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Specific Indicator (specific + indicator)
Selected AbstractsTransport of phosphatidylinositol 3-phosphate into the vacuole via autophagic membranes in Saccharomyces cerevisiaeGENES TO CELLS, Issue 6 2008Keisuke Obara Vps34, the sole PtdIns 3-kinase in yeast, is essential for autophagy. Here, we show that the lipid-kinase activity of Vps34 is required for autophagy, implying an essential role of its product PtdIns(3)P. The protein-kinase activity of Vps15, a regulatory subunit of the PtdIns 3-kinase complex, is also required for efficient autophagy. We monitored the distribution of PtdIns(3)P in living cells using a specific indicator, the 2xFYVE domain derived from mammalian Hrs. PtdIns(3)P was abundant at endosomes and on the vacuolar membrane during logarithmic growth phase. Under starvation conditions, we observed massive transport of PtdIns(3)P into the vacuole. This accumulation was dependent on the membrane dynamics of autophagy. Notably, PtdIns(3)P was highly enriched and delivered into the vacuole as a component of autophagosome membranes but not as a cargo enclosed within them, implying direct involvement of this phosphoinositide in autophagosome formation. We also found a possible enrichment of PtdIns(3)P on the inner autophagosomal membrane compared to the outer membrane. Based on these results we discuss the function of PtdIns(3)P in autophagy. [source] Oxidative damage is a potential cause of cone cell death in retinitis pigmentosaJOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2005JiKui Shen Retinitis pigmentosa (RP) is a prevalent cause of blindness caused by a large number of different mutations in many different genes. The mutations result in rod photoreceptor cell death, but it is unknown why cones die. In this study, we tested the hypothesis that cones die from oxidative damage by performing immunohistochemical staining for biomarkers of oxidative damage in a transgenic pig model of RP. The presence of acrolein- and 4-hydroxynonenal-adducts on proteins is a specific indicator that lipid peroxidation has occurred, and there was strong immunofluorescent staining for both in cone inner segments (IS) of two 10-month-old transgenic pigs in which almost all rods had died, compared to faint staining in two 10-month-old control pig retinas. In 22- and 24-month-old transgenic pigs in which all rods and many cones had died, staining was strong in cone axons and some cell bodies as well as IS indicating progression in oxidative damage between 10 and 22 months. Biomarkers for oxidative damage to proteins and DNA also showed progressive oxidative damage to those macromolecules in cones during the course of RP. These data support the hypothesis that the death of rods results in decreased oxygen consumption and hyperoxia in the outer retina resulting in gradual cone cell death from oxidative damage. This hypothesis has important therapeutic implications and deserves rapid evaluation. © 2005 Wiley-Liss, Inc. [source] Early childhood temperament in Pediatric bipolar disorder and attention deficit hyperactivity disorderJOURNAL OF CLINICAL PSYCHOLOGY, Issue 4 2008Amy E. West Abstract Recent theories suggest that children with pediatric bipolar disorder (PBD) may exhibit more difficult temperaments premorbidly, including traits such as behavioral disinhibition and difficulty with emotion regulation. We investigated temperament characteristics retrospectively during infancy and toddlerhood in subjects with PBD (n=25), attention-deficit/hyperactivity disorder (ADHD; n=25), and healthy controls (n=25). Children with PBD were reported to experience increased difficult temperament in both infancy and toddlerhood compared to children with ADHD. Several characteristics of difficult temperament were associated with residual symptoms of mania and depression. Difficult premorbid temperament characteristics may be a specific indicator of a bipolar diathesis, or might signal underlying dysfunction in affective processes that significantly increase risk for a mood disorder. © 2008 Wiley Periodicals, Inc. J Clin Psychol 64:1,20, 2008. [source] The role of edema and demyelination in chronic T1 black holes: A quantitative magnetization transfer study,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2005Ives Levesque MSc Abstract Purpose To use quantitative magnetization transfer imaging (qMTI) in an investigation of T1 -weighted hypointensity observed in clinical magnetic resonance imaging (MRI) scans of multiple sclerosis (MS) patients, which has previously been proposed as a more specific indicator of tissue damage than the more commonly detected T2 hyperintensity. Materials and Methods A cross-sectional study of 10 MS patients was performed using qMTI. A total of 60 MTI measurements were collected in each patient at a resolution of 2 × 2 × 7 mm, over a range of saturation pulses. The observed T1 and T2 were also measured. qMT model parameters were estimated using a voxel-by-voxel fit. Results A total of 65 T2 -hyperintense lesions were identified; 53 were also T1 hypointense. In these black holes, the qMTI-derived semisolid pool fraction F correlated negatively with T1,obs (r2 = 0.76; P < 0.0001). The water pool absolute size (PDf) showed a weaker correlation with T1,obs (positive, r2 = 0.53; P < 0.0001). The magnetization transfer ratio (MTR) showed a similarly strong correlation with F and a weaker correlation with PDf (r2 = 0.18; P < 0.04). Conclusion T1 increases in chronic black holes strongly correlated with the decline in semisolid pool size, and somewhat less to the confounding effect of edema. MTR was less sensitive than T1,obs to liquid pool changes associated with edema. J. Magn. Reson. Imaging 