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Selected AbstractsReduced Activity of CD13/Aminopeptidase N (APN) in Aggressive Meningiomas Is Associated with Increased Levels of SPARCBRAIN PATHOLOGY, Issue 1 2010Christian Mawrin Abstract Meningiomas are the second most common brain tumors in adults, and meningiomas exhibit a tendency to invade adjacent structures. Compared with high-grade gliomas, little is known about the molecular changes that potentially underlie the invasive behavior of meningiomas. In this study, we examined the expression and function of the membrane alanyl-aminopeptidase [mAAP, aminopeptidase N (APN), CD13, EC3.4.11.2] zinc-dependent ectopeptidase in meningiomas and meningioma cell lines, based on its prior association with tumor invasion in colorectal and renal carcinomas. We found a significant reduction of APNmRNA and protein expression, as well as enzymatic activity, in high-grade meningiomas. While meningioma tumor cell proliferation was not affected by either pharmacologic APN inhibition or siRNA-mediated APN silencing, APN pharmacologic and siRNA knockdown significantly reduced meningioma cell invasion in vitro. Next, we employed pathway-specific cDNA microarray analyses to identify extracellular matrix and adhesion molecules regulated by APN, and found that APN-siRNA knockdown substantially increased the expression of secreted protein, acidic and rich in cysteine (SPARC)/osteonectin. Finally, we demonstrated that SPARC, which has been previously associated with meningioma invasiveness, was increased in aggressive meningiomas. Collectively, these results suggest that APN expression and enzymatic function is reduced in aggressive meningiomas, and that alterations in the balance between APN and SPARC might favor meningioma invasion. [source] Objective measurement of motor activity during cognitive performance in adults with attention-deficit/hyperactivity disorderACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2010S. Lis Lis S, Baer N, Stein-en-Nosse C, Gallhofer B, Sammer G, Kirsch P. Objective measurement of motor activity during cognitive performance in adults with attention-deficit/hyperactivity disorder. Objective:, This study investigates whether hyperactivity, i.e. an increased level of motor activity, can be observed in adults with attention-deficit/hyperactivity disorder (ADHD). Method:, An infrared motion-tracking system was used to measure motor activity in 20 unmedicated adults with ADHD and 20 matched healthy controls (HC) during a 1-back working memory task. Results:, Motor activity was higher in ADHD. It increased with the duration of testing and co-varied with cognitive performance in ADHD only. Subjective and objective measurements of motor activity were related in HC, but not in ADHD. Conclusion:, Higher levels of motor activity in ADHD are objectively measurable not only in children, but in adults as well. It is linked to cognitive performance arguing against distinguishable diagnostic subtypes. The objective measurement of motor activity seems to extend the description of ADHD symptoms derived from rating scales and might thus help to bridge the gap between psychopathological symptom description and neurobiological alterations. [source] War, Livelihoods and Vulnerability in Sri LankaDEVELOPMENT AND CHANGE, Issue 2 2004Benedikt Korf As the number of de-stabilized regions of warfare or post-war conditions worldwide continues to grow, this article investigates how civilians survive in the context of a civil war. It analyses livelihood strategies of farmers in the war-torn areas of Sri Lanka, using an analytical framework based on a revised form of DFID's sustainable rural livelihoods approach, placing particular attention on the institutional reproduction of household capital assets in the war economy. The author delineates a three pillar model of household livelihood strategies focusing on how households (1) cope with the increased level of risk and uncertainty; (2) adjust their economic and social household assets for economic survival; and (3) use their social and political assets as livelihood strategies. Empirical evidence comes from four case study villages in the east of Sri Lanka. Although the four case studies were very close together geographically, their livelihood outcomes differed considerably depending on the very specific local political geography. The role of social and political assets is essential: while social assets (extended family networks) were important to absorb migrants, political assets (alliances with power holders) were instrumental in enabling individuals, households or economic actors to stabilize or even expand their livelihood options and opportunities. The author concludes that civilians in conflict situations are not all victims (some may also be culprits in the political economy of warfare), and that war can be both a threat and an opportunity, often at the same time. [source] Social consumption of alcohol in adolescents with Type 1 diabetes is associated with increased glucose lability, but not hypoglycaemiaDIABETIC MEDICINE, Issue 8 2006D. Ismail Abstract Aims To determine the effects of social consumption of alcohol by diabetic adolescents on glycaemic control. Methods Fourteen (five male) patients aged > 16 years were recruited from the diabetes clinic at the Royal Children's Hospital. The continuous glucose monitoring system (CGMS) was attached at a weekend when alcohol consumption was planned for one night only. For each patient, the 12-h period from 18.00 h to 06.00 h for the night with alcohol consumption (study period) was compared with the same period with non-alcohol consumption (control period) either 24 h before or after the alcohol study night. Thus, each subject was his/her own control. Glycaemic outcomes calculated from continuous glucose monitoring included mean blood glucose (MBG), percentage of time spent at low glucose levels (CGMS < 4.0 mmol/l), normal glucose levels (CGMS 4.0,10.0 mmol/l) and high glucose levels (> 10.0 mmol/l) and continuous overall net glycaemic action (CONGA). Results The mean number of standard alcohol drinks consumed during the study period was 9.0 for males and 6.3 for females. There was no difference in percentage of time at high and normal glucose levels in the study and control periods. During the control period, there was a higher percentage of time with low glucose levels compared with the study period (P < 0.05). There was an increased level of glycaemic variation during the study time when compared with the control period. Conclusions In an uncontrolled, social context, moderately heavy alcohol consumption by adolescents with Type 1 diabetes appears to be associated with increased glycaemic variation, but not with low glucose levels. [source] Randomized controlled trial of cognitive,behavioural therapy for coexisting depression and alcohol problems: short-term outcomeADDICTION, Issue 