bluuebunny/crossref_metadata_2025 huggingface dataset:
High frequency of factor V Leiden in surgical patients with symptomatic venous thromboembolism despite prophylaxis
Authors: Baba-Ahmed Mohamed , Le Gal Grégoire , Couturaud Francis , Lacut Karine , Oger Emmanuel , Leroyer Christophe
Published: June 2007

Among candidate risk factors associated with postoperative venous thromboembolism (VTE), the role of factorV Leiden (FVL) mutation remains unclear. We performed a case-control study to assess the potential significance of FVL mutation in postoperative VTE cases despite prophylaxis. We used data from the ongoing case-control “EDITH” study. We extracted 133VTE cases and 144 controls who had undergone either surgery or had plaster cast in the previous three months. Prophylaxis adequacy with regard to the recommendations published by theAmerican College of Chest Physicians was retrospectively assessed. FVL mutation was present in 20VTE cases and four controls (OR 5.9, 95% CI 2–18). Prophylaxis was judged as adequate in 116 cases (88.5 %) and in 129 controls (87.2 %) (p = 0.66). The frequency of FVL mutation was not different in VTE cases occurring while on adequate prophylaxis and in VTE cases occurring after the end of adequate prophylaxis (p = 0.27). FVL mutation was closely associated with postoperative VTE in patients classified as having received an adequate prophylaxis (8.4; 95% CI, 2.4 to 29). This study shows a close association between the presence of factorV Leiden mutation in symptomaticVTE occurring after surgery despite prophylaxis.
Functional promoter polymorphism in the VKORC1 gene is no major genetic determinant for coronary heart disease in Northern Germans
Authors: Eddine El Mokhtari Nour , Ivandic Boris , Müller Jens , Schreiber Stefan , Watzka Matthias , Nebel Almut , Oldenburg Johannes
Published: June 2007

Recently, the C-allele of polymorphism rs2359612 (VKORC1: c.283+837C>T) in the VKORC1 gene has been reported to represent a major risk factor for coronary heart disease (CHD), stroke, and aortic dissection in Chinese patients. VKOR activity itself is the rate-limiting step in gamma-carboxylation of vitamin K-dependent coagulation factors (factors II, VII, IX, X, protein C, S, and Z) and proteins of calcium metabolism (matrix Gla protein and osteocalcin). Gamma-carboxylation is essential for the biological activity of these proteins that have been previously hypothesised to play a role in the pathogenesis of atherosclerosis. It was the objective of this study to analyse the VKORC1 genotype frequency in patients with CHD and controls from Northern Germany and to investigate the association of VKORC1 and CHD risk in patients with an European background. CHD paients (n = 901) and healthy controls (n = 521) were part of the PopGen biobank. Case and control samples were matched for ethnic and geographic origin, age and gender. After typing German CHD patients and control individuals, no evidence for a statistically significant association was detected between VKORC1 genotype and CHD phenotype. Also stratification for gender and myocardial infarction yielded no significant results. In conclusion, the discrepant association findings in Chinese and German populations may be explained by ethnic differences in genetic and perhaps environmental predisposition, modifying the polygenic CHD phenotype by interacting withVKORC1 variants and thus conferring disease susceptibility in some populations, but not in others.
Murine monoclonal antibodies against murine uPA receptor produced in gene-deficient mice: Inhibitory effects on receptormediated uPA activity in vitro and in vivo
Authors: Pass Jesper , Jögi Annika , Lund Ida , Rønø Birgitte , Rasch Morten , Gårdsvoll Henrik , Lund Leif , Ploug Michael , Rømer John , Danø Keld , Høyer-Hansen Gunilla
Published: June 2007

Binding of urokinase plasminogen activator (uPA) to its cellular receptor, uPAR, potentiates plasminogen activation and localizes it to the cell surface. Focal plasminogen activation is involved in both normal and pathological tissue remodeling processes including cancer invasion. The interaction between uPA and uPAR therefore represents a potential target for anti-invasive cancer therapy. Inhibitors of the human uPA-uPAR interaction have no effect in the murine system. To enable in-vivo studies in murine cancer models we have now generated murine monoclonal antibodies (mAbs) against murine uPAR (muPAR) by immunizing uPAR-deficient mice with recombinant muPAR and screened for antibodies, which inhibit the muPA-muPAR interaction. Two of the twelve mAbs obtained, mR1 and mR2, interfered with the interaction between muPAR and the amino-terminal fragment of muPA (mATF) when analyzed by surface plasmon resonance. The epitope for mR1 is located on domain I of muPAR, while that of mR2 is on domains (II-III). In cell binding experiments using radiolabelled mATF, the maximal inhibition obtained with mR1 was 85% while that obtained with mR2 was 50%. The IC50 value for mR1 was 0.67 nM compared to 0.14 nM for mATF. In an assay based on modified anthrax toxins, requiring cell-bound muPA activity for its cytotoxity, a ~50% rescue of the cells could be obtained by addition of mR1. Importantly, in-vivo efficacy of mR1 was demonstrated by the ability of mR1 to rescue mice treated with a lethal dose of uPA-activatable anthrax toxins.
Venous thromboembolism during pregnancy or postpartum: Findings from the RIETE Registry
Authors: Blanco-Molina Angeles , Trujillo-Santos Javier , Criado Juan , Lopez Luciano , Lecumberri Ramón , Gutierrez Reyes , Monreal Manuel ,   for the RIETE Investigators
Published: June 2007

