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21.
ATRX encodes a novel member of the SNF2 family of proteins: mutations point to a common mechanism underlying the ATR-X syndrome 总被引:11,自引:3,他引:11
Picketts DJ; Higgs DR; Bachoo S; Blake DJ; Quarrell OW; Gibbons RJ 《Human molecular genetics》1996,5(12):1899-1907
It was shown recently that mutations of the ATRX gene give rise to a
severe, X-linked form of syndromal mental retardation associated with alpha
thalassaemia (ATR-X syndrome). In this study, we have characterised the
full-length cDNA and predicted structure of the ATRX protein. Comparative
analysis shows that it is an entirely new member of the SNF2 subgroup of a
superfamily of proteins with similar ATPase and helicase domains. ATRX
probably acts as a regulator of gene expression. Definition of its genomic
structure enabled us to identify four novel splicing defects by screening
52 affected individuals. Correlation between these and previously
identified mutations with variations in the ATR-X phenotype provides
insights into the pathophysiology of this disease and the normal role of
the ATRX protein in vivo.
相似文献
22.
Honey K Benlagha K Beers C Forbush K Teyton L Kleijmeer MJ Rudensky AY Bendelac A 《Nature immunology》2002,3(11):1069-1074
CD1d antigen presentation to natural killer T (NKT) cells expressing the semi-invariant T cell receptor V(alpha)14J(alpha)18 requires CD1d trafficking through endosomal compartments; however, the endosomal events remain undefined. We show that mice lacking the endosomal protease cathepsin L (catL) have greatly reduced numbers of V(alpha)14(+)NK1.1(+) T cells. In addition, catL expression in thymocytes is critical not only for selection of these cells in vivo but also for stimulation of V(alpha)14(+)NK1.1(+) T cells in vitro. CD1d cell-surface expression and intracellular localization appear normal in catL-deficient thymocytes, as does the lysosomal morphology; this implies a specific role for catL in regulating presentation of natural CD1d ligands mediating V(alpha)14(+)NK1.1(+) T cell selection. These data implicate lysosomal proteases as key regulators of not only classical major histocompatibility complex class II antigen presentation but also nonclassical CD1d presentation. 相似文献
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26.
A randomized trial of a program to reduce the use of psychoactive drugs in nursing homes. 总被引:10,自引:0,他引:10
J Avorn S B Soumerai D E Everitt D Ross-Degnan M H Beers D Sherman S R Salem-Schatz D Fields 《The New England journal of medicine》1992,327(3):168-173
BACKGROUND. Although psychoactive medications have substantial side effects in the elderly, these drugs are used frequently in nursing homes. Few interventions have succeeded in changing this situation, and little is known about the clinical effects of such interventions. METHODS. We studied six matched pairs of nursing homes; at one randomly selected nursing home in each pair, physicians, nurses, and aides participated in an educational program in geriatric psychopharmacology. At base line we determined the type and quantity of drugs received by all residents (n = 823), and a blinded observer performed standardized clinical assessments of the residents who were taking psychoactive medications. After the five-month program, drug use and patient status were reassessed. RESULTS. Scores on an index of psychoactive-drug use, measuring both the magnitude and the probable inappropriateness of medication use, declined significantly more in the nursing homes in which the program was carried out (experimental nursing homes) than in the control nursing homes (decrease, 27 percent vs. 8 percent; P = 0.02). The use of antipsychotic drugs was discontinued in more residents in the experimental nursing homes than in the control nursing homes (32 percent vs. 14 percent); the comparable figures for the discontinuation of long-acting benzodiazepines were 20 percent vs. 9 percent, and for antihistamine hypnotics, 45 percent vs. 21 percent. In the experimental nursing homes residents who were initially taking antipsychotic drugs showed less deterioration on several measures of cognitive function than similar residents in the control facilities, but they were more likely to report depression. Those who were initially taking benzodiazepines or antihistamine hypnotic agents reported less anxiety than controls but had more loss of memory. Most other measures of clinical status remained unchanged in both groups. CONCLUSIONS. An educational program targeted to physicians, nurses, and aides can reduce the use of psychoactive drugs in nursing homes without adversely affecting the overall behavior and level of functioning of the residents. 相似文献
27.
G J Beers A P Carter B Leiter J H Shapiro 《Journal of computer assisted tomography》1984,8(2):232-236
Three cases are presented with computed tomographic evidence of gas in retroperitoneal soft tissues in association with the so-called "vacuum phenomenon" (Knutsson sign) in lumbar disks. We review the explanations of Knutsson sign and offer an explanation of how extradiscal gas can occur in association with it. 相似文献
28.
