bluuebunny/crossref_metadata_2025_split huggingface dataset:
IS ATHEROSCLEROSIS A DISEASE OF THE OUTSIDE OF ARTERIES?
Authors: Booth R F G , Martin J F , Moncada S , Honey A C 
Published: August 2018

The early stages of atherosclerosis are characterised by: (i) Intimal infiltration by macrophages, (ii) Intimal smooth muscle cell (SMC) proliferation and (iii) Accumulation of cholesterol within the vessel wall. Many studies have suggested that these changes occur subsequent to endothelial cell (EC) damage and platelet deposition. We now describe a new animal model with characteristics of early human atherosclerosis but without observable EC damage or platelet deposition. 12 rabbits were separated into 2 groups; each was fed normal laboratory chow and one group was supplemented with lg/day cholesterol. At day 0, under anaesthesia, a silastic collar (internal volume 0.3ml) was placed around the left carotid artery. The collar was filled with whole blood and sealed without causing Constriction of the vessel. The right carotid arteries were sham operated. The vessels were replaced and the animals allowed to recover. After 14 days both carotids were perfuse-fixed in situ. The left carotid arteries were separated into:(A)A mid-region from within the collar,(B)A region proximal to the collar and (C)A distal region. These regions were subdivided for histology and scanning E.M. Medial/Intimal ratios of transverse sections of each region were analysed by computerised image analysis and shown below.Histology demonstrated an intense proliferation within 14 days which resembled early atherosclerosis. There was intimal monocyte infiltration and SMC proliferation and loss of SMC from the medial layer. Scanning E.M. revealed no observable EC damage or platelet adhesion. The lesion was highly focal and generally restricted to the collar region. Dietary cholesterol did not enhance proliferation but did cause foam cell formation. Sham operated vessels showed no significant atherosclerotic changes. Thus, early atherosclerotic lesions may be the result of damage to the outer layers of blood vessels.
INTERACTIONS OF CULTURED HUMAN ENDOTHELIAL CELLS WITH MODIFIED AND UNMODIFIED POLY(ETHYLENE TEREPHTHALATE); AN ULTRASTRUCTURAL STUDY
Authors: van Wachem P B , Schakenraad J M , Feijen J , Beugeling T , Blaauw E H , Nieuwenhuis P , Molenaar I , van Aken W G 
Published: August 2018

A fundamental study of the influence of polymer surface properties on interactions with cultured human endothelial cells (HEC) may lead to the development of improved i.e. endothelium-lined vascular grafts.We have previously demonstrated that HEC adhere preferably onto moderately wettable polymers.Here we present the results of spreading measurements and scanning- and transmission- electron microscope investigations on the interactions of HEC with moderately wettable tissue culture polyethylene terephthalate (TCPETP) and more hydrophobic PETP. The numbers of adhering HEC on TCPETP were always found to be much higher than the numbers of HEC adhering onto PETP. However, similar adhesion behavior, occurring in both the presence and absence of serum in the incubation medium, was observed at both TCPETP and PETP surfaces during the first 30 minute period after cell seeding. In contrast with PETP, which showed a decrease in cell spreading during further incubation in the presence of serum, cell spreading increased on TCPETP, resulting in a confluent monolayer at two hours. The decrease of spreading on PETP was a result of detachment of cells. On PETP different structured cells, such as cells with detached central portions or cells, which internalized another cell were observed.When HEC were first seeded onto PETP in the absence of serum, no decrease but rather an increase in cell spreading occurred after the addition of serum and during further incubation.HEC spreading on PETP also occurred, when PETP was first precoated with cell adhesion promoting protein(s), such as whole blood, plasma or fibronectin. However, proliferation results indicated that HEC did not form a confluent monolayer after the pretreatment of (TC)PETP with plasma.
MOLECULAR MARKERS OF ENDOTHELIAL CELL DYSFUNCTION: OBSERVATIONS ON EXTRINSIC FIBRINOLYSIS IN SURVIVORS OF MYOCARDIAL INFARCTION AND IN TYPE-1 DIABETES MELLITUS
Authors: Nilsson T , Johnson O , Lithner F 
Published: August 2018