Venous thromboembolism (VTE) occurs infrequently during pregnancy, and issues concerning its natural history, prevention and therapy remain unresolved. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we compared the clinical characteristics and outcome for all enrolled pregnant and postpartum women with acuteVTE, and all non-pregnant women in the same age range. Up to May 2005, 11,630 patients were enrolled in RIETE, of whom 848 (7.3%) were women aged < 47 years. Of them, 72 (8.5%) were pregnant, 64 (7.5%) postpartum. Pregnant women presented less often with symptomatic pulmonary embolism (11%) than non-pregnant women (39%). VTE developed during the first trimester in 29 (40%) pregnant patients; in the second in 13; in the third in 30. Thrombophilia tests were m Venous thromboembolism (VTE) occurs infrequently during pregnancy, and issues concerning its natural history, prevention and therapy remain unresolved. RIETE is an ongoing registry of consecutive patients with objectively confirmed, symptomatic acute VTE. In this analysis, we compared the clinical characteristics and outcome for all enrolled pregnant and postpartum women with acuteVTE, and all non-pregnant women in the same age range. Up to May 2005, 11,630 patients were enrolled in RIETE, of whom 848 (7.3%) were women aged < 47 years. Of them, 72 (8.5%) were pregnant, 64 (7.5%) postpartum. Pregnant women presented less often with symptomatic pulmonary embolism (11%) than non-pregnant women (39%). VTE developed during the first trimester in 29 (40%) pregnant patients; in the second in 13; in the third in 30. Thrombophilia tests were m
Parnaparin, a low-molecular-weight heparin, prevents P-selectindependent formation of platelet-leukocyte aggregates in human whole blood
Authors: Di Fabio Giovannina , Barbanti Miriam , de Gaetano Giovanni , Benedetta Donati Maria , Cerletti Chiara , Maugeri Norma
Published: June 2007

Parnaparin, a low-molecular-weight heparin (LMWH), prevents platelet activation and interaction with polymorphonuclear leukocyte (PMN) in a washed cell system. The in-vitro effect of parnaparin was studied here on platelet-PMN aggregates formed with more physiologic approaches in whole blood, in parallel with unfractionated heparin and enoxaparin, another LMWH. Citrated blood from healthy subjects was stimulated: i) from passage through the “Platelet Function Analyzer” (PFA-100), a device that exposes blood to standardized high shear flow through collagen/ADP cartridges; ii) by collagen and ADP (2 and 50 µg/ml, respectively) added in combination under stirring in an aggregometer cuvette; iii) with recombinant Tissue Factor, to generate thrombin concentrations able to activate platelets without inducing blood clotting, or iv) the Thrombin Receptor Activating Peptide-6 (TRAP-6). Platelet P-selectin and platelet-PMN aggregates were measured by flow cytometry upon stimulation of blood. Fibrinogen binding to platelets and markers of PMN activation were also detected. Platelet P-selectin expression and platelet-PMN aggregate formation were induced in all four activation conditions tested. Parnaparin prevented in a concentration-dependent manner (0.3–0.8 IUaXa/ml) the expression of P-selectin and the formation of mixed aggregates, while the two reference heparin preparations had a much weaker effect. Platelet fibrinogen binding and PMN activation markers (fibrinogen binding, CD11b and CD40) were also prevented by parnaparin. These data extend in more physiological systems of platelet activation, the anti-inflammatory profile of parnaparin, previously reported in washed cells. The greater effect of parnaparin, as compared to the reference heparins, could be due to chemico-physical differences possibly unrelated to their anticoagulant effect.
Calcium-binding sites of the thrombin-thrombomodulin-protein C complex: Possible implications for the effect of platelet factor 4 on the activation of vitamin K-dependent coagulation factors
Authors: Yang Likui , Rezaie Alireza
Published: June 2007

The Ca2+-dependence of protein C activation by thrombin in complex with thrombomodulin (TM) containing chondroitin sulfate (CS) exhibits saturation at ~0.5–1 mM Ca2+, but withTM lacking CS, it has a distinct optimum at ~0.1 mM Ca2+. Since the substrate protein C has multiple Ca2+-binding sites, and the cofactor TM also interacts with Ca2+, the basis for differences in Ca2+ effect on protein C activation by thrombin in complex with TM containing or lacking CS is not known. In this study, by using full-length and Gla-domainless mutants of protein C whose activation by thrombin is independent of either Ca2+ or both Ca2+ and TM, we demonstrate that i) the Ca2+ occupancy of a high-affinity binding site in TM is essential for the high-affinity interaction of the cofactor with thrombin, ii) the Ca2+ occupancy of a binding site (KD ~50 μM) in the catalytic domain of protein C is required for the substrate recognition by the thrombin-TM complex, however, at this concentration of Ca2+ the Gla domain of protein C is not folded properly and thus interacts with exosite-2 of thrombin in complex with TM that lacks CS but not withTM that contains CS, and finally iii) platelet factor 4 can nonspecifically interact with the Gla domain of protein C and other coagulation factors to influence their activation only at subphysiological concentrations of Ca2+.
Characterisation of five factor XI mutations
Authors: Dai Letian , Clarke John , Bolton-Maggs Paula , Savidge Geoffrey , Alhaq Anwar , Mitchell Michael
Published: June 2007

