bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacterial Transcriptional Regulators for Degradation Pathways of Aromatic Compounds
Authors: Tropel David , van der Meer Jan Roelof 
Published: September 2004

SUMMARYHuman activities have resulted in the release and introduction into the environment of a plethora of aromatic chemicals. The interest in discovering how bacteria are dealing with hazardous environmental pollutants has driven a large research community and has resulted in important biochemical, genetic, and physiological knowledge about the degradation capacities of microorganisms and their application in bioremediation, green chemistry, or production of pharmacy synthons. In addition, regulation of catabolic pathway expression has attracted the interest of numerous different groups, and several catabolic pathway regulators have been exemplary for understanding transcription control mechanisms. More recently, information about regulatory systems has been used to construct whole-cell living bioreporters that are used to measure the quality of the aqueous, soil, and air environment. The topic of biodegradation is relatively coherent, and this review presents a coherent overview of the regulatory systems involved in the transcriptional control of catabolic pathways. This review summarizes the different regulatory systems involved in biodegradation pathways of aromatic compounds linking them to other known protein families. Specific attention has been paid to describing the genetic organization of the regulatory genes, promoters, and target operon(s) and to discussing present knowledge about signaling molecules, DNA binding properties, and operator characteristics, and evidence from regulatory mutants. For each regulator family, this information is combined with recently obtained protein structural information to arrive at a possible mechanism of transcription activation. This demonstrates the diversity of control mechanisms existing in catabolic pathways.
Single-Cell Microbiology: Tools, Technologies, and Applications
Authors: Brehm-Stecher Byron F. , Johnson Eric A. 
Published: September 2004

SUMMARYThe field of microbiology has traditionally been concerned with and focused on studies at the population level. Information on how cells respond to their environment, interact with each other, or undergo complex processes such as cellular differentiation or gene expression has been obtained mostly by inference from population-level data. Individual microorganisms, even those in supposedly “clonal” populations, may differ widely from each other in terms of their genetic composition, physiology, biochemistry, or behavior. This genetic and phenotypic heterogeneity has important practical consequences for a number of human interests, including antibiotic or biocide resistance, the productivity and stability of industrial fermentations, the efficacy of food preservatives, and the potential of pathogens to cause disease. New appreciation of the importance of cellular heterogeneity, coupled with recent advances in technology, has driven the development of new tools and techniques for the study of individual microbial cells. Because observations made at the single-cell level are not subject to the “averaging” effects characteristic of bulk-phase, population-level methods, they offer the unique capacity to observe discrete microbiological phenomena unavailable using traditional approaches. As a result, scientists have been able to characterize microorganisms, their activities, and their interactions at unprecedented levels of detail.
THE SMOLYANOV SURFACE MEASURE ON TRAJECTORIES IN A RIEMANNIAN MANIFOLD
Authors: SIDOROVA NADEZDA A. 
Published: September 2004

It has been shown in Refs. 2–6 that two natural definitions of surface measures, on the space of continuous paths in a compact Riemannian manifold embedded into ℝn, introduced in the paper by Smolyanov1 are equivalent; this means that there exists a natural object — the surface measure, which we call the Smolyanov surface measure. Moreover, it has been shown2–6 that this surface measure is equivalent to the Wiener measure and the corresponding density has been found. But the known proof of the equivalence of the two definitions of the surface measure is rather nonexplicit; in fact the densities of the measures corresponding to the two different definitions were found independently and only a posteriori it was discovered that those densities coincided. Our aim is to give a direct proof of this fact. We introduce a more restrictive definition of the surface measure as the weak limit of a standard Brownian motion in ℝn conditioned to be in the tubular ε-neighborhood of the manifold at times 0=t0<t1<⋯<tn-1<tn= 1 as both ε and the diameter of the partition tend to zero. Letting ε and then the diameter of the partition tend to zero and vice versa, we arrive at the two definitions above. We prove the existence of the Smolyanov surface measure using our definition, show that this measure is equivalent to the law of a Brownian motion on the manifold, and compute the corresponding density in terms of the curvature of the manifold. As a special case of this, we again obtain the results of Refs. 2–6.
Low molecular weight heparin (tinzaparin) therapy for moderate risk thromboprophylaxis during pregnancy
Authors: Bonnar John , Smith Mark , Steer Philip , Savidge Geoff , Norris Lucy 
Published: September 2004

