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61.
The human follicle-stimulating hormone receptor (FSH-R) consists of two distinct domains of >330 amino acids, the N-terminal extracellular exodomain and membrane-associated endodomain. The exodomain alone binds hormone with high affinity, whereas the endodomain is the site of receptor activation. Coordination of these two domains is essential for successful hormone action but little is known about their functional and structural relationship. In this communication, we report that exoloop 3 of FSH-R constrains follicle-stimulating hormone binding to the exodomain. When the FSH-R exodomain was prepared by truncating its endodomain, the hormone binding affinity of the exodomain was slightly improved, compared with the wild type receptor. The binding affinity was further improved by >3-fold when the exodomain was attached to the membrane-associated domain of CD8. These results suggest that the FSH-R endodomain attenuates hormone binding at the exodomain. As a first step to test this hypothesis, the 11 amino acids except Ala589 of exoloop 3 were individually substituted with Ala. Ala substitution for Leu583 or Ile584 improved the hormone binding affinity by 4-6-fold while totally abolishing cAMP induction, indicating an inverse relationship. The Ala substitution for Lys580 or Pro582 had a similar trend but to a lesser extent. This significant improvement in the binding affinity suggests that the four residues at the N-terminal region of exoloop 3 interact with the exodomain and constrain the hormone binding in the wild type receptor. This effect is specific since substitutions for other than the 4 residues did not improve the hormone binding affinity. Computer modeling shows that the 4 residues can be positioned on one side of exoloop 3. This result and the apparent inverse relationship of hormone binding and cAMP induction suggest that these two essential functions may work against each other. Therefore, hormone binding might be compromised to preserve cAMP inducibility while maintaining a reasonably high, but below maximum, binding affinity. 相似文献
62.
RL Hughson JK Shoemaker ME Tschakovsky JM Kowalchuk 《Canadian Metallurgical Quarterly》1996,81(4):1619-1626
The hypothesis that the rate of increase in muscle O2 uptake (VO2mus) at the onset of exercise is influenced by muscle blood flow was tested during forearm exercise with the arm either above or below heart level to modify perfusion pressure. Ten young men exercised at a power of approximately 2.2 W, and five of these subjects also worked at 1.4 W. Blood flow to the forearm was calculated from the product of blood velocity and cross-sectional area obtained with Doppler techniques. Venous blood was sampled from a deep forearm vein to determine O2 extraction. The rate of increase in VO2mus and blood flow was assessed from the mean response time (MRT), which is the time to achieve approximately 63% increase from baseline to steady state. In the arm below heart position during the 2.2-W exercise, blood flow and VO2mus both increased, with a MRT of approximately 30 s. With the arm above the heart at this power, the MRTs for blood flow [79.8 +/- 15.7 (SE)s] and VO2mus (50.2 +/- 4.0 s) were both significantly slower. Consistent with these findings were the greater increases in venous plasma lactate concentration over resting valued in the above heart position (2.8 +/- 0.4 mmol/l) than in the below heart position (0.9 +/- mmol/l). At the lower power, both blood flow and VO2mus also increased more rapidly with the arm below compared with above the heart. These data support the hypothesis that changes in blood flow at the onset of exercise have a direct effect on oxidative metabolism through alterations in O2 transport. 相似文献
63.
OBJECTIVE: The objective of this review was to evaluate the clinical and research literature on professionally-led support groups for cancer patients and to propose an approach that would address patients' needs from diagnosis through survivorship. METHOD: Computerized and manual searches, including Medline and Psychlit searches, were completed for reviews of the literature. Twelve research studies were identified that met our criteria for in-depth review. A clinical model emerged from discussions of an oncology study group based on theoretical formulations and clinical experience with oncology patients. RESULTS: We found that recent research suggests that professionally-led support groups are increasing in number and that participation in such groups seems to enhance patients' quality, and possibly even quantity, of survival. Despite this, little effort has been made to determine what type of group may be appropriate for which patients and when in their course of care. CONCLUSIONS: If psychosocial intervention, in the form of professionally-led support groups for cancer patients, is to be more effective, it should be guided by a model which takes into consideration the changing needs and concerns of patients over the course of illness and, in many cases, recovery. The authors present an outline delineating what such a model might entail. 相似文献
64.
