Renal excretory responses produced by the delta opioid agonist, BW373U86, in conscious rats

This study compared the traditional two-compartment (fat mass or FM; fat free mass or FFM) hydrodensitometric method of body composition measurement, which is based on body density, with three (FM, total body water or TBW, fat free dry mass)- and four (FM, TBW, bone mineral mass or BMM, residual)-compartment models in highly trained men (n = 12), sedentary men (n = 12), highly trained women (n = 12), and sedentary women (n = 12). The means and variances for the relative body fat (%BF) differences between the two- and three-compartment models [2.2 +/- 1.6 (SD) % BF; n = 48] were significantly greater (P 相似文献   

REM sleep behavior disorder and degenerative dementia: an association likely reflecting Lewy body disease

It is commonly believed that MgATP2- is the substrate of F1-ATPases and ATP4- acts as a competitive inhibitor. However, the velocity equation for such competitive inhibition is equivalent to that for a rapid equilibrium ordered binding mechanism in which ATP4- adds first and the binding of Mg2+ is dependent on the formation of the E x ATP4- complex. According to this ordered-binding model, solution formed MgATP2- is not recognized by the ATPase as a direct substrate, and the high-affinity binding of Mg2+ to the E x ATP4- complex is the key reaction towards the formation of the ternary complex. These models (and others) were tested with an F1- ATPase, isolated from Halobacterium saccharovorum, by evaluating the rate of ATP hydrolysis as a function of free [ATP4-] or free [Mg2+]. The rates were asymmetrical with respect to increasing [ATP4-] versus increasing [Mg2+]. For the ordered-binding alternative, a series of apparent dissociation constants were obtained for ATP4-(K(A)aPP), which decreased as [Mg2+] increased. From this family of K(A)aPP the true K(A) was retrieved by extrapolation to [Mg2+] = 0 and was found to be 0.2 mM. The dissociation constants for Mg2+, established from these experiments, were also apparent (K(B)aPP) and dependent on [ATP4-] as well as on the pH. The actual K(B) was established from a series of K(B)aPP by extrapolating to [ATP4-] = infinity and to the absence of competing protons, and was found to be 0.0041 mM. The pKa of the protonable group for Mg2+ binding is 8.2. For the competitive inhibition alternative, rearrangement of the constants and fitting to the velocity equation gave an actual binding constant for MgATP2- (K(EAB)) of 0.0016 mM and for ATP4- (K(EA)) of 0.2 mM. Decision between the two models has far-reaching mechanistic implications. In the competitive inhibition model MgATP2- binds with high affinity, but Mg2+ cannot bind once the E x ATP4- complex is formed, while in the ordered-binding model binding of Mg2+ requires that ATP4- adds first. The steric constraints evident in the diffraction structure of the ATP binding site in the bovine mitochondrial F-ATPase [Abrahams, J. P., Leslie, A. G. W., Lutter, R. & Walker, J. E. (1994) Nature 370, 621-628] tend to favor the ordered-binding model, but the final decision as to which kinetic model is valid has to be from further structural studies. If the ordered-binding model gains more experimental support, a revision of the current concepts of unisite catalysis and negative cooperativity of nucleotide binding will be necessary.     

Treatment of fulminant hepatic failure with intravenous prostaglandin E1

We studied 32 patients with the thickened lesions of the wall of the gallbladder by using dynamic MRI. We tried the differential diagnosis of gallbladder lesions according to the time intensity curve (TIC) and enhanced pattern. TIC of carcinoma was elevated more seeply from plain to arterial phase than the inflammatory diseases. The Inflammatory diseases were keeping three-layer structures of the wall of the gallbladder, but gallbladder carcinoma destroys the wall-structure. We could diagnose as direct liver invasion of the carcinoma clearly. We could exactly diagnose adenomyomatosis in dynamic MRI by small low intensity spots within the wall of the gallbladder. In the patients with gall stones, the wall of the gallbladder were more clearly observed in dynamic MRI compared with US and EUS.     

Monocusp valve and transannular patch reconstruction of the right ventricular outflow tract: an experimental study

Repair of congenital right ventricular outflow tract obstruction often requires reconstruction with a transannular patch to alleviate pulmonary stenosis. Post repair pulmonary insufficiency with right ventricular dilatation and volume overload may result and lead to acute or progressive right heart failure. The use of a monocusp valve has been proposed as a means to prevent this problem. Fresh pericardium is well known to fail clinically, leading to pulmonary insufficiency limiting mid- and long-term results. In a chronic dog model (147 +/- 34 days), three valve types were evaluated: 1) polytetrafluoroethylene (PTFE; n = 9), 2) fresh pericardium (PERI; n = 6), and glutaraldehyde fixed pericardium (GLU; n = 6). Hemodynamics, angiography, and echocardiography were performed at implantation and sacrifice. Gross and microscopic pathology were evaluated. No significant differences were found among the three groups with regard to stenosis as evaluated by echocardiography, measured right ventricular wall thickness, and hemodynamic pressure gradients across the valve. By echocardiography, both PTFE (1 of 9) and GLU (0 of 6) showed less regurgitation than PERI (5 of 6) (p < 0.05). This was confirmed by angiography. PTFE showed less neo-intimal hyperplasia, less thrombus formation, and less calcification than GLU or PERI (p = NS). The PTFE monocusp developed no prohibitive gradients, no early pathologic deterioration, and maintained competence compared with the GLU and PERI groups. Although continued investigation of long-term durability and competence of the PTFE monocusp valve is warranted, both PTFE and GLU values seem to demonstrate less regurgitation than the PERI monocusp valve in an adult dog model of right ventricular outflow tract reconstruction.     

