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941.
Scott S Auerbach Joshua G Dekeyser Matthew A Stoner Curtis J Omiecinski 《Drug metabolism and disposition》2007,35(3):428-439
The constitutive androstane receptor (CAR; NR1I3) regulates the expression of genes involved in xenobiotic metabolism. Alternative splicing of the human CAR gene yields an array of mRNAs that encode structurally diverse proteins. One form of CAR, termed CAR2, contains an additional four amino acids (SPTV) that are predicted to reshape the ligand-binding pocket. The current studies show a marked, ligand-independent, CAR2-mediated transactivation of reporters containing optimal DR-3, DR-4, and DR-5 response elements, and reporters derived from the natural CYP2B6 and CYP3A4 gene promoters. Overexpression of the RXRalpha ligand binding domain was critical for achieving these effects. CAR2 interaction with SRC-1 was similarly dependent on the coexpression of RXRalpha. Mutagenesis of Ser233 (SPTV) to an alanine residue yielded a receptor possessing higher constitutive activity. Alternatively, mutating Ser233 to an aspartate residue drastically reduced the transactivation capacity of CAR2. The respective abilities of these mutagenized forms of CAR2 to transactivate a DR-4 x 3 reporter element correlated with their ability to interact with RxRalpha and to recruit SRC-1 in a ligand-regulated manner. Together, these results demonstrate a robust RXRalpha-dependent recruitment of coactivators and transactivation by CAR2. In addition, CAR2 displays novel dose responses to clotrimazole and androstanol compared with the reference form of the receptor while at the same time retaining the ability to bind CITCO. This result supports a hypothesis whereby the four-amino-acid insertion in CAR2 structurally modifies its ligand binding pocket, suggesting that CAR2 is regulated by a set of ligands distinct from those governing the activity of reference CAR. 相似文献
942.
This was a retrospective observational study of 11 consecutive patients of major primary postpartum haemorrhage (PPH) who had the B-Lynch suture at the time of caesarean section, performed between 1 March 2001 and 31 March 2004 at a teaching hospital in Scotland. Case-note review was performed in 123 patients, who had major primary PPH to identify patients who had B-Lynch sutures at the time of caesarean section. The patient's age, parity, gestation of pregnancy at which the B-Lynch suture was performed, the indication for caesarean section and the cause of primary major PPH were recorded. The operative details, intraoperative and immediate postoperative complications and the need for subsequent hysterectomy were noted. The patients were followed-up with clinic visits at 6 weeks and any further hospital referral for late postoperative complications and whether subsequent successful pregnancy was achieved, were documented. The incidence of major PPH in our centre was 0.5% of the total deliveries, of which 11 cases had the B-Lynch suture applied at the time of caesarean section. The patients were aged between 25 and 38 years old (mean 31 years). Parity ranged from 0 to 1 and the gestational age at which the procedure was performed ranged from 34 to 41 weeks (mean 38 weeks). Ten operations (91%) were performed by senior registrars supervised by the consultant on call and one (9%) case was performed by a consultant on call. All cases had the B-Lynch sutures performed for major primary PPH caused by uterine atony at the time of caesarean section. The weight of the babies delivered ranged between 2,110 - 4,820 g (mean 3,500 g). The total blood loss at surgery ranged from 2,000 - 10,000 ml (mean 3,500 ml). Only three patients (28%) required hysterectomy. All the patients made a good postoperative recovery. The hospital stay ranged from 4 - 24 days (mean 8 days). The patient who remained in hospital for 24 days did so because her baby was admitted into the neonatal unit. All the patients were reviewed 6 weeks postnatally. There was no significant morbidity. A subsequent successful pregnancy has been achieved in one patient. 相似文献
943.
944.
945.
