Nocturnal recovery of gastric acid secretion with twice-daily dosing of proton pump inhibitors

The Internet is a rapidly developing and useful tool for emergency physicians. A brief history of the development of the Internet and applications to Emergency Medicine are reviewed. A listing of many useful Internet resources is included.     

Heterogeneous fate of perfusion and contraction after anterior wall acute myocardial infarction and effects on left ventricular remodeling

After acute myocardial infarction, patency of infarct vessel and extent of left venticular (LV) dysfunction are major determinants of ventricular remodeling. Spontaneous, delayed reperfusion in the infarct zone occurs in a sizeable number of patients well after the subacute phase. The aim of this study was to determine the relation between the occurrence of this spontaneous, delayed reperfusion and LV remodeling. In 84 patients, resting LV volumes, topography, regional function, and perfusion were quantitatively evaluated by 2-dimensional echocardiography and sestamibi tomography 5 weeks (study 1) and 7 months (study 2) after anterior Q-wave infarction. At study 2, LV end-diastolic volume increased by > 15% in 17 patients (20%, LV remodeling); they had already had at study 1 significantly larger LV volumes, more severe hypoperfusion and wall motion abnormalities, and greater regional dilation than patients with stable LV volumes. Delayed reperfusion occurred in 8 of 17 patients with and in 42 of 67 patients without LV remodeling (47% vs 63%; p=NS). At study 2, LV regional dilation and end-diastolic volumes were stable in patients with, but increased in patients without, spontaneous reperfusion (from 25+/-24% to 29+/-26% at study 2 [p<0.05] and from 65+/-14 to 68+/-18 ml/m2 [p <0.05]). At multivariate analysis, however, regional ventricular dilation at study 1 was the sole predictor of further LV remodeling. Thus, after acute myocardial infarction, spontaneous reperfusion occurring after 5 weeks plays only a minor role in influencing LV remodeling. Benefits from delayed reperfusion seem limited to patients with preserved LV volumes; patients with an enlarged left ventricle 5 weeks after acute infarction are prone to further LV remodeling, irrespective of delayed reperfusion.     

Thy-1 and AvGp50 signal transduction complex in the avian nervous system: c-Fyn and G alpha i protein association and activation of signalling pathways

A unique property of smooth muscle is its ability to maintain force with a very low expenditure of energy. This characteristic is highly expressed in molluscan smooth muscles, such as the anterior byssus retractor muscle (ABRM) of Mytilus edulis, during a contractile state called 'catch'. Catch occurs following the initial activation of the muscle, and is characterized by prolonged force maintenance in the face of a low [Ca2+]i, high instantaneous stiffness, a very slow cross-bridge cycling rate, and low ATP usage. In the intact muscle, rapid relaxation (release of catch) is initiated by serotonin, and mediated by an increase in cAMP and activation of protein kinase A. We sought to determine which proteins undergo a change in phosphorylation on a time-course that corresponds to the release of catch in permeabilized ABRM. Only one protein consistently satisfied this criterion. This protein, having a molecular weight of approximately 600 kDa and a molar concentration about 30 times lower than the myosin heavy chain, showed an increase in phosphorylation during the release of catch. Under the mechanical conditions studied (rest, activation, catch, and release of catch), changes in phosphorylation of all other proteins, including myosin light chains, myosin heavy chain and paramyosin, are minimal compared with the cAMP-induced phosphorylation of the approximately 600 kDa protein. Under these conditions, somewhat less than one mole of phosphate is incorporated per mole of approximately 600 kDa protein. Inhibition of A kinase blocked both the cAMP-induced increase in phosphorylation of the protein and the release of catch. In addition, irreversible thiophosphorylation of the protein prevented the development of catch. In intact muscle, the degree of phosphorylation of the protein increases significantly when catch is released with serotonin. In muscles pre-treated with serotonin, a net dephosphorylation of the protein occurs when the muscle is subsequently put into catch. We conclude that the phosphorylation state of the approximately 600 kDa protein regulates catch.     

Modeling of nucleotide binding domains of ABC transporter proteins based on a F1-ATPase/recA topology: structural model of the nucleotide binding domains of the cystic fibrosis transmembrane conductance regulator (CFTR)

Members of the ABC transporter superfamily contain two nucleotide binding domains. To date, the three dimensional structure of no member of this super-family has been elucidated. To gain structural insight, the known structures of several other nucleotides binding proteins can be used as a framework for modeling these domains. We have modeled both nucleotide binding domains of the protein CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) using the two similar domains of mitochondrial F1-ATPase. The models obtained, provide useful insights into the putative functions of these domains and their possible interaction as well as a rationale for the basis of Cystic Fibrosis causing mutations. First, the two nucleotide binding domains (folds) of CFTR are each predicted to span a 240-250 amino acid sequence rather than the 150-160 amino acid sequence originally proposed. Second, the first nucleotide binding fold, is predicted to catalyze significant rates of ATP hydrolysis as a catalytic base (E504) resides near the y phosphate of ATP. This prediction has been verified experimentally [Ko, Y.H., and Pedersen, P.L. (1995) J. Biol. Chem. 268, 24330-24338], providing support for the model. In contrast, the second nucleotide binding fold is predicted at best to be a weak ATPase as the glutamic acid residue is replaced with a glutamine. Third, F508, which when deleted causes approximately 70% of all cases of cystic fibrosis, is predicted to lie in a cleft near the nucleotide binding pocket. All other disease causing mutations within the two nucleotide binding domains of CFTR either reside near the Walker A and Walker B consensus motifs in the heart of the nucleotide binding pocket, or in the C motif which lies outside but near the nucleotide binding pocket. Finally, the two nucleotide binding domains of CFTR are predicted to interact, and in one of the two predicted orientations, F508 resides near the interface. This is the first report where both nucleotide binding domains of an ABC transporter and their putative domain-domain interactions have been modeled in three dimensions. The methods and the template used in this work can be used to analyze the structures and function of the nucleotide binding domains of all other members of the ABC transporter super-family.     