A large scale factor XI (FXI) mutation screening program identified a number of novel candidate mutations and previously reported mutations and polymorphisms. Five potential missense mutations were selected for further study; these included two novel missense mutations – Met-18Ile (p.Met1Ile) and Met102Thr (p.Met120Thr), two previously reported missense mutations – Tyr133Ser (Tyr151Ser) and Thr575Met (Thr593Met), and one amino acid substitution previously reported as a polymorphism – Arg378Cys (Arg396Cys). The substitutions were recreated by the site-directed mutagenesis of a FXI cDNA and stably expressed in a BHK-570 cell line. Subsequent analysis of both the conditioned media and cell lysates showed that three of the substitutions, Met-18Ile, Met102Thr andTyr133Ser, prevented secretion of the mutated protein from the transfected cell line, resulting in a cross-reactive material negative (CRM-) phenotype. The remaining two mutants, Thr575Met and Arg378Cys, secreted significant levels of FXI into the conditioned media; however, these mutant FXIs were shown to have negligible factor IX activation activity in an APTT based assay. These results confirmed all five of the missense mutations as being causative of factor XI deficiency, despite one having been previously reported as a polymorphism (Arg378Cys) and one (Tyr133Ser) as a mild mutation – FXI:C 38 U/dl in a homozygous patient.
Fibrinogen and fibrin induce synthesis of proinflammatory cytokines from isolated peripheral blood mononuclear cells
Authors: Kierulf Peter , Sandset Per , Klingenberg Olav , Joø Gunn , Godal Hans , Skjønsberg Ole , Jensen Torstein
Published: June 2007

Fibrinogen in plasma includes three main fractions; high-molecular- weight (HMW) -fibrinogen, low-molecular-weight (LMW) -fibrinogen, and very-low-molecular-weight (LMW`) -fibrinogen. During acute-phase conditions, plasma fibrinogen levels and the HMW-/LMW-fibrinogen ratio increase rapidly due to increased synthesis of HMW-fibrinogen. The consequences of elevated plasma fibrinogen levels and local deposition of fibrin in inflammatory tissues observed during acute-phase conditions are not clear.We wanted to investigate proinflammatory effects of fibrinogen and fibrin on peripheral blood mononuclear cells (PBMC) as reflected by altered mRNA expression and synthesis of the proinflammatory cytokines IL-6,TNF- α and IL-1 β, and to explore the significance of altered HMW-/LMW-fibrinogen ratio. PBMC were isolated from whole blood using Lymphoprep® . HMW-fibrinogen was separated from unfractioned fibrinogen by ammonium sulphate precipitation. Cells were incubated with unfractioned fibrinogen, HMW-fibrinogen or fibrin. Cytokine levels in cell lysates were determined using ELISA assays. Real-time PCR was used for mRNA quantification. We found that fibrinogen significantly increased mRNA levels, and induced synthesis of the proinflammatory cytokines IL-6 and TNF- α in PBMC in a dose dependent manner. Median (25, 75 percentile) IL-6 and TNF- α concentrations were 12 (5, 40) pg/ ml and 16 (0,61) pg/ml,respectively.Median mRNA quantity was increased 12.3– (6.6, 48.6) and 1.7– (1.5, 6.5) fold for IL-6 and TNF- α compared to controls.The stimulatory effect of unfractioned fibrinogen was not significantly different from HMW-fibrinogen. Fibrinogen and fibrin were equally effective in promoting cytokine synthesis from PBMC.The results support that fibrin and fibrinogen may actively modulate the inflammatory process by inducing synthesis of proinflammatory cytokines from PBMC.
Rivaroxaban for thromboprophylaxis after orthopaedic surgery: Pooled analysis of two studies
Authors: Eriksson Bengt , Bauer Kenneth , Borris Lars , Dahl Ola , Gent Michael , Haas Sylvia , Homering Martin , Huisman Menno , Kakkar Ajay , Kälebo Peter , Kwong Louis , Misselwitz Frank , Turpie Alexander , Fisher William
Published: June 2007

Rivaroxaban (BAY 59-7939) is an oral, direct factor Xa inhibitor in clinical development for the prevention and treatment of venous thromboembolism (VTE). This analysis of pooled results from two phase II studies of rivaroxaban for VTE prevention after major orthopaedic surgery aimed to strengthen the conclusions of the individual studies. One study was conducted in patients undergoing total hip replacement (THR; N=722), and one in patients undergoing total knee replacement (TKR; N=621). In both studies, patients were randomized, doubleblind, to oral, twice-daily (bid) rivaroxaban beginning after surgery, or subcutaneous enoxaparin (40 mg once daily beginning before THR, and 30 mg bid beginning after TKR). Treatment continued until mandatory bilateral venography was performed 5–9 days after surgery. Total VTE (deep vein thrombosis, pulmonary embolism, and all-cause mortality) occurred in 16.1–24.4% of per-protocol patients receiving rivaroxaban 5–60 mg, and 27.8% receiving enoxaparin (n=914). There was a flat dose response relationship between rivaroxaban and total VTE (p=0.39). Major bleeding (safety population, n=1,317) increased dose-dependently with rivaroxaban (p<0.001), occurring in 0.9%, 1.3%, 2.1%, 3.9%, and 7.0% of patients receiving rivaroxaban total daily doses of 5, 10, 20, 40, and 60 mg, respectively, versus 1.7% of patients receiving enoxaparin. No routine coagulation monitoring was performed, and there were no significant differences between dose response relationships with rivaroxaban after THR and TKR. Overall, rivaroxaban total daily doses of 5–20 mg had the most favorable balance of efficacy and safety, relative to enoxaparin, for the prevention of VTE after major orthopaedic surgery.
Eosinophilic synovitis of the tarsocrural joint in a horse
Authors: Climent F. , Cuenca R. , Prades M. , Carmona J. U.
Published: June 2007

Eosinophilic synovitis (ES) is a rare disease described in human and veterinary medicine. Only three cases have been reported in the horse. A case of tarsocrural synovitis in an Hispano-Arabian gelding is presented in this report. The patient presented with severe joint effusion and lameness of the right tarsocrural joint on admission. Synovial fluid analysis revealed an increased WBC of 12800 leukocytes/microliter with 76% of eosinophils. Lavage of the diseased joint and medical treatment with antibiotics and non-steroidal anti-inflammatory drugs produced remission of the clinical problem.
Long-Term Progression and Outcomes With Aging in Patients With Lone Atrial Fibrillation
Authors: Jahangir Arshad , Lee Victor , Friedman Paul A. , Trusty Jane M. , Hodge David O. , Kopecky Stephen L. , Packer Douglas L. , Hammill Stephen C. , Shen Win-Kuang , Gersh Bernard J.
Published: June 2007

Background—

The long-term natural history of lone atrial fibrillation is unknown. Our objective was to determine the rate and predictors of progression from paroxysmal to permanent atrial fibrillation over 30 years and the long-term risk of heart failure, thromboembolism, and death compared with a control population.

