bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Dense Granule Specific Membrane Proteins in Bovine Platelets that Are Absent in the Chediak-Higashi Syndrome
Authors: Meyers Kenneth , Seachord Carrie 
Published: July 2018

SummaryPlatelets from cattle with the Chediak-Higashi syndrome (CHS) have a platelet dense granule deficiency. One hypothesis for the platelet dense granule deficiency is that the granule is simply not formed in CHS megakaryocytes (MK). Alternative hypotheses include that the granule is assembled in CHS MK but a functional amino-nucleotide-cation storage complex cannot be formed or that the dense granule or its precursor fuses with other granules. This study was undertaken to determine if membrane proteins specific for platelet dense granules can be identified in membranes of other granules in CHS platelets. Platelets were disrupted; a mixed-granule fraction and alpha-granule enriched, mitochondrial-enriched, and dense granule-enriched subfractions were obtained. Membrane proteins in these intact granules were radiolabeled and the granule underwent hypotonic lysis. Membrane proteins were extracted from granule “ghosts”, separated, and then visualized by autoradiography. Three major proteins were identified in platelet dense granule membrane subfractions. Two of these proteins could be identified in membrane extracts from the mixed-granule fraction from normal platelets. They could neither be identified in extracts from the mixed granule fraction of CHS platelets nor in membranes from alpha granule-enriched and mitochondrial-enriched subfractions. The absence of dense granule membrane proteins in membranes of other organelles within CHS platelets suggests that fusion of dense granules or its precursor with other granules cannot account for the platelet dense granule deficiency in CHS platelets.
Formation and Persistence of Procoagulant and Fibrinolytic Activities in Circulation after Strenuous Physical Exercise
Authors: Hansen John-Bjarne , Wilsgård Line , Olsen Jan Ole , Østerud Bjarne 
Published: July 2018

SummarySeven healthy male volunteers were subjected to exercise of short (STR; 1.7 km), middle (MTR; 4.8 km) and long (LTR; 10.5 km) term runs at a speed close to maximal capacity. Blood samples were drawnbefore, immediately after exercise and at intervals over the next 10 h. FVTIIR: Ag (von Willebrand factor) rose 2.2–3.2 fold and persisted at higher levels than baseline during the observation time. A spontaneous drop in FVII (p <0.03) was found immediately after STR(13.5 ± 2.5%) and LTR (18.3 ± 2.4%), whereas only a minor decrease (7.5 ± 6.5%) occurred in MTR. The procoagulant activity of monocytesisolated from whole blood exposed to LPS showed a striking enhancement in STR and MTR. An immediate enhancement in fibrinolytic activity was found in all groups (p <0.03) assessed by increased plasma levels of t-PA and shortened whole blood clot lysis time (WBCLT). The transient shortening of WBCLT was succeeded by a tendency to prolongation of the lysis time. A 45-year old male differed markedly from the others by demonstrating an extreme and consistent prolongation of WBCLT. Thus, it hasbeen speculated that strenuous exercise possibly makes a subject more susceptible to a thrombotic event.
Identification of Platelet Antigens by Immunoprecipitation of Unlabelled Platelet Glycoproteins
Authors: Stenziger Werner , Kehrel Beate , van de Loo Jürgen 
Published: July 2018

SummaryA time-saving and sensitive method for the identification of antigens on unlabelled platelet glycoproteins (GP) based on immunoprecipitation has been developed. Platelet solubilisates
were incubated with antibodies to form GP-antibody complexes that were precipitated with Protein G Sepharose 4 Fast Flow (PGS). Pcs-bound material was eluted, separated by SDSPAGE under reducing conditions and visualized by silver staining. The method was designed as an alternative to radioimmunoprecipitation
for laboratories not equipped to work with radioactive substances. It is proposed as a complementary procedure for the characterization of platelet GP antigens by murine monoclonal antibodies and human alloantibodies.
Properties of Thrombolytic Agents in Vitro Using a Perfusion Circuit Attaining Shear Stress at Physiological Levels
Authors: Nishino N , Scully M F , Rampling M W , Kakkar V V 
Published: July 2018

