Plateaus during the rise of contraceptive prevalence.
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Africa↗
Biomedical subjects
John Ross
Publications and source records attributed to John Ross.
Spontaneous dissection of the left main coronary artery.
Spontaneous coronary artery dissection remains a rare but important cause of acute coronary syndromes. Presentation depends on the extent of the dissection, the vessels involved and the rate of its development, and can encompass the entire spectrum of coronary syndromes, with some patients being asymptomatic and others presenting with angina, non-ST segment elevation myocardial infarction, ST-elevation myocardial infarction and sudden cardiac death. The authors describe a 33-year-old pregnant woman who presented with a non-ST segment elevation myocardial infarction secondary to a spontaneous dissection of the left main coronary artery.
Adult↗
Intracoronary myocardial contrast echocardiography in a patient with drug refractory hypertrophic obstructive cardiomyopathy revealing extensive myocardium at risk for infarction with alcohol septal ablation.
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Cardiac Pacing, Artificial↗
Saccades actively maintain perceptual continuity.
People make saccades--rapid eye movements to a new fixation--approximately three times per second. This would seemingly disrupt perceptual continuity, yet our brains construct a coherent, stable view of the world from these successive fixations. There is conflicting evidence regarding the effects of saccades on perceptual continuity: some studies report that they are disruptive, with little information carryover between saccades; others report that carryover is substantial. Here we show that saccades actively contribute to perceptual continuity in humans in two different ways. When bistable stimuli are presented intermittently, saccades executed during the blank interval shorten the duration of states of ambiguous figures, indicating that saccades can erase immediately past perceptual states. On the other hand, they prolong the McCollough effect, indicating that saccades strengthen learned contingencies. Our results indicate that saccades help, rather than hinder, perceptual continuity.
Adult↗
Sarcoplasmic reticulum calcium defect in Ras-induced hypertrophic cardiomyopathy heart.
The small G protein Ras-mediated signaling pathway has been implicated in the development of hypertrophy and diastolic dysfunction in the heart. Earlier cellular studies have suggested that the Ras pathway is responsible for reduced L-type calcium channel current and sarcoplasmic reticulum (SR) calcium uptake associated with sarcomere disorganization in neonatal cardiomyocytes. In the present study, we investigated the in vivo effects of Ras activation on cellular calcium handling and sarcomere organization in adult ventricular myocytes using a newly established transgenic mouse model with targeted expression of the H-Ras-v12 mutant. The transgenic hearts expressing activated Ras developed significant hypertrophy and postnatal lethal heart failure. In adult ventricular myocytes isolated from the transgenic hearts, the calcium transient was significantly depressed but membrane L-type calcium current was unchanged compared with control littermates. The expressions of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA)2a and phospholamban (PLB) were significantly reduced at mRNA levels. The amount of SERCA2a protein was also modestly reduced. However, the expression of PLB protein and gross sarcomere organization remained unchanged in the hypertrophic Ras hearts, whereas Ser(16) phosphorylation of PLB was dramatically inhibited in the Ras transgenic hearts compared with controls. Hypophosphorylation of PLB was also associated with a significant induction of protein phosphatase 1 expression. Therefore, our results from this in vivo model system suggest that Ras-induced contractile defects do not involve decreased L-type calcium channel activities or disruption of sarcomere structure. Rather, suppressed SR calcium uptake due to reduced SERCA2a expression and hypophosphorylation of PLB due to changes in protein phosphatase expression may play important roles in the diastolic dysfunction of Ras-mediated hypertrophic cardiomyopathy.
Animals↗
Neural correlates of implied motion.
Current views of the visual system assume that the primate brain analyses form and motion along largely independent pathways; they provide no insight into why form is sometimes interpreted as motion. In a series of psychophysical and electrophysiological experiments in humans and macaques, here we show that some form information is processed in the prototypical motion areas of the superior temporal sulcus (STS). First, we show that STS cells respond to dynamic Glass patterns, which contain no coherent motion but suggest a path of motion. Second, we show that when motion signals conflict with form signals suggesting a different path of motion, both humans and monkeys perceive motion in a compromised direction. This compromise also has a correlate in the responses of STS cells, which alter their direction preferences in the presence of conflicting implied motion information. We conclude that cells in the prototypical motion areas in the dorsal visual cortex process form that implies motion. Estimating motion by combining motion cues with form cues may be a strategy to deal with the complexities of motion perception in our natural environment.
