bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue factor-positive microparticles: Cellular origin and association with coagulation activation in patients with colorectal cancer
Authors: Hron Gregor , Kollars Marietta , Weber Heinz , Sagaster Verena , Quehenberger Peter , Eichinger Sabine , Kyrle Paul A. , Weltermann Ansgar
Published: June 2007

The pathogenesis of hypercoagulability in cancer is not entirely understood. We hypothesized that in cancer patients circulating tissue factor-positive microparticles (TF+ MPs) are increased and associated with hemostatic system activation. In 20 patients with advanced colorectal cancer and in 20 age- and sex-matched controls, number and cellular origin of TF+ MPs were determined in plasma by flow cytometry. D-dimer was determined as an indicator of hemostatic system activation. Compared to controls, the median (interquartile range) number of TF+ MPs was two-fold higher in cancer patients: 25.9 (15.4 – 42.0) × 103 /ml plasma versus 13.1 (11.9 – 19.7) × 103 /ml plasma, p = 0.007. This was mainly due to a higher amount of TF+ MPs from platelets (13.4 [5.0 – 17.4] × 103 /ml plasma vs. 5.8 [4.5 – 7.5] × 103 /ml plasma, p = 0.017). TF+ MPs correlated with D-dimer (ρ = 0.48, p = 0.002). High levels of TF+ MPs in cancer patients and their correlation with D-dimer suggest that TF+ MPs might be involved in hemostasis activation in cancer patients.
Danaparoid sodium reduces ischemia/reperfusion-induced liver injury in rats by attenuating inflammatory responses
Authors: Harada Naoaki , Kohmura Hidefumi , Uchiba Mitsuhiro , Tomita Tsutomu , Okajima Kenji
Published: June 2007

This study was undertaken to examine the mechanism by which danaparoid sodium (DS), a heparinoid that contains mainly heparan sulfate, prevents reperfusion-induced hepatic damage in a rat model of ischemia/reperfusion (I/R)-induced liver injury. Administration of DS significantly reduced liver injury and inhibited the decrease in hepatic tissue blood flow in rats. DS attenuated hepatic I/R-induced increases in hepatic tissue levels of tumor necrosis factor (TNF) and myeloperoxidase (MPO) in vivo. In contrast, neither monocytic TNF production nor neutrophil activation was inhibited by DS in vitro. DS enhanced I/R-induced increases in levels of calcitonin-gene related peptide (CGRP), a neuropeptide released from sensory neurons, and of 6-ketoprostaglandin (PG) F1α, a stable metabolite of PGI2, in liver tissues. The therapeutic effects of DS were not seen in animals pretreated with capsazepine, an inhibitor of sensory neuron activation. The distribution of heparan sulfate in the perivascular area was significantly increased by DS administration in this rat model. DS significantly increased CGRP release from isolated rat dorsal root ganglion neurons (DRG) in vitro, while DX-9065a, a selective inhibitor of activated factor X, did not. DS enhanced anandamide-induced CGRP release from DRG in vitro. These observations strongly suggested that DS might reduce I/R-induced liver injury in rats by attenuating inflammatory responses. These therapeutic effects of DS might be at least partly explained by its enhancement of sensory neuron activation, leading to the increase the endothelial production of PGI2.
Polymorphism A36G of the tumor necrosis factor receptor 1 gene is associated with PAI-1 levels in obese women
Authors: Mavri Alenka , Bastelica Delphine , Poggi Marjorie , Morange Pierre , Peiretti Franck , Verdier Monique , Juhan-Vague Irène , Alessi Marie-Christine
Published: June 2007

The tumor necrosis factor (TNF) pathway may be implicated in etiopathogenesis of PAI-1 overexpression during obesity. The aim of this study was to investigate the influence of polymorphismA36G of the TNF receptor 1 (TNFRSF1A +36A/G) on plasma concentrations of PAI-1 in 163 obese (31 with the metabolic syndrome, MetS) and 150 lean, healthy women. Genotypic and allele frequencies did not significantly differ between obese and lean subjects. TNFRSF1A genotypes were significantly associated with sTNFR1 plasma levels in obese women only (p<0.01); TNFRSF1A +36G/G obese carriers exhibited higher sTNFR1 and PAI-1 levels than A carriers (p<0.01 and p<0.05, respectively). In obese women, the presence of the MetS significantly potentiated the elevation of sTNFR1 and PAI-1 levels observed in the TNFRSF1A+36G/G carriers. Our results suggest that association between TNFRSF1A +36G/G genotype and the MetS renders obese women more prone to activation of the TNF pathway reflected by high circulating sTNFR1 and PAI-1 levels.
The F11 receptor (F11R/JAM-A) in atherothrombosis: Overexpression of F11R in atherosclerotic plaques
Authors: Babinska Anna , Azari Bani , Salifu Moro , Liu Ruijie , Jiang Xian-Cheng , Sobocka Malgorzata , Boo Dorothy , Khoury George , Deitch Jonathan , Marmur Jonathan , Ehrlich Yigal , Kornecki Elizabeth
Published: June 2007

