bluuebunny/crossref_metadata_2025 huggingface dataset:
Commentary: Dancing the Kochari: Challenging the U.S. Perspective on Communication in Newly Democratic Cultures
Authors: Harootunian Gil
Published: November 2006

Research on professional communication in the former Soviet republics and satellite countries was by and large closed to American scholars until recent years. This commentary offers a critical introduction to the forces of globalization, discourse, and democracy in that region, offering to U.S. readers a corrective lens that challenges the American view of the role of writing in regions where democratization is new, fragile, and even alien to the culture. A great part of our work as professional communicators rests on Western, particularly democratic, theoretical assumptions, mainly derived from Greco-Roman assumptions. Too often we do not confront the real otherness of practices that poach on Western assumptions or practices for nondemocratic ends, but we face increasing pressure to do so as our work is relentlessly internationalized.
Perceptions and Beliefs About Body Size, Weight, and Weight Loss Among Obese African American Women: A Qualitative Inquiry
Authors: Befort Christie A. , Thomas Janet L. , Daley Christine M. , Rhode Paula C. , Ahluwalia Jasjit S.
Published: November 2006

The purpose of this qualitative study was to explore perceptions and beliefs about body size, weight, and weight loss among obese African American women in order to form a design of weight loss intervention with this target population. Six focus groups were conducted at a community health clinic. Participants were predominantly middle-aged with a mean Body Mass Index of 40.3 ± 9.2 kg/m2. Findings suggest that participants (a) believe that people can be attractive and healthy at larger sizes; (b) still feel dissatisfied with their weight and self-conscious about their bodies; (c) emphasize eating behavior as the primary cause for weight gain; (d) view pregnancy, motherhood, and caregiving as major precursors to weight gain; (e) view health as the most important reason to lose weight; (f) have mixed experiences and expectations for social support for weight loss; and (g) prefer treatments that incorporate long-term lifestyle modification rather than fad diets or medication.
Toward a Model of Prostate Cancer Information Seeking
Authors: Ross Levi , Kohler Connie L. , Grimley Diane M. , Green B. Lee , Anderson-Lewis Charkarra
Published: November 2006

Public health actions to improve African American men's ability to make informed decisions about participation in prostate cancer control activities have a greater likelihood of success when they are theory driven and informed by members of the target population. This article reports on formative research to evaluate the usefulness of the theory of reasoned action as a model to explain and predict prostate cancer information-seeking behavior by African American men. Fifty-two men participated in eight focus group interviews. Positive behavioral beliefs for obtaining prostate cancer information from physicians included increasing awareness of and obtaining accurate information about the disease, early detection and screening, and treatment. Negative beliefs included fear, distrust, and inconvenience. Significant others, peers, siblings, and religious leaders were identified as individuals who could influence this behavior. These findings provide additional insight into ways to reach and intervene with African American men to influence this important cancer control activity.
Indigenous, ethnic and cultural articulations of new media
Authors: Srinivasan Ramesh
Published: November 2006

This article extends a lineage of research that reveals possibilities by which indigenous and ethnic communities have appropriated media technologies to serve their own cultural, political and social visions. This article focuses on networked and database-driven ‘new’ media and information systems, and the possibilities and potentialities these hold within cultural scenarios. A case is presented that has focused on Native communities within the United States. Through this case study, I present a methodology, process and analysis of the means by which information systems can enable culturally and community-focused goals.
BMUS British Australian Exchange 2006
Authors: Chung Emma M. L.
Published: November 2006

It has been over 10 years since Australian researchers visited Leicester Royal Infirmary to learn about the emerging applications of transcranial Doppler ultrasound to embolus detection. Thanks to an award from the British Medical Ultrasound Society, the author was able to make a welcome return visit to the National Stroke Research Institute in Australia.
A Legal Perspective Within the NHS
Authors: Ashton Vanessa
Published: November 2006

3D and 4D scanning technology are driving forward the capability to diagnose fetal disorders at an accelerating pace. However, unless departments have staff with the skills and training necessary to operate the equipment correctly, and the ability to interpret the image, then they will be open to potential claims for negligence and or breach of duty.
Sonographic Appearances of Salivary Gland Involvement in Human Immunodeficiency Virus (HIV) Infection
Authors: Lewis Khari , Siddique Lisa , Howlett David
Published: November 2006

Human Immunodeficiency Virus (HIV) infection may involve the salivary glands, although the sonographic appearances are not well described. In this article, we describe three patients with known HIV infection who presented with salivary gland enlargement, associated neck lymphadenopathy, and no other symptoms or signs of underlying Sjögren's syndrome. In each of the patients, ultrasound examination demonstrated salivary gland appearances identical to those described in Sjögren's syndrome with lymphadenopathy also present in the neck. HIV infection may cause sonographic appearances identical to Sjögren's syndrome within the salivary glands and should be considered in the differential diagnosis if such features are observed.
Transcranial Doppler Embolus Detection: A Primer
Authors: Chung Emma M. L.
Published: November 2006

Blood clots and pieces of plaque can detach from the insides of arteries and move to the brain with devastating consequences. In this primer, I describe how this process of embolization can be detected by harnessing the Physics of transcranial Doppler ultrasound.
Characterisation of surface texture using AFM with trimmed probe tip
Authors: Ali M. Y. , Lim B. H.
Published: November 2006

