bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Inflammatory and Acute-Phase Responses in the Brain and Peripheral Organs of the ME7 Model of Prion Disease
Authors: Cunningham Colm , Wilcockson David C. , Boche Delphine , Perry V. Hugh
Published: March 2005

Chronic neurodegenerative diseases such as prion disease and Alzheimer's disease (AD) are reported to be associated with microglial activation and increased brain and serum cytokines and acute-phase proteins (APPs). Unlike AD, prion disease is also associated with a peripheral component in that the presumed causative agent, PrPSc, also accumulates in the spleen and other lymphoreticular organs. It is unclear whether the reported systemic acute-phase response represents a systemic inflammatory response to prion disease or merely reflects central nervous system (CNS) inflammation. For this study, we investigated whether intracerebrally initiated prion disease (ME7 model) provokes splenic, hepatic, or brain inflammatory and acute-phase responses. We detected no significant elevation of proinflammatory cytokines or activation of macrophages in the spleens of these animals, despite clear PrPScdeposition. Similarly, at 19 weeks we detected no significant elevation of transcripts for the APPs serum amyloid A, complement C3, pentraxin 3, and α2-antiplasmin in the liver, despite CNS neurodegeneration and splenic PrPScdeposition at this time. However, despite the low CNS expression levels of proinflammatory cytokines, there was robust expression of these APPs in degenerating brains. These findings suggest that PrPScis not a stimulus for splenic macrophages and that neither peripheral PrPScdeposition nor CNS neurodegeneration is sufficient to produce a systemic acute-phase response. We also propose that serum cytokine and APP measurements are not useful during preclinical disease. Possible consequences of the clear chronic elevation of APPs in the CNS are discussed.
A Novel Assay Allows Genotyping of the Latent Reservoir for Human Immunodeficiency Virus Type 1 in the Resting CD4+T Cells of Viremic Patients
Authors: Monie Daphne , Simmons Rachel P. , Nettles Richard E. , Kieffer Tara L. , Zhou Yan , Zhang Haili , Karmon Sharon , Ingersoll Roxann , Chadwick Karen , Zhang Hao , Margolick Joseph B. , Quinn Thomas C. , Ray Stuart C. , Wind-Rotolo Megan , Miller Michael , Persaud Deborah , Siliciano Robert F.
Published: March 2005

A latent reservoir for human immunodeficiency virus type 1 (HIV-1) consisting of integrated provirus in resting memory CD4+T cells prevents viral eradication in patients on highly active antiretroviral therapy (HAART). It is difficult to analyze the nature and dynamics of this reservoir in untreated patients and in patients failing therapy, because it is obscured by an excess of unintegrated viral DNA that constitutes the majority of viral species in resting CD4+T cells from viremic patients. Therefore, we developed a novel culture assay that stimulates virus production from latent, integrated HIV-1 in resting CD4+T cells in the presence of antiretroviral drugs that prevent the replication of unintegrated virus. Following activation, resting CD4+T cells with integrated HIV-1 DNA produced virus particles for several days, with peak production at day 5. Using this assay, HIV-1polsequences from the resting CD4+T cells of viremic patients were found to be genetically distinct from contemporaneous plasma virus. Despite the predominance of a relatively homogeneous population of drug-resistant viruses in the plasma of patients failing HAART, resting CD4+T cells harbored a diverse array of wild-type and archival drug-resistant viruses that were less fit than plasma virus in the context of current therapy. These results provide the first direct evidence that resting CD4+T cells serve as a stable reservoir for HIV-1 even in the setting of high levels of viremia. The ability to analyze archival species in viremic patients may have clinical utility in detecting drug-resistant variants not present in the plasma.
In Vivo Evidence for Instability of Episomal Human Immunodeficiency Virus Type 1 cDNA
Authors: Sharkey Mark , Triques Karine , Kuritzkes Daniel R. , Stevenson Mario
Published: March 2005

Current regimens for the management of human immunodeficiency virus type 1 (HIV-1) infection suppress plasma viremia to below detectable levels for prolonged intervals. Nevertheless, there is a rapid resumption in plasma viremia if therapy is interrupted. Attempts to characterize the extent of viral replication under conditions of potent suppression and undetectable plasma viremia have been hampered by a lack of convenient assays that can distinguish latent from ongoing viral replication. Using episomal viral cDNA as a surrogate for ongoing replication, we previously presented evidence that viral replication persists in the majority of infected individuals with a sustained aviremic status. The labile nature of viral episomes and hence their validity as surrogate markers of ongoing replication in individuals with long-term-suppressed HIV-1 infection have been analyzed in short-term in vitro experiments with conflicting results. Since these in vitro experiments do not shed light on the long-term in vivo dynamics of episomal cDNA or recapitulate the natural targets of infection in vivo, we have analyzed the dynamics of episomal cDNA turnover in vivo by following the emergence of an M184V polymorphism in plasma viral RNA, in episomal cDNA, and in proviral DNA in patients on suboptimal therapies. We demonstrate that during acquisition of drug resistance, wild-type episomal cDNAs are replaced by M184V-harboring episomes. Importantly, a complete replacement of wild-type episomes with M184V-containing episomes occurred while proviruses remained wild type. This indicates that episomal cDNAs are turned over by degradation rather than through death or tissue redistribution of the infected cell itself. Therefore, evolution of episomal viral cDNAs is a valid surrogate of ongoing viral replication in HIV-1-infected individuals
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Weak Palindromic Consensus Sequences Are a Common Feature Found at the Integration Target Sites of Many Retroviruses
Authors: Wu Xiaolin , Li Yuan , Crise Bruce , Burgess Shawn M. , Munroe David J.
Published: March 2005

