bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE DYSFIBRINOGEN OF CHILDHOOD NEPHROSIS
Authors: Abshire T , Fink L , Christian J , O'Connell J , Hathaway W 
Published: August 2018

An abnormal fibrinogen (Fib) related to increased sialic acid (SA) has been described in adults with liver disease. This dysfibrinogen (Dysfib) seems most like fetal Fib. A review of 11 patients with nephrosis revealed an unexplained prolonged thrombin time (TT) and otherwise normal coagulation studies. Based on these observations, we sought to answer whether the prolonged TT defined a Dysfib and if this abnormal Fib was similar to fetal Fib. Pooled adult, fetal plasma, and the plasma of 3 patients with nephrosis were studied with TT and reptilase times (RT). Fib was measured by functional (Fib-act) and immunologic (Fib-ag) assays. An enzyme linked immunosorbent assay (ELISA) was established using antifibrinogen as the first antibody and either peroxidase conjugated Fib or a lectin (Limulus Polyphemus) specific for SA as the second antibody. The optical density was recorded per μgm Fib for both conjugated antifibrinogen or lectin and the ratio compared in order to estimate SA reactivity. Patient 3 was also studied by: 1) crossed immunoelectrophoresis (CIE) employing lectin in the first dimension and 2) polyacrylamide gel electrophoresis (PAGE) with transfer to nitrocellulose paper using Western Blot technique.Results of the CIE showed patient 3 and fetal plasma were similar in electrophoretic pattern and different from adult plasma. The PAGE with Western Blot revealed a similar pattern of Fib for patient 3, fetal and adult plasma. We conclude that the prolonged TT and RT, the greater amount of Fib-ag when compared to Fib-act in patients 1-3 and fetal plasma and the absence of evidence for Fib degradation products, support the diagnosis of Dysfib. The similarity of the CIE for patient 3 and fetal plasma and the difference between ELISA lectin/Fib ratio of patients 1-3 and fetal compared with adult plasma suggest that the Dysfib of nephrosis may be similar to fetal Fib.
A NEW THROMBOTIC DYSFIBRINOGENEMIA PRESENT IN SEVERAL MEMBERS OF A VENEZUELAN FAMILY
Authors: Arocha Piñango C L , Torres A , Marchi R , Rodríguez S , Camarillo H , Muller-Soyano A , Bosch N B 
Published: August 2018

Up to the present, 16 dysfibrinogenemias have been described with thrombotic symptomatology, of which 3 cases showed low affinity of the fibrin for thrombin.In this study, we describe a family with an elevated frequency of thrombotic episodes which may be due to an alteration in the fibrinogen molecule causing a defective adsorption of thrombin by the fibrin formed.Two women, mother and daughter, were admitted to our clinic with a history of repeated pulmonary thromboembolisms. Coagulation studies (which included Antithrombin III, Protein C, etc.) revealed only a prolonged thrombin time with high fibrinogen levels (500 mg/dl) by the clot weight and immunological methods. More detailed studies on fibrinogen function showed:1) Abnormal monomers aggregation and polymerization rate, ho changes were observed in the latter when induced by reptilase followed by thrombin.2) Normal fibrinopeptide release3) Normal cross-linked and uncross-linked fibrin chains.4) Low affinity of fibrin for thrombin5) Normal plasmin degradation6) The electron microscopy showed a normal fibrin net with the characteristic periodic cross-striations pattern but which formed more slowly than normal.Both patients were treated with oral anticoagulants. The mother has not suffered any thromboembolic episodes in two years of treatment but the daughter has shown clinical signs of minor episodes of pulmonary thromboembolism which were confirmed by perfussion gammagraphy. In the family study, 4 members have died due to either venous or arterial thrombotic accidents. Fibrinogen function studies carried out on 8 members from 3 generations showed a prolonged thrombin time with delayed polymerization in 4 of the 8 (1 adult, 3 children), none of which have suffered any thrombotic manifestations up to the time of the study.The name of Caracas V is proposed for this new dysfibrino-genemia.
THE EFFECTS OF ISCHAEMIC METABOLITES ON THE ENDOCARDIAL ENDOTHELIUM
Authors: Carter G , Gavin J B 
Published: August 2018

