bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine regulation of Na+-K+-ATPase requires the PDZ-2 domain of sodium hydrogen regulatory factor-1 (NHERF-1) in opossum kidney cells
Authors: Salyer Sarah , Lesousky Nina , Weinman Edward J. , Clark Barbara J. , Lederer Eleanor D. , Khundmiri Syed J.
Published: December 2010

Na+-K+-ATPase activity in renal proximal tubule is regulated by several hormones including parathyroid hormone (PTH) and dopamine. The current experiments explore the role of Na+/H+ exchanger regulatory factor 1 (NHERF-1) in dopamine-mediated regulation of Na+-K+-ATPase. We measured dopamine regulation of ouabain-sensitive 86Rb uptake and Na+-K+-ATPase α1 subunit phosphorylation in wild-type opossum kidney (OK) (OK-WT) cells, OKH cells (NHERF-1-deficient), and OKH cells stably transfected with full-length human NHERF-1 (NF) or NHERF-1 constructs with mutated PDZ-1 (Z1) or PDZ-2 (Z2) domains. Treatment with 1 μM dopamine decreased ouabain-sensitive 86Rb uptake, increased phosphorylation of Na+-K+-ATPase α1-subunit, and enhanced association of NHERF-1 with D1 receptor in OK-WT cells but not in OKH cells. Transfection with wild-type, full-length, or PDZ-1 domain-mutated NHERF-1 into OKH cells restored dopamine-mediated regulation of Na+-K+-ATPase and D1-like receptor association with NHERF-1. Dopamine did not regulate Na+-K+-ATPase or increase D1-like receptor association with NHERF-1 in OKH cells transfected with mutated PDZ-2 domain. Dopamine stimulated association of PKC-ζ with NHERF-1 in OK-WT and OKH cells transfected with full-length or PDZ-1 domain-mutated NHERF-1 but not in PDZ-2 domain-mutated NHERF-1-transfected OKH cells. These results suggest that NHERF-1 mediates Na+-K+-ATPase regulation by dopamine through its PDZ-2 domain.
Modulation by endogenously released ATP and opioids of chromaffin cell calcium channels in mouse adrenal slices
Authors: Hernández A. , Segura-Chama P. , Jiménez N. , García A. G. , Hernández-Guijo J. M. , Hernández-Cruz A.
Published: December 2010

Modulation of high-threshold voltage-dependent calcium channels by neurotransmitters has been the subject of numerous studies in cultures of neurons and chromaffin cells. However, no studies on such modulation exist in chromaffin cells in their natural environment, the intact adrenal medullary tissue. Here we performed such a study in voltage-clamped chromaffin cells of freshly prepared mouse adrenal slices under the whole cell configuration of the patch-clamp technique. The subcomponents of the whole cell inward Ca2+ current ( ICa) accounted for 49% for L-, 28% for N-, and 36% for P/Q-type channels. T-type Ca2+ channels or residual R-type Ca2+ currents were not seen. However, under the perforated-patch configuration, 20% of ICa accounted for a toxin-resistant R-type Ca2+ current. Exogenously applied ATP and methionine-enkephalin (Met-enk) inhibited ICa by 33%. Stop-flow and Ca2+ replacement by Ba2+, which favored the release of endogenous ATP and opioids, also inhibited ICa, with no changes in activation or inactivation kinetics. This inhibition was partially voltage independent and insensitive to prepulse facilitation. Furthermore, in about half of the cells, suramin and naloxone augmented ICa in the absence of exogenous application of ATP/Met-enk. No additional modulation of ICa was obtained after bath application of exogenous ATP and opioids to these already inhibited cells. Augmentation of ICa was also seen upon intracellular dialysis of guanosine 5′-[β-thio]diphosphate (GDPβS), indicating the existence in the intact slice of a tonic inhibition of ICa in resting conditions. These results suggest that in the intact adrenal tissue a tonic inhibition of ICa exists, mediated by purinergic and opiate receptors.
Influence of acetaminophen and ibuprofen on skeletal muscle adaptations to resistance exercise in older adults
Authors: Trappe Todd A. , Carroll Chad C. , Dickinson Jared M. , LeMoine Jennifer K. , Haus Jacob M. , Sullivan Bridget E. , Lee Jonah D. , Jemiolo Bozena , Weinheimer Eileen M. , Hollon Chris J.
Published: December 2010

Evidence suggests that consumption of over-the-counter cyclooxygenase (COX) inhibitors may interfere with the positive effects that resistance exercise training has on reversing sarcopenia in older adults. This study examined the influence of acetaminophen or ibuprofen consumption on muscle mass and strength during 12 wk of knee extensor progressive resistance exercise training in older adults. Thirty-six individuals were randomly assigned to one of three groups and consumed the COX-inhibiting drugs in double-blind placebo-controlled fashion: placebo (67 ± 2 yr; n = 12), acetaminophen (64 ± 1 yr; n = 11; 4 g/day), and ibuprofen (64 ± 1 yr; n = 13; 1.2 g/day). Compliance with the resistance training program (100%) and drug consumption (via digital video observation, 94%), and resistance training intensity were similar ( P > 0.05) for all three groups. Drug consumption unexpectedly increased muscle volume (acetaminophen: 109 ± 14 cm3, 12.5%; ibuprofen: 84 ± 10 cm3, 10.9%) and muscle strength (acetaminophen: 19 ± 2 kg; ibuprofen: 19 ± 2 kg) to a greater extent ( P < 0.05) than placebo (muscle volume: 69 ± 12 cm3, 8.6%; muscle strength: 15 ± 2 kg), when controlling for initial muscle size and strength. Follow-up analysis of muscle biopsies taken from the vastus lateralis before and after training showed muscle protein content, muscle water content, and myosin heavy chain distribution were not influenced ( P > 0.05) by drug consumption. Similarly, muscle content of the two known enzymes potentially targeted by the drugs, COX-1 and -2, was not influenced ( P > 0.05) by drug consumption, although resistance training did result in a drug-independent increase in COX-1 (32 ± 8%; P < 0.05). Drug consumption did not influence the size of the nonresistance-trained hamstring muscles ( P > 0.05). Over-the-counter doses of acetaminophen or ibuprofen, when consumed in combination with resistance training, do not inhibit and appear to enhance muscle hypertrophy and strength gains in older adults. The present findings coupled with previous short-term exercise studies provide convincing evidence that the COX pathway(s) are involved in the regulation of muscle protein turnover and muscle mass in humans.
Increased renal ENaC subunits and sodium retention in rats with chronic heart failure
Authors: Zheng Hong , Liu Xuefei , Rao U. S. , Patel Kaushik P.
Published: December 2010

