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Potential Pathways (potential + pathway)
Selected AbstractsEpidemiology, risk factors, and pathogenesis of cholangiocarcinomaHPB, Issue 2 2008S. A. KHAN Abstract Cholangiocarcinoma (CCA) is a fatal cancer of the biliary epithelium, arising either within the liver (intrahepatic, ICC) or in the extrahepatic bile ducts (extrahepatic ECC). Globally, CCA is the second most common primary hepatic malignancy. Several recent epidemiological studies have shown that the incidence and mortality rates of ICC are increasing. This review of the literature on the international epidemiological rates of CCA, both intra- and extrahepatic, explores possible explanations for the trends found. The possible role of epidemiological artifact in the findings is discussed and the known risk factors for CCA are summarized. These include primary sclerosing cholangitis, liver fluke infestation, congenital fibropolycystic liver, bile duct adenomas, and biliary papillomatosis, hepatolithiasis, chemical carcinogens such as nitrosamines, Thorotrast, chronic viral hepatitis, cirrhosis, chronic non-alcoholic liver disease and obesity. Potential pathways involved in the molecular pathogenesis of CCA are also summarized. [source] Exploring the perspective of midwives involved in offering serum screening for Down's syndrome in Northern IrelandJOURNAL OF CLINICAL NURSING, Issue 20 2009Jennifer McNeill Aims., To explore the perspective of midwives offering serum screening for Down's syndrome. Background., Previous literature has indicated that the offer and discussion of prenatal serum screening tests with women is complex, and health professionals may influence women's decisions to accept or decline screening. Midwives are usually the key professional to offer serum screening for Down's syndrome in the UK but their perspective is relatively neglected in the literature. Design., An explorative qualitative interview study with 15 midwives employed in a maternity unit in Northern Ireland involved in offering prenatal screening to pregnant women. Data were collected from 1 July 2005,31 October 2005. Methods., A focused ethnographic approach was used to explore the perspective of midwives. Results., Midwives reported difficulty in explaining the test to women and felt unable to provide the necessary information to adequately inform women within their appointment time. The test offered (the triple test) and potential pathway of subsequent care, were identified as sources of professional and personal conflict by midwives. The expectation that midwives would provide a universal offer of Down's syndrome serum screening but be unable to support women regarding termination of pregnancy also created dissonance. Conclusions., The feasibility of proceeding with a universal serum screening programme for Down's syndrome is questionable in countries which legally or culturally oppose termination of pregnancy. Professionals practising within environments such as this experience conflict in their role, which affects communication with women when discussing screening tests. Relevance to clinical practice., As midwives are often, the primary health professional providing information to women, it is important that midwives are key participants in ongoing planning and discussions about screening policy to ensure programmes are implemented successfully. [source] Common carp tissue reactions to surgically implanted radio tags with external antennasJOURNAL OF FISH BIOLOGY, Issue 1 2007C. Bauer Examination of common carp Cyprinus carpio, carrying implanted telemetry transmitters, showed that wound healing was incomplete after 4 months and completed after 1 year. Granulation tissue, which encapsulated the transmitter, adhered to the intestine and liver. The liver was infiltrated by the granulation tissue after 1 year. Epidermal tissue grew down the channel for the antenna, establishing a potential pathway for pathogens. No signs of infections, however, were found. [source] Activation of AMP-activated protein kinase by adiponectin rescues salivary gland epithelial cells from spontaneous and interferon-,,induced apoptosisARTHRITIS & RHEUMATISM, Issue 2 2010Stergios Katsiougiannis Objective Primary Sjögren's syndrome (SS) is an autoimmune disease characterized by lymphocytic infiltrates associated with destruction of salivary gland epithelial cells (SGECs) induced mainly by apoptosis. Adiponectin is an immunoregulatory hormone. We have previously shown that SGECs from patients with primary SS as well as from controls differentially express adiponectin. SGECs derived from patients with primary SS constitutively produce and secrete adiponectin in higher quantities. The aim of this study was to investigate the effect of adiponectin on the proliferation and apoptosis of SGECs. Methods Cultured, non-neoplastic SGECs were treated with recombinant human adiponectin, and the rate of cell proliferation was assessed. Spontaneous and interferon-, (IFN,),induced apoptosis was evaluated with a specific single-stranded DNA enzyme-linked immunosorbent assay. The AMP-activated protein kinase (AMPK) inhibitor Compound C was used to test the involvement of AMPK in adiponectin effects. Western blotting was applied to detect the phosphorylation levels of AMPK after adiponectin treatment. Results Adiponectin treatment resulted in a dose-dependent suppression of proliferation of SGECs from patients with primary SS and control donors. Adiponectin protected cells from spontaneous