bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats
Authors: Malone John I , Cuthbertson David D , Malone Michael A , Schocken Douglas D
Published: January 2006

Background

Streptozotocin-induced diabetes (STZ-D) in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement.

Aim

The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats.

Methods

Wistar rats (48) were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24) were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA) were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks.

Results

The heart rates for the STZ-D rats (290 ± 19 bpm) were less than control rats (324 ± 20 bpm) (p < 0.05). After 4 weeks of oral carnitine supplementation, the serum carnitine and heart rates of the STZ-D rats returned to normal. Dobutamine stress increased the heart rates of all study animals, but the increase in STZ-D rats (141 ± 8 bpm) was greater than controls (79 ± 8 bpm) (p < 0.05). The heart rates of STZ-D rats given oral carnitine, however, were no different than controls (94 ± 9 bpm). The left ventricular mass/body weight ratio (LVM/BW) in the diabetic animals (2.7 ± 0.5) was greater than control animals (2.2 ± 0.3) (p < 0.05) after 18 weeks of diabetes. In contrast, the LVM/BW (2.3 ± .2) of the STZ-D animals receiving supplemental carnitine was the same as the control animals at 18 weeks.

Conclusion

Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model.
Real-time quantitative PCR with SYBR Green I detection for estimating copy numbers of nine drug resistance candidate genes in Plasmodium falciparum
Authors: Ferreira Isabel D , do Rosário Virgílio E , Cravo Pedro VL
Published: January 2006

Background

Evaluating copy numbers of given genes in Plasmodium falciparum parasites is of major importance for laboratory-based studies or epidemiological surveys. For instance, pfmdr1 gene amplification has been associated with resistance to quinine derivatives and several genes involved in anti-oxidant defence may play an important role in resistance to antimalarial drugs, although their potential involvement has been overlooked.

Methods

The ΔΔCt method of relative quantification using real-time quantitative PCR with SYBR Green I detection was adapted and optimized to estimate copy numbers of three genes previously indicated as putative candidates of resistance to quinolines and artemisinin derivatives: pfmdr1, pfatp6 (SERCA) and pftctp, and in six further genes involved in oxidative stress responses.

Results

Using carefully designed specific RT-qPCR oligonucleotides, the methods were optimized for each gene and validated by the accurate measure of previously known number of copies of the pfmdr1 gene in the laboratory reference strains P. falciparum 3D7 and Dd2. Subsequently, Standard Operating Procedures (SOPs) were developed to the remaining genes under study and successfully applied to DNA obtained from dried filter blood spots of field isolates of P. falciparum collected in São Tomé & Principe, West Africa.

Conclusion

The SOPs reported here may be used as a high throughput tool to investigate the role of these drug resistance gene candidates in laboratory studies or large scale epidemiological surveys.
Inductively-overcoupled coil design for high resolution magnetic resonance imaging
Authors: Bilgen Mehmet
Published: January 2006

Background

Maintaining the quality of magnetic resonance images acquired with the current implantable coil technology is challenging in longitudinal studies. To overcome this challenge, the principle of 'inductive overcoupling' is introduced as a method to tune and match a dual coil system. This system consists of an imaging coil built with fixed electrical elements and a matching coil equipped with tuning and matching capabilities. Overcoupling here refers to the condition beyond which the peak of the current in the imaging coil splits.

Methods

The combined coils are coupled inductively to operate like a transformer. Each coil circuit is electrically represented by equivalent lumped-elements. A theoretical analysis is given to identify the frequency response characteristics of the currents in each coil. The predictions from this analysis are translated into experiments and applied to locally image rat spinal cord at 9.4 T using an implantable coil as the imaging coil and an external volume coil as the matching coil.

Results

The theoretical analysis indicated that strong coupling between the coils divides the resonance peaks on the response curves of the currents. Once these newly generated peaks were tuned and matched to the desired frequency and impedance of operation, in vivo images were acquired from the rat spinal cord at high quality and high resolution.

