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71.
Larsen MV Lundegaard C Lamberth K Buus S Brunak S Lund O Nielsen M 《European journal of immunology》2005,35(8):2295-2303
Reverse immunogenetic approaches attempt to optimize the selection of candidate epitopes, and thus minimize the experimental effort needed to identify new epitopes. When predicting cytotoxic T cell epitopes, the main focus has been on the highly specific MHC class I binding event. Methods have also been developed for predicting the antigen-processing steps preceding MHC class I binding, including proteasomal cleavage and transporter associated with antigen processing (TAP) transport efficiency. Here, we use a dataset obtained from the SYFPEITHI database to show that a method integrating predictions of MHC class I binding affinity, TAP transport efficiency, and C-terminal proteasomal cleavage outperforms any of the individual methods. Using an independent evaluation dataset of HIV epitopes from the Los Alamos database, the validity of the integrated method is confirmed. The performance of the integrated method is found to be significantly higher than that of the two publicly available prediction methods BIMAS and SYFPEITHI. To identify 85% of the epitopes in the HIV dataset, 9% and 10% of all possible nonamers in the HIV proteins must be tested when using the BIMAS and SYFPEITHI methods, respectively, for the selection of candidate epitopes. This number is reduced to 7% when using the integrated method. In practical terms, this means that the experimental effort needed to identify an epitope in a hypothetical protein with 85% probability is reduced by 20-30% when using the integrated method.The method is available at http://www.cbs.dtu.dk/services/NetCTL. Supplementary material is available at http://www.cbs.dtu.dk/suppl/immunology/CTL.php. 相似文献
72.
73.
P. M. T. Deen Søren Nielsen René J. M. Bindels Carel H. van Os 《Pflügers Archiv : European journal of physiology》1997,433(6):780-787
Aquaporin-1 is present in the apical and basolateral membranes in proximal tubules and descending limbs of Henlé’s loop.
In order to be able to study the routing of Aquaporin-1 and the regulation of Aquaporin-1-mediated transcellular water flow,
we stably transfected LLC-PK1 and MDCK-HRS cell lines with an Aquaporin-1 expression construct. LLC-PK1 clone 7 and MDCK clone K integrated two and one copies, respectively, which was reflected in the amount of Aquaporin-1 mRNA expressed in both clones. The Aquaporin-1 protein levels, however, were similar. In both clones, immuno-electronmicroscopy
showed extensive labelling of Aquaporin-1 on the basolateral plasma membrane, endosomal vesicles and the apical plasma membrane,
including the microvilli. To measure transcellular water permeation, a simple method was applied using phenol-red as a cell-impermeant
marker of concentration. In contrast to the native cell lines, both clones revealed a high transcellular osmotic water permeability,
which could not be influenced by forskolin add/3-isobutyl-1-methylxanthine (IBMX) or the phorbol ester 12-O-tetradecanoyl 13-acetate (TPA). After glutaraldehyde fixation, it was inhibitable by HgCl2. These results indicate that targeting of Aquaporin-1 to the apical and basolateral plasma membrane is independent of cell
type and show for the first time that water flow through a cultured epithelium can be blocked by mercurial compounds.
Received: 9 October 1996 / Received after revision: 3 January 1997 / Accepted: 8 January 1997 相似文献
74.
Circulating immune complexes in ulcerative colitis.--II. Correlation with serum protein concentrations and complement conversion products 总被引:2,自引:0,他引:2 下载免费PDF全文
Several serum proteins were quantified in twenty-two patients with active ulcerative colitis, and the findings were related to disease activity and occurrence of circulating immune complexes (IC). Conversion of C3 was significantly more frequent in the IC-positive group (eight patients) as compared to the IC-negative group (fourteen patients). Factor B was demonstrable in fifteen out of the twenty-two patients and seven out of the eight IC-positive patients had detectable levels of factor B. There was no difference between the IC-positive and the IC-negative group as regards serum concentrations of the complement factors C3, C4 and factor B, or serum orosomucoid, albumin, IgM and IgG. In contrast, the serum IgA levels tended to be reduced in the IC-positive group. C3 and factor B were significantly elevated in four patients with severe disease activity. In addition, C3, factor B and C4 concentrations showed a positive correlation to the serum orosomucoid levels. The serum concentrations of orosomucoid and albumin were inversely correlated to each other. 相似文献
75.
76.
Svendsen UG, Frølund L, Heinig JH, Madsen F, Nielsen NH, Weeke B. High-dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function.
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV1 FVC, PEF or the histamine PC20 . Asthma severity, symptom score and inhaled bronchodilator use showed the same results after both treatments. It is concluded that inhalations of budesonide and beclomethasone dipropionate in high doses are equally potent in the treatment of severe asthma. There is no significant influence on the adrenal function and no significant side effects during a period equal to that of the present study. 相似文献
The efficacy of budesonide (800 μg b.d.) and beclomethasone dipropionate (750 μg b.d.) in controlling the symptoms of asthma, pulmonary function, bronchial responsiveness to histamine, and adrenal function, was assessed in a double-blind, double-dummy cross-over study of 36 adult chronic asthmatic patients. The patients, the majority of whom were assessed to be affected to a severe degree, were insufficiently controlled in their current regimen of inhaled steroids and/or inhaled and oral bronchodilators. A 2 weeks baseline period preceded 6 weeks of treatment with each of the study drugs. Both treatment groups showed improvements from baseline in clinical assessment of lung function carried out after the first 6 weeks of treatment. No significant differences were seen throughout the entire 12 weeks study, when comparing the effects of the treatments on FEV
77.
