bluuebunny/crossref_metadata_2025 huggingface dataset:
Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals
Authors: Yoder Mervin C. , Mead Laura E. , Prater Daniel , Krier Theresa R. , Mroueh Karim N. , Li Fang , Krasich Rachel , Temm Constance J. , Prchal Josef T. , Ingram David A.
Published: October 2006

The limited vessel-forming capacity of infused endothelial progenitor cells (EPCs) into patients with cardiovascular dysfunction may be related to a misunderstanding of the biologic potential of the cells. EPCs are generally identified by cell surface antigen expression or counting in a commercially available kit that identifies “endothelial cell colony-forming units” (CFU-ECs). However, the origin, proliferative potential, and differentiation capacity of CFU-ECs is controversial. In contrast, other EPCs with blood vessel-forming ability, termed endothelial colony-forming cells (ECFCs), have been isolated from human peripheral blood. We compared the function of CFU-ECs and ECFCs and determined that CFU-ECs are derived from the hematopoietic system using progenitor assays, and analysis of donor cells from polycythemia vera patients harboring a Janus kinase 2 V617F mutation in hematopoietic stem cell clones. Further, CFU-ECs possess myeloid progenitor cell activity, differentiate into phagocytic macrophages, and fail to form perfused vessels in vivo. In contrast, ECFCs are clonally distinct from CFU-ECs, display robust proliferative potential, and form perfused vessels in vivo. Thus, these studies establish that CFU-ECs are not EPCs and the role of these cells in angiogenesis must be re-examined prior to further clinical trials, whereas ECFCs may serve as a potential therapy for vascular regeneration.
Ape1 regulates hematopoietic differentiation of embryonic stem cells through its redox functional domain
Authors: Zou Gang-Ming , Luo Mei-Hua , Reed April , Kelley Mark R. , Yoder Mervin C.
Published: October 2006

Ape1 is a molecule with dual functions in DNA repair and redox regulation of transcription factors. In Ape1-deficient mice, embryos do not survive beyond embryonic day 9, indicating that this molecule is required for normal embryo development. Currently, direct evidence of the role of Ape1 in regulating hematopoiesis is lacking. We used the embryonic stem (ES) cell differentiation system and an siRNA approach to knockdown Ape1 gene expression to test the role of Ape1 in hematopoiesis. Hemangioblast development from ES cells was reduced 2- to 3-fold when Ape1 gene expression was knocked down by Ape1-specific siRNA, as was primitive and definitive hematopoiesis. Impaired hematopoiesis was not associated with increased apoptosis in siRNA-treated cells. To begin to explore the mechanism whereby Ape1 regulates hematopoiesis, we found that inhibition of the redox activity of Ape1 with E3330, a specific Ape1 redox inhibitor, but not Ape1 DNA repair activity, which was blocked using the small molecule methoxyamine, affected cytokine-mediated hemangioblast development in vitro. In summary, these data indicate Ape1 is required in normal embryonic hematopoiesis and that the redox function, but not the repair endonuclease activity, of Ape1 is critical in normal embryonic hematopoietic development.
The shape of human gene family phylogenies
Authors: Cotton James A , Page Roderic DM
Published: October 2006

Background

The shape of phylogenetic trees has been used to make inferences about the evolutionary process by comparing the shapes of actual phylogenies with those expected under simple models of the speciation process. Previous studies have focused on speciation events, but gene duplication is another lineage splitting event, analogous to speciation, and gene loss or deletion is analogous to extinction. Measures of the shape of gene family phylogenies can thus be used to investigate the processes of gene duplication and loss. We make the first systematic attempt to use tree shape to study gene duplication using human gene phylogenies.

Results

We find that gene duplication has produced gene family trees significantly less balanced than expected from a simple model of the process, and less balanced than species phylogenies: the opposite to what might be expected under the 2R hypothesis.

Conclusion

While other explanations are plausible, we suggest that the greater imbalance of gene family trees than species trees is due to the prevalence of tandem duplications over regional duplications during the evolution of the human genome.
Reduction in psychotic symptoms as a predictor of patient satisfaction with antipsychotic medication in schizophrenia: Data from a randomized double-blind trial
Authors: Gharabawi Georges M , Greenspan Andrew , Rupnow Marcia FT , Kosik-Gonzalez Colette , Bossie Cynthia A , Zhu Young , Kalali Amir H , Awad A George
Published: October 2006

Background

Patient satisfaction with antipsychotic treatment is important. Limited evidence suggests that satisfaction is associated with symptom improvement and compliance. Predictors of patient satisfaction with antipsychotic medication were examined in a study of patients with a recent exacerbation of schizophrenia.

Methods

Data are from a randomized, double-blind trial comparing risperidone (n = 152), quetiapine (n = 156), and placebo (n = 73). Medication Satisfaction Questionnaire (MSQ) was completed after 14 days of treatment and after 6 weeks at last study visit.

Results

Medication satisfaction at both time points was significantly associated in multiple regression analysis with improvement on 3 Positive and Negative Syndrome Scale (PANSS) factor scores (positive symptoms p < .01; uncontrolled hostility/excitement, p < .0005; anxiety/depression, p < .04) and treatment with risperidone (p < .03); at day 14, significant association was also found with older age (p = .01). At both time points, predictor variables explained over 30% of the variance in medication satisfaction. Change in Hamilton Depression Scale, prolactin levels, sex, and reported adverse events of extrapyramidal symptoms, sedation, and movement disorders were not significant predictors of satisfaction. Lower level of medication satisfaction at day 14 was associated with earlier discontinuation in the trial at week 6 end point. A focused principal components analysis of PANSS factors and MSQ suggested that medication satisfaction relates to 3 groups of factors in descending order of magnitude: lower levels of (a) uncontrolled hostility/excitement, (b) positive symptoms, and (c) negative symptoms, disorganized thoughts, and anxiety/depression.

