent with the model that the parasympathetic system is involved when affect is regulated by social engagement. Quality of parent–adolescent interactive behaviour was overall lower in the clinical sample. Individual and relationship‐based processes of affect regulation may be simultaneously assessed, highlighting the continuing importance of the parent–child relationship in adolescence for affect regulation and mental health. Copyright © 2008 John Wiley & Sons, Ltd. 相似文献
17.
Incipient ovarian failure and premature ovarian failure show the same immunological profile 总被引:4,自引:0,他引:4
van Kasteren YM von Blomberg M Hoek A de Koning C Lambalk N van Montfrans J Kuik J Schoemaker J 《American journal of reproductive immunology (New York, N.Y. : 1989)》2000,43(6):359-366
PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual cycles, infertility and a raised early-follicular FSH in women under 40. IOF might be a precursor or a mitigated form of premature ovarian failure (POF). Disturbances in the immune system may play a role in ovarian failure. METHOD OF STUDY: Autoantibodies and lymphocyte subsets were determined in 63 POF patients, 50 IOF patients, and 27 controls. RESULTS: The prevalence of autoantibodies did not differ between the groups. There was a statistically significant difference in lymphocyte subsets between the control group and the POF group, with the IOF group taking an intermediate position. We found a decrease in percentage of T-suppressor cells with a rise in T-helper/T-suppressor cell ratio, a decrease in natural killer cells, and an increase in B lymphocytes and HLA-DR positive T cells. CONCLUSIONS: These data support the concept that IOF is a mitigated form of POF. The question remains whether these changes are the cause or the consequence of the ovarian failure. 相似文献
18.
de Koning F. L. Binkhorst R. A. Vos J. A. van 't Hof M. A. 《European journal of applied physiology》1985,54(1):89-94
Summary The force-velocity curve (FVC) of arm flexion was established in 123 untrained males and 110 untrained females aged from 15 to 36 years, and 48 arm-trained athletes competing in different sport disciplines. The FVC was described by Hill's equation and defined by the parameters: maximal static moment (M0), maximal angular velocity (0), maximal power (P0) and the concavity of the FVC (H). Within the given age range the level of the curve parameters of both untrained men and women was independent of age.On average, H was the same in all three groups. As compared to M0 of the untrained males, M0 of the athletes was 33% higher and M0 of the females was 38% lower; with regard to P0 these differences were +30% and –43% respectively. 0 was the same for trained and untrained males, wherease 0 of the women was 10% lower than 0 of the men. 相似文献
19.
Claudia Teresa Vieira de Souza Theresa Diaz Frits Sutmoller Francisco Inácio Bastos 《Journal of acquired immune deficiency syndromes (1999)》2002,29(1):95-100
To evaluate the relation between illicit drug use, sexual practices, and socioeconomic status, we analyzed data from the baseline interview of a cohort of 675 men who have sex with men conducted from 1994 to 1999 in Rio de Janeiro, Brazil. Bivariate analyses of factors associated with crack/cocaine use with sex revealed that men who reported crack/cocaine use were significantly ( p <.05) more likely than men who did not report drug use to be unemployed (42.7% vs. 29.1%), to have an income of <$250 per month (70.7% vs. 60.9%), to have <8 years of education (69.5% vs. 50.9%), to report bisexual activity (81.7% vs. 41.7%), and to engage in commercial sex (72.0% vs. 37.9%). Multivariate analysis of factors associated with unprotected anal sex with casual male partners in the last 6 months demonstrated that the following variables were associated with this outcome: an income <$250 per month (adjusted odds ratio [AOR] = 1.73, 95% confidence interval [CI]: 1.04-2.87), less than 8 years of education (AOR = 2.21, CI: 1.38-3.53), a greater sense of vulnerability (AOR = 2.58, CI: 1.54-4.33), a willingness to participate in vaccine trials (AOR = 1.91, CI: 1.20-3.05), and use of crack/cocaine (AOR = 1.91, CI: 1.05-3.46). Our findings suggest that HIV prevention programs for these men need to address drug use and how drug use may influence sexual behaviors. 相似文献
20.
Frank A. W. Verreck Anja van de Poel Annemarie Termijtelen Jan-Wouter Drijfhout Frits Koning Reinout Amons 《European journal of immunology》1994,24(2):375-379
Molecules of the major histocompatibility complex (MHC) present antigenic peptides to T cells. Sequencing peptide pools eluted from MHC class I molecules has established allele-specific peptide binding motifs. We applied pool sequencing to analyze human MHC class II-bound peptides and found that HLA-DQ2-eluted peptides predominantly contained lysine, isoleucine, and phenylalanine at relative position i, i + 3 and i + 8, respectively. These residues putatively represent anchor residues for MHC binding. Analysis of a heterogeneous HLA-DPw3/DPw4-eluted peptide pool yielded a sequence matching an epitope from the endogeneous enzyme glyceraldehyde-3-phosphate dehydrogenase. This self-peptide and a partially identical, known allo-epitope bound specifically to DPw3 and DR13 molecules, suggesting the sharing of a binding motif. In particular, the presence of an arginine at relative position 4 appeared important for binding to these HLA class II specificities. Thus, pool sequencing is applicable for the analysis of MHC class II-eluted peptides. 相似文献