as well as from IFN,-induced apoptosis. Furthermore, the antiapoptotic effects of adiponectin were dependent upon AMPK phosphorylation at Thr172, since pretreatment of SGECs with Compound C abolished the adiponectin protective effect. Conclusion Adiponectin exerted antiproliferative effects on SGECs without inducing apoptosis and protected SGECs from spontaneous as well as from IFN,-induced apoptosis through an AMPK-dependent pathway. Our observations suggest that adiponectin may protect SGECs in this specific inflammatory milieu, providing a potential pathway through which AMPK may regulate cell survival under energy stress conditions such as autoimmune inflammation. [source] THE ADAPTIVE SIGNIFICANCE OF TEMPERATURE-DEPENDENT SEX DETERMINATION: EXPERIMENTAL TESTS WITH A SHORT-LIVED LIZARDEVOLUTION, Issue 10 2005Daniel A. Warner Abstract Why is the sex of many reptiles determined by the temperatures that these animals experience during embryogenesis, rather than by their genes? The Charnov-Bull model suggests that temperature-dependent sex determination (TSD) can enhance maternal fitness relative to genotypic sex determination (GSD) if offspring traits affect fitness differently for sons versus daughters and nest temperatures either determine or predict those offspring traits. Although potential pathways for such effects have attracted much speculation, empirical tests largely have been precluded by logistical constraints (i.e., long life spans and late maturation of most TSD reptiles). We experimentally tested four differential fitness models within the Charnov-Bull framework, using a short-lived, early-maturing Australian lizard (Amphibolurus muricatus) with TSD. Eggs from wild-caught females were incubated at a range of thermal regimes, and the resultant hatchlings raised in large outdoor enclosures. We applied an aromatase inhibitor to half the eggs to override thermal effects on sex determination, thus decoupling sex and incubation temperature. Based on relationships between incubation temperatures, hatching dates, morphology, growth, and survival of hatchlings in their first season, we were able to reject three of the four differential fitness models. First, matching offspring sex to egg size was not plausible because the relationship between egg (offspring) size and fitness was similar in the two sexes. Second, sex differences in optimal incubation temperatures were not evident, because (1) although incubation temperature influenced offspring phenotypes and growth, it did so in similar ways in sons versus daughters, and (2) the relationship between phenotypic traits and fitness was similar in the two sexes, at least during preadult life. We were unable to reject a fourth model, in which TSD enhances offspring fitness by generating seasonal shifts in offspring sex ratio: that is, TSD allows overproduction of daughters (the sex likely to benefit most from early hatching) early in the nesting season. In keeping with this model, hatching early in the season massively enhanced body size at the beginning of the first winter, albeit with a significant decline in probability of survival. Thus, the timing of hatching is likely to influence reproductive success in this short-lived, early maturing species; and this effect may well differ between the sexes. [source] Arsenic in Glacial Drift Aquifers and the Implication for Drinking Water,Lower Illinois River BasinGROUND WATER, Issue 3 2001Kelly L. Warner The lower Illinois River Basin (LIRB) covers 47,000 km2 of central and western Illinois. In the LIRB, 90% of the ground water supplies are from the deep and shallow glacial drift aquifers. The deep glacial drift aquifer (DGDA) is below 152 m altitude, a sand and gravel deposit that fills the Mahomet Buried Bedrock Valley, and overlain by more than 30.5 m of clayey till. The LIRB is part of the USGS National Water Quality Assessment program, which has an objective to describe the status and trends of surface and ground water quality. In the DGDA, 55% of the wells used for public drinking-water supply and 43% of the wells used for domestic drinking water supply have arsenic concentrations above 10 ,g/L (a new U.S. EPA drinking water standard). Arsenic concentrations greater than 25 ,g/L in ground water are mostly in the form of arsenite (AsIII). The proportion of arsenate (AsV) to arsenite does not change along the flowpath of the DGDA. Because of the limited number of arsenic species analyses, no clear relations between species and other trace elements, major ions, or physical parameters could be established. Arsenic and barium concentrations increase from east to west in the DGDA and are positively correlated. Chloride and arsenic are positively correlated and provide evidence that arsenic may be derived locally from underlying bedrock. Solid phase geochemical analysis of the till, sand and gravel, and bedrock show the highest presence of arsenic in the underlying organic-rich carbonate bedrock. The black shale or coal within the organic-rich carbonate bedrock is a potential source of arsenic. Most high arsenic concentrations found in the DGDA are west and downgradient of the bedrock structural features. Geologic structures in the bedrock are potential pathways for recharge to the DGDA from surrounding bedrock. [source] Deterministic and Stochastic Modeling of Aquifer Stratigraphy, South CarolinaGROUND WATER, Issue 2 2000Russell B. Miller Deterministic and stochastic methods of three-dimensional hydrogeologic modeling are applied to