bluuebunny/crossref_metadata_2025 huggingface dataset:
Modification of stretch tolerance in a stooping position
Authors: Læssøe U. , Voigt M.
Published: July 2004

A stooping (slump) position is believed to add tension to the nerve tissue complex. This study was designed to determine whether this position would have an effect on the stretch tolerance in a passive knee extension. Thirteen healthy individuals were tested. The knee extension was stopped by the subjects at “onset of pain”. Joint range of motion and passive resistance to the extension were recorded in four test situations: upright sitting and stooping position, with the ankle joint in either the neutral or maximal dorsi‐flexed position.

A significant decrease in range of motion was seen when shifting from upright to stooping position: Δangle −2.4° (P<0.01). According to this, the passive tissue tension was accepted at significantly lower values in stooping position: Δtorque −1.2 N m (P<0.01). Testing with maximal dorsi‐flexion of the ankle showed more pronounced changes: Δangle −3.4° (P<0.001); Δtorque −2.3 N m (P<0.001), but the effect of foot position was not significant.

Knee joint range of motion was acutely diminished in a stooping position. Thus, stretch tolerance was affected by manipulation of structures, which were not directly mechanically related to this joint. An influence from the nerve tissue complex must be considered to be a factor when describing the mechanisms behind altered stretch tolerance.
Gender, eating behavior, and personality characteristics in physically active students
Authors: Kjelsås Einar , Augestad Liv Berit
Published: July 2004

The aim of this paper was to examine associations between personality traits, eating disorder (ED) behavior, exercise, and gender. The participants (n=1482: 905 women and 577 men) were students from four universities in Norway. The subjects filled out a compound questionnaire including demographics, weekly hours of exercise, type of sport, Karolinska Scales of Personality (KSP), and the Eating Disorder Inventory (EDI). Because of the data collection procedure, it is difficult to provide a clear‐cut response rate in this study. The results showed that the risk ratio for women who scored 40 or higher on the EDI was three times higher compared with men. ED behavior did not seem to be associated with high weekly hours of physical activity in general. There were significant gender differences in personality traits. However, women and men with high scores on the EDI showed no differences on the KSP scales, except on “detachment” and “indirect aggression”. The most important predictors for weekly hours of physical activity were the EDI scales “drive for thinness” and “body dissatisfaction”, and the personality variables “extraversion” and “neuroticism”. The factors that contributed most to the differences between students who scored 40 or higher on the EDI and those who scored below 40 on the EDI were neuroticism, BMI, gender, and age.
Isokinetic performance at diagonal pattern and shoulder mobility in elite overhead athletes
Authors: Baltaci Gul , Tunay Volga Bayrakci
Published: July 2004

The purpose of this study was to measure isokinetically glenohumeral joint movement peak torque and work in professional basketball, volleyball, handball and baseball players and determine whether significant differences exist between the dominant and non‐dominant extremity in athletes and controls. Eighty healthy professional overhead athletes (basketball, volleyball, handball and baseball players) and 20 controls were tested bilaterally on a CYBEX 6000 isokinetic dynamometer at 60° and 180° s−1 for diagonal pattern of the glenohumeral joint. A standardized protocol and testing guidelines were strictly followed. The range of motion of internal rotation (IR) on the dominant side of baseball players was significantly smaller than those on the dominant side of basketball, handball and volleyball players, and controls (P<0.01). Flexion/abduction/external rotation were consistently higher on the dominant arm (8.5%) for peak torque at 60° s−1 in baseball players, and bilateral ratios were lower on the dominant arm (14.8%) for peak torque at 180° s−1 in basketball players. The results of this study are important for the application and interpretation of isokinetic data and flexibility and mobility characteristics on unilaterally dominant overhead athletes. Functional weakness in external rotators, mobility impairments in IR and muscle imbalance have been shown in the dominant arm of these overhead athletes.
Myocardial perfusion after marathon running
Authors: Kalliokoski Kari K. , Laaksonen Marko S. , Luotolahti Matti , Laine Hanna , Takala Teemu O. , Nuutila Pirjo , Knuuti Juhani
Published: July 2004

We investigated the effects of acute prolonged exercise (marathon running) on cardiac function and myocardial perfusion. Cardiac dimensions and function were measured in seven endurance‐trained men using echocardiography before and repeatedly after marathon (42.2 km) running (at 10 min, 150 min, and 20 h). Myocardial perfusion and perfusion resistance were measured using positron emission tomography and 15O‐H2O before and 85–115 min after running. Echocardiographic indices showed only mild and clinically non‐significant changes in cardiac function after running. Rate‐pressure‐corrected basal myocardial perfusion (0.89±0.13 vs. 1.20±0.32 mL min−1 g−1, P=0.04) was increased after running. Also, adenosine‐stimulated perfusion tended to be higher (3.67±0.81 vs. 4.47±0.52 mL min−1 g−1, P=0.12) and perfusion resistance during adenosine stimulation was significantly lower after running (26±6 vs. 18±3 mmHg min g mL−1, P=0.03). Plasma free fatty acid (FFA) concentration was significantly increased after running. These results show that marathon running does not cause marked changes in cardiac function in healthy men. Basal perfusion was increased after exercise, probably reflecting changes in fuel preferences to increased use of FFAs. Strenuous exercise also seems to enhance coronary reactivity, which could thereby serve as a protective mechanism to vascular events after exercise.
Back muscle fatigue during intermittent prone back extension exercise
Authors: Plamondon A. , Trimble K. , Larivière C. , Desjardins P.
Published: July 2004