SummaryA perfusion circuit was designed to investigate in vitro some of the factors which may influence the success of thrombolytic treatment in vivo. The rate of lysis of clotted plasma and different types of artificial thrombi (fibrin thrombi or whole blood thrombi) was measured in citrated plasma or whole blood under static conditions or under shear stress equivalent to the arterial or venous circulation. With both streptokinase (SK) and tissue-type plasminogen activator (t-PA) the rate of lysis of fibrin thrombi and whole blood thrombi was reduced significantly, when compared to the conventional plasma gel clot model (25-fold and 8fold, respectively). This occurred particularly with SK which showed a reduction (4-fold) in potency relative to t-PA under these conditions. Lysis of thrombi by both activators was observed to be faster in plasma than whole blood, and also faster with whole blood thrombi than fibrin thrombi. High shear stress, generally, caused a reduction in the rate of lysis of fibrin thrombi and an increase in the rate of lysis of whole blood thrombi compared to lysis rates under static conditions. Under all conditions of flow the lysis rate observed at 50 units t-PA per ml was much faster than that at 500 units per ml unlike the conventional plasma gel clot model.
The Platelet Extinction Coefficient Measured by Aggregometry Is Dependent on Platelet Composition rather than Size: Implications for Studies of Platelet Heterogeneity and Abnormalities
Authors: Frojmovic Mony M , Wong Truman 
Published: July 2018

SummaryExtinction (E) or light transmission measurements of platelet suspensions have been widely used to evaluate platelet structure and aggregation for platelet populations of varying mean platelet size (V). However, useful comparisons of platelet suspensions from donors having abnormally-sized platelets with those from healthy controls require a knowledge of the dependence of E on V. We have analyzed the extinction per platelet (e) as a function of the geometric scattering cross-section of equivalent spheres, V2/3, related to the apparent mean platelet optical efficiency, k. Such an analysis using data previously reported by Holme et al., for healthy controls and a variety of platelet-associated disorders showed e/V2/3 or k to be constant over an eight-fold variation in V. The outstanding exception was platelet suspensions from myeloproliferative disorder patients (MPD) which showed ˜25% reduction in k values. When we analyzed e/V2/3 data for differentsized platelet subpopulations which were isolated by elutriation from healthy donors, we found that k doubled with a doubling in V from small to large platelets. It appears that the use of aggregometry devices with wide light acceptance angles yields k values for platelets which are insensitive to variations in V, but rather are sensitive to the expected variations in refractive index associated with distinct platelet internal composition and organization expected for different-sized normal subpopulations and “diseased” platelets as found in MPD. We relate these observations to photometric studies of platelet heterogeneity and of aggregation of platelets with different V and k values.
B Cell Dysfunction in Haemophilia in the Absence and Presence of HIV-1 Infection
Authors: Madhok R , Gracie J A , Forbes C D , Lowe G D O 
Published: July 2018

Summary56 haemophiliacs selected on the basis of HIV-1 antibody status, liver disease grade and mean annual dose of clotting factor concentrate used were studied. Spontaneous and stimulated IgG and IgM production in vitro were measured. HIV-1 infection was associated with increased spontaneous immunoglobulin production and an impaired response to pokeweed mitogen and Staph Aureus protein A. Implying a shift in the proportions of partially and fully activated B cells.In the absence of HIV-L infection there was a shift to a greater proportion of partially activated B cells in patients with severe liver disease. The remainder had in vitro immunoglobulin production comparable to controls. B cell abnormalities occur early in the course of HIV-1 infection. Liver disease and not clotting factor concentrate treatment cause B cell abnormalities in the absence of HIV-1 infection in haemophilia.
Electroimmunoassay of Plasma Subunits-A and -S in a Case of Congenital Fibrin Stabilizing Factor Deficiency
Authors: Barbui T , Cartei G , Chisesi T , Dini E 
Published: July 2018

SummaryAntigenic material related to the fibrin stabilizing factor (Factor XIII-FSF) has been found in all the examined patients with congenital deficiency, albeit in reduced amount.Recently, Bohn et al. (1973) and Israels et al. (1973) showed that plasma Factor- XIII is composed by two subunits, A (or a) and S (or b); the former active protein, the latter probably FSF-binding protein.Using specific anti-S and anti-A antisera the Authors found, in a case of congenital deficiency of factor XIII, absence of subunit A. Subunit S presented abnormal behaviour as demonstrated by means of quantitative immunoelectrophoresis according to Laurell.
Hypercoagulability State in Patients with Chronic Obstructive Pulmonary Disease
Authors: Alessandri Cesare , Basili Stefania , Violi Francesco , Ferroni Patrizia , Gazzaniga Pier Paolo , Cordova Corrado ,   C.O.B.H. Group
Published: July 2018

