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排序方式: 共有210条查询结果,搜索用时 15 毫秒
51.
52.
The enhancer-like sequence 3' to the A gamma gene is polymorphic in human populations 总被引:1,自引:0,他引:1
Bouhassira EE; Krishnamoorthy R; Ragusa A; Driscoll C; Labie D; Nagel RL 《Blood》1989,73(4):1050-1053
Cloning and sequencing of the enhancer 3' of the A gamma globin gene of a particularly low G gamma and HbF sickle cell anemia (SCA) patient unexpectedly revealed three base changes (T----C, C----A, and A----G at sites +2285, +2460, and +2676) previously associated with the Seattle- type HPFH, thus leading the authors to suspect that the three mutations were polymorphic. The determination of the incidence of the mutations among various ethnic groups allowed the authors to conclude that this is a widely spread polymorphism, thus excluding any role of these base changes in the determination of the hereditary persistence of fetal hemoglobin (HPFH) phenotype. The origin of these three mutations is not clear because they appear linked, and the same bases (C, A, G) are found in homologous position in the 3' of the normal G gamma gene. As C, A, G at positions +2285, +2460, and +2676 are found with a 100% frequency in African SS patients and presumably among normal Africans (to explain the extremely high frequency among normal American blacks), it is likely that this was the sequence preceding the division of races. The presence of T, C, and A at the same positions apparently occurred after the divergence between blacks and the other races, that is, within the last 1 million years. 相似文献
53.
Background and purpose
Arginase and nitric oxide (NO) synthase share the common substrate L-arginine, and arginase inhibition is proposed to increase NO production by increasing intracellular levels of L-arginine. Many different inhibitors are used, and here we have examined the effects of these inhibitors on vascular tissue.Experimental approach
Each arginase inhibitor was assessed by its effects on isolated rings of aorta and mesenteric arteries from rats by: (i) their ability to preserve the tolerance to repeated applications of the endothelium-dependent agonist acetylcholine (ACh); and (ii) their direct vasorelaxant effect.Key results
In both vessel types, tolerance (defined as a reduced response upon second application) to ACh was reversed with addition of L-arginine, (S)-(2-boronethyl)-L-cysteine HCl (BEC) or NG-Hydroxy-L-arginine (L-NOHA). On the other hand, Nω-hydroxy-nor-L-arginine (nor-NOHA) significantly augmented the response to ACh, an effect that was partially reversed with L-arginine. No effect on tolerance to ACh was observed with L-valine, nor-valine or D,L, α-difluoromethylornithine (DFMO). BEC, L-NOHA and nor-NOHA elicited endothelium-independent vasorelaxation in both endothelium intact and denuded aorta while L-valine, DFMO and nor-valine did not.Conclusions and implications
BEC and L-NOHA, but not nor-NOHA, L-valine, DFMO or nor-valine, significantly reversed tolerance to ACh possibly conserving L-arginine levels and therefore increasing NO bioavailability. However, both BEC and L-NOHA caused endothelium-independent vasorelaxation in rat aorta, suggesting that these inhibitors have a role beyond arginase inhibition alone. Our data thus questions the interpretation of many studies using these antagonists as specific arginase inhibitors in the vasculature, without verification with other methods. 相似文献54.
M Silengo E Belligni C Molinatto G Baldassare E Biamino N Chiesa O Zuffardi S Girirajan EE Eichler GB Ferrero 《Clinical genetics》2010,77(1):28-31
Silengo M, Belligni E, Molinatto C, Baldassare G, Biamino E, Chiesa N, Zuffardi O, Girirajan S, Eichler EE, Ferrero GB. Eyebrow anomalies as a diagnostic sign of genomic disorders. Microdeletions and microduplications in the human genome, termed genomic disorders, contribute to a high proportion of human multisystemic neurodevelopmental diseases and are detected by array‐based comparative genomic hybridization (aCGH). In general, most genomic disorders are associated with craniofacial and skeletal features and behavioural abnormalities, in addition to learning disability and developmental delay (LD/DD). Specifically, recognition of a characteristic ‘acial gestalt’ has been the key to distinguish one genomic disorder from the other. Here, we report our experience concerning the relevance of abnormal eyebrow pattern as a diagnostic indicator of specific genomic disorders. 相似文献
55.
