bluuebunny/crossref_metadata_2025 huggingface dataset:
Image denoising via an improved non‐local total variation model
Authors: Bai Yunjiao , Liu Yi , Zhang Quan , Jia Lina , Gui Zhiguo
Published: July 2018

This study presents an improved non‐local total variation (NLTV) model by using the block‐matching and three‐dimensional filtering (BM3D) algorithm for image denoising. First, the preprocessed image is obtained with the BM3D algorithm. Then, taking the place of the noisy image, the preprocessed image is used to construct the fidelity term of the energy functional and calculate the weight function in NLTV regularisation term. Finally, the energy functional is solved by the split Bregman algorithm. Experimental results demonstrate that the proposed model achieves better denoising performance than the original NLTV model in the visual appearance and objective indices, especially for the highly degenerated images. In addition, the proposed model can effectively suppress the appearance of the false information in the flat region, which overcomes the problem faced by the BM3D algorithm.
Reliability and performance of optimised Schmitt trigger gates
Authors: Tache Mihai , Ibrahim Walid , Kharbash Fekri , Beiu Valeriu
Published: July 2018

This study compares the performance and reliability of classical complementary metal‐oxide‐semiconductor (CMOS) gates with Schmitt trigger (ST) ones. The ST hysteresis, caused by the added positive feedback transistors, improves the design static noise margin (SNM) and offers noise immune operation. Hence, ST‐based circuits are expected to operate more reliably than the ones implemented using classical CMOS. Although many research papers have been focused lately on using ST design concepts for implementing more reliable static random access memory (SRAM) cells, significantly less work was devoted to the application of ST concepts in the combinatorial logic domain. Moreover, available research on ST‐based logic gates had only focused on the low‐voltage/power applications range. The authors are going to look at the whole voltage range and performance spectrum to compare and understand not only the SNMs and the power consumption (at different frequencies and voltage levels) but also the delay and the power‐delay‐product of ST‐based logic gates. These will be compared with classical CMOS as well as with optimally sized CMOS and ST‐based logic gates. This study should give a clear picture of the potential advantages ST could offer for combinatorial logic in advanced CMOS technology nodes and of their application range.
Neurophysiologie de l’occlusion : des sciences fondamentales à la pratique clinique
Authors: FOUGERONT Nicolas
Published: July 2018

L’absence de relation biunivoque entre
une modalité occlusale particulière
et la mastication est due à la grande variabilité
de la mastication, tant interindividuelle
qu’intra-individuelle au cours d’une même
séquence de mastication. Cependant,
l’occlusion d’intercuspidie maximale demeure
une référence. La variabilité de la mastication
ne signifie pas absence de relation entre
occlusion et fonction. Car malgré la faible
durée des contacts dento-dentaires par
nychtémère, ces derniers influencent
la fonction des points de vue dynamique
et cinématique. Ces relations sont le fait
de contrôles sensorimoteurs segmentaires
et suprasegmentaires. Généralement
le sujet sain (indemne de douleur) s’adapte
à une modification de l’occlusion car à très
court terme, les régulations sensorimotrices sont
efficaces. À plus long terme, ces adaptations
feraient intervenir des phénomènes de
neuroplasticité du cortex sensorimoteur primaire
de la face. Par contre chez le sujet douloureux,
les régulations sensorimotrices sont inefficaces
(les réflexes trigéminaux nociceptif et myotatique
sont déficients). Peut-être y aurait-il aussi
des phénomènes de neuroplasticité
corticale maladaptative. Ceci expliquerait
pourquoi certains patients ne s’adaptent pas
à une modification de l’occlusion.
Factor VII-Deficient Substrate Plasmas Depleted of Protein C Raise the Sensitivity of the Factor VII Bio-Assay to Activated Factor VII: an International Study
Authors: Miller G J , Stirling Y , Esnouf M P , Heinrich J , van de Loo J , Kienast J , Wu K K , Morrissey J H , Meade T W , Martin J C , Imeson J D , Cooper J A , Finch A
Published: July 2018

Plasma from healthy individuals, pregnant women and patients on warfarin were distributed to 3 laboratories supporting major cardiovascular surveys (Northwick Park, Muenster and Houston) for assay of factor VII coagulant activity (VIIC) with their own bio-assays. The mean VIIC in 147 samples agreed to within 1% of standard in Northwick Park and Houston, but was 14% of standard lower in Muenster owing to its more potent standard. In samples with an increased VIIC the Northwick Park assay gave a higher result than the other assays owing to its increased responsiveness to activated factor VII (VIIa). Thus when VIIa concentrations were determined directly with a clotting assay which utilises a soluble recombinant tissue factor, the increase in VIIC with increase in VIIa was considerably greater with the Northwick Park assay than the Muenster assay. This feature of the Northwick Park assay was traced to the virtual absence of protein C in its substrate plasma. Factor Va appears rate-limiting for the coagulant expression of VIIa in test plasma. If the thrombotic response to release of tissue factor is determined by the circulating concentration of VIIa, then the Northwick Park factor VII bio-assay may be preferable to other bio-assays currently employed to estimate risk of acute coronary events.
Comparison of the Effects of Two Diets Rich in Monounsaturated Fatty Acids Differing in their Linoleic/α-Linolenic Acid Ratio on Platelet Aggregation
Authors: Freese Riitta , Mutanen Marja , Valsta Liisa M , Salminen Irma
Published: July 2018