Integration into the host genome is one of the hallmarks of the retroviral life cycle and is catalyzed by virus-encoded integrases. While integrase has strict sequence requirements for the viral DNA ends, target site sequences have been shown to be very diverse. We carefully examined a large number of integration target site sequences from several retroviruses, including human immunodeficiency virus type 1, simian immunodeficiency virus, murine leukemia virus, and avian sarcoma-leukosis virus, and found that a statistical palindromic consensus, centered on the virus-specific duplicated target site sequence, was a common feature at integration target sites for these retroviruses.
Induction of Apoptosis by Rewiring the Signal Transduction of Epstein-Barr Virus Oncoprotein LMP1 toward Caspase Activation
Authors: Hatzivassiliou Eudoxia G. , Tsichritzis Theodore , Mosialos George
Published: March 2005

The Epstein-Barr virus latent membrane protein 1 (LMP1) is an oncoprotein which mimics activated tumor necrosis factor receptor family members. Here we demonstrate the principle that an inducible association of the LMP1 cytoplasmic carboxyl terminus with caspase-8 by a heterodimerizing agent causes apoptosis. This process depends on the catalytic activity of caspase-8 and the ability of LMP1 to oligomerize constitutively at the plasma membrane. Our data indicate that chemical inducers of the association of the LMP1 carboxyl terminus with caspase-8 can kill LMP1-expressing cells selectively. Such compounds could be used as chemotherapeutic agents for LMP1-associated malignancies.
Tissue-Resident Macrophages Are Productively Infected Ex Vivo by Primary X4 Isolates of Human Immunodeficiency Virus Type 1
Authors: Jayakumar Prerana , Berger Irina , Autschbach Frank , Weinstein Mark , Funke Benjamin , Verdin Eric , Goldsmith Mark A. , Keppler Oliver T.
Published: March 2005

Infection of macrophages has been implicated as a critical event in the transmission and persistence of human immunodeficiency virus type 1 (HIV-1). Here, we explore whether primary X4 HIV-1 isolates can productively infect tissue macrophages that have terminally differentiated in vivo. Using immunohistochemistry, HIV-1 RNA in situ hybridization, and confocal immunofluorescence microscopy, we demonstrate that macrophages residing in human tonsil blocks can be productively infected ex vivo by primary X4 HIV-1 isolates. This challenges the model in which macrophage tropism is a key determinant of the selective transmission of R5 HIV-1 strains. Infection of tissue macrophages by X4 HIV-1 may be highly relevant in vivo and contribute to key events in HIV-1 pathogenesis.
Ex Vivo Stimulation of B Cells Latently Infected with Gammaherpesvirus 68 Triggers Reactivation from Latency
Authors: Moser Janice M. , Upton Jason W. , Gray Kathleen S. , Speck Samuel H.
Published: March 2005

Murine gammaherpesvirus 68 (γHV68) infection of mice results in the establishment of a chronic infection, which is largely maintained through latent infection of B lymphocytes. Acute virus replication is almost entirely cleared by 2 weeks postinfection. Spontaneous reactivation of γHV68 from latently infected splenocytes upon ex vivo culture can readily be detected at the early stages of infection (e.g., day 16). However, by 6 weeks postinfection, very little spontaneous reactivation is detected upon explant into tissue culture. Here we report that stimulation of latently infected splenic B cells harvested at late times postinfection with cross-linking surface immunoglobulin (Ig), in conjunction with anti-CD40 antibody treatment, triggers virus reactivation. As expected, this treatment resulted in B-cell activation, as assessed by upregulation of CD69 on B cells, and ultimately B-cell proliferation. Since anti-Ig/anti-CD40 stimulation resulted in splenic B-cell proliferation, we assessed whether this reactivation stimulus could overcome the previously characterized defect in virus reactivation of a v-cyclin null γHV68 mutant. This analysis demonstrated that anti-Ig/anti-CD40 stimulation could drive reactivation of the v-cyclin null mutant virus in latently infected splenocytes, but not to the levels observed with wild-type γHV68. Thus, there appears to be a role for the v-cyclin in B cells following anti-Ig/anti-CD40 stimulation independent of the induction of the cell cycle. Finally, to assess signals that are not mediated through the B-cell receptor, we demonstrate that addition of lipopolysaccharide to explanted splenocyte cultures also enhanced virus reactivation. These studies complement and extend previous analyses of Epstein-Barr virus and Kaposi's sarcoma-associated virus reactivation from latently infected cell lines by investigating reactivation of γHV68 from latently infected primary B cells recovered from infected hosts.
Identification of a New Quaternary Neutralizing Epitope on Human Immunodeficiency Virus Type 1 Virus Particles
Authors: Gorny Miroslaw K. , Stamatatos Leonidas , Volsky Barbara , Revesz Kathy , Williams Constance , Wang Xiao-Hong , Cohen Sandra , Staudinger Robert , Zolla-Pazner Susan
Published: March 2005

The selection of human monoclonal antibodies (MAbs) specific for human immunodeficiency virus (HIV) type 1 by binding assays may fail to identify Abs to quaternary epitopes on the intact virions. The HIV neutralization assay was used for the selection of human MAb 2909, which potently neutralizes SF162 and recognizes an epitope on the virus surface but not on soluble proteins. Three regions of gp120, the V2 and V3 loops and the CD4 binding domain, contribute to the epitope recognized by MAb 2909. The existence of such a unique MAb, which defines a complex epitope formed by a quaternary structure, suggests that there may be other new neutralizing HIV epitopes to target with vaccines.
Incidence of sports and recreation related injuries resulting in hospitalization in Wisconsin in 2000
Authors: Dempsey R L , Layde P M , Laud P W , Guse C E , Hargarten S W
Published: April 2005

Objective:To describe the incidence and patterns of sports and recreation related injuries resulting in inpatient hospitalization in Wisconsin. Although much sports and recreation related injury research has focused on the emergency department setting, little is known about the scope or characteristics of more severe sports injuries resulting in hospitalization.