65.
BACKGROUND: Australia has a high rate of cardiovascular disease mortality and also a significant proportion of migrants. Little is known about the morbidity experience or cardiovascular risk factors among the larger migrant groups, and this is especially true of the Arabic-speaking population. OBJECTIVES: The objectives of the study were to identify the health profile of Arabic-speaking people in Sydney, Australia, to explore the relationship between level of acculturation and health indicators and to identify the morbidity profile of patients presenting to Arabic-speaking general practitioners (GPs). DESIGN: Adult Arabic-speaking patients aged 18-70 years attending 20 Arabic-speaking GPs in Canterbury, Sydney, during the 2-week study period were asked to complete a self-administered questionnaire in Arabic or English while waiting to see the GP. Data on cardiovascular risk factors, level of acculturation and reasons for seeing the GP were collected. RESULTS: Data were collected from 851 patients (62% response rate). Almost three-quarters (73%) of males and 36% of females were considered overweight or obese (body mass index > 25). Of concern, 37% of males and 28% of females were smokers. Females were significantly less likely to have been tested for diabetes (p < .05) or raised blood pressure (p < 0.05) compared with females in NSW. Respondents consumed less bread per day and more fruits than in NSW overall. Respiratory complaints (flu and colds) were the most frequently reported reasons for patient encounters. Except for the youngest age group, males gave more reasons for encounters than females. CONCLUSIONS: Consecutive sampling of ethnic patients attending a GP who speaks their language holds promise as a method of needs assessment with migrant populations. Further, our results suggest that smoking and weight reduction programs are priorities in the Arabic-speaking community. These risk factors are ideal for intervention by GPs speaking the same language. 相似文献
66.
Balfour Louise; White Donna Romano; Schiffrin Alicia; Dougherty Geoffrey; Dufresne Jackie 《Canadian Metallurgical Quarterly》1993,12(1):33
Examining the relationship of stress, dietary disinhibition, and blood glucose control in diabetic young women was the goal of this study. 65 diabetic girls and women, ranging in age from 12 to 26 yrs, completed eating behaviors and perceived stress scales during regular clinic visits. Blood glucose control was assessed by concurrent glycosylated hemoglobin measurements. Multiple regression analyses indicated that high levels of perceived stress predicted dietary disinhibition and that within the age range studied, young women were more likely than early adolescent girls to perceive their life as stressful. Contrary to previous findings that failed to show that stress can indirectly affect glucose control by interfering with compliance behaviors, the present work indicated a Stress?×?Dietary Disinhibition interaction in predicting glucose control. Blood glucose control was poorest in those diabetic women who both perceived their lives as stressful and reported medium to high disinhibition. Blood glucose control was unrelated to stress in young women who reported low levels of disinhibition. These results have implications for the development of specific interventions for young diabetic women who perceive their lives as stressful and who may respond to stress by eating. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
67.
