bluuebunny/crossref_metadata_2025 huggingface dataset:
Sequence Analysis of the
msp4
Gene of
Anaplasma phagocytophilum
Strains
Authors: de la Fuente José , Massung Robert F. , Wong Susan J. , Chu Frederick K. , Lutz Hans , Meli Marina , von Loewenich Friederike D. , Grzeszczuk Anna , Torina Alessandra , Caracappa Santo , Mangold Atilio J. , Naranjo Victoria , Stuen Snorre , Kocan Katherine M.
Published: March 2005

The causative agent of human granulocytic ehrlichiosis was recently reclassified as
Anaplasma phagocytophilum
, unifying previously described bacteria that cause disease in humans, horses, dogs, and ruminants. For the characterization of genetic heterogeneity in this species, the homologue of
Anaplasma marginale
major surface protein 4 gene (
msp4
) was identified, and the coding region was PCR amplified and sequenced from a variety of sources, including 50 samples from the United States, Germany, Poland, Norway, Italy, and Switzerland and 4 samples of
A. phagocytophilum
-like organisms obtained from white-tailed deer in the United States. Sequence variation between strains of
A. phagocytophilum
(90 to 100% identity at the nucleotide level and 92 to 100% similarity at the protein level) was higher than in
A. marginale
. Phylogenetic analyses of
msp4
sequences did not provide phylogeographic information but did differentiate strains of
A. phagocytophilum
obtained from ruminants from those obtained from humans, dogs, and horses. The sequence analysis of the recently discovered
A. phagocytophilum msp2
gene corroborated these results. The results reported here suggest that although
A. phagocytophilum
-like organisms from white-tailed deer may be closely related to
A. phagocytophilum
, they could be more diverse. These results suggest that
A. phagocytophilum
strains from ruminants could share some common characteristics, including reservoirs and pathogenicity, which may be different from strains that infect humans.
Epidemiology of Human Sporotrichosis Investigated by Amplified Fragment Length Polymorphism
Authors: Neyra Edgar , Fonteyne Pierre-Alain , Swinne Danielle , Fauche Frederic , Bustamante Beatriz , Nolard Nicole
Published: March 2005

Amplified fragment length polymorphism (AFLP) was used to analyze the genetic diversity of Peruvian strains of
Sporothrix schenckii
and to compare them to a panel of non-Peruvian strains. AFLP analysis suggests that the Peruvian strains can be divided into two homogeneous clusters with no reference to geographical origin or the clinical form of sporotrichosis. The strains from abroad present heterogeneous profiles, with the Bolivian strain and the Colombian strains related to one of the Peruvian population. Sequencing of internal transcribed spacer 2, used to examine the relationships over a longer distance, confirmed the division of Peruvian strains into two populations that can be identified on the basis of a single but specific sequence divergence. This paper introduces automated AFLP analysis as a valuable tool for further investigation of the epidemiology and ecology of
S. schenckii
.
Predominance ofafr2andralFimbrial Genes Related to Those Encoding the K88 and CS31A Fimbrial Adhesins in EnteropathogenicEscherichia coliIsolates from Rabbits with Postweaning Diarrhea in Central Europe
Authors: Dow Mohamed A. , Tóth István , Alexa Pavel , Davies Michael , Malik Anna , Oswald Eric , Nagy Béla
Published: March 2005

PCR tests designed in these studies identified three rabbit adhesive factor genes among 43 enteropathogenicE. coli(EPEC) strains:afr1(2 strains), the F4(K88)/CS31A-relatedafr2(10 strains), andral(15 strains). Several EPEC strains (i.e., O153:H7 and O157:H2) lacked these genes but did adhere to HeLa cells and produced attaching and effacing lesions in rabbits.
Confirming Positive Results of Nucleic Acid Amplification Tests (NAATs) for
Chlamydia trachomatis
: All NAATs Are Not Created Equal
Authors: Schachter J. , Hook E. W. , Martin D. H. , Willis D. , Fine P. , Fuller D. , Jordan J. , Janda W. M. , Chernesky M.
Published: March 2005

The Centers for Disease Control and Prevention recommended confirming positive screening tests for
Chlamydia trachomatis
when positive predictive values are <90%. It is accepted that less sensitive tests (i.e., culture and immunoassays) should not be used to confirm the results of more sensitive nucleic acid amplification tests (NAATs). We show that the same principle applies when NAATs are used for confirmation.
Serotype G9 Rotavirus Infections in Adults in Sweden
Authors: Rubilar-Abreu Elba , Hedlund Kjell-Olof , Svensson Lennart , Mittelholzer Christian
Published: March 2005

Rotavirus is a major cause of acute gastroenteritis. By examining 1,517 stool samples collected in 2001 and 2002 from Swedish adults with acute diarrhea, rotavirus was found in 3.2%, with the emerging G9P[8] serotype being the one most commonly identified (42.9%). This is the first documentation of G9 infections in adults in Europe.
Predominance of Porcine Rotavirus G9 in Japanese Piglets with Diarrhea: Close Relationship of Their VP7 Genes with Those of Recent Human G9 Strains
Authors: Teodoroff Tamara A. , Tsunemitsu Hiroshi , Okamoto Kiyotora , Katsuda Ken , Kohmoto Mariko , Kawashima Kenji , Nakagomi Toyoko , Nakagomi Osamu
Published: March 2005

