bluuebunny/crossref_metadata_2025 huggingface dataset:
Overexpression of Aβ is associated with acceleration of onset of motor impairment and superoxide dismutase 1 aggregation in an amyotrophic lateral sclerosis mouse model
Authors: Li Qiao‐Xin , Mok Su San , Laughton Katrina M. , McLean Catriona A. , Volitakis Irene , Cherny Robert A. , Cheung Nam Sang , White Anthony R. , Masters Colin L.
Published: March 2006

Transgenic mice carrying mutant Cu/Zn superoxide dismutase (SOD1) recapitulate the motor impairment of human amyotrophic lateral sclerosis (ALS). The amyloid‐β (Aβ) peptide associated with Alzheimer's disease is neurotoxic. To investigate the potential role of Aβ in ALS development, we generated a double transgenic mouse line that overexpresses SOD1G93A and amyloid precursor protein (APP)‐C100. The transgenic mouse C100.SOD1G93A overexpresses Aβ and shows earlier onset of motor impairment but has the same lifespan as the single transgenic SOD1G93A mouse. To determine the mechanism associated with this early‐onset phenotype, we measured copper and zinc levels in brain and spinal cord and found both significantly elevated in the single and double transgenic mice compared with their littermate control mice. Increased glial fibrillary acidic protein and decreased APP levels in the spinal cord of C100.SOD1G93A mice compared with the SOD1G93A mice agree with the neuronal damage observed by immunohistochemical analysis. In the spinal cords of C100.SOD1G93A double transgenic mice, soluble Aβ was elevated in mice at end‐stage disease compared with the pre‐symptomatic stage. Buffer‐insoluble SOD1 aggregates were significantly elevated in the pre‐symptomatic mice of C100.SOD1G93A compared with the age‐matched SOD1G93A mice, correlating with the earlier onset of motor impairment in the C100.SOD1G93A mice. This study supports abnormal SOD1 protein aggregation as the pathogenic mechanism in ALS, and implicates a potential role for Aβ in the development of ALS by exacerbating SOD1G93A aggregation.
Mechanisms of anabolic androgenic steroid inhibition of mammalian ɛ‐subunit‐containing GABAA receptors
Authors: Jones Brian L. , Whiting Paul J. , Henderson Leslie P.
Published: March 2006

GABAergic transmission regulates the activity of gonadotrophin‐releasing hormone (GnRH) neurons in the preoptic area/hypothalamus that control the onset of puberty and the expression of reproductive behaviours. One of the hallmarks of illicit use of anabolic androgenic steroids (AAS) is disruption of behaviours under neuroendocrine control. GnRH neurons are among a limited population of cells that express high levels of the ɛ‐subunit of the GABAA receptor. To better understand the actions of AAS on neuroendocrine mechanisms, we have characterized modulation of GABAA receptor‐mediated currents in mouse native GnRH neurons and in heterologous cells expressing recombinant α2β3ɛ‐receptors. GnRH neurons exhibited robust currents in response to millimolar concentrations of GABA and a picrotoxin (PTX)‐sensitive, bicuculline‐insensitive current that probably arises from spontaneous openings of GABAA receptors. The AAS 17α‐methyltestosterone (17α‐MeT) inhibited spontaneous and GABA‐evoked currents in GnRH neurons. For recombinant α2β3ɛ‐receptors, 17α‐MeT inhibited phasic and tonic GABA‐elicited responses, accelerated desensitization and slowed paired pulse response recovery. Single channel analysis indicated that GABA‐evoked events could be described by three open dwell components and that 17α‐MeT enhanced residence in the intermediate dwell state. This AAS also inhibited a PTX‐sensitive, spontaneous current (open probability, ∼0.15–0.2) in a concentration‐dependent fashion (IC50≈ 9 μm). Kinetic modelling indicated that the inhibition induced by 17α‐MeT occurs by an allosteric block in which the AAS interacts preferentially with a closed state and promotes accumulation in that state. Finally, studies with a G302S mutant ɛ‐subunit suggest that this residue within the transmembrane domain TM2 plays a role in mediating AAS binding and modulation. In sum, our results indicate that inclusion of the ɛ‐subunit significantly alters the profile of AAS modulation and that this allosteric inhibition of native GnRH neurons should be considered with regard to AAS disruption of neuroendocrine control.
Characterizing the Effect of theStaphylococcus aureusVirulence Factor Regulator, SarA, on Log-Phase mRNA Half-Lives
Authors: Roberts Corbette , Anderson Kelsi L. , Murphy Ellen , Projan Steven J. , Mounts William , Hurlburt Barry , Smeltzer Mark , Overbeek Ross , Disz Terrence , Dunman Paul M.
Published: March 2006

Bacterial pathogens regulate virulence factor expression at both the level of transcription initiation and mRNA processing/turnover. WithinStaphylococcus aureus, virulence factor transcript synthesis is regulated by a number of two-component regulatory systems, the DNA binding protein SarA, and the SarA family of homologues. However, little is known about the factors that modulate mRNA stability or influence transcript degradation within the organism. As our entree to characterizing these processes,S. aureusGeneChips were used to simultaneously determine the mRNA half-lives of all transcripts produced during log-phase growth. It was found that the majority of log-phase transcripts (90%) have a short half-life (<5 min), whereas others are more stable, suggesting thatcis- and/ortrans-acting factors influenceS. aureusmRNA stability. In support of this, it was found that two virulence factor transcripts,cnaandspa, were stabilized in asarA-dependent manner. These results were validated by complementation and real-time PCR and suggest that SarA may regulate target gene expression in a previously unrecognized manner by posttranscriptionally modulating mRNA turnover. Additionally, it was found thatS. aureusproduces a set of stable RNA molecules with no predicted open reading frame. Based on the importance of theS. aureus agrRNA molecule, RNAIII, and small stable RNA molecules within other pathogens, it is possible that these RNA molecules influence biological processes within the organism.
The Response Regulator CroR Modulates Expression of the Secreted Stress-Induced SalB Protein in
Enterococcus faecalis
Authors: Muller Cécile , Le Breton Yoann , Morin Thierry , Benachour Abdellah , Auffray Yanick , Rincé Alain
Published: March 2006

