Sex-based differences in early mortality of patients undergoing primary angioplasty for first acute myocardial infarction. (17/211)

BACKGROUND: Morbidity and mortality after an acute myocardial infarction (AMI) has been reported to be higher in women than men. However, in some prior reports, women were not treated as aggressively as men, suggesting a treatment bias. We sought to determine whether sex influenced short-term outcomes in a cohort of AMI patients, all of whom underwent primary angioplasty. METHODS AND RESULTS: We conducted a retrospective cohort study of all patients undergoing primary angioplasty for a first AMI in New York State in 1995. A total of 1044 patients, 317 women and 727 men, were identified. Mean age was 59+/-12 years in men and 65+/-12 years in women (P<0.05). Women had a higher prevalence of hypertension (59% versus 44%, P<0.05), diabetes (19% versus 14%, P<0.05), and peripheral vascular or carotid disease (9.5% versus 5.5%, P<0.05) than men. Men were more likely to be treated earlier (within 6 hours) from the time of symptom onset than women (74% versus 63%, P<0.05). Women had a higher incidence of shock or hemodynamic instability than men (25% versus 17%, P<0.05). The unadjusted in-hospital mortality rate was 7.9% in women and 2.3% in men (P<0.05). After multivariate logistic regression analysis, women maintained a 2.3-fold higher risk of in-hospital death compared with their male counterparts (95% confidence interval [CI], 1.2 to 4.6, P=0.016). CONCLUSIONS: After correcting for age and baseline risk differences, women undergoing primary angioplasty for AMI have a significantly higher in-hospital mortality rate than men.  (+info)

Nonequilibrium phenomena in the phase separation of a two-component lipid bilayer. (18/211)

Lipid bilayers composed of two phospholipids with significant acyl-chain mismatch behave as nonideal mixtures. Although many of these systems are well characterized from the equilibrium point of view, studies concerning their nonequilibrium dynamics are still rare. The kinetics of lipid demixing (phase separation) was studied in model membranes (large unilamellar vesicles of 1:1 dilauroylphosphatidylcholine (C(12) acyl chain) and distearoylphosphatidylcholine (C(18) acyl chain)). For this purpose, photophysical techniques (fluorescence intensity, anisotropy, and fluorescence resonance energy transfer) were applied using suitable probes (gel phase probe trans-parinaric acid and fluid phase probe N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-dilauroylphosphatidylethanolamine). The nonequilibrium situation was induced by a sudden thermal quench from a one-fluid phase equilibrium situation (higher temperature) to the gel/fluid coexistence range (lower temperature). We verified that the attainment of equilibrium is a very slow process (occurs in a time scale of hours), leading to large domains at infinite time. The nonequilibrium structure stabilization is due essentially to temporarily rigidified C(12) chains in the interface between gel/fluid domains, which decrease the interfacial tension by acting as surfactants. The relaxation process becomes faster with the increase of the temperature drop. In addition, heterogeneity is already present in the supposed homogeneous fluid mixture at the higher temperature.  (+info)

Biodegradation of 1,2,3- and 1,2,4-trichlorobenzene in soil and in liquid enrichment culture. (19/211)

The biodegradation of radiochemically pure (99%) 1,2,3- and 1,2,4-trichlorobenzene (TCB) in soil was investigated. Experimental difficulties posed by the high volatility and slow biodegradation rate of the TCBs were partially overcome by using a specially designed incubation and trapping apparatus. Evolution of (14)CO(2) from active versus poisoned soil dosed with 50 mug of the individual TCBs per g gave conclusive proof that both isomers are biodegradable. At 20 degrees C, 1,2,4-TCB was mineralized at an approximate rate of 1 nmol/day per 20 g of soil sample, and 1,2,3-TCB was mineralized at one-half to one-third that rate. Mineral fertilizers or cosubstrates failed to increase TCB mineralization rates in soil. Anaerobic conditions had a negative effect on mineralization, and increased temperatures had a positive effect. With increasing 1,2,4-TCB concentrations, (14)CO(2) evolution exhibited saturation kinetics with an apparent K(m) of 55.5 nmol per g of soil. Recovery of total radioactivity was good from soil containing high organic matter concentrations. From low-organic-matter soil, some of the radioactivity was recovered only on combustion, and overall recovery was lower. In soil-inoculated liquid culture, the cosubstrates glucose and benzene caused a slight stimulation of 1,2,4-TCB mineralization. Cochromatography of known standards with the extracts of soil pretreated with [(14)C]TCBs indicated that 3,4,5-trichlorophenol, 2,6-dichlorophenol and, to a lesser degree, 2,3-dichlorophenol were present in soils incubated with 1,2,3-TCB. 2,4-, 2,5-, and 3,4-dichlorophenol were present in soils incubated with 1,2,4-TCB.  (+info)

