bluuebunny/crossref_metadata_2025_split huggingface dataset:
VMAT2 binding is elevated in dopa‐responsive dystonia: Visualizing empty vesicles by PET
Authors: De La Fuente‐Fernández Raúl , Furtado Sarah , Guttman Mark , Furukawa Yoshiaki , Lee Chong S. , Calne Donald B. , Ruth Thomas J. , Stoessl A. Jon 
Published: April 2003

AbstractDopa‐responsive dystonia (DRD) is a lifelong disorder in which dopamine deficiency is not associated with neuronal loss and therefore it is an ideal human model for investigating the compensatory changes that occur in response to this biochemical abnormality. Using positron emission tomography (PET), we examined the (±)‐α‐[11C]dihydrotetrabenazine ([11C]DTBZ) binding potential of untreated DRD patients and normal controls. Two other PET markers of presynaptic nigrostriatal function, d‐threo‐[11C]methylphenidate ([11C]MP) and 6‐[18F]fluoro‐L‐dopa ([18F]‐dopa), and [11C]raclopride were also used in the study. We found increased [11C]DTBZ binding potential in the striatum of DRD patients. By contrast, no significant changes were detected in either [11C]MP binding potential or [18F]‐dopa uptake rate constant. In addition, we found evidence for increased dopamine turnover in one DRD patient by examining changes in [11C]raclopride binding potential in relation to levodopa treatment. We propose that the increase in [11C]DTBZ binding likely reflects the dramatic decrease in the intravesicular concentration of dopamine that occurs in DRD; upregulation of vesicular monoamine transporter type 2 (VMAT2) expression may also contribute. Our findings suggest that the striatal expression of VMAT2 (as estimated by [11C]DTBZ binding) is not coregulated with dopamine synthesis. This is in keeping with a role for VMAT2 in other cellular processes (i.e., sequestration and release from the cell of potential toxic products), in addition to its importance for the quantal release of monoamines. Synapse 49:20–28, 2003. © 2003 Wiley‐Liss, Inc.
β‐Funaltrexamine, a gauge for the recognition site of wildtype and mutant H297Q μ‐opioid receptors
Authors: Spivak Charles E. , Beglan Carol L. , Zöllner Christian , Surratt Christopher K. 
Published: April 2003

AbstractThe antagonist β‐funaltrexamine (β‐FNA), known to bind covalently to μ‐opioid receptors by a two‐step, doubly discriminating sequence, was used as a sensitive gauge to compare wildtype to mutant H297Q μ‐opioid receptors. We addressed whether this mutation, which enhances the intrinsic activities of alkaloid μ‐receptor agents, affects both the reversible and covalent phases of β‐FNA binding. Such altered binding serves as a reporter for the dimensions and topography of the receptor's recognition site. Using the voltage‐clamped Xenopus oocyte expression system with coexpressed GIRK potassium channels, we found that β‐FNA blocked the wildtype and mutant H297Q receptors both reversibly and irreversibly, indicating overall conserved tertiary structure in the mutant. The mutant H297Q receptor, however, was more resistant to both phases of blockade, indicating some disturbance of the mutant H297Q receptor recognition site. β‐FNA acted as a partial agonist at the mutant H297Q receptor expressed in both oocytes, as measured by the activation of GIRK channels, and in COS‐7 cells assayed by GTPγ35S binding. β‐FNA showed no activity at the wildtype receptor expressed in oocytes, but surprisingly induced binding of GTPγ35S in transfected COS‐7 cells. Thus, the topography of the mutant H297Q receptor recognition site is sufficiently conserved to allow the selective binding of β‐FNA, but the decrease in binding affinity and increase in efficacy in oocytes demonstrates clear differences from the wildtype receptor. Synapse 49:55–60, 2003. © 2003 Wiley‐Liss, Inc.
Requirement of a critical period of GABAergic receptor blockade for induction of a cAMP‐mediated long‐term depression at CA3‐CA1 synapses
Authors: Yu Tzu‐Ping , Lester Henry A. , Davidson Norman 
Published: April 2003

