bluuebunny/crossref_metadata_2025_split huggingface dataset:
NOVEL TECHIQUES FOR QUANTIFICATION OF RBC-SHAPE (RS) AND SHEAR INDUCED RBC ELONGATION (SIRE): APPLICATION FOR ANALYSIS OF DRUG INDUCED ALTERATIONS
Authors: Artmann G , Grebe R , Wolff H , Degenhardt R , Schmid-SchÖnbein H 
Published: June 2019

In the past, red cell resting shape could only be assessed by subjective scaling, red cell deformability by a variety of rheological tests that are extremelydifficult to standardize and which all subject the RBC to high deforming forces. None of the latter have been accepted as reference in haematology, haemorheologyor pharmacology. A recent development from our group now allows objective, numerical analysis of red cell membrane curvature (i.e. the echinocytic or stomatocytic deviation from the discocytic resting shape) by a tangent count procedure in optical sections through freely suspended, randomly oriented RBC: (Grebe et al. Biorheology 22(6), 1985). Also, the deformation of point attached erythrocytes under the influence of extremely low shear stresses (0.05 Pa to 0.5 Pa, ARTOANN:Clin. Hemorheology 6, 1986), which are at least two orders of magnitude lower thanthat in any routinely available filtration method allows for the first time to model in vitro the extreme low flow states that occur in severe forms of haemodynamic insufficiency. These two methods in combination are ideally suited for routine tests of drug effects on normal human RBC: the drug action on RS can be monitored continuously during the action of drugs in the suspending medium; likewise, RISA can be recorded automatically on one population of adherent RBC while altering the composition and the drug concentration in the superfusate. The two methods were applied in combination to test rheological and membranological effects of two distinctly different compounds, namely Bencyclan (Bencylan-Hydrogen-Fumarate) and Vinpocitin (Aethyl vincamin) in normal cells and in cells after exposure to "stress conditions", i.e. hyperosmolarity and lactacidosis. Both olrugs given to n o r m a 1 RBC produce stomatocytosis in a done dependent fashion (1-100 uMolar). At shear stresses above o.6 Pa, the RISA is identical to controls, but is oxmsiderably less pronounced at lower shear stresses (T < 0.2 Pa). Thus, drugs of completely olifferent pharmacological action produce clear cut rheological effects on RBC in the micrcmolar concentration range; the combination of methods employed opens new possibilities for the systematic development of haemorheologically active drugs.Supported by DFG:Grant Gr 902/1-1
SYSTEMIC FIBRINOLYSIS AND PLASMA VISCOSITY REDUCTION: A SECOND BENEFIT
Authors: Moriarty A J , Hughes R , Nelson S D , Balnave K 
Published: June 2019

The aim of this study on a small cohort of patients (N = 30) with acute myocardial infarction (AMI) receiving systemic streptokinase (STK) thrombolytic therapy was to measure the decrease in plasma viscosity concomitant with fibrinogen depletion.Serial measurements of plasma viscosity, plasma fibrinogen and haematocrit were undertaken in treatment and control groups at times t = 0, 1 hour, 6 hours, 12 hours, 24 hours and daily thereafter over a period of six days. Viscosity was measured at 25°C using a Wells-Brookfield cone/plate digital viscometer, and fibrinogen determination was by the method of Clauss.Results indicated a mean percentage drop in plasma viscosity of −17% in the STK-treated group with a maximum drop in any one patient in excess of −30%. This contrasted with a mean viscosity rise of almost +20% in the control group with a maximum rise in any one patient of almost +44%, parallelling the rise in plasma fibrinogen as an acute phase reactant.Correlation studies between viscosity and plasma fibrinogen were strongly positive with mean r-values of 0.74 and 0.66 respectively. Interestingly, mean plasma viscosity in the STK-treated group was still reduced by −5% at 6 days post-therapy.The conclusions drawn from these data are that the benefit of systemic STK treatment in AMI may in part be due to reduced myocardial workload and oxygen consumption at a critical time through afterload reduction, and improved collateral circulation and microcirculation consequent on the reduced plasma viscosity. Clearly there may be implications for newer tissue-specific agents which do not have a substantial systemic effect.
THE PREVELANCE OF ANTIPHOSPHOLIPID ANTIBODIES, BY ELISA TECHNIQUE, IN PATIENTS WITH THE LUPUS ANTICOAGULANT
Authors: Brien W , Denome G , O’Keefe B 
Published: June 2019

