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排序方式: 共有802条查询结果,搜索用时 15 毫秒
1.
Donor interleukin-4 promoter gene polymorphism influences allograft rejection after heart transplantation. 总被引:3,自引:0,他引:3
Femke J Bijlsma Joyce vanKuik Marcel G J Tilanus Nicolaas deJonge Erik H Rozemuller Jan G van den Tweel Frits H J Gmelig-Meyling Roel A deWeger 《The Journal of heart and lung transplantation》2002,21(3):340-346
BACKGROUND: The cytokine interleukin-4 (IL-4) is secreted mainly by activated T lymphocytes and characterizes the T-helper 2 (Th2) sub-type. In transplantation Th2 cells are believed to induce graft tolerance. Previous studies revealed that patients with a relatively high frequency of IL-4 producing helper T lymphocytes (HTL) before heart transplantation (HTX) had no or less rejection episodes compared with patients with a low frequency of IL-4 producing HTL. Three single nucleotide polymorphisms (SNPs) have been identified in the promoter region of the IL-4 gene, which influence promoter strength. We investigated whether there was a correlation between SNP genotypes in the IL-4 promoter and heart failure, and rejection after HTX. METHODS: Seventy HTX patients, 61 donors, and 36 controls were genotyped for the 3 SNPs by sequencing. RESULTS: Of the SNPs at -285 and -81, only the C and A alleles, respectively, were found in this study. Both alleles were found for the -590 SNP. No relation between patient genotype of the SNP at -590 and heart failure and rejection was found. However, incidence of rejection was significantly lower in patients that received a donor heart with the T-positive genotype compared with patients that received a heart from a T-negative donor. Patients who had the T-negative genotype and received a heart from a T-positive donor, suffered significantly less from rejection than T-negative patients that received a T-negative donor heart. This was not significant in the T-positive patient group. CONCLUSIONS: This indicates that IL-4 production within the donor heart and by cells from the donor is important for reducing incidence of episodes of rejection. 相似文献
2.
DNA-binding polarity of human replication protein A positions nucleases in nucleotide excision repair 总被引:15,自引:0,他引:15
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Wouter L. de Laat Esther Appeldoorn Kaoru Sugasawa Eric Weterings Nicolaas G.J. Jaspers Jan H.J. Hoeijmakers 《Genes & development》1998,12(16):2598-2609
The human single-stranded DNA-binding replication A protein (RPA) is involved in various DNA-processing events. By comparing the affinity of hRPA for artificial DNA hairpin structures with 3′- or 5′-protruding single-stranded arms, we found that hRPA binds ssDNA with a defined polarity; a strong ssDNA interaction domain of hRPA is positioned at the 5′ side of its binding region, a weak ssDNA-binding domain resides at the 3′ side. Polarity appears crucial for positioning of the excision repair nucleases XPG and ERCC1–XPF on the DNA. With the 3′-oriented side of hRPA facing a duplex ssDNA junction, hRPA interacts with and stimulates ERCC1–XPF, whereas the 5′-oriented side of hRPA at a DNA junction allows stable binding of XPG to hRPA. Our data pinpoint hRPA to the undamaged strand during nucleotide excision repair. Polarity of hRPA on ssDNA is likely to contribute to the directionality of other hRPA-dependent processes as well. 相似文献
3.
