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Variable Levels (variable + level)
Selected AbstractsCostimulatory molecule B7-H1 in primary and metastatic clear cell renal cell carcinomaCANCER, Issue 10 2005R. Houston Thompson M.D. Abstract BACKGROUND Cancer cell expression of costimulatory molecule B7-H1 has been implicated as a potent inhibitor of T-cell,mediated antitumoral immunity. The authors recently reported that B7-H1 is aberrantly expressed in primary renal cell carcinoma (RCC). Blockade of B7-H1, as demonstrated in several murine cancer models, now represents a promising therapeutic target in RCC. However, the potential expression of B7-H1 in metastatic RCC has not been investigated. In the current study, the authors updated their primary RCC results with additional follow-up and investigated the potential role of B7-H1 in metastatic RCC. METHODS Between 2000 and 2004, 196 patients underwent nephrectomy and 26 patients had resection of RCC metastases for clear cell RCC. Immunohistochemical analysis was performed on tumor cryosections using a B7-H1 monoclonal antibody (clone 5H1). A urologic pathologist quantified the percentage of B7-H1,positive tumor cells and lymphocytes. RESULTS Variable levels of B7-H1 were expressed on primary RCC tumor cells (n = 130 [66.3%]) and primary tumor-infiltrating lymphocytes (n = 115 [58.7%]). Patients with high expression of B7-H1 on primary tumor cells and/or lymphocytes were significantly more likely to die of RCC compared with patients with low B7-H1 expression (risk ratio [RR] = 4.17; 95% confidence interval [95% CI], 1.97,8.84; P < 0.001) and this risk persisted in multivariate analysis after adjusting for the Mayo Clinic stage, size, grade, and necrosis score (RR = 2.63; 96% CI, 1.23,5.64; P = 0.013). Of the 26 metastatic specimens, cancer cell and lymphocyte B7-H1 expression were demonstrated in 17 (65.4%) and 18 (69.2%) specimens, respectively. In total, 14 (54.3%) metastatic specimens had high aggregate B7-H1 levels compared with 44.4% in primary RCC specimens. CONCLUSIONS Patients with RCC with high B7-H1 expression were significantly more likely to die even after multivariate analysis. The authors also demonstrated that a high percentage of RCC metastases similarly harbored B7-H1. The authors surmised that B7-H1 blockade may augment current immunotherapy, including patients treated for metastases after cytoreductive nephrectomy. Cancer 2005. © 2005 American Cancer Society. [source] Colonic short-chain fatty acids inhibit encystation of Entamoeba invadensCELLULAR MICROBIOLOGY, Issue 2 2005Jennifer Byers Summary Entamoeba parasites multiply as trophozoites in the layer of mucus that overlies the colonic epithelium. In response to stimuli that are not understood, trophozoites stop multiplying and differentiate into cysts that are released to infect another host. In the colon, Entamoeba trophozoites are exposed to the large variety of biochemicals that are carried into or are produced within this organ. The normal bacterial population of the colon releases large amounts of short-chain fatty acids (SCFAs). These compounds have effects on the growth, differentiation and repair of the colonic epithelium that correlate with de-creased activity of a Class I/II histone deacetylase (HDAC). We found that the formation of cysts, but not the growth of trophozoite-stage Entamoeba invadens parasites, was inhibited by physiologic concentrations of SCFAs. Variable levels of cyst formation did occur if SCFA concentrations were lowered. Specific inhibitors of Class I/II-type HDACs also prevented encystation, and trophozoites exposed to these compounds had increased levels of acetylation of histone H4 and other nuclear proteins. These results suggest that production of the infectious cyst stage of Entamoeba parasites is regulated in part by the levels of SCFAs made by the bacterial population of the colon. [source] The broom and nonroutine processes: a metaphor for understanding variability in organizationsKNOWLEDGE AND PROCESS MANAGEMENT: THE JOURNAL OF CORPORATE TRANSFORMATION, Issue 3 2002Paul Lillrank Organizations are challenged to be simultaneously creative and predictable, flexible and efficient. These results are achieved by standard, routine and nonroutine elements requiring different kinds of management approaches. These types are often overlapping and difficult to articulate. This paper proposes a metaphor: the Broom, that can help explore the nature and dynamics of processes with a variable level of repetition and predictability. The hard, stick-end of the Broom illustrates repetitive processes that can be standardized, the opposite end nonroutines and chaos. The middle part represents routines, processes that are repeated in similar, but not identical ways. A task, process or organization can be positioned at the Broom depending on the level of repetition and predictability found in assessed input conditions, the mixture of tacit and explicit knowledge in the process algorithm linking assessment to action, and the degree to which targets are known and evaluated. Copyright © 2002 John Wiley & Sons, Ltd. [source] Dissecting the molecular architecture and origin of Bayash Romani patrilineages: Genetic influences from South-Asia and the BalkansAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 3 2009Irena Martinovi, Klari Abstract The Bayash are a branch of Romanian speaking Roma living dispersedly in Central, Eastern, and Southeastern Europe. To better understand the molecular architecture and origin of the Croatian Bayash paternal gene pool, 151 Bayash Y chromosomes were analyzed for 16 SNPs and 17 STRs and compared with European Romani and non-Romani majority populations