bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable low-level expression of p21WAF1/CIP1 in A549 human bronchogenic carcinoma cell line-derived clones down-regulates E2F1 mRNA and restores cell proliferation control
Authors: Graves Timothy G , Harr Michael W , Crawford Erin L , Willey James C 
Published: January 2006

AbstractBackgroundDeregulated cell cycle progression and loss of proliferation control are key properties of malignant cells. In previous studies, an interactive transcript abundance index (ITAI) comprising three cell cycle control genes, [MYC × E2F1]/p21 accurately distinguished normal from malignant bronchial epithelial cells (BEC), using a cut-off threshold of 7,000. This cut-off is represented by a line with a slope of 7,000 on a bivariate plot of p21 versus [MYC × E2F1], with malignant BEC above the line and normal BEC below the line. This study was an effort to better quantify, at the transcript abundance level, the difference between normal and malignant BEC. The hypothesis was tested that experimental elevation of p21 in a malignant BEC line would decrease the value of the [MYC × E2F1]/p21 ITAI to a level below this line, resulting in loss of immortality and limited cell population doubling capacity. In order to test the hypothesis, a p21 expression vector was transfected into the A549 human bronchogenic carcinoma cell line, which has low constitutive p21 TA expression relative to normal BEC.ResultsFollowing transfection of p21, four A549/p21 clones with stable two-fold up-regulated p21 expression were isolated and expanded. For each clone, the increase in p21 transcript abundance (TA) was associated with increased total p21 protein level, more than 5-fold reduction in E2F1 TA, and 10-fold reduction in the [MYC × E2F1]/p21 ITAI to a value below the cut-off threshold. These changes in regulation of cell cycle control genes were associated with restoration of cell proliferation control. Specifically, each transfectant was capable of only 15 population doublings compared with unlimited population doublings for parental A549. This change was associated with an approximate 2-fold increase in population doubling time to 38.4 hours (from 22.3 hrs), resumption of contact-inhibition, and reduced dividing cell fraction as measured by flow cytometric DNA analysis.ConclusionThese results, likely due to increased p21-mediated down-regulation of E2F1 TA at the G1/S phase transition, are consistent with our hypothesis. Specifically, they provide experimental confirmation that a line with slope of 7,000 on the p21 versus [MYC × E2F1] bivariate plot quantifies the difference between normal and malignant BEC at the level of transcript abundance.
Health-related quality of life in patients waiting for major joint replacement. A comparison between patients and population controls
Authors: Hirvonen Johanna , Blom Marja , Tuominen Ulla , Seitsalo Seppo , Lehto Matti , Paavolainen Pekka , Hietaniemi Kalevi , Rissanen Pekka , Sintonen Harri 
Published: January 2006

Abstract

Background
Several quality-of-life studies in patients awaiting major joint replacement have focused on the outcomes of surgery. Interest in examining patients on the elective waiting list has increased since the beginning of 2000. We assessed health-related quality of life (HRQoL) in patients waiting for total hip (THR) or knee (TKR) replacement in three Finnish hospitals, and compared patients' HRQoL with that of population controls.

Methods
A total of 133 patients awaiting major joint replacement due to osteoarthritis (OA) of the hip or knee joint were prospectively followed from the time the patient was placed on the waiting list to hospital admission. A sample of controls matched by age, gender, housing and home municipality was drawn from the computerised population register. HRQoL was measured by the generic 15D instrument. Differences between patients and the population controls were tested by the independent samples t-test and between the measurement points by the paired samples t-test. A linear regression model was used to explain the variance in the 15D score at admission.

Results
At baseline, 15D scores were significantly different between patients and the population controls. Compared with the population controls, patients were worse off on the dimensions of moving (P < 0.001), sleeping (P < 0.001), sexual activity (P < 0.001), vitality (P < 0.001), usual activities (P < 0.001) and discomfort and symptoms (P < 0.001). Further, psychological factors – depression (P < 0.001) and distress (P = 0.004) – were worse among patients than population controls. The patients showed statistically significantly improved average scores at admission on the dimensions of moving (P = 0.026), sleeping (P = 0.004) and discomfort and symptoms (P = 0.041), but not in the overall 15D score compared with the baseline. In patients, 15D score at baseline (P < 0.001) and body mass index (BMI) (P = 0.020) had an independent effect on patients' 15D score at hospital admission.