This paper discusses the scanning performance of a trimmed atomic force microscope (AFM) tip. A standard tip was trimmed by focused ion beam (FIB) sputtering to achieve a higher aspect ratio and sharpness. Microfeatures produced by FIB sputtering on a single crystal silicon substrate were scanned by AFM tapping mode using both untrimmed and trimmed probe tip. A comparison of the scanning results with analytical calculation showed that the trimmed tips were superior in imaging the profile for both the hole shaped and pin shaped microfeatures. But when using the trimmed high aspect ratio tip, the scanning speed was significantly low. Higher scanning speed usually resulted to tip breakage. The trimmed tips were expensive and justified for special applications.
Modelling of kinetics of nitriding titanium alloys
Authors: Zhecheva A. , Malinov S. , Katzarov I. , Sha W.
Published: November 2006

Models for simulation and monitoring of the evolution of surface layers during gas nitriding of titanium alloys were developed using own experimental results. They are based on analytical and numerical solutions of the diffusion equation and model the nitrogen distribution, the thickness of the nitrided layers and the incubation time for the formation of layers on the surface of titanium alloys.
Deformation and fracture of polymer coated metal sheets: Characterisation and degradation
Authors: Zumelzu E. , Rull F. , Boettcher A. A.
Published: November 2006

The present work intends to understand the failure mechanism of polymer coated metal sheets during deep drawing. Characterisation and degradation evaluations of the metal–polymer protective substrates were carried out by scanning electron microscopy, X-ray diffraction and electrochemical trials. Attenuated total reflection, Fourier transform infrared and confocal Raman spectroscopy were employed to analyse the structural changes of the polyethylene teraphtalate coatings on the electrolytic chromium coated steel plates resulting from the manufacturing processes by deep drawing and the electrochemical degradation caused by citric citrate solutions.
Defective apoptosis of peripheral-blood lymphocytes in hyper-IgD and periodic fever syndrome
Authors: Bodar Evelien J. , van der Hilst Jeroen C.H. , van Heerde Waander , van der Meer Jos W. M. , Drenth Joost P. H. , Simon Anna
Published: November 2006

Hereditary periodic fever syndromes are characterized by incapacitating attacks of fever and generalized inflammation. While the mutated genes for the major syndromes in this group are known, the pathogenesis remains unclear. The aim of this study was to investigate apoptosis in patients with periodic fever as a possible pathogenic factor. We measured anisomycin-induced apoptosis with annexin-V flow cytometry and caspase-3/7 activity in peripheral-blood lymphocytes from symptom-free patients with hyper-IgD and periodic fever syndrome (HIDS; n = 10), TNF-receptor–associated periodic syndrome (TRAPS; n = 7), and familial Mediterranean fever (FMF; n = 2). HIDS lymphocytes showed a decreased percentage of apoptosis during remission by both methods compared with controls (17.8% vs 55.4%), whereas no difference was observed in TRAPS or FMF lymphocytes. This defective apoptosis of lymphocytes may be a central pathogenic mechanism in HIDS, since dysfunction of one of the inhibitory mechanisms to curtail the immunologic response could cause an unbridled generalized inflammation after a trivial stimulus.
Spi-1/PU.1 participates in erythroleukemogenesis by inhibiting apoptosis in cooperation with Epo signaling and by blocking erythroid differentiation
Authors: Rimmelé Pauline , Kosmider Olivier , Mayeux Patrick , Moreau-Gachelin Françoise , Guillouf Christel
Published: November 2006

Overexpression of the transcription factor Spi-1/PU.1 in mice leads to acute erythroleukemia characterized by a differentiation block at the proerythroblastic stage. In this study, we made use of a new cellular system allowing us to reach graded expression of Spi-1 in preleukemic cells to dissect mechanisms of Spi-1/PU-1 in erythroleukemogenesis. This system is based on conditional production of 1 or 2 spi-1–interfering RNAs stably inserted into spi-1 transgenic proerythroblasts. We show that Spi-1 knock-down was sufficient to reinstate the erythroid differentiation program. This differentiation process was associated with an exit from the cell cycle. Evidence is provided that in the presence of erythropoietin (Epo), Spi-1 displays an antiapoptotic role that is independent of its function in blocking erythroid differentiation. Apoptosis inhibited by Spi-1 did not involve activation of the Fas/FasL signaling pathway nor a failure to activate Epo receptor (EpoR). Furthermore, we found that reducing the Spi-1 level yields to ERK dephosphorylation and increased phosphorylation of AKT and STAT5, suggesting that Spi-1 may affect major signaling pathways downstream of the EpoR in erythroid cells. These findings reveal 2 distinct roles for Spi-1 during erythroleukemogenesis: Spi-1 blocks the erythroid differentiation program and acts to impair apoptotic death in cooperation with an Epo signaling.
HIV-1 infection and pathogenesis in a novel humanized mouse model
Authors: Zhang Liguo , Kovalev Grigoriy I. , Su Lishan
Published: November 2006