The
Enterococcus faecalis
two-component signal transduction system CroRS, also referred as the RR-HK05 pair, is required for intrinsic β-lactam resistance (Y. R. Comenge, R. Quintiliani, Jr., L. Li, L. Dubost, J. P. Brouard, J. E. Hugonnet, and M. Arthur, J. Bacteriol. 185:7184-7192, 2003) and is also suspected to be involved in the expression of
salB
(previously referred to as
sagA
), a gene important for resistance to environmental stress and cell morphology (Y. Le Breton, G. Boël, A. Benachour, H. Prévost, Y. Auffray, and A. Rincé, Environ. Microbiol. 5:329-337, 2003). In this report, we provide genetic and biochemical evidence that
salB
encodes a secreted protein that is expressed from a monocistronic stress-inducible operon. Consistent with CroR being a direct transcriptional activator of the
salB
expression, CroR was found to bind to the
salB
promoter region in electrophoretic mobility shift assays. Interestingly, we provide evidence that SalB does not play a role in the intrinsic β-lactam resistance associated with CroRS. We also show that the CroRS system is able to regulate its own expression. The sequence of the CroRS binding site in the
salB
and
croR
promoter regions was determined using DNase I footprinting assays.
Evaluation of an occupational health intervention programme on whole-body vibration in forklift truck drivers: a controlled trial
Authors: Hulshof C T J , Verbeek J H A M , Braam I T J , Bovenzi M , van Dijk F J H
Published: March 2006

Objectives:To evaluate process and outcome of a multifaceted occupational health intervention programme on whole-body vibration (WBV) in forklift truck drivers.

Methods:An experimental pretest/post-test control group study design. The authors trained occupational health services (OHS) in the experimental group in the use of the programme. OHS in the control group were asked to deliver care as usual. In total, 15 OHS, 32 OHS professionals, 26 companies, and 260 forklift drivers were involved. Post-test measurements were carried out one year after the start of the programme.

Results:Baseline data before the start of the programme showed no difference between experimental and control group. Results of the outcome evaluation indicate a slight, although not statistically significant, reduction of WBV exposure in the experimental group (p = 0.06). Process evaluation revealed a positive influence on company policy toward WBV, attitude and intended behaviour of forklift drivers, and a trend towards an increase in knowledge of OHS professionals and company managers. The number of observed control measures with a major impact (levelling of surface and reduction of speed) was rather low. In those cases where control measures had been taken, there was a significant reduction in WBV exposure. This limited effect of the programme might be caused by the short period of follow up and the dropout of participants. The feasibility and the usefulness of the programme within the OHS setting were rated good by the participants.

Conclusions:This programme to decrease WBV exposure was partially effective. Significant effects on intermediate objectives were observed. More research on the effectiveness of intervention in the field of WBV is needed.
Cross shift changes in lung function among bar and restaurant workers before and after implementation of a smoking ban
Authors: Skogstad M , Kjærheim K , Fladseth G , Gjølstad M , Daae H L , Olsen R , Molander P , Ellingsen D G
Published: March 2006

Objective:To study possible cross shift effects of environmental tobacco smoke (ETS) on pulmonary function among bar and restaurant employees before and after the implementation of a smoking ban in Norway.

Methods:The study included 93 subjects employed in 13 different establishments in Oslo. They were examined at the beginning and end of a workshift both while ETS exposure was present and when smoking was banned. The mean exposure level of nicotine and total dust before the ban was 28 μg/m3(range 3–65) and 275 μg/m3(range 81–506), respectively. Following the smoking ban, the mean level of nicotine and total dust was 0.6 μg/m3and 77 μg/m3, respectively. Assessment of lung function included dynamic lung volumes and flows.

Results:The cross shift reduction in forced vital capacity (FVC) among 69 subjects participating in both examinations changed from 81 ml (SD 136) during exposure to ETS to 52 ml (SD 156) (p = 0.24) following the smoking ban. The reduction in forced expired volume in one second (FEV1) during a workshift, was borderline significantly reduced when comparing the situation before and after the intervention, by 89 ml (SD = 132) compared to 46 ml (SD = 152) (p = 0.09), respectively. The reduction in forced mid-expiratory flow rate (FEF25–75%) changed significantly from 199 ml/s (SD = 372) to 64 ml/s (SD = 307) (p = 0.01). Among 26 non-smokers and 11 asthmatics, the reduction in FEV1 and FEF25–75%was significantly larger during ETS exposure compared to after the smoking ban. There was an association between the dust concentration and decrease in FEF25–75%before the ban among non-smokers (p = 0.048).

