bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness of tuberculosis control strategies among immigrants and refugees
Authors: Dasgupta K. , Menzies D.
Published: June 2005

Today, in Western Europe, Canada and the USA, more than half of all new active tuberculosis (TB) cases occur among foreign-born migrants. This article examines the impact of migration from high TB-incidence to low TB-incidence countries, and compares the cost-effectiveness of different TB control strategies.

A Medline search was conducted to identify relevant English language publications prior to December 2003. Additional articles were identified from the reference lists from these publications.

Despite the high proportion of active cases in low-incidence countries attributable to foreign-born residents, the public health impact is relatively low. Current chest radiograph screening programmes have little impact and are not cost-effective. Screening with sputum culture would improve cost-effectiveness marginally. Treatment of latent infection detected through screening with tuberculin skin testing or chest radiographs may require coercive measures to maximise impact and cost-effectiveness. In contrast, contact tracing, particularly within ethnic communities, appears to be more cost-efficient and less intrusive.

In low-incidence countries, screening of migrants at entry has little overall impact and is not a very cost-effective tuberculosis control strategy. More effective alternatives include contact tracing delivered through primary care and increased investment in global tuberculosis control.
Susceptibility to air pollution in elderly males and females
Authors: Boezen H. M. , Vonk J. M. , van der Zee S. C. , Gerritsen J. , Hoek G. , Brunekreef B. , Schouten J. P. , Postma D. S.
Published: June 2005

It is important to know which individuals in the general population have increased susceptibility to air pollution. The aim of this study was to identify susceptible subgroups by studying airways hyperresponsiveness (AHR), high total immunoglobulin (Ig)E and sex.

Diary data on lower and upper respiratory symptoms (LRS and URS, respectively), cough, and morning and evening peak expiratory flow (PEF) were collected in 327 elderly patients (50–70 yrs) for a period of 3 months. Acute effects of particulate matter with a diameter <10 µm, black smoke, sulphur dioxide and nitrogen dioxide on symptoms and PEF were estimated using logistic regression.

In total, 48 (14.7%) subjects had AHR+/IgE+, 112 (34.3%) had AHR−/IgE+, 42 (12.8%) had AHR+/IgE− and 125 (38.2%) had AHR−/IgE−. In the AHR+/IgE+ group, each 10 µg·m−3increase in air pollution was associated with a significant increase in prevalence of URS (odds ratio ranging 1.03–1.19), cough (1.03–1.08) and fall in morning PEF (1.04–1.26). In the AHR+/IgE+ group, males responded predominantly with symptoms and females with a fall in morning PEF.

In conclusion, elderly individuals with both airway hyperresponsiveness and high total immunoglobulin E are especially susceptible to air pollution. Identifying susceptible subgroups might enlarge insight into the actual mechanisms by which air pollution evokes specific modes of response.
Expression of tumour necrosis factor receptors by bronchoalveolar cells in hypersensitivity pneumonitis
Authors: Chen B. , Tong Z. , Ye Q. , Nakamura S. , Costabel U. , Guzman J.
Published: June 2005

Tumour necrosis factor receptors (TNFR) and the Fas receptor (FasR) have been implicated in the pathogenesis of interstitial lung diseases. The current authors examined the expression of TNFR-1, TNFR-2 and FasR by bronchoalveolar cells in hypersensitivity pneumonitis (HP).

Cell surface receptor expression on bronchoalveolar lavage cells was analysed by immunocytochemistry in 11 HP patients, 11 idiopathic pulmonary fibrosis (IPF) patients and 10 controls.

TNFR-1, TNFR-2 and FasR were expressed on a higher percentage of alveolar macrophages (AM) in HP compared with controls and IPF patients. TNFR-2 and FasR expression on lymphocytes was also higher in HP than in controls and in IPF. TNFR-1, TNFR-2 and FasR expression correlated positively with the percentage of lymphocytes, and negatively with the percentage of AM in HP. Expression of TNFR-1 on AM and TNFR-2 on lymphocytes correlated with the percentage of neutrophils in HP.

In conclusion, this study shows evidence of altered expression of tumour necrosis factor superfamily receptors in hypersensitivity pneumonitis.
Smoking reduction and the rate of decline in FEV1: results from the Lung Health Study
Authors: Simmons M. S. , Connett J. E. , Nides M. A. , Lindgren P. G. , Kleerup E. C. , Murray R. P. , Bjornson W. M. , Tashkin D. P.
Published: June 2005

Previous findings from the Lung Health Study have shown that smoking cessation and sustained abstinence substantially reduce the rate of decline in forced expiratory volume (FEV1) among smokers with early chronic obstructive pulmonary disease (COPD) when compared with continuing smoking. Intermittent quitters demonstrated rates of FEV1decline intermediate between those of sustained quitters and continuing smokers.

In this study, data from 1,980 participants were analysed from 10 centres of the Lung Health Study in the USA and Canada. All participants were smokers with mild-to-moderate COPD who were unable to quit smoking at any time during the 1st yr of the study.

No linear relationship was found between reduction in cigarettes per day and changes in FEV1during the 1st yr of the study. However, examination of the data revealed that this relationship was nonlinear. Further analysis found that smokers who reduced their cigarettes per day to very low amounts had smaller declines in FEV1than those who did not. Reduction in cigarettes per day was associated with only minimal changes in the presence of chronic respiratory symptoms.