The Rag2-γC double-knockout (DKO) mouse lacks T, B, and natural killer (NK) cells, and allows development of a functional human immune system with human CD34+ hematopoietic stem/progenitor cells (DKO-hu HSCs). Normal human T, B, and dendritic cells are present in peripheral blood, thymus, spleen, and lymph nodes. We report that both CCR5 and CXCR4 are expressed on human immature and mature T cells. DKO-hu HSC mice allow efficient HIV-1 infection with plasma high viremia. High levels of productive infection occur in the thymus, spleen, and lymph nodes. Human CD4+ T cells are gradually depleted by HIV-1 in a dose-dependent manner. In addition, HIV-1 infection persists in infected DKO-hu HSC mice for at least 19 weeks, with infectious HIV-1 in lymphoid tissues. Thus, the DKO-hu HSC mouse can serve as a relevant in vivo model to investigate mechanisms of HIV-1 infection and immunopathogenesis as well as to develop anti–HIV-1 therapeutics.
Changes in HRCT findings in patients with respiratory bronchiolitis-associated interstitial lung disease after smoking cessation
Authors: Nakanishi M. , Demura Y. , Mizuno S. , Ameshima S. , Chiba Y. , Miyamori I. , Itoh H. , Kitaichi M. , Ishizaki T.
Published: November 2006

High-resolution computed tomography (HRCT) findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are varied and nonspecific. There is no known report of changes in HRCT findings and respiratory function test results for RB-ILD patients following the cessation of smoking.

Five patients with RB-ILD, confirmed by surgical lung biopsy, were retrospectively studied. Each stopped cigarette smoking and did not receive corticosteroid therapy after diagnosis. The clinical symptoms, respiratory function test results and HRCT findings obtained at the final observation were compared with those from the time of diagnosis.

Ground-glass opacity and centrilobular nodules corresponding to pathological respiratory bronchiolitis, as well as intralobular fine linear-reticular opacity corresponding to fibrosis involving the subpleural alveolar septa, showed computed tomography–pathological correlations. Both clinical symptoms and the diffusing capacity of the lungs for carbon monoxide improved significantly following smoking cessation, as did ground-glass opacity and centrilobular nodules seen during the initial HRCT examination.

Centrilobular nodules and ground-glass opacity, which are the main features of high-resolution computed tomography of respiratory bronchiolitis-associated interstitial lung disease patients and represent pathological respiratory bronchiolitis, can be improved by smoking cessation. The diffusing capacity of the lung for carbon monoxide in respiratory function tests can be also improved.
Pulmonary artery distensibility in pulmonary arterial hypertension: an MRI pilot study
Authors: Jardim C. , Rochitte C. E. , Humbert M. , Rubenfeld G. , Jasinowodolinski D. , Carvalho C. R. R. , Souza R.
Published: November 2006

Pulmonary arterial hypertension (PAH) is a disease of the small vessels in which there is a substantial increase in pulmonary vascular resistance leading to right ventricle failure and death. Invasive haemodynamic evaluation is mandatory not only for diagnosis confirmation but also to address prognosis and eligibility for the use of calcium-channel blockers through an acute vasodilator challenge. Noninvasive surrogate response markers to the acute vasodilator test have been sought.

In the present study, the relationship between pulmonary artery distensibility, assessed using magnetic resonance imaging (MRI), and response to acute vasodilator tests was investigated. In total, 19 patients diagnosed with idiopathic PAH without any specific treatment were evaluated. Within a 48-h window after pulmonary artery catheterisation, patients underwent cardiac MRI.

Cardiac index, calculated after the determination (invasively and noninvasively) of cardiac output, showed excellent correlation, as did right atrial pressure and right ventricle ejection fraction. Pulmonary artery distensibility was significantly higher in responders. A receiver operating characteristic curve analysis has shown that 10% distensibility was able to differentiate responders from nonresponders with 100% sensitivity and 56% specificity.

The present findings suggest that magnetic resonance imaging and pulmonary artery distensibility may be useful noninvasive tools for the evaluation of patients with pulmonary hypertension.
Effect of indacaterol, a novel long-acting β2-agonist, on isolated human bronchi
Authors: Naline E. , Trifilieff A. , Fairhurst R. A. , Advenier C. , Molimard M.
Published: November 2006

Indacaterol is a novel β2-adrenoceptor agonist in development for the once-daily treatment of asthma and chronic obstructive pulmonary disease. The present study evaluated the relaxant effect of indacaterol on isolated human bronchi obtained from lungs of patients undergoing surgery for lung carcinoma.

Potency (-logEC50), maximal relaxant effect (Emax) and onset of action were determined at resting tone. Duration of action was determined against cholinergic neural contraction induced by electrical field stimulation (EFS).

At resting tone, -logEC50and Emaxvalues were 8.82±0.41 and 77±5% for indacaterol, 9.84±0.22 and 94±1% for formoterol, 8.36±0.16 and 74±4% for salmeterol, and 8.43±0.22 and 84±4% for salbutamol, respectively.

In contrast to salmeterol, indacaterol did not antagonise the isoprenaline response. Indacaterol's onset of action (7.8±0.7 min) was not significantly different from that of formoterol (5.8±0.7 min) or salbutamol (11.0±4.0 min), but it was significantly faster than that of salmeterol (19.4±4.3 min). EFS-induced contractions were inhibited with -logIC50values of 6.96±0.13 (indacaterol), 8.96±0.18 (formoterol), 7.18±0.34 (salmeterol) and 6.39±0.26 (salbutamol). Duration of action was >12 h for indacaterol and salmeterol, and 35.3±8.8 and 14.6±3.7 min for formoterol and salbutamol, respectively.

In isolated human bronchi, indacaterol behaved as a long-acting β2-adrenoceptor agonist with high intrinsic efficacy and fast onset of action.
Respiratory infections associated with nontuberculous mycobacteria in non-HIV patients
Authors: Dailloux M. , Abalain M. L. , Laurain C. , Lebrun L. , Loos-Ayav C. , Lozniewski A. , Maugein J. ,   the French Mycobacteria Study Group
Published: November 2006

The incidence of nontuberculous mycobacteria (NTM) pulmonary diseases in HIV-negative patients was studied prospectively from January 1, 2001 to December 31, 2003 by 32 sentinel sites distributed throughout France.

