bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protransglutaminase (Factor XIII) Mediated Crosslinking of Fibrinogen and Fibrin*
Authors: Meh David , Mosesson Michael , Siebenlist Kevin 
Published: March 2018

SummaryPlasma factor XIII (plasma protransglutaminase) circulates as an A2B2 tetramer bound to the γ’ variant chains of fibrinogen “2”. During clotting the A subunits of fXIII are cleaved by thrombin to form fXIIIa (transglutaminase) and in the presence of calcium ions, activated A2* subunits dissociate from the B subunits. When purified plasma fXIII or recombinant cellular factor XIII (A2) was incubated with fibrinogen in the presence of calcium ions (≥50 μM) a non-synerizing gel formed concomitant with formation of γ dimers, followed by A γ polymers, and eventually γ trimers and γ tetramers. As is the case of fXIIIa, the fXIII-mediated crosslinking rate was enhanced in the presence of thiols. After an initial lag period, fXIII catalyzed fibrinogen cross-linking at ~75% of the rate of fXIIIa under typical crosslinking conditions (100 Loewy u/ml, 5 mM CaCl2 & 500 μM DTT). Fibrin was crosslinked about 8 times more rapidly by fXIII than was fibrinogen, and after an initial lag period fXIII crosslinked fibrin at nearly the same rate as fXIIIa. Substituting plasma for purified fXIII as the source for fXIII resulted in robust fibrinogen crosslinking activity. In contrast to the high level of fXIII-mediated crosslinking activity observed with fibrinogen or fibrin as substrates, when transglutamination was measured using cadaverine incorporation into casein, fXIII was 30-fold less active than fXIIIa. Thus, factor XIII displays constitutive enzymatic activity with respect to fibrinogen and fibrin. The results further indicate that uncleaved fXIII in plasma provides a potent source of readily available crosslinking activity in clotting blood. Fibrinogen 2, whose γ’chains bind fXIII B subunits, was crosslinked 3.5 times more slowly by fXIII than was fibrinogen 1 (lacking γ’ chains), suggesting that complex formation between fibrinogen 2 and plasma fXIII plays a significant role in down-regulating potential plasma fXIII-mediated crosslinking activity. Since fibrin is a considerably better substrate for fXIII than is fibrinogen, the rate at which crosslinking takes place in a fibrinogen-containing plasma environment is much lower than it would be if fibrin were present.
Bilinexin, a Snake C-type Lectin from Agkistrodon bilineatus Venom Agglutinates Platelets via GPIb and α2β1
Authors: Du Xiao-Yan , Navdaev Alexey , Clemetson Jeannine , Magnenat Edith , Wells Timothy , Clemetson Kenneth 
Published: March 2018

SummaryA new snake protein, named bilinexin, has been purified from Agkistrodon bilineatus venom by ion-exchange chromatography and gel filtration chromatography. Under non-reducing conditions it has a mass of 110 kDa protein on SDS-PAGE. On reduction, it can be separated into five subunits with masses in the range 13-25 kDa. The N-terminal sequences of these subunits are very similar to those of convulxin or the alboaggregins, identifying bilinexin as a new member of the snake C-type lectin family, unusual in having multiple subunits. Bilinexin agglutinates fixed platelets, washed platelets and platelet rich plasma (PRP) without obvious activation (shape change) as confirmed by light microscope examination. Both inhibitory and binding studies indicate that antibodies against α2β1 inhibit not only platelet agglutination induced by bilinexin, but also bilinexin binding to platelets. VM16d, a monoclonal anti-GPIbα antibody, completely inhibits platelet agglutination induced by bilinexin, and polyclonal antibodies against GPIbα prevent its binding to platelets. However, neither convulxin, polyclonal anti-GPVI antibodies, nor GPIIb/IIIa inhibitors affect its binding to and agglutination of platelets. Bilinexin neither activates GPIIb/IIIa integrin on platelets nor induces tyrosine phosphorylation of platelet proteins, nor increases intracellular Ca2+ in platelets. Like alboaggregin B, bilinexin agglutinates platelets, which makes it a good tool to investigate the differences in mechanism between snake C-type lectins causing platelet agglutination and those that induce full activation.
Usefulness and Limitations of Animal Models of Venous Thrombosis
Authors: Dörffler-Melly Janine , Johnson Gerhard , Drouet Ludovic , Badimon Lina , Levi Marcel 
Published: March 2018