Evaluation of Hemagglutinin Protein-Specific Immunoglobulin M for Diagnosis of Measles by an Enzyme-Linked Immunosorbent Assay Based on Recombinant Protein Produced in a High-Efficiency Mammalian Expression System
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Fabienne B. Bouche Nicolaas H. C. Brons Sophie Houard Francois Schneider Claude P. Muller 《Journal of clinical microbiology》1998,36(12):3509-3513
Recombinant hemagglutinin (H) of the measles virus (MV) expressed in a mammalian high-expression system based on the Semliki Forest virus replicon was used in an enzyme-linked immunosorbent assay (ELISA) for the detection of specific immunoglobulin M (IgM) and IgG in patients with acute-phase measles. One hundred twelve serum specimens from 70 patients with measles were analyzed. Case definition was based on a commercial IgM ELISA that utilizes MV-infected cells (MV-ELISA) (Enzygnost; Behring Diagnostics); the clinical criteria of the Centers for Disease Control and Prevention (Atlanta, Ga.); and/or the increase in hemagglutinin test titers, neutralization test titers, and levels of MV-specific IgG whenever paired sera were available. The initial time courses of the IgM signal after the onset of rash are similar in the H- and MV-ELISAs. On days 0 to 19, both ELISAs detected IgM in 67 of 68 (98.5%) sera. Average maximal levels of IgM seem to persist, however, about 10 days longer in the MV-ELISA (up to day 25) than in the H-ELISA (day 15). From days 20 to 29 and 30 to 59, the H-ELISA detected only 64.3 (9 of 14) and 19.2% (5 of 26), respectively, of sera that were IgM positive by MV-ELISA. At least up to day 30, the performance of the H-ELISA seemed to be similar to that reported for commercial ELISAs based on whole MV. Our results demonstrate that MV H-specific IgM can be used to diagnose most measles cases from a single serum specimen collected within 19 days after the onset of rash and that the recombinant protein used in this study is suitable for this purpose. 相似文献
4.
Pieter Sipkema Ricky D. Latham Nicolaas Westerhof Bernard J. Rubal David M. Slife 《Annals of biomedical engineering》1990,18(5):491-503
A setup consisting of a high-performance hydraulic pump connected to the ascending part of an isolated aorta, including all
major distal branches, each loaded with calibrated artificial resistors, was developed. The system was used to study total
aortic compliance of the baboon as a function of mean aortic pressure (n=5). The aorta loaded with the resistors was mounted
in a custom-designed sink table, such that it was submersed in physiological saline maintained at 37°C. Mean distending pressure
in the entire aortic compliance from pressure and flow waves generated by the pump. Total aortic compliance as a function
of mean pressure was fitted with a logarithmic function: Ln (Compliance)=A+B * P. The value of A(±SE) was: 1.565±0.319 and
B: −0.020±0.003 (P<0.001). The results were compared with previously published results (also using the same three-element
Windkessel fit) obtained in three of the same animalsin vivo. Thein vivo data were A: 1.095±0.235 and B: −0.019±0.003.In vitro data had a significantly higher value of A thanin vivo (P=0.017), implying a significantly higher aortic compliancein vitro thanin vivo.
Occlusion of the proximal descending aorta was performed at a low distending pressure (55 mm Hg) to determine the proximal
complicance. It was found (n=4) that 46±11% (SD) of the total arterial compliance is to be attributed to the ascending and
proximal descending aorta.
This work was supported in part by Grant RG 86/0066 from the scientific affairs division of Nato. 相似文献
5.
Claude P. Muller Daniela Handtmann Nicolaas H. C. Brons Martin Weinmann Karl-Heinz Wiesmü ller Gü nther Spahn Michael Wiesneth Francois Schneider Gü nther Jung 《Virus research》1993,30(3):271-280
The measles virus induces a life-long immune response associated with antibodies specific for the fusion protein. To map the linear immunodominant recognition sites of the fusion (F) protein of the measles virus, we have reacted a complete set of 108 overlapping pentadecapeptides with purified IgG obtained from donor sera with elevated anti-measles titers. The antibodies recognized about 20% of the peptides and generated a characteristic binding pattern, defining about 6 or 7 distinctive regions (31–75; 111–145; 151–165; 191–215; 271–320; 421–440; 481–530) which include the major hydrophobic segment (111–145) of the intersubunit region and the C-terminal Cys-cluster region. The binding sites were located in close proximity of the few experimentally defined T cell epitopes. This pairing of T and B cell epitopes was corroborated by computer-assisted T cell prediction. The significance of a non-random association of T and B cell epitopes for processing and presentation is discussed. It is speculated that in long-term immunity against measles (F protein), B cells of the same sIg specificity play an important role both as antigen presenting cells and as antibody producing cells. In contrast to human sera from late convalescent donors, mouse and rabbit MV antisera with high neutralizing titers as well as neutralizing MV-F specific monoclonal antibodies did not react with the peptides. 相似文献
6.