Methods and Results—

A previously characterized Olmsted County, Minnesota, population with first episode of documented atrial fibrillation between 1950 and 1980 and no concomitant heart disease or hypertension was followed up long term. Of this unique cohort, 76 patients with paroxysmal (n=34), persistent (n=37), or permanent (n=5) lone atrial fibrillation at initial diagnosis met inclusion criteria (mean age at diagnosis, 44.2±11.7 years; male, 78%). Mean duration of follow-up was 25.2±9.5 years. Of 71 patients with paroxysmal or persistent atrial fibrillation, 22 had progression to permanent atrial fibrillation. Overall survival of the 76 patients with lone atrial fibrillation was 92% and 68% at 15 and 30 years, respectively, similar to 86% and 57% survival for the age- and sex-matched Minnesota population. Observed survival free of heart failure was slightly worse than expected (
P
=0.051). Risk for stroke or transient ischemic attack was similar to the expected population risk during the initial 25 years of follow-up but increased thereafter (
P
=0.004), although CIs were wide. All patients who had a cerebrovascular event had developed ≥1 risk factor for thromboembolism.

Conclusions—

Comorbidities significantly modulate progression and complications of atrial fibrillation. Age or development of hypertension increases thromboembolic risk.
Heritability, Linkage, and Genetic Associations of Exercise Treadmill Test Responses
Authors: Ingelsson Erik , Larson Martin G. , Vasan Ramachandran S. , O’Donnell Christopher J. , Yin Xiaoyan , Hirschhorn Joel N. , Newton-Cheh Christopher , Drake Jared A. , Musone Stacey L. , Heard-Costa Nancy L. , Benjamin Emelia J. , Levy Daniel , Atwood Larry D. , Wang Thomas J. , Kathiresan Sekar
Published: June 2007

Background—

The blood pressure (BP) and heart rate responses to exercise treadmill testing predict incidence of cardiovascular disease, but the genetic determinants of hemodynamic and chronotropic responses to exercise are largely unknown.

Methods and Results—

We assessed systolic BP, diastolic BP, and heart rate during the second stage of the Bruce protocol and at the third minute of recovery in 2982 Framingham Offspring participants (mean age 43 years; 53% women). With use of residuals from multivariable models adjusted for clinical correlates of exercise treadmill testing responses, we estimated the heritability (variance-components methods), genetic linkage (multipoint quantitative trait analyses), and association with 235 single-nucleotide polymorphisms in 14 candidate genes selected a priori from neurohormonal pathways for their potential role in exercise treadmill testing responses. Heritability estimates for heart rate during exercise and during recovery were 0.32 and 0.34, respectively. Heritability estimates for BP variables during exercise were 0.25 and 0.26 (systolic and diastolic BP) and during recovery, 0.16 and 0.13 (systolic and diastolic BP), respectively. Suggestive linkage was found for systolic BP during recovery from exercise (locus 1q43−44, log-of-the-odds score 2.59) and diastolic BP during recovery from exercise (locus 4p15.3, log-of-the-odds score 2.37). Among 235 single-nucleotide polymorphisms tested for association with exercise treadmill testing responses, the minimum nominal probability value was 0.003, which was nonsignificant after adjustment for multiple testing.

Conclusions—

Hemodynamic and chronotropic responses to exercise are heritable and demonstrate suggestive linkage to select loci. Genetic mapping with newer approaches such as genome-wide association may yield novel insights into the physiological responses to exercise.
Prevention of Erythropoietin-Associated Hypertension
Authors: Lee Mary S. , Lee John S. , Lee Jong Y.
Published: June 2007

Hypertension is the most significant complication from treatment with erythropoietin (Epo). Can Epo-induced hypertension be eliminated? We examined systemic and local effects of our genetically engineered products, Epo-binding protein (Epo-bp) and anti–Epo-bp antibodies, on randomly assigned Sprague–Dawley rats at midnight, 4
am
, 8
am
, noon, 4
pm
, and 8
pm
. Blood pressure, hematocrit, and body weight were measured immediately before and after the completion of a 4-week, twice-weekly course of Epo (50 U/kg), Epo-bp, anti–Epo-bp antibodies, or physiological saline injections. Epo treatment increased hematocrit markedly overall as compared with the saline, Epo-bp, and anti–Epo-bp antibody groups (0.616 versus 0.427, 0.439, and 0.441, respectively) and at each of the 6 test times (all
P
<0.0001). Epo-bp and anti–Epo-bp antibody treatment with Epo had almost no effect on the Epo-induced hematocrit increase (0.616 versus 0.580 or 0.591, respectively). Circadian blood pressures for Epo versus saline, Epo-bp, and anti–Epo-bp antibody groups were 136.2±2.3 versus 116.2±1.7, 118.4±2.1, and 116.6±2.1 mm Hg, respectively (each
P
<0.0001). Significantly increased blood pressure was detected at noon, 4
pm
, 8
pm
, and midnight in Epo treatment. When Epo was given with Epo-bp or anti–Epo-bp antibodies, blood pressure was maintained at similar levels as in saline treatment (each
P
<0.0001) as compared with Epo treatment alone. Overall, body, brain, and heart weights were significantly lower in Epo treatment than those of other groups. Thus, Epo-bp and anti–Epo-bp antibodies eliminate Epo-induced hypertension without affecting hematocrit and blood volume.
“Ladies” or “Loudies”?
Authors: Morris Edward W.
Published: June 2007