Setting:The Wisconsin Bureau of Health Information (BHI) maintains hospital inpatient discharge data through a statewide mandatory reporting system. The database contains demographic and health information on all patients hospitalized in acute care non-federal hospitals in Wisconsin.

Methods:The authors developed a classification scheme based on the International Classification of Diseases External cause of injury code (E code) to identify hospitalizations for sports and recreation related injuries from the BHI data files (2000). Due to the uncertainty within E codes in specifying sports and recreation related injuries, the authors used Bayesian analysis to model the incidence of these types of injuries.

Results:There were 1714 (95% credible interval 1499 to 2022) sports and recreation-related injury hospitalizations in Wisconsin in 2000 (32.0 per 100 000 population). The most common mechanisms of injury were being struck by/against an object in sports (6.4 per 100 000 population) and pedal cycle riding (6.2 per 100 000). Ten to 19 year olds had the highest rate of sports and recreation related injury hospitalization (65.3 per 100 000 population), and males overall had a rate four times higher than females.

Conclusions:Over 1700 sports and recreation related injuries occurred in Wisconsin in 2000 that were treated during an inpatient hospitalization. Sports and recreation activities result in a substantial number of serious, as well as minor injuries. Prevention efforts aimed at reducing injuries while continuing to promote participation in physical activity for all ages are critical.
BONDING PROPERTIES AND TEMPERATURE DEPENDENCE CHARACTERISTIC OF AMORPHOUS CARBON NITRIDE THIN FILMS PREPARED BY PULSED LASER DEPOSITION FOR SOLAR CELL APPLICATIONS
Authors: RUSOP M. , SOGA T. , JIMBO T. , UMENO M.
Published: March 2005

Amorphous carbon nitride (a-C:N) thin films are deposited by pulsed laser deposition technique at room temperature using a camphoric carbon target with different nitrogen partial pressures in the range from 0.1 to 800 mTorr. The room temperature conductivity (σ RT ) is found to increase with N incorporation, which may be due to the lattice vibrations leading to the scattering of the charge carriers by the N atoms and the more amorphous nature of the carbon films. Study of activation energy reveals that the Fermi level of the a-C:N film moves from the valence band to near the conduction band edge through the midgap. The current–voltage photovoltaic characteristics of a-C:N/p-Si cells under 1 sun air-mass 1.5 (AM 1.5) illumination condition (100 mW/cm2, 25°C) are improved up to 30 mTorr and deteriorate thereupon. The maximum of open-circuit voltage (V oc ) and short-circuit current density (J sc ) for the cells are observed to be approximately 292 mV and 9.02 mA/cm2, respectively. The highest energy conversion efficiency (η) and fill factor (FF) were found to be approximately 1.47% and 56%, respectively.
MAGNETIC PROPERTIES OF GdxY1-xLaAl4 SYSTEM
Authors: LUPSA ILEANA
Published: March 2005

The magnetic and structural study of Gd x Y 1-x LaAl 4 system was performed. The magnetic properties investigated in the 4–600 K temperature range and fields up to 80 kOe showed the ferromagnetic order for x≤0.8. For low gadolinium concentration, x≤0.4, the magnetic moment and the transition temperature values are lower than expected for Gd 3+ ion. It is considered that the dilution allows the formation of substitutional and atomic disorder, leading to modifications in the exchange interactions and determining a random-distribution configuration for gadolinium moments.
OPTICAL ABSORPTION AND ESR SPECTRAL STUDIES ON COPPER-DOPED LEAD-CADMIUM GLASSES
Authors: PRASAD M. , CHANDRASEKHAR M. , CHANDRA MOULI V.
Published: March 2005

The electron spin resonance and optical absorption spectra of PbO-CdO glasses containing 1 mole% CuO have been investigated at room temperature. The optical absorption spectra of all glass samples have exhibited a broad asymmetric absorption band, which corresponds to a d–d transition of Cu 2+ ions. The prepared glass samples have been analyzed as a function of the photon energy. The results are interpreted based on the optical absorption spectral profiles and also the edge values upon the application of Davis and Mott's theory. From the ESR spectral features, the spin Hamiltonian parameters have been evaluated. The bonding coefficients were obtained, in order to elucidate the information on the Cu 2+ ligand bond nature.
POSITRON FACILITIES TESTS OF THE X-RAYS PRODUCED BY CRYSTALLINE UNDULATORS
Authors: BELLUCCI S.
Published: March 2005

One of the main involvements of the INFN-Laboratori Nazionali di Frascati group in channeling researches is described, i.e. the crystal undulator R & D, with the characterization of the crystal undulator prototypes with SEM and the positron beam. We consider a precise determination of the optimal experimental conditions for channeling of this kind of accelerated particles through such microstructured crystals, as promising candidates for producing X-ray beams.
CHARACTERISTIC ASPECTS OF CERAMIC COMPOUNDS CONTAINING YTTERBIUM
Authors: REDAC TEODOR-RADU
Published: March 2005

This paper presents experimental data obtained by its author on superconductive ceramics of type 1-2-3, with ytterbium as the element of rare earth. Thermal, electric and magnetic analyses are presented.