IntroductionTo study the pathogenesis of in vivo thrombus formation and to evaluate novel preventive or therapeutic strategies, animal models of venous thrombosis have been in use for more than 50 years. In the past decades numerous animal models of venous thrombosis have been developed and have been applied for a variety of objectives and mostly without certain predictive value for the relevance to human venous thrombosis. The Subcommittee on Animal, Cellular, and Molecular Models of Thrombosis and Haemostasis of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis decided to systematically review the various animal models of venous thrombosis and to analyze the contribution of these models to the study of the pathogenesis and treatment of venous thrombosis. This manuscript summarizes the results of this analysis and it draws some conclusions on the appropriate use of animal models for venous thrombosis.
Diagnostic Accuracy of Compression Ultrasonography for the Detection of Asymptomatic Deep Venous Thrombosis in Medical Patients
Authors: Bressollette Luc , Nonent Michel , Garcia Jean-François , Larroche Pascal , Guias Bruno , Scarabin Pierre-Yves , Mottier Dominique , Oger Emmanuel 
Published: March 2018

SummaryWe assessed the accuracy of venous compression ultrasonography (CUS) for the detection of asymptomatic deep vein thrombosis in 122 consecutive patients, with a mean age of 69 years, who were hospitalised in an internal medicine unit. All included patients had CUS within 48 h of admission. Twelve out of 17 patients with a positive CUS underwent phlebography, as the others withdrew their consent, whereas the remaining 105 patients with a negative serial CUS testing were clinically followed-up at 3 months. We found that CUS had a sensitivity and a specificity of respectively 1 (95% CI, 0.73 to 1) and 1 (95% CI, 0.96 to 1) for the detection of asymptomatic deep vein thrombosis. Kappa-coefficients for intra-observer and inter-observer agreements were respectively 0.88 and 0.56. We concluded that venous compression ultrasonography, performed as described, fulfils requirements of a screening test that could be available for prophylactic clinical trials or epidemiological researches.
A Cross Sectional Study of Antiphospholipid-protein Antibodies in Patients with Venous Thromboembolism
Authors: Amiral Jean , Martin Luc de Saint , Mottier Dominique , Pasquier Elisabeth 
Published: March 2018

Summary
Objective: To look for an association between venous thromboembolism (VTE) and antiphospholipid antibodies (aPL) in patients without Systemic Lupus Erythematosus (SLE) when implementing, beside conventional assays, new tests for aPL screening directed towards purified proteic targets. Methods: We conducted a cross-sectional, hospital-based study of consecutive unselected outpatients. We compared VTE+ patients to VTE- among 398 consecutive unselected outpatients referred for clinical suspicion of VTE. To detect aPL, the following ELISAs were performed : 1) a conventional standardized ELISA 2) an improved APA assay, 3) an anti-Beta2GPI ELISA, 4) an anti-Annexin V ELISA, 5) an anti-Prothrombin ELISA. We sought an association between VTE and aPL through a quantitative (t-test) and a qualitative comparison (chi-square test, according to the cut-off values set as the 95th percentile of aPL distribution). First we conducted an analysis of all patients. Then we stratified them into 2 subgroups, with or without a wellknown risk factor for VTE (prolonged immobilization >72h, surgery or trauma within the past three months, current malignancy). Results: 61% of patients were classified as VTE-positive. Before stratification, we did not find any significant association between the VTE status and aPL. However, after stratification, in the subgroup without risk factors for VTE, the frequency of positive values as regards the anti Prothrombin antibodies detection was significantly higher in VTE+ patients (p = 0,04). Conclusion: The presence of anti Prothrombin antibodies might be an independent risk factor of VTE. However systematic screening for aPL in non SLE patients referred for VTE suspicion at the time of the thromboembolic event has little clinical relevance.
Hospitalisation for Upper Gastrointestinal Bleeding Associated with Use of Oral Anticoagulants
Authors: Sørensen Henrik Toft , Mellemkjœr Lene , Blot William , Nielsen Gunnar Lauge , McLaughlin Joseph , Olsen Jørgen , Johnsen Søren 
Published: March 2018