Although much scholarship has focused on the schooling experiences of African American boys, this article demonstrates that African American girls encounter unique educational perceptions and obstacles. Black girls in a predominately minority school performed well academically, but educators often questioned their manners and behavior. Some tried to mold many of these girls into “ladies,” which entailed curbing behavior perceived as “loud” and assertive. This article advances theories of intersectionality by showing how race and class shape perceptions of femininity for Black girls, and how the encouragement of more traditionally feminine behavior could ultimately limit their academic potential.
Construction and characterization of a full-length cDNA library for the wheat stripe rust pathogen (Puccinia striiformis f. sp. tritici)
Authors: Ling Peng , Wang Meinan , Chen Xianming , Campbell Kimberly Garland
Published: June 2007

Background

Puccinia striiformis is a plant pathogenic fungus causing stripe rust, one of the most important diseases on cereal crops and grasses worldwide. However, little is know about its genome and genes involved in the biology and pathogenicity of the pathogen. We initiated the functional genomic research of the fungus by constructing a full-length cDNA and determined functions of the first group of genes by sequence comparison of cDNA clones to genes reported in other fungi.

Results

A full-length cDNA library, consisting of 42,240 clones with an average cDNA insert of 1.9 kb, was constructed using urediniospores of race PST-78 of P. striiformis f. sp. tritici. From 196 sequenced cDNA clones, we determined functions of 73 clones (37.2%). In addition, 36 clones (18.4%) had significant homology to hypothetical proteins, 37 clones (18.9%) had some homology to genes in other fungi, and the remaining 50 clones (25.5%) did not produce any hits. From the 73 clones with functions, we identified 51 different genes encoding protein products that are involved in amino acid metabolism, cell defense, cell cycle, cell signaling, cell structure and growth, energy cycle, lipid and nucleotide metabolism, protein modification, ribosomal protein complex, sugar metabolism, transcription factor, transport metabolism, and virulence/infection.

Conclusion

The full-length cDNA library is useful in identifying functional genes of P. striiformis.
Neointimal hyperplasia persists at six months after sirolimus-eluting stent implantation in diabetic porcine
Authors: Zhang Qi , Lu Lin , Pu LiJin , Zhang RuiYan , Shen Jie , Zhu ZhengBing , Hu Jian , Yang ZhenKun , Chen QiuJin , Shen WeiFeng
Published: June 2007

Background

Observational clinical studies have shown that patients with diabetes have less favorable results after percutaneous coronary intervention compared with the non-diabetic counterparts, but its mechanism remains unclear. The aim of this study was to examine the changes of neointimal hyperplasia after sirolimus-eluting stent (SES) implantation in a diabetic porcine model, and to evaluate the impact of aortic inflammation on this proliferative process.

Methods

Diabetic porcine model was created with an intravenous administration of a single dose of streptozotocin in 15 Chinese Guizhou minipigs (diabetic group); each of them received 2 SES (Firebird, Microport Co, China) implanted into 2 separated major epicardial coronary arteries. Fifteen non-diabetic minipigs with SES implantation served as controls (control group). At 6 months, the degree of neointimal hyperplasia was determined by repeat coronary angiography, intravascular ultrasound (IVUS) and histological examination. Tumor necrosis factor (TNF)-α protein level in the aortic intima was evaluated by Western blotting, and TNF-α, interleukin (IL)-1β and IL-6 mRNA levels were assayed by reverse transcription and polymerase chain reaction.

Results

The distribution of stented vessels, diameter of reference vessels, and post-procedural minimal lumen diameter were comparable between the two groups. At 6-month follow-up, the degree of in-stent restenosis (40.4 ± 24.0% vs. 20.2 ± 17.7%, p < 0.05), late lumen loss (0.33 ± 0.19 mm vs. 0.10 ± 0.09 mm, p < 0.001) by quantitative angiography, percentage of intimal hyperplasia in the stented area (26.7 ± 19.2% vs. 7.3 ± 6.1%, p < 0.001) by IVUS, and neointimal area (1.59 ± 0.76 mm2 vs. 0.41 ± 0.18 mm2, p < 0.05) by histological examination were significantly exacerbated in the diabetic group than those in the controls. Significant increases in TNF-α protein and TNF-α, IL-1β and IL-6 mRNA levels were observed in aortic intima in the diabetic group.

Conclusion

Neointimal hyperplasia persisted at least up to 6 months after SES implantation in diabetic porcine, which may be partly related to an exaggerated inflammatory response within the blood vessel wall. Our results provide theoretical support for potential direct beneficial effects of anti-diabetic and anti-inflammation medications in reducing the risk of restenosis after stenting.
Successful management of elderly breast cancer patients treated without radiotherapy
Authors: Valassiadou Kalliope , Morgan David AL , Robertson John FR , Pinder Sarah E , Cheung Kwok-Leung
Published: June 2007

Background

Breast cancer in the elderly may follow a less aggressive course. There are data suggesting that radiotherapy (RT) following breast conserving surgery (BCS) for invasive carcinoma may not be necessary in some elderly patients. The addition of RT to surgery might constitute an imposition to such patients due to age-related factors. The aim of this study was to assess the efficacy of BCS without adjuvant RT in this group of patients.

