bluuebunny/crossref_metadata_2025 huggingface dataset:
CONSERVATION OF THE STRESS TENSOR IN PERTURBATIVE INTERACTING QUANTUM FIELD THEORY IN CURVED SPACETIMES
Authors: HOLLANDS STEFAN , WALD ROBERT M.
Published: May 2005

We propose additional conditions (beyond those considered in our previous papers) that should be imposed on Wick products and time-ordered products of a free quantum scalar field in curved spacetime. These conditions arise from a simple "Principle of Perturbative Agreement": for interaction Lagrangians L1 that are such that the interacting field theory can be constructed exactly — as occurs when L1 is a "pure divergence" or when L1 is at most quadratic in the field and contains no more than two derivatives — then time-ordered products must be defined so that the perturbative solution for interacting fields obtained from the Bogoliubov formula agrees with the exact solution. The conditions derived from this principle include a version of the Leibniz rule (or "action Ward identity") and a condition on time-ordered products that contain a factor of the free field φ or the free stress-energy tensor Tab. The main results of our paper are (1) a proof that in spacetime dimensions greater than 2, our new conditions can be consistently imposed in addition to our previously considered conditions and (2) a proof that, if they are imposed, then for any polynomial interaction Lagrangian L1 (with no restriction on the number of derivatives appearing in L1), the stress-energy tensor Θab of the interacting theory will be conserved. Our work thereby establishes (in the context of perturbation theory) the conservation of stress-energy for an arbitrary interacting scalar field in curved spacetimes of dimension greater than 2. Our approach requires us to view time-ordered products as maps taking classical field expressions into the quantum field algebra rather than as maps taking Wick polynomials of the quantum field into the quantum field algebra.
LATTICE THERMAL CONDUCTIVITY IN A HOLLOW SILICON NANOWIRE
Authors: HUANG WEI-QING , CHEN KE-QIU , SHUAI Z. , WANG LINGLING , HU WANGYU
Published: May 2005

We theoretically investigate the lattice thermal conductivity of a hollow Si nanowire under the relaxation time approximation. The results show that the thermal conductivity in such structure is decreased markedly below the bulk value due to phonon confinement and boundary scattering. The thermal conductivities under different scattering mechanisms are given, and it is found that the boundary scattering is dominant resistive process for the decrease of the thermal conductivity.
COMPARISION OF CRITICAL PARAMETERS OF POLYMERIZATION AND GELATION PROCESSES: A FAST TRANSIENT FLUORESCENCE STUDY
Authors: KAYA DEMET , PEKCAN ÖNDER
Published: May 2005

The fast transient fluorescence technique was used to study free-radical polymerization and crosslinking copolymerization of styrene. Ethylene glycol dimethacrylate and Pyrene were used as crosslinking agent and fluorescence probe, respectively. The fluorescence lifetimes of Pyrene from its decay traces were measured and used to monitor the vitrification processes at various temperatures. Changes in the viscosity due to polymer formation dramatically enhanced the fluorescent yield of pyrene molecules. This effect is used to monitor the polymerization and crosslinking copolymerization of Styrene as a function of time, at various temperatures. The results are interpreted in the view of static percolation theory. The critical exponents β and γ for vitrified fraction and average degree of polymerization were found to be 0.39±0.012; 1.62±0.036 and 0.39±0.004; 1.69±0.064 in agreement with percolation results for polymerization and gelation processes, respectively. Activation energies for polymerization and gelation (ΔEP and ΔEG) were measured and found to be 112.0±4 and 86.9±4 kJ mol-1, respectively.
THERMODYNAMIC PROPERTIES OF 4f- AND 5f-SHELL METALS AT FINITE TEMPERATURES: MEAN-FIELD POTENTIAL APPROACH IN CONJUNCTION WITH LOCAL PSEUDOPOTENTIAL
Authors: BHATT N. K. , VYAS P. R. , JANI A. R. , GOHEL V. B.
Published: May 2005

The thermodynamic properties of 4f- and 5f-shell metals have been studied at high temperatures using mean-field potential approach. The MFP seen by the lattice ion is constructed in terms of the total energy-volume relation using local pseudopotentials due to Pandya et al. [Physica B 307, 138 (2001)]. We have calculated static compression, shock-wave compression, volume thermal expansion, isothermal and adiabatic bulk moduli ( BTand BS), specific heats ( CVand CP), thermodynamic Grüneisen parameter (γth), anharmonic contribution to the specific heat and temperature along shock Hugoniot for 4f (γ- Ce )- and 5f (fcc-Th) -shell metals. The results are well compared with the other theoretical and experimental findings, which ensure the use of pseudopotentials for studying thermodynamic properties at higher temperatures in case of lanthanides and actinides.
GENERALIZED KINETIC AND EVOLUTION EQUATIONS IN THE APPROACH OF THE NONEQUILIBRIUM STATISTICAL OPERATOR
Authors: KUZEMSKY A. L.
Published: May 2005

The method of the nonequilibrium statistical operator developed by D. N. Zubarev is employed to analyze and derive generalized transport and kinetic equations. The degrees of freedom in solids can often be represented as a few interacting subsystems (electrons, spins, phonons, nuclear spins, etc.). Perturbation of one subsystem may produce a nonequilibrium state which is then relaxed to an equilibrium state due to the interaction between particles or with a thermal bath. The generalized kinetic equations were derived for a system weakly coupled to a thermal bath to elucidate the nature of transport and relaxation processes. It was shown that the "collision term" had the same functional form as for the generalized kinetic equations for the system with small interactions among particles. The applicability of the general formalism to physically relevant situations is investigated. It is shown that some known generalized kinetic equations (e.g. kinetic equation for magnons, Peierls equation for phonons) naturally emerges within the NSO formalism. The relaxation of a small dynamic subsystem in contact with a thermal bath is considered on the basis of the derived equations. The Schrödinger-type equation for the average amplitude describing the energy shift and damping of a particle in a thermal bath and the coupled kinetic equation describing the dynamic and statistical aspects of the motion are derived and analyzed. The equations derived can help in the understanding of the origin of irreversible behavior in quantum phenomena.
SPIN FILTERING IN THE DOUBLE-BARRIER STRUCTURE
Authors: LAI HUAN-WEN , ZHAO XUEAN , LI YOU-QUAN
Published: May 2005