Although mural thrombosis is an important complication of myocardial infarction, little is known of the mechanisms by which death of underlying myocytes initiates thrombus fooiation cm the endocardiim. The sequence of morphological changes which develop in the endocardiim when exposed to ischaemic metabolites was determined in isolated beating rat hearts perfused with oxygenated Krebs-Henseleit buffer (KHB). Lactate (pH7.4), hydrogen ions (HC1, pH6.4) and lactic acid (pH6.4) were passed through a two-way concentric catheter ligated into the left ventricles for periods of 1,2,4,6 and 8 hours (n=4 in each group). Ventricles were then flushed with KHB, fixed in 2.5% glutaraldehyde and examined by scanning and transmission electron microscopy. The morphological changes observed wene qualitatively similar following the infusion of each solution, and all changes increased in severity and extent from one to four hours exposure. Quantitatively the most severe changes were observed with lactic acid. After one hour exposure to lactic acid 3.16 ± 2.35% of the endothelial cells on the papillary muscle showed separation and 7.85 ± 2.44% of cells had exfoliated exposing the basal lamina and after four hours 6.68 ± 2.0% of cells had separated and 16.05 ± 2.67% had been lost. Some exposed connective tissue fibres were evident after one hour (0.94 ± 1.19% of surface area exposed) and the smooth basal lamina had been lost from 4.67 ± 1.04% of the surface with subsequent exposure of the connective tissue after four hours. In all groups mitochondria of endothelial cells were swollen, their matrix electron-lucent and their cristae distorted and fragmented; the endoplasmic reticulun was diluted; and chromatin of nuclei was marginated and clmped (H+ ions and lactic acid only). Superficial myocytes showed similar changes. Electron dense inclusions were also observed in the mitochondria of myocytes exposed to hydrogen ions and lactic acid. Thus perfusion of the ventricle with ischaemic metabolites, which could diffuse from an infarct in vivo, can cause substantial damage to the endocardial endothelium.Research supported by the Medical Research Council of New Zealand
MODULATION OF ANTITHROMBOTIC EFFECTS OF CULTURED HUMAN ENDOTHELIAL CELLS BY INHIBITORS OF CYCLOOXIGENASE OR PHOSPHODIESTERASE
Authors: Müller T H , Rühr K , Callisen H H , Eisert W G 
Published: August 2018

Intact endothelial cells are known to form a non-thrombogenic surface and to actively restrict the extent of thrombus formation on denuded vessel walls via such mechanisms as the binding of thrombin and activation of protein C, or the synthesis and release of prostacyclin. In an in vitro system, we have investigated how platelet inhibitors modulate the antithrombotic effects of human endothelial cells. Human endothelial cells isolated from umbilical veins were plated on one half of a subendothelial matrix (SEM) harvested from bovine cornea endothelial cells. The endothelial cells were preincubated with a drug and then exposed to anticoagulated whole blood from human donors in the presence or absence of the same drug and agitated for 15 min. The number and size of platelets interacting with the SEM were quantified by morphometric analysis.In our in vitro system, platelet aggregates on SEM that was partially covered with human endothelial cells were significantly smaller than on uncovered SEM. No difference in platelet adhesion was observed. In the absence of endothelial cells, the cyclooxigenase inhibitors acetylsalicylic acid (ASA) and flurbiprofen strongly reduced the size of aggregates formed on the SEM. Pretreatment of only the endothelial cells with ASA increased the size of the aggregates, while ASA treatment of endothelial cells as well as the whole blood did not reduce the mean aggregate size below that of controls. in contrast, the platelet phosphodiesterase inhibitors AHP 719 and UDCG 212 strongly decreased platelet aggregation without reducing platelet adhesion not only in the absence but also in the presence of endothelial cells pretreated with the inhibitors.Our results demonstrate that this in vitro model of a partially injured vessel wall is well suited to study the effects of endothelial cells on platelet function. Moreover, inhibitors of phosphodiesterase in contrast to ASA have profound antithrombotic effects in this model.
PLATELET ADHESION TO THROMBIN-TREATED HUMAN ENDOTHELIAL CELLS
Authors: Murata M , Araki Y , Murakami H , Sato K , Ogawa T , Yamamoto M , Watanabe K , Ando Y , Ikeda Y 
Published: August 2018

