uPA (urokinase-type plasminogen activator) activates plasminogen with high efficiency when bound to its cellular receptor uPAR, but only after a prolonged lag phase during which generated plasmin activates pro-uPA. How the activity of this proteolytic system might be rapidly initiated is unknown. We have now found that 2 monocytic cell lines display distinct patterns of plasminogen activation. U937 cells, but not THP-1 cells, displayed the expected lag phase, suggesting a constitutive initiation mechanism on the latter. This was shown to be due to the plasmin-independent activation of uPAR-bound pro-uPA by a cell surface-associated protease and to correlate with the expression of matriptase, a type II transmembrane serine protease that was highly expressed in THP-1 cells but undetectable in U937 cells. Kinetic analysis demonstrated that matriptase is a relatively poor activator of pro-uPA in solution, approximately 100-fold less efficient than plasmin (k(cat)/K(m) 1.16 x 10(5) M(-1)s(-1) cf 1.21 x 10(7) M(-1)s(-1)). However, down-regulation of matriptase expression in THP-1 cells by siRNA reduced the activation of cell-associated pro-uPA and the subsequent rapid initiation of plasminogen activation by 76% to 93%. Matriptase was also found to be expressed by peripheral blood monocytes and may therefore be a specific mechanism for the rapid initiation and regulation of plasminogen activation by these cells.
Chewing sugarless gum following elective intestinal resection is associated with improved outcomes. Insufficient data were available to demonstrate a reduced rate of clinical complications or reduced cost. An adequately powered, methodologically rigorous trial of gum chewing is required to confirm if there are any benefits and if these result in differences in clinical outcomes such as infection.
Monte Carlo techniques have been applied to a study of two related quasi-two-dimensional microscopic interaction models which describe the phase behavior of phospholipid bilayers. The two models are Ising-like lattice models in which (a) the acyl chains of the phospholipids interact via anisotropic van der Waals forces and (b) the rotational isomerism of the chains is accounted for by two and ten selected conformational states, respectively. Monte Carlo experiments are performed on both models so as to determine whether the static thermodynamic properties of lipid bilayers are most accurately represented by a simple two state gel–fluid concept or whether a more complicated melting process involving intermediate states takes place. To this purpose, the temperature dependence of several static thermodynamic properties has been calculated for both models. This includes the chain cross-sectional area, the internal and free energies, the coherence length, the lateral compressibility, and the specific heat. Particular care has been devoted to the transition region, since no analytical results are available in this region for either model. The comparison between the Monte Carlo results for the two models demonstrates that, whereas the two-state model has a first-order transition with jumplike behavior in the transition region the ten-state model exhibits a first-order transition associated with a closed hysteresis loop. Next, the Monte Carlo results for cross-sectional areas per lipid chain, coherence lengths and lateral compressibilities are discussed in the context of experimental results for dipalmitoyl phosphatidylcholine (DPPC). A detailed comparison is made with the results of molecular field calculations throughout the paper. Finally, a Monte Carlo analysis of bilayers composed of both DPPC and cholesterol shows that a two-state model does not adequately describe the thermodynamic behavior of lipid–cholesterol mixtures implying that intermediate states have to be introduced to account for the experimental data.
Experiments to determine the kinetics of the thermal decomposition of MgOHCl were performed. It was found that the decomposition of MgOHCl commenced at 649 K, and it directly converted into MgO and HCl without undergoing any intermediate step. Decomposition vs time data showed that the thermal decomposition of MgOHCl was a first-order process with respect to the amount of MgOHCl remaining, and the mass transfer of the product HCl gas away from the interface was likely the ratelimiting step. It was also found that the time required to completely decompose MgOHCl into MgO, more than 20 minutes, at the operating temperatures of electrolytic magnesium production processes, 600 °C Ϯ 50 °C, was significantly longer than the time required, less than 1 minute, to digest the solid magnesium chloride containing feed material into the molten salt electrolyte in these processes. Such delay in the decomposition would mean that any MgOHCl produced during heating and digestion of the feed would not be decomposed by the heat of the electrolyte and thus the persistent MgOHCl would dissolve into the molten salt electrolyte with potentially severe negative consequences on electrolysis cell operation.
The results from CaPS and our meta-analysis are consistent and suggest that, if anything, higher levels of thyroxine in the normal range are associated with increased risk of depression. The effects of thyroid hormone on mood may differ in normal populations and patients with clinical thyroid dysfunction.
On page 356, left hand column, line 2, " 2,3-or 17,18-double bonds" should read '' 17,18-or 2,3-double bonds," In the Communication by R. F. CHILDS and A. W. JOHNSON, Chem. Comm., 1965, 95, the title should read " Rearrangement Reactions of Dimethyl 4-chloromethyl-1,4-dihydro-1,2,6-trimethylpyridJne-3,5-dicarboxylate "
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