bluuebunny/crossref_metadata_2025 huggingface dataset:
Elevated factor VII as a risk factor for recurrent fetal loss
Authors: De Staercke Christine , Benson Jane , Hooper Craig , Dilley Anne , Evatt Bruce , Benito Carlos , Patterson-Barnett Anne , Eller Daniel , Philipp Claire , Miller Connie
Published: May 2005

Haemostatic abnormalities can be detected in a portion of the women who have recurrent fetal loss. We measured factor VII coagulant activity (FVII:C) in 65 women with 3 or more fetal losses (recurrent cases), 31 women with one 2nd or 3rd trimester loss (late loss cases), and 81 women with only live births (controls). FVII:C was greater than 2 standard deviations above the mean for controls in 9 recurrent cases (13.8%) and 2 controls (2.5%) for an odds ratio of 6.35 (95% CI 1.32–30.52, p=0.012). In recurrent cases, mean levels were significantly higher than controls for FVII:C (p=0.003), FVII antigen (p=0.024), and FVIIa (p=0.001). Late loss cases had an odds ratio of 4.23 (95% CI 0.67–26.67, p=0.098) with FVII:C, FVII antigen, and FVIIa not significantly different from the controls. DNA was examined for the presence of mutations or polymorphisms in the promoter region of the FVII gene, using denaturing HPLC. Abnormal patterns were confirmed with direct sequencing. A previously reported polymorphism,–402 G>A, was found to be present in 11/14 subjects with elevated FVII:C (79%) and 43% of those with normal levels (p=0.029). FVII:C, FVII antigen and FVIIa varied significantly with genotype; however, genotype frequencies did not differ between controls and either case group. No other promoter polymorphisms were identified. This is the first report of a significant elevation of FVII in a population with recurrent fetal loss. These data suggest the need for further investigation of this potential risk factor.
Platelet P2Y12 receptors enhance signalling towards procoagulant activity and thrombin generation
Authors: van der Meijden Paola , Feijge Marion , Giesen Peter , Huijberts Maya , van Raak Lisette , Heemskerk Johan
Published: May 2005

Activated platelets participate in arterial thrombosis by forming aggregates and potentiating the coagulation through exposure of procoagulant phosphatidylserine. The function of the two receptors for ADP, P2Y1 and P2Y12, is well-established in aggregation, but is incompletely understood in the platelet procoagulant response. We established that, in PRP from healthy subjects, ADP accelerated and potentiated tissue factor-induced throm-bin generation exclusively via stimulation of P2Y12 and not via P2Y1 receptors. The P2Y12 receptors also mediated the potentiating effect of PAR-1 stimulation on thrombin generation. Furthermore, ADP enhanced in a P2Y12-dependent manner the Ca2+ response induced by thrombin, which was either added externally or generated in-situ. This ADP effect was in part dependent of phosphoinositide 3-kinase and was paralleled by increased phosphatidylserine exposure. In PRP from (young) patients with either stroke or type-II diabetes, platelet-dependent thrombin generation was similarly enhanced by ADP or SFLLRN as in healthy subjects. In PRP from stroke patients of older age, the P2Y12-mediated contribution to thrombin generation was variably reduced by two weeks of clopidogrel medication. Remaining P2Y12 activity after medication correlated with remaining P2Y12-dependent P-selectin exposure, i.e. Ca2+-dependent secretion, likely due to incomplete antagonism of P2Y12 receptors. Together, these results indicate that physiological platelet agonists amplify phosphatidylserine exposure and subsequent thrombin generation by release of ADP and P2Y12-receptor stimulation. This P2Y12 response is accomplished by a novel Ca2+ signalling pathway. It is similarly active in platelets from control subjects and patients at thrombotic risk. Finally, the thrombo-gram method is useful for measuring incomplete P2Y12 inhibition with clopidogrel.
High utilization rate of vena cava filters in deep vein thrombosis
Authors: Goldhaber Samuel , Tapson Victor , Jaff Michael
Published: May 2005

The objective was to investigate newly diagnosed patients with deep vein thrombosis (DVT) who received inferior vena cava filters (IVCFs). A prospective registry enrolled 5451 patients from 183 US study sites. In all patients, examination by venous duplex ultrasound confirmed the diagnosis of DVT. We collected and analyzed data on 781 patients who received an IVCF . The most frequently prescribed treatments were low–molecular-weight heparin and unfractionated heparin, which were used as a bridge to warfarin in 39% (n=2143) and 35% (n=1926) of patients, respectively. Of the total population, 781 (14%) (235 outpatients, 546 inpatients) underwent IVCF placement. The most common reasons for IVCF placement were contraindication to anticoagulation (n = 271), prophylaxis (n = 259), major bleeding related to anticoagulation therapy (n = 92), and anticoagulation failure (n = 73). Multivariate analysis revealed that patients were more likely to undergo IVCF insertion with multiple system organ failure (odds ratio [OR], 3.6; 95% CI, 1.48–8.60), previous stroke (OR, 3.2; 95% CI, 2.11–4.74), or history of pulmonary embolism (OR, 2.4; 95% CI, 1.95–2.91). In conclusion, a surprisingly high 14% (781) of patients with confirmed DVT received an IVCF. Many of these patients may have warranted less invasive methods of venous thromboembolism prophylaxis. Improved physician education regarding mechanical and pharmacologic prophylaxis alternatives might reduce the use of IVCFs.
Downregulation of vascular endothelial-cadherin expression is associated with an increase in vascular tumor growth and hemorrhagic complications
Authors: Zanetta Lucia , Corada Monica , Lampugnani Maria , Zanetti Adriana , Breviario Ferruccio , Moons Lieve , Carmeliet Peter , Pepper Michael , Dejana Elisabetta
Published: May 2005