Patients and methods

A retrospective review of 92 elderly (median age 75 years; range: 70 – 87 years) patients (analysed as 93 'patients' due to one patient having bilateral cancers) managed in a dedicated breast clinic and who underwent BCS for invasive carcinoma was carried out. Eighty-three patients did not receive postoperative RT to the breast (no-RT group) whereas the remaining 10 had RT (RT-group).

Results

The median age in this group was 75 (range 70 – 87) years. The mean tumour size was 18 mm with a median follow-up of 37 (range 6 – 142) months. In the no RT group, adjuvant endocrine therapy with tamoxifen was given to 40/53 patients. No patients in the oestrogen receptor (ER) negative group received tamoxifen. The local recurrence (LR) rate in this group was 8.4% (2.4% per year, n = 7/83), with median time to LR of 17 months. In this no-RT group LR was correlated to ER status (2/53 ER+, 5/26ER-, p = 0.024) and margins of excision (n = 1/54 >5 mm, 2/17 1–5 mm, 4/12 <1 mm, p = 0.001). Within the ER positive group the LR rate was 0.92% per annum (0.62% per annum in patients treated with adjuvant tamoxifen, regardless of margin status). Breast cancer specific survival was correlated to histological grade (p < 0.05) and ER status (p < 0.05).

Conclusion

It would appear that omission of RT following successful BCS in elderly patients with ER positive tumours receiving adjuvant tamoxifen may be acceptable. The LR rate as shown in this retrospective study is highly comparable to that of younger patients treated by conventional therapy. This concept is now being evaluated prospectively following a change in treatment practice.
Erratum To: five-year predictors of physical activity decline among adults in low-income communities: a prospective study
Authors: Weiss Deborah R , O'Loughlin Jennifer L , Platt Robert W , Paradis Gilles
Published: June 2007

After publication it was brought to our attention that the information for one of the variables in Table 1 was incorrect (Weiss, O'Loughlin et al. International Journal of Behavioral Nutrition and Physical Activity 2007, 4:2). The variable in question is "Use of a neighborhood facility for activity". In the first column, the first row should read "yes", and the second row, "no". In the second column, the first row should read 25.8 (41) and the second row, 41.3 (152).
Table 1

Unadjusted and adjusted Odds Ratios for potential predictors of becoming inactive [1].

Potential predictor
Participants who became inactive
Unadjusted OR (95% CI)
Adjusted OR (95% CI)

Sex, % (n)

   Male
31.1 (77)
1.00 (Ref.)
1.00 (Ref.)

   Female
41.6 (116)
1.58 (1.10, 2.27)
1.63 (1.09, 2.43)

Age (years), mean (SD)
39.5 (12.2)
1.03 (1.01, 1.05)
1.02 (1.01, 1.04)

Self-rated health, % (n)

   Excellent
29.8 (50)
1.70 (1.35, 2.16)
1.39 (1.05, 1.84)

   Good
32.6 (84)

   Average
57.8 (48)

   Poor/Very poor
64.7 (11)

BMIa, % (n)

   <25
32.1 (117)
1.00 (Ref.)
1.00 (Ref.)

   =25
46.6 (76)
1.84 (1.26, 2.69)
1.57 (1.03, 2.40)

Smoking status, % (n)

   Current smoker
37.5 (77)
1.00 (Ref.)
1.00 (Ref.)

   Past/Never smoker
36.2 (121)
1.06 (0.73, 1.53)
0.98 (0.78, 1.23)

Income, % (n)

   <20,000
39.5 (68)
0.82 (0.65, 1.03)
0.95 (0.73, 1.24)

   20,000–40,000
35.8 (62)

   40,000+
30.2 (42)

Self-efficacy score, mean (SD)
2.2 (0.6)
1.61 (1.20, 2.26)
1.46 (1.00, 2.14)

Use of a neighborhood facility for activity, % (n)

   Yes
25.8 (41)
1.00 (Ref.)
1.00 (Ref.)

   No
41.3 (152)
2.03 (1.34, 3.06)
1.61 (1.02, 2.55)

Education, % (n)

   Elementary/some secondary
52.6 (50)
0.74 (0.63, 0.86)
N/A*

   Completed secondary/some college
40.2 (47)

   Completed college
32.5 (27)

   Some post-secondary
29.8 (67)

Receives encouragement for activity, % (n)

   No
35.2 (113)
1.00 (Ref.)
N/A*

   Yes
38.5 (79)
0.87 (0.60, 1.25)

aBody Mass Index

* Not included in final model
Human Polycomb groupEED protein negatively affects HIV-1 assembly and release
Authors: Rakotobe Dina , Tardy Jean-Claude , André Patrice , Hong Saw See , Darlix Jean-Luc , Boulanger Pierre
Published: June 2007

Background

The human EED protein, a member of the superfamily of Polycomb group (PcG) proteins with WD-40 repeats, has been found to interact with three HIV-1 components, namely the structural Gag matrix protein (MA), the integrase enzyme (IN) and the Nef protein. The aim of the present study was to analyze the possible biological role of EED in HIV-1 replication, using the HIV-1-based vector HIV-Luc and EED protein expressed by DNA transfection of 293T cells.

