bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors Involved In the Plasminogen Activation System in Human Breast Tumours
Authors: Damjanovich László , Turzó Csaba , Ádány Róza 
Published: July 2018

SummaryThe plasminogen activation system is a delicately balanced assembly of enzymes which seems to have primary influence on tumour progression. The conversion of plasminogen into serine protease plasmin with fibrinolytic activity depends on the actual balance between plasminogen activators (urokinase type; u-PA and tissue type; t-PA) and their inhibitors (type 1 and 2 plasminogen activator inhibitors; PAI-1 and PAI-2). The purpose of this study was to determine the exact histological localization of all the major factors involved in plasminogen activation, and activation inhibition (plasmin system) in benign and malignant breast tumour samples. Our results show that factors of the plasmin system are present both in benign and malignant tumours. Cancer cells strongly labelled for both u-PA and t-PA, but epithelial cells of fibroadenoma samples were also stained for plasminogen activators at least as intensively as tumour cells in cancerous tissues. In fibroadenomas, all the epithelial cells were labelled for PAM. Staining became sporadic in malignant tumours, cells located at the periphery of tumour cell clusters regularly did not show reaction for PAI-1. In the benign tumour samples the perialveolar connective tissue stroma contained a lot of PAI-1 positive cells, showing characteristics of fibroblasts; but their number was strongly decreased in the stroma of malignant tumours. These findings indicate that the higher level of u-PA antigen, detected in malignant breast tumour samples by biochemical techniques, does not necessarily indicate increased u-PA production by tumour cells but it might be owing to the increased number of cells producing u-PA as well. In malignant tumours PAI-1 seems to be decreased in the frontage of malignant cell invasion; i.e. malignant cells at the host/tumour interface do not express PAI-1 in morphologically detectable quantity and in the peritumoural connective tissue the number of fibroblasts containing PAI-1 is also decreased.
Thrombelastography during and after Elective Abdominal Surgery
Authors: Butler J M 
Published: July 2018

SummaryThrombelastography has been performed on recalcified whole blood from 50 patients before, during and after elective abdominal surgery. The characteristic changes of the thrombelastographic indices r, k and mA are described.During operation r and k shortened, but no change in mA was observed. This response was in part associated with an increase in factor VIII activity. Following operation, while r time was somewhat shortened, much more marked changes in k and mA were evident. Increasing fibrinogen concentration was the dominant factor in determining the post-operative changes in the thrombelastograph.
Measurement of Thrombin Generation in Whole Blood - The Effect of Heparin and Aspirin
Authors: Kessels Han , Béguin Suzette , Andree Harry , Coenraad Hemker H 
Published: July 2018

SummaryA technique has been developed to monitor the development of thrombin in freshly collected whole blood in the absence of anticoagulants. It is based on the centrifugal separation of the cellular components from subsamples of blood drawn from non-anticoagulated clotting whole blood which are diluted in buffer containing a chromogenic substrate.It is shown that the burst of thrombin generation after triggering coagulation with trace amounts of tissue thromboplastin occurs sooner in non-anticoagulated whole blood than in citrated whole blood. Heparin is shown to prolong the lag-time of thrombin generation more in native blood than in recalcified citrated blood.It is also demonstrated that intake of 500 mg of aspirin significantly delays and inhibits thrombin generation in non-anticoagulated, thromboplastin triggered whole blood, whereas it has no effect on the coagulation in citrated plasma. The effect of aspirin intake on thrombin generation in blood is roughly equal to that of 0.03 U/ml of unfractionated heparin. This demonstrates that platelet reactions and the coagulation system are closely linked processes. It further lends support to the hypothesis that inhibition of thrombin generation is a common denominator of antithrombotic therapy.
Pulmonary Embolism in Patients with Upper Extremity DVT Associated to Venous Central Lines - A Prospective Study
Authors: Monreal Manuel , Raventos Antoni , Lerma Rosa , Ruiz Joan , Lafoz Elena , Alastrue Antoni , Llamazares Jaume F 
Published: July 2018