In conclusion, compensatory changes in smoking behaviour may account for the limited and unpredictable impact of smoking reduction on lung function decline and symptom prevalence when compared with smoking cessation.
Correlates ofMycobacterium tuberculosisinfection in a prison population
Authors: Carbonara S. , Babudieri S. , Longo B. , Starnini G. , Monarca R. , Brunetti B. , Andreoni M. , Pastore G. , De Marco V. , Rezza G. ,   and GLIP (Gruppo di Lavoro Infettivologi Penitenziari)
Published: June 2005

Prisons represent a crucial setting for tuberculosis control. Currently, there is scarce information concerningMycobacterium tuberculosis(MT) infection in European prisons, and no data are available for Italy. This study aims to describe the prevalence and correlates of MT infection in an Italian prison population.

In this multicentre cross-sectional study, 1,247 inmates from nine prisons were recruited and asked to undergo questioning regarding socio-economic and demographic variables, tuberculin skin testing (TST), chest radiographs and testing for HIV, hepatitis B and hepatitis C virus infection.

TST was positive in 17.9% of the 448 evaluable subjects. With multivariate logistic regression (performed among male inmates), MT infection was correlated with age (adjusted odds ratio (OR) 4.12 for inmates aged 31–40 yrs; 3.78 for those aged >40 yrs), being foreign-born (OR = 4.9), education ≤5 yrs (OR = 1.88) and length of detention (increased risk per yr: 11%).

As with elsewhere in the world, the prison system in Italy features a population with an increased rate ofMycobacterium tuberculosisinfection and at-risk rate forMycobacterium tuberculosistransmission. Improved tuberculosis surveillance and control measures are deemed necessary in correctional facilities nationwide, especially for subjects with the above risk factors and those who are HIV infected, in whom the tuberculin skin testing can be misleading. The screening of entrants is particularly important to avoid undiagnosed smear-positive tuberculosis cases.
The association of prolonged breastfeeding and allergic disease in poor urban children
Authors: Obihara C. C. , Marais B. J. , Gie R. P. , Potter P. , Bateman E. D. , Lombard C. J. , Beyers N. , Kimpen J. L. L.
Published: June 2005

The fact that breastfeeding may protect against allergic disease remains controversial, with hardly any reports from developing countries. This study investigated the association between allergic disease in children and prolonged breastfeeding.

Data were collected from a 15% random sample of households from two poor suburbs of Cape Town, South Africa. Parents completed a validated International Study on Asthma and Allergies in Childhood questionnaire on allergic diseases for children aged 6–14 yrs. Other questions included breastfeeding duration, maternal smoking and parental allergy. Results were adjusted for possible confounders and for possible clustering within the household.

Out of the 861 children included in the study, allergic disease in general, and hay fever in particular, were significantly less frequent in those with prolonged (≥6 months) breastfeeding. There was a significant linear inverse association between breastfeeding duration and allergic disease in children without allergic parents, but not in children with an allergic predisposition.

In conclusion, these results from a developing country suggest a protective effect of prolonged breastfeeding on the development of allergic disease, particularly hay fever, in children born to nonallergic parents. This protective effect was not found in children with an allergic predisposition.
COPD: current therapeutic interventions and future approaches
Authors: Barnes P. J. , Stockley R. A.
Published: June 2005

Although long-acting bronchodilators have been an important advance for the management of chronic obstructive pulmonary disease (COPD), these drugs do not deal with the underlying inflammatory process. No currently available treatments reduce the progression of COPD or suppress the inflammation in small airways and lung parenchyma. Several new treatments that target the inflammatory process are now in clinical development. Some therapies, such as chemokine antagonists, are directed against the influx of inflammatory cells into the airways and lung parenchyma that occurs in COPD, whereas others target inflammatory cytokines such as tumour necrosis factor-α.

Broad spectrum anti-inflammatory drugs are now in phase III development for COPD, and include phosphodiesterase-4 inhibitors. Other drugs that inhibit cell signalling include inhibitors of p38 mitogen-activated protein kinase, nuclear factor-κB and phosphoinositide-3 kinase-γ. More specific approaches are to give antioxidants, inhibitors of inducible nitric oxide synthase and leukotriene B4antagonists. Other treatments have the potential to combat mucus hypersecretion, and there is also a search for serine proteinase and matrix metalloproteinase inhibitors to prevent lung destruction and the development of emphysema.

More research is needed to understand the cellular and molecular mechanisms of chronic obstructive pulmonary disease and to develop biomarkers and monitoring techniques to aid the development of new therapies.
Determination of thermodynamic parameters of Xerocomus chrysenteron lectin interactions with N-acetylgalactosamine and Thomsen-Friedenreich antigen by isothermal titration calorimetry
Authors: Damian Luminita , Fournier Didier , Winterhalter Mathias , Paquereau Laurent
Published: June 2005

Background

Lectins are carbohydrate-binding proteins which potentially bind to cell surface glycoconjugates. They are found in various organisms including fungi. A lectin from the mushroom Xerocomus chrysenteron (XCL) has been isolated recently. It shows insecticidal activity and has antiproliferative properties.

