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排序方式: 共有1166条查询结果,搜索用时 15 毫秒
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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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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Xin Hong Larry N Thibos Arthur Bradley Russell L Woods Raymond A Applegate 《Optometry and vision science》2003,80(1):15-25
Repeated measures of wavefront aberrations were taken along the line-of-sight of seven eyes using two instruments: an objective, cross-cylinder aberroscope (OA) and a Shack-Hartmann (SH) aberrometer. Both instruments were implemented on the same optical table to facilitate interleaved measurements on the same eyes under similar experimental conditions. Variability of repeated measures of individual coefficients tended to be much greater for OA data than for SH data. Although Zernike coefficients obtained from a single measurement were generally larger when measured with the OA than with the SH, the averages across five trials were often smaller for the OA. The Zernike coefficients obtained from the two instruments were not significantly correlated. Radial modulation-transfer functions and point-spread functions derived from the two sets of measurements were similar for some subjects, but not all. When average Zernike coefficients were used to determine optical quality, the OA indicated superior optics in some eyes, but the reverse trend was true if Zernike coefficients from individual trials were used. Possible reasons for discrepancies between the OA and SH measurements include difference in sampling density, quality of data images, alignment errors, and temporal fluctuations. Multivariate statistical analysis indicated that the SH aberrometer discriminated between subjects much better than did the objective aberroscope. 相似文献
6.
What is the nature of the kindling process? We hypothesize that kindling is a discontinuous process involving discrete, stepwise transitions from one state of neural organization to another. Our data from the kindling antagonism paradigm argue that there are two critical transitions in the kindling process. These transitions constitute major steps in kindled seizure development. They act as "gates" controlling the ability of afterdischarge (AD) activity to effect the necessary reorganization of neural function which drives the kindling process. We identify two critical gates: 1) a forebrain gate which is dependent on norepinephrine (NE) and effects a discrete transition from nonconvulsive, stage 1 and 2 behaviors to stage 3 seizures, and 2) a brainstem gate which is also NE-dependent and effects a transition from stage 3 seizures to stage 4 and 5 seizures. These gates separate the kindling process into 3 "phases" which are different from, but overlap, the traditional behavioral stages of kindling defined by Racine. Current data suggest that these phases involve independent neural circuitry. They may also involve different physiological mechanisms, but this remains to be determined. This hypothesis is designed to provide a framework for the kindling process within which to search for kindling mechanisms. 相似文献
7.
Detection of chromosomes and estimation of aneuploidy in human spermatozoa using fluorescence in-situ hybridization 总被引:11,自引:0,他引:11
The development and application of fluorescence in-situ hybridization
(FISH) has opened the way for comprehensive studies on numerical chromosome
abnormalities in human spermatozoa. FISH can be rapidly applied to large
numbers of spermatozoa and thus overcomes the major limitation of
karyotyping spermatozoa after penetration of zona-free hamster oocytes. The
simultaneous hybridization of two or more chromosome-specific probes to
spermatozoa and subsequent detection of the bound probes using different
fluorescent detection systems enables two or more chromosomes to be
localized simultaneously in the same spermatozoon and provides a technique
for undertaking reasonable estimates of aneuploidy. The most commonly used
probes are those which bind to the centromeric region of specific
chromosomes. Most studies to date have concentrated on estimating
aneuploidy in spermatozoa from normospermic men, although reports are
beginning to appear on aneuploidy in spermatozoa from subfertile and
infertile men. Multi- probe FISH studies have generally reported disomy
(hyperhaploidy) estimates of 0.05-0.2% per chromosome. There is preliminary
evidence that some chromosomes such as X, Y and 21 are predisposed towards
higher rates of non-disjunction during spermatogenesis. There are also
suggestions of inter-donor variability in aneuploidy frequencies for
specific chromosomes, although this requires confirmation in larger
studies. While FISH is clearly a powerful technique that has many
applications in reproductive medicine, it must also be realized that it
does have limitations and the technology itself is still evolving and has
yet to be fully validated on spermatozoa.
相似文献
8.
