bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wheel running from a juvenile age delays onset of specific motor deficits but does not alter protein aggregate density in a mouse model of Huntington's disease
Authors: van Dellen Anton , Cordery Patricia M , Spires Tara L , Blakemore Colin , Hannan Anthony J 
Published: April 2008

Abstract

Background
Huntington's disease (HD) is a neurodegenerative disorder predominantly affecting the cerebral cortex and striatum. Transgenic mice (R6/1 line), expressing a CAG repeat encoding an expanded polyglutamine tract in the N-terminus of the huntingtin protein, closely model HD. We have previously shown that environmental enrichment of these HD mice delays the onset of motor deficits. Furthermore, wheel running initiated in adulthood ameliorates the rear-paw clasping motor sign, but not an accelerating rotarod deficit.

Results
We have now examined the effects of enhanced physical activity via wheel running, commenced at a juvenile age (4 weeks), with respect to the onset of various behavioral deficits and their neuropathological correlates in R6/1 HD mice. HD mice housed post-weaning with running wheels only, to enhance voluntary physical exercise, have delayed onset of a motor co-ordination deficit on the static horizontal rod, as well as rear-paw clasping, although the accelerating rotarod deficit remains unaffected. Both wheel running and environmental enrichment rescued HD-induced abnormal habituation of locomotor activity and exploratory behavior in the open field. We have found that neither environment enrichment nor wheel running ameliorates the shrinkage of the striatum and anterior cingulate cortex (ACC) in HD mice, nor the overall decrease in brain weight, measured at 9 months of age. At this age, the density of ubiquitinated protein aggregates in the striatum and ACC is also not significantly ameliorated by environmental enrichment or wheel running.

Conclusion
These results indicate that enhanced voluntary physical activity, commenced at an early presymptomatic stage, contributes to the positive effects of environmental enrichment. However, sensory and cognitive stimulation, as well as motor stimulation not associated with running, may constitute major components of the therapeutic benefits associated with enrichment. Comparison of different environmental manipulations, performed in specific time windows, can identify critical periods for the induction of neuroprotective 'brain reserve' in animal models of HD and related neurodegenerative diseases.
Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection
Authors: Goffinet Marine , Chinestra Patrick , Lajoie-Mazenc Isabelle , Medale-Giamarchi Claire , Favre Gilles , Faye Jean-Charles 
Published: April 2008

Abstract

Background
The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv) that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings.

Results
After five rounds of phage selection using a constitutively activated mutant of RhoB (RhoBQ63L), three scFvs (A8, C1 and D11) were selected for subsequent analysis. Further biochemical characterization was pursued for the single clone, C1, exhibiting an scFv structure. C1 was selective for the GTP-bound form of RhoA, RhoB, as well as RhoC, and failed to recognize GTP-loaded Rac1 or Cdc42, two other members of the Rho family. To enhance its production, soluble C1 was expressed in fusion with the N-terminal domain of phage protein pIII (scFv C1-N1N2), it appeared specifically associated with GTP-loaded recombinant RhoA and RhoB via immunoprecipitation, and endogenous activated Rho in HeLa cells as determined by immunofluorescence.

Conclusion
We identified an antibody, C1-N1N2, specific for the GTP-bound form of RhoB from a phage library, and confirmed its specificity towards GTP-bound RhoA and RhoC, as well as RhoB. The success of C1-N1N2 in discriminating activated Rho in immunofluorescence studies implies that this new tool, in collaboration with currently used RhoA and B antibodies, has the potential to analyze Rho activation in cell function and tumor development.
HIV transfer between CD4 T cells does not require LFA-1 binding to ICAM-1 and is governed by the interaction of HIV envelope glycoprotein with CD4
Authors: Puigdomènech Isabel , Massanella Marta , Izquierdo-Useros Nuria , Ruiz-Hernandez Raul , Curriu Marta , Bofill Margarita , Martinez-Picado Javier , Juan Manel , Clotet Bonaventura , Blanco Julià 
Published: April 2008