The purpose of this study was to estimate the level of muscular activation and muscle fatigue of the low back muscles during the performance of an intermittent prone back extension (PBE) exercise. Forty‐one healthy students (24 males and 17 females) lying prone on a bench with the legs fixed performed two maximal voluntary contractions (MVC) in extension, a maximum of 100 repetitions of an intermittent PBE exercise immediately followed by a final MVC in extension. In addition, 12 subjects (11 males and one female) repeated the PBE exercise but with the addition of a 45‐N weight on the back. The PBE exercise consisted of a task broken into four 1‐s segments, while lying prone on a bench (10° below horizontal): (1) raising the trunk to a horizontal position; (2) holding the trunk in the static phase (10° above horizontal); (3) returning to the original position; and (4) resting on the bench. Electromyography (EMG) was used to measure the level of muscle activity (erector spinae (ES), gluteus maximus (GM), hamstrings (HA)) relative to the maximum voluntary EMG (MVE). Results: Most of the subjects (34 out of 41) completed the 100 repetitions without excessive muscle fatigue according to the post‐exercise MVC values. The intermittent PBE increased fatigue in the lumbar and hip extensor muscles in terms of: (1) a decrease in the MVC; (2) an increase in the level of muscle activation; and (3) a decline of the median frequency (MF). There was no gender difference in all EMG measurements. The level of muscle activation in the hip extensors (GM and HA) was associated with task failure (number of repetitions <100) for some subjects and the addition of a weight of 45 N had more impact on HA than ES. In conclusion, the PBE exercise as performed in the present study (including rest intervals), although not very strenuous for our healthy subjects, seems an adequate exercise to measure and train the aerobic capacity of the back muscles. However, to train specifically the back muscles, the exercise must be adjusted to avoid task failure due to possible hip extensor fatigue.
Protein Kinase C‐α and ‐δ Are Required for FcαR (CD89) Trafficking to MHC Class II Compartments and FcαR‐Mediated Antigen Presentation
Authors: Chen Yih‐Wen , Lang Mark L. , Wade William F.
Published: July 2004

Studies have demonstrated that receptor‐mediated signaling, receptor/antigen complex trafficking, and major histocompatibility complex class II compartments (MIIC) are critically related to antigen presentation to CD4+ T cells. In this study, we investigated the role of protein kinase C (PKC) in FcαR/γγ (CD89, human IgA receptor)‐mediated internalization of immune complexes and subsequent antigen presentation. The classical and novel PKC inhibitor, Calphostin C, inhibits FcαR‐mediated antigen presentation and interaction of MIIC and cargo vesicle (receptor and antigen). PKC‐α, PKC‐δ, and PKC‐ε were recruited to lipid rafts following FcαR crosslinking, the extent of which was determined by the phenotype of the γ chain. Mutant γ chain with an FcγRIIA ITAM (immunoreceptor tyrosine‐based activation motif) insert was less able to recruit PKC and trigger antigen presentation. Both PKC isoform‐specific peptide inhibitors and short interfering RNA (siRNA) showed that PKC‐α and PKC‐δ, but not PKC‐ε, were required for association of cargo vesicle and MIIC and for FcαR‐mediated and soluble antigen presentation. Inhibition of PKC (classical and novel) did not alter major histocompatibility class II biosynthesis, assembly, transport, or plasma membrane stability. PKC's role in facilitating interaction of cargo vesicle and MIIC is likely due to regulation of vesicle biology required for fusion of cargo vesicles to MIIC.
Peripheral chemoreceptor control of ventilation following sustained hypoxia in young and older adult humans
Authors: Vovk Andrea , Smith W. Donald F. , Paterson Nicole D. , Cunningham David A. , Paterson Donald H.
Published: July 2004

The rate and duration of peripheral chemoreceptor resensitization following sustained hypoxia was characterized in young and older (74‐year‐old) adults. In addition, cerebral blood velocity (CBV) was measured in young subjects during and following the relief from sustained hypoxia. Following 20 min of sustained eucapnic hypoxia (50 mmHg), subjects were re‐exposed to brief (1.5 min) hypoxic pulses (50 mmHg), and the magnitude of the ventilatory response was used to gauge peripheral chemosensitivity. Five minutes after the relief from sustained hypoxia, ventilation

increased to 40.3 ± 4.5% of the initial hypoxic ventilatory response, and by 36 min

increased to 100%, indicating that peripheral chemosensitivity to hypoxia was restored. The

response magnitude plotted versus time demonstrated that

, hence peripheral chemosensitivity, was restored at a rate of 1.9% per minute. Cerebral blood flow (CBF, inferred from CBV) remained constant during sustained hypoxia and increased by the same magnitude during the hypoxic pulses, suggesting that CBF has a small, if any, impact on the decline in

during hypoxia and its subsequent recovery. To address the issue of whether hypoxic pulses affect subsequent challenges, series (continuous hypoxic pulses at various recovery intervals) and parallel (only 1 pulse per trial) methods were used. There were no differences in the ventilatory responses between the series and parallel methods. Older adults demonstrated a similar rate of recovery as in the young, suggesting that ageing in active older adults does not affect the peripheral chemoreceptor response.
L‐thyroxine increases susceptibility of adult rats to low K+‐induced ventricular fibrillation, and sinus rhythm restoration in old rats
Authors: Tribulova Narcis , Knezl Vladimir , Okruhlicova Ludmila , Drimal Jan , Lamosova Dalma , Slezak Jan , Styk Jan
Published: July 2004

