bluuebunny/crossref_metadata_2025 huggingface dataset:
Crystal structure of the human T cell receptor CD3εγ heterodimer complexed to the therapeutic mAb OKT3
Authors: Kjer-Nielsen Lars , Dunstone Michelle A. , Kostenko Lyudmila , Ely Lauren K. , Beddoe Travis , Mifsud Nicole A. , Purcell Anthony W. , Brooks Andrew G. , McCluskey James , Rossjohn Jamie
Published: May 2004

The CD3εγ heterodimer is essential for expression and function of the T cell receptor. The crystal structure of the human CD3εγ heterodimer is described to 2.1-Å resolution complexed with OKT3, a therapeutic mAb that not only activates and tolerizes mature T cells but also induces regulatory T cells. The mode of CD3εγ dimerization provides a general structural basis for CD3 assembly and maps candidate T cell antigen receptor docking sites, including a duplicated linear region rich in acidic residues that is unique to human CD3ε. OKT3 binds to an atypically small area of CD3ε and has a low affinity for the isolated CD3εγ heterodimer. The structure of the OKT3/CD3εγ complex has implications for T cell signaling and therapeutic design.
Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography
Authors: Xi Chuanwu , Marks Daniel L. , Parikh Devang S. , Raskin Lutgarde , Boppart Stephen A.
Published: May 2004

To achieve high mixing efficiency in microfluidic devices, complex designs are often required. Microfluidic devices have been evaluated with light and confocal microscopy, but fluid-flow characteristics at different depths are difficult to separate from the
en face
images produced. By using optical coherence tomography (OCT), an imaging modality capable of imaging 3D microstructures at micrometer-scale resolutions over millimeter-size scales, we obtained 3D dynamic functional and structural data for three representative microfluidic mixers: a Y channel mixer, a 3D serpentine mixer, and a vortex mixer. In the serpentine mixer, OCT image analysis revealed that the mixing efficiency was linearly dependent on the Reynolds number, whereas it appeared to have exponential dependence when imaged with light microscopy. The visual overlap of fluid flows in light-microscopy images leads to an overestimation of the mixing efficiency, an effect that was eliminated with OCT imaging. Doppler OCT measurements determined velocity profiles at various points in the serpentine mixer. Mixing patterns in the vortex mixer were compared with light-microscopy and OCT image analysis. These results demonstrate that OCT can significantly improve the characterization of 3D microfluidic device structure and function.
Neutralizing antibodies to hepatitis C virus (HCV) in immune globulins derived from anti-HCV-positive plasma
Authors: Yu Mei-ying W. , Bartosch Birke , Zhang Pei , Guo Zheng-ping , Renzi Paula M. , Shen Li-ming , Granier Christelle , Feinstone Stephen M. , Cosset François-Loïc , Purcell Robert H.
Published: May 2004

The role of humoral immunity in hepatitis C virus (HCV) infections is uncertain. Nevertheless, there is increasing evidence for neutralizing antibodies to HCV in the serum or plasma of chronically infected individuals. Immune globulins prepared by ethanol fractionation of plasma had long been considered safe until a commercial immune globulin product, Gammagard, prepared from plasma from which units containing anti-HCV had been excluded, transmitted HCV to recipients. Studies suggested that the exclusion might have removed neutralizing antibodies from the plasma and hence compromised the safety of the resulting immune globulins. In the present study, by using chimpanzees and a recently validated
in vitro
system based on neutralization of infectious HCV pseudoparticles, we found broadly reactive neutralizing and protective antibodies in experimental immune globulin preparations made from anti-HCV-positive donations. Neutralizing antibodies were also found in Gammagard lots made from unscreened plasma that did not transmit hepatitis C but not in Gammagard lots, which were prepared from anti-HCV-screened plasma, that did transmit hepatitis C. The results provide an explanation for the mechanism by which the safety of this product was compromised. Immune globulins made from anti-HCV-positive plasma and containing broadly reactive neutralizing antibodies may provide a method of preventing HCV infection.
The UbcH8 ubiquitin E2 enzyme is also the E2 enzyme for ISG15, an IFN-α/β-induced ubiquitin-like protein
Authors: Zhao Chen , Beaudenon Sylvie L. , Kelley Melissa L. , Waddell M. Brett , Yuan Weiming , Schulman Brenda A. , Huibregtse Jon M. , Krug Robert M.
Published: May 2004

Ubiquitin-(Ub) like proteins (Ubls) are conjugated to their targets by an enzymatic cascade involving an E1 activating enzyme, an E2 conjugating enzyme, and in some cases an E3 ligase. ISG15 is a Ubl that is conjugated to cellular proteins after IFN-α/β stimulation. Although the E1 enzyme for ISG15 (Ube1L/E1
ISG15
) has been identified, the identities of the downstream components of the ISG15 conjugation cascade have remained elusive. Here we report the purification of an E2 enzyme for ISG15 and demonstrate that it is UbcH8, an E2 that also functions in Ub conjugation.
In vitro
assays with purified Ub E2 enzymes and
in vivo
RNA interference assays indicate that UbcH8 is a major E2 enzyme for ISG15 conjugation. These results indicate that the ISG15 conjugation pathway overlaps or converges with the Ub conjugation pathway at the level of a specific E2 enzyme. Furthermore, these results raise the possibility that the ISG15 conjugation pathway might use UbcH8-competent Ub ligases
in vivo
. As an initial test of this hypothesis, we have shown that a UbcH8-competent Ub ligase conjugates ISG15 to a specific target
in vitro
. These results challenge the concept that Ub and Ubl conjugation pathways are strictly parallel and nonoverlapping and have important implications for understanding the regulation and function of ISG15 conjugation in the IFN-α/β response.
Risk and panic in late modernity: implications of the converging sites of social anxiety
Authors: Hier Sean P.
Published: May 2004

