bluuebunny/crossref_metadata_2025 huggingface dataset:
SLC26 anion exchangers of guinea pig pancreatic duct: molecular cloning and functional characterization
Authors: Stewart Andrew K. , Shmukler Boris E. , Vandorpe David H. , Reimold Fabian , Heneghan John F. , Nakakuki M. , Akhavein Arash , Ko Shigeru , Ishiguro Hiroshi , Alper Seth L.
Published: May 2011

The secretin-stimulated human pancreatic duct secretes HCO3−-rich fluid essential for normal digestion. Optimal stimulation of pancreatic HCO3− secretion likely requires coupled activities of the cystic fibrosis transmembrane regulator (CFTR) anion channel and apical SLC26 Cl−/HCO3− exchangers. However, whereas stimulated human and guinea pig pancreatic ducts secrete ∼140 mM HCO3− or more, mouse and rat ducts secrete ∼40–70 mM HCO3−. Moreover, the axial distribution and physiological roles of SLC26 anion exchangers in pancreatic duct secretory processes remain controversial and may vary among mammalian species. Thus the property of high HCO3− secretion shared by human and guinea pig pancreatic ducts prompted us to clone from guinea pig pancreatic duct cDNAs encoding Slc26a3, Slc26a6, and Slc26a11 polypeptides. We then functionally characterized these anion transporters in Xenopus oocytes and human embryonic kidney (HEK) 293 cells. In Xenopus oocytes, gpSlc26a3 mediated only Cl−/Cl− exchange and electroneutral Cl−/HCO3− exchange. gpSlc26a6 in Xenopus oocytes mediated Cl−/Cl− exchange and bidirectional exchange of Cl− for oxalate and sulfate, but Cl−/HCO3− exchange was detected only in HEK 293 cells. gpSlc26a11 in Xenopus oocytes exhibited pH-dependent Cl−, oxalate, and sulfate transport but no detectable Cl−/HCO3− exchange. The three gpSlc26 anion transporters exhibited distinct pharmacological profiles of 36Cl− influx, including partial sensitivity to CFTR inhibitors Inh-172 and GlyH101, but only Slc26a11 was inhibited by PPQ-102. This first molecular and functional assessment of recombinant SLC26 anion transporters from guinea pig pancreatic duct enhances our understanding of pancreatic HCO3− secretion in species that share a high HCO3− secretory output.
Enhanced survival of skeletal muscle myoblasts in response to overexpression of cold shock protein RBM3
Authors: Ferry Amy L. , Vanderklish Peter W. , Dupont-Versteegden Esther E.
Published: May 2011

Cold-inducible RNA-binding protein (RBM3) is suggested to be involved in the regulation of skeletal muscle mass. Cell death pathways are implicated in the loss of muscle mass and therefore the role of RBM3 in muscle apoptosis in C2C12 myoblasts was investigated in this study. RBM3 overexpression was induced by either cold shock (32°C exposure for 6 h) or transient transfection with a myc-tagged RBM3 expression vector. Cell death was induced by H2O2 (1,000 μM) or staurosporine (StSp, 5 μM), and it was shown that cold shock and RBM3 transfection were associated with attenuation of morphological changes and an increase in cell viability compared with normal temperature or empty vector, respectively. No changes in proliferation were observed with either cold shock or RBM3 transfection. DNA fragmentation was not increased in response to H2O2, and a cell permeability assay indicated that cell death in response to H2O2 is more similar to necrosis than apoptosis. RBM3 overexpression reduced apoptosis and the collapse of the membrane potential in response to StSp. Moreover, the increase in caspase-3, -8, and -9 activities in response to StSp was returned to control levels with RBM3 overexpression. These results indicate that increased RBM3 expression decreases muscle cell necrosis as well as apoptosis and therefore RBM3 could potentially serve as an intervention for the loss of muscle cell viability during muscle atrophy and muscle diseases.
Ion channels and transporters in cancer. 4. Remodeling of Ca2+ signaling in tumorigenesis: role of Ca2+ transport
Authors: Lee Jane M. , Davis Felicity M. , Roberts-Thomson Sarah J. , Monteith Gregory R.
Published: May 2011

The Ca2+ signal has major roles in cellular processes important in tumorigenesis, including migration, invasion, proliferation, and apoptotic sensitivity. New evidence has revealed that, aside from altered expression and effects on global cytosolic free Ca2+ levels via direct transport of Ca2+, some Ca2+ pumps and channels are able to contribute to tumorigenesis via mechanisms that are independent of their ability to transport Ca2+ or effect global Ca2+ homeostasis in the cytoplasm. Here, we review some of the most recent studies that present evidence of altered Ca2+ channel or pump expression in tumorigenesis and discuss the importance and complexity of localized Ca2+ signaling in events critical for tumor formation.
Electroacupuncture improves rectal distension-induced delay in solid gastric emptying in dogs
Authors: Yin Jieyun , Chen Jiande D. Z.
Published: May 2011

