bluuebunny/crossref_metadata_2025 huggingface dataset:
Increase in efficiency and reduction in Ca2+ dependence of exocytosis during development of mouse inner hair cells
Authors: Johnson Stuart L. , Marcotti Walter , Kros Corné J.
Published: December 2004

Developmental changes in the coupling between Ca2+ entry and exocytosis were studied in mouse inner hair cells (IHCs) which, together with the afferent endings, form the primary synapse of the mammalian auditory system. Ca2+ currents (ICa) and changes in membrane capacitance (ΔCm) were recorded using whole‐cell voltage clamp from cells maintained at body temperature, using physiological (1.3 mm) extracellular Ca2+. The magnitudes of both ICa and ΔCm increased with maturation from embryonic stages until postnatal day 6 (P6). Subsequently, ICa gradually declined to a steady level of about −100 pA from P13 while the Ca2+‐induced ΔCm remained relatively constant, indicating a developmental increase in the Ca2+ efficiency of exocytosis. Although the size of ICa changed during development, its activation properties did not, suggesting the presence of a homogeneous population of Ca2+ channels in IHCs throughout development. The Ca2+ dependence of exocytosis changed with maturation from a fourth power relation in immature cells to an approximately linear relation in mature cells. This change applies to the release of both a readily releasable pool (RRP) and a slower secondary pool of vesicles, implying a common release mechanism for these two kinetically distinct pools that becomes modified during development. The increased Ca2+ efficiency and linear Ca2+ dependence of mature IHC exocytosis, especially over the physiological range of intracellular Ca2+, could improve the high‐fidelity transmission of both brief and long‐lasting stimulation. These properties make the mature cell ideally suited for fine intensity discrimination over a wide dynamic range.
An electrical description of the generation of slow waves in the antrum of the guinea‐pig
Authors: Edwards F. R. , Hirst G. D. S.
Published: December 2004

This paper provides an electrical description of the generation of slow waves in the guinea‐pig gastric antrum. A short segment of a circular smooth muscle bundle with an attached network of myenteric interstitial cells of Cajal (ICC‐MY) and longitudinal muscle sheet was modelled as three electrical compartments with resistive connexions between the ICC‐MY compartment and each of the smooth muscle compartments. The circular smooth muscle layer contains a proportion of intramuscular interstitial cells of Cajal (ICC‐IM), responsible for the regenerative component of the slow wave. Hence the equivalent cell representing the circular muscle layer incorporated a mechanism, modelled as a two stage reaction, which produces an intracellular messenger. The first stage of the reaction is proposed to be activated in a voltage‐dependent manner as described by Hodgkin and Huxley. A similar mechanism was incorporated into the equivalent cell describing the ICC‐MY network. Spontaneous discrete transient depolarizations, termed unitary potentials, are detected in records taken from either bundles of circular smooth muscle containing ICC‐IM or from ICC‐MY. In the simulation the mean rate of discharge of unitary potentials was allowed to vary with the concentration of messenger according to a conventional dose–effect relationship. Such a mechanism, which describes regenerative potentials generated by the circular muscle layer, also simulated the plateau component of the pacemaker potential in the ICC‐MY network. A voltage‐sensitive membrane conductance was included in the ICC‐MY compartment; this was used to describe the primary component of the pacemaker potential. The model generates a range of membrane potential changes with properties similar to those generated by the three cell types present in the intact tissue.
Stress singularities in classical elasticity—II: Asymptotic identification
Authors: Sinclair GB
Published: December 2004

This review article (Part II) is a sequel to an earlier one (Part I) that dealt with means of removal and interpretation of stress singularities in elasticity, as well as their asymptotic and numerical analysis. It reviews contributions to the literature that have actually effected asymptotic identifications of possible stress singularities for specific configurations. For the most part, attention is focused on 2D elastostatic configurations with constituent materials being homogeneous and isotropic. For such configurations, the following types of stress singularity are identified: power singularities with both real and complex exponents, logarithmic intensification of power singularities with real exponents, pure logarithmic singularities, and log-squared singularities. These identifications are reviewed for the in-plane loading of angular elastic plates comprised of a single material in Section 2, and for such plates comprised of multiple materials in Section 3. In Section 4, singularity identifications are examined for the out-of-plane shear of elastic wedges comprised of single and multiple materials, and for the out-of-plane bending of elastic plates within the context of classical and higher-order theory. A review of stress singularities identified for other geometries is given in Section 5, axisymmetric and 3D configurations being considered. A limited examination of the stress singularities identified for other field equations is given as well in Section 5. The paper closes with an overview of the status of singularity identification within elasticity. This Part II of the review has 227 references.
Analysis of Flow Maldistribution of Fuel and Oxidant in a PEMFC
Authors: Mohan Ganesh , Rao B. Prabhakara , Das Sarit K. , Pandiyan S. , Rajalakshmi N. , Dhathathreyan K. S.
Published: December 2004

The flow of fuel and oxidant through a PEMFC is analyzed for prediction of maldistribution. Flow distribution of both fuel and oxidant from the port to the individual cells critically control the performance of a PEMFC stack in combination. The distribution of fluids was simulated by analytical approach utilizing flow channeling model of a manifold. A detailed numerical modeling is also carried out considering flow in each cell between the electrodes as flow through an equivalent porous medium offering identical resistance. The results show a close match between the analytical and numerical results. The parametric study reveals that flow rate and port size plays major role determining maldistribution of the fluids, which can be considerably skewed when large numbers of cells are stacked for larger power output.
A Pumping System to Enhance Production From Gas Wells
Authors: Rudolf Jeffrey J. , Heidrick Ted R. , Fleck Brian A. , Ridley Rodney K. , Rajan Raj V. S. V.
Published: December 2004