1 2010Amanda L. Baker ABSTRACT Aims Alcohol use disorders and depression co-occur frequently and are associated with poorer outcomes than when either condition occurs alone. The present study (Depression and Alcohol Integrated and Single-focused Interventions; DAISI) aimed to compare the effectiveness of brief intervention, single-focused and integrated psychological interventions for treatment of coexisting depression and alcohol use problems. Methods Participants (n = 284) with current depressive symptoms and hazardous alcohol use were assessed and randomly allocated to one of four individually delivered interventions: (i) a brief intervention only (single 90-minute session) with an integrated focus on depression and alcohol, or followed by a further nine 1-hour sessions with (ii) an alcohol focus; (iii) a depression focus; or (iv) an integrated focus. Follow-up assessments occurred 18 weeks after baseline. Results Compared with the brief intervention, 10 sessions were associated with greater reductions in average drinks per week, average drinking days per week and maximum consumption on 1 day. No difference in duration of treatment was found for depression outcomes. Compared with single-focused interventions, integrated treatment was associated with a greater reduction in drinking days and level of depression. For men, the alcohol-focused rather than depression-focused intervention was associated with a greater reduction in average drinks per day and drinks per week and an increased level of general functioning. Women showed greater improvements on each of these variables when they received depression-focused rather than alcohol-focused treatment. Conclusions Integrated treatment may be superior to single-focused treatment for coexisting depression and alcohol problems, at least in the short term. Gender differences between single-focused depression and alcohol treatments warrant further study. [source] Metabotropic glutamate receptor 5 localized in the limbic forebrain is critical for the development of morphine-induced rewarding effect in miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2004Takeshi Aoki Abstract The aim of the present study was to clarify the role of the metabotropic glutamate 5 (mGlu5) receptor subtype in the development of rewarding effect induced by a prototypical µ-opioid receptor agonist morphine in the mouse. In the conditioned place preference paradigm, intracerebroventricular (i.c.v.) administration of a selective mGlu5 receptor antagonist, 2-methyl-6-(phenylethynyl)-pyridine (MPEP), attenuated the morphine-induced rewarding effects. Using immunoblot analysis, we confirmed that the increased level of protein kinase C, (PKC,) isoform was observed in the limbic forebrain of ICR mice conditioned with morphine. Here we found for the first time that the treatment with MPEP significantly inhibited the up-regulation of PKC, isoform in the limbic forebrain of mice showing the significant place preference. Furthermore, it should be mentioned that the protein level of mGlu5 was significantly increased in membrane preparations of the limbic forebrain obtained from morphine-conditioned mice compared to those from saline-conditioned mice. As well as the result from the immunoblot analysis, we demonstrated using the receptor binding assay that the number of mGlu5 receptors in the mouse limbic forebrain was significantly increased by morphine conditioning. The present data provide direct evidence that the activation of mGlu5 receptor linked to the increased PKC, isoform in the mouse limbic forebrain is implicated in the development of rewarding effect of morphine. [source] Degree of conversion and permeability of dental adhesivesEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2005Milena Cadenaro The aim of this study was to analyse the extent of polymerization of different adhesive films in relation to their permeability. One adhesive of each class was investigated: OptiBond FL; One-Step; Clearfil Protect Bond; and Xeno III. Adhesive films were prepared and cured with XL-2500 (3M ESPE) for 20, 40 or 60 s. Polymerization kinetic curves of the adhesives tested were obtained with differential scanning calorimetry (DSC) and data were correlated with microhardness. The permeability of the adhesives under the same experimental conditions was evaluated on human extracted teeth connected to a permeability device and analysed statistically. The results showed that the extent of polymerization obtained from DSC exotherms was directly correlated with microhardness. An increased level of polymerization after prolonged light-curing was confirmed for all adhesives. Simplified adhesives exhibited a lower extent of polymerization and showed incomplete polymerization, even after 60 s. An inverse correlation was found between the degree of cure and the permeability. This study supports the hypothesis that the permeability of simplified adhesives is correlated with incomplete polymerization of resin monomers and the extent of light exposure. These adhesives may be rendered less permeable by using longer curing times than those recommended by the respective manufacturer. [source] STRINGS ATTACHED: NEW PUBLIC MANAGEMENT, COMPETITIVE GRANT FUNDING AND SOCIAL CAPITALFINANCIAL ACCOUNTABILITY & MANAGEMENT, Issue 2 2009Helen Irvine This paper first investigates the impact of New Public Management (NPM) practices, particularly competitive grant funding, on Bushcare New South Wales (NSW), an Australian environmental volunteering organisation. Secondly, identifying such local volunteering organisations as repositories of valuable social capital, it explores the link between volunteering and social capital. Using mixed methods and institutional theory, the study reveals that an increased level of professionalism and accountability is required of Bushcare groups, and that local coordinators face a challenge in balancing local, regional and national priorities without sacrificing Bushcare's mission. These dynamics, it is proposed, have potentially serious social capital implications. [source] Genetic loss of D-amino acid oxidase activity reverses schizophrenia-like phenotypes in miceGENES, BRAIN AND BEHAVIOR, Issue 1 2010V. Labrie Reduced function of the N -methyl- d -aspartate receptor (NMDAR) has been implicated in the pathophysiology of schizophrenia. The NMDAR contains a glycine binding site in its NR1 subunit that may be a useful target for the treatment of schizophrenia. In this study, we assessed the therapeutic potential of long-term increases in the brain levels of the endogenous NMDAR glycine site agonist D-serine, through the genetic inactivation of its catabolic enzyme D-amino acid oxidase (DAO) in mice. The effects of eliminating DAO function were investigated in mice that display schizophrenia-related behavioral deficits due to a mutation (Grin 1D481N) in the NR1 subunit that results in a reduction in NMDAR