bluuebunny/crossref_metadata_2025_split huggingface dataset:
High-Dose Intravenous Immunoglobulin Treatment of a Pregnant Patient with an Antiphospholipid Syndrome: Immunological Changes Associated with a Successful Outcome
Authors: Arnout J , Spitz B , Wittevrongel C , Vanrusselt M , Assche A Van , Vermylen J 
Published: July 2018

SummaryA patient with a history of habitual abortion, deep venous thrombosis, thrombocytopenia, high titer IgG anticardiolipin antibodies and a clearly positive lupus anticoagulant, was treated during her seventh pregnancy with high-dose intravenous immunoglobulins (IVIg) from the third month onwards. Every month, a daily infusion of 400 mg immunoglobulins per kg body weight was given during five consecutive days. The patient’s pregnancy ended preterm with a live birth, delivered by caesarian section because of a placental abruption. The 1070 g (P20-P25) weighing girl was in good health, apart from a bradycardia, due to dysfunction of the atrioventricular conduction.Each treatment with IVIg resulted in a slight reduction of both anticardiolipin antibodies and lupus anticoagulant levels and in an increase in platelet count. During the six-month observation period, a gradual decline in antiphospholipid antibodies and an increase in platelet count was found. The potential role of anti-idiotypic antibodies, present in the IVIg used for treatment, was studied. In vitro, IVIg were able to reduce the binding of the patient’s anticardiolipin antibodies to cardiolipin coated microtiter plates. The presence of anti-idiotypic antibodies in IVIg was further documented by affinity chromatography and by realtime biospecific interaction analysis (BIA) on a BIA-core instrument. Affinity purified anticardiolipin antibodies were retarded on a column of insolubilized IVIg and a weak interaction was found between IVIg and affinity purified patient antiphospholipid antibodies, coupled to the BIA-core biosensor. In addition, the same technology revealed increased levels of anti-antiphospholipid antibodies in the patient’s plasma following IVIg therapy. The partial and transient reduction of anti-phospholipid antibody levels observed immediately following each treatment course seems compatible with low affinity complexation of idiotype-antiidiotypes, resulting in an accelerated clearance of the autoantibodies. Despite the low affinity for the patient’s idiotypes, the beneficial long term effects observed could be related to an immune regulatory role of these anti-idiotypic antibodies on the synthesis of antiphospholipid antibodies.
Influence of Six Mutations of the Protein C Gene on the Gla Domain Conformation and Calcium Affinity
Authors: Gaussem Pascale , Gandrille Sophie , Duchemin Jérôme , Emmerich Joseph , Alhenc-Gelas Martine , Aillaud Marie-Françoise , Aiach Martine 
Published: July 2018

SummaryThe protein C Gla domain was studied in six families presenting a type II hereditary deficiency characterized by low activity in a coagulation assay and normal activity in an amidolytic assay. Five of these mutations, previously described by our group, affected Arg-5, Arg-1, Arg 229 and Ser 252. We report here the first natural Glu 7 to Asp mutation in a sixth family.We evaluated the binding of the mutated protein C to Hn, a monoclonal antibody (mAb) known to recognize the sequence Phe 4 to Arg 9 of the Gla domain; the presence of calcium ions suppresses the recognition of this epitope by Hn. Mutation of Arg 229 to Gin and Ser 252 to Asn did not modify the inhibition of protein C binding, whereas the Arg-1 to His mutation resulted in a loss of inhibition in the presence of CaCl2. This suggests that the protein C of this patient shows impaired carboxylation.The protein C from patients bearing the mutations Arg-5 to Trp, Arg-1 to Cys and Glu 7 to Asp bound poorly to Hn mAb, even in the absence of calcium ions. The calcium affinity of the Gla domain was studied by pseudo-affinity chromatography, in which protein C was successively eluted from a Mono Q column by CaCl210 mM and NaCl 0.6 M. Protein C from the patient bearing the Arg-5 to Asp mutation had a normal elution profile, suggesting that a modification of the propeptide cleavage site impairs the conformation of the Gla domain but not carboxylation. Conversely, the patient bearing the mutation Arg-1 to Cys had an abnormal elution profile, showing that calcium binding affinity was impaired probably due to a defective carboxylation (the behaviour of the Glu 7 to Asp mutant lacking one Gla residue validated our experimental approach).These results confirm that mutations in the serine protease domain do not modify the conformation of the N-terminal part of the Gla domain. Arg-1 to His, Arg-1 to Cys and Glu 7 to Asp mutations strongly modified affinity for calcium ions, whereas the Arg-5 to Trp mutation probably modifies the conformation of the Gla domain.
The Effect of Prostacyclin (PGI2) on Platelet Behaviour. Thrombus Formation in Vivo and Bleeding Time
Authors: Ubatuba Fernando B , Moncada Salvador , Vane John R 
Published: July 2018