The aim of this study was to investigate the effects and mechanisms of electroacupuncture (EA) on rectal distension (RD)-induced delay in solid gastric emptying in dogs. Gastric emptying of solids was assessed in 12 dogs chronically implanted with a duodenal cannula by collecting samples at different time points from the cannula and measuring the dried weights of the samples. Bethanechol and atropine were used to qualitatively validate the method. In separate experiments, gastric emptying of solids was measured in a number of sessions: control, RD, RD + sham-EA, RD + EA of 6 mA, RD + EA of 3 mA, and RD + EA + naloxone. The method of gastric emptying by collecting and drying gastric chyme from the duodenal cannula was found to be accurate and reliable. Using the method, we found gastric emptying to be accelerated with bethanechol (70.01 ± 8.10% vs. 82.61 ± 4.15%, P = 0.04, vs. control) and delayed with atropine (4.31 ± 1.57%, P < 0.001, vs. control). RD substantially and significantly delayed gastric emptying. EA, but not sham-EA, attenuated delayed gastric emptying induced by RD (sham-EA: 48.79 ± 9.47% vs. EA: 74.28 ± 5.96%, P < 0.01). The effect was more potent with EA of 6 mA than EA of 3 mA and blocked by naloxone. EA is able to attenuate RD-induced delay in gastric emptying of solids, and this ameliorating effect may be mediated via the opioid pathway. EA may have a therapeutic potential for treating delayed gastric emptying attributed to lower gut distension.
Prenatal glucocorticoid exposure in the sheep alters renal development in utero: implications for adult renal function and blood pressure control
Authors: Moritz Karen M. , De Matteo Robert , Dodic Miodrag , Jefferies Andrew J. , Arena Debbie , Wintour E. Marelyn , Probyn Megan E. , Bertram John F. , Singh Reetu R. , Zanini Simone , Evans Roger G.
Published: May 2011

Treatment of the pregnant ewe with glucocorticoids early in pregnancy results in offspring with hypertension. This study examined whether glucocorticoids can reduce nephron formation or alter gene expression for sodium channels in the late gestation fetus. Sodium channel expression was also examined in 2-mo-old lambs, while arterial pressure and renal function was examined in adult female offspring before and during 6 wk of increased dietary salt intake. Pregnant ewes were treated with saline (SAL), dexamethasone (DEX; 0.48 mg/h) or cortisol (CORT; 5 mg/h) over days 26–28 of gestation (term = 150 days). At 140 days of gestation, glomerular number in CORT and DEX animals was 40 and 25% less, respectively, compared with SAL controls. Real-time PCR showed greater gene expression for the epithelial sodium channel (α-, β-, γ-subunits) and Na+-K+-ATPase (α-, β-, γ-subunits) in both the DEX and CORT group fetal kidneys compared with the SAL group with some of these changes persisting in 2-mo-old female offspring. In adulthood, sheep treated with dexamethasone or cortisol in utero had elevated arterial pressure and an apparent increase in single nephron glomerular filtration rate, but global renal hemodynamics and excretory function were normal and arterial pressure was not salt sensitive. Our findings show that the nephron-deficit in sheep exposed to glucocorticoids in utero is acquired before birth, so it is a potential cause, rather than a consequence, of their elevated arterial pressure in adulthood. Upregulation of sodium channels in these animals could provide a mechanistic link to sustained increases in arterial pressure in cortisol- and dexamethasone-exposed sheep, since it would be expected to promote salt and water retention during the postnatal period.
Influence of acetaminophen and ibuprofen on in vivo patellar tendon adaptations to knee extensor resistance exercise in older adults
Authors: Carroll C. C. , Dickinson J. M. , LeMoine J. K. , Haus J. M. , Weinheimer E. M. , Hollon C. J. , Aagaard P. , Magnusson S. P. , Trappe T. A.
Published: May 2011

Millions of older individuals consume acetaminophen or ibuprofen daily and these same individuals are encouraged to participate in resistance training. Several in vitro studies suggest that cyclooxygenase-inhibiting drugs can alter tendon metabolism and may influence adaptations to resistance training. Thirty-six individuals were randomly assigned to a placebo (67 ± 2 yr old), acetaminophen (64 ± 1 yr old; 4,000 mg/day), or ibuprofen (64 ± 1 yr old; 1,200 mg/day) group in a double-blind manner and completed 12 wk of knee extensor resistance training. Before and after training in vivo patellar tendon properties were assessed with MRI [cross-sectional area (CSA) and signal intensity] and ultrasonography of patellar tendon deformation coupled with force measurements to obtain stiffness, modulus, stress, and strain. Mean patellar tendon CSA was unchanged ( P > 0.05) with training in the placebo group, and this response was not influenced with ibuprofen consumption. Mean tendon CSA increased with training in the acetaminophen group (3%, P < 0.05), primarily due to increases in the mid (7%, P < 0.05) and distal (8%, P < 0.05) tendon regions. Correspondingly, tendon signal intensity increased with training in the acetaminophen group at the mid (13%, P < 0.05) and distal (15%, P = 0.07) regions. When normalized to pretraining force levels, patellar tendon deformation and strain decreased 11% ( P < 0.05) and stiffness, modulus, and stress were unchanged ( P > 0.05) with training in the placebo group. These responses were generally uninfluenced by ibuprofen consumption. In the acetaminophen group, tendon deformation and strain increased 20% ( P < 0.05) and stiffness (−17%, P < 0.05) and modulus (−20%, P < 0.05) decreased with training. These data suggest that 3 mo of knee extensor resistance training in older adults induces modest changes in the mechanical properties of the patellar tendon. Over-the-counter doses of acetaminophen, but not ibuprofen, have a strong influence on tendon mechanical and material property adaptations to resistance training. These findings add to a growing body of evidence that acetaminophen has profound effects on peripheral tissues in humans.
Changes in reward contingency modulate the trial-to-trial variability of hippocampal place cells
Authors: Wikenheiser Andrew M. , Redish A. David
Published: May 2011

