bluuebunny/crossref_metadata_2025 huggingface dataset:
Oxygen Sensing by Primary Cardiac Fibroblasts
Authors: Roy Sashwati , Khanna Savita , Bickerstaff Alice A. , Subramanian Sukanya V. , Atalay Mustafa , Bierl Michael , Pendyala Srikanth , Levy Dana , Sharma Nidhi , Venojarvi Mika , Strauch Arthur , Orosz Charles G. , Sen Chandan K.
Published: February 2003

In mammalian organs under normoxic conditions, O
2
concentration ranges from 12% to <0.5%, with O
2
≈14% in arterial blood and <10% in the myocardium. During mild hypoxia, myocardial O
2
drops to ≈1% to 3% or lower. In response to chronic moderate hypoxia, cells adjust their normoxia set point such that reoxygenation-dependent relative elevation of P
o
2
results in perceived hyperoxia. We hypothesized that O
2
, even in marginal relative excess of the P
o
2
to which cardiac cells are adjusted, results in activation of specific signal transduction pathways that alter the phenotype and function of these cells. To test this hypothesis, cardiac fibroblasts (CFs) isolated from adult murine ventricle were cultured in 10% or 21% O
2
(hyperoxia relative to the P
o
2
to which cells are adjusted in vivo) and were compared with those cultured in 3% O
2
(mild hypoxia). Compared with cells cultured in 3% O
2
, cells that were cultured in 10% or 21% O
2
demonstrated remarkable reversible G
2
/M arrest and a phenotype indicative of differentiation to myofibroblasts. These effects were independent of NADPH oxidase function. CFs exposed to high O
2
exhibited higher levels of reactive oxygen species production. The molecular signature response to perceived hyperoxia included (1) induction of p21, cyclin D1, cyclin D2, cyclin G1, Fos-related antigen-2, and transforming growth factor-β1, (2) lowered telomerase activity, and (3) activation of transforming growth factor-β1 and p38 mitogen-activated protein kinase. CFs deficient in p21 were resistant to such O
2
sensitivity. This study raises the vital broad-based issue of controlling ambient O
2
during the culture of primary cells isolated from organs.
Shear Stress Causes Nuclear Localization of Endothelial Glucocorticoid Receptor and Expression From the GRE Promoter
Authors: Ji Julie Y. , Jing Huiyan , Diamond Scott L.
Published: February 2003

We tested the hypothesis that steady laminar shear stress activates the glucocorticoid receptor (GR) and its transcriptional signaling pathway in an effort to investigate the potential involvement of GR in shear stress-induced antiatherosclerosis actions in the vasculature. In both bovine aortic endothelial cells (BAECs) and NIH3T3 cells expressing GFP-GR chimeric protein, wall shear stress of 10 or 25 dynes/cm
2
caused a marked nuclear localization of GFP-GR within 1 hour to an extent comparable to induction with 25 μmol/L dexamethasone. The shear mediated nuclear localization of GFP-GR was significantly reduced by 25 μmol/L of the MEK1 inhibitor (PD098059) or the PI 3-kinase inhibitor (LY294002). Also, Western blots demonstrated translocation of endogenous GR into nucleus of sheared BAECs. Promoter construct studies using glucocorticoid response element (GRE)-driven expression of secreted alkaline phosphatase (SEAP) indicated that BAECs exposed to shear stress of 10 and 25 dynes/cm
2
for 8 hours produced >9-fold more SEAP (n=6;
P
<0.005) than control cells, a level comparable to that observed with dexamethasone. Shear stress enhanced SEAP expression at 6 hours was reduced 50% (n=5;
P
<0.005) by MEK1/2 or PI 3-kinase inhibitors, but not by the NO inhibitor, L-NAME. Finally, in human internal mammary artery, endothelial GR is found to be highly nuclear localized. We report a new shear responsive transcriptional element, GRE. The finding that hemodynamic forces can be as potent as high dose glucocorticoid steroid in activating GR and GRE-regulated expression correlates with the atheroprotective responses of endothelial cells to unidirectional arterial shear stress.
The Studierstube Augmented Reality Project
Authors: Schmalstieg Dieter , Fuhrmann Anton , Hesina Gerd , Szalavári Zsolt , Encarnação L. Miguel , Gervautz Michael , Purgathofer Werner
Published: February 2003

Our starting point for developing the Studierstube system was the belief that augmented reality, the less obtrusive cousin of virtual reality, has a better chance of becoming a viable user interface for applications requiring manipulation of complex three-dimensional information as a daily routine. In essence, we are searching for a 3-D user interface metaphor as powerful as the desktop metaphor for 2-D. At the heart of the Studierstube system, collaborative augmented reality is used to embed computer-generated images into the real work environment. In the first part of this paper, we review the user interface of the initial Studierstube system, in particular the implementation of collaborative augmented reality, and the Personal Interaction Panel, a two-handed interface for interaction with the system. In the second part, an extended Studierstube system based on a heterogeneous distributed architecture is presented. This system allows the user to combine multiple approaches— augmented reality, projection displays, and ubiquitous computing—to the interface as needed. The environment is controlled by the Personal Interaction Panel, a twohanded, pen-and-pad interface that has versatile uses for interacting with the virtual environment. Studierstube also borrows elements from the desktop, such as multitasking and multi-windowing. The resulting software architecture is a user interface management system for complex augmented reality applications. The presentation is complemented by selected application examples.
Building Virtual Worlds for Informal Science Learning (SciCentr and SciFair) in the Active Worlds Educational Universe (AWEDU)
Authors: Corbit Margaret
Published: February 2003