Conclusions:This first study of cross shift changes before and after the implementation of a smoking ban in restaurants and bars shows a larger cross shift decrease in lung function before compared with after the implementation of the ban.
QCD Factorization and Rare B Meson Decays
Authors: DU DONGSHENG
Published: March 2006

Some recent progress in China in the study of charmless B decays with QCD factorization is reviewed. Chirally enhanced power corrections and infrared divergence problem are stressed.
LATTICE CHIRALITY AND ITS USES AT LARGE Nc
Authors: NARAYANAN RAJAMANI , NEUBERGER HERBERT
Published: March 2006

A brief overview of the authors' work on lattice chirality and its application to the numerical study of planar QCD is presented.
SCALARS IN THE HADRON WORLD: THE HIGGS SECTOR OF THE STRONG INTERACTION
Authors: PENNINGTON M. R.
Published: March 2006

Scalar mesons are a key expression of the strong physics regime of QCD and the role condensates, particularly [Formula: see text], play in breaking chiral symmetry. What new insights have been provided by recent experiments on D, Ds and J/ψ decays to light hadrons is discussed. We need to establish whether all the claimed scalars σ, κ, f0(1370), etc., really exist and with what parameters before we can meaningfully speculate further about which is transiently [Formula: see text], [Formula: see text], multi-meson molecule or largely glue.
Production and decay of the meson Bc
Authors: Chang (Zhao-Xi Zhang) Chao-Hsi
Published: March 2006

Studies on the decay and production of [Formula: see text] meson are briefly reviewed. Considering RUN-II of Tevatron and the schedule of LHC, the theoretical studies of Bc meson will jump to a new stage not only for itself but also to implement the studies of the heavy quarkonia etc.
Concluding Talk: QCD 2005
Authors: ALTARELLI GUIDO
Published: March 2006

This is neither a summary talk (too much for too short a talk) nor a conclusion (a gigantic work is in progress and we are not at the end of a particular phase), rather an overview of the field as reflected at this Conference.
EXPLORING THE SPECTRUM OF QCD USING A SPACE-TIME LATTICE
Authors: MORNINGSTAR COLIN
Published: March 2006

Some past and ongoing explorations of the spectrum of QCD using Monte Carlo simulations on a space-time lattice are described. Glueball masses in the pure-gauge theory are reviewed, and the energies of gluonic excitations in the presence of a static quark-antiquark pair are discussed. Current efforts to compute the baryon spectrum using extended three-quark operators are also presented, emphasizing the need to use irreducible representations of the cubic point group to identify spin quantum numbers in the continuum limit.
DYNAMICAL STUDY OF γ* N ↔ Δ TRANSITION WITH N(e,e′p)π
Authors: YANG SHIN NAN , KAMALOV SABIT S.
Published: March 2006

The Dubna-Mainz-Taipei (DMT) dynamical model for pion electromagnetic production, which describe well the existing data from threshold up to 1 GeV photon lab energy is presented and used to analyze recent data in the Δ region. We find that within DMT model, the bare Δ is almost spherical while the physical Δ is oblate. The deformation is almost saturated by the pion cloud effects.
MATCHING MESON RESONANCES TO OPE IN QCD
Authors: Andrianov A. A. , Afonin S. S. , Espriu D. , Andrianov V. A.
Published: March 2006

We investigate the possible corrections to the linear Regge trajectories for the light-quark meson sector by matching two-point correlators of quark currents to the Operator Product Expansion. We find that the allowed modifications to the linear behavior must decrease rapidly with the principal quantum number. After fitting the lightest states in each channel and certain low-energy constants the whole spectrum for meson masses and residues is obtained in a satisfactory agreement with phenomenology. The perturbative corrections to our results are discussed.
Pion Electromagnetic Form Factor in the KT Factorization Formulae
Authors: Wu Xing-Gang , Huang Tao
Published: March 2006

Based on the light-cone (LC) framework and the kT factorization formalism, the transverse momentum effects and the different helicity components' contributions to the pion form factor Fπ(Q2) are recalculated. In particular, the contribution to the pion form factor from the higher helicity components (λ1 + λ2 = ±1), which come from the spin-space Wigner rotation, are analyzed in the soft and hard energy regions respectively. Our results show that the right power behavior of the hard contribution from the higher helicity components can only be obtained by fully keeping the kT dependence in the hard amplitude, and that the kT dependence in LC wavefunction affects the hard and soft contributions substantially. A model for the twist-3 wavefunction ψp(x,k⊥) of the pion has been constructed based on the moment calculation by applying the QCD sum rules, whose distribution amplitude has a better end-point behavior than that of the asymptotic one. With this model wavefunction, the twist-3 contributions including both the usual helicity components (λ1 + λ2 = 0) and the higher helicity components (λ1 + λ2 = ±1) to the pion form factor have been studied within the modified pQCD approach. Our results show that the twist-3 contribution drops fast and it becomes less than the twist-2 contribution at Q2~10GeV2. The higher helicity components in the twist-3 wavefunction will give an extra suppression to the pion form factor. When all the power contributions, which include higher order in αs, higher helicities, higher twists in DA and etc., have been taken into account, it is expected that the hard contributions will fit the present experimental data well at the energy region where pQCD is applicable.
UNDERSTANDING MAGNETIC INSTABILITY IN GAPLESS SUPERCONDUCTORS
Authors: Huang Mei
Published: March 2006

Magnetic instability in gapless superconductors still remains as a puzzle. In this article, we point out that the instability might be caused by using BCS theory in mean-field approximation, where the phase fluctuation has been neglected. The mean-field BCS theory describes very well the strongly coherent or rigid superconducting state. With the increase of mismatch between the Fermi surfaces of pairing fermions, the phase fluctuation plays more and more important role, and "soften" the superconductor. The strong phase fluctuation will eventually quantum disorder the superconducting state, and turn the system into a phase-decoherent pseudogap state.
MIXED QCD AND WEAK CORRECTIONS TO $t\bar{t}$ PRODUCTION BY QUARK-ANTIQUARK ANNIHILATION
Authors: Bernreuther W. , Fücker M. , Si Z. G.
Published: March 2006