CB Granger J Hirsch RM Califf J Col HD White A Betriu LH Woodlief KL Lee EG Bovill RJ Simes EJ Topol 《Canadian Metallurgical Quarterly》1996,93(5):870-878
BACKGROUND: Although intravenous heparin is commonly used after thrombolytic therapy, few reports have addressed the relationship between the degree of anticoagulation and clinical outcomes. We examined the activated partial thromboplastin time (aPTT) in 29,656 patients in the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO-I) trial and analyzed the relationship between the aPTT and both baseline patient characteristics and clinical outcomes. METHODS AND RESULTS: Intravenous heparin was administered as a 5000-U bolus followed by an initial infusion of 1000 U/h, with dose adjustment to achieve a target aPTT of 60 to 85 seconds. aPTTs were collected 6, 12, and 24 hours after thrombolytic administration. Higher aPTT at 24 hours was strongly related to lower patient weight (P < .00001) as well as older age, female sex, and lack of cigarette smoking (all PT< .0001). At 12 hours, the aPTT associated with the lowest 30-day mortality, stroke, and bleeding rates was 50 to 70 seconds. There was an unexpected direct relationship between the aPTT and the risk of subsequent reinfarction. There was a clustering of reinfarction in the first 10 hours after discontinuation of intravenous heparin. CONCLUSIONS: Although the relationship between aPTT and clinical outcome was confounded to some degree by the influence of baseline prognostic characteristics, aPTTs higher than 70 seconds were found to be associated with higher likelihood of mortality, stroke, bleeding, and reinfarction. These findings suggest that until proven otherwise, we should consider the aPTT range of 50 to 70 seconds as optimal with intravenous heparin after thrombolytic therapy. 相似文献
68.
In rats, the phosphorothionate insecticide parathion exhibits greater toxicity than chlorpyrifos, while in catfish the toxicities are reversed. The in vitro inhibition of brain acetylcholinesterase (AChE) by the active metabolites of the insecticides and the rates at which these inhibitor-enzyme complexes undergo reactivation/ aging were investigated in both species. Rat AChE was more sensitive to inhibition than catfish AChE as demonstrated by greater bimolecular rate constants (ki) in rats than in catfish. In both species, chlorpyrifos-oxon yielded higher ki's than paraoxon. The higher association constant (KA) of chlorpyrifos-oxon than paraoxon in both species and the lack of significant differences in the phosphorylation constants (kp) suggest that association of the inhibitor with AChE is the principal factor in the different potencies between these two inhibitors. In catfish, the ki of chlorpyrifos-oxon was 22-fold greater than that of paraoxon, while in rats it was 9-fold greater, suggesting that target site sensitivity is an important factor in the higher toxicity of chlorpyrifos to catfish but not in the higher toxicity of parathion to rats. No spontaneous reactivation of phosphorylated catfish AChE occurred and there were no differences in the first oder aging constants (ka) between compounds. For phosphorylated rat AChE, there were no differences in the first order reactivation constants (kr) but the ka for chlorpyrifos-oxon was significantly greater than that for paraoxon. This difference suggests that the steric positioning of the diethyl phosphate in the esteratic site is not the same between the two compounds, leading to differences in aging. 相似文献
69.
The biological consequences of O6-methylguanine (m6G) in DNA are well recognized. When template m6G is encountered by DNA polymerases, replication is hindered and trans-lesion replication results in the preferential incorporation of dTMP opposite template m6G. Thus, unrepaired m6G in DNA is both cytotoxic and mutagenic. Yet, cell lines tolerant to m6G in DNA have been isolated, which indicates that some cellular DNA polymerases may replicate m6G-containing DNA with reasonable efficiency. Previous reports suggested that mammalian pol beta could not replicate m6G-containing DNA, but we find that pol beta can catalyze trans-lesion replication; however, the lesion must reside in the optimal context for pol beta activity, single- or short nucleotide gapped substrates. Primed single-stranded DNA templates, with or without template m6G, were poor substrates for pol beta as reported in earlier studies. In contrast, trans-lesion replication by bacteriophage T4 DNA polymerase was observed for primed single-stranded DNA templates. Replication of m6G-containing DNA by T4 DNA polymerase required the gp45 accessory protein that clamps the polymerase to the DNA template. The rate-limiting step in replicating m6G-containing DNAs by both DNA polymerases tested was incorporation of dTMP across from the lesion. 相似文献
70.
RL Simpson 《Canadian Metallurgical Quarterly》1997,28(7):17-18
Nurses now have a central place to check standards and evaluate systems. The Nursing Information and Data Set Evaluation Center develops, disseminates and evaluates nursing practice sets used by vendors. This center, established by the American Nurses Association, ensures that interventions and outcomes related to nursing diagnosis are appropriate and accurate. 相似文献