bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Chemoreceptor Modification on Assembly and Activity of the Receptor-Kinase Complex in
Escherichia coli
Authors: Liberman Louisa , Berg Howard C. , Sourjik Victor 
Published: September 2004

ABSTRACT
Bacterial chemoreceptors are embedded in the inner cell membrane in tight clusters. We show that changes in receptor methylation that generate large changes in kinase activity have relatively little effect on cluster morphology. Thus, changes in receptor activity do not appear to be mediated by changes in receptor-kinase assembly.
DNA Binding Activity of theEscherichia coliNitric Oxide Sensor NorR Suggests a Conserved Target Sequence in Diverse Proteobacteria
Authors: Tucker Nicholas P. , D'Autréaux Benoît , Studholme David J. , Spiro Stephen , Dixon Ray 
Published: September 2004

ABSTRACTTheEscherichia colinitric oxide sensor NorR was shown to bind to the promoter region of thenorVWtranscription unit, forming at least two distinct complexes detectable by gel retardation. Three binding sites for NorR and two integration host factor binding sites were identified in thenorR-norVintergenic region. The derived consensus sequence for NorR binding sites was used to search for novel members of theE. coliNorR regulon and to show that NorR binding sites are partially conserved in other members of the proteobacteria.
Channel-Forming (Porin) Activity in
Herpetosiphon aurantiacus
Hp a2
Authors: Harwardt Rainer , Maier Elke , Reichenbach Hans , Weckesser Jürgen , Benz Roland 
Published: September 2004

ABSTRACT

Detergent extracts of cell envelopes of the gliding bacterium
Herpetosiphon aurantiacus
formed channels in lipid bilayers. Fast protein liquid chromatography across a HiTrap-Q cation-exchange column demonstrated that a 45-kDa protein forms the channel. The observation of a channel-forming protein suggests that
Herpetosiphon aurantiacus
Hp a2 has a permeability barrier on its surface.
Supervisory behaviour as a predictor of return to work in employees absent from work due to mental health problems
Authors: Nieuwenhuijsen K , Verbeek J H A M , de Boer A G E M , Blonk R W B , van Dijk F J H 
Published: September 2004

Aims:To study supervisory behaviour as a predictive factor for return to work of employees absent due to mental health problems; and to explore the association between conditional factors and supervisory behaviour.Methods:Eighty five supervisors of employees were interviewed by telephone. Questionnaires providing information on person related factors, depressive symptoms, and sickness absence were sent to the employees at baseline, three months, six months, and after one year. Three aspects of supervisory behaviour during the period of absence were measured: communication with the employee, promoting gradual return to work, and consulting of other professionals.Results:Better communication between supervisor and employee was associated with time to full return to work in non-depressed employees. For employees with a high level of depressive symptoms, this association could not be established. Consulting other professionals more often was associated with a longer duration of the sickness absence for both full and partial return to work. If sickness absence had financial consequences for the department, the supervisor was more likely to communicate frequently with the employee. Supervisors who were responsible for return to work in their organisation were more likely to communicate better and to consult more often with other professionals.Conclusion:Supervisors should communicate more frequently with employees during sickness absence as well as hold follow up meetings more often as this is associated with a faster return to work in those employees.
Distribution of sickness absence in the European Union countries: Table 1
Authors: Gimeno D , Benavides F G , Benach J , Amick B C 
Published: September 2004

Aims:To determine the sickness absence frequency in European Union (EU) countries.Methods:Sickness absence was measured by questionnaire using the Third European Survey on Working Conditions. Employees were considered to have sickness absence if they reported to be absent at least one day in the past 12 months because of an accident at work, work related problems, or by other health problems.Results:Sickness absence percentages were lower in Southern European countries compared with Central and Northern European countries, and, in general, slightly higher in men than in women.Conclusion:This is the first description of sickness absence in each of the 15 EU countries. Examination of the sickness absence patterning between EU countries could indicate countries where important lessons to reduce sickness absence are to be learned and diffused across the EU.
Silicosis prevalence and exposure-response relations in South African goldminers
Authors: Churchyard G J , Ehrlich R , teWaterNaude J M , Pemba L , Dekker K , Vermeijs M , White N , Myers J 
Published: September 2004