The pathogenesis of vascular tumors such as angiosarcomas is poorly understood. Cadherin expression inversely correlates with tumor malignancy and the endothelial specific VE-cadherin is low or absent in angiosarcomas, suggesting an inhibitory role for this protein in tumor progression. In this paper we report that Pmy T VE-cadherin null (VEC null) endothelial cells form larger vascular tumors in nude mice when injected subcutaneously as compared to isogenic VE-cadherin positive (VEC pos) cells. This effect requires the association of β-catenin to VE-cadherin, since a VE-cadherin mutant lacking the domain responsible for β-catenin binding (Δβcat) cannot rescue the phenotype. In VEC null cells β-catenin is phosphorylated and partly degraded. N-cadherin is increased and detected at junctions. VEC null cells also present an altered fibrinolytic activity with increases in tPA, uPA, uPAR and a strong reduction in PAI-1, which may be correlated to the high incidence of abrupt hemorrhages in VEC null tumors. Overall, these data strongly suggest that downregulation of VE-cadherin in endothelial tumors may have important consequences for tumor growth and bleeding complications.
Angiotensin II enhances thrombosis development in renovascular hypertensive rats
Authors: Mogielnicki Andrzej , Chabielska Ewa , Pawlak Robert , Szemraj Janusz , Buczko Wlodzimierz
Published: May 2005

There is an increased number of in vitro evidence that angioten-sin II (Ang II) may promote thrombosis. However there are no in vivo experiments exploring the effect of Ang II on thrombus formation. In the present study we have investigated the influence of Ang II on venous thrombosis in renovascular hypertensive rats. Furthermore, we examined the role of AT1 receptor and Ang II metabolites: angiotensin III (Ang III) and angioten-sin IV (Ang IV) in the mechanisms of Ang II action. The contribution of coagulation and fibrinolytic systems in the mode of Ang II action was also determined. Venous thrombosis was induced by ligation of vena cava. Ang II infused into rats developing venous thrombosis caused dose-dependent increase in thrombus weight, which was partially reversed by losartan, selective AT1 antagonist. Ang III did not influence the thrombus formation in hypertensive rats, while Ang IV caused a marked increase in thrombus weight only in one of the used doses. Our study shows that Ang II via AT1 receptor enhances thrombosis development. The prothrombotic effect of Ang II may partially depend on enhanced leukocytes adhesion to endothelial cells accompanied by accelerated fibrin formation and increased plasma level of PAI-1. Moreover, Ang II action is partially mediated by one of its metabolites – Ang IV.
Molecular design and characterization of recombinant long half-life mutants of human tissue factor pathway inhibitor
Authors: Bai Hao , Zhang Yu-Gao , Zhang Nong , Kong De-Sheng , Guo Hong-Shen , Mo Wei , Tang Qi-Qun , Song Hou-Yan , Ma Duan
Published: May 2005

Tissue factor pathway inhibitor (TFPI) is a physiological inhibitor of extrinsic pathway of coagulation and has biological functions of anticoagulation and anti-inflammation. Although TFPI has been proved to be a good therapeutic agent of sepsis, inflammatory shock, and DIC, the clinical application and therapeutic effects of TFPI are impeded because of its short half-life in vivo. In order to prolong the half-life of TFPI, homology modeling and molecule docking were performed on a computer workstation principally in protein structural biology and binding characteristics between TFPI and its receptor LRP (low-density lipoprotein receptor related protein). Two recombinant long half-life human TFPI mutants coined TFPI-Mut1 and TFPI-Mut4 were designed and expressed in E.coli. In comparison with the wild-type TFPI, TFPI-Mut1 and TFPI-Mut4 presented a few of changes in spatial configuration and a decrease in relative Gibbs free energy of docking complex by 17.3% and 21.5%, respectively, as indicated by a computer simulation. After refolding and purification, anticoagulant activities, anti-TF/FVIIa and anti-FXa activities of the mutants were found to be the same as those of wide-type TFPI. The pharmacokinetics research indicated that alpha phase half-life (t1/2α) of TFPI-Mut1 and TFPI-Mut4 were prolonged 1.33-fold and 1.96-fold respectively, beta phase half-life (t1/2 β) of TFPI-Mut1 and TFPI-Mut4 were prolonged 1.62-fold and 4.22-fold respectively. These results suggested that TFPI-Mut1 and TFPI-Mut4 maintained the bioactivities of wild-type TFPI, prolonged half-life in vivo simultaneously and were expected for better clinical value and therapeutic effect.
Deletion of the 60-loop provides new insights into the substrate and inhibitor specificity of thrombin
Authors: Yang Likui , Rezaie Alireza
Published: May 2005