F11R is the gene name for an adhesion protein, called the F11-receptor, aka JAM-A, which under normal physiological conditions is expressed constitutively on the surface of platelets and localized within tight junctions of endothelial cells (EC). Previous studies of the interactions between human platelets and EC suggested that F11R/JAM-A plays a crucial role in inflammatory thrombosis and atherosclerosis. The study reported here obtained in-vivo confirmation of this conclusion by investigating F11R/JAM-A protein and mRNA in patients with aortic and peripheral vascular disease and in an animal model of atherosclerosis. Molecular and immunofluorescence determinations revealed very high levels of F11R/JAM-A mRNA and F11R/JAM-A protein in atherosclerotic plaques of cardiovascular patients. Similar results were obtained with 12-week-old atherosclerosis-prone apoE-/- mice, an age in which atherosclerotic plaques are well established. Enhanced expression of the F11R/JAM-A message in cultured EC from human aortic and venous vessels was observed following exposure of the cells to cytokines. Determinations of platelet adhesion to cultured EC inflamed by combined cytokine treatment in the presence of F11R/JAM-A – antagonists provided data indicating that de novo expression of F11R/JAM-A on the luminal surface of inflamed EC has an important role in the conversion of EC to a thrombogenic surface. Further studies of these interactions under flow conditions and under in-vivo settings could provide a final proof of a causal role for F11R/JAM-A in the initiation of thrombosis. Based on our invitro and in-vivo studies to date, we propose that therapeutic drugs which antagonize the function of F11R/JAM-A should be tested as novel means for the prevention and treatment of atherosclerosis, heart attacks and stroke.
Comparison of the pharmacokinetics of two von Willebrand factor concentrates [Biostate and AHF (High Purity)] in people with von Willebrand disorder
Authors: Lloyd John , Rowell John , Baker Ross , Rickard Kevin , Kershaw Geoff , Street Alison , Scarff Kate , Barrese Giulio , Maher Darryl , McLachlan Andrew , Favaloro Emmanuel
Published: June 2007

Plasma-derived factor concentrates are important in the management of von Willebrand disorder (VWD). In our geographic locality, a single viral inactivation step concentrate (AHF [High Purity]), has been replaced with one using a double viral inactivation step (Biostate®). The aim of this study was to compare the pharmacokinetics of von Willebrand factor (VWF) and factor VIII (FVIII) after administration of AHF (High Purity) and Biostate®. This study was a single-blind, randomised cross-over, multi-centre investigation in twelve people with VWD, comprising four type 3, two type 2B, one type 2M and five type 1 VWD. The subjects received a single infusion of 60 IU/kg ristocetin cofactor activity (VWF:RCo) of either AHF (High Purity) or Biostate®, and after a minimum 15-day wash-out period they received the alternative product. Blood samples were collected for up to 48 hours after each dose for assay of FVIII coagulant activity (FVIII:C) and VWF by VWF:RCo, collagen binding capacity (VWF:CB) and antigen (VWF:Ag). As a measure of delivered VWF ‘functionality’ we calculated the area-under-the-concentration-time-curve (AUC) ratios of VWF:RCo to VWF:Ag and VWF:CB to VWF:Ag. The effect on platelet adhesiveness by PFA-100 closure times (CTs) was measured prior to and 30 minutes post infusion. VWF multimers were also assessed pre and post infusion. Pharmacokinetic parameters after AHF (High Purity) and Biostate® were in close agreement for VWF:RCo (confirming dosing equivalence). Parameters for other study markers were also similar, although Biostate® tended to yield relatively lower VWF:Ag and higher VWF:CB levels. Although AHF (High Purity) and Biostate® resulted in similar levels of high-molecular-weight (HMW) multimers post-infusion, the relative level of HMW to low-molecular-weight (LMW) multimers were determined to be higher following Biostate®. The relative levels of functional VWF (i.e. VWF:CB and VWF:RCo) to VWF:Ag were also higher in Biostate® compared to AHF (High Purity). With both study products, PFA-100 CTs 30 minutes post infusion showed minor improvement for only some subjects. In conclusion, the pharmacokinetics of FVIII:C and VWF are not significantly different after administration of AHF (High Purity) and Biostate®. Study parameters considered as ‘in-vitro’ markers of VWF ‘functionality’ or potential clinical efficacy (i.e. VWF:CB and VWF:RCo relative to VWF:Ag, level of HMW VWF relative to LMW-VWF) were determined to be higher for Biostate® than AHF (High Purity). PFA-100 CTs did not adequately reflect changes in these VWF parameters. Based on these results, one would expect Biostate® to be at least as effective, if not superior to AHF (High Purity) for the treatment of VWD.
Coagulation and endothelial dysfunction during longterm hyperdynamic porcine bacteremia – effects of selective inducible nitric oxide synthase inhibition
Authors: Krouzecky Ales , Radej Jaroslav , Rokyta Richard , Kralova Hana , Radermacher Peter , Novak Ivan , Matejovic Martin
Published: June 2007

Coagulation abnormalities have been implicated in the pathogenesis of sepsis and organ dysfunction. Nitric oxide (NO) is regarded as a critical mediator of many vascular pathologies, including sepsis. However, limited evidence is available to document a relationship between NO generated by inducible NO synthase (iNOS) and hemostatic abnormalities in sepsis. Therefore, we evaluated the effects of selective iNOS inhibition on markers of endothelial and coagulation homeostasis in a clinically relevant model of porcine bacteremia induced and maintained for 24 hours (h) with a continuous infusion of live P. aeruginosa. After 12 h of sepsis, animals received either vehicle (Control, n = 7) or continuous infusion of selective iNOS inhibitor L-NIL (n=7). Before as well as 12, 18 and 24 h after starting P. aeruginosafollowing variables related to i) endothelial dysfunction (von Willebrand factor [vWf]; tissue plasminogen activator activity [t-PA]; ii) coagulation (thrombin-antithrombin complexes [TAT]; platelet count); iii) fibrinolysis (t-PA activity, activity of plasminogen activator inhibitor type 1 (PAI-1 act); and iv) oxidative/ nitrosative stress (isoprostanes, nitrate/nitrite levels) were measured. L-NIL inhibited sepsis-induced increase in plasma nitrate/nitrite and isoprostanes concentrations, prevented hypotension and acidosis. L-NIL significantly attenuated sepsisinduced rise in plasma vWF and TAT. P. aeruginosa-induced drop in t-PA activity was blunted by iNOS inhibition, while increased PAI-1 and reduced platelet count were not reversed by the treatment. In conclusion, selective iNOS inhibition was associated with attenuation of sepsis-induced coagulation and endothelial dysfunction suggesting the interplay between mediators of vascular system and hemostatic balance. Reduction of oxidative stress probably contributes to the beneficial effects afforded by iNOS blockade.
Rapid activation of haemostasis after hormonal emergency contraception
Authors: Silveira Angela , Thomassen Stella , Hansson Lars-Olof , Rosing Jan , Hamsten Anders , Bremme Katarina , van Rooijen Marianne
Published: June 2007