Results

During the early phase of HIV-1 infection, a slight negative effect on virus infectivity occurred in EED-expressing cells, which appeared to be dependent on EED-MA interaction. At late times post infection, EED caused an important reduction of virus production, from 20- to 25-fold as determined by CAp24 immunoassay, to 10- to 80-fold based on genomic RNA levels, and this decrease was not due to a reduction of Gag protein synthesis. Coexpression of WTNef, or the non-N-myristoylated mutant NefG2A, restored virus yields to levels obtained in the absence of exogenous EED protein. This effect was not observed with mutant NefΔ57 mimicking the Nef core, or with the lipid raft-retargeted fusion protein LAT-Nef. LATAA-Nef, a mutant defective in the lipid raft addressing function, had the same anti-EED effect as WTNef. Cell fractionation and confocal imaging showed that, in the absence of Nef, EED mainly localized in membrane domains different from the lipid rafts. Upon co-expression with WTNef, NefG2A or LATAA-Nef, but not with NefΔ57 or LAT-Nef, EED was found to relocate into an insoluble fraction along with Nef protein. Electron microscopy of HIV-Luc producer cells overexpressing EED showed significant less virus budding at the cell surface compared to control cells, and ectopic assembly and clustering of nuclear pore complexes within the cytoplasm.

Conclusion

Our data suggested that EED exerted an antiviral activity at the late stage of HIV-1 replication, which included genomic RNA packaging and virus assembly, resulting possibly from a mistrafficking of viral genomic RNA (gRNA) or gRNA/Gag complex. Nef reversed the EED negative effect on virus production, a function which required the integrity of the Nef N-terminal domain, but not its N-myristoyl group. The antagonistic effect of Nef correlated with a cellular redistribution of both EED and Nef.
Sequential use of bronchial aspirates, biopsies and washings in the preoperative management of lung cancers
Authors: Piaton Eric , Djelid Djamal , Duvert Bernard , Perrichon Marielle , Saugier Bernard
Published: June 2007

Background

The combination of cytology and biopsies improves the recognition and typing of small cell (SCLC) versus non small cell (NSCLC) lung cancers in the fiberoptic bronchoscopy assessment of centrally located tumours.

Methods

We studied whether bronchial aspirates performed before biopsies (BA) and washings performed after biopsies (BW) could increase the diagnostic yield of fiberoptic bronchoscopy. A series of 334 consecutive samples taken in patients with suspicious fiberoptic bronchoscopy findings was studied. Two hundred primary tumours were included in the study. The actual diagnosis was based on surgical tissue specimen analysis and/or imaging techniques. The typing used was that of the 1999 WHO/IASLC classification.

Results

The diagnosis of malignancy and tumour typing were analyzed according to the sequential (combined) or single use of tests. Malignancy was assessed by cytology in 144/164 (87.8%) positive biopsy cases and in 174/200 tumour cases (87.0%). BA before biopsies allowed 84.0% of cancers to be diagnosed, whereas BW after biopsies allowed 79.0% of cancers to be found (p = ns). However, combining biopsies with BW allowed 94.0% of cancers to be diagnosed, whereas 82.0% were diagnosed by biopsies alone (p < 0.001). The highest diagnostic yield was obtained with the combination of BA, biopsies and BW, with 97.0% sensitivity. Exact concordance in typing was obtained in 83.8% of cases. The six surgically resected cases (3.0%) with negative cytology and biopsy results included four squamous cell carcinomas with necrotizing or fibrous surface and two adenocarcinomas, pT1 stage.

Conclusion

Fiberoptic bronchoscopy may reach a yield of close to 100% in the diagnosis and typing of centrally located, primary lung cancers by combining bronchial aspirates, biopsies and washings.
Antisense RNA directed to the human papillomavirus type 16 E7 mRNA from herpes simplex virus type 1 derived vectors is expressed in CaSki cells and downregulates E7 mRNA
Authors: Kari Ilkka , Syrjänen Stina , Johansson Bo , Peri Piritta , He Bin , Roizman Bernard , Hukkanen Veijo
Published: June 2007

Background

Human papillomavirus (HPV) infection is known to be the most important etiologic factor of cervical cancer. There is no HPV specific therapy available for treatment of invasive squamous cell carcinoma of the cervix and its precursor lesions. The present study elucidates the potential to use herpes simplex virus (HSV) derived vectors for expression of antisense RNA to HPV -16 E7 oncogene.

Results

We have constructed replication competent, nonneuroinvasive HSV-1 vectors, deleted of the γ134.5 gene. The vectors express RNA antisense to the first 100 nucleotides of the HPV-16 E7 gene. We assayed the ability of the antisense E7 vectors R5225 (tk-) and R5226 (tk+), to produce antisense RNA, as well as the consequent effects on E7 mRNA and protein levels in HPV-16 positive CaSki cells. Anti-E7 RNA was expressed by both constructs in a dose-dependent manner. Expression of HPV-16 E7 mRNA was downregulated effectively in CaSki cells infected with the tk- recombinant R5225 or with R5226. The tk+ recombinant R5226 was effective in downregulating E7 protein expression.

Conclusion

We have shown that anti-E7 RNA expressed from an HSV vector could efficiently downregulate HPV-16 E7 mRNA and E7 protein expression in CaSki cells. We conclude that HSV vectors may become a useful tool for gene therapy of HPV infections.
Skeletonization of radial and gastroepiploic conduits in coronary artery bypass surgery
Authors: Massey Rachel M , Warren Oliver J , Szczeklik Michal , Wallace Sophie , Leff Daniel R , Kokotsakis John , Darzi Ara , Athanasiou Thanos
Published: June 2007