Conclusion

After proper implementation, inductive overcoupling provides a unique opportunity for tuning and matching the coil system, and allows reliable and repeatable acquisitions of magnetic resonance data. This feature is likely to be useful in experimental studies, such as those aimed at longitudinally imaging the rat following spinal cord injury.
An extensible spatial and temporal epidemiological modelling system
Authors: Ford Daniel Alexander , Kaufman James H , Eiron Iris
Published: January 2006

Background

This paper describes the Spatiotemporal Epidemiological Modeller (STEM) which is an extensible software system and framework for modelling the spatial and temporal progression of multiple diseases affecting multiple populations in geographically distributed locations. STEM is an experiment in developing a software system that can model complex epidemiological scenarios while also being extensible by the research community. The ultimate goal of STEM is to provide a common modelling platform powerful enough to be sufficient for all modelling scenarios and extensible in a way that allows different researchers to combine their efforts in developing exceptionally good models.

Results

STEM is a powerful modelling system that allows researchers to model scenarios with unmixed populations that are not uniformly distributed and in which multiple populations exist that are being infected with multiple diseases. It's underlying representational framework, a graph, and its software architecture allow the system to be extended by incorporating software components developed by different researchers.

Conclusion

This approach taken in the design of STEM creates a powerful platform for epidemiological research collaboration. Future versions of the system will make such collaborative efforts easy and common.
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

Background

Deregulated 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.

Results

Following 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.

Conclusion

These 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

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

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

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

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

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.

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

Methylphenidate (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

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

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

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

The 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.
Upregulated but insufficient generation of activated protein C is associated with development of multiorgan failure in severe acute pancreatitis
Authors: Lindstrom Outi , Kylanpaa Leena , Mentula Panu , Puolakkainen Pauli , Kemppainen Esko , Haapiainen Reijo , Fernandez Jose A , Griffin John H , Repo Heikki , Petaja Jari
Published: January 2006

Introduction

Disturbed protein C (PC) pathway homeostasis might contribute to the development of multiple organ failure (MOF) in acute pancreatitis (AP). We therefore evaluated circulating levels of PC and activated protein C (APC), evaluated monocyte deactivation in AP patients, and determined the relationship of these parameters to MOF.

Patients and methods

Thirty-one patients in the intensive care unit were categorized as cases (n = 13, severe AP with MOF) or controls (n = 18, severe AP without MOF). Blood samples were drawn every second day to determine the platelet count, the levels of APC, PC, and D-dimer, and the monocyte HLA-DR expression using flow cytometry. The APC/PC ratio was used to evaluate turnover of PC to APC.

Results

During the initial two weeks of hospitalization, low PC levels (<70% of the adult mean) occurred in 92% of cases and 44% of controls (P = 0.008). The minimum APC level was lower in cases than in controls (median 85% versus 97%, P = 0.009). Using 87% as the cut-off value, 8/13 (62%) cases and 3/18 (17%) controls showed reduced APC levels (P = 0.021). A total of 92% of cases and 50% of controls had APC/PC ratios exceeding the upper normal limit (P = 0.013). Plasma samples drawn before MOF showed low PC levels and high APC/PC ratios. HLA-DR-positive monocytes correlated with PC levels (r = 0.38, P < 0.001) and APC levels (r = 0.27, P < 0.001), indicating that the PC pathway was associated with systemic inflammation-triggered immune suppression.

Conclusion

PC deficiency and decreased APC generation in severe AP probably contributed to a compromised anticoagulant and anti-inflammatory defence. The PC pathway defects were associated with the development of MOF. The data support feasibility of testing the use of APC or PC to improve the clinical outcome in AP.
Hepatic platelet and leukocyte adherence during endotoxemia
Authors: Croner Roland S , Hoerer Elfie , Kulu Yakup , Hackert Tilo , Gebhard Martha-Maria , Herfarth Christian , Klar Ernst
Published: January 2006

Introduction

Liver microcirculation disturbances are a cause of hepatic failure in sepsis. Increased leukocyte-endothelial interaction, platelet adherence and impaired microperfusion cause hepatocellular damage. The time course and reciprocal influences of ongoing microcirculatory events during endotoxemia have not been clarified.