characterization of contaminated Eocene aquifers at the Savannah River Site, South Carolina. The results address several important issues, including the use of multiple types of data in creating high-resolution aquifer models and the application of sequence-stratigraphic constraints. Specific procedures used include defining grid architecture stratigraphically, upscaling, modeling lithologic properties, and creating multiple equiprobable realizations of aquifer stratigraphy. An important question answered by the study is how to incorporate gamma-ray borehole-geophysical data in areas of anomalous log response, which occurs commonly in aquifers and confining units of the Atlantic Coastal Plain and other areas. To overcome this problem, gamma-ray models were conditioned to grain-size and lithofacies realizations. The investigation contributes to identifying potential pathways for downward migration of contaminants, which have been detected in confined aquifers at the modeling site. The approach followed in this investigation produces quantitative, stratigraphically constrained, geocellular models that incorporate multiple types of data from borehole-geophysical logs and continuous cores. The use of core-based stochastic realizations in conditioning deterministic models provides the advantage of incorporating lithologic information based on direct observations of cores rather than using only indirect measurements from geophysical logs. The high resolution of the models is demonstrated by the representation of thin, discontinuous clay beds that act as local barriers to flow. The models are effective in depicting the contrasts in geometry and heterogeneity between sheet-like nearshore-transgressive sands and laterally discontinuous sands of complex shoreline environments. [source] Fibroblast activation protein increases apoptosis, cell adhesion, and migration by the LX-2 human stellate cell line,HEPATOLOGY, Issue 4 2005Xin Maggie Wang Injury and repair in chronic liver disease involve cell adhesion, migration, apoptosis, proliferation, and a wound healing response. In liver, fibroblast activation protein (FAP) has both collagenase and dipeptidyl peptidase IV (DPIV) activities and is expressed only by activated hepatic stellate cells (HSC) and myofibroblasts, which produce and degrade extracellular matrix (ECM). FAP was colocalized with collagen fibers, fibronectin, and collagen type I in human liver. FAP function was examined in vitro by expressing green fluorescent protein FAP fusion protein in cell lines cultured on collagen-I, fibronectin, and Matrigel. Glutamates at 203 and 204 as well as serine624 of FAP were essential for peptidase activity. Human embryonic kidney 293T cells overexpressing FAP showed reduced adhesion and migration. FAP overexpression in the human HSC line LX-2 caused increased cell adhesion and migration on ECM proteins as well as invasion across transwells in the absence or presence of transforming growth factor beta-1. FAP overexpression enhanced staurosporine streptomyces,stimulated apoptosis in both cell lines. Interestingly, the enzyme activity of FAP was not required for these functions. Overexpressing FAP increased the expression of matrix metalloproteinase-2 and CD44 and reduced integrin-,1 expression in 293T cells, suggesting potential pathways of FAP-mediated impairment of cell adhesion and migration in this epithelial cell line. In conclusion, these findings further support a pro-fibrogenic role for FAP by indicating that, in addition to its enzymatic functions, FAP has important nonenzymatic functions that in chronic liver injury may facilitate tissue remodeling through FAP-mediated enhancement of HSC cell adhesion, migration, and apoptosis. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005;42:935,945.) [source] Solute movement through intact columns of cryoturbated Upper ChalkHYDROLOGICAL PROCESSES, Issue 13 2008M. Mahmood-ul-Hassan Abstract Cryoturbated Upper Chalk is a dichotomous porous medium wherein the intra-fragment porosity provides water storage and the inter-fragment porosity provides potential pathways for relatively rapid flow near saturation. Chloride tracer movement through 43 cm long and 45 cm diameter undisturbed chalk columns was studied at water application rates of 0·3, 1·0, and 1·5 cm h,1. Microscale heterogeneity in effluent was recorded using a grid collection system consisting of 98 funnel-shaped cells each 3·5 cm in diameter. The total porosity of the columns was 0·47 ± 0·02 m3 m,3, approximately 13% of pores were , 15 µm diameter, and the saturated hydraulic conductivity was 12·66 ± 1·31 m day,1. Although the column remained unsaturated during the leaching even at all application rates, proportionate flow through macropores increased as the application rate decreased. The number of dry cells (with 0 ml of effluent) increased as application rate decreased. Half of the leachate was collected from 15, 19 and 22 cells at 0·3, 1·0, 1·5 cm h,1 application rates respectively. Similar breakthrough curves (BTCs) were obtained at all three application rates when plotted as a function of cumulative drainage, but they were distinctly different when plotted as a function of time. The BTCs indicate that the columns have similar drainage requirement irrespective of application rates, as the rise to the maxima (C/Co) is almost similar. However, the time required to achieve that leaching requirement varies with application rates, and residence time was less in the case of a higher application