glycine affinity. Grin 1D481N mice show deficits in sociability, prolonged latent inhibition, enhanced startle reactivity and impaired spatial memory. The hypofunctional Dao 1G181R mutation elevated brain levels of D-serine, but alone it did not affect performance in the behavioral measures. Compared to animals with only the Grin 1D481N mutation, mice with both the Dao1G181R and Grin 1D481N mutations displayed an improvement in social approach and spatial memory retention, as well as a reversal of abnormally persistent latent inhibition and a partial normalization of startle responses. Thus, an increased level of D-serine resulting from decreased catalysis corrected the performance of mice with deficient NMDAR glycine site activation in behavioral tasks relevant to the negative and cognitive symptoms of schizophrenia. Diminished DAO activity and elevations in D-serine may serve as an effective therapeutic intervention for the treatment of psychiatric symptoms. [source] Self-Assembly of a Donor-Acceptor Dyad Across Multiple Length Scales: Functional Architectures for Organic ElectronicsADVANCED FUNCTIONAL MATERIALS, Issue 15 2009Jeffrey M. Mativetsky Abstract Molecular dyads based on polycyclic electron donor (D) and electron acceptor (A) units represent suitable building blocks for forming highly ordered, solution-processable, nanosegregated D-A domains for potential use in (opto)electronic applications. A new dyad, based on alkyl substituted hexa- peri -hexabenzocoronene (HBC) and perylene monoimide (PMI) separated by an ethinylene linker, is shown to have a high tendency to self-assemble into ordered supramolecular arrangements at multiple length scales: macroscopic extruded filaments display long-range crystalline order, nanofiber networks are produced by simple spin-coating, and monolayers with a lamellar packing are formed by physisorption at the solution-HOPG interface. Moreover, highly uniform mesoscopic ribbons bearing atomically flat facets and steps with single-molecule heights self-assemble upon solvent-vapor annealing. Electrical measurements of HBC-PMI films and mesoscopic ribbons in a transistor configuration exhibit ambipolar transport with well balanced p- and n-type mobilities. Owing to the increased level of order at the supramolecular level, devices based on ribbons show mobility increases of more than one order of magnitude. [source] Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in miceIMMUNOLOGY, Issue 2 2010Baojing Lu Summary Nasal administration has emerged as a promising and attractive route for vaccination, especially for the prophylaxis of respiratory diseases. Our previous studies have shown that severe acute respiratory syndrome coronavirus (SARS-CoV) virus-like particles (VLPs) can be assembled using a recombinant baculovirus (rBV) expression system and such VLPs induce specific humoral and cellular immune responses in mice after subcutaneous injection. Here, we investigated mucosal immune responses to SARS-CoV VLPs in a mouse model. Mice were immunized in parallel, intraperitoneally or intranasally, with VLPs alone or with VLPs plus cytosine,phosphate,guanosine (CpG). Immune responses, including the production of SARS-CoV-specific serum immunoglobulin G (IgG) and secretory immunoglobulin A (sIgA), were determined in mucosal secretions and tissues. Both immunizations induced SARS-CoV-specific IgG, although the levels of IgG in groups immunized via the intraperitoneal (i.p.) route were higher. sIgA was detected in saliva in groups immunized intranasally but not in groups immunized intraperitoneally. CpG had an adjuvant effect on IgA production in genital tract washes when administered intranasally but only affected IgA production in faeces samples when administered intraperitoneally. In addition, IgA was also detected in mucosal tissues from the lung and intestine, while CpG induced an increased level of IgA in the intestine. Most importantly, neutralization antibodies were detected in sera after i.p. and intranasal (i.n.) immunizations. Secretions in genital tract washes from the i.n. group also showed neutralization activity. Furthermore, VLPs that were administered intraperitoneally elicited cellular immune responses as demonstrated by enzyme-linked immunospot (ELISPOT) assay analyses. In summary, our study indicates that mucosal immunization with rBV SARS-CoV VLPs represent an effective means for eliciting protective systemic and mucosal immune responses against SARS-CoV, providing important information for vaccine design. [source] Detainment and health: The case of the Lebanese hostages of warINTERNATIONAL JOURNAL OF MENTAL HEALTH NURSING, Issue 2 2010Laila F. Farhood ABSTRACT The purpose of the current research was to compare former detainees of Khiam prison to a comparison group regarding depression, anxiety, presence of chronic diseases, smoking, and alcohol drinking. The sample consisted of 118 ex-detainees and 90 community controls. The Beck Depression Inventory, the Hamilton Anxiety Scale, the Clinician-Administered Post-Traumatic Stress Disorder Scale, and the Harvard Trauma Questionnaire were used. The ex-detainees suffered from an increased level of depression, high anxiety scores, increased chronic diseases, smoked more, and consumed more alcohol than their comparison group. Regression analyses showed that detainment independently predicted depression and anxiety. [source] Interventions to reduce psychosocial disturbance following humanitarian relief efforts involving natural disasters: An integrative reviewINTERNATIONAL JOURNAL OF NURSING PRACTICE, Issue 4 2009Denise Susan Walsh MSN RN Because of the increased level of post-traumatic stress disorder (PTSD) reported post disaster work, it is imperative that governmental and non-governmental agencies consider predisaster training of volunteers in not only clinical skills, but also communication and team building. When these concepts are combined with ongoing support post disaster, a decrease in the frequency and severity of PTSD has been reported. A review of 12 studies examined responses of relief workers to various disaster situations. Experiences were extracted, categorized, and a data reduction model was developed to illustrate the characteristics of the experiences and subsequent interventions that were reported. Three interventions that positively affected the responses of relief workers to disaster experiences emerged: debriefing, team building and preparation. [source] DROUGHT STRESS: Role of Carbohydrate Metabolism in Drought-Induced Male Sterility in Rice Anthers,JOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 5 2010G. N. Nguyen Abstract Rice plants exposed to three consecutive days of water stress (,0.5 MPa) show a reduction in male fertility and grain set, which is attributed to increased levels of reactive oxygen species (ROS) and activation of a programmed cell death. This current research was conducted