bluuebunny/crossref_metadata_2025 huggingface dataset:
Constructing Masculinities and Experiencing Loss
Authors: Truong Nhan
Published: November 2005

Chinese American men live in partially hostile environments where they confront discrimination and stereotypes that can undermine their sense of manhood. Through a critical analysis of autobiographies, this study explores how two Chinese American men, Yi-Fu Tuan and Ben Fong-Torres, poignantly construct viable masculinities. In the face of discrimination, they experience conflicting selves as they negotiate between their gender, race, class, and cultural and sexual identities: a process that involved search for empowerment, splitting of selves, and painful loss. Life studies as a method of doing masculinity research reveals the complexities of men's experiences and the need to examine how gender, race, class, culture, and sexuality together both limit and allow possibilities for being men.
Convergence Towards a European Strategic Culture? A Constructivist Framework for Explaining Changing Norms
Authors: Meyer Christoph O.
Published: November 2005

The article contributes to the debate about the emergence of a European strategic culture to underpin a European Security and Defence Policy. Noting both conceptual and empirical weaknesses in the literature, the article disaggregates the concept of strategic culture and focuses on four types of norms concerning the means and ends for the use of force. The study argues that national strategic cultures are less resistant to change than commonly thought and that they have been subject to three types of learning pressures since 1989: changing threat perceptions, institutional socialization, and mediatized crisis learning. The combined effect of these mechanisms would be a process of convergence with regard to strategic norms prevalent in current EU countries. If the outlined hypotheses can be substantiated by further research the implications for ESDP are positive, especially if the EU acts cautiously in those cases which involve norms that are not yet sufficiently shared across countries.
Behaviour of Stock Markets in South Asia
Authors: Gunasinghe W.I.C.S.
Published: November 2005

This paper examines the integration behaviour and volatility spillover transmissions across the stock markets of Sri Lanka, India and Pakistan, after liberalization policies initiated in the early 1990s. The paper examines ways in which these two issues could relate to movements of stock prices and then investigates the impact of this on the corresponding stock markets using correlation analysis, a multivariate co-integration test and generalized impulse response (GIR) functions based on a one factor model. The estimated correlation results show a marginal growth of integration for India-Sri Lanka and India-Pakistan combinations for the period 1997–2002 compared to 1992–96. The multivariate co-integration test does not provide evidence on any long-run relation across these markets. However, as co-integration test does not consider a gradual integration process among these markets, the rejection of the presence of a long-run relationship does not imply that these markets are totally independent of one another. Results of the GIRs test used to answer the second issue raised in the paper confirm that a sudden change of the Indian stock market may have some marginal spillover effects on Sri Lanka and Pakistan stock price movements.
Is the Indian Stock Market Integrated with the US and Japanese Markets?
Authors: Ahmad Khan Masood , Ashraf Shahid , Ahmed Shahid
Published: November 2005

The paper attempts to understand the interlinkages and causal relationship between the Nasdaq composite index in the US, the Nikkei in Japan with that of NSE Nifty and BSE Sensex in India during the period January 1999 to August 2004, using daily closing data. The Johansen co-integration test is applied to measure the long-term relationship between the two indices and the Granger-causality test is used to check the short-term causal relationship.

The analysis reveals that there is no long-term relationship of the Indian equity market with that of the US and Japanese equity markets. Further, Nasdaq and Nikkei have stronger causal relationship in 1999–2001 which becomes either very weak or disappears in 2002–2004. There seems to be a disassociation in the movements of the Nasdaq and Nikkei with that of the Sensex and Nifty. When the stock markets have no tendency to move together in the long-term and causal effects become weak in the short-term then the markets are segmented and provide ample room for diversification of investments. The recent surge of FII investments to the Indian equity market is primarily a reflection of this trend.
The Twin Deficits Problem in Sri Lanka
Authors: Saleh Ali Salman , Nair Mahendhiran , Agalewatte Tikiri
Published: November 2005

Many economists have argued that prolonged fiscal expansions contribute to current account imbalances. The purpose of this paper is to explore this phenomenon in the case of Sri Lanka during the period 1970 to 2003. In this study, the autoregressive distributed lag (ARDL) model and the bounds test for cointegration (Pesaran et al. 2001) were used to assess the long-run dynamics between the twin deficits in Sri Lanka. The empirical analysis in this paper supports the Keynesian view that there is a long-run relationship between current account imbalances and budget deficit. The empirical results also show that the direction of causality runs from the budget deficit to the current account deficit. Thus, any policy measures to reduce the budget deficit in Sri Lanka could well assist in reducing the current account imbalances. Strategies and policies to manage the twin-deficits are discussed in this paper.
Shifting in the Ruins
Authors: Melville Stephen
Published: November 2005

This article attempts to set current discussions of art history and visual culture in the context of what Bill Readings has described as ‘the university of excellence’. It then interprets the relation between these two fields in terms of both a certain temporal displacement (here following leads offered by Marshall Brown, Georges Didi-Huberman and Heinrich Wölfflin) and a contrast between ‘scientific’ and disciplinary models of knowledge or objectivity.
Dreaming the Face, Screening the Death: Reflections for Jean-Louis Schefer on La Jetée
Authors: Pollock Griselda
Published: November 2005