In total, 262 patients who yielded NTM isolates from respiratory clinical specimens, met the bacteriological, radiological and clinical criteria established by the American Thoracic Society for NTM respiratory disease. Among the 262 NTM isolates, 234 were slow-growing mycobacteria (125Mycobacterium avium-intracellularecomplex (MAC), 66M. xenopi, 34M. kansasii) and 28 were rapidly growing mycobacteria (25M. abscessuscomplex). In the Paris area,M. xenopiwas the most frequently isolated species, followed by MAC.

Most patients (>50%), except those withM. kansasii, had underlying predisposing factors such as pre-existing pulmonary disease or immune deficiency. Asthenia, weight loss, chronic cough and dyspnoea were the most common clinical symptoms. The classical radiological appearance of NTM infections was indistinguishable from that observed in patients with pulmonary tuberculosis.

In summary, the incidence of nontuberculous mycobacteria pulmonary infections in HIV-negative patients was estimated at 0.74, 0.73 and 0.72 cases per 100,000 inhabitants in 2001, 2002 and 2003, respectively.
Cis-motifs upstream of the transcription and translation initiation sites are effectively revealed by their positional disequilibrium in eukaryote genomes using frequency distribution curves
Authors: Berendzen Kenneth W , Stüber Kurt , Harter Klaus , Wanke Dierk
Published: November 2006

Background

The discovery of cis-regulatory motifs still remains a challenging task even though the number of sequenced genomes is constantly growing. Computational analyses using pattern search algorithms have been valuable in phylogenetic footprinting approaches as have expression profile experiments to predict co-occurring motifs. Surprisingly little is known about the nature of cis-regulatory element (CRE) distribution in promoters.

Results

In this paper we used the Motif Mapper open-source collection of visual basic scripts for the analysis of motifs in any aligned set of DNA sequences. We focused on promoter motif distribution curves to identify positional over-representation of DNA motifs. Using differentially aligned datasets from the model species Arabidopsis thaliana, Caenorhabditis elegans, Drosophila melanogaster and Saccharomyces cerevisiae, we convincingly demonstrated the importance of the position and orientation for motif discovery. Analysis with known CREs and all possible hexanucleotides showed that some functional elements gather close to the transcription and translation initiation sites and that elements other than the TATA-box motif are conserved between eukaryote promoters. While a high background frequency usually decreases the effectiveness of such an enumerative investigation, we improved our analysis by conducting motif distribution maps using large datasets.

Conclusion

This is the first study to reveal positional over-representation of CREs and promoter motifs in a cross-species approach. CREs and motifs shared between eukaryotic promoters support the observation that an eukaryotic promoter structure has been conserved throughout evolutionary time. Furthermore, with the information on positional enrichment of a motif or a known functional CRE, it is possible to get a more detailed insight into where an element appears to function. This in turn might accelerate the in depth examination of known and yet unknown cis-regulatory sequences in the laboratory.
Inhibition of inducible Nitric Oxide Synthase by a mustard gas analog in murine macrophages
Authors: Qui Min , Paromov Victor M , Yang Hongsong , Smith Milton , Stone William L
Published: November 2006

Background

2-Chloroethyl ethyl sulphide (CEES) is a sulphur vesicating agent and an analogue of the chemical warfare agent 2,2'-dichlorodiethyl sulphide, or sulphur mustard gas (HD). Both CEES and HD are alkylating agents that influence cellular thiols and are highly toxic. In a previous publication, we reported that lipopolysaccharide (LPS) enhances the cytotoxicity of CEES in murine RAW264.7 macrophages. In the present investigation, we studied the influence of CEES on nitric oxide (NO) production in LPS stimulated RAW264.7 cells since NO signalling affects inflammation, cell death, and wound healing. Murine macrophages stimulated with LPS produce NO almost exclusively via inducible nitric oxide synthase (iNOS) activity. We suggest that the influence of CEES or HD on the cellular production of NO could play an important role in the pathophysiological responses of tissues to these toxicants. In particular, it is known that macrophage generated NO synthesised by iNOS plays a critical role in wound healing.

Results

We initially confirmed that in LPS stimulated RAW264.7 macrophages NO is exclusively generated by the iNOS form of nitric oxide synthase. CEES treatment inhibited the synthesis of NO (after 24 hours) in viable LPS-stimulated RAW264.7 macrophages as measured by either nitrite secretion into the culture medium or the intracellular conversion of 4,5-diaminofluorescein diacetate (DAF-2DA) or dichlorofluorescin diacetate (DCFH-DA). Western blots showed that CEES transiently decreased the expression of iNOS protein; however, treatment of active iNOS with CEESin vitrodid not inhibit its enzymatic activity

Conclusion

CEES inhibits NO production in LPS stimulated macrophages by decreasing iNOS protein expression. Decreased iNOS expression is likely the result of CEES induced alteration in the nuclear factor kappa B (NF-κB) signalling pathway. Since NO can act as an antioxidant, the CEES induced down-regulation of iNOS in LPS-stimulated macrophages could elevate oxidative stress. Since macrophage generated NO is known to play a key role in cutaneous wound healing, it is possible that this work has physiological relevance with respect to the healing of HD induced skin blisters.
Genome-wide loss of heterozygosity and copy number alteration in esophageal squamous cell carcinoma using the Affymetrix GeneChip Mapping 10 K array
Authors: Hu Nan , Wang Chaoyu , Hu Ying , Yang Howard H , Kong Li-Hui , Lu Ning , Su Hua , Wang Quan-Hong , Goldstein Alisa M , Buetow Kenneth H , Emmert-Buck Michael R , Taylor Philip R , Lee Maxwell P
Published: November 2006

Background

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide. Comprehensive genomic characterization of ESCC will further our understanding of the carcinogenesis process in this disease.