Crystal structure of the F87W/Y96F/V247L mutant of cytochrome P-450cam with 1,3,5-trichlorobenzene bound and further protein engineering for the oxidation of pentachlorobenzene and hexachlorobenzene. (20/211)

We reported previously that the F87W/Y96F/V247L mutant of cytochrome P-450cam (CYP101) from Pseudomonas putida catalyzed the rapid oxidation of lightly chlorinated benzenes, but pentachlorobenzene oxidation was slow (Jones, J. P., O'Hare, E. J., and Wong, L. L. (2001) Eur. J. Biochem. 268, 1460-1467). In the present work, we determined the crystal structure of this mutant with bound 1,3,5-trichlorobenzene. The substrate was bound to crystallographically independent CYP101 molecules in at least three different orientations, which were distinguished by the angle between the benzene ring and the porphyrin, and one orientation contained an Fe-Cl interaction. In another orientation, the substrate was almost parallel to the heme, with a C-H bond closest to the iron. The enzyme/substrate contacts suggested that the L244A mutation should promote the binding of pentachlorobenzene and hexachlorobenzene by creating space to accommodate the extra chlorines. The F87W/Y96F/L244A/V247L mutant thus designed was found to oxidize pentachlorobenzene at a rate of 82.5 nmol (nmol CYP101)(-1) min(-1), 45 times faster than the F87W/Y96F/V247L parent mutant. The rate of hexachlorobenzene oxidation was increased 200-fold, to 2.0 min(-1). Both substrates are oxidized to pentachlorophenol, which is degraded by micro-organisms. In principle, the F87W/Y96F/L244A/V247L mutant could have applications in the bioremediation of polychlorinated benzenes.  (+info)

Substituent effects on substrate activation and Michaelis-Menten Kinetic parameters in the alpha-chymotrypsin-catalyzed hydrolysis of phenyl acetates. (21/211)

The effects of substituents on the steady state and pre-steady state kinetics in alpha-chymotrypsin [EC 3.4.21.1]-catalyzed hydrolysis were studied using substituted phenyl acetates. In the steady state hydrolysis, substrate activation, which had been observed and studied previously for p-nitrophenyl acetate, was also observed for p-bromo, p-chloro-, and m-methylphenyl acetates. Little activation was observed for p-acetyl-, m-nitro-, p-methyl-, and p-methoxyphenyl acetates. Addition of p-dichlorobenzene increased kcat for all substrates examined and greatly diminished the substrate activation for the activatable substrate(s) to activator binding site(s). The value of kcat decreased in accordance with increase of the sigma-value of substituents. On the other hand, kcat/Km (app) showed an opposite sigma- dependence, as was previously observed. In pre-steady state measurements, little burst was observed for more electron-donating substituents than m-nitro. The sigma dependence of kcat is apparently not consistent with the prediction derived from that of kcat/Km (app) on the basis of the usual two-step mechanism with a common acetyl-enzyme intermediate.  (+info)

Analysis of photodecomposition of gaseous chlorobenzene by KrF excimer laser. (22/211)

Gaseous monochlorobenzene was irradiated with KrF excimer laser (248 nm) under reduced pressure. The photodecomposition was an apparent first order reaction. When the system contained no additive gas, the photolysis was found to give benzene (conversion yield: 49%) in the gas phase and many unidentified products in the solid phase. On the other hand, in the presence of oxygen, carbon dioxide (10%), carbon monoxide (16%), hydrogen chloride (52%) and acetylene (2%) are produced and the peaks shown on the gas chromatogram of the solid phase were effectively suppressed.  (+info)