Renal tubular dysfunction could be involved in the increased sodium and water reabsorption in chronic heart failure (CHF). The goal of the present study was to examine the molecular basis for the increased renal sodium and water retention in CHF. We hypothesized that dysregulation of renal epithelial sodium channels (ENaC) could be involved in the pathogenesis of CHF. The left coronary ligation-induced model of heart failure in the rat was used. Real-time PCR and Western blot analysis indicated that the mRNA and protein abundance of α-, β-, and γ-subunits of ENaC were significantly increased by in the cortex (mRNA: α-ENaC Δ104 ± 24%, β-ENaC Δ47 ± 16%, γ-ENaC Δ55 ± 18%; protein: α-ENaC Δ114 ± 28%, β-ENaC Δ150 ± 31%, γ-ENaC Δ39 ± 5% compared with sham rats) and outer medulla (mRNA: α-ENaC Δ52 ± 18%, β-ENaC Δ38 ± 8%, γ-ENaC Δ39 ± 13%; protein: α-ENaC Δ88 ± 16%, β-ENaC Δ94 ± 28%, γ-ENaC Δ45 ± 9% compared with sham rats) of CHF compared with sham-operated rats. Immunohistochemistry microscopy confirmed the increased labeling of α-, β-, and γ-ENaC subunits in the collecting duct segments in rats with CHF. Furthermore, there was a significant increase in diuretic (7-fold compared with sham) and natriuretic responses (3-fold compared with sham) to ENaC inhibitor benzamil in the rats with CHF. Absence of renal nerves produced a greater contribution of ENaC in sodium retention in rats with CHF. These results suggest that the increased expression of renal ENaC subunits may contribute to the renal sodium and water retention observed during CHF.
Store-operated Ca2+ entry suppresses distention-induced ATP release from the urothelium
Authors: Matsumoto-Miyai Kazumasa , Kagase Ai , Yamada Erika , Yoshizumi Masaru , Murakami Manabu , Ohba Takayoshi , Kawatani Masahito
Published: December 2010

Epithelial cells in the urinary bladder (urothelium) trigger sensory signals in micturition by releasing ATP in response to distention of the bladder wall. Our previous study revealed the distinct roles of extracellular Ca2+ and the Ca2+ stores in the endoplasmic reticulum (ER) in urothelial ATP release. In the present study, we investigated the regulation of urothelial ATP release by Ca2+ influx from the extracellular space and Ca2+ release from the ER using a distention assay of the mouse bladder wall in a small Ussing chamber. Stimulation of Ca2+ release from the ER in the mucosal side of the bladder induced significant ATP release without distention. Blockade of the inositol 1,4,5-triphosphate receptor reduced distention-induced ATP release, suggesting that Ca2+ release from the ER is essential for the induction of urothelial ATP release. On the other hand, blockade of store-operated Ca2+ entry (SOCE) from the extracellular space significantly enhanced distention-induced ATP release. Thus Ca2+ release from the ER causes urothelial ATP release and depletion of Ca2+ stores in the ER, which in turn causes the depletion-inducing SOCE to suppress the amount of urothelial ATP released.
Saccadic Foveation of a Moving Visual Target in the Rhesus Monkey
Authors: Fleuriet Jérome , Hugues Sandrine , Perrinet Laurent , Goffart Laurent
Published: December 2010

When generating a saccade toward a moving target, the target displacement that occurs during the period spanning from its detection to the saccade end must be taken into account to accurately foveate the target and to initiate its pursuit. Previous studies have shown that these saccades are characterized by a lower peak velocity and a prolonged deceleration phase. In some cases, a second peak eye velocity appears during the deceleration phase, presumably reflecting the late influence of a mechanism that compensates for the target displacement occurring before saccade end. The goal of this work was to further determine in the head restrained monkey the dynamics of this putative compensatory mechanism. A step-ramp paradigm, where the target motion was orthogonal to a target step occurring along the primary axes, was used to estimate from the generated saccades: a component induced by the target step and another one induced by the target motion. Resulting oblique saccades were compared with saccades to a static target with matched horizontal and vertical amplitudes. This study permitted to estimate the time taken for visual motion-related signals to update the programming and execution of saccades. The amplitude of the motion-related component was slightly hypometric with an undershoot that increased with target speed. Moreover, it matched with the eccentricity that the target had 40–60 ms before saccade end. The lack of significant difference in the delay between the onsets of the horizontal and vertical components between saccades directed toward a static target and those aimed at a moving target questions the late influence of the compensatory mechanism. The results are discussed within the framework of the “dual drive” and “remapping” hypotheses.
Measures of Cortical Inhibition by Paired-Pulse Transcranial Magnetic Stimulation in Anesthetized Rats
Authors: Vahabzadeh-Hagh Andrew M. , Muller Paul A. , Pascual-Leone Alvaro , Jensen Frances E. , Rotenberg Alexander
Published: December 2010