Pyramidal cells in the rodent hippocampus often exhibit clear spatial tuning. Theories of hippocampal function suggest that these “place cells” implement multiple, independent neural representations of position (maps), based on different reference frames or environmental features. Consistent with the “multiple maps” theory, previous studies have shown that manipulating spatial factors related to task performance modulates the within-session variability (overdispersion) of cells in the hippocampus. However, the influence of changes in reward contingency on overdispersion has not been examined. To test this, we first trained rats to collect food from three feeders positioned around a circular track (task1). When subjects were proficient, the reward contingency was altered such that every other feeder delivered food (task2). We recorded ensembles of hippocampal neurons as rats performed both tasks. Place cell overdispersion was high during task1but decreased significantly during task2, and this increased reliability could not be accounted for by changes in running speed or familiarity with the task. Intuitively, decreased variability might be expected to improve neural representations of position. To test this, we used Bayesian decoding of hippocampal spike trains to estimate subjects' location. Neither the amount of probability decoded to subjects' position (local probability) nor the difference between estimated position and true location (decoding accuracy) differed between tasks. However, we found that hippocampal ensembles were significantly more self-consistent during task2performance. These results suggest that changes in task demands can affect the firing statistics of hippocampal neurons, leading to changes in the properties of decoded neural representations.
Effect of presynaptic membrane potential on electrical vs. chemical synaptic transmission
Authors: Evans Colin G. , Ludwar Bjoern Ch. , Kang Timothy , Cropper Elizabeth C.
Published: May 2011

The growing realization that electrical coupling is present in the mammalian brain has sparked renewed interest in determining its functional significance and contrasting it with chemical transmission. One question of interest is whether the two types of transmission can be selectively regulated, e.g., if a cell makes both types of connections can electrical transmission occur in the absence of chemical transmission? We explore this issue in an experimentally advantageous preparation. B21, the neuron we study, is an Aplysia sensory neuron involved in feeding that makes electrical and chemical connections with other identified cells. Previously we demonstrated that chemical synaptic transmission is membrane potential dependent. It occurs when B21 is centrally depolarized prior to and during peripheral activation, but does not occur if B21 is peripherally activated at its resting membrane potential. In this article we study effects of membrane potential on electrical transmission. We demonstrate that maximal potentiation occurs in different voltage ranges for the two types of transmission, with potentiation of electrical transmission occurring at more hyperpolarized potentials (i.e., requiring less central depolarization). Furthermore, we describe a physiologically relevant type of stimulus that induces both spiking and an envelope of depolarization in the somatic region of B21. This depolarization does not induce functional chemical synaptic transmission but is comparable to the depolarization needed to maximally potentiate electrical transmission. In this study we therefore characterize a situation in which electrical and chemical transmission can be selectively controlled by membrane potential.
Nicotinic excitation of serotonergic projections from dorsal raphe to the nucleus accumbens
Authors: Chang Ben , Daniele Claire A. , Gallagher Keith , Madonia Michelle , Mitchum Robert D. , Barrett Lindy , Vezina Paul , McGehee Daniel S.
Published: May 2011

Tobacco use is a major public health problem, and although many smokers report that they want to quit, only a small percentage succeed. Side effects associated with nicotine withdrawal, including depression, anxiety, and restlessness, certainly contribute to the low success rate. The dorsal raphe nucleus (DRN) is a serotonergic center with many functions, including control of mood and emotional state. We investigated the effect of nicotine on DRN neurons that project to the nucleus accumbens (NAc), an area involved in reward-related behaviors. Using a retrograde labeling method, we found that 75% of DRN-NAc projection neurons are serotonergic. In coronal slices that include the DRN, whole cell recordings were conducted on neurons identified by fluorescent backlabeling from NAc or randomly selected within the nucleus. Nicotine increased action potential firing rates in a subset of DRN neurons. Voltage-clamp recording revealed nicotinic acetylcholine receptor (nAChR)-mediated inward currents that contribute to the nicotine-induced excitation. Nicotinic receptors also indirectly affect excitability by modulating synaptic inputs to these neurons. Nicotine enhanced excitatory glutamatergic inputs to a subset of DRN-NAc projection neurons, while inhibitory γ-aminobutyric acid (GABA)ergic inputs were modulated either positively or negatively in a subset of these neurons. The net effect of nAChR activation is enhancement of serotonergic output from DRN to the NAc, which may contribute to the effects of nicotine on mood and affect.
Tradeoffs to Thermal Acclimation: Energetics and Reproduction of a Reef Coral with Heat TolerantSymbiodiniumType-D
Authors: Jones Alison M. , Berkelmans Ray
Published: May 2011

The photo-physiological characteristics of thermo-tolerantSymbiodiniumtypes have been postulated to have negative effects on the energetics of the reef corals by reducing fitness. To investigate this, two key and inextricably coupled indicators of fitness, lipids and reproduction, were monitored in colonies of the broadcast-spawning coralAcropora milleporaover a two-year period that included a natural bleaching event. In the absence of bleaching ITS1-type clade D predominant colonies had 26% lower stored lipids compared to C2 colonies. At spawning time, this correlated with 28% smaller eggs in type-D colonies. This energetic disparity is expected to have reduced larval duration and settlement-competency periods in type-D compared to type-C2 colonies. More importantly, irrespective of the effect of genotype, the fitness of all corals was adversely affected by the stress of the bleaching event which reduced prespawning lipids by 60% and halved the number of eggs compared to the previous year. Our results extend work that has shown that direct temperature stress and symbiont change are likely to work in concert on corals by demonstrating that the lipids and reproduction of the reef building corals on tropical reefs are likely to be impaired by these processes as our climate warms.
Survivable Self-Organization for Prolonged Lifetime in Wireless Sensor Networks
Authors: Hasan Mohammad M. , Jue Jason P.
Published: May 2011