from Europe, Turkey, and South Asia. Two main layers of Bayash paternal gene pool were identified: ancestral (Indian) and recent (European). The reduced diversity and expansion signals of H1a patrilineages imply descent from closely related paternal ancestors who could have settled in the Indian subcontinent, possibly as early as between the eighth and tenth centuries AD. The recent layer of the Bayash paternal pool is dominated by a specific subset of E1b1b1a lineages that are not found in the Balkan majority populations. At least two private mutational events occurred in the Bayash during their migrations from the southern Balkans toward Romania. Additional admixture, evident in the low frequencies of typical European haplogroups, J2, R1a, I1, R1b1b2, G, and I2a, took place primarily during the early Bayash settlement in the Balkans and the Romani bondage in Romania. Our results indicate two phenomena in the Bayash and analyzed Roma: a significant preservation of ancestral H1a haplotypes as a result of considerable, but variable level of endogamy and isolation and differential distribution of less frequent, but typical European lineages due to different patterns of the early demographic history in Europe marked by differential admixture and genetic drift. Am J Phys Anthropol, 2009. © 2008 Wiley-Liss, Inc. [source] Child Behavior Checklist Juvenile Bipolar Disorder (CBCL-JBD) and CBCL Posttraumatic Stress Problems (CBCL-PTSP) scales are measures of a single dysregulatory syndromeTHE JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY AND ALLIED DISCIPLINES, Issue 10 2009Lynsay Ayer Background:, The Child Behavior Checklist Juvenile Bipolar Disorder (CBCL-JBD) profile and Posttraumatic Stress Problems (CBCL-PTSP) scale have been used to assess juvenile bipolar disorder (JBD) and posttraumatic stress disorder (PTSD), respectively. However, their validity is questionable according to previous research. Both measures are associated with severe psychopathology often encompassing multiple DSM-IV diagnoses. Further, children who score highly on one of these scales often have elevated scores on the other, independent of PTSD or JBD diagnoses. We hypothesized that the two scales may be indicators of a single syndrome related to dysregulated mood, attention, and behavior. We aimed to describe and identify the overlap between the CBCL-JBD profile and CBCL-PTSP scales. Method:, Two thousand and twenty-nine (2029) children from a nationally representative sample (1073 boys, 956 girls; mean age = 11.98; age range = 6,18) were rated on emotional and behavior problems by their parents using the CBCL. Comparative model testing via structural equation modeling was conducted to determine whether the CBCL-JBD profile and CBCL-PTSP scale are best described as measuring separate versus unitary constructs. Associations with suicidality and competency scores were also examined. Results:, The CBCL-JBD and CBCL-PTSP demonstrated a high degree of overlap (r = .89) at the latent variable level. The best fitting, most parsimonious model was one in which the CBCL-JBD and CBCL-PTSP items identified a single latent construct, which was associated with higher parental endorsement of child suicidal behavior, and lower functioning. Conclusions:, The CBCL-JBD profile and CBCL-PTSP scale overlap to a remarkable degree, and may be best described as measures of a single syndrome. This syndrome appears to be related to severe psychopathology, but may not conform to traditional DSM-IV classification. These results contribute to the ongoing debate about the utility of the CBCL-JBD and CBCL-PTSP profiles, and offer promising methods of empirically based measurement of disordered self-regulation in youth. [source] Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosisARTHRITIS & RHEUMATISM, Issue 4 2009Patrizia Fuschiotti Objective T lymphocytes play an important role in systemic sclerosis (SSc), a connective tissue disease characterized by inflammation, fibrosis, and vascular damage. While their precise role and antigen specificity are unclear, T cell,derived cytokines likely contribute to the induction of fibrosis. The aim of this study was to establish the role of cytokine dysregulation by T cells in the pathogenesis of SSc. Methods To identify relationships between a specific cytokine, T cell subset, and the disease course, we studied a large cohort of patients with diffuse cutaneous SSc (dcSSc) or limited cutaneous SSc (lcSSc). Using Luminex analysis and intracellular cytokine staining, we analyzed the intrinsic ability of CD4+ and CD8+ T cell subsets to produce cytokines following in vitro activation. Results High levels of the profibrotic type 2 cytokine interleukin-13 (IL-13) were produced following activation of peripheral blood effector CD8+ T cells from SSc patients as compared with normal controls or with patients with rheumatoid arthritis. In contrast, CD4+ T cells showed a lower and more variable level of IL-13 production. This abnormality correlated with the extent of fibrosis and was more pronounced in dcSSc patients than in lcSSc patients. Conclusion Dysregulated IL-13 production by effector CD8+ T cells is important in the pathogenesis of SSc and is critical in the predisposition to more severe forms of cutaneous disease. Our study is the first to identify a specific T cell phenotype that correlates with disease severity in SSc and can be used as a marker of immune dysfunction in SSc and as a novel therapeutic target. [source] Influence of hormones and hormone metabolites on the growth of schwann cells derived from embryonic stem cells and on tumor cell lines expressing variable levels of neurofibromin,DEVELOPMENTAL DYNAMICS, Issue 2 