Conclusion

Results give further support that treatment satisfaction is positively associated with symptom improvement, particularly psychotic symptoms, and suggest that satisfaction may also be related to compliance, as those who were more satisfied remained in the trial for a longer period of time.

Trial registration number

Trial registration number NCT00061802
Transcriptional response to alcohol exposure in Drosophila melanogaster
Authors: Morozova Tatiana V , Anholt Robert RH , Mackay Trudy FC
Published: October 2006

Background

Alcoholism presents widespread social and human health problems. Alcohol sensitivity, the development of tolerance to alcohol and susceptibility to addiction vary in the population. Genetic factors that predispose to alcoholism remain largely unknown due to extensive genetic and environmental variation in human populations. Drosophila, however, allows studies on genetically identical individuals in controlled environments. Although addiction to alcohol has not been demonstrated in Drosophila, flies show responses to alcohol exposure that resemble human intoxication, including hyperactivity, loss of postural control, sedation, and exposure-dependent development of tolerance.

Results

We assessed whole-genome transcriptional responses following alcohol exposure and demonstrate immediate down-regulation of genes affecting olfaction, rapid upregulation of biotransformation enzymes and, concomitant with development of tolerance, altered transcription of transcriptional regulators, proteases and metabolic enzymes, including biotransformation enzymes and enzymes associated with fatty acid biosynthesis. Functional tests of P-element disrupted alleles corresponding to genes with altered transcription implicated 75% of these in the response to alcohol, two-thirds of which have human orthologues.

Conclusion

Expression microarray analysis is an efficient method for identifying candidate genes affecting complex behavioral and physiological traits, including alcohol abuse. Drosophila provides a valuable genetic model for comparative genomic analysis, which can inform subsequent studies in human populations. Transcriptional analyses following alcohol exposure in Drosophila implicate biotransformation pathways, transcriptional regulators, proteolysis and enzymes that act as metabolic switches in the regulation of fatty acid metabolism as important targets for future studies of the physiological consequences of human alcohol abuse.
CD16+ monocytes produce IL-6, CCL2, and matrix metalloproteinase-9 upon interaction with CX3CL1-expressing endothelial cells
Authors: Ancuta Petronela , Wang Jianbin , Gabuzda Dana
Published: October 2006

The CD16+ subset of peripheral blood monocytes (Mo) is expanded dramatically during inflammatory conditions including sepsis, HIV-1 infection, and cancer. CD16+ express high levels of CX3CR1, which mediates arrest onto CX3CL1-expressing endothelial cells (EC) under flow conditions. In contrast, attachment of CD16− Mo onto cytokine-activated EC is independent of CX3CL1. Here, we investigate the ability of CD16+ and CD16− Mo to produce proinflammatory cytokines upon interaction with CX3CL1-expressing HUVEC. We demonstrate that CD16+ but not CD16− Mo produce high levels of IL-6, CCL2, and matrix metalloproteinase (MMP)-9 when cocultured with TNF/IFN-γ-activated HUVEC or nonactivated HUVEC expressing CX3CL1. Furthermore, supernatants from Mo cocultured with cytokine-activated HUVEC induce neuronal death in vitro. These results suggest that membrane-bound CX3CL1 stimulates production of IL-6, CCL2, and MMP-9 by CD16+ Mo, likely via engagement of CX3CR1. Thus, expansion of CD16+ Mo and their accumulation onto CX3CL1-expressing EC may result in recruitment of Mo and T cell subsets at sites of inflammation in response to CCL2, IL-6-induced cell activation and/or differentiation, and MMP-9-mediated vascular and tissue injury.
Intervention of MAdCAM-1 or fractalkine alleviates graft-versus-host reaction associated intestinal injury while preserving graft-versus-tumor effects
Authors: Ueha Satoshi , Murai Masako , Yoneyama Hiroyuki , Kitabatake Masahiro , Imai Toshio , Shimaoka Takeshi , Yonehara Shin , Ishikawa Sho , Matsushima Kouji
Published: October 2006

Coincidence of the beneficial graft-vs.-tumor (GVT) effects and the detrimental graft-vs.-host disease (GVHD) remains the major obstacle against the widespread use of allogeneic bone marrow transplantation (BMT) as tumor immunotherapy. We here demonstrate that intervention of MAdCAM-1 (mucosal vascular addressin cell adhesion molecule-1) or fractalkine/CX3CL1 after the expansion of allo-reactive donor CD8 T cells selectively inhibits the recruitment of effector donor CD8 T cells to the intestine and alleviates the graft-vs.-host reaction (GVHR) associated intestinal injury without impairing GVT effects. In a nonirradiated acute GVHD model, donor CD8 T cells up-regulate the expression of intestinal homing receptor α4β7 and chemokine receptors CXCR6 and CX3CR1, as they differentiate into effector cells and subsequently infiltrate into the intestine. Administration of anti-MAdCAM-1 antibody or anti-fractalkine antibody, even after the expansion of alloreactive donor CD8 T cells, selectively reduced the intestine-infiltrating donor CD8 T cells and the intestinal crypt cell apoptosis without affecting the induction of donor derived anti-host CTL or the infiltration of donor CD8 T cells in the hepatic tumor. Moreover, in a clinically relevant GVHD model with myeloablative conditioning, these antibodies significantly improved the survival and loss of weight without impairing the beneficial GVT effects. Thus, interruption of α4β7-MAdCAM-1 or CX3CR1-fractalkine interactions in the late phase of GVHD would be a novel therapeutic approach for the separation of GVT effects from GVHR-associated intestinal injury.
Mechanisms underlying TGF-β1-induced expression of VEGF and Flk-1 in mouse macrophages and their implications for angiogenesis
Authors: Jeon Seong-Hyun , Chae Byung-Chul , Kim Hyun-A , Seo Goo-Young , Seo Dong-Wan , Chun Gie-Taek , Kim Nam-Soo , Yie Se-Won , Byeon Woo-Hyeon , Eom Seok-Hyun , Ha Kwon-Soo , Kim Young-Myeong , Kim Pyeung-Hyeun
Published: October 2006