Type G9 of group A rotavirus (GAR) was shown to be predominant in a survey of VP7 (G) and VP4 (P) genotypes among porcine GARs associated with outbreaks of diarrhea in young pigs in Japan between 2000 and 2002. Comparison of the G9 VP7 gene sequences showed that the porcine G9 strains were more closely related to human G9 strains reemerging globally since the mid-1990s than to those from the mid-1980s. The VP7 gene sequences of porcine G9 strains from different farms were divergent (6.1 to 7.2% difference in nucleotides), suggesting that these G9 VP7 genes were not the result of recent introduction into the porcine population. Regarding the P genotype specificities of porcine G9 strains, while the majority of strains were close to unusual porcine P types (P[13] and P[23]), two strains were of the P[6] type, which has closer sequence identity with the human AU19 strain than with the porcine Gottfried strain. These unexpected results suggest that G9 GARs in the porcine population have spread more widely than previously thought and that the VP7 genes of porcine G9 strains and those of some human G9 strains detected recently may have a common progenitor.
Use of Microsatellite Markers and Gene Dosage To Quantify Gene Copy Numbers in
Candida albicans
Authors: Costa J.-M. , Eloy O. , Botterel F. , Janbon G. , Bretagne S.
Published: March 2005

With microsatellite marker typing, the number of alleles must be known for calculation of allelic frequencies in the diploid
Candida albicans
for a given locus. We describe a gene dosage with a double real-time PCR. Such a dosage should also be useful in exploring the loss of heterozygosity in
C. albicans
.
Genetic Diversity of Multidrug-Resistant
Mycobacterium tuberculosis
Isolates and Identification of 11 Novel
rpoB
Alleles in Taiwan
Authors: Jou Ruwen , Chen Huang-Yau , Chiang Chen-Yuan , Yu Ming-Chih , Su Ih-Jen
Published: March 2005

Of 162 multidrug-resistant
Mycobacterium tuberculosis
isolates from Taiwan, 60.5% were found to belong to the Beijing family on the basis of spoligotyping results. IS
6110
restriction fragment length polymorphism fingerprinting showed genetic diversity among the multidrug-resistant isolates. Furthermore, 90.1% of the multidrug-resistant isolates had mutations in the
rpoB
gene, and 11 novel alleles were recognized.
Diminished Replicative Fitness of Primary Human Immunodeficiency Virus Type 1 Isolates Harboring the K65R Mutation
Authors: Weber Jan , Chakraborty Bikram , Weberova Jitka , Miller Michael D. , Quiñones-Mateu Miguel E.
Published: March 2005

The human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) resistance mutation K65R confers intermediate levels of resistance to several RT inhibitors, including a three- to fourfold reduction of tenofovir susceptibility. Here, we have used for the first time primary HIV-1 isolates from individuals who developed the K65R mutation while enrolled in a clinical trial of tenofovir to analyze the impact of this mutation on HIV-1 replicative fitness. A marked impairment in replicative fitness was observed in association with the selection of viruses carrying the K65R mutation in all patients. The mean replicative fitness among these viruses was 20% relative to the corresponding baseline wild-type virus, ranging from 10 to 32% depending on the accompanying RT mutations. These results support a reduction in in vivo replication for K65R mutant viruses.
Infective Endocarditis Caused by
Granulicatella elegans
Originating in the Oral Cavity
Authors: Ohara-Nemoto Yuko , Kishi Kayo , Satho Mamoru , Tajika Shihoko , Sasaki Minoru , Namioka Akiko , Kimura Shigenobu
Published: March 2005

We studied the pheno- and genotypes of an oral
Granulicatella elegans
strain in comparison with those of a blood-derived isolate which caused infective endocarditis. The two isolates exhibited identical biochemical characteristics and had the same drug MICs. Their genotypes were indistinguishable, indicating that these were from the same clone. The transmission of
G. elegans
from the oral cavity thus should be noted as a possible cause of infective endocarditis.
Detection of Human Metapneumovirus RNA Sequences in Nasopharyngeal Aspirates of Young French Children with Acute Bronchiolitis by Real-Time Reverse Transcriptase PCR and Phylogenetic Analysis
Authors: Bouscambert-Duchamp Maude , Lina Bruno , Trompette Aurélien , Moret Hélène , Motte Jacques , Andréoletti Laurent
Published: March 2005

Human metapneumovirus (HMPV) was the unique viral pathogen detected by a real-time reverse transcriptase PCR (RT-PCR) assay in 6 (6.4%) of 94 consecutive French children hospitalized for acute bronchiolitis from September 2001 to June 2002. This virus was identified as the third etiological cause of bronchiolitis, after respiratory syncytial virus and rhinovirus (35 [37%] and 21 [22%] of 94 cases, respectively). Phylogenetic analysis of F-gene sequences demonstrated the cocirculation of distinct HMPV genotypes during this study. These findings highlight the need to implement a rapid HMPV RT-PCR detection assay for the clinical diagnosis of respiratory infections in pediatric patients with bronchiolitis.
Survey of
emm
-Like Gene Sequences from Pharyngeal Isolates of Group C and Group G Streptococci Collected in Spain
Authors: Albertí Sebastián , García-Rey Cesar , García-Laorden María Isabel , Dal-Ré Rafael , García-de-Lomas Juan
Published: March 2005

We conducted a nationwide surveillance of the variable 5′
emm
-like (M-like protein gene) sequences from 214 pharyngeal group C and group G streptococci. Almost 75% of the isolates exhibited
emm
or
emm
-like sequences previously described. We identified six new 5′
emm
-like regions, and almost 23% of the isolates were nontypeable. Five
emm
-like sequences accounted for more than 50% of the isolates in group C and group G, suggesting horizontal gene transfer between strains of different species.
False-Positive
Histoplasma capsulatum
Gen-Probe Chemiluminescent Test Result Caused by a
Chrysosporium
Species
Authors: Brandt Mary E. , Gaunt Dennis , Iqbal Naureen , McClinton Shirley , Hambleton Sarah , Sigler Lynne
Published: March 2005