We report on our computation of the mixed QCD and weak corrections to [Formula: see text] including t, [Formula: see text] spin effects, in particular on single top spin asymmetries.
ON THE DISTRIBUTION OF PARTONS IN THE TRANSVERSE PLANE
Authors: DIEHL M.
Published: March 2006

Elastic nucleon form factors constrain the spatial distribution of quarks in the impact parameter plane. A recent analysis found that the average impact parameter of quarks strongly depends on their longitudinal momentum, and obtained an estimate of the orbital angular momentum carried by valence quarks in the proton.
FAR-INFRARED MAGNETO-OPTICAL TRANSITIONS IN SELF-ASSEMBLED SEMICONDUCTOR QUANTUM-RINGS
Authors: COMAS F. , GONDAR J. L.
Published: March 2006

The oscillator strength for magneto-optical transitions in the far-infrared spectral region is investigated considering one-electron states in a semiconductor quantum-ring (QR) nanostructure subjected to a constant external magnetic field. We analytically solve the stationary Schrödinger equation by applying hard-wall confinement conditions to a model system of the QR using the cylindrical geometry. The energy levels of this model system are calculated after solving the secular equation in a way that is independent of the particular material involved. The approach permits us to obtain universal results in the above sense. Dipole-allowed magneto-optical transitions are studied by calculating their oscillator-strength. We also analyze the persistent current due to the magnetic flux threaded by the QR. The results obtained are discussed in detail and comparison with previous works on this subject are made.
LIMIT CYCLE AND CONSERVED DYNAMICS
Authors: ZHU X.-M. , YIN L. , AO P.
Published: March 2006

We demonstrate here that the potential can coexist with limit cycle in nonlinear dissipative dynamics, where the potential plays the driving role for dynamics and determines the final steady state distribution in a manner similar to other situations in physics. First, we show the existence of limit cycle from a typical physics setting by an explicit construction: the potential is of the Mexican-hat shape, the strength of the magnetic field scales with that of the potential gradient near the limit cycle, and the friction goes to zero faster than that of potential gradient when approaching to the limit cycle. The dynamics at the limit cycle is conserved in this limit. The diffusion matrix is nevertheless finite at the limit cycle. Second, based on the physics knowledge, we construct the potential in the dynamics with limit cycle in a typical dynamical systems setting. Third, we argue that such a construction can be, in principle, carried out in a general situation combined with a novel method. Our present result may be useful in many applications, such as in the discussion of metastability of limit cycle and in the construction of Hopfield potential in the neural network computation.
STRUCTURAL PROPERTIES OF AMORPHOUS SILICON MODELS GENERATED WITH REVERSE MONTE-CARLO METHOD
Authors: SINGH RANBER , ZETTERSTRÖM PER , MOHAN INDER , AHLUWALIA P. K.
Published: March 2006

The structural properties of amorphous silicon models generated with Reverse Monte-Carlo Modeling techniques are presented. The structure factors and radial distribution functions of the generated models closely resemble with the experimental data, but show some dependence on the sample size. However, the coordination defects show no direct correlation with the size of the sample. There exists no peak at 60° in the Si–i–Si bond angle distributions in these samples. The Si–Si–Si bond angle distributions in these samples are quite in good agreement with the Monte-Carlo and Molecular Dynamics simulations data.
PSEUDOPOTENTIAL INVESTIGATION OF ELECTRONIC PROPERTIES OF C54- AND C49-TiSi2
Authors: WANG TAO , CHEN JI-AN , LING XING , DAI YONG-BING , DAI QING-YUAN
Published: March 2006

The letter casts some light on the structural, elastic and electronic properties of C49- and C54-TiSi 2, using an ab initio plane-wave ultrasoft pseudopotential method based on generalized gradient approximation (GGA). An intrinsic advantage in the growth stage for C49 phase might explain its kinetically favored phenomena in a solid-state reaction.
STUDY OF CHARGES IN FLUORINATED POLYIMIDE FILM BY USING CAPACITANCE-VOLTAGE METHOD
Authors: LEE YONG K.
Published: March 2006

The deviations of ideality, such as shifts or distortions, in the Capacitance-Voltage (C-V) curve were examined to characterize charges in fluorinated polyimide film in MPOS ( Cu -fluorinated polyimide film- SiO 2 -Si ) test structure. It was observed that charges in fluorinated polyimide film hard baked at 325°C and annealed at 425°C were mobile and positive charged. The mobile charge concentration was 1011/ cm 2 and the activation energy of the drift of positive mobile charge was 0.6 V.
Electrophysiological and Anatomical Characterization of PDF-Positive Clock Neurons in the Intact Adult Drosophila Brain
Authors: Park Demian , Griffith Leslie C.
Published: March 2006

Daily biological rhythms in both prokaryotes and eukaryotes are controlled by circadian clocks. In Drosophila, there is a good basic understanding of both the molecular and anatomical components of the clock. In this study we directly measure, for the first time, electrophysiological properties and anatomy of individual filled large lateral PDF-positive clock neurons, a cell group believed to be involved in synchronization of the clock in constant conditions. We find that the large PDF-positive neurons are morphologically homogeneous and that their resting membrane potential is modulated both by the clock and by light inputs. Expression of a leak channel, dORK-ΔC, which has been shown to disrupt circadian locomotor rhythms, hyperpolarizes these neurons, and blocks firing. These data imply that the firing properties of large PDF neurons are both regulated by and critical for clock function.
Same Spinal Interneurons Mediate Reflex Actions of Group Ib and Group II Afferents and Crossed Reticulospinal Actions
Authors: Cabaj A. , Stecina K. , Jankowska E.
Published: March 2006