As a focus of its exploration of desktop 3-D environments for science outreach, the Cornell Theory Center (CTC), Cornell University's high-performance computing center, has been exploring the use of the Active Worlds client/server technology for implementation of a 3-D multiuser virtual science museum, SciCentr, that incorporates interactive simulation-based exhibits. We present here early lessons in accommodating the needs of several interconnected user groups as we move forward with establishing the SciCentr community within the greater educational community of Active Worlds Educational Universe (AWEDU) and the Contact Consortium's VLearn3D initiative. We learned that we must provide the user communities with both social and spatial frameworks within which to work and play. Social support ranges from one-on-one, over-the-shoulder help, to guidance and training within the environment, to coordination of “inworld” activities and inperson pizza parties. Spatial design requirements depend on the activities of the user group and benefit from study of real and virtual world examples. Our experience to date with a pilot group of teenaged participants is encouraging, and we believe that this medium has potential as a resource for constructivist informal science and technology education.
An Experiment on Public Speaking Anxiety in Response to Three Different Types of Virtual Audience
Authors: Pertaub David-Paul , Slater Mel , Barker Chris
Published: February 2003

This paper describes an experiment to assess the anxiety responses of people giving 5 min. presentations to virtual audiences consisting of eight male avatars. There were three different types of audience behavior: an emotionally neutral audience that remained static throughout the talk, a positive audience that exhibited friendly and appreciative behavior towards the speaker, and a negative audience that exhibited hostile and bored expressions throughout the talk. A second factor was immersion: half of the forty subjects experienced the virtual seminar room through a head-tracked, head-mounted display and the remainder on a desktop system. Responses were measured using the standard Personal Report of Confidence as a Public Speaker (PRCS), which was elicited prior to the experiment and after each talk. Several other standard psychological measures such as SCL-90-R (for screening for psychological disorder), the SAD, and the FNE were also measured prior to the experiment. Other response variables included subjectively assessed somaticization and a subject self-rating scale on performance during the talk. The subjects gave the talk twice each to a different audience, but in the analysis only the results of the first talk are presented, thus making this a between-groups design. The results show that post-talk PRCS is significantly and positively correlated to PRCS measured prior to the experiment in the case only of the positive and static audiences. For the negative audience, prior PRCS was not a predictor of post-PRCS, which was higher than for the other two audiences and constant. The negative audience clearly provoked an anxiety response irrespective of the normal level of public speaking confidence of the subject. The somatic response also showed a higher level of anxiety for the negative audience than for the other two, but self-rating was generally higher only for the static audience, each of these results taking into account prior PRCS.
Putting the Virtual into Reality: Assessing Object-Presence with Projection-Augmented Models
Authors: Stevens Brett , Jerrams-Smith Jennifer , Heathcote David , Callear David
Published: February 2003

A projection-augmented model is a type of nonimmersive, coincident haptic and visual display that uses a physical model as a three-dimensional screen for projected visual information. Supporting all physiological depth cues and two sensory modalities should create a strong sense of the object's existence. However, conventional measures of presence have been defined only for displays that surround and isolate a user from the real world. The idea of object-presence is thus suggested to measure “the subjective experience that a particular object exists in a user's environment, even when that object does not” (Stevens & Jerrams-Smith, 2000). A correlation study was conducted to demonstrate the reliability and validity of objectpresence as a construct. The results of a modified Singer and Witmer Presence Questionnaire suggest the existence of a reliable construct that exhibits face validity. However, the Presence Questionnaire did not correlate significantly with a user's tendency to become immersed in traditional media, which would support the assertion that this construct was object-presence. Considering previous work, the results of the current correlation study exhibited a pattern evident in previous studies of presence suggesting that object-presence and presence could be gender biased by the task to be completed or by the presence measure.
Gas tungsten arc welding studies on similar and dissimilar combinations of Al-Zn-Mg alloy RDE 40 and Al-Li alloy 1441
Authors: Shelwatkar D. A. , Reddy G. Madhusudhan , Gokhale A. A.
Published: February 2003

The present study is concerned with gas tungsten arc welding of two high strength aluminium alloys, namely, an Al-Zn-Mg alloy (RDE 40) and an Al-Li based alloy of Russian grade 1441. One of the critical requirements of these two alloys is that they should be weldable. In the present work, weldability aspects of these alloys were studied in terms of solidification cracking tendency, microstructure, tensile properties, and microhardness across the welds. These studies were extended to dissimilar welds between RDE 40 and 1441 produced via conventional gas tungsten arc (GTA) welding as well as pulsed current GTA welding. It was found that RDE 40 welds were less sensitive to solidification cracking and weld metal porosity compared with 1441 alloy. The superior weldability of RDE 40 was related to the equiaxed nature of the fusion zone and a lower sensitivity to moisture pickup. It was possible to produce RDE 40-1441 welds without defects. Pulsed current welding of RDE 40 to 1441 showed improved mechanical properties compared with conventional GTA welding, and these were related to the refinement of the fusion zone microstructure.
Dilution and microsegregation in dissimilar metal welds between super austenitic stainless steel and nickel base alloys
Authors: Banovic S. W. , Dupont J. N. , Marder A. R.
Published: February 2003

