bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of the BRCA1 Tumor Suppressor in DNA Double-Strand Break Repair
Authors: Zhang Junran , Powell Simon N. 
Published: October 2005

Abstract
The tumor suppressor gene BRCA1 was cloned in 1994 based on its linkage to early-onset breast and ovarian cancer. Although the BRCA1 protein has been implicated in multiple cellular functions, the precise mechanism that determines its tumor suppressor activity is not defined. Currently, the emerging picture is that BRCA1 plays an important role in maintaining genomic integrity by protecting cells from double-strand breaks (DSB) that arise during DNA replication or after DNA damage. The DSB repair pathways available in mammalian cells are homologous recombination and nonhomologous end-joining. BRCA1 function seems to be regulated by specific phosphorylations in response to DNA damage and we will focus this review on the roles played by BRCA1 in DNA repair and cell cycle checkpoints. Finally, we will explore the idea that tumor suppression by BRCA1 depends on its control of DNA DSB repair, resulting in the promotion of error-free and the inhibition of error-prone recombinational repair.
Chemokines in Children With Heterozygous Familiar Hypercholesterolemia
Authors: Holven Kirsten B. , Damås Jan K. , Yndestad Arne , Wæhre Torgun , Ueland Thor , Halvorsen Bente , Heggelund Lars , Sandberg Wiggo J. , Semb Anne G. , Frøland Stig S. , Ose Leiv , Nenseter Marit S. , Aukrust Pål 
Published: October 2005

Objective—Increasing data support the involvement of chemokines in atherogenesis. However, although several studies have shown increased chemokine levels in adult patients, the literature is virtually devoid of data on chemokines in children with hypercholesterolemia.Methods and Results—We examined the gene expression of chemokines in peripheral blood mononuclear cells (PBMCs) from clinically healthy children with and without heterozygous familial hypercholesterolemia (FH). Our main findings were: (1) compared with healthy controls, PBMCs from FH children showed significantly higher mRNA levels of RANTES, but not of the other examined chemokines; (2) an opposite pattern was seen in adult FH subjects, with markedly enhanced expression of macrophage inflammatory peptide-1α, but not of RANTES; (3) this increased gene expression of RANTES in PBMCs from FH children seemed to reflect enhanced RANTES expression in monocytes but not in T cells; (4) FH children also had raised serum levels of neopterin, additionally suggesting monocyte/macrophage activation in these children; and (5) PBMCs from both FH children and controls showed enhanced release of interleukin 8 on RANTES stimulation in vitro.Conclusions—Our findings support a role of inflammation also in the early stages of atherogenesis possibly involving monocyte-derived RANTES as an important mediator.
Role of Blood Cell–Associated AT1 Receptors in the Microvascular Responses to Hypercholesterolemia
Authors: Petnehazy Thomas , Stokes Karen Y. , Wood Katherine C. , Russell Janice , Granger D. Neil 
Published: October 2005

Objective—Hypercholesterolemia elicits a proinflammatory and prothrombogenic phenotype in the microvasculature that is characterized by activation and adhesion of blood cells. The angiotensin II receptor-1 antagonist Losartan prevents the induction of these responses. The objective of this study was to determine the relative contributions of blood cell-associated versus endothelium-associated AT1a-R to these hypercholesterolemia-induced microvascular alterations.Methods and Results—Leukocyte adhesion and emigration and platelet adhesion were quantified by intravital microscopy in postcapillary venules. C57Bl/6 mice were placed on a normal (ND) or high-cholesterol (HCD) diet for 2 weeks. AT1a-R bone marrow chimeras that express AT1a-R on the vessel wall but not blood cells and AT1a-R knockouts were placed on HCD. Venular shear rate was comparable in all groups. Platelet and leukocyte adhesion and leukocyte emigration were significantly increased in HCD mice versus ND. Leukocyte recruitment was significantly reduced in the HCD-AT1a-R bone marrow chimera group, whereas platelet adhesion remained at HCD levels. However, in HCD-AT1a-R knockout mice, platelet and leukocyte adhesion were reduced to ND levels.Conclusions—These data indicate that the platelet-vessel wall adhesion elicited by hypercholesterolemia is mediated by AT1a-R engagement on the endothelial cell rather than the platelet, whereas leukocyte recruitment is mediated by blood cell-associated AT1a-R.
The role of surfactant protein D in the colonisation of the respiratory tract and onset of bacteraemia during pneumococcal pneumonia
Authors: Jounblat R , Clark H , Eggleton P , Hawgood S , Andrew PW , Kadioglu A 
Published: October 2005