AbstractBackgroundCell-to-cell HIV transmission requires cellular contacts that may be in part mediated by the integrin leukocyte function antigen (LFA)-1 and its ligands intercellular adhesion molecule (ICAM)-1, -2 and -3. The role of these molecules in free virus infection of CD4 T cells or in transinfection mediated by dendritic cells (DC) has been previously described. Here, we evaluate their role in viral transmission between different HIV producing cells and primary CD4 T cells.ResultsThe formation of cellular conjugates and subsequent HIV transmission between productively infected MOLT cell lines and primary CD4 T cells was not inhibited by a panel of blocking antibodies against ICAM-1, ICAM-3 and α and β chains of LFA-1. Complete abrogation of HIV transmission and formation of cellular conjugates was only observed when gp120/CD4 interactions were blocked. The dispensable role of LFA-1 in HIV transmission was confirmed using non-lymphoid 293T cells, lacking the expression of adhesion molecules, as HIV producing cells. Moreover, HIV transmission between infected and uninfected primary CD4 T cells was abrogated by inhibitors of gp120 binding to CD4 but was not inhibited by blocking LFA-1 binding to ICAM-1 or ICAM-3. Rather, LFA-1 and ICAM-3 mAbs enhanced HIV transfer. All HIV producing cells (including 293T cells) transferred HIV particles more efficiently to memory than to naive CD4 T cells.ConclusionIn contrast to other mechanisms of viral spread, HIV transmission between infected and uninfected T cells efficiently occurs in the absence of adhesion molecules. Thus, gp120/CD4 interactions are the main driving force of the formation of cellular contacts between infected and uninfected CD4 T cells whereby HIV transmission occurs.
Phase II Study of Dose-Adjusted EPOCH and Rituximab in Untreated Diffuse Large B-Cell Lymphoma With Analysis of Germinal Center and Post-Germinal Center Biomarkers
Authors: Wilson Wyndham H. , Dunleavy Kieron , Pittaluga Stefania , Hegde Upendra , Grant Nicole , Steinberg Seth M. , Raffeld Mark , Gutierrez Martin , Chabner Bruce A. , Staudt Louis , Jaffe Elaine S. , Janik John E. 
Published: April 2008

PurposeTo assess the clinical outcome and the influence of biomarkers associated with apoptosis inhibition (Bcl-2), tumor proliferation (MIB-1), and cellular differentiation on the outcome with dose-adjusted (DA) EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) plus rituximab (R) infusional therapy in diffuse large B-cell lymphoma (DLBCL) with analysis of germinal center B-cell (GCB) and post-GCB subtypes by immunohistochemistry.Patients and MethodsPhase II study of 72 patients with untreated de novo DLBCL who were at least 18 years of age and stage II or higher. Radiation consolidation was not permitted.ResultsPatients had a median age of 50 years (range, 19 to 85) and 40% had a high-intermediate or high International Prognostic Index (IPI). At 5 years, progression-free survival (PFS) and overall survival (OS) were 79% and 80%, respectively, with a median potential follow-up of 54 months. PFS was 91%, 90%, 67%, and 47%, and OS was 100%, 90%, 74%, and 37%, for 0 to 1, 2, 3, and 4 to 5 IPI factors, respectively, at 5 years. The Bcl-2 and MIB-1 biomarkers were not associated with PFS or OS. Based on DA-EPOCH historical controls, rituximab only benefited Bcl-2 positive tumors. Bcl-6 expression was associated with higher PFS whereas GCB exhibited a marginally significant higher PFS compared with post-GCB DLBCL.ConclusionDA-EPOCH-R outcome was not affected by tumor proliferation and rituximab appeared to overcome the adverse effect of Bcl-2. Bcl-6 may identify a biologic program associated with a superior outcome. Overall, DA-EPOCH-R shows promising outcome in low and intermediate IPI groups. A molecular model of treatment outcome with rituximab and chemotherapy is presented.
Effects of morin on the pharmacokinetics of nicardipine after oral and intravenous administration of nicardipine in rats
Authors: Piao Yong-Ji , Choi Jun-Shik 
Published: April 2008