In this paper, we study the electron transport properties in the double non-collinear δ-magnetic barriers within 2-dimensional electron gas. We find that the transmission of spin current depends on the relative orientation of each magnetic barrier. In addition to the well-known unpolarized configurations in an antiparallel magnetic barrier structure, we also find that there exists infinite unpolarized structures due to the time-reversal symmetry. These structures will be important in the designs of spin valve.
SUPERCONDUCTIVITY IN TWO-BAND SYSTEM WITH LOW CARRIER DENSITY
Authors: PALISTRANT M. E.
Published: May 2005

The review of works about the study of the thermodynamic properties of the superconductors with energy bands overlapping on Fermi surface is done. The base of the review is Moscalenco's model1 with the formation of cooper pairs of electrons inside each energy band and their transition as a whole entity from one band to another. The model was generalized in order to consider the interband pairings of electrons in addition to the pairings that have been taken into account in Ref. 1. The main system of equations in this theory of superconductivity is derived for the two-band systems at arbitrary density of charge carriers (including the very low densities). The detailed studies of dependences of the temperature of superconducting transition TC, the jump of heat capacity (CS-CN), as well as the chemical potential μ on the density of charge carriers are made. Singularities in the behavior of the two-band superconductors at low densities of charge carriers (μ~TC) are revealed. There has been studies on the influence of the additional pairings of electrons that result in the formation of the cooper pairs of electrons from different energy bands on the thermodynamic properties of the system. Both phonon and non-phonon mechanisms of superconductivity in the BCS scenario of the formation of superconducting pairs (μ>0) have been taken into account. The theory of superconductivity in the mean-field approximation at T = 0 in the picture of Bose condensation of localized pairs (Schaffroth's scenario μ<0) is built. The technique of functional integration with regard to the two-band system is developed and the crossover from Fermi to Bose picture of elementary excitations at T≠0 with the two-particle bound state in the system has been shown. The temperature of Bose condensation TK is determined and the influence of the overlapping of energy bands on Fermi surface onto Bose condensation of localized pairs is studied.
FORMATION AND STABILITY OF A STRONG-COUPLING LARGE BIPOLARON IN THE LIGHTLY DOPED CUPRATES
Authors: DUSHANOV E. , DZHUMANOV S.
Published: May 2005

The ground-state energies of large polaron Ep and bipolaron EB in three-dimensional lightly doped cuprates are calculated variationally taking into account the short- and long-range electron-phonon interactions and Coulomb correlation in the continuum model and adiabatic approximation. The binding energy of a large bipolaron and its stability region are determined as a function of the ratio of dielectric constants η = ε∞/ε0. It is found that the large bipolaron is stable in a broad region of η.
COMBINING MODELICA MODELS WITH DISCRETE EVENT FORMALISMS FOR SIMULATION USING THE DES/M ENVIRONMENT
Authors: PEREIRA REMELHE MANUEL A. , ENGELL SEBASTIAN
Published: May 2005

Technical systems that include complex physical dynamics as well as extensive discrete event control, require powerful modeling and simulation techniques. As the most adequate means for modeling hybrid physical systems, we advocate the use of object-oriented modeling languages such as Modelica. However, the discrete event models often require the use of dedicated graphical editors that cannot be defined appropriately using Modelica. The purpose of the DES/M modeling environment [10] is to provide such editors for different discrete event formalisms and to translate discrete event models automatically into Modelica components such that a discrete event controller can be integrated easily into Modelica models and simulated using standard Modelica software tools. This contribution presents the main concepts used for the representation of several discrete event formalisms in the Modelica language and discusses the class of discrete event formalisms that can be supported by the DES/M environment.
P2X2receptors are essential for [Ca2+]iincreases in response to ATP in cultured rat myenteric neurons
Authors: Ohta Toshio , Kubota Akane , Murakami Matsuka , Otsuguro Ken-ichi , Ito Shigeo
Published: May 2005

We characterized ATP-induced changes in intracellular Ca2+concentration ([Ca2+]i) and membrane current in cultured rat myenteric neurons using ratiometric Ca2+imaging with fura-2 and the whole cell patch-clamp technique, respectively. Neuronal cells were functionally identified by [Ca2+]iresponses to high K+and nicotine, which occurred only in cells positive for neuron-specific protein gene product 9.5 immunoreactivity. ATP evoked a dose-dependent increase of [Ca2+]ithat was greatly decreased by the removal of extracellular Ca2+concentration ([Ca2+]o). The amplitude of the [Ca2+]iresponse to ATP was reduced by half in the presence of voltage-dependent Ca2+channel blockers. In [Ca2+]o-free solution, ATP produced a small transient rise in [Ca2+]isimilar to that induced by P2Y agonists. At −60 mV, ATP evoked a slowly inactivating inward current that was suppressed by the removal of extracellular Na+concentration. The current-voltage relation for ATP showed an inward rectification with the reversal potential of about 0 mV. The apparent rank order of potency for the purinoceptor agonist-induced increases of [Ca2+]iwas ATP ≥ adenosine 5′- O-3-triphosphate ≥ CTP ≥ 2-methylthio-ATP > benzoylbenzoyl-ATP. A similar potency order was obtained with current responses to these agonists. P2 antagonists inhibited inward currents induced by ATP. Ca2+and Mg2+suppressed the ATP-induced current, and Zn2+, Cu2+, and protons potentiated it. RT-PCR and immunocytochemical studies showed the expression of P2X2receptors in cultured rat myenteric neurons. These results suggest that ATP mainly activates ionotropic P2X2receptors, resulting in a [Ca2+]iincrease dependent on [Ca2+]oin rat myenteric neurons. A small part of the ATP-induced [Ca2+]iincrease may be also mediated via a P2Y receptor-related mechanism.
Characterization of the human peptide transporter PEPT1 promoter: Sp1 functions as a basal transcriptional regulator of human PEPT1
Authors: Shimakura Jin , Terada Tomohiro , Katsura Toshiya , Inui Ken-Ichi
Published: May 2005

