bluuebunny/crossref_metadata_2025 huggingface dataset:
Histamine Induces Tissue Factor Expression
Authors: Steffel Jan , Akhmedov Alexander , Greutert Helen , Lüscher Thomas F. , Tanner Felix C.
Published: July 2005

Background—

Histamine can induce coronary vasospasm, leading to variant angina and acute myocardial infarction. However, the role of histamine in thrombus formation is ill defined. Hence, this study investigates whether histamine induces tissue factor (TF) expression in vascular cells.

Methods and Results—

Histamine (10
−8
to 10
−5
mol/L) induced TF expression in a concentration-dependent manner in human aortic endothelial and vascular smooth muscle cells, whereas TF pathway inhibitor expression remained unaffected. RT-PCR and Northern blotting revealed that histamine stimulated TF mRNA transcription, peaking at 1 hour. Protein expression increased 18-fold (
P
<0.02) with a maximum at 5 hours, which was paralleled by a 4-fold augmentation in surface activity (
P
<0.01). These effects were completely prevented by pretreatment with the H
1
receptor antagonists mepyramine (
P
<0.0001), chlorpheniramine, and diphenhydramine but not the H
2
receptor antagonist cimetidine (
P
=NS). Histamine induced a time-dependent, H
1
receptor–mediated activation of p38 MAP kinase (p38), p44/42 MAP kinase (ERK), and c-jun terminal NH
2
kinase (JNK). Blocking of p38, ERK, or JNK with SB203580 (
P
<0.0001), PD98059 (
P
<0.0001), or SP600125 (
P
<0.0001), respectively, impaired histamine-induced TF expression in a concentration-dependent manner. In contrast, histamine-stimulated TF expression was increased by phosphatidylinositol 3-kinase inhibition with LY294002 or wortmannin, whereas it was not affected by Rho-kinase inhibition with Y-27632 or hydroxyfasudil.

Conclusions—

Histamine induces expression of TF, but not TF pathway inhibitor, in vascular cells via activation of the H
1
, but not H
2
, receptor. This effect is mediated by the MAP kinases p38, ERK, and JNK. This observation may open novel perspectives in the treatment of variant angina and acute coronary syndromes.
Karl Marx as a Conservative Thinker
Authors: Shandro Alan
Published: July 2005

According to a long-standing conservative critique, the proponents of fundamental or revolutionary social change necessarily fail by sacrificing the organic complexity of society and the individual upon a procrustean bed of dogmatic and rigid universal principles. I will argue that Marx's concept of proletarian self-emancipation is not only compatible with this conservative critique but is appropriately understood as a variant of it. The self-emancipation of the working class is the core of Marx's critique of the Utopian socialists, for whom socialism is the instantiation of universal ideals rather than the product of class struggle. This critique should be construed, not as a theoretical promissory note for the realisation of these ideals through the agency of the workers, but as a criticism of the very project of founding political ethics on the basis of universal ideals. Marx's political thought bears a structural similarity to conservative thought in that each seeks to ground its political programme upon the study of society as it actually exists, rather than upon a vision of human nature considered apart from society. If Marx's critique of Utopian socialism holds water, the intellectual roots of Stalinist authoritarianism may be traced, not to the failure of Marx fully to outline the ideal communist society, but to the assimilation of elements of his thought to the Utopian style and tradition of political thought. There should be no surprise, therefore, when attempts to transcend Stalinism by basing radical politics upon sanitised versions of a socialist Utopia or socialist renditions of such universal liberal principles as human rights prove counter-productive.
Reply to Lebowitz
Authors: Shortall Felton
Published: July 2005

As Michael Lebowitz, in his extended review points out, The Incomplete Marx is part of ‘a growing body of work which challenges the exclusive preoccupation with Capital of so many academic Marxists’. Like Lebowitz's own work in this area, The Incomplete Marx is part of the project which seeks to go beyond the ‘logic of capital’ that we find in Capital, ‘which yields a one-sided understanding of capitalism’, in order to grasp the other essential aspect of capitalism – class struggle and proletarian subjectivity.
Reflections on NATO's New Mission: Conflict Prevention in the Struggles for Ethnic Self-Determination
Authors: Gabor Francis
Published: July 2005

During the Cold War, both NATO's role and purpose were clearly defined by the existence of the threat posed by the Soviet Union. The traditional confrontation between the NATO and the Warsaw Pact military organizations effectively has ceased to exist. The dissolution of the Warsaw Pact—combined with the emerging constitutional democracies in Central and Eastern Europe and the transformation of the Russian Federation—has essentially assured that the future threat of a confrontation between the major armies on the European continent is highly unlikely. However, it soon became obvious that several non-traditional, and quite unexpected, risks would give NATO a new mission and new challenges. One of the greatest challenges for post-Cold War Eastern Europe lies in the unresolved questions of ethnic self-determination. The unprecedented human tragedy of two world wars failed to resolve these questions. The concept of ethnic self-determination has been the central theme of the conflicts in the Yugoslav civil wars. NATO played a significant, if not central, role in the final resolution of the Yugoslav civil wars, particularly in the case of Kosovo. The Kosovo experience creates a real challenge for NATO and international legal scholars to create a more precisely defined body of international law to protect ethnic minorities and to build an effective institutional framework for the observation and implementation of so-called minority rights. which would have prevented the tragedy of the Yugoslavian civil war and can prevent future conflicts.
Potential-Vorticity Characteristics of the Faroe Bank Channel Deep-Water Overflow
Authors: Lake Iréne , Borenäs Karin , Lundberg Peter
Published: July 2005