AbstractPrevious reports show that bath application of the adenosine 3′ : 5′‐cyclic monophosphate (cAMP) analog, Sp‐cAMPS, induces a protein kinase A (PKA)‐dependent and protein synthesis‐dependent long‐term potentiation (LTP) at hippocampal CA3‐CA1 synapses. Recently, we reported a novel form of long‐term depression (LTD) induced by concurrent application of Sp‐cAMPS and picrotoxin, the γ‐aminobutyric acid type A (GABAA) receptor antagonist. In the present study, we further investigated the mechanisms underlying such cAMP‐mediated LTD. Synaptically connected CA3 and CA1 cells of hippocampal slice cultures were impaled by sharp electrodes. Excitatory postsynaptic potentials recorded from a CA1 pyramidal cell were evoked by single action potentials in a CA3 cell. Picrotoxin was applied to slices at various time points after Sp‐cAMPS was perfused. We found that Sp‐cAMPS‐induced potentiation could be converted to depression when picrotoxin was applied within 30 min after perfusion of Sp‐cAMPS. Picrotoxin applied 1 h after perfusion of Sp‐cAMPS had no effect on Sp‐cAMPS‐induced synaptic potentiation. Once LTP was induced by Sp‐cAMPS and expressed for 1 h, the subsequent application of Sp‐cAMPS and picrotoxin produced no new changes in synaptic strength. Also, once LTD was induced and expressed for 1 h, subsequent Sp‐cAMPS produced no new changes in synaptic strength. These findings suggest that a synapse is committed irreversibly to cAMP‐mediated LTP or LTD during a critical period and that later signals cannot interconvert these two fates. Synapse 49:12–19, 2003. © 2003 Wiley‐Liss, Inc.
Behavioral/neurophysiological investigation of effects of combining a quinolinic acid entopeduncular lesion with a fetal mesencephalic tissue transplant in striatum of the 6‐OHDA hemilesioned rat
Authors: Olds M.E. , Jacques D.B. , Kpoyov O. 
Published: April 2003

AbstractBehavioral and electrophysiological methods were used to investigate the effects of combining a unilateral quinolinic acid lesion of the entopeduncular nucleus (QA/EP) with a striatal transplant of fetal ventral mesencephalic tissue in the 6‐hydroxydopamine (6‐OHDA) hemilesioned rat model for Parkinson's disease. The subjects were 6‐OHDA‐lesioned rats selected because their response to amphetamine treatment was a strongly biased rotation toward the side of the 6‐OHDA lesion in the substantia nigra, at the expense of other evoked behaviors associated with amphetamine. Two experiments were performed. In the first, the motor effects of the QA/EP lesion alone and of the combination of QA/EP lesion with striatal transplant were determined by measuring six aspects of the motor response. In the second the electrophysiological effects of the two interventions on the responses of neurons in the subthalamic nucleus to amphetamine and apomorphine were determined in the 6‐OHDA‐lesioned rats. The results of the first experiment show that the QA/EP lesion by itself produced an attenuation of the rotation response and, simultaneously, an increase of oral stereotypy. They also show that the combination of QA/EP lesion with striatal transplant was more effective than the single intervention, inducing more attenuation of rotation and more oral stereotypy. The results of the second experiment show that the responses of subthalamic neurons to amphetamine in the behaving hemiparkinsonian rat with combined QA/EP lesion and transplant were larger than the responses in the hemiparkinsonian rat with the QA/EP lesion alone. However, even these larger responses in the rats with combined intervention were not as large as those recorded at the same time in the subthalamus in the opposite, intact, hemisphere. The results of the two experiments, both of which show enhanced motor and neuronal sensitivity to amphetamine after the combined intervention, suggest that such a multiple approach might prove more beneficial than a one‐site intervention targeting either the EP or the striatum. Synapse 49:1–11, 2003. © 2003 Wiley‐Liss, Inc.
Role of epinephrine stimulation of CNS α1‐adrenoceptors in motor activity in mice
Authors: Stone Eric A. , Grunewald Gary L. , Lin Yan , Ahsan Rashedul , Rosengarten Helen , Kramer H. Kenneth , Quartermain David 
Published: April 2003

AbstractThe role of brain epinephrine (EPI) in the regulation of motor activity and movement in mice was examined. Blockade of EPI synthesis with i.p. 2,3‐dichloro‐α‐methylbenzylamine (DCMB) or LY134046 was found to produce marked behavioral inactivity which could be significantly reversed by intraventricular injection of EPI and by three other α1‐adrenoceptor agonists, norepinephrine (NE), 6‐fluoronorepinephrine (6FNE), and phenylephrine (PE), as well as by serotonin (5HT). EPI had the largest effect of these agonists and also was the only one that reversed nondrug‐induced inactivity of mice in their home cages during the light phase. The effects of EPI were blocked by coinfusion of an α1‐adrenoceptor antagonist (terazosin) but not of an α2‐(atipamezole) or β1 (betaxolol)‐blocker. The rank order of maximal behavioral responses to EPI, 6FNE, and PE in DCMB‐treated mice was the same as the rank order of their maximal stimulation of hydrolysis of phosphatidylinositol at cloned α1B‐adrenoceptors in cell culture. On the basis of the above findings and of the central distributions of adrenergic neurons and α1‐adrenoceptors, the existence of a central EPI‐innervated α1‐adrenergic receptor system is postulated which serves to coexcite or enhance signaling in several monoaminergic brain regions involved in movement and motor activity. Synapse 49:67–76, 2003. © 2003 Wiley‐Liss, Inc.
Reliability analysis of wind response of flexibly supported tall structures
Authors: Halabian A. M. , El Naggar M. H. , Vickery B. J. 
Published: April 2003

