bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tissue factor expression by a human kidney proximal tubular cell line in vitro: a model relevant to urinary tissue factor secretion in disease?
Authors: Lwaleed Bashir A , Vayro Steven , Racusen Lorraine C , Cooper Alan J 
Published: December 2006

Aim:To study baseline and stimulated tissue factor (TF) production from a normal, albeit immortalised, human kidney proximal tubular cell line (HKC-5), in order to establish a model for investigating the role of inflammatory mediators in the increased urinary TF (uTF) seen in inflammatory and neoplastic disease.Methods:TF procoagulant activity, expression and secretion in HKC-5 cells were investigated using TF activity and antigen assays, fluorescence confocal microscopy and immunocytochemistry. TF expression in the HKC-5 cells was also studied using reverse transcription (RT)-PCR and its synthesis was suppressed using antisense oligodeoxynucleotide (ODN), directed against human TF mRNA. Cells were stimulated, after serum deprivation, with bacterial lipopolysaccharide (LPS), an agonist known to enhance TF expression in monocytes. They were also subject to serum starvation.Results:Analysis by RT-PCR showed TF production by stimulated and actively metabolising HKC-5 cells. Antisense ODN treatment resulted in approximately 50% suppression of TF synthesis compared to a mismatch ODN. The amount of TF produced by the HKC-5 cells was time dependent and coincides with a decrease in the intracellular TF levels. LPS up-regulated TF production in HKC-5 cells. Reducing fetal calf serum concentrations in the culture medium decreased TF production and secretion.Conclusion:Stimulated TF synthesis and secretion in vitro by HKC-5 cells is consistent with the hypothesis that uTF is produced by tubular cells influenced by mediators of disease states and provides a model for further mechanistic investigations.
Hodgkin’s lymphoma associated T-cells exhibit a transcription factor profile consistent with distinct lymphoid compartments
Authors: Atayar Çiğdem , van den Berg Anke , Blokzijl Tjasso , Boot Marcel , Gascoyne Randy D , Visser Lydia , Poppema Sibrand 
Published: December 2006

Background:Hodgkin’s lymphoma (HL) is characterised by an ineffective immune response that is predominantly mediated by CD4+T-cells.Aims:To analyse the expression of the key regulatory T-cell transcription factors (TFs) in the T-cells of HL involved tissues in order to assess the nature of the THimmune response in HL.Methods and results:By immunohistochemistry, GATA3 was strongly and T-bet exclusively expressed in a subset of interfollicular lymphocytes in the reactive lymphoid tissues. In classical HL (CHL), which is generally located in the interfollicular zones, a predominance of T-bet+T-cells and lesser amounts of GATA3+and c-Maf+T-cells was found, concordant with the pattern of the normal interfollicular compartment. In reactive lymphoid tissues, c-Maf was observed mostly in T-lymphocytes within the germinal centres (GCs). Nodular lymphocyte predominance type of Hodgkin’s lymphoma (NLPHL) and progressively transformed germinal centres cases, showed a majority of c-Maf+T-cells, consistent with the pattern in normal GCs. NLPHL cases uniformly showed c-Maf+/CD57+T-cell rosettes around the neoplastic cells; these rosettes were absent in “paragranuloma-type” T-cell/histiocyte rich B-cell lymphoma.Conclusions:T-cell TF expression profiles of the reactive T-cells in both subtypes of HL are in accordance with the expression profile observed in the distinct lymphoid compartments.
Naturally-occurring regulatory T cells are increased in inflamed portal tracts with cholangiopathy in primary biliary cirrhosis
Authors: Sasaki Motoko , Ikeda Hiroko , Sawada Seiko , Sato Yasunori , Nakanuma Yasuni 
Published: December 2006

