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Kinds of ABC Terms modified by ABC Selected AbstractsAvoiding Accounting Fixation: Determinants of Cognitive Adaptation to Differences in Accounting Method,CONTEMPORARY ACCOUNTING RESEARCH, Issue 2 2005DAVID T. DEARMAN Abstract Much research over the last 30 years has provided evidence that individuals display accounting fixation; that is, their cognitive process does not appropriately adapt to cross-sectional or temporal differences in an accounting method. This paper presents the results of a quasi-experimental test of the hypothesis that cognitive adaptation to a change in accounting method is an ordinal interactive function of three person characteristics: relevant accounting knowledge, general problem-solving ability, and intrinsic motivation to appropriately engage in the decision task. Based on a product-pricing decision task in which participants are provided with product costs reported by two generally employed product-costing methods (activity-based costing [ABC] and volume-based costing), the results show that the majority of participants did not change their cognitive behavior when there was a change in the costing method. Further, those participants who did adapt to the change in accounting method, and thus avoided accounting fixation, did so by debiasing costs reported by volume-based costing but not by ABC. Finally, these adapters generally exhibited high values for all three of the person characteristics compared with those who did not adapt. [source] Discrepancy in measuring CD4 expression on T-lymphocytes using fluorescein conjugates in comparison with unimolar CD4-phycoerythrin conjugates,,CYTOMETRY, Issue 6 2007Lili Wang Abstract Background: Numerous methods for quantitative fluorescence calibration (QFC) have been developed to quantify receptor expression on lymphocytes. However, the results from the use of these different QFC methods vary considerably in the literature. To better identify the causes of these discrepancies, we measured CD4 expression using FITC and phycoerythrin (PE) conjugates to stain CYTO-TROLÔ Control Cells and T-lymphocytes in whole blood and isolated cell preparations. We further examined pH of the cellular microenvironment as a cause of discordant results obtained with the FITC conjugate. Methods: Calibration with Quantibrite PE-labeled microspheres and the use of unimolar CD4-PE conjugates provided direct measurement of the antibody bound per cell value (ABC) for CD4 expression on normal T-lymphocytes. Calibration for CD4-FITC monoclonal antibody (Mab) labeled CYTO-TROL Control Cells and normal T-lymphocytes was based on molecules of equivalent soluble fluorochrome (MESF) as determined by FITC-labeled microspheres traceable to NIST RM 8640. The MESF value for CD4-FITC Mab was determined that enabled the conversion of the MESF values obtained for CYTO-TROL cells to ABC. We investigated the likely pH change in the fluorescein microenvironments within FITC-labeled Mab and cells stained with FITC-labeled Mab using a pH sensitive indicator. Results: The mean ABC value for T-lymphocytes prepared from fresh whole blood using CD4-PE conjugate (48,321) was consistent with previous results, and it was much higher than the mean ABC using CD4-FITC Mab (22,156). The mean ABC value for CYTO-TROL cells using CD4-PE conjugate (43,090) was also higher than that using CD4-FITC conjugate (34,734), although the discrepancy was not as great. Further studies suggested the discrepancy in CYTO-TROL results may be accounted for by the low pH of the membrane microenvironment, but the greater discrepancy in T-lymphocytes could not be fully explained. Conclusion: CD4 expression on fresh normal whole blood samples and CYTO-TROL cells can be consistently quantified in ABC units using Quantibrite PE quantification beads and unimolar CD4-PE conjugates. Quantification with CD4-FITC conjugate is not as consistent, but may be improved by the use of CD4 T-cells as biological calibrators. This approximation is valid only for surface receptors with consensus ABC values measured by different QFC methods serving as biological standards. Published 2007 Wiley-Liss, Inc. [source] Performance of calibration standards for antigen quantitation with flow cytometry in chronic lymphocytic leukemiaCYTOMETRY, Issue 6 2007Eva D. Rossmann Abstract Background: The fluorescence intensities of CD3, CD4 on T cells and CD20, CD22 molecules on B cells were quantitatively measured on lymphocytes from chronic lymphocytic leukemia (CLL) patients and healthy donors. Methods: The performance of three different types of microbeads was compared, i.e. Quantum molecules of equivalent soluble fluorochrome (Q-MESF), Quantum simply cellular (QSC), and QuantiBRITEÔ (QB). As all PE-conjugates had a F/P ratio of 1:1, the MESF units represented also the antibody binding capacity (ABC). Results: The ABCs of CD4 and CD20 antigens estimated with QSC (ABCQSC) were higher than those assigned with QB (ABCQB) with an average difference 49%. Higher numbers of antigenic sites were obtained with Q-MESF than with QSC for CD20 antigen. On the contrary, CD4 antigenic sites numbers estimated with QSC were higher than those estimated with Q-MESF. ABC values estimated with Quantum MESF PE (ABCQ-MESF) were ,15% higher than ABCQSC, whereas ABCQ-MESF was ,49% higher than ABCQB. Statistically significant correlations were found between the values obtained using various standards. The present study is the first to report down-regulation of CD3 antigen on T cells from patients with CLL. Conclusions: This study emphasizes the relevance of quantitative measurement of fluorescence intensity by flow cytometry as a standardized approach to measure and interpret the expression of some CLL markers and reduce variability of results obtained at different sites in multi-center clinical studies. © 2007 Clinical Cytometry Society [source] Single-cell image analysis to assess ABC-transporter,mediated efflux in highly purified hematopoietic progenitorsCYTOMETRY, Issue 4 2002H.G.P. Raaijmakers Abstract Background Normal and malignant hematopoietic stem cells are characterized by their capacity to actively extrude fluorescent dyes. The contribution of different ATP-binding cassette (ABC) transporters to this