A new pumping concept has been developed and patented by the Alberta Research Council to address the problem of liquid loading in natural gas wells at low, depleted pressures. This concept consists of a pump installed at the bottom of the wellbore that is driven by the reservoir gas pressure to bring the produced liquids to the surface as they accumulate thereby improving gas production from shallow gas wells. The above pump concept has been investigated in two stages of research. In the first stage, a mathematical model was developed to estimate the minimum reservoir pressure required to prevent liquid build up in a gas well with either: 1) the reservoir pressure (and flow) itself carrying the produced liquids to the surface in a two-phase flow or 2) the reservoir gas pressure powering a pumping system to carry the produced liquids to the surface in the most efficient manner possible. The objective of the second stage of this investigation was to look at the feasibility of using a reciprocating pump powered by gas pressure. In particular, the effect of the pump Area Ratio (ratio of the area being pushed by the gas to the area pushing the liquid) on the use of reservoir gas pressure was investigated. There are approximately 75,000 flowing gas wells in western Canada and these gas wells were categorized by depth and production rate. From this list of gas wells, a typical well was chosen and its production data and well characteristics were incorporated into the mathematical model. The model was tested in both the above-mentioned investigations and the results show that there is a significant increase in the operating range when the reservoir pressure is used more efficiently to produce gas from the well. It was determined that higher pump-area ratios lead to a more efficient use of reservoir pressure and for the gas well investigated in this study, an optimum area ratio of 40 was identified as the best design. The concept of multistage pumping was also investigated. The results presented are the basis for experiments presently being designed that will validate the current model of the system and allow for possible improvements.
Transient Stress Analysis and Fatigue Life Estimation of Turbine Blades
Authors: Dhar Deepak , Sharan A. M. , Rao J. S.
Published: December 2004

This paper is concerned with life estimation of a turbine blade taking into account the combined effects of centrifugal stresses, vibratory stresses and thermal stresses. The stresses are determined by accounting for the rotor acceleration. The blades are subjected to aerodynamic excitation force obtained from thin cambered aerofoil theory under incompressible flow. The thermo-elastic forces are obtained from the three-dimensional non-linear heat transfer equations using the finite element analysis. The fatigue life is estimated using two well known theories, from the number of cycles in various blocks during start-up and shut-down periods of the turbine operation when the stresses peak.
Existence and Stability of Localized Oscillations in 1-Dimensional Lattices With Soft-Spring and Hard-Spring Potentials
Authors: Panagopoulos Panagiotis , Bountis Tassos , Skokos Charalampos
Published: December 2004

In this paper, we use the method of homoclinic orbits to study the existence and stability of discrete breathers, i.e., spatially localized and time-periodic oscillations of a class of one-dimensional (1D) nonlinear lattices. The localization can be at one or several sites and the 1D lattices we investigate here have linear interaction between nearest neighbors and a quartic on-site potential Vu=12Ku2±14u4, where the (+) sign corresponds to “hard spring” and (−) to “soft spring” interactions. These localized oscillations—when they are stable under small perturbations—are very important for physical systems because they seriously affect the energy transport properties of the lattice. Discrete breathers have recently been created and observed in many experiments, as, e.g., in the Josephson junction arrays, optical waveguides, and low-dimensional surfaces. After showing how to construct them, we use Floquet theory to analyze their linear (local) stability, along certain curves in parameter space (α,ω), where α is the coupling constant and ω the frequency of the breather. We then apply the Smaller Alignment Index method (SALI) to investigate more globally their stability properties in phase space. Comparing our results for the ± cases of Vu, we find that the regions of existence and stability of breathers of the “hard spring” lattice are considerably larger than those of the “soft spring” system. This is mainly due to the fact that the conditions for resonances between breathers and linear modes are much less restrictive in the former than the latter case. Furthermore, the bifurcation properties are quite different in the two cases: For example, the phenomenon of complex instability, observed only for the “soft spring” system, destabilizes breathers without giving rise to new ones, while the system with “hard springs” exhibits curves in parameter space along which the number of monodromy matrix eigenvalues on the unit circle is constant and hence breather solutions preserve their stability character.
Dynamic Analysis of a Protein-Ligand Molecular Chain Attached to an Atomic Force Microscope
Authors: Tang Deman , Dowell Earl H.
Published: December 2004

Dynamic numerical simulation of a protein-ligand molecular chain connected to a moving atomic force microscope (AFM) has been studied. A sinusoidal base excitation of the cantilevered beam of the AFM is considered in some detail. A comparison between results for a single molecule and those for multiple molecules has been made. For a small number of molecules, multiple stable static equilibrium positions are observed and chaotic behavior may be generated via a period-doubling cascade for harmonic base excitation of the AFM. For many molecules in the chain, only a single static equilibrium position exists. To enable these calculations, reduced-order (dynamic) models are constructed for fully linear, combined linear/nonlinear and fully nonlinear systems. Several distinct reduced-order models have been developed that offer the option of increased computational efficiency at the price of greater effort to construct the particular reduced-order model. The agreement between the original and reduced-order models (ROM) is very good even when only one mode is included in the ROM for either the fully linear or combined linear/nonlinear systems provided the excitation frequency is lower than the fundamental natural frequency of the linear system. The computational advantage of the reduced-order model is clear from the results presented.
Internal Resonance Phenomena of the Jeffcott Rotor With Nonlinear Spring Characteristics
Authors: Ishida Yukio , Inoue Tsuyoshi
Published: December 2004