to further investigate the association of sugar metabolism with microspore abortion in rice anthers. Biochemical assays showed that sucrose, glucose and fructose contents were found to be significantly increased in anthers from water stressed plants compared with the control. qRT-PCR analyses and in situ hybridization of metabolic genes (sugar transporters, invertase and phosphotransferase/kinases) demonstrated that the supply of sugars for developing microspores and the initial steps of sugar utilization e.g. glycolysis, were not repressed. However, it appears that the accumulation of sugars in stressed anthers might involve a reduction of mitochondrial activity during the tricarboxylic acid cycle, which could result in excessive production of ROS and a depletion of the ATP pool. These results also suggest that higher levels of sugars at all stages of anther development seemed to be associated with some measure of protection to the anthers against oxidative stress. Induced expression of sugar transporter genes might have maintained the high levels of sugar in the tapetum and the locules, which alleviated oxidant damage caused by excessive ROS generation. Thus, the increased level of sugars might potentially be a natural response in providing protection against oxidant damage by strengthening the antioxidant system in anthers. [source] Rheological behavior of polymer melts in monodimensional flow through low-angle convergence and spiralling diesADVANCES IN POLYMER TECHNOLOGY, Issue 2 2001L. Mascia An experimental study was carried out to examine the rheological behavior of polymer melts in laminar flows through channels with small-angle convergences (2,3°) and spiralling walls (6°/mm along the flow direction), using an extrusion grade of low-density polyethylene. The results show that convergence is the main factor responsible for the observed deviations from steady state laminar shear flow, particularly with respect to additional pressure requirements to maintain a constant mass output. The swell ratio, calculated from the dimensions of the channel at the exit, was found to be considerably higher for flow-through converging channels. Only a small increase in swell ratio could be attributed, on the other hand, to the rotational elements of the die configuration. It is inferred that even for small angles of convergence the increased level of swelling is associated with elongational stress components, which were grouped together and denoted as the "additional stress." This was obtained from the difference between the calculated average shear stress at the wall, using the recorded pressure at the die entry, and the value of the average shear stress at the wall calculated from the shear viscosity data for the melt. © 2001 John Wiley & Sons, Inc. Adv Polym Techn 20: 99,107, 2001 [source] Use of a systematic review to assist the development of Campylobacter control strategies in broilersJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2006A. Adkin Abstract Aims:, Produce an evidence-based ranking of the major contributing factors and sources of Campylobacter occurrence in broilers produced in England, Scotland and Wales , Great Britain (GB). Method and Results:, Relevant data were extracted from 159 research papers and findings were grouped into 14 sources of on-farm contamination and 37 contributing factors. A relevancy score was developed to take into account various measures from each study of applicability to GB broilers and strength of findings. Results indicate that major sources of Campylobacter include a depopulation event, another house on-farm, on-farm staff, and other animals on farm. The depopulation schedule (staggered slaughter) and multiple houses on-farm were identified as contributing factors associated with increasing the risk, and those decreasing the risk were use of a hygiene barrier, parent company and certain seasons of rearing. Conclusions:, Although the review was more resource intensive compared to narrative studies, the system allows an increased level of transparency and the ability to investigate patterns and trends. Significance and Impact of the Study:, This paper provides the first evidence-based ranking of the major sources and contributing factors for Campylobacter presence in broilers in GB using a systematic review. [source] The effect of superoxide dismutase deficiency on cadmium stressJOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 1 2004Paula D. B. Adamis Abstract Saccharomyces cerevisiae mutant strains deficient in superoxide dismutase (Sod), an antioxidant enzyme, were used to analyze cadmium absorption and the oxidation produced by it. Cells lacking the cytosolic Sod1 removed twice as much cadmium as the control strain, while those deficient in the mitochondrial Sod2 exhibited poor metal absorption. Interestingly, the sod1 mutant did not become more oxidized after exposure to cadmium, as opposed to the control strain. We observed that the deficiency of Sod1 increases the expression of both Cup1 (a metallothionein) and Ycf1 (a vacuolar glutathione S-conjugate pump), proteins involved with protection against cadmium. Furthermore, when sod1 cells were exposed to cadmium, the ratio glutathione oxidized/glutathione reduced did not increase as expected. We propose that a high level of metallothionein expression would relieve glutathione under cadmium stress, while an increased level of Ycf1 expression would favor compartmentalization of this metal into the vacuole. Both conditions would reduce the level of glutathione-cadmium complex in cytosol, contributing to the high capacity of absorbing cadmium by the sod1 strain. Previous results showed that the glutathione-cadmium complex regulates cadmium uptake. These results indicate that, even indirectly, metallothionein also regulates cadmium transport. © 2004 Wiley Periodicals, Inc. J Biochem Mol Toxicol 18:12,17, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.20000 [source] Enhanced Chondrogenesis and Wnt Signaling in PTH-Treated Fractures,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 12 2007Sanjeev Kakar Abstract Studies have shown that systemic PTH treatment enhanced the rate of bone repair in rodent models. However, the mechanisms through which PTH affects bone repair have not been elucidated. In these studies we show that PTH primarily enhanced the earliest stages of endochondral bone repair by increasing chondrocyte recruitment and rate of differentiation. In coordination with these cellular events, we observed an increased level of canonical Wnt-signaling in PTH-treated bones at multiple time-points across the time-course of fracture repair, supporting the conclusion that PTH responses are at least in part mediated through Wnt signaling. Introduction: Since FDA approval of PTH [PTH(1,34); Forteo] as a treatment for osteoporosis, there has been interest in its use in other musculoskeletal conditions. Fracture