More often than not, wireless sensor networks (WSNs) are deployed in adverse environments, where failures of sensor nodes and disruption of connectivity are regular phenomena. Therefore, the organization or clustering of WSNs needs to be survivable to the changing situations. On the other hand, energy efficiency in WSNs remains the main concern to achieve a longer network lifetime. In this work, we associate survivability and energy efficiency with the clustering of WSNs and show that such a proactive scheme can actually increase the lifetime. We present an easy-to-implement method named DED (distributed, energy-efficient, and dual-homed clustering) which provides robustness for WSNs without relying on the redundancy of dedicated sensors, that is, without depending on node density. DED uses the information already gathered during the clustering process to determine backup routes from sources to observers, thus incurring low message overhead. It does not make any assumptions about network dimension, node capacity, or location awareness and terminates in a constant number of iterations. The correctness of the algorithm is proved analytically. Simulation results comparing with contemporary approaches demonstrate that our approach is effective both in providing survivability and in prolonging the network lifetime.
Comparison between Certain Equivalent Norms Regarding Some Familiar Properties Implying WFPP
Authors: Fetter Helga , Gamboa de Buen Berta
Published: May 2011

In a Banach space with a basis we define a similar norm to the
norm shown by Lin to make l1 into a space with FPP and make a comparative study of certain geometric properties such as the Opial property, WNS, and uniform nonsquareness of the original space and the space with the new norm.
Aerodynamic Optimization of an Over‐the‐Wing‐Nacelle‐Mount Configuration
Authors: Sasaki Daisuke , Nakahashi Kazuhiro
Published: May 2011

An over‐the‐wing‐nacelle‐mount airplane configuration is known to prevent the noise propagation from jet engines toward ground. However, the configuration is assumed to have low aerodynamic efficiency due to the aerodynamic interference effect between a wing and a nacelle. In this paper, aerodynamic design optimization is conducted to improve aerodynamic efficiency to be equivalent to conventional under‐the‐wing‐nacelle‐mount configuration. The nacelle and wing geometry are modified to achieve high lift‐to‐drag ratio, and the optimal geometry is compared with a conventional configuration. Pylon shape is also modified to reduce aerodynamic interference effect. The final wing‐fuselage‐nacelle model is compared with the DLR F6 model to discuss the potential of Over‐the‐Wing‐Nacelle‐Mount geometry for an environmental‐friendly future aircraft.
KIR/HLA Interactions and Pathogen Immunity
Authors: Jamil Khaleel M. , Khakoo Salim I.
Published: May 2011

The innate immune system is the first line of defence in response to pathogen infection. Natural killer (NK) cells perform a vital role in this response with the ability to directly kill infected cells, produce cytokines, and cross‐talk with the adaptive immune system. These effector functions are dependent on activation of NK cells which is determined by surface receptor interactions with ligands on target cells. Of these receptors, the polymorphic killer immunoglobulin‐like receptors (KIRs), which interact with MHC class 1 (also highly polymorphic), are largely inhibitory, and exhibit substantial genetic diversity. The result is a significant variation of NK cell repertoire between individuals and also between populations, with a multitude of possible KIR:HLA combinations. As each KIR:ligand interaction may have differential effects on NK cell activation and inhibition, this diversity has important potential influences on the host response to infections. Genetic studies have demonstrated associations between specific KIR:ligand combinations and the outcome of viral (and other) infections, in particular hepatitis C and HIV infection. Detailed functional studies are not required to define the mechanisms underpinning these disease associations.
Multiphoton Ionization and Fragmentation of Hydrogen Chloride: A Diatomic Still Good for a Surprise
Authors: Maul Christof , Chichinin Alexey I. , Gericke Karl-Heinz
Published: May 2011

The competition between multiphoton ionization and fragmentation in the diatomic molecule hydrogen chloride is reviewed. Emphasis is laid on recent experimental results employing chemical imaging methods in order to obtain kinetic energy distributions and angular distributions of photoproducts. The energy range considered is 15 to 20 eV, equivalent to the absorption of three or four photons in the ultraviolet wavelength range.
The role of Rydberg states as resonantly excited intermediate states in the ionization/fragmentation processes is assessed. Mixing among Σ1+ states gives rise to peculiarly shaped double minimum potential energy curves which allow for the production of hydrogen and chlorine atomic and ionic fragments via several competing pathways, in addition to the production of molecular HCl+ ions.
States with different electronic properties show a qualitatively different behaviour from Σ+ states. Accidental resonances between states of differing orbital angular momentum or multiplicity serve to override these differences and cause subtle as well as significant deviations from the unperturbed behaviour.
Impact of a Multimodal Antimicrobial Stewardship Program onPseudomonas aeruginosaSusceptibility and Antimicrobial Use in the Intensive Care Unit Setting
Authors: Slain Douglas , Sarwari Arif R. , Petros Karen O. , McKnight Richard L. , Sager Renee B. , Mullett Charles J. , Wilson Alison , Thomas John G. , Moffett Kathryn , Palmer H. Carlton , Dedhia Harakh V.
Published: May 2011