The Jeffcott rotor is a two-degree-of-freedom linear model with a disk at the midspan of a massless elastic shaft. This model, executing lateral whirling motions, has been widely used in the linear analyses of rotor vibrations. In the Jeffcott rotor, the natural frequency of a forward-whirling mode pf>0 and that of a backward-whirling mode pb<0 have the relation of internal resonance pf:pb=1:−1. Recently, many researchers analyzed nonlinear phenomena by using the Jeffcott rotor with nonlinear elements. However, they did not take this internal resonance relationship into account. Furthermore in many practical rotating machines, the effect of gyroscopic moments are relatively small. Therefore, the one-to-one internal resonance relationship holds approximately between forward and backward natural frequencies in such machinery. In this paper, nonlinear phenomena in the vicinity of the major critical speed and the rotational speeds of twice and three times the major critical speed are investigated in the Jeffcott rotor and rotor systems with a small gyroscopic moment. The influences of internal resonance on the nonlinear resonances are studied in detail. The following were clarified theoretically and experimentally: (a) the shape of resonance curves becomes far more complex than that of a single resonance; (b) almost periodic motions occur; (c) these phenomena are influenced remarkably by the asymmetrical nonlinearity and gyroscopic moment; and (d) the internal resonance phenomena are strongly influenced by the degree of the discrepancies among critical speeds. The results teach us that the usage of the Jeffcott rotor in nonlinear analyses of rotor systems may induce incorrect results.
Local Velocity Measurements and Computational Fluid Dynamics (CFD) Simulations of Swirling Flow in a Cylindrical Cyclone Separator
Authors: Erdal Ferhat M. , Shirazi Siamack A.
Published: December 2004

Local measurements and 3D CFD simulations in gas-liquid cylindrical cyclone separators are scarce. The main objective of this study is to conduct local measurements and 3D CFD simulations to understand the swirling flow behavior in a cylindrical cyclone with one inclined tangential inlet. Axial and tangential velocities and turbulent kinetic energy across the cylinder diameter ID=0.089m were measured at 24 different axial locations (0.32–0.90 m below the inlet) by using a laser Doppler velocimeter (LDV). The liquid flow rate was 16.4m3/h, which corresponds to an average axial velocity of 0.732 m/s and Reynolds number of 66,900. Measurements are used to create color contour plots of axial and tangential velocity and turbulent kinetic energy. Color contour maps revealed details of the flow behavior. Additionally, 3D CFD simulations with different turbulence models are conducted. Simulations results are compared to LDV measurements.
Fallacies of a Hydrogen Economy: A Critical Analysis of Hydrogen Production and Utilization
Authors: Kreith Frank , West Ron
Published: December 2004

This article presents a critical analysis of all the major pathways to produce hydrogen and to utilize it as an energy carrier to generate heat or electricity. The approach taken is to make a cradle to grave analysis including the production of hydrogen, the conversion of hydrogen to heat or electricity, and finally the utilization of that heat or electricity for a useful purpose. This methodology shows that no currently available hydrogen pathway, irrespective of whether it uses fossil fuels, nuclear fuels, or renewable technology as the primary energy source to generate electricity or heat is as efficient as using the electric power or heat from any of these sources directly. Furthermore, electric vehicles using batteries to store electricity are shown to be more efficient and less polluting than fuel cell powered vehicles using energy stored in hydrogen.
Increased cholesterol decreases uterine activity: functional effects of cholesterol alteration in pregnant rat myometrium
Authors: Smith R. D. , Babiychuk E. B. , Noble K. , Draeger A. , Wray Susan
Published: December 2004

Uterine quiescence is essential for successful pregnancy. Cholesterol and triglycerides are markedly increased in pregnancy. Cholesterol is enriched in microdomains of the plasma membrane known as rafts and caveolae. Both lipid rafts and caveolae have been implicated in cellular signaling cascades. The purpose of this work was to investigate whether manipulation of cholesterol content alters uterine contractility. Late pregnancy (19–21 days) rats were humanely euthanized and strips of longitudinal myometrium were then dissected. Force and Ca2+measurements were simultaneously recorded and cholesterol increased by the addition of 5 mg/ml cholesterol or 0.25 mg/ml low-density lipoproteins (LDLs) or reduced by 2% methyl-β-cyclodextrin (MCD) or 2 U/ml cholesterol oxidase addition to the perfusate. Both LDLs and cholesterol profoundly inhibited spontaneous uterine force production and associated Ca2+transients; frequency, amplitude, and duration of contraction were all significantly reduced compared with preceding control contractions. Force and Ca2+were also reduced by cholesterol when 1 nM oxytocin was used to stimulate the myometrium. Uterine activity was significantly increased by cholesterol extraction with MCD or cholesterol oxidase treatment. Electron microscopy confirmed the lipid raft disrupting effect of MCD, as formerly electron microscopy-visible caveolae in the myometrial cell membrane all but disappeared after MCD treatment. These data show that uterine smooth muscle cell cholesterol content is critically important for functional activity. A novel finding of our study is that cholesterol is inhibitory for force generation. It may be one of the mechanisms operating to maintain uterine quiescence throughout gestation and may also contribute to difficulties in labor suffered by obese women.
Age-related differences in skeletal muscle protein synthesis: relation to markers of immune activation
Authors: Toth Michael J. , Matthews Dwight E. , Tracy Russell P. , Previs Michael J.
Published: December 2004

