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991.
van den Hurk MJ Cruijsen PM Schoeber JP Scheenen WJ Roubos EW Jenks BG 《General and comparative endocrinology》2008,157(2):156-164
The extracellular calcium-sensing receptor (CaR) is expressed in various types of endocrine pituitary cell, but the intracellular mechanism this G protein-coupled receptor uses in these cells is not known. In the present study we investigated possible intracellular signal transduction pathway(s) utilized by the CaR of the endocrine melanotrope cells in the intermediate pituitary lobe of the South African-clawed toad Xenopus laevis. For this purpose, the effects of various pharmacological agents on CaR-evoked secretion of radiolabeled secretory peptides from cultured melanotrope cells were assessed. CaR-evoked secretion, induced by the potent CaR agonist l-phenylalanine (l-Phe), could not be inhibited by cholera toxin, nor by NPC-15437 and PMA, indicating that neither Gs/PKA nor Gq/PKC pathways are involved. However, pertussis toxin (Gi/o protein inhibitor), genistein (inhibitor of PTKs), wortmannin/LY-294002 (PI3-K inhibitor) and U-0126 (inhibitor of extracellular signal-regulated kinase, ERK) all substantially inhibited CaR-evoked secretion, indicating that the Xenopus melanotrope cell possesses a PI3-K/MAPK system that plays some role in CaR-signaling. Since no direct effect of l-Phe on ERK phosphorylation could be shown it is concluded that CaR must act primarily through another, still unknown, signaling pathway in Xenopus melanotropes. Our results indicate that the PI3-K/MAPK system has a facilitating effect on CaR-induced secretion, possibly by sensitizing the CaR. 相似文献
992.
Stephanie M Hamilton Amy E Bryant Karen C Carroll Vivian Lockary Yongsheng Ma Eric McIndoo Loren G Miller Francoise Perdreau-Remington John Pullman George F Risi Daniel B Salmi Dennis L Stevens 《Clinical infectious diseases》2007,45(12):1550-1558
BACKGROUND: Community-acquired methicillin-resistant Staphylococcus aureus strains have recently been associated with severe necrotizing infections. Greater than 75% of these strains carry the genes for Panton-Valentine leukocidin (PVL), suggesting that this toxin may mediate these severe infections. However, to date, studies have not provided evidence of toxin production. METHODS: Twenty-nine community-acquired methicillin-resistant Staphylococcus aureus and 2 community-acquired methicillin-susceptible S. aureus strains were collected from patients with infections of varying severity. Strains were analyzed for the presence of lukF-PV and SCCmecA type. PVL production in lukF-PV gene-positive strains was measured by ELISA, and the amount produced was analyzed relative to severity of infection. RESULTS: Only 2 of the 31 strains tested, 1 methicillin-resistant Staphylococcus aureus abscess isolate and 1 nasal carriage methicillin-susceptible S. aureus isolate, were lukF-PV negative. All methicillin-resistant Staphylococcus aureus strains were SCCmec type IV. PVL was produced by all strains harboring lukF-PV, although a marked strain-to-strain variation was observed. Twenty-six (90%) of 29 strains produced 50-350 ng/mL of PVL; the remaining strains produced PVL in excess of 500 ng/mL. The quantity of PVL produced in vitro did not correlate with severity of infection. CONCLUSIONS: Although PVL likely plays an important role in the pathogenesis of these infections, its mere presence is not solely responsible for the increased severity. Factors that up-regulate toxin synthesis in vivo could contribute to more-severe disease and worse outcomes in patients with community-acquired methicillin-resistant Staphylococcus aureus infection. 相似文献
993.
Bax JJ Poldermans D Elhendy A Boersma E van der Wall EE 《Current cardiology reports》2005,7(2):124-129
The assessment of myocardial viability has become important in the diagnostic and prognostic work up of patients with ischemic
cardiomyopathy. Patients with viable myocardium may benefit from revascularization in terms of improvement of function, symptoms,
and prognosis. In contrast, patients without viable myocardium do not benefit and should be treated conservatively. Various
nuclear imaging techniques are available. 相似文献
994.
McClung CA Sidiropoulou K Vitaterna M Takahashi JS White FJ Cooper DC Nestler EJ 《Proceedings of the National Academy of Sciences of the United States of America》2005,102(26):9377-9381
Although there are clear interactions between circadian rhythms and drug addiction, mechanisms for such interactions remain unknown. Here we establish a role for the Clock gene in regulating the brain's reward circuit. Mice lacking a functional Clock gene display an increase in cocaine reward and in the excitability of dopamine neurons in the midbrain ventral tegmental area, a key brain reward region. These phenotypes are associated with increased expression and phosphorylation of tyrosine hydroxylase (the rate-limiting enzyme in dopamine synthesis), as well as changes in several genes known to regulate dopamine activity in the ventral tegmental area. These findings demonstrate the involvement of a circadian-associated gene, Clock, in regulating dopamine function and cocaine reward. 相似文献
995.