Hypokalaemia increases the risk for life‐threatening arrhythmias; however, data about interaction with thyroid status are lacking. The aim of this study was to investigate vulnerability ofl‐thyroxine (T4)‐treated adult and old rats to low K+‐induced ventricular fibrillation (VF) as well as the ability of the heart to recover sinus rhythm. The experiments were performed on isolated heart preparations using the heart of 4‐ and 20‐month‐old female Wistar rats without and with feeding with T450 μg (100 g day)−1over a period of 2 weeks. Perfusion of the isolated heart with oxygenated Krebs–Henseleit solution at constant pressure was followed by perfusion with K+‐deficient solution until occurrence of VF (< 10 min). After 2 min of sustained VF, the heart was perfused with normal solution for 10 min, during which sinus rhythm was restored. ECG, left ventricular pressure (LVP) and coronary flow were continuously monitored. The results showed that compared with untreated rats, the onset of low K+‐induced ventricular premature beats was delayed and their number was significantly decreased in both T4‐treated groups. Nevertheless, VF occurred earlier in T4‐treated than in non‐treated adult rats (6.78 ± 0.28vs.9.59 ± 0.55 min,P< 0.05), whereas the difference was not significant in aged animals. Furthermore, sinus rhythm appeared earlier in old T4‐treated rats compared with non‐treated rats (7.18 ± 0.57vs.8.94 ± 0.64 min,P< 0.05), whereas in adult hearts it set in at practically the same time regardless of treatment. In conclusion, our results indicate that administration of a pharmacological dose of T4can increase the risk of low K+‐induced VF in adult but not in old animals; in the latter it even facilitated restoration of sinus rhythm. Moreover, enhanced mechanical function was observed in both adult and old T4‐treated hearts.
Reliability of isolated isometric function measures in rat muscles composed of different fibre types
Authors: Gallo Maria , Gordon Tessa , Tyreman Neil , Shu Yang , Putman Charles T.
Published: July 2004

The present study investigated the absolute reliability (RAb) of isometric measures of time‐to‐peak tension (TTP), half‐rise time (½RT), half‐fall time (½FT), twitch force (TWf) tetanic force (TETf) and the sag ratio as applied to the slow soleus (SOL) and the fast‐twitch extensor digitorum longus (EDL) and medial gastrocnemius (MG) muscles of the rat hindlimb. In addition, the relationship of each individual isometric measure was examined with regard to the pattern of myosin heavy chain (MHC) isoform expression. Measures of TTP, ½RT, ½FT and sag ratio were negatively correlated with MHCIId(x) and MHCIIb (P < 0.0001), and positively correlated with MHCI (P < 0.0001). TWf and TETf were negatively correlated with MHCI content (P < 0.0001) and positively with MHCIId(x) (P < 0.0001) and MHCIIb (P < 0.001). Comparisons of isometric measures using a paired Student's t test revealed that they were not different between the right and left legs; all measures displayed high correlations between the left and right legs (r= 0.71–0.85, P < 0.0001). In contrast to standard tests of statistical significance, these functional measures exhibited a considerable range of RAb when individual muscles were studied in only one hindlimb. When averaged across all muscles, however, the ½FT, ½RT, TWf and TTP measures possessed high overall reliability; measures of TETf and sag ratio were moderately reliable. The results of this study show that the isometric measures studied possess significant predictive value with regard to MHC isoform content; the left and right legs are interchangeable but display a considerable range of reliability when only one hindlimb is studied.
Resistance to fatigue of individual Xenopus single skeletal muscle fibres is correlated with mitochondrial volume density
Authors: Stary Creed M. , Mathieu‐Costello Odile , Hogan Michael C.
Published: July 2004

The purpose of the present study was to compare the individual fatigue characteristics of isolated single skeletal muscle fibres with their mitochondrial volume density (MVD), using direct histological morphometry. Single muscle fibres (n= 14) were microdissected from lumbrical muscle of adult female Xenopus laevis, and force was measured while fibres were stimulated (tetanic contractions of 200 ms trains with 70 Hz stimuli at 9 V) at progressively increasing frequencies (2 min each at 0.25, 0.33, 0.5 and 1 contractions s−1) until fatigue (<50% initial maximal force) had been established. Following the end of the fatigue protocol, MVD was determined by electron microscopy. Time to fatigue varied among the individual fibres from 3.3 to 10 min. MVD of individual fibres ranged from 3.0 to 9.2% and was positively correlated (r= 0.93) with time to fatigue of corresponding fibres. These results, using direct histological measurements of MVD: (1) support on a single cell basis the notion that oxidative capacity is a major determinant of muscle fatigue resistance; and (2) show that the fatigue profile of a single cell can be used to predict oxidative capacity.
Functional organization of respiratory neurones: a brief review of current questions and speculations
Authors: Duffin James
Published: July 2004

This article presents a short overview of current knowledge about the medullary respiratory neurones and the generation of breathing rhythm. The background respiratory neurophysiology of the medulla and pons is briefly reviewed, with some current ideas about the organization of the pontine–medullary respiratory control system and its development. Questions and speculations about the organization and generation of respiratory rhythm are included, with a view to stimulating experiments to provide answers.
Hyperpolarized shifts in the voltage dependence of fast inactivation of Nav1.4 and Nav1.5 in a rat model of critical illness myopathy
Authors: Filatov Gregory N. , Rich Mark M.
Published: July 2004