SummaryLow molecular weight heparin (LMWH) is used increasingly for prophylaxis and treatment of venous thromboembolism during pregnancy. However, the prophylactic dose for patients at moderate risk varies between centers, and the recommended LMWH dose for the non pregnant patient is frequently used in pregnant women. The aim of this study was to investigate the effects of pregnancy on the pharmacokinetics of anti-Xa levels during moderate risk thromboprophylaxis with the LMWH, tinzaparin. In 24 pregnant women, one of three doses of tinzaparin (50, 75 or 100 IU/kg) were given according to the treating physician’s assessment of their risk profile. Four-hour peak anti-Xa levels were measured throughout pregnancy and 24-hour profiles were measured at 28 and 36 weeks gestation. Doses were adjusted when peak anti-Xa levels fell below 0.1 IU/ml and, in some cases, when levels at 10 and 18 hours post injection were undetectable (<0.05 IU/ml). Our results showed that women receiving tinzaparin (50 IU/kg) frequently had peak (4 hour) anti-Xa levels below 0.1IU/ml and that 46% of these patients required dose adjustment. Similarly anti-Xa levels were also found to be low over the 24-hour period. A starting dose of 75 IU/kg, once daily, gave greater anti-Xa cover over the 24-hour period and may avoid the need for dose adjustment. The results suggest that the pharmacokinetics of tinzaparin are affected by pregnancy. Larger studies are required to determine whether an increased tinzaparin dose (75 IU/kg) would be more effective in the prevention of thrombosis during pregnancy than 50 IU/kg
Development of selected coagulation factors and anticoagulants in preterm infants by the age of six months
Authors: Riikonen Pekka , Vahtera Elina , Mahlamäki Eija , Heinonen Kirsti , Kekomäki Riitta , Salonvaara Marjut 
Published: September 2004

SummaryThe development of the coagulation and anticoagulation system in preterm infants was assessed, with special emphasis on extremely low birth weight (ELBW) infants and haemorrhagic or other complications after birth. Coagulation factors II (prothrombin),V (FV),VII (FVII) and X (FX) were analysed at birth and at a corrected age of six months. In addition, antithrombin (AT), protein C (PC) and protein S (PS) were measured at six months, and DNA samples were tested for Factor V Leiden (R506Q). Eighty-two infants, with a median gestational age (GA) of 32 weeks (range 24–36) and a median birth weight of 1562 g (range 695–3520), were studied. Fifteen of these were ELBW infants (range 695-1000g). Prothrombin, FV, FVII and FX reached healthy term six-month-old infant activity levels. Prothrombin and FX did not reach adult values; median activity levels remained at 82% and 78%, respectively. During the follow up, the FV and FVII levels of the ELBW infants (GA 24-27 weeks) increased more than those of the preterm infants born with higher GA (p < 0.001). At birth, prothrombin correlated significantly with FV, FVII and FX (p < 0.001). FVII at birth and at six months correlated significantly with PC (p= 0.021 and p= 0.009, respectively). These findings indicate that the gain in the coagulation factor concentrations in infancy is greatest in infants with the lowest GA at birth. Interesting new inter-relations of coagulation factor and physiological anticoagulant levels may indicate that there are still unrecognised pathways in the function of newborn haemostasis.
Expression of transcription factor Oct-4 and other embryonic genes in CD133 positive cells from human umbilical cord blood
Authors: Baal Nelli , Reisinger Kerstin , Jahr Henning , Bohle Rainer , Liang Olin , Münstedt Karsten , Rao C.V. , Preissner Klaus , Zygmunt Marek 
Published: September 2004