Aging is associated with decreased skeletal muscle mass and function. These changes are thought to derive, in part, from a reduction in skeletal muscle protein synthesis. Although some studies have shown reduced postabsorptive muscle protein synthesis with age in humans, recent studies have failed to find an age effect. In addition to this disparity, few studies have attempted to characterize the hormonal factors that may contribute to changes in protein synthesis. Thus we examined the effect of age on skeletal muscle protein metabolism, with a specific emphasis on myosin heavy chain (MHC) protein, and the relationship of protein synthesis rates to plasma hormone levels. We measured body composition, muscle function, muscle protein synthesis, MHC and actin protein content, MHC isoform distribution, and plasma concentrations of cytokines and insulin-like growth factor-I (IGF-I) in 7 young [29 ± 2 (SE) yr] and 15 old (72 ± 1 yr; P < 0.01) volunteers. Mixed-muscle (−19%; P = 0.11), MHC (−22%; P = 0.08), and nonmyofibrillar (−17%; P = 0.10) protein synthesis all tended to be lower in old volunteers. Old volunteers were characterized by increased circulating tumor necrosis factor-α receptor II ( P < 0.05) and reduced IGF-I ( P < 0.01). In addition, plasma C-reactive protein, interleukin-6, and tumor necrosis factor-α receptor II concentrations were negatively related to mixed-muscle and MHC protein synthesis rates (range of r values: −0.422 to −0.606; P < 0.05 to <0.01). No differences in MHC or actin protein content were found. Old volunteers showed reduced ( P < 0.05) MHC IIx content compared with young volunteers but no differences in MHC I or IIa. Our data show strong trends toward reduced postabsorptive muscle protein synthesis with age. Moreover, reduced muscle protein synthesis rates were related to increased circulating concentrations of several markers of immune activation.
Insulin resistance in the skeletal muscle of women with PCOS involves intrinsic and acquired defects in insulin signaling
Authors: Corbould Anne , Kim Young-Bum , Youngren Jack F. , Pender Celia , Kahn Barbara B. , Lee Anna , Dunaif Andrea
Published: December 2004

Insulin resistance in polycystic ovary syndrome (PCOS) is due to a postbinding defect in signaling that persists in cultured skin fibroblasts and is associated with constitutive serine phosphorylation of the insulin receptor (IR). Cultured skeletal muscle from obese women with PCOS and age- and body mass index-matched control women ( n = 10/group) was studied to determine whether signaling defects observed in this tissue in vivo were intrinsic or acquired. Basal and insulin-stimulated glucose transport and GLUT1 abundance were significantly increased in cultured myotubes from women with PCOS. Neither IR β-subunit abundance and tyrosine autophosphorylation nor insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase activity differed in the two groups. However, IRS-1 protein abundance was significantly increased in PCOS, resulting in significantly decreased PI 3-kinase activity when normalized for IRS-1. Phosphorylation of IRS-1 on Ser312, a key regulatory site, was significantly increased in PCOS, which may have contributed to this signaling defect. Insulin signaling via IRS-2 was also decreased in myotubes from women with PCOS. In summary, decreased insulin-stimulated glucose uptake in PCOS skeletal muscle in vivo is an acquired defect. Nevertheless, there are intrinsic abnormalities in glucose transport and insulin signaling in myotubes from affected women, including increased phosphorylation of IRS-1 Ser312, that may confer increased susceptibility to insulin resistance-inducing factors in the in vivo environment. These abnormalities differ from those reported in other insulin resistant states consistent with the hypothesis that PCOS is a genetically unique disorder conferring an increased risk for type 2 diabetes.
Association of an aromatase TTTA repeat polymorphism with circulating estrogen, bone structure, and biochemistry in older women
Authors: Dick I. M. , Devine A. , Prince R. L.
Published: December 2004

Osteoporosis is a disease that is strongly genetically determined. Aromatase converts androgens to estradiol in postmenopausal women, therefore polymorphisms of the gene for this enzyme may be associated with bone mass and fracture. We investigated the association of the TTTA microsatellite polymorphism in intron 4 of the aromatase (CYP19) gene with bone mineral density (BMD) and fracture in 1,257 women aged 70 yr and greater. The data obtained were stratified based on the presence or absence of a [TTTA]n of 7 (A2), determined from a preliminary analysis of hip dual-energy X-ray absorptiometry BMD, which was present in 27% of the population. The presence of an A2 allele was associated with a higher free estradiol index (0.52 ± 0.49, P = 0.049) compared with the absence of an A2 allele (0.47 ± 0.45); higher BMD at all sites of the hip (3.4% total hip, 2.3% femoral neck, 3.6% intertrochanter, 4.1% trochanter) and the lumbar spine (12.7%); higher values for the calcaneal quantitative ultrasound parameters broadband ultrasound (1.3%), speed of sound (0.4%), and stiffness (3.7%); and higher peripheral quantitative computed tomography measures for total (3.4%), trabecular (3.3%), and cortical BMD (3.3%) and the derived stress strain index (SSI) parameters SSI polar (6.4%) and SSI × (6.8%) values. A lower deoxypryridinoline creatinine ratio was observed in subjects with an A2 allele (30.3 ± 10.4 vs. 27.1 ± 9.1, P = 0.03). The A2 allele was associated with a lower prevalence of vertebral fracture in subjects who were osteoporotic (odds ratio 0.27, confidence interval 0.09–0.79). Therefore, a common polymorphism of the aromatase gene, perhaps in linkage disequilibrium with a functionally significant CYP19 polymorphism, is associated with bone structure and bone turnover, either by local effects or by effects on circulating bioactive estrogen.
Calorie restriction increases the ratio of phosphatidylinositol 3-kinase catalytic to regulatory subunits in rat skeletal muscle
Authors: McCurdy Carrie E. , Davidson Robert T. , Cartee Gregory D.
Published: December 2004