Hormonal emergency contraception (EC) is a well established contraceptive method, recommended to all women, although the effects on haemostais are not fully evaluated. The aim of this study was to evaluate whether exposure to EC has effects on well established cardiovascular risk factors, and also to examine whether differences exist between two EC treatments. In a prospective randomized cross over design 11 women used two different EC methods, one with estrogen and levonorgestrel (EE-EC) and one with levonorgestrel only (LNG-EC). Plasma concentrations of haemostatic factors (APC resistance, antithrombin, fibrinogen, prothrombin fragment 1+2, free protein S, factor VII and PAI-1), sex-hormone-binding globulin (SHBG), the apolipoprotein (apo)B/apoA1 ratio and C-reactive protein (CRP) were followed frequently during the following 48 h A rapid haemostatic activation was induced with both treatments, although more pronounced with EE-EC. Already two hours after EC, the plasma concentrations of haemostatic parameters and SHBG were significantly different from baseline concentrations. An ETP-based APC-resistance method showed increased APC resistance with EE-EC and decreased APC resistance with LNG-EC. The ApoB/ApoA1 ratio was affected in a favourable direction with EE-EC.CRP increased slightly regardless of treatment. Even a very short exposure to exogenous sex hormones causes prompt effects on hepatic protein synthesis and the coagulation system. This must be taken into consideration whenever exogenous steroid hormones are administered, especially to individuals with a genetic predisposition to thrombosis or transiently disturbed haemostasis.
Comparative characterization of cellular and molecular anti-restenotic profiles of paclitaxel and sirolimus
Authors: Blaich Birgit , Siham BelAiba Rachida , Merl Sabine , Görlach Agnes , Kastrati Adnan , Schömig Albert , Wessely Rainer
Published: June 2007

Pleiotropic anti-restenotic properties of drugs that are eluted from coated stents are critical for efficacy and safety. Little is known about comparative drug properties in appropriate human coronary target cell lines for the two compounds that are utilized on FDA-approved drug-eluting stent (DES) platforms, paclitaxel (PTX) and sirolimus (SRL). Target cell lines that play a pivotal role for the pathogenesis of restenosis and vascular healing include human coronary artery smooth muscle (CASMC) and endothelial cells (CAEC). PTX and SRL inhibited CASMC and CAEC proliferation and migration efficiently. However, there was a differential effect on proliferation and migration in CAEC with a more profound inhibition of both parameters by PTX, even at low dosages. Induction of cytotoxicity and apoptosis was pronounced in PTX- and very modest in SRL-treated CASMC and CAEC. PTX increased eNOS activity and nitric oxide (NO) release from CAEC. Neutrophilic leukocyte activation and transmigration, which should be avoided since it may precipitate adverse coronary events such as restenosis and stent thrombosis, was suppressed by SRL, whereas PTX tended to increase neutrophilic leucocyte activity. Therefore, although the primary drug target, inhibition of mitogen-mediated CASMC proliferation, is effectively accomplished by both drugs, auxiliary pharmacological properties that are crucial for the anti-restenotic drug effect and vascular healing are considerably different between PTX and SRL. In comparison with PTX, SRL shows minor interference with endothelial cell proliferation and migration, lower levels of cytotoxicity and apoptosis, a broader therapeutic range and distinctive immunosuppressive properties.
Chemokines in ischemia and reperfusion
Authors: Frangogiannis Nikolaos
Published: June 2007

Chemokine signaling plays an important role in the postischemic inflammatory response. Overlapping pathways involving reactive oxygen intermediates,Toll-like receptor (TLR) activation, the complement cascade and the nuclear factor (NF)- κ B system induce both CXC and CC chemokines in ischemic tissues. Reperfusion accentuates chemokine expression promoting an intense inflammatory reaction. ELR-containing CXC chemokines regulate neutrophil infiltration in the ischemic area, whereas CXCR3 ligands may mediate recruitment of Th1 cells. CC chemokines, on the other hand, induce mononuclear cell infiltration and macrophage activation.Evidence suggests that chemokine signaling mediates actions beyond leukocyte chemotaxis and activation, regulating angiogenesis and fibrous tissue deposition. Effective repair of ischemic tissue is dependent on a wellorchestrated cellular response and on timely induction and suppression of chemokines in a locally restricted manner. This manuscript reviews the evidence suggesting a role for chemokine- mediated effects in ischemia/reperfusion and discusses the potential significance of these interactions in injury and repair of ischemic tissues.
Upward fixation of the patella in the horse
Authors: Pille F. , Desmet P. , Dewulf J. , Steenhaut M. , Gasthuys F. , Martens A. , Dumoulin M.
Published: June 2007

The objective of the present study was to assess the incidence of upward fixation of the patella (UFP) in different types of patients and to evaluate the outcome of conservative and surgical treatment for correcting this condition. A particular attempt was made to find out whether corrective trimming and/or shoeing (CTS) is efficient in the conservative treatment of UFP, and whether a longer postoperative resting period reduces the risk of complications after medial patellar desmotomy (MPD). Medical records of 78 horses with intermittent or permanent UFP were analyzed retrospectively. Young animals and ponies were mostly affected, mainly during winter (P<0.05). Seventy-six horses with UFP were treated conservatively, with follow-up being possible in 64 of them. This treatment, in which CTS seemed the most important aspect, was fully successful in 51.6% of these patients; 20.3% of them improved partially. In case of no response to conservative treatment, or in case of a permanent fixation, MPD was performed in 20 horses, which corrected UFP completely in 17 of the 18 followed-up patients. However, gait abnormalities were seen in seven of those 17 horses postsurgically, but with the incidence being lower in horses that had rested for at least three months (25%) compared to horses that had only rested for less than one month (66.6%). Results indicate that conservative treatment, with special attention for CTS, is worth trying before performing more radical procedures to correct UFP, and that a longer convalescence period after MPD is desirable.
The effect of computed tomographical gantry angle on the measurement of the canine intercondylar notch
Authors: Sellmeyer T. W. H. , Wilson E. R. , Lineberger J. A. , Henrikson T. D. , Lehenbauer T. W. , Allen D. A.
Published: June 2007