Drawing on Cathy Caruth’s reading of trauma in Lacan’s interpretation of the burning child dream in Freud’s Interpretation of Dreams, this article offers a feminist response to Jean-Louis Schefer’s study of Chris Marker’s canonical film on time and memory: La Jetée. The question of the trauma of life and awakening is shifted by a non-phallic, matrixial reading that attends to a haunting sense of presence. One vision sees the subject as traumatically quickened to a living that is forever haunted by what it cannot remember, trapped into a return that will take it forward to its death. A different vision senses some supplementary dimensions of the subject that is never a purely solitary One, outcast from an originary unity, but is co-emergent, traumatically (as any encounter with the real must be) in tune with, and witness to, all the burdens and hurts of the Other that must be shared. The article suggests, therefore, that the grace of this deeply fetishistic, psychically masculine film, nonetheless, lies at a psychic level only just emerging into theorization on the far border of Lacan’s poetic revision of psychoanalysis through the feminist attentiveness to, and desire to know of, a sexual difference in, of and from the feminine.
Spooks/Postmortem TV
Authors: Marriott David
Published: November 2005

This article explores John Edgar Wideman’s reflections on the ways in which US television and news media reflect the political paranoias and traumatic histories of race in America - reflections that emphasize the spectral and symbolic life of race in public and private monitorings of selfhood and difference. Read in the context of contemporary and retrospective responses to 9/11, Wideman’s discussion is used to examine the place of racial profiling in the television genre of ‘infotainment’, with its heavy reliance on data taken from closed circuit public television systems (CCTV). Looking at the monitoring gaze of CCTV images, the article concludes with a discussion of its mediating role in UK public responses to the murders of two Nigerian boys in London, Damilola Taylor and ‘Adam’.
Is Law a Humanity
Authors: Howarth David
Published: November 2005

Law often appears to be in a limbo between the Social Sciences and the Humanities. Movements within legal scholarship itself, the law and economics movement and the law and literature movement, represent efforts to portray law as a social science or as a humanity. But if one looks at what lawyers do, one finds that law is more like engineering–lawyers make social devices and structures for their clients just as engineers make physical devices and structures. Just as engineers can usefully draw on scientific knowledge, lawyers can usefully draw on the Social Sciences and the Humanities in making their devices, but lawyers, like engineers, also have their own autonomous concerns about design and effectiveness. Legal education, however, tends to stress only one element in legal design, the validity of legal rules. The position of judges and academic lawyers has a special feature that, unlike practising lawyers, their client is the whole of society or the whole of humanity. This presents academic lawyers and judges with special ethical problems beyond those faced by ordinary professionals. It also brings them close to the practical and normative humanities, such as ethics and political philosophy.
Balancing Institutional, Disciplinary and Faculty Priorities with Public and Social Needs
Authors: Diamond Robert M. , Adam Bronwyn E.
Published: November 2005

By virtue of their education, training, and experience, college and university faculty are a rich national resource. Opportunities abound for faculty scholars to apply their knowledge and expertise to pressing community and public issues and problems. Yet, narrow definitions of scholarship embedded in higher education practice act as disincentives to such faculty work. After a brief discussion of the problem, this article reviews efforts made in the US to expand the definition of scholarship and proposes a conception of scholarship that works across disciplinary contexts and addresses 21st-century challenges.
Writing and Teaching the Disciplines in France
Authors: Donahue Christiane
Published: November 2005

Writing in the disciplines (WiD) and writing across the curriculum (WAC) are important university-wide intellectual projects often grounded in liberal arts and general education philosophies. In France, WiD/WAC discussions are growing out of the curricular realities of writing as central to success in all disciplines and of a new student population obtaining access to higher education. These curricular issues are framed by a complex history of who takes responsibility for teaching writing and for researching the teaching of writing.This article presents the threads of these discussions at two recent French conferences, where debate about writing to learn, writing as meaning-making, writing in the disciplines, argument strategies across disciplines, forms of voice, intertextuality, and writing as membership in a domain were central. WiD programs of the kind supported by Cornell’s Knight Institute for Writing in the Disciplines might be quite effective in this very different cultural setting.
School to University
Authors: Smith Keverne
Published: November 2005

This article continues the debate about the transition from school to university begun in the international forum in volume 2(1) of this journal and developed in the thoughtful response from Michael Marland in volume 2(2). It examines some of the many points made there in relation to students’ own views. Interested colleagues at different institutions were invited to issue a short questionnaire to first-year undergraduates studying English, to discover how well prepared they felt for specified aspects of this transition. Some of the outcomes have discipline-specific implications, but others may be applied more widely. The article focuses on students’ responses to the different teaching methods used, the amount of reading required of them, and essay writing. It identifies areas where the transition is fairly smooth, but highlights others where student responses suggest that all those involved, including policy makers and politicians, need to rethink.
Circulating thrombopoietin as an in vivo growth factor for blast cells in acute myeloid leukemia
Authors: Corazza Francis , Hermans Christophe , D'Hondt Stéphanie , Ferster Alina , Kentos Alain , Benoît Yves , Sariban Eric
Published: November 2005