Aims:To measure the prevalence of silicosis among black migrant contract workers on a South African goldmine and to investigate exposure-response relations with silica dust.Methods:In a cross sectional study, 520 black goldminers (aged >37 years) were interviewed and had chest radiographs taken. Silicosis was defined as International Labour Organisation Classification radiological profusion of 1/1 or greater.Results:Mean length of service was 21.8 years (range 6.3–34.5). The mean intensity of respirable dust exposure was 0.37 mg/m3(range 0–0.70) and of quartz 0.053 mg/m3(range 0–0.095). The prevalence of silicosis was 18.3–19.9% depending on reader. Significant trends were found between the prevalence of silicosis and length of service, mean intensity of exposure, and cumulative exposure.Conclusion:Results confirm a large burden of silicosis among older black workers in the South African goldmining industry, which is likely to worsen as such miners spend longer periods in continuous employment in dusty jobs. An urgent need for improved dust control in the industry is indicated. If the assumption of stability of average dust concentrations on this mine over the working life of this group of workers is correct, these workers developed silicosis while exposed to a quartz concentration below the recommended occupational exposure limit (OEL) of 0.1 mg/m3. This accords with a mounting body of evidence that an OEL of 0.1 mg/m3is not protective against silicosis.
Cross-shift changes in FEV1in relation to wood dust exposure: the implications of different exposure assessment methods
Authors: Schlünssen V , Sigsgaard T , Schaumburg I , Kromhout H 
Published: September 2004

Background:Exposure-response analyses in occupational studies rely on the ability to distinguish workers with regard to exposures of interest.Aims:To evaluate different estimates of current average exposure in an exposure-response analysis on dust exposure and cross-shift decline in FEV1among woodworkers.Methods:Personal dust samples (n = 2181) as well as data on lung function parameters were available for 1560 woodworkers from 54 furniture industries. The exposure to wood dust for each worker was calculated in eight different ways using individual measurements, group based exposure estimates, a weighted estimate of individual and group based exposure estimates, and predicted values from mixed models. Exposure-response relations on cross-shift changes in FEV1and exposure estimates were explored.Results:A positive exposure-response relation between average dust exposure and cross-shift FEV1was shown for non-smokers only and appeared to be most pronounced among pine workers. In general, the highest slope and standard error (SE) was revealed for grouping by a combination of task and factory size, the lowest slope and SE was revealed for estimates based on individual measurements, with the weighted estimate and the predicted values in between. Grouping by quintiles of average exposure for task and factory combinations revealed low slopes and high SE, despite a high contrast.Conclusion:For non-smokers, average dust exposure and cross-shift FEV1were associated in an exposure dependent manner, especially among pine workers. This study confirms the consequences of using different exposure assessment strategies studying exposure-response relations. It is possible to optimise exposure assessment combining information from individual and group based exposure estimates, for instance by applying predicted values from mixed effects models.
Psychological, musculoskeletal, and respiratory problems and sickness absence before and after involvement in a disaster: a longitudinal study among rescue workers: Table 1
Authors: Dirkzwager A J E , Yzermans C J , Kessels F J M 
Published: September 2004

Background:On 13 May 2000 a firework depot situated in a residential area in the Netherlands exploded. Many rescue workers were involved in the aftermath of this explosion.Aims:To examine the longitudinal course of psychological, musculoskeletal, and respiratory problems and sickness absence among rescue workers involved.Methods:The study population was composed of 1036 rescue workers. Data on health and sickness absence both before and after the disaster were collected from the electronic database of the rescue workers’ occupational physicians. Health problems were coded according to an adapted version of the ICD-10.Results:After the disaster a long term increase was found in psychological, musculoskeletal, and respiratory problems. Compared to six months before the disaster, the average length of sickness absence in the first half year after the disaster increased from 6.6 to 11.6 days, and decreased slowly in the following six month periods.Conclusions:Rescue workers involved in a disaster may experience subsequent impairment in occupational functioning.
Smoothing in occupational cohort studies: an illustration based on penalised splines
Authors: Eisen E A , Agalliu I , Thurston S W , Coull B A , Checkoway H 
Published: September 2004