H+-coupled peptide transporter 1 (PEPT1, SLC15A1) localized at the brush-border membranes of intestinal epithelial cells plays an important role in the intestinal absorption of small peptides and a variety of peptidemimetic drugs. PEPT1 is regulated by various factors, including hormones, dietary conditions, some pharmaceutics, and diurnal rhythm. But there is little information about the transcriptional regulation of PEPT1. In the present study, therefore, we cloned the human (h)PEPT1 promoter region and examined its promoter activity using a human intestinal cell line, Caco-2. Deletion analysis of the hPEPT1 promoter suggested that the region spanning −172 to −35 bp was essential for basal transcriptional activity. This region lacked a TATA-box but contained some GC-rich sites that supposedly bind with the transcription factor Sp1. Mutational analysis revealed that three of these putative Sp1 sites contributed to the transcriptional activity. EMSA showed that Sp1 bound to two GC-rich sites. Furthermore, inhibition of Sp1 binding by mithramycin A treatment significantly reduced the transcriptional activity. Finally, overexpression of Sp1 increased the transcriptional activity in a dose-dependent manner. This study reports the first characterization of the hPEPT1 promoter and shows the significant role of Sp1 in the basal transcriptional regulation of hPEPT1.
A novel small molecule CFTR inhibitor attenuates HCO3− secretion and duodenal ulcer formation in rats
Authors: Akiba Yasutada , Jung Michael , Ouk Samedy , Kaunitz Jonathan D.
Published: May 2005

The cystic fibrosis (CF) transmembrane conductance regulator (CFTR) plays a crucial role in mediating duodenal bicarbonate (HCO3−) secretion (DBS). Although impaired DBS is observed in CF mutant mice and in CF patients, which would predict increased ulcer susceptibility, duodenal injury is rarely observed in CF patients and is reduced in CF mutant mice. To explain this apparent paradox, we hypothesized that CFTR dysfunction increases cellular [HCO3−] and buffering power. To further test this hypothesis, we examined the effect of a novel, potent, and highly selective CFTR inhibitor, CFTRinh-172, on DBS and duodenal ulceration in rats. DBS was measured in situ using a standard loop perfusion model with a pH stat under isoflurane anesthesia. Duodenal ulcers were induced in rats by cysteamine with or without CFTRinh-172 pretreatment 1 h before cysteamine. Superfusion of CFTRinh-172 (0.1–10 μM) over the duodenal mucosa had no effect on basal DBS but at 10 μM inhibited acid-induced DBS, suggesting that its effect was limited to CFTR activation. Acid-induced DBS was abolished at 1 and 3 h and was reduced 24 h after treatment with CFTRinh-172, although basal DBS was increased at 24 h. CFTRinh-172 treatment had no effect on gastric acid or HCO3− secretion. Duodenal ulcers were observed 24 h after cysteamine treatment but were reduced in CFTRinh-172-pretreated rats. CFTRinh-172 acutely produces CFTR dysfunction in rodents for up to 24 h. CFTR inhibition reduces acid-induced DBS but also prevents duodenal ulcer formation, supporting our hypothesis that intracellular HCO3− may be an important protective mechanism for duodenal epithelial cells.
NF-κB activation in Kupffer cells after partial hepatectomy
Authors: Yang Liu , Magness Scott T. , Bataller Ramon , Rippe Richard A. , Brenner David A.
Published: May 2005

The transcription factor nuclear factor-κB (NF-κB) is activated during liver regeneration after partial hepatectomy. However, the physiological role and cellular localization of NF-κB activation are unresolved. In this study, we used an adenoviral vector expressing a mutated form of IκBα to inhibit NF-κB activity during liver regeneration. After partial hepatectomy in mice, introduction of Ad5IκB, but not a control virus (Ad5GFP), resulted in increased liver injury and decreased hepatocyte proliferation. Hepatocyte apoptosis was not observed. To investigate the kinetics and cellular localization of NF-κB-induced transcription during liver regeneration, we generated a transgenic mouse expressing enhanced green fluorescent protein (EGFP) under the transcriptional control of NF-κB cis elements ( cis-NF-κB-EGFP). During liver regeneration, EGFP expression was detected within 12 h and was primarily located in Kupffer cells. Our data demonstrate that activation of NF-κB initially occurs in Kupffer cells after partial hepatectomy in mice.
Ethanol inhibits monocyte chemotactic protein-1 expression in interleukin-1β-activated human endothelial cells
Authors: Cullen John P. , Sayeed Shariq , Jin Ying , Theodorakis Nicholas G. , Sitzmann James V. , Cahill Paul A. , Redmond Eileen M.
Published: May 2005

