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31.
Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations 总被引:9,自引:1,他引:9
Meyer J; Sudbeck P; Held M; Wagner T; Schmitz ML; Bricarelli FD; Eggermont E; Friedrich U; Haas OA; Kobelt A; Leroy JG; Van Maldergem L; Michel E; Mitulla B; Pfeiffer RA; Schinzel A; Schmidt H; Scherer G 《Human molecular genetics》1997,6(1):91-98
It has previously been shown that, in the heterozygous state, mutations in
the SOX9 gene cause campomelic dysplasia (CD) and the often associated
autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one
recurrent mutation were characterized in one SOX9 allele each, and in one
case, no mutation was found. Four missense mutations are all located within
the high mobility group (HMG) domain. They either reduce or abolish the
DNA-binding ability of the mutant SOX9 proteins. Among the five nonsense
and three frameshift mutations identified, two leave the C-terminal
transactivation (TA) domain encompassing residues 402-509 of SOX9 partly or
almost completely intact. When tested in cell transfection experiments, the
recurrent nonsense mutation Y440X, found in two patients who survived for
four and more than 9 years, respectively, exhibits some residual
transactivation ability. In contrast, a frameshift mutation extending the
protein by 70 residues at codon 507, found in a patient who died shortly
after birth, showed no transactivation. This is apparently due to
instability of the mutant SOX9 protein as demonstrated by Western blotting.
Amino acid substitutions and nonsense mutations are found in patients with
and without XY sex reversal, indicating that sex reversal in CD is subject
to variable penetrance. Finally, none of 18 female patients with XY gonadal
dysgenesis (Swyer syndrome) showed an altered SOX9 banding pattern in SSCP
assays, providing evidence that SOX9 mutations do not usually result in XY
sex reversal without skeletal malformations.
相似文献
32.
Pérez-Caballero D Albertí S Vivanco F Sánchez-Corral P Rodríguez de Córdoba S 《European journal of immunology》2000,30(4):1243-1253
Group A Streptococcus (GAS), the most frequent bacterial cause of suppurative infections in humans, expresses on the cell surface M proteins with capacity to bind factor H, FHL-1 and C4b binding protein (C4BP). This has been interpreted as a mechanism developed by this pathogen to decrease phagocytosis by macrophages and polymorphonuclear cells. We report the analysis of the capacity to bind factor H, FHL-1 and C4BP of 69 clinical isolates from 19 different serotypes. We show that strains binding complement regulators (30/69) belong to specific M serotypes. Of these, M18 strains are relatively frequent and interact with all three complement regulators simultaneously. However, the most virulent M1 and M3 strains did not bind complement regulators in our assays. The relevance of the interaction between complement regulators and S. pyogenes was analyzed using different approaches with the conclusion that under physiological conditions only FHL-1 and C4BP bind to streptococci. We show that FHL-1 presents a higher binding affinity for S. pyogenes than factor H because it carries a hydrophobic, high-affinity, GAS binding site in addition to the heparin binding site in SCR7. Using synthetic peptides we provide evidence that the high-affinity GAS binding site in FHL-1 involves the hydrophobic tail (Ser-Phe-Thr-Leu) that distinguishes FHL-1 from factor H. 相似文献
33.
The amygdala is part of the behavioural reinforcement system modulating long-term potentiation in rat hippocampus 总被引:1,自引:0,他引:1
Long-term potentiation (LTP) in the dentate gyrus can be modulated and prolonged by emotional/motivational influences when concurrently activated. A similar effect on LTP can be obtained by stimulating the amygdala, suggesting that this limbic structure might be part of the neural system involved in behavioural reinforcement. To confirm this we have performed a series of experiments in which the basolateral amygdala was either temporary inactivated by injection of lidocaine or permanently lesioned electrolytically. Both manipulations completely blocked the reinforcing effect of a motivational stimulus (drinking after 24-h deprivation) on LTP at the perforant pathway-dentate gyrus synapses, whilst leaving intact the non-reinforced potentiation. These results demonstrate that the basolateral amygdala is a key structure within the system involved in the modulatory interaction between the affective status of the animal and the mechanisms of functional plasticity. 相似文献
34.
Ivana Vančurová Miroslav Flieger Jindřich Volc Milan J. Beneš Jana Novotná Jiří Neužil Vladislav Běhal 《Journal of basic microbiology》1987,27(9):529-533
Anhydrotetracycline oxygenase was purified both by affinity chromatography and by hydrophobic interaction chromatography. Molecular weight of anhydrotetracycline oxygenase was determined to be 115,000 by Sephadex G-200 gel filtration. Using preparative isoelectric focusing the isoelectric point of the enzyme was estimated to be 5.3. The enzyme showed a sensitivity to thiol-specific inhibitors. During the hydrophobic interaction purification step, the activity dropped considerably. Reactivation occurred when a heat treated crude extract was added to the reaction mixture. 相似文献
35.