repair is one area in which PTH may have a significant clinical impact. Multiple animal studies have shown that systemic PTH treatment of healing fractures increased both callus volume and return of mechanical competence in models of fracture healing. Whereas the potential for PTH has been established, the mechanism(s) by which PTH produces these effects remain elusive. Materials and Methods: Closed femoral fractures were generated in 8-wk-old male C57Bl/6 mice followed by daily systemic injections of either saline (control) or 30 ,g/kg PTH(1,34) for 14 days after fracture. Bones were harvested at days 2, 3, 5, 7, 10, 14, 21, and 28 after fracture and analyzed at the tissue level by radiography and histomorphometry and at the molecular and biochemical levels level by RNase protection assay (RPA), real-time PCR, and Western blot analysis. Results: Quantitative ,CT analysis showed that PTH treatment induced a larger callus cross-sectional area, length, and total volume compared with controls. Molecular analysis of the expression of extracellular matrix genes associated with chondrogenesis and osteogenesis showed that PTH treated fractures displayed a 3-fold greater increase in chondrogenesis relative to osteogenesis over the course of the repair process. In addition, chondrocyte hypertrophy occurred earlier in the PTH-treated callus tissues. Analysis of the expression of potential mediators of PTH actions showed that PTH treatment significantly induced the expression of Wnts 4, 5a, 5b, and 10b and increased levels of unphosphorylated, nuclear localized ,-catenin protein, a central feature of canonical Wnt signaling. Conclusions: These results showed that the PTH-mediated enhancement of fracture repair is primarily associated with an amplification of chondrocyte recruitment and maturation in the early fracture callus. Associated with these cellular effects, we observed an increase in canonical Wnt signaling supporting the conclusion that PTH effects on bone repair are mediated at least in part through the activation of Wnt-signaling pathways. [source] Differential expression of proteins in kidney, eye, aorta, and serum of diabetic and non-diabetic ratsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006William C. Cho Abstract Diabetes mellitus (DM) is a chronic progressive disease that often results in microvascular and macrovascular complications, yet its pathogenesis is not clear. Automated proteomic technology, coupled with powerful bioinformatics and statistical tools, can provide new insights into the molecular alterations implicated in DM. Following our previous findings of redox changes in the eye and aorta of diabetic rats, as well as the activities of different antioxidant enzymes during the development of DM, this study is further launched to find potential biomarkers by comparing the serum and tissue samples of 26 diabetic rats (8 weeks after streptozotocin [STZ] administration) with 29 normal controls using surface enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) technology. Eight potential biomarkers were found in the serum, one potential biomarker was found in the kidney and eye, respectively, whereas three potential biomarkers were discovered in the aorta. One of the serum biomarker candidates was found to match the C-reactive protein (CRP) in the Swiss-Prot knowledgebase. Further validation has been conducted by ELISA kit to confirm the role of CRP during the development of DM. To conclude, the increased level of CRP in diabetic serum demonstrated in this study indicates that the development of DM is associated with inflammation. This is also the first report demonstrating that some potential lysate biomarkers in the kidney, eye, and aorta may be involved in the development of diabetes and its complications. Further identification and evaluation of these potential biomarkers will help unravel the underlying mechanisms of the disease. J. Cell. Biochem. © 2006 Wiley-Liss, Inc. [source] Sequential loss of cell cycle checkpoint control contributes to malignant transformation of murine embryonic fibroblasts induced by 20-methylcholanthreneJOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Sudeshna Mukherjee Definitive information about the number and nature of discrete steps of tumorigenesis is enigmatic. To understand the multistep nature of carcinogenesis, an in vitro model of 20-Methylcholanthrene-treated primary fibroblast cells CNCI-PM-20, from 20-day old Swiss mouse embryo was used. Visible neoplastic changes with distinct morphological variations along with specific chromosomal aberrations like Robertsonian metacentrics, double and single-minute chromosomes and aneuploidy were observed from Passage-20 onwards. The cell cycle profile showed gradual increase in G2/M population till P-32, followed by evasion of block from P-36 onwards. Gradual increase in expression of C-myc, CyclinD1 and a decrease in expression of P21 was observed from P-20 onwards. CDC25A expression was significantly increased at P-27 and remained more or less constant in subsequent passages. Additionally, an increased P16 and P53 expression were seen at P-20 followed by their significant down-regulation at P-32. An increased level of phosphorylated retinoblastoma (ppRb) was observed from P-27, probably responsible for a compromised G1/S checkpoint. The inactivation of p21 and p16 might be due to their promoter hyper-methylation as suggested through de-methylation experiment by 5-aza-deoxycytidine at P-42. G2/M checkpoint abrogation was marked by gradual increase in expression of CyclinB1 and Cdc20, and a significant increase of Mad2 at P-20. Interestingly, increased expression of phospho-ATM, ATR and phospho-Chk1 were also seen at P-20 followed by their down-regulation at subsequent passages, indicating a perturbation of DNA damage response pathway at early passages. Our findings therefore dramatize the multiple genetic events that can cooperate to promote tumorigenesis. J. Cell. Physiol. 