Results

As the monosaccharide binding specificity is an important determinant of lectin function, we determined the affinity of XCL for the galactose moiety. Isothermal titration calorimetry studies revealed a dissociation constant Kd of 5.2 μM for the XCL:N-acetylgalactosamine interaction at 27degreesC. Higher affinities were observed at lower temperatures and higher osmotic pressures. The dissociation constant was five hundred times higher for the disaccharide beta-D-Gal(1–3)-D-GalNAc, Thomsen-Friedenreich (TF) antigen (Kd of 0.94 μM). By using fetuin and asialofetuin in interaction with the XCL, we revealed its ability to recognize the Thomsen-Friedenreich motif on glycoproteins.

Conclusion

The XCL antiproliferative effect and the TF antigen specificity presented in this work suggest that XCL and ABL may have similar binding mechanisms. The recent structure determination of these two proteins lead us to analyse these interactions in the light of our thermodynamic data. The understanding of this type of interaction may be a useful tool for the regulation of cell proliferation.
Comparative analysis of chromatin landscape in regulatory regions of human housekeeping and tissue specific genes
Authors: Ganapathi Mythily , Srivastava Pragya , Sutar Sushanta Kumar Das , Kumar Kaushal , Dasgupta Dipayan , Pal Singh Gajinder , Brahmachari Vani , Brahmachari Samir K
Published: May 2005

Background

Global regulatory mechanisms involving chromatin assembly and remodelling in the promoter regions of genes is implicated in eukaryotic transcription control especially for genes subjected to spatial and temporal regulation. The potential to utilise global regulatory mechanisms for controlling gene expression might depend upon the architecture of the chromatin in and around the gene. In-silico analysis can yield important insights into this aspect, facilitating comparison of two or more classes of genes comprising of a large number of genes within each group.

Results

In the present study, we carried out a comparative analysis of chromatin characteristics in terms of the scaffold/matrix attachment regions, nucleosome formation potential and the occurrence of repetitive sequences, in the upstream regulatory regions of housekeeping and tissue specific genes. Our data show that putative scaffold/matrix attachment regions are more abundant and nucleosome formation potential is higher in the 5' regions of tissue specific genes as compared to the housekeeping genes.

Conclusion

The differences in the chromatin features between the two groups of genes indicate the involvement of chromatin organisation in the control of gene expression. The presence of global regulatory mechanisms mediated through chromatin organisation can decrease the burden of invoking gene specific regulators for maintenance of the active/silenced state of gene expression. This could partially explain the lower number of genes estimated in the human genome.
SeqDoC: rapid SNP and mutation detection by direct comparison of DNA sequence chromatograms
Authors: Crowe Mark L
Published: June 2005

Background

This paper describes SeqDoC, a simple, web-based tool to carry out direct comparison of ABI sequence chromatograms. This allows the rapid identification of single nucleotide polymorphisms (SNPs) and point mutations without the need to install or learn more complicated analysis software.

Results

SeqDoC produces a subtracted trace showing differences between a reference and test chromatogram, and is optimised to emphasise those characteristic of single base changes. It automatically aligns sequences, and produces straightforward graphical output. The use of direct comparison of the sequence chromatograms means that artefacts introduced by automatic base-calling software are avoided. Homozygous and heterozygous substitutions and insertion/deletion events are all readily identified. SeqDoC successfully highlights nucleotide changes missed by the Staden package 'tracediff' program.

Conclusion

SeqDoC is ideal for small-scale SNP identification, for identification of changes in random mutagenesis screens, and for verification of PCR amplification fidelity. Differences are highlighted, not interpreted, allowing the investigator to make the ultimate decision on the nature of the change.
Evolutionary history of Wolbachia infections in the fire ant Solenopsis invicta
Authors: Ahrens Michael E , Shoemaker Dewayne
Published: June 2005

Background

Wolbachia are endosymbiotic bacteria that commonly infect numerous arthropods. Despite their broad taxonomic distribution, the transmission patterns of these bacteria within and among host species are not well understood. We sequenced a portion of the wsp gene from the Wolbachia genome infecting 138 individuals from eleven geographically distributed native populations of the fire ant Solenopsis invicta. We then compared these wsp sequence data to patterns of mitochondrial DNA (mtDNA) variation of both infected and uninfected host individuals to infer the transmission patterns of Wolbachia in S. invicta.

Results

Three different Wolbachia (wsp) variants occur within S. invicta, all of which are identical to previously described strains in fire ants. A comparison of the distribution of Wolbachia variants within S. invicta to a phylogeny of mtDNA haplotypes suggests S. invicta has acquired Wolbachia infections on at least three independent occasions. One common Wolbachia variant in S. invicta (wSinvictaB) is associated with two divergent mtDNA haplotype clades. Further, within each of these clades, Wolbachia-infected and uninfected individuals possess virtually identical subsets of mtDNA haplotypes, including both putative derived and ancestral mtDNA haplotypes. The same pattern also holds for wSinvictaA, where at least one and as many as three invasions into S. invicta have occurred. These data suggest that the initial invasions of Wolbachia into host ant populations may be relatively ancient and have been followed by multiple secondary losses of Wolbachia in different infected lineages over time. Finally, our data also provide additional insights into the factors responsible for previously reported variation in Wolbachia prevalence among S. invicta populations.