2005;21:103,110. © 2005 Wiley-Liss, Inc. [source] Prognostic significance of CEA levels and detection of CEA mRNA in draining venous blood in patients with colorectal cancerJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2006Ioannis Kanellos MD Abstract Background and Objectives: The aims of this study were to determine carcinoembryonic antigen (CEA) levels and incidence of tumor cells using the RT-PCR technique in draining venous blood of patients with colorectal cancer, correlate the results with various histopathologic factors and determine their significance as prognostic factors. Methods: From 1995 to 2000, 108 patients with adenocarcinoma of the colon or rectum, underwent curative surgery and enrolled in this prospective study. Results: The 5-year survival group had significantly lower portal CEA levels compared to the hepatic metastasis outcome group. CEA mRNA was positive in the draining venous blood from 12 (11.1%) out of 108 patients included in the study. The rate of positive tumor cell detection in portal blood was significantly higher in the hepatic metastasis outcome group than in the 5-year survival and recurrence group. The proportion of patients with portal CEA ,5 ng/ml was greater in patients with higher stage than in patients with lower stage. Conclusions: Positive CEA mRNA in draining venous blood predicted hepatic metastases and local recurrence with accuracy over 80% but with low sensitivity of 30% and 9%, respectively. Moreover, CEA level was a sensitive indicator in hepatic metastases as sensitivity was 95% and a specific indicator in predicting 5-year survival with specificity 84%. J. Surg. Oncol. 2006;94:3,8. © 2006 Wiley-Liss, Inc. [source] Mitochondrial morphology transition is an early indicator of subsequent cell death in ArabidopsisNEW PHYTOLOGIST, Issue 1 2008Iain Scott Summary ,,Mitochondrial morphology and dynamics were investigated during the onset of cell death in Arabidopsis thaliana. Cell death was induced by either chemical (reactive oxygen species (ROS)) or physical (heat) shock. ,,Changes in mitochondrial morphology in leaf tissue, or isolated protoplasts, each expressing mitochondrial-targeted green fluorescent protein (GFP), were observed by epifluorescence microscopy, and quantified. ,,Chemical induction of ROS production, or a mild heat shock, caused a rapid and consistent change in mitochondrial morphology (termed the mitochondrial morphology transition) that preceded cell death. Treatment of protoplasts with a cell-permeable superoxide dismutase analogue, TEMPOL, blocked this morphology change. Incubation of protoplasts in micromolar concentrations of the calcium channel-blocker lanthanum chloride, or the permeability transition pore inhibitor cyclosporin A, prevented both the mitochondrial morphology transition and subsequent cell death. ,,It is concluded that the observed mitochondrial morphology transition is an early and specific indicator of cell death and is a necessary component of the cell death process. [source] DNA image cytometry in malignant and benign sweat gland tumoursBRITISH JOURNAL OF DERMATOLOGY, Issue 4 2000M. Vogelbruch The histopathological differentiation between well-differentiated carcinomas and atypical adenomas of sweat gland origin may be difficult, even if immunohistochemical methods are used. Therefore, additional techniques may be helpful. We previously demonstrated that DNA image cytometry (ICM-DNA) can be useful in distinguishing between malignant and benign clear cell hidradenoma. In the present study, a larger series of sweat gland tumours, with a clear-cut diagnosis as malignant or benign on histopathological criteria, was examined by ICM-DNA. Enzymatic cell separation specimens were prepared from paraffin-embedded tissues of 18 sweat gland carcinomas (14 porocarcinomas, one classic eccrine adenocarcinoma, two microcystic adnexal carcinomas and one mostly ductal apocrine carcinoma) and 47 benign sweat gland tumours (three syringocystadenomas, five spiradenomas, 14 cylindromas, three syringomas, seven nodular hidradenomas, 10 cutaneous mixed tumours, four poromas and one apocrine hidrocystoma). Specimens were examined by ICM-DNA according to the current recommendations of the European Society for Analytical Cellular Pathology with the AutoCyte QUIC-DNA workstation using mesenchymal cells as an internal reference. DNA aneuploidy was detected by the stemline interpretation according to Böcking and/or at least three 5[c]-exceeding events. DNA aneuploidy was detected in 16 of 18 (89%) of the sweat gland carcinomas, but in none of the 47 adenomas. These results suggest that the detection of DNA aneuploidy in sweat gland tumours using ICM-DNA is a clear and specific indicator of prospective malignancy. [source] INDUSTRIAL SHIFT, POLARIZED LABOR MARKETS AND URBAN VIOLENCE: MODELING THE DYNAMICS BETWEEN THE ECONOMIC TRANSFORMATION AND DISAGGREGATED HOMICIDE,CRIMINOLOGY, Issue 3 2004KAREN F. PARKER Industrial restructuring marks the removal of a manufacturing and production-based economy in urban areas, which had served as a catalyst in concentrating disadvantage and polarizing labor markets since the 1970s. Although scholars have established a relationship between concentrated disadvantage , poverty, joblessness, racial residential segregation , and urban violence in cross-sectional studies, this literature has yet to estimate whether economic restructuring contributed to the change in urban homicide over time. Modeling this relationship requires an analytical strategy that incorporates specific indicators of (race and gender) polarized labor markets, separate from indicators of urban disadvantage, on disaggregated homicides while taking into account the growing dependency