Results

Genome-wide detection of chromosomal changes was performed using the Affymetrix GeneChip 10 K single nucleotide polymorphism (SNP) array, including loss of heterozygosity (LOH) and copy number alterations (CNA), for 26 pairs of matched germ-line and micro-dissected tumor DNA samples. LOH regions were identified by two methods – using Affymetrix's genotype call software and using Affymetrix's copy number alteration tool (CNAT) software – and both approaches yielded similar results. Non-random LOH regions were found on 10 chromosomal arms (in decreasing order of frequency: 17p, 9p, 9q, 13q, 17q, 4q, 4p, 3p, 15q, and 5q), including 20 novel LOH regions (10 kb to 4.26 Mb). Fifteen CNA-loss regions (200 kb to 4.3 Mb) and 36 CNA-gain regions (200 kb to 9.3 Mb) were also identified.

Conclusion

These studies demonstrate that the Affymetrix 10 K SNP chip is a valid platform to integrate analyses of LOH and CNA. The comprehensive knowledge gained from this analysis will enable improved strategies to prevent, diagnose, and treat ESCC.
Interleukin-4 induction of the CC chemokine TARC (CCL17) in murine macrophages is mediated by multiple STAT6 sites in the TARC gene promoter
Authors: Liddiard Kate , Welch John S , Lozach Jean , Heinz Sven , Glass Christopher K , Greaves David R
Published: November 2006

Background

Macrophages (Mθ) play a central role in the innate immune response and in the pathology of chronic inflammatory diseases. Macrophages treated with Th2-type cytokines such as Interleukin-4 (IL-4) and Interleukin-13 (IL-13) exhibit an altered phenotype and such alternatively activated macrophages are important in the pathology of diseases characterised by allergic inflammation including asthma and atopic dermatitis. The CC chemokine Thymus and Activation-Regulated Chemokine (TARC/CCL17) and its murine homologue (mTARC/ABCD-2) bind to the chemokine receptor CCR4, and direct T-cell and macrophage recruitment into areas of allergic inflammation. Delineating the molecular mechanisms responsible for the IL-4 induction of TARC expression will be important for a better understanding of the role of Th2 cytokines in allergic disease.

Results

We demonstrate that mTARC mRNA and protein are potently induced by the Th2 cytokine, Interleukin-4 (IL-4), and inhibited by Interferon-γ (IFN-γ) in primary macrophages (Mθ). IL-4 induction of mTARC occurs in the presence of PI3 kinase pathway and translation inhibitors, but not in the absence of STAT6 transcription factor, suggesting a direct-acting STAT6-mediated pathway of mTARC transcriptional activation. We have functionally characterised eleven putative STAT6 sites identified in the mTARC proximal promoter and determined that five of these contribute to the IL-4 induction of mTARC. Byin vitrobinding assays and transient transfection of isolated sites into the RAW 264.7 Mθ cell-line, we demonstrate that these sites have widely different capacities for binding and activation by STAT6. Site-directed mutagenesis of these sites within the context of the mTARC proximal promoter revealed that the two most proximal sites, conserved between the human and mouse genes, are important mediators of the IL-4 response.

Conclusion

The induction of mTARC by IL-4 results from cooperative interactions between STAT6 sites within the mTARC gene promoter. Significantly, we have shown that transfer of the nine most proximal mTARC STAT6 sites in their endogenous conformation confers potent (up to 130-fold) IL-4 inducibility on heterologous promoters. These promoter elements constitute important and sensitive IL-4-responsive transcriptional units that could be used to drive transgene expression in sites of Th2 inflammationin vivo.
Urokinase-type plasminogen activator supports liver repair independent of its cellular receptor
Authors: Shanmukhappa Kumar , Sabla Gregg E , Degen Jay L , Bezerra Jorge A
Published: November 2006

Background

The urokinase-type (uPA) and tissue-type (tPA) plasminogen activators regulate liver matrix remodelling through the conversion of plasminogen (Plg) to the active protease plasmin. Based on the efficient activation of plasminogen when uPA is bound to its receptor (uPAR) and on the role of uPA in plasmin-mediated liver repair, we hypothesized that uPA requires uPAR for efficient liver repair.

Methods

To test this hypothesis, we administered one dose of carbon tetrachloride (CCl4) to mice with single or combined deficiencies of uPA, uPAR and tPA, and examined hepatic morphology, cellular proliferation, fibrin clearance, and hepatic proteolysis 2–14 days later.

Results

Absence of uPAR alone or the combined absence of uPAR and tPA had no impact on the resolution of centrilobular injury, but the loss of receptor-free uPA significantly impaired the clearance of necrotic hepatocytes up to 14 days after CCl4. In response to the injury, hepatocyte proliferation was normal in mice of all genotypes, except for uPAR-deficient (uPAR°) mice, which had a reproducible but mild decrease by 33% at day 2, with an appropriate restoration of liver mass by 7 days similar to experimental controls. Immunostaining and zymographic analysis demonstrated that uPA alone promoted fibrin clearance from centrilobular regions and efficiently activated plasminogen.