AbstractWe have shown previously that surfactant protein D (SP-D) binds and agglutinatesStreptococcus pneumoniae in vitro. In this study, the role of SP-D in innate immunity againstS. pneumoniaewas investigatedin vivo, by comparing the outcome of intranasal infection in surfactant protein D deficient (SP-D-/-) to wildtype mice (SP-D+/+). Deficiency of SP-D was associated with enhanced colonisation and infection of the upper and lower respiratory tract and earlier onset and longer persistence of bacteraemia. Recruitment of neutrophils to inflammatory sites in the lung was similar in both strains mice in the first 24 hrs post-infection, but different by 48 hrs. T cell influx was greatly enhanced in SP-D-/- mice as compared to SP-D+/+ mice. Our data provides evidence that SP-D has a significant role to play in the clearance of pneumococci during the early stages of infection in both pulmonary sites and blood.
Limitations of mRNA amplification from small-size cell samples
Authors: Nygaard Vigdis , Holden Marit , Løland Anders , Langaas Mette , Myklebost Ola , Hovig Eivind 
Published: October 2005

AbstractBackgroundGlobal mRNA amplification has become a widely used approach to obtain gene expression profiles from limited material. An important concern is the reliable reflection of the starting material in the results obtained. This is especially important with extremely low quantities of input RNA where stochastic effects due to template dilution may be present. This aspect remains under-documented in the literature, as quantitative measures of data reliability are most often lacking. To address this issue, we examined the sensitivity levels of each transcript in 3 different cell sample sizes. ANOVA analysis was used to estimate the overall effects of reduced input RNA in our experimental design. In order to estimate the validity of decreasing sample sizes, we examined the sensitivity levels of each transcript by applying a novel model-based method, TransCount.ResultsFrom expression data, TransCount provided estimates of absolute transcript concentrations in each examined sample. The results from TransCount were used to calculate the Pearson correlation coefficient between transcript concentrations for different sample sizes. The correlations were clearly transcript copy number dependent. A critical level was observed where stochastic fluctuations became significant. The analysis allowed us to pinpoint the gene specific number of transcript templates that defined the limit of reliability with respect to number of cells from that particular source. In the sample amplifying from 1000 cells, transcripts expressed with at least 121 transcripts/cell were statistically reliable and for 250 cells, the limit was 1806 transcripts/cell. Above these thresholds, correlation between our data sets was at acceptable values for reliable interpretation.ConclusionThese results imply that the reliability of any amplification experiment must be validated empirically to justify that any gene exists in sufficient quantity in the input material. This finding has important implications for any experiment where only extremely small samples such as single cell analyses or laser captured microdissected cells are available.
A framework to evaluate research capacity building in health care
Authors: Cooke Jo 
Published: October 2005

Abstract

Background
Building research capacity in health services has been recognised internationally as important in order to produce a sound evidence base for decision-making in policy and practice. Activities to increase research capacity for, within, and by practice include initiatives to support individuals and teams, organisations and networks. Little has been discussed or concluded about how to measure the effectiveness of research capacity building (RCB)

Discussion
This article attempts to develop the debate on measuring RCB. It highlights that traditional outcomes of publications in peer reviewed journals and successful grant applications may be important outcomes to measure, but they may not address all the relevant issues to highlight progress, especially amongst novice researchers. They do not capture factors that contribute to developing an environment to support capacity development, or on measuring the usefulness or the 'social impact' of research, or on professional outcomes.
The paper suggests a framework for planning change and measuring progress, based on six principles of RCB, which have been generated through the analysis of the literature, policy documents, empirical studies, and the experience of one Research and Development Support Unit in the UK. These principles are that RCB should: develop skills and confidence, support linkages and partnerships, ensure the research is 'close to practice', develop appropriate dissemination, invest in infrastructure, and build elements of sustainability and continuity. It is suggested that each principle operates at individual, team, organisation and supra-organisational levels. Some criteria for measuring progress are also given.

Summary
This paper highlights the need to identify ways of measuring RCB. It points out the limitations of current measurements that exist in the literature, and proposes a framework for measuring progress, which may form the basis of comparison of RCB activities. In this way it could contribute to establishing the effectiveness of these interventions, and establishing a knowledge base to inform the science of RCB.
Distribution of cytochrome P450 2C, 2E1, 3A4, and 3A5 in human colon mucosa
Authors: Bergheim Ina , Bode Christiane , Parlesak Alexandr 
Published: October 2005