Comparing moral panic with the potential catastrophes of the risk society, Sheldon Ungar contends that new sites of social anxiety emerging around nuclear, medical, environmental and chemical threats have thrown into relief many of the questions motivating moral panic research agendas. He argues that shifting sites of social anxiety necessitate a rethinking of theoretical, methodological and conceptual issues related to processes of social control, claims making and general perceptions of public safety. This paper charts an alternative trajectory, asserting that analytic priority rests not with an understanding of the implications of changing but converging sites of social anxiety. Concentrating on the converging sites of social anxiety in late modernity, the analysis forecasts a proliferation of moral panics as an exaggerated symptom of the heightened sense of uncertainty purported to accompany the ascendency of the risk society.
Neutralization theory and the denial of risk: some evidence from cannabis use among French adolescents*
Authors: Peretti‐Watel Patrick
Published: May 2004

In contemporary societies, risk culture and risk profiling lead to the stigmatization of unhealthy behaviours as ‘risky’. Risk denial theory refers to a cognitive way to deal with risky behaviours and can be considered as an updated variant of Sykes and Matza's neutralization theory. People neutralize the ‘risky’ label using specific techniques that must be added to those previously enlisted by Sykes and Matza. This paper introduces and discusses three techniques of risk denial: scapegoating, self‐confidence and comparison between risks. As it is usually defined and studied as a ‘risky behaviour’, cannabis use provides a relevant example to illustrate these types of risk denial, thanks to various ethnographic studies (including Becker's seminal work on marijuana smokers) and quantitative French data from the 1999 European School Survey on Alcohol and Other Drugs (ESPAD). In order to deny the ‘risky’ label, cannabis users scapegoat ‘hard drugs’ users, they emphasize their own ability to control their consumption personally, or they compare cannabis and alcohol risks. The paper concludes with suggestions for further analyses of risk denial.
The revival of death: expression, expertise and governmentality
Authors: Árnason Arnar , Hafsteinsson Sigurjón Baldur
Published: May 2004

This paper discusses Walter's (1994) assertion that death in the West has recently undergone a revival. In particular it focuses on his claim that this revival is composed of two different strands: a late modern strand and a postmodern strand. The former, according to Walter, is driven by experts who seek to control death, the latter by ordinary people who seek to express their emotions freely. Describing the history and work of Cruse Bereavement Care, the largest bereavement counselling organization in the UK, we question Walter's distinction. We then problematize Walter's suggestion that the revival of death is caused by general social transformations. In contrast we evoke Rose's (1996) work on ‘subjectification’ and seek to link recent changes in the management of death and grief to permutations in governmental rationality.
Mythscapes: memory, mythology, and national identity
Authors: Bell Duncan S. A.
Published: May 2004

In this paper I seek to challenge the dominant modes of conceiving the relationship between memory and national identity, and in so doing offer analysts of nationalism an improved understanding of the dynamics of national identity formation. The concept of collective memory is invoked regularly in attempts to explain the pervasiveness and power of nationalism. I argue that the concept is misused routinely in this context, and instead I employ a ‘social agency’ approach to theorizing, whereby memory is conceived in a more limited and cogent manner. I argue that it is important to distinguish clearly between memory and mythology, both of which are essential to understanding national identity, for not only are the two concepts distinct, they can also act in opposition to each other. Following from this I introduce the notion of a ‘mythscape’, the temporally and spatially extended discursive realm in which the myths of the nation are forged, transmitted, negotiated, and reconstructed constantly. Through employing the idea of a mythscape we can relate memory and mythology to each other in a theoretically profitable way.
Intermarriage and the demography of secularization
Authors: Voas David
Published: May 2004

One way of measuring religious affiliation is to look at rites of initiation such as baptism. English statistics show that for the first time since the Church of England was founded, less than half the nation is Anglican on this criterion. The pattern of formal religious transmission changed during the Second World War. Previously christening was quasi‐universal, and the Church of England was the preferred provider. By the end of the war baptism was evidently optional, and chosen principally by parents whose religious identities matched. Further analysis suggests that affiliation now tends to be lost following marriage to someone from a different religious background, though the USA differs from Europe in this respect. A demographic theory of advanced secularization is outlined that specifies a proximal cause for declining religious affiliation, and provides tools for predicting the changes to be expected over future decades. The theory also helps to explain why affiliation may fall most quickly where there is most religious diversity.
A life‐course perspective on social exclusion and poverty
Authors: Dewilde Caroline
Published: May 2004