Calorie restriction [CR; 60% of ad libitum (AL) intake] improves insulin-stimulated glucose transport, concomitant with enhanced phosphorylation of Akt. The mechanism(s) for the CR-induced increase in Akt phosphorylation of insulin-stimulated muscle is unknown. The purpose of this study was to determine whether CR increased the ratio of catalytic to regulatory subunits favoring enhanced phosphatidylinositol (PI) 3-kinase signaling, which may contribute to increases in Akt phosphorylation and glucose transport in insulin-stimulated muscles. We measured the PI 3-kinase regulatory (p85α/β, p50α, and p55α) and catalytic (p110) subunits abundance in skeletal muscle from male F344B/N rats after 8 wk of AL or CR treatment. In CR compared with AL muscles, regulatory isoforms, p50α and p55α abundance were ∼40% lower ( P < 0.01) with unchanged p85α/β levels. There was no diet-related change in catalytic subunit abundance. Despite lower IRS-1 levels (∼35%) for CR vs. AL, IRS-1-p110 association in insulin-stimulated muscles was significantly ( P < 0.05) enhanced by ∼50%. Downstream of PI 3-kinase, CR compared with AL significantly enhanced Akt serine phosphorylation by 1.5-fold higher ( P = 0.01) and 3- O-methylglucose transport by ∼20% in muscles incubated with insulin. The increased ratio of PI 3-kinase catalytic to regulatory subunits favors enhanced insulin signaling, which likely contributes to greater Akt phosphorylation and improved insulin sensitivity associated with CR in skeletal muscle.
Inhibition of cGMP-specific phosphodiesterase type 5 reduces sodium excretion and arterial blood pressure in patients with NaCl retention and ascites
Authors: Thiesson Helle C. , Jensen Boye L. , Jespersen Bente , Schaffalitzky de Muckadell Ove B. , Bistrup Claus , Walter Steen , Ottosen Peter D. , Veje Annegrete , Skøtt Ole
Published: December 2004

In the present study, we tested the hypothesis that inhibition of renal phosphodiesterase type 5 (PDE5) in patients with liver cirrhosis and ascites increases sodium excretion. The effect of sildenafil citrate was studied in a randomized double-blind. placebo-controlled crossover study. Diuretics were withdrawn, and a fixed sodium diet (100 mmol/day) was given to the patients for 5 days before both study days. After a 60-min basal period, eight patients received either oral sildenafil (50 mg) or placebo. Glomerular filtration rate (GFR) and renal blood flow (RBF) were determined by99mTc-diethylenetriamine-pentaacetate and131I-hippuran clearances. In human nephrectomy specimens, PDE5 mRNA was expressed at similar levels in the cortex ( n = 6) and inner medulla ( n = 4). Histochemical staining showed PDE5 immunoreactivity in collecting ducts and vascular smooth muscle. At baseline, cirrhotic patients exhibited elevated plasma concentrations of ANP, renin, ANG II, and aldosterone that did not differ on the 2 study days. Basal sodium excretion was similar at the 2 study days (median 17 and 18 mmol, respectively), and patients were in positive sodium balance. Sildenafil increased heart rate, plasma renin activity, plasma ANG II, and aldosterone concentrations significantly after 60 min. Plasma cGMP concentration was increased after 120 and 180 min, and urinary sodium excretion and mean arterial blood pressure were decreased significantly at 120 and 180 min. Plasma ANP concentration, GFR, and RBF did not change after sildenafil. In patients with ascites and cirrhosis, inhibition of PDE5 did not promote natriuresis but led to increased plasma levels of the renin-angiotensin-aldosterone system.
Influence of genetic background and gender on hypertension and renal failure in COX-2-deficient mice
Authors: Yang Tianxin , Huang Yuning G. , Ye Wenling , Hansen Pernille , Schnermann Jurgen B. , Briggs Josephine P.
Published: December 2004