Critical illness myopathy is a disorder in which skeletal muscle becomes electrically inexcitable. We previously demonstrated that a shift in the voltage dependence of fast inactivation of sodium currents contributes to inexcitability of affected fibres in an animal model of critical illness myopathy in which denervated rat skeletal muscle is treated with corticosteroids (steroid‐denervated; SD). In the current study we examined whether expression of Nav1.5 contributes to the altered voltage dependence of sodium channel inactivation in SD muscle. We used TTX and μ‐conotoxin GIIIB to selectively block Nav1.4 in SD muscle and found that the level of Nav1.5 did not correlate closely with the shift in fast inactivation. Surprisingly, we found that the voltage dependence of inactivation of Nav1.4 was similar to that of Nav1.5 in skeletal muscle in vivo. In severely affected fibres, inactivation of both Nav1.4 and Nav1.5 was shifted towards hyperpolarized potentials. We examined the role of denervation and steroid treatment in the shift of the voltage dependence of inactivation and found that both denervation and steroid treatment contribute to the shift in inactivation. Our results suggest that modulation of the voltage dependence of inactivation of both Nav1.4 and Nav1.5 in vivo contributes to loss of electrical excitability in SD muscle.
Cholinergic regulation of the evoked quantal release at frog neuromuscular junction
Authors: Nikolsky Eugeny E. , Vyskočil František , Bukharaeva Ella A. , Samigullin Dmitry , Magazanik Lev G.
Published: July 2004

The effects of cholinergic drugs on the quantal contents of the nerve‐evoked endplate currents (EPCs) and the parameters of the time course of quantal release (minimal synaptic latency, main modal value of latency histogram and variability of synaptic latencies) were studied at proximal, central and distal regions of the frog neuromuscular synapse. Acetylcholine (ACh, 5 × 10−4m), carbachol (CCh, 1 × 10−5m) or nicotine (5 × 10−6m) increased the numbers of EPCs with long release latencies mainly in the distal region of the endplate (90–120 μm from the last node of Ranvier), where the synchronization of transmitter release was the most pronounced. The parameters of focally recorded motor nerve action potentials were not changed by either ACh or CCh. The effects of CCh and nicotine on quantal dispersion were reduced substantially by 5 × 10−7m (+)tubocurarine (TC). The muscarinic agonists, oxotremorine and the propargyl ester of arecaidine, as well as antagonists such as pirenzepine, AF‐DX 116 and methoctramine, alone or in combination, did not affect the dispersion of the release. Muscarinic antagonists did not block the dispersion action of CCh. Cholinergic drugs either decreased the quantal content mo (muscarinic agonist, oxotremorine M, and nicotinic antagonist, TC), or decreased mo and dispersed the release (ACh, CCh and nicotine). The effects on mo were not related either to the endplate region or to the initial level of release dispersion. It follows that the mechanisms regulating the amount and the time course of transmitter release are different and that, among other factors, they are altered by presynaptic nicotinic receptors.
Dendritically released transmitters cooperate via autocrine and retrograde actions to inhibit afferent excitation in rat brain
Authors: Hirasawa Michiru , Schwab Yannick , Natah Sirajedin , Hillard Cecilia J. , Mackie Ken , Sharkey Keith A. , Pittman Quentin J.
Published: July 2004

Oxytocin is released from supraoptic magnocellular neurones and is thought to act at presynaptic receptors to inhibit transmitter release. We now show that this effect is mediated by endocannabinoids, but that oxytocin nonetheless plays an important role in endocannabinoid signalling. WIN55,212‐2, a cannabinoid receptor agonist, mimicked the action of oxytocin and occluded oxytocin‐induced presynaptic inhibition. The cannabinoid action is at the presynaptic terminal as shown by alteration in paired pulse ratio, a reduction in miniature EPSC frequency and immunohistochemical localization of CB1 receptors on presynaptic terminals. AM251, a CB1 receptor antagonist, blocked both the WIN55,212‐2 and the oxytocin‐induced presynaptic inhibition of EPSCs. Depolarization of postsynaptic magnocellular neurones (which contain fatty acid amide hydrolase, a cannabinoid catabolic enzyme) caused a transient inhibition of EPSCs that could be blocked by both the AM251 and Manning compound, an oxytocin/vasopressin receptor antagonist. This indicates that somatodendritic peptide release and action on previously identified autoreceptors facilitates the release of endocannabinoids that act as mediators of presynaptic inhibition.
Elevated renal perfusion pressure does not contribute to natriuresis induced by isotonic saline infusion in freely moving dogs
Authors: Seeliger Erdmann , Andersen Jens Lundbæk , Bie Peter , Reinhardt H. Wolfgang
Published: July 2004