The aim of this study was to determine the effect of ethanol (EtOH) on endothelial monocyte chemotactic protein-1 (MCP-1) expression. IL-1β increased the production of MCP-1 by human umbilical vein endothelial cells from undetectable levels to ∼900 pg/ml at 24 h. EtOH dose-dependently inhibited IL-1β-stimulated MCP-1 secretion as determined by ELISA: 25 ± 1%, 35 ± 7%, and 65 ± 5% inhibition for 1, 10, and 100 mM EtOH, respectively, concomitant with inhibition of monocyte adhesion to activated endothelial cells. Similarly, EtOH dose-dependently inhibited IL-1β-stimulated MCP-1 mRNA expression. Experiments with actinomycin D demonstrated that EtOH decreased the stability of MCP-1 mRNA. In addition, EtOH significantly reduced NF-κB and AP-1 binding activity induced by IL-1β and inhibited MCP-1 gene transcription. Binding of 125I-labeled MCP-1 to its receptor (CCR2) on THP-1 human monocytic cells was not affected by EtOH treatment. Modulation of the expression of MCP-1 represents a mechanism whereby EtOH could inhibit atherogenesis by blocking the crucial early step of monocyte adhesion and subsequent recruitment to the subendothelial space. These actions of EtOH may underlie, in part, its cardiovascular protective effects in vivo.
Paracrine stimulation of surfactant secretion by extracellular ATP in response to mechanical deformation
Authors: Patel Anand S. , Reigada David , Mitchell Claire H. , Bates Sandra R. , Margulies Susan S. , Koval Michael
Published: May 2005

We developed a heterologous system to study the effect of mechanical deformation on alveolar epithelial cells. First, isolated primary rat alveolar type II (ATII) cells were plated onto silastic substrata coated with fibronectin and maintained in culture under conditions where they become alveolar type I-like (ATI) cells. This was followed by a second set of ATII cells labeled with the nontransferable, vital fluorescent stain 5-chloromethylfluorescein diacetate to distinguish them from ATI cells. By morphometric analysis, equibiaxial deformation (stretch) of the silastic substratum induced comparable changes in cell surface area for both ATII and ATI cells. Surfactant lipid secretion was measured using cells metabolically labeled with [3H]choline. In response to 21% tonic stretch for 15 min, ATII cells seeded with ATI cells secreted nearly threefold more surfactant lipid compared with ATII cells seeded alone. ATI cells did not secrete lipid in response to stretch. The enhanced lipid secretion by ATII plus ATI cocultures was inhibited by treatment with apyrase and adenosine deaminase, suggesting that ATP release by ATI cells enhanced surfactant lipid secretion at 21% stretch. This was confirmed using a luciferase assay where, in response to 21% stretch, ATI cells released fourfold more ATP than ATII cells. Because ATI cells release significantly more ATP at a lower level of stretch than ATII cells, this supports the hypothesis that ATI cells are mechanosensors in the lung and that paracrine stimulation of ATII cells by extracellular ATP released from ATI cells plays a role in regulating surfactant secretion.
Bioinformatic identification of novel early stress response genes in rodent models of lung injury
Authors: Ma Shwu-Fan , Grigoryev Dmitry N. , Taylor Angela D. , Nonas Stephanie , Sammani Saad , Ye Shui Qing , Garcia Joe G. N.
Published: May 2005

Acute lung injury is a complex illness with a high mortality rate (>30%) and often requires the use of mechanical ventilatory support for respiratory failure. Mechanical ventilation can lead to clinical deterioration due to augmented lung injury in certain patients, suggesting the potential existence of genetic susceptibility to mechanical stretch ( 6 , 48 ), the nature of which remains unclear. To identify genes affected by ventilator-induced lung injury (VILI), we utilized a bioinformatic-intense candidate gene approach and examined gene expression profiles from rodent VILI models (mouse and rat) using the oligonucleotide microarray platform. To increase statistical power of gene expression analysis, 2,769 mouse/rat orthologous genes identified on RG_U34A and MG_U74Av2 arrays were simultaneously analyzed by significance analysis of microarrays (SAM). This combined ortholog/SAM approach identified 41 up- and 7 downregulated VILI-related candidate genes, results validated by comparable expression levels obtained by either real-time or relative RT-PCR for 15 randomly selected genes. K-mean clustering of 48 VILI-related genes clustered several well-known VILI-associated genes (IL-6, plasminogen activator inhibitor type 1, CCL-2, cyclooxygenase-2) with a number of stress-related genes (Myc, Cyr61, Socs3). The only unannotated member of this cluster ( n = 14) was RIKEN_1300002F13 EST, an ortholog of the stress-related Gene33/Mig-6 gene. The further evaluation of this candidate strongly suggested its involvement in development of VILI. We speculate that the ortholog-SAM approach is a useful, time- and resource-efficient tool for identification of candidate genes in a variety of complex disease models such as VILI.
Effect of a protein preload on food intake and satiety feelings in response to duodenal fat perfusions in healthy male subjects
Authors: Oesch Sibylle , Degen Lukas , Beglinger Christoph
Published: May 2005

The control of food intake and satiety requires a coordinated interplay. Oral protein and duodenal fat inhibit food intake and induce satiety, but their interactive potential is unclear. Our aim was therefore to investigate the interactions between an oral protein preload and intraduodenal (ID) fat on food intake and satiety feelings. Twenty healthy male volunteers were studied in a randomized, double-blind, four-period crossover design. On each study day, subjects underwent one of the following treatments: 1) water preload plus ID saline perfusion, 2) water preload plus ID fat perfusion, 3) protein preload plus ID saline perfusion, or 4) protein preload plus ID fat perfusion. Subjects were free to eat and drink as much as they wished. An oral protein preload significantly reduced caloric intake (19%, P < 0.01). Simultaneous administration of an oral protein preload and ID fat did not result in a positive synergistic effect with respect to caloric consumption, rejecting the initial hypothesis that the two nutrients exert a positive synergistic effect on food intake. An oral protein preload but not ID fat altered the feelings of hunger and fullness. These data indicate that the satiety effect of an oral protein preload is not amplified by ID fat; indeed, the effect of a protein preload does not seem to be mediated by cholecystokinin, glucagon-like peptide-1, or peptide YY. Much more information is necessary to understand the basic physiological mechanisms that control food intake and satiety.
Copper inHelix pomatia(Gastropoda) is regulated by one single cell type: differently responsive metal pools in rhogocytes
Authors: Dallinger Reinhard , Chabicovsky Monika , Hödl Elisabeth , Prem Caroline , Hunziker Peter , Manzl Claudia
Published: May 2005