Thrombopoietin (TPO), the major growth factor for cells of the megakaryocytic lineage, is removed from circulation by binding to c-mpl receptors present on platelets and megakaryocytes. We studied patients with acute lymphoblastic leukemia (ALL) or acute myeloblastic leukemia (AML) and used TPO-induced c-fos protein up-regulation as a marker of c-mpl functionality and observed that c-mpl-presenting blast cells were present in 62% (37 of 60) of patients with ALL but that c-mpl was nonfunctional in 0 of 28 patients and that they were present in 56% (22 of 39) of patients with AML and were functional in 43% (12 of 28). Adequate increases in serum TPO level in response to thrombocytopenia were seen in patients with ALL and with c-mpl-deficient (c-mpl-) AML. In contrast, in patients with c-mpl-proficient (c-mpl+) AML, TPO levels were found to be inappropriately low but increased to expected values during induction chemotherapy as blasts disappeared. In vitro significant TPO-associated blast cell proliferation or decreased apoptosis was observed only in patients with c-mpl+ AML compared with ALL or c-mpl- AML and was highly correlated with low in vivo TPO levels (P < .001). These data suggest that, in patients with AML, inadequate TPO levels are secondary to TPO clearing by functional c-mpl receptor myeloid blast cells and that TPO may serve as an in vivo myeloid leukemic growth factor in a significant number of patients. (Blood. 2006; 107:2525-2530)
A novel murine model of fetal and neonatal alloimmune thrombocytopenia: response to intravenous IgG therapy
Authors: Ni Heyu , Chen Pingguo , Spring Christopher M. , Sayeh Ebrahim , Semple John W. , Lazarus Alan H. , Hynes Richard O. , Freedman John
Published: November 2005

Fetal and neonatal alloimmune thrombo cytopenia (FNAITP) is a life-threatening bleeding disorder caused by maternal antibodies directed against fetal platelet antigens. The immunoreactive epitopes in FNAITP are primarily located in the extracellular regions of the platelet glycoprotein IIIa (β3 integrin). Here we have established a novel animal model of FNAITP using β3 integrin–deficient (β3-/-) mice. We demonstrated first that these mice are immunoresponsive to β3 integrin; β3-/- mice transfused with wild-type platelets generated specific anti–β3 antibodies which were able to induce thrombocytopenia in wild-type mice. Subsequently, β3-/- female mice (both naive and immunized) were bred with wild-type male mice to recapitulate the features of FNAITP. The titer of generated maternal antibodies correlated with the severity of FNAITP. High titer maternal anti–β3 anti-bodies caused severe fetal thrombocytopenia, intracranial hemorrhage, and even miscarriage. Furthermore, maternal administration of intravenous immunoglobulin G (IgG) ameliorated FNAITP and down-regulated pathogenic antibodies in both the maternal and fetal circulations.
Array comparative genomic hybridization reveals genomic copy number changes associated with outcome in diffuse large B-cell lymphomas
Authors: Chen Weiyi , Houldsworth Jane , Olshen Adam B. , Nanjangud Gouri , Chaganti Seeta , Venkatraman Ennapadem S. , Halaas Jeffrey , Teruya-Feldstein Julie , Zelenetz Andrew D. , Chaganti R. S. K.
Published: November 2005

To identify, in high-resolution regions of DNA, the copy number changes associated with outcome in patients with diffuse large B-cell lymphoma (DLBCL), a disease with an approximately 50% mortality rate, we performed array comparative genomic hybridization (array-CGH) on specimens from 64 patients with newly diagnosed DLBCL treated with anthracycline-based chemotherapy. For the entire cohort, 55 commonly gained/lost regions, ranging in size from less than 1 Mbp to entire chromosomes, were identified using 1- to 2-Mbp and 2- to 4-Mbp resolution BAC arrays. Copy number changes of 9 minimal regions significantly correlated with overall survival, of which 6 were 10 Mbp or smaller. On multivariate analysis, loss of chromosomes 2 (2.4-4.1 Mbp) and 16 (33.8-35.6 Mbp) were found to be prognostic indicators of poor survival, independent of clinical features routinely used to predict outcome. Loss of chromosome 1 (78.2-79.1 Mbp) was predictive of good outcome. For a subset of 55 specimens classified according to cell-of-origin expression signature subtype, gain of chromosome 12 (45.4-53.8 Mbp) was found to be significantly associated with the germinal center B-cell-like DLBCL subtype. Overall, array-CGH identified relatively small genomic regions associated with outcome, which, along with follow-up expression studies, may reveal target genes important in DLBCL clinical behavior. (Blood. 2006;107:2477-2485)
T-helper cell type-2 regulation in allergic disease
Authors: Georas S. N. , Guo J. , De Fanis U. , Casolaro V.
Published: November 2005

Substantial experimental evidence now supports the notion that allergic diseases are characterised by a skewing of the immune system towards a T-helper cell type-2 (Th2) phenotype.

Studies using both human and mouse model systems have provided key evidence for the role that Th2 cytokines play in driving many of the hallmarks of allergic inflammation. Furthermore, the signalling pathways by which Th2 cytokines exert their effects on airway target cells are rapidly being elucidated, and antagonists of the Th2 pathway are under active development.