Conclusion
Although patients' HRQoL did not deteriorate while waiting, a consistently worse HRQoL was observed in patients waiting for major joint replacement compared with population controls.
Factor correction as a tool to eliminate between-session variation in replicate experiments: application to molecular biology and retrovirology
Authors: Ruijter Jan M , Thygesen Helene H , Schoneveld Onard JLM , Das Atze T , Berkhout Ben , Lamers Wouter H 
Published: January 2006

Abstract

Background
In experimental biology, including retrovirology and molecular biology, replicate measurement sessions very often show similar proportional differences between experimental conditions, but different absolute values, even though the measurements were presumably carried out under identical circumstances. Although statistical programs enable the analysis of condition effects despite this replication error, this approach is hardly ever used for this purpose. On the contrary, most researchers deal with such between-session variation by normalisation or standardisation of the data. In normalisation all values in a session are divided by the observed value of the 'control' condition, whereas in standardisation, the sessions' means and standard deviations are used to correct the data. Normalisation, however, adds variation because the control value is not without error, while standardisation is biased if the data set is incomplete.

Results
In most cases, between-session variation is multiplicative and can, therefore, be removed by division of the data in each session with a session-specific correction factor. Assuming one level of multiplicative between-session error, unbiased session factors can be calculated from all available data through the generation of a between-session ratio matrix. Alternatively, these factors can be estimated with a maximum likelihood approach. The effectiveness of this correction method, dubbed "factor correction", is demonstrated with examples from the field of molecular biology and retrovirology. Especially when not all conditions are included in every measurement session, factor correction results in smaller residual error than normalisation and standardisation and therefore allows the detection of smaller treatment differences. Factor correction was implemented into an easy-to-use computer program that is available on request at: biolab-services@amc.uva.nl?subject=factor.

Conclusion
Factor correction is an effective and efficient way to deal with between-session variation in multi-session experiments.
SUV39H1 interacts with HTLV-1 Tax and abrogates Tax transactivation of HTLV-1 LTR
Authors: Kamoi Koju , Yamamoto Keiyu , Misawa Aya , Miyake Ariko , Ishida Takaomi , Tanaka Yuetsu , Mochizuki Manabu , Watanabe Toshiki 
Published: January 2006

Abstract

Background
Tax is the oncoprotein of HTLV-1 which deregulates signal transduction pathways, transcription of genes and cell cycle regulation of host cells. Transacting function of Tax is mainly mediated by its protein-protein interactions with host cellular factors. As to Tax-mediated regulation of gene expression of HTLV-1 and cellular genes, Tax was shown to regulate histone acetylation through its physical interaction with histone acetylases and deacetylases. However, functional interaction of Tax with histone methyltransferases (HMTase) has not been studied. Here we examined the ability of Tax to interact with a histone methyltransferase SUV39H1 that methylates histone H3 lysine 9 (H3K9) and represses transcription of genes, and studied the functional effects of the interaction on HTLV-1 gene expression.

Results
Tax was shown to interact with SUV39H1 in vitro, and the interaction is largely dependent on the C-terminal half of SUV39H1 containing the SET domain. Tax does not affect the methyltransferase activity of SUV39H1 but tethers SUV39H1 to a Tax containing complex in the nuclei. In reporter gene assays, co-expression of SUV39H1 represses Tax transactivation of HTLV-1 LTR promoter activity, which was dependent on the methyltransferase activity of SUV39H1. Furthermore, SUV39H1 expression is induced along with Tax in JPX9 cells. Chromatin immunoprecipitation (ChIP) analysis shows localization of SUV39H1 on the LTR after Tax induction, but not in the absence of Tax induction, in JPX9 transformants retaining HTLV-1-Luc plasmid. Immunoblotting shows higher levels of SUV39H1 expression in HTLV-1 transformed and latently infected cell lines.