Results from a 71-day deployment of three ADCP current meters on a section across the sill region of the Faroe Bank Channel are reported. The characteristic density structure of the channel, with warm, highly saline North Atlantic Ocean surface water overlying colder, less-saline deep water originating from the Nordic seas, lends itself well to a two-layer description of flow processes in this region. The dataset has been analyzed to describe the spatial and temporal characteristics of the deep-water potential vorticity. The most striking feature is a persistent cross-channel variation of this quantity, with higher values on the Faroe Bank side. In the 1½-layer hydraulic calculations that were undertaken the potential vorticity was approximated as a linear distribution. The ADCP observations indicated that the deep-water flow was hydraulically controlled, and, using the direct observed transport, the analysis yielded diagnostic results for the upstream reservoir interface level that were in good agreement with observations. It was also concluded that the deviation of the potential vorticity from a constant value had no significant effects on the deep-water transport.
Do Eddies Play a Role in the Momentum Balance of the Leeuwin Current?
Authors: Feng Ming , Wijffels Susan , Godfrey Stuart , Meyers Gary
Published: July 2005

The Leeuwin Current is a poleward-flowing eastern boundary current off the western Australian coast, and alongshore momentum balance in the current has been hypothesized to comprise a southward pressure gradient force balanced by northward wind and bottom stresses. This alongshore momentum balance is revisited using a high-resolution upper-ocean climatology to determine the alongshore pressure gradient and altimeter and mooring observations to derive an eddy-induced Reynolds stress. Results show that north of the Abrolhos Islands (situated near the shelf break between 28.2° and 29.3°S), the alongshore momentum balance is between the pressure gradient and wind stress. South of the Abrolhos Islands, the Leeuwin Current is highly unstable and strong eddy kinetic energy is observed offshore of the current axis. The alongshore momentum balance on the offshore side of the current reveals an increased alongshore pressure gradient, weakened alongshore wind stress, and a significant Reynolds stress exerted by mesoscale eddies. The eddy Reynolds stress has a −0.5 Sv (Sv ≡ 106 m3 s−1) correction to the Indonesian Throughflow transport estimate from Godfrey’s island rule. The mesoscale eddies draw energy from the mean current through mixed barotropic and baroclinic instability, and the pressure gradient work overcomes the negative wind work to supply energy for the instability process. Hence the anomalous large-scale pressure gradient in the eastern Indian Ocean drives the strongest eddy kinetic energy level among all the midlatitude eastern boundary currents.
Cross-Shelf Exchange Driven by Oscillatory Barotropic Currents at an Idealized Coastal Canyon
Authors: Haidvogel D. B.
Published: July 2005

Numerical simulations are used to study on-shelf transport of dense water by oscillatory barotropic currents incident upon an isolated coastal canyon. The physical system is a laboratory-scale annulus in which forcing is provided by an oscillatory modulation in the rotation rate and for which the external nondimensional parameters match those from an appropriate oceanic analog. The numerical simulations were conducted for comparison with a companion set of laboratory experiments, and these prior studies have shown good qualitative and quantitative agreement between the two. Here the numerical simulations are examined in further detail to determine the three-dimensional structure of the time-mean currents and density field on the shelf, to quantify the resulting onshore transport of dense water, and to expose the underlying nondimensional parameter dependencies. The incident barotropic currents produce, in equilibrium, an extensive pool of anomalously dense fluid on the shelf surrounding the canyon. This dense pool is maintained on the shelf by a combination of cross-shelf mean and eddy density fluxes. The associated time-mean pools of dense water on the shelf have considerable spatial structure, most prominently a vertically thick lens of anomalously dense water along the upstream limb of the canyon, accompanied by strong anticyclonic residual currents. The dense pool occupies an area and volume that are large when compared with that of the canyon itself. Several bulk measures of on-shelf exchange of dense water are devised to facilitate comparison across the simulations performed. This comparison of bulk measures indicates that net on-shelf transport of dense water varies linearly with forcing period (inverse temporal Rossby number) and quadratically with forcing strength (Rossby number). Variations in on-shelf pumping with Burger number are found to be weak. A simple dynamical scaling argument is consistent with the observed dependencies.
The Tsushima Warm Current through Tsushima Straits Estimated from Ferryboat ADCP Data
Authors: Takikawa Tetsutaro , Yoon Jong-Hwan , Cho Kyu-Dae
Published: July 2005