TGF-β induces vascular endothelial growth factor (VEGF), a potent angiogenic factor, at the transcriptional and protein levels in mouse macrophages. VEGF secretion in response to TGF-β1 is enhanced by hypoxia and by overexpression of Smad3/4 and hypoxia-inducible factor-1α/β (HIF-1α/β). To examine the transcriptional regulation of VEGF by TGF-β1, we constructed mouse reporters driven by the VEGF promoter. Overexpression of HIF-1α/β or Smad3/4 caused a slight increase of VEGF promoter activity in the presence of TGF-β1, whereas cotransfection of HIF-1α/β and Smad3/4 had a marked effect. Smad2 was without effect on this promoter activity, whereas Smad7 markedly reduced it. Analysis of mutant promoters revealed that the one putative HIF-1 and two Smad-binding elements were critical for TGF-β1-induced VEGF promoter activity. The relevance of these elements was confirmed by chromatin immunoprecipitation assay. p300, which has histone acetyltransferase activity, augmented transcriptional activity in response to HIF-1α/β and Smad3/4, and E1A, an inhibitor of p300, inhibited it. TGF-β1 also increased the expression of fetal liver kinase-1 (Flk-1), a major VEGF receptor, and TGF-β1 and VEGF stimulated pro-matrix metalloproteinase 9 (MMP-9) and active-MMP-9 expression, respectively. The results from the present study indicate that TGF-β1 can activate mouse macrophages to express angiogenic mediators such as VEGF, MMP-9, and Flk-1.
Endothelium-Derived Steroidogenic Factor Enhances Angiotensin II-Stimulated Aldosterone Release by Bovine Zona Glomerulosa Cells
Authors: Hanke Craig J. , Holmes Blythe B. , Xu Yafei , Nithipatikom Kasem , Campbell William B.
Published: October 2006

Endothelium-derived steroidogenic factor (EDSF) is an endothelial peptide that stimulates aldosterone release from bovine adrenal zona glomerulosa (ZG) cells. The regulation of aldosterone release by combinations of EDSF and angiotensin II (AII) or EDSF and ACTH was investigated. Endothelial cells (ECs) and EC-conditioned media (ECCM) increased aldosterone release from ZG cells, an activity attributed to EDSF. AII (10−12 to 10−8m) and ACTH (10−12 to 10−9m) also stimulated the release of aldosterone from ZG cells. The stimulation by AII, but not ACTH, was greatly enhanced when ZG cells were coincubated with ECs. AII was metabolized by ECs to peptides identified by mass spectrometry as angiotensin (1-7) and angiotensin IV. There was very little metabolism of AII by ZG cells. Neither of these two AII metabolites altered aldosterone release from ZG cells, so they could not account for the enhanced response with ECs. AII-induced aldosterone release from ZG cells was enhanced by ECCM but not cell-free conditioned medium. This enhanced response was not due to increased EDSF release from ECs by AII. The synergistic effect of EDSF and AII was apparent when AII was added during or after the generation of ECCM and not observed when the AII component of the enhancement was blocked by the AII antagonist, losartan. These studies indicate that EDSF enhances the steroidogenic effect of AII. In the adrenal gland, ECs are in close anatomical relationship with ZG cells and may sensitize ZG cells to the steroidogenic action of AII by releasing EDSF.
Definition of the Molecular Basis for Estrogen Receptor-Related Receptor-α-Cofactor Interactions
Authors: Gaillard Stéphanie , Dwyer Mary A. , McDonnell Donald P.
Published: October 2006

Estrogen receptor-related receptor-α (ERRα) is an orphan nuclear receptor that does not appear to require a classical small molecule ligand to facilitate its interaction with coactivators and/or hormone response elements within target genes. Instead, the apo-receptor is capable of interacting in a constitutive manner with coactivators that stimulate transcription by acting as protein ligands. We have screened combinatorial phage libraries for peptides that selectively interact with ERRα to probe the architecture of the ERRα-coactivator pocket. In this manner, we have uncovered a fundamental difference in the mechanism by which this receptor interacts with peroxisome proliferator-activated receptor-γ coactivator-1α, as compared with members of the steroid receptor coactivator subfamily of coactivators. Our findings suggest that it may be possible to develop ERRα ligands that exhibit different pharmacological activities as a consequence of their ability to differentially regulate coactivator recruitment. In addition, these findings have implications beyond ERRα because they suggest that subtle alterations in the structure of the activation function-2 pocket within any nuclear receptor may enable differential recruitment of coactivators, an observation of notable pharmaceutical importance.
Diagnosis of α-1-Antitrypsin Deficiency: An Algorithm of Quantification, Genotyping, and Phenotyping
Authors: Snyder Melissa R , Katzmann Jerry A , Butz Malinda L , Yang Ping , Dawson D Brian , Halling Kevin C , Highsmith W Edward , Thibodeau Stephen N
Published: October 2006

Background: Laboratory testing in suspected α-1-antitrypsin (A1AT) deficiency involves analysis of A1AT concentrations and identification of specific alleles by genotyping or phenotyping. The purpose of this study was to define and evaluate a strategy that provides reliable laboratory evaluation of A1AT deficiency.