The aim of the paper is to put in evidence the effect of the substitution of Yb or Cu with Ga in the compound YbBa 2 Cu 3 O 7-δ, in order to compare these properties of this compound with other compounds from the same class having Y or Eu as rare earth ions.
COMPACT REPRESENTATIONS OF SEARCH IN COMPLEX DOMAINS
Authors: BEN-ASHER YOSI , FARCHI EITAN
Published: April 2005

We introduce a new zero-sum matrix game for modeling search in structured domains. In this game, one player tries to find a "bug" while the other tries to hide it. Both players exploit the structure of the "search" domain. Intuitively, this search game is a mathematical generalization of the well known binary search. The generalization is from searching over totally ordered sets to searching over more complex search domains such as trees, partial orders and general set systems. As there must be one row for every search strategy, and there are exponentially many ways to search even in very simple search domains, the game's matrix has exponential size ("space"). In this work we present two ways to reduce the space required to compute the Nash value (in pure strategies) of this game:

• First we show that a Nash equilibrium in pure strategies can be computed by using a backward induction on the matrices of each "part" or sub structure of the search domain. This can significantly reduce the space required to represent the game.

• Next, we show when general search domains can be represented as DAGs (Directed Acycliqe Graphs). As a result, the Nash equilibrium can be directly computed using the DAG. Consequently the space needed to compute the desired search strategy is reduced to O(n2) where n is the size of the search domain.
REDUCING FUZZY ALGEBRA TO CLASSICAL ALGEBRA
Authors: WEINBERGER ARTHUR
Published: April 2005

This paper presents three main ideas. They are the Metatheorem, the lattice embedding for sets, and the lattice embedding for algebras.

The Metatheorem allows you to convert existing theorems about classical subsets into corresponding theorem about fuzzy subsets. The concept of a fuzzyfiable operation on a powerset is defined. The main result states that any implication or identity which can be stated using fuzzyfiable operations is true about fuzzy subsets if and only if it is true about classical subsets.

The lattice embedding theorem for sets shows that for any set X, there is a set Y such that the lattice of fuzzy subsets of X is isomorphic to a sublattice of the classical subsets of Y. In fact it is further proved that if X is infinite, then we can choose Y = X and get the surprising result that the lattice of fuzzy subsets of X is isomorphic to a sublattice of the classical subsets of X itself. The idea is illustrated with an example explicitly showing how the lattice of fuzzy subsets of the closed unit interval 𝕀 = [0,1] embeds into the lattice of classical subsets of 𝕀.

The lattice embedding theorem for algebras shows that under certain circumstances the lattice of fuzzy subalgebras of an algebra A embeds into the lattice of classical subalgebras of a closely related algebra A′. The following sample use of this embeding theorem is given. It is a well known fact that the lattice of normal subgroups of a group is a modular lattice. The embeding theorem is used here to conclude that lattice of fuzzy normal subgroups of a group is a modular lattice too.
THE APPRENTICE WIZARD: MONTETARY POLICY, COMPLEXITY AND LEARNING
Authors: GATTI DOMENICO DELLI , GAFFEO EDOARDO , GALLEGATI MAURO , PALESTRINI ANTONIO
Published: April 2005

This paper investigates some central issues of monetary policy by offering a model in which a central bank tries to stabilize fluctuations in aggregate output and inflation in an adaptive complex economy. We resort to evolutionary algorithms to model the central bank behaviour under discretion, and confront the efficiency of discretion with the choice of full commitment to a fixed rule.
Integrated pharmacological preconditioning and memory of cardioprotection: role of protein kinase C and phosphatidylinositol 3-kinase
Authors: Okada Takayuki , Otani Hajime , Wu Yue , Uchiyama Takamichi , Kyoi Shiori , Hattori Reiji , Sumida Tomohiko , Fujiwara Hiroyoshi , Imamura Hiroji
Published: April 2005

Although protein kinase C (PKC) and phosphatidylinositol 3 (PI3)-kinase are implicated in cardioprotective signal transduction mediated by ischemic preconditioning, their role in pharmacological preconditioning (PPC) has not been determined. Cultured neonatal rat cardiomyocytes (CMCs) were subjected to simulated ischemia for 2 h followed by 15 min of reoxygenation. PPC of CMCs consisted of administration of 50 μM adenosine, 50 μM diazoxide, and 50 μM S-nitroso- N-acetylpenicillamine (SNAP), each alone or in combination, for 15 min followed by 30 min of washout before simulated ischemia. Although PKC-ε and PI3-kinase were significantly activated during treatment with adenosine, activation of these kinases dissipated after washout. In contrast, PPC combined with adenosine, diazoxide, and SNAP elicited sustained activation of PKC-ε and PI-3 kinase after washout. The combined-PPC, but not the single-PPC, protocol conferred antiapoptotic and antinecrotic effects after reoxygenation. The PKC inhibitor chelerythrine (5 μM) or the PI3-kinase inhibitor LY-294002 (10 μM) given during the washout period partially blocked the activation of PKC-ε and PI3-kinase mediated by the combined-PPC protocol, whereas combined addition of chelerythrine and LY-294002 completely inhibited activation of PKC-ε and PI3-kinase. Chelerythrine or LY-294002 partially blocked antiapoptotic and antinecrotic effects mediated by the combined-PPC protocol, whereas combined addition of chelerythrine and LY-294002 completely abrogated antiapoptotic and antinecrotic effects. These results suggest that the combined-PPC protocol confers cardioprotective memory through sustained and interdependent activation of PKC and PI3-kinase.
Blue flicker modifies the subfoveal choroidal blood flow in the human eye
Authors: Lovasik John V. , Kergoat Hélène , Wajszilber Marcelo A.
Published: April 2005