We describe a case in which the
Histoplasma capsulatum
AccuProbe test displayed cross-reactivity with a respiratory isolate thought to be
Histoplasma
but not morphologically consistent with
H. capsulatum
. The isolate was later identified as the
Chrysosporium
anamorph of
Nannizziopsis vriesii
by sequence analysis and phenotypic data.
Osteomyelitis Caused by
Enterobacter cancerogenus
Infection following a Traumatic Injury: Case Report and Review of the Literature
Authors: Garazzino S. , Aprato A. , Maiello A. , Massé A. , Biasibetti A. , De Rosa F. G. , Di Perri G.
Published: March 2005

We report a case of osteomyelitis caused by
Enterobacter cancerogenus
resistant to aminopenicillins in a 56-year-old male who had a motorcycle accident and suffered from multiple bone fractures with abundant environmental exposure.
E. cancerogenus
has rarely been associated with human infections, and its clinical significance remains unclear.
Typhoid Fever Associated with Acute Appendicitis Caused by an H1-j Strain of
Salmonella enteric
a Serotype Typhi
Authors: Lau Susanna K. P. , Woo Patrick C. Y. , Chan Clair Y. F. , Woo Wai-Lan , Woo Gibson K. S. , Yuen Kwok-Yung
Published: March 2005

While most strains of
Salmonella enterica
serotype Typhi, the etiologic agent of typhoid fever, have only a phase 1 flagellar antigen, H1-d, variations of the flagellar antigen have been observed. Although H1-j strains (one of the flagellar antigen variants) account for 10 to 50% of
S. enterica
serotype Typhi strains found in Indonesia, there have been no published data to suggest its existence in other parts of the world. We describe a case of typhoid fever associated with acute appendicitis caused by an
S. enterica
serotype Typhi H1-j strain in a Chinese woman in Hong Kong. A gram-negative, motile rod was recovered from her blood and stool cultures. Conventional biochemical tests and the Vitek system (GNI+) showed that the bacterium was
S. enterica
serotype Typhi. The isolate agglutinated with poly(O), 9O, Vi and H1-j
Salmonella
antisera but not with poly(H) antisera. The patient developed antibodies against only
S. enterica
serotype Typhi O antigens but not against H1-d antigen by the Widal test. Flagellin C gene (
fliC
) sequencing showed a 261-bp deletion in the
fliC
gene of the isolate, confirming that the isolate possessed the H1-j antigen. The patient had no past history of travel to Indonesia or personal contact with any Indonesian. She recovered with appendectomy and antibiotic treatment. Further studies should be performed to determine the prevalence of this unusual
S. enterica
serotype Typhi strain in our locality.
A migrating pacemaker
Authors: Gale C P , Mulley G P
Published: March 2005

A deceased 79 year old man with a permanent cardiac pacemaker was due to be cremated, but the pacemaker generator was not detectable by palpation. A hand held metal detector to locate the device so that it could be extracted before cremation.
Drunken patients in the general hospital: their care and management
Authors: Malone D , Friedman T
Published: March 2005

In Britain alcohol consumption is increasing, 1 in 4 men and 1 in 10 women drink hazardously, 1 in 3 young men, and 1 in 4 young women regularly binge drink. Mortality rates attributable to alcohol have doubled; with 1 in 5 male inpatients having an alcohol related problem. The increasing problem of managing drunken behaviour in accident and emergency departments is discussed. Although an alcohol history is recommended for all admissions, because of various reasons, hazardous drinkers continue to miss the opportunity of effective interventions. In addition to the more formal treatments for alcohol problems, there is a wealth of evidence reporting the effectiveness of brief interventions carried out by a range of health professionals can lead to long term reductions in alcohol consumption. This review discusses practical and legal issues of the assessment, screening tools, and management of intoxicated patients.
Informed consent in renal transplantation
Authors: Edwards A G , Weale A R , Morgan J D
Published: March 2005

Purpose

This study was performed to assess how well completed the new consent forms are for patients undergoing renal transplantation.

Methodology

100 patients were randomly selected from the 160 who had a renal transplantation, at a single centre in the UK, over an 18 month period. The notes were located and the consent forms scrutinised.

Findings

Seven sets of notes could not be traced and 10 did not contain a relevant consent form. Forty eight per cent of completed forms mentioned the source of organ while 8% mentioned on which side the operation was to be performed. Twelve risks and complications were identified as being relevant to this procedure but no single form mentioned all 12. In most cases a senior member of the surgical team obtained consent.

Implications

The demonstrated variability in the amount of detail on consent forms lends weight to the call for the use of procedure specific forms. While such variability does not necessarily equate with not gaining valid, informed consent, this form, at present, serves as the only record of what has been discussed with the patient. These findings should encourage all surgeons to complete the forms themselves, be as detailed as possible, and ensure that the form is filed in the patients’ notes.
Access to health care for ethnic minority populations
Authors: Szczepura A
Published: March 2005

This paper reviews the research evidence on access to health care by ethnic minority populations, and discusses what might need to be done to improve access to services. Research on the process of care, and the quality of care received, is considered as well as studies examining uptake of services. Changes in legal context are increasing the pressure on healthcare organisations to examine and adapt their services to ensure equitable access. Examples presented include a new UK population cancer screening programme. The main challenges for clinicians, managers, and policy makers in ensuring equitable access are discussed.
DEVELOPING TIME-BASED CLUSTERING NEURAL NETWORKS TO USE CHANGE-POINT DETECTION: APPLICATION TO FINANCIAL TIME SERIES
Authors: OH KYONG JOO , ROH TAE HYUP , MOON MYUNG SANG
Published: March 2005