rate. A two-region convection,dispersion model was used to describe the BTCs and fitted well (r2 = 0·97,0·99). There was a linear relationship between dispersion coefficient and pore water velocity (correlation coefficient r = 0·95). The results demonstrate the microscale heterogeneity of hydrodynamic properties in the Upper Chalk. Copyright © 2007 John Wiley & Sons, Ltd. [source] Physical and chemical considerations of damage induced in protein crystals by synchrotron radiation: a radiation chemical perspectiveJOURNAL OF SYNCHROTRON RADIATION, Issue 6 2002Peter O'Neill Radiation-induced degradation of protein or DNA samples by synchrotron radiation is an inherent problem in X-ray crystallography, especially at the `brighter' light sources. This short review gives a radiation chemical perspective on some of the physical and chemical processes that need to be considered in understanding potential pathways leading to the gradual degradation of the samples. Under the conditions used for X-ray crystallography at a temperature of <100,K in the presence of cryoprotectant agents, the majority of radiation damage of the protein samples arises from direct ionization of the amino acid residues and their associated water molecules. Some of the chemical processes that may occur at these protein centres, such as bond scission, are discussed. Several approaches are discussed that may reduce radiation damage, using agents known from radiation chemistry to minimize radical-induced degradation of the sample. [source] Future Progress In Diabetic NeuropathyJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2000Jd Ward Over three decades much knowledge regarding the pathogenesis of diabetic neuropathy has been gathered but sadly this has led to very little understanding. This final review lecture of the symposium will attempt to analyse why progress has been so slow and look to the future for signs of inventive improvement. Papers presented during the symposium will be reviewed to allow estimate of future success and where perhaps efforts should be focused. At present the best we can do for our patients is to control blood glucose as rigidly as possible for preventative therapy and logical interventional drugs are not available. Hopefully the symposium will provide new insights into future investigations and potential pathways. [source] Plaque progression and regression in atherothrombosisJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2007B. IBANEZ Summary., Atherosclerotic disease is a pathological process characterized by the deposition of lipid and other blood-borne material within the arterial wall. The deposition of these materials and the subsequent thickening of the wall may significantly compromise the vessel lumen. Atherosclerosis is a diffuse disease with focal clinical manifestations that are the consequence of thrombotic complications on disrupted atherosclerotic lesions. Until recently, atherosclerosis development was envisaged as an incessant progressing process; however, new evidence has shown that atherosclerotic plaque homeostasis is not necessarily a constantly progressing process. There are many data showing that atherosclerotic plaque formation can be slowed, stopped or even reversed. Comprehension of the underlying mechanisms involved in the homeostasis of atherosclerotic plaque (progression/regression) should allow the development of interventions enhancing the regression pathway. Novel imaging technology has allowed the accurate evaluation of plaque progression, vital in the assessment of the efficacy of interventions. In this review we discuss the processes involved in the formation and progression of atherosclerotic lesions, the triggers for plaque disruption, as well as new therapies. We also deal with the potential pathways of plaque regression, as well as tools for accurate serial atherosclerotic quantification. [source] Tracing the geographical origin of Megastigmus transvaalensis (Hymenoptera: Torymidae): an African wasp feeding on a South American plant in North AmericaMOLECULAR ECOLOGY, Issue 2 2003Sonja J. Scheffer Abstract Determining the geographical origin of an introduced organism can be critical to understanding or managing a non-native species, but is often difficult when the organism is small or inconspicuous. We used a phylogeographical approach to identify the region of endemism and determine the geographical origin of world populations of the seed-feeding wasp Megastigmus transvaalensis (Hussey). This wasp feeds on African Rhus species and South American Schinus species in various locations around the world. Because it is present both in Africa and in South America, it is unclear whether the wasp was originally an African Rhus -feeder that has begun feeding on Schinus or a South American Schinus -feeder that has started feeding on Rhus. Phylogenetic analysis of 800 bp of mitochondrial cytochrome oxidase I sequence data found extensive variation and phylogeographical structure within African M. transvaalensis. Specimens from other locations around the world were all identical in COI sequence and were phylogenetically nested within the African samples. We conclude that M. transvaalensis was originally an African Rhus -feeder that readily attacks Schinus. We evaluate potential pathways of introduction of this wasp to the New World, and we discuss implications of our results for biocontrol efforts against invasive Schinus populations. [source] Health-risk behaviours: examining social disparities in the