Nitric oxide modulates the c-Jun N-terminal kinase/stress-activated protein kinase activity through activating c-Jun N-terminal kinase kinase

Nitric oxide is a signaling molecule that has a broad range of physiological functions, including neurotransmission, macrophage activation, and vasodilation. The mechanism by which nitric oxide regulates signal transduction mediating diverse biological activities is not fully understood, however. Here, we demonstrate that nitric oxide induced the stimulation of c-Jun NH2-terminal kinase (JNK)/stress-activated protein kinase (SAPK) in intact cells. Exposure of cultured HEK293 cells to sodium nitroprusside, a nitric oxide releasing agent, resulted in the stimulation of JNK1 activity. The sodium nitroprusside-induced stimulation of JNK1 activity was abolished by treatment of cells with N-acetylcysteine. Nitric oxide production from HEK293 cells ectopically expressing nitric oxide synthases resulted in the stimulation of JNK1 activity, while JNK1 stimulation in nitric oxide synthase-overexpressing cells was abrogated by a nitric oxide synthase inhibitor, NG-nitro-L-arginine. Furthermore, exposure of cells to sodium nitroprusside resulted in the stimulation of JNK kinase (JNKK1/SEK1). Taken together, our data suggest that nitric oxide modulates the JNK activity through activating JNKK1/SEK1.     

Acoustic field interaction with a boiling system under terrestrial gravity and microgravity

Pool boiling experiments from a platinum wire heater in FC-72 liquid were conducted under terrestrial and microgravity conditions, both with and without the presence of a high-intensity acoustic standing wave within the fluid. The purpose of this research was to study the interaction between an acoustic field and a pool boiling system in normal gravity and microgravity. The absence of buoyancy in microgravity complicates the process of boiling. The acoustic force on a vapor bubble generated from a heated wire in a standing wave was shown to be able to play the role of buoyancy in microgravity. The microgravity environment was achieved with 0.6 and 2.1-s drop towers. The sound was transmitted through the fluid medium by means of a half wavelength sonic transducer driven at 10.18 kHz. At high enough acoustic pressure amplitudes cavitation and streaming began playing an important role in vapor bubble dynamics and heat transfer. Several different fixed heat fluxes were chosen for the microgravity experiment and the effects of acoustics on the surface temperature of the heater were recorded and the vapor bubble movement was filmed. Video images of the pool boiling processes and heat transfer data are presented.     

Variables controlling contrast generation in a urinary bladder model

An ultrasound system has been developed to generate microbubbles in vivo for use as ultrasound contrast agent. Possible application include diagnosis of reflux in the urinary tract. In experiments designed to elucidate the contrast microbubble generation process, acoustic bursts (at 1.8 MHz, 125 ms) were propagated through a latex rubber balloon, modeled after a rabbit urinary bladder, containing fluids of various air and carbon dioxide saturations and concentrations of cavitation nuclei (0.198-micron-diam polystyrene particles). The peak rarefactional pressure threshold for contrast microbubble generation, as visualized with a diagnostic ultrasound system, decreased approximately a factor of 2 for increasing particle concentration from 10(8) to 10(10) particles/cc, with the lowest threshold of 5.24 MPa. For samples with gas saturations below 50% and 10(10) particles/cc, the average thresholds were at least twice as high as those of more saturated fluids (with mean threshold for saturated fluids of 6.45 MPa), and samples containing CO2 had considerably lower thresholds than respective under-saturations in air. At a fixed pressure amplitude, echogenicity tended to increase with both increasing particle concentration and gas saturation; this was more favorable for samples containing CO2. Even in a restricted-nuclei environment such as the urinary bladder, generation of vaporous cavitation should be possible; however, subsequently, abundant gas is needed to grow vaporous bubbles to persistent and imageable sizes, to assist in the diagnosis of urinary reflux.     

The role of dispositional and situational factors in cognitive interference

Two studies investigated the cross-temporal stability and cross-situational consistency of cognitive interference. In Study 1, 70 college students reported on the intrusive thoughts they experienced during 2 course examinations and a self-reflective task. In Study 2, 55 college athletes reported on intrusive thoughts following 2 course examinations and 2 regular season football games. Major findings were (a) cognitive interference showed both cross-temporal stability and cross-situational consistency, (b) it was predicted by a measure of dispositional intrusive thinking, (c) the link between cognitive interference and dispositional intrusive thinking was not accounted for by indices of depressive symptomatology and trait anxiety, and (d) the degree of cross-situational consistency of cognitive interference and the content of these intrusive thoughts were influenced by situational factors.