Objective. To study the impact of our multimodal antibiotic stewardship program onPseudomonas aeruginosasusceptibility and antibiotic use in the intensive care unit (ICU) setting.Methods. Our stewardship program employed the key tenants of published antimicrobial stewardship guidelines. These included prospective audits with intervention and feedback, formulary restriction with preauthorization, educational conferences, guidelines for use, antimicrobial cycling, and de-escalation of therapy. ICU antibiotic use was measured and expressed as defined daily doses (DDD) per 1,000 patient-days.Results. Certain temporal relationships between antibiotic use and ICU resistance patterns appeared to be affected by our antibiotic stewardship program. In particular, the ICU use of intravenous ciprofloxacin and ceftazidime declined from 148 and 62.5 DDD/1,000 patient-days to 40.0 and 24.5, respectively, during 2004 to 2007. An increase in the use of these agents and resistance to these agents was witnessed during 2008–2010. Despite variability in antibiotic usage from the stewardship efforts, we were overall unable to show statistical relationships withP. aeruginosaresistance rate.Conclusion. Antibiotic resistance in the ICU setting is complex. Multimodal stewardship efforts attempt to prevent resistance, but such programs clearly have their limits.
Innate Immune Sensors and Gastrointestinal Bacterial Infections
Authors: Hold Georgina L. , Mukhopadhya Indrani , Monie Tom P.
Published: May 2011

The gastrointestinal microbiota is a major source of immune stimulation. The interaction between host pattern-recognition receptors and conserved microbial ligands profoundly influences infection dynamics. Identifying and understanding the nature of these interactions is a key step towards obtaining a clearer picture of microbial pathogenesis. These interactions underpin a complex interplay between microbe and host that has far reaching consequences for both. Here, we review the role of pattern recognition receptors in three prototype diseases affecting the stomach, the small intestine, and large intestine, respectively (Helicobacter pyloriinfection,Salmonellainfection, and inflammatory bowel disease). Specifically, we review the nature and impact of pathogen:receptor interactions, their impact upon pathogenesis, and address the relevance of pattern recognition receptors in the development of therapies for gastrointestinal diseases.
L X-Rays RYIED Oscillations and Proton-NMRD of Gd2O3 Nanoparticles
Authors: Taborda A. , Reis M. A. , Chaves P. C. , Carvalho A.
Published: May 2011

Recently, it was shown that relative yields of X-rays induced by ion impact are not constant but depend on beam energy. In the framework of this problem, pellets of Gd2O3 and a Gd chelate, Gd-DOTA, as well as a 5 nm in diameter Gd2O3 nanoparticles dispersion on a polycarbonate Nuclepore filter, were studied. In this work, it is shown that after subtraction of known matrix effects, relative yield
variations still present different patterns for Gd2O3 pellet and Gd2O3 nanoparticles. Proton NMRD T1(ω) data for Gd2O3 nanoparticles and Gd-DOTA water solutions published by Bridot et al. and Toth et al., respectively, were reproduced using a model for paramagnetic substances in water solutions and identical electronic relaxation times. The analysis of both techniques results points collective electron behaviour as the explanation for the different observations on X-ray data of Gd2O3 nanoparticles and bulk material.
The Spectral Scale of a Self‐Adjoint Operator in a Semifinite von Neumann Algebra
Authors: Pavone Christopher M.
Published: May 2011

We extend Akemann, Anderson, and Weaver′s Spectral Scale
definition to include selfadjoint operators from semifinite von Neumann algebras.
New illustrations of spectral scales in both the finite and semifinite
von Neumann settings are presented. A counterexample to a conjecture made
by Akemann concerning normal operators and the geometry of the their perspective
spectral scales (in the finite setting) is offered.
Idealization of Some Topological Concepts
Authors: Al-Nashef B. , Al-Zoubi K.
Published: May 2011

An approach is followed here to generate a new topology on a set X from an ideal ℐ and a family 𝒮 of subsets of X. The so‐obtained topology is related to other known topologies on X. The cases treated here include the one when 𝒮 = Tα is taken, then the case when 𝒮 = RO(X, T) is considered. The approach is open to apply to other choices of 𝒮. As application, some known results are obtained as corollaries to those results appearing here. In the last part of this work, some ideal‐continuity concepts are studied, which originate from some previously known terms and results.
The Stability Cone for a Matrix Delay Difference Equation
Authors: Kipnis M. M. , Malygina V. V.
Published: May 2011

We construct a stability cone, which allows us to analyze the stability of the
matrix delay difference equation xn = Axn−1 + Bxn−k. We assume that A and B are
m × m simultaneously triangularizable matrices. We construct m points in ℝ3 which are
functions of eigenvalues of matrices A,  B such that the equation is asymptotically stable
if and only if all the points lie inside the stability cone.
Prevalence of Metabolic Syndrome in Urban India
Authors: Sawant Apurva , Mankeshwar Ranjit , Shah Swarup , Raghavan Rani , Dhongde Gargi , Raje Himanshu , D'souza Shoba , Subramanium Aarti , Dhairyawan Pradnya , Todur Seema , Ashavaid Tester F.
Published: May 2011