The present study was undertaken to determine whether the severity of renal failure or hypertension in homozygous cyclooxygenase (COX)-2-deficient (COX-2−/−) mice affected by genetic background or gender. COX-2 deletion was introduced into three congenic genetic backgrounds, 129/Sv (129/COX-2−/−), C57/BL6 (C57/COX-2−/−), and BALB/c (BALB/COX-2−/−), by backcrossing the original mixed-background knockout mice with the respective inbred strains for 9 or 10 generations. Evaluation of the severity of hypertension and renal failure was performed in knockout and wild-type mice at the age of 2.5–3.5 mo. Blood pressure measured by tail-cuff plethysmography was significantly elevated in the male 129/COX-2−/− mice (165.8 ± 9.2 vs. 116 ± 5.1 mmHg, P < 0.05), and to a much lesser extent in the female 129/COX-2−/− mice (127.4 ± 3.3 vs. 102.4 ± 3.3), whereas it was unchanged in the C57- or BALB/COX-2−/− mice regardless of gender. Urinary excretion of albumin, determined by EIA, was remarkably increased in the 129/COX-2−/− (16.4 ± 4.1 vs. 0.16 ± 0.043 mg albumin/mg creatinine, P < 0.001), and to a lesser extent in the male C57/COX-2−/− mice (0.595 ± 0.416 vs. 0.068 ± 0.019). Albumin excretion was not elevated in the male BALB/COX-2−/− or in female COX-2−/− mice on any of the three genetic backgrounds. Histological analysis showed abundant protein casts, dilated tubules, and infiltration of inflammatory cells in the male 129/COX-2−/− mice, but not in COX-2−/− mice in other strains or gender. However, the presence of small glomeruli in the nephrogenic zone was observed in all strains of COX-2 knockout mice, regardless of genetic background and gender. Therefore, we conclude that the severity of hypertension and renal failure in COX-2-deficient mice is influenced by genetic background and gender, whereas the incomplete maturation of outer cortical nephrons appears to be independent of genetic background effects.
Substrate interactions in the human type IIa sodium-phosphate cotransporter (NaPi-IIa)
Authors: Virkki Leila V. , Forster Ian C. , Biber Jürg , Murer Heini
Published: December 2004

We have characterized the kinetics of substrate transport in the renal type IIa human sodium-phosphate cotransporter (NaPi-IIa). The transporter was expressed in Xenopus laevis oocytes, and steady-state and pre-steady-state currents and substrate uptakes were characterized by voltage-clamp and isotope flux. First, by measuring simultaneous uptake of a substrate (32Pi,22Na) and charge in voltage-clamped oocytes, we established that the human NaPi-IIa isoform operates with a Na:Pi:charge stoichiometry of 3:1:1 and that the preferred transported Pispecies is HPO42−. We then probed the complex interrelationship of substrates, pH, and voltage in the NaPi-IIa transport cycle by analyzing both steady-state and pre-steady-state currents. Steady-state current measurements show that the apparent HPO42−affinity is voltage dependent and that this voltage dependency is abrogated by lowering the pH or the Na+concentration. In contrast, the voltage dependency of the apparent Na+affinity increased when pH was lowered. Pre-steady-state current analysis shows that Na+ions bind first and influence the preferred orientation of the transporter in the absence of Pi. Pre-steady-state charge movement was partially suppressed by complete removal of Na+from the bath, by reducing extracellular pH (both in the presence and absence of Na+), or by adding Pi(in the presence of 100 mM Na). None of these conditions suppressed charge movement completely. The results allowed us to modify previous models for the transport cycle of NaPi-II transporters by including voltage dependency of HPO42−binding and proton modulation of the first Na+binding step.
Effect of Contrast on the Active Control of a Moving Line
Authors: Li Li , Sweet Barbara T. , Stone Leland S.
Published: December 2004

In many passive visual tasks, human perceptual judgments are contrast dependent. To explore whether these contrast dependencies of visual perception also affect closed-loop manual control tasks, we examined visuomotor performance as humans actively controlled a moving luminance-defined line over a range of contrasts. Four subjects were asked to use a joystick to keep a horizontal line centered on a display as its vertical position was perturbed by a sum of sinusoids under two control regimes. The total root mean square (RMS) position error decreased quasi-linearly with increasing log contrast across the tested range (mean slope across subjects: −8.0 and −7.7% per log2 contrast, for the two control regimes, respectively). Frequency–response (Bode) plots showed a systematic increase in open-loop gain (mean slope: 1.44 and 1.30 dB per log2 contrast, respectively), and decrease in phase lag with increasing contrast, which can be accounted for by a decrease in response time delay (mean slope: 32 and 40 ms per log2 contrast, respectively). The performance data are well fit by a Crossover Model proposed by McRuer and Krendel, which allowed us to identify both visual position and motion cues driving performance. This analysis revealed that the position and motion cues used to support manual control under both control regimes appear equally sensitive to changes in stimulus contrast. In conclusion, our data show that active control of a moving visual stimulus is as dependent on contrast as passive perception and suggest that this effect is attributed to a shared contrast sensitivity early in the visual pathway, before any specialization for motion processing.
Effect of Saccadic Adaptation on Localization of Visual Targets
Authors: Awater Holger , Burr David , Lappe Markus , Morrone M. Concetta , Goldberg Michael E.
Published: December 2004

Objects flashed briefly around the time of a saccadic eye movement are grossly mislocalized by human subjects, so they appear to be compressed toward the endpoint of the saccade. In this study, we investigate spatial localization during saccadic adaptation to examine whether the focus of compression tends toward the intended saccadic target or at the endpoint of the actual (adapted) movement. We report two major results. First, that peri-saccadic focus of the compression did not occur at the site of the initial saccadic target, but tended toward the actual landing site of the saccade. Second, and more surprisingly, we observed a large long-term perceptual distortion of space, lasting for hundreds of milliseconds. This distortion did not occur over the whole visual field but was limited to a local region of visual space around the saccade target, suggesting that saccadic adaptation induces a visuo-topic remapping of space. The results imply that the mechanisms controlling saccadic adaptation also affect perception of space and point to a strong perceptual plasticity coordinated with the well-documented plasticity of the motor system.
Dissecting tBHQ induced ARE-driven gene expression through long and short oligonucleotide arrays
Authors: Li Jiang , Spletter Maria L. , Johnson Jeffrey A.
Published: December 2004