The aim of the study was to analyze interactions between neuronal networks mediating centrally initiated movements and reflex reactions evoked by peripheral afferents; specifically whether interneurons in pathways from group Ib afferents and from group II muscle afferents mediate actions of reticulospinal neurons on spinal motoneurons by contralaterally located commissural interneurons. To this end reticulospinal tract fibers were stimulated in the contralateral medial longitudinal fascicle (MLF) in chloralose-anesthetized cats in which the ipsilateral half of the spinal cord was transected rostral to the lumbosacral enlargement. In the majority of interneurons mediating reflex actions of group Ib and group II afferents, MLF stimuli evoked either excitatory or inhibitory postsynaptic potentials (EPSPs and IPSPs, respectively) or both EPSPs and IPSPs attributable to disynaptic actions by commissural interneurons. In addition, in some interneurons EPSPs were evoked at latencies compatible with monosynaptic actions of crossed axon collaterals of MLF fibers. Intracellular records from motoneurons demonstrated that both excitation and inhibition from group Ib and group II afferents are modulated by contralaterally descending reticulospinal neurons. The results lead to the conclusion that commissural interneurons activated by reticulospinal neurons affect motoneurons not only directly, but also by enhancing or weakening activation of premotor interneurons in pathways from group Ib and group II afferents. The results also show that both excitatory and inhibitory premotor interneurons are affected in this way and that commissural interneurons may assist in the selection of reflex actions of group Ib and group II afferents during centrally initiated movements.
Behaviors Used by Men to Protect Themselves against Prostate Cancer
Authors: Kunkel Elisabeth J. S. , Meyer Birgit , Daskalakis Constantine , Cocroft James , Jennings-Dozier Kathleen , Myers Ronald E.
Published: March 2006

This paper reports on behaviors men use to protect themselves against prostate cancer. Data were collected via a telephone or mailed survey from 353 men enrolled in two studies of prostate cancer screening. Respondents reported behaviors they used to protect themselves against prostate cancer, and responses were coded as conventional care, self-care, or nothing. Men who reported using both conventional care and self-care were categorized as conventional care users. Polytomous logistic regression was conducted to evaluate the association between sociodemographic background, prior prostate screening, and cognitive, affective, and social support and influence factors with protective behavior type.

The distribution of protective behaviors was as follows: conventional care, 63%; self-care only, 19%; and nothing, 18%. In multivariable analyses, higher education level was found to be positively associated with conventional care use. Perceived salience and coherence of prostate cancer screening was positively associated with conventional care use among men in one of the two studies. Low concern about screening was positively associated with self-care use, as was mailed survey completion.

This study presents self-report data regarding prostate cancer protection behaviors. Most men in the study reported using some type of prostate cancer protective behavior. Decision-making about whether or not to take protective action and what type of behavior to use may be influenced by socioeconomic background, cognitive perceptions related to behavioral options, and concern about risk.
Delivery of Tea Polyphenols to the Oral Cavity by Green Tea Leaves and Black Tea Extract
Authors: Lee Mao-Jung , Lambert Joshua D. , Prabhu Saileta , Meng Xiaofeng , Lu Hong , Maliakal Pius , Ho Chi-Tang , Yang Chung S.
Published: March 2006

Catechins and theaflavins, polyphenolic compounds derived from tea (Camellia sinensis, fam. Theaceae), have been reported to have a wide range of biological activities including prevention of tooth decay and oral cancer. The present study was undertaken to determine the usefulness of green tea leaves and black tea extract for the delivery of catechins and theaflavins to the oral cavity. After holding either green tea leaves (2 g) or brewed black tea (2 g of black tea leaves in 100 ml) in the mouth for 2–5 min and thoroughly rinsing the mouth, high concentrations of catechins (Cmax = 131.0–2.2 μm) and theaflavins (Cmax = 1.8–0.6 μm) were observed in saliva in the 1st hour. Whereas there was significant interindividual variation in the peak levels of catechins and theaflavins, the overall kinetic profile was similar, with t1/2 = 25–44 min and 49–76 min for catechins and theaflavins, respectively (average coefficient of variation in t1/2 was 23.4%). In addition to the parent catechin and theaflavin peaks, five unidentified peaks were also observed in saliva after black tea treatment. Hydrolysis of theaflavin gallates, apparently by salivary esterases, was observed in vitro and in vivo. These results indicate that tea leaves can be used as a convenient, slow-release source of catechins and theaflavins and provide information for the possible use of tea in the prevention of oral cancer and dental caries.
DNA Repair Gene
XRCC1
and
XPD
Polymorphisms and Risk of Prostate Cancer
Authors: Rybicki Benjamin A. , Conti David V. , Moreira Andrea , Cicek Mine , Casey Graham , Witte John S.
Published: March 2006

