实施民用建筑节能标准的经济和环境影响测算研究

建立了实施民用建筑节能标准的经济和环境影响测算模型.与以往的粗略估计不同,该模型将实施民用建筑节能标准与其引起的环境经济结构变化相联系,采用4个指标评价实施民用建筑节能标准的直接经济影响、5个指标评价直接环境影响、3个指标评价完全经济影响.在两种情境假定下,应用模型进行了测算.然后对模型中的主要参数和变量进行了敏感度分...     

A comparative study of the thermal stability of phenylalanyl tRNA synthetase from Escherichia coli MRE-600 and Thermus thermophilus HB 8

The thermal stability of phenylalanyl-tRNA-synthetase (PTS) from E. coli and T.thermophilus HB 8 was studied in solution at various conditions by scanning microcalorimetry. It has been shown that the value of heating rate, concentration of the enzyme and Mg2+ ions in the solution affects the parameters of thermal denaturation of both enzymes. The higher thermal stability of PTS from T. thermophilus was observed as well as the independence of its properties upon broad variations of experimental conditions. The role of thermostability of the enzymes are discussed with respect to the biological properties of E. coli and T.thermophilus.     

Comparison of metoprolol and sotalol in preventing ventricular tachyarrhythmias after the implantation of a cardioverter/defibrillator

The purpose of this prospective study was to evaluate, on an intention-to-treat basis, the efficacy of d,l-sotalol and metoprolol with regards to the recurrence of arrhythmic events after implantable cardioverter defibrillator (ICD) implantation. After ICD implantation, 70 patients were randomly assigned to treatment with either metoprolol (mean dosage 104+/-37 mg/day in 35 patients) or d,l-sotalol (mean dosage 242+/-109 mg/day in 35 patients). During follow up ventricular tachycardia (VT), fast VT, and ventricular fibrillation (VF) episodes were calculated. Metoprolol treatment led to a marked reduction in the recurrence of arrhythmic events. Actuarial rates for absence of VT recurrence at 1 and 2 years were significantly higher in the metoprolol group compared with the d,l-sotalol group (83% and 80% vs 57% and 51%, respectively, p=0.016). The actuarial rates for absence of fast VT or VF were 80% in the metoprolol group compared with 46% in the d,l-sotalol group (p=0.002). During a follow up of 26+/-16 months, there were 3 deaths in the metoprolol group compared with 6 deaths in the d,l-sotalol group. Actuarial rates of overall survival were not significantly different in the 2 groups (91% vs 83%, p=0.287). In this prospective, randomized, controlled study the recurrence rate of ventricular tachyarrhythmias in patients treated with metoprolol was lower than in patients treated by d,l-sotolol.     

A novel, multifuntional c-Cbl binding protein in insulin receptor signaling in 3T3-L1 adipocytes

The protein product of the c-Cbl proto-oncogene is prominently tyrosine phosphorylated in response to insulin in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. After insulin-dependent tyrosine phosphorylation, c-Cbl specifically associates with endogenous c-Crk and Fyn. These results suggest a role for tyrosine-phosphorylated c-Cbl in 3T3-L1 adipocyte activation by insulin. A yeast two-hybrid cDNA library prepared from fully differentiated 3T3-L1 adipocytes was screened with full-length c-Cbl as the target protein in an attempt to identify adipose-specific signaling proteins that interact with c-Cbl and potentially are involved in its tyrosine phosphorylation in 3T3-L1 adipocytes. Here we describe the isolation and the characterization of a novel protein that we termed CAP for c-Cbl-associated protein. CAP contains a unique structure with three adjacent Src homology 3 (SH3) domains in the C terminus and a region showing significant sequence similarity with the peptide hormone sorbin. Both CAP mRNA and proteins are expressed predominately in 3T3-L1 adipocytes and not in 3T3-L1 fibroblasts. CAP associates with c-Cbl in 3T3-L1 adipocytes independently of insulin stimulation in vivo and in vitro in an SH3-domain-mediated manner. Furthermore, we detected the association of CAP with the insulin receptor. Insulin stimulation resulted in the dissociation of CAP from the insulin receptor. Taken together, these data suggest that CAP represents a novel c-Cbl binding protein in 3T3-L1 adipocytes likely to participate in insulin signaling.     

