Mutational analysis of the candidate internal fusion peptide of the avian leukosis and sarcoma virus subgroup A envelope glycoprotein

The transmembrane subunit (TM) of the avian leukosis and sarcoma virus (ALSV) envelope glycoprotein (Env) contains a stretch of conserved hydrophobic amino acids internal to its amino terminus (residues 21 to 42). By analogy with similar sequences in other viral envelope glycoproteins, this region has been proposed to be a fusion peptide. We investigated the role of this region by changing each of three hydrophobic residues (Ile-21, Val-30, and Ile-39) to glutamatic acid and lysine in the ALSV subgroup A Env. Like wild-type (wt) Env, all six mutant Env proteins were proteolytically processed, oligomerized, and expressed at the cell surface in a form that bound Tva, the ALSV subgroup A receptor. Like wt Env, Ile21Glu, Ile21Lys, Va30Glu, and Val30Lys changed conformation upon binding Tva, as assayed by sensitivity to thermolysin. Ile39Glu and Ile39Lys were cleaved by thermolysin in both the absence and presence of Tva. Although incorporated into virus particles at approximately equal levels, all mutant Envs were compromised in their ability to support infection. The mutants at residues 21 and 30 showed levels of infection 2 to 3 orders of magnitude lower than that of wt Env. The mutants at residue 39 were noninfectious. Furthermore, none of the mutants displayed activity in a cell-cell fusion assay. Our results support the contention that residues 21 to 42 of ALSV subgroup A Env constitute its fusion peptide.     

A technique for identifying the subgroup membership of certain misarticulating children

Cluster analysis was used to identify two homogeneous clusters of 8-9 1/2-year-old children who misarticulated /s/, /r/, or both. The analysis was based on the children's scores on 40 measures of language, reading, auditory processing, and other variables. Discriminant function analysis was then used to identify a subset of five measures and a means of computing classification scores. These measures and the classification scores can be used to identify the cluster membership of new subjects. The use of classification scores for identifying cluster membership was cross-validated against cluster analysis of a second group of children. The two clusters are described in terms of their performance on language and reading measures.     

US medical researchers, the Nuremberg Doctors Trial, and the Nuremberg Code. A review of findings of the Advisory Committee on Human Radiation Experiments

The Advisory Committee on Human Radiation Experiments (ACHRE), established to review allegations of abuses of human subjects in federally sponsored radiation research, was charged with identifying appropriate standards to evaluate the ethics of cold war radiation experiments. One central question for ACHRE was to determine what role, if any, the Nuremberg Code played in the norms and practices of US medical researchers. Based on the evidence from ACHRE's Ethics Oral History Project and extensive archival research, we conclude that the Code, at the time it was promulgated, had little effect on mainstream medical researchers engaged in human subjects research. Although some clinical investigators raised questions about the conduct of research involving human beings, the medical profession did not pursue this issue until the 1960s.     

A Randomized Trial of Methods to Help Clinicians Learn Motivational Interviewing.

The Evaluating Methods for Motivational Enhancement Education trial evaluated methods for learning motivational interviewing (MI). Licensed substance abuse professionals (N = 140) were randomized to 5 training conditions: (a) clinical workshop only; (b) workshop plus practice feedback; (c) workshop plus individual coaching sessions; (d) workshop, feedback, and coaching; or (e) a waiting list control group of self-guided training. Audiotaped practice samples were analyzed at baseline, posttraining, and 4, 8, and 12 months later. Relative to controls, the 4 trained groups showed larger gains in proficiency. Coaching and/or feedback also increased posttraining proficiency. After delayed training, the waiting list group showed modest gains in proficiency. Posttraining proficiency was generally well maintained throughout follow-up. Clinician self-reports of MI skillfulness were unrelated to proficiency levels in observed practice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of cigarette smoking on the angiographic evolution of coronary atherosclerosis. A Canadian Coronary Atherosclerosis Intervention Trial (CCAIT) Substudy. CCAIT Study Group