A successful pilot study of a videoconferenced multidisciplinary genitourinary tumor board involving 21 physicians over six geographic sites for a 6-month period is reported. The majority of cases presented at the tumor board were of prostate or bladder origin. Specific recommendations around management, patient referral or clinical trial eligibility were made in the majority of cases presented. Physician satisfaction with the rounds was high and participation beyond the pilot has continued. Scheduling in order to provide maximum access/participation has been the main logistical challenge with the rounds. 相似文献
996.
Ole Dyg Pedersen Peter S?ndergaard Tonny Nielsen S?ren Junge Nielsen Eric Steen Nielsen Niels Falstie-Jensen Ingolf Nielsen Lars K?ber Hans Burchardt Marie Seibaek Christian Torp-Pedersen 《European heart journal》2006,27(23):2866-2870
AIMS: Atrial fibrillation (AF) is a risk factor for death in patients with a myocardial infarction, but highly variable results are reported in patients with heart failure. We studied the prognostic impact of AF in heart failure patients with and without ischaemic heart disease. METHODS AND RESULTS: During a period of 2 years, 3587 patients admitted to hospital because of heart failure were included in this study. All patients were examined by echocardiography and the presence of AF was recorded. Follow-up was available for 8 years. Twenty four percent of those discharged alive from hospital had AF. After 4 and 8 years of follow-up, mortality was higher in patients with AF than in patients without, 56 vs. 52% and 77 vs. 73%, respectively. Cox multivariable regression analysis showed a small but significant importance of AF for long-term mortality [hazard ratio (HR) 1.12, 95% confidence limits (CI), 1.02-1.23, P=0.018]. There was a significant interaction between the importance of AF and the presence of ischaemic heart disease (P=0.034). In patients with AF at the time of discharge and ischaemic heart disease, HR was 1.25 (95% CI: 1.09-1.42) and P<0.001; in patients with AF at discharge and without ischaemic heart disease, HR was 1.01 (95% CI: 0.88-1.16) and P=0.88. CONCLUSION: AF is associated with increased risk of death only in patients with ischaemic heart disease. This finding may explain the variable results of studies of the prognosis associated with AF in heart failure. 相似文献
997.
Melloni C Alexander KP Milford-Beland S Newby LK Szczech LA Pollack CV Kirk JD Christenson RH Harrington RA Gibler WB Ohman EM Peterson ED Roe MT;Crusade Investigators 《Clinical cardiology》2008,31(3):125-129
BACKGROUND: The prognostic value of cardiac troponins (cTn) in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS) and chronic kidney disease (CKD) is debated. HYPOTHESIS: We tested the performance of cTnI and cTnT for risk stratification in patients with CKD and evaluated the prognostic significance of cTnI and cTnT elevations by their magnitude across the range of CKD severity. METHODS: We examined correlations among cTn elevation, CKD, and in-hospital mortality in 31,586 high-risk patients with NSTE ACS included in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines initiative (CRUSADE). Cardiac tropinins I and T levels were categorized as ratios of each site's upper limit of normal (ULN) for myocardial necrosis: normal (cTn ratio < or =1 x ULN), mild (cTn ratio > 1-3 x ULN), and major (cTn ratio > 3 x ULN) elevation. Estimated glomerular filtration rate (eGFR) was calculated using the abbreviated Modification of Diet in Renal Disease equation. Stages of CKD were categorized as normal to mild (eGFR > 60 mL/min), moderate (eGFR 30-60 mL/min), or severe (eGFR < 30 mL/min). RESULTS: Mortality increased more steeply across CKD stages (2.0%-12.9%) than across cTn ratio categories (2.7%-5.4%). In normal or mild CKD, mortality was low regardless of cTn elevations. In moderate CKD, mortality increased incrementally with cTnI (3.3% versus 5.4% versus 7.4%) and cTnT (3.7% versus 5.3% versus 7.3%) elevation. Among severe CKD patients, only major cTn elevations further distinguished risk (cTnI: 10.1% versus 9.7% versus 14.6%; cTnT: 7.0% versus 5.7% versus 14.0%). CONCLUSIONS: In patients with CKD, cTnI and cTnT perform equally in differentiating short-term prognosis following NSTE ACS; however, the prognostic impact of cTn is dependent upon the degree of CKD severity. 相似文献
998.
Methylation of TIMP3 in esophageal squamous cell carcinoma 总被引:1,自引:0,他引:1
Smith E De Young NJ Tian ZQ Caruso M Ruszkiewicz AR Liu JF Jamieson GG Drew PA 《World journal of gastroenterology : WJG》2008,14(2):203-210
AIM: To measure the frequency of DNA methylation of the tissue inhibitor of metalloproteinase 3 (TIMP3) promoter and relate this to any change of gene expression in esophageal squamous cell carcinoma in patients from a region of high incidence in China. METHODS: Cancer cell lines were treated with or without the demethylating reagent 5-aza-2′-deoxycytidine. Methylation of the TIMP3 promoter was assessed in three regions by melt curve analysis and its expression was assessed by real-time RT-PCR. Tumors and proximal resection margins were obtained from 64 patients with esophageal squamous cell carcinoma from a region of high incidence in China. Methylation was assessed by melt curve analysis and expression by immunohistochemistry.