Conclusion
Our study revealed for the first time the interaction between Tax and SUV39H1 and apparent tethering of SUV39H1 by Tax to the HTLV-1 LTR. It is speculated that Tax-mediated tethering of SUV39H1 to the LTR and induction of the repressive histone modification on the chromatin through H3 K9 methylation may be the basis for the dose-dependent repression of Tax transactivation of LTR by SUV39H1. Tax-induced SUV39H1 expression, Tax-SUV39H1 interaction and tethering to the LTR may provide a support for an idea that the above sequence of events may form a negative feedback loop that self-limits HTLV-1 viral gene expression in infected cells.
The prevalence of stillbirths: a systematic review
Authors: Say Lale , Donner Allan , Gülmezoglu A Metin , Taljaard Monica , Piaggio Gilda 
Published: January 2006

Abstract

Background
Stillbirth rate is an important indicator of access to and quality of antenatal and delivery care. Obtaining overall estimates across various regions of the world is not straightforward due to variation in definitions, data collection methods and reporting.

Methods
We conducted a systematic review of a range of pregnancy-related conditions including stillbirths and performed meta-analysis of the subset of studies reporting stillbirth rates. We examined variation across rates and used meta-regression techniques to explain observed variation.

Results
We identified 389 articles on stillbirth prevalence among the 2580 included in the systematic review. We included 70 providing 80 data sets from 50 countries in the meta-analysis. Pooled prevalence rates show variation across various subgroup categories. Rates per 100 births are higher in studies conducted in less developed country settings as compared to more developed (1.17 versus 0.50), of inadequate quality as compared to adequate (1.12 versus 0.66), using sub-national sample as compared to national (1.38 versus 0.68), reporting all stillbirths as compared to late stillbirths (0.95 versus 0.63), published in non-English as compared to English (0.91 versus 0.59) and as journal articles as compared to non-journal (1.37 versus 0.67). The results of the meta-regression show the significance of two predictor variables – development status of the setting and study quality – on stillbirth prevalence.

Conclusion
Stillbirth prevalence at the community level is typically less than 1% in more developed parts of the world and could exceed 3% in less developed regions. Regular reviews of stillbirth rates in appropriately designed and reported studies are useful in monitoring the adequacy of care. Systematic reviews of prevalence studies are helpful in explaining sources of variation across rates. Exploring these methodological issues will lead to improved standards for assessing the burden of reproductive ill-health.
HIV/AIDS mitigation strategies and the State in sub-Saharan Africa – the missing link?
Authors: Mohiddin Abdu , Johnston Deborah 
Published: January 2006

Abstract

Background
The HIV/AIDS pandemic in sub-Saharan Africa is widely recognised as a development disaster threatening poverty reduction, economic growth and not merely a health issue. Its mitigation includes the societal-wide adoption and implementation of specific health technologies, many of which depend on functional institutions and State.

Discussion
Donor and International Institutions' strategies to mitigate HIV/AIDS in sub-Saharan Africa are premised on a single optimal model of the State, one which focuses on the decentralised delivery of public goods alone (such as healthcare) – the service delivery state. The empirical evidence, though sparse, of "successful" and "unsuccessful" sub-Saharan Africa states' performance in mitigating HIV/AIDS does not support this model. Rather, the evidence suggests an alternative model that takes a country context specific approach – encompassing political power, institutional structures and the level of health technology needed. This model draws on the historical experience of East Asian countries' rapid development.

Summary
For international public health policies to be effective, they must consider a country tailored approach, one that advocates a coordinated strategy designed and led by the State with involvement of wider society specific to each country's particular history, culture, and level of development.
Influence of methylphenidate on brain development – an update of recent animal experiments
Authors: Grund Thorsten , Lehmann Konrad , Bock Nathalie , Rothenberger Aribert , Teuchert-Noodt Gertraud 
Published: January 2006