The study was designed to determine to what extent moderate elevation of renal perfusion pressure (RPP) via the mechanism of ‘pressure natriuresis’ contributes to the natriuresis induced by acute i.v. saline loading. Nine Beagle dogs maintained on ample sodium intake (5.5 mmol (kg body mass)−1 day−1) were chronically equipped with an aortic occluder to servocontrol RPP, a bladder catheter to measure renal function, and catheters for measurement of RPP and mean arterial blood pressure (MABP). A swivel system allowed free movement in the kennel during experiments. Isotonic saline loading (500 ml in 100 min) was studied as follows: with and without servocontrol of RPP, and these two protocols repeated in the presence of angiotensin‐converting enzyme inhibition (ACEI, Enalapril, 2 mg (kg body mass)−1). Saline loading increased MABP by about 12 mmHg and sodium excretion from about 28 μmol min−1 up to about 350 μmol min−1. Without ACEI, servocontrol of RPP at 10% below control 24 h MABP slightly delayed the onset of the saline‐induced natriuresis, but did not reduce peak sodium excretion or cumulative sodium excretion. The slight delay most probably resulted from pressure‐controlled renin release because, with ACEI, servocontrol of RPP did not delay or reduce the saline‐induced natriuresis. In conclusion, pressure natriuresis does not contribute to the natriuresis following acute saline loading.
Spectral indices of human cerebral blood flow control: responses to augmented blood pressure oscillations
Authors: Hamner J. W. , Cohen Michael A. , Mukai Seiji , Lipsitz Lewis A. , Taylor J. Andrew
Published: July 2004

We set out to fully examine the frequency domain relationship between arterial pressure and cerebral blood flow. Oscillatory lower body negative pressure (OLBNP) was used to create consistent blood pressure oscillations of varying frequency and amplitude to rigorously test for a frequency‐ and/or amplitude‐dependent relationship between arterial pressure and cerebral flow. We also examined the predictions from OLBNP data for the cerebral flow response to the stepwise drop in pressure subsequent to deflation of ischaemic thigh cuffs. We measured spectral powers, cross‐spectral coherence, and transfer function gains and phases in arterial pressure and cerebral flow during three amplitudes (0, 20, and 40 mmHg) and three frequencies (0.10, 0.05, and 0.03 Hz) of OLBNP in nine healthy young volunteers. Pressure fluctuations were directly related to OLBNP amplitude and inversely to OLBNP frequency. Although cerebral flow oscillations were increased, they did not demonstrate the same frequency dependence seen in pressure oscillations. The overall pattern of the pressure–flow relation was of decreasing coherence and gain and increasing phase with decreasing frequency, characteristic of a high‐pass filter. Coherence between pressure and flow was increased at all frequencies by OLBNP, but was still significantly lower at frequencies below 0.07 Hz despite the augmented pressure input. In addition, predictions of thigh cuff data from spectral estimates were extremely inconsistent and highly variable, suggesting that cerebral autoregulation is a frequency‐dependent mechanism that may not be fully characterized by linear methods.
Coexistence of gamma and high‐frequency oscillations in rat medial entorhinal cortex in vitro
Authors: Cunningham M. O. , Halliday David M. , Davies Ceri H. , Traub Roger D. , Buhl Eberhard H. , Whittington Miles A.
Published: July 2004

High frequency oscillations (> 80–90 Hz) occur in neocortex and hippocampus in vivo where they are associated with specific behavioural states and more classical EEG frequency bands. In the hippocampus in vitro these oscillations can occur in the absence of pyramidal neuronal somatodendritic compartments and are temporally correlated with on‐going, persistent gamma frequency oscillations. Their occurrence in the hippocampus is dependent on gap‐junctional communication and it has been suggested that these high frequency oscillations originate as collective behaviour in populations of electrically coupled principal cell axonal compartments. Here we demonstrate that the superficial layers of medial entorhinal cortex can also generate high frequency oscillations associated with gamma rhythms. During persistent gamma frequency oscillations high frequency oscillations occur with a high bispectral coherence with the field gamma activity. Bursts of high frequency oscillations are temporally correlated with both the onset of compound excitatory postsynaptic potentials in fast‐spiking interneurones and spikelet potentials in both pyramidal and stellate principal neurones. Both the gamma frequency and high frequency oscillations were attenuated by the gap junction blocker carbenoxolone. These data suggest that high frequency oscillations may represent the substrate for phasic drive to interneurones during persistent gamma oscillations in the medial entorhinal cortex.
An amiloride‐sensitive H+‐gated Na+ channel in Caenorhabditis elegans body wall muscle cells
Authors: Jospin Maëlle , Allard Bruno
Published: July 2004

About 30 genes are predicted to encode degenerin/epithelial sodium channels (DEG/ENaCs) in Caenorhabditis elegans but the gating mode of these channels has not been determined. Using the whole‐cell configuration of the patch‐clamp technique in acutely dissected C. elegans, we investigated the effects of H+ as a potential activating factor of DEG/ENaCs on electrical properties of body wall muscle cells. Under current‐clamp conditions, decreasing external pH from 7.2 to 6.1 led to a reversible depolarization of muscle cells associated with a decrease in input resistance which was partially inhibited by amiloride. Under voltage‐clamp conditions, extracellular acidification activated an inward desensitizing current at −60 mV. In the absence of external Ca2+, H+‐gated channels were found to be slightly more permeable to Na+ than to K+ and were blocked by amiloride with a K0.5 of 31 μm at −60 mV. An inward current could be also activated by protons in a GABA receptor null mutant in the presence of d‐tubocurare and in an unc‐105 null mutant. These results demonstrate that ion channels sharing common properties with mammalian acid‐sensing ion channels (ASICs) are functional in C. elegans muscle which should prove useful for understanding proton sensing in animals.
The Evolution of Modern Eukaryotic Phytoplankton
Authors: Falkowski Paul G. , Katz Miriam E. , Knoll Andrew H. , Quigg Antonietta , Raven John A. , Schofield Oscar , Taylor F. J. R.
Published: July 2004