In this review, the current knowledge of the role of T-helper cell type-2 cells in asthma is summarised, focusing on how and where T-helper cell type-2 cells differentiate from naïve precursors. The signalling molecules and transcription factors involved in T-helper cell type-2 differentiation will be reviewed in detail, in an attempt to translate studies using genetically modified mice into meaningful insights about asthma and other allergic diseases.
From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung
Authors: Ioachimescu O. C. , Mehta A. C.
Published: November 2005

Bronchioloalveolar carcinoma (BAC) of the lungs is a known morphological subtype of nonsmall cell cancer. The current study presents several carcinogenetic theories of BAC and the possible relationship with atypical adenomatous hyperplasia and congenital pulmonary airway malformation (CPAM).

The authors present an unusual case of BAC developed in an area of CPAM, with subsequent progression to metastatic adenocarcinoma (AC). The case is unique due to the combination of: early age of presentation; neoplastic transformation of a CPAM; unaltered course over 15 yrs; and its particular pattern of slow morphogenesis and degeneration into an invasive AC of the lung.

The case also presents the unique features of a long-standing, unaltered natural course of paediatric BAC towards invasive and metastatic AC, illustrating that lack of growth over many years cannot be entirely trusted as a criterion of benignity.

In conclusion, clinicians and pathologists need to be aware of the fact that congenital pulmonary airway malformation so far represents the only known pre-invasive lesion for mucinous bronchioloalveolar carcinoma.
What are the questionnaire items most useful in identifying subjects with occupational asthma?
Authors: Vandenplas O. , Ghezzo H. , Munoz X. , Moscato G. , Perfetti L. , Lemière C. , Labrecque M. , L'Archevêque J. , Malo J-L.
Published: November 2005

The present study assessed the usefulness of key items obtained from a clinical “open” questionnaire prospectively administered to 212 subjects, referred to four tertiary-care hospitals for predicting the diagnosis of occupational asthma (OA). Of these subjects, 72 (34%) were diagnosed as OA (53% with OA due to high-molecular-weight agents) according to results of specific inhalation challenges, and 90 (42%) as non-OA.

Wheezing at work occurred in 88% of subjects with OA and was the most specific symptom (85%). Nasal and eye symptoms were commonly associated symptoms. Wheezing, nasal and ocular itching at work were positively, and loss of voice negatively associated with the presence of OA in the case of high-, but not low molecular-weight agents.

A prediction model based on responses to nasal itching, daily symptoms over the week at work, nasal secretions, absence of loss of voice, wheezing, and sputum, correctly predicted 156 out of 212 (74%) subjects according to the presence or absence of OA by final diagnosis.

In conclusion, key items,i.e.wheezing, nasal and ocular itching and loss of voice, are satisfactorily associated with the presence of occupational asthma in subjects exposed to high-molecular-weight agents. Therefore, these should be addressed with high priority by physicians. However, no questionnaire-derived item is helpful in subjects exposed to low-molecular-weight agents.
Quality control of spirometry: a lesson from the BRONCUS trial
Authors: Pellegrino R. , Decramer M. , van Schayck C. P. O. , Dekhuijzen P. N. R. , Troosters T. , van Herwaarden C. , Olivieri D. , Del Donno M. , De Backer W. , Lankhorst I. , Ardia A.
Published: November 2005

This report describes the quality control programme used within the Bronchitis Randomized on N-acetylcysteine (NAC) Cost-Utility Study, a trial designed to assess the decline in lung function, exacerbation rate, health status, and cost-effectiveness with NAC or a placebo in 523 patients with chronic obstructive pulmonary disease over a 3-yr period.

Spirometry was scored from 0 (worst quality) to 6 (best quality). The mean score of 314 spirometries from 243 patients evaluated during the trial was 5.63±0.83. Linear regression analysis of the scores of 47 participating centres plotted against the time at which spirometries were performed yielded an intercept of 5.7±0.5 and a slope of -0.0001±0.001, which suggests that the initial high quality was maintained over time.

Retrospective examination of a further 345 postbronchodilator spirometries from 208 patients with a forced expiratory volume at one second exceeding the mean individual value recorded over the study in excess of 20% revealed a slightly lower quality of the start-of-test manoeuvre compared with the 314 spirometries.

In conclusion, these findings would suggest that the quality control programme is likely to have helped achieve and maintain long-term spirometry performance in the Bronchitis Randomized on N-acetylcysteine (NAC) Cost-Utility Study trial. Special care should be paid to the spirometries whose forced expiratory volume in one second values exceed the mean value.
Autofluorescence videothoracoscopy in exudative pleural effusions: preliminary results
Authors: Chrysanthidis M. G. , Janssen J. P.
Published: November 2005

Videothoracoscopy has been proven to be a safe tool to establish the diagnosis in >90% of patients with exudative pleural effusions of unknown origin. In the majority of patients with malignant pleural diseases, the endoscopic appearance of pleural lesions during white light thoracoscopy is suggestive of malignancy, but could be misleading in some cases. The aim of the present study was to estimate whether the combination of thoracoscopy with autofluorescence modalities would be useful to further improve the diagnostic accuracy of the conventional method.

The present study displays early results of thoracoscopy performed consecutively with a normal light source and with autofluorescence light in 24 patients with exudative pleural effusion during 2003–2004.

In all cases of malignant pleuritis (carcinoma or mesothelioma), the colour of the affected area of the pleura changed from white/pink to red (sensitivity 100%). However, in two cases of chronic pleuritis, a colour change from white/pink to orange/red was recorded (specificity 75%).