The X-ray repair cross-complementing group 1 (XRCC1) and xeroderma pigmentosum group D (XPD) genes are involved in base excision repair and nucleotide excision repair of DNA repair pathways, respectively. A growing body of evidence suggests that XRCC1 and XPD are important in environmentally induced cancers, and polymorphisms in both genes have been identified. To determine whether the XRCC1 (codon Arg399Gln) and XPD (codon Asp312Asn and codon Lys751Gln) polymorphisms are associated with prostate cancer susceptibility, we genotyped these polymorphisms in a primarily Caucasian sample of 506 sibships (n = 1,117) ascertained through a brother with prostate cancer. Sibships were analyzed with a Cox proportional hazards model with age at prostate cancer diagnosis as the outcome. Of the three polymorphisms investigated, only the XPD codon 312 Asn/Asn genotype had an odds ratio (OR) significantly different from one (OR, 1.61; 95% CI, 1.03–2.53). Analyses stratified by the clinical characteristics of affected brothers in the sibship did not reveal any significant heterogeneity in risk. In exploring two-way gene interactions, we found a markedly elevated risk for the combination of the XPD codon 312 Asn/Asn and XRCC1 codon 399 Gln/Gln genotypes (OR, 4.81; 95% CI, 1.66–13.97). In summary, our results suggest that the XPD codon 312 Asn allele may exert a modest positive effect on prostate cancer risk when two copies of the allele are present, and this effect is enhanced by the XRCC codon 399 Gln allele in its recessive state.
Dietary Glycemic Load and Breast Cancer Risk in the Women’s Health Study
Authors: Higginbotham Susan , Zhang Zuo-Feng , Lee I-Min , Cook Nancy R. , Buring Julie E. , Liu Simin
Published: March 2006

A diet with a high glycemic load (GL) may contribute to a metabolic environment that enhances tumorigenesis. Little is known, however, about whether high glycemic diets increase breast cancer risk in women. We examined the associations between baseline measurements of dietary GL and overall glycemic index (GI) and subsequent breast cancer in a cohort of 39,876 women, ages 45 years or older, participating in the Women’s Health Study. During a mean of 6.8 years of follow-up there were 946 confirmed cases of breast cancer. We found no association between dietary GL [multivariable-adjusted relative risk (RR), 1.01; confidence interval (CI), 0.76–1.35, comparing extreme quintiles; P for trend = 0.96] or overall GI (corresponding RR, 1.03; CI, 0.84–1.28; P for trend = 0.66) and breast cancer risk in the cohort as a whole. Exploratory analyses stratified by baseline measurements of menopausal status, physical activity, smoking history, alcohol use, and history of diabetes mellitus, hypertension, or hypercholesterolemia showed no significant associations, except in the subgroup of women who were premenopausal and reported low levels of physical activity (GL multivariable-adjusted RR, 2.35; CI, 1.03–5.37; P for trend = 0.07; GI multivariable-adjusted RR, 1.56; CI, 0.88–2.78; P for trend = 0.02, comparing extreme quintiles). Although we did not find evidence that a high glycemic diet increases overall breast cancer risk, the increase in risk in premenopausal women with low levels of physical activity suggests the possibility that the effects of a high glycemic diet may be modified by lifestyle and hormonal factors. Prospective studies of a larger sample size and longer duration are warranted to confirm our findings.
Cigarette Smoking and Testicular Cancer
Authors: Srivastava Anil , Kreiger Nancy
Published: March 2006

The purpose of this study was to determine the relation between testicular cancer and cigarette smoking. Data were collected between 1995 and 1996 in Ontario, Canada, as part of the Enhanced Cancer Surveillance Study. Pack-years and years of smoking were examined among all subjects (212 cases and 252 controls) and former and current smokers. Years since quitting and age at smoking initiation were examined among former and current smokers only. Independent of smoking status, significant associations were noted among those who smoked between 12 and 24 pack-years [odds ratio (OR) = 1.96 (95% confidence interval (CI): 1.04–3.69), relative to nonsmokers] or greater [>24 pack-years, OR = 2.31 (95% CI: 1.12–4.77), relative to nonsmokers], and among those who smoked >21 years [OR = 3.18 (95% CI: 1.32–7.64), relative to nonsmokers]. Quitting smoking was not found to result in a reduction of risk. No association was observed for smoking at adolescence relative to a later period. Results from the study suggest that cigarette smoking exerts an adverse influence on testicular cancer risk that is not mitigated by smoking cessation and not altered by age at initiation.
Natural History of Human Papillomavirus Type 16 Virus-Like Particle Antibodies in Young Women
Authors: Ho Gloria Y. F. , Studentsov Yevgeniy Y. , Bierman Robert , Burk Robert D.
Published: March 2006

Immunization with a vaccine of human papillomavirus (HPV) type 16 virus-like particles (VLPs) can reduce incidence of HPV-16 infection and its related cervical intraepithelial neoplasia. However, development of detectable antibodies to VLPs does not always occur after natural HPV infection. This study examined prospectively for seroconversion and duration of antibodies to HPV-16 VLPs and their associated host and viral factors. Six-hundred eight subjects were tested for HPV DNA biannually and for IgG and IgA antibodies to HPV-16 VLPs annually for 3 years. Both IgG and IgA antibodies to HPV-16 VLPs were predominantly type specific. Women with cervicovaginal HPV-16 infection were 8–10 times more likely to seroconvert than those with infection of HPV-16-related types. Among subjects who had an incident infection with HPV-16, a maximum of 56.7% became seropositive for IgG within 8.3 months and 37.0% had IgA within 14 months. Detectable seroconversion was a slow process that required sufficient antigenic exposure associated with either a high viral load (relative risk = 5.7 for IgG) or persistent infection of HPV-16 (relative risk = 3.4 for IgA). The median duration for both types of antibodies was ∼36 months. Antibodies could persist for a long period of time if the initial antibody levels were high or if there was continued antigenic exposure.
Arterial Ischemic Stroke and Cerebral Venous Thrombosis in Children: A 12-Year Argentinean Registry
Authors: Bonduel Mariana , Sciuccati Gabriela , Hepner Mirta , Pieroni Graciela , Torres Aurora Feliú , Frontroth Juan Pablo , Tenembaum Silvia
Published: March 2006