This study suggests time-based clustering models integrating change-point detection and neural networks, and applies them to financial time series forecasting. The basic concept of the proposed models is to obtain intervals divided by change points, to identify them as change-point groups, and to involve them in the forecasting model. The proposed models consist of two stages. The first stage, the clustering neural network modeling stage, is to detect successive change points in the dataset, and to forecast change-point groups with backpropagation neural networks (BPNs). In this stage, three change-point detection methods are applied and compared. They are: (1) the parametric approach, (2) the nonparametric approach, and (3) the model-based approach. The next stage is to forecast the final output with BPNs. Through the application to financial time series forecasting, we compare the proposed models with a neural network model alone and, in addition, determine which of three change-point detection methods performs better. Furthermore, we evaluate whether the proposed models play a role in clustering to reflect the time. Finally, this study examines the predictability of the integrated neural network models based on change-point detection.
APPLYING REAL OPTIONS AND THE MAXIMUM NPV RULE TO MARKET ENTRY/EXIT STRATEGIES
Authors: LIN TYRONE T. , SHIH TUNG-LI
Published: March 2005

This study applies the real options approach to examine the maximum net present value of the market entry/exit thresholds given uncertain cash flows. The discount and growth factors are determined in the proposed entry/exit models, facilitating the complex calculation of the discount and growth rates to determine the present value of cash flow streams. Accordingly, this work successfully combines the maximum net present value method and the real options approach for decision-making by simply considering the discount and growth factors.
BAYESIAN STUDY OF A TWO-COMPONENT SYSTEM WITH COMMON-CAUSE SHOCK FAILURES
Authors: YADAVALLI V. S. S. , BEKKER A. , PAUW J.
Published: March 2005

The steady-state availability of a two-component system in series and parallel subject to individual failures (I-failures) and common-cause shock (CCS) failures is studied from a Bayesian viewpoint with different types of priors assumed for the unknown parameters in the system. Monte Carlo simulation is used to derive the posterior distribution for the steady-state availability and subsequently the highest posterior density intervals. A numerical example illustrates the results.
GROUPS OF LOCALLY-FLAT DISK KNOTS AND NON-LOCALLY-FLAT SPHERE KNOTS
Authors: FRIEDMAN GREG
Published: March 2005

The classical knot groups are the fundamental groups of the complements of smooth or piecewise-linear (PL) locally-flat knots. For PL knots that are not locally-flat, there is a pair of interesting groups to study: the fundamental group of the knot complement and that of the complement of the "boundary knot" that occurs around the singular set, the set of points at which the embedding is not locally-flat. If a knot has only point singularities, this is equivalent to studying the groups of a PL locally-flat disk knot and its boundary sphere knot; in this case, we obtain a complete classification of all such group pairs in dimension ≥6. For more general knots, we also obtain complete classifications of these group pairs under certain restrictions on the singularities. Finally, we use spinning constructions to realize further examples of boundary knot groups.
VASSILIEV INVARIANTS FOR VIRTUAL LINKS, CURVES ON SURFACES AND THE JONES–KAUFFMAN POLYNOMIAL
Authors: MANTUROV VASSILY O.
Published: March 2005

We discuss the strong invariant of virtual links proposed in [23]. This invariant is obtained as a generalization of the Jones–Kauffman polynomial (generalized Kauffman's bracket) by adding to the sum some equivalence classes of curves in two-dimensional surfaces. Thus, the invariant is valued in the infinite-dimensional free module over Z[q,q-1].

We prove that this invariant can be decomposed into finite type Vassiliev invariant of virtual links (in Kauffman's sense); thus we present new infinite series of Vassiliev invariants.

It is also proved that this invariant is strictly stronger than the Jones–Kauffman polynomial for virtual knots proposed by Kauffman. Some examples when the invariant can recognize virtual knots that can not be recognized by other invariants are given.
ON TOPOLOGICAL CORRELATIONS IN TRIVIAL KNOTS: FROM BROWNIAN BRIDGES TO CRUMPLED GLOBULES
Authors: NECHAEV SERGEI , VASILYEV OLEG
Published: March 2005

We study, analytically and by numerical simulations, a mathematical model of closed unknotted polymer chains. The polymers are modeled by what we call "densely packed knots", which are knot diagrams entirely covering a long rectangular lattice, with randomly generated overpasses and underpasses at the nodes of the lattice. We are interested in the probability of the "knottedness" (the "knot complexity") of densily packed knots, which we measure via the degree of their Jones–Kauffman polynomial. In particular, we find the mean complexity of "daughter knots", obtained by cutting off a part of a trivial (i.e. unknotted) "parent" densily packed knot and closig up the "open tails" (the loose ends of the cut strands). We present arguments supporting the conjecture that the knot complexity n* of a daughter knot of an unknotted parent one grows as [Formula: see text] where N is the total number of vertices on the lattice. This result gives a strong support for the conjectured "crumpled globule" structure of collapsed unknotted closed polymer chains, in which the polymer forms a system of densely packed folds, mutually separated in a broad range of scales.
CALIBRATED OPTION BOUNDS
Authors: KING ALAN J. , KOIVU MATTI , PENNANEN TEEMU
Published: March 2005

This paper proposes a numerical approach for computing bounds for the arbitrage-free prices of an option when some options are available for trading. Convex duality reveals a close relationship with recently proposed calibration techniques and implied trees. Our approach is intimately related to the uncertain volatility model of Avellaneda, Levy and Parás, but it is more general in that it is not based on any particular form of the asset price process and does not require the seller's price of an option to be a differentiable function of the cash-flows of the option. Numerical tests on S&P500 options demonstrate the accuracy and robustness of the proposed method.
BEFORE EIA: DEFINING THE SCOPE OF INFRASTRUCTURE PROJECTS IN THE NETHERLANDS
Authors: ARTS JOS , VAN LAMOEN FRANK
Published: March 2005

This article discusses recent developments in integrated planning for the national road infrastructure in the Netherlands. It lays emphasis on project definition as a "missing link" between strategic planning and operational planning.