Super austenitic stainless steels are often welded using high Mo, Ni base filler metals to maintain the corrosion resistance of the weld. An important aspect of this processing is the weld metal dilution level, which will control the composition and resultant corrosion resistance of the weld. In addition, the distribution of alloying elements within the weld will also significantly affect the corrosion resistance. Dissimilar metal welds between a super austenitic stainless steel (AL-6XN) and two Ni base alloys (IN625 and IN622) were characterised with respect to their dilution levels and microsegregation patterns. Single pass welds were produced over the entire dilution range using the gas tungsten arc welding process. Microstructural characterisation of the welds was conducted using light optical microscopy, scanning electron microscopy, and quantitative image analysis. Bulk and local chemical compositions were obtained through electron probe microanalysis. The quantitative chemical information was used to determine the partition coefficients k of the elements in each dissimilar weld. The dilution level was found to decrease as the ratio of volumetric filler metal feedrate to net arc power increased. Reasons for this behaviour are discussed in terms of the distribution of power required to melt the filler metal and base metal. In addition, the segregation potential of Mo and Nb was observed to increase (i.e. their k values decreased) as the Fe content of the weld increased. This effect is attributed to the decreased solubility of Mo and Nb in austenite with increasing Fe additions. Since the Fe content of the weld is controlled by dilution, which in turn is controlled by the welding parameters, the welding parameters have an indirect influence on the segregation potential of Mo and Nb. The results of the present work provide practical insight for corrosion control of welds in super austenitic stainless steels.
Comparative evaluation of tungsten inert gas and laser welding of AZ31 magnesium alloy
Authors: Sun Z. , Pan D. , Wei J.
Published: February 2003

Welding of AZ31 Mg alloy was conducted using various welding techniques, namely, tungsten inert gas (TIG) welding with Ar shielding gas, TIG welding with He shielding gas, CO2 laser welding, and YAG laser welding. The results were comparatively evaluated in terms of weld bead formation and microstructural characterisation. It was found that TIG welding with both Ar and He gas shielding produced good welds without major defects. The penetration capacity can be improved using He gas shielding. Owing to their high energy density, CO2 and YAG lasers can produce weld beads having high aspect ratio. Among the four techniques used, the YAG laser produced the finest weld microstructure, whereas TIG with Ar gas shielding produced the coarsest microstructure. Shielding is a key factor controlling the O contents in the welds. The more effective the shielding provided the lower the O content in the weld. Hardness reduction in the weld metals and heat affected zones was observed for all the techniques owing to the elimination of strengthening effects by the welding operation. In summary, the present study demonstrated advantages and limitations of the various welding techniques and provided an in depth understanding of the weldability of AZ31 Mg alloy.
Liquid zinc corrosion of steel welds
Authors: Suzuki K. , Aihara S. , Ichikawa K. , Yajima H. , Shinozaki K. , Yamamoto M.
Published: February 2003

Long term liquid zinc corrosion characteristics, up to 3000 h at 450°C, were investigated for the base metal and for multipass all weld metal deposits and weld joints produced via the gas shielded metal arc welding (GMAW and submerged arc welding (SAW) processes. The purpose of the present work was to determine the possibility of replacing the present shielded metal arc welding (SMAW) technique with the former two processes since they can offer demonstrably higher productivity than conventional SMAW in the fabrication process of hot dip galvanising baths. Regression analyses were also attempted to determine the corrosion rate quantitatively and thereby to establish a reasonable life prediction technique for such baths. It was found that the corrosion rate of the weld metal depends on the chemical composition, particularly on silicon concentration. Selection of low silicon (less than about 2.0 mass%) containing welding materials is thus vital to suppress the liquid zinc corrosion. Iron loss from the weld metal into the liquid zinc can be practically predicted with the selection of an appropriate magnitude of the parabolic rate constant. The information obtained in the present work confirmed that SMAW could safely be substituted by higher efficiency welding methods such as GMAW and SAW, subject to the restriction of the silicon concentration of the welding consumables.
Spot plunged arc welding using covered electrode
Authors: Tušek J.
Published: February 2003

The present paper reports on spot plunged arc welding with a covered electrode, for which it is possible to obtain a penetration depth of 25 mm (or greater) in a single spot. Covered electrodes are used in the process. The electrode coverings contain ‘active’ elements to increase the molten pool movement and the arc constriction. The two effects combine to give a penetration that is deeper than that obtained in the usual manual arc welding process with a covered electrode. The majority of the present paper is focused on a description of the spot plunged arc welding process with a covered electrode. A diagram shows movement of the cold and hot electrode ends during welding. The welding process is described in seven phases in terms of the covered electrode movement. A table gives an approximate chemical composition of the coating of the covered electrode. Several macrographs of spot welds in lap joints made on plates of different thicknesses are shown. Chemical compositions of the weld metal and the parent metal are given. As an indicator of the economy of spot plunged arc welding, a melting rate is indicated. Several figures show the shape and volume of the melted parent metal and filler material.
Development of adaptive control system for alternating current pulsed metal inert gas welding parameters
Authors: Tong H. , Era T. , Ueyama T.
Published: February 2003