Background:Primary biliary cirrhosis (PBC) is an autoimmune liver disease targeting the intrahepatic small bile ducts showing chronic non-suppurative destructive cholangitis (CNSDC). Recent studies suggest that naturally-occurring CD4+CD25highregulatory T cells (Tregs) expressing Forkhead box P3 (Foxp3) play an active role in immunological self-tolerance.Aims:To investigate whether Foxp3+Tregs are involved in the pathogenesis of PBC.Methods:Foxp3+Tregs was detected immunohistochemically in livers from patients with PBC (n = 27), chronic viral hepatitis (CVH) (n = 15), and normal subjects (n = 10). The distribution of Tregs in portal tracts was semi-quantitatively evaluated in each groups. Levels of Foxp3, IL-10, TGFβ, IFNγ and TNFα mRNA was evaluated in PBC (n = 15) and control livers (n = 21) using semi-quantitative reverse transcriptase-PCR.Results:In PBC and CVH livers, the amounts of infiltrating Foxp3+Tregs in portal tracts were in parallel with the degree of portal inflammation irrespective of disease. The infiltration of Foxp3+Tregs into portal tracts with CNSDC in PBC was foremost in comparison with inflamed portal tracts in CVH or those without CNSDC in PBC (p<0.05). Focally, Tregs infiltrated into the biliary epithelial layer at the site of CNSDC. The level of Foxp3, IL-10 and TGFβ mRNA expression was high in PBC compared with normal livers (p<0.05). IFNγ and TNFα mRNA was high in early PBC and CVH livers.Conclusion:Results of this evaluation of Foxp3+Tregs do not suggest that the reduced regulatory function accounts for the development of CNSDC in PBC.
Comparison of Effects of Vitamin E and Wen-jing-tang (Unkei-to), An Herbal Medicine, on Peripheral Blood Flow in Post-menopausal Women with Chilly Sensation in the Lower Extremities: A Randomized Prospective Study
Authors: Ushiroyama Takahisa , Sakuma Kou , Nosaka Sakura 
Published: December 2006

We examined the association between blood flow and chilly sensation in the lower extremities, comparing the changes in blood flow induced by the vitamin E and herbal therapy (Wen-jing-tang) in perimenopausal women with chilly sensation. One hundred sixty-one perimenopausal women aged 42–61 years (mean: 50.4 ± 3.8 years) with chilly sensation in the lower extremities participated in the study. The participants were randomized for treatment with Wen-jing-tang or a vitamin E preparation containing 600 mg tocopherol nictinate per day for 8 weeks. Blood flow measurement was performed by laser Doppler fluxmetry to determine tissue under the jaw, in the middle finger, and in the third toe. Wen-jing-tang significantly increased the peripheral blood flow in the skin surface in the tiptoe (12.8 ± 8.8, p = 0.0068) from basal levels (6.0 ± 5.1), although no significant change was observed in the blood flow in fingertip or under the jaw during treatment. The rate of increase of blood flow in the skin surface of in the lower extremities was significantly higher in the Wen-jing-tang treating group (116.4 ± 46.5%) than in the vitamin E group (39.8 ± 21.3%)( p < 0.0001). When the effects of herbal treatment and vitamin E treatment were compared in the subjects with baseline upper extremity blood flow above the mean + 1.5 SD, mean blood flow through the upper extremities was found to have been significantly decreased after Wen-jing-tang treatment (from 57.7 ± 4.8 to 43.1 ± 4.2, p = 0.0277), whereas it remained unchanged after treatment with vitamin E. Classical monographs described Wen-jing-tang as being particularly useful in curing chilly sensation in lower extremities. The present study using a laser Doppler fluxmeter demonstrated that treatment with this herbal medicine significantly increased blood flow through the periphery of lower extremities in patients with chilly sensation. It also showed that this herbal medicine suppresses excessive blood flow through the upper half of the body and thus stimulates restoration of physiological distribution of blood flow throughout the entire body.
Use of calibrated automated thrombinography ± thrombomodulin to recognise the prothrombotic phenotype
Authors: Trzeciak M. , Bordet Jean , Ninet Jacques , Negrier Claude , Dargaud Yesim 
Published: December 2006

SummaryThere is currently no validated method to detect a prothrombotic phenotype. The question remains, can tissue factor (TF) induced thrombin generation (TG), as measured with the calibrated automated thrombinography (CAT) technique, according to Hemker et al., recognise a prothrombotic state either as such, or when the activated proteinC (APC)-system is boosted with thrombomodulin (TM)? We determined the normal range of CAT-TG ± TM in a group of 71 healthy blood donors, in 11 healthy women using oral contraceptives (OC), and in 89 patients with a history of venous thromboembolism (VTE), divided into a group of 50 in whicha prothrombotic risk factor could be found (VTEprf+) and 39 others (VTEprf-). The endogenous thrombin potential (ETP) in the OC, VTEprf+ and VTEprf-group was significantly higher than for the controls. In the presence of TM, the differences were significantly higher than in its absence. The VTEprf+ group had a higher ETP, ± TM than the VTEprf group. In conclusion,TG, measured with the CAT technique in the presence of TM is capable of detecting the prothrombotic phenotype with a high sensitivity of 0.93 (95% confidence limits 0.82–0.99).
Management of cutaneous type IV hypersensitivity reactions induced by heparin
Authors: Schindewolf Marc , Utikal Jochen , Lindhoff-Last Edelgard , Boehncke Wolf-Henning , Ludwig Ralf 
Published: December 2006