BACKGROUND: Although smoking increases both the risk of developing coronary disease and the risk of coronary events in patients with known coronary atherosclerosis, the effect of smoking on the evolution of coronary atherosclerosis as assessed by serial angiography is poorly defined. METHODS AND RESULTS: Ninety smokers with coronary atherosclerosis shown on a recent angiogram and with fasting cholesterol levels between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial of cholesterol-lowering therapy, along with 241 nonsmokers and exsmokers. Lovastatin at a mean dose of 36 mg/d lowered total and LDL cholesterol by 21 +/- 11% and 29 +/- 11%, respectively, but these levels changed by < 2% in placebo-treated patients. Coronary arteriography was repeated after 2 years in 72 smokers and their 557 lesions were measured blindly with an automated quantitative system, along with 1752 lesions in 227 nonsmokers. Coronary change score, the per-patient mean of the minimal lumen diameter changes for all qualifying lesions, worsened by 0.16 +/- 0.16 mm in smokers and by 0.07 +/- 0.15 mm in nonsmokers in the placebo group (P < .001). Lovastatin-treated smokers had less worsening (0.07 +/- 0.15 mm) than placebo-treated smokers (P = .024). One or more coronary lesions progressed in 16 of 34 lovastatin-treated smokers and in 28 of 38 placebo-treated smokers (47% versus 74%, P < .001). In the placebo group, new coronary lesions developed in 21 of 38 smokers and in 28 of 115 nonsmokers (55% versus 24%, P < .001); fewer lovastatin-treated smokers developed new lesions (15% versus 55%, P < .001). CONCLUSIONS: Smoking accelerates coronary progression and new lesion formation as assessed by serial quantitative coronary arteriography. Lovastatin slows the progression of coronary atherosclerosis and prevents the development of new coronary lesions in smokers.     

高磷锰矿微波辐射-强磁选联合工艺试验研究

在-0．20mm粒级用微波辐射一强磁选联合选矿工艺和单纯强磁选工艺进行对比试验。结果表明；前者比后者富锰效应更佳，一次锰产率提高20％达70％，给矿锰品位提高3．49％～7．70％达5．31％～36％，锰回收率提高5．08％～11．42％达82％～88％，且有一定降磷作用，给矿降磷率为10．71％～48．00％，但精矿磷含量没有降低，提示微波强磁联合选矿工艺在氧化脱磷方面仍需进一步研究。     

A message from the Texas Bureau of Radiation Control

A new anti-reflux procedure, cardiac oblique invagination, was designed. Having succeeded in animal experiment, we performed this procedure clinically. Sixteen patients with sliding hiatus hernia and one with paraesophageal hernia were operated on. Reflux symptoms disappeared postoperatively. Esophageal manometric study showed that the pressure of HPZ elevated and no abnormal reflux was found by 24-hour esophageal pH monitoring. The effectiveness of this method was assumed that the abdominal segment of the esophagus, His angle, and cardiac rosette were well established and, also, this procedure fitted in with LaPlace's law. The method was simple, transabdominal, easy to teach, and it provided excellent short-term result.     

Coronary vascular response to the cerebral ischemia reflex

Most centrally mediated sympathoexcitatory reflexes produce increases in arterial pressure, heart rate, and peripheral vascular resistance, including coronary vasoconstriction. Cerebral ischemia also causes large increases in arterial pressure and peripheral vasoconstriction but with modest or variable changes in heart rate. To examine the effect of cerebral ischemia on coronary vascular resistance, we produced cerebral ischemia in 14 cats by occluding the right brachiocephalic and left subclavian arteries for 30 seconds. After vagotomy and beta-blockade, a marked increase in arterial pressure (89 +/- 14%) and coronary vascular resistance (52 +/- 7%) was seen. After inhibition of the carotid baroreceptor reflex by surgical denervation and application of topical lidocaine, the increase in arterial pressure to cerebral ischemia was not affected, but the increase in coronary vascular resistance was attenuated (33 +/- 6%; p < 0.05 versus before denervation) to a level expected with autoregulation. To evaluate the possible contribution of the chemoreflex on coronary blood flow during cerebral ischemia, we conducted separate experiments in which nicotine was injected into both carotid arteries. Coronary constriction was not observed. Adrenalectomy and upper extremity ischemia likewise did not alter coronary vascular resistance. We conclude that cerebral ischemia elicits neurally mediated coronary vasoconstriction as a result of baroreceptor hypotension rather than directly. The relative absence of neurogenic coronary constriction and changes in heart rate suggest that sympathoexcitation during cerebral ischemia is directed more toward the peripheral vasculature than the heart.     