Cation modulation of bicelle size and magnetic alignment as revealed by solid-state NMR and electron microscopy. (23/211)

The influence of salts (KCl, NaCl, CaCl(2), and MgCl(2)) on bicelles (bilayered micelles) made of dimyristoylphosphatidylcholine (DMPC, molar fraction X = 78%) and dicaproylphosphatidylcholine (DCPC) was investigated by solid-state (31)P- and (2)H NMR as well as by freeze-fracture electron microscopy. Sizes were determined from (2)H- and (31)P NMR on the basis of a model that incorporated a planar bilayer and a (half-torus) curved rim representing the DMPC and DCPC regions of the bicelle, respectively. Good agreement was shown with sizes determined independently from freeze-fracture electron microscopy images. In the presence of K(+) and Na(+), bicelles have diameters of approximately 300 A while in the presence of Ca(2+) and Mg(2+); their diameter increases to approximately 500 A. Bicelle magnetic alignment is considerably improved by the presence of salts. The optimum salt concentration for such an effect ranges from 50 to 200 mM. Bicelles are magnetically aligned for temperatures roughly ranging from 30 degrees C to 40 degrees C with monovalent cations; this range is slightly extended in the presence of divalent salts. In this temperature range, the dynamics of the long-chain hydrocarbon region of the bicelle (leading to a bicelle thickness of 38 A) and of water is about the same independently of cation nature and concentration. However, at higher temperatures, considerable differences in water dynamics are observed between systems with monovalent and divalent cations. In these conditions, the system consists of a mixture of micelles and extended bilayers, which show residual macroscopic alignment in the magnetic field.  (+info)

Effects of the selective inhibition of platelet thromboxane synthesis on the platelet-subendothelium interaction. (24/211)

1. Drugs that inhibit TxA(2) synthesis are used to reduce platelet aggregation. The aim of this study was to compare the effects of a cyclo-oxygenase (COX) inhibitor (acetylsalicylic acid, ASA), a thromboxane synthetase (TxS) inhibitor (dazoxiben) and a dual TxS inhibitor and TxA(2) receptor blocker (DT-TX 30) on platelet aggregation and the platelet-subendothelium interaction in flow conditions. 2. The techniques used in this in vitro study were platelet aggregometry in whole blood, and measurement of platelet thromboxane B(2) and prostaglandin E(2) production and leucocyte production of 6-keto-PGF(1alpha). The platelet-subendothelium interaction was evaluated in rabbit aorta subendothelium preparations exposed to flowing blood at a shear stress of 800 s(-1). Morphometric methods were used to calculate the percentage of subendothelium occupied by platelets. 3. The 50% inhibitory concentration (IC(50)) of DT-TX 30 in whole blood was in the range of 10(-7) micro M (induced with collagen or arachidonic acid) to 10(-5) micro M (induced with thrombin) or 10(-4) (induced with ADP). IC(50) values under all experimental conditions were lower with DT-TX 30 than with ASA. For thromboxane B(2) the IC(50) were: ASA 0.84+/-0.05 micro M, dazoxiben 765+/-54 micro M, DT-TX 30 8.54+/-0.60 micro M. Prostaglandin E(2) was inhibited only by ASA (IC(50) 1.21+/-0.08 micro M). Leucocyte 6-keto-PGF(1alpha) was inhibited by ASA (IC(50) 6.58+/-0.76 micro M) and increased by dazoxiben and DT-TX 30. The greatest reduction in percentage subendothelial surface occupied by platelets after blood perfusion was seen after treatment with DT-TX 30 in the range of concentrations that inhibited collagen-induced platelet aggregation (control group: 31.20+/-3.8%, DT-TX 30 at 0.1 micro M: 10.71+/-0.55%, at 1.0 micro M: 6.53+/-0.44%, at 5.0 micro M; 1.48+/-0.07%). All three drugs reduced thrombus formation, although ASA (unlike dazoxiben or DT-TX 30) increased the percentage surface occupied by adhesions. 4. In conclusion, the effect of specific blockage of TxS together with blockage of membrane receptors for TxA(2) can surpass the effect of ASA in inhibiting the platelet-subendothelium interaction in flow conditions.  (+info)