Road development projects may have considerable negative impacts. Projects, however, are often too narrowly focused on road (re)construction alternatives and pay too less attention to the relationships with other spatial developments. As a consequence, the scope of project Environmental Impact Assessments (EIAs) is too narrow and opportunities are missed to enhance the spatial and environmental quality of the regions concerned. These problems are best tackled early in the planning process when the "degrees of freedom" in shaping the project are relatively large.

Using the case of the A27 motorway a new guideline for explorative studies is introduced. The instrument described (called "reconnaissance study") aims to connect the planning arenas of Strategic Environmental Assessment and EIA, thus achieving more sustainable planning. It focuses on the early stage of project development in which the scope of projects is defined by "zooming in" from the national to a regional setting and translation of abstract policy goals to a "real world" situation. Key elements are a transparent process in which problem analysis and development of solutions are seperated, involvement of external parties and a broad study scope.
EMERGING APPROACHES TO URBAN ECOSYSTEM MANAGEMENT: THE POTENTIAL OF LOW IMPACT URBAN DESIGN AND DEVELOPMENT PRINCIPLES
Authors: VAN ROON MARJORIE
Published: March 2005

The incorporation of integrated water cycle management into urban design is essential for urban sustainability. This paper provides insight into the evolution of Low Impact Urban Design and Development (LIUDD). It explores changes in urban design and infrastructure that reduce or avoid adverse biophysical effects that have contributed to the decline of aquatic biotic integrity following urban intensification in catchments. Recent practices in Canada, the United States and New Zealand offset receiving water ecosystem degradation by maximising catchment stormwater infiltration at source, contaminant containment and catchment revegetation. Local soil, climate, maturity and density of urban form, and vegetation characteristics determine the balance between infiltration and evapotranspiration in application of techniques. Examples are cited of brownfield stormwater infiltration in the Netherlands (Ruwenbosch, Enschede), neighbourhood containment of water and waste cycles in Germany (Leipzig) and site-specific developments proving the cost-effectiveness of LIUDD. LIUDD, which is evolving from its origins in stormwater management, is making a major contribution to many facets of urban sustainability, including improved urban amenity and recreation, cost-effective infrastructure and biodiversity enhancement.
THE SUSTAINABILITY OF "SUSTAINABILITY" — A STUDY INTO THE CONCEPTUAL FOUNDATIONS OF THE NOTION OF "SUSTAINABILITY"
Authors: FABER NIELS , JORNA RENÉ , VAN ENGELEN JO
Published: March 2005

The new challenge for organisations is to deal with the complex issue of sustainability. However, the confusion surrounding "sustainability" hinders its implementation. This article formulates a framework consisting of three aspects to analyse the conceptual developments that underlie "sustainability": the artefact ("what"), goal orientation ("relative versus absolute") and (behavioural) interaction ("static versus dynamic"). The study of conceptual foundations underpins the framework. Contributions in both the theoretical (definitions) and the practical (indicators) spheres are analysed. The discussion about sustainability takes place in firms. Therefore, organisational developments are used as a reference timeline. Based on observations and analyses, this article suggests a new course for the sustainability discussion and its implications for the organisational context: a knowledge approach focussing on transparency and dialogue. This also implies that the emphasis in the sustainability discussion is changing from a merely environmental to an organisational and societal perspective.
Extracellular cysteine/cystine redox regulates the p44/p42 MAPK pathway by metalloproteinase-dependent epidermal growth factor receptor signaling
Authors: Nkabyo Yvonne S. , Go Young-Mi , Ziegler Thomas R. , Jones Dean P.
Published: March 2005

Previous research shows that stimulation of proliferation of colon carcinoma (Caco-2) cells by a more reduced extracellular cysteine/cystine (Cys/CySS) redox state occurs with no apparent effect on intracellular glutathione and that this stimulation is lost on addition of epidermal growth factor. The purpose of the present study was to determine whether a more reduced extracellular Cys/CySS redox state activates the mitogenic p44/p42 mitogen-activated protein kinase (MAPK) pathway and whether this is signaled through the epidermal growth factor receptor (EGFR). Caco-2 cells were exposed to a range of physiological extracellular redox conditions from −150 to 0 mV. In the absence of added growth factors, the most reduced (−150 mV) redox state induced an 80% increase in EGFR phosphorylation, and this was followed by a marked increase in phosphorylation of p44/p42 MAPK. Inhibitors of EGFR (AG1478) and p44/p42 MAPK (U0126) phosphorylation blocked redox-dependent p44/p42 phosphorylation, indicating that signaling occurred by EGFR. These effects were inhibited by pretreatment with a nonpermeant alkylating agent, showing that signaling involved thiols accessible to the extracellular space. The EGFR ligand TGF-α was increased in culture medium at more reduced redox states. Redox-dependent phosphorylation of EGFR was completely prevented by a metalloproteinase inhibitor (GM6001), and an antibody to TGF-α partially inhibited the phosphorylation of p44/p42 MAPK by redox. Thus the data show that a redox-dependent activation of metalloproteinase can stimulate the mitogenic p44/p42 MAPK pathway by a TGF-α-dependent mechanism. Because Cys availability and Cys/CySS redox are dependent on nutrition, disease, and environmental exposures, the results suggest that cell proliferation could be influenced physiologically by Cys-dependent redox effects on growth factor signaling pathways.
Strain-dependent β-adrenergic receptor function influences myocardial responses to isoproterenol stimulation in mice
Authors: Faulx Michael D. , Ernsberger Paul , Vatner Dorothy , Hoffman Robert D. , Lewis William , Strachan Ryan , Hoit Brian D.
Published: March 2005