SummaryLocalized hypersensitivity reactions to subcutaneous heparin injections have been described since 1952. Yet, the incidence of these reactions, which are distinct from skin lesions associated with heparin-induced thrombocytopenia type II (HIT II), remains uncertain. However, in the last 10 years an increasing number of patients have been reported, leading to the assumption that cutaneous hypersensitivity reactions towards heparin are underreported. Clinically patients present with itching, sometimes infiltrated, and blistering erythemas at the injection sites of heparins. The diagnosis of cutaneous heparin allergy may, on the one hand, lead to delay of required medical or surgical treatment. On the other hand, delayed initiation of treatment may lead to a generalized eczematous reaction. Hence, from review of 223 cases of patients with cutaneous hypersensitivity reactions to heparin, we here summarize the clinical picture of cutaneous type IV allergic reactions, define risk factors on both the patient- and drug-side, and give an overview of principle therapeutic alternatives, as well as recommendations for treatment options for emergency and elective patients. As the proposed management of patients with cutaneous hypersensitivity reactions to heparin may have fatal consequences when applied in patients with HIT type II, diagnosis of skin lesions in heparin-treated patients needs to be precise.
SELDI-TOF plasma profiles distinguish individuals in a protein C-deficient family with thrombotic episodes occuring before age 40
Authors: Svensson Annika , Whiteley Gordon , Callas Peter , Bovill Edwin 
Published: December 2006

SummaryWe tested the hypothesis that differences in the low-molecularweight (500–20,000 Da) proteomic profile of plasma may be detectable between members ofa protein C-deficient family who have suffered thrombotic events before age 40 compared to family members without a history of venous thrombosis. Unfractionated plasma samples from members of a previously described large thrombophilic kindred with type I protein C deficiency were applied to ProteinChip weak cation exchange interaction arrays (WCX2; Ciphergen Biosystems, Fremont, CA, USA) and subjected to SELDI-TOF (surface-enhanced laser desorption/ionization time-of-flight) mass spectrometry using the Ciphergen PBSII ProteinChip System (Ciphergen Biosystems). Profiles were analyzed by a boosted decision-tree algorithm. When individuals who had presented with deep venous thrombosis (DVT) before the age of 40 (n=21) were compared to age-matched, healthy family members (n=50), the proteomic patterns defined by the decision-tree analysis could classify the entity of DVT before age 40 with 67% sensitivity, ata specificity of 86%.Whena small group of cases with history of superficial venous thrombosis (n=6) was added to the case group, the sensitivity was 87.5% at a specificity of 80%.These data support the hypothesis that members of the protein C deficient Vermont kindred II who suffer a thrombotic event before age 40 display significant differences in low-molecular-weight proteomics profile compared to those who remain disease-free.This is the first study to apply SELDI-TOF technology in conjunction with a bioinformatics tool to analyze low-molecular-weight proteomic patterns in patients with venous thrombosis.The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organization imply endorsement by the U. S. Government.
Anti-metastatic effect of a non-anticoagulant low-molecular-weight heparin versus the standard low-molecular-weight heparin, enoxaparin
Authors: Linhardt Robert , Francis John , Amirkhosravi Ali , Mousa Shaker 
Published: December 2006