The effect of dietary linoleic/α-linolenic acid ratio on human platelet aggregation in vitro was investigated using low-erucic acid rapeseed oil and high-oleic acid sunflower oil as the major fat sources. In a cross-over study 20 healthy male subjects, average age 29 year (range 20–46 yr), followed experimental rapeseed oil (RO) and Trisun-sunflower oil (TSO) diets after their habitual diet for six weeks. Subjects were provided most of the fat containing foods but were allowed to eat other foods almost freely. Fatty acid compositions of the diets calculated from dietary records were as follows (saturated/monounsaturated/polyunsaturated fatty acids): RO diet 12.4/18.6/8.9% of total energy (en%) (linoleic/α-linolenic acid ratio 2.8) and TSO diet 11.8/17.8/8.3 en% (linoleic/α-linolenic acid ratio 28), respectively. Plasma cholesterol ester fatty acid composition proved compliance to the experimental diets. Platelet aggregations induced by ADP (1,2 and 3 μM) or thrombin (0.12, 0.15 and 0.18 NIH/ml) were significantly enhanced and collagen- (1.5, 2.5 and 5.0 μg/ml) induced aggregation tended to be enhanced after the TSO diet compared with the RO diet. After the TSO diet platelet aggregation was enhanced from the level of the habitual diets by one thrombin (0.18 NIH/ml), one collagen (1.5 μg/ml) and all three ADP concentrations. The diets had no effect on antithrombin III activity. Results show that platelet aggregation in vitro decreases as the ratio of linoleic acid to a-linolenic acid decreases in diets rich in monounsaturated fatty acids.
Inhibitor-Resistant Tissue-Type Plasminogen Activator: An Improved Thrombolytic Agent In Vitro
Authors: Shohet R V , Spitzer S , Madison E L , Bassel-Duby R , Gething M-J , Sambrook J F
Published: July 2018

Platelet-rich clots are inefficiently lysed by current fibrinolytic agents. Platelets contain a great deal of plasminogen activator inhibitor 1 (PAI-1), the principal endogenous inhibitor of tissue-type plasminogen activator (t-PA). We have tested whether PAI-1 resistant t-PAs would be more effective thrombolytic agents in an in vitro model of platelet rich clots. Clots were formed with recalcified human plasma without or with the addition of platelets. The lysis of these clots was followed by the release of incorporated 125I-fibrinogen. Mutant and wild-type t-PA were almost equally effective against clots lacking platelets but the mutant was twice as effective at lysing platelet-rich clots. A mechanism for this effect is suggested by the demonstration that a complex between wild-type t-PA and extruded platelet contents resembles that between purified t-PA and PAI-1 and that the PAI-1 resistant t-PA does not interfere with formation of this adduct. Because of its enhanced ability to lyse platelet-rich clots in vitro, further in vivo work may find that PAI-1 resistant t-PA is a more efficacious therapeutic agent than wild-type t-PA in situations where platelets contribute to the failure of thrombolysis.
Thrombogenicity of the Injured Vessel Wall – Role of Antithrombin and Heparin
Authors: Frebelius Siw , Hedin Ulf , Swedenborg Jesper
Published: July 2018

The thrombogenicity of the vessel wall after endothelial denudation is partly explained by an impaired inhibition of thrombin on the subendothelium. We have previously reported that thrombin coagulant activity can be detected on the vessel wall after balloon injury in vivo. The glycosaminoglycans of the subendothelium differ from those of the endothelium and have a lower catalyzing effect on antithrombin III, but inhibition of thrombin can still be augmented by addition of antithrombin III to the injured vessel surface.

In this study the effect of antithrombin III and heparin on thrombin coagulant activity on the vessel wall was studied after in vivo balloon injury of the rabbit aorta using biochemical and immunohistochemical methods and thrombin was analysed after excision of the vessel. Continuous treatment with heparin, lasting until sacrifice of the animal, or treatment with antithrombin III resulted in significant reduction of thrombin coagulant activity on the injured aorta. Heparin given only in conjunction with the injury did not prevent thrombin coagulant activity or deposition of fibrin on the surface.

The capacity of the injured vessel wall to inhibit thrombin in vitro was improved on aortic segments obtained from animals receiving antithrombin III but not from those given heparin. It is concluded that treatment with antithrombin III interferes with thrombin appearance on the vessel wall after injury and thereby reduces the risk for thrombosis.
Radioimmunoassay of an Early Plasmin Degradation Product of Human Fibrinogen, “Fragment A”, and its Clinical Application
Authors: Takagi Kimiteru , Kawai Tadashi
Published: July 2018

Upon the plasmin digestion of human fibrinogen, an early cleavage product, which has been designated as fragment A, was isolated, and to study the action of plasmin in the circulation, radioimmunoassay for fragment A was carried out. This assay used rabbit immune serum obtained by injection of fragment A mixed with complete Freund’s adjuvant, and fragment A was labeled with 125I using the Chloramin-T method.