Background. Metabolic syndrome (MS) is characterised by a constellation of individual risk factors of cardiovascular disease. Materials and Methods. The current study was a population-based survey of cohort of subjects in the metropolitan city of Mumbai. A total of 548 subjects, who attended the CARDIAC evaluation camp, were recruited in the study. Participants with complete fasting lipid profiles, blood glucose, and known cardiac risk markers were evaluated. Results. On applying modified NCEP ATP III, we found out that nearly of the subjects had at least one abnormal parameter. We found the prevalence of MS in our study population to be . The prevalence of MS in males was almost double than females (). The overall prevalence of BMI (>23 kg/m2) was . Increased hypertriglyceridemia and decreased levels of HDL-C were found to be more in males (). Conclusion. The low percentage of subjects with normal and controlled parameters suggests that there is a need for awareness programs and lifestyle interventions for the prevention and control of MS.
A Novel Function of Junctional Adhesion Molecule-C in Mediating Melanoma Cell Metastasis
Authors: Langer Harald F. , Orlova Valeria V. , Xie Changping , Kaul Sunil , Schneider Darius , Lonsdorf Anke S. , Fahrleitner Manuela , Choi Eun Young , Dutoit Vanessa , Pellegrini Manuela , Grossklaus Sylvia , Nawroth Peter P. , Baretton Gustavo , Santoso Sentot , Hwang Sam T. , Arnold Bernd , Chavakis Triantafyllos
Published: May 2011

Hematogenous dissemination of melanoma is a life-threatening complication of this malignant tumor. Here, we identified junctional adhesion molecule-C (JAM-C) as a novel player in melanoma metastasis to the lung. JAM-C expression was identified in human and murine melanoma cell lines, in human malignant melanoma, as well as in metastatic melanoma including melanoma lung metastasis. JAM-C expressed on both murine B16 melanoma cells as well as on endothelial cells promoted the transendothelial migration of the melanoma cells. We generated mice with inactivation of JAM-C. JAM-C−/− mice as well as endothelial-specific JAM-C–deficient mice displayed significantly decreased B16 melanoma cell metastasis to the lung, whereas treatment of mice with soluble JAM-C prevented melanoma lung metastasis. Together, JAM-C represents a novel therapeutic target for melanoma metastasis. Cancer Res; 71(12); 4096–105. ©2011 AACR.
IL-7 Contributes to the Progression of Human T-cell Acute Lymphoblastic Leukemias
Authors: Silva Ana , Laranjeira Angelo B.A. , Martins Leila R. , Cardoso Bruno A. , Demengeot Jocelyne , Yunes J. Andrés , Seddon Benedict , Barata João T.
Published: May 2011

The importance of microenvironmental factors for driving progression in leukemia has been debated. Previous evidence has pointed to interleukin-7 (IL-7), a fundamental cytokine to normal T-cell development and homeostasis, as an important determinant of the viability and proliferation of T-cell acute lymphoblastic leukemia (T-ALL) cells in vitro. In this study, we report that IL-7 is also a critical determinant of T-ALL progression. T-ALL cell lines and primary T-ALL samples initiated leukemia more slowly when engrafted to immunocompromised Rag2−/−IL2rg−/− mice lacking IL-7. This effect was not related to reduced engraftment or homing of transplanted cells to the bone marrow. Instead, IL-7 deficiency diminished expansion of leukemia cells in the bone marrow and delayed leukemia-associated death of transplanted mice. Moreover, infiltration of different organs by T-ALL cells, which characterizes patients with advanced disease, was more heterogeneous and generally less efficient in IL-7–deficient mice. Leukemia progression was associated with increased Bcl-2 expression and cell viability, reduced p27Kip1 expression, and decreased cell-cycle progression. Clinical measurements of IL-7 plasma levels and IL-7 receptor (IL-7R) expression in T-ALL patients versus healthy controls confirmed that IL-7 stimulates human leukemia cells. Our results establish that IL-7 contributes to the progression of human T-cell leukemia, and they offer preclinical validation of the concept that targeting IL-7/IL-7R signaling in the tumor microenvironment could elicit therapeutic effects in T-ALL. Cancer Res; 71(14); 4780–9. ©2011 AACR.
Telomere Dysfuction Promotes Metastasis in a TERC Null Mouse Model of Head and Neck Cancer
Authors: Bojovic Bojana , Crowe David L.
Published: May 2011

Squamous cell carcinoma arises from highly proliferative basal layer epithelial cells, which normally divide for a short time before detaching from the basement membrane and undergoing terminal differentiation. Basal layer cells in stratified epithelia express the reverse transcriptase known as telomerase. Most human cells do not express telomerase and therefore are subject to loss of telomeric DNA with age due to the inability of lagging strand synthesis to completely replicate chromosomal ends. Late generation telomerase deficient mice exhibit signs of premature aging including reduced function of proliferating cellular compartments. We examined development of squamous cell carcinoma in a telomerase deficient murine background with long and short telomeres. G1 Terc-/- mice (long telomeres) had fewer lymph node metastases, which correlated with increased numbers of apoptotic cells in these tumors compared with wild-type mice. However, G5 Terc-/- mice with short telomeres had increased metastatic tumor burden similar to wild type mice. This increased metastasis correlated with genomic instability and aneuploidy in tumor cells from G5 Terc-/- mice. A number of similarities with human SCC were noted in the mouse model, and dramatic differences in global gene expression profiles were shown between primary and metastatic tumors. We concluded that telomere shortening promotes metastatic tumor development in a Terc null mouse model of head and neck cancer. Mol Cancer Res; 9(7); 901–13. ©2011 AACR.
Chronic Urticaria: Etiology and Natural Course in Children
Authors: Sahiner Umit M. , Civelek Ersoy , Tuncer Ayfer , Yavuz S. Tolga , Karabulut Erdem , Sackesen Cansin , Sekerel Bülent E.
Published: May 2011