occurrence of stillbirthPAEDIATRIC & PERINATAL EPIDEMIOLOGY, Issue 4 2008Jennifer Goy Summary While an association between low socio-economic status (SES) and increased risk of stillbirth has been observed consistently over several decades, the pathways through which SES exerts these effects have not been established. Given that some key health-risk behaviours for stillbirth, including smoking and pre-pregnancy obesity, have strong relationships with SES, health-risk behaviours may serve as a channel through which low SES contributes to stillbirth outcomes. The objective of this study was to estimate the proportion of the relationship between low SES and the occurrence of stillbirth that is explained by health-risk behaviours in populations of Eastern Ontario and Nova Scotia (112 stillbirth cases and 398 controls). Both area and individual level influences of SES were assessed. The study population consisted of 112 cases (women delivering stillborn infants) and 398 controls. Odds ratios and 95% confidence intervals estimated by multivariable logistic regression were used to approximate relative risks. The contribution of health-risk behaviours to relationships between SES and stillbirth was assessed by a change in the relative risk estimate following omission of each health-risk behaviour from the model. Of the three measures of individual level SES examined (household income, education, Blishen occupational index), only household income was a statistically significant predictor of stillbirth. After controlling for individual level SES, no community level SES effects were observed for stillbirth. Adjustments for key health-risk behaviours (smoking) resulted in an 18.5% reduction in the odds ratio estimate for low SES, from 3.31 to 2.79. This large unexplained SES effect that remained highlights the need for research into other potential pathways that may account for increased risk of stillbirth among those of lower SES. [source] Mediating Pathways Explaining Psychosocial Functioning and Revictimization as Sequelae of Parental Violence Among Adolescent MothersAMERICAN JOURNAL OF ORTHOPSYCHIATRY, Issue 2 2009Taryn Lindhorst PhD Adolescent mothers are at high risk for negative life events, such as previous childhood physical abuse, impaired psychosocial functioning, and young adulthood revictimization. However, little is known about the potential pathways in these events; hence, little is known about opportunities for intervention. This study used structural equation modeling to investigate mediators of the effects of parental child abuse on later psychosocial functioning and revictimization (in the form of intimate partner violence and sexual violence) among adolescent mothers, with longitudinal data spanning 2.4 years. On psychological distress in the final time period, parental physical child abuse had an early and then maintained effect but also effects mediated by earlier psychological distress and revictimization. Psychological distress rather than substance use appeared as the primary psychosocial factor mediating the effects of parental violence on both future distress and revictimization. For prevention of further psychosocial impairment and revictimization, these findings indicate the need for early intervention with adolescent mothers who come from abusive families and who display higher levels of psychological distress. [source] Gene expression profile in the salivary glands of primary Sjögren's syndrome patients before and after treatment with rituximabARTHRITIS & RHEUMATISM, Issue 8 2010Valérie Devauchelle-Pensec Objective Primary Sjögren's syndrome (SS) is a complex disorder, in part due to B cell abnormalities. Although anti,B cell therapy is promising in primary SS, no treatment has yet been demonstrated to modify the disease course. This open-label study was undertaken to evaluate the efficacy of rituximab in primary SS and to investigate whether expression of specific genes is associated with efficacy of this treatment. Methods Fifteen patients with primary SS were treated in an open-label trial. Salivary gland biopsy specimens were obtained, and total RNA was extracted and amplified. Microarray analysis with the Affymetrix Human Genome U133 Plus 2.0 Array was used to analyze >54,000 transcripts, and potential pathways were identified. Results With gene expression data obtained before treatment, patients could be correctly classified in terms of whether they would be responders or nonresponders to rituximab. Gene pathway analysis demonstrated that the B cell signaling pathway was the most profoundly differentially expressed before treatment in the responders compared with nonresponders. Subclassification of patients based on the level of infiltration also demonstrated differential expression of genes belonging to the interferon (IFN) pathway between responders and nonresponders. Furthermore, unsupervised analysis based on gene expression modification before and after treatment allowed identification of 8 genes that were differentially expressed between responders and nonresponders, with the difference remaining significant after Bonferroni correction. Conclusion Our results demonstrate the ability to elaborate a set of genes predictive of rituximab efficacy and highlight the importance of studying the differential expression of B cell and IFN pathway signaling molecules in relation to the response to anti-CD20 treatment. A randomized controlled study is currently ongoing to confirm these results. [source] | ||||||||||||||||