SummarySince there is some clinical evidence that the clinical course of patients with chronic obstructive pulmonary disease (COPD) may be complicated by thrombosis in the pulmonary vessels, we studied whether a hypercoagulability state (HS) does occur in COPD. Plasma levels of prothrombin F1+2 fragment, a marker of thrombin generation, D-dimer, a marker of in vivo thrombin and plasmin activation, and fibrinogen were measured in 37 COPD patients and in 30 controls matched for sex and age. COPD patients had significantly higher values of F1+2 (p = 0.0001) and fibrinogen (p = 0.0005) than healthy subjects. The difference persisted after excluding smoking patients. F1+2 was not correlated with PaO2 (r = 0.02, p >0.05) and PaCO2 (p = 0.12, p >0.05). In six patients with stable COPD and F1+2 greater than 1.65 nM (mean + 2SD of controls) subcutaneous calcium-heparin therapy (5000 IU t.i.d. for 15 days) significantly reduced F1+2 (p = 0.03) and PaCO2 (p = 0.01). This study shows that COPD patients have an ongoing prothrombotic state which could potentially account for thrombosis occurring in pulmonary vessels. The effect of calcium-heparin treatment on clotting system activation and blood gas may suggest this treatment as potential candidate for prospective study in COPD patients.
Effects of DX-9065a, an Orally Active, Newly Synthesized and Specific Inhibitor of Factor Xa, against Experimental Disseminated Intravascular Coagulation in Rats
Authors: Yamazaki Masahide , Asakura Hidesaku , Aoshima Keiji , Saito Masanori , Jokaji Hiroshi , Uotani Chika , Kumabashiri Ichir , Morishita Eriko , Ikeda Takayuki , Matsuda Tamotsu 
Published: July 2018

SummaryWe investigated the protective effects of DX-9065a, an orally active, newly synthesized and specific inhibitor of factor Xa, against two kinds of experimental disseminated intravascular coagulation (DIC) in rats. Endotoxin-induced experimental DIC was induced by a 4-h sustained infusion of endotoxin at a dose of 100 mg/kg. Thromboplastin-induced experimental DIC was induced by a bolus injection of thromboplastin at a dose of 150 mg/kg. The rats were orally administered DX-9065a at 10, 30 or 100 mg/kg 30 min before endotoxin or thromboplastin injection.In both DIC models, DX-9065a showed a protective effect against DIC, at all doses and in all parameters, including fibrin/fibrinogen degradation products (FDP), fibrinogen level, prothrombin time, activated partial thromboplastin time, platelet count and the number of renal glomeruli with fibrin thrombi.When DX-9065a was orally administrated at 100 mg/kg without endotoxin or thromboplastin, no significant changes were seen in hemostatic parameters except PT and APTT, and no fibrin thrombi or abnormal bleeding were seen in renal specimens.These findings suggest that the new oral anti-Xa drug, DX-9065a, has an effect in reducing the severity of DIC. However, further dose-finding and safety studies of this drug have still to be assessed.
Elevated Thrombomodulin Plasma Levels as a Result of Endothelial Involvement in Plasmodium falciparum Malaria
Authors: Hemmer Christoph J , Bierhaus A , Riedesel J v , Gabat S , Liliensiek B , Pitronik P , Lin J , Grauer A , Amiral J , Ziegler R , Schieffer S , Kern P , Seitz R , Egbring R , Dietrich M , Nawroth P P 
Published: July 2018