Conclusion

The history of Wolbachia infections in S. invicta is rather complex and involves multiple invasions or horizontal transmission events of Wolbachia into this species. Although these Wolbachia infections apparently have been present for relatively long time periods, these data clearly indicate that Wolbachia infections frequently have been secondarily lost within different lineages. Importantly, the uncoupled transmission of the Wolbachia and mtDNA genomes suggests that the presumed effects of Wolbachia on mtDNA evolution within S. invicta are less severe than originally predicted. Thus, the common concern that use of mtDNA markers for studying the evolutionary history of insects is confounded by maternally inherited endosymbionts such as Wolbachia may be somewhat unwarranted in the case of S. invicta.
Biomarker metabolites capturing the metabolite variance present in a rice plant developmental period
Authors: Tarpley Lee , Duran Anthony L , Kebrom Tesfamichael H , Sumner Lloyd W
Published: June 2005

Background

This study analyzes metabolomic data from a rice tillering (branching) developmental profile to define a set of biomarker metabolites that reliably captures the metabolite variance of this plant developmental event, and which has potential as a basis for rapid comparative screening of metabolite profiles in relation to change in development, environment, or genotype. Changes in metabolism, and in metabolite profile, occur as a part of, and in response to, developmental events. These changes are influenced by the developmental program, as well as external factors impinging on it. Many samples are needed, however, to characterize quantitative aspects of developmental variation. A biomarker metabolite set could benefit screening of quantitative plant developmental variation by providing some of the advantages of both comprehensive metabolomic studies and focused studies of particular metabolites or pathways.

Results

An appropriate set of biomarker metabolites to represent the plant developmental period including the initiation and early growth of rice tillering (branching) was obtained by: (1) determining principal components of the comprehensive metabolomic profile, then (2) identifying clusters of metabolites representing variation in loading on the first three principal components, and finally (3) selecting individual metabolites from these clusters that were known to be common among diverse organisms. The resultant set of 21 biomarker metabolites was reliable (P = 0.001) in capturing 83% of the metabolite variation in development. Furthermore, a subset of the biomarker metabolites was successful (P = 0.05) in correctly predicting metabolite change in response to environment as determined in another rice metabolomics study.

Conclusion

The ability to define a set of biomarker metabolites that reliably captures the metabolite variance of a plant developmental event was established. The biomarker metabolites are all commonly present in diverse organisms, so studies of their quantitative relationships can provide comparative information concerning metabolite profiles in relation to change in plant development, environment, or genotype.
Hepatocellular carcinoma and the penetrance of HFEC282Y mutations: a cross sectional study
Authors: Willis Gavin , Bardsley Vicky , Fellows Ian W , Lonsdale Ray , Wimperis Jennie Z , Jennings Barbara A
Published: June 2005

Background

Although most patients with hereditary haemochromatosis have HFE C282Y mutations, the lifetime risk to HFE C282Y homozygotes of developing fatal diseases such as hepatocellular carcinoma is uncertain. We have carried out a cross-sectional study to determine the proportion of diagnosed hepatocellular carcinoma patients who are homozygous for the HFE C282Y mutation; and to estimate the penetrance of this genotype with respect to hepatocellular carcinoma in East Anglia.

Methods

Tissue biopsies were analysed from 144 cases of hepatocellular carcinoma for HFE C282Y mutations; the data produced were compared with the frequency of HFE mutations in a large sample of the local population. Data were also retrieved from the East Anglian Cancer Intelligence Unit to determine the annual incidence of hepatocellular carcinoma; and from appropriate life tables.

Results

Eight out of 144 of the cases were homozygous for the HFE C282Y mutation, all 8 cases were male. 6 of these 8 cases had a previous diagnosis of hereditary haemochromatosis. Male HFE C282Y homozygotes were more likely to be diagnosed with hepatocellular carcinoma (odds ratio [OR] = 14, 95% confidence interval [CI] = 5–37). For this population, we estimate that the penetrance of the HFE C282Y homozygous genotype, with respect to hepatocellular carcinoma, was between 1.31 % and 2.1% for males and was zero for females.

Conclusion

In this population, we found that only a very small proportion of homozygotes for the HFE C282Y mutation developed hepatocellular carcinoma. However, individuals with this genotype have a significantly increased risk of this rare disease relative to those who do not carry the mutations.
An IGF-I promoter polymorphism modifies the relationships between birth weight and risk factors for cardiovascular disease and diabetes at age 36
Authors: te Velde Saskia J , van Rossum Elisabeth FC , Voorhoeve Paul G , Twisk Jos WR , van de Waal Henriette A Delemarre , Stehouwer Coen DA , van Mechelen Willem , Lamberts Steven WJ , Kemper Han CG
Published: June 2005

Objective

To investigate whether IGF-I promoter polymorphism was associated with birth weight and risk factors for cardiovascular disease (CVD) and type 2 diabetes (T2DM), and whether the birth weight – risk factor relationship was the same for each genotype.

Design and participants

264 subjects (mean age 36 years) had data available on birth weight, IGF-I promoter polymorphism genotype, CVD and T2DM risk factors. Student's t-test and regression analyses were applied to analyse differences in birth weight and differences in the birth weight – risk factors relationship between the genotypes.