Animals↗
Advantages of external periodic events to the evolution of biochemical oscillatory reactions.
We compare, by calculations on a simple model of glycolysis, the evolutionary development of oscillatory reaction mechanisms in the presence and absence of external periodic events, such as an oscillatory or constant influx of glucose in an open reaction system. The chosen model has autonomous oscillations for given choices of the parameters of the feedback loops responsible for the oscillations, and for a given range of the total adenylate pool concentration. We change first one, then two of the parameters, so that there are no autonomous oscillations, and then vary these parameters with a genetic algorithm method in which the parameters are represented by binary strings that evolve by selection, crossover, and mutations; the optimization goal is the attainment of a high ATP/ADP concentration ratio in the system. This goal is taken to provide evolutionary advantages and is shown to be achieved more quickly in the presence of external periodic events, rather than constant influx of glucose. The results suggest the possibility of the enhanced evolutionary development of oscillatory biological reactions at shores where waves impinge on rocks and bring nutrients periodically. Measurements have shown that animals and plants grow more rapidly in the presence of such wave action than in its absence.
Adenosine Diphosphate↗
The deltaC isoform of CaMKII is activated in cardiac hypertrophy and induces dilated cardiomyopathy and heart failure.
Recent studies have demonstrated that transgenic (TG) expression of either Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) or CaMKIIdeltaB, both of which localize to the nucleus, induces cardiac hypertrophy. However, CaMKIV is not present in heart, and cardiomyocytes express not only the nuclear CaMKIIdeltaB but also a cytoplasmic isoform, CaMKIIdeltaC. In the present study, we demonstrate that expression of the deltaC isoform of CaMKII is selectively increased and its phosphorylation elevated as early as 2 days and continuously for up to 7 days after pressure overload. To determine whether enhanced activity of this cytoplasmic deltaC isoform of CaMKII can lead to phosphorylation of Ca2+ regulatory proteins and induce hypertrophy, we generated TG mice that expressed the deltaC isoform of CaMKII. Immunocytochemical staining demonstrated that the expressed transgene is confined to the cytoplasm of cardiomyocytes isolated from these mice. These mice develop a dilated cardiomyopathy with up to a 65% decrease in fractional shortening and die prematurely. Isolated myocytes are enlarged and exhibit reduced contractility and altered Ca2+ handling. Phosphorylation of the ryanodine receptor (RyR) at a CaMKII site is increased even before development of heart failure, and CaMKII is found associated with the RyR in immunoprecipitates from the CaMKII TG mice. Phosphorylation of phospholamban is also increased specifically at the CaMKII but not at the PKA phosphorylation site. These findings are the first to demonstrate that CaMKIIdeltaC can mediate phosphorylation of Ca2+ regulatory proteins in vivo and provide evidence for the involvement of CaMKIIdeltaC activation in the pathogenesis of dilated cardiomyopathy and heart failure.
Animals↗
Experimental test of a method for determining causal connectivities of species in reactions.
Theoretical analysis has shown the possibility of determining causal connectivities of reacting species and the reaction mechanism in complex chemical and biochemical reaction systems by applying pulse changes of concentrations of one or more species, of arbitrary magnitude, and measuring the temporal response of as many species as possible. This method, limited to measured and pulsed species, is given here an experimental test on a part of glycolysis including the sequence of reactions from glucose to fructose 1,6-biphosphate, followed by the bifurcation of that sequence into two branches, one ending in glycerol 3-phosphate, the other in glyceraldehyde 3-phosphate. Pulses of concentrations of one species at a time are applied to the open system in a non-equilibrium stationary state, and the temporal responses in concentrations of six metabolites are measured by capillary zone electrophoresis. From the results of these measurements and the use of the theory for their interpretation, we establish the causal connectivities of the metabolites and thus the reaction mechanism, including the bifurcation of one chain of reactions into two. In this test case of the pulse method, no prior knowledge was assumed of the biochemistry of this system. We conclude that the pulse method is relatively simple and effective in determining reaction mechanisms in complex systems, including reactants, products, intermediates, and catalysts and their effectors. The method is likely to be useful for substantially more complex systems.