This article assesses whether it is possible to reconceptualize the traditional research approaches to the relationship between poverty and the life cycle on the basis of different sociological perspectives on the life course found in the literature. While the family‐cycle approach, which was originally formulated by Seebohm Rowntree (1902), is criticized for being static, descriptive, normative and inflexible, dynamic poverty research is mostly confined to the quantitative analysis of income trajectories, and thus offers only a partial solution to our problem. However, the life‐course perspective allows us to combine the best elements of these traditional approaches and to reconceptualize them into a general framework for the study of social exclusion and poverty. To this end, three sociological perspectives on the life course are considered: the traditional North‐American life‐course perspective formulated by Elder (1974), the Continental institutional approach, and a combined approach which we label the ‘political economy of the life course’. Drawing from these three perspectives, we propose a general framework of analysis and formulate hypotheses regarding the phenomena of social exclusion and poverty over the life course which can subsequently be empirically validated.
What Drives the Configuration of Information Technology Projects? Exploratory Research in 10 Organizations
Authors: Martin Andrew
Published: May 2004

The development of high quality technical systems is an ongoing important element of information systems success. This paper investigates the current practice of information technology project configuration from a management viewpoint. It is based on a series of semi-structured interviews across a range of medium to large organizations in the UK, including both users and providers of IT services. It finds that project requirements, strategic IT policies, risk management, pragmatic considerations, the managed exploitation of experience and the managed adoption of new technologies drive individual project configuration. The paper proposes a new integrated model that explicitly identifies the drivers of project configuration management. It illustrates the model using a published case study and generates directions for further research and implications for practitioners.
Opportunities to Learn from ‘Failure’ with Electronic Commerce: A Case Study of Electronic Banking
Authors: Huang Jimmy , Makoju Enesi , Newell Sue , Galliers Robert D.
Published: May 2004

This study reports on the experience of the First Atlantic Bank of Nigeria as it embarked on the implementation and introduction of Internet and mobile banking services. Based on the concept of a logic of opposition the study conceptualizes the case company's effort with a specific emphasis on the mode and impact of learning that occurred intra- and inter-organizationally. The case considers how being a first mover in a given market can be crucial, not necessarily because of the immediate commercial benefit, but more because of the opportunity for developing customers’ trust in order to ensure the success of future innovations. In addition, the case illustrates the problematic nature of evaluating the success or failure of an innovation. Further, it shows how failure can be an intermediate step to future success, while making the point, counter-intuitively perhaps, that blindly listening to customers may prove to be a barrier to successful innovations. Thus, firms might capitalize from what might initially be perceived as failure, in particular through transforming an opposing force into a promoting one.
Overcoming Stakeholder Barriers in the Automotive Industry: Building to Order with Extra-Organizational Systems
Authors: Howard Mickey , Vidgen Richard , Powell Philip
Published: May 2004

The automotive industry must significantly change its outdated and unprofitable ‘sell-from-stock’ business model to a streamlined ‘build-to-order’ model. Extra-organizational systems (EOS) enable multiple firms to share industry-level systems linked by electronic portals and hubs. Successful EOS implementation requires a coordinated effort among various stakeholders including customers, dealers, vehicle manufacturers, first- and second-tier suppliers and logistics firms. However, each of these stakeholders erects different but significant structural, managerial, user and technical barriers to EOS. This paper analyses these stakeholder barriers and prescribes how they must be managed in order to implement EOS successfully. Three recommendations raise concern over (1) the differentiation between EOS and inter-organizational systems, (2) industry dynamics, particularly the role of suppliers and customers and (3) supply topology, i.e. the importance of World Wide Web services and standards in creating electronic markets.
Writing Case Studies in Information Systems Research
Authors: van der Blonk Heico
Published: May 2004

Case study research can be reported in different ways. This paper explores the various ways in which researchers may choose to write down their case studies and then introduces a subsequent typology of writing case studies. The typology is based on a 2 × 2 matrix, resulting in four forms of writing case studies: chronology, play, biography and voices. The four forms are characterized and discussed and some methodological issues concerning the writing of case studies are highlighted.
What Will it Take for China to Become a Competitive Force in Offshore Outsourcing? An Analysis of the Role of Transaction Costs in Supplier Selection
Authors: Zhonghua Qu , Brocklehurst Michael
Published: May 2004

Using transaction costs theory this paper argues that transaction costs are almost as significant as production costs when it comes to offshore outsourcing and, moreover, that it is in the field of transaction costs where China has been unable to compete with India in the supply of information technology outsourcing. The paper outlines a framework for analysing transaction costs and uses the framework for pinpointing where China is unable to compete. The paper concludes with a review of the policy implications for the Chinese Government.
Remembering the Forgotten? Reminiscence, Hypermnesia and Memory for Order
Authors: Kelley Matthew R. , Nairne James S.
Published: May 2004

Three experiments established that repeated testing affects item and order retention differently: Hypermnesia was found with repeated free recall tests, whereas net performance declined significantly across successive free reconstruction of order tests. Overall order performance declined over tests under a variety of encoding conditions (pictures, words, and relational and item-specific processing) and retrieval conditions (intentional and incidental learning). Although net performance dropped across tests, participants did show reliable order recovery (reminiscence) between tests. The implications of these data for general theories of hypermnesia and order are discussed.
Risk factors of perinatal mortality in Lithuania, 1997 - 1998
Authors: Gaižauskienė Aldona , Padaiga Žilvinas , Basys Vytautas , Grigorjev Grigorij , Mizerienė Rūta
Published: May 2004