The objective of the present study was to reveal an interaction between choroidal blood flow (ChBF) and light-induced photoreceptor activity, a physiological coupling that has been already demonstrated for retinal blood flow but rejected for ChBF. Ten healthy adults volunteered for this study. A real-time recording near-infrared laser-Doppler flowmeter was used to quantify the subfoveal ChBF while the luminance of blue flicker between 1 and 64 Hz was first increased and then decreased by 4.0 log units in 1.0-log unit steps between 0.0375 and 375 cd/m2. In separate testing, flash electroretinograms (ERGs) provided electrophysiological indexes of the relative response of short-wave cones (s-cones) and rods to blue light stimulation. Group-averaged, normalized ChBF measurements revealed that it was modulated by ∼9% by flicker frequency. Increasing the blue flicker luminance from low to high attenuated the subfoveal ChBF, volume, and velocity by ∼32%, ∼30%, and ∼5%, respectively. Decreasing the luminance from high to low over the same range had no effect on the subfoveal choroidal hemodynamics. The markedly different effects of reversed directions of change in blue flicker luminance on the subfoveal ChBF were linked to transitions between rod-dominated and s-cone-dominated retinal responses. Collectively, these findings indicate that the blue light-induced photoreceptor response is associated with a differential distribution of the ChBF across the ocular fundus according to the degree and type of retinal photoreceptor stimulated.
Specific carotid body chemostimulation is sufficient to elicit phrenic poststimulus frequency decline in a novel in situ dual-perfused rat preparation
Authors: Day Trevor A. , Wilson Richard J. A.
Published: April 2005

Time-dependent ventilatory responses to hypoxic and hypercapnic challenges, such as posthypoxic frequency decline (PHxFD) and posthypercapnic frequency decline (PHcFD), could profoundly affect breathing stability. However, little is known about the mechanisms that mediate these phenomena. To determine the contribution of specific carotid body chemostimuli to PHxFD and PHcFD, we developed a novel in situ arterially perfused, vagotomized, decerebrate rat preparation in which central and peripheral chemoreceptors are perfused separately (i.e., a nonanesthetized in situ dual perfused preparation). We confirmed that 1) the perfusion of central and peripheral chemoreceptor compartments was independent by applying specific carotid body hypoxia and hypercapnia before and after carotid sinus nerve transection, 2) the Pco2 chemoresponse of the dual perfused preparation was similar to other decerebrate preparations, and 3) the phrenic output was stable enough to allow investigation of time-dependent phenomena. We then applied four 5-min bouts (separated by 5 min) of specific carotid body hypoxia (40 Torr Po2 and 40 Torr Pco2) or hypercapnia (100 Torr Po2 and 60 Torr Pco2) while holding the brain stem Po2 and Pco2 constant. We report the novel finding that specific carotid body chemostimuli were sufficient to elicit several phrenic time-dependent phenomena in the rat. Hypoxic challenges elicited PHxFD that increased with bout, leading to progressive augmentation of the phrenic response. Conversely, hypercapnia elicited short-term depression and PHcFD, neither of which was bout dependent. These results, placed in the context of previous findings, suggest multiple physiological mechanisms are responsible for PHxFD and PHcFD, a redundancy that may illustrate that these phenomena have significant adaptive advantages.
Acoustic rhinometry in humans: accuracy of nasal passage area estimates, and ability to quantify paranasal sinus volume and ostium size
Authors: Tarhan Erkan , Coskun Mehmet , Cakmak Ozcan , Çelik Hüseyin , Cankurtaran Mehmet
Published: April 2005

A comprehensive study that compared acoustic rhinometry (AR) data to computed tomography (CT) data was performed to evaluate the accuracy of AR measurements in estimating nasal passage area and to assess its ability of quantifying paranasal sinus volume and ostium size in live humans. Twenty nasal passages of 10 healthy adults were examined by using AR and CT. Actual cross-sectional areas of the nasal cavity, sinus ostia sizes, and maxillary and frontal sinus volumes were determined from CT sections perpendicular to the curved acoustic axis of the nasal passage. Nasal cavity volume (from nostril to choana) calculated from the AR-derived area-distance curve was compared with that from the CT-derived area-distance curve. AR measurements were also done on pipe models that featured a side branch (Helmholtz resonator of constant volume but two different neck diameters) simulating a paranasal sinus. In the anterior nasal cavity, there was good agreement between the cross-sectional areas determined by AR and CT. However, posterior to the sinus ostia, AR overestimated cross-sectional area. The difference between AR nasal volume and CT nasal volume was much smaller than the combined volume of the maxillary and frontal sinuses. The results suggest that AR measurements of the healthy adult nasal cavity are reasonably accurate to the level of the paranasal sinus ostia. Beyond this point, AR overestimates cross-sectional area and provides no quantitative data for sinus volume or ostium size. The effects of paranasal sinuses and acoustic resonances in the nasal cavity are not accounted for in the present AR algorithms.
Selective α2-adrenergic properties of dexmedetomidine over clonidine in the human forearm
Authors: Masuki Shizue , Dinenno Frank A. , Joyner Michael J. , Eisenach John H.
Published: April 2005