2008Therese M. Roth Abstract Loss of neurofibromin, the protein product of the tumor suppressor gene neurofibromatosis type 1 (NF1), is associated with neurofibromas, composed largely of Schwann cells. The number and size of neurofibromas in NF1 patients have been shown to increase during pregnancy. A mouse embryonic stem cell (mESC) model was used, in which mESCs with varying levels of neurofibromin were differentiated into Schwann-like cells. NF1 cell lines derived from a malignant and a benign human tumor were used to study proliferation in response to hormones. Estrogen and androgen receptors were not expressed or expressed at very low levels in the NF1+/+ cells, at low levels in NF1+/,cells, and robust levels in NF1,/,cells. A 17,-estradiol (E2) metabolite, 2-methoxy estradiol (2ME2) is cytotoxic to the NF1,/, malignant tumor cell line, and inhibits proliferation in the other cell lines. 2ME2 or its derivatives could provide new treatment avenues for NF1 hormone-sensitive tumors at times of greatet hormonal influence. Developmental Dynamics 237:513,524, 2008. © 2008 Wiley-Liss, Inc. [source] Genes involved in the RNA interference pathway are differentially expressed during sea urchin developmentDEVELOPMENTAL DYNAMICS, Issue 11 2007Jia L. Song Abstract RNA-mediated interference (RNAi) is a conserved gene silencing mechanism that involves double-stranded RNA as a signal to trigger the sequence-specific degradation of target mRNA, resulting in posttranscriptional silencing and/or translational repression. Bioinformatic searches in the sea urchin genome database identified homologs of Drosha, DGCR5, Dicer, TRBP, Exportin-5, and Argonautes. Quantitative, real-time polymerase chain reaction indicated that all mRNA accumulate in eggs and in variable levels throughout early development. Whole-mount in situ RNA hybridization showed that all of the important players of the RNAi silencing pathway have abundant mRNA accumulation in oocytes and eggs, but have distinct spatial and temporal expression patterns throughout development. Sequence analysis revealed that each of the four Argonautes examined contain conserved residues important for RNAseH activity within the Piwi domain. This study elucidated that genes involved in the RNAi silencing pathway have dynamic expression and, thus, may have regulatory roles during germ cell development and embryogenesis. Developmental Dynamics 236:3180,3190, 2007. © 2007 Wiley-Liss, Inc. [source] Toxicity and chemistry of aspen wood leachate to aquatic life: Field studyENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 9 2003Barry R. Taylor Abstract A dark, toxic leachate has been observed around woodpiles of trembling aspen (Populus tremuloides Michx.) cut in winter for pulp or structural lumber. We measured production of leachate from 18 m3 of harvestable aspen logs stacked in an open field near Dawson Creek, British Columbia, Canada. The logpile began producing leachate during the first winter thaw and continued to do so for the duration of the two-year study (mean, 250 L/collection). Aspen leachate was characterized by dark color, acidic pH (5.0-6.5), elevated conductivity (200-500 ,S/cm), high to very high biochemical oxygen demand (500-5,000 mg/L) and total organic carbon concentrations (500-2,000 mg/L), variable levels of phenolic compounds (2-27 mg/L), and low dissolved oxygen tensions (<2 mg/L). In tests with rainbow trout (Oncorhynchus mykiss), Daphnia magna, and luminescent bacteria, the leachate varied from weakly toxic (median lethal concentration, >10%) to very toxic (median lethal concentration, <1%). The volume of leachate generated by the logpile was correlated with total precipitation (rain or snow) since the last collection. Loads of chemical constituents or toxicity (lethal concentration × volume) in the leachate did not decline over the duration of the study. Less than 10% of the total mass of leachable material in the aspen logs was removed during two years of exposure. [source] Environmental Predictors of Geographic Variation in Human Mating PreferencesETHOLOGY, Issue 4 2002Kevin J. McGraw Sexual selection theory classically posits consistent and directional mate-preferences for male traits that provide benefits to females. However, flexible mate-choice tactics may persist within a species when males display multiple desirable features that confer different benefits to females under variable environmental conditions. Ecological factors such as population density, resource demand, and sex ratio can influence the value that female animals place on certain male characteristics across mating environments. In this study, I used human mate-preference data from `lonely hearts' advertisements in the newspapers of 23 cities in the USA to assess geographic differences in female preferences for male traits (e.g. physical attributes, resource-holding potential, emotional characteristics, personal interests) in relation to these ecological parameters. I found that females placed more emphasis on the resource-accruing ability of prospective mates in densely populated cities and cities having greater resource demands (higher cost of living). In contrast, women from densely populated or resource-demanding cities placed less emphasis on the emotional aspects or personal interests of males. Preferences for physical features were not environmentally linked, but instead were a function of the degree to which females advertised their own physical attractiveness. Collectively, these results suggest that certain mate-choice criteria employed by women are sensitive to variation in local environmental conditions and that variable levels of resource or mate availability may favor different mating