Conclusion

uPA activates plasminogen and promotes liver matrix proteolysis during repair via a process that neither requires its receptor uPAR nor requires a contribution from its functional counterpart tPA.
Identification of the first intragenic deletion of the PITX2 gene causing an Axenfeld-Rieger Syndrome: case report
Authors: de la Houssaye Guillaume , Bieche Ivan , Roche Olivier , Vieira Véronique , Laurendeau Ingrid , Arbogast Laurence , Zeghidi Hatem , Rapp Philippe , Halimi Philippe , Vidaud Michel , Dufier Jean-Louis , Menasche Maurice , Abitbol Marc
Published: November 2006

Background

Axenfeld-Rieger syndrome (ARS) is characterized by bilateral congenital abnormalities of the anterior segment of the eye associated with abnormalities of the teeth, midface, and umbilicus. Most cases of ARS are caused by mutations in the genes encoding PITX2 or FOXC1. Here we describe a family affected by a severe form of ARS.

Case presentation

Two members of this family (father and daughter) presented with typical ARS and developed severe glaucoma. The ocular phenotype was much more severe in the daughter than in the father. Magnetic resonance imaging (MRI) detected an aggressive form of meningioma in the father. There was no mutation in the PITX2 gene, determined by exon screening. We identified an intragenic deletion by quantitative genomic PCR analysis and characterized this deletion in detail.

Conclusion

Our findings implicate the first intragenic deletion of the PITX2 gene in the pathogenesis of a severe form of ARS in an affected family. This study stresses the importance of a systematic search for intragenic deletions in families affected by ARS and in sporadic cases for which no mutations in the exons or introns of PITX2 have been found. The molecular genetics of some ARS pedigrees should be re-examined with enzymes that can amplify medium and large genomic fragments.
INSIG-2 promoter polymorphism and obesity related phenotypes: association study in 1428 members of 248 families
Authors: Hall Darroch H , Rahman Thahira , Avery Peter J , Keavney Bernard
Published: November 2006

Background

Obesity is a major public health problem. Body mass index (BMI) is a highly heritable phenotype but robust associations of genetic polymorphisms to BMI or other obesity-related phenotypes have been difficult to establish. Recently a large genetic association study showed evidence for association of the single nucleotide polymorphism (SNP) rs7566605, which lies 10 Kb 5' to the first exon of the insulin-induced gene 2 (INSIG-2), with obesity in several cohorts. We tested this polymorphism for association with body mass related phenotypes in a large family study whose mean BMI was consistent with moderate overweight.

Methods

We studied 1428 members of 248 British Caucasian families who had been ascertained through a proband with hypertension. We measured BMI, waist and hip circumference, and plasma levels of leptin. We genotyped the rs7566605 SNP using a restriction fragment length polymorphism assay, and carried out a family-based association test for quantitative traits related to obesity using the statistical programs MERLIN and QTDT.

Results

We observed no significant association between genotype at rs7566605 and covariate-adjusted (for age, sex, alcohol consumption, smoking and exercise habit) log-transformed BMI, waist measurement, hip measurement, waist-to-hip ratio, or plasma levels of leptin.

Conclusion

There was no association between genotype at rs7566605 and obesity-related phenotypes in this British Caucasian population. These families were in general moderately overweight, few members being severely obese. Our result indicates that this polymorphism has little if any effect on BMI within the normal to moderately overweight range. The effects of this polymorphism on body mass may be restricted to those already predisposed to at least moderate obesity as a result of environmental factors and other predisposing genotypes.
Genetic polymorphisms of MMP1, MMP3 and MMP7gene promoter and risk of colorectal adenoma
Authors: Lièvre Astrid , Milet Jacqueline , Carayol Jérôme , Le Corre Delphine , Milan Chantal , Pariente Alexandre , Nalet Bernard , Lafon Jacques , Faivre Jean , Bonithon-Kopp Claire , Olschwang Sylviane , Bonaiti-Pellié Catherine , Laurent-Puig Pierre ,   members of the ANGH group
Published: November 2006

Background

Matrix metalloproteinases (MMP) have been shown to play a role in colorectal cancer (CRC). More recently, MMP1, MMP3 and MMP7 functional gene promoter polymorphisms have been found to be associated with CRC occurrence and prognosis. To document the role of MMP polymorphisms in the early step of colorectal carcinogenesis, we investigated their association with colorectal adenoma risk in a case-control study comprising 295 patients with large adenomas (LA), 302 patients with small adenomas (SA) and 568 polyp-free (PF) controls.

Methods

Patients were genotyped using automated fragment analysis for MMP1 -1607 ins/del G and MMP3 -1612 ins/delA (MMP3.1) polymorphisms and allelic discrimination assay for MMP3 -709 A/G (MMP3.2) and MMP7 -181 A/G polymorphisms. Association between MMP genotypes and colorectal adenomas was first tested for each polymorphism separately and then for combined genotypes using the combination test. Adjustment on relevant variables and estimation of odds ratios were performed using unconditional logistic regression.