224:49,58, 2010 © 2010 Wiley-Liss, Inc. [source] Quantitative assessment of fetal bowel echogenicity: Comparison of harmonic, compound, and fundamental sonographic imagesJOURNAL OF CLINICAL ULTRASOUND, Issue 6 2003Hak Jong Lee MD Abstract Purpose The aims of this study were to assess normal fetal bowel echogenicity quantitatively and to compare the levels of bowel echogenicity observed with the use of 3 different sonographic image-processing techniques,harmonic plus compound imaging, harmonic imaging alone, and fundamental imaging,and 2 different broadband transducers. Methods Women with normal singleton second-trimester fetuses underwent sonographic scanning with both a 2,5-MHz and a 4,7-MHz transducer. The use of the 3 imaging techniques and the 2 transducers resulted in 6 types of images: 2,5-HC (harmonic plus compound images), 2,5-H (harmonic images), and 2,5-F (fundamental images), and 4,7-HC, 4,7-H, and 4,7-F images. The relative echogenicities (brightness) of the fetal bowel and iliac bone were measured, and bowel echogenicity ratios (bowel echogenicity/iliac bone echogenicity × 100) were calculated using graphics software. The resulting data were analyzed to evaluate differences in echogenicity ratios between the 6 types of images. Results We examined 37 fetuses during the study period. The bowel echogenicity ratios were highest on the images obtained with harmonic and compound,imaging techniques (2,5-HC, 84.7 ± 23.4%; 4,7-HC, 98.5 ± 36.4%). The bowel echogenicity ratio for the 2,5-HC images was significantly higher than those for the 2,5-H and the 2,5-F images (p < 0.01 and p < 0.001, respectively), and those for the 4,7-HC and 4,7-H images were higher than that for the 4,7-F images (p < 0.01 for both comparisons). Conclusions A sonographic finding of echogenic fetal bowel should be interpreted cautiously because the use of special image-processing techniques can artificially enhance the apparent level of echogenicity of the bowel. We recommend rescanning without the use of those techniques if the fetal bowel appears to have an increased level of echogenicity. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:302,307, 2003 [source] Bacterial enteritis and the development of the larval digestive tract in olive flounder, Paralichthys olivaceus (Temminck & Schlegel)JOURNAL OF FISH DISEASES, Issue 9 2004D-H Kim Abstract Three bacterial isolates obtained from diseased olive flounder larvae, Paralichthys olivaceus, were identified as Vibrio ichthyoenteri based on the results of phenotypic characterization and 16S rRNA gene sequencing studies. Bacterial enteritis was reproduced in 16 and 22 days post-hatch (dph) larvae by administering brine shrimp nauplii, Artemia salina, dosed with the environmental isolates and reference strains of V. ichthyoenteri. To investigate the effect of the disease on development of the stomach, a pepsin activity assay and reverse transcription-polymerase chain reaction (RT-PCR) analysis of the expression of the pepsinogen gene were performed. Expression of olive flounder pepsinogen was detected from 30-dph larvae and the increased level of pepsin activity coincided with reduced susceptibility to the disease. Growth rates of V. ichthyoenteri, V. anguillarum and Edwardsiella tarda were tested in artificial stomach conditions using HCl and porcine pepsin. All the strains of V. ichthyoenteri were inhibited by low pH conditions which corresponded with an increase in pepsin levels. This suggests that differentiation of the stomach in olive flounder larvae and juveniles, an essential physiological development, also provides the host with a non-immunological defence mechanism. [source] Implication of Rho-associated kinase in the elevation of extracellular dopamine levels and its related behaviors induced by methamphetamine in ratsJOURNAL OF NEUROCHEMISTRY, Issue 2 2003Minoru Narita Abstract A growing body of evidence suggests that several protein kinases are involved in the expression of pharmacological actions induced by a psychostimulant methamphetamine. The present study was designed to investigate the role of the Rho/Rho-associated kinase (ROCK)-dependent pathway in the expression of the increase in extracellular levels of dopamine in the nucleus accumbens and its related behaviors induced by methamphetamine in rats. Methamphetamine (1 mg/kg, subcutaneously) produced a substantial increase in extracellular levels of dopamine in the nucleus accumbens, with a progressive augmentation of dopamine-related behaviors including rearing and sniffing. Methamphetamine also induced the decrease in levels of its major metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA). Both the increase in extracellular levels of dopamine and the induction of dopamine-related behaviors by methamphetamine were significantly suppressed by pretreatment with an intranucleus accumbens injection of a selective ROCK inhibitor Y-27632. In contrast, Y-27632 had no effect on the decrease in levels of DOPAC and HVA induced by methamphetamine. Under these conditions, there were no changes in protein levels of membrane-bound RhoA in the nucleus accumbens following methamphetamine treatment. It is of interest to note that the microinjection of Y-27632 into the nucleus accumbens failed to suppress the increases in extracellular levels of dopamine, DOPAC, and HVA in the nucleus accumbens induced by subcutaneous injection of a prototype of µ-opioid receptor agonist morphine (10 mg/kg). Furthermore, perfusion of a selective blocker of voltage-dependent Na+ channels, tetrodotoxin (TTx) into the rat nucleus accumbens did not affect the increase in extracellular levels of dopamine in the rat nucleus accumbens by methamphetamine, whereas the morphine-induced dopamine elevation was eliminated by this application of TTx. The extracellular level of dopamine in the nucleus accumbens was also increased by perfusion of a selective dopamine re-uptake inhibitor 1-[2-[bis(4-fluorophenyl)methoxy]-4-(3-phenylpropyl)piperazine (GBR-12909) in the nucleus accumbens. This effect was not affected by pretreatment with intranucleus accumbens injection of Y-27632. These findings provide first evidence that Rho/ROCK pathway in the nucleus accumbens may contribute to the increase in extracellular levels of dopamine in the nucleus accumbens evoked by a single subcutaneous injection of methamphetamine. In contrast, this pathway is not essential for the increased level of dopamine in this region induced by morphine, providing further evidence for the different mechanisms of dopamine release by methamphetamine and morphine in rats. [source] A novel role of hippocalcin in bFGF-induced neurite outgrowth of H19-7 cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2008Doo-Yi Oh Abstract Hippocalcin is a Ca2+ -binding protein that is expressed mainly in pyramidal nerve cells of the hippocampus. However, its functions and mechanism in the brain remain unclear. To elucidate the role of hippocalcin, we used a conditionally immortalized hippocampal cell line (H19-7) and showed that bFGF treatment increased the expression of hippocalcin during bFGF-induced neurite outgrowth of H19-7 cells. Overexpression of hippocalcin dramatically elongated neurites and increased the expression of basic helix,loop,helix transcription factor, that is, NeuroD without bFGF stimulation. Treatment of the cells with hippocalcin siRNA completely blocked bFGF-induced neurite outgrowth and NeuroD expression. bFGF stimulation resulted in activation of phospholipase C,, (PLC-,) and an increased level of intracellular Ca2+. Hippocalcin expression by bFGF stimulation was fully blocked by both the PLC-, inhibitor U73122 and BAPTA-AM, a chelator of intracellular Ca2+, suggesting that hippocalcin expression by bFGF is dependent on PLC-, and Ca2+. Moreover, both U73122 and BAPTA-AM completely blocked bFGF-induced neurite outgrowth and