bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pleiotrophin receptor RPTP‐ζ/β expression is up‐regulated by l‐DOPA in striatal medium spiny neurons of parkinsonian rats
Authors: Ferrario Juan Esteban , Rojas‐Mayorquín Argelia Esperanza , Saldaña‐Ortega Marisa , Salum Cristiane , Gomes Margarete Zanardo , Hunot Stéphane , Raisman‐Vozari Rita 
Published: August 2008

Abstract l‐DOPA is still the drug of choice to treat Parkinson’s disease although adverse side effects appear after several years of treatment. These are thought to be the consequence of plastic re‐arrangements of the nigrostriatal connections, such as sprouting of the dopaminergic terminals or post‐synaptic changes. Pleiotrophin, a trophic factor that we have shown to be up‐regulated in the striatum of parkinsonian rats after long‐term l‐DOPA treatment may play a role in these plastic changes. To determine whether one of the three known pleiotrophin receptors [N‐syndecan, receptor protein tyrosine phosphatase type zeta beta (RPTP‐ζ/β) and anaplastic lymphoma kinase] might be implicated in these putative plastic effects, we quantified their expression levels by real‐time RT‐PCR in the striatum and mesencephalon of rats with partial lesions of the nigrostriatal pathway undergoing l‐DOPA treatment. Both pleiotrophin and RPTP‐ζ/β expression was up‐regulated in the striatum but not in the mesencephalon of lesioned rats and RPTP‐ζ/β expression was even further increased by l‐DOPA. The levels of the RPTP‐ζ/β protein were also increased in the striatum of l‐DOPA‐treated lesioned rats. Immunofluorescence labeling showed the protein to be constitutively expressed in striatal medium spiny neurons, which are innervated by both the corticostriatal glutamatergic and nigrostriatal dopaminergic systems. RPTP‐ζ/β might therefore be implicated in the plastic changes triggered by l‐DOPA treatment and might merit further study as a potential candidate for Parkinon’s disease therapy.
Age‐dependent effects of chronic stress on brain plasticity and depressive behavior
Authors: Toth Erika , Gersner Roman , Wilf‐Yarkoni Adi , Raizel Hagit , Dar Dalit E. , Richter‐Levin Gal , Levit Ofir , Zangen Abraham 
Published: August 2008

AbstractExposure to chronic mild stress (CMS) is known to induce anhedonia in adult animals, and is associated with induction of depression in humans. However, the behavioral effects of CMS in young animals have not yet been characterized, and little is known about the long‐term neurochemical effects of CMS in either young or adult animals. Here, we found that CMS induces anhedonia in adult but not in young animals, as measured by a set of behavioral paradigms. Furthermore, while CMS decreased neurogenesis and levels of brain‐derived neurotrophic factor (BDNF) in the hippocampus of adult animals, it increased these parameters in young animals. We also found that CMS altered α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA) receptor GluR1 subunit levels in the hippocampus and the nucleus accumbens of adult, but not young animals. Finally, no significant differences were observed between the effects of CMS on circadian corticosterone levels in the different age groups. The substantially different neurochemical effects chronic stress exerts in young and adult animals may explain the behavioral resilience to such stress young animals possess.
Variation in mitochondrial genotype has substantial lifespan effects which may be modulated by nuclear background
Authors: Clancy David J. 
Published: August 2008

SummaryMitochondria are thought to play a central role in aging. In humans, specific naturally occurring mitochondrial genetic variants are overrepresented among centenarians, but only in certain populations; therefore, we cannot tell whether this effect is due solely to mitochondrial genetics or to nuclear‐mitochondrial gene complexes, nor do we know the magnitude of the effect in terms we can relate to, such as mean lifespan differences. To examine the effects of natural mitochondrial DNA (mtDNA) variation on lifespan, we need to vary the mitochondrial genotype while controlling the nuclear genotype. Here, nuclear genome replacement is achieved using strains ofDrosophila melanogasterbearing multiply inverted ‘balancer’ chromosomes that suppress recombination, and an isogenic donor strain, thus forcing replacement of entire chromosomes in a single cross while suppressing recombination. Lifespans of wild‐type mtDNA variants on the chromosome replacement background vary substantially, and sequencing of the entire protein coding mitochondrial genomes indicates that these lifespan differences are sometimes associated with single amino acid differences. On other nuclear genetic backgrounds, the magnitude and direction of these lifespan effects can change dramatically, and this can be due to changes in baseline mortality risk, rate of aging and/or time of onset of aging. The limited mtDNA variation inD. melanogastermakes it an ideal organism for biochemical studies to link genotype and aging phenotype.
The LoTrach™ system: its role in the prevention of ventilator‐associated pneumonia
Authors: Fletcher Andrew JW , Ruffell Alison J , Young Peter J 
Published: August 2008

