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71.
Menno Hoekstra Dan Ye Reeni B. Hildebrand Ying Zhao Bart Lammers Miranda Stitzinger Johan Kuiper Theo J. C. Van Berkel Miranda Van Eck 《Journal of lipid research》2009,50(6):1039-1046
Impaired scavenger receptor class B type I (SR-BI)-mediated uptake of HDL-cholesterol esters (HDL-CE) induces adrenal insufficiency in mice. Humans contain an alternative route of HDL-CE clearance, namely through the transfer by cholesteryl ester transfer protein (CETP) to apolipoprotein B lipoproteins for subsequent uptake via the LDL receptor. In this study, we determined whether CETP can compensate for loss of adrenal SR-BI. Transgenic expression of human CETP (CETP Tg) in SR-BI knockout (KO) mice increased adrenal HDL-CE clearance from 33–58% of the control value. SR-BI KO/CETP Tg and SR-BI KO mice displayed adrenal hypertrophy due to equally high plasma adrenocorticotropic hormone levels. Adrenal cholesterol levels and plasma corticosterone levels were 38–52% decreased in SR-BI KO mice with and without CETP expression. SR-BI KO/CETP Tg mice also failed to increase their corticosterone level after lipopolysaccharide challenge, leading to an identical >4-fold increased tumor necrosis factor-α response compared with controls. These data indicate that uptake of CE via other routes than SR-BI is not sufficient to generate the cholesterol pool needed for optimal adrenal steroidogenesis. In conclusion, we have shown that CETP-mediated transfer of HDL-CE is not able to reverse adrenal insufficiency in SR-BI knockout mice. Thus, SR-BI-mediated uptake of serum cholesterol is essential for optimal adrenal function. 相似文献
72.
Rakesh S. Birjmohun Menno Vergeer Erik S. G. Stroes Manjinder S. Sandhu Sally L. Ricketts Michael W. Tanck Nicholas J. Wareham J. Wouter Jukema John J. P. Kastelein Kay-Tee Khaw S. Matthijs Boekholdt 《PloS one》2009,4(8)
Background
Paraoxonase-1 (PON1) is an antioxidant enzyme, that resides on high-density lipoprotein (HDL). PON1-activity, is heavily influenced by the PON1-Q192R polymorphism. PON1 is considered to protect against atherosclerosis, but it is unclear whether this relation is independent of its carrier, HDL. In order to evaluate the atheroprotective potential of PON1, we assessed the relationships among PON1-genotype, PON1-activity and risk of future coronary artery disease (CAD), in a large prospective case-control study.Methodology/Principal Findings
Cases (n = 1138) were apparently healthy men and women aged 45–79 years who developed fatal or nonfatal CAD during a mean follow-up of 6 years. Controls (n = 2237) were matched by age, sex and enrollment time. PON1-activity was similar in cases and controls (60.7±45.3 versus 62.6±45.8 U/L, p = 0.3) and correlated with HDL-cholesterol levels (r = 0.16, p<0.0001). The PON1-Q192R polymorphism had a profound impact on PON1-activity, but did not predict CAD risk (Odds Ratio [OR] per R allele 0.98[0.84–1.15], p = 0.8). Using conditional logistic regression, quartiles of PON1-activity showed a modest inverse relation with CAD risk (OR for the highest versus the lowest quartile 0.77[0.63–0.95], p = 0.01; p-trend = 0.06). PON1-activity adjusted for Q192R polymorphism correlated better with HDL-cholesterol (r = 0.26, p<0.0001) and more linearly predicted CAD risk (0.79[0.64–0.98], p = 0.03; p-trend = 0.008). However, these relationships were abolished after adjustment for HDL (particles-cholesterol-size) and apolipoproteinA-I (0.94[0.74–1.18], p-trend = 0.3).Conclusions/Significance
This study, shows that PON1-activity inversely relates to CAD risk, but not independent of HDL, due to its close association with the HDL-particle. These data strongly suggest that a low PON1-activity is not a causal factor in atherogenesis. 相似文献73.