Electrophoresis, Capillary↗
Di-alkyl phosphate biomonitoring data: assessing cumulative exposure to organophosphate pesticides.
The 1996 Food Quality Protection Act (FQPA) requires the evaluation of both aggregate and cumulative health risks from pesticides (FFDCA 408(b)(2)(D)(v) and (vi).) Organophosphate (OP) pesticides are the first class of chemicals to undergo FQPA mandated aggregate and cumulative assessments. In this report, summary data on biomonitoring for urinary levels of six alkyl phosphate (AP) metabolites of OPs, as reported in the initial, March 2001, U.S. Centers for Disease Control and Prevention's (CDC) "National Report on Human Exposure to Environmental Chemicals," are compared to EPA modeled estimates of OP exposure reported in Registration Eligibility Decision documents (REDs), Interim REDs and to currently reported cumulative exposure estimates in the EPA's Cumulative Risk Assessment of the Organophosphate Pesticides. This comparison indicates that EPA's aggregate exposure estimates (dietary, drinking water, and non-dietary residential exposures) for many individual OPs were greater than the cumulative estimate for all OPs combined based on the CDC AP biomonitoring data. The results also suggest that EPA's screening level assessments of OPs, while being qualitative indicators of the relative importance of various exposure sources, are not good quantitative indicators of actual exposures. However, the mean biomonitoring estimate of cumulative OP exposure appears to exceed the EPA's subsequent preliminary estimate of cumulative OP exposure by as much as the REDs appear to overestimate the biomonitoring results. While the conservatism, tendency to overestimate exposure, in the individual REDs is readily acknowledged, the conservatism and limitations of applying currently available CDC AP biomonitoring data to evaluate human exposure to OPs are not as readily apparent. We postulate that oral absorption of non-anti cholinergic, pre-hydrolyzed OPs, sources of APs other than pesticides, and the conservative result of summing exposure from each AP at the geometric mean contribute to non-quantified overestimates of absorbed dosage from the CDC biomonitoring data reported in March 2001. CDC AP biomonitoring data may serve a useful purpose in providing an upper bound estimate of absorbed dosage for "ground truthing" aggregate exposure estimated from first tier models used in REDs, but at best may provide only a credible "target" for the complex cumulative exposure assessment models currently under development. The reliability of quantitative estimates of OP exposure levels will improve as cumulative risk exposure models are validated over time and under use conditions prevalent at the time the AP biomonitoring samples are collected. Analyses contained herein should be revisited and compared to the CDC Second National Report on Human Exposure to Environmental Chemicals ( http://www.cdc.gov/exposurereport), released to the public on January 31, 2003, and the final EPA OP Cumulative Risk Assessment.
Environmental Exposure↗
New approaches to the deduction of complex reaction mechanisms.
The formulation of a macroscopic reaction mechanism, the sequence of elementary reaction steps by which reactants are turned into products, is difficult. We review several new methods of determining the causal connectivity of chemical species, the reaction pathway (the sequence of chemical species), and the reaction mechanisms of complex reaction systems from prescribed measurements and theories.
Algorithms↗
Calcium and heart failure: the cycle game.
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Animals↗
Visual discrimination of number without counting.
Observers in this study judged which of two fields contained the greater number of spots. Spots had difference-of-Gaussian luminance profiles and could differ in contrast polarity or were of uniform luminance and could differ in size. Weber fractions for all observers except one varied little except when spots varied in size. It is suggested that the results of this and previous studies might be explained by the existence of neurons tuned for number.
Discrimination, Psychological↗
Mach bands change asymmetrically during solar eclipses.
Observations made during two partial eclipses of the Sun show that the Mach bands on shadows cast by the Sun disappear and reappear asymmetrically as an eclipse progresses. These changes can be explained as due to changes in the shape of the penumbras of shadows as the visible portion of the Sun forms crescents of different orientation.
Humans↗
Differential role of PTK and ERK MAPK in superoxide impairment of K(ATP) and K(Ca) channel cerebrovasodilation.