SummaryWe used thrombomodulin (TM) to assess the participation of the vascular endothelium in human Plasmodium falciparum (P. F.) malaria. Before therapy TM plasma levels were elevated in P. F. malaria and fell to normal values during therapy. Parasitemia, TNFα, elastase and TAT levels correlated directly with TM. Elevated TM levels can not be explained by increased synthesis, since incubating HUVEC with pretherapy serum of patients with P. F. malaria, but not reconvalescence serum, suppressed TM transcription. This was partially prevented by adding a TNFα neutralizing antibody to patient serum before incubation with HUVEC. However, TNFα does not release TM from cultured HUVEC in vitro. Coincubation of HUVEC with pretherapy serum together with neutrophils resulted in endothelial cell destruction, which could be partly prevented by a TNFα neutralizing antibody. Hence the increase of TM during P. F. malaria might reflect the concerted action of cytokines and neutrophils on HUVEC.
Low-Dose Heparin Or Aspirin-Dipyridimole In Prevention Of Postoperative Deep Venous Thrombosis
Authors: Kennedy J H 
Published: July 2018

Venous thrombosis and pulmonary embolism remain a serious threat to postoperative patients. Kakker et al have reported favorable effects of low-dose heparin in a prospective study in 4,121 patients in 23 hospitals.In a prospective randomized study, between May 1978 and August 1980, 375 patients were collated into 7 groups 146 were excluded because of a contraindication to Heparin or lack of general anesthesia; those over 45 vho received a general anesthesia were given either 2,500 u Heparin with premedication and daily until discharge (Group V) or 1 Gram Aspirin-100 mgm Dipyridimole on the same schedule (Group VI); the remainder served as controls.The results supported protective treatment of over 45 who receive a general anaesthetic and surgery; in unteated patients there were 6 nonfatal thrombotic episodes in 1397 patient-days at risk, but none in either treatment group., together totalling 756 patient- days at risk for the Heparin group and 238 patient-days at risk for the Aspirin-Dipyridimole group.
Systematic Use Of Heparin In The Continuous Flow Centrifuge (CFC) For Blood Cell Separation
Authors: Morales M R , Pizzuto J , Reyna Ma , Castro G 
Published: July 2018

To date the use of heparin in the CFC has not been adequately controlled, thus exposing donors and patients to coagulation disorders. For this reason, we decided to evaluate the use of heparin by continuous infusion in dosages that would be modified by a simultaneous assessment of its anticoagulant effect, as shown by the thrombin time dilution test (TTDT).The study was performed during 46 leukopher- esis and 27 plasmapheresis. It was ascertained that heparin is an efficient anticoagulant in the CFC, using the TTDT as an effective and reliable method for its control. The initial dose in leukopheresis is one unit per milliliter of blood during the first hour, then half the dose during the next hour, and then a quarter of the dose until the procedure is completed. A TTDT performed every hour will indicate whether the amount of heparin used should be modified. For plasmapheresis, it is neccesary to establish a specific dose in each instance, using the TTDT as described. In most of the subjects, the anticoagulant level was exactly right. There was no case of bleeding or extracorporeal coagulation of the blood.On the basis of these findings, we recommend the use of heparin in the CFC, applying the results of the TTDT as a guide for its dosage level.
Heparin-Induced Thrombocytopenia
Authors: Caprini J A , Sholder A J , Vagher J P , Mitchell J 
Published: July 2018

Review of 6,000 patient records from our laboratory showed 609 individuals who received continuous intravenous infusion heparin therapy for thromboembolic disease. 40/609 (6.5%) of these patients were found to have a platelet count of less than 150,000 cell/mm . Of this group, 34/40 (85%) exhibited thrombocytopenia prior to heparin therapy that was attributable to consumptive coagulopathy in 21/40 (52.5%), sepsis or malignancy in 11/40 (27.5%), and cimetidine or sulfisoxazole in 2/40 (5%). Heparin therapy had no adverse effect on the platelet count in these individuals, and the count returned to normal in surviving individuals if the underlying cause was successfully treated or the offending drug removed.Only 6/40 (15%) of the patients developed low platelet counts during the course of heparin therapy; this represents 6/609 (0.98%) of the population receiving heparin. The etiology of thrombocytopenia in 5/6 (83%) of the cases was traced to metastatic cancer (3), burn wound sepsis (1), and septic shock (1). Only 1/609 (0.16%) of these patients developed low platelet count that could be attributed to heparin. Thus, the incidence of heparin-induced thrombocytopenia is extremely rare in our hospital population.
Urokinase Therapy Of Deep Vein Thrombosis Of The Lower Limb
Authors: Zimmermann R , Harenberg J , Mörl H , Rieben F W , Götz R 
Published: July 2018