In 20 normal healthy donors its serum level was 3.57 ± 1.62 μg/ml (mean ± SD), and it was increased significantly in certain diseases, such as acute leukemias, cardiovascular disorders, malignancies, renal failure, systemic lupus erythematosus and sepsis.
A Rapid Turbidimetric Determination of Fibrinogen Degradation Products (FDP)
Authors: Verbruggen H W , Wessels J M C
Published: July 2018

A rapid and simple turbidimetric determination of fibrinogen degradation products is described. This method is based on the increase of the turbidity due to the formation of precipitating antigen-antibody complexes after addition of rabbit antihuman fibrinogen antiserum to human serum. The increase in turbidity correlates very well with results obtained with the haemagglutination inhibition technique and has the advantage of a more objective quantitation. The reproducibility appears to be quite good. The turbidimetric method is independent of the colour of serum samples.
Effect of Orthostatic Changes on Urokinase Excretion
Authors: Wilcox Gilbert M , Hial Valdemar , Horwitz David , Pisano John J , Keiser Harry R
Published: July 2018

The effects of orthostatic changes on the excretion of urokinase were studied in healthy normal volunteers. Urokinase excretion rose (average +69%) significantly (p<.005) while urine volume fell (average–59%) significantly (p <.001) after the subjects had been standing. There was no difference between men and women nor was there an apparent diurnal variation in urokinase excretion of recumbent subjects. A relationship between urokinase excretion and sympathetic nervous system activity is suggested.
Immobilization of Plasminogen Activator, Urokinase, on Nylon
Authors: Sugitachi Akio , Taragi Kunihiko , Imaoka Shingi , Kosaki Goroh
Published: July 2018

Urokinase (UK), a fibrinolytic enzyme activator purified from human material was immobilized on nylon using different procedures. One was a modified method of immobilization of antigen or antibody initially carried out by Edelman and others in 1971 (Procedure I). The other was our newly devised method (Procedure II) (Sugitachi et al. 1976).

Major specificities of the immobilized UK are as follows:

1. The UK revealed properties of a plasminogen activator and the optimum pH of the immobilized UK was between 7.2 and 7.4, these values being in good parallel with that of soluble UK. The immobilized UK maintained a stable fibrinolytic activity after long-term preservation and heat-treatment.

2. As the fibrinolytic activity of immobilized UK was found to be inhibited by the antiplasmin in human plasma, an antiplasmin inhibitor was immobilized on the nylon together with the UK.

The antiplasmin activity was to some extent prevented using this procedure.

3. Nylon tubes immobilized with UK and antiplasmin inhibitor were used for thrombotic coagulation studies carried out according to the method of Chandler. Thrombus formation time (TFT) of UK-immobilized tubes was 30 min, while that of the non-treated tubes was no longer than 10 min.
Immunologic Studies of Antithrombin III Heparin Cofactor in the Newborn
Authors: Hathaway W E , Neumann L L , Borden C A , Jacobson L J
Published: July 2018

Serial quantitative immunoelectrophoretic (IE) measurements of antithrombin III heparin cofactor (AT III) were made in groups of well and sick newborn infants classified by gestational age. Collection methods (venous vs. capillary) did not influence the results; serum IE measurements were comparable to AT III activity by a clotting method. AT III is gestational age-dependent, increasing from 28.7% of normal adult values at 28-32 weeks to 50.9% at 37-40 weeks, and shows a gradual increase to term infant levels (57.4%) by 3-4 weeks of age. Infants with the respiratory distress syndrome (RDS) show lower levels of AT III in the 33-36 week group, 22% vs. 44% and in the 37-40 week group, 33.6% vs. 50.9%, than prematures without RDS. Infants of 28-32 week gestational age had only slight differences, RDS = 24%, non-RDS = 28.7%. The lowest levels of AT III were seen in patients with RDS complicated by disseminated intravascular coagulation and those with necrotizing enterocolitis. Crossed IE on representative infants displayed a consistent pattern which was identical to adult controls except for appropriate decreases in the amplitude of the peaks. The thrombotic complications seen in the sick preterm infant may be related to the low levels of AT III.
Thrombin Generation and Neutralization Test (TGNT) - a Simple, Practical, and Sensitive Assay for Plasma Heparin Quantitation
Authors: Stavridis I C , Vorias N I
Published: July 2018

A simple, quantitative method for detection of small amounts of heparin in human plasma is described. This method is based on the activation of coagulation factor X to its enzymatic form (Xa), by a mixture of RVV platelet substitute (Esnouf and Williams 1962, Esnouf and Jobin 1967) in a plasma rendered fibrinogen free without affecting other clotting factores (Bell et al. 1968, Bell 1973), by Arvin (Ancrod).

Activation of factor X, results in thrombin generation. Thrombin inactivation by its natural inhibitors depends on the time elapsed from the start-point of activation. The inactivation process is enhanced by heparin (Biggs et al. 1970, Blomback et al. 1963) and this enhancement depends on the quantity of heparin in the plasma.
Acquired Inhibitors of Factor V
Authors: Feinstein Donald I
Published: July 2018

The clinical and laboratory data on the 12 patients with an acquired inhibitor to factor V have been reviewed. The degree of clinical bleeding in these patients varied from none to severe, and in most patients the inhibitor was transient. The combination of a markedly prolonged partial thromboplastin time and Quick prothrombin time and failure of normal plasma to correct these tests, in the presence of a normal thrombin and prothrombin and proconvertin time, seems to be pathognomonic for a factor V inhibitor. The inhibitors have physicochemical properties of immunoglobulins and a few have been characterized as polyclonal IgG antibodies or a mixture of IgM and IgG antibodies. The etiology and pathophysiologic mechanism of their development is unknown, but there seems to be a close relationship to major surgery. When tested with inhibitor plasma, the plasmas from 9 patients with hereditary factor V deficiency from 7 unrelated families did not contain factor V antibody-neutralizing material.
The Effect of ICI 55,897 and Clofibrate on Platelet Function and Other Tests Abnormal in Atherosclerosis
Authors: O’Brien J R , Etherington M D , Jamieson Sandra , Sussex Janet , Shuttleworth R D
Published: July 2018