Like all other animal species, terrestrial pulmonate snails require Cu as an essential trace element. On the other hand, elevated amounts of Cu can exert toxic effects on snails. The homeostatic regulation of Cu must therefore be a pivotal goal of terrestrial pulmonates to survive. Upon administration of Cu, snails accumulate the metal nearly equally in most of their organs. Quantitative studies in connection with HPLC and electrospray ionization mass spectrometry reveal that a certain fraction of Cu in snails is bound to a Cu-metallothionein (Cu-MT) isoform that occurs in most organs at constant concentrations, irrespective of whether the animals had been exposed to physiological or elevated amounts of Cu. In situ hybridization demonstrates that at the cellular level, the Cu-binding MT isoform is exclusively expressed in the so-called pore cells (or rhogocytes), which can be found in all major snail organs. The number of pore cells with Cu-MT mRNA reaction products remains unaffected by Cu exposure. Rhogocytes also are major storage sites of Cu in a granular form, the metal quickly entering the snail tissues upon elevated exposure. The number of rhogocytes with granular Cu precipitations strongly increases upon Cu administration via food. Thus, whereas Cu-MT in the rhogocytes represents a stable pool of Cu that apparently serves physiological tasks, the granular Cu precipitations form a second, quickly inducible, and more easily available pool of the metal that serves Cu regulation by responding to superphysiological metal exposure.
Vasodilator tone in the llama fetus: the role of nitric oxide during normoxemia and hypoxemia
Authors: Sanhueza Emilia M. , Riquelme Raquel A. , Herrera Emilio A. , Giussani Dino A. , Blanco Carlos E. , Hanson Mark A. , Llanos Aníbal J.
Published: May 2005

The fetal llama responds to hypoxemia, with a marked peripheral vasoconstriction but, unlike the sheep, with little or no increase in cerebral blood flow. We tested the hypothesis that the role of nitric oxide (NO) may be increased during hypoxemia in this species, to counterbalance a strong vasoconstrictor effect. Ten fetal llamas were operated under general anesthesia. Mean arterial pressure (MAP), heart rate, cardiac output, total vascular resistance, blood flows, and vascular resistances in cerebral, carotid and femoral vascular beds were determined. Two groups were studied, one with nitric oxide synthase (NOS) blocker NG-nitro-l-arginine methyl ester (l-NAME), and the other with 0.9% NaCl (control group), during normoxemia, hypoxemia, and recovery. During normoxemia, l-NAME produced an increase in fetal MAP and a rapid bradycardia. Cerebral, carotid, and femoral vascular resistance increased and blood flow decreased to carotid and femoral beds, while cerebral blood flow did not change significantly. However, during hypoxemia cerebral and carotid vascular resistance fell by 44% from its value in normoxemia after l-NAME, although femoral vascular resistance progressively increased and remained high during recovery. We conclude that in the llama fetus: 1) NO has an important role in maintaining a vasodilator tone during both normoxemia and hypoxemia in cerebral and femoral vascular beds and 2) during hypoxemia, NOS blockade unmasked the action of other vasodilator agents that contribute, with nitric oxide, to preserving blood flow and oxygen delivery to the tissues.
Response of membrane potential and intracellular pH to hypercapnia in neurons and astrocytes from rat retrotrapezoid nucleus
Authors: Ritucci Nick A. , Erlichman Joseph S. , Leiter J. C. , Putnam Robert W.
Published: May 2005

We compared the response to hypercapnia (10%) in neurons and astrocytes among a distinct area of the retrotrapezoid nucleus (RTN), the mediocaudal RTN (mcRTN), and more intermediate and rostral RTN areas (irRTN) in medullary brain slices from neonatal rats. Hypercapnic acidosis (HA) caused pHo to decline from 7.45 to 7.15 and a maintained intracellular acidification of 0.15 ± 0.02 pH unit in 90% of neurons from both areas ( n = 16). HA excited 44% of mcRTN (7/16) and 38% of irRTN neurons (6/16), increasing firing rate by 167 ± 75% (chemosensitivity index, CI, 256 ± 72%) and 310 ± 93% (CI 292 ± 50%), respectively. These responses did not vary throughout neonatal development. We compared the responses of mcRTN neurons to HA (decreased pHi and pHo) and isohydric hypercapnia (IH; decreased pHi with constant pHo). Neurons excited by HA (firing rate increased 156 ± 46%; n = 5) were similarly excited by IH (firing rate increased 167 ± 38%; n = 5). In astrocytes from both RTN areas, HA caused a maintained intracellular acidification of 0.17 ± 0.02 pH unit ( n = 6) and a depolarization of 5 ± 1 mV ( n = 12). In summary, many neurons (42%) from the RTN are highly responsive (CI 248%) to HA; this may reflect both synaptically driven and intrinsic mechanisms of CO2 sensitivity. Changes of pHi are more significant than changes of pHo in chemosensory signaling in RTN neurons. Finally, the lack of pHi regulation in response to HA suggests that astrocytes do not enhance extracellular acidification during hypercapnia in the RTN.
Importance of cytoskeletal elements in volume regulatory responses of trout hepatocytes
Authors: Ebner Hannes L. , Cordas Alexandra , Pafundo Diego E. , Schwarzbaum Pablo J. , Pelster Bernd , Krumschnabel Gerhard
Published: May 2005