This paper compares the gene expression profiles identified by short (Affymetrix U95AV2) or long (Agilent Hu1A) oligonucleotide arrays on a model for upregulation of a cluster of antioxidant responsive element-driven genes by treatment with tert-butylhydroquinone. MAS 5.0, dCHIP, and RMA were applied to normalize the Affymetrix data, and Lowess regression was considered for Agilent data. SAM was used to identify the differential gene expression. A set of biological markers and housekeeping genes were chosen to evaluate the performance of multiple normalization approaches. Both arrays illustrated a definite set of overlapping genes between the data sets regardless of data mining tools used. However, unique gene expression profiles based on the platform used were also revealed and confirmed by quantitative RT-PCR. Further analysis of the data revealed by alternative approaches suggested that alternative splicing, multiple vs. single probe(s) measurement, and use or nonuse of mismatch probes may account for the discrepant data. Therefore, these two microarray technologies offer relatively reliable data. Integration of the gene expression profiles from different array platforms may not only help for cross-validation but also provide a more complete view of the transcriptional scenario.
T(α,β)‐spaces and the Wallman compactification
Authors: Belaid Karim , Echi Othman , Lazaar Sami
Published: December 2004

Some new separation axioms are introduced and studied. We also deal
with maps having an extension to a homeomorphism between the
Wallman compactifications of their domains and ranges.
Renal Outcome and Predictors of Clinical Renal Involvement in Patients with Silent Lupus Nephritis
Authors: Wada Yoko , Ito Satoshi , Ueno Mitsuhiro , Nakano Masaaki , Arakawa Masaaki , Gejyo Fumitake
Published: December 2004

Objectives: We investigated the development of clinically overt nephritis in patients with silent lupus nephritis in an effort to determine predictors of onset. Methods: We selected 31 patients with systemic lupus erythematosus (SLE) who were diagnosed as having silent lupus nephritis between 1985 and 1995. Urinalysis, blood cell count, serum creatinine, complement levels, and anti-double-stranded DNA antibody (anti-dsDNA antibody) levels were followed retrospectively for at least 60 months in each patient. Results: During the follow-up period, 8 patients developed clinical renal disease and 23 had no renal impairment. The mean time of overt nephritis onset was 58 months and renal function deteriorated mildly in 3 patients. Although clinical and laboratory findings were not significantly different at SLE onset, patients with overt nephritis showed both persistent elevation of anti-dsDNA antibodies and persistently low levels of serum C3 and CH50 for at least 24 months before the onset of overt nephritis. Conclusions: Although the renal prognosis was relatively favorable, 25.8% of patients developed overt nephritis during the follow-up period. Elevation of anti-dsDNA antibodies with hypocomplementemia was persisted in these patients, suggesting the utility of these factors as predictors of clinical renal involvement in silent lupus nephritis.
Does Angiotensin II Modulate Erythropoietin Production in HepG2 Cells?
Authors: Benöhr Peter , Harsch Simone , Proksch Barbara , Gleiter Christoph H.
Published: December 2004

Background: In humans, infusion of angiotensin II increases erythropoietin (EPO) serum levels in a dose-dependent manner. However, it is not known whether angiotensin II stimulates EPO-producing renal fibroblasts directly via a receptor or by alteration of renal hemodynamics with a consecutive decrease of renal blood flow. The purpose of this study was to investigate EPO secretion and gene expression under direct angiotensin II stimulation in a cell model thereby excluding hemodynamic effects. Methods: In an established EPO-secreting cell line (HepG2), EPO concentrations were measured under various conditions (normoxia and hypoxia) and different angiotensin II concentrations. mRNA levels of EPO were analyzed by LightCycler quantitative PCR after reverse transcription normalized to the housekeeping gene cyclophilin. Results: Angiotensin II did not affect EPO production in any concentration (1 nM or 100 µM) under conditions of normoxia. Reduced oxygen tension (1% O2) led to the expected increase of EPO and EPO gene expression. EPO secretion stimulated by hypoxia is not significantly changed by any concentration of angiotensin II. Conclusion: In summary, this study shows that angiotensin II does not alter EPO production in HepG2 cell culture under normoxic or hypoxic conditions. This might point towards the hypothesis that in vivo renal cortical blood flow and consecutively the decrease of oxygen tension may lead to an increase of EPO secretion.
Outpatient Management of Malignant Pleural Effusions with Small-Bore, Tunneled Pleural Catheters
Authors: Musani Ali I. , Haas Andrew R. , Seijo Luis , Wilby Mary , Sterman Daniel H.
Published: December 2004