Current structures across the Tsushima Straits are studied using results from long-term acoustic Doppler current profiler (ADCP) observations by a ferryboat between Hakata and Pusan conducted since February 1997. Two maxima of the northeastward current are observed in the central parts of the eastern and western channels, and the maximum velocity in the western channel is stronger than that of the eastern channel. Downstream of the Tsushima Islands, a southwestward countercurrent is observed associated with a pair of cyclonic and anticyclonic eddies. In the western channel, the deep countercurrent is observed pronouncedly on the bottom slope of the Korean side from summer to winter. The volume transport of the Tsushima Warm Current through the straits has strong seasonal variation with a minimum in January and two maxima from spring to autumn (double peaks). The spring peak of the volume transport through the eastern channel is more pronounced than the autumn peak, and the autumn peak of the western channel is more pronounced than the spring peak. The inflow volume transport into the Japan Sea through the western channel significantly increases in autumn because of an incrementation of the freshwater transport. The total volume transport averaged over the observation period (5.5 yr) is 2.64 Sv (Sv ≡ 106 m3 s−1). The average volume transports through the eastern and western channels are 1.10 and 1.54 Sv, respectively.
The Structure and Driving Mechanisms of the Baltic Intrusions
Authors: Kuzmina Natalia , Rudels Bert , Stipa Tapani , Zhurbas Victor
Published: July 2005

Data from closely spaced CTD profiling performed in the eastern Gotland Basin after the 1993 inflow event are used to study thermohaline intrusions in the Baltic Sea. Two CTD cross sections display abundant intrusive layers in the permanent halocline. Despite the overwhelming dominance of the salinity stratification, diffusive convection is shown to work in the Baltic halocline enhancing diapycnical mixing. To understand the driving mechanisms of observed intrusions, these are divided into different types depending on their structural features. Only two types of observed intrusions are suggested to be strongly influenced by diffusive convection: 1) relatively thin (3–5 m) and long (up to 8 km) intrusions inherent to high-baroclinicity regions and 2) relatively thick (∼10 m) and short (2–5 km) intrusions inherent to low-baroclinicity regions. To verify this hypothesis the linear stability models of 3D and 2D double-diffusive interleaving in approximation of a finite-width front were used. It is shown that the horizontal and vertical scales of thick and short intrusions correspond well to the 3D rotational mode for a pure thermohaline front. Since mesoscale thermohaline fronts in the Baltic halocline are shown to be essentially baroclinic, the influence of baroclinicity on the rotational mode was studied, which resulted in more adequate estimates of the growth rate of the unstable modes. The thin and long intrusions are shown to be likely driven by 2D baroclinic instability triggered by diffusive convection. The model results demonstrated that diffusion convection can be considered as a possible driver for some intrusions observed in the Baltic halocline, while most of the intrusions have a non-double-diffusive origin. Nevertheless, diffusive convection can affect all types of observed intrusions, for example, by tilting them relative to isopycnals and thereby promoting diapycnal mixing and ventilation in the Baltic halocline.
Politics in the Supermarket: Political Consumerism as a Form of Political Participation
Authors: Stolle Dietlind , Hooghe Marc , Micheletti Michele
Published: July 2005

Both anecdotal and case-study evidence have long suggested that consumer behavior such as the buying or boycotting of products and services for political and ethical reasons can take on political significance. Despite recent claims that such behavior has become more widespread in recent years, political consumerism has not been studied systematically in survey research on political participation. Through the use of a pilot survey conducted among 1015 Canadian, Belgian, and Swedish students, we ascertain whether political consumerism is a sufficiently consistent behavioral pattern to be measured and studied meaningfully. The data from this pilot survey allow us to build a “political consumerism index” incorporating attitudinal, behavioral, and frequency measurements. Our analysis of this cross-national student sample suggests that political consumerism is primarily a tool of those who are distrustful of political institutions. However, political consumers have more trust in other citizens, and they are disproportionately involved in checkbook organizations. They also tend to score highly on measures of political efficacy and post-materialism. We strongly suggest including measurements of political consumerism together with other emerging forms of activism in future population surveys on political participation.
Mapping Out Political Europe: Coalition Patterns in EU Decision-Making
Authors: Kaeding Michael , Selck Torsten J.
Published: July 2005

This article evaluates member states’ and supranational institutions’ preference patterns in European Union decision-making. We present a research design that encompasses data on the policy profiles of the 15 member states, the Commission, and the European Parliament for 70 European legal acts that were negotiated just before the May 2004 enlargement. We apply principal-component analysis which results in reduction of the different policy issues into a three-dimensional solution. The Commission and the European Parliament are much more favorable toward increased integration than the Council members are. Thus, there appears to be a “north versus south” coalition pattern rather than a “Franco-German axis.” The positions of Ireland and Belgium indicate that the member states’ status as net contributors or net receivers of European Union subsidies are important. Our findings do not support the pro-less integrationist argument nor the left-right dimension that reconciles economic and sociopolitical issues.
Contentious Collective Action and the Breakdown of Authoritarian Regimes
Authors: Ulfelder Jay
Published: July 2005

Prior research indicates that different types of authoritarian regimes break down in different ways because key cadres in those regimes have different interests and face different strategic environments. Building on that theoretical foundation, I use event history models to examine the effects of contentious collective action on the likelihood of authoritarian breakdown. This analysis shows that some kinds of autocracy are more vulnerable to breakdown in the wake of contentious events than others, and that the strength and direction of this effect varies not only across types of authoritarianism, but across forms of collective action as well.
Anterior Cruciate Ligament Reconstruction in Patients Older than 40 Years
Authors: Barrett Gene , Stokes David , White Miranda
Published: July 2005

Background

Anterior cruciate ligament reconstruction is the recommended treatment for patients of all ages who are involved in sports and have symptoms of knee instability.