tactics across human populations. [source] DENSITY DEPENDENCE AND COOPERATION: THEORY AND A TEST WITH BACTERIAEVOLUTION, Issue 9 2009Adin Ross-Gillespie Although cooperative systems can persist in nature despite the potential for exploitation by noncooperators, it is often observed that small changes in population demography can tip the balance of selective forces for or against cooperation. Here we consider the role of population density in the context of microbial cooperation. First, we account for conflicting results from recent studies by demonstrating theoretically that: (1) for public goods cooperation, higher densities are relatively unfavorable for cooperation; (2) in contrast, for self-restraint,type cooperation, higher densities can be either favorable or unfavorable for cooperation, depending on the details of the system. We then test our predictions concerning public goods cooperation using strains of the pathogenic bacterium Pseudomonas aeruginosa that produce variable levels of a public good,iron-scavenging siderophore molecules. As predicted, we found that the relative fitness of cheats (under-producers) was greatest at higher population densities. Furthermore, as assumed by theory, we show that this occurs because cheats are better able to exploit the cooperative siderophore production of other cells when they are physically closer to them. [source] Serum amyloid A has antiviral activity against hepatitis C virus by inhibiting virus entry in a cell culture system,HEPATOLOGY, Issue 6 2006Muriel Lavie Serum amyloid A (SAA) is an acute phase protein produced by the liver. SAA concentration increases markedly in the serum following inflammation and infection. Large increases in SAA concentration during the acute phase response suggest that SAA has a beneficial role in host defense. This study sought to determine the effect of SAA on hepatitis C virus (HCV) infectivity using retroviral particles pseudotyped with HCV envelope glycoproteins (HCVpp) and the recently developed cell culture system for HCV (HCVcc). SAA inhibited HCVpp and HCVcc infection in a dose-dependent manner by affecting an early step of the virus life cycle. Further characterization with HCVpp indicated that SAA blocks virus entry by interacting with the viral particle. In addition, the antiviral activity of SAA was strongly reduced when high-density lipoproteins (HDL) were coincubated with SAA. However, HDL had only a slight effect on the antiviral activity of SAA when HCVpp was first preincubated with SAA. Furthermore, analyses of SAA in sera of chronic HCV patients revealed the presence of variable levels of SAA with abnormally elevated concentrations in some cases. However, no obvious clinical correlation was found between SAA levels and HCV viral loads. In conclusion, our data demonstrate an antiviral activity for SAA and suggest a tight relationship between SAA and HDL in modulating HCV infectivity. (HEPATOLOGY 2006;44:1626,1634.) [source] Characteristics of hepatocellular carcinoma in a murine model of alpha-1-antitrypsin deficiencyHEPATOLOGY RESEARCH, Issue 6 2010Nancy Y. Marcus Aim:, Individuals with homozygous (ZZ) alpha-1-antitrypsin (,1AT) deficiency are at an increased risk for liver damage, cirrhosis and hepatocellular carcinoma (HCC). The transgenic PiZ mouse, expressing the human ,1AT mutant Z gene, is a valuable model for this disease. We studied PiZ mice in order to identify and characterize mechanisms involved in the development of HCC. Methods:, Tumor incidence and histology were studied, gene expression levels were surveyed with microarrays, RNA quantified with quantitative real time polymerase chain reaction and protein levels determined with immunoblots and immunohistochemistry. Results:, By 16,19 months of age, approximately 69% of the PiZ mice had developed tumors. HCC was present with no evidence of benign adenomas as pre-cancerous lesions. Tumors showed abnormal mitochondria, variable levels of steatosis, globular inclusions of ,1AT mutant Z protein and metastases. PiZ mice that subsequently developed liver tumors had higher serum levels of ,1AT mutant Z protein than those that did not develop tumors. Cyclin D1, a cell cycle protein, was upregulated in PiZ livers without tumors compared to Wt. cFOS, a component of AP-1 that may be involved in transforming cells and MCAM, an adhesion molecule likely involved in tumorigenesis and metastases, were elevated in tumors compared with livers without tumors. Conclusion:, In the PiZ model, many of the histological characteristics of HCC recapitulated features seen in human HCC, whether from individuals with homozygous ZZ liver disease or from unrelated causes in individuals that were not homozygous ZZ. The accumulation of mutant Z protein altered the regulation of several genes driving proliferation and tumorigenesis. [source] Endogenous DNA damage and testicular germ cell tumorsINTERNATIONAL JOURNAL OF ANDROLOGY, Issue 6 2009M. B. Cook Summary Testicular germ cell tumors are comprised of two histologic groups, seminomas and non-seminomas. We postulated that the possible divergent pathogeneses of these histologies may be partially explained by variable levels of net endogenous DNA damage. To test our hypothesis, we conducted a case,case analysis of 51 seminoma and 61 non-seminoma patients using data and specimens from the Familial Testicular Cancer study and the U.S. Radiologic Technologists cohort. A lymphoblastoid cell line was cultured for each patient and the alkaline comet assay was used to determine four parameters: tail DNA, tail length, comet distributed moment (CDM) and Olive tail moment (OTM). Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated using logistic regression. Values for tail length, tail DNA, CDM and OTM were modelled as categorical variables using the 50th and 75th percentiles of the seminoma group. Tail DNA was significantly associated with non-seminoma compared with seminoma (OR50th percentile = 3.31, 95% CI: 1.00, 10.98; OR75th percentile = 3.71, 95% CI: 1.04, 13.20; p for trend = 0.039). OTM exhibited similar, albeit statistically non-significant, risk estimates (OR50th percentile = 2.27, 95% CI: 0.75, 6.87; OR75th percentile = 2.40, 95% CI: 0.75, 7.71; p for trend = 0.12) whereas tail length and CDM showed no association. In conclusion, the results for tail DNA and OTM indicate that net endogenous levels are higher in patients who develop non-seminoma compared with seminoma. This may partly explain the more aggressive biology and younger age-of-onset of this histologic subgroup compared with the relatively less aggressive, later-onset seminoma. [source] Population management of rhinoceros in captivityINTERNATIONAL ZOO YEARBOOK, Issue 1 2006T. J. FOOSE Captive-breeding programmes are important components of conservation strategies for rhinoceros. Rhinoceros in zoos can serve as (1) genetic and demographic reservoirs to reinforce wild populations as the need and opportunity occur, and (2) ambassadors to increase public awareness and support, especially financial, for conservation of wild populations. However, for these functions, rhinoceros in captivity must be managed scientifically and co-operatively to produce viable populations. Population-management programmes for Black rhinoceros Diceros bicornis, White rhinoceros Ceratotherium simum and Indian rhinoceros Rhinoceros unicornis are operating in various regions of the zoo world, especially North America [Species Survival Plans (SSP)] and Europe [European Endangered Species Programmes (EEP)]. Analyses indicate that rhinoceros populations in captivity are achieving variable levels of viability. In SSP and EEP populations Black rhinoceros and White rhinoceros are genetically but not demographically satisfactory, while Indian rhinoceros is healthy demographically but limited genetically. Improvement is needed and could be achieved through better management. [source] Reactive grafting of glycidyl methacrylate onto polypropyleneJOURNAL OF APPLIED POLYMER SCIENCE, Issue 5 2010Emma-Louise Burton Abstract This work explored the melt-phase grafting of glycidyl methacrylate (GMA) onto polypropylene on a closely intermeshing corotating twin-screw extruder (16-mm screws, 40 : 1 length/diameter ratio). The modification of the base polypropylene to produce GMA-grafted polypropylene was achieved via peroxide-induced hydrogen abstraction from the polypropylene followed by the grafting of the GMA monomer or by the grafting of styrene followed by copolymerization with the GMA. In this study, both the position and order of the reactant addition were investigated as a route to improving graft yields and reducing side reactions (degradation). For the peroxide,GMA system, adding GMA to the melt before the peroxide resulted in significant improvements in the graft levels because of the improved dispersion of GMA in the melt. The addition of a comonomer (styrene) was explored as a second route to improving the graft yield. Although the addition of the comonomer led to a considerable rise in the level of grafted GMA, altering the order of the reactant addition was not found to contribute to an increase in the grafted GMA levels. However, variable levels of grafted styrene were achieved, and this may play an important role in the development of grafted polymers to suit specific needs. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010 [source] MMP-7 (matrilysin) expression in human brain tumorsMOLECULAR CARCINOGENESIS, Issue 6 2007Claire Rome Abstract Matrix metalloproteinases (MMP) which degrades protein components of the extra-cellular matrix and basement membrane seems to be largely involved in cancer invasiveness. MMP proteolitic activity essentially comes from stromal cells but matrilysin (MMP-7) is produced by the tumor itself. Thus, MMP-7 is investigated to address the particular invasive behavior of human glioma. Both MMP-7 mRNA and protein were clearly identified in human glioma. MMP-7 mRNA expression was highly variable within our glioma population. When analyzing MMP-7 mRNA expression in different primary brain tumors, we found highly variable levels of expression not related to their invasive behavior. In successive biopsies obtained in the same patients with glioblastoma, MMP-7 mRNA was quantified and appeared variable, but intra-individual variations were lower than inter-individual differences. With a xenograft model of U87 human tumors in RAG2/,c immune-deficient mice, the strict tumor origin of MMP-7 was shown. Additionally, MMP-7 expression by U87 cells which is low in culture was stimulated by these cells while forming tumors and the level of expression was higher when the tumor cells were implanted within the brain. These data provide some consistent information about cross-talk occurring between the tumor and the surrounding stroma to regulate MMP-7 expression. © 2007 Wiley-Liss, Inc. [source] Normal ranges of angiogenesis regulatory proteins in human platelets,AMERICAN JOURNAL OF HEMATOLOGY, Issue 7 2010Jon E. Peterson Platelets sequester angiogenesis regulatory proteins early in tumor growth, which suggests a new avenue for monitoring disease. To date, there are no clinically relevant reference ranges for markers of early angiogenesis. We introduce a new ELISA-based method for accurate and reproducible measurement of vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), platelet factor 4 (PF4), thrombospondin-1 (TSP-1), fibroblast growth factor, basic (bFGF), and endostatin in platelets. To facilitate clinical applicability, the platelet levels in isolated samples were determined utilizing a new actin ELISA method. Platelets from healthy donors at single and repetitive time points were used for the assessment of normal ranges of these proteins. The physiological levels in platelets were: VEGF (0.74 ± 0.37 pg/106 platelets); PDGF (23 ± 6 pg/106); PF4 (12 ± 5 ng/106); TSP-1 (31 ± 12 ng/106); bFGF (0.44 ± 0.15 pg/106); and endostatin (5.6 ± 3.0 pg/106). There was an excellent correlation (R2 = 0.7) between the platelet levels calculated with the actin ELISA and complete blood count. The levels of the platelets were higher than those in platelet-poor plasma by factors of: VEGF (215-fold); PDGF (914-fold); PF-4 (516-fold); TSP-1 (813-fold); and bFGF (17-fold). The endostatin levels were nearly equivalent. The biovariability of the platelet proteins in eight healthy subjects over a 5-week period was found to be minimal. We describe accurate and direct measurements of the concentrations of VEGF, bFGF, PDGF, TSP-1, endostatin, and PF4 in platelets of healthy human subjects. In contrast to the highly variable levels in plasma and serum, the platelet-derived measurements were accurate and reproducible with minimal biovariability. Am. J. Hematol., 2010. © 2010 Wiley-Liss, Inc. [source] Loss of Nkx3.1 expression in the transgenic adenocarcinoma of mouse prostate modelTHE PROSTATE, Issue 16 2007Carlise R. Bethel Abstract BACKGROUND The transgenic adenocarcinoma of mouse prostate (TRAMP) model has been extensively characterized at the histological and molecular levels, and has been shown to mimic significant features of human prostate cancer. However, the status of Nkx3.1 expression in the TRAMP model has not been elucidated. METHODS Immunohistochemical analyses were performed using dorsal, lateral, and ventral prostate (VP) lobes from ages 6 to 30 weeks. Quantitative RT-PCR analyses were performed to determine relative mRNA expression. RESULTS Heterogeneous loss of Nkx3.1 was observed in hyperplastic lesions of the ventral, dorsal, and lateral lobes. At 6 weeks of age, the ventral lobe displayed profound loss of Nkx3.1. Diminished Nkx3.1 protein was observed in well- to moderately-differentiated cancer lesions of all lobes. Poorly differentiated (PD) tumors stained negatively for Nkx3.1. Quantitative RT-PCR analyses revealed the presence of Nkx3.1 mRNA in each lobe at all ages, albeit reduced to variable levels. CONCLUSIONS These data suggest that disease progression in the TRAMP model may be driven by loss of function of Nkx3.1, in addition to p53 and Rb. Lobe-specific disease progression in the TRAMP model correlates with the reduction of Nkx3.1 protein. Regulation of Nkx3.1 expression during tumorigenesis appears to occur by post-transcriptional and post-translational mechanisms. Prostate 67: 1740,1750, 2007. © 2007 Wiley-Liss, Inc. [source] Presence and distribution of PAHs, PCBs and DDE in feed and sediments under salmon aquaculture cages in the Bay of Fundy, New Brunswick, CanadaAQUATIC CONSERVATION: MARINE AND FRESHWATER ECOSYSTEMS, Issue 4 2005J. Hellou Abstract 1.Wastes from feed and faeces can result in the deposition of contaminants in sediments around aquaculture sites. Five types of feed pellet, a commercial fish oil and 76 sediment samples collected under and up to 100 m away from salmon aquaculture cages in the south-western Bay of Fundy between 1998 and 2000 were analysed for polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and chlorinated pesticides. 2.Five alkylated naphthalenes (aNAs) were consistently detected in fish oil (116,180 ng g,1, per aNA), in pellets (25,51 ng g,1, dry weight, per aNA), and sediments (<1,45 ng g,1, dry weight, per aNA). Other PAHs were detected at variable levels in feed or in sediments. 3.IUPAC congener 153 (a PCB) and p,p,-dichlorodiphenyldichloroethylene (p,p,-DDE) were detected more frequently than other chlorinated targets in oil (108 ng g,1 and 176 ng g,1 respectively), feed (<1,14 ng g,1 and 1.7,28.2 ng g,1 respectively) and sediments (<0.08,3 ng g,1 and <0.5,7 ng g,1 respectively). 4.Trends were observed during the first year of sediment sampling (1998), with higher organic carbon, PCBs and p,p,-DDE levels below the cages than 50 m away. The PAHs other than aNA showed an opposite trend with distance. In 1999, levels of p,p,-DDE and PCBs were somewhat reduced under the cages, but were detected up to 100 m away from the cages. 5.Levels of aNA tended to be higher at some sites in 1999 relative to 1998, reflecting variability in feed and/or differential transport or degradation of contaminants relative to the environmental background. When detected, mean levels of PCBs and DDE were 2,10 times lower in 2000 than in 1999, and PAHs were 30,40% lower in 2000 than in 1999. 