We tested the hypothesis that dexmedetomidine (Dex) has greater α2- vs. α1 selectivity than clonidine and causes more α2-selective vasoconstriction in the human forearm. After local β-adrenergic blockade with propranolol, forearm blood flow (plethysmography) responses to brachial artery administration of Dex, clonidine, and phenylephrine (α1-agonist) were determined in healthy young adults before and after α2-blockade with yohimbine ( n = 10) or α1-blockade with prazosin ( n = 9). Yohimbine had no effect on phenylephrine-mediated vasoconstriction but blunted Dex-mediated vasoconstriction (mean ± SE: −41 ± 5 vs. −11 ± 2%; before vs. after yohimbine) more than clonidine-mediated vasoconstriction (−39 ± 5 vs. −28 ± 4%; before vs. after yohimbine) ( P < 0.02). Prazosin blunted phenylephrine-mediated vasoconstriction (−39 ± 4 vs. −8 ± 2%; before vs. after prazosin) but had similar effects on both Dex- (−30 ± 4 vs. −39 ± 6%; before vs. after prazosin) and clonidine-mediated vasoconstriction (−29 ± 3 vs. −41 ± 7%; before vs. after prazosin) ( P > 0.7). Both Dex and clonidine reduced deep forearm venous norepinephrine concentrations to a similar extent (−59 ± 12 vs. −55 ± 10 pg/ml; Dex vs. clonidine, P > 0.6); this effect was abolished by yohimbine and blunted by prazosin. These results suggest that Dex causes more α2-selective vasoconstriction in the forearm than clonidine. The similar vasoconstrictor responses to both drugs after prazosin might be explained by the presynaptic effects on norepinephrine release.
Epithelial cell deformation during surfactant-mediated airway reopening: a theoretical model
Authors: Naire Shailesh , Jensen Oliver E.
Published: April 2005

A theoretical model is presented describing the reopening by an advancing air bubble of an initially liquid-filled collapsed airway lined with deformable epithelial cells. The model integrates descriptions of flow-structure interaction (accounting for nonlinear deformation of the airway wall and viscous resistance of the airway liquid flow), surfactant transport around the bubble tip (incorporating physicochemical parameters appropriate for Infasurf), and cell deformation (due to stretching of the airway wall and airway liquid flows). It is shown how the pressure required to drive a bubble into a flooded airway, peeling apart the wet airway walls, can be reduced substantially by surfactant, although the effectiveness of Infasurf is limited by slow adsorption at high concentrations. The model demonstrates how the addition of surfactant can lead to the spontaneous reopening of a collapsed airway, depending on the degree of initial airway collapse. The effective elastic modulus of the epithelial layer is shown to be a key determinant of the relative magnitude of strains generated by flow-induced shear stresses and by airway wall stretch. The model also shows how epithelial-layer compressibility can mediate strains arising from flow-induced normal stresses and stress gradients.
Anatomically based finite element models of the human pulmonary arterial and venous trees including supernumerary vessels
Authors: Burrowes Kelly S. , Hunter Peter J. , Tawhai Merryn H.
Published: April 2005

Studies of the origin of pulmonary blood flow heterogeneity have highlighted the significant role of vessel branching structure on flow distribution. To enable more detailed investigation of structure-function relationships in the pulmonary circulation, an anatomically based finite element model of the arterial and venous networks has been developed to more accurately reflect the geometry found in vivo. Geometric models of the arterial and venous tree structures are created using a combination of multidetector row X-ray computed tomography imaging to define around 2,500 vessels from each tree, a volume-filling branching algorithm to generate the remaining accompanying conducting vessels, and an empirically based algorithm to generate the supernumerary vessel geometry. The explicit generation of supernumerary vessels is a unique feature of the computational model. Analysis of branching properties and geometric parameters demonstrates close correlation between the model geometry and anatomical measures of human pulmonary blood vessels. A total of 12 Strahler orders for the arterial system and 10 Strahler orders for the venous system are generated, down to the equivalent level of the terminal bronchioles in the bronchial tree. A simple Poiseuille flow solution, assuming rigid vessels, is obtained within the arterial geometry of the left lung, demonstrating a large amount of heterogeneity in the flow distribution, especially with inclusion of supernumerary vessels. This model has been constructed to accurately represent available morphometric data derived from the complex asymmetric branching structure of the human pulmonary vasculature in a form that will be suitable for application in functional simulations.
Thromboxane inhibition reduces an early stage of chronic hypoxia-induced pulmonary hypertension in piglets
Authors: Fike Candice D. , Zhang Yongmei , Kaplowitz Mark R.
Published: April 2005

The pulmonary vasoconstrictor, thromboxane, may contribute to the development of pulmonary hypertension. Our objective was to determine whether a combined thromboxane synthase inhibitor-receptor antagonist, terbogrel, prevents pulmonary hypertension and the development of aberrant pulmonary arterial responses in newborn piglets exposed to 3 days of hypoxia. Piglets were maintained in room air (control) or 11% O2 (hypoxic) for 3 days. Some hypoxic piglets received terbogrel (10 mg/kg po bid). Pulmonary arterial pressure, pulmonary wedge pressure, and cardiac output were measured in anesthetized animals. A cannulated artery technique was used to measure responses to acetylcholine. Pulmonary vascular resistance for terbogrel-treated hypoxic piglets was almost one-half the value of untreated hypoxic piglets but remained greater than values for control piglets. Dilation to acetylcholine in preconstricted pulmonary arteries was greater for terbogrel-treated hypoxic than for untreated hypoxic piglets, but it was less for pulmonary arteries from both groups of hypoxic piglets than for control piglets. Terbogrel may ameliorate pulmonary artery dysfunction and attenuate the development of chronic hypoxia-induced pulmonary hypertension in newborns.
Early Dynamics of Hepatitis C Virus in the Circulation of Chimpanzees with Experimental Infection
Authors: Tanaka Junko , Katayama Keiko , Kumagai Junko , Komiya Yutaka , Yugi Hisao , Kishimoto Shinya , Mizui Masaaki , Tomoguri Tetsushi , Miyakawa Yuzo , Yoshizawa Hiroshi
Published: April 2005