of urban cities on formal social control (via police presence and rise in incarceration). In this study I provide a theoretical rationale for linking industrial restructuring to urban homicide. Using a multivariate strategy to capture the shift in labor market forces and disaggregated homicides from 1980 to 1990, I also estimate the impact of this relationship. The results provide evidence of the industrial ship and documents both the decline in Manufacturing jobs for black males and black females and a growth in the service sector opportunities for white males only. I also find that industrial restructuring had a unique impact on disaggregated homicide beyond what has previously been established in cross-sectional studies. [source] Relations between open-field, elevated plus-maze, and emergence tests in C57BL/6J and BALB/c mice injected with GABA- and 5HT-anxiolytic agentsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2010Robert Lalonde Abstract Two 5HT1A receptor agonists and chlordiazepoxide were examined in open-field, elevated plus maze, and emergence tests. At doses with no effect in the open-field, chlordiazepoxide increased open and open/total arm visits as well as open arm duration in the elevated plus maze, whereas 5HT1A receptor agonists showed an anxiolytic response on a single measure. The anxiolytic action of chlordiazepoxide was limited to the less active BALB/c strain. Unlike the 5HT1A receptor agonists, chlordiazepoxide was also anxiolytic in the emergence test, once again only in BALB/c and not C57BL/6J mice. Significant correlations were found between emergence latencies and specific indicators of anxiety in the elevated plus-maze in chlordiazepoxide-treated but not in mice treated with buspirone and 8-OH-DPAT. These results indicate that elevated plus-maze and emergence tests depend on benzodiazepine receptors. In contrast, 5HT1A receptor agonists were ineffective in the emergence test and no correlation was found between emergence latencies and specific indicators of anxiety in the elevated plus-maze. Though superficially similar, the emergence test seems to tap into a partially separate facet of anxiety. [source] Measuring the quality of hospital care: an inventory of indicatorsINTERNAL MEDICINE JOURNAL, Issue 6 2009B. Copnell Abstract Background: Development of indicators to measure health-care quality has progressed rapidly. This development has, however, rarely occurred in a systematic fashion, and some aspects of care have received more attention than others. The aim of this study is to identify and classify indicators currently in use to measure the quality of care provided by hospitals, and to identify gaps in current measurement. Methods: A literature search was undertaken to identify indicator sets. Indicators were included if they related to hospital care and were clearly being collected and reported to an external body. A two-person independent review was undertaken to classify indicators according to aspects of care provision (structure, process or outcome), dimensions of quality (safety, effectiveness, efficiency, timeliness, patient-centredness and equity), and domain of application (hospital-wide, surgical and non-surgical clinical specialities). Results: 383 discrete indicators were identified from 22 source organizations or projects. Of these, 27.2% were relevant hospital-wide, 26.1% to surgical patients and 46.7% to non-surgical specialities, departments or diseases. Cardiothoracic surgery, cardiology and mental health were the specialities with greatest coverage, while nine clinical specialities had fewer than three specific indicators. Processes of care were measured by 54.0% of indicators and outcomes by 38.9%. Safety and effectiveness were the domains most frequently represented, with relatively few indicators measuring the other dimensions. Conclusion: Despite the large number of available indicators, significant gaps in measurement still exist. Development of indicators to address these gaps should be a priority. Work is also required to evaluate whether existing indicators measure what they purport to measure. [source] dUTP Pyrophosphatase, its appearance in extracellular compartment may serve as a potential biomarker for N -methyl- N' -nitro- N -nitrosoguanidine exposure in mammalian cellsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 10 2006Meiping Wu Abstract The monofunctional alkylating agent N -methyl- N' -nitro- N -nitrosoguanidine (MNNG) is a model chemical widely used for studying the molecular events induced by the widespread environmental N -nitroso alkylating carcinogen. Many studies have focused on understanding MNNG-induced mutagenesis and carcinogenesis. However, the search for specific indicators of MNNG exposure is still underway. In this study, we analyzed the proteins in culture medium of human amnion epithelial cells (FL,cells) exposed to MNNG by 2-DE followed by MALDI-TOF,MS, in the hope of finding a specific protein marker suitable for MNNG risk assessment. Image visualization and statistical analysis indicated that 12,spots appeared and 4,spots up-regulated after MNNG exposure. Most of them were identified by MS. These proteins include nuclear isoform of dUTP pyrophosphatase (DUT-N), phosphoglycerate mutase,1, heparan sulfate proteoglycan perlecan, etc., which are involved in multiple cellular functions. Interestingly, 2-DE and MS analyses of cell lysate exposed to MNNG revealed that DUT-N was down-regulated. The appearance of DUT-N in culture medium and its down-regulation in cell lysate was confirmed by Western blot. These data suggest that these proteins, especially DUT-N, could be used as candidate biomarkers for monitoring MNNG exposure. [source] | |||||||||||||