Paired-pulse transcranial magnetic stimulation (ppTMS) is a noninvasive method to measure cortical inhibition in vivo. Long interpulse interval (50–500 ms) ppTMS (LI-ppTMS) provokes intracortical inhibitory circuits and can reveal pathologically impaired cortical inhibition in disorders such as epilepsy. Adaptation of ppTMS protocols to rodent disease models is highly desirable to facilitate basic and translational research. We previously adapted single-pulse TMS (spTMS) methods to rats, but ppTMS has yet to be applied. Specifically, whether ppTMS elicits an inhibitory response in rodents is unknown. ppTMS in rats also requires anesthesia, a setting under which the preservation of these measures is undetermined. We therefore tested, in anesthetized rats, whether anesthetic choice affects spTMS-motor-evoked potentials (MEPs), LI-ppTMS in rats, as in humans, elicits intracortical inhibition of the MEP, and rat LI-ppTMS inhibition is acutely impaired in a seizure model. Rats were anesthetized with pentobarbital (PB) or ketamine-atropine-xylazine (KAX) and stimulated unilaterally over the motor cortex while recording bilateral brachioradialis MEPs. LI-ppTMS was applied analogous to human long interval intracortical inhibition (LICI) protocols, and acute changes in inhibition were evaluated following injection of the convulsant pentylenetetrazole (PTZ). We find that spTMS-evoked MEPs were reliably present under either anesthetic, and that LI-ppTMS elicits inhibition of the conditioned MEP in rats, similar to human LICI, by as much as 58 ± 12 and 71 ± 11% under PB and KAX anesthesia, respectively. LI-ppTMS inhibition was reduced to as much as 53% of saline controls following PTZ injection, while spTMS-derived measures of corticospinal excitability were unchanged. Our data show that regional inhibition, similar to human LICI, is present in rats, can be elicited under PB or KAX anesthesia, and is reduced following convulsant administration. These results suggest a potential for LI-ppTMS as a biomarker of impaired cortical inhibition in murine disease models.
Mapping brain networks in awake mice using combined optical neural control and fMRI
Authors: Desai M. , Kahn I. , Knoblich U. , Bernstein J. , Atallah H. , Yang A. , Kopell N. , Buckner R. L. , Graybiel A. M. , Moore C. I. , Boyden E. S.
Published: December 2010

Behaviors and brain disorders involve neural circuits that are widely distributed in the brain. The ability to map the functional connectivity of distributed circuits, and to assess how this connectivity evolves over time, will be facilitated by methods for characterizing the network impact of activating a specific subcircuit, cell type, or projection pathway. We describe here an approach using high-resolution blood oxygenation level-dependent (BOLD) functional MRI (fMRI) of the awake mouse brain-to measure the distributed BOLD response evoked by optical activation of a local, defined cell class expressing the light-gated ion channel channelrhodopsin-2 (ChR2). The utility of this opto-fMRI approach was explored by identifying known cortical and subcortical targets of pyramidal cells of the primary somatosensory cortex (SI) and by analyzing how the set of regions recruited by optogenetically driven SI activity differs between the awake and anesthetized states. Results showed positive BOLD responses in a distributed network that included secondary somatosensory cortex (SII), primary motor cortex (MI), caudoputamen (CP), and contralateral SI (c-SI). Measures in awake compared with anesthetized mice (0.7% isoflurane) showed significantly increased BOLD response in the local region (SI) and indirectly stimulated regions (SII, MI, CP, and c-SI), as well as increased BOLD signal temporal correlations between pairs of regions. These collective results suggest opto-fMRI can provide a controlled means for characterizing the distributed network downstream of a defined cell class in the awake brain. Opto-fMRI may find use in examining causal links between defined circuit elements in diverse behaviors and pathologies.
Voluntary Breathing Influences Corticospinal Excitability of Nonrespiratory Finger Muscles
Authors: Li Sheng , Rymer William Zev
Published: December 2010

The present study aimed to investigate neurophysiologic mechanisms mediating the newly discovered phenomenon of respiratory–motor interactions and to explore its potential clinical application for motor recovery. First, young and healthy subjects were instructed to breathe normally (NORM); to exhale (OUT) or inhale (IN) as fast as possible in a self-paced manner; or to voluntarily hold breath (HOLD). In experiment 1 ( n = 14), transcranial magnetic stimulation (TMS) was applied during 10% maximal voluntary contraction (MVC) finger flexion force production or at rest. The motor-evoked potentials (MEPs) were recorded from flexor digitorum superficialis (FDS), extensor digitorum communis (EDC), and abductor digiti minimi (ADM) muscles. Similarly, in experiment 2 ( n = 11), electrical stimulation (ES) was applied to FDS or EDC during the described four breathing conditions while subjects maintained 10%MVC of finger flexion or extension and at rest. In the exploratory clinical experiments ( experiment 3), four patients with chronic neurological disorders (three strokes, one traumatic brain injury) received a 30-min session of breathing-controlled ES to the impaired EDC. In experiment 1, the EDC MEP magnitudes increased significantly during IN and OUT at both 10%MVC and rest; the FDS MEPs were enhanced only at 10%MVC, whereas the ADM MEP increased only during OUT, compared with NORM for both at rest and 10%MVC. No difference was found between NORM and HOLD for all three muscles. In experiment 2, when FDS was stimulated, force response was enhanced during both IN and OUT, but only at 10%MVC. When EDC was stimulated, force response increased at both 10%MVC and rest, only during IN, but not OUT. The averaged response latency was 83 ms for the finger extensors and 79 ms for the finger flexors. After a 30-min intervention of ES to EDC triggered by forced inspiration in experiment 3, we observed a significant reduction in finger flexor spasticity. The spasticity reduction lasted for ≥4 wk in all four patients. TMS and ES data, collectively, support the phenomenon that there is an overall respiration-related enhancement on the motor system, with a strong inspiration–finger extension coupling during voluntary breathing. As such, breathing-controlled electrical stimulation (i.e., stimulation to finger extensors delivered during the voluntary inspiratory phase) could be applied for enhancing finger extension strength and finger flexor spasticity reduction in poststroke patients.
Incomplete Inactivation and Rapid Recovery of Voltage-Dependent Sodium Channels During High-Frequency Firing in Cerebellar Purkinje Neurons
Authors: Carter Brett C. , Bean Bruce P.
Published: December 2010