A three-dimensional laser sensor is combined with an alternating current pulsed metal inert gas welding robot system to detect information about the variation of joint gap width and deviation of the joint position relative to the welding torch. Together with the joint tracking and torch direction adjustment, electrode negative polarity ratio and welding speed are also controlled adaptively according to the variation of joint gap width during welding. As a result, a high tolerance of joint gap variation is obtained and bead shape becomes more uniform and of reasonable quality in welding of aluminium alloy sheets.
Effect of normalising heat treatment on microstructure and properties of nickel alloyed C-Mn weld metals
Authors: Utterberg B. , Svensson L.-E.
Published: February 2003

Five different basic manual metal arc welding electrodes, containing varying amounts of nickel (from 0 to 3.5%) were deposited in an all weld metal joint. Mechanical testing and microstructure examination was performed in the as deposited and heat treated conditions. The heat treatment was carried out at three different temperatures (930, 980, and 1030° C) for 20 min. The tensile strength was decreased by the heat treatment, but the magnitude of the decrease varied between the weld metals. The impact properties were also affected by the heat treatment. For impact properties, however, a decrease was found at low testing temperatures, whereas an increase was observed at higher testing temperatures. The decrease in tensile strength after normalisation, compared with the as deposited condition, is due to an increasing grain size and a decreasing dislocation content. The strength achieved by the different weld metals in the normalised condition can be explained by the variation in solid solution hardening resulting from differences in the alloying content.Two factors seemed to be especially important in determining the variations in impact properties between weld metals in the as deposited condition. The nitrogen content of the weld metals decreased the impact toughness, whereas increasing nickel content was associated with improved impact toughness. In the normalised condition, reduced at lower testing temperatures, because cleavage fracture started readily in the resulting coarser grains. Furthermore, traces of segregated bands of microphases probably acted as initiation sites for cleavage cracks. At higher testing temperatures, higher impact toughness was obtained, owing to the lower strength of the weld metals. One of the electrodes showed superior impact toughness values to the other electrodes, in both the as deposited and heat treated conditions. The main reason for the high toughness in the as deposited condition was the ability of this electrode to refine previously deposited beads to a high degree. The reason for the high toughness after normalising is still not certain, but it was noted that this weld metal had a very low oxygen content and also a comparatively low volume fraction of segregated microphases. These factors might be important in achieving the very high impact toughness observed.
Processes and properties of deposits in electrospark deposition
Authors: Lešnjak A. , Tušek J.
Published: February 2003

In the electrospark deposition of a material, a high current is conducted through an oscillating electrode and a substrate for a very short period of time. When the electrode is moved away from the surface, an arc is formed momentarily, causing melting of the electrode surface for a short time. In the present work, the process was monitored in real time using a high speed camera, permitting determination of the mode of mass transfer from the electrode to the substrate, the number and size of droplets, and arc guidance (i.e. spark guidance in the present process) during deposition. The variations of welding current, welding voltage, and pulse frequency were analysed using a high performance oscilloscope. One of the applications of the process is the deposition of hard layers on die casting tools for aluminium. The analysis was carried out using a scanning electron microscope and an X-ray diffraction microanalyser. Energy input was also studied.
Weldability criteria for mash seam tailored blank welds in ultralow carbon steel applied to automotive bodies
Authors: Han C.-W. , Uhm S.-H. , Lee C.-H.
Published: February 2003

Mash seam (MS) tailored blank (TB) welding is a production method for blanks involving welding together blanks of different material, thickness, and coating and is an attractive method for manufacturing car bodies because it leads to lighter parts, and can save cost and time in manufacture. However, quantified criteria to evaluate the quality of TB welds have not been developed. In the present work, the failure height ratio (FHR) was introduced to assess the weldability of MS welds, and the applicability of the FHR was confirmed via actual auto body forming and forming limit diagram tests. Furthermore, a new parameter, namely, a heat number based on the heat input calculated according to Q=I2Rt, was proposed and assessed. It was found that this heat number could be used to evaluate the soundness of MS welds.
In situ observation of interlayer growth during heat treatment of friction weld joint between pure titanium and pure aluminium
Authors: Fuji A.
Published: February 2003

The growth of an intermediate layer, consisting of an intermetallic compound phase, in a friction welded joint between pure Ti and pure Al heated at 853 K for up to 173 ks (580°C, 48 h) was elucidated via an in situ (direct) and continuous observation method using a high temperature optical microscope. The following conclusions were reached. The layer grew from the Al substrate to the Ti substrate, and neither a linear nor a parabolic time dependence could be used to describe the rate of layer growth. The layer growth stopped for some time (i.e. several hours) after every heating interval of approximately 36 ks (10 h). That is, several plateaus appeared during heat treatment. It is thought that nucleation, and growth of such nuclei, of the Al- Ti binary intermetallic phase are necessary for layer growth. The interlayer growth rate for joints between pure Ti and highly pure Al was higher than that for joints between pure Ti and commercially pure Al. This is due to the Si content in the Al base metal. There was a slight variation of the layer growth rate with location along the radius of the joint and with friction time.
Testosterone levels in men with chronic obstructive pulmonary disease with or without glucocorticoid therapy
Authors: Kamischke A , Kemper DE , Castel MA , Luthke M , Rolf C , Behre HM , Magnussen H , Nieschlag E
Published: February 2003

