A novel allosteric pathway of thrombin inhibition: Exosite II mediated potent inhibition of thrombin by chemo-enzymatic, sulfated dehydropolymers of 4-hydroxycinnamic acids.

Thrombin and factor Xa, two important pro-coagulant proteinases, can be regulated through direct and indirect inhibition mechanisms. Recently, we designed sulfated dehydropolymers (DHPs) of 4-hydroxycinnamic acids that displayed interesting anticoagulant properties (Monien, B. H.

Segregation of platelet aggregatory and procoagulant microdomains in thrombus formation: regulation by transient integrin activation.

Objective: Platelets play a dual role in thrombosis by forming aggregates and stimulating coagulation. We investigated the commitment of platelets to these separate functions during collagen-induced thrombus formation in vitro and in vivo.

Methods And Results: High-resolution 2-photon fluorescence microscopy revealed that in thrombus formation under flow, fibrin(ogen)-binding platelets assembled into separate aggregates, whereas distinct patches of nonaggregated platelets exposed phosphatidylserine.

Exosites in the substrate specificity of blood coagulation reactions.

The specificity of blood coagulation proteinases for substrate, inhibitor, and effector recognition is mediated by exosites on the surfaces of the catalytic domains, physically separated from the catalytic site. Some thrombin ligands bind specifically to either exosite I or II, while others engage both exosites. The involvement of different, overlapping constellations of exosite residues enables binding of structurally diverse ligands.

Anatomical reconstruction for Reverse Hill-Sachs lesions after posterior locked shoulder dislocation fracture: a case series of six patients.

Introduction: Posterior locked shoulder dislocation fracture is a rare injury. Impression fractures of the humeral articular surface are common with this injury. Different methods exist to restore impression fractures.

Expression of allosteric linkage between the sodium ion binding site and exosite I of thrombin during prothrombin activation.

The specificity of thrombin for procoagulant and anticoagulant substrates is regulated allosterically by Na+. Ordered cleavage of prothrombin (ProT) at Arg320 by the prothrombinase complex generates proteolytically active, meizothrombin (MzT), followed by cleavage at Arg271 to produce thrombin and fragment 1.2.

Modulation of stretch reflex excitability during quiet human standing.

Stretch reflex excitability was measured during quiet standing by using a bilateral electro-hydraulic actuator to apply perturbations of angular position to the ankle. Subjects were instructed to stand quietly while pulse displacements were applied at random time intervals. Position, torque, gastrocnemius soleus EMG, tibialis anterior EMG, heel position, tibia angle, femur angle, and sacrum angle were measured.

Animal experiments with ultra-high molecular weight polyethylene (UHMW-PE) stabilised with alpha-tocopherol used for articulating surfaces in joint endoprostheses.

Numerous investigations proved the impressive suitability of alpha-tocopherol as a stabilizer for ultra-high molecular weight polyethylene (UHMW-PE) used for endoprostheses. Regarding the biocompatibility of this new biomaterial, in-vitro celltoxicity tests gave no hint for a cyto- or genotoxic activity. In this study, animal experiments are carried out to further ensure the biocompatibility of this biomaterial.

LipoCardium: endothelium-directed cyclopentenone prostaglandin-based liposome formulation that completely reverses atherosclerotic lesions.

Atherosclerosis is a multifactorial inflammatory disease of blood vessels which decimates one in every three people in industrialized world. Despite the important newest clinical approaches, currently available strategies (e.g.

Mammary gland secretory concretions contain non-collagenous bone matrix proteins.

Secretory concretions in mammary gland alveoli are commonly of microscopical size. However, some concretions reach clinically palpable dimensions and may occlude teat canals and obstruct milk flow. We studied secretory concretions in sheep, goat and cow mammary glands, using routine histological staining methods, conventional histochemistry and electron microscopy.

Influence of high tibial osteotomy on bone marrow edema in the knee.

To determine the influence of high tibial osteotomy on subchondral bone marrow edema in medial osteoarthritis of the varus knee, full leg-length radiographs and magnetic resonance imaging were performed in 20 patients (20 knees) before surgery, 1 year postoperatively, and at a mean of 7 years postoperatively. The extent of bone marrow edema in the medial compartment was quantified with magnetic resonance imaging in two planes using the formula for a prolate ellipsoid as follows: length x width x depth x pi/6. We used the Japanese Orthopaedic Association knee score for clinical evaluation.

Binding of the COOH-terminal lysine residue of streptokinase to plasmin(ogen) kringles enhances formation of the streptokinase.plasmin(ogen) catalytic complexes.

Streptokinase (SK) activates human fibrinolysis by inducing non-proteolytic activation of the serine proteinase zymogen, plasminogen (Pg), in the SK.Pg* catalytic complex. SK.

Comparative anatomical study of internal brooding in three anascan bryozoans (Cheilostomata) and its taxonomic and evolutionary implications.

The anatomical structure of internal sacs for embryonic incubation was studied using SEM and light microscopy in three cheilostome bryozoans-Nematoflustra flagellata (Waters,1904), Gontarella sp., and Biflustra perfragilis MacGillivray, 1881. In all these species the brood sac is located in the distal half of the maternal (egg-producing) autozooid, being a conspicuous invagination of the body wall.

Novel fluorescent prothrombin analogs as probes of staphylocoagulase-prothrombin interactions.