SummaryProstacyclin (PGI2) infused intravenously into anaesthetized rabbits inhibited electrically-induced thrombus formation in the carotid artery, increased bleeding time and inhibited ex vivo platelet aggregation induced by ADP or arachidonic acid. The increase in bleeding time and the inhibition of ex vivo platelet aggregation lasted for as long as the infusion of PGI2 was maintained but rapidly disappeared after infusion was stopped.Prostacyclin is a more potent inhibitor of platelet function, in vivo than prostaglandin E1 (PGE1) or prostaglandin D2 (PGD2).The effects of prostacyclin on all parameters studied except blood pressure were potentiated by the concomitant administration of theophylline, a phosphodiesterase inhibitor.
Mode of Action of Ticlopidine in Inhibition of Platelet Aggregation in the Rat
Authors: Ashida Shin-Ichiro , Abiko Yasushi 
Published: July 2018

SummaryTiclopidine, when orally administered to rats, resulted in activation of basal and prostaglandin E1 (PGE1)-stimulated adenylate cylase activity through increase in affinity of the cyclase in platelet membrane to PGE1, although it failed to affect adenosine- or sodium fluoride-stimulated activity of the enzyme. In washed platelets, Ticlopidine also activated basal and PGE1-stimulated activity of the cyclase and prevented reduction in the cyclase activity caused by low concentrations of PGE2. Furthermore, Ticlopidine inhibited malondialdehyde formation in platelets induced by thrombin but failed to inhibit that caused by exogenous arachidonic acid. Adenosine 3’,5’-cyclic monophosphate (c-AMP): phosphodiesterase activity of platelet lysate was not significantly affected by Ticlopidine treatment.These findings indicate that Ticlopidine inhibits platelet aggregation and prostaglandin synthesis from endogenous substrate through activating basal and PGE1-stimulated activity of the cyclase, preventing PGE2-induced depression of the cyclase activity and thus increasing platelet c-AMP level.
Effects of Adenosine Diphosphate, Colchicine and Temperature on Size of Human Platelets
Authors: Laufer N , Grover N B , Ben-Sasson S , Freund H 
Published: July 2018

SummaryAn improved measuring system based on the Coulter principle and developed in our laboratory is used to size human blood platelets.The mean volume of platelets in 24 healthy subjects is found to be 8.45 μm3 with a standard deviation of 1.07 μm3; the typical size-distribution curve is unimodal and asymmetrical, with a marked skew to the right.The effects of different reagents on platelet size (shape factor × volume) are evaluated. Platelets increase in size by 23% following suspension in isotonic, phosphate-buffered saline and incubation with 10 μM adenosine diphosphate; no change is observed when the suspending medium is autologous plasma. Cooling the platelets to 0-4° C results in a size increase of 25%; rewarming to 37° C restores them to their initial size within 2 hr. A similar increase occurs when the platelets are incubated with 1-10 mM colchicine.It is proposed that these reagents, which are known to produce changes in the orientation of the marginal bundle of microtubules, cause platelets to undergo disc-sphere transformations.Calculations are made which show that such transformations increase platelet size by 27% as measured electrically, and we conclude that the so-called volume changes reported in the literature reflect shape changes only and that no true volume increase actually takes place.
Measurement of the Heparin Neutralizing Capacity of Protamine
Authors: Graham David T , Pomeroy Alan R , Smythe David B 
Published: July 2018