NeuroD expression. Taken together, these results suggest for the first time that bFGF induces hippocalcin expression in H19-7 cells through PLC-, activation, which leads to neurite outgrowth. © 2008 Wiley-Liss, Inc. [source] Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2003Chisa Hidaka Background: Cartilage has a limited capacity to heal. Although chondrocyte transplantation is a useful therapeutic strategy, the repair process can be lengthy. Previously we have shown that over expression of bone morphogenetic protein-7 (BMP-7) in chondrocytes by adenovirus-mediated gene transfer leads to increased matrix synthesis and cartilage-like tissue formation in vitro. In this context we hypothesized that implantation of genetically modified chondrocytes expressing BMP-7 would accelerate the formation of hyaline-like repair tissue in an equine model of cartilage defect repair. Methods: Chondrocytes treated with adenovirus vector encoding BMP-7 (AdBMP-7) or as control, an adenovirus vector encoding an irrelevant gene (Escherichia coli cytosine deaminase, AdCD) were implanted into extensive (15 mm diameter) articular cartilage defects in the patellofemoral joints of 10 horses. Biopsies were performed to evaluate early healing at 4 weeks. At the terminal time point of 8 months, repairs were assessed for morphology, MRI appearance, compressive strength, biochemical composition and persistence of implanted cells. Results: Four weeks after surgery AdBMP-7-treated repairs showed an increased level of BMP-7 expression and accelerated healing, with markedly more hyaline-like morphology than control. Quantitative real-time polymerase chain reaction (PCR) analysis of the repair tissue 8 months after surgery showed that few implanted cells persisted. By this time, the controls had healed similarly to the AdBMP-7-treated defects, and no difference was detected in the morphologic, biochemical or biomechanical properties of the repair tissues from the two treatment groups. Conclusions: Implantation of genetically modified chondrocytes expressing BMP-7 accelerates the appearance of hyaline-like repair tissue in experimental cartilage defects. Clinical relevance: Rehabilitation after cell-based cartilage repair can be prolonged, leading to decreased patient productivity and quality of life. This study shows the feasibility of using genetically modified chondrocytes to accelerate cartilage healing. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Osteoprotegerin induces osteopontin via syndecan-1 and phosphoinositol 3-kinase/Akt in human periodontal ligament cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 6 2009T. Yongchaitrakul Background and Objective:, Our previous study found that thrombin induced osteoprotegerin synthesis in human periodontal ligament cells. As elevated levels of osteoprotegerin can exert biological effects on various cell types, in the present study we investigated the effect of osteoprotegerin on the expression of osteopontin in human periodontal ligament cells. Material and Methods:, Cultured human periodontal ligament cells were treated with recombinant human osteoprotegerin (0,100 ng/mL) for 24,48 h. The expression of osteopontin mRNA and protein was analyzed using reverse transcription,polymerase chain reaction and western blot analyses, respectively. Phosphoinositol 3-kinase inhibitor, Akt inhibitor, heparinase, neutralizing antibody against receptor activator of nuclear factor-,B ligand (RANKL) and syndecan-1, and small interfering RNA against syndecan-1, were used to determine the mechanism involved. Results:, Osteoprotegerin up-regulated the mRNA and protein expression of osteopontin in human periodontal ligament cells in a dose-dependent manner. Addition of neutralizing antibody against RANKL attenuated the inductive effect of osteoprotegerin on osteopontin expression. In addition, the inductive effect of osteoprotegerin was abolished by phosphoinositol 3-kinase and Akt inhibitors, as well as by syndecan-1 antibody or syndecan-1 small interfering RNA. None of the inhibitors had any effect on the background level of osteopontin expression. Conclusion:, An increased level of osteoprotegerin can generate signals via a RANKL/syndecan-1/phosphoinositol 3-kinase/Akt pathway. The results also suggest that osteopontin is one of the downstream targets of the pathway mediated by osteoprotegerin in human periodontal ligament cells. Thus, in addition to counteracting RANKL in the RANKL,osteoprotegerin system, osteoprotegerin may play a role in periodontal tissue remodeling through modulation of the extracellular matrix. [source] Oral malodorous compound causes apoptosis and genomic DNA damage in human gingival fibroblastsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2008K. Yaegaki Background and Objective:, Volatile sulfur compounds are the main cause of halitosis. Hydrogen sulfide is one of these volatile sulfur compounds and the principal malodorous compound in physiological halitosis. Periodontally pathogenic activities of hydrogen sulfide have been previously reported. Hydrogen sulfide induces apoptotic cell death in aorta smooth muscle cells and in other tissues. Apoptosis plays an important role in the onset and progress of periodontitis. The objective of this study was to determine whether hydrogen sulfide causes apoptosis in human gingival fibroblasts. Material and methods:, Necrotic cells were detected using a lactate dehydrogenase assay. Apoptosis was ascertained using a histone-complexed DNA fragment assay and flow cytometry. The level of caspase 3, a key enzyme in apoptotic signaling, was also measured, and the effects of hydrogen sulfide on reactive oxygen species and superoxide dismutase were assessed. DNA damage caused by hydrogen sulfide was examined by means of single-cell gel electrophoresis. Results:, After 72 h of incubation with 100 ng/mL of hydrogen sulfide, necrosis was found in less than 10% of human gingival fibroblasts, whereas apoptosis was significantly increased (p < 0.05). Superoxide dismutase activity was strongly inhibited, and reactive oxygen species production was enhanced, after 48 and 72 h of incubation. Caspase 3 activity was also increased after 72 h of incubation (p < 0.01). Tail length, percentage of DNA in tail, and tail moment, measured by single-cell gel electrophoresis, were also intensified after 72 h of incubation (p < 0.001). Conclusion:, Hydrogen sulfide caused apoptosis and DNA damage in human gingival fibroblasts. An increased level of reactive oxygen species stimulated by hydrogen sulfide may induce apoptosis and DNA strand breaks. [source] WHO/ISBRA Study on State and Trait Markers of Alcohol Use and Dependence: Analysis of Demographic, Behavioral, Physiologic, and Drinking Variables That Contribute to Dependence and Seeking TreatmentALCOHOLISM, Issue 7 2002Jason Glanz Background Discussions between the World Health Organization (WHO) and the International