SummaryA significant number of hematopoietic stem/progenitor cells (HSPC) in human umbilical cord blood could serve as a reservoir for the placental vasculature, yet, their morphological and functional features are not completely understood. Here, we describe the characterization of purified CD133+ progenitor cells from umbilical cord blood, a subset of CD34+ hematopoietic progenitors that were grown in proliferation medium containing Flt3-ligand, thrombopoietin and stem cell factor. Following isolation and enrichment of the CD133+ cells by immunomagnetic cell sorting, they remained non-adherent for up to 40 days in culture and expressed different pluripotency markers including Sox-1, Sox-2, FGF-4, Rex-1 and Oct-4. Oct-4 expression was confirmed by laser-assisted single cell picking with subsequent quantitative real-time RT-PCR.The expression of Oct-4 indicates a pluripotent phenotype of CD133+ cells and appears to be of functional relevance: After three weeks in endothelial differentiation medium, suspended cells became adherent, developed an endothelial cell-like morphology, bound fluoresceine isothiocyanate-labeled Ulex europaeus agglutinin-1, took up acetylated Di-LDL, and expressed other endothelial markers such as PECAM-1 or VEGFR-2. Concomitantly, Oct-4 expression was significantly reduced. Moreover, following treatment with retinoic acid, CD133+ cells exhibited neural morphology associated with the expression of β-III-tubulin. CD133+ cells were found to express the luteinizing hormone/human chorionic gonadotropin (LH/hCG) receptor, detected by RT-PCR and immunocytochemistry. The recombinant human chorionic gonadotropin induced proliferation of the CD133+ cells in a dose-specific manner. Our results indicate that CD133+ HSPC from umbilical cord blood may have a greater differentiation potential than previously recognized and give rise to proliferative endothelial cells participating in placental vasculogenesis.
Ultrasound affects distribution of plasminogen and tissuetype plasminogen activator in whole blood clots in vitro
Authors: Gherardini Lisa , Mayer Christoph , Gröschl Martin , Kaun Christoph , Benes Ewald , Tschachler Erwin , Huber Kurt , Maurer Gerald , Devcic-Kuhar Branka , Pfaffenberger Stefan , Wojta Johann , Gottsauner-Wolf Michael 
Published: September 2004

SummaryUltrasound of 2 MHz frequency and 1.2 W/cm2 acoustic intensity was applied to examine the effect of sonication on recombinant tissue-type plasminogen activator (rt-PA)-induced thrombolysis as well as on the distribution of plasminogen and t-PA within whole blood clots in vitro. Thrombolysis was evaluated quantitatively by measuring clot weight reduction and the level of fibrin degradation product D-dimer (FDP-DD) in the supernatant. Weight reduction in the group of clots treated both with ultrasound and rt-PA was 35.2% ± 6.9% which is significantly higher (p<0.0001) than in the group of clots treated with rt-PA only (19.9% ± 4.3%). FDP-DD level in the supernatants of the group treated with ultrasound and rt-PA increased sevenfold compared to the group treated with rt-PA alone, (14895 ± 2513 ng/ml vs. 2364 ± 725 ng/ml). Localization of fibrinolytic components within the clots was accomplished by using gel-entrapping technique and immunohistochemistry. Spatial distributions of t-PA and plasminogen showed clearly that ultrasound promoted the penetration of rt-PA into thrombi significantly (p<0.0001), and broadened the zone of lysis from 8.9 ± 2.6 µm to 21.2 ± 7.2 µm. We speculate that ultrasound enhances thrombolysis by affecting the distribution of rt-PA within the clot.
Fibrinogen adsorption and platelet adhesion to metal and carbon coatings
Authors: Santin Matteo , Denyer Stephen , Lloyd Andrew , G.Teer Dennis , Field Sue , Mikhalovsky Sergey , Mikhalovska Lyuba 
Published: September 2004

SummaryIn order to study the haemocompatibility of metal and carbon coatings, fibrinogen adsorption and platelet adhesion to various coatings have been investigated.Two metallic coatings titanium and zirconium, and two carbon coatings isotropic diamondlike and isotropic graphite-like coatings, were prepared by plasma vapour deposition onto stainless steel substrate. It has been shown that the adsorption of fibrinogen to metal and carbon coatings and its post-adsorptive transition are dependent on both the material properties and the fibrinogen environment. The adsorption of fibrinogen from human plasma on titanium and zirconium coatings is similar to that on uncoated stainless steel surface. Both carbon coatings adsorb much greater amount of fibrinogen from plasma, and fibrinogen retention by carbon surfaces is also greater than by metal surfaces. Increased numbers of adhered platelets have been found on both carbon coatings in comparison to the metal materials, although this does not correlate with the amount of adsorbed fibrinogen.
P-selectin-targeting of the fibrin selective thrombolytic Desmodus rotundus salivary plasminogen activator α1
Authors: Dong Ningzheng , Da Cunha Valdeci , Citkowicz Andrej , Wu Faye , Vincelette Jon , Larsen Brent , Wang Yi-Xin , Ruan Changgeng , Dole William , Morser John , Wu Qingyu , Pan Junliang 
Published: September 2004

