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71.
F(ab)'2-mediated neutralization of C3a and C5a anaphylatoxins: a novel effector function of immunoglobulins 总被引:2,自引:0,他引:2
Basta M Van Goor F Luccioli S Billings EM Vortmeyer AO Baranyi L Szebeni J Alving CR Carroll MC Berkower I Stojilkovic SS Metcalfe DD 《Nature medicine》2003,9(4):431-438
High-dose intravenous immunoglobulin (IVIG) prevents immune damage by scavenging complement fragments C3b and C4b. We tested the hypothesis that exogenous immunoglobulin molecules also bind anaphylatoxins C3a and C5a, thereby neutralizing their pro-inflammatory effects. Single-cell calcium measurements in HMC-1 human mast cells showed that a rise in intracellular calcium caused by C3a and C5a was inhibited in a concentration-dependent manner by IVIG, F(ab)2-IVIG and irrelevant human monoclonal antibody. C3a- and C5a-induced thromboxane (TXB2) generation and histamine release from HMC-1 cells and whole-blood basophils were also suppressed by exogenous immunoglobulins. In a mouse model of asthma, immunoglobulin treatment reduced cellular migration to the lung. Lethal C5a-mediated circulatory collapse in pigs was prevented by pretreatment with F(ab)2-IVIG. Molecular modeling, surface plasmon resonance (SPR) and western blot analyses suggested a physical association between anaphylatoxins and the constant region of F(ab)2. This binding could interfere with the role of C3a and C5a in inflammation. 相似文献
72.
van Haeringen WA van de Goor LH Panneman H van Lith HA van Haeringen H van Zutphen LF 《Molecular biotechnology》2003,23(2):117-125
A novel DNA technology enables the detection of universal variable fragments (UVF), thus revealing genetic variation without
a priori sequence information. The detection of UVF markers is based on two amplifications of genomic DNA with the polymerase chain
reaction. In the first amplification, two short oligonucleotide primers produce a large number of fragments. One primer is
based on a microsatellite sequence, whereas the second primer can have any sequence. In the second amplification, the length
of the primers is increased in order to decrease the number of amplicons. This enables the selection of polymorphic fragments.
Restriction digestion can be used to further increase the number of polymorphisms. Until now, we have demonstrated UVF in
several different species. In addition, with the present study we have contributed to the linkage map of the rabbit by localizing
11 UVF markers on different linkage groups. Mendelian inheritance was shown in this linkage study through a backcross of two
inbred rabbit strains. The power of the UVF technique is based on the selection for microsatellite variation in combination
with the detection of single-nucleotide polymorphisms. UVF thus offers the possibility of increasing the clustering of markers
and localizing genes in species for which sequence information is either not present or only scarcely present. 相似文献
73.
Ben A. Oostra Bert Zantinge Aly L. van Goor Albert J.J. van Ooyen Max Gruber 《Analytical biochemistry》1976,74(2):496-502
A rapid and sensitive liquid hybridization-competition method for the assay of in vitro synthesized Escherichia coli rRNA was developed. Hybridization with homologous DNA and with heterologous DNA from Proteus vulgaris was compared. Besides unfractionated DNA we used DNA enriched for the sites complementary to ribosomal RNA by chromatography on methylated albumin Kieselguhr. Hybridization with heterologous enriched DNA is the method of choice due to its low background and high hybridization efficiency. 相似文献
74.
Vallance BA Dijkstra G Qiu B van der Waaij LA van Goor H Jansen PL Mashimo H Collins SM 《American journal of physiology. Gastrointestinal and liver physiology》2004,287(4):G865-G874
The role of nitric oxide (NO) in inflammatory bowel diseases has traditionally focused on the inducible form of NO synthase (iNOS). However, the constitutive endothelial (eNOS) and neuronal (nNOS) isoforms may also impact on colitis, either by contributing to the inflammation or by regulating mucosal integrity in response to noxious stimuli. To date, studies examining the roles of the NOS isoforms in experimental colitis have been conflicting, and the mechanisms by which these enzymes exert their effects remain unclear. To investigate and clarify the roles of the NOS isoforms in gut inflammation, we induced trinitrobenzenesulfonic acid colitis in eNOS, nNOS, and iNOS knockout (KO) mice, assessing the course of colitis at early and late times. Both eNOS and iNOS KO mice developed a more severe colitis compared with wild-type mice. During colitis, iNOS expression dramatically increased on epithelial and lamina propria mononuclear cells, whereas eNOS expression remained localized to endothelial cells. Electron and fluorescence microscopy identified bacteria in the ulcerated colonic mucosa of eNOS KO mice, but not in wild-type, iNOS, or nNOS KO mice. Furthermore, eNOS KO mice had fewer colonic goblet cells, impaired mucin production, and exhibited increased susceptibility to an inflammatory stimulus that was subthreshold to other mice. This susceptibility was reversible, because the NO donor isosorbide dinitrate normalized goblet cell numbers and ameliorated subsequent colitis in eNOS KO mice. These results identify a protective role for both iNOS and eNOS during colitis, with eNOS deficiency resulting in impaired intestinal defense against lumenal bacteria and increased susceptibility to colitis. 相似文献
75.