phenomenon is largely unknown due to the small stem cell numbers limiting the use of standard methods to assess functional efflux. Methods We used epifluorescence microscopy (EFM) in combination with single-cell image analysis to study ABC-transporter,mediated efflux in highly purified, viable, CD34+CD38- cells sorted on an adhesive biolayer. P-glycoprotein and multidrug-resistant protein (MRP)-mediated efflux were quantitated using fluorescent substrates (rhodamine-123 and calcein acetoxymethyl ester [calcein-AM]) and specific inhibitors (verapamil and probenecid, respectively). Results The feasibility, sensitivity, and reproducibility of rhodamine-123 efflux quantitation using single-cell EFM was shown in cell lines and compared with standard flow cytometric assessment. P-glycoprotein,mediated transport was higher in CD34+CD38- cells than in more differentiated progenitors (mean efflux index = 2.24 ± 0.35 and 1.14 ± 0.11, respectively; P = 0.01). P-glycoprotein,mediated transport was the main determinant of the rhodamine "dull" phenotype of these cells. In addition, significant MRP-mediated efflux was demonstrated in CD34+CD38- and CD38+ cells (mean efflux index = 1.42 ± 0.19 and 1.28 ± 0.18, respectively). Conclusion The described method is a valuable tool for assessing ABC-transporter,mediated efflux in highly purified single cells. Both P-glycoprotein and MRP-mediated efflux are present in human CD34+CD38- hematopoietic stem cells. Cytometry 49:135,142, 2002. © 2002 Wiley-Liss, Inc. [source] RE ,ABC 2'; SEVERAL PACES FORWARD BUT A BIG LEAP BACK FOR CERVICAL CANCER AUDITCYTOPATHOLOGY, Issue 2 2001C. Womack No abstract is available for this article. [source] Mutation in the abcb7 gene causes abnormal iron and fatty acid metabolism in developing medaka fishDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 9 2008Akimitsu Miyake The medaka fish (Oryzias latipes) is an emerging model organism for which a variety of unique developmental mutants have now been generated. Our recent mutagenesis screening of the medaka isolated a unique mutant that develops a fatty liver at larval stages. Positional cloning identified the responsible gene as medaka abcb7. Abcb7, a mitochondrial ABC (ATP binding cassette) half-transporter, has been implicated in iron metabolism. Recently, human Abcb7 was found to be mutated in X-linked sideroblastic anemia with cerebellar ataxia (XLSA/A). The homozygous medaka mutant exhibits abnormal iron metabolism in erythrocytes and accumulation of lipid in the liver. Microarray and in situ hybridization analyses demonstrated that the expression of genes involved in iron and lipid metabolisms are both affected in the mutant liver, suggesting novel roles of Abcb7 in the development of physiologically functional liver. The medaka abcb7 mutant thus could provide insights into the pathogenesis of XLSA/A as well as the normal function of the gene. [source] Increase in multidrug transport activity is associated with oocyte maturation in sea stars,DEVELOPMENT GROWTH & DIFFERENTIATION, Issue 9 2006Troy A. Roepke In this study, we report on the presence of efflux transporter activity before oocyte maturation in sea stars and its upregulation after maturation. This activity is similar to the multidrug resistance (MDR) activity mediated by ATP binding cassette (ABC) efflux transporters. In sea star oocytes the efflux activity, as measured by exclusion of calcein-am, increased two-fold 3 h post-maturation. Experiments using specific and non-specific dyes and inhibitors demonstrated that the increase in transporter activity involves an ABCB protein, P-glycoprotein (P-gp), and an ABCC protein similar to the MDR-associated protein (MRP)-like transporters. Western blots using an antibody directed against mammalian P-gp recognized a 45 kDa protein in sea star oocytes that increased in abundance during maturation. An antibody directed against sea urchin ABCC proteins (MRP) recognized three proteins in immature oocytes and two in mature oocytes. Experiments using inhibitors suggest that translation and microtubule function are both required for post-maturation increases in transporter activity. Immunolabeling revealed translocation of stored ABCB proteins to the plasma cell membrane during maturation, and this translocation coincided with increased transport activity. These MDR transporters serve protective roles in oocytes and eggs, as demonstrated by sensitization of the oocytes to the maturation inhibitor, vinblastine, by MRP and PGP-specific transporter inhibitors. [source] Repulsive guidance of axons of spinal sensory neurons in Xenopus laevis embryos: Roles of Contactin and notochord-derived chondroitin sulfate proteoglycansDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 7 2005Naoko Fujita An immunoglobulin superfamily neuronal adhesion molecule, Contactin, has been implicated in axon guidance of spinal sensory neurons in Xenopus embryos. To identify the guidance signaling molecules that Contactin recognizes in tailbud embryos, an in situ binding assay was performed using recombinant Contactin-alkaline phosphatase fusion protein (Contactin-AP) as a probe. In the assay of whole-mount or sectioned embryos, Contactin-AP specifically bound to the notochord and its proximal regions. This binding was completely blocked by either digestion of embryo sections with chondroitinase ABC or pretreatment of Contactin-AP with chondroitin sulfate A. When the spinal cord and the notochord explants were co-cultured in collagen gel, growing Contactin-positive spinal axons were repelled by notochord-derived repulsive activity. This repulsive activity was abolished by the addition of either a monoclonal anti-Contactin antibody, chondroitin sulfate A or chondroitinase ABC to the culture medium. An antibody that recognizes chondroitin sulfate A and C labeled immunohistochemically the notochord in embryo sections and the collagen gel matrix around the cultured notochord explant. Addition of chondroitinase ABC into the culture eliminated the immunoreactivity in the gel matrix. These results suggest that the notochord-derived chondroitin sulfate proteoglycan acts as a repulsive signaling molecule that is recognized by Contactin on spinal sensory axons. [source] Activity-dependent formation and functions of chondroitin