We have studied the extrinsic fibrinolytic system in survivors, below 70 years, from myocardial infarction (AMI) treated in Umeci during 1983; in 43 type-1 diabetics; and in controls. Elderly controls underwent chest x-ray, ECG, EEG, brain CT scan to verify their health. Tissue plasminogen activator (tPA) activity was measured with a fibrin-stimulated rate assay, before and after a 10 min venous occlusion test (VO), tPA antigen (Ag) with an ELISA, and plasminogen activator inhibitor (PAI) by incubating samples with purified tPA and measuring remaining tPA with a polylysine-stimulated rate assay.In the diabetics, PAI and tPA:Ag were similar to the controls. tPA:Ag correlated with age (r=0.6). Diabetics had much higher specific activity of tPA (61,300 vs 21,900), and had also much higher tPA activity after VO (2.2 vs 1.2 U/ml). The tPA activities after VO correlated well with HbA1c (r=0.39). A significant effect of smoking was disclosed. Smoking diabetics had higher PAI and tPA antigen but also lower specific activity of tPA (60,600 vs 115,700 U/mg). Ex-smokers were very similar to smokers, not to the non-smokers. Retinopathy, nephropathy, or hypertension didn’t appear to affect fibrinolysis independently.In the AMI survivors (sampled 3 months after discharge from hospital), PAI was 6-fold higher than in elderly controls (p less than 0.0001). tPA activity after VO was much higher (3.2 vs 1.2 U/ml), as was tPA:Ag. tPA specific activity was lower. Among AMI patients with PAI over 10 U/ml, PAI correlated with triglycerides (r=0.4) and negatively with age (r=™0.4): these relations were not seen in the patients with PAI less than 10. The effects of smoking seen in diabetics were not observed among the AMI patients, von Willebrand factor was not increased among AMI nor diabetic patients, except for those with retinopathy.The results suggest that the tPA/PAI system is a more sensitive indicator than vWF of endothelial cell dysfunction. It relates to effects of age, atherosclerotic vascular disease, and among diabetics also to degree of metabolic control and to tobacco smoking habits.
DISTINCTIVE FEATURES OF PROCOAGULANT RESPONSE OF MONOCYTES FROM DIABETIC PATIENTS
Authors: JUDE B , WATEL A , FONTAINE D , FONTAINE P , COSSON A 
Published: August 2018

Hypercoagulability is one of the possible factors reported in genesis or aggravation of vascular complications in diabetes mellitus. We therefore examined procoagulant activity (PCA) of disrupted monocytes frcm 26 patients with Type I diabetes and 6 with Type II, versus 32 control subjects (male/ female ratio = 1 in each group).Diabetes monocytes exhibited a slight but detectable PCA before any incubation or in vitro stimulation, whereas control monocytes did not. Data obtained with coagulation factor deficient plasmas or phospholipase C indicated that PCA was tissue factor (TF) alone in 22 cases and TF associated with a significant amount of factor VII/VIIa activity in 10 cases.Incubation in serum free medium led to significant raise of PCA in diabetes cells when stimulated with endotoxin or not, and in control cells only after stimulation. Furthermore, PCA appeared earlier in diabetes monocytes than in control ones, (4 hours, versus 20 hours). PCA frcm control cells was FT-like. PCA frcm diabetes cells was FT-like when no VII/VIIa activity was present on non-stimulated cells, and prothrombinase-like when VII/VIIa activity was early associated with the cells. In the latter case, trace amounts of factor X activity were also detectable. Whether factor VII and factor X activities were of plasmatic origin and associated to the cells, or synthesized in vitro by the cells remains unclear. The characteristics of PCA were net correlated with clinical features (age, diabetic complications) nor with the type of diabetes.Our data suggest that in diabetes patients, monocytes exhibit an increased PCA, possibly corresponding to a baseline stimulation, or at least a higher responsiveness to undergoing stimuli in vitro.
A NEW QUANTITATIVE ENZYME-IMMUNOASSAY FOR FIBRIN DEGRADATION PRODUCTS (FbDP) IN PLASMA, BASED ON MONOCLONAL ANTIBODIES
Authors: Koppert P W , Hoegee-de Nobel E , Nieuwenhuizen W 
Published: August 2018