AbstractMethylphenidate (MPH) is the most commonly used drug to treat attention deficit/hyperactivity disorder (ADHD) in children effectively and safely. In spite of its widespread application throughout one of the most plastic and sensitive phases of brain development, very little is known to date about its long-term effects on brain structure and function. Hence, this short review updates the influence of MPH on brain development, since recent human and animal studies suggest that MPH alters the dopaminergic system with long-term effects beyond the termination of treatment.Animal studies imply that the effects of MPH may depend on the neural responder system: Whereas structural and functional parameters are improved by MPH in animals with psychomotor impairments, they remain unaltered or get worse in healthy controls. While recent behavioural studies do not fully support such a differential effect of MPH in ADHD, the animal studies certainly prompt for further investigation of this issue. Furthermore, the abuse of MPH, when (rarely) intravenously applied, may even impair the maturation of dopaminergic fibres in subcortical brain areas. This argues for careful clinical assessment and diagnostics of ADHD symptomatology not only in conjunction with the prescription of MPH. Hence, one should be assured that MPH is only given to children with clear ADHD symptomatology leading to psychosocial impairment. The animal data suggest that under these conditions MPH is supportive for brain development and the related behaviour in children with ADHD.
How sulfadoxine-pyrimethamine (SP) was perceived in some rural communities after phasing out chloroquine (CQ) as a first-line drug for uncomplicated malaria in Tanzania: lessons to learn towards moving from monotherapy to fixed combination therapy
Authors: Nsimba Stephen ED 
Published: January 2006

Abstract
Malaria is a leading cause of death in Sub-Saharan Africa. Tanzania changed its malaria treatment policy from chloroquine (CQ) to Sulphadoxine-Pyrimethamine (SP) as first line drug in August 2001. We wanted to assess the perception and behaviour about SP after phasing out chloroquine which was very popular, cheap, available, and was preferred by many people for self-medication in homes as it was considered to have minimal side effects.
Focus Group Discussions (FGDs) were carried out after one year of the anti-malarial drug treatment policy change in the country. The FGD themes were on malaria for under-five children and other age groups, anti-malarial drug use through self-medications, specific experiences people had about SP drug for both mothers/guardians, men in the communities and health workers. A total of twelve FGDs were performed with mothers/guardians, men and health workers in the selected public health care facilities in the district.
In the FGDs people feared adverse reactions from SP; its slow ability of reducing fever and self-treatment in this case was less reported from the mothers/guardians groups. However, SP was reported by health workers to be administered using the direct observation approach under supervision in their health care facilities. This was done in order to increase compliance as there were worries that some mothers were throwing away the drug if they were instructed by health workers to go and administer SP to their sick children at home.
Based on this information, it is obvious that fear and negative perceptions about SP drug was common in the study setting. As evidence of this, there was less reported home-stocking and self-medication in the discussions for this particular recommended new first-line anti-malarial. The public has demonstrated a lack of confidence in SP. Furthermore, some health workers expressed obvious fear and negative perceptions towards the drug despite the fact that some FGDs with health workers considered the drug to be good and effective against malaria. Such negative perception towards SP highlights the need to start earlier sensitization and educational campaigns to the rural communities for a new drug program to ensure its success. Messages should clearly state what should be expected from the new drug (Coartem), before its introduction. This is important especially as Tanzania is expected to move towards the expensive but efficacious and effective fixed-combination (Coartem) anti-malarial therapy early next year (2006).
A molecular epidemiological study of rabies epizootics in kudu (Tragelaphus strepsiceros) in Namibia
Authors: Mansfield Karen , McElhinney Lorraine , Hübschle Otto , Mettler Felix , Sabeta Claude , Nel Louis H , Fooks Anthony R 
Published: January 2006

Abstract

Background
A panel of 37 rabies virus isolates were collected and studied, originating mainly from the northern and central regions of Namibia, between 1980 and 2003.

Results
These virus isolates demonstrated a high degree of genetic similarity with respect to a 400 bp region of the nucleoprotein gene, with the virus isolates originating from kudu antelope (n = 10) sharing 97.2–100% similarity with jackal isolates, and 97–100% similarity with those isolated from domestic dogs. Phylogenetic analysis suggested that these viruses were all of the canid rabies biotype of southern Africa. The viruses from kudu were closely associated with jackal isolates (n = 6), bat-eared fox isolates (n = 2) and domestic dog isolates (n = 2) at the genetic level and identical at the amino acid level, irrespective of the year of isolation.