AbstractObjectives:  To discuss the development of the LoTrach™ system in light of current evidence around the prevention of ventilator‐associated pneumonia (VAP) and its practical application in the intensive care setting.Background:  VAP causes substantial morbidity and mortality in ventilated patients in the Intensive Care Unit (ICU), increases length of stay in ICU and is extremely costly. Strategies are needed to reduce the risk of VAP.Method:  We examine the need for an endotracheal tube (ETT) specifically designed for the critically‐ill patient, the development of the LoTrach system from conception to production, and the role of the various components of the system in preventing VAP. Early issues in implementing this revolutionary equipment into ICU are explored and three case studies highlight advantages of this system.Conclusion:  The LoTrach system has been designed to facilitate the provision of a number of evidence‐based interventions that have been shown to reduce VAP. Pulmonary aspiration is ubiquitous with conventional cuffs but prevented by the cuff of the LoTrach system when held at a constant and safe pressure against the tracheal wall with a cuff pressure controller. Other aspects incorporated in the ETT are aimed at clearing the secretions from the subglottic space, preventing tube occlusion and accidental extubation, and avoiding damage to the airway. In this way the LoTrach system employs a multifactorial approach to the prevention of VAP and the cost savings from LoTrach rather than a standard ETT will be considerable because of an average 3 day reduction in ICU length of stay related to this. It thus has the potential to be a very useful tool in the ICU setting in the prevention of VAP.
Ventilator‐associated pneumonia in paediatric intensive care: a literature review
Authors: Turton Patrick 
Published: August 2008

AbstractBackground:  Ventilator‐associated pneumonia (VAP) has been identified as the most common nosocomial infection in intensive care units (ICUs) with associated health and financial costs. To date, more research has been carried out in adult ICUs than in paediatric units, thus prompting a review and investigation of the implications for paediatric practice.Aims:  To identify relevant paediatric literature surrounding VAP and use this in association with research carried out in the adult environment to establish the implications of VAP and possible management strategies.Search strategies:  A literature search was undertaken using databases within DialogDatastar to identify the extent to which VAP has been researched in both paediatric and adult centres. This information was used to try and gain a clearer concept of the impact and management of VAP in the paediatric setting. Key words and combinations included VAP, intensive care, paediatric, antibiotics, positioning, suction, economics, management, nosocomial and morbidity and mortality.Results of analysis:  Despite the documented significance of VAP in terms of its financial and health implications, discrepancies and inconsistencies exist surrounding the identification and treatment of VAP. This is reflected in paediatric centres by a dearth of literature on the subject and the lack of a national standard as to the management and prevention of VAP. Inappropriate management of VAP plays an important role in the development and spread of multiresistant bacteria within hospitals.Conclusions:  While inadequate paediatric research exists, extrapolating from adult research suggests that the financial and health costs of VAP are substantial and can be reduced by introducing simple low‐cost measures. Such measures include improving education surrounding VAP and its implications and making small changes in practice to improve and maintain oral hygiene standards.Implications:  With a growing cohort of paediatric patients requiring short‐ and long‐term ventilation, progress must be made in identifying the extent and impact of VAP in paediatric ICUs and among the community ventilated patients. This will require changes in practice and attitudes towards VAP for which an appropriate knowledge base would need to be established using audit and research. These issues are particularly relevant in the current environment given the links with multiresistant strains of bacteria within hospitals and the community.
Mentoring in times of change
Authors: Hurley Ciarán , Snowden Sally 
Published: August 2008