This study was conducted to evaluate the clinical application of computed tomography of the canine femoral intercondylar notch. The canine femoral intercondylar notch is angled 12 degrees from the dorsal plane and obliqued 7 degrees proximolateral to distomedial in the sagittal plane. Measurements of the notch were performed with eight, 12, and 16 degrees of gantry tilt. With the exception of proximal opening notch angle, significant differences were not detected in measurements referenced to 12 degrees of gantry tilt. Evidence from this study indicated that a ± 4 degree variation in gantry tilt angle from a desired angle of 12 degrees did not significantly affect clinical interpretations of intercondylar notch measurements or notch width index ratios.
The use of an external skeletal traction device for distal fractures in the dog
Authors: Verleyen P. , van Bree H. , Verhoeven G. , Risselada M.
Published: June 2007

Metacarpal and metatarsal fractures in 11 patients were treated ‘closed’ with a specially designed External Skeletal Fixation (ESF) frame with a walking bar and traction applied to the digits. Mediolateral angulation had improved postoperatively in 10 of the 11 patients. Craniocaudal angulation had improved in eight patients and could not be evaluated in three due to ESF frame superimposition. At follow-up, eight patients had a good clinical function, whereas three patients were still slightly lame. Only minor ESF-related complications were seen (pin loosening, pin tract infection, cerclage wire breakage and bending of the frame), which resolved without intervention after frame removal.
Vascular Cytochrome P450 4A Expression and 20-Hydroxyeicosatetraenoic Acid Synthesis Contribute to Endothelial Dysfunction in Androgen-Induced Hypertension
Authors: Singh Harpreet , Cheng Jennifer , Deng Huan , Kemp Rowena , Ishizuka Tsuneo , Nasjletti Alberto , Schwartzman Michal Laniado
Published: June 2007

Epidemiological evidence suggests a role for sex-dependent mechanisms in the pathophysiology of hypertension. It has been shown that 5α-dihydrotestosterone (DHT) administration (56 mg/kg of body weight per day IP for 14 days) increases blood pressure, cytochrome P450 4A expression, and 20-hydroxyeicosatetraenoic acid synthesis in rats. We examined whether increased vascular 20-hydroxyeicosatetraenoic acid synthesis underlies endothelial dysfunction and hypertension in DHT-treated male Sprague–Dawley rats by using HET0016, a selective cytochrome P450 4A inhibitor. Coadministration of HET0016 (10 mg/kg per day IP for 14 days) to DHT-treated rats markedly reduced DHT-induced interlobar arterial production of 20-hydroxyeicosatetraenoic acid (14.3±1.5 versus 1.5±0.5 ng/mg of protein per hour;
P
<0.05), superoxide anion (246±47 versus 31±8 cpm/μg of protein), and the levels of gp91-phox, p47-phox, and 3-nitrosylated proteins. Moreover, the maximal relaxing response to acetylcholine in phenylephrine-preconstricted renal interlobar arteries from DHT-treated rats (42.8±4.8%) significantly (
P
<0.05) increased in the presence of HET0016 (81.5±10.8%). Importantly, the administration of HET0016 negated DHT-induced hypertension; systolic blood pressure was reduced from 146±2 mm Hg in DHT-treated rats to 130±1 mm Hg (
P
<0.05). The results strongly implicate vascular cytochrome P450 4A–derived 20-hydroxyeicosatetraenoic acid in the development of androgen-induced endothelial dysfunction and hypertension.
Social Evaluations of Stereotypic Images in Video Games
Authors: Brenick Alaina , Henning Alexandra , Killen Melanie , O'Connor Alexander , Collins Michael
Published: June 2007

The aim of this study is to assess late adolescents' evaluations of and reasoning about gender stereotypes in video games. Female ( n = 46) and male ( n = 41) students, predominantly European American, with a mean age 19 years, are interviewed about their knowledge of game usage, awareness and evaluation of stereotypes, beliefs about the influences of games on the players, and authority jurisdiction over three different types of games: games with negative male stereotypes, games with negative female stereotypes, and gender-neutral games. Gender differences are found for how participants evaluated these games. Males are more likely than females to find stereotypes acceptable. Results are discussed in terms of social reasoning, video game playing, and gender differences.
The Role of Information-Processing Capacity and Goals in Attitude-Congruent Selective Exposure Effects
Authors: Smith Steven M. , Fabrigar Leandre R. , Powell Deborah M. , Estrada Marie-Jöelle
Published: June 2007

Two experiments explored the role of information-processing capacity and strategies in regulating attitude-congruent selective exposure. In Experiment 1, participants were placed under time pressure and randomly assigned to conditions in which either an attitude-expressive or no-information processing goal was made salient. Analyses revealed an attitude-congruent selective exposure effect and indicated that this effect was stronger when an attitude-expressive goal was made salient than when no goal was made salient. In Experiment 2, information-processing goals and time pressure were factorially manipulated. Analyses revealed an attitude-congruent selective exposure effect and indicated that this effect was especially strong when time pressure was high and an attitude-expressive goal was made salient. In both experiments, bias at exposure was found to predict bias at later stages of information processing (attention and memory). Supplementary analyses and data confirmed that the attitude-expressive goal manipulation activated its intended motivational processing strategy.
Testicular involution prior to sex change in gilthead seabream is characterized by a decrease in DMRT1 gene expression and by massive leukocyte infiltration
Authors: Liarte Sergio , Chaves-Pozo Elena , García-Alcazar Alicia , Mulero Victoriano , Meseguer José , García-Ayala Alfonsa
Published: June 2007

Background

Leukocytes are found within the testis of most, if not all, mammals and are involved in immunological surveillance, physiological regulation and tissue remodelling. The testis of seasonal breeding fish undergoes a regression process. In the present study, the second reproductive cycle (RC) of the protandrous seasonal teleost fish, gilthead seabream, was investigated and the presence of leukocytes analysed. Special attention has been paid to the testicular degenerative process which is particularly active in the last stage of the second RC probably due to the immediacy of the sex change process.