There is considerable evidence that the quantity or quality of plasma lipids influences platelet function tests, and clofibrate reduces high plasma lipids and alters some platelet tests. Clofibrate was accordingly given to patients with vascular disease who were at risk of thrombosis. The heparin thrombin clotting time (HTCT), initially short and thus possibly reflecting increased activation, was regularly returned to normal after about a month’s delay. The fibrinogen was also normalized but the initially abnormal anti-thrombic activity became more abnormal. ICI 55,897, an analogue of clofibrate, also normalized the HTCT and the fibrinogen and had no adverse effect on the anti-thrombin levels. This compound has no effect on plasma lipids. If it can be shown that the correction of abnormal tests conveys clinical benefit these findings suggest that ICI 55,897 might clinically be more beneficial than clofibrate. However, direct comparison of clofibrate and ICI 55,897 suggests that clofibrate is more effective in normalizing the HTCT. The mechanisms underlying these drug-induced changes are unknown but they cannot be directly related to lipid changes.
In Vitro Interaction between Cultured Cells and Human Blood Platelets
Authors: Holme Randi , Oftebro Reidar , Hovig Torstein
Published: July 2018

The effects of washed human cultured cells (tumour cells and Chang liver cells) on human blood platelets in heparinized plasma were studied. Platelet aggregation was induced by suspensions of the tumour cells. Ultrastructural examination showed that the platelets, especially in the central regions of the aggregates, were tightly packed and the α-granules were mostly present. In the periphery of the aggregates the platelets appeared swollen and devoid of organelles, and fibrin strands were seen. The platelet aggregation was not completely abolished by incubation with apyrase. The washing fluids from the tumour cells also induced platelet aggregation, but the aggregation could be abolished by incubation with apyrase.

When three different lines of the Chang cells were used, suspensions of two lines of these cells induced platelet aggregation, but the third line did not. Presence of ADP could be demonstrated in the washing fluids from the cultured cells, except for the one line of Chang cells which did not induce platelet aggregation. The experiments indicated that the platelet aggregation induced by the various types of cells was mediated via ADP, but with a possible additional effect of coagulation activity.
Altered Factor VIII Complexes in Patients with Acute Respiratory Insufficiency
Authors: Grant K , Rodvien R , Mielke C H
Published: July 2018

Acute respiratory failure is an often-fatal syndrome of multiple etiologies in which altered factor VIII may be a marker of endothelial disease. 12 women with overwhelming viral pneumonia were studied with serial factor VIII antigen, procoagulant activity, and von Willebrand’s factor assays. Antigen levels were elevated (range: 86-1644%) out of proportion to procoagulant activity (range: 35-521 % by a one-stage assay), and factor VIII antigen to activity ratios were as high as 16:1. Von Willebrand’s factor was normal but correlated best with procoagulant activity. All patients had abnormal antigen patterns on crossed immunoelectrophoresis, with increases in protein of both fast and slow mobility. These changes in factor VIII correlated with the patients’ clinical courses.
Heparin from Intestine and Lung Source Administered in Large Dose to Dogs with Acute Myocardial Ischemia
Authors: Saliba Michael J , Pavalec Richard J
Published: July 2018

Intestinal mucosa heparin (IMH) and beef lung heparin (BLH) were infused into dogs subjected to myocardial ischemia by intermittent coronary artery occlusions. The IMH was from a mixture of beef, sheep, and pig intestinal mucosa. Initial control occlusion and recovery was followed by a second occlusion with 60,000 units of IMH or BLH added. Electrocardiographic S-T segment elevations (ST) were measured acutely. There were no significant differences in ST in non-ischemic myocardium before occlusions or with occlusions. In ischemic myocardium, IMH significantly lowered control ST 84% in amount (t = 6.1 p <0.00005), and 76% in number (t = 11.6 p <0.00001). BLH lowered control ST a significant, lesser, 36% in amount (t = 3.6 p <0.008), and 35% in number (t = 3.2 p <0.01). The difference between IMH and BLH in ischemic myocardium was a significant 48% in amount (t = 4.0 p <0.0007), and 41% in number (t = 2.0 p <0.06). Myocardial adenosine triphosphate (ATP) levels were assayed after 90 min. ATP levels were 31% higher in both ischemic and non-ischemic myocardium in IMH-treated dogs than in BLH- treated. It was concluded that IMH and BLH are functionally different, and IMH was significantly more effective.
Relationship of Factor IX Antigen and Coagulant in Hemophilia B Patients and Carriers
Authors: Pechet Liberto , Tiarks Cheryl Y , Stevens Joyce , Sudhindra Ramakrishna R , Lipworth Leslie
Published: July 2018

A neutralizing and precipitating monospecific antiserum to human factor IX was developed. Plasmas from 224 hemophilia B patients, 39 obligatory and 38 possible carriers were studied by coagulant assays and Laurell’s electroimmunoassays. Based on factor IX coagulant (IX-C) to IX antigen (IX-Ag) ratios, the patients were classified as being either concordant (ratios ≥0.71) or discordant (<0.71). The diagnostic classification into concordant and discordant patterns is difficult in patients with low levels of antigen where the two forms may merge due to the insensitivity of the assay below 12%. Of the total cases studied by us, 36% were discordant (excess antigen). This is in agreement with 33.66%, a composite figure representing 199 cases described in five recently published papers, and indicates that approximately one-third of the hemophilia B population is of the discordant type. The pattern, when established, was found consistent in each kinship studied.