SummarySeveral methods of estimating the heparin neutralizing capacity of protamine were investigated for their reliability and practicability. The results from two chemical methods were compared with those from two in vitro biological assays, one of which was the method of the British Pharmacopoeia (1973). An in vivo method using mice was used to assess the accuracy of the in vitro test methods. Three standard heparin preparations were tested against the W.H.O. 1st International Reference Preparation for Protamine. Two of the heparin preparations were of mucosal origin, one of which was the 3rd International Standard, and the third heparin preparation was of lung origin (the 2nd International Standard for Heparin).The mean neutralization values (all methods) of heparin by protamine for a House Reference Preparation and the 3rd and 2nd International Standards for Heparin were 95.8, 109.8 and 89.9 units per mg of Protamine, respectively. All the methods read the House Reference Preparation to have a lower value than the 3rd International Standard, which had a higher value than the 2nd International Standard for Heparin. There was a constant relationship between the results of any one method and those of another. The chemical and in vitro biological methods gave results of comparable precision although the latter required a greater degree of technical skill and time to perform.
Factor XII-Dependent Fibrinolysis: A Double Function of Plasma Kallikrein and the Occurrence of a Previously Undescribed Factor XII- and Kallikrein-Dependent Plasminogen Proactivator
Authors: Kluft C , Trumpi-Kalshoven M M , Jie A F H , Veldhuyzen-Stolk E C 
Published: July 2018

SummaryFibrinolytic studies in euglobulin fractions of Fletcher trait plasma (deficient in prekallikrein) revealed reduced activities as compared to normal plasma. A quantitative assay for total plasminogen activator plus proactivator in plasma showed that the amount in Fletcher trait patients is about half of normal (normal = ± 100 blood activator units [BAU]/ ml). Plasma kallikrein partially purified in a high and low molecular weight form exerted plasminogen activator activity amounting to 10–15 BAU/ml plasma. So, the absence of kallikrein in the deficient plasma can not fully account for the reduction in activator activity. Additions of kallikrein preparations or normal plasma fractions resulted in additional activator activity in Fletcher trait plasma which was assessed at 30–40 BAU/ml. This activity was assumed to originate from a previously undescribed plasminogen proactivator whose activation is kallikrein- and factor XH-dependent.Fractionation experiments demonstrated the presence of two major activities and a minor activity caused by kallikrein in normal plasma.It is concluded that plasma kallikrein has two functions in the generation of factor XII- dependent fibrinolytic activity: one as a direct plasminogen activator and another as a factor in the activation of a major factor XH-dependent plasminogen proactivator.
Abnormalities of Platelet Adenine Nucleotides in Patients with Myeloproliferative Disorders
Authors: Nishimura Junji , Okamoto Seiki , Ibayashi Hiroshi 
Published: July 2018

SummaryPlatelet aggregation and adenine nucleotides in platelets have been studied in thirteen patients with myeloproliferative disorders. ADP induced aggregation was abnormal in two patients, but collagen induced aggregation was impaired in 11 patients. The concentrations of ATP and ADP in resting platelets in the patients with abnormal aggregation were significantly less than those in normal subjects. Marked reduction of the amounts of both nucleotides released into plasma was also observed after stimulation of collagen in these patients. Platelets in the patients with normal functions contained almost normal amounts of adenine nucleotides. We discussed the relationship between platelet dysfunction and adenine nucleotides in platelets of myeloproliferative disorders and concluded that platelet dysfunction was mainly attributable to reduction of releasable ADP.
Outcome of Disseminated Intravascular Coagulation in Relation to the Score when Treatment was Begun
Authors: Wada Hideo , Wakita Yoshihiro , Nakase Tutomu , Shimura Minori , Hiyoyama Katsuyo , Nagaya Shousaburou , Mori Yoshitaka , Shiku Hiroshi ,   the Mie DIC study group
Published: July 2018

SummaryWe examined 395 patients with disseminated intravascular coagulation (DIC) divided into two groups: non-leukemic and leukemic. In 58% of the patients as a whole, treatment of DIC resulted in complete or partial remission, while exacerbation and death occurred in 31%. The efficacy of DIC treatment in the non-leukemic group was less than that in the leukemic group, indicating that the outcome of DIC depended, in part, on the underlying disease. We examined hemostatic indicators in relation to DIC score: prothrombin time (PT) ratio, FDP, platelet count, and fibrinogen levels were found to be important indicators for the diagnosis of DIC, but not for Pre-DIC. Plasma levels of fibrin-D-dimer, thrombin-antithrombin complex (TAT), and plasmin- plasmin inhibitor complex (PPIC) were significantly increased in pre-DIC. The efficacy of treatment in relation to the DIC score when the treatment was begun showed that greater efficacy was achieved in pre-DIC than in DIC patients. The outcome was poorer with increasing DIC score, suggesting that early diagnosis and early treatment are important. On examining the relationship between outcome and hemostatic indicators, we found that the PT ratio and the levels of antithrombin, plasminogen, PPIC, the PPIC/TAT ratio, and thrombomodulin were related to outcome, suggesting that very high consumption of blood coagulation factors, liver dysfunction, hypofibrinolysis, or organ failure caused a poor outcome. Although the outcome in DIC patients may not depend substantially on plasma levels of TAT and fibrin-D- dimer, we can use these indicators to treat DIC patients at an early stage.
The International and “NIH” Units for Thrombin - How Do They Compare?
Authors: Gaffney Patrick J , Edgell Tracey A 
Published: July 2018