Aim: The aim of this paper is to determine the risk factors of perinatal mortality in Lithuania during 1997 - 1998. Methods: The focus of the study is the 1997-1998 Medical Birth Register Database (N=75,178) covering social-demographic factors, the obstetric anamnesis of previous pregnancies, as well as mothers health behaviour and pathology of the current pregnancy, delivery and obstetric aid. The multivariate analysis assessing odds ratios of risk factors for perinatal mortality using logistic regression has been carried out and related population attributable risk fractions were calculated. Results: A statistically significant (p<0.01) model predicting perinatal mortality has been obtained in which 19 out of 76 analysed factors have been distinguished to be statistically significant. The septic state of the mother during the delivery (OR=13.3; CI=8.9 - 19.9) and haemorrhage due to a premature placental separation (OR=11.6; CI=7.9 - 16.9) were associated with substantial increased risks of the foetus. Factors from other groups (perinatal pathology during previous pregnancies and social, behavioural or environmental factors) had somewhat lower, though significant, risk on perinatal mortality. The highest population attributable risk fraction (PARF) was found for the breech birth and foetal growth retardation (PARF=13 percent and PARF=9.7 percent, respectively). It should be pointed out that the impact of marital status on perinatal mortality was very high (PARF=6.4 percent), even higher than that of some clinical factors, though its odds ratio was among the lowest (OR=1.5; CI=1.2 - 1.7). Conclusion: During 1997 - 1998, the highest risk for perinatal mortality in Lithuania was associated with obstetric aid during delivery and pathology of current pregnancy. These groups of risk factors had also the highest population attributable risk fraction.
Optoelectronic Logical Gates “AND”, “OR” and “NOT”
Authors: Porada Zbigniew , Schabowska-Osiowska Elzbieta
Published: May 2004

Optoelectronic AND, OR and NOT logical gates were composed of thin film photoconducting and electroluminescent elements, made of cadmium sulphide and zinc sulphide, respectively, doped with copper, chlorine and manganese. The gates consisted of several photoconducting elements and one electroluminescent element suitably connected and supplied with a sinusoidal voltage. In such circuits the functions of product, sum
and negation for input light signals illuminating the photoconducting elements were realized, and the output signal was the light emitted by the electroluminescent element.
The immunoregulatory and allergy‐associated cytokines in the aetiology of the otitis media with effusion
Authors: Smirnova Marina G. , Birchall John P. , Pearson Jeffrey P.
Published: May 2004

Inflammation in the middle ear mucosa, which can be provoked by different primary factors such as bacterial and viral infection, local allergic reactions and reflux, is the crucial event in the pathogenesis of otitis media with effusion (OME). Unresolved acute inflammatory responses or defective immunoregulation of middle inflammation can promote chronic inflammatory processes and stimulate the chronic condition of OME. Cytokines are the central molecular regulators of middle ear inflammation and can switch the acute phase of inflammation in the chronic stage and induce molecular‐pathological processes leading to the histopathological changes accompanying OME. In this review we present cytokines identified in otitis media, immunoregulatory [interleukin (IL)‐2, IL‐10, transforming growth factor‐β]) and allergy associated (IL‐4, IL‐5, granulocyte‐macrophage colony‐stimulating factor), as crucial molecular regulators, responsible for chronic inflammation in the middle ear and the chronic condition of OME.
Developing students’ conceptions of quality in geography
Authors: Davies Peter , Durbin Chris , Clarke Jon , Dale Julie
Published: May 2004

In this article we present evidence linking an improvement in students’ conceptions of quality in their work in geography with improvements in the outcomes of their learning. In the first part of the article we develop a rationale for the approach to formative assessment employed in this research. Our results are derived from testing this approach in three schools using control and intervention groups. In the light of these results we comment on some dichotomies in assessment and learning that have been suggested in previous research.
A longitudinal study of teacher change: what makes professional development effective?
Authors: Boyle Bill , While David , Boyle Trudy
Published: May 2004

This preliminary analysis is part of the baseline phase of a longitudinal study designed to investigate the professional development of primary and secondary teachers across England. The study addresses four key research areas. The prevailing models of professional development for teachers in England are identified in this baseline phase and the scene is set for the remaining areas of investigation to be addressed (annual data collection sweeps will continue).
Abuses of grammar teaching: the role of crisis discourse in appropriating a potentially innovative language syllabus for Singapore schools
Authors: Kramer‐Dahl Anneliese
Published: May 2004

In 1999 the issue of grammar and its teaching re‐emerged in Singapore as a topic of great intensity in a government‐managed media debate. As studies in other educational contexts have shown, debates about grammar in political discussions and in the media typically proceed in terms of a discourse of crisis and falling standards. More specifically, in Singapore this anxiety over language and correctness has repeatedly served to take attention away from a concern with how literacy is effectively taught. My particular interest is in the ways in which this discourse of crisis fuelled by the media, and the nationwide in‐service English grammar course which was offered in its wake as a quick‐fix solution, impacted on the English Language Syllabus that was introduced at the same time. I undertake a critical reading of the English grammar course materials for teachers, their assumptions about grammar and what grammar teaching is for, and how they could seriously interfere with, and co‐opt, a potentially innovative syllabus which foregrounds generic competency and grammar as a social meaning‐making resource.
Microcirculatory Heterogeneity in the Rat Small Intestine During Compromised Flow Conditions
Authors: VAJDA KORNÉL , SZABÓ ANDREA , KUCSA KATALIN , SUKI BÉLA , BOROS MIHÁLY
Published: May 2004

Objective: To characterize and compare microcirculatory changes in the rat small intestinal tissue layers when temporal or spatial microvascular perfusion heterogeneity is present.