Conclusion
These data suggest that jackal and kudu may form part of the same epidemiological cycle of rabies in Namibian wildlife, and might demonstrate the close-relationship between rabies virus strains that circulate within Namibia and those that circulate between Namibia and its neighbouring countries such as Botswana and South Africa.
Radiographic joint damage in rheumatoid arthritis is associated with differences in cartilage turnover and can be predicted by serum biomarkers: an evaluation from 1 to 4 years after diagnosis
Authors: Verstappen SMM , Poole AR , Ionescu M , King LE , Abrahamowicz M , Hofman DM , Bijlsma JWJ , Lafeber FPJG ,   the Utrecht Rheumatoid Arthritis Cohort Study group (SRU)
Published: January 2006

Abstract
Introduction
The objective of this study was to determine whether serum biomarkers for degradation and synthesis of the extracellular matrix of cartilage are associated with, and can predict, radiographic damage in patients with rheumatoid arthritis (RA).

Methods
Clinical and radiographic data of 87 RA patients were recorded 1 year after disease onset and then annually up to four years. Serum concentrations of four cartilage biomarkers were determined at these time points: a neoepitope formed by collagenase cleavage of type II collagen (C2C), a neoepitope formed by collagenase cleavage of type II collagen as well as type I collagen (C1,2C), a carboxy propeptide of type II procollagen formed during synthesis (CPII), and a cartilage proteoglycan aggrecan turnover epitope (CS846-epitope). Biomarker concentrations between patients with rapid radiographic progression (>7.3 Sharp/van der Heijde units per year) and those with slow radiographic progression (<2.3 units per year) were compared. In addition, we evaluated the long-term and short-term predictive value of each biomarker for progression of radiographic damage.

Results
Patients with rapid radiographic progression had higher C2C, higher C1,2C, and higher CS846-epitope levels than slow progressors. CPII levels showed no differences. Most importantly, the long-term radiographic progression for C2C, for C1,2C, and for CS846-epitope can be predicted by the biomarker value at year 1 after disease onset. C2C was also a predictor for joint space narrowing and annual radiographic damage during the subsequent year.

Conclusion
This study shows that the concentration of serum biomarkers of cartilage collagen breakdown and proteoglycan turnover, but not of collagen synthesis, are related to joint destruction in RA. The use of these biomarkers may be of value when studying progression of joint damage in patients with RA.
Association between microscopic brain damage as indicated by magnetization transfer imaging and anticardiolipin antibodies in neuropsychiatric lupus
Authors: Steens Stefan CA , Bosma Gerlof PTh , Steup-Beekman Gerda M , le Cessie Saskia , Huizinga Tom WJ , van Buchem Mark A 
Published: January 2006

AbstractThe pathogenetic role of anticardiolipin antibodies (aCLs) in patients with neuropsychiatric systemic lupus erythematosus (NPSLE) without cerebral infarcts remains elusive. Magnetization transfer imaging (MTI) has proved to be a sensitive tool for detecting diffuse microscopic brain damage in NPSLE patients. In this study we examined the correlation between grey and white matter magnetization transfer ratio (MTR) parameters and the presence of IgM and IgG aCLs and lupus anticoagulant in 18 patients with systemic lupus erythematosus and a history of NPSLE but without cerebral infarcts on conventional magnetic resonance imaging. Lower grey matter mean MTR (P < 0.05), white matter mean MTR (P < 0.05), white matter peak location (P < 0.05) and grey matter peak location (trend toward statistical significance) were observed in IgM aCL-positive patients than in IgM aCL-negative patients. No significant differences were found in MTR histogram parameters with respect to IgG aCL and lupus anticoagulant status, nor with respect to anti-dsDNA or anti-ENA (extractable nuclear antigen) status. This is the first report of an association between the presence of aCLs and cerebral damage in grey and white matter in NPSLE. Our findings suggest that aCLs are associated with diffuse brain involvement in NPSLE patients.