AbstractObjective:  The aim of this study was to establish the barriers to nurses performing the mentor role in three critical care wards.Background:  Imminent changes affecting mentors to preregistration students in our wards and our awareness of their ill‐preparedness prompted us to design interventions to prepare colleagues for the changes. Literature shows a range of perceived barriers to mentoring, we wanted to compare these to our colleagues’ perceptionsDesign:  Prospective, self‐administered service evaluation questionnaire of a saturation sample of nurses in intensive care and high dependency wards.Results:  Of the 118 questionnaire proformas issued, 43 were returned (36%). Key results include: lack of time to perform the mentor role because of patient care workload, lack of opportunity to update knowledge and skills of mentoring and lack of familiarity with the programme of study and the documents used to record assessment of a student’s proficiency.Conclusions:  Mentor update opportunities must be delivered alongside the competing demands of safe and effective patient care and the need to ensure the development of individuals as well as the profession as a whole through fostering its students.Relevance to practice:  To ensure future generations of patients enjoy quality critical care, we must invest time and resources in mentoring the nurses who will deliver critical care in the future.
The Role of GABRA2 in Alcohol Dependence, Smoking, and Illicit Drug Use in an Australian Population Sample
Authors: Lind Penelope A. , Macgregor Stuart , Agrawal Arpana , Montgomery Grant W. , Heath Andrew C. , Martin Nicholas G. , Whitfield John B. 
Published: August 2008

Background:  Multiple studies have shown that genetic variation in the α‐2 subunit of the gamma‐aminobutyric acid type A (GABAA) receptor (GABRA2) is associated with risk for alcohol dependence. Recent reports have suggested that GABRA2 may exert its influence on dependence through factors such as sensitivity to alcohol’s intoxicating effects and that GABRA2 may also contribute to a common underlying genetic vulnerability to both alcohol and drug dependence. The present study tested for association between GABRA2 and alcohol dependence, smoking, and illicit drug use within the Australian population.Methods:  We genotyped 11 single nucleotide polymorphisms (SNPs) within or flanking GABRA2 in 4597 subjects (34.6% males) from 2618 families comprising 814 monozygotic pairs, 1177 dizygotic pairs, and 627 twins whose co‐twin did not participate. Family‐based association tests were conducted for binary and quantitative measures of alcohol dependence, smoking, and cannabis and other illicit drug use.Results:  We observed evidence of association (p < 0.05) between multiple GABRA2 SNPs and quantitative measures of alcohol dependence, including symptom scores and principal component factor scores from the 9 criteria for DSM‐IV alcohol dependence, in the opposite direction to that previously reported. In contrast, GABRA2 was not associated overall with dichotomous measure of alcohol dependence nor with smoking, cannabis, or illicit drug use.Conclusions:  The GABRA2 allelic associations found in clinical case–control studies have detectable but minor effects on DSM‐defined alcohol dependence in the general community. Systematic comparisons of allelic effects on alcohol dependence in clinical cases and in the general community are required.
Non‐canonical effects of anthrax toxins on haematopoiesis: implications for vaccine development
Authors: Liu Katherine , Wong Elaine W. , Schutzer Steven E. , Connell Nancy D. , Upadhyay Alok , Bryan Margarette , Rameshwar Pranela 
Published: August 2008

AbstractAnthrax receptor (ATR) shares similarities with molecules relevant to haematopoiesis. This suggests that anthrax proteins might bind to these mimicking molecules and exert non‐specific haematopoietic effects. The haematopoietic system is the site of immune cell development in the adult. As such, ATR ligand, protective antigen (PA) and the other anthrax proteins, lethal factor, edema factor, could be significant to haematopoietic responses against Bacillus anthracis infection. Because haematopoiesis is the process of immune cell development, effects by anthrax proteins could be relevant to vaccine development. Here, we report on effects of anthrax proteins and toxins on early and late haematopoiesis. Flow cytometry shows binding of PA to haematopoietic cells. This binding might be partly specific because flow cytometry and Western blots demonstrate the presence of ATR1 on haematopoietic cell subsets and the supporting stromal cells. Functional studies with long‐term initiating cell and clonogenic assays determined haematopoietic suppression by anthrax toxins and stimulation by monomeric proteins. The suppressive effects were not attributed to cell death, but partly through the induction of haematopoietic suppressors, interleukin (IL)‐10 and CCL3 (MIP‐1α). In summary, anthrax proteins affect immune cell development by effects on haematopoiesis. The type of effect, stimulation or suppression, depend on whether the stimulator is a toxin or monomeric protein. The studies show effects of anthrax proteins beginning at the early stage of haematopoiesis, and also show secondary mediators such as IL‐10 and CCL3. The roles of other cytokines and additional ATR are yet to be investigated.
Functional linkage of Na+‐Ca2+‐exchanger to sarco/endoplasmic reticulum Ca2+ pump in coronary artery: comparison of smooth muscle and endothelial cells
Authors: Davis Kim A. , Samson Sue E. , Hammel Kaitlin E. , Kiss Lorand , Fulop Ferenc , Grover Ashok K. 
Published: August 2008