SummaryWe performed a prospective study in 86 consecutive patients with central vein catheter-related deep venous thrombosis (DVT) of the upper extremity, to evaluate the prevalence of pulmonary embolism (PE), and to identify clinical variables that would increase the likelihood of developing PE in an individual patient.Since upper-extremity DVT was established, all patients received intravenous heparin therapy. Then, a ventilation-perfusion lung scan was obtained within 24 h of DVT diagnosis, whether respiratory symptoms were present or not. Six points of clinical information were recorded on entering in the study, and then compared with the scintigraphic findings: age, sex, the underlying disease, the catheter material, the character of the infusate, and the duration of cannulation.Thirteen patients were considered to have PE. Sixty-six patients were finally classified as having a normal lung scan, and 7 patients were excluded from the study (because of indeterminate lung scan 6; because of femoropopliteal thrombosis simultaneously present 1). Two out of the 13 patients with PE subsequently died because of recurrent, massive embolism, despite adequate heparin therapy. PE was more commonly present in patients with polyvinyle chloride or polyethylene catheters (10/38,26%) as compared to patients with either polyurethane or siliconized catheters (3/41, 7%; p <0.05, Chi-Square test; Odds Ratio = 4.52,95% Cl 1.01-23.07).We conclude that PE is not a rare event in these patients, and it may be life-threatening even despite adequate heparin therapy. Since the more recently available soft catheters seem to carry a lower risk of developing PE, there seems to be no reason to continue to use polyvinyl chloride or polyethylene catheters.
Effect of Oestrogen Dose on Whole Blood Platelet Activation in Women Taking New Low Dose Oral Contraceptives
Authors: Norris Lucy A , Bonnar John 
Published: July 2018

SummaryOral contraceptive use is known to cause changes in the haemostatic system. These changes are thought to be related to oestrogen dose and to provide a possible link between the increased risk of thromboembolic disease known to occur in women taking oestrogen containing oral contraceptives. This study measured whole blood platelet activation, serially, in women taking oral contraceptives containing 20 μg and 30 μg ethinyloestradiol combined with desogestrel. Increased levels of ADP and arachidonic acid induced aggregation were observed in women taking the 30 μg ethinyloestradiol combination. Platelet release of β-thromboglobulin (βTG) was also significantly increased. Increased collagen induced aggregation was observed but this failed to reach statistical significance for the individual treatment groups. In women taking the 20 μg ethinyloestradiol combination, a significant increase was only observed when platelets were stimulated with arachidonic acid. Platelet factor 4 (PF4) levels were unchanged in both groups. Significantly higher levels of βTG were observed in women taking the 30 μg ethinyloestradiol combination compared with women taking the 20 μg ethinyloestradiol combination. These results show that oral contraceptive use is associated with platelet activation. Women taking the 20 μg ethinyloestradiol combination show less changes in platelet activation than women taking the 30 μg ethinyloestradiol combination. This lower dose pill may therefore be particularly suitable for high risk women wishing to use oral contraception.
Association of Antibodies to Heat-Shock Protein-65 with Percutaneous Transluminal Coronary Angioplasty and Subsequent Restenosis
Authors: Mukherjee Manjari , De Benedictis Christine , Jewitt David , Kakkar Vijay V 
Published: July 2018

SummaryHeat-shock protein (HSP)-65 of mycobacterial origin has been implicated in the mediation of atherosclerosis by immune mechanisms. Any role of HSP-65 in mediating restenosis is however not clear. We determined the anti-HSP-65 antibodies in 28 patients, 25 male and 3 female, aged 35 to 78 years, with coronary artery disease (CAD) and undergoing percutaneous transluminal coronary angioplasty (PTCA). Of the 28 patients, 12 suffered restenosis five to seven months later.The serum levels of antibody were measured at baseline, immediately after PTCA, before discharge from the hospital, and at 6 weeks, 3 and 6 months after the performance of PTCA. The antibody levels were expressed in OD U/log titre, as explained in the text, and termed estimated OD or EOD. The control group consisted of 29 healthy volunteers, 16 male and 13 female, aged 24 to 59 years. The mean Eod of the patients at baseline was higher than that of the controls (0.60 ± 0.12, SD; 95% Cl 0.56-0.64 compared with 0.53 ± 0.13; 0.48-0.58; p < 0.01). There was no correlation between age and EOD of patients, controls or both taken together, ruling out the influence of age on the EOD changes in the given age range. The mean antibody levels of the patients with CAD were similar whether or not they suffered subsequent restenosis (0.61 ± 0.15; 0.53-0.69 in the patency group, and 0.60 ± 0.10; 0.54-0.66 in the restenosis group). However, the patients who did not develop restenosis had a drop in their antibody levels immediately after PTCA (0.51 ± 0.14; 0.48-0.55; 2-tailed p = 0.029), and at discharge from the hospital (0.52 ± 0.15; 0.44-0.60; p = 0.036) as compared with the baseline. This decrease of antibodies was not observed in the restenosis group. Furthermore, the anti-HSP-65 antibody levels remained slightly low throughout the 6-month follow-up in the patients with patent coronaries as compared with patients who reste-nosed, but the decrease was statistically not significant at 5% level at any stage. Besides the anti-HSP-65 antibodies, the levels of anticardio-lipin (ACL) antibody were also measured in all the patients. The levels of the ACL antibody were found to be within the normal range before and at all stages after PTCA, ruling out the PTCA-associated change in the anti-HSP-65 antibody as a non-specific occurrence. Thus, a drop in the level of antibody against HSP-65 after PTCA seemed to be associated with a favourable outcome, and may serve as a useful prognostic marker of coronary angioplasty
The Production of Heparin Cofactor li Is Not Regulated by Inflammatory Cytokines in Human Hepatoma Cells: Comparison with Plasminogen Activator Inhibitor Type-1
Authors: Kolke Chisato , Hayakawa Yumiko , Niiya Kenji , Sakuragawa Nobuo , Sasaki Hideo 
Published: July 2018