Eichler EE; Macpherson JN; Murray A; Jacobs PA; Chakravarti A; Nelson DL 《Human molecular genetics》1996,5(3):319-330
To understand the origins of the fragile X syndrome and factors
predisposing alleles to instability and hyperexpansion, we have compared
the haplotype (using markers FRAXAC1, FRAXAC2, and DXS548) and AGG
interspersion patterns of the FMR1 CGG repeat for 214 normal and 16
premutation chromosomes. Association testing between interspersion pattern
and haplotype reveals a highly significant (P < 0.002) non- random
distribution, indicating that all three markers are useful in phylogenetic
reconstruction of mutational change. Parsimony analysis of the FMR1 CGG
repeat substructure predicts that loss of AGG interruptions has occurred
independently on many haplotypes associated with the fragile X syndrome,
partially explaining the haplotype diversity of this disease. Among
haplotypes found in linkage disequilibrium with the fragile X mutation, two
different modes of mutation and predisposition to instability have been
identified. One pathway has involved the frequent and recurrent loss of AGG
interruptions from rare asymmetrical ancestral array structures.
Intergenerational transmission studies suggest that these predisposed
chromosomes progress relatively rapidly to the disease state. In contrast,
the second mutational pathway involves a single haplotype which has
maintained two AGG interruptions. Parsimony analysis of CGG repeat
substructure within this haplotype suggests that larger alleles have been
generated by gradual increments of CGG repeats distal to the most 3'
interruption. Pedigree analysis of the intergenerational stability of
alleles of this haplotype confirms a gradual progression toward instability
thresholds. As a result, a large reservoir of chromosomes carrying large
repeats on this haplotype exists. These chromosomes are predisposed to
disease. The present data support a model in which there are at least two
different mutational pathways predisposing alleles to instability and
hyperexpansion associated with the fragile X syndrome.
相似文献
56.
Arici A; Oral E; Bahtiyar O; Engin O; Seli E; Jones EE 《Human reproduction (Oxford, England)》1997,12(6):1233-1239
Leukaemia inhibitory factor (LIF) is a 43 kDa glycoprotein with a
remarkable range of biological actions in different tissue systems. LIF
improves the rate of fertilization of mouse oocytes in vitro and up-
regulates aromatase enzyme. We postulated that LIF may be an important
modulator of ovarian function and may also improve embryo quality in
humans. Follicular fluid samples from patients undergoing in-vitro
fertilization (IVF) and embryo transfer (n = 123), from women undergoing
ovarian stimulation (n = 4) and from women undergoing laparoscopy for tubal
ligation during their follicular phase (n = 3) were used. Follicular fluid
LIF, oestradiol, and progesterone were measured and embryo quality was
assessed. Granulosa-lutein cells were cultured for 3 days in Ham's
F-12:Dulbecco's modified Eagle's medium (DMEM). Ovarian stromal cells,
isolated by enzymatic dispersion of ovarian tissue, were also cultured in
the same medium. Following experimental treatments, LIF mRNA and protein
concentrations were quantified. The concentration of LIF was 0.8 +/- 0.3
(mean +/- SEM) pg/ml in pre-human chorionic gonadotrophin (HCG) follicular
fluid samples and 13.0 +/- 1.1 pg/ml in post-HCG follicular fluid samples
(P < 0.05). LIF levels were undetectable in three follicular fluid
samples obtained during unstimulated follicular phase. There was a
correlation between follicular fluid LIF and follicular fluid oestradiol
concentrations (r = 0.36; P = 0.0001) and the number of grade I embryos (r
= 0.62; P = 0.01). LIF mRNA and the protein were expressed constitutively
but in low amounts in the ovarian stromal cell cultures. The concentrations
of LIF mRNA as well as protein were increased by interleukin (IL)-1alpha
and tumour necrosis factor alpha (TNF alpha) in a time- and
concentration-dependent manner. Purified granulosa-lutein cells expressed
low amounts of LIF mRNA and protein which were not significantly increased
by IL-1alpha or TNF alpha. Our findings suggest that HCG stimulates the
expression of LIF in follicular fluid. Both granulosa-lutein and ovarian
stromal cells express the LIF mRNA and produce the protein. Modulation of
LIF in these cells may play an important role in the physiology of
ovulation and early embryo development.