Methods

Male Wistar rats (232 ± 17 g) underwent cecal ligation and puncture (CLP). Intravital microscopy (IVM) was performed 0, 1, 3, 5, 10 and 20 hours after CLP. Mean erythrocyte velocity, leukocyte and platelet rolling in postsinusoidal venules and sticking of leukocytes and platelets in postsinusoidal venules and hepatic sinusoids were determined. Heart rate (HR), mean arterial pressure (MAP) and portal venous blood flow (PBF) were measured. Blood count and investigation of hepatic enzyme release was performed after each IVM time point.

Results

Hepatic platelet-endothelial adherence in liver sinusoids and postsinusoidal venules occurred one hour after the induction of endotoxemia. Leukocyte-endothelial interaction started three to five hours after CLP. A decrease of hepatic microperfusion could be observed at three hours in sinusoids and ten hours in postsinusoidal venules after CLP, although PBF was reduced one hour after CLP. HR remained stable and MAP decreased ten hours after CLP. Hepatic enzymes in blood were significantly elevated ten hours after CLP.

Conclusion

Hepatic platelet-endothelial interaction is an early event during endotoxemia. Leukocyte adherence occurs later, which underlines the probable involvement of platelets in leukocyte recruitment. Although PBF is reduced immediately after CLP, the later onset of hepatic microperfusion decrease makes the existence of autoregulatory liver mechanisms likely.
Solving the Emotion Paradox: Categorization and the Experience of Emotion
Authors: Barrett Lisa Feldman
Published: January 2006

In this article, I introduce an emotion paradox: People believe that they know an emotion when they see it, and as a consequence assume that emotions are discrete events that can be recognized with some degree of accuracy, but scientists have yet to produce a set of clear and consistent criteria for indicating when an emotion is present and when it is not. I propose one solution to this paradox: People experience an emotion when they conceptualize an instance of affective feeling. In this view, the experience of emotion is an act of categorization, guided by embodied knowledge about emotion. The result is a model of emotion experience that has much in common with the social psychological literature on person perception and with literature on embodied conceptual knowledge as it has recently been applied to social psychology.
How Interpersonal Motives Clarify the Meaning of Interpersonal Behavior: A Revised Circumplex Model
Authors: Horowitz Leonard M. , Wilson Kelly R. , Turan Bulent , Zolotsev Pavel , Constantino Michael J. , Henderson Lynne
Published: January 2006

Circumplex models have organized interpersonal behavior along 2 orthogonal dimensions-communion (which emphasizes connection between people) and agency (which emphasizes one person's influence over the other). However, many empirical studies have disconfirmed certain predictions from these models. We therefore revised the model in 4 ways that highlight interpersonal motives. In our revision: (a) the negative pole of communion is indifference, not hostility; (b) a given behavior invites (not evokes) a desired reaction from the partner; (c) the complement of a behavior is a reaction that would satisfy the motive behind that behavior; (d) noncomplementary reactions induce negative affect. If the motive is unclear, the meaning of the behavior is ambiguous. This ambiguity helps explain failures in social support, miscommunications in everyday life, and features of most personality disorders. The model emphasizes measurable individual differences: Reactions that are complementary for one person need not be complementary for another.
URI-1 is required for DNA stability inC. elegans
Authors: Parusel Christine T. , Kritikou Ekaterini A. , Hengartner Michael O. , Krek Wilhelm , Gotta Monica
Published: January 2006

Unconventional prefoldin RPB5 interactor (URI), an evolutionary conserved member of the prefoldin family of molecular chaperones, plays a central role in the regulation of nutrient-sensitive, TOR (target-of-rapamycin)-dependent gene expression programs in yeast. Mammalian URI has been shown to associate with key components of the transcriptional machinery, including RPB5, a shared subunit of all three RNA polymerases, the ATPases TIP48 and TIP49, which are present in various chromatin remodeling complexes, and human PAF1 and parafibromin, which are components of a transcription elongation complex. Here, we provide the first functional characterization of a URI-1 homolog in a multicellular organism and show that the C. elegans gene uri-1 is essential for germ cell proliferation. URI-1-deficient cells exhibit cell cycle arrest and display DNA breaks as evidenced by TUNEL staining and the appearance of HUS-1::GFP foci formation. In addition, uri-1(lf) mutants and uri-1(RNAi) worms show a p53-dependent increase in germline apoptosis. Our findings indicate that URI-1 has an important function in the mitotic and meiotic cell cycles. Furthermore, they imply that URI-1 participates in a pathway(s) that is associated with the suppression of endogenous genotoxic DNA damage and highlight a role for URI-1 in the control of genome integrity.
Liposomal Sorting onto Substrate through Ion Recognition by Gemini Peptide Lipids
Authors: Otsuki Masashi , Sasaki Yoshihiro , Iwamoto Shintaro , Kikuchi Jun-ichi
Published: January 2006