Methods: Intravital videomicroscopy with an orthogonal polarization spectral imaging technique was used to visualize the microcirculation of the intestinal mucosa and the longitudinal muscle during systemic (hemorrhagic shock, endotoxemia, and nitric oxide synthesis inhibition) and local (ischemia–reperfusion) circulatory disorders. The average capillary red blood cell velocity (A‐RBCV) was calculated from the relative durations of the observed velocity or as a function of the perfused area, respectively.

Results: During hemorrhagic hypotension/resuscitation, timewise (flowmotion) and spatial heterogeneity were found to evolve in the mucosal villi and muscle layer. During resuscitation, the A‐RBCV decreased by 40% in the villi and by 60% in the muscle. Reperfusion after a 30‐min period of mesenteric ischemia caused a 20% reduction in A‐RBCV in both layers, while endotoxin infusion caused a temporary 20% decrease in the mucosa, and a persistent, > 25% decrease in the muscle. Nitric oxide synthesis inhibition resulted in spatial heterogeneity within the villi and in a 40% decrease in A‐RBCV in both structures.

Conclusions: Calculations of timewise variability and of heterogeneity within and between layers can be used for the comparison of distinct intramural microcirculatory changes.
Measurement of Muscle Microvascular Oxygen Pressures: Compartmentalization of Phosphorescent Probe
Authors: POOLE DAVID C. , BEHNKE BRAD J. , McDONOUGH PAUL , McALLISTER RICHARD M. , WILSON DAVID F.
Published: May 2004

Objective: To determine whether the phosphorescent probe Oxyphor R2 (a palladium porphyrin dendrimer) becomes extravasated within normotensive skeletal muscle, R2 perfusion and washout studies were performed using a perfused rat hindlimb preparation.

Methods: Phosphorescence signals were monitored in tibialis anterior muscles after 35 min of R2 blood perfusion and across a subsequent washout period that included vasodilation (sodium nitroprusside, SNP, ∼3 × 10−2 M).

Results: Two responses were evident: Group 1 (n = 4)—Inflowing blood pressure and vascular conductance remained stable close to initial values and subsequently a marked vasodilation was evident with SNP (vascular conductance; R2 blood perfusion, 0.096 ± 0.005; washout, pre‐SNP, 0.085 ± 0.005, post‐SNP, 0.110 ± 0.005 mL/min/mmHg, p < .05, for pre‐ vs. post‐SNP). Baseline phosphorescence signals could be monitored up to 99 ± 36 s post‐SNP when the phosphorescence signal disappeared. For these muscles, palladium content was undetectable. Group 2 (n = 3)—Inflowing blood pressure increased 112% and vascular conductance fell ∼ 50%. These hindlimbs were unresponsive to SNP, phosphorescence signal was undiminished by washout and SNP, and muscles became edematous.

Conclusions: These results suggest that in normotensive muscle (i.e., Group 1 above), extravasation of phosphorescent probe R2 over 35 min of perfusion is insufficient to yield a detectable phosphorescence signal in skeletal muscle.
Impact of the Fåhraeus Effect on NO and O2 Biotransport: A Computer Model
Authors: LAMKIN‐KENNARD KATHLEEN A. , JARON DOV , BUERK DONALD G.
Published: May 2004

Nitric oxide (NO) and oxygen (O2) transport in the microcirculation are coupled in a complex manner, since enzymatic production of NO depends on O2 availability, NO modulates vascular tone and O2 delivery, and tissue O2 consumption is reversibly inhibited by NO. The authors investigated whether NO bioavailability is influenced by the well‐known Fåhraeus effect, which has been observed for over 70 years. This phenomenon occurs in small‐diameter blood vessels, where the tube hematocrit is reduced below systemic hematocrit as a plasma boundary layer forms near the vascular wall when flowing red blood cells (rbcs) migrate toward the center of the bloodstream. Since hemoglobin in the bloodstream is thought to be the primary scavenger of NO in vivo, this might have a significant impact on NO transport. To investigate this possibility, the authors developed a multilayered mathematical model for mass transport in arterioles using finite element numerical methods to simulate coupled NO and O2 transport in the blood vessel lumen, plasma layer, endothelium, vascular wall, and surrounding tissue. The Fåhraeus effect was modeled by varying plasma layer thickness while increasing core hematocrit based on conservation of mass. Key findings from this study are that (1) despite an increase in the NO scavenging rate in the core with higher hematocrit, the model predicts enhanced vascular wall and tissue NO bioavailability due to the relatively greater resistance for NO diffusion through the plasma layer; (2) increasing the plasma layer thickness also increases the resistance for O2 diffusion, causing a larger PO2 gradient near the vascular wall and decreasing tissue O2 availability, although this can be partially offset with inhibition of O2 consumption by higher tissue NO levels; (3) the Fåhraeus effect can become very significant in smaller blood vessels (diameters < 30 μm); and (4) models that ignore the Fåhraeus effect may underestimate NO concentrations in blood and tissue.
Retention of Albumin in the Circulation is Governed by Saturable Renal Cell‐Mediated Processes
Authors: KOLTUN MARIA , COMPER WAYNE D.
Published: May 2004