AbstractAn increase in cytosolic Ca2+ concentration in coronary artery smooth muscle causes a contraction but in endothelium it causes relaxation. Na+‐Ca2+‐exchanger (NCX) may play a role in Ca2+ dynamics in both the cell types. Here, the NCX‐mediated 45Ca2+ uptake was compared in Na+‐loaded pig coronary artery smooth muscle and endothelial cells. In both the cell types, this uptake was inhibited by KB‐R7943, SEA 0400 and by monensin, but not by cariporide. Prior loading of the cells with the Ca2+ chelator BAPTA increased the NCX‐mediated 45Ca2+ uptake in smooth muscle but not in endothelial cells. In the presence or absence of BAPTA loading, the Na+‐mediated 45Ca2+ uptake was greater in endothelial than in smooth muscle cells. In smooth muscle cells without BAPTA loading, thapsigargin diminished the NCX‐mediated 45Ca2+ entry. This effect was not observed in endothelial cells or in either cell type after BAPTA loading. The results in the smooth muscle cells are consistent with a limited diffusional space model in which the NCX‐mediated 45Ca2+ uptake was enhanced by chelation of cytosolic Ca2+ or by its sequestration by the sarco/endoplasmic reticulum Ca2+ pump (SERCA). They suggest a functional linkage between NCX and SERCA in the smooth muscle but not in the endothelial cells. The concept of a linkage between NCX and SERCA in smooth muscle was also confirmed by similar distribution of NCX and SERCA2 proteins when detergent‐treated microsomes were fractionated by flotation on sucrose density gradients. Thus, the coronary artery smooth muscle and endothelial cells differ not only in the relative activities of NCX but also in its functional linkage to SERCA.
Raman tweezers provide the fingerprint of cells supporting the late stages of KSHV reactivation
Authors: Dyson Ossie F. , Ford Patrick W. , Chen De , Li Yong‐Qing , Akula Shaw M. 
Published: August 2008

AbstractKaposi’s sarcoma‐associated herpesvirus (KSHV) has both latent and lytic phases of replication. The molecular switch that triggers a reactivation is still unclear. Cells from the S phase of the cell cycle provide apt conditions for an active reactivation. In order to specifically delineate the Raman spectra of cells supporting KSHV reactivation, we followed a novel approach where cells were sorted based on the state of infection (latent versus lytic) by a flow cytometer and then analysed by the Raman tweezers. The Raman bands at 785, 813, 830, 1095 and 1128 cm−1 are specifically altered in cells supporting KSHV reactivation. These five peaks make up the Raman fingerprint of cells supporting KSHV reactivation. The physiological relevance of the changes in these peaks with respect to KSHV reactivation is discussed in the following report.
Prognostic role of global DNA‐methylation and histone acetylation in pT1a clear cell renal carcinoma in partial nephrectomy specimens
Authors: Minardi D. , Lucarini G. , Filosa A. , Milanese G. , Zizzi A. , Primio R. Di , Montironi R. , Muzzonigro G. 
Published: August 2008