Purkinje neurons can spike very rapidly for sustained periods. We examined the cycle of sodium channel gating during high-frequency firing of Purkinje neurons, focusing on the kinetics of sodium channel inactivation and recovery during and after spikes. To analyze sodium channel availability during spiking, we recorded the firing patterns of acutely dissociated Purkinje neurons in current clamp and used these records as command voltages in voltage-clamp experiments in the same cell, adding step depolarizations at various points to assay availability. Sodium channel availability decreased abruptly during the spike, as expected, but never reached zero. During spontaneous firing (∼40 Hz at 37°C), availability decreased from nearly 90% before the spike to about 10–20% after the spike. With fast steady firing stimulated by current injection (∼300 Hz at 37°C), the availability decreased from about 60% between spikes to roughly 15–20% after the spike. Thus even at the fastest firing rates, sodium channel inactivation is incomplete after a spike, leaving a substantial fraction of sodium channels immediately available for activation. Also, inactivation recovered quickly during the early interspike interval (time constant ∼1 ms at 37°C), but developed slowly during the depolarization of the late interspike interval, ensuring high availability until spike threshold. These features of sodium channel gating, especially the availability remaining after the spike, reduce the refractory period and facilitate rapid repetitive firing.
Remarks on Asymptotic Centers and Fixed Points
Authors: Kaewkhao A. , Sokhuma K.
Published: December 2010

We introduce a class of nonlinear continuous mappings defined on a bounded closed
convex subset of a Banach space X. We characterize the Banach spaces in which every
asymptotic center of each bounded sequence in any weakly compact convex subset is
compact as those spaces having the weak fixed point property for this type of mappings.
Extensions of Certain Classical Summation Theorems for the Series 2 F 1, 3 F 2, and 4 F 3 with Applications in Ramanujan′s Summations
Authors: Kim Yong Sup , Rakha Medhat A. , Rathie Arjun K.
Published: December 2010

Motivated by the extension of classical Gauss′s summation theorem for the series 2 F 1 given in the literature, the authors aim
at presenting the extensions of various other classical summation theorems such as those of Kummer, Gauss′s second, and
Bailey for the series 2 F 1, Watson, Dixon and Whipple for the series 3 F 2, and a few other hypergeometric identities for the
series 3 F 2 and 4 F 3. As applications, certain very interesting summations due to Ramanujan have been generalized.
The results derived in this paper are simple, interesting, easily established, and may be useful.
Multifocal Aggressive Squamous Cell Carcinomas Induced by Prolonged Voriconazole Therapy: A Case Report
Authors: Morice C. , Acher A. , Soufir N. , Michel M. , Comoz F. , Leroy D. , Verneuil L.
Published: December 2010

Voriconazole is a treatment for severe fungal infections. Prolonged voriconazole therapy may induce skin reactions, with 1% of severe photosensitivity accidents. Recently the imputability of voriconazole in skin carcinogenesis has been suggested. This report concerns a 55-year-old man suffering from pulmonary aspergillosis who presented a phototoxic reaction a few months after introduction of voriconazole, followed by multiple squamous cell carcinomas of sun-exposed skin areas. After voriconazole discontinuation, no new carcinoma was observed. The detection of EBV and HPV in skin lesions was negative. Exploration of gene mutations involved in skin carcinogenesis showed two variants of theMICRgene. The occurrence of multiple, recurrent, aggressive squamous cell carcinomas is rare with voriconazole, but its imputability is strongly suggested. A plausible hypothesis is that several factors including voriconazole uptake, immunosuppression, and genetic background could explain the phenotype of fast-developing skin carcinomas. Voriconazole therapy should be accompanied by stringent photoprotection and skin monitoring.
Survival of Viral Biowarfare Agents in Disinfected Waters
Authors: Wade Mary Margaret , Chambers Amanda E. , Insalaco Joseph M. , Zulich Alan W.
Published: December 2010

Protecting civilian and military water supplies has received more attention since the United States began its war on terror in 2001. Both chlorine and bromine are used by branches of the U.S. military for disinfecting water supplies; however, limited data exists as to the effectiveness of these additives when used against viral biowarfare agents. The present study sought to evaluate the survival of selected viral biothreat agents in disinfected water. Disinfected water samples were spiked with vaccinia virus strain WR and Venezuelan equine encephalitis (VEE) virus strain TC-83 each separately to a final concentration of approximately1×106PFU/mL, and survival was assessed by plaque assay. Both viruses were inactivated by 1 mg/L free available chlorine (FAC) and 2mg/L total bromine within one hour. In conclusion, these results demonstrate that both chlorine and bromine are effective disinfectants against vaccinia virus and VEE strain TC-83 at the concentrations tested.
Extended and Unscented Kalman Filtering Applied to a Flexible‐Joint Robot with Jerk Estimation
Authors: Badamchizadeh Mohammad Ali , Hassanzadeh Iraj , Abedinpour Fallah Mehdi
Published: December 2010