Molecular evolution of cdc2 pseudogenes in spruce (Picea)

The p34cdc2 protein and other cyclin-dependent protein kinases (CDK) are important regulators of eukaryotic cell cycle progression. We have previously cloned a functional cdc2 gene from Picea abies and found it to be part of a family of related sequences, largely consisting of pseudogenes. We now report on the isolation of partial cdc2 pseudogenes from Picea engelmannii and Picea sitchensis, as well as partial functional cdc2 sequences from P. engelmannii, P. sitchensis and Pinus contorta. A high level of conservation between species was detected for these sequences. Phylogenetic analyses of pseudogene and functional cdc2 sequences, as well as the presence of shared insertions or deletions, support the division of most of the cdc2 pseudogenes into two subfamilies. New cdc2 pseudogenes appear to have been formed in Picea at a much higher rate than they have been obliterated by neutral mutations. The pattern of nucleotide changes in the cdc2 pseudogenes, as compared to a presumed ancestral functional cdc2 gene, was similar to that previously found in mammalian pseudogenes, with a strong bias for the transitions C to T and G to A, and the transversions C to A and G to T.     

Establishing mechanisms to conduct multi-institutional research--fatigue in patients with cancer: an exercise intervention

PURPOSES/OBJECTIVES: To describe the process of establishing a multi-institutional interdisciplinary team of oncology researchers and conducting a pilot study of an exercise intervention for fatigue. DATA SOURCES: Project meeting minutes and records, research team members' logs, subjects' research records, the research study proposal, and team members' individual and collective shared experiences. DATA SYNTHESIS: Site investigators established research teams at five academic medical centers. Fifty subjects were enrolled in the study and tested during their cancer treatment. Study methods, including instrumentation, were evaluated carefully and revised. CONCLUSIONS: The multi-institutional network of researchers is an effective and efficient model for testing an intervention to manage fatigue during cancer treatment. IMPLICATIONS FOR NURSING PRACTICE: Exercise is a feasible and potentially beneficial intervention to combat distressing cancer treatment-related fatigue. A pilot study is essential to determine the best methods for conducting a clinical trial and to develop the teams of researchers necessary for such a project.     

Comparison of serum PSMA, PSA levels with results of Cytogen-356 ProstaScint scanning in prostatic cancer patients

The development and evaluation of new drugs often rely on surrogacy. An intermediate outcome becomes a surrogate outcome if it fulfils certain criteria, it should be easier to measure compared with the clinical outcome, a statistical relationship should exist between the clinical outcome and the surrogate outcome, a relation should exist allowing prediction of the degree of clinical effect based on the measured effect on the surrogate outcome. Development and authorization of drugs today often rely on so-called surrogate outcomes. Is this use sound? The validity of such outcomes has been reviewed in different therapeutic areas: hypertension, venous thromboembolism, AIDS, osteoporosis, hepatitis C. Based on this review, a pragmatic strategy is proposed which allows for the validation and proper use of surrogate outcomes.     

Intrauterine tracheal obstruction, a new treatment for congenital diaphragmatic hernia, decreases amniotic fluid sodium and chloride concentrations in the fetal lamb

The chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) interacts with neutrophils, generating signals that induce activation of the superoxide anion/hydrogen peroxide-producing NADPH-oxidase. Low temperature binding of fMLP to its neutrophil surface receptors is associated with a desensitization of the cells with respect to activation of the oxidase. Other stimuli can still activate the oxidase (in fact even induce a primed response), indicating that the observed phenomenon is stimulus specific and could not be accounted for by an effect on the oxidase itself. Furthermore, no desensitization is obtained in the presence of cytochalasin B, suggesting that the cytoskeleton is involved in the process leading to desensitization. Okadaic acid is a toxin produced by dinoflagellates and exerts its effects by an inhibition of cellular phosphatases. To investigate the role of phosphorylation/dephosphorylation events in the desensitization process we used okadaic acid as a scientific tool. We show that neutrophils treated with okadaic acid are primed with respect to the fMLP-induced production of superoxide anion, and that no desensitization is obtained in toxin-treated cells. Because the recovery of ligand-receptor complexes in a Triton X-100-insoluble fraction is very low in the cells treated with okadaic acid, we suggest that protein dephosphorylation is required to obtain binding to the cytoskeleton of occupied fMLP receptors; binding of the occupied receptors to the cell cytoskeleton being the mechanism behind desensitization.     

Crystal structure of a trapped phosphoenzyme during a catalytic reaction

The crystal structure of the fructose-2,6-bisphosphatase domain trapped during the reaction reveal a phosphorylated His 258, and a water molecule immobilized by the product, fructose-6-phosphate. The geometry suggests that the dephosphorylation step requires prior removal of the product for an 'associative in-line' phosphoryl transfer to the catalytic water.