Results

No association was observed between the polymorphisms and LA when compared to PF or SA. When comparing SA to PF controls, analysis revealed a significant association between MMP3 -1612 ins/delA polymorphism and SA with an increased risk associated with the 6A/6A genotype (OR = 1.67, 95%CI: 1.20–2.34). Using the combination test, the best association was found for MMP3.1-MMP1 (p = 0.001) with an OR of 1.88 (95%CI: 1.08–3.28) for the combined genotype 2G/2G-6A/6A estimated by logistic regression.

Conclusion

These data show a relation between MMP1 -1607 ins/del G and MMP3 -1612 ins/delA combined polymorphisms and risk of SA, suggesting their potential role in the early steps of colorectal carcinogenesis.
Asthma out of control? A structured review of recent patient surveys
Authors: Holgate Stephen T , Price David , Valovirta Erkka
Published: November 2006

Background

An understanding of the needs and behaviors of asthma patients is important in developing an asthma-related healthcare policy. The primary goal of the present review was to assess patient perspectives on key issues in asthma and its management, as captured in patient surveys.

Methods

Local, national, and multinational asthma surveys were reviewed to assess patient perspectives, and where possible healthcare provider (HCP) perspectives, on key issues, including diagnosis, treatment, control, quality of life, and other patient-centered outcomes. Twenty-four surveys, conducted or published between 1997 and 2003 in Europe and North America, were included in this review. Substantial differences among studies prevented a formal meta-analysis; instead, data were pooled to allow for general comparisons and qualitative analysis.

Results

The results indicate that patients' knowledge of the underlying causes of asthma and treatment options remains inadequate. Moreover, patients often tolerate poor symptom control, possess meager knowledge of correct drug usage, and display insufficient adherence to therapy. Many patients have a low expectation of receiving an appropriate therapy or of having a positive encounter with the HCP. Among HCPs, there is evidence of inadequate understanding of disease etiology and poor or unstructured communication with patients, resulting often in inaccurate assessment of disease severity. Moreover, patients often underreport their symptoms and severity, which in turn could lead to misclassification and undertreatment.

Conclusion

Improving patient education about the importance of achieving optimal asthma control, along with improved communication between patients and HCPs, emphasizing treatment options and optimal treatment of inflammation, may lead to better outcomes and improved asthma management in daily practice.
The pendulum test as a tool to evaluate passive knee stiffness and viscosity of patients with rheumatoid arthritis
Authors: Valle Maria S , Casabona Antonino , Sgarlata Rosaria , Garozzo Rosaria , Vinci Maria , Cioni Matteo
Published: November 2006

Background

The pendulum test of Wartenberg is a technique commonly used to measure passive knee motion with the aim to assess spasticity. We used this test to evaluate changes of the knee angular displacement, passive stiffness and viscosity in rheumatoid arthritis patients. Stiffness and viscosity represent passive resistances to joint motion associated with the structural properties of the joint tissue and of the muscular-tendon complex. Stiffness can be considered an intrinsic property of the tissues to resist deformation, while viscosity is related to cohesive forces between adjacent layers of tissues. Both parameters may influence the joint range of motion affecting angular displacement.

Methods

Nine women with rheumatoid arthritis were compared with a group of healthy women. With the subject half-lying, the relaxed knee was dropped from near-full extension and the characteristics of the ensuring damped unsustained knee oscillation evaluated. The kinematics of leg oscillations was recorded using ultrasonic markers (Zebris CMS HS 10) and the kinetic data were calculated from kinematic and anthropometric measures.

Results

Knee stiffness significantly increased (p < 0.001) in patients with respect to the control group, while differences in viscosity were not significant. Moreover, the amplitudes of first knee flexion (the maximal flexion excursion after knee release) and first knee extension (the maximal extension excursion after the first knee flexion) were significantly decreased (p < 0.001). A regression analysis showed that disease severity correlated moderately with stiffness (R2 = 0.68) and first flexion (R2 = 0.78). Using a multivariate regression, we found that increasing stiffness was the main factor for the reduction of flexion and extension motions.

Conclusion

We showed that the Wartenberg test can be considered a practical tool to measure mechanical changes of knee caused by rheumatoid arthritis. This novel application of Wartenberg test could be useful to follow up the effects of pharmacological and rehabilitative interventions in this disease.
Socioeconomic status and hospital utilization among younger adult pneumonia admissions at a Canadian hospital
Authors: McGregor Margaret J , Reid Robert J , Schulzer Michael , Fitzgerald J Mark , Levy Adrian R , Cox Michelle B
Published: November 2006

Background

Although the general association between socioeconomic status (SES) and hospitalization has been well established, few studies have considered the relationship between SES and hospital length of stay (LOS), and/or hospital re-admission. The primary objective of this study therefore, was to examine the relationship of SES to LOS and early re-admission among adult patients hospitalized with community-acquired pneumonia in a setting with universal health insurance.

Methods

Four hundred and thirty-four (434) individuals were included in this retrospective, longitudinal cohort analysis of adult patients less than 65 years old admitted to a large teaching hospital in Vancouver, British Columbia. Hospital chart review data were linked to population-based health plan administrative data. Chart review was used to gather data on demographics, illness severity, co-morbidity, functional status and other measures of case mix. Two different types of administrative data were used to determine hospital LOS and the occurrence of all-cause re-admission to any hospital within 30 days of discharge. SES was measured by individual-level financial hardship (receipt of income assistance or provincial disability pension) and neighbourhood-level income quintiles.

Results

Those with individual-level financial hardship had an estimated 15% (95% CI -0.4%, +32%, p = 0.057) longer adjusted LOS and greater risk of early re-admission (adjusted OR 2.65, 95% CI 1.38, 5.09). Neighbourhood-level income quintiles, showed no association with LOS or early re-admission.