Crossed antigen-antibody electrophoresis did not reveal any abnormalities in the hemophilia B plasmas with measurable IX-Ag.

We found a low incidence of the BM variety. Determining this type of hemophilia B did not appear to increase the degree of predictability of the carrier state.

Studies of carriers demonstrated that immunologic techniques did not contribute to the predictability of the carrier state in pedigrees of the concordant variety. In the discordant group a factor IX-C/IX-Ag ratio of 0.7 or less indicated that a female was very likely to be a carrier. An improvement in the prediction of the carrier state in females of the discordant pattern was demonstrated.
Factor VII Antigen Levels in a Healthy Blood Donor Population
Authors: Howard P R , Bovill E G , Pike J , Chruch W R , Tracy R P
Published: July 2018

We determined factor VII antigen (FVIIag) levels in 705 healthy blood donors ranging in age from 17 to 79 years using a two-site solid-phase enzyme immunoassay developed in our laboratory. The mean (± SD) FVIIag level for the total population was 102 ± 31%. FVIIag levels for men (n = 375) and women (n = 330) were 101 ± 28% and 103 ± 33%, respectively. A significant increase in FVIIag was observed with age in both men (r = 0.25, p <0.0001) and women (r = 0.35, p <0.0001). FVIIag levels were significantly higher in women > 60 years when compared to men (median women: 125%; median men: 111%; p <0.05). On a subset of the study group (n = 45), FVIIag levels were correlated to total cholesterol (r = 0.27, p = 0.08) and triglyceride (r = 0.41, p <0.01). Assuming the commonly used reference interval of 60-140% for FVII, the frequencies of FVIIag values for <60% and >140% using our assay were 2.1% and 9.2%, respectively. Gender and age-related differences in FVIIag levels must be considered in a reference interval. We further suggest that assay-specific reference ranges be established, which may include values outside the commonly used values of 60-140%.
Increased Mononuclear Cell Tissue Factor and Type-2 Plasminogen Activator Inhibitor and Reduced Plasma Fibrinolytic Capacity in Children with Lymphoma
Authors: Semeraro N , Montemurro P , Giordano P , Santoro N , De Mattia D , Colucci M
Published: July 2018

Blood clotting activation and fibrin deposition are common findings in lymphoma patients. We evaluated the capacity of peripheral blood mononuclear cells to produce procoagulant activity (PCA) and plasminogen activator inhibitor (PAI) in 12 children with newly diagnosed lymphoma (8 non-Hodgkin’s, 4 Hodgkin’s) and in 12 matched healthy donors. In the same subjects we also measured plasma antigen levels of tissue-type PA (t-PA), urokinase-type PA (u-PA), PAI-1, PAI-2, and D-dimer. PCA generated by mononuclear cells after incubation for 20 h at 37° C was significantly higher in patients than in controls (p = 0.027). In all samples it was identified as tissue factor by functional criteria (dependence on factor VII). Moreover, culture medium obtained from patients’ mononuclear cells after incubation for 20 h at 37° C contained significantly higher amounts of PAI activity and PAI-2 antigen than control samples (p <0.001). Plasma PAI-1 and t-PA antigens were significantly augmented in patients (p <0.005), the mean increase of PAI-I being about 5 times higher than that of t-PA. Plasma levels of D-dimer wete markedly increased in the patients’ group (p <0.001), whereas u-PA and PAI-2 antigens did not differ from controls. It is suggested that monocytes from lymphoma patients are endowed with functional abnormalities leading to the simultaneous expression of tissue factor and antifibrinolytic activity. These abnormalities, coupled with a reduced plasma fibrinolytic potential, could play an important pathogenetic role in blood clotting activation and fibrin deposition associated with lymphoma.
Six Novel and Three Recurrent Mutations in Nine Austrian Patients with Hemophilia B
Authors: Walter J , Pabinger-Fasching I , Watzke H H
Published: July 2018

In this report we describe the molecular basis of the factor IX (FIX) deficiency in nine patients with severe (n = 6), moderate (n = 1) or mild (n = 2) hemophilia B. The following genetic defects were identified by enzymatic amplification with the polymerase chain reaction (PCR) and subsequent direct sequencing of all exons and exon-intron-junctions: patient B.B. (FIX “Vienna I”): deletion of nucleotides 6343 to 6362; patient M.H. and W. J. (FIX “Vienna II”): nucleotide 17704 (C to G), Gin 97 to Glu; patient L. K. (FIX “Vienna III”): nucleotide 17761 (C to T), Arg 116 to stop; patient U. A. (FIX “Vienna IV”): nucleotide 10415 (C to G), Pro 55 to Ala; patient H.G. (FIX “Vienna V”): nucleotide 6488 (C to T), Thr 38 to lie; patient H. M. (FIX “Vienna VI”): nucleotide 31276 (G to C), Trp 385 to Cys; patient L. C. (FIX “Vienna VII”): deletion of nucleotide 6700; patient S.F. (FIX “Vienna VIII”): nucleotide 10392 (A to T), Asp 47 to Val. The causative mutation was detected in the FIX gene in each of the nine patients with hemophilia B. There was one small deletion, one point deletion and seven point mutations. The latter include six missense mutations and one nonsense mutation. The mutations in Vienna III, IV and V have already been described in previous studies. The two deletions, Vienna I and Vienna VII have not been reported previously. The genetic defects observed in Vienna II, VI and VIII are novel missense mutations which result in amino acid changes at residues 97,47 and 385, respectively.
D-Dimer Determination to Exclude Pulmonary Embolism: a Two-Step Approach Using Latex Assay as a Screening Tool
Authors: de Moerloose P , Minazio Ph , Reber G , Perrier A , Bounameaux H
Published: July 2018

