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排序方式: 共有2899条查询结果,搜索用时 15 毫秒
31.
Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis 总被引:7,自引:2,他引:7
Li DY; Toland AE; Boak BB; Atkinson DL; Ensing GJ; Morris CA; Keating MT 《Human molecular genetics》1997,6(7):1021-1028
Supravalvular aortic stenosis (SVAS) is an inherited obstructive vascular
disease that affects the aorta, carotid, coronary and pulmonary arteries.
Previous molecular genetic data have led to the hypothesis that SVAS
results from mutations in the elastin gene, ELN. In these studies, the
disease phenotype was linked to gross DNA rearrangements (35 and 85 kb
deletions and a translocation) in three SVAS families. However, gross
rearrangements of ELN have not been identified in most cases of autosomal
dominant SVAS. To define the spectrum of ELN mutations responsible for this
disorder, we refined the genomic structure of human ELN and used this
information in mutational analyses. ELN point mutations co-segregate with
the disease in four familial cases and are associated with SVAS in three
sporadic cases. Two of the mutations are nonsense, one is a single base
pair deletion and four are splice site mutations. In one sporadic case, the
mutation arose de novo. These data demonstrate that point mutations of ELN
cause autosomal dominant SVAS.
相似文献
32.
Nash GB Abbitt KB Tate K Jetha KA Egginton S 《Pflügers Archiv : European journal of physiology》2001,442(5):762-770
Changes in the rheological properties of neutrophils may influence flow in microvessels that are cooled below normal body temperature. We investigated the effects of temperature on the mechanical and adhesive properties of human neutrophils by measuring transit times for individual cells flowing through 8-microm-pores in filters, and adhesion to P-selectin for cells perfused over a monolayer of activated platelets. Pore transit time increased as temperature was decreased from 37 degrees C to 0 degrees C. Upon rapid cooling, there was an instantaneous increase attributable to changes in aqueous viscosity. Interestingly, at 10 degrees C specifically, there was an additional increase in transit time, which was abolished by the inhibitor of actin polymerization, cytochalasin B. This meant that by 15 min, transit time at 10 degrees C was greater than at 0 degrees C. Most adherent cells on P-selectin were rolling, rather than stationary, at 10, 26 or 37 degrees C. The velocity of rolling slowed with decreasing temperature. The total number of adherent cells decreased with increasing wall shear rate, but for a given shear rate there was relatively little effect of temperature on attachment. However, when adhesion at 10, 26 or 37 degrees C was compared at equal shear stress (taking into account fluid viscosity), adhesion was greatest at 10 degrees C. Measurements of immunofluorescence showed that exposure to 10 degrees C gradually increased expression of beta2-integrin CD11b/CD18, but this did not cause transformation to stationary adhesion with time in the flow assay. Thus, neutrophils show an anomalous rheological response around 10 degrees C, which may impair local microcirculation in the cold. On rewarming, "activated" cells might inhibit recovery or become released into the systemic circulation. 相似文献
33.
34.
Shumikhina S Guay J Duret F Molotchnikoff S 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2004,158(2):223-232
Synchronization of neuronal activity has been proposed as a binding mechanism for integration of image properties into one coherent percept. In the present study, we investigated the contextual modulation of synchronization to random dot patterns. Coherent motion of random dots evoked well synchronized responses in area 17 of anaesthetized cats when the stimulus was presented in the compound receptive field of recorded sites. Gradually changing the directional coherence of random dots in the surround while maintaining fully coherent motion of the stimulus in the receptive field significantly suppressed synchronization of neuronal activity for some stimulus conditions. However, usually one or two peaks of increased synchronization were found in the surround coherence tuning curves with low (8–12%) and/or moderate (25–50%) coherence in the surround. At the population level, synchronization was significantly depressed with incoherent motion in the receptive field and when both the surround and the receptive field were jointly stimulated with 0% coherence. The intriguing finding was the discovery of two distinct groups of cells with opposite synchronization changes dependent on the presence or absence of significant synchronization in their spontaneous activity. The latter group of neurons showed peaks of increased synchronization with lower surround coherence, thus probably being more sensitive to the direction of the surround motion. Overall, our findings support the notion that binding of stimulus properties can be achieved by synchronized activity of cortical cells. However, our findings go further than the original hypothesis of feature binding by synchrony to show that synchronization of cortical activity may be directly related to the decision making processes, which in turn are related to the threshold of perception of coherent motion. 相似文献
35.
Mutations in Emery-Dreifuss muscular dystrophy and their effects on emerin protein expression 总被引:2,自引:1,他引:2
Manilal S; Recan D; Sewry CA; Hoeltzenbein M; Llense S; Leturcq F; Deburgrave N; Barbot J; Man N; Muntoni F; Wehnert M; Kaplan J; Morris GE 《Human molecular genetics》1998,7(5):855-864
Seventeen families with Emery-Dreifuss muscular dystrophy (EDMD) have been
studied both by DNA sequencing and by emerin protein expression. Fourteen
had mutations in the X-linked emerin gene, while three showed evidence of
autosomal inheritance. Twelve of the 14 emerin mutations caused early
termination of translation. An in-frame deletion of six amino acids from
the C-terminal transmembrane helix caused almost complete absence of emerin
from muscle with no localization to the nuclear membrane, although mRNA
levels were normal. This shows that mutant emerin proteins are unstable if
they are unable to integrate into a membrane. A 22 bp deletion in the
promoter region was expected to result in reduced emerin production, but
normal amounts of emerin of normal size were found in leucocytes and
lymphoblastoid cell lines. This shows that DNA analysis is necessary to
exclude emerin mutations in suspected X-linked EDMD. Emerin levels in
female carriers often deviated from the expected 50% and this was due, in
at least two families, to skewed emerin mRNA expression from the normal and
mutated alleles. In one family with a novel deletion of the last three
exons of the emerin gene, a carrier had a cardiomyopathy and very low
emerin levels (<5% of normal) due to skewed X-inactivation. In the three
autosomal cases of EDMD, emerin was normal on western blots of blood cells,
which suggests that autosomal EDMD is not caused by indirect reduction of
emerin levels.