Lisa Woodbine Sofia Grigoriadou Aaron A. Goodarzi Enriqueta Riballo Christopher Tape Antony W. Oliver Menno C. van Zelm Matthew S. Buckland E. Graham Davies Laurence H. Pearl Penny A. Jeggo 《DNA Repair》2010,9(9):1003-1010
Artemis is required for V(D)J recombination and the repair of a subset of radiation-induced DNA double strand breaks (DSBs). Artemis-null patients display radiosensitivity (RS) and severe combined immunodeficiency (SCID), classified as RS-SCID. Strongly impacting hypomorphic Artemis mutations confer marked infant immunodeficiency and a predisposition for EBV-associated lymphomas. Here, we provide evidence that a polymorphic Artemis variant (c.512C > G: p.171P > R), which has a world-wide prevalence of 15%, is functionally impacting. The c.512C > G mutation causes an ~3-fold decrease in Artemis endonuclease activity in vitro. Cells derived from a patient who expressed a single Artemis allele with the polymorphic mutational change, showed radiosensitivity and a DSB repair defect in G2 phase, with Artemis cDNA expression rescuing both phenotypes. The c.512C > G change has an additive impact on Artemis function when combined with a novel C-terminal truncating mutation (p.436C > X), which also partially inactivates Artemis activity. Collectively, our findings provide strong evidence that monoallelic expression of the c.512C > G variant impairs Artemis function causing significant radiosensitivity and a G2 phase DSB repair defect. The patient exhibiting monoallelic c.512C > G-Artemis expression showed immunodeficiency only in adulthood, developed bilateral carcinoma of the nipple and myelodysplasia raising the possibility that modestly decreased Artemis function can impact clinically. 相似文献
74.
Claase MB Olde Riekerink MB de Bruijn JD Grijpma DW Engbers GH Feijen J 《Biomacromolecules》2003,4(1):57-63
In previous studies in rats and goats, hydrophilic compositions of the PEOT/PBT block copolymer family have shown in vivo calcification and bone bonding. These copolymers are therefore interesting candidates as scaffolding materials in bone tissue engineering applications. Model studies using goat bone marrow stromal cells, however, showed that it was not possible to culture bone marrow stromal cells in vitro on these hydrophilic copolymers. In this paper two ways of surface modifying these materials to improve in vitro bone marrow stromal cell attachment and growth are discussed. Two different approaches are described: (1) blending of hydroxyapatite (HA) followed by CO(2) gas plasma etching; (2) surface modification using CO(2) gas plasma treatments. It was observed that not only HA but also the CO(2) plasma treatment by itself has a positive effect on bone marrow stromal cell attachment and growth. Gas plasma treatment appeared to be the most successful approach, resulting in a large increase in the amount of bone marrow stromal cells present on the surface (determined by a DNA assay). The amount of DNA present on the plasma-treated copolymer 1000/70/30 PEOT/PBT, based on poly(ethylene oxide, M(w) = 1000, 70 m% soft segment), was comparable to the amount present on PDLLA and significantly higher than the amount present on PCL after 7 days of cell culturing. The fact that after gas plasma treatment bone marrow stromal cells do attach to PEOT/PBT copolymers, enables in vitro bone marrow stromal cell culturing, making bone tissue engineering applications of these materials possible. 相似文献
75.
Ultraviolet B radiation induces a transient appearance of IL-4+ neutrophils, which support the development of Th2 responses 总被引:4,自引:0,他引:4
Teunissen MB Piskin G di Nuzzo S Sylva-Steenland RM de Rie MA Bos JD 《Journal of immunology (Baltimore, Md. : 1950)》2002,168(8):3732-3739
UVB irradiation can cause considerable changes in the composition of cells in the skin and in cutaneous cytokine levels. We found that a single exposure of normal human skin to UVB induced an infiltration of numerous IL-4(+) cells. This recruitment was detectable in the papillary dermis already 5 h after irradiation, reaching a peak at 24 h and declining gradually thereafter. The IL-4(+) cells appeared in the epidermis at 24 h postradiation and reached a plateau at days 2 and 3. The number of IL-4(+) cells was markedly decreased in both dermis and epidermis at day 4, and at later time points, the IL-4 expression was absent. The IL-4(+) cells did not coexpress CD3 (T cells), tryptase (mast cells), CD56 (NK cells), and CD36 (macrophages). They did coexpress CD15 and CD11b, showed a clear association with elastase, and had a multilobed nucleus, indicating that UVB-induced infiltrating IL-4(+) cells are neutrophils. Blister fluid from irradiated skin, but not from control skin, contained IL-4 protein as well as increased levels of IL-6, IL-8, and TNF-alpha. In contrast to control cultures derived from nonirradiated skin, a predominant type 2 T cell response was detected in T cells present in primary dermal cell cultures derived from UVB-exposed skin. This type 2 shift was abolished when CD15(+) cells (i.e., neutrophils) were depleted from the dermal cell suspension before culturing, suggesting that neutrophils favor type 2 T cell responses in UVB-exposed skin. 相似文献
76.