Niggli HJ Tudisco S Privitera G Applegate LA Scordino A Musumeci F 《Journal of biomedical optics》2005,10(2):024006
Photobiological research in the last 30 yr has shown the existence of ultraweak photon emission in biological tissue, which can be detected with sophisticated photomultiplier systems. Although the emission of this ultraweak radiation, often termed biophotons, is extremely low in mammalian cells, it can be efficiently increased by ultraviolet light. Most recently it was shown that UV-A (330 to 380 nm) releases such very weak cell radiation in differentiated human skin fibroblasts. Based on these findings, a new and powerful tool in the form of UV-A-laser-induced biophotonic emission of cultured cells was developed with the intention to detect biophysical changes between carcinogenic and normal cells. With suspension densities ranging from 1 to 8 x 10(6) cells/mL, it was evident that an increase of the UV-A-laser-light induced photon emission intensity could be observed in normal as well as melanoma cells. Using this new detection procedure of ultraweak light emission, photons in cell suspensions as low as 100 microL could be determined, which is a factor of 100 lower compared to previous procedures. Moreover, the detection procedure has been further refined by turning off the photomultiplier system electronically during irradiation leading to the first measurements of induced light emission in the cells after less than 10 micros instead of 150 ms, as reported in previous procedures. This improvement leads to measurements of light bursts up 10(7) photons/s instead of several hundred as found with classical designs. Overall, we find decreasing induction ratings between normal and melanoma cells as well as cancer-prone and melanoma cells. Therefore, it turns out that this highly sensitive and noninvasive device enables us to detect high levels of ultraweak photon emission following UV-A-laser-induced light stimulation within the cells, which enables future development of new biophysical strategies in cell research. 相似文献
9.
Vaughan JR; Farrer MJ; Wszolek ZK; Gasser T; Durr A; Agid Y; Bonifati V; DeMichele G; Volpe G; Lincoln S; Breteler M; Meco G; Brice A; Marsden CD; Hardy J; Wood NW 《Human molecular genetics》1998,7(4):751-753
A mutation in exon 4 of the human alpha-synuclein gene was reported
recently in four families with autosomal dominant Parkinson's disease (PD).
In order to examine whether mutations in this exon or elsewhere in the gene
are common in familial PD, all seven exons of the alpha- synuclein gene
were amplified by PCR from index cases of 30 European and American
Caucasian kindreds affected with autosomal dominant PD. Each product was
sequenced directly and examined for mutations in the open reading frame. No
mutations were found in any of the samples examined. We conclude that the
A53T change described in the alpha- synuclein gene is a rare cause of PD or
may even be a rare variant. Mutations in the regulatory or intronic regions
of the gene were not excluded by this study.
相似文献
10.
Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography 总被引:10,自引:17,他引:10
Payne D; Flaherty SP; Barry MF; Matthews CD 《Human reproduction (Oxford, England)》1997,12(3):532-541
In this study, we have used time-lapse video cinematography to study
fertilization in 50 human oocytes that had undergone intracytoplasmic sperm
injection (ICSI). Time-lapse recording commenced shortly after ICSI and
proceeded for 17-20 h. Oocytes were cultured in an environmental chamber
which was maintained under standard culture conditions. Overall, 38 oocytes
(76%) were fertilized normally, and the fertilization rate and embryo
quality were not significantly different from 487 sibling oocytes cultured
in a conventional incubator. Normal fertilization followed a defined course
of events, although the timing of these events varied markedly between
oocytes. In 35 of the 38 fertilized oocytes (92%), there were circular
waves of granulation within the ooplasm which had a periodicity of 20-53
min. The sperm head decondensed during this granulation phase. The second
polar body was then extruded, and this was followed by the central
formation of the male pronucleus. The female pronucleus formed in the
cytoplasm adjacent to the second polar body at the same time as, or
slightly after, the male pronucleus, and was subsequently drawn towards the
male pronucleus until the two abutted. Both pronuclei then increased in
size, the nucleoli moved around within the pronuclei and some nucleoli
coalesced. During pronuclear growth, the organelles contracted from the
cortex towards the centre of the oocyte, leaving a clear cortical zone. The
oocyte decreased in diameter from 112 to 106 microm (P < 0.0001) during
the course of the observation period. The female pronucleus was
significantly smaller in diameter than the male pronucleus (24.1 and 22.4
microm respectively, P = 0.008) and contained fewer nucleoli (4.2 and 7.0
respectively, P < 0.0001). After time-lapse recording, oocytes were
cultured for 48 h prior to embryo transfer or cryopreservation. Embryo
quality was related to fertilization events and periodicity of the
cytoplasmic wave, and it was found that good quality embryos arose from
oocytes that had more uniform timing from injection to pronuclear abuttal
and tended to have a longer cytoplasmic wave. In conclusion, we have shown
that time-lapse video cinematography is an excellent tool for studying
fertilization and early embryo development, and have demonstrated that
human fertilization comprises numerous complex dynamic events.
相似文献