Aims:To illustrate the contribution of smoothing methods to modelling exposure-response data, Cox models with penalised splines were used to reanalyse lung cancer risk in a cohort of workers exposed to silica in California’s diatomaceous earth industry. To encourage application of this approach, computer code is provided.Methods:Relying on graphic plots of hazard ratios as smooth functions of exposure, the sensitivity of the curve to amount of smoothing, length of the exposure lag, and the influence of the highest exposures was evaluated. Trimming and data transformations were used to down-weight influential observations.Results:The estimated hazard ratio increased steeply with cumulative silica exposure before flattening and then declining over the sparser regions of exposure. The curve was sensitive to changes in degrees of freedom, but insensitive to the number or location of knots. As the length of lag increased, so did the maximum hazard ratio, but the shape was similar. Deleting the two highest exposed subjects eliminated the top half of the range and allowed the hazard ratio to continue to rise. The shape of the splines suggested a parametric model with log hazard as a linear function of log transformed exposure would fit well.Conclusions:This flexible statistical approach reduces the dependence on a priori assumptions, while pointing to a suitable parametric model if one exists. In the absence of an appropriate parametric form, however, splines can provide exposure-response information useful for aetiological research and public health intervention.
Validation of specific inhalation challenge for the diagnosis of occupational asthma due to persulphate salts
Authors: Muñoz X , Cruz M J , Orriols R , Torres F , Espuga M , Morell F 
Published: September 2004

Background:The significant value of tests used to certify the diagnosis of occupational asthma due to persulphate salts remains uncertain.Aims:To validate the specific inhalation challenge (SIC) test for the diagnosis of occupational asthma.Methods:Eight patients with occupational asthma due to persulphate salts, eight patients with bronchial asthma who were never exposed to persulphate salts, and ten healthy subjects were studied. Clinical history taking, spirometry, bronchial challenge with methacholine, skin prick testing to common inhalant allergens and persulphate salts, total IgE levels, and SIC to potassium persulphate were carried out in all subjects. The SIC used increasing concentrations of potassium persulphate (5, 10, 15, and 30 g) mixed with 150 g of lactose. Patients tipped the mixture from one tray to another at a distance of 30 cm from the face for 10 minutes in a challenge booth.Results:The SIC was positive in all subjects with persulphate induced asthma and in one patient with bronchial asthma who had never been exposed to persulphate salts. Sensitivity was 100% (95% CI 67.6 to 100) and specificity was 87.5% (95% CI 52.9–97.8) when patients with occupational asthma due to persulphate salts were compared with those with bronchial asthma never exposed to persulphate salts.Conclusions:SIC to persulphate salts performed according to the protocol described appears to be useful for the diagnosis of occupational asthma secondary to inhalation of this substance.
POTENTIALS AND RISKS OF BENCHMARKING
Authors: DE BRUIJN HANS , VAN WENDEL DE JOODE RUBEN , VAN DER VOORT HAIKO 
Published: September 2004

This article aims to explore some potentials and risks of benchmarking in environmental assessment. The dominant image derived from theory and empirical data is that benchmark tests tend to be based on quantitative measures, which, under certain conditions, produces perverse effects and bureaucracy.The answer to the central question — Can benchmarks be useful in environmental assessment? — is affirmative. The problem, however, is that due to an inherent characteristic of environmental issues, using quantitative measures will create perverse effects and bureaucracy thus reducing their effectiveness. This article proposes the formulation of rules of the game to increase the effectiveness of benchmarking. These rules are mutual agreements that regulate for instance who are allowed to use and interpret the figures.
A novel therapeutic approach for thrombocytopenia by minibody agonist of the thrombopoietin receptor
Authors: Orita Tetsuro , Tsunoda Hiroyuki , Yabuta Naohiro , Nakano Kiyotaka , Yoshino Takeshi , Hirata Yuichi , Ohtomo Toshihiko , Nezu Jun-ichi , Sakumoto Hirofumi , Ono Kouichiro , Saito Mikiyoshi , Kumagai Eiji , Nanami Masahiko , Kaneko Akihisa , Yoshikubo Takashi , Tsuchiya Masayuki 
Published: September 2004