The effect of fibrinolytic therapy with urokinase in deep vein thrombosis is not clearly establ- shed so far. Previous communications demonstrated success rates of only 26-33 % of complete and partial recanalization by application of 1 (-2) Mio IU urokinase/24 hours.In the present study in 80 patients with deep vein thrombosis of the lower limb,urokinase therapy was therefore performed at higher dosages in combination with heparin. After a loading dose of 250,000 IU,urokinase was given at a rate of 1300 IU/kg/h (51 cases) or 2000 IU/kg/h (29 cases). Concomitantly 15-20 U heparin/kg/h were administered. The fibrinolytic therapy was mainly controlled by determination of the thrombin clotting time,aPTT and fibrinogen. The further therapy was adjusted to attain a prolongation of the thrombin clotting time 2-4 times the normal value, the aPTT to 60-100 sec and a reduction of the fibrinogen concentration to 50-100 mg% (Clauss method).The thrombolytic effect was established by repeated phlebography. In recently developed venous thrombosis (<10 days) a complete recanalization could be seen in 50% and a partial success in an additional 26% (dosage regimen 2000 IU/kg/h). Under treatment with a maintenance dosage of 1300 IU/kg/h a complete success rate of 31 and partial successes in 30% of the cases could be observed. Only few serious side reactions were observed.Our therapeutic results demonstrate that under therapy with higher dosages of urokinase a more pronounced rate of recanalization can be observed. The higher dosage regimen presented here seems to be an adequate schedule in therapy of deep vein thrombosis without an increasing of bleeding.
Urokinase Treatment Of Phlegmasia Cerulea Dolens
Authors: Zimmermann R , Mörl H , Harenberg J , Brockhaus W , Walter E , Diehm C 
Published: July 2018

Phlegmasia cerulea dolens is the most severe form of venous thrombotic disease and continues to have a mortality rate of about 10 %. Most of the authors propagate the rapid thrombectomy as an only effective therapeutic regimen. However,the success of the surgical procedure is questionable when older or recurrent thromboses preceded or when a critical general condition does not allow surgery.In 3 patients (71,76 and 59 years old) with phlegmasia cerulea dolens surgical treatment had been refused. In view of the great age of the first 2 patients fibrinolytic therapy with streptokinase was disaproved. In the third case treatment with streptokinase was performed previously. In all patients thrombolysis with urokinase 2-5 Mio IU/24 h in combination with heparin (25.000-40.000 U/ 24 h) was started. An impressive improvement of the local findings with almost complete normalization of the lower leg could be observed. In the first and third case with already developed necrosis of the forefoot area, a marked regression of the necrosis was attained. A boundary zone amputation became necessary in the first patient while in the third case a spontaneous demarcation of the necrotic area was observed. In the second patient restitutio ad integrum could be attained. The reported cases suggest that fibrinolytic therapy with urokinase constitutes an alternative to venous thrombectomy and thrombolysis with streptokinase even in the most severe form of phlebothrombosis. Treatment with urokinase should be regarded, if contraindications for thrombectomy or thrombolysis with streptokinase are present.
Fibrinolytic Activity In Metastatic Tumors And Tumor Thrombi
Authors: Yuen P , Rwaan H C 
Published: July 2018

In an attempt to clarify the conflicting reports of plasminogen activator and lack of fibrinolytic activity in tumor tissues, the fibrinolytic activity of 62 metastatic tumors and 5 tumor thrombi from autopsy and biopsy specimens was studied by the fibrin slide technique. Metastatic tumors involved lymph nodes, liver, lung, brain and ovary. Tumor thrombi were mainly comprised of hepatoma thrombi in branches of either hepatic or portal veins.The lack of fibrinolytic activity was graded according to the focal lysis time of vascular tissues within the tumor and in the case of lymphnodes, lymphatic channels. A complete lack of fibrinolytic activity was observed in metastatic tumors and tumor thrombi, a finding similar to that observed in primary tumors.Immunofluorescent studies on the tumors revealed the presence of antigenic material identical to fibrin, platelets and alpha2 plasmin inhibitor.