bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood Coagulation in High Altitude Pulmonary Hypertension
Authors: Singh I. , Chohan I.S. 
Published: May 2019

Blood coagulation studies were carried out in 38 Indian soldiers who were resident at altitudes between 3690 and 5540 m for 2 years. Compared with 16 sea-level controls, 6 of these 38 subjects who had developed pulmonary hypertension during their stay at high altitude showed a significant increase of plasma fibrinogen, fibrinolytic activity, platelet adhesiveness, platelet factor 3, factor V, and factor VIII. In the remaining 32 subjects who did not develop pulmonary hypertension there was a significant increase of plasma fibrinogen and fibrinolytic activity only.The above differences between subjects who develop pulmonary hypertension at high altitude and those who do not develop pulmonary hypertension suggest that high altitude pulmonary hypertension is of occlusive origin and is dependent on changes in blood coagulation at high altitude.
Factor VIII Concentrates - Forces of Supply and Demand
Authors: Britten Anthony F. H. 
Published: May 2019

Some surprisingly simple artificial factors influence the availability of factor VIII for hemophilia treatment. Demand is affected by choice of product, and choice of treatment style (episodic vs. prophylactic), and also by availability funds.Autobiographic data suggest the feasibility of long-term low dosage prophylaxis (6u/KgA8 hrs.). This tentative conclusion is based on 2½yrs. of unprecedented near-total freedom from hemorrhage. The significance is the potential saving of 60% of factor VIII concentrate, compared with the more orthodox dose (15u/KgA8 hrs.) which has been shown to increase factor VIII usage by 2.5–3 times compared with episodic therapy.The American Red Cross produced 293,332 units of cryoprecipitate from 4,690,217 whole blood donations in 1975-6 (6.25% of blood collected). Production could readily be increased if the demand existed. The following artificial factors have an influence on cryoprecipitate production: health insurance policies; price structure; the international market for factor VIII.It is concluded that there is no shortage of available factor VIII, that more could readily be made available, that prophylaxis may be possible without increasing demand for factor VIM, that financial considerations are seriously distorting hemophi1ia treatment, that hemophilia treatment in the United States is being subsidised by other countries, and that understanding of these factors can help to overcome them.
Electroimmunoassay of Factor IX in the Detection of Haemophilia B Carriers
Authors: Panicucci F. , Baicchi U. , Sagripanti A. , Pinori E. 
Published: May 2019

Parallel determinations of factor IX activity and factor IX antigen were carried out on 28 haemophilia B carriers and on 20 normal women. Factor IX activity was measured by a one stage method. Factor IX antigen was quantified by electroimmuno assay in agarose gel containing heterologous monospecific antiserum against human factor IX.The activity was observed to be at the same level as the antigen in normal women. Discrepancy was not found between the antigen and the activity in almost all of carriers: only in the mothers of haemophiliacs Bor B+ or BM the factor IX antigen resulted greater than that activity. Our results show that electroimmuno-assay may be used to study carriers of haemophilia B genetic variants and confirm that in the majority of cases they can probably be diagnosed on the basis of factor IX activity alone.
The Role of the Consumer-Patient in the Growth of a Comprehensive Hemophilia Care Unit
Authors: Child Dorothy , Kopicki John , VanHarlingen David 
Published: May 2019

The most efficient means for dealing with the myriad problems of hemophilia is through a comprehensive hemophilia care center involving medical and paramedical personnel, as well as numerous non-medical supportive services. As in all consumer services, however, problems arise when the care center team and the individuals who comprise it are unaware of the true needs of the patients they serve. To reduce such problems, an active and vocal group of hemophilia families and friends can provide insights otherwise unattainable. Working in cooperation with the center, they can provide guidance and seek funding to reduce the cost paid by the patient.We describe the role of consumer-patients in the initiation and development of New Jersey’s first and only comprehensive care center for hemophilia. We also present a detailed examination of the kinds of assistance which has been provided and which is being provided in the growth and expansion of the center’s team and its activities. A plan for a statewide treatment network centered around this treatment facility will be presented.
The Activity of Heparin Preparations Studied by Amidolytic and Clotting Methods
Authors: Teien A.N. , Abildgaard U. , Höök M. , Lindahl U. 
Published: May 2019