Background: Chronic spontaneous urticaria (CSU) in childhood is infrequent, and information about the disease in children is limited. We attempted to investigate its etiologic factors, natural course, and predictors of prognosis. Methods: All children aged ≤18 years followed for CSU during an 8-year period were analyzed retrospectively, and the final outcomes were queried via a telephone interview. Results: One hundred patients (male/female ratio 1.27) with a median age of 9.2 years (range 0.7–17.2) at symptoms onset were evaluated. The median follow-up was 2.5 years (range 0.2–18.1). An autologous serum skin test was positive in 46.7% of the subjects (n = 45), with a female predominance (71.4%) (p = 0.023). In 13.8% of the children, ANA titers were over 1/100. Food allergy (n = 1), thyroid autoantibodies (n = 3), possible collagen disease (n = 1), and drug usage (deferoxamine) (n = 1) were found to be associated factors. Infections could not be confirmed as the cause of CSU. Recovery was seen in 16.5, 38.8, and 50.0% of the children after 12, 36, and 60 months, respectively. Though in multivariate analysis none of the factors, including age, gender, autologous serum skin test positivity, the presence of angioedema, or other allergic diseases, appeared to predict the prognosis, in univariate analysis being female and being older than 10 years of age predicted an unfavorable prognosis. Conclusion: The etiology of CSU in children is mainly related to an autoreactive background, as in adults. CSU has a favorable prognosis, and resolution is seen in half of the children within 5 years. Girls older than 10 years may have an unfavorable prognosis.
Incidence of Anaphylaxis in Hospitalized Patients
Authors: Tejedor Alonso Miguel A. , Moro Mar Moro , Hernández Jesús Esteban , Múgica García Maria V. , Albelda Concepcion Vila , Ingelmo Ana Rosado , Encinas Montserrat Pérez , Lorena Wendy , Abreu Almanzar
Published: May 2011

Background: Only two studies have analyzed the incidence of anaphylaxis during admission to hospital. We have analyzed the incidence of anaphylaxis among hospitalized patients and determined the timing of and risk factors for episodes of anaphylaxis. Methods: Our study was performed between 1999 and 2005. We used the definition of anaphylaxis of the NIAID-FAAN symposium. Cases of anaphylaxis were extracted from an official database of discharge diagnoses coded according to the International Classification of Diseases, Clinical Modification, Ninth Revision (ICD-9-CM), Sixth Edition. Specific and generic codes related to anaphylaxis were chosen. This strategy revealed 83.3% (95% confidence interval, CI, 47–99%) of all episodes of anaphylaxis in a pilot study. The incidence of episodes of anaphylaxis and the hazard ratios were calculated for the different variables. Results: We observed a crude cumulative incidence of 1.5 episodes of anaphylaxis (95% CI, 0.9–1.9) in 5,000 admissions. The cumulative incidence according to the Standardized European Population was 1.6 cases in 5,000 admissions (95% CI, 0.8–2.3). Cox regression analysis showed that anaphylaxis occurs mainly in young people (0.97; 95% CI, 0.95–0.99) and its incidence differs according to the clinical unit. The Vascular Surgery Unit had the highest incidence rate (hazard ratio 7.7; 95% CI, 2.1–28.6). Males had a lower risk of suffering from anaphylaxis than females (0.5; 95% CI, 0.2–0.9). Conclusions: Anaphylaxis is a very rare event among hospitalized patients. Female gender, young age and admission to the Vascular Surgery Unit favored the occurrence of episodes of anaphylaxis among hospitalized patients.
Bone Cell Autophagy Is Regulated by Environmental Factors
Authors: Zahm Adam M. , Bohensky Jolene , Adams Christopher S. , Shapiro Irving M. , Srinivas Vickram
Published: May 2011

The goal of this investigation was to ascertain whether bone cells undergo autophagy and to determine if this process is regulated by environmental factors. We showed that osteocytes in both murine and human cortical bone display a punctuate distribution of microtubule-associated protein light chain 3, indicative of autophagy. In addition, we noted a basal level of autophagy in preosteocyte-like murine long bone-derived osteocytic (MLO)-A5 cells. Autophagy was upregulated following nutrient deprivation and hypoxic culture, stress conditions that osteocytes encounter in vivo. Furthermore, in response to calcium stress, the transcription factor hypoxia inducible factor 1 regulated MLO-A5 autophagy. Finally, we showed that the more differentiated MLO-Y4 osteocyte-like cells exhibited a significant basal autophagic flux. Based on these findings, we suggest that raising the level of autophagic flux is a mechanism by which differentiated bone cells survive in a stressful environment.
Beyond Antiangiogenesis: Intratumorally Injected Bevacizumab Plays a Cisplatin-Sensitizing Role in Squamous Cell Carcinomas in Mice
Authors: Wang Yixiang , Dong Ling , Bi Qingwei , Ge Xiyuan , Zhang Xiaoxia , Wu Dengcheng , Fu Jia , Zhang Chengfei , Wang Cunyu , Li Shenglin
Published: May 2011

Background: The anticancer mechanism of bevacizumab beyond antiangiogenesis remains unclear. Here, we investigated whether intratumorally injected bevacizumab could serve as an effective cisplatin sensitizer in squamous cell carcinoma (SCC) in vivo. Methods: Hela and SCC-VII experimental SCC models were established to investigate the anticancer effect of bevacizumab plus cisplatin and the underlying mechanism using immunostaining, TUNEL, and Western blot assays. Results: Bevacizumab-cisplatin therapy markedly inhibited tumor growth and significantly increased survival in both Hela- and SCC-VII-bearing mice compared with single-agent treatments and the untreated control, respectively. Immunostaining of CD34 showed that intratumorally injected bevacizumab significantly reduced microvessel density in bevacizumab-cisplatin and bevacizumab-alone groups of Hela xenografts. TUNEL assay showed that bevacizumab-cisplatin significantly promoted tumor cell apoptosis compared with single-agent treatments and untreated controls in these 2 models. Western blot showed that upregulation of cleaved caspase-3 and downregulation of Bcl-2 and p-Erk expressions are part of the molecular mechanisms beyond angiogenesis which contribute to the cooperative effect of bevacizumab plus cisplatin in the 2 SCC models. Conclusions: Bevacizumab functions not only as an angiogenesis inhibitor but also as a chemosensitizer which enhances the cytotoxicity of cisplatin and promotes apoptosis of SCC cells.
Hemodynamic Impact of Fetal-Variant Willisian Circle on Cerebral Circulation: A Duplex Ultrasonography Study
Authors: Hong Ji Man , Lee Jin Soo , Shin Dong Hoon , Yong Seok Woo
Published: May 2011