SummaryDuring thrombosis, P-selectin is expressed on the surface of activated endothelial cells and platelets. We hypothesized that targeting a plasminogen activator (PA) to P-selectin would enhance local thrombolysis and reduce bleeding risk. Previously, a urokinase (uPA)/anti-P-selectin antibody (HuSZ51) fusion protein was shown to increase fibrinolysis in a hamster pulmonary embolism model. To explore the therapeutic potential of this targeting strategy, we fused the fibrin-selective Desmodus rotundus salivary PA α1 (dsPAα1) to HuSZ51 and compared the fibrinolytic activity of P-selectin-targeted dsPAα1 (HuSZ51-dsPAα1) to unmodified dsPAα1 in vitro and in vivo. HuSZ51-dsPAα1 and dsPAα1 were expressed in CHO cells and purified to homogeneity by affinity chromatography. HuSZ51dsPAα1 bound to thrombin-activated human and dog platelets with comparable affinities to that of parental antibody SZ51. The fusion protein retained the catalytic activities of dsPAα1 in chromogenic and clot lysis assays, indicating that dsPAα1 is fully functional when fused to HuSZ51. Compared to dsPAα1, HuSZ51-dsPAα1 had similar thrombolytic efficacy in a rat pulmonary embolism model and anti-thrombotic potency in a dog model of femoral artery thrombosis. However, HuSZ51dsPAα1 was less effective in lysis of preexisting arterial thrombi in the dog model. The reduced arterial thrombolysis was not due to the pharmacokinetic properties of HuSZ51-dsPAα1 because antigen level and amidolytic activity were higher in plasma from HuSZ51-dsPAα1-treated groups than corresponding dsPAα1-treated groups. These data indicate that the thrombolytic efficacy of HuSZ51-dsPAα1 varied dependent on the physical composition of thrombi. The lack of stimulation by fibrin in arterial thrombi may contribute to the attenuated thrombolytic efficacy of HuSZ51-dsPAα1 in the dog model.
On the mode of action of thrombin-induced angiogenesis: thrombin peptide, TP508, mediates effects in endothelial cells via αvβ3 integrin
Authors: Tsopanoglou Nikos , Papaconstantinou Matthew , Flordellis Christodoulos , Maragoudakis Michael 
Published: September 2004

SummaryIn a previous report we have presented evidence that thrombin interacts with αvβ3
integrin in endothelial cells at the molecular and cellular level. This interaction was shown to be of functional significance in vitro and in vivo and contributed to activation of angiogenesis by thrombin. In the present study, we have used a synthetic thrombin peptide, TP508, which represents residues 183 to 200 of human thrombin. This peptide lacks the catalytic site of thrombin but contains the thrombin RGD sequence. Immobilized (surface-coated) TP508 peptide, like thrombin, supported αvβ3
integrin-dependent endothelial cell attachment and haptotactic migration. These effects were specific (a scrambled TP508 peptide was without effect), and dosedependent. The RGD sequence was essential since a modified TP508 peptide, which contained RAD sequence instead of RGD, was inactive. Immobilized TP508 peptide stimulated phosphorylation of mitogen-activated protein kinases and focal adhesion kinase, the signal transduction pathways characteristic for integrin activation. On the other hand, TP508 peptide, when in solution, did not mimic other thrombin-promoted angiogenic effects, such as that of activation gelatinase A, upregulation of expression of vascular endothelial growth factor receptor mRNA or prostacyclin PGI2 release in endothelial cells. On the contrary, soluble TP508 acted as an antagonist for the aforementioned effects of thrombin. TP508 peptide inhibited these thrombin-induced effects through a RGD and α.
vβ3-related mechanism. The antagonism with thrombin or thrombin receptor activating peptide was specific and involved at least in part mitogen-activated protein kinases activation. These results point to the importance of RGD sequence of thrombin in mediating effects on endothelial cells and angiogenesis.
An in vitro study on the mechanisms of coagulation activation in acute myelogenous leukemia (AML): role of tissue factor regulation by cytotoxic drugs and GM-CSF
Authors: Amirkhosravi Ali , Loges Sonja , Meyer Todd , Eifrig Barbara , Hossfeld Dieter , Fiedler Walter , Francis John , Langer Florian 
Published: September 2004