Methods

Sexually mature specimens (n = 10–18 fish/month) were sampled during the second RC. Some specimens were intraperitoneally injected with bromodeoxyuridin (BrdU) before sampling. Light and electron microscopy was used to determine the different stages of gonadal development and the presence of leukocytes and PCR was used to analyse the gene expression of a testis-differentiating gene and of specific markers for macrophages and B and T lymphocytes. Immunocytochemistry and flow cytometry were performed using a specific antibody against acidophilic granulocytes from the gilthead seabream. Cell proliferation was detected by immunocytochemistry using an anti-BrdU antibody and apoptotic cells by in situ detection of DNA fragmentation.

Results

The fish in the western Mediterranean area developed as males during the first two RCs. The testis of all the specimens during the second RC underwent a degenerative process, which started at post-spawning and was enhanced during the testicular involution stage, when vitellogenic oocytes appeared in the ovary accompanied by a progressive increase in the ovarian index. However, only 40% of specimens were females in the third RC. Leukocytes (acidophilic granulocytes, macrophages and lymphocytes) were present in the gonad and acidophilic granulocyte infiltration occurred during the last two stages. At the same time DMRT1 gene expression decreased.

Conclusions

The results demonstrate that innate and adaptive immune cells are present in the gonads of gilthead seabream. Moreover, the whole fish population underwent a testicular degenerative process prior to sex change, characterized by high rates of apoptosis and necrosis and accompanied by an infiltration of acidophilic granulocytes and a decrease in DMRT1 levels.
Increased platelet expression of FcGammaRIIa and its potential impact on platelet reactivity in patients with end stage renal disease
Authors: Serrano Feliciano A , El-Shahawy Mohamed , Solomon Richard J , Sobel Burton E , Schneider David J
Published: June 2007

Background

Increased platelet reactivity has been implicated in cardiovascular disease – the major cause of death in patients with end stage renal disease (ESRD). FcGammaRIIA is a component of glycoprotein VI and Ib-IX-V that mediate activation of platelets by collagen and von Willebrand factor. To determine whether expression of FcGammaRIIA impacts platelet reactivity we quantified its expression and platelet reactivity in 33 patients with ESRD who were undergoing hemodialysis.

Methods

Blood samples were obtained from patients immediately before hemodialysis and before administration of heparin. Platelet expression of FcGammaRIIA and the activation of platelets in response to low concentrations of convulxin (1 ng/ml, selected to mimic effects of collagen), thrombin (1 nM), adenosine diphosphate (ADP, 0.2 uM), or platelet activating factor (PAF, 1 nM) were determined with the use of flow cytometry in samples of whole blood anticoagulated with corn trypsin inhibitor (a specific inhibitor of Factor XIIa).

Results

Patients were stratified with respect to the median expression of FcGammaRIIA. Patients with high platelet expression of FcGammaRIIA exhibited 3-fold greater platelet reactivity compared with that in those with low expression in response to convulxin (p < 0.01) and 2-fold greater activation in response to thrombin, ADP, and PAF (p < 0.05 for each). For each agonist, expression of FcGammaRIIA correlated modestly but positively with platelet reactivity. The strongest correlation was with thrombin-induced activation (r = 0.6, p < 0.001).

Conclusion

Increased platelet reactivity in response to low concentrations of diverse agonists is associated with high expression of FcGammaRIIA and may contribute to an increased risk of thrombosis in patients with ESRD.
The role of CDK in the initiation step of DNA replication in eukaryotes
Authors: Tanaka Seiji , Tak Yon-Soo , Araki Hiroyuki
Published: June 2007

Cyclin-dependent kinases (CDKs) regulate the progression of the cell cycle in eukaryotes. One of the major roles of CDK is to promote chromosomal DNA replication. However, how CDKs promote DNA replication has been a long-standing question, because all the essential CDK substrates in DNA replication have not been identified yet. Recently Sld2 and Sld3 were identified as essential substrates of CDKs in the initiation step of DNA replication in budding yeast. Moreover, bypass of their phosphorylations is sufficient to promote DNA replication. Phosphorylation of Sld2 and Sld3 by CDKs enhances the formation of complex(es) with a BRCT (BRCA1 C-Terminal)-containing replication protein, Dpb11. We further propose that multiple phosphorylation by CDKs controls this process in budding yeast. Even though Sld3 orthologues in multicellular eukaryotes have not been identified, similar complex formation and, therefore, a similar mechanism of initiation control might be employed in eukaryotes.
Influence of different treatment techniques on radiation dose to the LAD coronary artery
Authors: Nieder Carsten , Schill Sabine , Kneschaurek Peter , Molls Michael
Published: June 2007

Background

The purpose of this proof-of-principle study was to test the ability of an intensity-modulated radiotherapy (IMRT) technique to reduce the radiation dose to the heart plus the left ventricle and a coronary artery. Radiation-induced heart disease might be a serious complication in long-term cancer survivors.

Methods

Planning CT scans from 6 female patients were available. They were part of a previous study of mediastinal IMRT for target volumes used in lymphoma treatment that included 8 patients and represent all cases where the left anterior descending coronary artery (LAD) could be contoured. We compared 6 MV AP/PA opposed fields to a 3D conformal 4-field technique and an optimised 7-field step-and-shoot IMRT technique and evaluated DVH's for several structures. The planning system was BrainSCAN 5.21 (BrainLAB, Heimstetten, Germany).