Structural data have indicated that the 60-loop of thrombin with 8–9 insertion residues is responsible for the restricted substrate and inhibitor specificity of thrombin. However, previous deletion of 3–4 residues of this loop (des-PPW and des-YPPW) did not widen the specificity of thrombin, but further restricted it. The partial deletion of this loop also dramatically impaired the reactivity of thrombin with antithrombin (AT), protein C and fibrinogen, implicating a role for the productive interaction of the 60-loop with the target macromolecules. To further investigate the role of this loop, a mutant of thrombin was expressed in mammalian cells in which all 8 residues (Tyr-Pro-Pro-Trp-Asp-Lys-Asn-Phe) of the 60-loop were deleted (des-60-loop). In contrast to the partially deleted loop mutants, it was discovered that the des-60-loop mutant cleaved small synthetic substrates, clotted purified fibrinogen, and activated protein C with a near normal catalytic efficiency; however, its activity toward cofactors V and VIII was impaired ~2–4-fold. Direct binding and AT inhibition studies in the presence of heparin revealed that the affinity of heparin for interaction with exosite-2 of des-60-loop thrombin was impaired, though the reactivity of the mutant with AT and other plasma serpins was not impaired, but rather improved ~2-fold. These results suggest that the 60-loop plays a key role in regulating the specificity of thrombin by shielding the active-site pocket, but its productive interaction with the target molecules may not be as critical as has been speculated in previous reports.
Retinal vein occlusion: A form of venous thrombosis or a complication of atherosclerosis?
Authors: den Heijer Martin , Cruysberg Johannes , Wollersheim Hub , Bredie Sebastian , Janssen Mirian
Published: May 2005

Previous studies have shown an increased risk of retinal vein occlusion (RVO) in patients with hypertension, hypercholesterolemia and diabetes mellitus. Literature on the association between thrombophilic factors and RVO consists of small studies and case reports. The objective was to determine the relationship between thrombophilic risk factors and RVO. Thrombophilic risk factors analyzed were hyperhomocysteinemia, MTHFR gene mutation, factor V Leiden mutation, protein C and S deficiency, antithrombin deficiency, prothrombin gene mutation, anticardiolipin antibodies and lupus anticoagulant. For all currently known thrombophilic risk factors odds ratios for RVO were calculated as estimates of relative risk. The odds ratios were 8.9 (95% CI 5.7 –13.7) for hyperhomocysteinemia, 3.9 (95% CI 2.3 – 6.7) for anticardiolipin antibodies, 1.2 (95% CI 0.9 –1.6) for MTHFR, 1.5 (95% CI 1.0 – 2.2) for factor V Leiden mutation and 1.6 (95% CI 0.8 – 3.2) for prothrombin gene mutation. In conclusion, regarding thrombophilic risk factors and RVO there is only evidence for an association with hyperhomocysteinemia and anticardiolipin antibodies, factors that are known as risk factors for venous thrombosis as well as for arterial vascular disease. The minor effect of factor V Leiden mutation and the protrombin gene mutation (risk factors for venous thrombosis only) suggests that atherosclerosis might be an important factor in the development of CRVO.
The role of CD40 in CD40L- and antibody-mediated platelet activation
Authors: Amirkhosravi Ali , Meyer Todd , Siddiqui Farooq , Ahmad Sarfraz , Walker Jamie , Amaya Mildred , Desai Hina , Francis John , Langer Florian , Ingersoll Susan
Published: May 2005

Our initial finding that CD40– and CD40 ligand (CD40L)-deficient mice displayed prolonged tail bleeding and platelet function analyzer (PFA-100) closure times prompted us to further investigate the role of the CD40-CD40L dyad in primary hemostasis and platelet function. Recombinant human soluble CD40L (rhs CD40L), chemical cross-linking of which suggested a trimeric structure of the protein in solution, activated platelets in a CD40-dependent manner as evidenced by increased CD62P expression. CD40 monoclonal antibody (mAb) M3, which completely blocked rhs CD40L-induced platelet activation, also prolonged PFA-100 closure times of normal human blood. In contrast, CD40 mAb G28–5 showed less potential in blocking rhs CD40L-induced CD62P expression and did not affect PFA-100 closure times. However, when added to the platelets after rhs CD40L, G28–5 significantly enhanced the platelet response by causing clustering of, and signaling through, FcγRII. Similarly, higher order multimeric immune complexes formed at a 1/3 molar ratio of M90, a CD40L mAb, to rhs CD40L induced strong FcγRII-mediated platelet activation when translocated to the platelet surface in a CD40-dependent manner, including the induction of morphological shape changes, fibrinogen binding, platelet aggregation, dense granule release, microparticle generation and monocyte-platelet-conjugate formation. The results suggest that CD40 may play a role in primary hemostasis and platelet biology by two independent mechanisms: First, by functioning as a primary signaling receptor for CD40L and, second, by serving as a docking molecule for CD40L immune complexes. The latter would also provide a potential mechanistic explanation for the unexpected high incidence of CD40L mAb-associated thrombotic events in recent human and animal studies.