AbstractBackgroundDespite the fact that the alimentary tract is part of the body's first line of defense against orally ingested xenobiotica, little is known about the distribution and expression of cytochrome P450 (CYP) enzymes in human colon. Therefore, expression and protein levels of four representative CYPs (CYP2C(8), CYP2E1, CYP3A4, and CYP3A5) were determined in human colon mucosa biopsies obtained from ascending, descending and sigmoid colon.MethodsExpression of CYP2C, CYP2E1, CYP3A4, and CYP3A5 mRNA in colon mucosa was determined by RT-PCR. Protein concentration of CYPs was determined using Western blot methods.ResultsExtensive interindividual variability was found for the expression of most of the genes. However, expression of CYP2C mRNA levels were significantly higher in the ascending colon than in the sigmoid colon. In contrast, mRNA levels of CYP2E1 and CYP3A5 were significantly lower in the ascending colon in comparison to the descending and sigmoid colon. In sigmoid colon protein levels of CYP2C8 were significantly higher by ~73% than in the descending colon. In contrast, protein concentration of CYP2E1 was significantly lower by ~81% in the sigmoid colon in comparison to the descending colon.ConclusionThe current data suggest that the expression of CYP2C, CYP2E1, and CYP3A5 varies in different parts of the colon.
Axial stent strut angle influences wall shear stress after stent implantation: analysis using 3D computational fluid dynamics models of stent foreshortening
Authors: LaDisa John F , Olson Lars E , Hettrick Douglas A , Warltier David C , Kersten Judy R , Pagel Paul S 
Published: October 2005

Abstract

Introduction
The success of vascular stents in the restoration of blood flow is limited by restenosis. Recent data generated from computational fluid dynamics (CFD) models suggest that the vascular geometry created by an implanted stent causes local alterations in wall shear stress (WSS) that are associated with neointimal hyperplasia (NH). Foreshortening is a potential limitation of stent design that may affect stent performance and the rate of restenosis. The angle created between axially aligned stent struts and the principal direction of blood flow varies with the degree to which the stent foreshortens after implantation.

Methods
In the current investigation, we tested the hypothesis that stent foreshortening adversely influences the distribution of WSS and WSS gradients using time-dependent 3D CFD simulations of normal arteries based on canine coronary artery measurements of diameter and blood flow. WSS and WSS gradients were calculated using conventional techniques in ideal (16 mm) and progressively foreshortened (14 and 12 mm) stented computational vessels.

Results
Stent foreshortening increased the intrastrut area of the luminal surface exposed to low WSS and elevated spatial WSS gradients. Progressive degrees of stent foreshortening were also associated with strut misalignment relative to the direction of blood flow as indicated by analysis of near-wall velocity vectors.

Conclusion
The current results suggest that foreshortening may predispose the stented vessel to a higher risk of neointimal hyperplasia.
Time course of exercise induced alterations in daily activity in chronic fatigue syndrome
Authors: Black Christopher D , McCully Kevin K 
Published: October 2005

Abstract
In a previous study we demonstrated that while people with CFS had lower daily activity levels than control subjects, they were able to increase daily activity via a daily walking program. We reanalyzed our data to determine the time course of activity changes during the walking program. Daily activity assessed via an accelometer worn at the hip was divided into sleep, active, and walking periods. Over the first 4–10 days of walking the subjects with CFS were able to reach the prescribed activity goals each day. After this time, walking and total activity counts decreased. Sedentary controls subjects were able to maintain their daily walking and total activity goals throughout the 4 weeks. Unlike our previous interpretation of the data, we feel this new analysis suggests that CFS patients may develop exercise intolerance as demonstrated by reduced total activity after 4–10 days. The inability to sustain target activity levels, associated with pronounced worsening of symptomology, suggests the subjects with CFS had reached their activity limit.
Dobutamine stress echocardiography in healthy adult male rats
Authors: Plante Eric , Lachance Dominic , Drolet Marie-Claude , Roussel Élise , Couet Jacques , Arsenault Marie 
Published: October 2005

AbstractBackgroundDobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response.Methods15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe.ResultsDobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate.ConclusionDSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.
Easy and rapid method for the determination of gene expression in cumulus cells incubated for oocyte maturation
Authors: Kumamoto Kanako , Wang Haifeng , Yamashiro Hideaki , Terada Takato 
Published: October 2005

Abstract

Background
The objectives of this study were to develop an easy and rapid method for measuring gene expression in a small number of cells by real-time PCR without RNA extraction and purification, and to use this method to determine more precisely IGF-I gene expression in the cumulus cells surrounding oocytes.

Methods
First, after small numbers of cumulus cells were lysed in cell lysis buffer, they were digested with various concentrations of DNase I for different periods at 37°C to determine the optimal conditions for digestion of genomic DNA in the lysate. Since nonspecific amplification was liable to occur when the non-purified RT product of the cell lysate was used for real-time PCR with the given primers, the optimal conditions for Mg2+ and annealing temperature were well investigated. Further, to create the same conditions as in the actual sample reaction for measurement by real-time PCR, RT-minus product was added to the reaction mixture of the standard curve, and then the amplification efficiency was assessed. Next, IGF-I gene expression in cumulus cells collected from cumulus oocyte complexes (COCs) every 4 h during maturation was determined using the developed method.