Robust nonlinear control of flexible‐joint robots requires that the link position, velocity, acceleration, and jerk be available. In this paper, we derive the dynamic model of a nonlinear flexible‐joint robot based on the governing Euler‐Lagrange equations and propose extended and unscented Kalman filters to estimate the link acceleration and jerk from position and velocity measurements. Both observers are designed for the same model and run with the same covariance matrices under the same initial conditions. A five‐bar linkage robot with revolute flexible joints is considered as a case study. Simulation results verify the effectiveness of the proposed filters.
Screening for Y Chromosome Microdeletion in a Nonobstructive Azoospermic Male Patient with Allogeneic Bone Marrow Transplantation from His Sister
Authors: Gurkan Hakan , Kucukdurmaz Faruk , Akman Tolga , Aydın Filiz , Kadioglu Ates
Published: December 2010

Genomic DNA of a patient diagnosed with nonobstructive azoospermia and with the history of allogenic bone marrow transplantation from his sister due to chronic myeloid leukemia was isolated from peripheral blood in order to screen Y chromosome microdeletions. 13 short tagged sites belonging to AZF a, b, and c loci were detected with multiplex polymerase chain reaction technique. Bands were determined in ZFX/ZFY wells, whereas no bands were determined in wells of other STS regions. DNA isolation was done from buccal mucosa smear to obtain genomic DNA from patient's own cells and multiplex polymerase chain reaction technique was performed again. Bands were seen in all wells of 13 STS regions. Y chromosome microdeletion was not detected in the patient. In conclusion, genomic DNA isolation in patients undergoing BMT should be done from patients' own cells.
Association between Participation in Outpatient Cardiac Rehabilitation and Self-Reported Receipt of Lifestyle Advice from a Healthcare Provider: Results of a Population-Based Cross-Sectional Survey
Authors: Johnson Natalie A. , Inder Kerry J. , Ewald Ben D. , James Erica L. , Bowe Steven J.
Published: December 2010

We test the hypothesis that the odds of self-reported receipt of lifestyle advice from a health care provider will be lower among outpatient cardiac rehabilitation (OCR) nonattendees and nonreferred patients compared to OCR attendees. Logistic regression was used to analyse cross-sectional data provided by 65% (4971/7678) of patients aged 20 to 84 years discharged from public hospitals with a diagnosis indicating eligibility for OCR between 2002 and 2007. Among respondents, 71% (3518) and 55% (2724) recalled advice regarding physical activity and diet, respectively, while 88% (592/674) of smokers recalled quit advice. OCR attendance was low: 36% (1764) of respondents reported attending OCR, 11% (552) did not attend following referral, and 45% (2217) did not recall being invited. The odds of recalling advice regarding physical activity and diet were significantly lower among OCR nonattendees compared to attendees (OR 0.34, 95% CI 0.21, 0.56 and OR 0.33, 95% CI 0.25, 0.44, resp.) and among nonreferred respondents compared to OCR attendees (OR 0.10, 95% CI 0.07, 0.15 and OR 0.17, 95% CI 0.14, 0.22, resp.). Patients hospitalised for coronary heart disease should be referred to OCR or a suitable alternative to improve recall of lifestyle advice that will reduce the risk of further coronary events.
Peripheral Neuropathy and VIth Nerve Palsy Related to Randall Disease Successfully Treated by High-Dose Melphalan, Autologous Blood Stem Cell Transplantation, and VIth Nerve Decompression Surgery
Authors: Foguem C. , Manckoundia P. , Pfitzenmeyer P. , Dupond J.-L.
Published: December 2010

Randall disease is an unusual cause of extraocular motor nerve (VI) palsy. A 35-year-old woman was hospitalized for sicca syndrome. The physical examination showed general weakness, weight loss, diplopia related to a left VIth nerve palsy, hypertrophy of the submandibular salivary glands, and peripheral neuropathy. The biological screening revealed renal insufficiency, serum monoclonal kappa light chain immunoglobulin, urinary monoclonal kappa light chain immunoglobulin, albuminuria, and Bence-Jones proteinuria. Bone marrow biopsy revealed medullar plasma cell infiltration. Immunofixation associated with electron microscopy analysis of the salivary glands showed deposits of kappa light chains. Randall disease was diagnosed. The patient received high-dose melphalan followed by autostem cell transplantation which led to rapid remission. Indeed, at the 2-month followup assessment, the submandibular salivary gland hypertrophy and renal insufficiency had disappeared, and the peripheral neuropathy, proteinuria, and serum monoclonal light chain had decreased significantly. The persistent diplopia was treated with nerve decompression surgery of the left extraocular motor nerve. Cranial nerve complications of Randall disease deserve to be recognized.
Encapsulation of Menthol in Beeswax by a Supercritical Fluid Technique
Authors: Zhu Linjing , Lan Hongqiao , He Bingjing , Hong Wei , Li Jun
Published: December 2010