Parts of this work have been presented on the 46th Annual Meeting of the American Society of Hematology (San Diego, 2004).
Long-term stability and reproducibility of Coagu Chek test strips
Authors: Hoekstra Martha , van den Besselaar Anton
Published: May 2005

Whole-blood point-of-care testing prothrombin time monitors are being used on an increasing scale for the monitoring of oral anticoagulant therapy. These monitors are used with disposable test strips containing tissue factor reagent. The purpose of the present study was to assess the stability of different Coagu-Chek-S strip lots for a period of one year. Ten strip lots introduced successively in the Netherlands were obtained from the manufacturer's representative and stored at 4–8°C. Six deep-frozen pooled plasmas were analyzed for the prothrombin time and INR with the strips at six or seven occasions spread over one year. The test plasmas were recalcified immediately before application to the Coagu Chek-S system. Regression analysis was performed on the clotting times obtained with each plasma. In the majority of cases (i.e. 95%), no significant change was observed at the 5% significance level. A significant change was observed in only 3 cases. In addition, a ranking statistic was used as test of a monotonic relationship in the two-way analysis of variance. The results of the ranking statistic were not significant for any strip lot, indicating that the test strips were stable under these storage conditions. The reproducibility of INR measured with the Coagu Chek-S was assessed. The mean within-run coefficient of variation (CV) of INR ranged from 2.58% to 3.36% (CV). The between-lot variation of the mean INR ranged from 3.2 to 4.5 % (CV). The over-all variation of single INR measurements, i.e. including between-lot and within-lot, ranged from 5.0 to 6.0 % (CV).
Anti-Xa effect of a low molecular weight heparin (dalteparin) does not accumulate in extended duration therapy for venous thromboembolism in cancer patients
Authors: Levine Mark , Keeney Michael , MacKinnon Karen , Lee Agnes , Kovacs Michael
Published: May 2005

Many patients with venous thromboembolism are being treated with low molecular weight heparin for extended periods of time. It is not certain if it is necessary to assess anti-Xa levels for extended treatment periods. This study is a prospective assessment of anti-Xa levels in patients on long-term therapy for acute venous thromboembolism who have active cancer. Consecutive consenting patients from one center in a multicenter trial that compared 6 months of low molecular weight heparin with oral anticoagulant therapy were treated with therapeutic doses of dalteparin (200 IU per kilogram) subcutaneously daily. Anti-Xa levels were assessed at the end of weeks 1 and 4, 4–6 hours after injection of dalteparin. Patients were followed for bleeding and recurrent venous thromboembolism. There were 24 patients who had anti-Xa levels measured at weeks 1 and 4. Two other patients had week 1 measurements performed but died before the week 4 sample was collected due to their underlying cancer. The mean anti-Xa levels at weeks 1 and 4 were 1.11 and 1.03 anti-Xa units/ml respectively (P=0.13). These results suggest that for patients with active cancer receiving extended duration therapy with low molecular weight heparin (dalteparin) there is no accumulation of anti-Xa effect over the first month of therapy. Monitoring of anti-Xa levels in this situation is usually not required.
A New Solution of a Nonlinear Model of Upwelling
Authors: Choboter P. F. , Samelson R. M. , Allen J. S.
Published: May 2005

A two-dimensional, frictionless, nonlinear model of coastal upwelling is reexamined. The model has been solved previously at steady state and as an initial-value problem. The previous solution to the initial-value problem is inconsistent with the steady-state solution. A new solution to the spinup problem is presented that approaches the existing steady-state solution. In the new solution, a surface equatorward jet develops more rapidly than a poleward undercurrent, but the surface jet is of limited strength so that the undercurrent velocity eventually surpasses that of the surface flow. Consideration of dimensional scales implies that the magnitude of the wind stress determines how quickly steady state is approached but does not affect the steady-state fields. Exact solutions found with an arbitrary alongshore pressure gradient imply that there is no poleward flow without a poleward pressure gradient.
Youth radio as ‘social object’: the social meaning of ‘free radio’ shows for young people in France
Authors: Glevarec Hervé
Published: May 2005

A distinctive aspect of French radio is the very liberal and open-minded ‘free radio’ phone-in programmes broadcast on young people’s radio stations (Skyrock, Fun Radio and NRJ). These programmes deal with ‘young people’s problems’, say the 15–16-year-olds we interviewed – that is, sexuality and relationships, teenage identity, drugs and sometimes political subjects. The article first shows how radio is a medium particularly able to exploit its dual nature as both conversation and device, text and frame, conversational exchange and social interaction. The phone hoax is a typical example of this. The ‘metatextuality’ of young people’s radio is characterized by ‘talk about’ television, magazines and other radio programmes. This article also proposes a new analysis of reception based on a ‘hermeneutic sociology’ – by which we do not mean textual analysis – applied to ‘free radio’ shows, which are neither conventional talk shows, news or current affairs, nor fiction. In order to analyse their reception by young people, the article asks: ‘What kind of “social object” is radio for teenagers?’ The question is not what use teenagers make of radio programmes or how they interpret or ‘read’ them, but what these programmes represent for them. The article analyses four types of ‘social object’ – radio as ‘common sphere’, as ‘quasi-institution’, as ‘social event/occasion’ and as ‘device’. It describes what these ‘objects’ indicate in relation to socially situated listeners and to different ‘free radio’ formats.
Creating immigrant identities in cybernetic space: examples from a non-resident Indian website
Authors: Mitra Ananda
Published: May 2005