RESULTS: Methylation in one of the three promoter regions assessed correlated with gene silencing in esophageal cell lines. A degree of methylation of TIMP3 was found in only four esophageal squamous cell carcinomas, and partial loss of TIMP3 protein expression in just one.
CONCLUSION: Methylation and loss of expression of TIMP3 occurs infrequently in esophageal squamous cell carcinoma in a region of high incidence in China. 相似文献
RESULTS: Methylation in one of the three promoter regions assessed correlated with gene silencing in esophageal cell lines. A degree of methylation of TIMP3 was found in only four esophageal squamous cell carcinomas, and partial loss of TIMP3 protein expression in just one.
CONCLUSION: Methylation and loss of expression of TIMP3 occurs infrequently in esophageal squamous cell carcinoma in a region of high incidence in China. 相似文献
999.
The effect of vagotomy on gallbladder function was investigated in a clinical and experimental study. In the clinical study both the size of the gallbladder and its capacity to respond to cholecystokinin were evaluated radiologically before and after vagotomy. In studies in the rabbit, both the immediate effect of vagotomy on the gallbladder and the effect of varying doses of cholecystokinin on gallbladder pressure were studied before and after vagotomy. In studies in the cat the long-term effect of vagotomy was studied with respect to the histology of the gallbladder and the composition of bile.The clinical investigation showed that vagotomy was followed by a significant increase in the volume of the gallbladder and that the effect of the cholecystokinin on the gallbladder remained unchanged after vagotomy. In experiments in the rabbit it was found that cholecystokinin in a dose of 1 unit/kg body weight exerted a somewhat lesser effect on gallbladder pressure after vagotomy than before, while after vagotomy a dose, approximately four times greater, resulted in a stronger gallbladder response. Further, the experiments showed that the chemical composition of the bile seemed to be altered after vagotomy, while the gallbladder remained histologically essentially unchanged. 相似文献
1000.
Cheung P Hall B Chugh A Good E Lemola K Han J Tamirisa K Pelosi F Morady F Oral H 《Journal of cardiovascular electrophysiology》2004,15(6):674-678
Introduction: During radiofrequency ablation to encircle or isolate the pulmonary veins (PVs), applications of radiofrequency energy within a PV may result in stenosis. The aim of this study was to determine whether monitoring of real-time impedance facilitates detection of inadvertent catheter movement into a PV.
Methods and Results: In 30 consecutive patients (mean age 53 ± 11 years) who underwent a left atrial ablation procedure, the three-dimensional geometry of the left atrium, the PVs, and their ostia were reconstructed using an electroanatomic mapping system. The PV ostia were identified based on venography, changes in electrogram morphology, and manual and fluoroscopic feedback as the catheter was withdrawn from the PV into the left atrium. Real-time impedance was measured at the ostium, inside the PV at approximately 1 and 3 cm from the ostium, in the left atrial appendage, and at the posterior left atrial wall. There was an impedance gradient from the distal PV (127 ± 30 Ω) to the proximal PV (108 ± 15 Ω) to the ostium (98 ± 11 Ω) in each PV (P < 0.01). There was no significant impedance difference between the ostial and left atrial sites. During applications of radiofrequency energy, movement of the ablation catheter into a PV was accurately detected in 80% of the cases (20) when there was an abrupt increase of ≥4 Ω in real-time impedance.
Conclusion: There is a significant impedance gradient from the distal PV to the left atrium. Continuous monitoring of the real-time impedance facilitates detection of inadvertent catheter movement into a PV during applications of radiofrequency energy. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-5, June 2004) 相似文献
Methods and Results: In 30 consecutive patients (mean age 53 ± 11 years) who underwent a left atrial ablation procedure, the three-dimensional geometry of the left atrium, the PVs, and their ostia were reconstructed using an electroanatomic mapping system. The PV ostia were identified based on venography, changes in electrogram morphology, and manual and fluoroscopic feedback as the catheter was withdrawn from the PV into the left atrium. Real-time impedance was measured at the ostium, inside the PV at approximately 1 and 3 cm from the ostium, in the left atrial appendage, and at the posterior left atrial wall. There was an impedance gradient from the distal PV (127 ± 30 Ω) to the proximal PV (108 ± 15 Ω) to the ostium (98 ± 11 Ω) in each PV (P < 0.01). There was no significant impedance difference between the ostial and left atrial sites. During applications of radiofrequency energy, movement of the ablation catheter into a PV was accurately detected in 80% of the cases (20) when there was an abrupt increase of ≥4 Ω in real-time impedance.
Conclusion: There is a significant impedance gradient from the distal PV to the left atrium. Continuous monitoring of the real-time impedance facilitates detection of inadvertent catheter movement into a PV during applications of radiofrequency energy. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-5, June 2004) 相似文献