Recently, we showed that compared with the A/J inbred mouse strain, C57BL/6J (B6) mice have an athlete's cardiac phenotype. We postulated that strain differences would result in greater left ventricular (LV) hypertrophy in response to isoproterenol in B6 than A/J mice and tested the hypothesis that a differential response could be explained partly by differences in β-adrenergic receptor (β-AR) density and/or coupling. A/J and B6 mice were randomized to receive daily isoproterenol (100 mg/kg sc) or isovolumic vehicle for 5 days. Animals were studied using echocardiography, tail-cuff blood pressure, histopathology, β-AR density and percent high-affinity binding, and basal and stimulated adenylyl cyclase activities. One hundred twenty-eight mice (66 A/J and 62 B6) were studied. Isoproterenol-treated A/J mice demonstrated greater percent increases in echocardiographic LV mass/body weight (97 ± 11 vs. 20 ± 10%, P = 0.001) and in gravimetric heart mass/body weight versus same-strain controls than B6 mice. Histopathology scores (a composite of myocyte hypertrophy, nuclear changes, fibrosis, and calcification) were greater in isoproterenol-treated A/J vs. B6 mice (2.8 ± 0.2 vs.1.9 ± 0.3, P < 0.05), as was quantitation of myocyte damage (22.3 ± 11.5 vs. 4.3 ± 3.5%). Interstrain differences in basal β-AR density, high-affinity binding, and adenylyl cyclase activity were not significant. However, whereas isoproterenol-treated A/J mice showed nonsignificant increases in all β-AR activity measures, isoproterenol-treated B6 mice had lower β-AR density (57 ± 6 vs. 83 ± 8 fmol/mg, P < 0.05), percent high-affinity binding (15 ± 2 vs. 26 ± 3%, P < 0.005), and GTP + isoproterenol-stimulated adenylyl cyclase activity (10 ± 1.1 vs. 5.8 ± 1.5 pmol cAMP·mg−1·min−1) compared with controls. High-dose, short-term isoproterenol produces greater macro- and microscopic cardiac hypertrophy and injury in A/J than B6 mice. A/J mice, unlike B6 mice, do not experience β-AR downregulation or uncoupling in response to isoproterenol. Abnormalities in β-adrenergic regulation may contribute to strain-related differences in the vulnerability to isoproterenol-induced cardiac changes.
Periprandial changes in growth hormone release in goldfish: role of somatostatin, ghrelin, and gastrin-releasing peptide
Authors: Canosa Luis Fabián , Unniappan Suraj , Peter Richard Ector
Published: March 2005

In goldfish, growth hormone (GH) transiently rises 30 min after meals, returning to baseline at 1 h postmeal. Somatostatin (SRIF) is the major inhibitor of GH release. Three cDNAs encoding pre-pro-SRIF (PSS) have been previously cloned from goldfish brain: PSS-I, which encodes SRIF-14; PSS-II, which is potentially processed into gSRIF-28 that has [Glu1,Tyr7,Gly10]SRIF-14 at the COOH terminus; and PSS-III, which encodes [Pro2]SRIF-14 at its COOH terminus. In goldfish, bombesin (BBS), mimicking the endogenous gastrin-releasing peptide (GRP), acutely suppresses food intake and also stimulates GH release. Ghrelin was recently characterized in goldfish as a GH secretagogue and an orexigen. In this paper, we studied the changes in SRIF mRNA levels during feeding and analyzed the influences of BBS and ghrelin peptides on forebrain PSS expression. The results showed a 60% reduction in PSS-II mRNA after meals, but no changes in the expression of PSS-I and PSS-III were found. Intraperitoneal injections of 100 ng/g body wt of BBS increased GH secretion and decreased PSS-I and PSS-II gene expression. Intraperitoneal injection of goldfish ghrelin (100 ng/g body wt) transiently increased the serum GH levels and increased PSS-I, while decreasing PSS-II mRNA levels. Ghrelin (50 ng/g body wt) blocked the effects of BBS (100 ng/g body wt) on PSS-I but not on PSS-II expression. Coadministration of BBS and ghrelin decreased only the PSS-II gene expression. We conclude that the interactions between BBS/GRP and ghrelin can account for the postprandial variations in serum GH levels and the forebrain expression of PSS-II. Furthermore, we demonstrate that intraperitoneal administration of BBS reduces the ghrelin expression levels in the gut. Thus the inhibition of production of ghrelin in the gut may contribute to the satiety effects of BBS/GRP peptides.
Force recovery after activated shortening in whole skeletal muscle: transient and steady-state aspects of force depression
Authors: Corr David T. , Herzog Walter
Published: March 2005

The depression of isometric force after active shortening is a well-accepted characteristic of skeletal muscle, yet its mechanisms remain unknown. Although traditionally analyzed at steady state, transient phenomena caused, at least in part, by cross-bridge kinetics may provide novel insight into the mechanisms associated with force depression (FD). To identify the transient aspects of FD and its relation to shortening speed, shortening amplitude, and muscle mechanical work, in situ experiments were conducted in soleus muscle-tendon units of anesthetized cats. The period immediately after shortening, in which force recovers toward steady state, was fit by using an exponential recovery function ( R2> 0.99). Statistical analyses revealed that steady-state FD (FDss) increased with shortening amplitude and mechanical work. This FDssincrease was always accompanied by a significant decrease in force recovery rate. Furthermore, a significant reduction in stiffness was observed after all activated shortenings, presumably because of a reduced proportion of attached cross bridges. These results were interpreted with respect to the two most prominent proposed mechanisms of force depression: sarcomere length nonuniformity theory ( 7 , 32 ) and a stress-induced inhibition of cross-bridge binding in the newly formed actin-myosin overlap zone ( 14 , 28 ). We hypothesized that the latter could describe both steady-state and transient aspects of FD using a single scalar variable, the mechanical work done during shortening. As either excursion (overlap) or force (stress) is increased, mechanical work increases, and cross-bridge attachment would become more inhibited, as supported by this study in which an increase in mechanical work resulted in a slower recovery to a more depressed steady-state force.
Association Between Serum Uric Acid, Metabolic Syndrome, and Carotid Atherosclerosis in Japanese Individuals
Authors: Ishizaka Nobukazu , Ishizaka Yuko , Toda Ei-Ichi , Nagai Ryozo , Yamakado Minoru
Published: March 2005