Background/Aims: The Willisian circle can redistribute the vertebrobasilar flow and the reduction of flow is attributable to orthrostatic presyncope. To evaluate this hemodynamic aspect, we investigated anterior and posterior cerebral blood flow (CBF) volume distributions according to the variation of the Willisian circle, and compared those between controls and patients with presyncope. Methods: Subjects underwent cerebral CT angiography and color-coded duplex sonography measuring flow volumes of the internal carotid artery (ICAs) and vertebral artery (VAs). According to clinical manifestations and Willisian configurations, CBF volume patterns were analyzed. Results: Between the presyncope (n = 25) and control groups (n = 76), the prevalence of fetal-variant Willisian configuration (48% vs. 21%, p = 0.004) and posterior CBF volume (126 ± 85 vs. 165 ± 64 ml/min, p = 0.015) was significantly different, but A1 morphology, anterior CBF, and total CBF volumes were not. Total CBF volume was 769 ± 176 ml/min (80% ICAs and 20% VAs). The posterior CBF volume lowered significantly (172 ± 70 vs. 122 ± 62 vs. 92 ± 44 ml/min; p < 0.001) toward the two-sided fetal type variation, although total CBF volume is similar among the three groups (p = 0.742). Conclusions: The present study suggests that Willisian configuration contributes to orthostatic presyncope and flow distribution of the cerebral circulation.
Paroxysmal Nocturnal Hemoglobinuria after Autologous Stem Cell Transplantation: Extinction of the Clone during Treatment with Eculizumab – Pathophysiological Implications of a Unique Clinical Case
Authors: Pulini Stefano , Marando Ludovica , Natale Annalisa , Pascariello Caterina , Catinella Virginia , Del Vecchio Luigi , Risitano Antonio M. , Fioritoni Giuseppe
Published: May 2011

The clinical and biological spectrum of paroxysmal nocturnal hemoglobinuria (PNH) is variable, ranging from classical hemolytic forms to PNH associated with aplastic anemia or other bone marrow (BM) failure syndromes. We report a previously undescribed case of PNH occurring after autologous stem cell transplantation (ASCT) in a patient affected by relapsing non-Hodgkin’s lymphoma. The intensive chemotherapy and the ASCT resulted in a contraction of the effective hematopoietic stem cell (HSC) pool and a derangement of the immune system. The delayed engraftment and the BM hypoplasia represented a favorable environment for the expansion of the pathological clone. This case is paradigmatic even for the unexpected trend of the PNH clone during treatment with the terminal complement inhibitor eculizumab; in fact, the clone reduced until undergoing unexpected extinction, i.e. the recovery of normal hematopoiesis. Eculizumab seems not to play a direct role in HSC kinetics; the clinical remission probably occurred because the environmental conditions that led to the expansion of the PNH clone were transient and disappeared.
Population Pharmacokinetics of a Novel Histone Deacetylase Inhibitor, Cyclo{(2S)-2-Amino-8-[(Aminocarbonyl)Hydrazono] Decanoyl-1-L-Tryptophyl-L-Isoleucyl-(2R)-2-Piperidinecarbonyl} (SD-2007), and Its Metabolic Conversion to Apicidin after Intravenous Injection and Oral Administration in Rats
Authors: Shin Beom Soo , Bulitta Jürgen B. , Hong Deok Ki , Kim Hye Youn , Kim Min Ki , Choi Yohan , Lee Jong Bong , Hwang Sang Wook , Lee Mann Hyung , Yoo Sun Dong
Published: May 2011

Background: This study assessed the population pharmacokinetics and metabolic conversion of a novel histone deacetylase (HDAC) inhibitor, SD-2007, into its active metabolite, apicidin, in rats. Methods: SD-2007 was given to rats by intravenous injection (4 mg/kg) and oral administration (40 mg/kg). Serum concentrations of SD-2007 and apicidin were determined by LC-MS/MS. All concentrations were analyzed using a population pharmacokinetic model with 9 compartments in S-ADAPT. Results: The area under the curve for apicidin was 96 ± 16 mg·h/ml after 4 mg/kg administered intravenously and 2,455 ± 1,211 mg·h/ml after 40 mg/kg given orally. The population pharmacokinetic model described all profiles well. After oral administration of SD-2007, the median absolute bioavailability of SD-2007 was 6.67% (range 3.83–9.89) and the median apparent bioavailability was 22.3% (range 15.7–35.8) for apicidin, whereas only a median of 8.85% (range 7.57–9.34) of an intravenous SD-2007 dose was converted to apicidin. Conclusions: Oral SD-2007 displayed a substantial presystemic metabolism to active apicidin. The high serum concentrations of apicidin after oral administration of SD-2007 may cause significant HDAC inhibition.