The community structure and ecological function of contemporary marine ecosystems are critically dependent on eukaryotic phytoplankton. Although numerically inferior to cyanobacteria, these organisms are responsible for the majority of the flux of organic matter to higher trophic levels and the ocean interior. Photosynthetic eukaryotes evolved more than 1.5 billion years ago in the Proterozoic oceans. However, it was not until the Mesozoic Era (251 to 65 million years ago) that the three principal phytoplankton clades that would come to dominate the modern seas rose to ecological prominence. In contrast to their pioneering predecessors, the dinoflagellates, coccolithophores, and diatoms all contain plastids derived from an ancestral red alga by secondary symbiosis. Here we examine the geological, geochemical, and biological processes that contributed to the rise of these three, distantly related, phytoplankton groups.
The Limb Bud Shh-Fgf Feedback Loop Is Terminated by Expansion of Former ZPA Cells
Authors: Scherz Paul J. , Harfe Brian D. , McMahon Andrew P. , Tabin Clifford J.
Published: July 2004

Vertebrate limb outgrowth is driven by a positive feedback loop involving
Sonic Hedgehog
(
Shh
),
Gremlin
, and
Fgf4
. By overexpressing individual components of the loop at a time after these genes are normally down-regulated in chicken embryos, we found that
Shh
no longer maintains
Gremlin
in the posterior limb.
Shh
-expressing cells and their descendants cannot express
Gremlin
. The proliferation of these descendants forms a barrier separating the Shh signal from
Gremlin
-expressing cells, which breaks down the Shh-Fgf4 loop and thereby affects limb size and provides a mechanism explaining regulative properties of the limb bud.
Phase-Resolved Spectroscopy of Geminga Shows Rotating Hot Spot(s)
Authors: Caraveo P. A. , De Luca A. , Mereghetti S. , Pellizzoni A. , Bignami G. F.
Published: July 2004

Isolated neutron stars are seen in x-rays through their nonthermal and/or surface thermal emissions. X-ray Multimirror Mission–Newton observations of the Geminga pulsar show a 43–electron volt spectrum from the whole neutron star surface, as well as a power-law component above 2 kiloelectron volts. In addition, we have detected a hot (170 electron volts) thermal emission from an ∼60-meter-radius spot on the pulsar's surface. Such a thermal emission, only visible at selected phase intervals, may be coming from polar hot spot(s), long thought to exist as a result of heating from magnetospheric accelerated particles. It may provide the missing link between the x-ray and gamma-ray emission of the pulsar.
Overriding Imatinib Resistance with a Novel ABL Kinase Inhibitor
Authors: Shah Neil P. , Tran Chris , Lee Francis Y. , Chen Ping , Norris Derek , Sawyers Charles L.
Published: July 2004

Resistance to the ABL kinase inhibitor imatinib (STI571 or Gleevec) in chronic myeloid leukemia (CML) occurs through selection for tumor cells harboring BCR-ABL kinase domain point mutations that interfere with drug binding. Crystallographic studies predict that most imatinib-resistant mutants should remain sensitive to inhibitors that bind ABL with less stringent conformational requirements. BMS-354825 is an orally bioavailable ABL kinase inhibitor with two-log increased potency relative to imatinib that retains activity against 14 of 15 imatinib-resistant BCR-ABL mutants. BMS-354825 prolongs survival of mice with BCR-ABL–driven disease and inhibits proliferation of BCR-ABL–positive bone marrow progenitor cells from patients with imatinib-sensitive and imatinib-resistant CML. These data illustrate how molecular insight into kinase inhibitor resistance can guide the design of second-generation targeted therapies.
Spatial Coordination of Cytokinetic Events by Compartmentalization of the Cell Cortex
Authors: Dobbelaere Jeroen , Barral Yves
Published: July 2004

During cytokinesis, furrow ingression and plasma membrane fission irreversibly separate daughter cells. How actomyosin ring assembly and contraction, vesicle fusion, and abscission are spatially coordinated was unknown. We found that during cytokinesis septin rings, located on both sides of the actomyosin ring, acted as barriers to compartmentalize the cortex around the cleavage site. Compartmentalization maintained diffusible cortical factors, such as the exocyst and the polarizome, to the site of cleavage. In turn, such factors were required for actomyosin ring function and membrane abscission. Thus, a specialized cortical compartment ensures the spatial coordination of cytokinetic events.
Phase and Antigenic Variation in Bacteria
Authors: van der Woude Marjan W. , Bäumler Andreas J.
Published: July 2004

Phase and antigenic variation result in a heterogenic phenotype of a clonal bacterial population, in which individual cells either express the phase-variable protein(s) or not, or express one of multiple antigenic forms of the protein, respectively. This form of regulation has been identified mainly, but by no means exclusively, for a wide variety of surface structures in animal pathogens and is implicated as a virulence strategy. This review provides an overview of the many bacterial proteins and structures that are under the control of phase or antigenic variation. The context is mainly within the role of the proteins and variation for pathogenesis, which reflects the main body of literature. The occurrence of phase variation in expression of genes not readily recognizable as virulence factors is highlighted as well, to illustrate that our current knowledge is incomplete. From recent genome sequence analysis, it has become clear that phase variation may be more widespread than is currently recognized, and a brief discussion is included to show how genome sequence analysis can provide novel information, as well as its limitations. The current state of knowledge of the molecular mechanisms leading to phase variation and antigenic variation are reviewed, and the way in which these mechanisms form part of the general regulatory network of the cell is addressed. Arguments both for and against a role of phase and antigenic variation in immune evasion are presented and put into new perspective by distinguishing between a role in bacterial persistence in a host and a role in facilitating evasion of cross-immunity. Finally, examples are presented to illustrate that phase-variable gene expression should be taken into account in the development of diagnostic assays and in the interpretation of experimental results and epidemiological studies.
Therapy of Falciparum Malaria in Sub-Saharan Africa: from Molecule to Policy
Authors: Winstanley Peter , Ward Stephen , Snow Robert , Breckenridge Alasdair
Published: July 2004