AbstractStatistics and probabilistic analyses and risk assessments can be very useful decision‐making tools when dealing with structural–geotechnical problems. Wind loads, dynamic properties of soil underneath the structure and material characteristics of the structure are important factors that affect the wind action on the structure and consequently the structural wind‐induced response. Uncertainties in the estimation of these factors as a result of human error or inherent variability are at the forefront for the use of reliability approaches to evaluate the risk of failure during the service period. In the present study, probabilistic base force analyses for tall structures are performed. The substructure approach in which the soil supporting the foundation is modeled by the foundation compliances as functions of soil shear wave velocity is used to account for the soil–structure interaction efficiently. A three‐variable probabilistic approach is used to account for the uncertainties in shear wave velocity of the soil underneath the foundation, the concrete strength and the design wind speed on the calculated response and the base forces. The second moment approximation using Taylor series expansion is used to perform the probabilistic analyses of the base cross‐section design and resistant forces of a free‐standing tower. The first‐order reliability method is used to examine the failure probability and the contribution to the total uncertainty. The results show that the dynamic response of the tower increases as soil shear wave velocity decreases. For the range of soil shear wave velocity encountered in practice, the base forces of the structure may increase by up to 20% as a result of the foundation flexibility. For the limit state considered in this study, it was found that the reliability index decreases by up to 15% and the probability of failure increases by up to one order of magnitude as a result of the soil–structure interaction effect. Copyright © 2003 John Wiley & Sons, Ltd.
Optimal compensation of differential column shortening in high‐rise buildings
Authors: Park H. S. 
Published: April 2003

AbstractTo avoid unexpected damage in structural and nonstructural elements, differential shortening between vertical members resulting from differing stress levels, loading histories, volume‐to‐surface ratios and other factors in a high‐rise building must be properly considered in the design process. While research activity has been reported in the literature on the development of estimation algorithms or prediction procedures for the elastic and inelastic shortenings of vertical members, no algorithms or systematic methods for the compensation of the differential shortenings have been reported. In this paper, a compensation method for the differential column shortening in a high‐rise building is formulated into an optimization problem. A simulated annealing algorithm is used to find optimal solutions. The proposed method is applied to the compensation of the differential shortening of the vertical members in two high‐rise buildings, including one verifying example of a 70‐storey building and a practical example of a 63‐storey building. As demonstrated in the examples, the differential shortenings of the examples are effectively controlled by the optimal compensation method. Copyright © 2003 John Wiley & Sons, Ltd.
Field measurements of wind effects on the tallest building in Hong Kong
Authors: Li Q. S. , Xiao Y. Q. , Wong C. K. , Jeary A. P. 
Published: April 2003

AbstractCentral Plaza has a height of approximately 374 m and is 78‐storeys tall. It is the tallest structure in Hong Kong and was the highest reinforced‐concrete building in the world when it was built several years ago. This paper describes some results obtained from the full‐scale measurements of wind effects on Central Plaza. The field data such as wind speed, wind direction and acceleration responses have been measured during the close passage of several typhoons in recent years. Detailed analysis of the field data is conducted to investigate wind effects on the tall building. The full‐scale measurements are compared with the wind tunnel results. The amplitude‐dependent characteristics of damping that were obtained by using the random decrement technique are investigated on the basis of the field measurements. Copyright © 2003 John Wiley & Sons, Ltd.
Effects of Nitric Oxide onPseudomonas aeruginosaInfection of Epithelial Cells from a Human Respiratory Cell Line Derived from a Patient with Cystic Fibrosis
Authors: Darling Katharine E. A. , Evans Thomas J. 
Published: April 2003