Objective: To examine the role of renal processing in the turnover of circulating albumin in the model of reversible overload proteinuria. Specifically, this study determines whether proteinuria due to hyperalbuminemia may be attributed to saturation of renal cell processing of albumin or alterations in diffusive/convective transport of albumin across the glomerular capillary wall.

Methods: Overload proteinuria was induced in male Wistar rats by daily intraperitoneal injections of 1.5 g bovine serum albumin (BSA; endotoxin free) for 3 days. Plasma concentration and urinary excretion of total protein and rat serum albumin (RSA) were determined by the biuret assay and radioimmunoassay, respectively. Glomerular size selectivity was assessed by examining the fractional clearance (FC) of neutral [3H]Ficoll using a short‐term, steady‐state approach. Cellular processing was examined by size exclusion chromatography analysis of urinary [14C]albumin and [14C]transferrin structural integrity.

Results: Total protein excretion (n = 4–15) increased 7‐fold in BSA‐treated rats (58 ± 26 mg/24 h at baseline vs. 417 ± 259 mg/24 h at day 3), while intact RSA excretion (n = 4–6) increased 200‐fold (0.27 ± 0.15 mg/24 h vs. 53 ± 26 mg/24 h) despite a significant decrease in its plasma concentration. Total protein and albumin excretion returned to basal levels by day 7 (82 ± 16 mg/24 h and 0.93 ± 0.42 mg/24 h, respectively). FC of [3H]Ficoll of equivalent size to albumin did not change in BSA‐treated rats as compared to vehicle controls. Tubular lysosomal processing of proteins was altered at peak proteinuria, as determined by changes in the structural integrity of urinary [14C]albumin, as well as [14C]transferrin, but returned to normal by day 7.

Conclusions: This study demonstrates the lack of proportionality between changes in plasma concentration and urinary excretion of albumin, as well as the lack of change in the glomerular size selectivity to albumin. The profound but reversible changes in the amount and integrity of excreted protein suggest that cell‐mediated processes are saturated by albumin concentrations, leading to the development of proteinuria in this model.
Differential Expression of E‐ and P‐Selectin in the Microvasculature of Sickle Cell Transgenic Mice
Authors: Wood Katherine , Russell Janice , Hebbel Robert P. , Granger D. Neil
Published: May 2004

Objective:There is a growing body of evidence that endothelial cells assume an inflammatory phenotype in sickle cell disease. The authors determined whether (1) the expression of E‐ and P‐selectin differs between sickle cell transgenic (βS) mice and their wild‐type counterparts, and (2) blood platelets and/or neutrophils contribute to the altered selectin expression.

Methods:Expression of E‐ and P‐selectin was measured in different regional vascular beds of wild‐type and βSmice (with or without thrombocytopenia or neutropenia) using the dual radiolabeled monoclonal antibody technique.

Results:Constitutive expression of P‐selectin was significantly increased in the heart, lungs, small bowel, large bowel, and penis of βSversus WT mice. While thrombocytopenia reduced P‐selectin expression in the small bowel and penis of βSmice, neutropenia was associated with a reduction in P‐selectin expression only in the penis. E‐selectin expression was not significantly elevated in any vascular bed except the penis of βSmice.

Conclusions:Sickle cell disease promotes an increased P‐selectin expression in several vascular beds. An accumulation of platelets may explain the increased P‐selectin expression observed in some vascular beds.
An Adenovirus‐Mediated Gene‐Transfer Model of Angiogenesis in Rat Mesentery
Authors: WANG WEN‐YING , WHITTLES CHERYL E. , HARPER STEVEN J. , BATES DAVID O.
Published: May 2004

Objective: To develop an adenovirus‐mediated angiogenesis model, dependent on VEGF, in a system amenable to functional characterization.

Methods: Adenovirus (AdV) expressing VEGF (Ad‐VEGF) or GFP (Ad‐EGFP) (1–3.3 × 108 TCID50/mL), and Monastral blue were injected into the fat pad on either side of a mesenteric connective tissue panel of halothane‐anesthetized male Wistar rats after intravital microscopic imaging. The intestine was replaced in the animal, the laparotomy was sutured, and the animal was allowed to recover. Six days later, the same connective tissue panel was identified from the Monastral blue depot and the mesentery was imaged as before, and then excised, fixed, and stained for endothelial cells (GSL isolectin‐1B4), proliferating cells, VEGF, VEGF‐R2, and actin. The increase in fractional microvascular area (FVA) was measured, and proliferating cell density, sprout density, vessel branch point density, vessel density, and mean vessel length were determined.