Patients with the Lupus Anticoagulant and/or anticardiolipin antibodies have been reported to be at increased risk of thrombosis and miscarriages. It has been proposed that the lupus anticoagulant is an antiphospholipid antibody.We evaluated 16 patients with the lupus anticoagulant for the presence of antiphospholipid antibodies. The lupus anticoagulant was documented by the presence of an abnormal APTT, abnormal mixing studies, positive tissue thromboplastin inhibition test and positive platelet neutralization test.Plasma from each patient was assessed for the presence of anticardiolipin, antiphosphatidylserine and antiphosphatidyl-glycerol antibodies by ELISAtechniques. As a control, a neutral phospholipid phosphatidylethanolamine was used. A positive result was established when a delta value of lipid minus control was greater than 3SD compared to a normal population (20 pt.).Using three different patient dilutions, positive results were obtained in 10/16 pt. for anticardiolipin, 11/16 pt. for antiphosphatidylserine and 5/16 pt. for antiphosphatidyl-glycerol antibodies. Three patients were negative for all lipids. If a neutral phospholipid was not used and a delta volume not obtained, 15/16 patients would have had positive results.Our results suggest 1) Not all patients with the Lupus Anticoagulant have antiphosphilipid antibodies by ELISA technique. In evaluating patients with thrombosis and/or miscarriages, both tests should be performed.2) Anticardiolipin antibodies are not present in all patients and with a panel of other negatively charged phospholipids more positive results are obtained. 3) A neutral lipid should be used as a control for non-specific binding of antibody and delta values obtained to see if the results obtained is truly against the negatively charged lipid.
THE CLINICAL SPECTRUM OF PROTEIN C DEFICIENCY IN A LARGE NEW ENGLAND KINDRED
Authors: Bovill E , Bauer K A , Callas P , West B , Dickerman J D 
Published: June 2019

A family with a high incidence of venous thromboembolism over six generations has been investigated. Medical histories have been obtained on 136 of the 368 members of the kindred which allowed assignment of individuals into positive, equivocal, or negative categories with respect to their thrombotic manifestations. Protein C levels were determined by antigenic assay. Patients with protein C levels less than 66% of normal (mean, minus 2 SD) were classified as having protein C deficiency.The mean age of onset of thrombotic manifestations in the 10 protein C deficient patients with a positive history was 33.8 ± 16.4 years while the mean age of the deficient group with a negative history was 22.0 ± 10.9 years. We conclude that there exists a striking association between thromboembolic disease and protein C deficiency within this large New England kindred.
Clinical Relevance of Blood Glucose Concentration and Hyperglycemia Management in Neurocritical Care Patients
Authors: Bilotta Federico , Qeva Ega , Prete Anna , Pugliese Francesco 
Published: June 2019

AbstractIn patients admitted to a neurocritical care (NCC) unit, management of blood glucose concentration (BGC) is a challenging clinical task. Several studies have shown that episodes of hypo- and hyperglycemia and high BGC variability are associated with poor short- and long-term outcomes. Optimal BGC target-range and BGC management in NCC patients have dramatically evolved in the past decades and new insulin infusion and adequate nutrition protocols are now available. The aim of this narrative review is to report the state-of-the-art on clinical relevance on BGC and hyperglycemia management in NCC patients.
Membrane Transports of Platelets Present in Plasma During Clotting and Lysis
Authors: Zuzel M. , Irving W. , Born G. V. R. 
Published: June 2019

During blood clotting and subsequent fibrinolysis a major proportion of platelets survive as single entities. Platelets exposed to thrombin in vivo or in vitro survive normally in the circulation (Reimers et al., 1973, Brit. J. Haemat., 25, 675), in spite of having undergone a release reaction.Our experiments were to find out whether clotting and lysis of plasma impair transport functions of platelet membranes. Human citrated platelet -rich plasma was incubated at 37° with thrombin plus fibrinolytic activator. Rapid clotting was followed by complete fibrinolysis within 3 min. By then about 60% of radioactive 5-hydroxytryptamine previously taken up by the platelets was released; this was accompanied by the loss of about 40% of platelet potassium which was subsequently re-accumulated. The initial velocities of uptakes of 5-hydroxytryptamine and adenosine were almost identical in platelets before and after clotting and lysis. Therefore, at least three energy-requiring transport processes in the platelet membrane were unaffected by the chemical events associated with clotting and lysis of platelet-rich plasma.
A High Titre Circulating Inhibitor of Human Factor V: Clinical, Biochemical and Immunological Features and its Treatment by Plasmapheresis
Authors: Grace G. S. , Wolf P. 
Published: June 2019