Results

IMRT maintained target volume coverage but resulted in better dose reduction to the heart, left ventricle and LAD than the other techniques. Selective dose reduction could be accomplished, although not to the degree initially attempted. The median LAD dose was approximately 50% lower with IMRT. In 5 out of 6 patients, IMRT was the best technique with regard to heart sparing.

Conclusion

IMRT techniques are able to reduce the radiation dose to the heart. In addition to dose reduction to whole heart, individualised dose distributions can be created, which spare, e.g., one ventricle plus one of the coronary arteries. Certain patients with well-defined vessel pathology might profit from an approach of general heart sparing with further selective dose reduction, accounting for the individual aspects of pre-existing damage.
Pivotal Advance: Inhibition of MyD88 dimerization and recruitment of IRAK1 and IRAK4 by a novel peptidomimetic compound
Authors: Loiarro Maria , Capolunghi Federica , Fantò Nicola , Gallo Grazia , Campo Silvia , Arseni Brunilde , Carsetti Rita , Carminati Paolo , De Santis Rita , Ruggiero Vito , Sette Claudio
Published: June 2007

MyD88 is an adaptor protein, which plays an essential role in the intracellular signaling elicited by IL-1R and several TLRs. Central to its function is the ability of its Toll/IL-1R translation initiation region (TIR) domain to heterodimerize with the receptor and to homodimerize with another MyD88 molecule to favor the recruitment of downstream signaling molecules such as the serine/threonine kinases IL-1R-associated kinase 1 (IRAK1) and IRAK4. Herein, we have synthesized and tested the activity of a synthetic peptido-mimetic compound (ST2825) modeled after the structure of a heptapeptide in the BB-loop of the MyD88-tIR domain, which interferes with MyD88 signaling. ST2825 inhibited MyD88 dimerization in coimmunoprecipitation experiments. This effect was specific for homodimerization of the TIR domains and did not affect homodimerization of the death domains. Moreover, ST2825 interfered with recruitment of IRAK1 and IRAK4 by MyD88, causing inhibition of IL-1β-mediated activation of NF-κB transcriptional activity. After oral administration, ST2825 dose-dependently inhibited IL-1β-induced production of IL-6 in treated mice. Finally, we observed that ST2825 suppressed B cell proliferation and differentiation into plasma cells in response to CpG-induced activation of TLR9, a receptor that requires MyD88 for intracellular signaling. Our results indicate that ST2825 blocks IL-1R/TLR signaling by interfering with MyD88 homodimerization and suggest that it may have therapeutic potential in treatment of chronic inflammatory diseases.
Plasma Testosterone and Prognosis of Postmenopausal Breast Cancer Patients
Authors: Micheli Andrea , Meneghini Elisabetta , Secreto Giorgio , Berrino Franco , Venturelli Elisabetta , Cavalleri Adalberto , Camerini Tiziana , Di Mauro Maria G. , Cavadini Elena , De Palo Giuseppe , Veronesi Umberto , Formelli Franca
Published: June 2007

Purpose

High endogenous testosterone is associated with increased breast cancer (BC) risk. We designed this study specifically to assess the long-term prognostic role of testosterone in a cohort of postmenopausal BC patients.

Patients and Methods

We considered 194 postmenopausal women, operated on for early BC (T1-2N0M0), who never received chemotherapy or hormonal therapy, and who participated in a fenretinide BC prevention trial as untreated controls. Blood samples were collected 3 months (median) after surgery; plasma samples, stored at −80°C, were radioimmunoassayed for testosterone. Median follow-up was 14 years. The main end point was any cancer event. Event-free survival was estimated by the Kaplan-Meier method. Hazard ratios (HRs) of events by testosterone level were estimated by the Cox model, adjusting for age, tumor size, and histology.

Results

Patients with high testosterone (≥ 0.40 ng/mL, median of distribution) had significantly lower event-free survival than those with low testosterone (log-rank P = .004). The adjusted HR of patients with high versus low testosterone was 2.05 (95% CI, 1.28 to 3.27). High testosterone was also associated with a significantly higher risk of BC events (relapse and second primary) with an adjusted HR of 1.77 (95% CI, 1.06 to 2.96). Eleven second primaries (non-BC) occurred in the high-testosterone group, four in the low-testosterone group.

Conclusion

High plasma testosterone strongly predicts poorer prognosis in postmenopausal BC patients not administered adjuvant therapy. Testosterone levels should be determined as part of the prognostic work-up.
Book Reviews
Authors: Lev Benjamin
Published: June 2007

The range of books reviewed is wide, covering theory and applications in operations research, statistics, management science, econometrics, mathematics, computers, and information systems (no software is reviewed). In addition, we include books in other fields that emphasize technical applications. Publishers who wish to have their books reviewed should send them to Professor Benjamin Lev. We list the books received; not all books received can be reviewed because space is limited. Those who would like to review books are urged to send me their names, addresses, and specific areas of expertise. We commission all reviews and do not accept unsolicited book reviews. Readers are encouraged to suggest books that might be reviewed or to ask publishers to send me copies of such books. The authors or editors of the books reviewed in this issue are C. Chandra, A. K. Kamrani, M. Fiedler, J. Nedoma, J. Ramik, J. Rohn, K. Zimmermann, P. Rossi, G. Allenby, R. McCulloch, L. Tesfatsion, and K. L. Judd.
Caveolin-1 Knockout Mice Have Increased Bone Size and Stiffness
Authors: Rubin Janet , Schwartz Zvi , Boyan Barbara D , Fan Xian , Case Natasha , Sen Buer , Drab Marcus , Smith Deborah , Aleman Maria , Wong Kevin L , Yao Hai , Jo Hanjoong , Gross Ted S
Published: June 2007

The skeletal phenotype of the cav-1−/− mouse, which lacks caveolae, was examined. μCT and histology showed increased trabecular and cortical bone caused by the gene deletion. Structural changes were accompanied by increased mechanical properties. Cell studies showed that cav-1 deficiency leads to increased osteoblast differentiation. These results suggest that cav-1 helps to maintain osteoblast progenitors in a less differentiated state.