The burden of falciparum malaria remains as great as ever, and, as has probably always been the case, it is carried mainly by tropical Africa. Of the various means available for the control of malaria, the use of effective drugs remains the most important and is likely to remain so for a considerable time to come. Unfortunately, the extensive development of resistance by the parasite threatens the utility of most of the affordable classes of drug: the development of novel antimalarials has never been more urgently needed. Any attempt to understand the vast complexities of falciparum malaria in Africa requires an ability to think “from molecule to policy.” In consequence, the review ambitiously tries to examine the current pharmacopeia, the process by which new drugs are developed and the ways in which drugs are actually used, in both the formal and informal health sectors. The informal sector is particularly important in Africa, where around half of all antimalarial treatments are bought from informal outlets and taken at home without supervision by health care professionals: the potential impact of adherence on clinical outcome is discussed. Given that the full costs are carried by the patient in a large proportion of cases, the importance of drug affordability is explored. The review also discusses the splicing of new drugs into national policy. The various parameters that feed into deliberations on changes in drug policy are discussed.
Competency Assessment in the Clinical Microbiology Laboratory
Authors: Sharp Susan E. , Elder B. Laurel
Published: July 2004

The laboratory comprises an invaluable part of the total health care provided to patients. Competency assessment is one method by which we can verify that our employees are competent to perform laboratory testing and report accurate and timely results. To derive the greatest benefit from the inclusion of competency assessment in the laboratory, we must be sure that we are addressing areas where our efforts can be best utilized to optimize patient care. To be competent, an employee must know how to perform a test, must have the ability to perform the test, must be able to perform the test properly without supervision, and know when there is a problem with the test that must be solved. In some cases, competency assessment protocols may demonstrate areas of competence but can fail to disclose incompetence. For example, challenges of low-complexity tasks (such as reading the technical procedure manual) are inferior to challenges that measure understanding and execution of a protocol, and poorly designed competency challenges will probably not detect substandard laboratory performance. Thus, if we are to receive the greatest benefit from our competency assessment programs, which may be time-consuming for the supervisors and the staff as well, we must not only meet the letter of the law but also find a way to make these assessments meaningful, instructive, and able to detect areas of concern. As we address competency assessment in our laboratories, we must understand that when done properly, competency assessment will reward our organizations and assist us in providing the best possible care to our patients.
Ergonomic stressors and upper extremity musculoskeletal disorders in automobile manufacturing: a one year follow up study
Authors: Punnett L , Gold J , Katz J N , Gore R , Wegman D H
Published: July 2004

Aims:To estimate the one year cumulative incidence and persistence of upper extremity (UE) soft tissue disorders, in a fixed cohort of automotive manufacturing workers, and to quantify their associations with ergonomic exposures.

Methods:At baseline and at follow up, cases of UE musculoskeletal disorders were determined by interviewer administered questionnaire and standardised physical examination of the upper extremities. The interview obtained new data on psychosocial strain and updated the medical and work histories. An index of exposure to ergonomic stressors, obtained at baseline interview, was the primary independent variable. Cumulative incidence and persistence of UE disorders (defined both by symptoms and by physical examination plus symptoms) were analysed in relation to baseline ergonomic exposures, adjusting for other covariates. The incidence of new disorders was modelled using multivariate proportional hazards regression among workers who were not cases in the first year and the prevalence on both occasions was modelled by repeated measures analysis.

Results:A total of 820 workers (69% of eligible cohort members) was examined. Follow up varied slightly by department group but not by baseline exposure level or other characteristics. Among the non-cases at baseline, the cumulative incidence of UE disorders was 14% by symptoms and 12% by symptoms plus examination findings. These rates increased with index of physical exposures primarily among subjects who had the same jobs at follow up as at baseline. Increased exposure during follow up increased risk of incidence. The persistence of UE disorders from baseline to follow up examination was nearly 60% and somewhat associated with baseline exposure score.

Conclusions:These longitudinal results confirm the previous cross sectional associations of UE musculoskeletal disorders with exposure to combined ergonomic stressors. The exposure-response relation was similar for incident cases defined by symptoms alone and those confirmed by physical examination.
Lung function changes in coke oven workers during 12 years of follow up
Authors: Wu J , Griffiths D , Kreis I A , Darling C
Published: July 2004

Aims:To investigate the effect of exposure to coke oven emissions on the lung function of coke oven workers.

Methods:The study population, followed from 1978 and 1990, was 580 male workers with at least two sets of lung function measurements (FVC, FEV1, FEV1/FVC, and FEF25–75%). An annual rate of change (time slope) for age and height adjusted lung function index was estimated for each subject. This “time slope” was then treated as the response variable in a weighted multiple regression analysis with selected predictors.