Methods: Samples from 512 individuals referred for A1AT phenotype analysis were analyzed by quantification, phenotype, and genotype. A1AT concentrations were measured by nephelometry. Phenotype analysis was performed by isoelectric focusing electrophoresis. The genotype assay detected the S and Z deficiency alleles by a melting curve analysis.

Results: Of the 512 samples analyzed, 2% of the phenotype and genotype results were discordant. Among these 10 discordant results, 7 were attributed to phenotyping errors. On the basis of these data we formulated an algorithm, according to which we analyzed samples by genotyping and quantification assays, with a reflex to phenotyping when the genotype and quantification results were not concordant. Retrospective analyses demonstrated that 4% of samples submitted for genotype and quantitative analysis were reflexed to phenotyping. Of the reflexed samples, phenotyping confirmed the genotype result in 85% of cases. In the remaining 15%, phenotyping provided further information, including identifying rare deficiency alleles and suggesting the presence of a null allele, and allowed for a more definitive interpretation of the genotype result.

Conclusions: The combination of genotyping and quantification, with a reflex to phenotyping, is the optimal strategy for the laboratory evaluation of A1AT deficiency.
Influence Tactics for Effective Adaptive Selling
Authors: McFarland Richard G. , Challagalla Goutam N. , Shervani Tasadduq A.
Published: October 2006

The adaptive selling literature identifies effective salespeople as those who match their influence tactics to suit the characteristics of buyers. However, prior research is largely silent on the specific influence tactics that salespeople use and the effectiveness of these tactics across different types of buyers. The authors propose a theoretical model that uses Kelman's (1961) underlying influence processes of internalization, compliance, and identification to identify the seller influence tactics that salespeople use and to assess which of these tactics will resonate with three types of buyers: task-oriented buyers, interaction-oriented buyers, and self-oriented buyers. The authors test their model with data from 193 bidirectionally matched buyer–seller dyads. The results strongly support the theoretical model and suggest that buyers are more complex than originally presumed. However, salespeople seem to recognize this complexity and use the combination of influence tactics prescribed by theory for persuading these types of buyers.
Brand Concept Maps: A Methodology for Identifying Brand Association Networks
Authors: John Deborah Roedder , Loken Barbara , Kim Kyeongheui , Monga Alokparna Basu
Published: October 2006

Understanding brand equity involves identifying the network of strong, favorable, and unique brand associations in memory. This article introduces a methodology, Brand Concept Maps, for eliciting brand association networks (maps) from consumers and aggregating individual maps into a consensus map of the brand. Consensus brand maps include the core brand associations that define the brand's image and show which brand associations are linked directly to the brand, which associations are linked indirectly to the brand, and which associations are grouped together. Two studies illustrate the Brand Concept Maps methodology and provide evidence of its reliability and validity.
A Three-Stage Model of Integrated Marketing Communications at the Marketing-Sales Interface
Authors: Smith Timothy M. , Gopalakrishna Srinath , Chatterjee Rabikar
Published: October 2006

The marketing and sales functions in many firms are often at odds despite their common goal of increasing revenue and profit. The finger pointing goes both ways: Marketing complains of poor lead follow-up by sales, and in turn, sales grumbles about the quality of leads generated by marketing. This disconnect can be damaging; high lead volumes generated through effective marketing campaigns could actually hurt downstream sales because of wasted effort on poorly qualified leads and/or delays in sales follow-up resulting from limited sales force capacity. To examine the revenue and profit implications of coordinated communications efforts at the marketing-sales interface, the authors develop a three-stage model that captures the effects of sequential marketing/sales communications on lead generation, appointment conversion, and sales closure. The results, which are based on a collaborative effort with a large home improvement retailer, suggest a complex interplay among marketing efforts (multiple media that generate leads), delays in follow-up (time lag between inquiry and sales force contact), and sales efficiencies (appointment and sales conversion). The findings underscore the impact of multimedia spending on the timing and effectiveness of subsequent communications, implying that improved internal collaboration between marketing and sales can offer significant upside potential for the firm. Finally, the authors develop a managerial decision support tool to simulate the impact of varying communications budgets, timing, and allocation on the marketing and sales planning system.
Optimal Pricing Strategies for an Automotive Aftermarket Retailer
Authors: Mantrala Murali K. , Seetharaman P.B. , Kaul Rajeeve , Gopalakrishna Srinath , Stam Antonie
Published: October 2006