Hypothesis

In patients older than 40 years, allograft reconstruction will have better subjective and objective results than autograft reconstruction, proving allograft to be a better graft source for this patient population.

Study Design

Cohort study; Level of evidence, 3.

Methods

The authors identified 63 patients meeting the criteria for this study, including 38 patients in the allograft group and 25 patients in the autograft group. All patients were older than 40 years and had at least 2 years’ follow-up. Objective parameters included preinjury and postoperative Tegner activity rating scale and Lysholm scores, range of motion, thigh circumference differences, side-to-side difference at maximum manual force in anterior displacement by KT-1000 arthrometer, and clinical examination for Lachman and pivot-shift tests. Using a 15-point visual analog scale, the authors performed subjective evaluations.

Results

Both groups’ Tegner activity rating scale scores returned to preoperative levels. Visual analog scales and range of motion data were similar for both groups. KT-1000 arthrometer data showed a mean maximum difference of 1.46 mm for the allograft group and 0.10 mm for the autograft group (P=. 398). Three patients in the allograft group showed greater than 5 mm difference, compared with none in the autograft group. There was 1 clinical failure in the allograft group. In the allograft group, 57% of patients had returned to sports by 6 months versus 25% of patients in the autograft group (P=. 005), increasing to 71% and 43%, respectively, at final follow-up (P=. 127).

Conclusion

Allograft bone–patellar tendon–bone advantages include quicker return to sporting activities; disadvantages include increased laxity and higher incidence of failure. The advantage of autograft bone–patellar tendon–bone is that it appears to be a tighter graft. The authors found that allograft was not a superior graft source in this patient population, leading them to offer both options.
Time-Dependent Changes in Failure Loads of 3 Biceps Tenodesis Techniques
Authors: Kilicoglu Onder , Koyuncu Ozgur , Demirhan Mehmet , Esenyel Cem Zeki , Atalar Ata Can , Ozsoy Serhat , Bozdag Ergun , Sunbuloglu Emin , Bilgic Bilge
Published: July 2005

Background

Failure load of the tendon–fixation material–bone unit has a crucial importance for the rehabilitation protocol after tenodesis procedures.

Purpose

To investigate and compare the time-dependent changes in fixation strengths of 3 proximal biceps tenodesis techniques.

Study Design

Controlled laboratory study.

Methods

Two intraosseous techniques (suture sling and tenodesis screw) and 1 extraosseous technique (2 suture anchors) were investigated. Biceps tenodesis was performed on 45 shoulders of 26 sheep, 15 shoulders for each technique. Twelve similar cadaveric sheep shoulders (4 for each technique) provided the day 0 results. Sheep were sacrificed at 3, 6, and 9 weeks, and specimens were tested for the failure load of the tenodeses.

Results

All 3 tenodesis techniques were found to have similar failure loads at all time intervals tested. All 3 curves remained below the failure load of the intact tendon (862 ± 96 N) and above their day 0 results for the study period; similarly, at each time interval, results tended to be better compared to the previous test. The tenodesis screw group exhibited significantly higher failure loads at week 3 (419 ± 53 N) compared to day 0 values (164 ± 45 N) (P=. 009). The same level of significance was observed at week 6 in the remaining 2 groups.

Conclusion

Tenodesis of the biceps tendon on the proximal humerus at an extra-articular site does not weaken after surgery. The tenodesis screw group had a significantly higher increase in the fixation strength within the first 3 weeks.

Clinical Relevance

No significant differences could be found between the failure loads of all 3 investigated tenodeses for the first 9 weeks.
The Work of Culture in the Treatment of Psychosis in Migrant Adolescents
Authors: Rousseau Cécile , Key Fiona , Measham Toby
Published: July 2005

Psychotic illness in an adolescent is a catastrophic event for families, particularly migrant families, who tend to use mental health services less than mainstream families. This article presents a clinical approach that takes into account the work of culture in the construction of meaning and the development of coping strategies for migrant families faced with the onset of psychosis in an adolescent. This approach transforms the therapeutic space into a transitional one that allows the interplay of many different interpretations and strategies to deal with the crisis. Recognizing the potential value of non-western systems of knowledge, offering help as the family grieves the loss of its expectations for their child, mobilizing support systems, and strengthening the therapeutic alliance are the key elements in this process.
An Evaluation of the Parents Plus Early Years Programme: A Video-based Early Intervention for Parents of Pre-school Children with Behavioural and Developmental Difficulties
Authors: Sharry John , Guerin Suzanne , Griffin Claire , Drumm Michael
Published: July 2005

This article describes the development of the Parents Plus Early Years Programme (PPEY): a video-based early intervention for parents of pre-school children with behavioural and developmental difficulties. PPEY combines individual parent-child sessions using video feedback with parenting group sessions using video-based teaching over a 12-week period. As well as detailing the research basis, theory and practice of the PPEY, the article describes the results of an initial study of 30 children, with a range of conduct, attention and developmental problems whose parents completed the programme. Results showed a significant drop in conduct problems and hyperactivity as measured by the Strengths and Difficulties Questionnaire, decreased parental stress as measured by Parent Stress Scale, and significant gains towards parent-defined goals. In addition, before and after video observation of parent-child interaction showed an increase in positive parent-child attention and a decrease in parent-child instructions, as measured by independent observers. Gains were maintained at 5-month follow-up. The article also includes some initial results of a follow-up qualitative evaluation of parents’ experience after attending the programme.
Prevalence of Emotional and Behavioural Disorders Among Strictly Orthodox Jewish Children in London
Authors: Frosh Stephen , Loewenthal Kate , Lindsey Caroline , Spitzer Esther
Published: July 2005