Brook RH Kamberg CJ Mayer-Oakes A Beers MH Raube K Steiner A 《Health policy (Amsterdam, Netherlands)》1990,14(3):225-242
Over the past 30 years, an explosion in health care expenditures has occurred. Prior to 1960, health care accounted for 4.4% of the U.S. Gross National Product; today it is 11%. Before rational solutions to controlling this rise can be proposed, we must determine whether the care that we are currently paying for is appropriate to the needs of the elderly. This paper analyzes the literature regarding appropriateness of acute care provided to the elderly. We identified 17 articles that explicitly cited appropriate or inappropriate care (including under-, over- and misuse) provided in hospital and ambulatory settings and for procedures, and 19 articles that presented data on the appropriateness of medication use in the elderly. Virtually every study included in this review found at least double-digit levels of inappropriate care. Perhaps as much as one-fifth to one-quarter of acute hospital services or procedures were felt to be used for equivocal or inappropriate reasons, and two-fifths to one-half of the medications studied were overused in outpatients. The few studies that examined underuse or misuse of services also documented the existence of these phenomena. This was especially true for the ambulatory care of chronic physical and mental conditions and concerned the use of low-cost technologies (visits, preventive services, some medications). Thus, we conclude that there appears to be a substantial problem in the matching of acute services to the needs of elderly patients. This mismatch occurs both in terms of overuse and underuse, at least for areas where research has been conducted. 相似文献
29.
Richard A. Beers Peter B. Kane Imad Nsouli Dennis Krauss 《Journal canadien d'anesthésie》1994,41(9):807-812
In this prospective, randomized study, 23 patients having spinal anaesthesia for transurethral prostatectomy (TURP) were evaluated for the adequacy of their block using a visual analog pain score (V4 PS). Each patient with a “standard”(≥T10) block level (n = 5) or “intermediate” (L1 or T12) block level (n = 5) found the block adequate. Sixty-two percent (8/13) of patients with a “low”-L3) block level found their block adequate. The VAPS was assessed every five minutes or whenever pain abruptly increased during TURP; an “inadequate block” was defined as a V4 PS ≥ 5 /10 during prostatic resection. Intravesical pressure was monitored and kept <15 mmHg to distinguish between pain from bladder distension and from prostatic resection. “Low” block patients (LBP) who found their block inadequate (n = 5) received supplemental intrathecal local anaesthetic given through a spinal catheter. The subsequent L1 block level was adequate for TURP. In LBP, who found their block adequate (n = 8), a higher (P < 0.01) VAPS was observed than in patients with a “standard” block level. However, a smaller (P < 0.05) maximum percent decrease in diastolic blood pressure was found in LBPs, than in “intermediate” or “standard” block patients. It is concluded that a spinal block ≥L1) is adequate during TURP when bladder pressure is monitored and kept low. Mid-lumbar block levels should be reserved for patients in whom the benefit of minimizing haemodynamic changes outweighs the risk of a “less complete” anaesthetic. 相似文献
30.
MR imaging of hypervascular liver tumors: timing optimization during the arterial phase 总被引:4,自引:0,他引:4
Van Beers BE Materne R Lacrosse M Jamart J Smith AM Horsmans Y Gigot JF Gilon R Pringot J 《Journal of magnetic resonance imaging : JMRI》1999,9(4):562-567
To analyze the optimal timing strategy for the detection of hypervascular liver tumors during the arterial phase of magnetic resonance (MR) imaging, a test examination after injection of 2 mL of gadopentetate dimeglumine was performed in 47 patients. The time course of the tumor-to-liver contrast-to-noise ratio (CNR) for all studies together was determined relative to the start of injection, the time of peak aortic enhancement, and the time of peak enhancement in the tumor. All studies were grouped together and the highest CNR was transiently observed at the time of peak tumor enhancement. This CNR was significantly higher than those observed at fixed delays after peak aortic enhancement. However, the CNRs at peak tumor enhancement+/-1.5 seconds did not differ significantly from those obtained after peak aortic enhancement. Finally, the CNRs obtained at fixed delays after the start of injection remained significantly lower. In hypervascular liver tumors, a higher CNR can be obtained during the arterial phase when the MR imaging delay is determined relative to the time of peak enhancement in the tumor or the aorta rather than being fixed after the start of contrast material injection. Timing based on the enhancement profile in the tumor rather than in the aorta should be performed only if rapid MR imaging is available with a time resolution of about 1.5 seconds to image the whole liver. 相似文献