Encapsulation of menthol in beeswax was prepared by a modified particles from gas-saturated solutions (PGSS) process with controlling the gas-saturated solution flow rate. Menthol/beeswax particles with size in the range of 2–50 μm were produced. The effects of the process conditions, namely, the pre-expansion pressure, pre-expansion temperature, gas-saturated solution flow rate, and menthol composition, on the particle size, particle size distribution, and menthol encapsulation rate were investigated. Results indicated that in the range of studied conditions, increase of the pressure, decrease of the gas-saturated solution flow rate, and decrease of the menthol mass fraction can decrease the particle size and narrow particle size distribution of the produced menthol/beeswax microparticles. An N2-blowing method was proposed to measure the menthol release from the menthol/beeswax microparticles. Results showed that the microparticles have obvious protection of menthol from its volatilization loss.
Ishikawa Iterative Process for a Pair of Single-valued and Multivalued Nonexpansive Mappings in Banach Spaces
Authors: Sokhuma K , Kaewkhao A
Published: December 2010

Let "Equation missing" be a nonempty compact convex subset of a uniformly convex Banach space "Equation missing", and let "Equation missing" and "Equation missing" be a single-valued nonexpansive mapping and a multivalued nonexpansive mapping, respectively. Assume in addition that "Equation missing" and "Equation missing" for all "Equation missing". We prove that the sequence of the modified Ishikawa iteration method generated from an arbitrary "Equation missing" by "Equation missing", "Equation missing", where "Equation missing" and "Equation missing", "Equation missing" are sequences of positive numbers satisfying "Equation missing", "Equation missing", converges strongly to a common fixed point of "Equation missing" and "Equation missing"; that is, there exists "Equation missing" such that "Equation missing".
Mode-Locked CO Laser for Isotope Separation of Uranium Employing Condensation Repression
Authors: Baranov Igor Y. , Koptev Andrey V.
Published: December 2010

In the present work, we have suggested a technical solution of a CO laser facility for industrial separation of uranium used in the production of fuel for nuclear power plants. There has been used a method of laser isotope separation of uranium, employing condensation repression in a free jet. The laser operation with nanosecond pulse irradiation can provide acceptable efficiency in the separating unit and the high effective coefficient of the laser with the wavelength of 5.3 μm. Receiving a uniform RF discharge under medium pressure and high Mach numbers in the gas stream solves the problem of an electron beam and cryogenic cooler of CO lasers. The laser active medium is being cooled while it is expanding in the nozzle; a low-current RF discharge is similar to a non-self-sustained discharge. In the present work, we have developed a calculation model of optimization and have defined the parameters of a mode-locked CO laser with an RF discharge in the supersonic stream. The CO laser average power of 3 kW is sufficient for efficient industrial isotope separation of uranium at one facility.
Investigations on Quasi-Steady Characteristics for an Airfoil Oscillating at Low Reduced Frequencies
Authors: Sharma Deepakkumar M. , Poddar Kamal
Published: December 2010

Wind tunnel experiments were conducted on NACA-0015 airfoil model to investigate the effect of the reduced frequency (κ=0.0001to 0.5) and that Reynolds number (Re=0.2E06to 0.7E06) on the aerodynamic characteristics and hysteresis behavior associated with the oscillating motion of the airfoil. Pressure measurements were conducted on the midspan of the airfoil for quantitative results. Although dynamic stall study has been conducted to greater extent of reduced frequencies, for current work, emphasis is made on investigating the low reduced frequency regimes up to which the steady conditions prevail under dynamic mode of operation. In present investigations of oscillating sinusoidalα=10∘+15∘sin(ωt)motion, the airfoil was allowed to execute oscillating motion from static to almost steady (quasi-steady) conditions with the incremental increase in the reduced frequency. The limiting conditions ofκandRefor quasi-steady state are carefully extracted and analyzed. Static and quasi-steady conditions are critically assessed in context of the existence of laminar separation bubble within the optedReregime. The flow separation was found to be trailing edge flow separation with existence of LSB upstream towards the leading edge with no evidence of unsteady flow reversals. Normal force defect and pitch damping factor are estimated for varied range ofReandκwithin the quasi-steady conditions. Re effect is dominant at steady and quasi-steady regimes while the effect of reduced frequency is negligible in this domain. Minor hysteresis effect associated with the stalling and reattachment point is due to existence of weak stall flutter which is further restrained by the oscillatory motion of the airfoil. Laminar separation bubble traced during steady condition is conserved in quasi-steady domain as well.
Surgical Treatment of a Giant Liposarcoma in a Japanese Man
Authors: Hashimoto Yasuhiro , Hatakeyama Shingo , Tachiwada Tokushi , Yoneyama Takahiro , Koie Takuya , Kamimura Noritaka , Yanagisawa Takeshi , Hakamada Kenichi , Ohyama Chikara
Published: December 2010

We report a case of a rapidly progressing giant retroperitoneal liposarcoma weighing 22 kg in a 41-year-old Japanese man, successfully treated with surgical excision. To our knowledge, this is the largest liposarcoma in the Japanese population reported in the literature.
Contact Endoscopy as a Novel Technique in the Detection and Diagnosis of Mucosal Lesions in the Head and Neck: A Brief Review
Authors: Szeto Christopher , Wehrli Bret , Whelan Fiona , Franklin Jason , Nichols Anthony , Yoo John , Fung Kevin
Published: December 2010