Results

Male variant carriers (VCs) of the IGF-I promoter polymorphism had a 0.2 kg lower birth weight than men with the wild type allele (p = 0.009). Of the risk factors for CVD and T2DM, solely LDL concentration was associated with the genotype for the polymorphism. Most birth weight – risk factor relationships were stronger in the VC subjects; among others the birth weight – systolic blood pressure relationship: 1 kg lower birth weight was related to an 8.0 mmHg higher systolic blood pressure

Conclusion

The polymorphism in the promoter region of the IGF-I gene is related to birth weight in men only, and to LDL concentration only. Furthermore, the genotype for this polymorphism modified the relationships between birth weight and the risk factors, especially for systolic and diastolic blood pressure.
Longitudinal assessment of PCBs and chlorinated pesticides in pregnant women from Western Canada
Authors: Jarrell John , Chan Siu , Hauser Russ , Hu Howard
Published: June 2005

Background

Maternal exposures to organochlorines prior to pregnancy are considered a risk to neonatal welfare, specifically in relation to neurocognitive functions. There is growing interest in the evaluation of maternal blood testing as a marker for fetal exposure as well as the variable geographic distribution of these priority chemicals.

Methods

Three hundred and twenty-three women in the second trimester of pregnancy entered the study at a prenatal clinic providing genetic counselling information. Subjects who had an indication for genetic amniocentesis based on late maternal age were eligible to participate. Two hundred and thirty-eight completed an environmental questionnaire. A sample of amniotic fluid was taken for karyotype analysis in 323 women and blood samples during pregnancy (209), at birth (105) and from the umbilical cord (97) and breast milk (47) were also collected. These samples were tested for 29 PCB congeners and organochlorine pesticides.

Results

The concentrations of PCB 153 in these media were relatively low in relation to other studies. Σ PCBs measurements in samples taken during the second trimester of pregnancy, at birth and in the umbilical cord were strongly correlated. Specific measurements of PCB 153 and PCB 180 among those subjects with completed sampling of blood samples from mothers and cord samples were significantly correlated. The concentrations of PCBs and pesticides did not differ in relation to prior spontaneous abortion history. There were no organochlorines present in the amniotic fluid at the current level of quantification.

Conclusion

Pregnant women from the Western Canada region of Calgary, Alberta are exposed to relatively low concentrations of organochlorines. Measurement of maternal blood during the second trimester of pregnancy can reliably estimate the fetal exposure to PCBs. This estimate is reliable for Group 2 and 3 PCBs as well as PCB 153 and PCB 180. The amniotic fluid does not contain measurable concentrations of pesticides and PCBs under the conditions of the levels of quantification.
A transcriptome map of cellular transformation by the fos oncogene
Authors: Ordway Jared M , Fenster Steven D , Ruan Hong , Curran Thomas
Published: May 2005

Background

The c-fos gene was originally identified as the cellular homolog of the oncogene v-fos carried by the Finkel-Biskis-Jenkins and Finkel-Biskis-Reilly murine osteogenic sarcoma retroviruses. Sustained expression of fos is sufficient to induce cellular transformation in vitro and tumorigenesis in vivo. Fos functions as a component of the AP-1 transcription factor complex to regulate gene transcription and several differentially expressed genes have been identified in cells transformed by fos. We have extended these studies by constructing a cellular system for conditional transformation by v-fos. Using Affymetrix-based DNA microarray technology, we analyzed transcriptional changes over the course of transformation and reversion in an inducible v-fos system.

Results

Microarray analyses of temporal gene expression during the process of v-fos mediated cellular transformation and morphological reversion revealed a remarkably dynamic transcriptome. Of the more than 8000 genes analyzed in this study, 3766 genes were categorized into 18 gene-expression patterns by using self-organizing map analysis. By combining the analysis of gene expression profiles in stably transformed cells with the analysis of sequential expression patterns during conditional transformation, we identified a relatively small cohort of genes implicated in v-fos mediated cellular transformation.

Conclusion

This approach defines a general conditional cell transformation system that can be used to study the endogenous transcription regulatory mechanisms involved in transformation and tumorigenesis. In addition, this study is the first reported analysis of dynamic changes in gene expression throughout experimentally controlled morphological transformation mediated by v-fos.
Left ventricular apical thrombus after systemic thrombolysis with recombinant tissue plasminogen activator in a patient with acute ischemic stroke
Authors: Doepp Florian , Sanad Wasiem , Schreiber Stephan J , Baumann Gert , Borges Adrian C
Published: May 2005

Background

Thrombolysis with recombinant tissue plasminogen activator (rtPA) is an established treatment in acute stroke. To prevent rethrombosis after rtPA therapy, secondary anticoagulation with heparin is commonly performed. However, the recommended time-point and extent of heparin treatment vary and are not well investigated.

Case presentation

We report a 61-year-old man who developed an acute global aphasia and right-sided hemiparesis. Cranial CT was normal and systemic thrombolytic therapy with tPA was started 120 minutes after symptom onset. Low-dose subcutaneous heparin treatment was initiated 24 hours later. Transthoracic echocardiography (TTE) 12 hours after admission showed slightly reduced left ventricular ejection fraction (LVEF) but was otherwise normal. 48 hours later the patient suddenly deteriorated with clinical signs of dyspnea and tachycardia. TTE revelead a large left ventricular apical thrombus as well as a reduction of LVEF to 20 %. Serial further TTE investigations demonstrated a complete resolution of the thrombus and normalisation of LVEF within two days.