SummaryLow-molecular-weight heparins (LMWH) exhibit potent anticoagulant efficacy via their plasmatic effects on thrombin and factor Xa. These agents are also effective in releasing endothelial tissue factor pathway inhibitor (TFPI),the natural inhibitor of tissue factor, and exhibit significant anti-metastatic effects in experimental animal models. However, the potential for bleeding complications has slowed down the more widespread adoption of LMWH therapy in cancer patients. In this study, the effect of a non-anticoagulant form of LMWH (NA-LMWH) on experimental lung metastasis and tumor cell-induced platelet aggregation in vivo was compared to the LMWH enoxaparin. Using the B16 melanoma mouse model of metastasis, subcutaneous (s.c.) injection of NA-LMWH or enoxaparin (10 mg/kg), three hours before intravenous (i.v.) injection of metastatic melanoma cells, followed by daily doses for 14 days, reduced lung tumor formation by 70% (P<0.001). I.v. injection of tumor cells resulted in a significant (50–62%, P<0.01) fall in platelet counts. Pre-injection (i.v.) of enoxaparin completely abolished the tumor cell-induced thrombocytopenia, whereas NA-LMWH had no effect. Four hours after a single s.c. dose, enoxaparin but not NALMWH prolonged the clotting time three-fold and delayed the time to clot initiation more than 10-fold as measured by a Sonoclot analyzer and by thromboelastography, respectively. Enoxaparin but not NA-LMWH demonstrated a significant anticoagulant effect in mice. Both NA-LMWH and enoxaparin caused similar TFPI release from endothelial cells in vitro.These data provide evidence to support the potential of NA-LMWH as an anti-metastatic agent without any significant impact on coagulation.
Monitoring unfractionated heparin with the aPTT: Time for a fresh look
Authors: Hirsh Jack , Eikelboom John 
Published: December 2006

SummaryLaboratory monitoring is widely recommended to measure the anticoagulant effect of unfractionated heparin and to adjust the dose to maintain levels in the target therapeutic range.The most widely used laboratory assay for monitoring unfractionated heparin therapy is the activated partial thromboplastin time (aPTT). A fixed therapeutic range for the aPTT of 1.5 to 2.5 times the control value has become widely accepted,but the evidence supporting this range is weak and the clinical validity of using the aPTT for predicting thrombotic or bleeding events is questionable. The aPTT test is also affected by numerous preanalytic and analytic variables that are unrelated to the anticoagulant effect of unfractionated heparin, further eroding its potential value for monitoring unfractionated heparin treatment. Unfractionated heparin dose appears to be more important than the aPTT in predicting clinical efficacy. Despite serious limitations,the reliance on the aPTT is likely to continue because of its ready availability and familiarity of clinicians with the test. The focus of clinicians who manage unfractionated heparin therapy should be to ensure that an adequate starting dose of unfractionated heparin is used and that the aPTT method is standardized. Future research efforts should be directed towards developing methods to improve standardization of the aPTT assay for monitoring unfractionated heparin. Direct measures of the concentration of unfractionated heparin in the blood are attractive because these assays are not affected by many of the biologic variables that interfere with the aPTT and may be suitable for automation. However, currently available unfractionated heparin assays are much more expensive than the aPTT, are not widely available, and their validity has not been adequately assessed in clinical outcome studies.
Prevention of distal embolization in patients undergoing mechanical revascularization for acute myocardial infarction
Authors: Suryapranata Harry , Chiariello Massimo , De Luca Giuseppe 
Published: December 2006

SummaryDistal embolization is a relatively common complication in primary angioplasty and is associated with poor perfusion and higher mortality. The aim of this article is to critically review literature on pharmacological and mechanical therapies to prevent distal embolization in patients undergoing primary angioplasty. The literature was scanned by formal searches of electronic databases (MEDLINE, Pubmed) from January 1990 to March 2006 and scientific session abstracts (from January 1990 to March 2006) and oral presentation and/or expert slide presentations (from January 2002 to March 2006) (on TCT, AHA, ESC, ACC and EuroPCR websites). No language restrictions were enforced. Several pharmacological and mechanical therapies have been investigated to prevent distal embolization.Abciximab has been shown to reduce mortality,and its early admin-istration may provide additional benefits in outcome due to improvement in preprocedural reperfusion.The results of randomized trials on adjunctive mechanical devices remain controversial. Even though they reduce distal embolization and improve myocardial perfusion, no benefits have been observed in terms of 30-day survival. Adjunctive abciximab has improved survival, and its early administration is to be recommended, particularly when transportation to a primary PCI center is needed. Pending the results of large randomized trials with long-term follow-up data, the routine use of adjunctive mechanical devices to prevent distal embolization cannot be recommended, though selective use of these devices might be considered when large thrombotic burden is present.
The UK National External Quality Assessment Scheme (UK NEQAS) for molecular genetic testing in haemophilia
Authors: Goodeve Anne , Hill Marian , Jennings Ian , Kitchen Steve , Walker Isobel , Perry David ,   UK NEQAS for Blood Coagulation
Published: December 2006