Under the clinical impression that patients with chronic obstructive pulmonary disease (COPD) may demonstrate signs compatible with hypogonadism, we investigated whether oral glucocorticoid therapy is associated with testosterone deficiency. Thirty six men with COPD of whom 16 were receiving oral glucocorticoid medication (mean+/-SEM dose 9.4+/-1.1 mg prednisolone) were investigated in a cross-sectional cohort study. Patients with or without oral glucocorticoid therapy were not different in terms of age, smoking history and additional therapy. Vital capacity, forced expiratory volume in one second, airway resistance, intrathoracic gas volume and blood gases at rest were not different between the groups. However, patients receiving glucocorticoids had a shorter 6 min walking distance (mean+/-SEM 205+/-27 versus 288+/-26 m; p=0.02) compared to patients without oral steroid therapy. Serum levels of testosterone (mean+/-SEM 13.7+/-0.9) were below normal (<12 nM) in 15 of 36 patients. Serum testosterone did not correlate with any other evaluated parameter. Serum levels of free testosterone (free T) (mean+/-SEM 172.3+/-7.8 pM) were decreased in 25 of the 36 patients, including all patients receiving glucocorticoid treatment. In the 16 patients taking glucocorticoids free T was correlated (p=0.016) with the current glucocorticoid dosage (r=-0.504; p=0.007) and the body mass index (r=0.241; p=0.037). All other parameters examined revealed no significant correlations in multiple regression analysis. Glucocorticoid treatment appears to aggravate hypogonadism and a therapeutic study using testosterone in patients with chronic obstructive pulmonary disease receiving glucocorticoid medication appears warranted.
Immunological findings in blood and bronchoalveolar lavage fluid in chronic bronchitis patients with recurrent infectious exacerbations
Authors: Qvarfordt I , Riise GC , Larsson S , Almqvist G , Rollof J , Bengtsson T , Andersson BA
Published: February 2003

Bronchial infections are common in smokers and seem to be related to the presence of chronic bronchitis (CB). Why only some smokers develop repeated bronchial infections is not known. The aim of this study was to screen for immunological changes associated with disease in patients with CB and recurrent infectious exacerbations compared to asymptomatic smokers. Sixteen smokers with stable CB and recurrent infectious exacerbations, and 18 asymptomatic smokers, all without any immunomodulating treatment, underwent bronchoscopy and bronchoalveolar lavage (BAL). Smoking history and current smoking status were comparable. Serum levels of immunoglobulin (Ig)A, IgM, IgG and IgG subclasses were measured. Blood and BAL lymphocyte phenotypes and proliferative responses of peripheral blood mononuclear cells (PBMCs) to various stimulators were analysed. Unstimulated and tetanus toxoid-stimulated production of cytokines in PBMC cultures was measured. Natural killer (NK-) cell activity was analysed. A significantly (p<0.05) lower level of IgG3 was found in the CB group, and a significantly (p<0.01) higher proliferative response of PBMCs was found in the CB group after stimulation with diphtheria toxoid. Detectable levels of interleukin (IL)-6, tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma, but not of IL-2, IL-4 or transforming growth factor-beta2, were found in supernatants from cultured cells in both study groups. Stimulated TNF-alpha production was significantly (p<0.05) higher in the CB group. NK-cell activity did not differ significantly between the study groups. There were no major differences between the groups in lymphocyte subpopulations in blood or BAL. In conclusion, no major alterations in the analysed indices of cell-mediated and humoral immunity were found in patients with chronic bronchitis prone to recurrent infectious exacerbations when compared with asymptomatic smoking controls.
Quality of life in patients with chronic respiratory disease: the Spanish version of the Chronic Respiratory Questionnaire (CRQ)
Authors: Guell R , Casan P , Sangenis M , Morante F , Belda J , Guyatt GH
Published: February 2003

The aim of this study was to translate the Chronic Respiratory Questionnaire (CRQ) into Spanish and to test its measurement properties. The study was performed in 60 patients with chronic obstructive pulmonary disease (forced expiratory volume in one second (FEV1) mean+/-SD 35+/-14% of reference value). A rigorous process of forward and back translation and review produced an easily comprehensible questionnaire, which was administered together with measures of pulmonary function and exercise capacity. The patients were randomly allocated to one of two groups: 30 received respiratory rehabilitation and the other 30 received standard community care only. Weak to moderate statistically significant correlations (0.2-0.38) were found between the domains of the CRQ and pulmonary function and exercise measures. For the three CRQ domains that measure differences between patients at a point in time, Crohnbach's alpha and intraclass correlation coefficients were: fatigue 0.80 and 0.80; emotional function 0.86 and 0.68; and mastery domains 0.84 and 0.67, respectively. Scores remained stable in patients who were deemed clinically stable, and showed large statistically significant improvement (p<0.0001) in patients in the rehabilitation programme. Only low correlations were found between the changes in CRQ and the changes in pulmonary function and exercise capacity. The index of responsiveness was 0.92 for fatigue, and 0.91 for dyspnoea, emotional function and mastery. In conclusion, the Spanish translation of the Chronic Respiratory Questionnaire is likely to be useful for measuring differences between patients, and particularly for measuring the effects of intervention on quality of life in chronic respiratory disease.
Reliability and validity of a Swedish version of the St George's Respiratory Questionnaire
Authors: Engstrom CP , Persson LO , Larsson S , Sullivan M
Published: February 2003