Looking at the Internet from the perspective of ‘voice’ and ‘space’, an argument is presented that suggests that the Internet offers the unique opportunity for marginal voices to be uttered in the public sphere. Numerous such utterances can begin to create a discursive space that eventually can become a ‘safe’ place for such voices. Finding such a safe space is particularly urgent for non-European immigrants in the Western hemisphere who are finding their identities being challenged and questioned following the 11 September 2001 terrorist attacks on the United States. Using examples from a website for non-resident Indians, it is possible to demonstrate that an unique cybernetic space is evolving in the synthesis of the ‘real’ spatial location of the immigrants from where the ‘virtual’ space is accessed thus offering the immigrants an opportunity to comfortably share their multi-faceted identity narratives using their unique and non-editorialized voices.
Entrepreneurial Teams within Franchise Firms
Authors: Clarkin John E. , Rosa Peter J.
Published: May 2005

In the research on franchising firms, several assumptions are generally made. One such assumption is that the role of the entrepreneur is predominantly associated with franchisors, and that franchisees operate under a uniformly regimented system of contractual obligations. Given the restrictions and rules, franchisees have few opportunities for entrepreneurial creativity, serving as owner-managers of a single outlet in a prescribed role of managerial convenience. This study reveals a much more complex and dynamic pattern of relationships between the franchisors and franchisees. Evidence of entrepreneurial teamwork is found, where creativity and adaptation is not always confined to franchisors, and several forms of nested teams within franchising firms are examined. Using both quantitative analysis of secondary data from 1201 North American franchises and in-depth interviews, evidence of entrepreneurial teamwork within the context of franchising firms is presented. The study reveals that restrictive franchise agreements were not always rigorously enforced unless problems occurred, allowing room for entrepreneurial activity by franchisees.
Letters to the Editor: A Feedback Opportunity Turned into a Marketing Tool
Authors: Raeymaeckers Karin
Published: May 2005

Letters to the editor are valuable tools improving feedback procedures for traditional print media, placing topics that occupy the public at large on the public agenda. In this article, the results of research on selection procedures and editing practices in Flemish newsrooms are presented. In addition to content analysis of published letters in several Flemish newspapers and in-depth interviews of the editors-in-chief, the study includes some qualitative, innovative and creative research techniques. In an attempt to analyse objectively the selection procedures, the researcher wrote more than 100 letters to the newspapers’ editorial offices. The outcome of this part of the study offers a thought-provoking insight into the selection criteria as well as the editing of the letters section.
‘A Small Country with a Big Ambition’
Authors: Boyle Raymond , Monteiro Cláudia
Published: May 2005

This article examines the way aspects of Portugal and Portuguese culture and society are talked about in and around the media coverage of a major international sporting event. It focuses on how things other than sport get talked about against the backdrop of a major international sporting and media event, and how these discourses connect with wider political, economic and cultural frames of reference. The research draws from newspaper coverage of Euro 2004 in the Portuguese and British newspaper markets. It examines the distinctive news sports agendas in both countries and shows how there is a growing distinction between the more European style of sports journalism in the British broadsheet/compact market and that of the tabloid newspapers in this country. It also outlines the differing versions of Portugal presented to the world from within two differing European newspaper markets.
The effects of high-dose and low-dose tryptophan depletion on mood and cognitive functions of remitted depressed patients
Authors: Booij Linda , Van der Does A. J. Willem , Haffmans P. M. Judith , Riedel Wim J. , Fekkes Durk , Blom Marc J. B.
Published: May 2005

It has frequently been demonstrated that acute tryptophan depletion (ATD) induces a transient depressed mood in some patients who are in remission from depression. However, the effects of ATD on cognitive processes in remitted depressed patients have not been investigated. The aim of the present study was to investigate the effects of different extents of depletion on mood and cognitive tasks involving neutral and emotional stimuli. Twenty patients in remission or in partial remission from depression received ATD in a double-blind, crossover design. Mood was assessed at both sessions before, at +6.5 h and +24 h afterdepletion. Cognitive assessment in both sessions started at +4.75 h, and also before and after the whole procedure. The ATD mixtures induced the expected reductions of plasma tryptophan levels. High-dose ATD induced a depressive response in a subsample of patients and impaired theprocessing of positive information independent of mood change. Attention for neutral stimuli (Stroop interference) improved in a dose-dependent manner. ATD may affect mood and cognition via different pathways: one implicated in mood regulation and the processing ofemotional information, and one for the processing of neutral information. The first pathway may be more important for discriminating vulnerability to impaired serotonin function. The comparison of the effects of high-dose and low-dose ATD is useful for those studies aiming to investigate the relationships among 5-HT, mood and cognition.
Cannabinoids in bipolar affective disorder: a review and discussion of their therapeutic potential
Authors: Ashton C. H. , Moore P. B. , Gallagher P. , Young A. H.
Published: May 2005

Bipolar affective disorder is often poorly controlled by prescribed drugs. Cannabis use is common in patients with this disorder and anecdotal reports suggest that some patients take it to alleviate symptoms of both mania and depression. We undertook a literature review of cannabis use by patients with bipolar disorder and of the neuropharmacological properties of cannabinoids suggesting possible therapeutic effects in this condition. No systematic studies of cannabinoids in bipolar disorder were found to exist, although some patients claim that cannabisrelieves symptoms of mania and/or depression. The cannabinoids Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) may exert sedative, hypnotic, anxiolytic, antidepressant, antipsychotic and anticonvulsant effects. Pure synthetic cannabinoids, such as dronabinol and nabilone and specific plant extracts containing THC, CBD, or amixture of the two in known concentrations, are available and can be delivered sublingually. Controlled trials of these cannabinoids as adjunctive medication in bipolar disorder are now indicated.
China's Comprador Capitalism Is Coming Home
Authors: Heartfield James
Published: May 2005