In conclusion, the calculated positive predictive value of colour change for malignant pleuritis during autofluorescence thoracoscopy in this study was 92%. However, the clinical value of autofluorescence thoracoscopy in daily practice remains to be proven.
Cytokine and chemokine expression in cigarette smoke-induced lung injury in guinea pigs
Authors: Kubo S. , Kobayashi M. , Masunaga Y. , Ishii H. , Hirano Y. , Takahashi K. , Shimizu Y.
Published: November 2005

The guinea pig model of cigarette smoke (CS)-induced lung injury is known to exhibit many pathophysiological similarities to chronic obstructive pulmonary disease (COPD), but the expression profiles of inflammatory mediators in the lung are poorly understood.

Quantitative real-time RT-PCR was used in this study to investigate the pulmonary expression profiles of cytokine and chemokine mRNA in response to single or repeated CS exposure in guinea pigs.

A single CS exposure did not induce obvious inflammatory cell infiltration into the lungs, but it led to significant increases in the mRNA expression of tumour necrosis factor-α, interleukin (IL)-1β, IL-8, and monocyte chemoattractant protein (MCP)-1, and decreases in IL-5 and granulocyte-macrophage colony-stimulating factor. Repeated CS exposure induced many features of COPD, such as marked accumulation of macrophages and neutrophils, augmented protease activities, lung structural alterations and increased airway resistance, accompanied by significant increases in the mRNA expression of IL-1β and MCP-1 and decreases in IL-2, IL-5, transforming growth factor-β, and eotaxin.

In conclusion, in guinea pigs, inflammatory mediator changes in the lungs following cigarette smoke exposure are largely similar to those reported for smokers and/or chronic obstructive pulmonary disease patients. This model will therefore be useful to further understand the pathogenesis of chronic obstructive pulmonary disease.
Mechanisms responsible for surfactant changes in sepsis-induced lung injury
Authors: Huang W. , McCaig L. A. , Veldhuizen R. A. W. , Yao L-J. , Lewis J. F.
Published: November 2005

Pulmonary surfactant is altered in sepsis, and these changes contribute to the predisposition of septic lungs to subsequent insults, ultimately leading to acute lung injury. Specifically, the total amount of surfactant is lower in sepsis, mainly due to decreased small aggregate (SA) surfactant pools. The amount of large aggregate (LA) surfactant is not altered.

To evaluate the mechanisms responsible for these alterations, trace doses of tritium-labelled dipalmitoylphosphatidylcholine (3H-DPPC)-labelled LA were instilled intratracheally into adult rats 20 hrs after caecal ligation and perforation (CLP) or sham surgery. Animals were sacrificed at 0, 1 and 4 h after instillation and recovery of3H-DPPC in alveolar macrophages (AM), LA and SA was measured. In separatein vitroexperiments, AM isolated from CLP/sham rats were incubated with LA or SA isolated from normal animals to evaluate the uptake of these aggregates into the AM.

Results showed increased surfactant radioactivity associated with AM of CLP animals compared with sham animals bothin vivoandin vitro. In addition, more3H-DPPC label remained in LA forms in the CLP animalsin vivocompared with sham.

These findings indicate that differences in surfactant aggregate uptake and large aggregate conversion occur in septic lungs, resulting in changes in surfactant pools.
Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis
Authors: Higashi A. , Higashi N. , Tsuburai T. , Takeuchi Y. , Taniguchi M. , Mita H. , Saito A. , Takatori K. , Arimura K. , Akiyama K.
Published: November 2005

The pathophysiology of extrinsic allergic alveolitis (EAA) involves oxidative lung damage as well as interstitial and alveolar inflammation. Macrophages and mast cells are inflammatory components of EAA that produce both leukotrienes (LTs) and prostaglandin D2(PGD2). In addition, PGD2is also produced by the free-radical-catalysed peroxidation of arachidonic acid during oxidative stress. Urinary 8-iso prostaglandin F2α (8-isoPGF2α) and serum surfactant protein D (SP-D) are considered appropriate biomarkers of oxidative stress and interstitial lung disease activity, respectively. The present study aimed to assess the association of these biomarkers with the pathophysiology of EAA.

Two cases of acute EAA caused by the inhalation of fungi spores were reported. Eight asthmatic patients and six healthy control subjects were also enrolled in the current study.

The serum SP-D and urinary eicosanoid (LTE4, PGD2metabolite (9α,11βPGF2), 8-isoPGF2α) concentrations markedly increased during the acute exacerbation phase. These concentrations decreased following corticosteroid therapy in the EAA patients. There was a significant correlation between serum SP-D and urinary 9α,11βPGF2concentrations in the EAA patients.

In conclusion, although the present study proposes that serum surfactant protein-D and urinary eicosanoids are new biomarkers involved in the various immunological responses in extrinsic allergic alveolitis, further large-scale studies are needed to investigate the role of these compounds, not just as biomarkers, but also as biological potentiators of extrinsic allergic alveolitis.
Effects of upper airway anaesthesia on respiratory-related evoked potentials in humans
Authors: Redolfi S. , Raux M. , Donzel-Raynaud C. , Morelot-Panzini C. , Zelter M. , Derenne J-P. , Similowski T. , Straus C.
Published: November 2005

Cortical potentials evoked by mid-inspiratory occlusion arise from numerous receptors, many of which are probably within the upper airway. Their precise nature is not known. The aim of the current study was to improve knowledge of this by studying the effects of topical upper airway anaesthesia on respiratory-related evoked potentials.