Abstract
This study investigated the effects of orally administered morin, an inhibitor of cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), on the pharmacokinetics of orally and intravenously administered nicardipine in rats. Nicardipine is reportedly a substrate for CYP3A4 and P-gp. Nicardipine was administered orally (12 mgkg−1) with or without orally administered morin (1.5, 7.5 and 15 mgkg−1), and intravenously (4 mgkg−1) with or without orally administered morin (7.5 and 15 mgkg−1). In the presence of morin, the pharmacokinetic parameters of nicardipine were significantly altered in the oral group but not in the intravenous group, suggesting that CYP3A-mediated metabolism of nicardipine in the liver is not significantly inhibited by morin. The presence of 7.5 and 15 mgkg−1 of morin significantly increased (P&lt; 0.01, 67.8–112%) the area under the plasma concentration-time curve and the peak plasma concentration (P&lt; 0.01, 53.5–93.1%) of orally administered nicardipine. The presence of 7.5 and 15 mgkg−1 of morin significantly decreased (P &lt; 0.01, 40.4–52.8%) the total body clearance of orally administered nicardipine compared with the control group. The enhanced oral bioavailability of nicardipine suggests that intestinal-mediated CYP3A4 metabolism and P-gp-mediated efflux of nicardipine are inhibited by morin. Based on these results, concomitant use of morin or morin-containing dietary supplements with nicardipine may require close monitoring for potential drug interactions.
ABCC2 haplotype is not associated with drug-resistant epilepsy
Authors: Seo Takayuki , Ishitsu Takateru , Oniki Kentaro , Abe Tomohide , Shuto Tsuyoshi , Nakagawa Kazuko 
Published: April 2008

Abstract
Several studies have investigated the association between the ABCB1 polymorphism and drug-resistant epilepsy. However, the effect of ABCC2 polymorphisms on anti-epileptic drug (AED) responsiveness remains unknown. The ABCC2 polymorphisms have been genotyped in 279 Japanese epileptic patients treated with AEDs. The association between the AED responsiveness and the polymorphisms was estimated by a haplotype-based analysis. No genotype or haplotype was associated with drug-resistant epilepsy. On the other hand, the delGCGC haplotype at G-1774delG, C-24T, G1249A and C3972T was over represented among the epileptic patients with a complication of mental retardation in comparison with those without (32.4% vs 22.0%; P = 0.009); and the G-1774delG allele was also associated with mental retardation (P = 0.03). No association between the ABCC2 genotypes or haplotypes, and the responsiveness of AEDs was observed, although this finding was inconclusive because of the small sample size.
The ability of selected pyridinium salts to increase the cytotoxic activity of vincristine but not doxorubicin towards sensitive and multidrug resistant promyelocytic leukaemia HL60 cells
Authors: Maruszewska Agnieszka , Kostrzewa-Nowak Dorota , Adamus Jan , Czupryńska Katarzyna , Maryniak Dominika , Gebicki Jerzy , Tarasiuk Jolanta 
Published: April 2008