AbstractAntibodies have brought valuable therapeutics in the clinical treatment of various diseases without serious adverse effects through their intrinsic features such as specific binding to the target antigen with high affinity, clinical safety as serum proteins, and long half-life. Agonist antibodies, furthermore, could be expected to maximize the value of therapeutic antibodies. Indeed, several IgG/IgM antibodies have been reported to induce cellular growth/differentiation and apoptosis. These agonist antibodies, however, should be further improved to exert more potent biologic activities and appropriate serum half-life depending upon the disease indications. Here, we report that IgG antibodies against the thrombopoietin receptor (Mpl), which have an absence or very weak agonist activity, can be engineered to be agonist minibodies, which include diabody or sc(Fv)2 as potent as natural ligand. Through this technological development, minibodies have been successfully constructed to bind and activate 2 types of dysfunctional mutant Mpls that cause congenital amegakaryocytic thrombocytopenia (CAMT). This drastic conversion of biologic activities by designing minibodies can be widely applicable to generate agonist minibodies for clinical application, which will constitute a new paradigm in antibody-based therapeutics.
Extracellular phosphorylation converts pigment epithelium–derived factor from a neurotrophic to an antiangiogenic factor
Authors: Maik-Rachline Galia , Shaltiel Shmuel , Seger Rony 
Published: September 2004

AbstractThe pigment epithelium–derived factor (PEDF) belongs to the superfamily of serine protease inhibitors (serpin). There have been 2 distinct functions attributed to this factor, which can act either as a neurotrophic or as an antiangiogenic factor. Besides its localization in the eye, PEDF was recently reported to be present also in human plasma. We found that PEDF purified from plasma is a phosphoprotein, which is extracellularly phosphorylated by protein kinase CK2 (CK2) and to a lesser degree, intracellularly, by protein kinase A (PKA). CK2 phosphorylates PEDF on 2 main residues, Ser24 and Ser114, and PKA phosphorylates PEDF on one residue only, Ser227. The physiologic relevance of these phosphorylations was determined using phosphorylation site mutants. We found that both CK2 and PKA phosphorylations of PEDF markedly affect its physiologic function. The fully CK2 phosphorylation site mutant S24, 114E abolished PEDF neurotrophic activity but enhanced its antiangiogenic activity, while the PKA phosphorylation site mutant S227E reduced PEDF antiangiogenic activity. This is a novel role of extracellular phosphorylation that is shown here to completely change the nature of PEDF from a neutrophic to an antiangiogenic factor.
Donor-derived IL-15 is critical for acute allogeneic graft-versus-host disease
Authors: Blaser Bradley W. , Roychowdhury Sameek , Kim Daniel J. , Schwind Noah R. , Bhatt Darshna , Yuan Weifeng , Kusewitt Donna F. , Ferketich Amy K. , Caligiuri Michael A. , Guimond Martin 
Published: September 2004

AbstractInterleukin-15 (IL-15) is a pleiotropic proinflammatory cytokine with inefficient posttranscriptional processing. We hypothesized that endogenous IL-15 could affect disease progression in the well-described C57Bl/6 (B6) → (C57Bl/6 × DBA/2) F1 hybrid (B6D2F1) murine model of acute allogeneic graft-versus-host disease (GVHD). B6D2F1 allogeneic recipients received transplants of IL-15-/- B6 bone marrow cells or B6 bone marrow cells expressing a murine IL-15 transgene (IL-15 tg) modified for efficient translation and secretion. Mice that received transplants of IL-15-/- B6 bone marrow cells displayed a significantly longer median survival time (MST) compared with mice that received transplants of wild-type (wt) B6 bone marrow; in contrast, mice that received transplants of IL-15 tg B6 bone marrow cells had a dramatically decreased MST. This decrease in survival was associated with a substantial activation and expansion of effector-memory (CD44highCD62Llow) CD8+ T lymphocytes. Finally, in vivo depletion of either CD4+ or CD8+ T lymphocyte subsets significantly prolonged survival in mice receiving IL-15 tg B6 marrow, while depletion of both CD4+ and CD8+ T cells provided complete protection from acute GVHD. We thus show that acute GVHD is attenuated in the absence of donor bone marrow–derived IL-15 and conclude that donor-derived IL-15 is a critical mediator of T-cell function in acute GVHD.
Regulation of vascular endothelial barrier function by Epac, a cAMP-activated exchange factor for Rap GTPase
Authors: Cullere Xavier , Shaw Sunil K. , Andersson Lorna , Hirahashi Junichi , Luscinskas Francis W. , Mayadas Tanya N. 
Published: September 2004