The extant retail category pricing optimization literature concentrates on grocery retailing. In contrast, this article focuses on the problem of determining profit-improving store-level prices of failure-related “hard-part” product categories at a U.S. specialty automotive part retailer with 3400 stores. There are some key institutional differences between automotive hard-part and grocery retailing: No syndicated data are available for hard parts; each subclass of a hard-part category contains variants that are ordered by quality (typically “Good,” “Better,” “Best”); there is intra- but no intersubclass competition; market shares of variants and their prices are not positively correlated within a subclass; a consumer enters the market only infrequently; and at a purchase occasion, a consumer buys one and only one variant within a subclass and one and only one unit of that variant. Using two years of weekly sales histories from 800 stores, the authors develop store-level demand models for 23 subclasses of a hard part and employ these with available product cost data to set prices of variants of each subclass at each store that increase profit. The authors test the model-recommended prices for 10 subclasses in a field experiment involving 500 stores, leading to a projection of an annual increase of more than $610,000 in the retailer's profit from these 10 subclasses if the new prices are applied at all stores. The empirical analysis also yields new insights into asymmetric price competition across quality variants and deviations of actual from optimal prices that run counter to previous grocery retailing-based findings.
Salesperson Adaptive Selling Behavior and Customer Orientation: A Meta-Analysis
Authors: Franke George R. , Park Jeong-Eun
Published: October 2006

The authors combine findings from 155 samples of more than 31,000 salespeople to test alternative models of antecedents and consequences of adaptive selling behavior (ASB) and customer orientation (CO). A random-effects meta-analysis yields average values for 28 different correlations ranging from -.16 to .35, 19 of which are significant. Controlling for salesperson gender and selling experience, structural equation modeling indicates that ASB increases self-rated, manager-rated, and objective measures of performance, whereas CO increases only self-rated performance. Both ASB and CO increase job satisfaction. Tests of reciprocal relationships indicate that ASB increases CO and job satisfaction increases performance rather than vice versa. Selling experience increases performance but not job satisfaction, and saleswomen rate their performance and satisfaction slightly higher than salesmen do. The magnitudes of the relationships indicate that ASB and selling experience have greater effects than CO and gender on salesperson performance.
Analysis of the VENUS-3 PWR Pressure Vessel Surveillance Benchmark Using TRIPOLI-4.3 Monte Carlo Code
Authors: Lee YK
Published: October 2006

This paper presents the analysis of the VENUS-3 PWR Pressure Vessel Surveillance Dosimetry Benchmark using the three-dimensional (3D) continuous-energy Monte Carlo code TRIPOLI-4.3. VENUS-3 benchmark specifications are taken from the 2004 release of the International Database for Integral Shielding Experiments (SINBAD) of OECD/NEA. Pointwise nuclear data library for TRIPOLI-4.3 transport calculations were prepared from ENDF/B-VI.4. Detector cross sections for 27 Al(n,φ), 58 Ni(n,p), and 115 n(n,n′) from IRDF-2002, IRDF-90.v2, and ENDF/B-VI.4 have been investigated. Two 235 U fission spectra, continuous Watt spectrum and 581 group ENDF/B-VI.4 spectrum have been compared. To speed up the simulation and to predict the axial (50-cm) and azimuthal (0̊-90̊) variation of the reaction rates for core barrel measurement points, variance reduction techniques using cylindrical surface detector and cylindrical biasing meshes have been applied and demonstrated. C/E values at 160 different locations have been evaluated. Without taking into account the uncertainty of the nuclear data in transport calculation and the uncertainty of the 3D neutron source distribution, a 10 % C/E tolerance margin should be accepted.
24 Years of Pneumoconiosis Mortality Surveillance in Australia
Authors: Smith Derek R. , Leggat Peter A.
Published: October 2006

24 Years of Pneumoconiosis Mortality Surveillance in Australia: Derek R. Smith, et al. International Center for Research Promotion and Informatics, National Institute of Occupational Safety and Health—Asbestosis, silicosis and Coal Worker's Pneumoconiosis (CWP) represent three of the most important occupationally‐related dust diseases in Australia. To gain a clear picture of pneumoconiosis trends over time, a 24‐yr retrospective analysis of national mortality data was performed for the period 1979 to 2002. Over 1,000 pneumoconiosis‐related fatalities occurred during this time, 56% of which were caused by asbestosis, 38% by silicosis and 6% by CWP. Between 1979 and 1981, silicosis accounted for 60% of all pneumoconiosis‐related fatalities in Australia, followed by asbestosis (31%). By 2002 however, asbestosis was causing 78% of all fatalities, while silicosis accounted for only 19%. Asbestos‐related mortality increased three‐fold between 1979 and 2002, with a clear excess risk demonstrated among males. On the other hand, mortality rates for silicosis and CWP declined significantly during the same time period. Overall, this study suggests that pneumoconiosis, particularly asbestosis, continues to be an important occupational disease in Australia. Although progress has been made in reducing deaths due to occupational silicosis and CWP, asbestosis rates continue to rise, reflecting the long latency between dust exposure and clinical disease. Countries which continue to use asbestos products in the workplace should note the tragic legacy of this material within contemporary Australia.
Hemoglobin Adducts as a Marker of Exposure to Chemical Substances, Especially PRTR Class I Designated Chemical Substances
Authors: Ogawa Masanori , Oyama Tsunehiro , Isse Toyohi , Yamaguchi Tetsunosuke , Murakami Tomoe , Endo Yoko , Kawamoto Toshihiro
Published: October 2006