Previously, superoxide (O2 -) has been observed to impair pial artery dilation (PAD) to activators of the ATP-sensitive (KATP) and calcium-sensitive (KCa) K+ channels. This study tested the hypothesis that activation of protein tyrosine kinase (PTK) and the ERK isoform of MAPK by O2 - contribute to impairment of KATP and KCa channel PAD. Exposure of the cerebral cortex to a xanthine oxidase O2 --generating system (OX) blunted PAD to cromakalim, a KATP agonist, but preadministration of genistein, a PTK antagonist, or U-0126, an ERK MAPK inhibitor, almost completely prevented such impairment (11 +/- 1 and 22 +/- 1 vs. 3 +/- 1 and 7 +/- 1 vs. 10 +/- 1 and 16 +/- 2% for cromakalim with 10-8 and 10-6 M PAD during control, OX, and OX + genistein conditions). In contrast, neither genistein nor U-0126 robustly protected PAD to NS-1619, a KCa agonist, after OX exposure (11 +/- 1 and 18 +/- 2 vs. 1 +/- 1 and 2 +/- 1 vs. 4 +/- 1 and 6 +/- 1% for 10-8 and 10-6 M NS-1619 during control, OX, and OX + genistein conditions). These data show that PTK and ERK MAPK activation contribute to O2 --induced KATP and KCa channel PAD impairment and suggest a differential greater role for PTK and ERK MAPK in KATP vs. KCa channel PAD impairment.
Adenosine Triphosphate↗
Septal ethanol ablation for hypertrophic obstructive cardiomyopathy: early and intermediate results of a Canadian referral centre.
BACKGROUND: Septal ethanol ablation (SEA) is a relatively new interventional nonsurgical treatment for patients with hypertrophic obstructive cardiomyopathy (HOCM). This procedure involves targeted infarction of the basal interventricular septum to reduce left ventricular outflow tract (LVOT) obstruction. OBJECTIVES: To describe the experience with this technique in a large tertiary care centre. METHODS AND RESULTS: Since 1998, 40 HOCM patients with disabling symptoms refractory to medical treatment have undergone SEA. Procedural success was 88% (35 of 40 patients). The LVOT gradient decreased from 86+/-38 mmHg to 16+/-16 mmHg. There were two major complications: one patient died of respiratory failure at 30 days following SEA, and one patient developed a major coronary dissection during the procedure and required emergency myectomy and coronary bypass surgery. There were two late failures (6% of initially successful cases). In both patients, the LVOT gradient and symptoms reappeared some months after the procedure and further interventions were required. In the remaining patients, the gradient continued to decrease to one year; 86% were asymptomatic or have mild symptoms compared with 94% with severe symptoms before SEA. Septal thickness decreased from 20.8+/-2.9 mm to 13.2+/-3.3 mm (P<0.001) at the site of the targeted septal infarct. CONCLUSION: SEA is a feasible option for suitable patients with HOCM.
Adolescent↗
Systematic derivation of reaction-diffusion equations with distributed delays and relations to fractional reaction-diffusion equations and hyperbolic transport equations: application to the theory of Neolithic transition.
We introduce a general method for the systematic derivation of nonlinear reaction-diffusion equations with distributed delays. We study the interactions among different types of moving individuals (atoms, molecules, quasiparticles, biological organisms, etc). The motion of each species is described by the continuous time random walk theory, analyzed in the literature for transport problems, whereas the interactions among the species are described by a set of transformation rates, which are nonlinear functions of the local concentrations of the different types of individuals. We use the time interval between two jumps (the transition time) as an additional state variable and obtain a set of evolution equations, which are local in time. In order to make a connection with the transport models used in the literature, we make transformations which eliminate the transition time and derive a set of nonlocal equations which are nonlinear generalizations of the so-called generalized master equations. The method leads under different specified conditions to various types of nonlocal transport equations including a nonlinear generalization of fractional diffusion equations, hyperbolic reaction-diffusion equations, and delay-differential reaction-diffusion equations. Thus in the analysis of a given problem we can fit to the data the type of reaction-diffusion equation and the corresponding physical and kinetic parameters. The method is illustrated, as a test case, by the study of the neolithic transition. We introduce a set of assumptions which makes it possible to describe the transition from hunting and gathering to agriculture economics by a differential delay reaction-diffusion equation for the population density. We derive a delay evolution equation for the rate of advance of agriculture, which illustrates an application of our analysis.
Biophysical Phenomena↗