Vincenza Gianfredi Annemarie Koster Anna Odone Andrea Amerio Carlo Signorelli Nicolaas C. Schaper Hans Bosma Sebastian Khler Pieter C. Dagnelie Coen D.A. Stehouwer Miranda T. Schram Martien C.J.M. van Dongen Simone J.P.M. Eussen 《Nutrients》2021,13(3)
Our aim was to assess the association between a priori defined dietary patterns and incident depressive symptoms. We used data from The Maastricht Study, a population-based cohort study (n = 2646, mean (SD) age 59.9 (8.0) years, 49.5% women; 15,188 person-years of follow-up). Level of adherence to the Dutch Healthy Diet (DHD), Mediterranean Diet, and Dietary Approaches To Stop Hypertension (DASH) were derived from a validated Food Frequency Questionnaire. Depressive symptoms were assessed at baseline and annually over seven-year-follow-up (using the 9-item Patient Health Questionnaire). We used Cox proportional hazards regression analyses to assess the association between dietary patterns and depressive symptoms. One standard deviation (SD) higher adherence in the DHD and DASH was associated with a lower hazard ratio (HR) of depressive symptoms with HRs (95%CI) of 0.78 (0.69–0.89) and 0.87 (0.77–0.98), respectively, after adjustment for sociodemographic and cardiovascular risk factors. After further adjustment for lifestyle factors, the HR per one SD higher DHD was 0.83 (0.73–0.96), whereas adherence to Mediterranean and DASH diets was not associated with incident depressive symptoms. Higher adherence to the DHD lowered risk of incident depressive symptoms. Adherence to healthy diet could be an effective non-pharmacological preventive measure to reduce the incidence of depression. 相似文献
7.
8.
Absorption Enhancing Effect of Cyclodextrins on Intranasally Administered Insulin in Rats 总被引:4,自引:0,他引:4
Merkus Frans W. H. M. Verhoef J. Coos Romeijn Stefan G. Schipper Nicolaas G. M. 《Pharmaceutical research》1991,8(5):588-592
The absorption enhancing effect of -, -, and -cyclodextrin (CD), dimethyl--cyclodextrin (DMCD), and hydroxypropyl--cyclodextrin (HPCD) on intranasally administered insulin was investigated in rats. Coadministration of 5% (w/v) DMCD to the insulin solution resulted in a high bioavailability, 108.9 ± 36.4% (mean ± SD, n = 6), compared to i.v. administration, and a strong decrease in blood glucose levels, to 25% of their initial values. Coadministration of 5% -CD gave rise to an insulin bioavailability of 27.7 ± 11.5% (mean ± SD, n = 6) and a decrease in blood glucose to 50% of its initial value. The rate of insulin absorption and the concomitant hypoglycemic response were delayed for the -CD-containing solution as compared to the DMCD preparation. The other CDs, HPCD (5%), -CD (1.8%), and -CD (5%), did not have significant effects on nasal insulin absorption. DMCD at a concentration of 5% (w/v) induces ciliostasis as measured on chicken embryo tracheal tissue in vitro, but this effect is reversible. In conclusion, DMCD is a potent enhancer of nasal insulin absorption in rats. 相似文献
9.
Nicolaas H Prins Michel R Briejer Jan A J Schuurkes 《British journal of pharmacology》1997,120(4):714-720
- Although conscious dogs have often been used for colonic motility studies with 5-hydroxytryptamine (5-HT), the effects of 5-HT on the isolated colon have not been thoroughly characterized yet. The current study was undertaken to characterize the response to 5-HT of the canine isolated colon longitudinal muscle.