The St George's Respiratory Questionnaire (SGRQ) was designed to measure quality of life (QoL) in obstructive pulmonary disease. Its reliability, validity and sensitivity have been demonstrated. The aim was to develop a Swedish version of the SGRQ and to confirm its scaling and clinical properties. The SGRQ was adapted for Swedish conditions following a translation-backtranslation procedure. The psychometric and clinical evaluation included 68 patients with chronic obstructive pulmonary disease (COPD). Supplementary QoL, clinical and physiological data were collected. A follow-up study was performed 1 yr later. Correlation analysis used a multitrait-multimethod model. Internal consistency reliability and discriminant validity were documented by performing a multitrait analysis. The results confirmed expected levels of associations. Correlation coefficients between the SGRQ total score and the Sickness Impact Profile Total score (a generic health measure), forced expiratory volume in one second (FEV1) and 6 min walking distance were 0.69, -0.42 and -0.61 respectively. The pattern of correlations in the Swedish data set was very similar to that of the original. The stability of the SGRQ scores was confirmed at follow-up after 1 yr. The reliability was satisfactory, with Cronbach's alpha coefficients >0.80 for the SGRQ and its subdimensions. In conclusion, the Swedish version of the St George's Respiratory Questionnaire is reliable, valid and compares well with the corresponding tests of the original version.
Empirical therapy for nonhospitalized patients with community-acquired pneumonia. Study Group of General Practitioners
Authors: Laurichesse H , Robin F , Gerbaud L , Pochet P , Gourdon F , Beytout J , Rey M
Published: February 2003

A prospective survey involving a group of 95 general practitioners (GPs) in France was conducted to describe antibiotic therapy prescribed for out-patients with community-acquired pneumonia (CAP). A total of 173 cases of CAP, defined by the association of fever and pulmonary focal crackles and/or radiological changes consistent with a pulmonary infection, were reported between February 1993 and March 1994: 84 males and 89 females (mean age: 48 yrs) of whom 45% had no underlying disease. Nineteen (11%) were immediately hospitalized and the remaining 154 out-patients were treated without microbiological investigation. First-line antibiotic therapy was amoxicillin or amoxicillin-clavulanic acid combination (57%), a first or second generation cephalosporin (12%), ceftriaxone (8%), oral broad-spectrum cephalosporin (3%), a macrolide (16%), a tetracycline (1%) and a fluoroquinolone (2%). A total of 120 (78%) patients recovered with no change in treatment and 34 (22%) patients failed to improve: 18 were hospitalized and 16 had a second-line therapy, mainly a macrolide or a quinolone. Five patients died at hospital. The overall mortality was 3%, and 14% in hospitalized patients. Empirical therapy using a betalactam to target a presumed pneumococcal infection, in agreement with European guidelines, is appropriate for out-patients with mild lobar community-acquired pneumonia.
Distribution of immunoreactive endothelin in the lungs of mice during respiratory viral infection
Authors: Carr MJ , Spalding LJ , Goldie RG , Henry PJ
Published: February 2003

Respiratory tract viral infections are associated with the generation of a wide array of pro-inflammatory cytokines, some of which enhance the release of the potent airway smooth muscle spasmogen, endothelin, from respiratory epithelial cells in tissue culture. The aim of this study was to determine whether the content and distribution of immunoreactive endothelin in the intact murine lung is increased during the course of a respiratory tract viral infection. Mice were inoculated intranasally with Influenza A/PR-8/34 virus or sterile vehicle and at various days postinoculation were sacrificed, and their lungs processed for either fluorescence immunohistochemistry with rabbit anti-endothelin sera or measurement of immunoreactive endothelin with an enzyme-linked immunosorbent assay (ELISA). At 2 and 4 days postinoculation, the content of immunoreactive endothelin in lung extracts of virus-infected mice was approximately twice that present in lung extracts from control mice (n=3-4, p<0.05). Consistent with this, an increased intensity and broader distribution of fluorescent immunohistochemical staining for endothelin was observed in the airway epithelium of the trachea and intrapulmonary airways of virus-infected mice. This study has clearly demonstrated that respiratory tract viral infection is associated with an increased content and broader distribution of immunoreactive endothelin within the lungs of mice. Whether the elevated content of endothelin contributes to the symptoms of virus-induced hyperresponsiveness or to virus-induced exacerbations of asthma remains to be established.
Adhesion molecule expression in the lung: a comparison between normal and diffuse interstitial lung disease
Authors: Southcott AM , Hemingway I , Lorimer S , Sugars K , Hellewell PG , Black CM , Jeffery PK , Gearing AJ , Haskard DO , du Bois RM
Published: February 2003