ABSTRACTCystic fibrosis (CF) is characterized by airway inflammation and chronic bacterial lung infection, most commonly withPseudomonas aeruginosa, an opportunistic human pathogen. Despite the persistent airway inflammation observed in patients with CF, although phagocyte inducible nitric oxide synthase (iNOS) production is upregulated, expression of iNOS in the respiratory epithelium is markedly reduced. Given the antimicrobial action of NO, this may contribute to the chronic airway infection of this disease. To define the role of epithelium-derived NO in airway defense againstP. aeruginosa, we infected differentiated human bronchial epithelial cells derived from a patient with CF (CFBE41o- cells) with different strains of this pathogen at low multiplicities of infection. Using cells transfected with human iNOS cDNA, we studied the effect of NO onP. aeruginosareplication, adherence, and internalization.P. aeruginosaadherence to iNOS-expressing cells was reduced by 44 to 72% (P= 0.02) compared with control values. AbsoluteP. aeruginosauptake into these cells was reduced by 44%, but uptake expressed as a percentage of adherent bacteria did not differ from the control uptake. Survival ofP. aeruginosawithin iNOS-expressing cells was reduced at late times postinfection (P= 0.034). NO production did not alter host cell viability. NO production reducedP. aeruginosaadherence to human bronchial epithelial cells and enhanced killing of internalized bacteria, suggesting that a lack of epithelial iNOS in patients with CF may contribute toP. aeruginosainfection and colonization.
Failure of Surface Ring Mutant Strains ofHelicobacter mustelaeTo Persistently Infect the Ferret Stomach
Authors: Patterson M. M. , O'Toole P. W. , Forester N. T. , Noonan B. , Trust T. J. , Xu S. , Taylor N. S. , Marini R. P. , Ihrig M. M. , Fox J. G. 
Published: April 2003

ABSTRACTHelicobacter mustelae, the gastric pathogen of ferrets, produces an array of surface ring structures which have not been described for any other member of the genusHelicobacter, includingH. pylori. The unique ring structures are composed of a protein named Hsr. To investigate whether the Hsr rings are important for colonization of the ferret stomach, ferrets specific pathogen free forH. mustelaewere inoculated with an Hsr-deficient mutant strain or the wild-typeH. mustelaestrain. Quantitative cultures from antral biopsy specimens obtained at 3, 6, and 9 weeks postinoculation demonstrated no significant difference in the levels of bacteria in the ferrets that received the Hsr-negative strain and the ferrets infected with the parent strain. However, when the ferrets were biopsied at 12 and 15 weeks and necropsied at 18 weeks after infection, the levels of bacteria of the Hsr-negative strain in the stomach antrum were significantly reduced. This decline contrasted the robust antral colonization by the wild-type strain. The Hsr-negative strain did not efficiently colonize the gastric body of the study ferrets. Histological examination at 18 weeks postinoculation revealed minimal gastric inflammation in the animals that received the mutantH. mustelaestrain, a finding consistent with its waning infection status, whereas lesions characteristic of helicobacter infection were present in ferrets infected with the wild-type strain. Scant colonization by the Hsr-negativeH. mustelaestrain at the end of the 18-week study, despite initial successful colonization, indicates an inability of the mutant to persist, perhaps due to a specific host response.
lvgA, a NovelLegionella pneumophilaVirulence Factor
Authors: Edelstein Paul H. , Hu Baofeng , Higa Futoshi , Edelstein Martha A. C. 
Published: April 2003

ABSTRACTSeveral novelLegionella pneumophilavirulence genes were previously discovered by use of signature-tagged mutagenesis (P. H. Edelstein, M. A. Edelstein, F. Higa, and S. Falkow, Proc. Natl. Acad. Sci. 96:8190-8195, 1999). One of these mutants appeared to be defective in multiplication in guinea pig lungs and spleens, yet it multiplies normally in guinea pig alveolar macrophages. Here we report further characterization of the mutated gene and its protein and the virulence role of the gene. The complete sequence of the gene, now calledlvgA, is 627 bp long, and its protein product is approximately 27 kDa in size.lvgAwas present in all 50 strains ofL. pneumophilatested. No significant nucleic acid or protein homology was found in the GenBank database for the gene, nor were any distinctive motifs discovered in a search of other databases. The expression of both DotA and IcmX in thelvgAmutant was normal. Subcellular fractionation studies localized LvgA to the outer membrane fraction, and protease digestion studies suggested that at least some of the protein is surface expressed. No change in bacterial lipopolysaccharide composition or reactivity to serogroup-specific antisera was detected in the mutant. Growth competition studies with alveolar macrophages showed that the mutant was outcompeted by its parent 3-fold in 24 h and 24-fold in 48 h, in contrast to what was observed with the null phenotype in parallel testing with alveolar macrophages or with the A549 alveolar epithelial cell line. This macrophage defect of the mutant bacterium was due to slower growth, as the mutant invaded alveolar macrophages normally. Electron microscopy showed that the mutant bacterium resided in a ribosome-studded phagosome in alveolar macrophages, with no distinction from its parent. ThelvgAmutant was outcompeted by its parent about sixfold in guinea pig lungs and spleens; prolonged observation of infected animals showed no late-onset virulence of the mutant. Transcomplementation of the mutant restored the parental phenotype in guinea pigs. ThelvgAmutant was twofold more susceptible to killing by human β-defensin 2 but not to killing by other cationic peptides, serum complement, or polymorphonuclear neutrophils.lvgAis a novel virulence gene that is responsible for pleiotropic functions involving both extracellular and intracellular bacterial resistance mechanisms.
Use of the
Galleria mellonella
Caterpillar as a Model Host To Study the Role of the Type III Secretion System in
Pseudomonas aeruginosa
Pathogenesis
Authors: Miyata Sachiko , Casey Monika , Frank Dara W. , Ausubel Frederick M. , Drenkard Eliana 
Published: April 2003

