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排序方式: 共有560条查询结果,搜索用时 62 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
2.
P. Hendrik Pretorius Michael A. King Howard C. Gifford Seth T. Dahlberg Frederick Spencer Ellen Simon Jason Rashkin Naomi Botkin William Berndt Manoj V. Narayanan Jeffrey A. Leppo 《Journal of nuclear cardiology》2005,12(3):284-293
BACKGROUND: Past receiver operating characteristic (ROC) studies have demonstrated that single photon emission computed tomography (SPECT) perfusion imaging by use of iterative reconstruction with combined compensation for attenuation, scatter, and detector response leads to higher area under the ROC curve (A(z)) values for detection of coronary artery disease (CAD) in comparison to the use of filtered backprojection (FBP) with no compensations. A new ROC study was conducted to investigate whether this improvement still holds for iterative reconstruction when observers have available all of the imaging information normally presented to clinical interpreters when reading FBP SPECT perfusion slices. METHODS AND RESULTS: A total of 87 patient studies including 50 patients referred for angiography and 37 patients with a lower than 5% likelihood for CAD were included in the ROC study. The images from the two methods were read by 4 cardiology fellows and 3 attending nuclear cardiologists. Presented for the FBP readings were the short-axis, horizontal long-axis, and vertical long-axis slices for both the stress and rest images; cine images of both the stress and rest projection data; cine images of selected cardiac-gated slices; the CEQUAL-generated stress and rest polar maps; and an indication of patient gender. This was compared with reading solely the iterative reconstructed stress slices with combined compensation for attenuation, scatter, and resolution. With A(z) as the criterion, a 2-way analysis of variance showed a significant improvement in detection accuracy for CAD for the 7 observers (P = .018) for iterative reconstruction with combined compensation (A(z) of 0.895 +/- 0.016) over FBP even with the additional imaging information provided to the observers when scoring the FBP slices (A(z) of 0.869 +/- 0.030). When the groups of 3 attending physicians or 4 cardiology fellows were compared separately, the iterative technique was not statistically significantly better; however, the A(z) for each of the 7 observers individually was larger for iterative reconstruction than for FBP. Compared with results from our previous studies, the additional imaging information did increase the diagnostic accuracy of FBP for CAD but not enough to undo the statistically significantly higher diagnostic accuracy of iterative reconstruction with combined compensation. CONCLUSIONS: We have determined through an ROC investigation that included two classes of observers (experienced attending physicians and cardiology fellows in training) that iterative reconstruction with combined compensation provides statistically significantly better detection accuracy (larger A(z)) for CAD than FBP reconstructions even when the FBP studies were read with all of the extra clinical nuclear imaging information normally available. 相似文献
3.
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
4.
5.
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
6.
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
7.
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
8.
Wylie JE Smith KR Botkin JR 《American journal of medical genetics. Part C, Seminars in medical genetics》2003,(1):35-44
Concerns about psychological distress have arisen regarding genetic testing for susceptibility to late-onset diseases such as breast and/or ovarian cancer. Early results do not show large-scale psychological distress among those tested; therefore, research is now focusing on identifying subgroups that may be at risk for negative outcomes. Social support has been shown to buffer both negative physical and psychological outcomes in health research. The role of spouses as part of the tested person's social support system is shown to be significant in a sample of 57 BRCA1 mutation carriers. Separately, the tested person's perception of his/her spouse's anxiety and his/her perception of the spouse's support at the time of testing are predictive of the tested person's psychological distress up to 2 years after testing. The interaction of the two variables is even more predictive. For those tested who perceived their spouse to be both anxious and nonsupportive at the time of testing, distress levels reached clinically significant levels 1 week after results were received and remained above clinical threshold measured 4 months, 1 year, and 2 years after testing. While the effects were greatest for women, they were significant for both male and female carriers. These findings are an important addition to the literature and will augment clinicians' ability to identify individuals potentially at risk for negative responses to adverse genetic test results. 相似文献
9.
María Jesús Fernández Aceñero MD PhD Cristina Díaz del Arco CDdA MD Carme Dinarés CD MD PhD Tania Labiano TL MD Eva Tejerina ET MD PhD Mª José Bernabé MJ B MD Elena Forcen EF MD Melchor Saiz-Pardo MSP MD Pablo Pérez PP MD Maria D. Lozano MDL MD PhD 《Diagnostic cytopathology》2023,51(1):26-35
Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples. 相似文献
10.
A simple auto-evaluation sheet is presented for the proper assessment of the patient's condition after surgery. Stress is
put not only on weight loss, but on other important factors as well. 相似文献