Two heparin standards, heparin isolated from human mastocytoma tissue, four commercial heparins and two heparin preparations separated by affinity chromatography (“High affinity heparin”=HAH and “Low affinity heparin”=LAH) were assayed by the activated partial thromboplastin time method (APTT), the calcium thrombin time method (CaTT) and two amidolytic methods (measuring the accelerating effect of heparin on the inactivation of thrombin or factor Xa by antithrombin III), with and without plasma in the test system. The specific activities of the various heparins were expressed relative to that of the 3rd. Int. Standard (=100). Found specific activities ranged 3 - 198 (LAH and HAH, respectively). In all assay systems HAH had the highest specific activity, followed by one of the commercial preparations and the 3rd Int. Standard. LAH and human heparin had very low specific activities, except in the APTT test system, an assay method which in addition mirrors other anticoagulant effects of heparin than the acceleration of antithrombin III. Apart from the higher effect of LAH and human heparin on the APTT, the difference in specific activities found for each individual heparin preparation with these various assay methods was slight.In view of the reproducibility and simplicity of the amidolytic methods, it is suggested that they be adapted for heparin standardization.
Evidence for a Central Role for Calcium Ions in Regulation of Platelet Function
Authors: Detwiler T.C. , Charo I.F. , Feinman R.D. 
Published: May 2019

It is generally believed that calcium ions play a key role in regulation of platelet function. This is based on 3 types of evidence.1. Analogies with other cells. Calcium ions are known to trigger secretion and contraction in many cells, possibly reflecting a general role for calcium in all secretion and contraction.2. Indirect evidence. Platelet aggregation and secretion are induced by divalent cation ionophores. The response to the ionophore A23187 is identical to that induced by other potent stimuli.3. Direct evidence. Platelet activation can be blocked by drugs (e.g., certain local anaesthetics) that block release of calcium ions from sarcoplasmic reticulum; the inhibition can be overcome by addition of extracellular calcium in the presence of a calcium ionophore.While this does not constitute definitive proof, the central role for calcium ions remains an attractive hypothesis that justifies attempts to further define calcium pools and fluxes in platelets.
The Role of Myosin Phosphorylation in Regulating Actin-Myosin Interaction in Human Blood Platelets
Authors: Adelstein R.S. , Barylko B. , Conti M.A. 
Published: May 2019

Human blood platelets contain actin and myosin which are similar in many of their structural and biochemical properties to the contractile proteins found in muscle. Platelet myosin is composed of six polypeptide chains, two heavy chains of 200,000 daltons and two pair of light chains of 20,000 and 15,000 daltons. Platelets also contain a specific enzyme capable of phosphory-lating the 20,000 dalton light chain of platelet myosin. The kinase has been purified 600-fold and has been shown not to require Ca2+ or cyclic AMP for its activity (Daniel, J.L. & Adelstein, R.S., Biochemistry 15, 2370, 1976). Phosphorylation of platelet myosin results in a 7-10 fold increase in the actin-activated myosin ATPase activity but has no effect on the myosin K+-EDTA ATPase activity measured in 0.5 M KCl. The phosphatase responsible for dephosphorylation of platelet myosin has been partially purified. Dephosphorylation of platelet myosin results in a decrease in the actin-activated myosin ATPase activity, without affecting the myosin ATPase activity measured in the presence of K+-EDTA in 0.5 M KCl.Thus, using the actin-activated ATPase activity as an indication of actin-myosin interaction, myosin phosphorylation-dephosphorylation appears to function as a reversible regulatory mechanism. That this type of regulation is not confined to platelets is indicated by finding a similar mechanism in proliferative rat myoblasts grown in culture (Scordilis, S.P., and Adelstein, R.S., Biophysical J., 17, 268a, 1977) and guinea pig vas deferens smooth muscle (Chacko, S., et al., PNAS. 74, 129, 1977).B.B. is on leave from the Nencki Institute, Warsaw, Poland.
Separation of Degranulated Platelets from Normal Platelets
Authors: Cieslar P. , Greenberg J.P. , Packham M.A. , Kinlough-Rathbone R.L. , Mustard J.F. 
Published: May 2019