SummaryUsing the Northern blot technique, we screened 6 human hepatoma cell lines to investigate the regulation mechanism of heparin cofactor II (HCII) biosynthesis. We found that HuH-7 and Hep G2 cells constitutively expressed the HC II gene. In conditioned medium, HuH-7 cells constantly produced HC II that was functionally active and formed a complex with thrombin in the presence of dermatan sulfate. HC II is thought be an acute phase reactant, and, therefore, we examined the effects of the major inflammatory cytokines, IL-6, IL-1β, and TNF-α, on the regulation of HC II production in HuH-7 and Hep G2 cells. In HuH-7 cells, the antigen and mRNA levels of plasminogen activator inhibitor type-1 (PAI-1), an acute phase protein produced by hepa-tocytes, were increased in response to stimulation with either IL-6 or IL-1 (3 or both, but HC II antigen and mRNA levels were not changed by the same stimulation. Even when Hep G2 cells were treated with a combination of three cytokines, IL-6, IL-1β, and TNF-α, HC II antigen and mRNA levels were not changed; however, PAI-1 antigen and mRNA levels were clearly increased. These results suggest that the production of HC II in hepatoma cells is not regulated by the major inflammatory mediators, IL-6, IL-iβ, and TNF-α.
The Risk of Abortion and Stillbirth in Antithrombin-, Protein C-, and Protein S-deficient Women
Authors: Jan Sanson Bernd , Friedrich Philip W , Simioni Paolo , Zanardi Sandra , Huisman Menno V , Girolami Antonio , Wouter ten Cate Jan , Prins Martin H 
Published: July 2018

SummaryHereditary deficiencies of the naturally occurring anticoagulants are well recognized conditions predisposing to recurrent venous thromboembolism. Since thrombotic phenomena have been implied as a cause of abortion and stillbirth, we hypothesized that these deficiencies increase the risk of fetal demise.A group of 129 female subjects who had been pregnant at least once and who had a family member with documented venous thrombosis associated with a deficiency of AT, PC or PS were studied. We first assessed the obstetric history and subsequently determined the deficiency status. In the 60 deficient subjects 42 (22.3%) of the 188 pregnancies resulted in miscarriage or stillbirth as compared to 23 (11.4%) of the 202 pregnancies in the 69 non-deficient subjects. The relative risk of abortion and stillbirth per pregnancy for deficient women as compared to non-deficient women was 2.0 (95% C.I. 1.2-3.3).
Hemorheological Changes in Elderly Subjects-Effect of Pentosan Polysulfate and Possible Role of Leucocyte Arachidonic Acid Metabolism
Authors: Freyburger G , Larrue F , Manciet G , Lorient-Roudaut M F , Larrue J , Boisseau M R 
Published: July 2018