Conclusion

Among hospitalized pneumonia patients less than 65 years, financial hardship derived from individual-level data, was associated with an over two-fold greater risk of early re-admission and a marginally significant longer hospital LOS. However, the same association was not apparent when an ecological measure of SES derived from neighbourhood income quintiles was examined. The ecological SES variable, while useful in many circumstances, may lack the sensitivity to detect the full range of SES effects in clinical studies.
Impact on and use of health services by international migrants: questionnaire survey of inner city London A&E attenders
Authors: Hargreaves Sally , Friedland Jon S , Gothard Philip , Saxena Sonia , Millington Hugh , Eliahoo Joseph , Le Feuvre Peter , Holmes Alison
Published: November 2006

Background

Changing immigration trends pose new challenges for the UK's open access health service and there is considerable speculation that migrants from resource-poor countries place a disproportionate burden on services. Data are needed to inform provision of services to migrant groups and to ensure their access to appropriate health care. We compared sociodemographic characteristics and impact of migrant groups and UK-born patients presenting to a hospital A&E/Walk-In Centre and prior use of community-based General Practitioner (GP) services.

Methods

We administered an anonymous questionnaire survey of all presenting patients at an A&E/Walk-In Centre at an inner-city London hospital during a 1 month period. Questions related to nationality, immigration status, time in the UK, registration and use of GP services. We compared differences between groups using two-way tables by Chi-Square and Fisher's exact test. We used logistic regression modelling to quantify associations of explanatory variables and outcomes.

Results

1611 of 3262 patients completed the survey (response rate 49.4%). 720 (44.7%) were overseas born, representing 87 nationalities, of whom 532 (73.9%) were new migrants to the UK (≤10 years). Overseas born were over-represented in comparison to local estimates (44.7% vs 33.6%; p < 0.001; proportional difference 0.111 [95% CI 0.087–0.136]). Dominant immigration status' were: work permit (24.4%), EU citizens (21.5%), with only 21 (1.3%) political asylum seekers/refugees. 178 (11%) reported nationalities from refugee-generating countries (RGCs), eg, Somalia, who were less likely to speak English. Compared with RGCs, and after adjusting for age and sex, the Australians, New Zealanders, and South Africans (ANS group; OR 0.28 [95% CI 0.11 to 0.71]; p = 0.008) and the Other Migrant (OM) group comprising mainly Europeans (0.13 [0.06 to 0.30]; p = 0.000) were less likely to have GP registration and to have made prior contact with GPs, yet this did not affect mode of access to hospital services across groups nor delay access to care.

Conclusion

Recently arrived migrants are a diverse and substantial group, of whom migrants from refugee-generating countries and asylum seekers comprise only a minority group. Service reorganisation to ensure improved access to community-based GPs and delivery of more appropriate care may lessen their impact on acute services.
A population-based study examining the emergence of community-associated methicillin-resistant Staphylococcus aureus USA300 in New York City
Authors: Bratu Simona , Landman David , Gupta Jyoti , Trehan Manoj , Panwar Monica , Quale John
Published: November 2006

Background

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a serious pathogen in several regions in the United States. It is unclear which populations are at high risk for the emergence of these strains.

Methods

All unique patient isolates of S. aureus were collected from hospitals in Brooklyn, NY over a three-month period. Isolates of MRSA that were susceptible to clindamycin underwent SCCmec typing. Isolates with the SCCmec type IV (characteristic of CA-MRSA strains) underwent ribotyping. Demographic information involving the neighborhoods of Brooklyn was also gathered and correlated with the prevalence of CA-MRSA strains.

Results

Of 1316 isolates collected during the surveillance, 217 were MRSA susceptible to clindamycin. A total of 125 isolates possessed SCCmec type IV; 72 belonged to the USA300 strain and five belonged to the USA400 strain. Hospitals in the eastern part of the city had the highest prevalence of USA300 strain. Individuals in the eastern region, when compared to the western region, were more likely to be Black, Hispanic, female, and < 18 years of age, and to have households of ≥ 3 persons. In addition, the median household income was lower, and the proportion of individuals on public assistance was higher, for the population in the eastern region.

Conclusion

The USA300 strain of CA-MRSA is emerging in New York City. In this population-based study, urban regions of lower socioeconomic status and with evidence of overcrowding appear to be at higher risk for the emergence of this pathogen.
Cerebral edema in a patient following cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemoperfusion
Authors: Nair Rajalakshmi L , Tobias Jonathan , Stemmerman Grant , Lowy Andrew M
Published: November 2006

Background

Cytoreductive surgery and intraoperative, intraperitoneal hyperthermic chemoperfusion (HIPEC) is increasingly used to treat peritoneal surface metastases. We describe a fatal case of cerebral edema in a patient with appendiceal carcinoma and an underlying seizure disorder who underwent cytoreductive surgery and HIPEC.

Case presentation

A case of fatal postoperative cerebral edema is presented in a patient with an underlying seizure disorder and recurrent mucinous adenocarcinoma of the appendix. The patient was treated with cytoreductive surgery and intraoperative intraperitoneal hyperthermic chemoperfusion. The details and implications of this complication are discussed.

Conclusion

The recognition of this potential complication is important for physicians performing cytoreductive surgery and HIPEC. Special caution should be taken when patients with seizure disorders are being considered for this treatment.