We have developed a sandwich-type enzyme immunoassay (EIA) for the quantitation of fibrin degradation products (FbDP) in plasma with a time-to-result of only 45 minutes. The assay is based on the combination of the specificities of two monoclonal antibodies (FDP-14 and DD-13), developed in our institute. FDP-14, the catching antibody, binds both fibrinogen degradation products (FbgDP) and FbDP. It has its epitope in the E-domain of the fibrinogen molecule on the BB-chain between amino acids 54-118 (Blood 68, 437, 1986). Antibody DD-13 was raised using D-dimer as antigen and was used as a tagging antibody, conjugated with horse-radish peroxidase.A strong positive reaction is obtained with a whole blood clot lysate (lysis induced by tissue-type plasminogen activator) which is used as a standard.The EIA does not detect FbgDP i.e. purified fragments X, Y, D:E complexes or FbgDP in plasma treated in vitro with streptokinase. This indicates that the assay is specific for fibrin degradation products.We have successfully applied this assay to the plasma of patients with a variety of diseases. In combination with the assays previously developed by us for FbgDP (Thromb. Haemostas. 1987, in press) and for the total amount (TDP) of FbgDP + FbDP in plasma (J. Lab. Clin. Med. 1987, in press), we are now able to study the composition of TDP in terms of FbgDP and FbDP in patients.
RISTOMYCIN (AGGRISTIN) PRECIPITATION TEST: A NEW, RAPID AND RELIABLE METHOD FOR THE DETECTION OF INTRAVASCULAR CLOTTING
Authors: Pfliegler G , Arnout J , Vermylen J 
Published: August 2018

The rapid and specific detection of fibrin monomers (fm) and fibrin degradation products (fdp) is of major importance in the laboratory diagnosis of disseminated intravascular coagulation, deep vein thrombosis or pulmonary embolism. Most methods in use are either time-consuming, needing special techniques, or insensitive and poorly specific. Some time ago, Watanabe and Tullis described a simple and rapid, semiquantitative test to detect fm and fdp in plasma, based on the finding that ristocetin in low concentrations (1.0-1.5 mg/ml) can specifically precipitate fm and fdp. To 0.4 ml ACD plasma, 0.1 ml ristocetin (2.5 mg/ml) is added and vortexed. The mixture is then incubated for 30 min at 20°C and centrifuged at 50xg for 5 min. The test is considered to be positive when fibrin-like strands or small or large pellets are observed on the bottom of the tube. More recently, Pfliegler et al. reported that ristomycin (AGGRISTIN), a structural analogue of ristocetin, can replace ristocetin in this test.Here we report on further results with the ristomycin (AGGRISTIN) precipitation test in 138 patients with various intravascular thrombotic events. The results of this test, performed on ACD plasma, were compared to the serum fdp values detected by immunoelectrophoresis (IEF) and by the haemagglutina-tion inhibition test (HIT). In all 30 cases with serum fdp above 30 ug/ml (HIT) or 28 pg/ml (IEF), the precipitation test was positive; at lower fdp concentrations, as detected by HIT or IEF, the test still was positive in 70 per cent of these thrombosis patients, suggesting a superior sensitivity. In 16 patients with elevated fibrinogen levels (but no evidence of thrombosis), the test was positive in only 3. No false positive results were detected in 16 healthy controls. Preliminary results show that the minor disadvantage of the test (blood collection on acid citrate dextrose) may readily be overcome by the in vitro adjustment of the pH of citrate plasma, commonly used for other haemostatic tests, to between 7.0 and 7.4.On the basis of our results we suggest that the AGGRISTIN (ristomycin) precipitation test is a simple, rapid and reliable method for the laboratory diagnosis of intravascular clotting.
DIAGNOSTIC VALUE OF D-DIMER, FIBRINOGEN DEGRADATION PRODUCTS, ETHANOL GEL TEST AND TRANSFER TEST IN DEEP VENOUS THROMBOSIS AND PULMONARY EMBOLISM
Authors: Wachel D , Segers M , Leautaud P , Rodzynek J J 
Published: August 2018

In order to determine the sensitivity and the specificity of laboratory tests in the diagnosis of thrombotic disease, D-Dimer (D-D) latex, Fibrin(ogen) Degradation Products (FDP), Ethanol Gel Test (EGT) and Transfer Test (TT) were performed in two groups of patients : group 1 = 199 consecutive patients without thrombotic disease, group 2 = 56 patients with thrombosis (Deep Venous Thrombosis confirmed by radiological phlebography, n=19, and Pulmonary Embolism confirmed by ventilation-perfusion lung scintigraphy, n=37). The sensitivity, the specificity, the positive and negative predictive values (PV+ and PV-) for the different tests appeared as follows :Conclusion :1) Among the different parameters which have been studied, D-Dimer latex appears to be the most useful in the clinical practice (sensitivity 98% and specificity 90%).2) Easy to perform, cheap, the results can be obtained within 20 minutes (for instance during the night in emergency situations).
FIBRINOLYTIC RESPONSE TO VENOUS OCCLUSION, AND FIBRIN FRAGMENT D-DIMER AND FIBRONECTIN LEVELS IN NORMAL AND COMPLICATED PREGNANCY
Authors: Mombaerta P , Ballegeer V , Declerck P , Van Assche F A , Collen D 
Published: August 2018