SummaryThe effects of pentosan polysulfate (PPS) on various hemorheological parameters were studied in a group of very elderly subjects in good general health. Alterations in blood viscosity and filterability were detected in these patients, without any concomitant changes in factors which are known to affect these parameters: notably hematocrit, fibrinogen and plasma lipid levels. The hemorheological abnormalities were considerably improved by twice daily treatment with 50 mg of PPS (i.m.).Apart from its anticoagulant activity, PPS has been shown to have an anti-inflammatory action. We were interested to investigate its effects on metabolism of exogenous arachidonic acid (AA) by both platelets and leucocytes. It is becoming increasingly recognized that metabolites of AA via the 5 LO pathway appear to play a role in inflammatory processes. In this study, PPS was found to inhibit leucocyte 5 LO activity. Reduction in the levels of these metabolites may therefore have an effect on whole blood rheology.
The Time Relation Between The Haemostatic Aggregation Of Platelets And Their Release Reaction In Vivo
Authors: Görög P , Born G V R 
Published: July 2018

The release reaction of platelets has been assumed to subserve a positive feedback mechanism responsible for their aggregation in haemostasis and thrombosis. This assumption is based mainly on in vitro experiments. Considerable uncertainty remains about the contribution of the release reaction to the initiation of haemostasis in vivo. The rapidity of the process and the presence of other tissues makes it impossible to follow the reaction quantitatively in vivo by methods which permit this in vitro. We have therefore applied quantitative electron microscopy to find out how quickly the concentration of dense bodies decreases in platelets during their haemostatic aggregation. In mice, platelets were enriched in dense bodies by pretreatment with serotonin.Mesenteric arteries were incised with a sharp blade. Bleeding was stopped by a micromanipulator-operated device about 15 sec and 60 sec after the cut. The cut segments were immediately fixed in situ with glutaraldehyde and postfixed. Serial sections were made for electron microscopy. Platelets isolated from peripheral blood of the same animal were prepared similarly. Electron micrographs were projected on to a television screen and numbers of dense bodies and total platelet areas were determined by an image analysing computer. After 15 sec there were no significant differences in numbers of dense bodies in platelets from different parts of the haemostatic plugs (8.31±0.57/100 μ2 mean ± s.e.m.) and in platelets from the blood (8.93±0.38). On the other hand, after 60 sec the parts furthest from the cut contained fewer dense bodies than the nearer parts and the overall dense body number (5.86±0.05) was considerably smaller (p<0.001) than that of platelets from the blood (14.45±0.09).The results suggest that haemostatic aggregation of platelets does not initially depend on their release reaction.
Oral Administration Of Concentrated Factor VIII Or Factor IX Preparations
Authors: Sakuragawa N , Takahashi K , Horikoshi I 
Published: July 2018

In current treatment and prophylaxis of bleeding of the patient of hemophiliacs, purified preparation of coagulation factors is administered intravenously, though some hemophiliacs developed hepatitis and antibody to factor VIII. If we can replenish coagulation factors orally, it will be of great benefit for hemophiliacs. Materials and methods: (1) Concentrated factor VIII( Con- coeight, Green-Cross, Osaka ) and factor IX( Konyne, Cutter ) were used. (2) Coagulation factors were enclosed in liposomes with addition of aprotinin, and the liposomes were further encapsulated in enteric capsules or suspended in milk to administer orally. (3) Coagulation studies were performed by assaying a-PTT, PT and coagulation assay methods.Results: (1) A concentrated factor IX preparation ( 400 units ) was given to dogs orally to find raised concentration of factors IX, X, VII and II from 100% to 150%. Konyne contained these factors mentioned above. When 1200 units of Konyne was given in the same way, intravascular coagulation was ocurred. These results showed factor IX including factors X, VII and II were absorbed from the intestine. (2) A concentrated factor VIII preparation ( 100 units ) was administered orally to hemophiliacs as volanteers to find raised concentrations of several percentage by biological activity and about 30% by immunological activity. (3) It is absolutely necessary to add aprotinin to prevent proteolysis by the proteases in the gastrointestinal tract in the intestine capsules. One of the absorption mechanism may be due to the fusion of the upper layer membrane of liposome with the gastrointestinal cell.
Cation Contributions To Potentiometric Dye Responses In Human Platelets
Authors: Miller Jonathan L , Mazer Theodore M 
Published: July 2018