A 44 year old male with a two month history of epistaxis and haematuria was admitted because of melaena. He had not received antibiotics or blood transfusions. Haemostatic studies showed a complete absence of Factor V activity and this was not corrected by the addition of an equal part of normal plasma. Incubation studies showed that the inhibitor was specific for human Factor V. Factor VIII and IX activities were low by one stage assay methods but were normal after the addition of bovine Factor V.The titre of the antibody was very high; a 900 fold dilution causing a 50% reduction in the Factor V level of an equal volume of normal plasma on incubation at 37° C for 30 mins. The inhibitor appeared in the second protein peak on Sephadex G200 fractionation and was neutralized by antihuman IgG antiserum. Kinetic studies showed the inhibition to be first order with respect to Factor V and inhibitor.The patient was treated with plasmapheresis on a IBM Celltrifuge. Four litres of plasma were removed on each of four occasions over a period of 14 days. The antibody titre dropped from 900 to about 100. Despite the addition of immunosuppresive therapy the antibody has persisted at a titre of about 200 and has now been present over 5 months. No anamnestic response occurred following multiple transfusions.
Immunochemical Studies on the NH2-Terminal “Disulfide Knot” and Related Structures
Authors: Kudryk B. , Blomback B. 
Published: June 2019

A radioimmunoassay for the NH2-terminal portion of human fibrinogen (N-DSK) was recently used to measure cross-reactivity between several related fragments (Eur. J. Biochem. 46: 141–147, 1974). The results obtained showed that “cold” N-DSK and the NH2-terminal portion of plasmic Fragment E (“E-knot”) were strong competitors while Fragment E itself was a poor competitor in the system 125I-labeled N-DSK/anti-N-DSK. In this paper we report results from further experiments designed to study the basis for the observed immunological difference between Fragment E and “E-knot”. Using the N-DSK radioimmunoassay system we have now shown that formic acid denaturation alone cannot account for this difference. Additionally, intact mixtures of CNBr-treated Fragment E competed to the same degree as “E-knot”. The latter finding would suggest that there appears to be no interaction of the split COOH-terminal peptides (from Fragment E) with “E-knot” resulting in the “masking” of epitopes. However, at this point we cannot be certain that such “masking” of epitopes by these peptides does in fact occur in intact Fragment E.In a related study we have also tested the cross-reactivity of a disulfide core fragment obtained from N-DSK by trypsin digestion. This fragment (DS-4) has an approximate molecular weight of 8,000 and has 4 disulfide bridges. The latter does not react on immunodiffusion using antisera to N-DSK. However, in the N-DSK radioimmunoassay system DS-4 showed very strong competition. Approximately 73% inhibition was observed at the 10 nmol level. The significance of these results with respect to the location of highly antigenic regions of N-DSK will be discussed.(Supported by N.I.H. grant HL 09011–11.)
Factors Influencing the Binding of Radiolabelled Collagen to Blood Platelets
Authors: Maclntyre D. E. , Gordon J. L. 
Published: June 2019

The binding of radiolabelle collagen to blood platelets has been investigated using a modification of the Ficoll density gradient centrifugation technique (Gordon and Dingle, 1974). The binding of 125I labelled neutral salt soluble rat skin collagen to rat platelets is maximal within 10 sec, increases with temperature (4°-37°), and with increasing pH (7.0–8.0). The extent of binding is similar in platelet-rich plasma anticoagulated with citrate (0.31% w/v final concentration in blood) heparin (5 IU/ml) or EDTA (0.1% w/v), and in washed platelet suspensions. The ability of collagen to bind to platelets is abolished by prior heating to 56° for 30 min, or by collagenase digestion (20 μg/ml, 30 min at 36° C). A range of known inhibitors of collagen-induced platelet aggregation were tested as potential inhibitors of binding. Aspirin (1.1 mM), PGEl5 (3 μM), glucosamine (1 mM) and Deoxyglucose (15 mM) in combination with Antimycin A (5 μg/ml) did not reduce the binding of collagen to platelets. Glutaraldehyde fixation of platelets (0.01%, 5 min at 20°) markedly reduced the extent of collagen binding, but binding to formaldehyde fixed platelets (5%, 30 min at 20°) was similar to controls.This study indicates that collagen tertiary and quarternary structure are necessary not only for platelet aggregating activity, but also for the initial binding of collagen to platelets. Binding is independent of platelet metabolic activity and is not readily susceptible to pharmacological inhibition.Gordon, J. L. and Dingle, J. T. (1974), J. Cell sci. 16; 157.
Antibiotics, Platelet Aggregation and Electrophoretic Mobility
Authors: Houbouyan L. L. , Stoltz J. F. , Goguel A. F. 
Published: June 2019