Teacher and parent ratings of emotional and behavioural disorders were made for children aged 5-15 years in the strictly orthodox Jewish community in North London, on the Strengths and Difficulties Questionnaire (SDQ; Goodman, 1997). We obtained 369 sets of teacher ratings and 226 parent ratings. Our parent ratings generally reflected less disturbance than did parent ratings in the national samples reported by Meltzer and colleagues (Meltzer, Gatward, Corbin, Goodman, & Ford, 2003; Meltzer, Gatward, Goodman, & Ford, 2000). Our teacher ratings reflected similar levels of disturbance to teacher ratings in the national sample, except that the older boys in this sample were rated as more disturbed by their teachers. Teacher ratings of disturbance were associated with perceived Special Educational Needs (SENs), and it was noted that statutory remedial help was said to be needed particularly urgently for older boys. In this community there is negligible statutory educational funding and remedial support for older boys is said to be particularly under-resourced. The strictly orthodox Jewish community is characterized by large family size and high levels of economic deprivation, and it might be expected that there would be high levels of associated emotional and behavioural disorders. The relatively low levels of behaviour disturbance found were suggested to be the result of moderating factors such as high levels of family cohesion, social support and religiosity.
Schizophrenia in Pre-school Children: Two Case Reports With Longitudinal Follow-up for 6 and 8 Years
Authors: Beresford Carol , Hepburn Susan , Ross Randal G.
Published: July 2005

Although schizophrenia is often thought of as an adolescent- or adult-onset disorder, there has been an increasing awareness over 90 years that schizophrenia can present in 6-12 year olds. There has been less focus on schizophrenia in children under the age of 6. We report here on two children diagnosed, at 4.25 and 5.92 years, with schizophrenia. Retrospectively, both children had psychotic symptoms documented during mental health evaluations prior to their fourth birthday. Both children had at least partial symptom reduction on antipsychotic medication, but both children were also highly sensitive to the side effects of treatment. Discussion focuses primarily on diagnostic issues, and provides some observations about treatment responsiveness.
Fear-avoidance in Recovered Burn Patients: Association with Psychological and Somatic Symptoms
Authors: Sgroi Maria Ingelsson , Willebrand Mimmie , Ekselius Lisa , Gerdin Bengt , Andersson Gerhard
Published: July 2005

Fear-avoidance, an important model in the understanding of chronic pain, has not yet been studied in patients with burns. The purpose of this study was to investigate if recovered burn patients have fear-avoidance beliefs and to explore the association with psychological and somatic symptoms. Eighty-four recovered burn patients completed self-report questionnaires. The results showed that there were fear-avoidance beliefs, but not to a large extent. Beta coefficients from multiple regression analyses indicated a strong association between fear-avoidance and problems with work, heat sensitivity and arousal symptoms. The model was capable of explaining 73 per cent of the variance in fear-avoidance beliefs.
MDM2 antagonists induce p53-dependent apoptosis in AML: implications for leukemia therapy
Authors: Kojima Kensuke , Konopleva Marina , Samudio Ismael J. , Shikami Masato , Cabreira-Hansen Maria , McQueen Teresa , Ruvolo Vivian , Tsao Twee , Zeng Zhihong , Vassilev Lyubomir T. , Andreeff Michael
Published: July 2005

Although TP53 mutations are rare in acute myeloid leukemia (AML), inactivation of wild-type p53 protein frequently occurs through overexpression of its negative regulator MDM2 (murine double minute 2). Recently, small-molecule antagonists of MDM2, Nutlins, have been developed that inhibit the p53-MDM2 interaction and activate p53 signaling. Here, we study the effects of p53 activation by Nutlin-3 in AML cells. Treatment with MDM2 inhibitor triggered several molecular events consistent with induction of apoptosis: loss of mitochondrial membrane potential, caspase activation, phosphatidylserine externalization, and DNA fragmentation. There was a positive correlation in primary AML samples with wild-type p53 between baseline MDM2 protein levels and apoptosis induced by MDM2 inhibition. No induction of apoptosis was observed in AML samples harboring mutant p53. Colony formation of AML progenitors was inhibited in a dose-dependent fashion, whereas normal CD34+ progenitor cells were less affected. Mechanistic studies suggested that Nutlin-induced apoptosis was mediated by both transcriptional activation of proapoptotic Bcl-2 family proteins, and transcription-independent mitochondrial permeabilization resulting from mitochondrial p53 translocation. MDM2 inhibition synergistically enhanced cytotoxicity of cytosine arabinoside and doxorubicin in AML blasts but not in normal hematopoietic progenitor cells. p53 activation by targeting the p53-MDM2 interaction might offer a novel therapeutic strategy for AML that retain wild-type p53.
The influence of N-linked glycosylation on the function of platelet glycoprotein VI
Authors: Kunicki Thomas J. , Cheli Yann , Moroi Masaaki , Furihata Kenichi
Published: July 2005