Results:For all 580 subjects, each year of working in the “operation” group (the most exposed) was found to increase the FVC decline by around 0.7 ml/year (95% CI 0.1 to 1.3 ml/year). After the exclusion of 111 subjects without detailed work history, the above finding was confirmed and each year of exposure in “operation” was also found to increase the FEV1decline by around 0.8 ml/year (95% CI 0.1 to 1.4 ml/year).

Conclusions:These findings are consistent with the results of previous cross-sectional studies. Work duration in the most exposed position in the coke ovens was associated with increased annual decline for FVC and FEV1. The estimated effect of one year of work exposure in “operation” is equivalent, in terms of the reduction in lung function, to an estimated 2.1 pack-years of smoking for FVC and 1.2 pack-years of smoking for FEV1.
The association between occupational factors and adverse health outcomes in chronic obstructive pulmonary disease
Authors: Blanc P D , Eisner M D , Trupin L , Yelin E H , Katz P P , Balmes J R
Published: July 2004

Background and Aims:Despite recognition that occupational exposures may make a substantive contribution to the aetiology of COPD, little is known about the potential role of work related factors in COPD related health outcomes.

Methods:Prospective cohort study using structured telephone interviews among a random sample of adults aged 55–75 reporting a COPD condition (emphysema, chronic bronchitis, or COPD). Using multivariate models adjusting for smoking and demographic factors, the separate and combined associations were estimated between occupational exposure to vapours, gas, dust, or fumes (VGDF) and leaving work due to lung disease (respiratory related work disability) with health outcomes and utilisation ascertained at one year follow up.

Results:Of 234 subjects, 128 (55%) reported exposure to VGDF on their longest held jobs, 58 (25%) reported respiratory related work disability, and 38 (16%) subjects reported both. Combined exposure to VGDF and respiratory related work disability (rather than either factor alone) was associated with the greatest risk at follow up of frequent (everyday) restricted activity days attributed to a breathing or lung condition (OR 3.8; 95% CI 1.4 to 10.1), emergency department (ED) visit (OR 3.9; 95% CI 1.4 to 10.5), and hospitalisation (OR 7.6; 95% CI 1.8 to 32).

Conclusions:Among persons with COPD, past occupational exposures and work disability attributed to lung disease, particularly in combination, appear to be risk factors for adverse health related outcomes.
ASSOCIATION-BASED INFORMATION FLOW CONTROL IN OBJECT-ORIENTED SYSTEMS
Authors: CHOU SHIH-CHIEN , WEN YING-KAI
Published: July 2004

Controlling information flows to prevent information leakage within an application is essential. According to the maturity of object-oriented techniques, many models were developed for the control in object-oriented systems. Since objects may be dynamically instantiated during program execution, controlling information flows among objects is difficult. Our research revealed that association is useful in the control. We developed an association-based information flow control model for object-oriented systems. It precisely controls information flows among objects through associations and constraints. It also offers features such as controlling method invocation through argument sensitivity, allowing declassification, allowing purpose-oriented method invocation, and precisely controlling write access. This paper proposes the model and the implementation of the model, which is composed of the language AbFlow (association-based flow) and its supporting environment.
DARK, ANTIDARK SOLITON-LIKE SOLUTIONS AND THEIR CONNECTION IN A FINITE DEEP NONLINEAR BRAGG GRATING WITH A MIRROR
Authors: ALATAS H. , ISKANDAR A. A. , TJIA M. O. , VALKERING T. P.
Published: July 2004

We report the results of our study on the in-gap soliton-like solutions in a system of a uniform finite deep nonlinear Bragg grating with a mirror and continuous light source on the opposite sides of the grating. The system was shown to exhibit a new feature consisting of homoclinic and heteroclinic orbits in phase plane associated with the in-gap bright and dark/antidark solitons respectively. The multi-valued connection between the dark and antidark solitons was explicitly displayed. It was further demonstrated that a transition from dark to antidark soliton could be affected by either changing the mirror position or changing the source intensity.
DIRECT CHARACTERIZATION OF STATES AND MODES IN DEFECT GRATING STRUCTURES
Authors: VAN GROESEN E. , SOPAHELUWAKAN A. , ANDONOWATI
Published: July 2004

For one-dimensional optical structures consisting of gratings surrounding a defect region, optical field solutions inside the bandgap are investigated that are steady states or fully transmitted modes. The observation that a mode is a suitable combination of two states, and that each state is a resonant phenomenon, implies that an accidental degeneracy condition has to be satisfied in order that two states occur at the same frequency. Finding the conditions, and thereby the required design-parameters of the structure, makes it possible to characterize the modes without the necessity to scan the whole bandgap for transmission properties. The mathematical formulation is based on the optical transfer map and leads to a non-standard, not well-studied, eigenvalue problem on the defect region with effective boundary conditions that simulate the surrounding gratings.
ENERGY TRANSMITTANCE AND SPATIAL PHASE IMPROVEMENT OF INTENSE ULTRASHORT LASER PULSES IN GAS-FILLED HOLLOW FIBER USING PRESSURE GRADIENT METHOD
Authors: NURHUDA MUHAMMAD , BUDIONO HERU , SUDA AKIRA , MIDORIKAWA KATSUMI
Published: July 2004

A pressure gradient method for spectral broadening of intense-femtosecond laser pulses in gas-filled hollow fiber is proposed. The simulations using input energy of 6 mJ and pulse duration of 40 fs have shown that using the same value of ∫ p(x)dx, the energy transmittance can be enhanced by a factor of 25% compared to that of using constant gas pressure while the global spatial phase is also improved.