Results
The optimal conditions for measuring gene expression using the cell lysate from a small number of cells were as follows: incubation of the cell lysate with 0.16 U/microL DNase I with 10 U/microL for 30 min, an Mg concentration of 1.5 mM for amplification of target gene by real-time PCR using RT-product of the cell lysate. When the RT-minus products added to the reaction mixture for the standard curve, which was prepared for purified 18SrRNA plasmid, the PCR efficiency was similar between the sample and the standard.
The IGF-I gene expression in the cumulus cells was elevated up through the first 8 h of the culture and then declined gradually by the end of maturation, with the maximal gene expression (778-fold) seen at 8 h.

Conclusion
It can be concluded that the method developed here, in which equivalent to cumulus cells collected from 0.03–0.075 COCs were employed per reaction, permits rapid and easy determination of target gene expression in a limited number of cells using real-time PCR without RNA extraction.
The effect of performance-related pay of hospital doctors on hospital behaviour: a case study from Shandong, China
Authors: Liu Xingzhu , Mills Anne 
Published: October 2005

Abstract

Background
With the recognition that public hospitals are often productively inefficient, reforms have taken place worldwide to increase their administrative autonomy and financial responsibility. Reforms in China have been some of the most radical: the government budget for public hospitals was fixed, and hospitals had to rely on charges to fill their financing gap. Accompanying these changes was the widespread introduction of performance-related pay for hospital doctors – termed the "bonus" system. While the policy objective was to improve productivity and cost recovery, it is likely that the incentive to increase the quantity of care provided would operate regardless of whether the care was medically necessary.

Methods
The primary concerns of this study were to assess the effects of the bonus system on hospital revenue, cost recovery and productivity, and to explore whether various forms of bonus pay were associated with the provision of unnecessary care. The study drew on longitudinal data on revenue and productivity from six panel hospitals, and a detailed record review of 2303 tracer disease patients (1161 appendicitis patients and 1142 pneumonia patients) was used to identify unnecessary care.

Results
The study found that bonus system change over time contributed significantly to the increase in hospital service revenue and hospital cost recovery. There was an increase in unnecessary care and in the probability of admission when the bonus system switched from one with a weaker incentive to increase services to one with a stronger incentive, suggesting that improvement in the financial health of public hospitals was achieved at least in part through the provision of more unnecessary care and drugs and through admitting more patients.

Conclusion
There was little evidence that the performance-related pay system as designed by the sample of Chinese public hospitals was socially desirable. Hospitals should be monitored more closely by the government, and regulations applied to limit opportunistic behaviour. Otherwise, the containment of government financing for public facilities may result in an increase in the provision of unnecessary care, an increase in health costs to society, and a waste in social resources.
"There's no place like home" A pilot study of perspectives of international health and social care professionals working in the UK
Authors: Moran Anna , Nancarrow Susan , Butler Allister 
Published: October 2005

Abstract

Background
Many countries are reporting health workforce shortages across a range of professions at a time of relatively high workforce mobility. Utilising the global market to supply shortage health skills is now a common recruitment strategy in many developed countries. At the same time a number of countries report a 'brain drain' resulting from professional people leaving home to work overseas. Many health and social care professionals make their way to the UK from other countries. This pilot study utilises a novel 'e-survey' approach to explore the motives, experiences and perspectives of non-UK health and social care professionals who were working or had worked in the UK. The study aims to understand the contributions of international health and social care workers to the UK and their 'home' countries. The purpose of the pilot study is also in part to test the appropriateness of this methodology for undertaking a wider study.

Results
A 24-item questionnaire with open-ended and multiple choice questions was circulated via email to 10 contacts who were from a country outside the UK, had trained outside the UK and had email access. These contacts were requested to forward the email to other contacts who met these criteria (and so on). The email was circulated over a one month pilot period to 34 contacts. Responses were from physiotherapists (n = 11), speech therapists (n = 4), social workers (n = 10), an occupational therapist (n = 1), podiatrists (n = 5), and others (n = 3). Participants were from Australia (n = 20), South Africa (n = 10), New Zealand (n = 3) and the Republic of Ireland (n = 1). Motives for relocating to the UK included travel, money and career opportunities. Participants identified a number of advantages and disadvantages of working in the UK compared to working in their home country health system. Respondents generally reported that by working in the UK, they had accumulated skills and knowledge that would allow them to contribute more to their profession and health system on their return home.

Conclusion
This pilot study highlights a range of issues and future research questions for international learning and comparison for the health and social care professions as a result of international workforce mobility. The study also highlights the usefulness of an e-survey technique for capturing information from a geographically diverse and mobile group of professionals.