Platelets do not, or hardly ever, adhere to normal endothelial cells (EC), although the reason is not completely clear. It is assumed that breakdown of this non-thrombogenic properties of EC may lead to initiation of thrombotic process. In this communication, we have clearly shown that significant number of platelets adhere to thrombin-treated EC.Platelet adhesion to cultured human umbilical vein EC was quantitatively determined according to the method of Curwen et al. using 3H-adenine-labelled human platelets. When EC were treated with human ±-thrombin (a generous gift of Dr. J.W.Fenton) at various concentrations (0.05-lU/ml) for 10 minutes followed by addition of hirudin, the number of attached platelets increased in a concentration dependent manner. When EC were preincubated with lU/ml α-thrombin for various time intervals (5-100 minutes), maximal adherence of platelets to EC was observed in 5 minutes' incubation. After treatment of EC with ±-thrombin for 60 minutes, the number of attached platelets returned to the basal level. EC were, then, maintained in M199-20%FCS for 24 hours and the same experiment was repeated. Again, α-thrombin caused the alteration of EC, which permitted platelets to adhere.The DNA content of monolayer cells was unchanged throughout the experiments indicating that no loss of EC occured during the procedures. Scanning electron microscopy showed that platelets tended to attach to the periphery of thrombin-treated EC. Treatment of EC with monoclonal anti-thrombomodulin IgG (a gift of Dr. I.Maruyama) had no inhibitory effect on thrombin-induced pla-telet-EC interaction.Our results may indicate that α-thrombin causes the temporary loss of non-thrombogenic properties of EC
EFFECTS OF I.V. AND I.A. PGE1-INFUSION IN DIFFERENT DOSES ON FIBRINOLYTIC ACTIVITY, PLATELET FUNCTION AND STABLE PGE1 METABOLITES
Authors: Fitscha P , Simmet T , Peskar B A , Tilsner V , Rogatti Waltraud , Sinzinger H 
Published: August 2018

As it is well known that PGE1 is degraded during lung passage to a major extent, we examined what the optimal route and dosage concerning platelet function and plasmatic coagulation would be.6 patients with peripheral vascular disease (PVD) stage lib according to Fontaine were treated either i.a. (1,25 or 2,50 ng PGE1 [Prostavasin]/kg/min) or i.v. (5 or 10 ng/PGEl/kg/min) for 120 minutes.Various parameters reflecting platelet function (βTG, PF4, serum TXB2, ADP-induced aggregation, platelet sensitivity to PGI2, intraplatelet cAMP) plasmatic coagulation and fibrinolytic activity were measured. Blood was drawn from the contralateral cubital vein avoiding occlusion before and 5,30,120,125 and 185 minutes after starting PGE1. Fibrinopeptide A (1,03±0,38 → 2,57±1,32; p<0,01), plasminogen (108,5+10,7 → 1,24±11,5; p<0,01), plasmin changed, whereas α2-anti-plasmin tissue plasminogen activator (72,7±34,7 → 94,0±32,5) and urokinase did not change (1,00±.0,41 → 1,30±0,95) significantly. The long-lasting influence on the fibrinolytic activity can not be explained by a direct action of PGE1 or 15-keto-13,14 DH-PGE1. RIA determination of 15-keto-13,14 DH-PGE1 exhibited a certain dose-dependent effect of PGE1 on the plasma levels of the immunoreactive substance. The findings are suggestive for a process persisting even after complete disappearance of the causative agent, or for a biological capacity of a so far unknown long-lived PGEl-metabolite. PGE1 did not significantly affect the platelet function parameters.
COVALENT BINDING OF CYCLOOXYGENASE AND LIPOXYGENASE PRODUCTS TO HUMAN PLATELET PROTEINS
Authors: Lecomte M , Boeynaems J M 
Published: August 2018

Several studies in acellular systems have shown a covalent binding of eicosanoids to proteins (1). We have therefore investigated whether eicosanoids bind covalently to proteins in intact platelets. After incubation of washed human platelets with 14C-arachidonic acid, ethanol precipitation followed by extractions, a small fraction of the radioactivity (0.3%) was tightly bound to the protein pellet. Four criteria suggest the covalent nature of this binding. The radioactivity remained bound after exhaustive extractions with solvents of various polarities, and was not removed by dialysis against SDS-buffer. 15 labelled protein bands could be separated by SDS-polyacrylamide gel electrophoresis (SDS-PAGE). Finally, exhaustive enzymatic hydrolysis of platelet proteins by several proteases liberated an amphipathic radioactive material which had a chromatographic behaviour similar to that of a known peptidolipid, leuko-triene c4 This covalent binding involved products of both cyclooxygenase and lipoxygenase pathways : it was partially inhibited by indomethacin (±40%) and completely abolished by eicosatetraynoic acid. The covalent binding was increased five-fold by dazoxiben, suggesting attachment of prostaglandin endoperoxydes , and by diamide (a glutathione depleting agent) (2) suggesting the involvement of 12-hydro-peroxyeicosatetraenoic acid. Dazoxiben and diamide intensified selectively the labelling of distinct protein bands, separated by SDS-PAGE. Further studies will be needed to evaluate the possible physiological significance of this covalent modification.(1) Wilson, A.G.E. et al. Prostaglandins 18: 409-422, 1979.(2) Bryant, R.W. et al., J. Biol. Chem. 257: 14937-14943, 1982
THE EFFECT OF COD LIVER OIL INTAKE ON THE STIMULATION OF BLOOD CELLS
Authors: Hansen J B , Olsen J O , Wilagård L , Østerud B 
Published: August 2018