SummaryThe incidence of hospitalisation for upper GI bleeding with use of oral anticoagulants (OA) alone or in combination with other drugs was examined in a cohort of 4,204 users of OA, identified through record linkage between a population-based prescription database and a hospital discharge registry in Denmark, and compared with the incidence in the general population not exposed to OA. The standardised incidence ratio (SIR) was 2.8 (95% CI = 1.6-4.5) for use of OA alone. SIRs tended to be higher for use of OA combined with acetaminophen alone (4.4, 95% CI = 1.2-11.4), non-aspirin NSAIDs alone (8.0, 95% CI = 2.1 to 20.4) or aspirin/corticosteroids alone (3.8, 95% CI = 0.8-11.0), respectively.These results indicate that use of OA is associated with a significantly increased risk of upper GI bleeding, with still higher risks associated with the concomitant use of other medications including acetaminophen. Further research is needed to clarify the extent to which drugs interacting with oral anticoagulants may cause GI bleeding and the mechanisms through which these associations operate.
Gene Therapy in Hemophilia: Clinical Trials Update
Authors: White Gilbert 
Published: March 2018

SummaryDisorders caused by inborn genetic errors have been a primary target for treatment by gene transfer. Hemophilia A and B have been considered especially important targets because the genes for factor VIII and IX are well characterized, levels of factor VIII and IX do not require complex regulation, small increases in factor level would have significant clinical benefits, good clinical and laboratory tests of efficacy exist, and excellent animal models of hemophilia are available. Four clinical trials of gene transfer in hemophilia, two in hemophilia A and two in hemophilia B, are currently underway or have been completed and two other trials have been approved. The collective interim results from these trials indicate that the current approaches and doses are safe and that low levels of expression are detected. These studies support the continued development of gene transfer as a potential treatment option for hemophilia.
The Role of ITAM- and ITIM-coupled Receptors in Platelet Activation by Collagen
Authors: Asazuma Naoki , Atkinson Ben , Berlanga Oscar , Best Denise , Bobe Regis , Jarvis Gavin , Marshall Stuart , Snell Daniel , Stafford Margaret , Tulasne David , Wilde Jonathan , Wonerow Peter , Frampton Jon , Watson Steve 
Published: March 2018

SummaryThe major activation-inducing collagen receptor glycoprotein VI (GPVI) has been cloned within the last two years. It is a member of the Ig superfamily of proteins and is constitutively associated with the ITAM-bearing Fc receptor γ-chain (FcR γ-chain). GPVI signals through a pathway that involves several of the proteins used by Fc, B- and T-lymphocyte receptors and which takes place in glycolipid-enriched membrane domains in the plasma membrane known as GEMs. Responses to GPVI are regulated by PECAM-1 (CD31) and possibly other ITIM-bearing receptors. Despite a pivotal role for GPVI, there are important differences between signalling events to collagen and GPVI-specific ligands. This may reflect a role for co-receptors in the response to collagen.
The Emerging Role of the Bone Marrow-Derived Stem Cells in (Therapeutic) Angiogenesis
Authors: Luttun Aernout , Carmeliet Peter 
Published: March 2018

SummaryProper formation of blood vessels (angiogenesis) is essential for development, reproduction and wound healing. When derailed, angiogenesis contributes to numerous lifethreatening disorders. While research has generally been focusing on the two main vascular cell types (endothelial and smooth muscle cells), recent evidence indicates that bone marrow may also contribute to this process, both in the embryo and the adult. Novel vascular progenitors, even one common to both endothelial and smooth muscle cells, have been identified in the embryo. An exciting observation is that endothelial precursors have also been identified in the adult bone marrow. Transplantation studies revealed that these precursors as well as other bone marrow-derived cells contribute to the growth of endothelium-lined vessels (angiogenesis) as well as the expansion of pre-existing collaterals (arteriogenesis) in ischemic disease. These findings have raised hopes that bone marrow-derived cells might one day become useful for cell-based angiogenic therapy.
Gene Expression in Atherogenesis
Authors: Monajemi Houshang , Arkenbout E. Karin , Pannekoek Hans 
Published: March 2018