Over a 12-year period, 112 consecutive children with arterial ischemic stroke (AIS) and 38 children with cerebral venous thrombosis (CVT) were prospectively recruited at a single pediatric center in Argentina. One or more underlying clinical conditions were identified in most patients (55%) with AIS and in almost all patients with CVT. Inherited and/or acquired prothrombotic disorders were detected in 17% of the patients with AIS and in 34% of the children with CVT. No associations between factor V Leiden or prothrombin G20210A mutation and children with AIS or CVT were found. Antithrombotic agents (i.e., aspirin, low-molecular-weight heparin and acenocoumarol) were administered without major hemorrhagic complications. In our cohorts, mortality due to the thrombotic episode was 1.8% in children with AIS. No child with CVT died from his or her thrombotic episodes. Three children (3.2%) and 1 adolescent (1.1%) with AIS had thrombotic progression and recurrence, respectively. A large percentage of children with AIS (68%) and CVT (32%) have had some kind of sequels that caused serious disability in approximately half the cases.
Venous Thromboembolism after Severe Injury in Children
Authors: Cyr Claude , Michon Bruno , Pettersen Géraldine , David Michèle , Brossard Josée
Published: March 2006

Background: Deep vein thrombosis and pulmonary embolism are considered common complications after major trauma. Their incidence and the associated risk factors have rarely been identified in injured children. Methods: Severely injured children (age <18 years; admitted in a pediatric intensive care unit or length of stay ≧72 h) with a discharge diagnosis of venous thromboembolism (VTE; deep venous thrombosis and/or pulmonary embolism) were identified from the institutional trauma registry between January 1, 1999 and April 31, 2002. The study centers included a dedicated pediatric trauma center and an adult trauma center with pediatric patients. Risk factors for VTE were identified using multivariate analysis. Results: VTE was found in 11 of the 3,291 admissions, for a rate of 3.3/1,000 admissions. Children with VTE were older and had higher Injury Severity Scores. Independent risk factors for VTE included thoracic injuries [odds ratio (OR): 6.9; 95% confidence interval (CI): 1.4–35.1] and spinal injuries (OR: 37.4; 95% CI: 3.5–396.7). The greatest risk of VTE was in children with central venous catheters (OR: 64.0; 95% CI: 16.8–243.9). Conclusion: Older children with high Injury Severity Scores, thoracic injuries, spinal injuries or venous catheters are at risk for VTE. Because VTE prophylaxis, screening and treatment are associated with complications and costs, it is essential to identify subgroups of pediatric patients in whom these strategies might be studied.
Endometriosis in Patients with Chronic Pelvic Pain: Is Staging Predictive of the Efficacy of Laparoscopic Surgery in Pain Relief?
Authors: Milingos Spyros , Protopapas Athanasios , Kallipolitis George , Drakakis Petros , Loutradis Dimitrios , Liapi Anthoula , Antsaklis Aris
Published: March 2006

Background/Aims: Endometriosis is considered an important cause of chronic pelvic pain. Despite its high prevalence, controversy still exists regarding the true association between the extent of endometriosis and the severity of symptoms. We conducted this prospective study to investigate the association between the stage of endometriosis and type and severity of pain, and to evaluate the efficacy of laparoscopic surgery in pain relief. Methods: Ninety-five patients complaining of chronic pain were diagnosed with endometriosis and were treated with laparoscopic surgery. The severity of pain was assessed in patients with an endometriosis AFS (American Fertility Society) score less than 16 (group 1) and those with an AFS score greater than or equal to 16 (group 2), preoperatively and 6 months after surgery, using a visual pain scale. Any reduction in pain scores by 2 points or more was considered to be an improvement. Results: Dysmenorrhea and deep dyspareunia, were significantly more frequent in patients of group 2. Preoperative pain scores were significantly higher for dysmenorrhea (p = 0.0022) and deep dyspareunia (p < 0.0001) but not for non-menstrual pain in group 2. Deep dyspareunia was correlated with the presence of dense pelvic adhesions. After surgery, dysmenorrhea improved in 43% of cases in group 1, vs. 66% of cases in group 2 (p = 0.0037). For deep dyspareunia, improvement was reported by 33% in group 1, vs. 67% in group 2 (p = 0.074). Improvement in non-menstrual pain was not significantly different between the two groups (67% vs. 56%). Conclusions: Advanced endometriosis is more frequently related to dysmenorrhea and deep dypareunia in comparison to early disease. Laparoscopic surgery may offer relief or improvement in the majority of patients with endometriosis and chronic pelvic pain. Cases with advanced disease seem to benefit the most.
Acute Interleukin-6 Infusion Increases IGFBP-1 but Has No Short-Term Effect on IGFBP-3 Proteolysis in Healthy Men
Authors: Pihl S. , Carlsson-Skwirut C. , Berg U. , Ekström K. , Bang P.
Published: March 2006