Market reforms in China have transformed relations between the mainland and its expatriate capitalist class, which is returning to participate in the country's economic resurgence. The “comprador” capitalism that China exported throughout East Asia is coming to an end, and with it the subservience of Chinese business to foreign capital. The transformation of China's relationship to its expatriate trading class is changing even the geography of the country. China has assimilated the foreign-ruled outposts on its borders—Hong Kong and Macao—and shifted the center of economic gravity to the southeastern coastal regions.
Herbal Product Contamination and Toxicity
Authors: Smolinske Susan C.
Published: May 2005

Herbal poisoning exposures reported to poison centers increased by 344% after passage of the Dietary Supplement Health and Education Act, with 24412 exposures reported in 2003. Increased toxicity is speculated to be related to lack of child-resistant packaging, new issues of contamination, proliferation of multiple ingredient products, excessive concentration of active ingredients, and discovery of new drug-herb interactions. This review addresses contamination issues such as heavy metals, pharmaceuticals, homeopathic remedies, microbes, insects, environmental chemicals, and mis-identification of one plant for another. Toxicity issues covered include carcinogenicity, delay in seeking medical treatment when using herbs to treat serious illness, toxic components, hypersensitivity reactions, hepatotoxins, nephrotoxins, epileptogenic compounds, cardiac toxins, gastrointestinal toxins, and hematologic toxins. Common drug-herb interactions are discussed. The pharmacist plays an important role in patient education and evaluation of potential toxicities related to herbal supplements.
Preventing Medication Errors at Home
Authors: John Jincy M.
Published: May 2005

Medication errors occur at the hands of not only health care professionals but also of in-home patient caregivers or the patients themselves. This article explores the various causes for therapeutic errors in pediatric as well as elderly patients within their home settings. In addition, suggestions are provided on educating the patients and their caregivers on the prevention of medication errors.
Prison (E)scapes and Body Tropes: Older Women in the Prison Time Machine
Authors: Wahidin Azrini , Tate Shirley
Published: May 2005

The focus of this article will be on inserting the words of older women in prison into debates on time, agency and gendered identities in total institutions. Specifically, the article will address the complexity and contradictions of the time of ‘a mediated real’, and how this impacts on embodied identities within prison timescapes. This will be explored through looking at how prison-time as a ‘somatic identity cipher’ functions performatively in the construction of older women’s identities. The article will also examine how female elders in prison become agents and negotiate techniques of discipline. The role of prison-time will be shown to be simultaneously experienced as further punishment while also being resisted as we draw out the relationship between temporality, spaces of incarceration and identification. First, we will locate the field in terms of issues of theory and method. Then we will look at performativity, identity and time in negotiating, acquiescing to and resisting the identity ‘prisoner’. This will enable us to understand the role and meaning of time in relation to how females in prison are compelled to reiterate and negotiate the identity ‘prisoner’ within the discipline of ‘the time of incarceration’. We hope to demonstrate through the voices of the women that there is no single abstract imprisoned body. These are real bodies, fleshy, sensate bodies that experience real pain; at the same time, these bodies are not simply given but also interpreted, mediated and in part constituted in social and cultural meanings. This enables us to show that the body can be both a generator and receptor of meanings.
Big Handsome Men, Bears and Others: Virtual Constructions of ‘Fat Male Embodiment’
Authors: Monaghan Lee F.
Published: May 2005

Using embodied sociology, this article offers a virtual ethnography of ‘fat male embodiment’. Reporting and analysing qualitative data generated online, it includes a typology of big/fat male body-subjects and supportive/admiring others. These fat-friendly typifications are unpacked by referencing advocated codes of self–body relatedness, sexualities and the relevance of food. The virtual construction of acceptable, admirable or resistant masculinities is then explored under the following headings: (1) appeals to ‘real’ or ‘natural’ masculinity; (2) the admiration and eroticization of fat men’s bodies; (3) transgression, fun and the carnivalesque; and (4) the pragmatics and politics of fat male embodiment. While alternative (positive) understandings of fatness are presented online, discrepancies between virtual and actual identities render stigma an ever-present possibility for those with ‘real’ fat male bodies.
Citizenship, Identity, Blood Donation
Authors: Valentine Kylie
Published: May 2005

Blood donation is broadly understood to be a public and altruistic act. However, new theories of citizenship and subjectivity suggest that the individual and embodied qualities of blood also need to be taken into account when examining donation. This article examines the relationship between public and private elements of blood donation. Donating blood is not an entirely public act, and does not provide an entirely impersonal resource. The embodied self is integral to public practices, and, equally, public domains are important to the constitution of private spaces. However, this study shows that recognition of the individuality of blood is often cast in moral terms. The exclusion of already marginalized people from donating blood presents a risk of further marginalization. If blood donation is understood to be a civic practice open to everyone, then it becomes too easy to see those who cannot donate as non-citizens. New vocabularies of difference are needed. It is an ongoing necessity that altruistic donors are valued; it is also important that those who cannot donate are not punished by this process of valuing.
Values in the practice of teaching, and questions for quality and equity in schools
Authors: Evans Cecilia Fierro
Published: May 2005