Background. There are a variety of described noninvasive optical detection techniques for evaluation of head and neck mucosal lesions. Contact endoscopy is a promising method ofin vivomicroscopic examination whereby a rigid telescope is placed on a previously dye-stained mucosa allowing evaluation of the superficial cell layers of the epithelium. This technique produces real-time, magnified images of cellular architecture of surface mucosa comparable to histology without the need for biopsy. In this review, we will briefly summarize the efficacy of CE in the detection of precancerous and cancerous mucosal lesions and its potential as a novel technique in early diagnosis, monitoring, and preoperative assessment of mucosal lesions of the head and neck.Methods. PUBMED, MEDLINE, and COCHRANE search revealed five prospective articles on contact endoscopy for the diagnosis of mucosal lesions in the head and neck.Results. The literature search yielded five prospective studies examining contact endoscopy for the diagnosis of benign versus malignant head and neck mucosal lesions. These reported a sensitivity and specificity of 77–100%, specificity of 66–100% and an accuracy of 72–92%.Conclusion. Contact endoscopy is a promising optical technology that may be a useful adjunct in the evaluation and diagnosis of benign and malignant head and neck mucosal lesions. Future prospective randomized double-blind studies of this detection method are required.
Lung Cancer Stem Cell: New Insights on Experimental Models and Preclinical Data
Authors: Rivera Caroline , Rivera Sofia , Loriot Yohann , Vozenin Marie-Catherine , Deutsch Eric
Published: December 2010

Lung cancer remains the leading cause of cancer death. Understanding lung tumors physiopathology should provide opportunity to prevent tumor development or/and improve their therapeutic management. Cancer stem cell (CSC) theory refers to a subpopulation of cancer cells, also named tumor-initiating cells, that can drive cancer development. Cells presenting these characteristics have been identified and isolated from lung cancer. Exploring cell markers and signaling pathways specific to lung CSCs may lead to progress in therapy and improve the prognosis of patients with lung cancer. Continuous efforts in developingin vitroandin vivomodels may yield reliable tools to better understand CSC abilities and to test new therapeutic targets. Preclinical data on putative CSC targets are emerging by now. These preliminary studies are critical for the next generation of lung cancer therapies.
Novel Perspectives on p53 Function in Neural Stem Cells and Brain Tumors
Authors: Hede Sanna-Maria , Nazarenko Inga , Nistér Monica , Lindström Mikael S.
Published: December 2010

Malignant glioma is the most common brain tumor in adults and is associated with a very poor prognosis. Mutations in the p53 tumor suppressor gene are frequently detected in gliomas. p53 is well-known for its ability to induce cell cycle arrest, apoptosis, senescence, or differentiation following cellular stress. That the guardian of the genome also controls stem cell self-renewal and suppresses pluripotency adds a novel level of complexity to p53. Exactly how p53 works in order to prevent malignant transformation of cells in the central nervous system remains unclear, and despite being one of the most studied proteins, there is a need to acquire further knowledge about p53 in neural stem cells. Importantly, the characterization of glioma cells with stem-like properties, also known as brain tumor stem cells, has opened up for the development of novel targeted therapies. Here, we give an overview of what is currently known about p53 in brain tumors and neural stem cells. Specifically, we review the literature regarding transformation of adult neural stem cells and, we discuss how the loss of p53 and deregulation of growth factor signaling pathways, such as increased PDGF signaling, lead to brain tumor development. Reactivation of p53 in brain tumor stem cell populations in combination with current treatments for glioma should be further explored and may become a viable future therapeutic approach.
RalA Function in Dermal Fibroblasts Is Required for the Progression of Squamous Cell Carcinoma of the Skin
Authors: Sowalsky Adam G. , Alt-Holland Addy , Shamis Yulia , Garlick Jonathan A. , Feig Larry A.
Published: December 2010

A large body of evidence has shown that stromal cells play a significant role in determining the fate of neighboring tumor cells through the secretion of various cytokines. How cytokine secretion by stromal cells is regulated in this context is poorly understood. In this study, we used a bioengineered human tissue model of skin squamous cell carcinoma progression to reveal that RalA function in dermal fibroblasts is required for tumor progression of neighboring neoplastic keratinocytes. This conclusion is based on the observations that suppression of RalA expression in dermal fibroblasts blocked tumorigenic keratinocytes from invading into the dermal compartment of engineered tissues and suppressed more advanced tumor progression after these tissues were transplanted onto the dorsum of mice. RalA executes this tumor-promoting function of dermal fibroblasts, at least in part, by mediating hepatocyte growth factor (HGF) secretion through its effector proteins, the Sec5 and Exo84 subunits of the exocyst complex. These findings reveal a new level of HGF regulation and highlight the RalA signaling cascade in dermal fibroblasts as a potential anticancer target. Cancer Res; 71(3); 758–67. ©2010 AACR.
Comprehensive Mapping of p53 Pathway Alterations Reveals an Apparent Role for Both SNP309 and MDM2 Amplification in Sarcomagenesis
Authors: Ito Moriko , Barys Louise , O'Reilly Terence , Young Sophie , Gorbatcheva Bella , Monahan John , Zumstein-Mecker Sabine , Choong Peter F. , Dickinson Ian , Crowe Philip , Hemmings Christine , Desai Jayesh , Thomas David M. , Lisztwan Joanna
Published: December 2010

Purpose: Reactivation of p53 tumor suppressor activity in diseases such as soft-tissue sarcoma is considered an attractive means of targeted therapy. By systematically assessing alterations affecting the p53 pathway, we aimed to (a) classify sarcoma subtypes, (b) define a potential role in malignancy, and (c) identify potential patient biomarkers in this heterogeneous disease.

Experimental Design: We have mapped mutational events in a panel of 192 benign or malignant bone and soft-tissue sarcomas. Analyses included TP53 and CDKN2A mutational and SNP status, MDM2 and MDM4 amplification and MDM2 SNP309 status.