Results: AdVEGF injection significantly increased the fractional vessel area (2.9 ± 0.4‐fold), proliferating endothelial cell density (1.7 ± 0.1‐fold), sprout density (3.1 ± 0.3‐fold), branch point density (1.9 ± 0.1‐fold), and the microvessel density (1.4 ± 0.1‐fold), and decreased the mean vessel length (0.69 ± 0.04‐fold). VEGF‐R2 staining was evident near sprouting tips of endothelial cells, but not on the tip itself, and evidence for arteriogenesis was observed as well as clear evidence of angiogenesis.

Conclusions: Ad‐VEGF injection into the fat pad of the rat induced significant angiogenesis in the mesentery. This two‐dimensional model of VEGF‐induced angiogenesis is amenable to physiological, biochemical, and molecular assessment and may be a useful tool to help understand mechanisms of angiogenesis.
Acetylcholine‐Induced Vasodilation and Reactive Hyperemia Are Not Affected by Acute Cyclo‐Oxygenase Inhibition in Human Skin
Authors: Dalle‐Ave Anne , Kubli Sandrine , Golay Sandrine , Delachaux Anne , Liaudet Lucas , Waeber Bernard , FEIHL FRANÇOIS
Published: May 2004

Objective:To examine whether prostaglandins are involved in endothelium‐dependent vasodilatory responses of the skin microcirculation.

Methods:Twenty‐three young male volunteers were studied on 2 different days 1–3 weeks apart. On each experimental day the forearm skin blood flow response to iontophoretically applied acetylcholine (Ach, an endothelium‐dependent vasodilator) was determined with laser Doppler imaging following the intravenous administration of either the cyclo‐oxygenase inhibitor lysine acetylsalicylate (L‐AS), 900 mg, or the oral intake of indomethacin, 75 mg. Acetylcholine was iontophoresed both in presence and in absence of surface anesthesia. In some subjects, the effects of L‐AS on skin reactive hyperemia were also assessed.

Results:Acute cyclo‐oxygenase inhibition with either drug influenced neither the skin blood flow response to 4 different doses of Ach (0.28, 1.4, 7, and 14 mC/cm2) nor reactive hyperemia. The peak vasodilatory response to Ach was significantly increased by skin anesthesia, regardless of whether the subjects received the cyclo‐oxygenase inhibitor or not. For example, the mean response (± SD) to the largest dose of Ach (tested in 6 subjects, expressed in perfusion units) were as follows: in absence of anesthesia: L‐AS 339 ± 105, placebo 344 ± 68; with anesthesia: L‐AS 453 ± 76, placebo 452 ± 65 (p< .01 for effect of anesthesia).

Conclusions:These data give no support for a contribution of prostaglandins to acetylcholine‐induced vasodilation or to reactive hyperemia in the skin microcirculation. In this vascular bed, local anesthesia seems to amplify acetylcholine‐induced vasodilation via a prostaglandin‐independent mechanism.
Functional ability in the elderly Finnish population: time period differences and associations, 1985—99
Authors: Sulander Tommi T. , Rahkonen Ossi J. , Uutela Antti K.
Published: May 2004

Aims: The aim of this study was to determine whether functional ability among 65- to 79-year-old Finnish men and women changed at population level from the 1980s to 1990s and how gender, age, previous occupation, and marital status are associated with functional ability and whether these associations have changed over time. Methods: Biennial surveys on health behaviour among Finnish elderly people were used to study 10,309 men and women from 1985 to 1999. Age, gender, previous occupation, and marital status were the demographic variables. Logistic regression was used to determine differences. Results: Functional ability deteriorated clearly with age, but was slightly better in the 1990s than 1980s. Gender differences of functional ability were small. Retired office employees had the best functional ability. Moreover, time changes of functional ability between occupational groups were a little more positive among men than among women. Functional ability of divorced and widowed elderly emerged as slightly worse than among married persons. Conclusions: Young age and non-manual occupation prior to retirement were associated with better functional ability. The overall improvement of self-reported functional ability among elderly people suggests that the onset of disabilities could be postponed, especially if health-related circumstances were more evenly distributed at the start of or even before retirement age.
Part process analysis: a qualitative method for studying provider—patient interaction
Authors: Steihaug Sissel , Malterud Kirsti
Published: May 2004

Aims: Communication between patients and healthcare providers is vital for quality care. Complaints about doctors often arise from unfortunate communication. Research methods suited for the study of relationship and interaction are essential to understand how communication can be improved. The principles and procedures of a qualitative research method with the capacity to explore details and foundations of interaction between patients and doctors is presented. Methods: Anne-Lise Løvlie Schibbye's Part Process Analysis Method is a qualitative approach for studying communication at the micro-level. Attention is drawn both to verbal dialogue and to body communication, and the method is particularly suited for studying relationships and change. Results: The application of the Part Process Analysis Method is described, exemplified by material from a group discussion between participants and leaders in a group-based treatment programme for women with chronic muscle pain. How the method can be used to explore reciprocity, relationships, and development is demonstrated in this context. Conclusions: The Part Process Analysis Method is proposed as a useful tool for studying communication between doctor and patient, providing knowledge about relationships and reciprocity, aspects that are important both in doctors' medical work and for patients' feeling of being understood.
Prevalence and incidence of prolonged and severe dyspareunia in women: results from a population study
Authors: Danielsson Ingela , Sjöberg Inga , Stenlund Hans , Wikman Marianne
Published: May 2004