Conclusion

Our case demonstrates an intracardiac thrombus formation following rtPA treatment of acute stroke, probably caused by secondary hypercoagulability. Rethrombosis or new thrombus formation might be an underestimated complication of rtPA therapy and potentially explain cases of secondary stroke progression.
Fallacies of preoperative lymphoscintigraphy in detecting sentinel node in breast cancer
Authors: Pandey Manoj , Deo Surya VS , Maharajan R
Published: June 2005

Background

Preoperative lymphoscintigraphy is one of the three methods of evaluating sentinel nodes in patients with breast cancer; however, it has been reported to have a high false negative rate.

Case presentations

We report here two cases where the preoperative lymphoscintigraphy was found to be fallacious. A 44-year-old female with T2N0 breast cancer underwent preoperative lymphoscintigraphy with Tc99 sulfur colloid which failed to show any uptake in axilla or internal mammary chain. Intraoperative scintigraphy with blue dye and hand held gamma probe identified sentinel lymph node in axilla. Another patient with T2N0 lesion underwent preoperative lymphoscintigraphy which showed a sentinel lymph node in axilla and another in supraclevicular fossa. Intraoperative scintigraphy failed to show supraclevicular node however axillary node was correctly identified.

Conclusion

These two cases further strengthen the need to carry out triple test in identification of sentinel lymph node in patients with breast cancer. It also demonstrates the fallacies of preoperative lymphoscintigraphy.
A mutation in the centriole-associated protein centrin causes genomic instability via increased chromosome loss in Chlamydomonas reinhardtii
Authors: Zamora Ivan , Marshall Wallace F
Published: June 2005

Background

The role of centrioles in mitotic spindle function remains unclear. One approach to investigate mitotic centriole function is to ask whether mutation of centriole-associated proteins can cause genomic instability.

Results

We addressed the role of the centriole-associated EF-hand protein centrin in genomic stability using a Chlamydomonas reinhardtii centrin mutant that forms acentriolar bipolar spindles and lacks the centrin-based rhizoplast structures that join centrioles to the nucleus. Using a genetic assay for loss of heterozygosity, we found that this centrin mutant showed increased genomic instability compared to wild-type cells, and we determined that the increase in genomic instability was due to a 100-fold increase in chromosome loss rates compared to wild type. Live cell imaging reveals an increased rate in cell death during G1 in haploid cells that is consistent with an elevated rate of chromosome loss, and analysis of cell death versus centriole copy number argues against a role for multipolar spindles in this process.

Conclusion

The increased chromosome loss rates observed in a centrin mutant that forms acentriolar spindles suggests a role for centrin protein, and possibly centrioles, in mitotic fidelity.
Mathematical models use varying parameter strategies to represent paralyzed muscle force properties: a sensitivity analysis
Authors: Frey Law Laura A , Shields Richard K
Published: June 2005

Background

Mathematical muscle models may be useful for the determination of appropriate musculoskeletal stresses that will safely maintain the integrity of muscle and bone following spinal cord injury. Several models have been proposed to represent paralyzed muscle, but there have not been any systematic comparisons of modelling approaches to better understand the relationships between model parameters and muscle contractile properties. This sensitivity analysis of simulated muscle forces using three currently available mathematical models provides insight into the differences in modelling strategies as well as any direct parameter associations with simulated muscle force properties.

Methods

Three mathematical muscle models were compared: a traditional linear model with 3 parameters and two contemporary nonlinear models each with 6 parameters. Simulated muscle forces were calculated for two stimulation patterns (constant frequency and initial doublet trains) at three frequencies (5, 10, and 20 Hz). A sensitivity analysis of each model was performed by altering a single parameter through a range of 8 values, while the remaining parameters were kept at baseline values. Specific simulated force characteristics were determined for each stimulation pattern and each parameter increment. Significant parameter influences for each simulated force property were determined using ANOVA and Tukey's follow-up tests (α ≤ 0.05), and compared to previously reported parameter definitions.

Results

Each of the 3 linear model's parameters most clearly influence either simulated force magnitude or speed properties, consistent with previous parameter definitions. The nonlinear models' parameters displayed greater redundancy between force magnitude and speed properties. Further, previous parameter definitions for one of the nonlinear models were consistently supported, while the other was only partially supported by this analysis.

Conclusion

These three mathematical models use substantially different strategies to represent simulated muscle force. The two contemporary nonlinear models' parameters have the least distinct associations with simulated muscle force properties, and the greatest parameter role redundancy compared to the traditional linear model.
Respiratory syncytial virus-induced acute and chronic airway disease is independent of genetic background: An experimental murine model
Authors: Chávez-Bueno Susana , Mejías Asunción , Gómez Ana M , Olsen Kurt D , Ríos Ana M , Fonseca-Aten Mónica , Ramilo Octavio , Jafri Hasan S
Published: May 2005

Background

Respiratory syncytial virus (RSV) is the leading respiratory viral pathogen in young children worldwide. RSV disease is associated with acute airway obstruction (AO), long-term airway hyperresponsiveness (AHR), and chronic lung inflammation. Using two different mouse strains, this study was designed to determine whether RSV disease patterns are host-dependent. C57BL/6 and BALB/c mice were inoculated with RSV and followed for 77 days. RSV loads were measured by plaque assay and polymerase chain reaction (PCR) in bronchoalveolar lavage (BAL) and whole lung samples; cytokines were measured in BAL samples. Lung inflammation was evaluated with a histopathologic score (HPS), and AO and AHR were determined by plethysmography.