SummaryAML patients may suffer from a disseminated coagulopathy, which can aggravate a pre-existing bleeding tendency due to thrombocytopenia and platelet dysfunction. The cellular and molecular mechanisms underlying this coagulopathy, however, are not completely understood. Indeed, the broad and increasing therapeutic use of cytotoxic drugs and growth factors is likely to contribute to the complexity of hemostatic abnormalities encountered in this hematologic malignancy. The nature of coagulation activation in AML was therefore investigated in vitro using the human leukemic cell line, HL60. Tissue factor (TF) was almost entirely located on the cell surface and bound factor VIIa, but only 15-25% of this TF was primarily functionally active. Treatment with increasing concentrations of daunorubicin or cytosine-β-D-arabinofuranoside, two cytotoxic drugs commonly used in AML therapy, induced apoptosis and secondary necrosis of HL60 cells and resulted in marked decryption of TF PCA independent of de novo protein synthesis. This PCAmodulating effect was concomitant with and functionally dependent on the exposure of phosphatidylserine on the outer membrane leaflet. Similar observations were made in analogous ex vivo studies on patient-derived myeloblasts. Incubation of HL60 cells with GM-CSF, a cytokine expressed in the bone marrow microenvironment and used as an adjunct to AML treatment, evoked a cellular response, which included both enhanced TF production and release of VEGF-A and uPA into the culture medium. We conclude that both decryption of preformed TF PCA by chemotherapeutic drugs and de novo induction of TF by cytokines such as GM-CSF can regulate the procoagulant phenotype of HL60 cells in vitro.
Delayed immunologic thrombocytopenia induced by abciximab
Authors: Clofent-Sanchez Gisèle , Jais Catherine , Bermejo Emilse , Leroux Lionel , Coste Pierre , Nurden Alan , Nurden Paquita 
Published: September 2004

SummaryAbciximab is an anti-GPIIb-IIIa drug widely used to prevent thrombotic complications during percutaneous coronary intervention. We now report on the immunologic origin of thrombocytopenia developing between 7 and 12 days after the onset of abciximab infusion. Antibodies directed against abciximabcoated platelets were located in 5 patients with delayed thrombocytopenia, just as they were present in a patient whose platelet count fell within a few hours after receiving the drug. Abciximab-dependent IgG antibody was revealed in serum using control platelets in the monoclonal antibody immobilization of platelet antigens assay (MAIPA) performed with SZ22, a MoAb to GPIIb. The presence of IgG antibodies specific for platelets sensitized with abciximab was confirmed by flow cytometry. They were not located in 13 patients receiving abciximab but whose platelet counts remained stable. For three patients, antibodies were transient and their presence related to the extent of the thrombocytopenia. Surprisingly, antibodycontaining plasma from three patients induced abciximabdependent activation and aggregation of normal platelets, a finding confirmed by electron microscopy. Immunogold labeling revealed that abciximab was associated with platelets in the aggregate, suggesting that its inhibitory effect was overcome by the platelet stimulation. In summary, these results show that abciximab-dependent thrombocytopenia can be delayed and potentially prothrombotic.
The effect of homocysteine reduction by B-vitamin supplementation on markers of endothelial dysfunction
Authors: Peeters Anita , van der Molen Els , Blom Henk , den Heijer Martin 
Published: September 2004

SummaryHyperhomocysteinemia is a risk factor for arterial vascular disease and venous thrombosis. The pathophysiology of this relation is unclear, but several studies suggest that hyperhomocysteinemia impairs endothelial function. We examined the effect of homocysteine lowering by B-vitamin supplementation on tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI) and von Willebrand factor (vWf) markers of endothelial dysfunction in hyperhomocysteinemic and normohomocysteinemic volunteers. A total of 123 healthy volunteers were randomized to placebo or B-vitamins (5 mg folic acid, 0.4 mg hydroxycobalamin and 50 mg pyridoxine) daily for 8 weeks. Before and after the intervention period, blood samples were taken for measurements of homocysteine, tPA, PAI and vWf.There was no evident association between homocysteine concentration and concentrations of markers of endothelial dysfunction at baseline.The mean reduction of homocysteine concentration was 31% (95%CI 22.7 to 39.1) in the B-vitamin group compared to 3% reduction in the placebo group. Concentrations of tPA, PAI and vWf did not change after supplementation of B-vitamins. In conclusion, the results of our study show that homocysteine reduction by B-vitamin supplementation has no effect on markers of endothelial dysfunction in healthy volunteers.