Using recombinant human glycoprotein VI (GPVI), we evaluated the effect of N-linked glycosylation at the consensus site Asparagine92-Glycine-Serine94 (N92GS94) on binding of this platelet-specific receptor to its ligands, human type I collagen, collagen-related peptide (CRP), and the snake venom C-type lectin convulxin (CVX). In COS-7 cells transiently transfected with GPVI, deglycosylation with peptide-N-glycosidase F (PNGase F; specific for complex N-linked glycans) or tunicamycin decreases the molecular weight of GPVI and reduces transfected COS-7 cell binding to both CRP and CVX. In stably transfected Dami cells, the substitutions N92A or S94A, but not L95H, resulted in a 30% to 40% decrease in adhesion to CVX, but a 90% or greater decrease in adhesion to CRP and a 65% to 70% decrease in adhesion to type I collagen. Treatment with PNGase F, but not Endoglycosidase H (Endo H) (specific for high-mannose N-linked glycans), produced an equivalent decrease in molecular weight. Neither N92A nor S94A affected the expression of GPVI, based on the direct binding of murine anti–human GPVI monoclonal antibody 204-11 to transfected Dami cells. These findings indicate that N-linked glycosylation at N92 in human GPVI is not required for surface expression, but contributes to maximal adhesion to type I collagen, CRP and, to a lesser extent, CVX.
The beta2 integrin CD11c distinguishes a subset of cytotoxic pulmonary T cells with potent antiviral effects in vitro and in vivo
Authors: Beyer Marc , Wang Hongwei , Peters Nina , Doths Sandra , Koerner-Rettberg Cordula , Openshaw Peter JM , Schwarze Jürgen
Published: July 2005

Background

The integrin CD11c is known as a marker for dendritic cells and has recently been described on T cells following lymphotropic choriomeningitis virus infection, a systemic infection affecting a multitude of organs. Here, we characterise CD11c bearing T cells in a murine model of localised pulmonary infection with respiratory syncytial virus (RSV).

Methods

Mice were infected intranasally with RSV and expression of β2 integrins and T lymphocyte activation markers were monitored by flow cytometry. On day 8 post RSV infection CD11c+ CD8+ and CD11c- CD8+ T cells were assessed for cytokine production, cytotoxic activity and migration. Expression of CD11c mRNA in CD8+ T cells was assessed by quantitative PCR.

Results

Following RSV infection CD11c+ CD8+ T cells were detectable in the lung from day 4 onwards and accounted for 45.9 ± 4.8% of CD8+ T cells on day 8 post infection, while only few such cells were present in mediastinal lymph nodes, spleen and blood. While CD11c was virtually absent from CD8+ T cells in the absence of RSV infection, its mRNA was expressed in CD8+ T cells of both naïve and RSV infected mice. CD11c+, but not CD11c-, CD8+ T cells showed signs of recent activation, including up-regulation of CD11a and expression of CD11b and CD69 and were recruited preferentially to the lung. In addition, CD11c+ CD8+ T cells were the major subset responsible for IFNγ production, induction of target cell apoptosis in vitro and reduction of viral titres in vivo.

Conclusion

CD11c is a useful marker for detection and isolation of pulmonary antiviral cytotoxic T cells following RSV infection. It identifies a subset of activated, virus-specific, cytotoxic T cells that exhibit potent antiviral effects in vivo.
Does Alendronate reduce the risk of fracture in men? A meta-analysis incorporating prior knowledge of anti-fracture efficacy in women
Authors: Sawka Anna M , Papaioannou Alexandra , Adachi Jonathan D , Gafni Amiram , Hanley David A , Thabane Lehana
Published: July 2005

Background

Alendronate has been found to reduce the risk of fractures in postmenopausal women as demonstrated in multiple randomized controlled trials enrolling thousands of women. Yet there is a paucity of such randomized controlled trials in osteoporotic men. Our objective was to systematically review the anti-fracture efficacy of alendronate in men with low bone mass or with a history of prevalent fracture(s) and incorporate prior knowledge of alendronate efficacy in women in the analysis.

Methods

We examined randomized controlled trials in men comparing the anti-fracture efficacy of alendronate to placebo or calcium or vitamin D, or any combination of these. Studies of men with secondary causes of osteoporosis other than hypogonadism were excluded. We searched the following electronic databases (without language restrictions) for potentially relevant citations: Medline, Medline in Process (1966-May 24/2004), and Embase (1996–2004). We also contacted the manufacturer of the drug in search of other relevant trials. Two reviewers independently identified two trials (including 375 men), which met all inclusion criteria. Data were abstracted by one reviewer and checked by another. Results of the male trials were pooled using Bayesian random effects models, incorporating prior information of anti-fracture efficacy from meta-analyses of women.

Results

The odds ratios of incident fractures in men (with 95% credibility intervals) with alendronate (10 mg daily) were: vertebral fractures, 0.44 (0.23, 0.83) and non-vertebral fractures, 0.60 (0.29, 1.44).