D-dimer (DD), when measured by a quantitative enzyme-linked immunosorbent assay (ELISA), is a valuable test to exclude venous thromboembolism (VTE). However, DD ELISA technique is not appropriate for emergency use and the available agglutination latex assays are not sensitive enough to be used as an alternative to rule out the diagnosis of VTE. Latex assays could still be used as screening tests. We tested this hypothesis by comparing DD levels measured by ELISA and latex assays in 334 patients suspected of pulmonary embolism. All but one patient with a positive (DD ≥500 ng/ml) latex assay had DD levels higher than 500 ng/ml with the ELISA assay. Accordingly, ELISA technique could be restricted to patients with a negative result in latex assay. This two-step approach would have spared about 50% of ELISA in our cohort. In conclusion, our data indicate that a latex test can be used as a first diagnostic step to rule out pulmonary embolism provided a negative result is confirmed by ELISA and the performance of the latex assay used has been assessed properly.
Circulating Endothelial Cell/Leukocyte Adhesion Molecules in Atherosclerosis
Authors: Blann Andrew D , McCollum Charles N
Published: July 2018

Soluble adhesion molecules E-selectin, intercellular adhesion molecule (sICAM) and vascular cell adhesion molecule (sVCAM) were measured alongside von Willebrand factor (vWf) in 40 patients with peripheral vascular disease (PVD), 43 with ischaemic heart disease (IHD) and in equal numbers of age and sex matched asymptomatic controls. Increased vWf was found in patients with IHD (p = 0.0008) and in patients with PVD (p = 0.0001) relative to their respective controls but levels did not differ between the two patient groups. Raised sICAM was found in both PVD (p = 0.0003) and IHD (p = 0.0059) compared to their respective controls and was higher in PVD than in IHD (p = 0.0088). In the subjects taken as a whole, there was no correlation between vWf and sICAM. Levels of soluble E-sel-ectin and sVCAM did not differ in patients or controls. These data suggest that soluble ICAM may be useful as an index of endothelial cell activation in clinical manifestations of atherosclerosis.
Meningioma of the Pineal Region — Differential Radiologic Aspects of Pineal Region Tumors Based on a Clinical Case
Authors: Avelar Tiago , Paiva Aline , Costa Márcio , Aguiar Guilherme , Vitorino João , Veiga José
Published: July 2018

Pineal region tumors are uncommon among neoplasm of the central nervous system, with this region being the most heterogeneous in terms of histological types. Meningiomas are rarer still, but can be found at this site, with origins in either the velum interpositum or falcotentorial junction. Neuroimaging exams can distinguish malignant from benign lesions besides helping to define the origin of the lesion as the pineal parenchymal or surrounding structures. We report the case of a woman with a pineal region tumor in which differential diagnoses included meningioma and germinoma, with confirmation of the former based on radiological characteristics and histopathology. In addition, a brief review of differential diagnoses and approaches for cases of lesions in this region is provided.
Antifibrinolytic Activity of Certain Pectins
Authors: Nilsson Inga Marie , Björkman Sven Erik , Studnitz Wilfried v. , Hallén Acke
Published: July 2018

Ingestion of wine and beer, but not of ethyl alcohol, produced a decrease of the blood fibrinolytic activity. In vitro experiments showed that wine and beer contained a principle which inhibited fibrinolytic activators. This principle was isolated from grape pulp, and upon analysis it was found to be a pectin-like substance.
The Formation of Intermediate Product I in a Purified System The Role of Factor IX or of its Precursor and of a Hageman Factor-PTA Fraction
Authors: Yin E. T , Duckert F
Published: July 2018

1. The role of two clot promoting fractions isolated from either plasma or serum is studied in a purified system for the generation of intermediate product I in which the serum is replaced by factor X and the investigated fractions.

2. Optimal generation of intermediate product I is possible in the purified system utilizing fractions devoid of factor IX one-stage activity. Prothrombin and thrombin are not necessary in this system.

3. The fraction containing factor IX or its precursor, no measurable activity by the one-stage assay method, controls the yield of intermediate product I. No similar fraction can be isolated from haemophilia B plasma or serum.

4. The Hageman factor — PTA fraction shortens the lag phase of intermediate product I formation and has no influence on the yield. This fraction can also be prepared from haemophilia B plasma or serum.
The Relation between a Naturally Occuring Inhibitor and Prothrombin in Intermediate Product I Formation
Authors: Yin E. T , Shanberge J. N , Duckert F
Published: July 2018

1. A method for the separation from clotting factors and the concentration of an inhibitor of intermediate product I present in adsorbed plasma and adsorbed serum is described.

2. This inhibitor is not only stable but also activated at 37° C. At 4° C it loses activity.

3. The inhibitory effect on the formation of intermediate product I is counteracted by small amounts of prothrombin or thrombin.

4. After addition of inhibitor prothrombin is necessary for the formation of intermediate product I in the purified system.

5. The discrepancy, in regard to the need for prothrombin (or thrombin) between the purified and the non-purified system can be explained by the relative amounts of inhibitor in the two systems.
The Prephase Accelerator. Present Status
Authors: Duckert F
Published: July 2018

The properties of the prephase accelerator (PPA) are indicated as well as its differentiation from other known clotting factors. PPA is either a reaction product or a degratation product. For its normal formation genuine factor IX, PTA and ? Hageman factor are necessary.