Objective—There are few data available on possible independent association between uric acid and carotid atherosclerosis. Here we first sought to investigate association between uric acid levels and metabolic syndrome in Japanese; second, we assessed whether there is an independent association of uric acid with prevalence of carotid atherosclerosis in individuals subdivided according to gender and metabolic syndrome status.

Methods and Results—Cross-sectional data from 8144 individuals who underwent general health screening were analyzed. After adjusting for age, total cholesterol, and smoking status, the odds ratios (95% CI) of sex-specific quartiles of serum uric acid for metabolic syndrome were 1.0, 1.06 (0.60 to 1.87), 2.18 (1.30 to 3.64), and 4.17 (2.56 to 6.79) in women, and 1.0, 0.92 (0.74 to 1.14), 1.52 (1.25 to 1.65), and 1.97 (1.61 to 2.40) in men. After adjusting for age, serum levels, total cholesterol, and smoking status, prevalence of carotid plaque was higher in subjects in the second, third, and fourth quartiles of uric acid level with odds ratios (95% CI) of 1.24 (1.01 to 1.52), 1.37 (1.11 to 1.68), and 1.31 (1.05 to 1.63), respectively, in men without metabolic syndrome but not in men with metabolic syndrome or in women with or without metabolic syndrome.

Conclusion—The prevalence of metabolic syndrome showed a graded increase according to serum uric acid values in both genders. In men who did not have metabolic syndrome, uric acid was found to be an independent risk factor for incidence of carotid plaque.
Matrix Metalloproteinase-9 Modulation by Resident Arterial Cells Is Responsible for Injury-Induced Accelerated Atherosclerotic Plaque Development in Apolipoprotein E–Deficient Mice
Authors: Choi Eric T. , Collins Emily T. , Marine Leopoldo A. , Uberti Maria G. , Uchida Hisashi , Leidenfrost Jeremy E. , Khan M. Faisal , Boc Kenneth P. , Abendschein Dana R. , Parks William C.
Published: March 2005

Objective—

Although matrix metalloproteinase-9 (MMP-9) has been implicated in atherosclerotic plaque instability, the exact role it plays in the plaque development and progression remains largely unknown. We generated apolipoprotein E (apoE)–deficient (apoE
−/−
) MMP-9–deficient (MMP-9
−/−
) mice to determine the mechanisms and the main cell source of MMP-9 responsible for the plaque composition during accelerated atherosclerotic plaque formation.

Methods and Results—

Three weeks after temporary carotid artery ligation revealed that while on a Western-type diet, apoE
−/−
MMP-9
−/−
mice had a significant reduction in intimal plaque length and volume compared with apoE
−/−
MMP-9
+/+
mice. The reduction in plaque volume correlated with a significantly lower number of intraplaque cells of resident cells and bone marrow–derived cells. To determine the cellular origin of MMP-9 in plaque development, bone marrow transplantation after total-body irradiation was performed with apoE
−/−
MMP-9
+/+
and apoE
−/−
MMP-9
−/−
mice, which showed that only MMP-9 derived from resident arterial cells is required for plaque development.

Conclusions—

MMP-9 is derived from resident arterial cells and is required for early atherosclerotic plaque development and cellular accumulation in apoE
−/−
mice.
NAD(P)H Oxidase Inhibition Attenuates Neuronal Chronotropic Actions of Angiotensin II
Authors: Sun Chengwen , Sellers Kathleen W. , Sumners Colin , Raizada Mohan K.
Published: March 2005

It is well established that the central cardiovascular effects of angiotensin II (Ang II) involve superoxide production. However, the intracellular mechanism by which reactive oxygen species (ROS) signaling regulates neuronal Ang II actions remains to be elucidated. In the present study, we have used neuronal cells in primary cultures from the hypothalamus and brain stem areas to study the role of ROS on the cellular actions of Ang II. Ang II increases neuronal firing rate, an effect mediated by the AT
1
receptor subtype and involving inhibition of the delayed rectifier potassium current (
I
Kv
). This increase in neuronal activity was associated with increases in NADPH oxidase activity and ROS levels within neurons, the latter evidenced by an increase in ethidium fluorescence. The increases in NADPH oxidase activity and ethidium fluorescence were blocked by either the AT
1
receptor antagonist losartan or by the selective NAD(P)H oxidase inhibitor gp91ds-tat. Extracellular application of the ROS scavenger, Tempol, attenuated the Ang II–induced increase in neuronal firing rate by 70%. In addition, gp91ds-tat treatment resulted in a 50% inhibition of Ang II–induced increase in firing rate. In contrast, the ROS generator Xanthine-Xanthine oxidase significantly increased neuronal firing rate. Finally, Ang II inhibited neuronal
I
Kv,
and this inhibition was abolished by gp91ds-tat treatment. These observations demonstrate, for the first time, that Ang II regulates neuronal activity via a series of events that includes ROS generation and inhibition of
I
Kv
. This signaling seems to be a critical cellular event in central Ang II regulation of cardiovascular function.
Study of the Relationship Between Social Deprivation and Outcome After Stroke
Authors: Weir Nicolas U. , Gunkel Alison , McDowall Michael , Dennis Martin S.
Published: March 2005

Background and Purpose—

Although the incidence and mortality of stroke are known to be inversely related to socioeconomic status (SES), the relationship between SES and recovery after stroke has been little-studied. This study has investigated the relationship between SES and case fatality, “death or dependency,” and “death or institutional care” at 6 months after stroke.