SummaryThe current International Standard (IS) for α-thrombin was established in 1991. It was related in unitage with the 1st IS for Thrombin established in 1975 and contains 100 IU of thrombin activity. The National Institute of Health (NIH) standard (Lot J) is in common use for the calibration of commercial thrombin reagents and this study reports on a comparison of the thrombin units defined by these 2 standards. This study has indicated that one “NIH” unit is equivalent to 1.1 to 1.3 IU of thrombin, depending on the influence of PEG in the assay. A unitage ratio figure of 1.15 was recommended following analysis of data obtained in the presence and absence of PEG in the comparative assays. This was confirmed by amidolytic assay data.
A Monoclonal Antibody against a peptide sequence of Fibrinogen Gamma Chain Acts as an Inhibitor of factor XIII-Mediated Crosslinking of Human Fibrin
Authors: Taubenfeld stephen M , Song Yeqing , Sheng DeQuan , Ball Evelyn L , Matsueda R Gary 
Published: July 2018

SummaryRecurrent hemorrhage has been reported in humans as a result of acquired antibody inhibitors which interfere with the crosslinking of fibrin by factor XIII. One type of these inhibitors (Type III) prevents activated factor XIII from acting on fibrin. We have generated an anti- fibrin monoclonal antibody, called mAb 4A5, which binds to a peptide sequence at the carboxyl-terminus of human fibrinogen γ-chains. MAb 4A5 acts like a Type III inhibitor and prevents proper factor XHI-mediated crosslinking. Pre-incubation of fibrinogen or pooled human plasma with mAb 4A5, but not mAb D2 (specific for the carboxyl terminus of fibrin α-chains), resulted in clots which are soluble in either 5 M urea or 1% monochloroacetic acid. SDS-PAGE and immunoblotting analysis of these clots confirmed that mAb 4A5 inhibited γ-chain crosslinking in plasma clots and fibrin clots. Results from a factor XIII activity assay demonstrated that biotinylcadaverine cross-linking into fibrin by factor XIII could be inhibited by mAb 4A5 but not mAb D2, arguing that mAb 4A5 acted by binding the crosslinking site of factor XIII. Studies of the immunoreactivity of these mAbs with 12 different animal species showed that the γ-chain epitope recognized by mAb 4A5 was more conserved than the α-chain epitope recognized by mAb D2. The species fibrinogens, recognized by mAb 4A5 in binding assays, also showed impaired crosslinking when mAb 4A5 was present during the clotting reaction.
Human Anti-Streptokinase Antibodies Induce Platelet Aggregation in an Fc Receptor (CD32) Dependent Manner
Authors: Lebrazi Jamal , Helft Gérard , Abdelouahed Mustapha , Elalamy Ismaïl , Mirshahi Massoud , Samama Michel Meyer , Lecompte Thomas 
Published: July 2018