Platelets degranulated by thrombin (TDP) can be recovered, are effective in hemostasis and survive normally upon infusion into rabbits. Two approaches to determine whether platelets have been degranulated in vivo are: (1) measurement of circulating released materials; (2) detection of circulating degranulated platelets. We have used arabino-galactan (Stractan II) density gradient centrifugation to separate normal and degranulated platelets. The following distribution was obtained with washed rabbit platelets.The serotonin, PF4 and adenine nucleotide contents of the TDP were less than those of normal platelets and the TDP in fraction I had the lowest amounts. When TDP were labeled with 51cr and mixed with equal numbers of normal platelets, 85% of the platelets in fraction I were found to be TDP. 51Cr-TDP were injected into normal rabbits and reharvested after 18 hours. The greatest proportion of TDP was isolated in fraction I. Thus this method may make it possible to separate platelets that have lost their granule contents during participation in reversible thrombus formation in vivo.(* Visiting Fellow from the Faculty of Medicine, Charles University, Prague, Czechoslovakia.)
Plasma from Patients with Hepatic or Renal Failure Stimulates Prostacyclin Release from “Exhausted” Rat Aorta Slices
Authors: Hoof Van A. , Chamone D.A.F. , Vermylen J. 
Published: May 2019

Slices of rat aorta (1.5 to 2 mg wet weight) were washed several times in tris buffer until no further release of anti-aggregating activity could be detected. These “exhausted” aorta fragments were then incubated for 60 to 120 min. at room temperature with 250 μl platelet-poor plasma from either a healthy subject or from a patient with hepatic or renal failure. 100 ul of supernatant plasma were subsequently added to 300 ul normal human platelet-rich plasma; the mixture was challenged one minute later with ADP (2 to 4 μM final concentration) and platelet aggregation recorded.The plasmas from 6/6 uraemic patients undergoing maintenance haemodialysis stimulated prostacyclin release more than the simultaneously studied normal plasmas.The 17 patients with liver disease were classified using Child’s criteria for hepatic functional reserve. Stimulation of prostacyclin release was found with the plasma of 4/4 patients with advanced hepatic dysfunction, 4/6 patients with moderately impaired hepatic function and 4/7 patients with good hepatic function.Enhanced prostacyclin release may play a role in the pathogenesis of the haemorrhage diathesis of patients with renal or hepatic failure.
Prothrombin Metz: Purification and Characterization of a Variant of Human Prothrombin
Authors: Rabiet M.J. , Elion J. , Labie D. , Josso F. 
Published: May 2019

For the purification of the abnormal prothrombin (Pt Metz), advantage has been taken of the existence in the family of three siblings who, being double heterozygotes for Pt Metz and a hypoprothrombinemia, have no normal Pt. Purification procedures included barium citrate adsorption and chromatography on DEAE Sephadex as for normal Pt. As opposed to some other variants (Pt Barcelona and Madrid), Pt Metz elutes as a single symetrical peak. By SDS Polyacrylamide gel electrophoresis, this material is homogeneous and appears to have the same molecular weight as normal Pt. Comigration of normal and abnormal Pt in the absence of SDS, shows a double band suggesting an abnormal charge for the variant. Pt Metz exhibits an identity reaction with the control by double immunodiffusion.Upon activation by factor Xa, Pt Metz can generate amydolytic activity on Bz-Phe-Va1-Arg-pNa (S2160), but only a very low clotting activity. Clear abnormalities are observed in the cleavage pattern of Pt Metz when monitored by SDS gel electrophoresis. The main feature are the accumulation of prethrombin 1 (P1) and the appearance of abnormal intermediates migra-ti ng faster than P1.
Evidence for the Presence of FVIII Subunits in Plasma and Clinical FVIII Concentrates Using Quantitative Electrophoresis
Authors: Seghatchian M.J. , Hirst K. 
Published: May 2019

X-Electrophoresis of normal plasma and low purity FVIII concentrates indicated two major peaks of cross reacting FVIIIR:Ag, extending from the front of fibrinogen to the α2 region. In high purity concentrates (Hemofil and Koate) smaller aggregates, with faster mobility predominated, confirming the heterogeneous nature of FVIII concentrate preparations.Analysis of the gel content for other FVIII related activities revealed that FVIIIR:RCF was associated only with larger aggregates, while FVIII:C as determined by both chromogenic and clotting techniques were mainly associated with the smaller forms. The coexistence of FVIII subunits, with an immunological identity line, is brought about by using high concentrations of FVIII. The presence of such an entity in plasma was confirmed by in vitro addition of high purity concentrate to plasma, FVIII:C neutralization activity and reduction with Dithiothereitol (D.T.T.). The subunits found after D.T.T. treatment gave a symetrical peak with similar molecular distribution of the fast moving peak, present in high purity concentrate.It is concluded that each population of FVIII aggregates would consist of the subunits cross-linked by disulphide bonds. The relative concentration of these aggregates, present in differing amounts in various preparations, could be determined quantitatively: Thus an extremely useful method for the identification of the native fonos of FVIII and the quality control of concentrate preparation is provided.
A Novel Dysfibrinogenemia with Abnormal γ-Chain(Fibrinogen Nagoya).
Authors: Takamatsu Junki , Oqata Kanji , Kamiya Tadashi , Koie Katsuo , Takashi Takagi , Iwanaga Sadaaki 
Published: May 2019