SummaryIt is conceivable that the extent and spatio-temperal expression of dozens or even a few hundred genes are significantly altered during the development and progression of atherosclerosis as compared to normal circumstances. Differential gene expression in vascular cells and in blood cells, due to gene-gene and gene-environment interactions can be considered the molecular basis for this disease. To comprehend the coherence of the complex genetic response to systemic and local atherosclerotic challenges, one needs accessible high through-put technologies to analyze a panel of differentially expressed genes and to describe the interactions between and among their gene products. Fortunately, new technologies have been developed which allow a complete inventory of differential gene expression, i.e. DD/RT-PCR, SAGE and DNA micro-array. The initial data on the application of these technologies in cardiovascular research are now being reported. This review summarizes a number of key observations. Special attention is paid to a few central transcription factors which are differentially expressed in endothelial cells, smooth muscle cells or monocytes/ macrophages. Recent data on the role of nuclear factor- B (NF-κB) and peroxisome proliferation-activating receptors (PPARs) are discussed. Like the PPARs, the NGFI-B subfamily of orphan receptors (TR3, MINOR and NOT) also belongs to the steroid/thryroid hormone receptor superfamily of transcription factors. We report that this subfamily is specifically induced in a sub-population of neointimal smooth muscle cells. Furthermore, intriguing new data implicating the Sp/XKLF family of transcription factors in cell-cell communication and maintenance of the atherogenic phenotype are mentioned. A member of the Sp/XKLF family, the shear stress-regulated lung Krüppel-like factor (LKLF) is speculated to be instrumental for the communication between endothelial cells and smooth muscle cells. Taken together, the expectation is that the fundamental knowledge obtained on atherogenesis and the data that will be acquired during the coming decade with the new, powerful high through-put methodologies will lead to novel modalities to treat patients suffering from cardiovascular disease. In view of the phenotypic changes of vascular and blood-borne cells during atherogenesis, therapeutic interventions likely will focus on reversal of an acquired phenotype by gene therapy approach or by using specific drugs which interfere with aberrant gene expression.
Transition von Kindern und Jugendlichen mit chronisch-entzündlichen Darmerkrankungen
Authors: Ballauff A. 
Published: March 2018

ZusammenfassungBei etwa 20 % aller Patienten mit chronisch-entzündlichen Darmerkrankungen wird die Diagnose vor dem 20. Lebensjahr gestellt. Die pädiatrische Betreuung erfolgt meist in Spezialambulanzen. Für Erwachsene ist die Betreuungsstruktur sehr unterschiedlich. Der Betreuungswechsel fällt in die Phase der Adoleszenz mit erhöhtem Risiko für eine schlechte Compliance und Einhaltung von Kontrolluntersuchungen. Um eine gute kontinuierliche Weiterbetreuung zu erreichen, ist ein strukturierter Transitionsprozess erforderlich. Die Übersicht beschreibt dafür notwendige Anforderungen an Patient und Eltern, Aufgaben an Pädiater und internistische Gastroenterologen sowie derzeitige gesundheitspolitische Bemühungen zur Klärung von Struktur- und Finanzierungsmöglichkeiten.
Partizipation und Bildung als Endpunkte in der pädiatrischen Versorgungsforschung
Authors: Gebhard B. , Philippi H. , De Bock F. , Urschitz M. S. 
Published: March 2018

ZusammenfassungAngesichts des sich wandelnden Krankheitsspektrums in der Pädiatrie ist eine gut organisierte pädiatrische Versorgungsforschung notwendig. Wir stellen in diesem Artikel aus entwicklungspädiatrischer Sicht ausschlaggebende, neue Endpunkte der pädiatrischen Versorgungsforschung vor, nämlich Partizipation (= soziale Teilhabe) und Bildung. Durch zwei derzeit in Deutschland laufende Validierungsstudien werden in absehbarer Zeit zwei soziokulturell adaptierte deutschsprachige Instrumente zur Messung von Partizipation zur Verfügung stehen (CASP bzw. CAPE). Eine weitere Studie wird erstmals in Deutschland die Zusammenhänge zwischen Gesundheitsstand und frühen Bildungsendpunkten am Übergang von der Kindergarten- zur Grundschulzeit darstellen. Bei der zukünftigen Evaluation von pädiatrischen Versorgungsangeboten und -strukturen muss der Fokus vermehrt darauf gelegt werden, ob Partizipation und Bildung verbessert werden. Um dies zu erreichen, wird eine intensivere Vernetzung von medizinischer Versorgung und pädagogischer Förderung im Vordergrund stehen.
Management von obstruktiven Harntransportstörungen
Authors: Dietz H. G. , Lange-Sperandio B. 
Published: March 2018