SummaryExposure to streptokinase (SK) elicits anti-SK antibodies (Abs), which inhibit fibrinolysis and induce platelet aggregation. The mechanism of the latter is not fully understood, although it seems to involve platelet binding by a plasminogen streptokinase and anti-SK ternary complex. Anti-SK Abs were purified by affinity chromatography from serum of patients having received SK for acute myocardial infarction (AMI), and were shown to be of the IgG type. Their effects were studied with (i) human platelets in citrated plasma in the presence of SK or acetylated plasminogen-SK activator complex (APSAC), and (ii) in washed platelets, resuspended in Tyrode buffer after lowering the ionic strength, in the presence of APSAC (which provides both SK and plasminogen). An antibody concentration-response curve was obtained, showing a plateau in the presence of 0.1 mg/ml IgG. By increasing the concentration of APSAC, we obtained a unimodal response curve, the optimal concentration of APSAC being 0.05 U/ml. Aggregation was suppressed by chelating calcium with EDTA, blocking fibrinogen binding by the synthetic peptide Arg-Gly-Asp-Ser (RGDS), and raising intraplatelet cAMP with Iloprost (a prostacyclin analogue). Aggregation required the interaction of the anti-SK Ab Fc domain with the platelet Fc-gamma receptor type II, also known as CD32, since: (i) it was blocked by the monoclonal antibody IV-3 directed against CD32, (ii) it did not occur with F(ab)’2 fragments, which block the response to the intact IgG. The clinical relevance of these platelet-activating anti-SK antibodies remains to be determined. Two factors might influence clinical outcome: (i) the amount and type of pre-existing anti-SK Abs; (ii) the known interindividual variability of the platelet response to binding and activation by IgG involving the CD32 molecule.
Comparison of Six Commercial Plasma References for Factor VIII, Factor IX and von Willebrand Factor
Authors: Kasper Carol K , Aronson David L , Davignon George , Foster Paul , Hillman-Wiseman Carol , Lusher Jeanne M , Manco-Johnson Marilyn , Meade James B , Montgomery Robert R , Rickies Frederick R , White Gilbert C 
Published: July 2018

SummarySix brands of normal reference plasma produced in the United States, with assigned assay values for factor VIII and IX and, in four instances, ristocetin cofactor and von Willebrand antigen, were assayed in nine coagulation laboratories in academic institutions in the same country. Differences in mean assays of reference plasmas, as a percent of labelled potency, were significant and were greater than differences among laboratories. Standard methods of assigning potency to commercial reference plasmas are recommended.
Influence of Various Heparin Preparations on Lipoproteins in Hemodialysis Patients: A Multicentre Study
Authors: Kronenberg Florian , König Paul , Neyer Ulrich , Auinger Martin , Pribasnig Andreas , Meisl Thomas , Pinter Georg , Dieplinger Hans 
Published: July 2018

SummaryRecent studies have indicated controversial effects of low molecular weight heparin (LMWH) on lipid metabolism in patients on chronic hemodialysis as compared to unfractionated heparin (UFH).We therefore conducted a cross-sectional multicentre study comparing 153 patients treated with LMWH and 153 patients with UFH, matched for sex, age and diabetes mellitus. Both groups have been treated with LMWH or UFH for six months or longer (14.9 vs.23.4 months). We observed no differences between the UFH and LMWH treatment groups for total cholesterol, LDL cholesterol, triglycerides, apoB, apoA-IV or Lp(a). The only significant differences were seen for HDL cholesterol and the corresponding apolipoprotein apoA-I, which were significantly higher in the UFH group (HDL cholesterol: 0.97 ± 0.35 mM/l vs. 0.87 ± 0.37 mM/l, p<0.05; apoA-I 1.23 ± 0.27 g/l vs. 1.15 ± 0.27 g/l, p <0.05).We conclude that the results of studies investigating the influence of LMWH on lipid metabolism are as heterogeneous as the substances themselves. This challenges the beneficial influence supposedly had by LMWH preparations on lipid metabolism.
The Factor V Leiden Mutation which Predisposes to Thrombosis Is Not Common in Patients with Antiphospholipid Syndrome
Authors: Dizon-Townson Donna , Hutchison Christopher , Silver Robert , Branch D Ware , Ward Kenneth 
Published: July 2018

SummaryAntiphospholipid syndrome is associated with venous, arterial, and placental thrombosis, possibly through autoantibody impairment of phospholipid-dependent protein C activation. Recently, a missense mutation in the factor V gene (1691 G → A) has been identified that results in an abnormal factor V product (1). This mutation, known as the Leiden mutation, causes an amino acid substitution of glutamine for arginine at position 506 in the factor V molecule and renders the protein resistant to proteolytic inactivation by activated protein C and thus predisposes to thrombosis (2, 3). We hypothesized that some individuals with antiphospholipid syndrome may also carry the Leiden mutation, and thus have a “second hit” predisposition to thrombosis. To test this hypothesis, allele-specific hybridization and allele-specific restriction analysis were used to test for the Leiden mutation in thirty women with the antiphospholipid syndrome, 10 of whom had a history of thrombosis. None of the women were heterozygous or homozygous for the factor V mutation. We conclude that the presence of the factor V Leiden mutation is not a prerequisite for the thrombotic events in patients with antiphospholipid syndrome, due to the occurrence of thrombosis seen in patients lacking the factor V mutation.