The role of cytoskeletal elements in volume regulation was studied in trout hepatocytes by investigating changes in F-actin distribution during anisotonic exposure and assessing the impact of cytoskeleton disruption on volume regulatory responses. Hypotonic challenge caused a significant decrease in the ratio of cortical to cytoplasmic F-actin, whereas this ratio was unaffected in hypertonic saline. Disruption of microfilaments with cytochalasin B (CB) or cytochalasin D significantly slowed volume recovery following hypo- and hypertonic exposure in both attached and suspended cells. The decrease of net proton release and the intracellular acidification elicited by hypotonicity were unaltered by CB, whereas the increase of proton release in hypertonic saline was dramatically reduced. Because amiloride almost completely blocked the hypertonic increase of proton release and cytoskeleton disruption diminished the associated increase of intracellular pH (pHi), we suggest that F-actin disruption affected Na+/H+exchanger activity. In line with this, pHirecovery after an ammonium prepulse was significantly inhibited in CB-treated cells. The increase of cytosolic Na+under hypertonic conditions was not diminished but, rather, enhanced by F-actin disruption, presumably due to inhibited Na+-K+-ATPase activity and stimulated Na+channel activity. The elevation of cytosolic Ca2+in hypertonic medium was significantly reduced by CB. Altogether, our results indicate that the F-actin network is of crucial importance in the cellular responses to anisotonic conditions, possibly via interaction with the activity of ion transporters and with signalling cascades responsible for their activation. Disruption of microtubules with colchicine had no effect on any of the parameters investigated.
Neural and metabolic mechanisms of excessive muscle fatigue in maintenance hemodialysis patients
Authors: Johansen Kirsten L. , Doyle Julie , Sakkas Giorgos K. , Kent-Braun Jane A.
Published: May 2005

Dialysis patients have severe exercise limitations related to metabolic disturbances, but muscle fatigue has not been well studied in this population. We investigated the magnitude and mechanisms of fatigue of the ankle dorsiflexor muscles in patients on maintenance hemodialysis. Thirty-three dialysis patients and twelve healthy control subjects performed incremental isometric dorsiflexion exercise, beginning at 10% of their maximal voluntary contraction (MVC) and increasing by 10% every 2 min. Muscle fatigue (fall of MVC), completeness of voluntary activation, and metabolic responses to exercise were measured. Before exercise, dialysis subjects exhibited reduced strength and impaired peripheral activation (lower compound muscle activation potential amplitude) but no metabolic perturbation. During exercise, dialysis subjects demonstrated threefold greater fatigue than controls with evidence of central activation failure but no change in peripheral activation. All metabolic parameters were significantly more perturbed at end exercise in dialysis subjects than in controls, including lower phosphocreatine (PCr) and pH, and higher Pi, Pi/PCr, and H2PO4−. Oxidative potential was markedly lower in patients than in controls [62.5 (SD 27.2) vs. 134.6 (SD 31.7), P < 0.0001]. Muscle fatigue was negatively correlated with oxidative potential among dialysis subjects ( r = −0.52, P = 0.04) but not controls. Changes in central activation ratio were also correlated with muscle fatigue in the dialysis subjects ( r = 0.59, P = 0.001) but not the controls. This study provides new information regarding the excessive muscular fatigue of dialysis patients and demonstrates that the mechanisms of this fatigue include both intramuscular energy metabolism and central activation failure.
Increasing oxidative stress with molsidomine increases blood pressure in genetically hypertensive rats but not normotensive controls
Authors: Fortepiani Lourdes A. , Reckelhoff Jane F.
Published: May 2005

Spontaneously hypertensive rats (SHR) have a higher level of oxidative stress and exhibit a greater depressor response to a superoxide scavenger, tempol, than normotensive Wistar-Kyoto rats (WKY). This study determined whether an increase in oxidative stress with a superoxide/NO donor, molsidomine, would amplify the blood pressure in SHR. Male SHR and WKY were given molsidomine (30 mg·kg−1·day−1) or vehicle (0.01% ethanol) for 1 wk, and blood pressure, renal hemodynamics, nitrate and nitrite excretion (NOx), renal superoxide production, and expression of renal antioxidant enzymes, Mn- and Cu,Zn-SOD, catalase, and glutathione peroxidase (GPx), were measured. Renal superoxide and NOx were higher in control SHR than in WKY. Molsidomine increased superoxide by ∼35% and NOx by 250% in both SHR and WKY. Mean arterial blood pressure (MAP) was also higher in control SHR than WKY. Molsidomine increased MAP by 14% and caused renal vasoconstriction in SHR but reduced MAP by 16%, with no effect on renal hemodynamics, in WKY. Renal expression of Mn- and Cu,Zn-SOD was not different between SHR and WKY, but expression of catalase and GPx were ∼30% lower in kidney of SHR than WKY. The levels of Mn- and Cu,Zn-SOD were not increased with molsidomine in either WKY or SHR. Renal catalase and GPx expression was increased by 300–400% with molsidomine in WKY, but there was no effect in SHR. Increasing oxidative stress elevated blood pressure further in SHR but not WKY. WKY are likely protected because of higher bioavailable levels of NO and the ability to upregulate catalase and GPx.
Role of IL-6 in systemic angiogenesis of the lung
Authors: McClintock Jessica Y. , Wagner Elizabeth M.
Published: May 2005

