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1.
Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT1 ) receptors in rabbit aorta and human recombinant AT1 receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'2 = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [125 I]AII binding to rabbit aortic membranes (AT, receptors) and [125 I][Sar1 , Ile8 ]AII binding to human recombinant AT1 receptors in a concentration-dependent manner with IC50 values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [125 I)AII binding to bovine cerebellum membranes (ÀT2 receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT1 receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT1 selective angiotensin receptor antagonist which exerts a competitive antagonism in the [125 I]AII binding assay and insurmountable AT1 receptor antagonism in the functional study. 相似文献
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S H Duda P E Huppert V Arndt M Wehrmann K K Haase C D Claussen 《Journal of vascular and interventional radiology : JVIR》1992,3(1):59-65
The suitability of a pulsed dye laser (504 nm) in experimental and clinical angioplasty was investigated. In an experimental study, the ablation thresholds were 3 J/cm2 +/- 8 (mean +/- standard deviation) for fibrofatty plaque and 25 J/cm2 for calcified tissues under saline. At a radiant exposure of 10 J/cm2 the etch rates were 1.7 microns per pulse +/- 0.3 for media, 2.8 microns/pulse +/- 0.4 for normal intima, and 3.9 microns/pulse +/- 1.1 for fibrofatty plaque (P less than .05). Pressure wave effects with a separation of tissue layers were predominantly localized at the internal elastic lamina. Thermal injury with vacuolations extended 15 microns +/- 6 into adjacent tissue. For clinical study, laser-assisted balloon angioplasty was performed in 10 patients (64 years +/- 14) with occlusions of peripheral arteries using a 9-F multifiber ring catheter. Lesion length ranged from 2 to 12 cm (mean, 7 cm). Laser angioplasty with an 80 mJ/pulse decreased the mean stenosis from 100% to 58% +/- 12% (P less than .005). The ankle-brachial index rose from a median of 0.48 to 0.88 (P less than .001). In 33% of patients, there were subintimal dissections after laser angioplasty. After a mean follow-up of 10.2 months, the overall clinical success was 70% with a primary patency of 78%. The over-the-wire approach with a pulsed dye laser may constitute a safe and feasible tool in laser angioplasty. 相似文献
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SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a). 相似文献
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Frauke Behrens Uwe Claussen Leslie M. Iyer Eric D. Green Bernhard Horsthemke Robert Williamson Clare Huxley Charles Coutelle 《Chromosome research》1997,5(4):215-220
Centromeres remain the least characterized regions of human chromosomes because they have a very high content of repetitive DNA. Here, we describe a micro-dissection library from the centromeric region of human chromosome 7 and its use for generating sequence tagged sites (STSs). The library contains about 1500 clones with an average insert size of 150 bp and only about 15% of the clones harbour repetitive human DNA. Seven clones hybridizing to alphoid DNA were found to correspond to a fragment of the D7Z2 alphoid array on chromosome 7, thus confirming the origin of the library. A number of clones not containing known repetitive DNA were used to generate STSs that identified yeast artificial chromosomes (YACs) and in turn allowed the STSs to be placed on the physical map. One STS is located between the two Genethon genetic markers closest to the centromere on the q side. Another STS was located 3–4 cM away in 7q11.2, while a third identified YACs containing both low-copy and alphoid sequences that are not yet mapped but are clearly centromeric. The library therefore comprises a collection of sequences from the centromeric region of chromosome 7 that can be used to generate STSs and to map the entire centromeric region.This revised version was published online in November 2005 with corrections to the Cover Date. 相似文献
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Wienberg J. Jauch A. Lüdecke H. -J. Senger G. Horsthemke B. Claussen U. Cremer T. Arnold N. Lengauer C. 《Chromosome research》1994,2(5):405-410
Fluorescencein situ hybridization (FISH) of microlibraries established from distinct chromosome subregions can test the evolutionary conservation of chromosome bands as well as chromosomal rearrangements that occurred during primate evolution and will help to clarify phylogenetic relationships. We used a DNA library established by microdissection and microcloning from the entire long arm of human chromosome 2 for fluorescencein situ hybridization and comparative mapping of the chromosomes of human, great apes (Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus) and Old World monkeys (Macaca fuscata andCercopithecus aethiops). Inversions were found in the pericentric region of the primate chromosome 2p homologs in great apes, and the hybridization pattern demonstrates the known phylogenetically derived telomere fusion in the line that leads to human chromosome 2. The hybridization of the 2q microlibrary to chromosomes of Old World monkeys gave a different pattern from that in the gorilla and the orang-utan, but a pattern similar to that of chimpanzees. This suggests convergence of chromosomal rearrangements in different phylogenetic lines. 相似文献
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Rudolph C Steinemann D Von Neuhoff N Gadzicki D Ripperger T Drexler HG Mrasek K Liehr T Claussen U Emura M Schrock E Schlegelberger B 《Cancer Genetics and Cytogenetics》2004,153(2):144-150
Combining fluorescence R-banding, fluorescence in situ hybridization and spectral karyotyping allowed us to precisely define chromosomal breakpoints, gains, losses and a newly detected amplification in the human mantle cell lymphoma (MCL) cell line GRANTA-519. GRANTA-519 is characterized by the t(11;14)(q13;q32) resulting in overexpression of cyclin D1, a key player in cell cycle control. Hitherto unresolved complex rearrangements involve 1p, 1q, 3cen, 9p, 11q, 12p, 12q, 16p, 17p, and 18cen. Moreover, a 4- to 6-fold gain of sequences on 18q leads to a low-level amplification of the BCL2 gene and to an overexpression of the BCL2 protein. These results provide the basis for the identification of not only candidate oncogenes responsible for MCL in gained regions, but also for the identification of putative tumor suppressor genes in commonly deleted regions like 1p22, which would eventually enable functional studies of these genes. 相似文献