sulfate-rich extracellular matrix of perineuronal netsDEVELOPMENTAL NEUROBIOLOGY, Issue 5 2007Alexander Dityatev Abstract Extracellular matrix molecules,including chondroitin sulfate proteoglycans, hyaluronan, and tenascin-R,are enriched in perineuronal nets (PNs) associated with subsets of neurons in the brain and spinal cord. In the present study, we show that similar cell type-dependent extracellular matrix aggregates are formed in dissociated cell cultures prepared from early postnatal mouse hippocampus. Starting from the 5th day in culture, accumulations of lattice-like extracellular structures labeled with Wisteria floribunda agglutinin were detected at the cell surface of parvalbumin-expressing interneurons, which developed after 2,3 weeks into conspicuous PNs localized around synaptic contacts at somata and proximal dendrites, as well as around axon initial segments. Physiological recording and intracellular labeling of PN-expressing neurons revealed that these are large fast-spiking interneurons with morphological characteristics of basket cells. To study mechanisms of activity-dependent formation of PNs, we performed pharmacological analysis and found that blockade of action potentials, transmitter release, Ca2+ permeable AMPA subtype of glutamate receptors or L-type Ca2+ voltage-gated channels strongly decreased the extracellular accumulation of PN components in cultured neurons. Thus, we suggest that Ca2+ influx via AMPA receptors and L-type channels is necessary for activity-dependent formation of PNs. To study functions of chondroitin sulfate-rich PNs, we treated cultures with chondroitinase ABC that resulted in a prominent reduction of several major PN components. Removal of PNs did not affect the number and distribution of perisomatic GABAergic contacts but increased the excitability of interneurons in cultures, implicating the extracellular matrix of PNs in regulation of interneuronal activity. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source] Spatial and temporal variation of abundance, biomass and diversity within marine reserves in the PhilippinesDIVERSITY AND DISTRIBUTIONS, Issue 4 2010Jonathan A. Anticamara Abstract Aim, The objective of this study was to investigate the influence of protection duration (years of fishing closure) and location (distance from shore) on reef fish diversity. Location, Danajon Double Barrier Reef, Bohol, Philippines. Methods, Reef fish abundance and size structure, by species, were obtained monthly using replicated underwater visual belt transects (n = 8; 70 × 5-m belt transects) over 3 years (2002,2005) at eight sites that included six marine reserves and two unprotected reef areas. We analysed species accumulation curves, diversity indices and abundance,biomass comparison (ABC) curves within and across the study sites to assess the influence of protection duration and location. Results, Analyses showed that longer protection duration impacted reef fish diversity at both inshore and offshore sites by shifting ABC curves from higher abundance than biomass curves at fished sites to higher biomass than abundance curves at most of the protected sites. Protection duration did not significantly influence either the rate of species accumulation within sites or the 12 diversity indices measured across the study sites. The offshore sites consistently showed higher rates of species accumulation and diversity indices values than inshore sites with similar protection duration. One protected offshore young marine reserve site that has been assessed as the least well-managed showed patterns more consistent with the fished sites. Main conclusions, Analyses showed that protection duration mainly impacted diversity by increasing the dominance of large-bodied species and enhancing total biomass. Besides protection duration, reserve location influenced species accumulation curves and diversity indices. [source] Mutagenicity of zidovudine, lamivudine, and abacavir following in vitro exposure of human lymphoblastoid cells or in utero exposure of CD-1 mice to single agents or drug combinations,,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3-4 2007Salina M. Torres Abstract Experiments were performed to investigate the impact of zidovudine (AZT), lamivudine (3TC), and abacavir (ABC) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using cell cloning assays for assessing the effects of individual drugs/drug combinations in (1) TK6 human lymphoblastoid cells exposed in vitro and (2) splenic lymphocytes from male CD-1 mice exposed transplacentally on days 12,18 of gestation. In TK6 cells, dose-related increases in HPRT and TK mutant frequencies were found following 3 days of exposure to AZT or 3TC alone (33, 100, or 300 ,M), or to equimolar amounts of AZT-3TC. Compared with single drug exposures, AZT-3TC coexposures generally yielded enhanced elevations in HPRT and TK mutant frequencies. Mutagenicity experiments with ABC alone, or in combination with AZT-3TC, were complicated by the extreme cytotoxicity of ABC. Exposure of cells either to relatively high levels of AZT-3TC short-term (100 ,M, 3 days), or to peak plasma-equivalent levels of AZT-3TC for an extended period (10 ,M, 30 days), resulted in similar drug-induced mutagenic responses. Among sets of mice necropsied on days 13, 15, or 21 postpartum, Hprt mutant frequencies in T-cells were significantly elevated in the AZT-only (200 mg/kg bw/day) and AZT-3TC (200 mg AZT + 100 mg 3TC/kg bw/day) groups at 13 days of age. These results suggest that the mutagenicity by these nucleoside analogs is driven by cumulative dose, and raises the question of whether AZT-3TC has greater mutagenic effects than AZT alone in perinatally exposed children. Environ. Mol. Mutagen. © 2007 Wiley-Liss, Inc. [source] Relative mutagenic potencies of several nucleoside analogs, alone or in drug pairs, at the HPRT and TK loci of human TK6 lymphoblastoid cells,ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 3-4 2007Meghan M. Carter Abstract Experiments were performed to investigate the impact of didanosine (ddI), lamivudine (3TC), and stavudine (d4T) on cell survival and mutagenicity in two reporter genes, hypoxanthine-guanine phosphoribosyltransferase (HPRT) and thymidine kinase (TK), using a cell cloning assay for assessing