Society on Biomedical Research on Alcoholism (ISBRA) identified the need for a multiple-center international study on state and trait markers of alcohol abuse and alcohol dependence. The reasoning behind the generation of such a project included the need to understand the alcohol use characteristics of diverse populations and the performance of biological markers of alcohol use in a variety of settings throughout the world. A second major reason for initiating this study was to collect DNA for well-structured and stratified association studies between genetic markers and/or "candidate" genes and behavioral/physiological phenotypes of importance to predisposition to alcohol dependence. Methods An extensive interview instrument was developed with leadership from the U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA). The instrument was translated from English to Finnish, French, German, Japanese, and Portuguese (Brazilian). One thousand eight hundred sixty-three subjects were recruited at five clinical centers (Montreal, Canada; Helsinki, Finland; Sapporo, Japan; São Paulo, Brazil; and Sydney, Australia). The subjects responded to the structured interview and provided blood and urine samples for biochemical analysis. This article focuses on the demographic characteristics of the study subjects, their drinking habits, alcohol-dependence characteristics, comorbid psychiatric and other drug variables, and predictors for seeking treatment for alcohol dependence. Multiple logistic regression models were constructed and used to explore variables that contribute to various levels of alcohol consumption, to a diagnosis of alcohol dependence, and to seeking treatment for alcohol dependence. ANOVA with post hoc comparisons, ,2, and Pearson moment calculations were used as necessary to assess additional relationships between variables. Results A number of factors previously noted in disparate studies were confirmed in our analysis. Men consumed more alcohol than women, Asians consumed less alcohol than whites or Blacks, alcohol-dependent subjects consumed more alcohol than nondependent subjects, alcohol consumption increased with age, and an increased level of education (university or postgraduate education) reduced the percentage of such individuals in the category designated as heavy drinkers (>210 g alcohol/week) and in the group who were currently in treatment for dependence. However, our analysis allowed for much more detailed comparisons; for example, although men drank more than women on a g/day basis, the differences were less pronounced on g/kg/day basis, and alcohol-dependent women drank equal amounts of alcohol as alcohol-dependent men on a g/kg/day basis. Antisocial personality characteristics or reports of trouble sleeping when an individual stops drinking were associated with higher alcohol intake. The most important of the tested factors that contributed to a DSM-IV diagnosis of dependence, however, was the report of anxiety if an individual stopped drinking. In terms of the various criteria within the DSM-IV criteria for alcohol dependence, no one criterion seemed to be prominent for individuals who sought alcohol dependence treatment, but the higher the number of criteria met by the individual, the higher was the probability that he or she would be in treatment. Conclusions This initial report is the beginning of the "data mining" of this rich data set. The cross-national/cross-cultural aspects of this study allowed for multiple comparisons of variables across several ethnic/racial groups and allowed for assessment of biochemical markers for alcohol intake and predisposition to alcohol dependence in diverse settings. [source] Influence of amylases on the rheological and molecular properties of partially damaged wheat starchJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 11 2006Pedro Leman Abstract The effects of Bacillus subtilis, porcine pancreatic and Aspergillus oryzae ,-amylases, sweet potato ,-amylase and Bacillus stearothermophilus maltogenic amylase (BStA) on the rheological properties (measured with a Rapid Visco Analyser) of partially damaged wheat starch were studied and the accompanying changes in starch molecular properties were analysed by high-performance size exclusion chromatography. Pasting and gelation of starch slurries (with an increased level of damaged starch) were significantly affected by the supplemented amylases and greatly depended on the mode of action and properties of the enzymes added. In general, at low endo-amylase concentrations, peak, hot paste and cold paste viscosities were more reduced for enzyme-supplemented partially damaged starch than for enzyme-supplemented native wheat starch, demonstrating the significance of damaged starch levels in determining amylase functionality. Higher dosages of thermostable amylases ruled out most of the differences between amylase-supplemented native starch and partially damaged starches, except for BStA. Furthermore, the (limited) endo-action of BStA determines to a great extent the rheological properties of the starch paste. These results contribute to a better understanding of (maltogenic) amylase functionality in processing (damaged) starch-containing foods. Copyright © 2006 Society of Chemical Industry [source] Inorganic phosphate has a crucial effect on Cry3Aa , -endotoxin productionLETTERS IN APPLIED MICROBIOLOGY, Issue 4 2005A. Kurt Abstract Aims:, The study aimed at increasing Cry3Aa , -endotoxin production by a local isolate of Bacillus thuringiensis (B.t. strain Mm2). To this end, different nutritional conditions were tested for their effects on Cry3Aa yields. Methods and Results:,Bacillus thuringiensis Mm2 was grown by shaking at 30°C in different media. Samples were taken from the cultures at intervals and used for protein extraction. SDS-PAGE was performed for toxin analysis. Inclusion of inorganic phosphate (Pi) into the Difco's sporulation medium at an increased level of 200 mmol l,1 caused a fivefold increase (from 3 to 15·6 ,g ml,1) in toxin production. Omission of FeSO4 from the medium decreased this yield by half. Resuspension experiments suggested catabolite repression of toxin biosynthesis by glucose. The inclusion of high Pi invariably increased toxin synthesis, even in the absence of sugars. Conclusions:, Inorganic phosphate had the most striking effect on toxin biosynthesis. Iron effect was found to be unique to our isolate whereas Pi effect seemed to be common to the biosynthesis of Cry3Aa-type toxins. Stimulation of toxin synthesis by Pi did not seem to represent a relief from glucose repression. Significance and Impact of the Study:,Bacillus thuringiensis is the most versatile biopesticide for use in pest management. Regarding cost-effectiveness of related fermentations, high Pi supplement drastically increases Coleoptera-specific toxin synthesis. [source] | ||||||||||||||||||||||||||||||||||||||||||||||