Selective liposomal assembling in aqueous solution was achieved by ion-recognizable gemini peptide lipids as an inducer. The methodology was extended to liposomal sorting on a substrate covered with a supported bilayer membrane, which was confirmed by means of fluorescence and atomic force microscopy, fluorescence spectroscopy, and quarts crystal microbalance measurements.
Rotaxane Synthesized by End-capping via Hydroruthenation of Axle Terminal Acetylene and Its Derivation to η3-Allylruthenium Complex-containing Rotaxane
Authors: Sasabe Hisahiro , Kihara Nobuhiro , Mizuno Kazuhiko , Ogawa Akiya , Takata Toshikazu
Published: January 2006

The hydroruthenation of pseudorotaxane 1·DB24C8 having an alkyne moiety at the axle terminal with RuHCl(CO)(PPh3)3 gave [2]rotaxane 2 with an alkenylruthenium complex moiety in a good yield. The carbometalation of allenes with 2 resulted in the formation of the corresponding [2]rotaxanes 3 with η3-allylruthenium complex moieties in good yields.
Importance of 3′-Hydroxyl Group of the Nucleosides for the Reactivity of Thymidine Phosphorylase from Escherichia coli
Authors: Hatano Akihiko , Harano Aiko , Kirihara Masayuki
Published: January 2006

Thymidine phosphorylase in phosphate buffer catalyzed the conversion of thymidine to unnatural nucleosides. The 3′-OH, but not the 5′-OH of ribosyl moiety is necessary to be recognized as a substrate. Thus 3′-deoxythymidine could not convert to 5-fluorouracil-2′,3′-dideoxyribose. However, 5′-deoxythymidine was converted to 5-fluorouracil-2′,5′-dideoxyribose.
A Two-Stage Model of the Promotional Performance of Pure Online Firms
Authors: Wu Jianan , Cook Victor J. , Strong Edward C.
Published: January 2006

Internet firms frequently employ a two-stage approach to promotional activities. In Stage 1, they attract customers to their websites through advertising. In Stage 2, firms generate sales transactions or sales leads through their website.

Comprehensive assessment of the promotional performance of pure online firms requires the study of Stage 1 and of Stage 2 jointly. In this paper we develop a joint two-stage conceptual and econometric model for assessing website promotion on three important dimensions: (1) how advertising response can be measured by linking media schedules to website log files; (2) how advertising and website characteristics jointly affect the desired system outcome of the promotion; and (3) whether the joint investigation of advertising response and desired system outcomes is essential to assess the results of website promotion.

Three general findings follow from application of our model to a pure online firm’s campaign to generate sales leads through print advertising. First, advertising and website characteristics affect sales leads in different ways. A characteristic may influence sales leads directly, or indirectly, or both. Second, assessing advertising effectiveness in an online environment may not require costly survey research data. Instead, secondary data available from website log files may be used for such assessment. Third, the interaction between the first and second stages of our two-stage model can lead to misspecifications that produce misleading inferences. This occurs because the unobserved characteristics in generating website visits and sales leads may be correlated.
Diagnoses and Antipsychotic Treatment Among Youths in a Public Mental Health System
Authors: Patel Nick C , Crismon M Lynn , Shafer Alan
Published: January 2006

Background:

The use of antipsychotics, namely newer atypical agents, has increased significantly in children and adolescents. It is important to examine diagnoses associated with antipsychotic treatment in youths.

Objective:

To evaluate trends in psychiatric diagnoses of children and adolescents in a public mental health system who were prescribed antipsychotics.

Methods:

Children and adolescents, up to the age of 19 years, who were prescribed an antipsychotic between January 1998 and December 2001 were identified using the Texas Medicaid Vendor Drug database. Patient identification numbers were then cross-linked to the Client Assignment and Registration database of the Texas Department of Mental Health and Mental Retardation to extract diagnostic data.

