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排序方式: 共有817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
2.
Rajabi-Siahboomi Ali R. Bowtell Richard W. Mansfield Peter Davies Martyn C. Melia Colin D. 《Pharmaceutical research》1996,13(3):376-380
Purpose. The purpose of this study was to characterise the water mobility in the gel layer of hydrating HPMC tablets. Water mobility in the gel layer of different HPMCs was studied.
Methods. NMR imaging, a non-invasive technique, has been used to measure the spatial distribution of self-diffusion coefficient (SDC) and T2 relaxation times across the gel layer.
Results. It has been shown that there is a water mobility gradient across the gel layer of HPMC tablets. Although SDC and T2 relaxation times in the outer parts of the gel layer approached that of free water, in the inner parts they decreased progressively. Water mobility and SDC in the gel layer of different HPMCs appeared to vary with degree of substitution of the polymer and the lowest values were obtained across the gel layer of K4M tablets.
Conclusions. Water mobility varies across the gel layer of hydrating HPMC tablets and it is dependent on the degree of substitution of the polymer. 相似文献
3.
Bronchial mucus hypersecretion in acute quadriplegia. Macromolecular yields and glycoconjugate composition 总被引:1,自引:0,他引:1
K R Bhaskar R Brown D D O'Sullivan S Melia M Duggan L Reid 《The American review of respiratory disease》1991,143(3):640-648
In acute quadriplegia we have noted that about one in five patients develops unexplained production of markedly excessive and tenacious bronchial mucus. Spontaneous recovery from mucus hypersecretion usually occurs within weeks to months. Mucus samples collected from 12 patients have been found to be abnormal. Macromolecular contents of single aspirates yielded as much as 500 mg. Analytical ultracentrifuge analysis showed the mucus to contain considerable epithelial glycoprotein (GP) of typical buoyant density; its amino acid and carbohydrate compositions were characteristic of the GP from hypersecretory bronchial mucus such as in chronic bronchitis and cystic fibrosis. In five patients studied after recovery from hypersecretion, there tended to be relatively less GP. The mucus samples contained a high density glycoconjugate (GC): this had sugars of GP but also reacted positively with a monoclonal antibody to keratan sulfate. Its amino acid composition was different from that of GP: threonine was lower and glycine was higher than in GP. In mucus from one patient who died, chondroitin sulfate ABC and hyaluronic acid were identified as well. This suggests proteoglycans are involved in the pathophysiology of mucus hypersecretion. The sudden onset and spontaneous recovery of hypersecretion suggests that it is not due to gland hypertrophy. We speculate that in acute quadriplegia it is due to disturbed neuronal control of bronchial mucus gland secretion, perhaps related to initial disappearance and later reappearance of peripheral sympathetic nervous system tone. 相似文献
4.
5.
Respiratory illness and home environment of ethnic groups 总被引:4,自引:0,他引:4
R J Melia S Chinn R J Rona 《British medical journal (Clinical research ed.)》1988,296(6634):1438-1441
Factors contributing to differences in the prevalences of respiratory symptoms and diseases among ethnic groups were studied in primary schoolchildren living in 20 inner city areas of England in 1983. The raised prevalences of respiratory symptoms in these groups were compared with results from a national representative sample of children studied in 1982. Data on age, sex, respiratory illness, and social and environmental variables were obtained by questionnaire for 4815 children living in inner cities. The children were classified as white, Afro-Caribbean, Urdu, Gujarati, Punjabi, other Asian, or "other." Significant differences in the prevalence of respiratory conditions were found among the ethnic groups after allowance was made for the effects of interfering variables. Except for asthma all conditions were most prevalent in Afro-Caribbeans and whites. In these two ethnic groups respiratory illness was significantly associated with belonging to a one parent family and the combined use of gas cookers and paraffin heaters at home. Respiratory illness was found to vary in prevalence among ethnic groups but may be perceived differently by different groups. Further studies, measuring lung function, are necessary. 相似文献
6.
A precision, adiabatic, vacuum calorimeter and a differential scanning calorimeter have been used to measure the heat capacities of two ethylene-propylene block copolymers containing 12 and 17 mole per cent ethylene, respectively, over the temperature range 80 to 500°K. An estimate has been made of heat capacity values below 80°K. Values of the heat capacity, entropy, enthalpy, and free energy are listed at lO°C intervals. Two first order transitions at 399 ± 3°K and 435 ± l°K were observed in both copolymers. These are attributed to the melting of ethylene and isotactic propylene blocks. Values for the heats of fusion of the copolymers are listed. 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.
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
9.
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
10.
Tudor Andrew M. Church Steven J. Hendra Patrick J. Davies Martyn C. Melia Colin D. 《Pharmaceutical research》1993,10(12):1772-1776
We analyzed binary mixtures of polymorphs A and B of chlorpropamide ((l-[4-chlorobenzenesulphonyl]-3-propyl urea)) by near-infrared Fourier transform Raman spectroscopy (FTRS). The individual polymorphs were prepared and characterized by differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) microscopy, and physical appearance. The FTR spectra of the two polymorphs showed distinct differences which result from "crystal splitting effects. A series of 13 different mixtures of polymorph A and B was prepared by geometric mixing and their FTR spectra statistically analysed by factor analysis programming. Predictions of the A/B polymorphic composition of mixtures were made and compared with the theoretical values. The results demonstrate that FTRS combined with factor analysis programming may be successfully applied to the in situ monitoring of the A/B polymorphic nature of a chlorpropamide sample. 相似文献