the effects of individual nucleoside analogs (NRTIs)/drug combinations in human TK6 B-lymphoblastoid cells. Three-day treatments with 0, 33, 100, or 300 ,M ddI, 3TC, or ddI-3TC produced positive trends for increased HPRT and TK mutant frequencies. While dose-related trends were too small to reach significance after treatments with d4T or d4T-3TC, pairwise comparisons with control cells indicated that exposure to 100 ,M d4T or d4T-3TC caused significant elevations in HPRT mutants. Measurements of mutagenicity in cells exposed to d4T (or d4T-3TC) were complicated by the cytotoxicity of this NRTI. Enhanced increases in mutagenic responses to combined NRTI treatments, compared with single drug treatments, occurred as additive to synergistic effects in the HPRT gene of cells exposed to 100 ,M ddI-3TC or 100 ,M d4T-3TC, and in the TK gene of cells exposed to 100 or 300 ,M ddI-3TC. Comparisons of these data to mutagenicity studies of other NRTIs in the same system (Meng Q et al. [2000c]: Proc Natl Acad Sci USA 97:12667,126671; Torres SM et al. [2007]: Environ Mol Mutagen) indicate that the relative mutagenic potencies for all drugs tested to date are: AZT-ddI > ddI-3TC > AZT-3TC , AZT-3TC-ABC (abacavir) > AZT ,ddI > d4T-3TC > 3TC > d4T , ABC. These collective data suggest that all NRTIs with antiviral activity against HIV-1 may cause host cell DNA damage and mutations, and impose a cancer risk. Environ. Mol. Mutagen., 2007. © 2007 Wiley-Liss, Inc. [source] Fas and Fas ligand expression on germinal center type-diffuse large B-cell lymphoma is associated with the clinical outcomeEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2006Yasushi Kojima Abstract:, In recent years, diffuse large B-cell lymphoma (DLBCL) has been classified by DNA microarray analysis into the germinal center B-cell-like (GC) type, the activated B-cell-like (ABC) type and type 3. The latter two types can be collectively categorized as the non-GC (NGC) type. From the prognostic perspective, the GC type has a favorable clinical outcome when compared with the NGC type. The protein Fas induces apoptosis of lymphocytes by binding with the Fas ligand (FasL), and escape from such apoptosis is considered to lead to malignant transformation of the cells and unrestricted growth of lymphoma. We proposed a hypothesis that Fas/FasL expression could be possibly related with a better survival of GC type DLBCL and evaluated 69 DLBCL cases immunohistochemically with CD10, Bcl-6, MUM1, Fas and FasL. These lymphomas were classified as GC type (positive for CD10 or Bcl-6 and negative for MUM1) or NGC type. The GC type had a better overall survival rate than the NGC type (P = 0.0723). Among markers as given above, positive CD10 was the most significant prognostic factor for overall survival in total DLBCL (P < 0.05). In the GC type, Fas and FasL expressions were significantly associated with a favorable overall survival (Fas: P < 0.005; FasL: P < 0.05). Hence, Fas or FasL expression might contribute to a better prognosis of this type of DLBCL. [source] Functional C3435T polymorphism of MDR1 gene: an impact on genetic susceptibility and clinical outcome of childhood acute lymphoblastic leukemiaEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 5 2004Krzysztof Jamroziak Abstract: The significance of genetic background in childhood acute lymphoblastic leukemia (ALL) is not well understood. Polymorphisms of genes encoding for xenobiotics and drug transporters are potential factors, which can influence the risk of developing ALL and its clinical outcome. P-glycoprotein (P-gp) is an adenosine triphosphate-binding cassette (ABC)-family transporter involved in protection against xenobiotics and multi-drug resistance. Recently, the single-nucleotide polymorphism C3435T of MDR1 gene has been found to be associated with altered tissue expression and function of P-gp. To evaluate whether C3435T MDR1 polymorphism is associated with the occurrence and outcome of ALL, 113 children with ALL (median age 5.1 yr) and 175 healthy individuals of Polish Caucasian origin were studied by polymerase chain reaction-restriction fragment-length polymorhism (PCR-RFLP) assay. The mutant homozygous TT genotype was found to be associated with occurrence of ALL (OR, 95% CI; 1.8, 1.1,3.1; P = 0.037). Besides, the analysis of factors influencing clinical outcome of our ALL patient cohort showed that CC genotype carriers had significantly lower event-free survival probability (pEFS) (0.62 vs. 0.87; P = 0.007) and overall survival probability (pOS) (0.72 vs. 0.91; P = 0.006). The Cox proportional hazards model-based analysis revealed that the hazard ratios for lower pEFS and lower pOS among CC homozygous subjects were 3.9 (P = 0.008) and 3.3 (P = 0.02), respectively. In conclusion, the results of the present study provide evidence that C3435T MDR1 polymorphism may involve both the susceptibility to and the clinical outcome of childhood ALL. Carriers of the TT genotype are more at risk of developing ALL than other individuals, whereas CC genotype carriers are supposed to have worse prognosis. [source] Molecular genetics of pseudoxanthoma elasticumEXPERIMENTAL DERMATOLOGY, Issue 4 2001F. Ringpfeil Abstract: Pseudoxanthoma elasticum (PXE), a systemic heritable connective tissue disorder, is characterized by progressive calcification of elastic structures in the skin, the eyes and the cardiovascular system, with considerable intra- and interfamilial phenotypic variability. Recently, underlying genetic defects have been identified in the ABCC6 gene, which resides on the chromosomal locus 16p13.1 and encodes the MRP6 protein, a member of the ATP-binding cassette (ABC) family of proteins. The affected individuals are homozygous or compound heterozygous for a spectrum of genetic lesions, including nonsense and missense mutations, or deletions and splice-site alterations, confirming the autosomal recessive nature of this condition. Analysis of the deduced primary sequence suggests that MRP6 is a transmembrane transporter, but its function has not been delineated yet. Surprisingly, however, MRP6 is expressed primarily, if not exclusively, in the liver and the kidneys, suggesting that PXE may be a primary metabolic disorder with secondary involvement of elastic fibers. Identification of mutations