In an in vitro model, stimulation of blood cells with a low concentration of lipopolysaccharides (LPS) revealed differences between women and men that possibly could be an explanation to why young women have less coronary heart disease than men (see abstract Hansen et al. “A model to--”).This model was also used to study the effect of intake of cod liver oil (CLO). 40 students (20 men and 20 women) were tested followed by an intake of 25 ml CLO daily for 2 months by 20 of the students.Heparinized blood samples were incubated with 2 ng LPS/ ml for 2 hours followed by isolation of plasma for thromboxane B2 and 6-keto-PG 1α quantitation.After the first 2 months period of CLO drinking we have the following results:The two months of CLO intake had no significant effect pn the thromboplastin induced synthesis in monocytes. In addition platelet aggregation was tested in a whole blood aggregometer using ADP addition to heparinized blood or collagen induced platelet aggregation in citrated whole blood. ADP aggregation was reduced from 75.9 ± 16.8% to 55.4 ± 19% in the CLO group of women, whereas the reduction in the CLO group of men was 70.1 ± 17.1% to 60.9±18.6%. Similar result were found with collagen aggregation (57% to 33% for women and 48% to 30% for men).It is concluded that CLO intake reduces TxA2 production and plateletaggregation without having reduced effect on PGI2 production in whole blood.
EFFECT OF POLLEN TYPHAE ON 6-KETO-PGF , TXB2, TOTAL CHOLESTEROL AND HDL-C IN RABBITS WITH CHRONIC HYPERLIPIDEMIA
Authors: Wang Z Y , Zhang L , Su Y L 
Published: August 2018

62 NZW rabbits were divided into 4 groups: (1) Control (C), (2) rabbits fed with high lipids diet (H), (3) H+pollen Typhae (H+P), (4) H+VitE (H+E). The following parameters were determined: (1) total cholesterol of aortic wall (WTC), (2) Serum TC (STC), High density lipoprotein cholesterol (HDL-C), (3) Plasma 6-keto-PGF1 (6-keto) and thromboxane B2 (TXB2), (4) 6-keto of aortic wall, (5) ratio of STC/HDL-C and plasma TXB2/6-ketoThe results showed that: (1) the level of WTC, STC and STC/HDL-C was significantly higher in the group H than in the group C, while that of 6-keto was lower (P < 0.01), (2) STC, WTC and plasma TXB2, TXB2 /6-keto all were significantly lower in the group H+P than m the group H, while wall's 6-keto was higher (P < 0.01).There was inverse correlation between plasma 6-keto and STC/HDL-C (P < 0.01), while positive correlation has been found between STC/HDL-C and plasma TXB2/6-keto (P < 0.05).In the group H+E, the plasma TXB2/6-keto, was lower than in the group H, the wall's 6-keto was higher, but there was no difference between the groups H+E and H+P. The STC and WTC were higher in the group H+E than in the group H+P, although lower than in the group H.It has been demonstrated in our Department that the Chinese traditional medicine Pollen Typhae had preventive effect on the experimental atherosclerosis in rabbit fed with high lipids diet, the mechanism would not only due to its effect lowering the STC, WTC and STC/HDL-C, but also to its action on the metabolism of prostaglandins. Its action on lowering STC and WTC appeared to be better than VitE, however, the latter had similar effect on the metabolism of prostaglandins as compared with Pollen Typhae.
SHORT TERM HIGH CHOLESTEROL DIET CAUSES CHANGES IN MEGAKARYOCYTE SIZE AND IN VASCULAR ULTRASTRUCTURE
Authors: Dalby Kristensen S , Roberts K M , Lawry J , Martin J F 
Published: August 2018