Introduction: The absence of caveolin-1 in cellular membranes causes dysregulated signaling. To understand the role of the caveolar microdomain in bone homeostasis, we examined the skeletal phenotype of 5- and 8-wk-old cav-1−/− mice.

Materials and Methods: High-resolution μCT imaging showed a region-specific effect of cav-1 deficiency on the skeleton. At 5 wk, cav-1−/− mice had increased epiphyseal bone volume (+58.4%, p = 0.05); at 8 wk, metaphyseal bone volume was increased by 77.4% (p = 0.008). Cortical bone at the femoral mid-diaphysis showed that the periosteal area of cav-1−/− mice significantly exceeded that of cav-1+/+ mice by 23.9% and 16.3% at 5 and 8 wk, respectively, resulting in increased mechanical properties (Imax: +38.2%, p = 0.003 and Imi: +23.7%, p = 0.03).

Results: Histomorphometry complemented μCT results showing increased bone formation rate (BFR) at trabecular and cortical sites at 5 wk, which supported findings of increased bone at 8 wk in cav-1−/− mice. Formal mechanical testing of the femoral diaphysis confirmed increased bone structure: stiffness increased 33% and postyield deflection decreased 33%. Stromal cells from cav-1−/− marrow showed a 23% increase in von Kossa–positive nodules; osteoclastogenesis was also modestly increased in cav-1–deficient marrow. Knockdown of cav-1 with siRNA in wildtype stromal cells increased alkaline phosphatase protein and expression of osterix and Runx2, consistent with osteoblast differentiation.

Conclusions: These data suggest that cav-1 helps to maintain a less differentiated state of osteoblast progenitor cells, and the absence of cav-1 causes bone to mature more rapidly. Caveolin-1 may thus be a target for altering skeletal homeostasis.
Solubility kinetics of a synthetic uranium(VI) oxide at different pH and controlled O2 partial pressure and evaluation of substantial interface properties
Authors: Roelofs Frank , Sonnefeld Jürgen , Vogelsberger Wolfram
Published: June 2007

The solubility behaviour of a synthetic uranium(VI) oxide was studied under inert conditions in aqueous NaClO4 solution at 25 ± 2 °C. The dissolution kinetics were investigated in respect of pH in solution and O2 partial pressure in the atmosphere. The actual uranium concentration was determined by ICP-MS measurements. Under acidic conditions we observed a moderate solubility which increases by lowering of the pH of solution yielding to a solubility constant of log10
K
sp = −24.38 ± 0.07. The influence of the ionic strength, I, on the dissolution kinetics could be observed which was evaluated using a theoretical model considering the electrical double layer at the surface of the oxide as well as all possible reaction pathways. As a result we could determine the acid-base equilibrium constants of the surface groups and the overall reaction rate, k
+, of dissolution process as a function of pH and I. On this basis we are able to determine the pzc of the uranium oxide, to be 7.28. It is in good accordance with a minimum in the tendency of the solid to dissolve which was observed in the pH range 6 to 8.
A feltárás és a komposztálás hatása a csontok trágyaszerként történő alkalmazhatóságára
Authors: Kovács Dénes , Kardos Györgyné , Füleky György
Published: June 2007

A csontok eredeti
állapotukban trágyázási célra alkalmatlanok, mert anyaguk a talajban majdnem
teljesen oldhatatlan, így az növényi tápanyagot nem képezhet. Az ásványi savak
a csont vízoldható foszfortartalmát megnövelik. Hazánkban évente közel 10 ezer
tonna csonthulladék képződik. Célszerű olyan korszerű és környezetbarát
csontfeltárási technológiát kidolgozni, melynek terméke talajjavító
trágyaszerként használható. Munkánk célja az eltérő kezeléssel feltárt, ill. az
üzemi körülmények között előállított csontlisztek komposztálhatóságának
vizsgálata, valamint a komposztok és a csontlisztek növényi növekedésre és
P-felvételre gyakorolt hatásának tanulmányozása volt. Laboratóriumi körülmények
között csontfeltárási kísérleteket állítottunk be kereskedelmi csontok, ill.
üzemi csontliszt felhasználásával. Elvégeztük a csontok vizes feltárását,
különböző hőmérsékleten, csont/víz aránynál, illetve különböző hőntartási
idővel. További kezelést alkalmaztunk eltérő koncentrációjú citrom- ill. tömény
salétrom- és kénsavval különböző hőmérsékleten, csont/sav aránynál és
hőntartási időnél. Modell-üzemi körülmények között elvégeztük az ipari
csontliszt komposztálását három nyersanyag-összetételben, almos csirketrágya,
csontliszt és csontlé felhasználásával. A különböző eljárással feltárt
csontlisztek felvehető foszfor elemtartalmát növényi teszttel, angolperje növénnyel értékeltük klímakamrában. A főtt csontok citrom- és kénsavas
kezelésével a vízoldható P-tartalom a vízzel kezelt csontokhoz képest a sav
mennyiségével arányosan növekedett. A salétromsavas kezeléssel előállított
csontlisztek vízoldható P-tartalma a vízzel feltárthoz képest közel 30-
szorosára növekedett (0,32-8,51 mg/100 mg). A tenyészedény-kísérletek
eredményeit összegezve megállapítható, hogy a csontliszttel, ill. a komposzttal
talajba juttatott foszfor tápelem közel azonosan hasznosult az angolperje
növények számára. Az egyetlen különbség az volt, hogy a komposztokban lévő
P-tartalom valószínűleg a lassabb feltáródás miatt a növények számára hosszabb
ideig hozzáférhető. Az egyes csontliszt feltárások között a növények P-ellátása
szempontjából nem volt jelentős különbség, talán csak a csontliszt kénsavas
feltárása (8. kezelés) maradt el többi kezelés hatékonyságától. A angolperje által felvett P-mennyiség alapján megállapíthatjuk,
hogy csontok komposztálásával (Komposzt I, II. és III. kezelés) kedvező
P-szolgáltató képesség érhető el. Ez jó esélyt teremt a hulladékként jelentkező
csontok agronómiai felhasználására.
Szennyvíziszap-kezelés hatása egy étkezési szárazbabfajta (Phaseolus vulgaris L.) növekedésére és rizoszférájának mikrobiális változására
Authors: Abdorhim Hamed , Bayoumi Hamuda Hosam E. A. F. , Khalif A. Abdoussalam , Oldal Bálint , Kecskés Mihály , Heltai György
Published: June 2007