- Longitudinal strips of canine midcolon deprived of (sub)mucosa were prepared for isotonic measurement. 5-HT induced contractions from 3 nM onwards, which were not affected by selective inhibition of 5-HT re-uptake, monoamine oxidase or blockade of α-adrenoceptors. Tetrodotoxin (0.3 μM) did not affect the responses to 5-HT, suggesting that smooth muscle 5-HT receptors are involved. The selective 5-HT4 receptor antagonist SB 204070 (10 nM) slightly enhanced contractions to 5-HT and therefore it was included in the organ bath solution in all further experiments. The 5-HT1 and 5-HT2 receptor antagonist methysergide (0.1 μM) depressed the curve to 5-HT, but the selective 5-HT3 receptor antagonist granisetron (0.3 μM) had no effect.
- Besides 5-HT, α-methyl-5-HT (α-Me-5-HT), 5-methoxytryptamine (5-MeOT), 2-methyl-5-HT (2-Me-5-HT) and 5-carboxamidotryptamine (5-CT) also induced contractions, with the following rank order of potency (pEC50 values in parentheses): 5-HT (6.9)=α-methyl-5-HT (6.9)>2-Me-5-HT (5.8)=5-MeOT (5.7)=5-CT (5.6), indicative of 5-HT2 receptor involvement. α-Me-5-HT produced a bell-shaped curve, which was not affected by α-adrenoceptor blockade. 5-HT, 5-MeOT, 2-Me-5-HT and 5-CT produced a monophasic concentration-response curve, consistent with an interaction with a single receptor site. 8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and tryptamine only induced contractions at a concentration exceeding 1 μM.
- The selective 5-HT2B receptor antagonist SB 204741 (0.3 μM) did not affect the curve to 5-HT. Ketanserin, cisapride and spiroxatrine behaved as competitive antagonists with pKb values of, respectively, 8.4, 8.1 and 6.7. Spiroxatrine (1 μM) shifted the curve to 5-MeOT rightward yielding an apparent pA2 of 7.1. Other antagonists at 5-HT2A receptors also surmountably inhibited the contractions to 5-HT (apparent pA2 value in parentheses): mesulergine (8.2), cinanserin (8.2), yohimbine (6.2) and mianserin (8.6). However, as well as a rightward shift, methiothepin (8.3), pizotifen (8.6) and spiperone (8.8) also caused a depression of the curve, indicative of ‘pseudo-irreversible'' antagonism. Taken together, the above mentioned affinity estimates most closely corresponded to literature affinity values for 5-HT2A receptors.
- It was concluded that 5-HT induces contractions of the canine midcolon longitudinal muscle primarily by stimulation of smooth muscle 5-HT2A receptors. The presence of inhibitory 5-HT4 receptors cannot be ruled out.
10.
Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk 总被引:1,自引:0,他引:1
Kleijer WJ van der Sterre ML Garritsen VH Raams A Jaspers NG 《Prenatal diagnosis》2007,27(12):1133-1137
OBJECTIVE: Evaluation of results in a consecutive series of 76 prenatal diagnoses for xeroderma pigmentosum (XP) and trichothiodystrophy (TTD) made since 1977. METHODS: UV-induced DNA repair synthesis was assessed by the autoradiographic measurement of the incorporation of (3)H-thymidine. RESULTS: XP was diagnosed in 19 of the 76 investigated pregnancies at risk; cultured chorionic villus (CV) cells were used in 33 pregnancies with ten affected fetuses and cultured amniocytes in 43 pregnancies with nine affected fetuses. In four cases, CVS results were corroborated by subsequent investigation of amniocytes because maternal cell contamination in the CV cell culture was either present or could not be excluded. Uncertain results in two other cases with intermediate DNA repair capacity and severe maternal cell contamination required further investigation. Median time needed for cell culture and analysis was 25 days. To reduce intra-assay variations, a modification of the DNA repair synthesis assay has recently been developed. In this assay, patients and controls are investigated simultaneously in mixed cultures of cells labelled with polystyrene beads. CONCLUSION: Reliable prenatal diagnosis for XP and TTD can be made by the demonstration of clearly reduced UV-induced DNA repair synthesis due to defective global genome nucleotide excision repair. 相似文献