Multiple intrahippocampal injections of gallamine impair performance of a representational memory task in rats. The binding of [3H]-(-)-quinuclidinyl benzilate (QNB) to rat brain sections was measured to determine if changes in receptor binding were associated with the deleterious effects of gallamine. [3H]-(-)-QNB binding to sections taken from gallamine-injected animals was compared with binding in saline-injected control animals. Autoradiographic analyses indicated an increase in [3H]-(-)-QNB binding sites within all layers of the cerebral cortex and in the superior colliculus in gallamine-treated animals as compared to saline-injected controls. Significant increases were noted in cortical layers IV and V (P less than 0.025) in gallamine-treated animals. No significant changes (P greater than 0.05) in the number of binding sites were observed in the hippocampus, neostriatum or various thalamic nuclei. The ability of unlabeled pirenzepine, gallamine and carbamylcholine to inhibit 0.2 nM [3H]-(-)-QNB binding also was measured to determine changes in the distribution of receptor subtypes. No significant changes were observed in any brain region for the binding of the selective antagonists pirenzepine and gallamine or the agonist carbamyl-choline. Although other possibilities are considered, the data suggest that an increase in the number of muscarinic receptors may contribute to the observed behavioral deficits associated with long-term gallamine treatment. 相似文献
946.
947.
The topic of condylar injury in adults has generated more discussion and controversy than any other in the field of maxillofacial trauma. It is an important subject because such injuries are common and complications of trauma to the temporomandibular joint (TMJ) are far-reaching in their effects. Why are there so many different methods to treat this injury? How can seemingly disparate treatment options all produce satisfactory outcomes in the majority of patients? The reason lies with the biological adaptations that occur within the masticatory system that are poorly understood, not readily quantifiable, and variable from one person to the next. This discussion presents our current understanding of the adaptations that must occur to provide the patient with a satisfactory outcome. The adaptations for patients treated open are different than for those treated closed. However, it is when these adaptations fail to occur that unsatisfactory outcomes occur, regardless of how they were treated. 相似文献
948.
Pressure ulcers are a high-risk, high-volume, and high-cost problem for persons with disabilities. This article describes four tools published in the literature and reports the validity, reliability, strengths, and limitations of each. These tools include the Pressure Ulcer Scale for Healing (PUSH), the Pressure Sore Status Tool (PSST), the Sussman Wound Healing Tool (SWHT), and the Sessing Scale. Rehabilitation nurses should use a consistent framework with accurate quantification to assess, document, and monitor changes in pressure ulcers over time. Such a measurement tool must prove valid for the disabled population in which the tool is used. This will enable healthcare providers to communicate more effectively and evaluate the therapeutic plan of care. 相似文献
949.
J S Carvalho 《Ultrasound in obstetrics & gynecology》2005,25(1):95; author reply 95-95; author reply 96
950.
A metropolitan experience with infrainguinal revascularization. Operative risk and late results in northeastern Ohio 总被引:1,自引:0,他引:1
T D Rafferty J C Avellone C J Farrell N R Hertzer F R Plecha R S Rhodes W V Sharp J M Rogers 《Journal of vascular surgery》1987,6(4):365-371
Despite being of fundamental importance, the late results of major arterial reconstruction rarely have been documented throughout a large metropolitan area. In this study of 932 patients entered into the computer registry of the Cleveland Vascular Society, 19 surgeons representing 13 community hospitals and referral centers in Cleveland and Akron report the intermediate-term outcome during a mean interval of 35 months after infrainguinal lower extremity revascularization performed in northeastern Ohio from 1978 through 1982. Operative risk (5%), the early amputation rate (7%), and actuarial 5-year survival (48% to 55%) for patients with rest pain or tissue necrosis were significantly worse (p less than 0.05) than comparable figures (0.6%, 0%, and 77%, respectively) for others who underwent procedures for disabling claudication. Although both materials had similar success above the knee, the cumulative 3-year patency rate of autogenous vein bypass to the distal popliteal (69% to 88%; p less than 0.05) and tibioperoneal arteries (43%; 0.05 less than p less than 0.1) was superior to the results of polytetrafluoroethylene grafts (32% to 50% and 19%, respectively). Moreover, polytetrafluoroethylene grafts required reoperations at three times the rate of vein grafts to maintain limb salvage. 相似文献