6.Interpretation of the results is done cautiously, since the exact locations of the sites sampled is only known to an intermediate facilitating the work between farmers and scientists. Levels of contaminants are compared with international results, interpreted relative to potential toxicity, uptake from feed, from deposited sediments, and in the framework of an aquaculture decision-support system published recently. Copyright © 2005 John Wiley & Sons, Ltd. [source] Do virus-resistant plants pose a threat to non-target ecosystems?AUSTRAL ECOLOGY, Issue 5 2009Abstract One key environmental risk associated with the release of novel disease-resistant plants is the potential for non-target host populations to acquire resistance genes and undergo enemy release, leading to damage to associated native plant populations in high conservation-value ecosystems. Unfortunately, the dynamics of most natural pathosystems are poorly understood, and risk assessment of disease-resistant plants remains a challenge. Here we describe the first stage of a multi-tiered risk assessment strategy aimed at quantifying potential ecological release in a model pathosystem (the weedy pasture species Trifolium repens infected with Clover yellow vein virus; ClYVV) in order to assess the level of risk posed by genetically modified and conventionally bred disease-resistant host genotypes to non-target plant communities in south-eastern Australia. Glasshouse inoculation and growth experiments using 14 ClYVV isolates and 20 wild T. repens lines collected from high conservation-value montane grassland and woodland communities show that viral infection reduces the survival and growth of host plants by on average 10,50%. However, T. repens lines exhibited variable levels of resistance and tolerance to virus infection and ClYVV isolates differed in infectivity and aggressiveness, with grassland isolates having a greater pathogenic effect on associated host plants than woodland isolates. We conclude that ClYVV potentially plays an important role in limiting the size of T. repens populations in some at-risk non-target ecosystems and that second-tier field experiments are required to adequately quantify the risk associated with the commercial release of V-R T. repens genotypes in Australia. [source] Artificial infestation of sorghum spikelets with eggs of Stenodiplosis sorghicola (Coquillett) (Diptera: Cecidomyiidae) by water injectionAUSTRALIAN JOURNAL OF ENTOMOLOGY, Issue 4 2001Adam T Hardy Abstract A technique for artificially infesting sorghum spikelets with eggs of sorghum midge is described and compared with natural oviposition achieved in a glasshouse cage trial. This technique was developed to facilitate antibiosis resistance related studies of midge biology, and to overcome the reduced and inconsistent oviposition achieved in sorghum lines that contain ovipositional-antixenosis resistance. Injecting an aqueous suspension of exactly two midge eggs between the glumes of individual sorghum spikelets using a micropipette produced consistent, low egg densities across five lines of varying resistance (0.8,1.2 eggs per spikelet; 50,70% infestation), while water injection of four to six eggs per spikelet in the same lines produced high and consistent egg densities (two to three eggs per spikelet; > 80% infestation). In contrast to both of the water-injection treatments, natural oviposition within the same five lines produced inconsistent egg densities, even when midge densities were adjusted to account for the variable levels of ovipositional antixenosis present in each line (one to four eggs per spikelet; 40,80% infestation). A bioassay was also conducted to determine the effect of suspending midge eggs in water on egg hatch, neonate survival and fitness. Aqueous suspensions of midge eggs stored for 4 h at room temperature produced 79% egg hatch. However, aqueous egg suspensions refrigerated at 4°C for 1,7 days reduced egg hatch (41,64%), lowered larval longevity and reduced maximum movement of neonate larvae. No eggs hatched after 14 days of refrigerated storage. [source] PATIENT VIEWS ON THE MANAGEMENT OF RHEUMATIC FEVER AND RHEUMATIC HEART DISEASE IN THE KIMBERLEY: A QUALITATIVE STUDYAUSTRALIAN JOURNAL OF RURAL HEALTH, Issue 6 2003Christine M. Mincham ABSTRACT Objective:,To describe, from a patient perspective, factors leading to suboptimal management of individuals with rheumatic fever (RF) and rheumatic heart disease (RHD) among members of the Kimberley population. Method:,Qualitative in-depth semistructured and repeated interviews of seven Kimberley patients, or parents of children, with rheumatic fever and/or rheumatic heart disease, during 1998. Results:,Participants showed variable levels of understanding about RF/RHD, often relating to the need for secondary prophylaxis. Compliance with medication was closely linked with positive patient,staff interactions. From the perspective of health care, living in a remote location was frequently described as a negative influence. Participants desire more accessible and culturally appropriate opportunities for learning about their disease. Conclusions:,Participants focused on issues closely related to effective and ineffective management of RF/RHD. The lessons learned are indicators for health staff attempting to improve the quality of management that people receive. [source] Effects of glucose and insulin on HepG2-C3A cell metabolismBIOTECHNOLOGY & BIOENGINEERING, Issue 2 2010Vidya V. Iyer Abstract HepG2, hepatocellular carcinoma cells, are used in drug toxicity studies and have also been explored for bioartificial livers. For these applications, the cells are under variable levels of nutrients and hormones, the effects of which on metabolism are poorly understood. In this study, HepG2-C3A cells were cultured under varying levels of glucose (high, low, and glucose-free) and insulin (without and with physiological levels of insulin) for 5 days. Cell growth was found to be comparable between high and low glucose media and lowest for glucose-free medium. Several features of central metabolism were affected profoundly by the medium glucose levels. Glucose consumption was greater for low glucose medium compared to high glucose medium, consistent with known glucose feedback regulation mechanisms. Urea productivity was highest in glucose-free medium. Further, it was seen that lactate acted as an alternative carbon source in the absence of glucose, whereas it acted as a sink for the high and low glucose media. Using a metabolic network