Background: Malignant pleural effusions (MPEs) can produce significant respiratory symptoms and diminished quality of life in patients with terminal malignancies. Control of MPEs to palliate respiratory symptoms can be performed via several different approaches. Ideally, a minimally invasive procedure to control MPEs and to provide relief of respiratory symptoms would be optimal. Objective: To ascertain if control of MPEs can be achieved by outpatient management via a small-bore pleural catheter (PC) without the need for sclerosing agents. Methods: Retrospective chart analysis of 24 patients after outpatient insertion of PCs for recurrent, symptomatic MPEs followed by frequent home drainage of pleural fluid to relieve respiratory symptoms. Results: Symptomatic relief of respiratory symptoms was achieved in 100% of patients, while pleurodesis was achieved in 58% of patients in a mean of 39 days. Five patients (6 PCs) expired with the catheters in place. In these patients, all catheters remained in position and functional until the patients ultimately died from nonpleural disease progression. No major complications occurred during insertion of the catheter. Late complications included localized cellulitis and bacterial superinfection in three patients and tumor growth at the catheter site in one patient. Conclusions: The PCs used in the present study provided an effective modality not only to alleviate respiratory symptoms associated with MPE, but also to achieve pleurodesis in 58% of our patients. These catheters may provide a significantly less invasive outpatient approach to the palliative management of MPEs.
Decreased Plasma Levels of Orexin-A in Sleep Apnea
Authors: Busquets Xavier , Barbé Ferran , Barceló Antonia , de la Peña Mónica , Sigritz Nathalie , Mayoralas Lola R. , Ladaria Antoni , Agustí Alvar
Published: December 2004

Background: Orexin-A, also known as hypocretin, is a neuropeptide implicated in appetite and sleep regulation. Because the obstructive sleep apnea syndrome (OSAS) is characterized by obesity and excessive daytime sleepiness, we hypothesized that orexin-A levels may be abnormal in patients with OSAS. Further, since treatment with continuous positive airway pressure (CPAP) in patients with OSAS is very effective in normalizing daytime sleepiness, we also hypothesized that the chronic use of CPAP may influence plasma levels of orexin-A in these patients. Objective: To evaluate plasma levels of orexin-A in patients with OSAS and the effect of CPAP treatment. Patients and Methods: We compared the plasma levels of orexin-A in 13 healthy controls, 27 untreated patients with OSAS and 14 patients treated with CPAP during at least 1 year (4.5 ± 0.5 h/night; mean ± SEM). All patients had severe OSAS (apnea-hypopnea index, 57 ± 4 h–1). Results: Orexin-A plasma levels were significantly lower in untreated (9.4 ± 1.9 pg·ml–1, p < 0.01) and treated patients with OSAS (4.2 ± 1.5 pg·ml–1, p < 0.001) than in healthy subjects (20.6 ± 4.5 pg·ml–1). In untreated patients, orexin-A levels were not significantly related to daytime somnolence assessed by Epworth scale (r = –0.18, p = 0.37) or the body mass index (r = –0.13, p = 0.52). Conclusions: Orexin-A plasma levels are abnormally low in patients with OSAS, independently of the level of somnolence and/or presence of obesity. These results suggest that these low orexin-A levels may be related to the pathogenesis of OSAS.
Direct Medical Cost of Asthma in Ankara, Turkey
Authors: Çelik Gülfem E. , Bavbek Sevim , Paşaoğlu Gülden , Mungan Dilşad , Abadoğlu Öznur , Harmancı Emel , Mısırlıgil Zeynep
Published: December 2004

Background: There has been no documented data regarding the cost of asthma in our country. Objective: In this 1-year prospective study, we aimed to determine the annual cost of asthma in Ankara, Turkey. Methods: Direct medical cost analysis was performed in 118 patients. Results: Mean annual direct medical costs of asthma were USD 1,465.7 ± 111.8 per capita. Medication cost comprised the majority (81%) of the total direct cost. Mean direct medical costs according to the stage of disease were USD 172.5 ± 51.7, 860.7 ± 70.2, 1,671.6 ± 141.8 and 3,491.9 ± 417.6 for stage 1 (n = 4), 2 (n = 54), 3 (n = 46) and 4 (n = 14) patients, respectively. Conclusions: In this first study to document the cost of asthma for our region, direct cost of asthma was found to be increased with the severity of the illness. Considering the fact that medication cost comprises the major fraction of the direct cost, cost-effectiveness trials to determine the effective treatment with optimal cost for different asthma stages should be the next step.
Distribution of Catecholaminergic Neurotransmitters and Related Receptors in Human Bronchus-Associated Lymphoid Tissue
Authors: Cavallotti Carlo , Bruzzone Paolo , Tonnarini Gianfranco , Cavallotti Daniela
Published: December 2004

Background: The functions of the bronchus-associated lymphoid tissue (BALT) are under the control of the autonomic nervous system (sympathetic and parasympathetic nerve fibers). Objectives: The relationships between the adrenergic nerve fibers and β-adrenergic receptors were studied in the human BALT with the aim to demonstrate a probable neuromodulation. Methods: Morphological observations (staining with hematoxylin-eosin and scanning electron microscopy images) were carried out on samples of human BALT harvested during autopsies. Moreover, histochemical staining for norepinephrine (adrenaline = adrenergic nerve fibers) as well as for other catecholamines was performed. Finally, β-adrenergic receptors were stained by means of a β-blocking, radiolabeled drug (pindolol 125I). All our data were submitted to morphometric analysis (quantitative analysis of images and statistical analysis of data). Results: Our results provide direct evidence of the presence and distribution of catecholaminergic nerve fibers and related β-adrenergic receptors in BALT. β-Adrenergic receptors are present above all in the most richly innervated part of the BALT, and are, therefore, in close relationship with their related adrenergic nerve fibers. Conclusions: Studies on the distribution of adrenergicneurotransmitters and related β-adrenergic receptors in the human BALT are the first step for the demonstration of a probable neuromodulation of BALT.