Conclusion

In conclusion, alendronate decreases the risk of vertebral fractures in men at risk. There is currently insufficient evidence of a statistically significant reduction of non-vertebral fractures, but the paucity of trials in men limit the statistical power to detect such an effect.
Naturopaths practice behaviour: provision and access to information on complementary and alternative medicines
Authors: Smith Caroline , Martin Karen , Hotham Elizabeth , Semple Susan , Bloustien Geraldine , Rao Deepa
Published: July 2005

Background

The increasing use of complementary and alternative medicines in Australia has generated concern regarding the information on these products available to both healthcare providers and the public. The aim of this study was to examine the practice behaviours of naturopaths in relation to both the provision of and access to information on complementary and alternative medicines (CAM).

Methods

A representative sample of 300 practicing naturopaths located nationally were sent a comprehensive survey which gathered data on self reported practice behaviour in relation to the provision of information on oral CAM to clients and the information needs of the practitioners themselves

Results

A response rate of 35% was achieved. Most practitioners (98%) have a dispensary within their clinic and the majority of practitioners perform the dispensing themselves. Practitioners reported they provided information to clients, usually in the form of verbal information (96%), handwritten notes (83%) and printed information (75%). The majority of practitioners (over 75%) reported always giving information on the full name of the product, reason for prescribing, expected response, possible interactions and contraindications and actions of the product. Information resources most often used by practitioners included professional newsletters, seminars run by manufacturers, patient feedback and personal observation of patients. Most practitioners were positive about the information they could access but felt that more information was required in areas such as adverse reactions and safe use of CAM in children, pregnancy and breastfeeding. Most naturopaths (over 96%) were informed about adverse events through manufacturer or distributor newsletters. The barriers in the provision of information to clients were misleading or incorrect information in the media, time constraints, information overload and complex language used in printed information. The main barrier to the practitioner in information access was seen as the perceived division between orthodox and complementary medicine practitioners.

Conclusion

Our data suggest most naturopaths were concerned about possible interaction between pharmaceuticals and CAM, and explore this area with their patients. There is scope to improve practitioners' access to information of adverse events including an increased awareness of sources of information such as the Australian Therapeutic Goods Administration (TGA) website.
Impact of two rounds of mass drug administration using diethylcarbamazine combined with albendazole on the prevalence of Brugia timoriand of intestinal helminths on Alor Island, Indonesia
Authors: Oqueka Tim , Supali Taniawati , Ismid Is Suhariah , Purnomo  , Rückert Paul , Bradley Mark , Fischer Peter
Published: July 2005

Background

Annual mass drug administration (MDA) using diethylcarbamizine (DEC, 6 mg/kg) combined with albendazole (alb, 400 mg) is recommended by the Global Programme to Eliminate Lymphatic Filariasis (GPELF). This strategy has been shown to be efficient in the of control bancroftian filariasis, but data on brugian filariasis as well as on the positive side effects on intestinal helminths are lacking.

Methods

The effect of one selective treatment and two rounds of MDA using DEC and alb on the prevalence and intensity of Brugia timori infection were studied on Alor island using a cross-sectional and a cohort approach. Before the campaign and ten months after each treatment cycle microfilariae (mf) were assessed by filtration of night blood. Before and ten months after MDA, stool samples were collected and the prevalence of intestinal helminths were determined.

Results

In all, the mf-rate dropped from 26.8% before any treatment to 3.8% following the second MDA. Almost all mf-positive, treated individuals showed very low mf densities. The crude prevalence of hookworm dropped from 25.3% to 5.9%. The reduction of prevalence of Ascaris lumbricoides (32.3% to 27.6%) and Trichuris trichiura (9.4% to 8.9%) was less pronounced. Within a cohort of 226 individuals, which was examined annually, the prevalence of A. lumbricoides dropped from 43.8% to 26.5% and of T. trichiura from 12.8% to 6.6%. The results indicate that this MDA approach reduces not only the mf prevalence of B. timori but also the prevalence of hookworm and to a lesser extent also of A. lumbricoides and T. trichiura.

Conclusion

The MDA using DEC and alb as recommended by GPELF is extremely effective for areas with brugian filariasis. The beneficial effect of MDA on intestinal helminths may strengthen the national programme to eliminate lymphatic filariasis in Indonesia and may set resources free which are otherwise used for deworming campaigns of schoolchildren.
Respiratory compliance but not gas exchange correlates with changes in lung aeration after a recruitment maneuver: an experimental study in pigs with saline lavage lung injury
Authors: Henzler Dietrich , Pelosi Paolo , Dembinski Rolf , Ullmann Annette , Mahnken Andreas H , Rossaint Rolf , Kuhlen Ralf
Published: July 2005

Introduction

Atelectasis is a common finding in acute lung injury, leading to increased shunt and hypoxemia. Current treatment strategies aim to recruit alveoli for gas exchange. Improvement in oxygenation is commonly used to detect recruitment, although the assumption that gas exchange parameters adequately represent the mechanical process of alveolar opening has not been proven so far. The aim of this study was to investigate whether commonly used measures of lung mechanics better detect lung tissue collapse and changes in lung aeration after a recruitment maneuver as compared to measures of gas exchange

Methods

In eight anesthetized and mechanically ventilated pigs, acute lung injury was induced by saline lavage and a recruitment maneuver was performed by inflating the lungs three times with a pressure of 45 cmH2O for 40 s with a constant positive end-expiratory pressure of 10 cmH2O. The association of gas exchange and lung mechanics parameters with the amount and the changes in aerated and nonaerated lung volumes induced by this specific recruitment maneuver was investigated by multi slice CT scan analysis of the whole lung.