Tenyészedény-kísérletet
folytattunk egy kommunális szennyvíziszap növény-talaj rendszerben való
alkalmazási lehetőségeinek modellezésére egy Magyarországon köztermesztésben
lévő, ellenálló étkezési szárazbabfajtával, mivel a szennyvíziszapok nagy
tápelemtartalmuk miatt a növénytápláláshoz kedvezően járulhatnak hozzá.
Üvegházi modellkísérletben neveltünk ellenálló Albamax fajtájú étkezési
szárazbab
(Phaseolus vulgaris
L.) növényeket; szennyvíziszapot különböző
arányban tartalmazó talajkultúrákban, majd 50 napos tenyészidőszak után a talaj
mikroorganizmus-közösségének állapotjelzőit elemeztük, az említett bab
jelzőnövénnyel. Megállapítottuk, hogy az iszapadagolás minden esetben növelte a
kontrollhoz képest az összes csíraszámot, különösen 30% iszaptartalom felett. A
kitenyészthető mikrobák között a rizoszférában minden szennyvíziszap-adagnál a
baktériumok, különösen a Gram-negatív típusúak dominálták, mely jelenség azzal
magyarázható, hogy e csoportban sok fermentatív (fakultatív anaerob)
mikroszervezet fordul elő. Az iszapadagolás következtében megnőtt a
redoxpotenciál és a hidrolitikus talajenzimek aktivitása (dehidrogenáz,
kataláz, proteáz, ureáz, β-glükozidáz és foszfatáz), s ezt a jelenlévő
nehézfémek számottevően nem gátolták. Az iszapkezelés kedvezően hatott a
növények fejlődésére, különösen a magasabb iszapkoncentrációknál (70-80%) nőtt
meg a hajtás/gyökér arány, azaz fokozódott a zöldtömeg felhalmozása. Az iszapok
rövid távú alkalmazásával ily módon a talaj termékenységére és fizikai, kémiai,
valamint biológiai tulajdonságaira kedvezően ható módszerhez juthatunk.
Mikrohullámú módszer nehézfémek meghatározására referencia-mintákban elektrotermikus atomizáció atomabszorpciós spektrometria (ETAAS) és atomabszorpciós spektrometria (AAS) alkalmazásával
Authors: Srogi Krystyna Z.
Published: June 2007

Simple and rapid
analytical procedures for the AAS (Atomic Absorption Spectrometry)
determination of Zn, Cd, Ni, Mo and Pb in biological, geological and soil
samples are described. Special attention was paid to sample preparation,
which is the step, most vulnerable to contaminants. Optimal conditions are
presented for the wet digestion of plant matrices, products and waste for the
coal treatment and soil matrices with different acids including: nitric,
perchloric, hydrochloric, hydrofluoric, sulfuric and hydrogen peroxide along
with optimal temperature programmes for subsequent electrothermal (ET)-AAS and
flame (F)-AAS determination of Zn, Cd, Ni, Mo and Pb. Results of the analysis
of all samples are discussed. The proposed method allows obviating the organic matrix (soil and plant)
destruction stage, shortening the analyte dissolution time, reducing cost, and
minimizing hazards of loss and contamination. The validity and versatility of the methods developed were verified by
the analysis of certified reference materials.
A talaj-mikrobióta vizsgálata foszfolipidek alapján
Authors: Halbritter András , Uzinger Nikolett
Published: June 2007

A talaj-mikrobióta
mennyiségi viszonyait, struktúráját és funkcióit célzó vizsgálatok komoly
bioindikációs értékűek lehetnek, jelentős gyakorlati segítséggel bírhatnak, ha
egy talaj állapotát, egy kezelés vagy szennyezés hatását próbáljuk megismerni.
Ilyen esetekben olyan könnyen kimutatható, jól követhető és lehetőleg
kvantitatív mérhető markerekre, indikátorokra van szükség, melyekből a talaj
belső történéseire, állapotára következtethetünk, és abból viselkedését
megfelelő megbízhatósággal jósolni tudjuk. A mikrobióta közvetett vizsgálatára
elméleti problémákkal a legkevésbé terhelt és a gyakorlatban is egyre terjedő
választás a foszfolipidekre irányul. A foszfolipid-zsírsav- (PLFA-) alapú
mikrobióta-vizsgálat előnyei a mennyiségi meghatározás és a specifikus mikrobacsoportok
kimutatásának kombinációjából fakadnak, valamint abból, hogy a foszfolipidek a
talajban gyorsan lebomlanak, így a PLFA-analízis mindig az aktuális
mikrobaközösségről ad információt. Hátránya, hogy az egyes zsírsavak mennyisége
környezeti tényezők hatására fajon belül is eltérhet, továbbá, hogy nagy az
átfedés a különböző zsírsavak előfordulása között, és viszonylag kevés a kellő
mértékben specifikus zsírsav. Az első életközösségi szintű
foszfolipid-analízist King és
munkatársai végezték 1977-ben. Azóta számos kutató alkalmazta és alkalmazza a
talaj mikrobiális biomasszájának becslésére, valamint a mikrobióta
struktúrájának meghatározásához a PLFA-analízist, például mezőgazdasági
talajhasználat, talajszennyezés hatásainak vizsgálatára, ökotoxikológiai
tesztekhez, jelölt szubsztrátok beépülésének vizsgálatára.