Abstract
Endothelial cell-cell junctional proteins and cortical actin are of central importance for regulating vascular permeability. Rap1, a member of the Ras family of GTPases, is enriched at endothelial cell-cell contacts and activated by cyclic AMP (cAMP) through a PKA-independent pathway. Activation of a cAMP-inducible guanine-exchange factor for Rap, Epac, results in markedly enhanced basal endothelial barrier function by increasing cortical actin and subsequent redistribution of adherens and tight junctional molecules to cell-cell contacts. Activation of Epac also counteracts thrombin-induced hyperpermeability through down-regulation of Rho GTPase activation, suggesting cross-talk between Rap and Rho GT-Pases. Thus, Epac/Rap activation represents a new pathway for regulating endothelial cell barrier function.
Cord blood CD4+CD25+-derived T regulatory cell lines express FoxP3 protein and manifest potent suppressor function
Authors: Godfrey Wayne R. , Spoden Darrin J. , Ge Ying G. , Baker Seth R. , Liu Baoling , Levine Bruce L. , June Carl H. , Blazar Bruce R. , Porter Stephen B. 
Published: September 2004

AbstractCD4+CD25+ T regulatory (Treg) cells have been shown to critically regulate self and allograft tolerance in mice. Studies of human Treg cells have been hindered by low numbers present in peripheral blood and difficult purification. We found that cord blood was a superior source for Treg-cell isolation and cell line generation compared with adult blood. Cord blood CD4+CD25+ cells were readily purified and generated cell lines that consistently exhibited potent suppressor activity, with more than 95% suppression of allogeneic mixed lymphocyte reactions (MLRs) (29 of 30 donors). Cultured Treg cells blocked cytokine accumulation in MLRs, with a less robust inhibition of chemokine production. These cell lines uniformly expressed CD25, CD62L, CCR7, CD27, and intracellular cytotoxic T-lymphocyte antigen-4 (CTLA4). FoxP3 protein, but not mRNA, was specifically expressed. Upon restimulation with anti-CD3/CD28 beads, the cultured Treg cells produced minimal cytokines (interleukin-2 [IL-2], interferon-γ [IFN-γ], and IL-10) and preferentially expressed tumor growth factor-β (TGF-β) latency associated protein. Cytokine production, however, was restored to normal levels by restimulation with phorbol myristate acetate (PMA)/ionomycin. Cord blood–derived cultured suppressor cell function was predominantly independent of IL-10 and TGF-β. These results demonstrate cord blood contains a significant number of Treg precursor cells capable of potent suppressor function after culture activation. Banked cord blood specimens may serve as a readily available source of Treg cells for immunotherapy.
FLT3 inhibition selectively kills childhood acute lymphoblastic leukemia cells with high levels of FLT3 expression
Authors: Brown Patrick , Levis Mark , Shurtleff Sheila , Campana Dario , Downing James , Small Donald 
Published: September 2004

AbstractFMS-like tyrosine kinase 3 (FLT3) is almost universally expressed in B-precursor childhood acute lymphoblastic leukemia (ALL). Cases of ALL with MLL gene rearrangements and those with high hyperdiploidy (&gt; 50 chromosomes) express the highest levels of FLT3, and activating mutations of FLT3 occur in 18% of MLL-rearranged and 28% of hyperdiploid ALL cases. We determined the antileukemic activity of CEP-701, a potent and selective FLT3 inhibitor, in 8 ALL cell lines and 39 bone marrow samples obtained at diagnosis from infants and children with various subtypes of ALL. CEP-701 induced pronounced apoptotic responses in a higher percentage of samples that expressed high levels of FLT3 (74%, n = 23) compared with samples with low levels of expression (8%, n = 13; P = .0003). Sensitivity to FLT3 inhibition was particularly high in samples with MLL gene rearrangements (82%, n = 11; P = .0005), high hyperdiploidy (100%, n = 5; P = .0007), and/or FLT3 mutations (100%, n = 4; P = .0021). Seven of 7 sensitive samples examined by immunoblotting demonstrated constitutively phosphorylated FLT3 that was potently inhibited by CEP-701, whereas 0 of 6 resistant samples expressed constitutively phosphorylated FLT3. We conclude that the FLT3 inhibitor CEP-701 effectively suppresses FLT3-driven leukemic cell survival. Clinical testing of CEP-701 as a novel molecularly targeted agent for the treatment of childhood ALL is warranted.