in the ABCC6 gene in PXE provides a means for prenatal and presymptomatic testing in families at risk for recurrence. DNA-based analyses will also identify heterozygous carriers who may be at risk for development of limited manifestations of the disease as a result of compounding genetic factors and/or environmental modifiers. [source] Nucleotide-binding domain 1 of cystic fibrosis transmembrane conductance regulatorFEBS JOURNAL, Issue 17 2000Production of a suitable protein for structural studies Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). This protein belongs to the large ATP-binding cassette (ABC) family of transporters. Most patients with cystic fibrosis bear a mutation in the nucleotide-binding domain 1 (NBD1) of CFTR, which plays a key role in the activation of the channel function of CFTR. Determination of the three dimensional structure of NBD1 is essential to better understand its structure,function relationship, and relate it to the biological features of CFTR. In this paper, we report the first preparation of recombinant His-tagged NBD1, as a soluble, stable and isolated domain. The method avoids the use of renaturing processes or fusion constructs. ATPase activity assays show that the recombinant domain is functional. Using tryptophan intrinsic fluorescence, we point out that the local conformation, in the region of the most frequent mutation ,F508, could differ from that of the nucleotide-binding subunit of histidine permease, the only available ABC structure. We have undertaken three dimensional structure determination of NBD1, and the first two dimensional 15N- 1H NMR spectra demonstrate that the domain is folded. The method should be applicable to the structural studies of NBD2 or of other NBDs from different ABC proteins of major biological interest, such as multidrug resistance protein 1 or multidrug resistance associated protein 1. [source] Deprogrammed sporulation in StreptomycesFEMS MICROBIOLOGY LETTERS, Issue 1 2002Yasuo Ohnishi Abstract The bacterial genus Streptomyces forms chains of spores by septation at intervals in aerial hyphae and subsequent maturation on solid medium. Substrate hyphae undergo extensive lysis, liberating nutrients on which aerial hyphae develop. Some mutant strains, however, ectopically form spores by septation in substrate hyphae on solid medium or in vegetative hyphae in liquid medium, which suggests that all hyphae have the potential to differentiate into spores. A Streptomyces griseus mutant strain NP4, which has a mutation in the regulatory system for an ATP-binding cassette (ABC) transporter gene, forms ectopic spores in substrate hyphae only on glucose-containing medium. In addition, overexpression of a substrate-binding protein of the ABC transporter in the wild-type strain causes ectopic septation in very young substrate hyphae and subsequent sporulation in response to glucose. These ectopic spores germinate normally. The ectopic sporulation is independent of A-factor, a microbial hormone that determines the timing of aerial mycelium formation during normal development. Thus, substrate hyphae of Streptomyces have a potential to develop into spores without formation of aerial hyphae. For programmed development, therefore, the strict repression of septum formation in substrate mycelium should be necessary, as well as the positive signal relay leading to aerial mycelium formation followed by septation and sporulation. [source] Super-channel in bacteria: function and structure of the macromolecule import system mediated by a pit-dependent ABC transporterFEMS MICROBIOLOGY LETTERS, Issue 2 2001Yumiko Mishima Abstract In a soil isolate, Sphingomonas sp. A1, the transport of a macromolecule (alginate: 27 kDa) is mediated by a pit-dependent ATP-binding cassette (ABC) transporter. The transporter is different from other ABC transporters so far analyzed in that its function is dependent on a pit, a mouth-like organ formed on the cell surface only when cells are compelled to assimilate macromolecules, and in that it allows direct import of macromolecules into cells. The ABC transporter coupled with the pit, which functions as a funnel and/or concentrator of macromolecules to be imported, was designated the ,super-channel', and in this review, we discuss the three-dimensional structure and specific function of the ,super-channel' for macromolecule import found for the first time in a bacterium. [source] Determination of ABCB1 polymorphisms and haplotypes frequencies in a French populationFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2007Elise Jeannesson Abstract The ATP-binding cassette (ABC) transporter ABCB1, or P-glycoprotein, is a transmembrane efflux pump well known for its implication in drug transport and chemoresistance. ABCB1 substrates include either drugs, such as antiretrovirals and immunomodulators, or physiological molecules like phospholipids. Pharmacogenetic analysis of ABCB1 polymorphisms, in addition to other xenobiotic metabolizing enzymes, might help to personalize and optimize drug therapy. Indeed, some polymorphisms of ABCB1 have been implicated in susceptibility to diseases, changes in drug pharmacokinetics, and in variation of the biological response to drug treatment. In addition, variant and haplotype distributions differ depending on ethnicity. Thus, some ethnies may be at higher risk for adverse events, inefficacy of treatment or prevalence of pathologies. This study aimed to determine frequencies of ABCB1 polymorphisms and haplotypes in a sample of French healthy individuals. DNA was isolated from blood-EDTA. Polymerase chain reaction-restriction fragment length polymorphism and TaqMan single nucleotide polymorphism genotyping assays were used to genotype 227 individuals for T-129C, G-1A, A61G, G1199A, C1236T, T-76A, G2677T/A and C3435T polymorphisms. The observed frequencies of the variant allele for these eight polymorphisms are 0.04, 0.08, 0.09, 0.06, 0.42, 0.46, 0.45 and 0.46 respectively. These polymorphisms are in linkage disequilibrium and haplotype frequencies were determined, the most frequent haplotype being the one with variants at position 1236, 2677 and 3435 and wild-type alleles at the other positions. Finally, the frequencies of these eight ABCB1 polymorphisms in our French individuals supposed