Noting that research on cognitive development and on values are normally separate, the author shows the connection by closely examining different ways in which teachers relate to students. Modes of discipline based on positional authority, and even force, rather than on an ethical dialogue, not only reduce students’ self-esteem but also limit their ability to reflect on situations with a degree of objectivity. In classrooms where the discourse is grounded in rational reflection, students develop greater self-esteem and engagement but also benefit cognitively through engagement in higher-level reasoning.
Doing empathy and sympathy: caring responses to troubles tellings on a peer support line
Authors: Pudlinski Christopher
Published: May 2005

Conversation analysis of 53 emotive responses to troubles tellings on a peer support line discovered eight different methods for expressing empathy and/or sympathy. Emotive reactions, assessments, and formulating the gist of the trouble typically occur early on in a troubles telling. Reporting one’s own reaction was found in the midst of troubles telling, as a second reaction to ‘bad’ news or after callers’ reports of their own feelings. Naming another’s feelings and using an idiom occur towards the end of a troubles telling. Sharing a similar experience of similar feelings and expressing one’s feelings were used in various places within a troubles telling and conveyed more than basic concern about the callers’ feelings. These and other differences between methods further detail the various ways support providers and recipients perform empathy and/or sympathy in situ.
Concise narratives: a structural analysis of political discourse
Authors: Shenhav Shaul R.
Published: May 2005

The article suggests a new framework for the structural analysis of political narratives using the concept of ‘concise narrative’. These are segments of a speech that contain its entire temporal range in a few paragraphs. Based on the analysis of Israeli ministerial discourse during the early years of the state, the article argues that these ‘concise narratives’ can shed light on the infrastructure of political narratives. A study of ‘concise narratives’ can also illuminate how political values, identities and ideologies are combined with day-to-day politics while being transferred from the speaker to his audience. The epilogue examines the intertextual relations between different political narratives, focusing on the transition of ‘concise narratives’ from the early days of Israeli politics to contemporary political discourse.
Conversational floors in synchronous text-based CMC discourse
Authors: Simpson James
Published: May 2005

This article presents a study of the discourse characteristics of interaction within a virtual community. The data are from the text-based chat forum of an online community of learners and teachers of English. The forum is the meeting place for community members, and is an international site of language use with participants from a range of linguistic backgrounds. Within this context, some pertinent themes are investigated which relate to a relatively recent form of discourse, synchronous text-based computer-mediated communication (SCMC). The discussion centres on the interplay between the technological attributes of the medium and the linguistic, discourse and sociocultural conditions within which the participants interact. How do these elements combine to shape the discourse? This question is addressed with reference to the cohesive feature of conversational floor. Because there is a lack of coordination of turn transfer in SCMC interaction, conversational floor emerges as an organizing principle in preference to models of conversation based on turn taking.
A Utilitarian Justification of Desert in Distributive Justice
Authors: Kristjánsson Kristján
Published: May 2005

We cannot conclude from the assumptions that justice is a virtue and desert is an ingredient in justice that desert claims themselves express a virtue. It could be that desert is morally neutral, or even immoral, and that there are other aspects of justice which make it all-in-all virtuous. We need, in other words, an independent moral justification of desert and desert-based emotions. In this paper I take on the challenge of articulating and defending a utilitarian justification of desert in distributive justice. I argue, first, that while there may be ways of accommodating desert-concerns in liberal theory, this cannot, in the view of liberals themselves, be done without considerable cost to the ideals that are closest to their hearts. By contrast, I suggest that a deceptively simple utilitarian (Millian) defence of desert can be made to work. Finally, I attempt to surmount various possible objections that might be raised against my utilitarian justification and conclude that none of them confutes it.
A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein β and NF-κB activity in Hodgkin and anaplastic large cell lymphomas
Authors: Jundt Franziska , Raetzel Nina , Müller Christine , Calkhoven Cornelis F. , Kley Katharina , Mathas Stephan , Lietz Andreas , Leutz Achim , Dörken Bernd
Published: May 2005

The immunosuppressive macrolide rapamycin and its derivative everolimus (SDZ RAD, RAD) inhibit the mammalian target of rapamycin (mTOR) signaling pathway. In this study, we provide evidence that RAD has profound antiproliferative activity in vitro and in NOD/SCID mice in vivo against Hodgkin lymphoma (HL) and anaplastic large cell lymphoma (ALCL) cells. Moreover, we identified 2 molecular mechanisms that showed how RAD exerts antiproliferative effects in HL and ALCL cells. RAD down-regulated the truncated isoform of the transcription factor CCAAT enhancer binding protein β (C/EBPβ), which is known to disrupt terminal differentiation and induce a transformed phenotype. Furthermore, RAD inhibited constitutive nuclear factor κB (NF-κB) activity, which is a critical survival factor of HL cells. Pharmacologic inhibition of the mTOR pathway by RAD therefore interferes with essential proliferation and survival pathways in HL and ALCL cells and might serve as a novel treatment option. (Blood. 2005;106: 1801-1807)
Lentiviral shRNA silencing of murine bone marrow cell CCR2 leads to persistent knockdown of CCR2 function in vivo
Authors: Bot Ilze , Guo Jian , Van Eck Miranda , Van Santbrink Peter J. , Groot Pieter H. E. , Hildebrand Reeni B. , Seppen Jurgen , Van Berkel Theo J. C. , Biessen Erik A. L.
Published: May 2005