The potentiometric dye, Di-S-C3(5) (0.9μM) was incubated with stirred suspensions of-3washed human platelets (5-6 × 104μl) in buffer containing 137mM NaCl, 2.7mM KCl, 0.2% dextrose, and 25mM Tris-HCl, pH 7.4 in an Ami neo-Bowman fluorometer, with excitation λ 620nm and emmision λ 680nm. Equilibrium levels of fluorescence (F) nearly doubled as external potassium concentration (K °) was increased from 2.7mM to 105.6mM. Addition of°2mM CaCl2 always produced immediate transient increases in F, regardless of K0 , in contrast to the increases or decreases produced by the potassium ionophore, valino- mycin (VAL) (5μM) in adherance to the electrochemical gradient determined by the choice of K°. Equilibrium F was also relatively insensitive to external calcium (Ca°) at either high or low levels of K . However, add?tion of the calcium ionophore, A23187 (10μM) produced immediate increases in F, with peak values (F-A23peak) increasing sharply with increasing Ca°. At a given Ca the F-A23peak was insensitve to K ° however, with the prior addition of VAL, F-A23peak became sensitive to K , particularly so at the lowest values of K° , where the F-A23peak was significantly lower in tne presence than in the absence of VAL. Replacement of sodium by choline had no significant effect on equilibrium F or on responses to VAL or to A23187- Platelet agglutination induced by ristocetin plus cryoprecipitate was not accompanied by similar increases in F.These findings suggest that Di – S–C3 F reflects a strong contribution of potassium permeability in the resting state, with relatively little contribution by calcium. Production of an activated state in platelets by A23187, in contrast, results in an increase in F that appears to reflect a major contribution by calcium.
Regulation Of The Fatty Acid Composition Of Platelet Phospholipids
Authors: McKean M L , Smith J B , Silver M J 
Published: July 2018

The fatty acid composition of cell membrane phospholipids does not remain constant after de novo biosynthesis, but undergoes continual remodelling. One of the major routes for remodelling probably includes the deacylation-reacylation steps of the Lands Pathway. This has been shown to be important for the incorporation of long chain, polyunsaturated fatty acids into phospholipids by liver and brain. An understanding of the mechanisms involved in these processes in platelets is especially important in light of the large stores of arachidonic acid (AA) in platelet phospholipids and the role of AA in hemostasis and thrombosis. Previous results from this laboratory have shown that the turnover of radioactive AA, 8,11,14-eicosatrienoic and 5,8,11,14,17-eicosapentaenoic acids in the phospholipids of resting platelets is more rapid than the turnover of radioactive C16 and C18 saturated and unsaturated fatty acids. However, little is known about how fatty acids, especially AA and its homologues, are incorporated into platelet phospholipids during de novo biosynthesis or how they are exchanged during remodelling.At least three enzymes are involved in the deacylation- reacylation of phospholipids: phospholipase A2; acyl CoA synthetase; and acyl CoA transferase. We have studied acyl CoA transferase and have found considerable activity in human platelet membranes. Experiments are in progress to determine the substrate specificity and other properties of this enzyme.
The Effects Of Defibrination Procedures In Plasma At III Assays
Authors: Philo R D , Gaffney P J 
Published: July 2018

Defibrination procedures using heat or ancrod (a coagulant fraction from Agkistrodon rhodostoma venom) are commonly used in heparin co-factor AT III assays which use a clotting time endpoint to measure residual thrombin. The test plasma is compared to a freeze-dried standard plasma which has been defined to contain a particular number of AT III units. This study examines the effects of both heat and ancrod defibrination of fresh and freeze-dried plasmas using a chromogenic-based AT III assay system in which no defibrination is necessary.The mean potency of the heat (56°C × 15 min) defibrinated freeze-dried standard plasma compared to the untreated standard was 0.51 (mean of 9 assays using a multidose bioassay design) whereas the corresponding figure for the frozen test plasmas was 0.72. Thus a test plasma would give falsely elevated readings for AT III compared to a freeze- dried plasma standard. Assays of ancrod (0.55 iu/ml) defibrinated plasma against untreated plasma gave mean potencies not significantly different from 1.0 for both the freeze-dried and frozen plasmas. Thus this form of defibrination allows a more valid comparison of fresh and freeze- dried plasmas.Analysis of these samples by crossed immunoelectrophoresis in the presence of heparin confirms that the ancrod defibrinated samples are essentially identical to the untreated ones whereas the heat defibrinated samples are altered, the freeze-dried plasmas markedly so.The data suggest that, should a defibrination step be used in the assay of AT III, the use of ancrod is preferred to heat. The heparin co-factor AT III assay using the chromogenic substrate, S-2238, to measure residual thrombin would seem the preferred method of assay in order to avoid any defibrination step.