AbstractSurgery is the main treatment for renal cell carcinoma (RCC); nephron sparing surgery can be performed as a treatment of choice for small peripheral lesions. Epigenetics configures a new entity that regulates gene expression throughout methylation, acetylation and chromatin remodelling. In addition to silencing as a result of mutations, loss of heterozygosity, or classic genetic events, epigenetic modification symbolizes essential events during carcinogenesis and tumour development. We investigated global methylation and histone acetylation expression in a series of small conventional clear cell renal carcinomas (i.e. less than 5 cm) (pT1a) treated with partial nephrectomy, to assess their possible role as diagnostic biomarkers. A total of 54 patients with conventional single RCC were selected and treated with partial nephrectomy; they were followed up to 186 months. Immunohistochemistry was performed on paraffin‐embedded sections, using anti‐5‐methylcytosine (5mc) and anti‐Acetyl‐Histone H3 (Lys 9). Our results confirm that the mean percentage of global cellular methylation in tumoural tissue was significantly higher compared to healthy peritumoural tissue, whereas the mean percentage of histone cellular acetylation in tumoural tissue was significantly lower. The percentage of methylation was significantly higher in grades 3 and 4 (P= 0.033), whereas the percentage of histone acetylation was significantly lower (P= 0.023), suggesting therefore that these markers could correlate with tumour aggressiveness in pT1a RCC. On univariate analysis of patient survival in relation to the different considered factors, Fuhrman grade was the most important survival factor. These epigenetic markers can give us interesting information about chromatin remodelling in RCCs; the percentage of global methylation increases with increasing Fuhrman grade, whereas histone acetylation decreases with increasing grade in small RCC; our results suggest that global hypermethylation and histone hypoacetylation can be assumed to be an early event in RCC and to correlate with tumour aggressiveness.
ORIGINAL ARTICLE: A Role for Mannose‐Binding Lectin, a Component of the Innate Immune System in Pre‐Eclampsia
Authors: Than Nandor Gabor , Romero Roberto , Erez Offer , Kusanovic Juan Pedro , Tarca Adi L. , Edwin Samuel S. , Kim Jung‐Sun , Hassan Sonia S. , Espinoza Jimmy , Mittal Pooja , Mazaki‐Tovi Shali , Friel Lara , Gotsch Francesca , Vaisbuch Edi , Camacho Natalia , Papp Zoltan 
Published: August 2008

Problem Mannose‐binding lectin (MBL) is a pattern‐recognition receptor that activates complement and modulates inflammation. Homozygosity for the most common allele of the MBL2 gene that is associated with high MBL serum concentrations is more prevalent among patients with pre‐eclampsia. The objective of this study was to determine maternal plasma MBL concentrations in normal pregnant women and patients with pre‐eclampsia.Method of study This cross‐sectional study included normal pregnant women (n = 187) and patients with pre‐eclampsia (n = 99). Maternal plasma MBL concentrations were determined by ELISA.Results Women with pre‐eclampsia had a higher median maternal plasma MBL concentration than normal pregnant women. MBL concentration distribution curves were three‐modal, the subintervals in normal pregnancy were low (<143.7), intermediate (143.7–1898.9) and high (>1898.9 ng/mL). The proportion of normal pregnant women was larger in the low subinterval, while the proportion of patients with pre‐eclampsia was larger in the high subinterval (P = 0.02). Normal pregnant women in the high subinterval had a larger rate of placental underperfusion than those in the low and intermediate subintervals (P = 0.02).Conclusions The median maternal plasma MBL concentration is elevated in patients with pre‐eclampsia and a larger proportion of these patients are in the high subinterval than normal pregnant women, suggesting that this component of the innate immune system is involved in the mechanisms of disease in pre‐eclampsia.
Effects of long‐term exogenous bovine somatotropin on glucose metabolism and the utilization of glucose by the mammary gland in different stages of lactation of crossbred Holstein cattle
Authors: CHAIYABUTR Narongsak , KOMOLVANICH Siripen , THAMMACHAROEN Sumpun , CHANPONGSANG Somchai 
Published: August 2008

ABSTRACTThe effects of long‐term administration of recombinant bovine somatotropin (rbST) on glucose turnover and the utilization of glucose in the mammary gland using a continuous infusion of [3‐3H]glucose and [U‐14C]glucose in lactating crossbred Holstein Friesian(HF) cattle were investigated. Glucose turnover of rbST‐treated animals was significantly higher than those of control animals (P < 0.05) in mid lactation, while plasma glucose concentrations were not affected. The utilization of glucose of non‐mammary tissues of rbST‐treated animals significantly increased (P < 0.05) as lactation advanced. The glucose taken up by the mammary gland in early lactation increased flux through the lactose synthesis and the pentose cycle pathway with significant increases in NADPH formation for fatty acid synthesis during rbST administration. The utilization of glucose carbon incorporation into milk appeared to increase in milk citrate and milk triacylglycerol but not for milk lactose as lactation advances in rbST‐treated animals. The stimulant effect for milk yield by rbST treatment was transiently and significantly increased in early lactation and was decreased in late lactation even though there was a high level of udder blood flow. These findings demonstrate that the regulation of biosynthetic capacity within the mammary gland would be influenced more by local than by systemic factors. The proportion of glucose would be metabolized less for lactose synthesis, but metabolized more via the Embden‐Meyerhof pathway and the tricarboxylic acid cycle as lactation advances.