Hemoglobin Adducts as a Marker of Exposure to Chemical Substances, Especially PRTR Class I Designated Chemical Substances: Masanori Ogawa, et al. Department of Environmental Health, University of Occupational and Environmental Health—Many new biomarkers are being studied, in addition to classical biomarkers, such as chemical substances and their metabolites in blood and urine and modified enzymes. Among these new biomarkers, hemoglobin adducts are thought to be especially useful for the estimation of chemical exposures. We review here the use of biomarkers for monitoring exposures to nine substances, mainly focusing on PRTR class I designated chemical substances, styrene, phenyloxirane (styrene oxide), 4,4’‐methylendiphenyl diisocyanate (MDI), 4,4’‐methylendianiline (MDA), 1,3‐butadiene, ethylene oxide, propylene oxide, acrylamide and acrylonitrile. Hemoglobin adduct levels were elevated after exposures to styrene, MDI, MDA, 1, 3‐butadiene, ethylene oxide, acrylamide and acrylonitrile. Moreover, hemoglobin adducts of butadiene, ethylene oxide, acrylamide and acrylonitrile have several useful advantages. For example, the hemoglobin adduct of 1,3‐butadiene is an even more useful biomarker of exposure than urinary metabolites, and in the case of ethylene oxide, even though the concentration of ethylene oxide‐Hb in the blood of workers did not exceed the value of the German exposure equivalent, a significant difference in it was found between workers and a control group. Also hemoglobin adducts of acrylamide and acrylonitrile can reflect their exposures because there are no urinary metabolites of acrylamide and acrylonitrile that are useful for exposure assessment. In addition to these advantages, hemoglobin adducts are superior to DNA adducts with respect to the availability of large amounts, availability of methods for chemical identification, and well‐defined life spans due to the absence of repair. Hemoglobin adducts can be effective biomarkers for assessing exposure to and the effects of chemicals.
Exposure to MTBE, TAME and Aromatic Hydrocarbons during Gasoline Pump Maintenance, Repair and Inspection
Authors: Vainiotalo Sinikka , Kuusimaki Leea , Pekari Kaija
Published: October 2006

Exposure to MTBE, TAME and Aromatic Hydrocarbons during Gasoline Pump Maintenance, Repair and Inspection: Sinikka Vainiotalo, et al. Finnish Institute of Occupational Health, Finland—The exposure of gasoline pump repairers and inspectors to gasoline was studied at service stations and repair shops in Finland in April–June 2004. The average air temperature ranged from 7°C to 16°C and wind speed from 2.5 to 7 m/s. The gasoline blends contained mixtures of methyl tert‐butyl ether (MTBE) and tert‐amyl methyl ether (TAME), the total content of oxygenates being 11–12%. The content of benzene was <1%. Breathing zone air was collected during the work task using passive monitors. The mean sampling period was 4.5 h. The mean TWA‐8 h concentrations for MTBE, TAME, hexane, benzene, toluene, ethylbenzene and xylene were 4.5, 1.3, 0.55, 0.23, 2.2, 0.26 and 1.1 mg/m3, respectively. None of the individual benzene concentrations exceeded the binding limit value for benzene (3.25 mg/m3). The sum concentration of MTBE and TAME in urine was between 8.9 and 530 nmol/l in individual post‐shift samples. The individual sum concentrations of the metabolites tert‐butyl alcohol and tert‐amyl alcohol collected the following morning after the exposure ranged from 81 to 916 nmol/l. All individual results were below corresponding biological action levels. Exposure to aromatic hydrocarbons was estimated from post‐shift urine samples, with benzene showing the highest concentration (range 4.4 and 35 nmol/l in nonsmokers). The exposure levels were similar to those measured in previous studies during unloading of tanker lorries and railway wagons. The results indicated a slightly higher exposure for inspectors, who calibrated fuel pump gauges at the service stations, than for pump repairers. No significant skin exposure occurred during the study.
Safety Practice and Professional Exposure to Blood and Blood‐Containing Materials in Serbian Health Care Workers
Authors: Jovic‐Vranes Aleksandra , Jankovic Slavenka , Vranes Boris
Published: October 2006

Safety Practice and Professional Exposure to Blood and Blood‐Containing Materials in Serbian Health Care Workers: Aleksandra Jovic‐Vranes, et al. Institute of Social Medicine, Medical School University of Belgrade, Servia and Montenegro—Safety practice is an important element of workplace safety and quality of health care. To investigate the safety practice and professional exposure to blood and blood‐containing materials during a one‐year period among Health Care Workers (HCWs) in Serbia. Cross‐sectional study of 1559 Serbian HCWs using a self‐administered questionnaire. Mantel‐Haenszel statistics and multiple logistic regression analysis were used in statistical analysis. Fifty‐nine percent (921) of HCWs had skin contact with patients blood, followed by 51% (791) with needle stick injuries, 38% (599) with cuts from sharp instruments, and 34% with contact of eye and other mucosa with patient's blood. Nurses reported professional exposure more often than others. Safety practices consisted of using appropriate barriers (gloves, mask, glasses) in all procedures with patients and were used by 58%, 23%, and 4% of HCWs, respectively. Doctors protected themselves more regularly than others. Hospital protocols for post exposure prophylaxis and safety disposal of medical waste are not common in Serbian health care settings. Safety practices in use were having hospital guidelines for safety practice in hospitals [odds ratio (OR)=1.58, 95% confidence interval (CI)=1.14–2.19], carrying out some form of intervention with risks of infection (OR=3.76, 95% CI=2.57–5.51), and HCWs aware of the professional risk of acquiring infection (OR=1.48, 95% CI=1.28–1.79). This study indicates that emphasis on work practice, attire, disposal systems and education strategies, should be employed to reduce professional exposure to blood and blood containing materials among HCWs in Serbia.
Componentes de resistência em cebola a Colletotrichum gloeosporioides
Authors: Pedrosa Raquel A. , Maffia Luiz A. , Mizubuti Eduardo S. G. , Brommonschenkel Sérgio H.
Published: October 2006