Cellular adhesion molecules are crucial determinants of the migration of immune effector cells to the tissues. In chronic inflammatory diseases, upregulation of the expression of these molecules may contribute to the persistent inflammatory process. The aim of this study was to determine whether there is evidence of adhesion molecule expression in chronically inflamed lung. Soluble adhesion molecules in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunoassay in 54 patients with chronic interstitial lung diseases and 16 normal controls. Adhesion molecule expression in fibrosing alveolitis (FA) lung and in control lung was assessed using immunohistology and reverse transcription-polymerase chain reaction (RT-PCR) amplification. Soluble intercellular adhesion molecule-1 (ICAM-1) was detected in all but two subjects. There was no difference in ICAM-1 concentration between disease groups and normal subjects. In contrast, soluble E-selectin was detected in 17 of the 70 subjects and was significantly associated with the presence of lung disease (p=0.0173). Furthermore, the presence of soluble E-selectin was associated with a raised lymphocyte percentage in BALF (p=0.0069). Soluble VCAM was only detected in five of the 70 subjects (two normals, three patients). There was no difference in adhesion molecule expression in lung parenchyma between FA and controls assessed by immunohistology and RT-PCR. The most striking finding of our study was the universal expression of intercellular adhesion molecule-1 in both normal and diseased lung, emphasizing the important role of the lung in immune function. Upregulation of E-selectin may contribute to inflammatory cell accumulation in chronic interstitial lung diseases.
Changing strategies of lung biopsies in diffuse lung diseases: the impact of video-assisted thoracoscopy
Authors: Ravini M , Ferraro G , Barbieri B , Colombo P , Rizzato G
Published: February 2003

The aims of this report were: 1) to compare the strategy of bioptic approach in Italy during the last 4 yrs with a previous period; and 2) to compare efficacy and safety of video-assisted thorascopic lung biopsy (VTLB) versus OLB. We retrospectively evaluated: 1) the strategy of the bioptic approach in the Milan Sarcoid Clinic in the years 1992-1995 (201 patients) versus 1988-1991 (197 patients); and 2) data from 65 VTLB procedures in the years 1992-1995 versus 68 OLB procedures in the years 1988-1991 performed in patients with diffuse lung disease. It was found that the use of OLB (17-9%), mediastinoscopy (15-5%), and scalene node biopsy (20-7%) decreased, whereas transbronchial biopsy (TBB) increased (11-17%). VTLB biopsy is now performed in 17% of patients. VTLB compares favourably with OLB as there is less need for analgesia (7.5+/-7.5 versus 17.5+/-8.0 methadone mg i.m.: p<0.001), lower blood loss (61+/-58 versus 156+/-84 mL in the first postoperative day: p<0.001), and shorter postoperative stay (4.7+/-1.6 versus 5.7+/-1.4 days: p<0.001). Specimen adequacy (98.6 versus 985%) and diagnostic accuracy (86.1% VTLB, versus 92.6% OLB: p>0.05) were the same in the two groups. In conclusion, video-assisted thoracoscopic lung biopsy is replacing both mediastinoscopy and open lung biopsy. It is at present the best option when a surgical procedure is required for histological confirmation of diffuse lung disease.
Elevated concentrations of defensins in bronchoalveolar lavage fluid in diffuse panbronchiolitis
Authors: Ashitani J , Mukae H , Nakazato M , Ihi T , Mashimoto H , Kadota J , Kohno S , Matsukura S
Published: February 2003

Human neutrophils contain three isoforms of antimicrobial and cytotoxic peptides in the azurophil granules, which belong to a family of mammalian neutrophil peptides named defensins. Here we investigate the role of these peptides in diffuse panbronchiolitis (DPB). Defensins (human neutrophil peptide-1, -2 and -3) were measured by radioimmunoassay in bronchoalveolar lavage fluid (BALF) of 30 patients with DPB, 16 patients with idiopathic pulmonary fibrosis (IPF) and 15 healthy adults. The concentration of defensins was higher in BALF of patients with DPB than in patients with IPF and healthy subjects. DPB and IPF patients also had significantly higher plasma concentrations of defensins than controls. In patients with DPB, BALF concentration of defensins correlated significantly with neutrophil count or BALF concentration of interleukin (IL)-8. Immunohistochemistry of open-lung biopsy specimens from four DPB patients showed localization of defensins in neutrophils and mucinous exudate in the airways, and on the surface of bronchiolar epithelial cells. In vitro studies showed an enhanced extracellular release of defensins following stimulation of neutrophils with phorbol myristate acetate, N-formyl-methionyl-leucyl-phenyalamine, and human recombinant IL-8. Treatment of DPB with macrolides for 6 months significantly reduced neutrophil count and concentrations of defensins and IL-8 in BALF. Our results indicate accumulation of neutrophil-derived defensins in the airway in diffuse panbronchiolitis, and suggest that defensins may be a marker of neutrophil activity in this disease.
Soluble complement receptor type 1 (CD35) in bronchoalveolar lavage of inflammatory lung diseases
Authors: Hamacher J , Sadallah S , Schifferli JA , Villard J , Nicod LP
Published: February 2003