Six individuals in 3 generations of Japanese family had prolonged thrombin clotting time, but no history of hemorrhagic or thrombotic disease. Very low fibrinogen levels were obtained by thrombin clottable protein, while immunological procedures gave normal values of fibrinogen. The serum contained 40-80μg/ml of unclottable fibrinogen related antigens. The patients’ plasma had an inhibitory effect on the fibrin formation in normal plasma. Major defect of this fibrinogen was a delayed aggregation of fibrin monomers.On CM-chromatography (CM-52) of the S-carboxymethylated fibrinogen, three different γ-chains, named γx, γL and γR, were separated. They did not differ in their electrophoretic mobilities in SDS-PAGE, but were distinguishable in PAGE containing 8M urea. Moreover, the amino acid compositions and tryptic peptide mappings of each chain revealed a little difference from those of normal fibrinogen γ chains, suggesting the difference in amino acid substitution or oligosaccharide chain structure.Based on these findings, we designated this fibrinogen as fibrinogen Nagoya; its possible identity without other dysfibrinogenemia has not been excluded.
The Role of Mitochondria in the Regulation of the Cytosolic Ca2+ levels in Human Blood Platelets
Authors: Scharf R.E. , Lüscher E.F. 
Published: May 2019

Mitochondria isolated by density gradient centrifugation from blood platelets show active Ca2+ transport. The required energy can be provided either by oxidation of succinate or by added ATP. The highest amounts of Ca2+ (30-32 nmoles Ca2+/mg protein) are taken up when both, succinate and ATP, are available. In the presence of selective inhibitors of mitochondrial metabolism such as antimycin A, oligomycin or with uncoupling agents only insignificant amounts of Ca2+ are accumulated. Strong inhibition is also exerted by ruthenium red and by Mg2+, whereas Pi acts as a stimulator of Ca2+ uptake. Basal mitochondrial respiratory activity is stimulated by Ca2+ (as well as by ADP).This suggests that mitochondria, besides other specialized structures, play a role in removing Ca2+ from the cytosol of blood platelets. Activation of platelets is linked to an increase in respiratory activity; therefore, mitochondria not only may be involved in the regulation of Ca2+ levels in the resting state, but may also contribute to the reversibility of Ca2+ dependent alterations which accompany the activated state.
Immunochemical Studies on Fibrinogen
Authors: Gollwitzer R. , Tanswell P. , Lotter H. , Henschen A. , Timpl R. 
Published: May 2019

The immunochemistry of fibrinogen has been subject of concise studies during the last years. Fibrinogen is a strong immunogen, based on a large variety of antigenic determinants located at different sites in the molecule. By using purified antibodies several of the surface and masked antigenic determinants on the individual chains and the large disulfide bonded CNBr-peptides were identified. According to these investigations the γ-chain is partially buried in the native molecule, whereas the antigenic determinants of a CNBr-peptide covering the C-terminal half of the α-chain are located on the surface of the protein. The structure of the antigenic determinants of this peptide which exhibits an extreme species variability has been more precisely defined in both bovine and human fibrinogen. A distinct structural variability was also observed for different antigenic determinants located in fi-brinopeptides A and B.Supported by the Deutsche Forschungsgemeinschaft, SFB 51.
Isolation of Fibrinogen Protomer by Partial Reduction of Disulfide Bonos in Concentrated Urea
Authors: Albert A. , Cacho F. , Saiz J. L. 
Published: May 2019