A antracnose foliar causada por Colletotrichum gloeosporioides é importante nas regiões cebolicultoras da América Latina, África e Ásia, mas há poucos estudos relacionados à resistência ao patógeno. Assim, neste trabalho, conduzido em condições de casa de vegetação, avaliaram-se componentes de resistência de oito cultivares e dois acessos de cebola (Allium cepa) a quatro isolados do patógeno, inoculados por atomização de suspensão de inóculo ou deposição de discos de micélio em folhas. Detectaram-se diferenças significativas entre cultivares/acessos, na inoculação por atomização, quanto à freqüência de infecção inicial e à taxa de progresso monocíclico da doença (r g) e, na inoculação com disco de micélio, quanto ao período de incubação e área da lesão. Determinaram-se os coeficientes de correlação (r) dos componentes de resistência estimados na inoculação por atomização. Os valores de r foram 0,98 entre severidade estimada visualmente aos nove dias da inoculação (SEV9) e área abaixo da curva de progresso da doença (AACPD); 0,80 entre SEV9 e severidade estimada por medidor de área foliar (SEV); 0,72 entre SEV9 e r g; 0,64 entre SEV9 e freqüência de infecção aos nove dias da inoculação; 0,81 entre SEV e AACPD e 0,64 entre SEV e r g. Em vista dos valores significativos de r associados a SEV9 e da não necessidade de escala para estimar esse componente, SEV9 é potencialmente útil na avaliação de germoplasma de cebola frente a C. gloeosporioides. Na inoculação por atomização, mais rápida e simples de execução, obtiveram-se maior eficiência de infecção e menor variabilidade de respostas, e deverá ser adotada em estudos futuros.
Ocorrência de pectobactérias em tubérculos de batata-semente no estado do Rio Grande do Sul
Authors: El Tassa Samira O. M. , Duarte Valmir
Published: October 2006

Tubérculos de batata (Solanum tuberosum)-semente, pré-básica, básica, registrada e certificada, de oito cultivares, oriundos de 21 lavouras localizadas nos municípios de Vacaria, Canguçu, Piratini e Ibiraiaras, no Rio Grande do Sul, foram coletados nos meses de maio a agosto de 2002. Cada tubérculo foi lavado em água corrente, deixado secar à temperatura ambiente, perfurado com palitos em dez lenticelas, coberto com fina camada de óleo de soja, colocado individualmente em cima de folha de papel toalha umedecida dentro de saco plástico transparente e incubado a 23 ºC por quatro dias. A incidência de podridão mole a partir das lenticelas variou de 20_100% entre as cultivares. Pectobacterium sp. foi constatada em tubérculos das 21 lavouras. Duzentos e vinte e três isolados de Pectobacterium sp. foram obtidos em meio CPG, a partir das lenticelas com podridão mole, e identificados por testes bioquímicos, fisiológicos e PCR em nível de subespécie. Cento e dezenove isolados foram identificados como P. carotovorum subsp. brasiliensis e e 96 com o P. carotovorum subsp. carotovorum. Oito isolados não se enquadraram na classificação bioquímica. Pectobacterium carotovorum subspp. estavam presentes em tubérculos de batata-semente, independente da cultivar, classe ou município de origem. Pectobacterium carotovorum subsp. atrosepticum, a principal responsável por causar canela preta em batata em outros países, não foi detectada.
Métodos de isolamento de bactérias do filoplano de tomateiro visando populações específicas e implicações como agentes de biocontrole
Authors: Halfeld-Vieira Bernardo A. , Romeiro Reginaldo S. , Mizubuti Eduardo S.G.
Published: October 2006

Em um processo de seleção de bactérias do filoplano de tomateiro (Lycopersicon esculentum) com potencial para o controle de doenças da parte aérea da cultura, diferentes métodos de isolamento foram utilizados visando obter isolados da população total, da população da superfície foliar e isolados que habitam locais protegidos do filoplano e/ou que toleram fatores de estresse. Foi testada a capacidade de 300 isolados em controlar in vivo, as doenças causadas por Alternaria solani, Pseudomonas syringae pv. tomato e Phytophthora infestans. Os testes foram repetidos para cada um dos antagonistas selecionados, estudando-se, também, a capacidade de controlar a mancha-bacteriana, causada por Xanthomonas vesicatoria. Os resultados demonstraram haver predomínio de antagonistas provenientes de folíolos do terço superior da planta de população total ou da superfície. Entretanto, o único antagonista selecionado, isolado de folíolos do terço inferior, foi obtido de locais protegidos do filoplano e/ou capaz de tolerar fatores de estresse.
Primeiro relato da podridão da estipe da pupunheira, causada por Phytophthora palmivora, no estado do Paraná
Authors: Santos Álvaro F. dos , Luz Edna Dora. M. N. , Finato Priscila D. , Tessmann Dauri J. , Vida João B.
Published: October 2006