The in vitro influence of twelve antibiotics (representing the principal classes: β-lactam group, aminoglycosides, polypeptidic antibiotics, antimitotics, . . .) on the ADP-induced Platelet Aggregation, the Screen Filtration Pressure test and the liquid phase Electrophoretic Mobility (E. M.) has been studied. According to the results formerly obtained on the interference Penicillin G-platelets, the authors have mainly investigated the β-lactam group (Penicillin G, Ampicillin, Carbenicillin, Cefalotin, Metampicillin, Methicillin, Oxacillin, . . .). This group seems particularly interesting as an antiaggregating effect has been found out for most of them; a parallel decrease of the E. M. has been generally observed.In attempts to elucidate the mechanism of physiochemical interaction with the membrane, the competitive effect of phospholipases and Penicillin G has been studied. The results seem to point out an interference of this antibiotic with the membrane phospholipids; this could be in accordance with the rheological data of Padefield and Kellaway. The interference with some other membrane groups has also been considered (carboxyl, phosphates . . .).An in vivo study has also been realized on patients massively perfused with some of these antibiotics (especially Penicillin G, Carbenicillin . . .).(This work was supported by Grant of the DRME (Biological Section).)
Purification and Immunological Studies of Factors XI and XI a
Authors: Connellan J. M. , Castaldi P. A. 
Published: June 2019

The inert form of factor XI has been purified from the supernatant of cryoprecipitated human plasma, and activated factor XI was prepared from the eluate of a celite extraction of human plasma. The purification steps involved were chromatography on both sepharose-heparin and hydroxylapatite columns, followed by preparative electrophoresis using 3.75% polyacrylamide in 8 M urea.Antibodies were raised in rabbits by injecting 50 μg quantities of the antigen in multiple subcutaneous sites using Freuds adjuvant. Neutralizing antibodies were detected after the third injection and the nature of the antibody was studied by immunodiffusion and cross-over electrophoresis.The antisera to factor XI a were monospecific and showed a biphasic precipitin line when human plasma was run in the first dimension. The antisera produced to factor XI contained an additional precipitin line which could be removed by absorption with plasma, which was depleted of factor XI by celite. Such antisera produced a monophasic precipitation reaction. These results suggest the possibility of distinguishing the inert and activated states of factor XI applicable to the investigation of thrombotic states.
The Change of Fibrin Split Products and Plasmin-Inhibitor in the Newborn Infant
Authors: Suzuki Shigenori 
Published: June 2019

It is very important for an newborn to keep a certain balance of its bloodcoagulation and fibrinolytic system in order to maintain extrauterine life.We have tried a follow up of coagulation abnormalities, fibrin split products and plasmininhibitors in severe asphyxia and respiratory distress syndrome. An other factor which is very dangerous for the fetus is acidosis.The following results were obtained from 102 newborns:1. A great number of FDP positive cases occurs in newborn who died from IRDS (80 μg/ml— 160μg/ml).2. The plasminogen levels of cases who died from IRDS and severe asphyxia are lower than that of normal newborn infants.3. α1-antitrypsin and antithrombin levels are relatively lower in the newborn period while the value of α1-macroglobulin maintains a normal level.4. Correlation was seen between the coagulation abnormalities and acid base status (below actual pH 7.1).The results shows the possibility that DIC is of great importants to RDS and FDP and are associated with hemorrhage and thrombosis.
Platelet Secretion Induced by Calcium Ionophores: Effect of Anti-Inflammatory Drugs
Authors: Mürer E. H. , Davenport K. , Day H. J. 
Published: June 2019