Results

Nonaerated lung correlated with shunt fraction (r = 0.68) and respiratory system compliance (r = 0.59). The arterial partial oxygen pressure (PaO2) and the respiratory system compliance correlated with poorly aerated lung volume (r = 0.57 and 0.72, respectively). The recruitment maneuver caused a decrease in nonaerated lung volume, an increase in normally and poorly aerated lung, but no change in the distribution of a tidal breath to differently aerated lung volumes. The fractional changes in PaO2, arterial partial carbon dioxide pressure (PaCO2) and venous admixture after the recruitment maneuver did not correlate with the changes in lung volumes. Alveolar recruitment correlated only with changes in the plateau pressure (r = 0.89), respiratory system compliance (r = 0.82) and parameters obtained from the pressure-volume curve.

Conclusion

A recruitment maneuver by repeatedly hyperinflating the lungs led to an increase of poorly aerated and a decrease of nonaerated lung mainly. Changes in aerated and nonaerated lung volumes were adequately represented by respiratory compliance but not by changes in oxygenation or shunt.
Expression and Reexpression of Recombination Activating Genes: Relevance to the Development of Autoimmune States
Authors: HILLION SOPHIE , ROCHAS CAROLINE , YOUINOU PIERRE , JAMIN CHRISTOPHE
Published: July 2005

Abstract: Like all antibodies, autoreactive antibodies are generated in developing B cells in the bone marrow by variable (V), diversity (D), and joining (J) recombination under the regulation of recombination activating gene (RAG) 1 and RAG2 proteins. Deletion, anergy, and receptor edition prevent the emergence of autoreactive B cells. In the periphery, somatic hypermutation during the course of germinal center responses can lead to the emergence of autoreactive and low‐affinity antibody‐producing B cells. Deletion and receptor revision regulate autoreactive and inappropriate B cells. Defects in central or peripheral tolerance mechanisms associated with RAG expression could contribute to the appearance of autoreactive B cells. We demonstrate the presence of RAG+ B cells in CD5‐expressing cells outside germinal centers. Our data suggest that receptor revision in the periphery also may occur in unusual sites when B cells are induced to express CD5. This revision may correspond to a novel regulation checkpoint in which impaired control of RAG expression could generate autoreactive B cells and lead to autoimmune states.
B Lymphocytes Are Required for Development and Treatment of Autoimmune Diseases
Authors: YOUINOU PIERRE , JAMIN CHRISTOPHE , PERS JACQUES‐OLIVIER , BERTHOU CHRISTIAN , SARAUX ALAIN , RENAUDINEAU YVES
Published: July 2005

Abstract: Recent studies have revealed that B cells serve extraordinarily diverse functions within the immune system in addition to antibody production. These functions contribute to autoimmunity. They initiate the development of lymphoid architecture and regulate dendritic and T‐cell function through cytokine production. Receptor editing is also essential to prevent autoimmunity. Both abnormalities in the distribution of B‐cell subsets and the benefits of ablative B‐cell therapy of autoimmune states confirm their importance. Results from transgenic models have demonstrated that the sensitivity of B cells to antigen receptor cross‐linking correlates to autoimmunity, with particular reference to negative signaling by CD5 and CD22. These mechanisms maintain tolerance by recruiting src‐homology 2 domain‐containing protein tyrosine phosphatase‐1. These findings open new prospects for immunotherapy of autoimmune diseases.
BAFF Overexpression Is Associated with Autoantibody Production in Autoimmune Diseases
Authors: PERS JACQUES‐OLIVIER , DARIDON CAPUCINE , DEVAUCHELLE VALÉRIE , JOUSSE SANDRINE , SARAUX ALAIN , JAMIN CHRISTOPHE , YOUINOU PIERRE
Published: July 2005

Abstract: The B‐cell activity factor (BAFF) acts as a positive regulator of B‐cell function. To gain further insight into the understanding of B‐cell hyperactivity in autoimmune diseases, the serum level of BAFF was determined in 43 systemic lupus erythematosus (SLE) patients, 58 primary Sjögren's syndrome (pSS) patients, 28 rheumatoid arthritis (RA) patients, and 68 normal control subjects using an in‐house sandwich ELISA. A commercial kit was used to detect soluble CD23 (sCD23) reflecting B‐cell activation. In‐house assays for the detection of autoantibodies also were used. We found an increased level of BAFF in SLE, pSS, and RA sera compared with normal subjects (respectively, 10.6 ± 8.5, 15.8 ± 12.9, 9.7 ± 1.5 ng/mL vs. 4.6 ± 2.9/ng/mL, P < .001). sCD23 released on B‐cell activation also was found to be elevated in SLE, pSS, and RA compared with normal sera. However, no correlation was found between the circulating BAFF and the level of sCD23. By contrast, we observed that high levels of BAFF were associated with the presence of autoantibodies (anti‐double‐stranded DNA antibodies in SLE, anti‐SSA antibodies in pSS, and rheumatoid factors in RA). Our data suggest that BAFF is influential in driving antibody production rather than activation of the B lymphocytes in autoimmune diseases.