Staphylocoagulase (SC) is a potent nonproteolytic prothrombin (ProT) activator and the prototype of a newly established zymogen activator and adhesion protein family. The staphylocoagulase fragment containing residues 1-325 (SC-(1-325)) represents a new type of nonproteolytic activator with a unique fold consisting of two three-helix bundle domains. The N-terminal, domain 1 of SC (D1, residues 1-146) interacts with the 148 loop of thrombin and prethrombin 2 and the south rim of the catalytic site, whereas domain 2 of SC (D2, residues 147-325) occupies (pro)exosite I, the fibrinogen (Fbg) recognition exosite.

Fibrinogen substrate recognition by staphylocoagulase.(pro)thrombin complexes.

Thrombin generation and fibrinogen (Fbg) clotting are the ultimate proteolytic reactions in the blood coagulation pathway. Staphylocoagulase (SC), a protein secreted by the human pathogen Staphylococcus aureus, activates prothrombin (ProT) without proteolysis. The SC.

Structural basis for reduced staphylocoagulase-mediated bovine prothrombin activation.

Staphylocoagulase (SC) is a protein secreted by the human pathogen, Staphylococcus aureus, that activates human prothrombin (ProT) by inducing a conformational change. SC-bound ProT efficiently clots fibrinogen, thus bypassing the physiological blood coagulation pathway. The crystal structure of a fully active SC fragment, SC-(1-325), bound to human prethrombin 2 showed that the SC-(1-325) N terminus inserts into the Ile(16) pocket of prethrombin 2, thereby inducing expression of a functional catalytic site in the cognate zymogen without peptide bond cleavage.

Ratcheting of the substrate from the zymogen to proteinase conformations directs the sequential cleavage of prothrombin by prothrombinase.

Prothrombinase catalyzes thrombin formation by the ordered cleavage of two peptide bonds in prothrombin. Although these bonds are likely approximately 36 A apart, sequential cleavage of prothrombin at Arg-320 to produce meizothrombin, followed by its cleavage at Arg-271, are both accomplished by equivalent exosite interactions that tether each substrate to the enzyme and facilitate presentation of the scissile bond to the active site of the catalyst. We show that impairing the conformational transition from zymogen to active proteinase that accompanies the formation of meizothrombin has no effect on initial cleavage at Arg-320 but inhibits subsequent cleavage at Arg-271.

Diagnostic performance of cardiovascular magnetic resonance in patients with suspected acute myocarditis: comparison of different approaches.

Objectives: The aim of this research was to identify the diagnostic performance of gadolinium-enhanced and T2-weighted cardiovascular magnetic resonance (CMR) in suspected acute myocarditis.

Background: Acute myocarditis is difficult to diagnose; CMR provides various means to visualize myocardial inflammatory changes. A CMR approach with clear-cut diagnostic criteria would be desirable.

Stenotic mitral valve prosthesis with left atrial thrombus.

We report the CMR findings of a patient with stenotic biological mitral valve prosthesis that was complicated by thrombus formation in the left atrium. The case illustrates the ability of CMR to assess biological prosthetic valves and to provide a comprehensive diagnostic approach in this clinical scenario.

Exosite-mediated substrate recognition of factor IX by factor XIa. The factor XIa heavy chain is required for initial recognition of factor IX.

Studies of the mechanisms of blood coagulation zymogen activation demonstrate that exosites (sites on the activating complex distinct from the protease active site) play key roles in macromolecular substrate recognition. We investigated the importance of exosite interactions in recognition of factor IX by the protease factor XIa. Factor XIa cleavage of the tripeptide substrate S2366 was inhibited by the active site inhibitors p-aminobenzamidine (Ki 28 +/- 2 microM) and aprotinin (Ki 1.

Digital cushions in horses comprise coarse connective tissue, myxoid tissue, and cartilage but only little unilocular fat tissue.

Digital cushions were studied in horses with particular reference to vascularization, tissue constituents and matrix components. The cushions mainly resembled a network of coarse collagen bundles. The areas inbetween the bundles were replenished with loosely woven interstitial connective tissue, myxoid tissue, and fibrocartilage.

Safety and efficacy of the long-term adjuvant treatment of primary intermediate- to high-risk malignant melanoma (UICC/AJCC stage II and III) with a standardized fermented European mistletoe (Viscum album L.) extract. Results from a multicenter, comparative, epidemiological cohort study in Germany and Switzerland.

Background: Mistletoe therapy is the most frequently used complementary treatment in cancer patients in Germany and Switzerland. However, its safety and efficacy were controversially discussed, also in case of malignant melanoma (MM).

Objectives: The present study should evaluate the therapeutic safety and efficacy of a long-term therapy with a standardized fermented European mistletoe (Viscum album L.

[The problematic nature of ectopic corpora lutea].

For educational reasons, 50 bovine ovaries were collected and macroscopically examined. In one case a well developed corpus luteum was seen as a separeted organ that was connected to the ovary by a delicate bridge of connective tissue. This excepctional material was preserved by formalin fixation, photographed and microscopically examined.

Role of the streptokinase alpha-domain in the interactions of streptokinase with plasminogen and plasmin.

The role of the streptokinase (SK) alpha-domain in plasminogen (Pg) and plasmin (Pm) interactions was investigated in quantitative binding studies employing active site fluorescein-labeled [Glu]Pg, [Lys]Pg, and [Lys]Pm, and the SK truncation mutants, SK-(55-414), SK-(70-414), and SK-(152-414). Lysine binding site (LBS)-dependent and -independent binding were resolved from the effects of the lysine analog, 6-aminohexanoic acid. The mutants bound indistinguishably, consistent with unfolding of the alpha-domain on deletion of SK-(1-54).