Community respiratory viral infection in adult lung transplant recipients

STUDY OBJECTIVE: To define the epidemiology, clinical manifestations, and long-term complications of respiratory viral infections in adult lung transplant recipients. DESIGN: Retrospective review of the records of 122 adult lung transplant recipients over a 5-year period at one institution. RESULTS: Ten episodes of infection with respiratory syncytial virus, parainfluenza, influenza, or adenovirus were identified. All patients presented with symptoms of respiratory tract infection. Two patients died acutely and four patients subsequently had development of obliterative bronchiolitis (OB). CONCLUSIONS: These data suggest community respiratory viral infections cause significant morbidity and mortality in lung transplant recipients. Further prospective studies are warranted to clarify the relationship between respiratory viral infection and OB and to define the optimal therapy for these viral infections.     

In vitro cleavage of internally quenched fluorogenic human proparathyroid hormone and proparathyroid-related peptide substrates by furin. Generation of a potent inhibitor

The cleavage of parathyroid hormone (PTH) from its precursor proparathyroid hormone (pro-PTH) is accomplished efficiently by the proprotein convertase furin (Hendy, G. N., Bennett, H. P. J., Gibbs, B. F., Lazure, C., Day, R., and Seidah, N. G. (1995) J. Biol. Chem. 270, 9517-9525). We also showed that a synthetic peptide comprising the -6 to +7 sequence of human pro-PTH is appropriately cleaved by purified furin in vitro. The human pro-PTH processing site Lys-Ser-Val-Lys-Lys-Arg differs from the consensus furin site Arg-Xaa-(Lys/Arg)-Arg that is represented by Arg-Arg-Leu-Lys-Arg in the cleavage site of pro-PTH-related peptide (pro-PTHrP). An earlier study demonstrated that an internally quenched fluorogenic substrate bearing an O-aminobenzoyl fluorescent donor at the NH2 terminus and an acceptor 3-nitrotyrosine near the COOH terminus was appropriately cleaved by the convertases furin and PC1 (Jean, F., Basak, A., DiMaio, J., Seidah, N. G., and Lazure, C. (1995) Biochem. J. 307, 689-695). Here, we have synthesized a series of internally quenched fluorogenic substrates based upon the pro-PTH and pro-PTHrP sequences to determine which residues are important for furin cleavage. Purified recombinant furin and PC1 cleaved the human pro-PTH internally quenched substrate at the appropriate site in an identical manner to that observed with the nonfluorescent peptide. Several substitutions in the P6-P3 sequence were well tolerated; however, replacement of the Lys at the P6 position with Gly and replacement of the P3 Lys by an acidic residue led to markedly compromised cleavage by furin. Furin activity was very sensitive to substitution in P' positions. Replacement of Ser at P1' with Gly and Val at P2' with Ala generated substrates that were less well cleaved. Substitution at the P1' position of Val for Ser in conjunction with Ala for Val at P2', as well as a single substitution of Lys for Val at P2', generated specific inhibitors of furin cleavage. The findings of this study open the way to the rational design of inhibitors of furin with therapeutic potential.     

The effect of the putative endogenous imidazoline receptor ligand, clonidine-displacing substance, on insulin secretion from rat and human islets of Langerhans

1. The effects of a rat brain extract containing clonidine-displacing substance (CDS), a putative endogenous imidazoline receptor ligand, on insulin release from rat and human isolated islets of Langerhans were investigated. 2. CDS was able to potentiate the insulin secretory response of rat islets incubated at 6 mM glucose, in a dose-dependent manner. The magnitude of this effect was similar to that in response to the well-characterized imidazoline secretagogue, efaroxan. 3. CDS, like other imidazoline secretagogues, was also able to reverse the inhibitory action of diazoxide on glucose-induced insulin release, in both rat and human islets. 4. These effects of CDS on secretion were reversed by the imidazoline secretagogue antagonists, RX801080 and the newly defined KU14R, providing the first evidence that imidazoline-mediated actions of CDS can be blocked by specific imidazoline antagonists. 5. The effects of CDS on insulin secretion were unaffected when the method of preparation involved centri-filtration through a 3,000 Da cut-off membrane or when the extract was treated with protease. These results confirm that the active principle is of low molecular weight and is not a peptide. 6. Overall, the data suggest that CDS behaves as a potent endogenous insulin secretagogue acting at the islet imidazoline receptor.