RPG1: an essential gene of Saccharomyces cerevisiae encoding a 110-kDa protein required for passage through the G1 phase 总被引:1,自引:0,他引:1
In Saccharomyces cerevisiae cells a number of genes are required for progression through, or else to pass beyond, the G1 phase. We characterized a novel gene, RPG1, which is also involved in this phase. RPG1 is an essential gene encoding a 110-kDa evolutionarily conserved protein. Elutriated or α-factor-synchronized cells of the rpg1-1 temperature-sensitive mutant were arrested in the first cell cycle when shifted to a non-permissive temperature. The cells
remained unbudded and neither grew nor duplicated DNA. rpg1-1 cells synchronized in S phase completed mitosis and arrested as unseparated G1 cells after a shift to a non-permissive temperature. Similarly, the asynchronous rpg1-1 cells accumulated in G1 at the non-permissive temperature, but mother and daughter cells did not separate. A bulk of Calcofluor-stained material
was localized in the region adjacent to the cell septum. Our data show that Rpg1p is required for passage through the G1 phase and may be involved in growth control. Data published recently indicate that Rpg1p exhibits significant sequence similarity
to a subunit of the mammalian translation initiation factor 3.
Received: 6 October 1997 / 8 November 1997 相似文献
36.
Ladislav Novotný Hassan Farghali Miloš Ryba Ivo Janků Jiří Beránek 《Cancer chemotherapy and pharmacology》1984,13(3):195-199
Summary Both transport and biotransformation processes for a series of pyrimidine nucleobases, ribonucleosides, 2-deoxyribonucleosides, and acetyl and 5-substituted derivatives of the cancerostatic agent araC were studied in the isolated everted rat jejunum with a continuous perfusion technique. Metabolic alterations during penetration were assessed by HPLC. 5-Halogeno and 5-deoxy derivatives of cytosine nucleosides exhibited higher transport rates and higher stability towards the deamination reaction than did unsubstituted derivatives. Octanol-buffer partition coefficients were estimated for the study compounds, and fragmental constants for the sugar moieties of nucleosides were assessed. With the present study compounds there was no correlation between lipophilicity and transport rate, as previously reported, but there was a correlation between lipophilicity and metabolic alteration of araC derivatives (r=0.99, n=5). 相似文献
37.
D. Finnerty A. Ní Eochagáin M. Ahmed A. Poynton J. S. Butler D. J. Buggy 《Anaesthesia》2021,76(11):1499-1503
Major spinal surgery causes significant postoperative pain. We tested the efficacy and safety of bilateral erector spinae block on quality of recovery and pain after thoracolumbar decompression. We randomly allocated 60 adults to standard care or erector spinae block. Erector spinae block improved the mean (SD) quality of recovery-15 score at 24 postoperative hours, from 119 (20) to 132 (14), an increase (95%CI) of 13 (4–22), p = 0.0044. Median (IQR [range]) comprehensive complication index was 1 (0–3 [0–5]) in the control group vs. 1 (0–1 [0–4]) after block, p = 0.4. Erector spinae block reduced mean (SD) area under the curve pain during the first 24 postoperative hours: at rest, from 78 (49) to 50 (39), p = 0.018; and on sitting, from 125 (51) to 91 (50), p = 0.009. The cumulative mean (SD) oxycodone consumption to 24 h was 27 (18) mg in the control group and 19 (26) mg after block, p = 0.20. In conclusion, erector spinae block improved recovery and reduced pain for 24 h after thoracolumbar decompression surgery. 相似文献
38.
39.
Lucie Bryndová Michal Bar Roman Herzig Robert Mikulík Jiří Neumann Daniel Šaňák Ondřej Škoda David Školoudík Daniel Václavík Aleš Tomek 《Health policy (Amsterdam, Netherlands)》2021,125(4):520-525
This article describes policy processes that have led to the re-organisation of stroke care in the Czech Republic since 2011, which has been part of a broader process of care concentration in several medical fields. Currently, stroke care is provided by 13 Comprehensive and 32 Primary Stroke Centres. The paper explains factors that supported the reform implementation, reviews implications, and discusses future challenges.Mandatory reporting of quality indicators, the introduction of a benchmarking system, integration with pre-hospital emergency care, and the introduction of countrywide patient triage have supported more timely treatment for stroke patients and better quality of care. Data from the Stroke Care Quality Indicators of the Czech Stroke Society show positive trends in many areas: the number of patients treated with intravenous thrombolysis quadrupled in eight years, with 26.4 % of all acute stroke patients receiving thrombolysis in 2018. Czech Republic now ranks third in Europe in the number of thrombolysis per population and second in the number of mechanical thrombectomies per population. The Czech experience provides an example of positive outcomes of concentrated stroke care, while highlighting the importance of proper implementation processes. In particular, it is essential to involve stakeholders and to provide reputational incentives through continuous benchmarking. 相似文献
40.
Tomás JM Camprubí S Merino S Parés R Llauradó X Julve J 《International journal of antimicrobial agents》1993,3(1):61-64
The inhibitory activity of different components from Candida albicans membrane protoplasts against clotrimazole and eberconazole was studied. The phospholipid fraction had the most inhibitory activity and the antimycotic activity of eberconazole was more affected than that of clotrimazole. 相似文献