We found that verapamil and its methoxy analogue, D600, were relatively potent (micromolar) inhibitors of Na+-dependent GABA uptake by a mouse brain microsomal subfraction (P3). Verapamil was competitive with GABA and uncompetitive with Na+ in the uptake assay with the P3 fraction. These substances were much less effective in inhibiting GABA binding in a receptor-related assay system with synaptosomal membranes. Inhibition by verapamil of Na+-dependent 45Ca++ uptake by the P3 particles was competitive with Ca++. A consideration of our results with those in the literature led to the suggestion that the interaction of verapamil and related substances with GABA and 45Ca uptake processes by the P3 fraction, as well as with many other membrane activities, may be allosteric in nature rather than directly competitive with specific ligands at their binding sites. 相似文献
76.
77.
Paria Mahboub Petra Ottens Marc Seelen Nails t Hart Harry Van Goor Rutger Ploeg Paulo Martins Henri Leuvenink 《PloS one》2015,10(12)
In this study we evaluated whether gradual rewarming after the period of cold ischemia would improve organ quality in an Isolated Perfused Kidney Model. Left rat kidneys were statically cold stored in University of Wisconsin solution for 24 hours at 4°C. After cold storage kidneys were rewarmed in one of three ways: perfusion at body temperature (38°C), or rewarmed gradually from 10°C to 38°C with stabilization at 10°C for 30 min and rewarmed gradually from 10°C to 38°C with stabilization at 25°C for 30 min. In the gradual rewarming groups the pressure was increased stepwise to 40 mmHg at 10°C and 70 mmHg at 25°C to counteract for vasodilatation leading to low perfusate flows. Renal function parameters and injury biomarkers were measured in perfusate and urine samples. Increases in injury biomarkers such as aspartate transaminase and lactate dehydrogenase in the perfusate were lower in the gradual rewarming groups versus the control group. Sodium re-absorption was improved in the gradual rewarming groups and reached significance in the 25°C group after ninety minutes of perfusion. HSP-70, ICAM-1, VCAM-1 mRNA expressions were decreased in the 10°C and 25°C groups. Based on the data kidneys that underwent gradual rewarming suffered less renal parenchymal, tubular injury and showed better endothelial preservation. Renal function improved in the gradual rewarming groups versus the control group. 相似文献
78.
Lei Chen Haley J. Abel Indraniel Das David E. Larson Liron Ganel Krishna L. Kanchi Allison A. Regier Erica P. Young Chul Joo Kang Alexandra J. Scott Colby Chiang Xinxin Wang Shuangjia Lu Ryan Christ Susan K. Service Charleston W.K. Chiang Aki S. Havulinna Johanna Kuusisto Ira M. Hall 《American journal of human genetics》2021,108(4):583-596
79.
Or David Shahar Ronen Gabizon Oren Feine Raphael Alhadeff Assaf Ganoth Liron Argaman Elee Shimshoni Assaf Friedler Michal Goldberg 《PloS one》2013,8(10)
Occurrence of DNA damage in a cell activates the DNA damage response, a survival mechanism that ensures genomics stability. Two key members of the DNA damage response are the tumor suppressor p53, which is the most frequently mutated gene in cancers, and MDC1, which is a central adaptor that recruits many proteins to sites of DNA damage. Here we characterize the in vitro interaction between p53 and MDC1 and demonstrate that p53 and MDC1 directly interact. The p53-MDC1 interaction is mediated by the tandem BRCT domain of MDC1 and the C-terminal domain of p53. We further show that both acetylation of lysine 382 and phosphorylation of serine 392 in p53 enhance the interaction between p53 and MDC1. Additionally, we demonstrate that the p53-MDC1 interaction is augmented upon the induction of DNA damage in human cells. Our data suggests a new role for acetylation of lysine 382 and phosphorylation of serine 392 in p53 in the cellular stress response and offers the first evidence for an interaction involving MDC1 that is modulated by acetylation. 相似文献
80.