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91.
G protein-coupled receptors (GPCRs) are important therapeutic targets for drug discovery. The identification and characterization of new ligands ideally requires the use of high throughput assays that are applicable to all GPCR subtypes. To circumvent the problem of different GPCRs coupling to distinct intracellular second messenger pathways, we describe a new method that uses the chimeric Galpha protein 16z25 to facilitate this process. Stably expressed in Chinese hamster ovary cells, 16z25 allows G(i/o)- and G(s)-coupled receptors to mobilize intracellular Ca(2+) upon agonist stimulation. We have generated nine cell lines each stably expressing 16z25 and a GPCR. All cell lines respond to appropriate agonist stimulation in fluorometric imaging plate reader (FLIPR) assays with robust and potent Ca(2+) mobilization. Several of these lines have been pharmacologically characterized using agonists and antagonists. We also demonstrate that the coexpression of GPCR and 16z25 does not interfere with the receptors' ability to activate endogenous signaling pathways. The ability of 16z25 to functionally mediate the agonist stimulation of a broad spectrum of GPCRs indicates that the use of cell lines stably coexpressing this chimera and GPCRs will simplify the drug screening process and aid in the deorphanization of new receptors. 相似文献
92.
Cheng JW Frank L Garrett SD Lu Y Sanoski CA White CM;Arnold Marie Schwartz College of Pharmacy Health Sciences Long Island University New York 《Pharmacotherapy》2004,24(2):248-279
Clinical studies are among the most important literature published in the area of cardiovascular pharmacotherapy and are the basis of many of the standards of practice today. We compiled a list of these clinical trials, as well as well-written, up-to-date review articles and important treatment guidelines, that focus on pharmacotherapeutic management of arrhythmias. This list should be useful not only to practitioners and trainees in cardiovascular pharmacotherapy, but also to other clinicians as an update. 相似文献
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95.
Body fatness as a determinant of menarche has been studied extensively, but limited to underweight females. Adolescent female patients were measured and interviewed. Subjects were divided into three groups based on body mass index (BMI) standard deviation score (SDS). Average age at menarche was 11.87 +/- 1.1 years in the obese group, 12.14 +/- 0.9 years in the overweight group, and 12.20 +/- 1.3 years in the normal weight group. Pearson correlation factor between BMI SDS and age at menarche was -0.24 (p < 0.01). These findings suggest an important role of increased body fatness on menarche that extends beyond underweight girls. 相似文献
96.
Marshall I Ugrasbul F Manginello F Wajnrajch MP Shackleton CH New MI Vogiatzi MV 《The Journal of clinical endocrinology and metabolism》2003,88(9):4144-4148
We are reporting a child with congenital panhypopituitarism, in whom deficient fetal steroidogenesis was suspected prenatally because of undetectable estriol levels measured in the maternal triple-marker screen. No fetal abnormalities were detected by ultrasonography. Amniocentesis demonstrated a normal 46,XX karyotype. Measurement of maternal urinary steroids failed to show elevation in the excretion of the major precursor for estriol, 16 alpha-hydroxydehydroepiandrosterone, indicating that the fetus did not have steroid sulfatase deficiency (placental sulfatase deficiency), the most common genetic cause of extremely low estriol. The steroid analysis excluded other rare single gene defects, including aromatase deficiency and 17 alpha-hydroxylase deficiency. We therefore suspected that the cause of low estriol in this fetus was adrenal insufficiency. Postnatal evaluation was consistent with panhypopituitarism, characterized by deficiency of all anterior pituitary hormones. Because this screen is now offered to more than half the pregnant women in the United States, reports of low estriol levels have become increasingly common. Therefore, it is essential that physicians be familiar with the various etiologies, perform the appropriate antenatal evaluation to determine the specific cause, and closely monitor both mother and child ante- and postnatally. 相似文献
97.
BACKGROUND: The introduction of a new information retrieval system for the use of health service staff at a large tertiary referral hospital provided an excellent opportunity for nurses to make greater use of evidence to inform their practice. However, the extent to which nurses were able to access the resource was unknown. AIM: The aim of the study was to obtain this information and to test nurses' knowledge of computers and their attitudes to using them in their practice. METHODS: During October 2001 a computer use questionnaire was attached to the pay advice slips of all nursing staff at the Royal Brisbane and Royal Women's Hospital (n = 1708). Staff were asked to return their completed questionnaire in a preaddressed return envelope. To encourage this, a prize (a Gold Class cinema pass for two) was offered. RESULTS: Of the 1708 questionnaires distributed, 590 were returned, giving a 34.5% response rate. Computer use was influenced by education, nursing seniority, age, and length of time in the service and, to a lesser extent, gender. CONCLUSIONS: Information from the study has assisted planners and educators to identify clusters of nurses to target for interventions in this area. Results will also be used to assess the success of any interventions. 相似文献
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99.
Medicinal plants represent precious resources from which bioactive compounds can be isolated and developed into invaluable therapeutic agents. With the advent of modern drug discovery technologies such as combinatorial chemistry and high-throughput drug screening platforms, there is an increasing interest in utilizing medicinal plants as a source of drug leads. A wide spectrum of bioassays can be employed for the detection of bioactivity in extracts, fractions, as well as purified compounds of herbal origin. Amongst the different types of bioassays, reporter gene assays are highly versatile and reliable. The present review provides an overview of the most popular reporter genes in terms of their basic methodology, capacities and limitations. The different types of intracellular and extracellular reporter gene products and their potential applications in bioassays of natural products are also discussed. 相似文献
100.
Smith RA Saslow D Sawyer KA Burke W Costanza ME Evans WP Foster RS Hendrick E Eyre HJ Sener S;American Cancer Society High-Risk Work Group;American Cancer Society Screening Older Women Work Group;American Cancer Society Mammography Work Group;American Cancer Society Physical Examination Work Group;American Cancer Society New Technologies Work Group;American Cancer Society Breast Cancer Advisory Group 《CA: a cancer journal for clinicians》2003,53(3):141-169
In 2003, the American Cancer Society updated its guidelines for early detection of breast cancer based on recommendations from a formal review of evidence and a recent workshop. The new screening recommendations address screening mammography, physical examination, screening older women and women with comorbid conditions, screening women at high risk, and new screening technologies. 相似文献