Abstract
The aim of this study was to examine the effect of selected pyridinium salts, 1-methyl-3-nitropyridine chloride (MNP+Cl−) and 3,3,6,6,10-pentamethyl-3,4,6,7-tetrahydro-[1,8(2H,5H)-dion]acridine chloride (MDION+Cl−), on the activity of doxorubicin (DOX) and vincristine (VINC) towards human promyelocytic leukaemia HL60 cells as well as its multidrug resistant (MDR) sublines exhibiting two different phenotypes of MDR related to the overexpression of P-glycoprotein (HL60/VINC) or MRP1 (HL60/DOX). MNP and MDION salts were much less cytotoxic themselves (about 100-fold and 2000-fold compared with DOX and VINC, respectively) against HL60 cells but, in contrast to DOX and VINC, they conserved an important cytotoxic activity towards resistant HL60/VINC and HL60/DOX cells (resistance factor, RF = 2–4.5). It was shown that MNP+Cl− and MDION+Cl− increased the cytotoxicity of non-bioreductive antitumour agent VINC towards human promyelocytic leukaemia HL60 cells and its resistant sublines HL60/VINC and HL60/DOX. However, in the case of DOX the decrease in its cytotoxic activity towards all studied cell lines was observed in the presence of MNP+Cl− and MDION+Cl−. Presented data suggest that the bioreductive drug DOX, in contrast to VINC, could compete with pyridinium salts (MNP+Cl− and MDION+Cl−) for NADPH-dependent oxidoreductases and for undergoing cellular reductive activation. This could explain the inefficiency of these salts to increase the cytotoxic activity of DOX against examined leukaemic HL60 cell line and its MDR sublines, HL60/VINC and HL60/DOX.
Importance of Early Neglect for Childhood Aggression
Authors: Kotch Jonathan B. , Lewis Terri , Hussey Jon M. , English Diana , Thompson Richard , Litrownik Alan J. , Runyan Desmond K. , Bangdiwala Shrikant I. , Margolis Benyamin , Dubowitz Howard 
Published: April 2008

OBJECTIVE. The goal was to examine the association between early childhood neglect (birth to age 2 years) and later childhood aggression at ages 4, 6, and 8 years, compared with aggression's associations with early childhood abuse and later abuse and neglect.METHODS. A prospective cohort of 1318 predominantly at-risk children, recruited from 4 US cities and 1 southern state, were monitored from birth to 8 years of age. Maltreatment was determined through review of local child protective services records. A hierarchical, linear model approach, a special case of general, linear, mixed modeling, was used to predict aggressive behavior scores, as reported by the child's primary caregiver at ages 4, 6, and 8 years.RESULTS. Only early neglect significantly predicted aggression scores. Early abuse, later abuse, and later neglect were not significantly predictive in a controlled model with all 4 predictors.CONCLUSION. This longitudinal study suggests that child neglect in the first 2 years of life may be a more-important precursor of childhood aggression than later neglect or physical abuse at any age.
Growth and Nutrient Intakes of Human Milk–Fed Preterm Infants Provided With Extra Energy and Nutrients After Hospital Discharge
Authors: O'Connor Deborah L. , Khan Sobia , Weishuhn Karen , Vaughan Jennifer , Jefferies Ann , Campbell Douglas M. , Asztalos Elizabeth , Feldman Mark , Rovet Joanne , Westall Carol , Whyte Hilary ,   on behalf of the Postdischarge Feeding Study Group
Published: April 2008

OBJECTIVES. The purpose of this pilot study was to determine whether mixing a multinutrient fortifier to approximately one half of the human milk fed each day for a finite period after discharge improves the nutrient intake and growth of predominantly human milk–fed low birth weight infants. We also assessed the impact of this intervention on the exclusivity of human milk feeding.
METHODS. Human milk–fed (≥80% feeding per day) low birth weight (750–1800 g) infants (n = 39) were randomly assigned at hospital discharge to either a control or an intervention group. Infants in the control group were discharged from the hospital on unfortified human milk. Nutrient enrichment of human milk in the intervention group was achieved by mixing approximately one half of the human milk provided each day with a powdered multinutrient human milk fortifier for 12 weeks after discharge. Milk with added nutrients was estimated to contain ∼80 kcal (336 kJ) and 2.2 g protein/100 mL plus other nutrients. Intensive lactation support was provided to both groups.
RESULTS. Infants in the intervention group were longer during the study period, and those born ≤1250 g had larger head circumferences than infants in the control group. There was a trend toward infants in the intervention group to be heavier at the end of the intervention compared with those in the control group. Mean protein, zinc, calcium, phosphorus, and vitamins A and D intakes were higher in the intervention group.
CONCLUSIONS. Results from this study suggest that adding a multinutrient fortifier to approximately one half of the milk provided to predominantly human milk–fed infants for 12 weeks after hospital discharge may be an effective strategy in addressing early discharge nutrient deficits and poor growth without unduly influencing human milk feeding when intensive lactation support is provided.
Vaccination Coverage by Special Health Care Needs Status in Young Children
Authors: O'Connor Kathleen S. , Bramlett Matthew D. 
Published: April 2008