flexibility analysis (MNFA) framework with stoichiometric and thermodynamic constraints, intracellular fluxes under varying levels of glucose and insulin were evaluated. The analysis indicates that urea production in HepG2-C3A cells arises via the arginase II pathway rather than from ammonia detoxification. Further, involvement of the putrescine metabolism with glutamine metabolism caused higher urea production in glucose-free medium consistent with higher glutamine uptake. MNFA indicated that in high and low glucose media, glycolysis, glutaminolysis, and oxidative phosphorylation were the main sources of energy (NADH, NADPH, and ATP). In the glucose-free medium, due to very low glycolytic flux, higher malate to pyruvate glutaminolytic flux and TCA cycle contributed more significantly to energy metabolism. The presence of insulin lowered glycerol uptake and corresponding fluxes involved in lipid metabolism for all glucose levels but otherwise exerted negligible effect on metabolism. HepG2-C3A cells thus show distinct differences from primary hepatocytes in terms of energy metabolism and urea production. This knowledge can be used to design media supplements and metabolically engineer cells to restore necessary hepatic functions to HepG2-C3A cells for a range of applications. Biotechnol. Bioeng. 2010;107: 347,356. © 2010 Wiley Periodicals, Inc. [source] Adiponectin inhibits the growth and peritoneal metastasis of gastric cancer through its specific membrane receptors AdipoR1 and AdipoR2CANCER SCIENCE, Issue 7 2007Makoto Ishikawa Adiponectin, a circulating peptide hormone produced in adipose tissue, has been shown to be reduced in the plasma of patients with cancer, suggesting that this adipokine may be mechanically involved in the pathogenesis of adiposity-related carcinogenesis. In this study, we examined the expression of adiponectin receptors (AdipoR1 and AdipoR2) and assessed the function of adiponectin in gastric cancer. All of the six gastric cancer cell lines significantly expressed mRNA and protein of both receptors with variable levels. Addition of 30 µg/mL adiponectin potently induced apoptosis and inhibited the proliferation of AZ521 and HCG27. Down-regulation of either AdipoR1 or AdipoR2 by specific siRNA significantly suppressed the growth inhibitory effects of adiponectin in both cell lines. Moreover, a local injection of adiponectin markedly inhibited the growth of AZ521 inoculated subcutaneously in nude mice. Similarly, the continuous intraperitoneal infusion of adiponectin effectively suppressed the development of peritoneal metastasis of AZ521. Adiponectin negatively regulates the progression of gastric cancer cells possibly through both AdipoR1 and AdipoR2. Although adiponectin was already reported to have antiangiogenic effects, our results suggest that the antitumor effect of adiponectin was, at least partially, dependent on the direct effects on tumor cells. (Cancer Sci 2007; 98: 1120,1127) [source] The lacrimal fascia redefinedCLINICAL ANATOMY, Issue 6 2001Harumichi Shinohara Abstract It has been commonly accepted that the lacrimal fascia is an intact septum, composed of connective tissue, that separates the orbital cavity into a large compartment, which contains the eyeball, and a small compartment, which contains the lacrimal sac and nasolacrimal duct. the septum, however, is not necessarily always intact. We found a circular or oval opening in the lacrimal fascia in 37 of 52 specimens (71.2%) examined. The opening, which we shall refer to as the lacrimal fascial foramen, was located at variable levels in the lacrimal fossa. The lacrimal fascial foramen was buried in fatty tissue through which passed a branch of either the inferior palpebral artery or the infraorbital artery and a vein of the nasolacrimal duct. The clinical implications of the lacrimal fascial foramen in obstruction of the nasolacrimal duct are discussed. Clin. Anat. 6:401,405, 2001. © 2001 Wiley-Liss, Inc. [source] Low-level glycopeptide resistance in methicillin-resistant Staphylococcus aureus and how to test itCLINICAL MICROBIOLOGY AND INFECTION, Issue 2009P. M. Hawkey Abstract Vancomycin resistance in Staphylococcus aureus has emerged over the last ten years due to varying mechanisms and giving variable levels of resistance to vancomycin. The most resistant strains (fortunately rare) bear the vanA gene cluster and these are generally recognisable as MICs of vancomycin are usually found to be in the range 32-64mg/L. It should be noted that some automated systems have failed to detect these isolates. The much more commonly encountered GISA and hGISA vancomycin resistant strains of MRSA and methicillin sensitive Staph. aureus (MSSA) exhibit lower levels of resistance and difficulty is encountered in reliably defining and identifying these strains in clinical laboratories. No single completely reliable, convenient test either phonotypical genetic currently exists which can be readily applied in the clinical laboratory for the detection of hGISA/GISA. The population analysis profile (PAP) method is currently regarded as the reference method but is slow and tedious to perform on a large number of isolates. This enables the differentiation of hGISA and GISA from fully vancomycin sensitive strains. In the clinical laboratory the use of Meuller-Hinton agar with 5mg/L teicoplanin and a 10,L innoculum of MacFarland 0.5 incubated for 48h represents the most reliable and economical screening test. Further confirmation would be required using either macrodilution Etest methodology using an MIC , 8mg/L of vancomycin and/or teicoplanin as the cut off for hGISA or the newer GRD (glycopeptide resistance detection) strip. [source] | ||||||||||||||||