The one-stage quantitative assay method for factor “IX” does not determine the factor lacking in haemophilia B. This method gives a measure of PPA.

Some practical observations are made concerning the value of the one-stage assay method for factor “IX” and of the thromboplastin generation test for the diagnosis of haemophilia B.
Some Observations on the Rôle of Hageman Factor in Blood Coagulation
Authors: Haanen C , Hommes F , Morselt Gerdy
Published: July 2018

The defective thromboplastin formation in Hageman factor deficient plasma is completely corrected using incubation tubes which have been coated previously with normal plasma. Positively or negatively charged molecules as protamin and sulphated polysaccharides interfere with this correction in a way that gives evidence Hageman factor is a positively charged protein.

The defective thromboplastin generation of Hageman factor deficient incubation mixtures is corrected by addition of a purified Hageman factor preparation. Pre-incubation of Hageman factor with HF deficient serum improves the thromboplastin formation further, while pre-incubation of Hageman factor with HF deficient plasma abolishes this correction complete. Possibly here lies the key for the fact that serum clotting factors augment and plasma factors deteriorate during the clotting process.
The Use of DEAE Cellulose in the Preparation of a Factor VIII (AHG)-free Bovine Fibrinogen Reagent
Authors: Stapp W. F
Published: July 2018

Adequate fibrinogen reactivity is suggested as an additional requirement for specific fibrinogen reagents, to be added to the well known requirements of protein concentration, optimum pH, and optimum ionic strength. Reasons and a method for testing are outlined.

A method for the preparation of a specific fibrinogen reagent, deficient in factor VIII, from BaSO4 adsorbed bovine plasma is described in detail. The method described utilizes either fresh or regenerated DEAE cellulose as an adsorbent in a non-column chromatographic adsorption procedure, associated with a dialysis procedure in which the final fibrinogen product is concentrated and precipitated as a “euglobulin”. The “euglobulin” fibrinogen precipitate was then dissolved/suspended in buffered saline at a specific pH and NaCl concentration. Essentially the method can be briefly outlined into 5 separate steps:

1. Dialysis of BaSO4 adsorbed bovine plasma against 0.5% NaCl at pH 6.6 in 0.005 M Imidazole-HCl buffer.

2. Washing of DEAE cellulose with the same type of buffered NaCl solution to specific conditions.

3. Mixing of the dialyzed BaSO4 adsorbed bovine plasma with the washed DEAE cellulose and separation by centrifugation.

4. Concentration of the cellulose adsorbed plasma as a “euglobulin” fibrinogen precipitate by dialysis against running tap water.

5. Dissolving of the “euglobulin” fibrinogen precipitate in 0.9% NaCl buffered at pH 6.8.

Fibrinogen preparations, prepared with the use of regenerated DEAE cellulose were found to be similar to those prepared by fresh DEAE cellulose in fibrinogen reactivity and deficiency in factor VIII activity, but were found to have less fibrinogen concentration than those prepared using fresh DEAE cellulose.

Suggestions were also made for possibly increasing the over-all yield of the fibrinogen reagent through use of a “washing-elution” procedure.

The procedure that was used for regenerating the DEAE cellulose was also described in detail and commented upon.
The Investigation of a Patient with an Unusual Coagulation Defect
Authors: Gomes Emiliano L. , Calicchio Therezinha R. , Biggs Rosemary
Published: July 2018

1. The coagulation defect of a patient whose blood contains an inhibitor is described.

2. The inhibitor lengthens the clotting time of plasma in the presence of weak thromboplastin and also interferes with the mechanism of glass contact activation.

3. It is suggested that the inhibitor is similar to those which occur in the blood of patients with disseminated lupus erythematosus.
On the Physiological Antiacogulating System
Authors: Kudrjashov B. A
Published: July 2018

1. The influence of intravenous injections of thrombin has been tested on frogs and rats.

2. After thrombin or thromboplastin injection the animals produce anticoagulant activity which is, to a certain extent, quantitatively related to the activity injected.

3. If the animals tested are under anaesthesia or if the medulla oblongata is switched off the humoral reflex reaction is blockaded.

4. The importance of these observations for the prophylaxis of early postoperative thromboses is discussed.

5. These results combined with the effect of thrombin injection on the clotting factors in vivo are used for the elaboration of a coagulation scheme.
The Influence of Fibrin Stabilizing Factor on the Growth of Fibroblats in vitro and Wound Healing
Authors: Beck E , Duckert F , Ernst M
Published: July 2018

Congenital deficiency of Fibrin Stabilizing Factor (FSF) is the cause of both pathological haemostasis and poor wound healing. Experiments with fibroblast cultures were carried out to characterize the latter. Growth of the cultures in the patient’s plasma was quantitatively and qualitatively inferior as compared with the growth in normal control plasma, which contained FSF. Only by addition of normal plasma and purified FSF the poor cell growth was corrected. The necessity of fibrin present in the first stage of wound healing and possible modes of action of FSF in haemostasis and wound healing are discussed.
A Modified Thromboplastin Screening Test
Authors: Macpherson Janet C. , Hardisty R. M
Published: July 2018

A modification of the thromboplastin screening test of Hicks and Pitney is described, in which the effect of surface contact on the test plasma is controlled by the addition of a suspension of kaolin to the incubation mixture before recalcification.