ZusammenfassungKongenitale obstruktive Harntransportstörungen bilden eine heterogene Gruppe von Erkrankungen, die durch einen unterschiedlichen natürlichen Verlauf gekennzeichnet sind. Obstruktive Harntransportstörungen können unilateral oder bilateral auftreten und entweder auf Höhe des ureteropelvinen Übergangs, im Bereich des distalen Harnleiters, auf Blasenausgangsebene oder im Bereich der Urethra liegen. Zu den häufigsten angeborenen obstruktiven Uropathien gehören die ureteropelvine Stenose, der primär obstruktive Megaureter sowie die Harnröhrenklappen bei Jungen. Während sich Obstruktionen des oberen Harntraktes häufig spontan zurückbilden, sind infravesikale Obstruktionen durch eine hohe Morbidität und Mortalität gekennzeichnet. Nach wie vor gehören die obstruktiven Uropathien zu den Hauptursachen chronisch terminaler Niereninsuffizienz im Kindesalter. Im Folgenden berichten wir über die Pathogenese, Diagnostik und Therapie einer kongenitalen obstruktiven Uropathie. Obstruktive Harntransportstörungen sind multifaktoriell bedingt und können potenziell zur Niereninsuffizienz im Kindesalter führen.
Interpretation von erhöhtem Troponin bei Patienten mit ischämischem Schlaganfall
Authors: Endres M. , Nolte C. H. , Scheitz J. F. 
Published: March 2018

ZusammenfassungKardiales Troponin (cTn) ist aufgrund der hohen Sensitivität und Spezifität für Myokardschädigungen obligater Bestandteil bei der Diagnosestellung eines akuten Myokardinfarktes. Allerdings zeigt ein erhöhtes cTn nicht die Entstehungsmechanismen der Myokardschädigung an. Bereits seit vielen Jahrzehnten ist bekannt, dass es im Rahmen akuter zerebrovaskulärer Ereignisse häufig zu kardialen Komplikationen wie Arrhythmien, kardialer Dysfunktion, autonomer Imbalance, EKG-Veränderungen und zum Anstieg kardialer Biomarker kommen kann. Dies kann im Einzelfall große differenzialdiagnostische Probleme bereiten. Die weite Verbreitung hochsensitiver cTn-Assays, die sehr geringe Mengen cTn nachweisen können, hat diese Situation weiter verschärft. Ziel dieses Übersichtsartikels ist es, die Literatur hinsichtlich Häufigkeit und prognostischer Bedeutung von cTn-Erhöhungen nach Schlaganfall zusammenzufassen, Entstehungsmechanismen von cTn-Erhöhungen nach Schlaganfall zu erläutern und dem Kliniker Hinweise für die Interpretation und den Umgang mit pathologischen cTn-Werten zu geben.
Zentraler neuropathischer Schmerz nach Schlaganfall
Authors: Jungehülsing G. J. , Krause T. 
Published: March 2018

ZusammenfassungEs besteht eine Vielzahl sich häufig überlappender Schmerzentitäten nach Schlaganfall. Zentraler neuropathischer Schmerz nach Schlaganfall (CPSP) findet sich bei ca. 8% aller Patienten. Eine direkte Schädigung des spinothalamischen Traktes ist eine Voraussetzung für die Entstehung von CPSP. Patienten weisen neben Veränderungen der Schmerz- und Temperaturwahrnehmung bilaterale Atrophien der grauen Substanz auf sowie sensorische Defizite auf der initial klinisch nicht betroffenen Körperhälfte. Für die Diagnose sind neben der zeitlichen und örtlichen (somatotopen) Korrelation zum Schlaganfall der Nachweis negativer oder positiver sensorischer Symptome sowie der Ausschluss anderer Schmerzursachen erforderlich. Die Behandlung des CPSP ist schwierig und die Studienlage für die medikamentöse Therapie unbefriedigend. Mittel der ersten Wahl sind Antikonvulsiva oder Antidepressiva unter Berücksichtigung anderer Begleiterkrankungen und gegebenenfalls in Kombination.
Alzheimer-Demenz
Authors: Fink G. R. , Kukolja J. 
Published: March 2018

ZusammenfassungDemenzielle Erkrankungen spielen aufgrund des demografischen Wandels eine zunehmende Rolle in unserer Gesellschaft und somit auch im klinischen Alltag. Die Weiterentwicklung diagnostischer Methoden wie das Amyloid-PET und die Biomarkerbestimmung im Liquor hat eine Wende in der Klassifikation der Demenzen herbeigeführt. Es ist mittlerweile nicht nur möglich, die Alzheimer-Erkrankung als häufigste Ursache der Demenz schon in Frühstadien sicher zu erkennen. Auch einige klinisch atypische Demenzen zeigen die charakteristische Alzheimer-Pathologie und werden dementsprechend als Alzheimer-Varianten aufgefasst. Ein relevanter Anteil alzheimerähnlicher Demenzen beruht hingegen nicht auf einer alzheimerdefinierenden Amyloid-Pathologie.In diesem Übersichtsartikel werden die Folgen der modernen diagnostischen Methoden auf die Klassifikation der Demenzen, deren Prävention und Therapie diskutiert.