Results: We found an inverse relationship between MDM2 amplification and TP53 mutations, with a predominantly wild-type CDKN2A background. A high rate of point mutations in TP53 was observed uniquely in leiomyosarcoma, osteosarcoma, and MFH. Both MDM2 and MDM4 were also amplified in a subtype-specific manner, which was frequently seen as a coamplification event. We have also analyzed the risk allele frequencies for MDM2 SNP309, and show that the G allele was strongly associated with both liposarcomas and MDM2 amplification.

Conclusions: Our data emphasize the critical role of p53 inactivation in sarcomagenesis, whereby different pathway alterations may be related to the heterogeneity of the disease. Moreover, we observed a strong association of malignancy with TP53 mutation, or MDM2 amplification and the presence of a G allele in SNP309, especially in lipoma versus liposarcoma. We propose, therefore, that MDM2 markers along with TP53 sequencing should be considered as patient biomarkers in clinical trials of sarcomas using MDM2 antagonists. Clin Cancer Res; 17(3); 416–26. ©2010 AACR.
Androgen Deprivation Boosts Prostatic Infiltration of Cytotoxic and Regulatory T Lymphocytes and Has No Effect on Disease-Free Survival in Prostate Cancer Patients
Authors: Sorrentino Carlo , Musiani Piero , Pompa Paolo , Cipollone Giuseppe , Di Carlo Emma
Published: December 2010

Purpose: The value of neoadjuvant hormone therapy (NHT) prior to radical prostatectomy as a means of restraining prostate cancer (PCa) and strengthening its immunotherapy is still uncertain. This article asks whether it subverts immunoregulatory pathways governing tumor microenvironments, and has an impact on patient outcome.

Experimental Design: We microdissected epithelium and stroma from cancerous and normal prostate specimens from 126 prostatectomized patients, of whom 76 had received NHT, to detect cytokine/chemokine gene expression levels by real-time reverse transcriptase PCR. Confocal microscopy was used to identify cytokine/chemokine cell sources, and immunostainings to characterize lymphocyte subsets whose prognostic effects were assessed by Kaplan–Meier analyses.

Results: NHT boosted the expression of IL-7 in the stroma and that of IFNγ-inducible protein-10/CXCL10 in the glandular epithelium of normal prostate tissue, and restored the CD8+ lymphocyte depletion occurring in PCa, whereas it significantly increased the CD4+ lymphocyte infiltrate. Lymphocytes, mostly with CD8+ phenotype, expressed the T-cell intracellular antigen-1, granzyme-B, and perforin, typical of cytotoxic-effector T cells. NHT also induced thymus and activation-regulated chemokine/CCL17 production by monocytes/macrophages in the prostate and draining lymph nodes, and increased the number of their Forkhead box P3 (Foxp3)+CD25+CD127− T regulatory (Treg) cells. The χ2 test disclosed the lack of association (P = 0.27) between NHT and the high intratumoral CD8+/Treg ratio indicative of a good prognosis.

Conclusions: Androgen withdrawal regulates cytokine/chemokine gene expression in normal prostate and lymphoid tissues, and this probably favors both CD8+ and Treg infiltrates, leaves their intratumoral balance unchanged, and thus has no impact on disease-free survival. Clin Cancer Res; 17(6); 1571–81. ©2010 AACR.
Urinary Biomarkers in Acute Kidney Transplant Dysfunction
Authors: Alachkar Nada , Rabb Hamid , Jaar Bernard G.
Published: December 2010

Background: Acute kidney injury (AKI) is a common medical problem among kidney transplant recipients, which may cause a significant impact on patient and allograft survival. Currently, an allograft biopsy remains the ‘gold standard’ for assessing the cause of impaired kidney function. Limitations of the allograft biopsy include the risk of bleeding, injury to the adjacent viscera, and the possibility of sampling error leading to an inadequate diagnosis. Methods: We conducted a comprehensive review of the literature and main published data that discussed the most relevant biomarkers in acute allograft dysfunction, along with their clinical significance. Results: There have been significant discoveries of several important biomarkers that correlated with biopsy findings, clinical outcomes and possibly graft survival. Conclusion: The discovery of surrogate biomarkers in kidney transplantation is an evolving field of crucial importance that mandates further collaborative efforts.
Infantile Intracranial Neoplasms: Characteristics and Surgical Outcomes of a Contemporary Series of 21 Cases in an Egyptian Referral Center
Authors: El-Gaidi Mohamed Ali , Eissa Ehab Mohamed
Published: December 2010

Objective: To investigate the demographic, clinical, radiological, pathological and surgical features and outcomes of infantile intracranial neoplasms, the second most common neoplasm in infants. Patients and Methods: We conducted a retrospective study in the Department of Pediatric Neurosurgery at the Abo El-Reish Children’s Hospital from 2005 to 2008. Results: Out of 451 patients with primary intracranial neoplasms (age 0–14 years), 21 infants (<1 year) underwent surgery, representing 4.7% of total cases. The most common tumor was choroid plexus papilloma (23.8%), followed by teratoma (19%) then astrocytoma and ependymoma (14.3% each). Of the 21 surgical cases, 90% were intra-axial, 80% were in the supratentorial region, and 57% were intraventricular. There was only 1 case of intraoperative mortality (4.8%). Gross total excision was achieved in 65%, debulking in 30%, and biopsy in 5%. Three patients received chemotherapy, but none received radiotherapy. The statistically significant predictors of prognosis were the extent of resection and tumor grade. Conclusion: Although the prognosis for infantile intracranial neoplasms is worse than for older children, an overall promising outcome with low operative morbidity and mortality was achieved using gross total excision and appropriate adjuvant chemotherapy as part of a multidisciplinary approach.