审判实践中罚金刑的适用

现行刑法扩大了罚金刑的适用范围,加大了罚金刑的适用力度,这是刑罚轻缓化和经济刑罚观的刑罚趋势.但实践中存在的问题使罚金刑的适用和收缴陷入了困境,罚金刑空判现象十分严重.文中从罚金刑适用与面临困境出发,谈关于罚金刑陷入困境的原因及摆脱困境的对策,同时也是我们追求刑罚轻型化理念的思路.     

Modifiable risk factors for vascular access site complications in the IMPACT II Trial of angioplasty with versus without eptifibatide. Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis

OBJECTIVES: This study was designed to identify potential predictors of vascular access site (VAS) complications in the large-scale Integrilin to Minimize Platelet Aggregation and Coronary Thrombosis (IMPACT) II trial, which studied angioplasty with versus without a new glycoprotein (GP) IIb/IIIa receptor inhibitor (eptifibatide). BACKGROUND: GP IIb/IIIa receptor inhibition during coronary interventions has been associated with excess VAS complications. If other predictors of VAS complications could be identified, they might be manipulated to reduce complications. METHODS: A total of 4,010 patients undergoing percutaneous transluminal coronary revascularization (PTCR) were randomized into one of three bolus/20- to 24-h infusion arms: placebo bolus/placebo infusion; 135-microg/kg body weight eptifibatide bolus/0.5-microg/kg per min eptifibatide infusion; or 135-microg/kg eptifibatide bolus/0.75-microg/kg per min eptifibatide infusion. Heparin during the procedure was weight adjusted and stopped 4 h before sheaths were removed. Logistic regression modeling was used to identify independent predictors of VAS complications. RESULTS: VAS complications were more common in patients treated with eptifibatide (9.9% vs. 5.9% placebo-treated patients, p < 0.001). Multivariate analysis identified eptifibatide therapy (p < 0.0001), advanced age (p = 0.0001), longer time to sheath removal (p = 0.0002), stent placement (with intense post-stent anticoagulation) (p = 0.0004), female gender (p = 0.0006), PTCR within 24 h of thrombolytic therapy (p = 0.002), larger heparin doses during PTCR (p = 0.009), major coronary dissection (p = 0.03) and placement of a venous sheath (p = 0.04) as independent predictors of VAS complications. CONCLUSIONS: VAS complications may be reduced by early sheath removal, by avoiding placement of venous sheaths and by limiting heparin dosing to avoid excessive activated clotting times. Early sheath removal during inhibition of platelet aggregation by eptifibatide is feasible.     

Evolution of the copia retrotransposon in the Drosophila melanogaster species subgroup

We report the results of a phylogenetic survey of the retrotransposon copia in the melanogaster subgroup of the Drosophila genus. The polymerase chain reaction was used to amplify the copia 5' long terminal repeat and the adjacent untranslated leader region from representative melanogaster subgroup species. Restriction and sequence analyses of this region reveal discrete classes of copia size variants within the melanogaster subgroup. Phylogenetic comparisons of copia sequence data indicate that the size variants represent different copia subfamilies which diverged prior to their distribution in the melanogaster subgroup. Our results also suggest that copia elements have been subject to horizontal and vertical transmission during their evolution.     

The Nuremberg Code and the Nuremberg Trial. A reappraisal

The Nuremberg Code includes 10 principles to guide physician-investigators in experiments involving human subjects. These principles, particularly the first principle on "voluntary consent," primarily were based on legal concepts because medical codes of ethics existent at the time of the Nazi atrocities did not address consent and other safeguards for human subjects. The US judges who presided over the proceedings did not intend the Code to apply only to the case before them, to be a response to the atrocities committed by the Nazi physicians, or to be inapplicable to research as it is customarily carried on in medical institutions. Instead, a careful reading of the judgment suggests that they wrote the Code for the practice of human experimentation whenever it is being conducted.     