to be healthy population are quite similar to those described in other Caucasian populations except for the C3435T polymorphism. [source] Genetic changes in the evolution of multidrug resistance for cultured human ovarian cancer cellsGENES, CHROMOSOMES AND CANCER, Issue 12 2007Timon P. H. Buys The multidrug resistant (MDR) phenotype is often attributed to the activity of ATP-binding cassette (ABC) transporters such as P-glycoprotein (ABCB1). Previous work has suggested that modulation of MDR may not necessarily be a single gene trait. To identify factors that contribute to the emergence of MDR, we undertook integrative genomics analysis of the ovarian carcinoma cell line SKOV3 and a series of MDR derivatives of this line (SKVCRs). As resistance increased, comparative analysis of gene expression showed conspicuous activation of a network of genes in addition to ABCB1. Functional annotation and pathway analysis revealed that many of these genes were associated with the extracellular matrix and had previously been implicated in tumor invasion and cell proliferation. Further investigation by whole genome tiling-path array CGH suggested that changes in gene dosage were key to the activation of several of these overexpressed genes. Remarkably, alignment of whole genome profiles for SKVCR lines revealed the emergence and decline of specific segmental DNA alterations. The most prominent alteration was a novel amplicon residing at 16p13 that encompassed the ABC transporter genes ABCC1 and ABCC6. Loss of this amplicon in highly resistant SKVCR lines coincided with the emergence of a different amplicon at 7q21.12, which harbors ABCB1. Integrative analysis suggests that multiple genes are activated during escalation of drug resistance, including a succession of ABC transporter genes and genes that may act synergistically with ABCB1. These results suggest that evolution of the MDR phenotype is a dynamic, multi-genic process in the genomes of cancer cells. © 2007 Wiley-Liss, Inc. [source] Success of activity management practices: the influence of organizational and cultural factorsACCOUNTING & FINANCE, Issue 1 2007Kevin Baird M40 Abstract This study examines the success of activity management practices and the organizational and cultural factors affecting success at each of Gosselin's (1997) three levels of activity analysis (AA), activity cost analysis (ACA) and activity-based costing (ABC). Data were collected by survey questionnaire from a random sample of managers of Australian business units. The results indicate that activity management is moderately successful in Australian organizations, with greater use associated with higher levels of success. Two organizational factors (top management support and link to quality) were associated with success at each of Gosselin's three levels, whereas training was associated at the AA and ACA levels. The cultural factor of outcome orientation was associated with success at each level, with attention to detail important at the ABC level. Organizational factors were more strongly associated with activity management success than cultural factors. [source] Distinctiveness of the cagA Genotype in Children and Adults with Peptic Symptoms in South ChinaHELICOBACTER, Issue 4 2009Juan Li Abstract Background:,Helicobacter pylori infection is different between children and adults, not only in infection rate but also in virulence genotypes. However, the 3, region of CagA, important in stomach carcinogenesis, still remains unclear in children. The present study aims to compare the frequency of cagA and the distribution of its subtypes between children and adults in South China. Materials and Methods:, One hundred and twenty-eight children and 99 adults with peptic symptoms were enrolled in our research. Histology, rapid urease test, and real-time polymerase chain reaction (PCR) assay were used to diagnose H. pylori infection. vacA s1 was detected by real-time PCR, and EPIYA motifs in the 3, region of CagA by conventional PCR and DNA sequencing. Results:,H. pylori infection was diagnosed in 53 children and 62 adults. vacA s1 was identified in 90.6% and 91.9% of infected children and adults, respectively. Furthermore, cagA was identified in 73.6% and 82.3% of infected children and adults, respectively. No patient with multiple cagA subtypes was observed. A higher prevalence of more virulent cagA genotype was found in children compared to adults (p < .05). Thirty-eight of 39 (97.4%) cagA -positive children were found to have EPIYA-ABD and only one (2.6%) with EPIYA-ABC. In adults, four types of EPIYA motifs , ABC (29.4%), ABD (64.7%), ABAB (2%), and AAD (3.9%) , were identified, and the ABD type was found more commonly in severe diseases, such as atrophic gastritis (53.3%) and gastric cancer (71.4%). Conclusion:,cagA genotypes in children and in adults are different, and EPIYA-ABD may have potential clinical implication in the development of gastric cancer in South China. [source] ABCG2 (BCRP) expression in normal and malignant hematopoietic cellsHEMATOLOGICAL ONCOLOGY, Issue 3 2003Brian L. Abbott Abstract ABCG2 (BCRP) is a member of the ATP-binding cassette (ABC) family of cell surface transport proteins. ABCG2 expression occurs in a variety of normal tissues, and is relatively limited to primitive stem cells. ABCG2 expression is associated with the side population (SP) phenotype of Hoechst 33342 efflux. The substrate profile of ABCG2 includes the antineoplastic drugs primarily targeting topoisomerases, including anthracyclines and camptothecins. More recently, pheophorbide, a chlorophyll-breakdown product, and protoporhyrin IX have been described as ABCG2 substrates, perhaps indicating a physiologic role of cytoprotection of primitive cells. Also, mice lacking ABCG2 expression have no intrinsic stem cell defects, although there is a remarkable increase in toxicity with antineoplastic drugs that are ABCG2 substrates, and also a photosensitivity resembling protoporphyria. Like other members of the ABC family, such as MDR1 and MRP1, ABCG2 is expressed in a variety of malignancies. Despite numerous reports of ABCG2 expression in AML, there is little evidence that ABCG2 expression is correlated with an adverse clinical outcome. This review will focus on the potential usefulness of ABCG2 