Ethylenediaminetetraacetic acid (disodium salt)-labile bovine immunoglobulin M Fc binding to Brucella abortus: a cause of nonspecific agglutination. 总被引:1,自引:2,他引:1 下载免费PDF全文
It was demonstrated by a radioimmunoassay procedure that Brucella abortus agglutinins from noninfected cattle sera, absorbed to B. abortus antigen and eluted with ethylenediaminetetraacetic acid (EDTA), was immunoglobulin M that bound to that bacterium by its Fc portion. The EDTA-eluted immunoglobulin M agglutinated intact B. abortus cells but not erythrocytes treated with B. abortus lipopolysaccharide. The specificity of the EDTA-eluted immunoglobulin was for B. abortus, although a small titer to Yersinia enterocolitica serotype O:9 was observed. In contrast, immunoglobulin M purified from the serum of a cow injected 7 days previously with heat-killed B. abortus bound to the antigen by its Fab portion, was not labile to EDTA treatment, cross-reacted extensively with Y. enterocolitica serotype O:9, and agglutinated various other bacterial antigens and normal erythrocytes. 相似文献
78.
Anders Rinnov Nielsen Remi Mounier Peter Plomgaard Ole Hartvig Mortensen Milena Penkowa Tobias Speerschneider Henriette Pilegaard Bente Klarlund Pedersen 《The Journal of physiology》2007,584(1):305-312
The cytokine interleukin-15 (IL-15) has been demonstrated to have anabolic effects in cell culture systems. We tested the hypothesis that IL-15 is predominantly expressed by type 2 skeletal muscle fibres, and that resistance exercise regulates IL-15 expression in muscle. Triceps brachii, vastus lateralis quadriceps and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers ( n = 14), because these muscles are characterized by having different fibre-type compositions. In addition, healthy, normally physically active male subjects ( n = 8) not involved in any kind of resistance exercise underwent a heavy resistance exercise protocol that stimulated the vastus lateralis muscle and biopsies were obtained from this muscle pre-exercise as well as 6, 24 and 48 h post-exercise. IL-15 mRNA levels were twofold higher in the triceps (type 2 fibre dominance) compared with the soleus muscle (type 1 fibre dominance), but Western blotting and immunohistochemistry revealed that muscle IL-15 protein content did not differ between triceps brachii, quadriceps and soleus muscles. Following resistance exercise, IL-15 mRNA levels were up-regulated twofold at 24 h of recovery without any changes in muscle IL-15 protein content or plasma IL-15 at any of the investigated time points. In conclusion, IL-15 mRNA level is enhanced in skeletal muscles dominated by type 2 fibres and resistance exercise induces increased muscular IL-15 mRNA levels. IL-15 mRNA levels in skeletal muscle were not paralleled by similar changes in muscular IL-15 protein expression suggesting that muscle IL-15 may exist in a translationally inactive pool. 相似文献
79.
Anderson RA; Wallace AM; Kicman AT; Wu FC 《Human reproduction (Oxford, England)》1997,12(8):1657-1662
Administration of supraphysiological doses of testosterone to normal men
causes inhibition of spermatogenesis, but while most become azoospermic,
30-55% maintain a low rate of spermatogenesis. We have investigated whether
there are differences in endogenous androgen production, of testicular and
adrenal origin, which may be related to the degree of suppression of
spermatogenesis. Thirty-three healthy Caucasian men were given weekly i.m.
injections of 200 mg testosterone oenanthate (TE), 18 became azoospermic,
while 15 remained oligozoospermic. Urinary excretion of epitestosterone, a
specific testicular product, was reduced to <10% of pretreatment values,
with no differences between the groups. Similar results were obtained for
other markers of testicular steroidogenesis. Urinary and plasma adrenal
androgens were also reduced during TE treatment: a statistically
significant decrease in both (P < 0.001 and P < 0.05 respectively)
was seen in the azoospermic but not oligozoospermic responders. These
results suggest that testicular steroidogenesis is decreased to <10% by
the administration of supraphysiological doses of exogenous testosterone.
Differences in the degree of ongoing steroidogenesis in the testis do not
appear to account for incomplete suppression of spermatogenesis, thus
differences in androgen metabolism may underlie this heterogeneous
response. A small but significant reduction in secretion of adrenal
androgens was also detectable, the relevance of which is unclear.
相似文献
80.
Maximum effort flow-static recoil curves were obtained in 5 healthy subjects breathing air, He/O2, and SF6/O2 mixtures. In 4 of them maximum effort flows corresponded to really maximal flows and their curves were transformed into compliance curves for the flow limiting segments of the airway and analyzed from the point of view of a previously presented lung model (Pedersen and Nielsen 1976). The results showed, that viscosity dependent pressure losses from the alveoli to the flow limiting segments were minimal for air and SF6/O2, but not for He/O2. When viscosity dependent pressure losses could be neglected, then expiration of gases of different densities gave almost identical compliance curves for the flow limiting segments. This supported the applicability of the model. The calculated compliance curves for the flow limiting segments were compared with data from the literature, and the findings indicated that flow limitation during expirations with just maximal flows throughout began in the extrapulmonary airways and moved upstream during the expiration. 相似文献