Randomized comparison of direct thrombin inhibition versus heparin in conjunction with fibrinolytic therapy for acute myocardial infarction: results from the GUSTO-IIb Trial. Global Use of Strategies to Open Occluded Coronary Arteries in Acute Coronary Syndromes (GUSTO-IIb) Investigators

OBJECTIVES: We sought to show that hirudin might interact differently with streptokinase (SK) and tissue-type plasminogen activator (t-PA), which could reduce the incidence of death or reinfarction at 30 days. BACKGROUND: In a large-scale trial of patients with acute coronary syndromes, hirudin provided modest benefit compared with heparin. However, the interaction with thrombolytic agents was not specifically assessed. METHODS: Patients with symptoms of acute myocardial infarction and electrocardiographic ST segment elevation were treated with thrombolytic therapy and randomly assigned to receive hirudin or heparin. RESULTS: A total of 2,274 patients received t-PA, and 1,015 received SK. Baseline characteristics were balanced by antithrombin assignment. Among SK-treated patients, death or reinfarction at 30 days occurred more often in those treated with adjunctive heparin (14.4%) rather than hirudin (8.6%, odds ratio [OR] 1.78, 95% confidence interval [CI] 1.20 to 2.66, p = 0.004). Among t-PA-treated patients, the rates were 10.9% with heparin and 10.3% with hirudin (OR 1.06, 95% CI 0.81 to 1.38, p = 0.68; for treatment heterogeneity: chi-square 4.20, degrees of freedom [df] 1, p = 0.04). After adjustment for baseline differences between thrombolytic groups, the rates were 9.1% for SK with hirudin, 10.3% for t-PA with hirudin, 10.5% for t-PA with heparin and 14.9% for SK with heparin (for treatment heterogeneity: chi-square 4.5, df 1, p = 0.03), suggesting that the beneficial treatment effect of hirudin was limited to the SK-treated patients. CONCLUSIONS: Hirudin interacts favorably with SK but not t-PA, highlighting the importance of thrombin activity after SK therapy and the potential for simulating the effects of a more potent fibrinolytic agent through direct antithrombin therapy.     

Predictors and sequelae of distal embolization during saphenous vein graft intervention from the CAVEAT-II trial. Coronary Angioplasty Versus Excisional Atherectomy Trial

BACKGROUND: The purpose of this study was to identify the predictors and sequelae of distal embolization from a multicenter, randomized trial of saphenous vein graft intervention. The CAVEAT-II trial demonstrated that saphenous vein graft directional coronary atherectomy (DCA) was associated with greater angiographic success and less need for repeat intervention compared with percutaneous transluminal coronary angioplasty (PTCA) but at the cost of more acute complications--notably distal embolization. METHODS AND RESULTS: In CAVEAT-II, 305 patients were randomly assigned to DCA (149 patients) or PTCA (156 patients) for lesions with > 60% diameter stenosis in vein grafts > or = 3 mm in diameter. Distal embolization occurred in 20 patients (13.4%) assigned to DCA and 8 patients (5.1%) assigned to PTCA (P = .011). Independent predictors of distal embolization were use of DCA (71% in distal embolization patients versus 47% in patients without distal embolization, P = .011) and presence of thrombus (39% in distal embolization patients versus 14% in patients without distal embolization, P < .00). In-hospital adverse events were more frequent after distal embolization; 71% versus 20%, odds ratio plus (95% confidence intervals) 9.87 (4.65, 20.94). At 12-month follow-up, adverse event rates were also higher in patients with distal embolization (odds ratio, 3.05 [1.95, 4.76]). CONCLUSIONS: In this first prospective multicenter trial of saphenous vein graft intervention, distal embolization was more common after DCA than PTCA and in lesions containing thrombus. It also was associated with worse in-hospital and 12-month outcomes. The risk and sequelae of distal embolization should be considered when choosing a treatment strategy for vein graft disease.