The use of a skeletonized internal thoracic artery in coronary artery bypass graft surgery has been shown to confer certain advantages over a traditional pedicled technique, particularly in certain patient groups. Recent reports indicate that radial and gastroepiploic arteries can also be harvested using a skeletonized technique. The aim of this study is to systematically review the available evidence regarding the use of skeletonized radial and gastroepiploic arteries within coronary artery bypass surgery, focusing specifically on it's effect on conduit length and flow, levels of endothelial damage, graft patency and clinical outcome. Four electronic databases were systematically searched for studies reporting the utilisation of the skeletonization technique within coronary revascularisation surgery in humans. Reference lists of all identified studies were checked for any missing publications. There appears to be some evidence that skeletonization may improve angiographic patency, when compared with pedicled vessels in the short to mid-term. We have found no suggestion of increased complication rates or increased operating time. Skeletonization may increase the length of the conduit, and the number of sequential graft sites, but no clear clinical benefits are apparent. Our study suggests that there is not enough high quality or consistent evidence to currently advocate the application of this technique to radial or gastroepiploic conduits ahead of a traditional pedicled technique.
Pilot study of fluvoxamine treatment for climacteric symptoms in Japanese women
Authors: Oishi Akira , Mochizuki Yoshiko , Otsu Reiko , Inaba Noriyuki
Published: June 2007

Background

Selective serotonin-reuptake inhibitors (SSRIs) are commonly prescribed for the treatment of depression and can be used as nonhormonal alternatives to manage hot flashes for women with a history of breast cancer and unable to take hormone replacement therapy. There are, however, few reports on the efficacy of SSRIs for the treatment of natural postmenopausal climacteric symptoms. In this pilot study, we evaluate the SSRI, fluvoxamine, for controlling climacteric symptoms and vasomotor symptoms, in particular.

Methods

Twenty-two patients were enrolled from our hospital. All were orally administered fluvoxamine (50 mg daily). Climacteric and depressive symptoms were assessed using simple menopausal index (SMI) and self-rating questionnaire for depression (SRQ-D), respectively, at baseline, and at 2 and 6 weeks post-treatment.

Results

Six weeks following drug administration, neither the SRQ-D nor SMI scores significantly decreased compared to baseline. The mean levels of vasomotor symptoms and mental symptoms decreased significantly following fluvoxamine administration, while skeletal muscle symptom scores did not.

Conclusion

We were able to demonstrate that fluvoxamine was effective in treating not only depressive moods in climacteric symptoms but also the associated vasomotor symptoms. There are several limitations to this preliminary study. Future controlled studies are needed to further evaluate the efficacy of fluvoxamine for climacteric disturbances.
Nucleated red blood cells in the blood of medical intensive care patients indicate increased mortality risk: a prospective cohort study
Authors: Stachon Axel , Segbers Elmar , Holland-Letz Tim , Kempf Reiner , Hering Steffen , Krieg Michael
Published: June 2007

Introduction

In critically ill patients, the appearance of nucleated red blood cells (NRBCs) in blood is associated with a variety of severe diseases. Generally, when NRBCs are detected in the patients' blood, the prognosis is poor.

Methods

In a prospective study, the detection of NRBCs was used for a daily monitoring of 383 medical intensive care patients.

Results

The incidence of NRBCs in medical intensive care patients was 17.5% (67/383). The mortality of NRBC-positive patients was 50.7% (34/67); this was significantly higher (p < 0.001) than the mortality of NRBC-negative patients (9.8%, 31/316). Mortality increased with increasing NRBC concentration. Seventy-eight point six percent of the patients with NRBCs of more than 200/μl died. The detection of NRBCs is highly predictive of death, the odds ratio after adjustment for other laboratory and clinical prognostic indicators being 1.987 (p < 0.01) for each increase in the NRBC category (0/μl, 1 to 100/μl, 101 to 200/μl, and more than 200/μl). Each step-up in the NRBC category increased the mortality risk as much as an increase in APACHE II (Acute Physiology and Chronic Health Evaluation II) score of approximately 4 points. The mortality of patients who were NRBC-positive on the day of relocation from the intensive care unit to a peripheral ward was 27.6% (8/27). This was significantly higher than the mortality of patients who were NRBC-negative on the relocation day (8.6%, 28/325; p < 0.01). On average, NRBCs were detected for the first time 14 days (median, 3 days) before death.

Conclusion

The routine analysis of NRBCs in blood is of high prognostic power with regard to mortality of critically ill patients. Therefore, this parameter may serve as a daily indicator of patients at high mortality risk. Furthermore, NRBC-positive intensive care patients should not be relocated to a normal ward but should obtain ongoing intensive care treatment.
Mixture modeling of transcript abundance classes in natural populations
Authors: Hsieh Wen-Ping , Passador-Gurgel Gisele , Stone Eric A , Gibson Greg
Published: June 2007

Background

Populations diverge in genotype and phenotype under the influence of such evolutionary processes as genetic drift, mutation accumulation, and natural selection. Because genotype maps onto phenotype by way of transcription, it is of interest to evaluate how these evolutionary factors influence the structure of variation at the level of transcription. Here, we explore the distributions of cis-acting and trans-acting factors and their relative contributions to expression of transcripts that exhibit two or more classes of abundance among individuals within populations.

Results

Expression profiling using cDNA microarrays was conducted in Drosophila melanogaster adult female heads for 58 nearly isogenic lines from a North Carolina population and 50 from a California population. Using a mixture modeling approach, transcripts were identified that exhibit more than one mode of transcript abundance across the samples. Power studies indicate that sample sizes of 50 individuals will generally be sufficient to detect divergent transcript abundance classes. The distribution of transcript abundance classes is skewed toward low frequency minor classes, which is reminiscent of the typical skew in genotype frequencies. Similar results are observed in reported data on gene expression in human lymphoblast cell lines, in which analysis of association with linked polymorphisms implies that cis-acting single nucleotide polymorphisms make only a modest contribution to bimodal distributions of transcript abundance.

Conclusion

Population surveys of gene expression may complement genetical genomics as a general approach to quantifying sources of transcriptional variation. Differential expression of transcripts among individuals is due to a complex interplay of cis-acting and trans-acting factors.