Respiratory-related evoked potentials were described through the averaging of electroencephalogram (EEG) epochs following mid-inspiratory occlusions (C3–CZ; C4–CZ). A total of 21 healthy volunteers (13 male, aged 22–52 yrs) were studied during mouth breathing, before and after topical upper airway anaesthesia (lidocaine). Moreover, 15 subjects were studied during nose breathing with and without anaesthesia. Six subjects were studied whilst inhaling L-menthol.

Typical potentials were present in all the subjects, their components featuring normal amplitudes and latencies. The route of breathing and upper airway anaesthesia did not modify the EEG responses to inspiratory occlusions, qualitatively or quantitatively, during mouth or nose breathing. L-menthol had no effect.

Upper airway receptors sensitive to topical anaesthesia are unlikely to contribute significantly to mid-inspiratory occlusion-evoked potentials. On the contrary, deeper receptors, such as joint and muscle receptors, could contribute dominantly to these potentials.
Sentinel-site surveillance ofMycobacterium aviumcomplex pulmonary disease
Authors: Maugein J. , Dailloux M. , Carbonnelle B. , Vincent V. , Grosset J. ,   the French Mycobacteria Study Group
Published: November 2005

The incidence ofMycobacterium aviumcomplex (MAC) pulmonary disease in HIV-negative patients was studied prospectively from January 1, 2000 to December 31, 2002 through 32 sentinel sites distributed all over France.

Among the 275 patients who yielded MAC isolates from respiratory clinical specimens, 101 (36.7%) met the bacteriological, radiographical and clinical criteria established by the American Thoracic Society for nontuberculous mycobacterial respiratory disease. Of these 101 patients, 81 had underlying lung disease, mainly previous tuberculosis, bronchectasis or chronic obstructive pulmonary disease.

Among the 20 patients with no underlying lung disease, 12 had a predisposing factor such as leukaemia or immunosuppressive treatment and eight had no predisposing factor. All patients with MAC respiratory disease had clinical symptoms, commonly cough and fatigue, and 52 (51.5%) were sputum smear positive for acid-fast bacillus.

The ratio of patients withMycobacterium aviumcomplex pulmonary disease to patients with pulmonary tuberculosis in France was estimated to be 3% and the incidence ofMycobacterium aviumcomplex pulmonary disease in France was 0.2 per 100,000 inhabitants.
An algorithm for the determination and quantification of components of nucleic acid mixtures based on single sequencing reactions
Authors: Pozhitkov Alexander , Stemshorn Kathryn , Tautz Diethard
Published: November 2005

Background

Determination and quantification of nucleic acid components in a mixture is usually accomplished by microarray approaches, where the mixtures are hybridized against specific probes. As an alternative, we propose here that a single sequencing reaction from a mixture of nucleic acids holds enough information to potentially distinguish the different components, provided it is known which components can occur in the mixture.

Results

We describe an algorithm that is based on a set of linear equations which can be solved when the sequencing profiles of the individual components are known and when the number of sequenced nucleotides is larger than the number of components in the mixture. We have implemented the procedure for one type of sequencing approach, pyrosequencing, which produces a stepwise output of peaks that is particularly suitable for the procedure. As an example we use signature sequences from ribosomal RNA to distinguish and quantify several different species in a mixture. Using simulations, we show that the procedure may also be applicable for dideoxy sequencing on capillary sequencers, requiring only some instrument specific adaptations of protocols and software.

Conclusion

The parallel sequencing approach described here may become a simple and cheap alternative to microarray experiments which aim at routine re-determination and quantification of known nucleic acid components from environmental samples or tissue samples.
Development of antibodies to human embryonic stem cell antigens
Authors: Cai Jingli , Olson Judith M , Rao Mahendra S , Stanley Marisa , Taylor Eva , Ni Hsiao-Tzu
Published: November 2005

Background

Using antibodies to specific protein antigens is the method of choice to assign and identify cell lineage through simultaneous analysis of surface molecules and intracellular markers. Embryonic stem cell research can be benefited from using antibodies specific to transcriptional factors/markers that contribute to the "stemness" phenotype or critical for cell lineage.

Results

In this report, we have developed and validated antibodies (either monoclonal or polyclonal) specific to human embryonic stem cell antigens and early differentiation transcriptional factors/markers that are critical for cell differentiation into definite lineage.

Conclusion

These antibodies enable stem cell biologists to conveniently identify stem cell characteristics and to quantitatively assess differentiation.
Astrocyte reactivity to Fas activation is attenuated in TIMP-1 deficient mice, an in vitrostudy
Authors: Ogier Crystel , Creidy Rita , Boucraut José , Soloway Paul D , Khrestchatisky Michel , Rivera Santiago
Published: November 2005

Background

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a multifunctional secreted protein with pleiotropic actions, including the inhibition of matrix metalloproteinases (MMPs), cell death/survival and growth promoting activities. After inflammatory challenge, the levels of TIMP-1 are highly and selectively upregulated in astrocytes among glial cells, but little is know about its role in these neural cells. We investigated the influence of TIMP-1 null mutation in the reactivity of cultured astrocytes to pro-inflammatory stimuli with TNF-α and anti-Fas antibody.