Phytophthora palmivora foi isolado de plantas de pupunheira (Bactris gasipaes) com sintomas de podridão da estipe, no Paraná, em 2002. Testes de patogenicidade e o subseqüente reisolamento do fungo confirmaram a hipótese de que P. palmivora é o agente causal da podridão do estipe. Este é o primeiro relato de P. palmivora causando podridão do estipe na pupunheira no estado do Paraná.
NG2 and Olig2 Expression Provides Evidence for Phenotypic Deregulation of Cultured Central Nervous System and Peripheral Nervous System Neural Precursor Cells
Authors: Dromard Cecile , Bartolami Sylvain , Deleyrolle Loïc , Takebayashi Hirohide , Ripoll Chantal , Simonneau Lionel , Prome Sylvie , Puech Sylvie , Tran Van Ba Christophe , Duperray Christophe , Valmier Jean , Privat Alain , Hugnot Jean-Philippe
Published: October 2006

Neural stem cells cultured with fibroblast growth factor 2 (FGF2)/epidermal growth factor (EGF) generate clonal expansions called neurospheres (NS), which are widely used for therapy in animal models. However, their cellular composition is still poorly defined. Here, we report that NS derived from several embryonic and adult central nervous system (CNS) regions are composed mainly of remarkable cells coexpressing radial glia markers (BLBP, RC2, GLAST), oligodendrogenic/neurogenic factors (Mash1, Olig2, Nkx2.2), and markers that in vivo are typical of the oligodendrocyte lineage (NG2, A2B5, PDGFR-α). On NS differentiation, the latter remain mostly expressed in neurons, together with Olig2 and Mash1. Using cytometry, we show that in growing NS the small population of multipotential self-renewing NS-forming cells are A2B5+ and NG2+. Additionally, we demonstrate that these NS-forming cells in the embryonic spinal cord were initially NG2− and rapidly acquired NG2 in vitro. NG2 and Olig2 were found to be rapidly induced by cell culture conditions in spinal cord neural precursor cells. Olig2 expression was also induced in astrocytes and embryonic peripheral nervous system (PNS) cells in culture after EGF/FGF treatment. These data provide new evidence for profound phenotypic modifications in CNS and PNS neural precursor cells induced by culture conditions.
Biology of Stem Cells in Human Umbilical Cord Stroma: In Situ and In Vitro Surveys
Authors: Karahuseyinoglu Sercin , Cinar Ozgur , Kilic Emine , Kara Fadil , Akay Guvem Gumus , Demiralp Duygu Özel , Tukun Ajlan , Uckan Duygu , Can Alp
Published: October 2006

Cells in the umbilical cord stroma have gained attention in recent years; however, differentiation to certain lineages in humans has been demonstrated in few studies. Unlike bone marrow MSCs, human umbilical cord stroma cells (HUCSCs) are far from being well characterized. This study attempts to describe proliferation, structural, and differentiation properties of these cells to account for their exceptional nature in many aspects. Cellular dynamics, cellular structure, and the degree of transformations during expansion and differentiation into mesenchymal and neuronal lineages were examined in vitro over a 10-month period. Comparisons with human bone marrow MSCs regarding differentiation were performed. HUCSCs in culture revealed two distinct cell populations, type 1 and type 2 cells, that possessed differential vimentin and cytokeratin filaments. Corresponding cells were encountered in cord sections displaying region-specific localization. α-Smooth muscle actin and desmin filaments, which were evident in cord sections, diminished through passages. No difference was noted regarding type 1 and type 2 cells in differentiation to chondrogenic, adipogenic, and osteogenic lineages, whereas a preferential differentiation was noted in neuronal lineage. Relative success was achieved by production of chondrocytic spheres and osteogenic monolayers, whereas adipocytes were immature compared with bone marrow MSCs. The presence of neuronal markers suggests that they transform into a certain state of maturity under neurogenic induction. Conclusively, HUCSCs retain their original phenotype in culture without spontaneous differentiation, have a limited lifespan, and bear multipotent stem cell characteristics. Given these characteristics, they may be generally considered progenitor cells if manipulated under appropriate conditions and deserve further study to be potentially used in cell-based therapies.
Derivation of Clinically Compliant MSCs from CD105+, CD24− Differentiated Human ESCs
Authors: Lian Qizhou , Lye Elias , Suan Yeo Keng , Khia Way Tan Eileen , Salto-Tellez Manuel , Liu Tong Ming , Palanisamy Nallasivam , El Oakley Reida Menshawe , Lee Eng Hin , Lim Bing , Lim Sai-Kiang
Published: October 2006

Adult tissue-derived mesenchymal stem cells (MSCs) have demonstrated therapeutic efficacy in treating diseases or repairing damaged tissues through mechanisms thought to be mediated by either cell replacement or secretion of paracrine factors. Characterized, self-renewing human ESCs could potentially be an invariable source of consistently uniform MSCs for therapeutic applications. Here we describe a clinically relevant and reproducible manner of generating identical batches of hESC-derived MSC (hESC-MSC) cultures that circumvents exposure to virus, mouse cells, or serum. Trypsinization and propagation of HuES9 or H1 hESCs in feeder- and serum-free selection media generated three polyclonal, karyotypically stable, and phenotypically MSC-like cultures that do not express pluripotency-associated markers but displayed MSC-like surface antigens and gene expression profile. They differentiate into adipocytes, osteocytes, and chondrocytes in vitro. Gene expression and fluorescence-activated cell sorter analysis identified CD105 and CD24 as highly expressed antigens on hESC-MSCs and hESCs, respectively. CD105+, CD24− monoclonal isolates have a typical MSC gene expression profiles and were identical to each other with a highly correlated gene expression profile (r2 > .90). We have developed a protocol to reproducibly generate clinically compliant and identical hESC-MSC cultures.