Platelets produced by megakaryocytes (MK) have a role in atherogenesis. Six pairs of male litter mate rabbits were randomised to feeding with either 2g of cholesterol daily in addition to their normal diet or normal diet alone. After seven days the animals were killed and serum cholesterol, platelet count, MK total, cytoplasmic and nuclear area (microscopic planimetry) and MK DNA content cell distribution (fluorescent activated cell sorting) were measured and compared between the two groups. The results are given in the table as medians with range values in brackets.After perfusion-fixation the aortas were examined by transmission electron microscopy. In the aortas from the animals on high cholesterol diet cells with ultrastructural features resembling smooth muscle cells were found in the intima. Changes in megakaryocyte size are associated with the occurrence of smooth muscle cell proliferation and migration. The platelet-megakaryocyte axis may be activated in early atherogenesis.
EXTRAVASCULAR INJURY CAUSES FOAM CELL FORMATION, ACCUMULATION OF CHOLESTEROL (C) and CHOLESTEROL ESTER (CE) IN THE CAROTID ARTERY
Authors: Hassall D C , Booth R F G , Honey A C , Martin J F 
Published: August 2018

In atherosclerotic arterial tissue, cholesterol is delivered to smooth muscle cells by low-density lipoprotein (LDL) and to macrophages via modified LDL. The reasons for accumulation of excess lipid are unknown although increased uptake of C and CE occurs in regions of arterial de-endothelialisation. We now report that the positioning of a silastic collar containing saline around the outside of arteries induces accumulation of C and CE within those tissues. 9 rabbits were separated into 3 groups, each group was fed a normal laboratory chow, 2 groups were supplemented with lg/day cholesterol; these rabbits were used for C and CE determinations. Three parallel groups of rabbits were set up for histological analysis. At day O, under anaesthesia, a silastic collar was* placed around the left carotid artery. The collar was filled with saline and carefully sealed without causing constriction of the vessel. The vessels were replaced and the animals allowed to recover. After 14 days the carotids from animals for C and CE determination were rapidly removed and divided up into a region from the middle of the collar, a region proximal to the collar and a distal region. The tissues were freeze clamped in liquid nitrogen and lipids extracted with C and CE determined for each region. The carotids for histological analysis were perfuse-fixed in situ and similarly subdivided.We conclude 1) Animals fed high cholesterol accumulate more C than CE within arterial tissue, furthermore this accumulation is greater than in animals fed a normal diet 2) In both normal diet and high cholesterol fed animals an enhanced accumulation of C + CE occurs within arteries with a collar 3) CE appears to be preferentially accumulated within the collar region.
TICLOPIDINE AND PREVENTION OF ARTERIAL REOCCLUSION AFTER DIRECT PERIPHERAL VASCULAR SURGERY
Authors: Castelli P , Basellini A , Agus G B , Martelli E , Zucca R 
Published: August 2018

Late thrombosis after arterial revascularization surgery is a relatively frequent complication especially when the more peripheral districts are involved. Among the causes of these failures, in addition to progression of the atherosclerotic disease, the behavior of platelet aggregation is of particular importance. With the aim of preventing this pathology we performed two controlled clinical 6-month studies on patients undergoing thrombo-endoarterectomy (TEA) of the femoropopliteal district and on patients undergoing aortobifemoral bypass.In the first study 47 patients were randomly allocated to receive ticlopidine, 500 mg/day, (23 patients) or placebo (24 patients), and in the second study 125 patients were evaluated (25 treated with ticlopidine, 500 mg/day, and 100 controls).Physical examination, doppler sonography, angiography, and blood tests were performed on all patients at baseline, during and at the end of treatment.In the patients who underwent TEA of the femoropopliteal district doppler sonography revealed 3 reocclusions in the ticlopidine-treated patients versus 6 reocclusions and 6 significant stenoses in the placebo group (p = 0.007).Furthermore, clinical symptomatology persisted or reappeared in 5 patients in the ticlopidine group versus 15 in the placebo group (p = 0.003).The active treatment significantly reduced the incidence of acute ischemia. In the. patients who underwent a bypass 5 reocclusions were observed in the control group, whereas the bypass remained patent in all the patients who received the active treatment. Ticlopidine was well tolerated in all the patients and no alterations of blood composition or other side effects were observed.