Complement receptor type 1 (CR1) (CD35; C3b/C4b receptor) is a transmembrane protein of many haematopoietic cells. Once cleaved, soluble complement receptor type 1 (sCR1) exerts opposite effects as a powerful inhibitor of complement. This study addressed both the question of whether sCR1 was found in bronchoalveolar lavage (BAL) of normals and patients with various inflammatory disease, and its possible origin. In this retrospective study covering specimen and clinical data of 124 patients with acute and chronic inflammatory lung pathologies, BAL supernatants were analysed by enzyme-linked immunosorbent assay technique for sCR1. Correlations were made between the sCR1 levels obtained and the constituents of BAL. Human alveolar macrophages were cultivated in order to determine their secretory capacity of sCR1. Alveolar macrophages from normal subjects were shown to release sCR1 in vitro. In addition, sCR1 was present in BAL of normal controls and was significantly increased in acute inflammatory lung diseases such as acute respiratory distress syndrome (ARDS), bacterial and Pneumocystis carinii pneumonia, as well as in chronic inflammatory diseases such as interstitial lung fibrosis and sarcoidosis. In BAL of ARDS, bacterial, and P. carinii pneumonia, there was a good correlation between sCR1 and the absolute neutrophil counts. In sarcoidosis, a correlation was found with BAL lymphocyte counts. Serum sCR1 was not increased in patients compared to controls. Soluble complement receptor type 1 (sCR1) is found in the bronchoalveolar lavage in health as well as in acute and chronic inflammatory disease. Alveolar macrophages are capable of releasing sCR1 in vitro and may be the main physiological source of sCR1 in the alveoli. The good correlation between sCR1 and the absolute neutrophil or lymphocyte numbers in bronchoalveolar lavage of inflammatory diseases suggests a predominant role of leucocytes for the release of sCR1 in such conditions. The release of this inhibitor of complement may be crucial to control and reduce complement activation and thus prevent lung injury.
Effects of long-term inhaled corticosteroids on skin collagen synthesis and thickness in asthmatic patients
Authors: Haapasaari K , Rossi O , Risteli J , Oikarinen A
Published: February 2003

There are only a few studies on the adverse effects of inhaled corticosteroids on the skin in asthmatic patients. Therefore, we evaluated the effect of inhaled corticosteroids on de novo collagen synthesis of skin and bone, skin thickness and the total amount of skin collagen. Twenty seven consecutive new asthmatic patients, on a moderate dose of budesonide or beclomethasone dipropionate, were invited to take part in this prospective study. Radioimmunological analyses of aminoterminal propeptides of type I and III procollagens (PINP, PIIINP, respectively) in suction blister fluid (SBF) of skin and in serum and carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carbox terminal telopeptide of type I collagen (ICTP) in serum were performed at entry and after 3 and 6 months of inhaled corticosteroid treatment. Ultrasound measurements of skin thickness at two sites were performed at entry, at 3 and 6 months and after 1-2 yrs of inhaled corticosteroid treatment in 20 patients, six of whom had been prescribed one or more courses of oral corticosteroids. Skin hydroxyproline of punch biopsies was determined to measure the total amount of skin collagen (males, at entry and at 6 months). Skin thickness and the total amount of skin collagen on the abdomen were unchanged after 1-2 yrs of inhaled corticosteroid use. A slight decrease was observed in the upper arm skin thickness, especially in those subjects who had received inhaled plus oral corticosteroids. The procollagen propeptide concentrations (PINP, PIIINP) were markedly decreased in SBF at 3 months and remained at this level at 6 months. In serum, a slight decrease was seen in the PINP, PIIINP and ICTP concentrations at 3 and 6 months. In conclusion, inhaled corticosteroids decrease the collagen synthesis of skin and bone, but skin thickness and the total amount of collagen in skin are not changed markedly after 1-2 yrs of treatment.
Effects of oral hyposensitization with recombinant Der f2 on immediate airway constriction in a murine allergic model
Authors: Yasue M , Yokota T , Yuasa M , Kajiwara Y , Suko M , Okudaira H
Published: February 2003

Recombinant Der f2 (rDer f2) has recently been developed as a promising allergen for the diagnosis and immunotherapy of house-dust mite allergy, and studies in immunology. The aim of the present study was to evaluate whether oral administration of rDer f2 could suppress an immediate allergic reaction in mice sensitized with mite allergen. We developed a murine allergic model that showed bronchoconstriction after inhalation of rDer f2, and studied the effect of oral administration of rDer f2 on the reaction. Seven week old male A/J mice were intranasally immunized with rDer f2 12 times. Sensitized mice showed anti-rDer f2 immunoglobulin (Ig)E production and immediate airway constriction after inhalation of 10 mg.mL(-1) of rDer f2, as determined by the Konzett-Rossler method. Immunized animals were divided into three groups, and fed phosphate-buffered saline (PBS), 0.1 mg.day(-1), or 1 mg.day(-1) of rDer f2 for 4 weeks, respectively. Seven days after the last feeding, the mice were examined for their immediate response. Animals fed with 1 mg.day(-1) rDer f2 showed significantly reduced bronchoconstriction after inhalation of both 2 mg.mL(-1) and 10 mg.mL(-1) of rDer f2 compared with PBS-fed mice. Similar results were obtained when we examined mice 10 weeks after the last feeding. Reactions in the 0.1 mg.day(-1) rDer f2-fed group also tended to decrease in comparison with PBS-fed animals. Plasma anti-rDer f2 IgE, IgG1, IgG2a, and IgG2b levels were not changed by feeding with rDer f2. We conclude that recombinant Der f2 exhibits both sensitizing and hyposensitizing activities in mice. rDer f2 may be useful in immunotherapy and diagnosis of house-dust mite allergy.