Results

When compared to WT, mutant astrocytes displayed an overall increased constitutive gelatinase expression and were less responsive to Fas-mediated upregulation of MMP-9, of monocyte chemoattractant protein-1 (MCP-1) and of intercellular cell adhesion molecule-1 (ICAM-1), all markers of astrocyte inflammatory response. In contrast, TNF-α treatment induced all these factors similarly regardless of the astrocyte genotype. The incorporation of3H-thymidin, a marker of cell proliferation, increased in wild-type (WT) astrocytes after treatment with anti-Fas antibody or recombinant TIMP-1 but not in mutant astrocytes. Finally, lymphocyte chemotaxis was differentially regulated by TNF-α in WT and TIMP-1 deficient astrocytes.

Conclusion

We provide evidence that the alteration of the MMP/TIMP balance in astrocytes influences their reactivity to pro-inflammatory stimuli and that Fas activation modulates the expression of members of the MMP/TIMP axis. We hypothesise that the Fas/FasL transduction pathway and the MMP/TIMP system interact in astrocytes to modulate their inflammatory response to environmental stimuli.
First-line therapy with gemcitabine and paclitaxel in locally, recurrent or metastatic breast cancer: A phase II study
Authors: Allouache Djelila , Gawande Sulochana R , Tubiana-Hulin Michele , Tubiana-Mathieu Nicole , Piperno-Neumann Sophie , Mefti Fawzia , Bozec Laurence , Genot Jean-Yves
Published: November 2005

Background

This phase II study evaluated the efficacy and safety of gemcitabine (G) plus paclitaxel (T) as first-line therapy in recurrent or metastatic breast cancer.

Methods

Patients with locally, recurrent or metastatic breast cancer and no prior chemotherapy for metastatic disease received G 1200 mg/m2 on days 1 and 8, and T 175 mg/m2 on day 1 (before G) every 21 days for a maximum of 10 cycles.

Results

Forty patients, 39 metastatic breast cancer and 1 locally-advanced disease, were enrolled. Their median age was 61.5 years, and 85% had a World Health Organization performance status (PS) of 0 or 1. Poor prognostic factors at baseline included visceral involvement (87.5%) and ≥2 metastatic sites (70%). Also, 27 (67.5%) patients had prior adjuvant chemotherapy, 25 of which had prior anthracyclines. A total of 220 cycles (median 6; range, 1–10) were administered. Of the 40 enrolled patients, 2 had complete response and 12 partial response, for an overall response rate of 35.0% for intent-to-treat population. Among 35 patients evaluable for efficacy the response rate was 40%. Additional 14 patients had stable disease, and 7 had progressive disease. The median duration of response was 12 months; median time to progression, 7.2 months; median survival, 25.7 months. Common grade 3/4 toxicities were neutropenia in 17 (42.5%) patients each, grade 3 leukopenia in 19 (47.5%), and grade 3 alopecia in 30 (75.0%) patients; 1 (2.5%) patient had grade 4 thrombocytopenia.

Conclusion

GT exhibited encouraging activity and tolerable toxicity as first-line therapy in metastatic breast cancer. Phase III trials for further evaluation are ongoing.
A liver fibrosis cocktail? Psoriasis, methotrexate and genetic hemochromatosis
Authors: Mathew Joseph , Leong May Y , Morley Nick , Burt Alastair D
Published: November 2005

Background

Pathologists are often faced with the dilemma of whether to recommend continuation of methotrexate therapy for psoriasis within the context of an existing pro-fibrogenic risk factor, in this instance, patients with genetic hemochromatosis.

Case presentations

We describe our experience with two male psoriatic patients (A and B) on long term methotrexate therapy (cumulative dose A = 1.56 gms and B = 7.88 gms) with hetero- (A) and homozygous (B) genetic hemochromatosis. These patients liver function were monitored with routine biochemical profiling; apart from mild perivenular fibrosis in one patient (B), significant liver fibrosis was not identified in either patient with multiple interval percutaneous liver biopsies; in the latter instance this patient (B) had an additional risk factor of partiality to alcohol.

Conclusion

We conclude that methotrexate therapy is relatively safe in patients with genetic hemochromatosis, with no other risk factor, but caution that the risk of fibrosis be monitored, preferably by non-invasive techniques, or by liver biopsy.
A cross-sectional study of the association between persistent organochlorine pollutants and diabetes
Authors: Rylander Lars , Rignell-Hydbom Anna , Hagmar Lars
Published: November 2005

Background

Experimental evidence supports the hypothesis that persistent organochlorine pollutants (POPs) may cause type 2 diabetes mellitus, whereas there is no fully convincing epidemiological evidence for such an association. In Sweden the most important source of POP exposure is fatty fish. We have assessed the association between serum levels of POPs and prevalence of diabetes in Swedish fishermen and their wives, with high consumption of fatty fish from the Baltic Sea.

Methods

In 196 men (median age 60 years) and 184 women (median age 64 years), we analyzed 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE) in serum using gas chromatography-mass spectrometry. The participants were asked if they had diabetes and, if so, since which year and about medication and diet. The Odds Ratios (OR) for diabetes with respect to continuous exposure variables were analyzed with logistic regression, adjusting for potential confounders. Moreover trends of diabetes prevalence with respect to trichotomized exposure variables were tested with Jonckheere-Terpstra's test.