Human conditions of elevated interleukin-6 (IL-6) and transgenic mice overexpressing IL-6 have increased proteolytic degradation of insulin-like growth factor binding protein (IGFBP)-3. In addition, IL-6 alters the hepatic expression of insulin-like growth factor-I (IGF-I) and the IGFBPs in vitro. The aim of the present study was to investigate whether moderately elevated IL-6 levels have short-term effects on circulating IGF-I, IGFBP-1 and IGFBP-3 proteolysis in vivo. Healthy men received a 3-h IL-6 (n = 6) or saline (n = 6) infusion and blood samples were collected prior to and up to 8 h after the start of infusion. Free IGF-I, total IGF-I, IGFBP-1, insulin and cortisol were measured using immunoassays. Serum IGFBP-3 proteolysis was analyzed by Western immunoblot and by in vitro degradation of 125I-IGFBP-3. We found that IL-6 concentrations reaching approximately 100 pg/ml significantly increased IGFBP-1 after the end of infusion in the absence of changes in insulin. In addition, plasma levels of cortisol were increased in response to IL-6 during and after infusion compared to saline. There was no effect of IL-6 on IGFBP-3 proteolysis, total IGF-I or free dissociable IGF-I. These data suggest that moderately elevated levels of IL-6 such as in the post-operative state or after exercise may contribute to increased levels of IGFBP-1. Although this study does not exclude that high levels and/or prolonged exposure to IL-6 may induce IGFBP-3 proteolysis in sepsis or chronic inflammatory disease, it suggests that IL-6 released from exercising skeletal muscle is not directly involved in proteolysis of circulating IGFBP-3.
Efficacy of Gene Transfer through the Round Window Membrane: An in vitro Model
Authors: Aarnisalo A.A. , Aarnisalo P. , Pietola L. , Wahlfors J. , Jero J.
Published: March 2006

The viral vector-transgene soaked gelatin-sponge method has been shown to be successful in mediating transgene expression across an intact round window membrane (RWM) in mouse in vivo. However, there are many confounding factors which make it difficult to evaluate the role of the RWM in gene transfer. We have created an in vitro model to test the feasibility of gene delivery through an intact RWM. The round window including the bony niche of a CD1 mouse was removed under an operating microscope and fixed with adhesive on the base of a petri dish through which a hole had been drilled. Toluidine blue was injected into the niche containing a hyaluronic acid ester sponge against the round window membrane. The niche was closed with a fascia. A plastic tube containing PBS was fixed on the opposite side, from where the samples were collected at different time points. The concentration of toluidine blue was evaluated spectrophotometrically. An adenoviral vector containing green fluorescent protein (GFP) marker gene was injected into the niche. Samples were collected from the opposite side at different time points. The presence of the vector was studied with GFP PCR. We also modulated the permeability of the RWM by treating it with clinically applicable detergents, histamine or silver nitrate. Silver nitrate and trichloracetic acid caused destruction of the surface epithelium of the RWM as shown by light microscopy. Both toluidine blue and adenoviral vectors passed through the RWM in a time-dependent fashion. RWM cells expressed GFP after Ad-GFP treatment. The permeability of the RWM was decreased after treatment with different detergents, histamine or silver nitrate. RWM offers an atraumatic route to the inner ear. Compared with more invasive gene delivery methods, this technique represents a safer and clinically more viable route of cochlear gene delivery.
A Forgotten Method to Induce Experimental Chronic Renal Failure in the Rat by Ligation of the Renal Parenchyma
Authors: Perez-Ruiz Luis , Ros-Lopez Susana , Cardús Anna , Fernandez Elvira , Valdivielso Jose M.
Published: March 2006

Background: Animal models of chronic renal failure have been widely used in the experimental nephrology laboratories. The most common technique used is the 5/6 reduction of renal mass, either by surgical resection or by infarction. Methods: In the present work, we describe a forgotten technique based in the ligation of the renal parenchyma in both renal poles. This technique combines the advantages of the resection model, like the reproducibility and homogeneity, with the ones of the infarction technique, like the absence of bleeding. Results: 8 weeks after the procedure, animals showed a decrease in creatinine clearance together with an increase in plasma creatinine. Furthermore, glomeruli of animals with 5/6 nephrectomy showed a marked hypertrophy, with a glomerular volume significantly higher than control animals. Serum levels of parathyroid hormone were also increased, consistent with the development of secondary hyperparathyroidism. Conclusions: We conclude that the present technique is a valid and improved tool for the study of chronic renal failure.
Renal Tubular Drug Transporters
Authors: Launay-Vacher Vincent , Izzedine Hassane , Karie Svetlana , Hulot Jean Sébastien , Baumelou Alain , Deray Gilbert
Published: March 2006

The kidney plays an important role in the elimination of numerous hydrophilic xenobiotics, including drugs, toxins, and endogenous compounds. It has developed high-capacity transport systems to prevent urinary loss of filtered nutrients, as well as electrolytes, and simultaneously to facilitate tubular secretion of a wide range of organic ions. Transport systems for organic anions and cations are primarily involved in the secretion of drugs in renal tubules. The identification and characterization of organic anion and cation transporters have been progressing at the molecular level. To date, many members of the organic anion transporter, organic cation transporter, and organic anion-transporting polypeptide families have been found to mediate the transport of diverse organic ions. It has also been suggested that ATP-dependent primary active transporters such as MDR1/P-glycoprotein and the multidrug resistance-associated protein family function as efflux pumps of renal tubular cells for more hydrophobic molecules and anionic conjugates. Tubular reabsorption of peptide-like drugs such as beta-lactam antibiotics across the brush-border membranes appears to be mediated by two distinct H+/peptide cotransporters: PEPT1 and PEPT2. Renal disposition of drugs occurs through interaction with these diverse secretory and absorptive transporters in renal tubules. Studies of the functional characteristics, such as substrate specificity and transport mechanisms, and of the localization of drug transporters could provide information regarding the cellular network involved in renal handling of drugs. Detailed information concerning molecular and cellular aspects of drug transporters expressed in the kidney has facilitated studies of the mechanisms underlying renal disposition as well as transporter-mediated drug interactions.