as a marker primitive stem cells and possible physiologic roles of ABCG2 in protection of primitive stem cell populations, and potential methods of overcoming ABCG2-associated drug resistance in anticancer therapy. Copyright © 2003 John Wiley & Sons, Ltd. [source] Multidrug resistance,associated proteins are crucial for the viability of activated rat hepatic stellate cells,,HEPATOLOGY, Issue 2 2008Rebekka A. Hannivoort Hepatic stellate cells (HSCs) survive and proliferate in the chronically injured liver. ATP-binding cassette (ABC) transporters play a crucial role in cell viability by transporting toxic metabolites or xenobiotics out of the cell. ABC transporter expression in HSCs and its relevance to cell viability and/or activation have not been reported so far. The aim of this study was to investigate the expression, regulation, and function of multidrug resistance,associated protein (Mrp)-type and multidrug resistance protein (Mdr),type ABC transporters in activated rat HSCs. Rat HSCs were exposed to cytokines or oxidative stress. ABC transporter expression was determined by quantitative polymerase chain reaction and immunohistochemistry. HSCs were exposed to the Mdr inhibitors verapamil and PSC-833 and the Mrp inhibitor MK571. Mdr and Mrp transporter function was evaluated with flow cytometry. Apoptosis was determined by activated caspase-3 and acridine orange staining, and necrosis was determined by Sytox green nuclear staining. An in vivo model of carbon tetrachloride (CCl4),induced liver fibrosis was used. With respect to hepatocytes, activated HSCs expressed high levels of Mrp1 and comparable levels of Mrp3, Mrp4, Mdr1a, and Mdr1b but not the hepatocyte-specific transporters bile salt export pump, Mrp2, and Mrp6. Mrp1 protein staining correlated with desmin staining in livers from CCl4 -treated rats. Mrp1 expression increased upon activation of HSCs. Cytokines induced Mdr1b expression only. Oxidative stress was not a major regulator of Mdr and Mrp transporter expression. Activated HSCs became necrotic when exposed to the Mrp inhibitors. Conclusion: Activated HSCs contain relatively high levels of Mrp1. Mrp-type transporters are required for the viability of activated HSCs. Mrp-dependent export of endogenous metabolites is important for the survival of activated HSCs in chronic liver diseases. (HEPATOLOGY 2008.) [source] Technological and organizational influences on the adoption of activity-based costing in AustraliaACCOUNTING & FINANCE, Issue 3 2004David A. Brown The present paper examines one set of potential reasons for the paradox as to why so few firms have adopted activity-based costing (ABC) despite the demonstrated benefits of this costing system. A cross-sectional survey of Australian firms is used to examine the influence of seven technological and organizational factors on firms' initial interest in ABC and their decision to adopt it or not. The organizational factors of top management support, the support of an internal champion, and organizational size were shown to be associated with initial interest in ABC. The decision to adopt or reject ABC had one organizational factor associated with it, the support of an internal champion. [source] Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumoursHISTOPATHOLOGY, Issue 1 2001P G Chu Cytokeratin 14 expression in epithelial neoplasms: a survey of 435 cases with emphasis on its value in differentiating squamous cell carcinomas from other epithelial tumours Aims:,The tissue distribution of cytokeratin 14 (CK14) in epithelial neoplasms is not well defined. We have evaluated 435 cases of epithelial neoplasm of various origins with cytokeratin 14 monoclonal antibody with special attention to possible use in differential diagnosis. Methods and results:,Immunohistochemistry (ABC,HRP method) was performed for detection of CK14. We found that the expression of cytokeratin 14 was generally restricted to: (i) the majority of cases of squamous cell carcinoma regardless of origin (67/74) and degree of differentiation; (ii) neoplasms with focal squamous differentiation, including endometrial, and ovarian adenocarcinoma, malignant mesothelioma and transitional cell carcinoma; (iii) thymoma (8/8); (iv) myoepithelial components of salivary gland pleomorphic adenoma (3/4); and (v) oncocytic neoplasms, including thyroid Hurthle cell adenoma (1/1) and salivary gland Warthin's tumour (2/2). Conclusion:,CK14 protein is a useful marker in differential diagnosis of squamous cell carcinomas. [source] Effect of concurrent zidovudine use on the resistance pathway selected by abacavir-containing regimensHIV MEDICINE, Issue 6 2004ER Lanier Objectives Abacavir (ABC) selects for four mutations (K65R, L74V, Y115F and M184V) in HIV-1 reverse transcriptase (RT), both in vitro and during monotherapy in vivo. The aim of this analysis was to compare the selection of these and other nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations by ABC-containing therapies in the presence and absence of concurrent lamivudine (3TC) and/or zidovudine (ZDV) and to assess the effect of these mutations on phenotypic susceptibility to the NRTIs. Design This study was a retrospective analysis of the patterns of NRTI-associated mutations selected following virological failure in six multicentre trials conducted during the development of ABC. Methods Virological failure was defined as confirmed vRNA above 400 HIV-1 RNA copies/mL. RT genotype and phenotype were determined using standard methods. Results K65R was selected infrequently by ABC-containing regimens in the absence of ZDV (13 of 127 patients), while L74V/I was selected more frequently (51 of 127 patients). Selection of both K65R and L74V/I was significantly reduced by co-administration of ZDV with ABC (one of 86 and two of 86 patients, respectively). Y115F was uncommon in the absence (seven of 127 patients) or presence (four of 86 patients) of ZDV. M184V was the most frequently selected mutation by ABC alone (24 of 70 patients) and by ABC plus 3TC (48 of 70 patients). Thymidine analogue mutations were associated with ZDV use. The K65R mutation conferred the broadest phenotypic cross-resistance of the mutations studied. Conclusions The resistance pathway selected upon virological failure of ABC-containing regimens is