The multifunctional cytokine interleukin (IL)-6 has been shown to modulate inflammation and angiogenesis. In a mouse model of lung angiogenesis induced by chronic left pulmonary artery ligation (LPAL), we previously showed increased expression of IL-6 mRNA in lung homogenates 4 h after the onset of pulmonary ischemia ( 31 ). To determine whether IL-6 influences both new vessel growth and inflammatory cell influx, we studied wild-type (WT) and IL-6-deficient C57Bl/6J (KO) mice after LPAL (4 h and 1, 7, 14 days). We measured IL-6 protein of the lung by ELISA, the lavage cell profile of the left lung, and new systemic vessel growth with radiolabeled microspheres (14 days after LPAL) in WT and KO mice. We confirmed a 2.4-fold increase in IL-6 protein in the left lung of WT mice compared with right lung 4 h after LPAL. A significant increase in lavaged neutrophils (7.5% of total cells) was observed only in WT mice 4 h after LPAL. New vessel growth was significantly attenuated in KO relative to WT (0.7 vs. 1.9% cardiac output). In an additional series, treatment of WT mice with anti-neutrophil antibody demonstrated a reduction in lavaged neutrophils 4 h after LPAL; however, IL-6 protein remained elevated and neovascularization to the left lung (2.3% cardiac output) was not altered. These results demonstrate that IL-6 plays an important modulatory role in lung angiogenesis, but the changes are not dependent on trapped neutrophils.
Biphasic tissue Doppler waveforms during isovolumic phases are associated with asynchronous deformation of subendocardial and subepicardial layers
Authors: Sengupta Partho P. , Khandheria Bijoy K. , Korinek Josef , Wang Jianwen , Belohlavek Marek
Published: May 2005

Subendocardial and subepicardial layers of the left ventricle (LV) are characterized with right- and left-handed helical orientations of myocardial fibers. We investigated the origin of biphasic deformations of the LV wall during isovolumic contraction (IVC) and relaxation (IVR). In eight open-chest adult pigs, strain rates were measured along the right- and left-handed helical directions in the LV anterior wall by implanting 16 sonomicrometry crystals. Sonomicrometry strain rates were compared with the longitudinal subendocardial strain rates obtained by tissue Doppler imaging. During ejection and diastolic filling, shortening and lengthening occurred synchronously along the right- and left-handed helical directions. However, during IVC and IVR, the deformations were dissimilar in the two directions. Transmural shortening during IVC occurred along the right-handed helical direction and was accompanied with transient lengthening in the left-handed helical direction. Conversely, during IVR, the LV lengthened along the left-handed helical direction and shortened in the right-handed helical direction. Peak subendocardial strain rates obtained by tissue Doppler imaging during IVC and IVR correlated with corresponding sonomicrometry strain rate values obtained along the right- and left-handed helical directions ( r = 0.81, P < 0.001 and r = 0.70, P = 0.001, respectively). Our data suggest that brief counterdirectional movements occur within the LV wall during IVC and IVR. Shortening along the right-handed helical direction is accompanied with reciprocal lengthening in the left-handed helical direction during IVC and vice versa during IVR. The results support an association between asynchronous deformation of subendocardial and subepicardial muscle fibers and the biphasic isovolumic movements observed with high-resolution tissue Doppler imaging.
Kinetics of glucose transport and sequestration in lactating bovine mammary glands measured in vivo with a paired indicator/nutrient dilution technique
Authors: Qiao Fulong , Trout Donald R. , Xiao Changting , Cant John P.
Published: May 2005

To quantify kinetics of mammary glucose utilization in vivo, 24 paired glucose and extracellular indicator ( p-aminohippuric acid) dilution curves across intact bovine mammary glands were obtained after bolus injections into the external iliac artery. Dilution curves were analyzed using a compartmental capillary, convolution integration model. Four candidate submodels of glucose transport and metabolism in capillary supply zones were fit to the glucose dilution curves and evaluated. Model I, with one extracellular compartment for glucose and first-order unidirectional uptake, failed, indicating that efflux of glucose from the intracellular space could not be ignored. Model II, with first-order exchanges between extracellular and intracellular compartments and sequestration from the latter, was overdefined because unidirectional clearance of glucose was at least five times the blood flow rate and 20 times the net clearance rate. Model III, combining extracellular and intracellular space into one compartment, was superior in its goodness-of-fit to curves and identifiability of parameters. Michaelis-Menten parameters of sequestration were not identifiable. Parameters of the optimal compartmental capillary, convolution integration model were applicable to both the dynamics of injected glucose dilution and the steady-state background arteriovenous difference of glucose. Glucose sequestration followed first-order kinetics between 0 and 7 mM extracellular glucose with an average rate constant of 0.006 s−1 or a clearance of 44 ml/s. The ratio of intracellular to extracellular glucose distribution space was 0.34, which is considerably lower than the expected intracellular volume and suggests an intracellular occlusion compartment with which extracellular glucose rapidly exchanges.
In vivo physiological cross-sectional area and specific force are reduced in the gastrocnemius of elderly men
Authors: Morse Christopher I. , Thom Jeanette M. , Reeves Neil D. , Birch Karen M. , Narici Marco V.
Published: May 2005