Methods—

Patients with acute stroke (n=2709) were identified using routine hospital discharge data and SES was measured using Carstairs scores (an ecological index of social deprivation). Case mix and treatment data were collected by medical chart review, case fatality by record linkage, and functional status and place of residence by questionnaire. Logistic regression was used to adjust the association of social deprivation and outcome for case mix and selected treatment variables.

Results—

With increasing social deprivation, patients were younger, more likely to live alone, and, on admission, more likely to need help to walk. Social deprivation was not associated with case fatality or with “death or institutional care” in any analysis. However, patients residing in the most deprived areas (deprivation categories 6 and 7) were significantly more likely to be dead or dependent than patients from more affluent areas. This association was weakened but remained after adjusting for case mix and treatment variables.

Conclusions—

These findings contribute to growing evidence of an inverse social gradient in disability after stroke. Institutionalization, as a proxy for functional outcome, may not reflect this fact. A marked social gradient in case fatality after stroke seems unlikely.
Adenovirus-Mediated Gene Transfer of Heparin-Binding Epidermal Growth Factor-Like Growth Factor Enhances Neurogenesis and Angiogenesis After Focal Cerebral Ischemia in Rats
Authors: Sugiura Shiro , Kitagawa Kazuo , Tanaka Shigeru , Todo Kenichi , Omura-Matsuoka Emi , Sasaki Tsutomu , Mabuchi Takuma , Matsushita Kohji , Yagita Yoshiki , Hori Masatsugu
Published: March 2005

Background and Purpose—

Recent studies have demonstrated that neurotrophic factors promote neurogenesis after cerebral ischemia. However, it remains unknown whether administration of genes encoding those factors could promote neural regeneration in the striatum and functional recovery. Here, we examined the efficacy of intraventricular injection of a recombinant adenovirus-expressing heparin-binding epidermal growth factor-like growth factor (HB-EGF) on neurogenesis, angiogenesis, and functional outcome after focal cerebral ischemia.

Methods—

Transient focal ischemia was induced by middle cerebral artery occlusion (MCAO) for 80 minutes with a nylon filament in Wistar rats. Three days after MCAO, either adenovirus-expressing HB-EGF (Ad-HB-EGF) or Ad-LacZ, the control vector, was injected into the lateral ventricle on the ischemic side. Bromodeoxyuridine (BrdU) was injected intraperitoneally twice daily on the sixth and seventh days. On the eighth or 28th day after MCAO, we evaluated infarct volume, neurogenesis, and angiogenesis histologically. Neurological outcome was serially evaluated by the rotarod test after MCAO.

Results—

There was no significant difference in infarct volume between the 2 groups. Treatment with Ad-HB-EGF significantly increased the number of BrdU-positive cells in the subventricular zone on the 8th day. In addition, on the 28th day, BrdU-positive cells differentiated into mature neurons in the striatum on the ischemic side but seldom the cells given Ad-LacZ. Enhancement of angiogenesis at the peri-infarct striatum was also observed on the eighth day in Ad-HB-EGF–treated rats. Treatment with Ad-HB-EGF significantly enhanced functional recovery after MCAO.

Conclusions—

Our data suggest that gene therapy using Ad-HB-EGF contributes to functional recovery after ischemic stroke by promoting neurogenesis and angiogenesis.
Identification of Embolic Stroke Patterns by Diffusion-Weighted MRI in Clinically Defined Lacunar Stroke Syndromes
Authors: Wessels Tiemo , Röttger Carina , Jauss Marek , Kaps Manfred , Traupe Horst , Stolz Erwin
Published: March 2005

Background—

A number of clinical syndromes describing the presentation of deep brain infarcts are called lacunar syndromes resulting from small vessel occlusion (SVO). To verify the reliability of the clinical diagnosis “lacunar syndrome,” the value was investigated with diffusion-weighted MRI (DWI).

Methods and Results—

A total of 73 patients (mean age 66 years; range 35 to 83 years) with sudden onset of a classical lacunar syndrome were enrolled. On the basis of the DWI findings, patients were divided into 3 groups: group 1, single subcortical lesion (<15-mm lesion; 43 patients; 59%); group 2, large (≥15 mm) or scattered lesions in 1 vascular territory (16 patients; 22%); and group 3, multiple lesions in multiple vascular territories (14 patients; 19%). A stroke mechanism other than SVO could be identified in 17 (23%) patients. Cardiac work-up revealed a cardiac embolic source in 8 patients (11%). Duplex sonography revealed symptomatic stenosis in 9 patients (12%). Based on the work-up information, 29 patients (40%) were found to have a potential cause of stroke other than SVO. A significant correlation with >1 single lesion on DWI-MRI and a clinical proven embolic source was observed (
P
=0.002). In 9 patients with MRI suspicious for a pathomechanism other than SVO, no embolic source was found.

Conclusions—

The use of DWI-MRI improves the accuracy of the subtype diagnosis of stroke. Inaccuracy has to be expected in approximately one third if lacunar diagnosis is based on clinical and computed tomography findings. Most of these “false-positive” cases are attributable to large artery or cardiogenic embolic stroke.