Comparative studies show the modified test to give more reproducible results than the standard method.
On the Behaviour of a Human Serum Proactivator Reacting with Streptokinase during Artificial Activation of the Fibrinolytic System
Authors: Doleschel W , Auerswald W
Published: July 2018

During “spontaneous” activation of a human euglobulin preparation in suitably spaced samples — while plasminogen became progressively converted into piasmin — the proactivator content was tested by addition of equal amounts of streptokinase and evaluation of the lytic activities on heated and normal bovine fibrin plates. Indepedently of the decreasing content of plasminogen the proactivator which could be activated by streptokinase showed no significant change of concentration. These observation indicate that plasminogen is not acting as proactivator and that there exists a separate proactivator-activator system of the fibrinolytic mechanism in human serum.
A Method for Measuring Antithrombin
Authors: Hallén Acke
Published: July 2018

A method is described for measuring antithrombin II and III for routine clinical use. The conditions of the test are well defined and the test measures a comparatively higher percentage of the total AT capacity of the plasma than methods hitherto available and gives results in AT units.
Some Effects of Metal Cations on Blood Coagulation
Authors: Vulpis Nicoletta , Giorgino Riccardo
Published: July 2018

The action of some metal cations on blood coagulation was studied by means of t.e. graphic tracings. They exerted a delaying effect on coagulation process, as shown by the r increase and ma decrease. It is probably due to the formation of complex and reversible compounds. Adding a strong chelating agent, EDTA, caused perceptible reversal of the cation activity.
Tooth Extractions in Hemophilia Control of Bleeding without Use of Blood, Plasma or Plasma Fractions
Authors: Lucas O. N , Carroll R.T , Finkelmann A , Tocantins L.M
Published: July 2018

Hypnotic suggestion, loose packing of sockets and protection of the extractions area when properly done make it possible to carry out virtually painless tooth extractions in even the most severe hemophilics, with a minimum of hemorrhage and of physical or psychic trauma.

Following the principles outlined 91 teeth were extracted from 20 hemophilic patients, 17 of whom had classical hemophilia “A” ranging in severity from mild to very severe (75 extractions), while 3 had hemophilia “B” (16 extractions). Fifty extractions were carried out without hospitalization.

None of the extractions required pre or postoperative transfusions of blood, plasma or plasma fractions and there was no abnormal postoperative bleeding in any of the patients.

A successful non-hemorrhagic extraction depends on effective cooperation between Oral Surgeon and Haematologist and the scrupulous execution of all three principles stated and not any single one in particular.
Préparation d’une fraction anti-hémophilique A à partir de plasma A.C.D. standard
Authors: Janiak Alina , Soulier J.-P
Published: July 2018

Une méthode d’adsorption préférentielle du facteur VIII à partir du plasma ACD par le phosphate tricalcique à pH 6 est décrite. Le facteur VIII est élue et concentré par fractionnement alcoolique. Afin de stabiliser le facteur VIII, au cours de la préparation, on ajoute 5 mg/cm3 d’acide epsilon-amino-caproïque.

Le produit final contient 3 à 10 fois l’activité d’un même volume de plasma ACD (la concentration par mg de protéines est en moyenne de 30 à 50 fois). Le rendement moyen est de l’ordre de 60 p. 100. A côté du facteur VIII, la fraction contient environ la moitié du facteur IX et 20 à 30% de complexe VII; par contre, il est à peu près totalement dépourvu de fibrinogène.

Des recherches demeurent nécessaires afin d’apprécier si cette technique peut être appliquée à un fractionnement semi-industriel.
Is there a Hemostatic Effect of Peanuts in Hemophilioid Disorders?
Authors: Brakman Pieter , Sjølin Knud-Erik , Astrup Tage
Published: July 2018

1. Data on the effect of defatted peanuts in hemophilioid patients (deficient in Factor VIII or Factor IX) are presented.

2. Oral administration of peanuts is regularly followed by a decrease in spontaneous fibrinolytic activity of the blood.

3. A clinical effect of peanuts is limited and seems to be present only in mild disorders and in periods of mild relapse.

4. The data supports the concept that the peanut effect is indirect and is caused by an antiprotease delaying fibrinolysis.
The Nature of the Thromboplastic Activity Appearing during the Clotting of Pig’s Plasma
Authors: Cross M. J
Published: July 2018

1 During clotting, pigs’ plasma developed thromboplastic activity. This activity was compared with that of thrombin in accelerating the clotting of platelet-deficient plasma and of fibrinogen in the presence and absence of calcium.

2. The thromboplastic activity of the plasma could be mimicked by a solution of thrombin of the right strength.

3. The thromboplastic activity could be stabilised by freezing but disappeared rapidly at 37° C. Thrombin added to the serum was inactivated at almost exactly the same rate; and the rates of loss of both activities were considerably reduced by cooling, by decalcification with sodium ethylene-diaminetetraacetate, and by acidification.

4. It is concluded that the thromboplastic activity of undiluted recalcified pigs’ plasma can be accounted for by its thrombin content alone. It also seems likely that the activity measured in the screening test for disorders of thromboplastin generation described by Hicks and Pitney (1957) can be attributed wholly to thrombin.
Essential Athrombia
Authors: Inceman Seref , Ünügür Asuman , Aran Metin
Published: July 2018

A severe hemorrhagic disease was observed in a 15 month old infant. The laboratory studies revealed only one anomaly in the hemostatic mechanism of the patient: an impairment of the functions of agglomeration and adhesivity of his platelets. The authors believe that this is the second case in literature. The agglomeration and adhesive faculty of blood platelets and the relation of these platelet functions with blood coagulation, clot retraction and viscous metamorphosis are discussed.