significantly altered by concurrent ZDV use, but not by concurrent 3TC use. These data may have important implications for the efficacy of subsequent lines of NRTI therapies. [source] Changes in employees' attitudes at work following an acquisition: a comparative study by acquisition typeHUMAN RESOURCE MANAGEMENT JOURNAL, Issue 3 2008Sylvie Guerrero The purpose of this paper is to examine how employee reaction varies in the event of an acquisition, and ultimately, to show that it depends on the acquisition context; specifically: (1) the legitimacy of the purchasing firm's identity, and (2) the extent of the organizational changes or discontinuity resulting from the acquisition. The research hypotheses considered are tested using a single questionnaire administered repeatedly over a five-year period to the employees of 85 sites belonging initially to three different firms: ABC (the acquiring firm), EFG (the firm taken over in a friendly acquisition) and XYZ (firm absorbed in a hostile acquisition). The results mainly show that employees working at sites belonging initially to EFG have higher organizational identification scores than those at sites belonging initially to XYZ. Insecurity scores increase at all sites after the acquisition period, even for employees who originally belonged to ABC. Finally, a temporal link is seen between organizational identification, insecurity and job satisfaction. [source] Why might language and motor impairments occur together?INFANT AND CHILD DEVELOPMENT, Issue 3 2003L.B. Estil Abstract A step-wise methodology is employed in order to identify common neurological factors underlying motor and language impairments where they occur together. A sample of 15 5,10-year-old children with predetermined language impairment was tested comprehensively using the Illinois Test of Psycholinguistic Ability (ITPA) and the Movement Assessment Battery for Children (Movement ABC). On the basis of these tests, only four of the sample were found to have generally poor performance both in psycholinguistic (particularly indexed by problems with visual closure and sound blending) and motor abilities (particularly indexed by manual dexterity problems,bimanual co-ordination and drawing,and static balance. Further detailed examination of the findings fostered a number of plausible hypotheses to account for this communality. The viability of these different alternatives is discussed. Copyright © 2003 John Wiley & Sons, Ltd. [source] The Measurement of Success of Activity-Based Costing and Its Determinants: A Study within Canadian Federal Government Organizations,/L'évaluation Du Succès De La Comptabilité Par Activités Et Ses Déterminants: Étude D'Organismes Du Gouvernement Fédéral Du CanadaACCOUNTING PERSPECTIVES, Issue 3 2007Anne Fortin ABSTRACT This research first measures the success of activity-based costing (ABC) implementation within Canadian federal government organizations along five constructs, which are the use and frequency of use of the ABC information, decision actions taken, financial improvements, evaluation by management as to overall success, and a composite measure of the four constructs. Second, it identifies the determinants of ABC success. The success determinants used in this study are organizational culture, involvement of a champion, change process, commitment, controls, and continuous education. Measures of ABC success and determinants were obtained using a survey of managers who have participated in ABC implementation in Canadian federal government organizations. The study found that the benefits derived from ABC implementation within Canadian public sector organizations do not measure up to the efforts invested, although respondents consider that some financial improvements have resulted from the implementations. Controls and culture proved to be the two variables that significantly relate to ABC success. The results could have implications for policymaking organizations such as the Treasury Board Secretariat of Canada and the Office of the Comptroller General (OCG). The latter should question the benefits of investments made in management accounting best practices in the federal government. The OCG could also direct departments and agencies to the right environment (success determinants) to be put in place in order to ensure the success of ABC initiatives. RÉSUMÉ Les auteurs évaluent le succès de la mise en ,uvre de la comptabilité par activités (CPA) au sein d'organismes du gouvernement fédéral du Canada selon cinq paramètres, soit l'utilisation et la fréquence d'utilisation de l'information produite par la CPA, les mesures décisionnelles prises, les améliorations financières, l'évaluation du succès global par la direction et une mesure composite regroupant ces quatre paramètres. Ils définissent ensuite les déterminants du succès de la CPA. Les déterminants utilisés dans la présente étude sont la culture organisationnelle, l'intervention d'un défenseur, le processus de changement, l'engagement, les contrôles et la formation continue. Les auteurs obtiennent les critères d'évaluation et les déterminants du succès de la CPA en procédant à un sondage auprès de cadres ayant participé à la mise en ,uvre de la CPA dans des organismes du gouvernement fédéral du Canada. Ils constatent que les avantages découlant de cet exercice au sein des organismes du secteur public canadien ne sont pas à la hauteur des efforts investis, même si les répondants estiment en avoir tiré certaines améliorations financières. Il semble que les variables des contrôles et de la culture soient celles qui se rattachent de façon significative au succès de la CPA. Les résultats de l'étude pourraient avoir des conséquences pour les organismes responsables de l'élaboration des politiques comme le Secrétariat du Conseil du Trésor du Canada et le Bureau du contrôleur général (BCG). Ce dernier devrait s'interroger sur ce que rapportent les sommes investies par le gouvernement fédéral dans les pratiques de comptabilité de management les meilleures. Le BCG pourrait également orienter les ministères et les organismes gouvernementaux vers l'environnement (ou les déterminants du succès) qu'il convient de mettre en place pour assurer la réussite des projets de CPA. 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