Two chimpanzees were inoculated with hepatitis C virus (HCV) and followed on a daily basis for 12 days. HCV RNA became detectable in their sera on day 5 by polymerase chain reaction with the detection limit of 102 copies/ml. Based on an exponential growth observed until 8 or 9 days after inoculation in their sera, the doubling time of HCV in the circulation was estimated at 6.3–8.6 h and log time (time required to grow 10-fold) at 31.3– 42.9 h. The exact doubling time of HCV determined in them would help plan an efficient strategy for screening out blood donors in the window period of infection between the exposure and the development of antibody to HCV in serum.
Langerhans Cells Stimulated by Mechanical Stress Are Susceptible to Measles Virus Infection
Authors: Watari Eiji , Shimizu Masumi , Takahashi Hidemi
Published: April 2005

Objective: Measles virus (MV) first infects the human respiratory tract, but the initial target cells are unknown. We examined whether MV infects Langerhans cell-like dendritic cells (LCs) generated from CD14+ monocytes in the presence of GM-CSF, IL-4, and TGF-β1. Methods: Cultured LCs were established as described recently [Biochem Biophys Res Commun 2003;306:674–679]. The expression of immunological markers was detected by FACScan. Infection with MV was assessed by syncytia formation, viral-specific fluorescence, and Western blotting. Results: MV did not infect and replicate the freshly established, unstimulated LCs expressing CD1a, E-cadherin and Langerin but not CD83. Also, CD150, a receptor for MV was not expressed on the surface of the LCs. However, LCs stimulated by mechanical stress such as washing and centrifugation became susceptible to MV infection. Conclusion: A subset of mechanically stimulated LCs but not unstimulated immature ones became susceptible to MV. The actual role of Langerhans cells in local immunity seems to be to suppress unfavorable reactions initiated by virus intrusion.
Visual Results after Primary Intraocular Lens Implantation or Contact Lens Correction for Aphakia in the First Year of Age
Authors: Autrata Rudolf , Řehuřek Jaroslav , Vodičková Kristina
Published: April 2005

Purpose: The optimal role of intraocular lenses (IOLs) in infants remains a controversial topic. Some ophthalmologists advocate correction with a contact lens (CL), whereas others recommend an IOL correction. Our study compared visual acuity, ocular alignment, retreatment rate and binocular vision outcomes in children treated with these two methods at our clinic. Methods: This study included 41 children with unilateral congenital cataract who underwent cataract surgery with posterior capsulorhexis and anterior vitrectomy, coupled with (IOL group, n = 18) or without (CL group, n = 23) primary IOL implantation. All infants underwent the first surgery during the first 12 months of their life and they were operated on in the period from 1994 to 1999. The mean age at surgery was 3.11 ± 2.65 months (range: 28 days to 11 months). All patients were prescribed the same half-time reduced occlusion therapy. Good cooperation of the parents and good compliance with patching were the necessary conditions to include a patient in the study. Between January and February 2003, the final visual acuity and binocular vision outcomes were examined. Results: The mean final visual acuity (logarithm of the minimum angle of resolution) of the operated eye was 0.43 ± 0.33 for the IOL group and 0.58 ± 0.39 for the CL group (p = 0.14). The mean interocular difference in visual acuity was 0.22 ± 0.29 for the IOL group and 0.56 ± 0.31 for the CL group (p = 0.042). The reoperation rate was 78% in the IOL group compared with 35% in the CL group (p = 0.017). Esotropia or exotropia of more than 8 prism diopters were present in 55% of children (10/18) in the IOL group compared with 83% of children (19/23) in the CL group (p = 0.039). Conclusions: We suggest that correction of aphakia after unilateral congenital cataract surgery with primary IOL implantation results in improved visual acuity, improved binocular vision outcome and less occurrence of strabismus, but a higher rate of complications requiring reoperation. Further studies with a larger pediatric patient group are necessary to confirm the optimal treatment of aphakia after unilateral congenital cataract extraction.
Failure to Detect Hepatitis B Virus in Vitreous by Polymerase Chain Reaction
Authors: Aras Cengiz , Ozdamar Akif , Ergin Sevgi , Ozturk Recep , Midilli Kenan , Karacorlu Murat , Ozkan Sehirbay
Published: April 2005

Purpose: To assay the vitreous of asymptomatic hepatitis B virus (HBV) carriers for the presence of HBV DNA using polymerase chain reaction (PCR). Methods: Vitreous and serum specimens were collected from 13 carriers of HBV. The presence of HBV DNA was investigated by using PCR and Digene’s Hybrid Capture System. The presence of hepatitis B surface antigen (HBsAg) in vitreous was also investigated by using the enzyme immunoassay (EIA). Results: The serum was positive for HBV DNA in3 of the 13 asymptomatic carriers using PCR. Vitreous samples of all the patients, including 3 patients who were positive for HBV DNA in serum, were negative for HBV DNA with PCR and were negative for HBsAg with EIA. Conclusion: There is no evidence of HBV in the vitreous of asymptomatic HBV carriers.
Multiple Visual Hallucinations and Pseudohallucinations in One Individual Patient: When the World Is Turning Upside Down and the Television Keeps Falling to the Ground while Dwarfs Are Parading on the Ceiling
Authors: Killer H.E. , Buettner U.W.
Published: April 2005