SummaryMolecular genetic analysis of families with haemophilia and other inherited bleeding disorders is nowa common laboratory investigation. In contrast to phenotypic testing in which strict quality control is adhered to, in haemophilia molecular genetic testing there has been a lack of any external quality assurance schemes. In 1998 the UK National External Quality Assessment Scheme (UK NEQAS) established a pilot quality assurance scheme for molecular genetic testing in haemophilia. Results from three initial surveys highlighted problems with the quality of samples when used to screen for the intron 22 inversion within the F8 gene. The scheme was re-launched in 2003, and since that time there have been five exercises involving whole blood or immortalised cell line DNA. The results together with an overall summary of the exercise are subsequently returned to participants. Exercises to date have focused exclusively on haemophilia A and QA, material has included screening for the intron 1 and intron 22 inversions as well as sequence analysis. A paper exercise circulated in 2003 highlighted problems with the format of reports and, following feedback to participants, onlya single error has been made in the subsequent four exercises. Participating laboratories now receive QA material every six months. Immortalised cell line material was introduced in 2005 and was shown to perform well. This will allow expansion of the scheme and a reduction in the dependence on blood donation.
No difference in the effects of clopidogrel and aspirin on inflammatory markers in patients with coronary heart disease
Authors: Pettersen Alf , Arnesen Harald , Seljeflot Ingebjørg , Solheim Svein 
Published: December 2006

SummaryAspirin reduces several pro-inflammatory markers in patients with coronary heart disease (CHD), while limited data exists with clopidogrel. The aim of the present substudy of ASCET was to assess the influence of clopidogrel as compared to aspirin on selected circulating inflammatory markers in patients with stable angiographically verified CHD. Patients on treatment with aspirin 160 mg/day for at least seven days were randomized to either aspirin 160 mg/day (n=105) or clopidogrel 75 mg/day (n=101). Fasting blood samples were drawn at baseline and after one month and after one year for determination of high sensitivity C-reactive protein, tumor necrosis factor α (TNFα), interleukin 6, monocyte chemoattractant protein 1(MCP-1), CD40L, P-selectin, interleukin 10 and transforming growth factor. The groups were similar regarding demographic variables. There were no differences in any variables including changes from baseline to one month and one year between the groups. In the aspirin group we found significantly lower levels of TNFα and MCP-1 after one year; 1.00 versus 1.16 pg/ml (p<0.001) and 245 versus 261 pg/ml (p<0.001), respectively. Likewise, in the clopidogrel group the level of TNFα was significantly reduced after one year; 0.99 versus 1.19 pg/ml (p<0.001). In patients with CHD we found no between-group differences in circulating markers of inflammation after one year treatment with clopidogrel 75 mg/day compared to aspirin 160 mg/day, but in both groups lower levels of TNFα were obtained. The present results indicate similar anti-inflammatory effects of the two drugs.
Immunohistochemistry of thrombi following iliac venous stenting: A novel model of venous thrombosis
Authors: Burches Bobby , Karnicki Krzysztof , Wysokinski Waldemar , McBane Robert 
Published: December 2006

SummaryStenting has become a common intervention for venous occlusive disease. Little is known regarding the composition of venous thrombi complicating stent placement. The optimal design of antithrombotic agents in this setting requires this knowledge. Quantitative immunohistochemistry was undertaken to define the platelet, fibrin(ogen) and leukocyte composition and spatial orientation of venous thrombi following percutaneous iliac stent placement in pigs. Venous stent thrombus size was measured by weight and scintillation detection of autologous 111In-platelets. Thrombi were divided in segments (cephalad to caudad), sectioned and stained with monoclonal anti-platelet glycoprotein Ib or polyclonal anti-fibrin(ogen) fluorescent antibodies. Thrombus platelet content was 100-fold greater than paired whole blood samples. The caudal-most segments contained platelet-rich aggregates (p<0.05) with abundant leukocytes (p<0.0001) relative to more cephalad segments. Platelet and fibrin(ogen) content varied over an eight-fold range between segments but were directly correlated with each other (r=0.77; p<0.0001). The platelet co-localization with fibrin(ogen) is consistent with the phospholipid dependence of prothrombin activation. The abundance and caudal distribution of platelet-leukocyte aggregates indicate their preferential accretion from flowing blood early in the genesis of venous stent thrombi. These may represent novel cellular targets for the prevention and treatment of venous thrombosis.