Partial reduction of human and bovine Fibrinogen (F), recently dissolved in 6 and 8M deionized urea, with different amounts of dithioeritritol (DTE) (10 to 60:100 DTE:F, w/w) has been carried out in nitrogen atmosphere. Disc gel electrophoresis in 0.1% SDS shows changing amounts of six molecular species depending on the reaction timeand DTE:F ratio. Three bands are identical with those obtained by total reduction of fibrinogen, one with unreduced material, the remaining two show mobilities corresponding to molecular weights of 170.000–190.000 (band H, with yields up to 40-50%) and 130.000-140.000 (band N).Totalreduction of the isolated species H shows identical composition in fibrinogen chains as the original material. Stabilization by alkylation of this species is only successful in 0.1% SDS. Comparative ultracentrifugation studies show sedimentation coefficients of 6.8 S for fibrinogen incubated with SDS and 4.1 S for the H species, which agree with a ratio 2:1 for their molecular weights.These results confirm the existence of two protomer entities easily cleaved by partial reduction but the need of high concentration of urea to separate the protomer, suggests the existence of additional strong non-covalent interactions between the two hemimolecules.
Functional Properties of Two Different Molecular Forms of α2-Plasmin Inhibitor
Authors: Clemmeneon I. , Thorsen S. , Müllertz S. 
Published: May 2019

The α2-plasmin inhibitor in plasma exists in at least two molecular forms (1). One form (PB) binds to plasminogen-Sepharose. The other form (NPB) comprising around 0.4 of the total amount of the inhibitor in plasma does not bind to plasminogen-Sepharose. PB was purified by affinity chromatography (1) while NPB was partially purified by conventional methods (2). Both inhibitor forms inhibited plasmin in a fast reaction and the change in catalytic concentration of plasmin with increasing concentrations of both forms was a linear function. At identical active site concentrations of the two forms (titrated with pNPGB-titrated plasmin) PB produced a more marked inhibition of urokinase-induced fibrinolysis. Similarily PB produced a more marked decrease of the binding af Lys-plasminogen to fibrin than NPB. The results indicate that an equilibrium between the 2 forms may be important for the biological regulation of the inhibition of plasmin.1: I. Clemmensen, The Physiological Inhibitors of Coagulation and Fibrinolysis; D. Collen, B. Wiman, M. Verstraete, eds., p. 131-136, Amsterdam 1978.2: U.Christansen & I. Clemmensen, Biochem. J., 175:635-641, 1978.
Red Cell Deformability and Risk Factors in one Hundred Patients with Cerebrovascular Thrombosis
Authors: Boisseau M. R. , Lorient M. F. , Bricaud H. 
Published: May 2019

Erythrocyte deformability measured by Nucleopore filtration method was significantly (p 0.001) decreased in patients with CVA (filtration time (FT) = 57 ± 28 s. × ml-1) compared with two hundred heathly subjects (FT = 33 ± 6 s. × ml-1). Among the risk factors erythrocyte deformability mainly depended upon the gravity of Hypertension (FT = 77 ± 35 s. × ml-1; p 0.001), Additionnai risk factors such as hyperlipemia, diabetes were less effective.In all cases high FT were observed in patients with widespread atherosclerotic lesions (carotid stenosis, arteritis).Finally in thrombotic states, as CVA, the decrease of red cell deformability appears to be strongly correlated to vascular diseases and risk factors.
Potential Sources of Emboli in Transient Cererral and Retinal Ischaemia
Authors: de Bono D. , Warlow C. , Hyman N. 
Published: May 2019

91 consecutive patients with transient ischaemic attacks (TIAs) were examined for potential source of emboli using echo cardiographyand ambulatory ECG monitoring in addition to clinical examination and angiography. Patients were divided into those with amaurosis fugax and/or carotid TIAs (45), “hemiphenomena” TIAs <26) and vertebrobasilar TIAs (20).“Structural” cardiac defects (of which mitral valve prolapse accounted for just under half) occurred in 34% of patients, significantly more than in age-matched controls. 40% of patients with amaurosis fugax and/or carotid TIAs had carotid artery lesions, as did 30% of those with “hemiphenomena” attacks.6 patients had both cardiac and carotid lesions. Arrhythmias were detected in 15% of patients and a similar proportion of controls. Hypertension and ischaemic heart disease were more common in the patients.Structural cardiac abnormalities, which may not be haemodynamically significant, might account for cerebral and retinal emboli in about a third of patients presenting with TIAs. The natural history and the most effective therapy of this subgroup require evaluation independently of patients with predominantly carotid atheromatous lesions.