A. van Huis P. W. Arendse M. Schilthuizen P. P. Wiegers H. Heering M. Hulshof N. K. Kaashoek 《Entomologia Experimentalis et Applicata》1994,70(1):41-53
The stored-product bruchid pests,Callosobruchus maculatus (Fabricius) andBruchidius atrolineatus (Pic) cause considerable production losses in cowpea in West Africa.Uscana lariophage Steffan parasitizes the eggs of the bruchids both in the field and in storage. As chemical control of bruchids in traditional
granaries is not appropriate for poor farmers, enhancement of the efficacy of the parasitoid by environmental manipulation
has been investigated. The effect of temperature on the capacity ofU. lariophaga to parasitize eggs has been studied at eleven constant and three fluctuating temperatures within the range 10 to 45°C. Longevity
of the female wasp decreased with increasing temperature. The rate of development increased linearly at temperatures from
17.5 to 35°C, but decreased from 35 to 40°C. Mortality of the developing wasp remained below 20% from 20 to 37.5°C, but outside
this range, mortality reached 100% at 15 at 42.5°C. Most parasitization occurred at temperatures of 25 and 30°C. Sex ratio
(percentage females) increased with temperature in the high temperature range. The intrinsic rate of increase (rm) forU. lariophaga was highest in the temperature range from 30 to 37.5°C and was higher than that ofC. maculatus at all temperatures. While the rm value ofC. maculatus did not vary much at temperatures from 25 to 35°C, the rm value of the wasp doubled. Relative humidity did not effect longevity, egg-laying capacity, mortality, development time and
sex ratio of the wasps withC. maculatus as host. However, withB. atrolineatus as the host, development time and mortality increased at lower relative humidity levels. The results indicate that temperature
is the major regulating factor on the parasitoid. As the type of storage structure and its location (sun or shade) affects
the temperature inside the store, ways are being investigated of manipulating the storage environment through temperature
regulation to increase the impact of the parasitoid. 相似文献
77.
Menno F. Kielman Ron Smits Tara S. Devi Riccardo Fodde Luigi F. Bernini 《Mammalian genome》1993,4(6):314-323
The human -globin gene cluster (30 kb) is embedded in a GC-rich isochore very close to the telomere of Chromosome (Chr) 16p. The -Locus Controlling Region (-LCR) is located upstream of the adult -globin genes and has been shown to be essential for their expression. In this study we have been looking for expressed genes in the region upstream of the -globin cluster to understand the role of the LCR-like element in the expression and replication timing of flanking gene clusters. We show that the upstream -globin region is conserved over a 75-kb range and includes at least two oppositely transcribed non-globin genes, here referred to as Mid1 and Dist1. Complementary DNA sequences of 250 bp and 2.5 kb from Mid1 (coordinate-68) and Dist1 (coordinate-90 to-99), respectively, were isolated from human and mouse. The deduced partial amino acid sequences of these cDNAs are 81% and 95% identical for the Mid1 and Dist1 gene respectively. We have cloned a mouse cosmid contig which includes Dist1, Mid1, and the entire murine -globin cluster. The murine homolog of the -LCR was mapped upstream of the mouse globin genes at approximately the same position as in the human locus. Our results indicate that, in mouse and human, the -globin loci and their flanking sequences are homologous over a range of at least 130 kb. The structural homology of this region in both mammals suggests also a functional one and indicates the mouse as a potential model for studying the role of the -LCR controlling element in the regulation of expression and replication timing of the flanking gene clusters.The nucleotide sequence data reported in this paper have been submitted to GenBank and have been assigned the accession numbers M99623, M99624, M99625, and M99626. 相似文献
78.
79.
80.
Ig gene rearrangement steps are initiated in early human precursor B cell subsets and correlate with specific transcription factor expression 总被引:3,自引:0,他引:3