相似文献
57.
Nebulized budesonide versus oral steroid in severe exacerbations of childhood asthma 总被引:10,自引:0,他引:10
EE Matthews PD Curtis BI McLain LS Morris ML Turbitt 《Acta paediatrica (Oslo, Norway : 1992)》1999,88(8):841-843
The aim of this study was to assess whether nebulized budesonide may substitute for oral prednisolone in the management of children whose asthma is severe enough to warrant hospital admission, but who have no life threatening features. In a prospective, double-blind, randomized study nebulized budesonide (2 mg 8 hourly) was compared with oral prednisolone (2 mg/kg at entry and again at 24 h) in 46 children admitted to hospital with severe asthma exacerbations. Efficacy variables (including lung function measurements such as the primary outcome variable, Forced Expiratory Volume in 1 second (FEV1) and symptoms) were measured 24 h after treatment initiation. FEV1 improved significantly compared to baseline in patients who received nebulized budesonide compared to the prednislone group. The data show nebulized budesonide to be at least as effective as oral steroid in improving lung function and symptom severity in severe exacerbations of childhood asthma. 相似文献
58.
59.
Detrano R; MacIntyre WJ; Salcedo EE; O'Donnell J; Underwood DA; Simpfendorfer C; Go RT; Jones H; Butters K; Leatherman J 《Radiology》1985,155(1):19-23
Forty-three patients who had undergone direct-contrast ventriculography were submitted to intravenous digital subtraction ventriculography and first-pass radionuclide ventriculography to compare the left ventricular ejection fractions obtained by each method. Ejection fractions were calculated by the area-length method from the direct contrast ventriculograms, by both area-length and videodensitometric methods from the digital subtraction ventriculograms, and by count densitometry from the radionuclide ventriculograms. Satisfactory correlations were found between values obtained by the late mask resubtracted videodensitometric method and the radionuclide method (r = 0.85) and by the digital ventriculographic area length method and direct-contrast method (r = 0.88). Videodensitometric methods may be an alternative way to estimate left ventricular ejection fractions accurately without reliance on geometric assumptions about the shape of the left ventricular cavity. 相似文献
60.
JA Low AB Froese RS Galbraith JT Smith EE Sauerbrei EJ Derrick 《Acta paediatrica (Oslo, Norway : 1992)》1993,82(5):433-437
Ninety-eight newborn infants, less than 34 weeks at birth, were studied to examine the relationship between newborn hypotension and hypoxemia and brain damage. Heart rate, blood pressure and oxygen tension were recorded continuously during the 96 h following delivery. Outcome measures included neuropathology in children who died, and motor and cognitive development at one year corrected age in children who survived. There were 22 children with a minor and 27 with a major abnormal outcome. There was a relationship between newborn hypotension, newborn hypoxemia and low birth weight, and a major abnormal outcome. The probability of a major abnormal outcome increased from 8% in newborns with no hypotension or hypoxemia, to 53% in children with both hypotension and hypoxemia. These findings support the contention that combinations of sustained newborn hypotension and hypoxemia are important factors in the development of brain damage, accounting for a major abnormal outcome. 相似文献