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1.
PJ Commerford 《Cardiovascular journal of Africa》2015,26(4):151-Aug;26(4):151
2.
Accumulation of 64Cu in the 14-d mouse fetus was measured following intravenous injection of the dam with 64CuHis2. Concentration of 64Cu in the placenta increased rapidly over the first 4 h, thereafter remaining constant. Transfer to the fetus was linear over 48 h with little evidence of storage in the liver. Maternal serum levels decreased initially, concurrently with increased 64Cu levels in the maternal liver, but did not subsequently increase. Immediately following injection, as much as 40% of the radioactivity was in the nonalbumin fraction, and approximately 37% of that fraction (18% of total) was greater than 30,000 molecular weight. After 24 h, up to 60% of the 64Cu was still found in the albumin peak. The data suggest that the fetus can obtain its Cu from maternal ceruloplasmin but does not exclude the possibility that transfer occurs from the exchangeable (albumin/amino acid) Cu pool of the maternal plasma. In a second experiment, mice at different stages of gestation were injected with 64Cu and killed 4 h later. Total Cu levels and 64Cu uptake into the maternal tissues or into the placenta did not change with increasing gestation. Both total Cu and 64Cu uptake in the fetus and fetal liver increased to a maximum on d 16. Levels in the liver decreased thereafter to term, whereas levels in the rest of the fetus remained approximately constant. The pattern was similar whether the results were expressed per organ or per gram of fresh weight.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
3.
PACAP is a hypothalamic hypophysiotropic factor that acts upon a number of pituitary cells, including gonadotrophs. In the gonadotroph-derived αT3-1 cell line, PACAP acts via PVR1 receptors to stimulate adenylyl cyclase and phosphoinositidase C. PACAP-stimulated cAMP accumulation is inhibited by protein kinase C-activating phorbol esters in these cells and the current work was undertaken primarily to establish whether it is also subject to homologous regulation. In acute experiments, PACAP27-stimulated cAMP accumulation (intracellular plus extracellular) was measured (in the presence of phosphodiesterase inhibitor) both in intact cells and in cell membranes. The peptide increased cAMP accumulation, but initial rates of PACAP27-stimulated cAMP accumulation were reduced to between 10 and 50% within 10 min of stimulation in both cells and membranes. The initial rate of forskolin-stimulated cAMP accumulation was maintained in membranes but not in intact cells (although the deviation from linearity was less pronounced than with PACAP27). Thus, rapid homologous desensitization to PACAP27 occurs in intact αT3-1 cells, but is not entirely receptor specific. Rapid homologous desensitization of PACAP27-stimulated cAMP accumulation also occurred in the presence of a protein kinase C activating phorbol ester, which inhibited cAMP accumulation without altering the kinetics of the PACAP27 effect. Brief pre-treatment (3 min) with PACAP27 also reduced the ability of PACAP27, but not gonadotrophin-releasing hormone, to cause a spike-type elevation of cytosolic Ca2+ concentration (a consequence of phosphoinositidase C activation). In chronic desensitization studies, pre-treatment for 6 h with PACAP27 caused a dose-dependent (IC50 approximately 10 nM) reduction of PACAP-stimulated cAMP accumulation and down regulated cell surface PVR1 receptors (to approximately 50%). Thus, it appears that PACAP27-stimulated (PVR-1 receptor mediated) adenylyl cyclase undergoes rapid homologous desensitization in αT3-1 cells, which is paralleled by homologous desensitization of PACAP27-stimulated phosphoinositidase C activity and involves mechanisms distinct from those underlying heterologous desensitization by phorbol esters. Chronic desensitization of PACAP-stimulated cAMP accumulation and down-regulation of cell surface PVR-1 receptors also occurs in these cells although the receptor loss may not entirely explain the observed desensitization. 相似文献
4.
Dolores Acevedo-Garcia Lisa M. Bates Theresa L. Osypuk Nancy McArdle 《Social science & medicine (1982)》2010
Global self-rated health (SRH) is increasingly a key indicator in the assessment of immigrant health. However, evidence of the impact on SRH of generational status, duration of residence in the US, and socioeconomic status (SES) among immigrants and their offspring is limited and inconsistent. We overcome limitations in existing research on this topic by using a uniquely large and diverse data source, the March Annual Social and Economic Supplement of the Current Population Survey (CPS; 2003–2007) (n = 637,209). As a result, we are able to disaggregate results by race/ethnicity, account for country of origin, and consider the role of multiple dimensions of SES. We find that overall first-generation immigrants in the US have lower odds of poor/fair SRH compared to the third-generation. This association is particularly strong for blacks and Hispanics but not significant for Asians. Among first-generation Asians and Hispanics, longer duration of residence is positively associated with poor/fair SRH. Finally, socioeconomic gradients in SRH tend to be less pronounced among the first-generation (versus the third) and, within the first-generation, among recent arrivals (versus those with longer durations). Our results highlight the importance of explicitly accounting for multiple immigration-related variables and their interactions with race/ethnicity and SES. Otherwise, studies may misestimate SRH differences by race/ethnicity and socioeconomic status. The continued growth of the US immigrant population and the second-generation underscore the need to examine patterns in immigrant health systematically. 相似文献
5.