A major barrier in hematopoietic gene function studies is posed by the laborious and time-consuming generation of knockout mice with an appropriate genetic background. Here we present a novel lentivirus-based strategy for the in situ generation of hematopoietic knockdowns. A short hairpin RNA (shRNA) was designed targeting murine CC-chemokine receptor 2 (CCR2), which was able to specifically blunt CCR2 expression at the mRNA, protein, and functional levels in vitro. Reconstitution of irradiated recipient mice with autologous bone marrow that had been ex vivo transduced with shRNA lentivirus led to persistent down-regulation of CCR2 expression, which translated into a 70% reduction in CCR2-dependent recruitment of macrophages to an inflamed peritoneal cavity without noticeable side effects on related chemokine receptors or general inflammation status. These findings clearly demonstrate the potential of shRNA lentivirus–infected bone marrow transplantation as a rapid and effective method to generate hematopoietic knockdowns for leukocyte gene function studies.
Bombay phenotype is associated with reduced plasma-VWF levels and an increased susceptibility to ADAMTS13 proteolysis
Authors: O'Donnell James S. , McKinnon Thomas A. J. , Crawley James T. B. , Lane David A. , Laffan Michael A.
Published: May 2005

ABO blood group is an important determinant of plasma von Willebrand factor antigen (VWF:Ag) levels, with lower levels in group O. Previous reports have suggested that ABO(H) sugars affect the susceptibility of VWF to ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type-1 repeats-13) cleavage. To further test this hypothesis, we collected plasma from individuals with the rare Bombay blood group. VWF:Ag levels were significantly lower in Bombay patients (median, 0.69 IU/mL) than in groups AB, A, or B (P < .05) and lower than in group O individuals (median, 0.82 IU/mL). Susceptibility of purified VWF fractions to recombinant ADAMTS13 cleavage, assessed using VWF collagen-binding assay (VWF:CB), was increased in Bombays compared with either group O or AB. Increasing urea concentration (0.5 to 2 M) increased the cleavage rate for each blood group but eliminated the differences between groups. We conclude that reduction in the number of terminal sugars on N-linked glycan increases susceptibility of globular VWF to ADAMTS13 proteolysis and is associated with reduced plasma VWF:Ag and VWF:CB levels.
Time-course analysis of hepcidin, serum iron, and plasma cytokine levels in humans injected with LPS
Authors: Kemna Erwin , Pickkers Peter , Nemeth Elizabeta , van der Hoeven Hans , Swinkels Dorine
Published: May 2005

Hepatic peptide hormone hepcidin is the key regulator of iron metabolism and the mediator of anemia of inflammation. Previous studies indicated that interleukin-6 (IL-6) mediates hepcidin increase and consequent hypoferremia during inflammation. Here we used an in vivo human endotoxemia model to analyze the effects of lipopolysaccharide (LPS) as a more upstream inflammation activator. The temporal associations between plasma cytokines, hepcidin levels, and serum iron parameters were studied in 10 healthy individuals after LPS injection. IL-6 was dramatically induced within 3 hours after injection, and urinary hepcidin peaked within 6 hours, followed by a significant decrease in serum iron. Serum prohepcidin showed no significant change within a 22-hour time frame. These in vivo human results confirm the importance of the IL-6-hepcidin axis in the development of hypoferremia in inflammation and highlight the rapid responsiveness of this iron regulatory system. (Blood. 2005;106: 1864-1866)
Persistence of lung inflammation and lung cytokines with high-resolution CT abnormalities during recovery from SARS
Authors: Wang Chun-Hua , Liu Chien-Ying , Wan Yung-Liang , Chou Chun-Liang , Huang Kuo-Hsiung , Lin Horng-Chyuan , Lin Shu-Min , Lin Tzou-Yien , Chung Kian Fan , Kuo Han-Pin
Published: May 2005

Background

During the acute phase of severe acute respiratory syndrome (SARS), mononuclear cells infiltration, alveolar cell desquamation and hyaline membrane formation have been described, together with dysregulation of plasma cytokine levels. Persistent high-resolution computed tomography (HRCT) abnormalities occur in SARS patients up to 40 days after recovery.

Methods

To determine further the time course of recovery of lung inflammation, we investigated the HRCT and inflammatory profiles, and coronavirus persistence in bronchoalveolar lavage fluid (BALF) of 12 patients at recovery at 60 and 90 days.

Results

At 60 days, compared to normal controls, SARS patients had increased cellularity of BALF with increased alveolar macrophages (AM) and CD8 cells. HRCT scores were increased and correlated with T-cell numbers and their subpopulations, and inversely with CD4/CD8 ratio. TNF-α, IL-6, IL-8, RANTES and MCP-1 levels were increased. Viral particles in AM were detected by electron microscopy in 7 of 12 SARS patients with high HRCT score. On day 90, HRCT scores improved significantly in 10 of 12 patients, with normalization of BALF cell counts in 6 of 12 patients with repeat bronchoscopy. Pulse steroid therapy and prolonged fever were two independent factors associated with delayed resolution of pneumonitis, in this non-randomized, retrospective analysis.

Conclusion

Resolution of pneumonitis is delayed in some patients during SARS recovery and may be associated with delayed clearance of coronavirus, Complete resolution may occur by 90 days or later.