Results

Viral load dynamics, histopathologic score (HPS), cytokine concentrations, AO and long-term AHR were similar in both strains of RSV-infected mice, although RSV-infected C57BL/6 mice developed significantly greater AO compared with RSV-infected BALB/c mice on day 5. PCR detected RSV RNA in BAL samples of RSV infected mice until day 42, and in whole lung samples through day 77. BAL concentrations of cytokines TNF-α, IFN-γ, and chemokines MIG, RANTES and MIP-1α were significantly elevated in both strains of RSV-infected mice compared with their respective controls. Viral load measured by PCR significantly correlated with disease severity on days 14 and 21.

Conclusion

RSV-induced acute and chronic airway disease is independent of genetic background.
Neutrophil elastase, an acid-independent serine protease, facilitates reovirus uncoating and infection in U937 promonocyte cells
Authors: Golden Joseph W , Schiff Leslie A
Published: June 2005

Background

Mammalian reoviruses naturally infect their hosts through the enteric and respiratory tracts. During enteric infections, proteolysis of the reovirus outer capsid protein σ3 is mediated by pancreatic serine proteases. In contrast, the proteases critical for reovirus replication in the lung are unknown. Neutrophil elastase (NE) is an acid-independent, inflammatory serine protease predominantly expressed by neutrophils. In addition to its normal role in microbial defense, aberrant expression of NE has been implicated in the pathology of acute respiratory distress syndrome (ARDS). Because reovirus replication in rodent lungs causes ARDS-like symptoms and induces an infiltration of neutrophils, we investigated the capacity of NE to promote reovirus virion uncoating.

Results

The human promonocyte cell line U937 expresses NE. Treatment of U937 cells with the broad-spectrum cysteine-protease inhibitor E64 [trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane] and with agents that increase vesicular pH did not inhibit reovirus replication. Even when these inhibitors were used in combination, reovirus replicated to significant yields, indicating that an acid-independent non-cysteine protease was capable of mediating reovirus uncoating in U937 cell cultures. To identify the protease(s) responsible, U937 cells were treated with phorbol 12-myristate 13-acetate (PMA), an agent that induces cellular differentiation and results in decreased expression of acid-independent serine proteases, including NE and cathepsin (Cat) G. In the presence of E64, reovirus did not replicate efficiently in PMA-treated cells. To directly assess the role of NE in reovirus infection of U937 cells, we examined viral growth in the presence of N-Ala-Ala-Pro-Val chloromethylketone, a NE-specific inhibitor. Reovirus replication in the presence of E64 was significantly reduced by treatment of cells with the NE inhibitor. Incubation of virions with purified NE resulted in the generation of infectious subviron particles that did not require additional intracellular proteolysis.

Conclusion

Our findings reveal that NE can facilitate reovirus infection. The fact that it does so in the presence of agents that raise vesicular pH supports a model in which the requirement for acidic pH during infection reflects the conditions required for optimal protease activity. The capacity of reovirus to exploit NE may impact viral replication in the lung and other tissues during natural infections.
Golf and upper limb injuries: a summary and review of the literature
Authors: McHardy Andrew J , Pollard Henry P
Published: May 2005

Background

Golf is a popular past time that provides exercise with social interaction. However, as with all sports and activities, injury may occur. Many golf-related injuries occur in the upper limb, yet little research on the potential mechanisms of these injuries has been conducted.

Objective

To review the current literature on golf-related upper limb injuries and report on potential causes of injury as it relates to the golf swing.

Discussion

An overview of the golf swing is described in terms of its potential to cause the frequently noted injuries. Most injuries occur at impact when the golf club hits the ball. This paper concludes that more research into golf-related upper limb injuries is required to develop a thorough understanding of how injuries occur. Types of research include epidemiology studies, kinematic swing analysis and electromyographic studies of the upper limb during golf. By conducting such research, preventative measures maybe developed to reduce golf related injury.
Phase I clinical study of the recombinant antibody toxin scFv(FRP5)-ETA specific for the ErbB2/HER2 receptor in patients with advanced solid malignomas
Authors: von Minckwitz Gunter , Harder Sebastian , Hövelmann Sascha , Jäger Elke , Al-Batran Salah-Eddin , Loibl Sibylle , Atmaca Akin , Cimpoiasu Christian , Neumann Antje , Abera Aklil , Knuth Alexander , Kaufmann Manfred , Jäger Dirk , Maurer Alexander B , Wels Winfried S
Published: June 2005

Introduction

ScFv(FRP5)-ETA is a recombinant antibody toxin with binding specificity for ErbB2 (HER2). It consists of an N-terminal single-chain antibody fragment (scFv), genetically linked to truncated Pseudomonas exotoxin A (ETA). Potent antitumoral activity of scFv(FRP5)-ETA against ErbB2-overexpressing tumor cells was previously demonstrated in vitro and in animal models. Here we report the first systemic application of scFv(FRP5)-ETA in human cancer patients.