相似文献
36.
Anxiety during pregnancy and fetal attachment after in-vitro fertilization conception 总被引:3,自引:4,他引:3
McMahon CA; Ungerer JA; Beaurepaire J; Tennant C; Saunders D 《Human reproduction (Oxford, England)》1997,12(1):176-182
The aim of this study was to compare 70 couples who had conceived by in-
vitro fertilization (IVF) with 63 matched controls for the prevalence of
anxiety and quality of attachment to the baby during pregnancy. Results for
mothers showed no group differences using a global measure of anxiety, the
Spielberger State-Trait Anxiety Inventory. However, pregnancy-specific
measures revealed significantly higher levels of anxiety in IVF mothers
about the survival and normality of their unborn babies, about damage to
their babies during childbirth and about separating from their babies after
birth. When IVF mothers were differentiated according to the number of
treatment cycles, more differences in anxiety level were revealed, with
most increases occurring in mothers who had experienced two or more
treatment cycles. IVF fathers did not differ from controls on the global
anxiety measure. No data on pregnancy-specific anxiety were available for
fathers. Neither IVF mothers nor IVF fathers differed from controls on
measures of attachment to the baby during pregnancy. Results are discussed
in the context of the need for researchers to employ differentiated and
issue-specific measures to identify concerns that may be unique to IVF
couples. Clinical implications regarding the need for psychological support
during pregnancy are also discussed.
相似文献
37.
38.
Small (SK) and intermediate (IK) conductance calcium-activated potassium channels are candidate ion channels for the regulation of excitability in nociceptive neurones. We have used unique peptide-directed antisera to describe the immunocytochemical distribution of the known isoforms of these ion channels in dorsal root ganglia (DRG) and spinal cord of the rat. These investigations sought to characterize further the phenotype and hence possible functions of nociceptive neurone subpopulations in the rat. In addition, using Western blotting, we sought to determine the level of protein expression of SK and IK channels in sensory nervous tissues following induction of inflammation (Freund's Complete Adjuvant (FCA) arthritis model) or nerve injury (chronic constriction injury model). We show that SK1, SK2, SK3 and IK1 are all expressed in DRG and spinal cord. Morphometric analysis revealed that SK1, SK2 and IK1 were preferentially localized to neurones having cell bodies <1000 microm2 (putative nociceptors) in DRG. Dual labeling immunocytochemistry showed that these ion channels co-localize with both CGRP and IB4, known markers of nociceptor sub-populations. SK2 was localized almost exclusively in the superficial laminae of the spinal cord dorsal horn, the region in which many sensory afferents terminate; the distribution of SK1 and IK1 was more widespread in spinal cord, although some preferential labeling within the dorsal horn was observed in the case of IK1. Here we show evidence for a distinctive pattern of expression for certain members of the calcium-activated potassium channel family in the rat DRG. 相似文献
39.
Tate AR Foxall PJ Holmes E Moka D Spraul M Nicholson JK Lindon JC 《NMR in biomedicine》2000,13(2):64-71
The technique of magic angle spinning (MAS) high resolution (1)H NMR spectroscopy applied to intact tissues provides excellent peak resolution and thus much biochemical information. The use of computer-based pattern recognition techniques to classify human renal cortex tissue samples as normal or tumour based on their (1)H MAS NMR spectra has been investigated. In this preliminary study of 22 paired control and tumour samples, exploratory data analysis using principal components based on NMR spectral intensities showed clear separation of the two classes. Furthermore, using the supervised method of linear discriminant analysis, based on individual data point intensities or on integrated spectral regions, it was possible to distinguish between the normal and tumour kidney cortex tissue with 100% accuracy, including a single example of a metastatic tumour from a primary lung carcinoma. A tumour sample from the collecting duct of the kidney showed a different NMR spectral profile, and pattern recognition indicated that this sample did not classify with the cortical tumours. 相似文献
40.
Varying expression of major histocompatibility complex antigens on human renal endothelium and epithelium 总被引:2,自引:0,他引:2
P R Evans L P Trickett J L Smith A G MacIver D Tate M Slapak 《British journal of experimental pathology》1985,66(1):79-87
Pre-anastomosis wedge biopsies from 14 cadaveric donor kidneys were examined for the expression of class I (HLA-ABC) and class II (HLA-DR) antigens in renal tissue. Two monoclonal antibodies to class I antigens and four to class II antigens were used in an indirect immunoperoxidase technique. Consistent expression of both antigens was demonstrated on the surface of glomerular, peritubular capillary and venous endothelial cells. Renal arteries contained only class I antigens. Proximal tubules contained varying amounts of each antigen in their cytoplasm. Sixteen human lymphocytotoxic allo-antisera showed marked variation in their ability to detect HLA antigens on the kidney. The selection of donors for recipients of renal allografts involves the complement-dependent cytotoxicity test and the failure of some lymphocytotoxic antisera to bind to the kidney indicates that some suitable patients may be incorrectly excluded. The use of a binding assay using an immunoperoxidase technique should be included in cross-match techniques particularly for patients who have high levels of circulating cytotoxic antibodies. 相似文献