Washed human platelets prelabeled with 3 H-serotonin and 14 C-adenine were incubated at 37° C with ionophores A23187 and X537A. 0.1 μM A23187 released the serotonin store of preincubated platelets after 1 min at 37° C, but was less effective when added in the cold. An increase in incubation time at 37° C did not result in increased release. Platelets preincubated with indomethacin showed reduction of up to 85% in released serotonin, while the metabolic parameters 14 C-ATP and 14 C-IMP were not significantly altered. The platelets from some donors did not show reduced release after treatment with indomethacin. This may indicate a variation in sensitivity to the release inducer similar to that described for Sr++-induced release (Biochim. Biophys. Acta 53-59, 362, 1974), or to the effect of indomethacin. 1 μM X537A caused a time-dependent serotonin release which increased from 2% at 1 min to 58% at 10 min incubation at 37° C. There was little change in 14 C-ATP following release and none in intra- or extracellular 14 C-IMP. 10 μM X537A caused release of 75-80% of the platelet serotonin after 1 min incubation. Longer incubation resulted in 14 C-IMP accumulation and leakage of 14 C-IMP to the surrounding medium. The results do not support the view that X537A and A23187 cause release from platelets by different mechanisms.(Supported by grant HL 14217 from NHLI. A23187 was a gift from Dr. R. L. Hamill, Eli Lilly and Co., Indianapolis, Ind., and X537A from Drs. Zane Gaut and W. E. Scott, Hoffmann-LaRoche, Inc., Nutley, N. J.)
Complete Primary Structure of Prothrombin. Partial Primary Structures oí Plasminogen and Hirudin
Authors: Magnusson S. , Sottrup-Jensen L. , Glaeys H. , Zajdel M. , Petersen T. E. 
Published: June 2019

The complete amino acid sequence (582 residues), positions of the twelve disulfide bridges and three carbohydrate substituents, position and identity of the ten vitamin Independent γ-carboxyglutamic acid (Gla) residues has been determined. A synthetic substrate specific for Factor Xa has been developed on the basis of the prothrombin structure. The primary structure of hirudin has been nearly completed and suggests a mechanism for its thrombin specificity.The pro-part of prothrombin contains two 83 residue regions with identical disulfide-bridge pattern and 31 sequence identities. These “kringle” structures show sequence similarities with the pancreatic secretory trypsin inhibitor and hirudin. A chymotryptic digest of CM-plasminogen was investigated to find the heavy chain-light chain overlap region. This was isolated and sequenced (28 from h.c., 10 from l.c.) to study the specificity of plasminogen activators. From the same digest sequence evidence has been obtained which indicates that the heavy chain part of plasmin consists mainly of four kringle structures like the two in prothrombin, suggesting a common general structure and evolutionary origin of these two large zymogen structures.
A New Case of Dysfibrinogenemia, Fibrinogen Marburg
Authors: Fuchs G. , Egbring R. , Havemann K. 
Published: June 2019

A new case of congenital dysfibrinogenemia has been discovered in a 20 years old female, who suffered severe postpartal hemorrhage after delivery of her first child, followed by repeated episodes of thrombosis. Coagulation studies revealed prolongation of thrombin time. Reptilase time and Arvin time was markly prolonged. Very low fibrinogen levels were obtained by techniques which depend on the rate of fibrin formation following addition of thrombin, while heating and immunological procedures gave normal values of fibrinogen.The patient’s fibrinogen had an inhibitory effect on the fibrin formation in normal plasma. Factor XIII activity was found to be normal using an isotopic method, whereas clot lysis time is shortened. The presence of an inhibitor and increased fibrinolysis were excluded. The coagulation studies indicate that delayed fibrin formation is due to a disturbance of fibrin monomer aggregation. In the turbidimetric assay patient’s monomers aggregated more slowly and incompletely compared to normal monomers.Preliminary studies suggest that the release of fibrinopeptides A and B is normal.
A New Congenital Dysfibrinogenemia with Hemorrhagic Diathesis (Fibrinogen Montreal II)
Authors: Angelo G. , Lacombe M. , Lemay J. , Lavallée R. , Bonny Y. , Boileau J. 
Published: June 2019

This report comprises of a new congenital dysfibrinogenemia in a Caucasian family with hemorrhagic diathesis.Based on a study of three generations it shows to be an autosomal-dominant hereditary transmission.The thrombin and the Reptilase time are prolonged, the prothrombin time and the partial thromboplastin slightly prolonged.The fibrinogen concentration is normal when tested immunologically spectrophoto-metrically or by the heat denaturation method.Abnormal aggregation of fibrin monomers, and low optical density polymerisation curve with a correcting effect whenever the ionic strength is decreased below 0.15 M.The patient’s plasma has no inhibitory effect on the coagulation of normal plasma or fibrinogen.Satisfactory results of treatment with fibrinogen during dental extraction will be presented.