Sarcopenia and muscle weakness are well-known consequences of aging. The aim of the present study was to ascertain whether a decrease in fascicle force (Ff) could be accounted for entirely by muscle atrophy. In vivo physiological cross-sectional area (PCSA) and specific force (Ff/PCSA) of the lateral head of the gastrocnemius (GL) muscle were assessed in a group of elderly men [EM, aged 73.8 yr (SD 3.5), height 173.4 cm (SD 4.4), weight 78.4 kg (SD 8.3); means (SD)] and for comparison in a group of young men [YM, aged 25.3 yr (SD 4.4), height 176.4 cm (SD 7.7), weight 79.1 kg (SD 11.9)]. GL muscle volume (Vol) and Achilles tendon moment arm length were evaluated using magnetic resonance imaging. Pennation angle and fiber fascicle length (Lf) were measured using B-mode ultrasonography during isometric maximum voluntary contraction of the plantar flexors. PCSA was estimated as Vol/Lf. GL Ff was calculated by dividing Achilles tendon force by the cosine of θ, during the interpolation of a supramaximal doublet, and accounting for antagonist activation level (assessed using EMG), Achilles tendon moment arm length, and the relative PCSA of the GL within the plantar flexor group. Voluntary activation of the plantar flexors was lower in the EM than in the YM (86 vs. 98%, respectively, P < 0.05). Compared with the YM, plantar flexor maximal voluntary contraction torque and Ff of the EM were lower by 47 and 40%, respectively ( P < 0.01). Both Vol and PCSA were smaller in the EM by 28% ( P < 0.01) and 16% ( P < 0.05), respectively. Also, pennation angle was 12% smaller in the EM, whereas there was no significant difference in Lf between the YM and EM. After accounting for differences in agonists and antagonists activation, the Ff/PCSA of the EM was 30% lower than that of the YM ( P < 0.01). These findings demonstrate that the loss of muscle strength with aging may be explained not only by a reduction in voluntary drive to the muscle, but mostly by a decrease in intrinsic muscle force. This phenomenon may possibly be due to a reduction in single-fiber specific tension.
Acute and severe hypobaric hypoxia increases oxidative stress and impairs mitochondrial function in mouse skeletal muscle
Authors: Magalhães José , Ascensão António , Soares José M. C. , Ferreira Rita , Neuparth Maria J. , Marques Franklim , Duarte José A.
Published: May 2005

Severe high-altitude hypoxia exposure is considered a triggering stimulus for redox disturbances at distinct levels of cellular organization. The effect of an in vivo acute and severe hypobaric hypoxic insult (48 h at a pressure equivalent to 8,500 m) on oxidative damage and respiratory function was analyzed in skeletal muscle mitochondria isolated from vitamin E-supplemented (60 mg/kg ip, 3 times/wk for 3 wk) and nonsupplemented mice. Forty male mice were randomly divided into four groups: control + placebo, hypoxia + placebo (H + P), control + vitamin E, and hypoxia + vitamin E. Significant increases in mitochondrial heat shock protein 60 expression and protein carbonyls group levels and decreases in aconitase activity and sulfhydryl group content were found in the H + P group when compared with the control + placebo group. Mitochondrial respiration was significantly impaired in animals from the H + P group, as demonstrated by decreased state 3 respiratory control ratio and ADP-to-oxygen ratio and by increased state 4 with both complex I- and II-linked substrates. Using malate + pyruvate as substrates, hypoxia decreased the respiratory rate in the presence of carbonyl cyanide m-chlorophenylhydrazone and also stimulated oligomycin-inhibited respiration. However, vitamin E treatment attenuated the effect of hypoxia on the mitochondrial levels of heat shock protein 60 and markers of oxidative stress. Vitamin E was also able to prevent most mitochondrial alterations induced by hypobaric hypoxia. In conclusion, hypobaric hypoxia increases mitochondrial oxidative stress while decreasing mitochondrial capacity for oxidative phosphorylation. Vitamin E was an effective preventive agent, which further supports the oxidative character of mitochondrial dysfunction induced by hypoxia.
Inherited pericentric inversion (X)(p11.4q11.2) associated with delayed puberty and obesity in two brothers
Authors: Talaban R. , Sellick G.S. , Spendlove H.E. , Howell R. , King C. , Reckless J. , Newbury-Ecob R. , Houlston R.S.
Published: May 2005

We report two brothers with hypogonadotropic hypogonadism (HH), obesity and short stature associated with a maternally inherited pericentric inversion (X)(p11.4q11.2). On the basis that either breakpoint might disrupt a gene whose function is critical to normal sexual development we mapped the chromosomal breakpoints using two-colour fluorescent in situ hybridisation (FISH). The position of both the Xp11.4 and Xq11.2 breakpoints was refined using a panel of ordered BAC clones. No known genes were shown to map to the breakpoint regions. While we cannot entirely exclude the possibility that association between the clinical and cytogenetic phenotypes in the family is coincidental, it is possible that the inversion is responsible for HH through alternative molecular mechanisms such as position effects.
An analphoid marker chromosome inv dup(15)(q26.1qter), detected during prenatal diagnosis and characterized via chromosome microdissection
Authors: Mahjoubi F. , Peters G.B. , Malafiej P. , Shalhoub C. , Turner A. , Daniel A. , Hill R.J.
Published: May 2005

A small, mosaic, C-band negative marker chromosome was detected in amniocyte cultures during prenatal diagnosis due to advanced maternal age. Following spontaneous premature labor at 29 weeks gestation, a dysmorphic infant was delivered, with flat nasal bridge, short palpebral fissures, micrognathia, high forehead, low-set ears, telecanthus and corneal dystrophy. Additional folds of skin were present behind the neck, and feet, fingers and toes were abnormally long. The child died at age five days, after two days of renal failure. The origin of the marker chromosome was subsequently identified from a cord blood sample, via chromosome microdissection. Through reverse FISH, we found the marker to be an inverted duplication of the region 15q26.1→qter. FISH with alphoid satellite probe was negative, while whole chromosome 15 paint was positive. Both ends of the marker chromosome were positive for the telomeric TTAGGG probe. These data, plus the G-banding pattern, identified the marker as an analphoid, inverted duplicated chromosome, lacking any conventional centromere. We discuss the etiology and clinical effects of this marker chromosome, comparing it to the few reported cases of “tetrasomy 15q” syndrome. We also discuss the possible mechanisms that are likely responsible for this neocentromere formation.