Results

Six percent of the men and 5% of the women had diabetes. After confounder adjustment CB-153 was significantly associated with diabetes prevalence using both categorized and continuous exposure data (an increase of 100 ng/g lipid corresponded to an OR of 1.16, 95% confidence interval [CI] 1.03, 1.32, p = 0.03). Similar associations were observed for p,p'-DDE (an increase of 100 ng/g lipid corresponded to an OR of 1.05, 95% CI 1.01, 1.09, p = 0.006). Gender stratified analyses showed among men consistent positive associations with CB-153, but a more ambiguous pattern with respect to DDE. In contrast, among the women the associations with p,p'-DDE were stronger than with CB-153.

Conclusion

The study provides support that POP exposure might contribute to type 2 diabetes mellitus.
Characterization of Toll-like receptors in primary lung epithelial cells: strong impact of the TLR3 ligand poly(I:C) on the regulation of Toll-like receptors, adaptor proteins and inflammatory response
Authors: Ritter Mirko , Mennerich Detlev , Weith Andreas , Seither Peter
Published: November 2005

Background

Bacterial and viral exacerbations play a crucial role in a variety of lung diseases including COPD or asthma. Since the lung epithelium is a major source of various inflammatory mediators that affect the immune response, we analyzed the inflammatory reaction of primary lung epithelial cells to different microbial molecules that are recognized by Toll-like receptors (TLR).

Methods

The effects of TLR ligands on primary small airway epithelial cells were analyzed in detail with respect to cytokine, chemokine and matrix metalloproteinase secretion. In addition, the regulation of the expression of TLRs and their adaptor proteins in small airway epithelial cells was investigated.

Results

Our data demonstrate that poly(I:C), a synthetic analog of viral dsRNA, mediated the strongest proinflammatory effects among the tested ligands, including an increased secretion of IL-6, IL-8, TNF-α, GM-CSF, GRO-α, TARC, MCP-1, MIP-3α, RANTES, IFN-β, IP-10 and ITAC as well as an increased release of MMP-1, MMP-8, MMP-9, MMP-10 and MMP-13. Furthermore, our data show that poly(I:C) as well as type-1 and type-2 cytokines have a pronounced effect on the expression of TLRs and molecules involved in TLR signaling in small airway epithelial cells. Poly(I:C) induced an elevated expression of TLR1, TLR2 and TLR3 and increased the gene expression of the general TLR adaptor MyD88 and IRAK-2. Simultaneously, poly(I:C) decreased the expression of TLR5, TLR6 and TOLLIP.

Conclusion

Poly(I:C), an analog of viral dsRNA and a TLR3 ligand, triggers a strong inflammatory response in small airway epithelial cells that is likely to contribute to viral exacerbations of pulmonary diseases like asthma or COPD. The pronounced effects of poly(I:C) on the expression of Toll-like receptors and molecules involved in TLR signaling is assumed to influence the immune response of the lung epithelium to viral and bacterial infections. Likewise, the regulation of TLR expression by type-1 and type-2 cytokines is important considering the impact of exogenous and endogenous TLR ligands on Th1 or Th2 driven pulmonary inflammations like COPD or asthma, respectively.
Long-term use of non-steroidal anti-inflammatory drugs and the risk of myocardial infarction in the general population
Authors: García Rodríguez Luis A , González-Pérez Antonio
Published: November 2005

Background

Recent data indicate that chronic use of coxibs leads to an increased occurrence of thrombotic cardiovascular events. This raises the question as to whether traditional non-steroidal anti-inflammatory drugs (tNSAIDs) might also produce similar hazards. Our aim has been to evaluate the association between the chronic use of tNSAIDs and the risk of myocardial infarction (MI) in patients.

Methods

We performed a nested case-control analysis with 4,975 cases of acute MI and 20,000 controls, frequency matched to cases by age, sex, and calendar year.

Results

Overall, current use of tNSAID was not associated with an increased risk of MI (RR:1.07;95%CI: 0.95–1.21). However, we found that the relative risk (RR) of MI for durations of tNSAID treatment of >1 year was 1.21 (95% CI, 1.00–1.48). The corresponding RR was 1.34 (95% CI, 1.06–1.70) for non-fatal MI. The effect was independent from dose. The small risk associated with long-term use of tNSAIDs was observed among patients not taking low-dose aspirin (RR: 1.29; 95% CI, 1.01–1.65). The effect of long-term use for individual tNSAIDs ranged from a RR of 0.87 (95% CI, 0.47–1.62) with naproxen to 1.38 (95% CI, 1.00–1.90) with diclofenac.

Conclusion

This study adds support to the hypothesis that chronic treatment with some tNSAIDs is associated with a small increased risk of non-fatal MI. Our data are consistent with a substantial variability in cardiovascular risks between individual tNSAIDs.
Lifetime risk of depression: restricted to a minority or waiting for most?
Authors: Andrews Gavin , Poulton Richie , Skoog Ingmar
Published: November 2005

Depression remits and recurs, but among what proportion of the population? Retrospective surveys report the lifetime risk to be around 10%. A modelling study and two prospective studies concur that close to half the population can expect one or more episodes of depression in their lifetime.