OBJECTIVE. The purpose of this study was to compare vaccination coverage among children 19 to 35 months of age with and without special health care needs overall and among demographic subgroups.METHODS. Data are from the National Survey of Children With Special Health Care Needs, a module of the State and Local Area Integrated Telephone Survey, which was sponsored by the Health Resources and Services Administration Maternal and Child Health Bureau and conducted in 2000–2002 by the Centers for Disease Control and Prevention National Center for Health Statistics. We used data from the National Immunization Survey and the National Survey of Children With Special Health Care Needs to examine immunization coverage rates for individual vaccines and an array of combined series vaccinations. The relationship between special needs and immunization status was analyzed by age, gender, and race or ethnicity of the child; the child's health insurance type; the mother's educational attainment and presence in the household; and household income relative to the federal poverty level.RESULTS. Overall, there were no significant differences between children with and without special needs for any of the individual antigens or combined immunization series. Some significant differences by special needs status were found within certain demographic subgroups.CONCLUSIONS. Our results suggest that, generally children with special health care needs have immunization rates that are very similar to typically developing children. There is some evidence that children with special health care needs are at risk for underimmunization if they are non-Hispanic white or live in an affluent household and are more likely to be immunized if they are Hispanic, poor, publicly insured, or if their mothers did not complete high school. These findings may be due to outreach or support programs that target disadvantaged children. However, it is important to note that the majority of comparisons within demographic subgroups show no significant differences between children with special health care needs and children without special health care needs.
Inattention, Hyperactivity, and School Performance in a Population of School-Age Children With Complex Congenital Heart Disease
Authors: Shillingford Amanda J. , Glanzman Marianne M. , Ittenbach Richard F. , Clancy Robert R. , Gaynor J. William , Wernovsky Gil 
Published: April 2008

INTRODUCTION. There is a growing interest in characterizing the neurodevelopmental outcomes of school-age survivors of cardiac surgery. The purpose of this study was to examine a population of 5- to 10-year-old children who underwent newborn cardiac surgery for complex congenital heart disease to characterize and assess risk factors for problems with inattention and hyperactivity, as well as the use of remedial school services.PATIENTS AND METHODS. This study was a cross-sectional analysis of patients who underwent newborn cardiac surgery and were enrolled in a neuroprotection trial conducted at our institution between 1992 and 1997. Parents and teachers completed questionnaires for the school-age child to elicit information pertaining to the child's general health and academic performance. The severity of hyperactivity and inattention were assessed by using 2 standardized questionnaires (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV and Behavior Assessment System for Children). In addition to calculating descriptive estimates of their occurrence, single-covariate logistic regression models were specified and tested by using 3 different outcomes (inattention, hyperactivity, and use of remedial school services) and 14 different covariates representing preoperative, intraoperative, and postoperative factors.RESULTS. Data were obtained from parents and/or teachers for 109 children. Fifty-three (49%) were receiving some form of remedial academic services, and 15% were assigned to a special-education classroom. The number of children receiving clinically significant scores for inattention and hyperactivity on the Behavior Assessment System for Children was 3 to 4 times higher than observed in the general population. On the Attention-Deficit/Hyperactivity Disorder Rating Scale-IV, 30% of the parents reported high-risk scores for inattention and 29% reported high-risk scores for hyperactivity. No perioperative factors were statistically associated with adverse outcomes.CONCLUSION. In this cohort of children with complex congenital heart disease, a significant proportion of the children were at risk for inattention and hyperactivity, and nearly half were using remedial school services. We did not identify any perioperative risk factors, which correlated with high-risk scores or the use of remedial school services. Ongoing neurodevelopmental follow-up and screening are recommended in this vulnerable population.