ABSTRACT

Nonvertebrate model hosts represent valuable tools for the study of host-pathogen interactions because they facilitate the identification of bacterial virulence factors and allow the discovery of novel components involved in host innate immune responses. In this report, we determined that the greater wax moth caterpillar
Galleria mellonella
is a convenient nonmammalian model host for study of the role of the type III secretion system (TTSS) in
Pseudomonas aeruginosa
pathogenesis. Based on the observation that a mutation in the TTSS
pscD
gene of
P. aeruginosa
strain PA14 resulted in a highly attenuated virulence phenotype in
G. mellonella
, we examined the roles of the four known effector proteins of
P. aeruginosa
(ExoS, ExoT, ExoU, and ExoY) in wax moth killing. We determined that in
P. aeruginosa
strain PA14, only ExoT and ExoU play a significant role in
G. mellonella
killing. Strain PA14 lacks the coding sequence for the ExoS effector protein and does not seem to express ExoY. Moreover, using Δ
exoU
Δ
exoY
, Δ
exoT
Δ
exoY
, and Δ
exoT
Δ
exoU
double mutants, we determined that individual translocation of either ExoT or ExoU is sufficient to obtain nearly wild-type levels of
G. mellonella
killing. On the other hand, data obtained with a Δ
exoT
Δ
exoU
Δ
exoY
triple mutant and a Δ
pscD
mutant suggested that additional, as-yet-unidentified
P. aeruginosa
components of type III secretion are involved in virulence in
G. mellonella
. A high level of correlation between the results obtained in the
G. mellonella
model and the results of cytopathology assays performed with a mammalian tissue culture system validated the use of
G. mellonella
for the study of the
P. aeruginosa
TTSS.
Differences in Gamma Interferon Production Induced by Listeriolysin O and Ivanolysin O Result in Different Levels of Protective Immunity in Mice Infected with
Listeria monocytogenes
and
Listeria ivanovii
Authors: Kimoto Terumi , Kawamura Ikuo , Kohda Chikara , Nomura Takamasa , Tsuchiya Kohsuke , Ito Yutaka , Watanabe Isao , Kaku Taijin , Setianingrum Endang , Mitsuyama Masao 
Published: April 2003

ABSTRACT

Two pathogenic species in the genus
Listeria, Listeria monocytogenes
and
Listeria ivanovii
, are characterized by the production of hemolysins belonging to cholesterol-dependent cytolysins, listeriolysin O (LLO) and ivanolysin O (ILO), respectively. LLO, produced by
L. monocytogenes
, is able to induce gamma interferon (IFN-γ) production and contributes to the generation of Th1-dependent protective immunity. On the other hand, nothing is known about the role of ILO, produced by
L. ivanovii
, in this regard. In this study, we immunized mice with 0.1 50% lethal dose (LD
50
) of
L. monocytogenes
and
L. ivanovii.
Protective immunity against a challenge with 10 LD
50
was generated in mice infected with
L. monocytogenes
, whereas
L. ivanovii
infection did not induce protection. After immunization, the level of IFN-γ in serum samples was increased in mice given
L. monocytogenes
but not in those given
L. ivanovii.
To determine the IFN-γ-inducing activity of cytolysins, recombinant protein was constructed. Recombinant ILO exhibited significantly lower IFN-γ-inducing activity than LLO. By comparing the IFN-γ-inducing activity of a chimera incorporating LLO and ILO, it was found that domains 1 to 3 of LLO were critical for IFN-γ-inducing activity while the counterpart in ILO was unable to induce cytokine production. These results suggested that the weak ability of ILO to induce IFN-γ production is responsible for the failure of
L. ivanovii
to generate effective protective immunity.