Methods

We have performed a phase I dose-finding study, with the objective to assess the maximum tolerated dose and the dose-limiting toxicity of intravenously injected scFv(FRP5)-ETA. Eighteen patients suffering from ErbB2-expressing metastatic breast cancers, prostate cancers, head and neck cancer, non small cell lung cancer, or transitional cell carcinoma were treated. Dose levels of 2, 4, 10, 12.5, and 20 μg/kg scFv(FRP5)-ETA were administered as five daily infusions each for two consecutive weeks.

Results

No hematologic, renal, and/or cardiovascular toxicities were noted in any of the patients treated. However, transient elevation of liver enzymes was observed, and considered dose limiting, in one of six patients at the maximum tolerated dose of 12.5 μg/kg, and in two of three patients at 20 μg/kg. Fifteen minutes after injection, peak concentrations of more than 100 ng/ml scFv(FRP5)-ETA were obtained at a dose of 10 μg/kg, indicating that predicted therapeutic levels of the recombinant protein can be applied without inducing toxic side effects. Induction of antibodies against scFv(FRP5)-ETA was observed 8 days after initiation of therapy in 13 patients investigated, but only in five of these patients could neutralizing activity be detected. Two patients showed stable disease and in three patients clinical signs of activity in terms of signs and symptoms were observed (all treated at doses ≥ 10 μg/kg). Disease progression occurred in 11 of the patients.

Conclusion

Our results demonstrate that systemic therapy with scFv(FRP5)-ETA can be safely administered up to a maximum tolerated dose of 12.5 μg/kg in patients with ErbB2-expressing tumors, justifying further clinical development.
Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiaeinteraction network
Authors: Zhang Lan V , King Oliver D , Wong Sharyl L , Goldberg Debra S , Tong Amy HY , Lesage Guillaume , Andrews Brenda , Bussey Howard , Boone Charles , Roth Frederick P
Published: June 2005

Background

Large-scale studies have revealed networks of various biological interaction types, such as protein-protein interaction, genetic interaction, transcriptional regulation, sequence homology, and expression correlation. Recurring patterns of interconnection, or 'network motifs', have revealed biological insights for networks containing either one or two types of interaction.

Results

To study more complex relationships involving multiple biological interaction types, we assembled an integrated Saccharomyces cerevisiae network in which nodes represent genes (or their protein products) and differently colored links represent the aforementioned five biological interaction types. We examined three- and four-node interconnection patterns containing multiple interaction types and found many enriched multi-color network motifs. Furthermore, we showed that most of the motifs form 'network themes' – classes of higher-order recurring interconnection patterns that encompass multiple occurrences of network motifs. Network themes can be tied to specific biological phenomena and may represent more fundamental network design principles. Examples of network themes include a pair of protein complexes with many inter-complex genetic interactions – the 'compensatory complexes' theme. Thematic maps – networks rendered in terms of such themes – can simplify an otherwise confusing tangle of biological relationships. We show this by mapping the S. cerevisiae network in terms of two specific network themes.

Conclusion

Significantly enriched motifs in an integrated S. cerevisiae interaction network are often signatures of network themes, higher-order network structures that correspond to biological phenomena. Representing networks in terms of network themes provides a useful simplification of complex biological relationships.
Graphical chain models for the analysis of complex genetic diseases: an application to hypertension
Authors: Di Serio C , Vicard P
Published: May 2005

A crucial task in modern genetic medicine is the understanding of complex genetic diseases. The main complicating features are that a combination of genetic and environmental risk factors is involved, and the phenotype of interest may be complex. Traditional statistical techniques based on lod-scores fail when the disease is no longer monogenic and the underlying disease transmission model is not defined. Different kinds of association tests have been proved to be an appropriate and powerful statistical tool to detect a ‘candidate gene’ for a complex disorder. However, statistical techniques able to investigate direct and indirect influences among phenotypes, genotypes and environmental risk factors, are required to analyse the association structure of complex diseases. In this paper, we propose graphical models as a natural tool to analyse the multifactorial structure of complex genetic diseases. An application of this model to primary hypertension data set is illustrated.
The role of perturbation in compositional data analysis
Authors: Aitchison J , Ng K W
Published: May 2005

In standard multivariate statistical analysis, common hypotheses of interest concern changes in mean vectors and subvectors. In compositional data analysis it is now well established that compositional change is most readily described in terms of the simplicial operation of perturbation and that subcompositions replace the marginal concept of subvectors. Against the background of two motivating experimental studies in the food industry, involving the compositions of cow’s milk and chicken carcasses, this paper emphasizes the importance of recognizing this fundamental operation of change in the associated simplex sample space. Well-defined hypotheses about the nature of any compositional effect can be expressed, for example, in terms of perturbation values and subcompositional stability and testing procedures developed. These procedures are applied to lattices of such hypotheses in the two practical situations. We identify the two problems as being the counterpart of the analysis of paired comparison or split plot experiments and of separate sample comparative experiments in the jargon of standard multivariate analysis.