Results:

Disruptive behavioral disorders accounted for the highest percentage (35%) of diagnoses associated with children and adolescents receiving antipsychotic treatment and mental healthcare services. Depressive disorders were the second most common diagnosis (18%), and bipolar disorders accounted for roughly 12% of all diagnoses. Approximately 3% of children and adolescents did not have a psychiatric diagnosis. The percentage of youths with comorbid psychiatric diagnoses decreased over time.

Conclusions:

Although disruptive behavioral disorders accounted for a large percentage of antipsychotic use in this population, these findings suggest that antipsychotics are being used to treat other psychiatric diagnoses, for which limited supporting data exist. Future research in children and adolescents should aim to provide needed efficacy and safety data of antipsychotics across the spectrum of neuropsychiatrie disorders.
Outcomes of Bupropion Therapy for Smoking Cessation During Routine Clinical Use
Authors: Paluck Elan C , McCormack James P , Ensom Mary HH , Levine Marc , Soon Judith A , Fielding David W
Published: January 2006

Background:

Knowledge pertaining to the effectiveness of smoking cessation treatments and patient characteristics that may affect success may enable smokers and clinicians to select individualized treatment for each patient and ultimately increase the success rate of smoking cessation in general.

Objective:

To evaluate the effectiveness of bupropion as a smoking cessation agent when used in routine clinical practice.

Methods:

This was a prospective, observational study with a one year follow-up period. Adult smokers presenting to community pharmacies in British Columbia, Canada, with an index prescription for bupropion for smoking cessation (N = 205) were eligible. The primary outcome was the biochemically validated 12 month point abstinence (PA) rate from smoking. Secondary outcomes included the frequency of adverse events, patterns of bupropion use in routine clinical practice, and possible predictors of bupropion effectiveness.

Results:

The validated 12 month PA rate was 21.0%. Of subjects who reported taking at least one dose of bupropion, 70.4% (126/179) experienced at least one adverse event and 29.6% (53/179) reported stopping the drug due to adverse effects. Greater length of time on bupropion (OR 0.98) and a lower cigarette pack-year history (OR 1.05) were associated with an increase in the odds of smoking cessation.

Conclusions:

Subjects receiving bupropion in a real-life setting exhibited a similar abstinence rate at 12 months as has been observed in the active drug groups of placebo-controlled clinical trials. However, the patterns of use and discontinuation rate due to adverse events differed substantially from those observed in early efficacy studies.
Measurement of Concrete Strength Using the Emission Intensity Ratio between Ca(II) 396.8 nm and Ca(I) 422.6 nm in a Nd:YAG Laser-Induced Plasma
Authors: Tsuyuki Kenichiro , Miura Satoru , Idris Nasrullah , Kurniawan Koo Hendrik , Lie Tjung Jie , Kagawa Kiichiro
Published: January 2006

An experiment to investigate the potential of a laser-induced plasma method for determining concrete compressive strength was conducted by focusing a Nd:YAG laser on concrete samples with different degrees of compressive strength. This technique was developed in light of the role of the shock wave in the generation of a laser-induced plasma. It was found that the speed of the shock front depends on the hardness of the sample. It was also found that a positive relationship exists between the speed of the shock front and the ionization rate of the ablated atoms. Hence, the ratio of the intensity between the Ca(II) 396.8 nm and Ca(I) 422.6 nm emission lines detected from the laser-induced plasma can be used to examine the hardness of the material. In fact, it was observed that the ratio changes with respect to the change in the concrete compressive strength. The findings also show that the ratio increases with time after the cement is mixed with water.
Edge monkeys - the design of habitat specific robots in buildings
Authors: Gage Stephen A. , Thorne Will
Published: January 2006

This paper presents a concept for using robots as part of a design strategy that encourages a ‘bottom-up’ approach to environmental control. Robot friendly environments within the building enclosure are proposed and an analogy is made to natural ‘ecosystems’.
Detail design issues are discussed, including the relationships that might occur between robots, building users and maintenance engineers. The concept is speculative in that it presents some of the implications of a mode of actuation that is radically different from the usual.