We report on a patient who experienced visual hallucinations and pseudohallucinations comprising palinopsia, peduncular hallucinosis, and oblique vision. The most probable etiologies of these phenomena are discussed with respect to clinical presentation and findings on computed tomography and magnetic resonance imaging.
Effect of Cytokines and Chemokines on Sickle Neutrophil Adhesion to Fibronectin
Authors: Assis Angêla , Conran Nicola , Canalli Andreia A. , Lorand-Metze Irene , Saad Sara T.O. , Costa Fernando F.
Published: April 2005

A role for leukocytes in sickle cell vaso-occlusive crisis is becoming increasingly recognized. Neutrophil counts are higher in sickle cell patients and neutrophils from these patients demonstrate increased adhesion to endothelial monolayers under certain circumstances. The effects of selected cytokines on the adhesion mechanisms of normal neutrophils and neutrophils from sickle cell anaemia patients (SCA neutrophils) were investigated. Neutrophils were separated from the blood of homozygous (HbSS) SCA patients and healthy controls. Following pre-incubation (25 min, 37°C) of the cells with cytokines, the adhesion of the cells to fibronectin (FN)-coated plates (20 µg/ml) was determined (60 min, 37°C, 5% CO2). Basal adhesion of normal and SCA neutrophils to FN was not statistically different. Pretreatment of normal neutrophils with either IL-6 (10–100 pg/ml), GCSF (1– 10 ng/ml) or IL-8 (1–100 ng/ml) had no significant effect upon their adhesion to FN. In contrast, SCA neutrophil adhesion to FN was increased significantly following pre-incubation with IL-6, G-CSF and IL-8 (p < 0.01). RANTES (1–100 ng/ml) had no significant effect on either normal or SCA neutrophil adhesion to FN. Flow-cytometric analyses demonstrated that IL-8 (10 ng/ml) significantly augments CD11b (Mac-1 integrin subunit) expression on SCA neutrophils, but not normal neutrophils. IL-6 and G-CSF (10 pg/ml and 10 ng/ml, respectively), however, had no effect on SCA neutrophil adhesion molecule expression. In conclusion, SCA neutrophil adhesion mechanisms may increase in the presence of certain cytokines, in vivo, and this activation may contribute to the physiopathology of sickle cell disease.
Autoimmune Disorders in Two Patients with Myelodysplastic Syndrome and 5q Deletion
Authors: Giagounidis A.A.N. , Haase S. , Germing U. , Heinsch M. , Aul C.
Published: April 2005

Autoimmune diseases occurring concurrently with myelodysplastic syndrome (MDS) with deletion del(5q) including band q31 are very rare and have only been reported twice in the medical literature. We present two additional cases, one patient with del(5q) and trisomy 21 who suffered from rheumatoid arthritis and one patient with isolated del(5q) and autoimmune hemolytic anemia. Both patients had mild leukopenia and severe transfusion-dependent anemia. The rheumatoid arthritis was treated with antirheumatics without additional immunosuppressive medication. Autoimmune hemolytic anemia was controlled with long-term steroid administration. This patient developed additional trisomy 21 2 years after the initial diagnosis of del(5q). Contrary to previous reports on autoimmune disorders in MDS mentioning improvements of hematological function in response to steroid administration, neither of our patients had a hematological improvement under corticosteroids.
Gastric Cancer: Who Is at Risk?
Authors: Zagari Rocco Maurizio , Bazzoli Franco
Published: April 2005

Gastric cancer is a multifactorial disease. Helicobacter pylori infection, host genetic factors and dietetic factors play an important role in the development of gastric cancer. Individuals with a positive family history of gastric cancer and/or pro-inflammatory polymorphisms of the interleukin-1 and tumor necrosis factor A genes infected by H. pylori virulent strains (cagA-, vacA s1-, vacA m1- and babA2-positive) have the highest risk of gastric cancer development. Diets rich in salted and smoked food and poor in fresh fruit and vegetables favor gastric carcinogenesis. Genetic combined with bacterial and host genotyping may allow for the identification of patients at high risk of gastric cancer who can benefit from preventive eradication therapy.
Treatment of Peritoneal Carcinomatosis in Gastric Cancers
Authors: Brigand C. , Arvieux C. , Gilly F.N. , Glehen O.
Published: April 2005

Peritoneal carcinomatosis may occur after curative surgery of any gastrointestinal carcinoma, but it is however the most frequent form of evolution after curative resection of gastric carcinoma and is present at the time of surgery in many cases. This locoregional extension of cancer has a poor prognosis, with a great mortality and a poor quality of life. It is sometimes considered of such a poor prognosis that patients do not go through any resection or palliative procedure. Techniques of radiotherapy, chemotherapy and intraperitoneal chemotherapy have been used with moderate clinical efficacy. Since the 1990s, intraoperative hyperthermic peritoneal chemotherapy combined with comprehensive cytoreductive surgery has been proposed to improve prognosis of patients with peritoneal carcinomatosis from gastric origin as well as carcinomatosis from colorectal origin or pseudomyxoma peritonei.