Ravindra Patel Joseph J. McArdle Timothy J. Regan 《Alcoholism, clinical and experimental research》1991,15(5):785-789
An increased incidence of sudden death has been reported in chronic alcoholism. To assess electrical vulnerability of the heart, action potential responses, and the role of the sympathetic system, a well-nourished canine model has been studied intact under chloralose anesthesia after 1 year of ethanol consumption at 36% of caloric intake. Two alcoholic groups were compared with controls (Group 1). In Group 2 myocardial vulnerability was assessed after chronic EtOH and superimposed acute administration. In Group 3 basal vulnerability was related to circulating norepinephrine and release of neurohormone from the myocardium. Subsequently the responsiveness to catecholamine infusion was determined. To assess vulnerability an electrode catheter was placed in the right ventricular apex. The basal ventricular fibrillation threshold (VFT) was reduced to 27 +/- 3 ma in Group 2 versus 43 +/- 1.0 in Group 1. Acute infusion of ethanol in Group 2 further reduced the threshold. Group 3 had a reduced basal VFT. Baseline arterial plasma levels of norepinephrine were 8-fold higher and coronary venous levels 13 times higher in the alcoholic group than in Group 1. However, VFT was not responsive to infused epinephrine, compared with Group 1 controls. In vitro study of superfused ventricular tissue from Group 3 revealed that basal action potential amplitude, overshoot, and resting potential were comparable with normals. Basal repolarization time (90%) was 198 +/- 12 msec in Group 3 versus 215 +/- 6 msec in Group 1 (p less than 0.05). After acute EtOH, repolarization time was shortened to 170 +/- 8.6 in Group 1 at 90 mg% ethanol (p less than 0.002), with minimal further change up to 280 mg%.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
6.
Christopher James Caunt Ann R Finch Kathleen R Sedgley Craig A McArdle 《Trends in Endocrinology and Metabolism》2006,17(8):308-313
Many hormones, neurotransmitters and growth factors influence their target cells by activation of mitogen-activated protein kinase cascades. The consequences of such activation reflect not only the magnitude, but also the kinetics and cellular compartmentalization of kinase activity. Gonadotropin-releasing hormone (GnRH) receptors are seven-transmembrane receptors that have undergone a period of rapidly accelerated molecular evolution in which the advent of type I mammalian GnRH receptors has been associated with the loss of the carboxyl-terminal tail, a structure present in all other seven-transmembrane receptors. Here, we review spatiotemporal aspects of extracellular-signal-regulated kinase activation by gonadotropin-releasing hormone receptors, emphasizing how the absence or presence of the carboxyl-terminal tail dictates the receptors' ability to engage and signal via arrestins. 相似文献
7.
1. The amplitude of endplate potentials was increased by concentrations of butanedione monoxime (BDM, 5-20 mM) that typically caused muscle paralysis. 2. Although BDM slowed the decay of spontaneous miniature endplate currents, the effect was insufficient to explain most of the large increase in amplitude of endplate potentials. 3. The quantal content of endplate potentials was increased by BDM in a reversible, concentration-dependent manner. 4. The frequency of miniature endplate potentials was not changed by 10 mM BDM in the presence of normal or raised potassium concentrations, indicating that BDM does not change quantal content by a direct effect on calcium channels or on steady-state intracellular calcium concentration. 5. A change in the time course of the extracellularly recorded nerve terminal action potential caused by BDM was similar to the change produced by 4-aminopyridine (4-AP). 6. The increase in quantal content produced by BDM was only slightly reduced in the presence of 1 mM tetraethylammonium (TEA) but was significantly reduced in the presence of 0.5 to 1 mM 4-AP. 7. It was concluded that BDM blocks a 4-AP-sensitive potassium conductance in motor nerve terminals and, by increasing the duration of the action potential in this way, increases evoked transmitter release. 相似文献
8.
Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease. There is variability of expression in Kennedy syndrome and repeat length even in siblings cannot be taken as a conclusive indicator of severity. CAG repeat length cannot be used to predict the natural history of Kennedy disease. The diagnosis of Kennedy syndrome should be considered in male patients presenting with atypical motor neurone disease. 相似文献
9.
Assessment of the analgesic efficacy of nefopam hydrochloride after upper abdominal surgery: a study using patient controlled analgesia 总被引:3,自引:0,他引:3
T T McLintock G N Kenny J C Howie C S McArdle S Lawrie H Aitken 《The British journal of surgery》1988,75(8):779-781
A randomized, double-blind, placebo-controlled study was performed to assess the analgesic efficacy of intramuscular nefopam hydrochloride after upper abdominal surgery. Patients received either 20 mg nefopam (n = 23) or matching placebo (n = 26), 90 min before surgery, immediately after surgery, and 6, 12 and 18 h after the end of surgery. The 24-h morphine requirements were measured using a patient-controlled analgesia system delivering on-demand intravenous bolus doses of morphine. Pain was assessed using visual analogue scales. Patients receiving nefopam had a mean (+/- s.e.m.) cumulative morphine consumption of 4.1 +/- 0.8 mg in the first hour, compared with 8.5 +/- 0.8 mg in the control group (P less than 0.01). After 24 h the consumptions were 44.1 +/- 7.2 mg and 62.5 +/- 6.9 mg respectively (P less than 0.05). The pain scores in both groups were similar. This study confirms that nefopam hydrochloride has significant analgesic effects and would be a useful supplement to morphine in the management of postoperative pain. 相似文献
10.