Aims: The principle aim of this study was to investigate the prevalence and incidence of prolonged (≥6 months) and severe dyspareunia in a non-patient population of women, and to explore the rate of recovery as well as the inclination to seek medical care. Another aim was to compare the use of oral contraceptives among women who had ever had dyspareunia and those who had not. Methods: A total of 3,017 women aged 20—60 participating in a screening program for cervical cancer answered a questionnaire about possible painful coitus. Results: The prevalence was 9.3% for the whole group and 13% for women aged 20—29 and 6.5% for the women aged 50—60, with a risk ratio of 2.0 (95% CI 1.4—2.8) for the youngest age group compared with the oldest. The incidence risk ratio was 9.3 (95% CI 2.8—30.9) for the youngest age group compared with the oldest. Using age-specific incidence rates, a rising incidence of dyspareunia in young women was demonstrated. Of the women who had ever had prolonged and severe dyspareunia 28% had consulted a physician for their symptoms; 20% recovered after treatment, while 31% recovered spontaneously. No differences were found in the use of oral contraceptives between the women who had had dyspareunia and those who had not. Conclusions: Prolonged and severe dyspareunia is a great health problem among all women and especially young women, for whom a rising incidence of dyspareunia is suggested and discussed. Surprisingly few women have consulted a physician, raising the question of why this is the case and what can be done about it.
Cost of dementia: impact of disease progression estimated in longitudinal data
Authors: Kronborg Andersen Christian , Lauridsen Jørgen , Andersen Kjeld , Kragh-Sørensen Per
Published: May 2004

Aims: Several studies have shown that health care costs are higher for demented than for non-demented persons and that health care costs are higher for more severe demented persons than less severe demented persons. However, most studies report on cross-sectional study designs, and thus fail to examine the influence of disease progression on changes in health care costs to individual persons. The objective of this study was, using longitudinal data, to examine changes in total health care costs with disease progression in demented persons. Methods: We assumed that disease progression could be characterised by transitions between different states of dementia which reflected the degree to which the disease progressed over time. Then, changes in health care costs were regressed on a set of explanatory variables including disease progression. A total of 465 demented and non-demented persons were interviewed twice. The time between interviews was about three years. Before each interview, the participant was examined for dementia and classified by type of dementia (Alzheimer's disease, vascular or other types of dementia) and degree of dementia (very mild, mild, moderate, severe). Results: The results of this longitudinal study confirmed that health care costs increased over time for non-demented as well as for demented persons and that health care costs increased with disease progression. In particular, the health care costs increased when the disease had progressed into the severe state of the dementia. Also, decline in functional abilities was an important factor for explaining changes in health care costs.
Women's experiences of long term sickness absence: implications for rehabilitation practice and theory
Authors: Ockander Marlene K. , Timpka Toomas
Published: May 2004

Background: In most European countries, spells of long-term absence contribute the largest number of days that are reimbursed as a result of sickness absence. This group is growing and it is constituted mainly of women. Aim: The present study seeks further knowledge about what happens then and there, i.e. how women on long-term sickness absence handle and explain, for themselves and others, this interruption in their daily life. Methods: Semi-structured interviews were performed with 82 middle-aged women with personal experience of long-term sickness absence. Results: The women's accounts of sickness absence contained interpretations of what had happened to them, how things were at present, and what they thought the future would bring. Three different accounts could be distinguished: crisis, breakpoint, and migration. The perception of their own situation and especially what they thought about their future was associated with their feeling of power to take the initiative, and their well-being. Conclusion: From this study the authors have found implications for central topics of importance: time elapse, sense of coherence, reorientation/adaptation, vital goals, and gender.
Social position and health in old age: the relevance of different indicators of social position
Authors: Avlund Kirsten , Holstein Bjørn E. , Osler Merete , Damsgaard Mogens T. , Holm-Pedersen Poul , Rasmussen Niels K.
Published: May 2004

Aims: An analysis was undertaken to investigate social inequalities in health among old men and women in relation to five indicators of social position. Methods: The study is based on a population-based cross-sectional survey among 748 75-year-old men and women, which was performed as clinical examinations and interviews in 1989 in Glostrup, a suburban area west of Copenhagen. Social position was measured by vocational education, occupation, social class, income, and housing tenure. Health was measured by number of chronic diseases, tiredness in relation to mobility, need of help in relation to mobility, oral health (number of teeth), and well-being (the CES-D Scale). The statistical analysis included bivariate contingency tables and logistic regression analyses. Results: Two material wealth variables (income and tenure) were consistently related to nearly all health measures while the relationships between the other social position variables and health showed no consistent patterns. Multiple logistic regression analyses with tenure and income as independent variables and each of the health variables as dependent variables and control for education and occupation showed different patterns for men and women. In men the odds ratios of housing tenure on four health variables were strong and unaffected by education and occupation while in women the odds ratios of income on three health variables were strong and unaffected by education and occupation. Conclusion: This study demonstrates strong, consistent associations between variables of material wealth indicators and various measures of health among 75-year-old men and women.