The fibrinolytic response to venous occlusion was assessed in pregnant women with measurements of total and free t-PA, using specific ELISAs based on monoclonal antibodies.Total t-PA levels increased after venous occlusion with 11±8 ng/ml (mean ± SD) in healthy fertile non-pregnant women (n=6), with 0.8 ± 1.3 ng/ml in 2nd trim. (n=5) and with 3.8 ± 3.9 ng/ml in 3rd trim. (n=4) healthy pregnant women. The increase in free t-PA was 12 ± 11; 1.2 ± 0.9 and 0 ng/ml respectively. The difference in post- and pre-occlusion levels in 3rd trim, pregnant women with insulin dependent diabetes mellitus IDDM (n=4) was 3.2 ± 4.2 ng/ml, with intrauterine growth retardation (IUGR) (n=4) 2.6 ± 3.0 ng/ml and with preeclampsia (n=5) 3.2 ± 3.5 ng/ml for total t-PA and 0, 0 and 0 ng/ml for free t-PA.Fibrin fragment D-dimer levels in plasma measured with a specific ELISA were 130 ± 36 ng/ml in healthy fertile non-pregnant women (n=8). A significant increase was found in 4 out of 5 1st trim., 25 out of 25 2nd trim, and 21 out of 22 3rd trim, normal pregnant women. In these groups, plasma levels were 340 ± 160, 400 ± 170 and 440 ± 220 ng/ml respectively.Fibronectin levels, measured with a Laurell electroimmunoassay and expressed as percentage of pooled human plasma (=330 yg/ml) were 83 ± 26% in 2nd trim, patients (n=24) and 102 ± 35% in 3rd trim, patients (n=17). Normal fibronectin levels were found in 4 patients with IDDM and in 6 with IUGR, whereas in 6 out of 8 preeclamptic patients significantly increased levels were observed.These results confirm, with the use of a newly developed free t-PA assay, that the fibrinolytic response to venous occlusion is completely inhibited in the 3rd trimester of pregnancy. A reduced release of t-PA from the vessel wall during venous occlusion and/or an increased inhibition of released t-PA were observed. No difference was found in the fibrinolytic response between normal and complicated pregnancy. D-dimer levels are significantly elevated during pregnancy. Finally, the usefulness of fibronectin for the diagnosis of preeclampsia is confirmed.
D-DIMER AND SERUM FDP IN GYNAECOLOGICAL SURGERY AND DIC PATIENTS
Authors: Legnani C , Palareti G , Maccaferri M , Bianchini B , Boggian O , Poggi M , Coccheri S 
Published: August 2018

We carried out in parallel plasma D-Dimer (Dimertest Latex assay, kindly supplied by Ortho Diagnostic Systems, Milan) and serum FDP measurements (ThrorriboWellcotest, Wellcome) in: 1) 35 gynaecological patients (Gyn. pts) pre and post- operatively (8th day); pts were treated with low dose heparin for thromboembolic prophylaxis and controlled with 1125- fibrinogen leg scanning (L.S.); 2) 20 pts from the intensive care unit (ICU) with DIC diagnosed by means of standardized laboratory criteria (DIC pts); tests were performed at admission to the ICU and 1 week later in the 15 survivors.In all Gyn. pts both D-Dimer and serum FDP tests were negative pre- operatively. At the 8th post-op. day 16 pts (45.7%) had a positive Dimertest, 8 of which had also positive, even if transient, leg scanning (out of 10 L.S. positive pts).Serum FDP were present in 5 pts (14.3%), 2 with negative Dimertest and 2 with positive l.s.. All the 20 DIC pts showed at first observation positive Dimertest and 19 had also serum FDP. After 1 week Dimertest was still positive in 12 and serum FDP in 10 pts. Considering five range levels of results (from normal to highly positive for both tests) we found a significant (p<0.05) correlation (Kendall’s T .non parametric test) between the results of the two tests in all observations (35 samples). In conclusion, Dimertest, but not serum FDP, seemed to be highly sensitive to post-operative hypercoagulability, with a specificity of 5C% for subclinical fibrin deposition as detected with L.S.. No relevant differences were appreciated in the usefulness of the two tests in DIC pts.
THE EFFECT OF DIETARY COD LIVER OIL SUPPLEMENTATION ON LEUKOCYTE PHYSIOLOGY; A POSSIBLE MEDIATOR OF THE ANTIATHEROGENIC EFFECT OF MARINE OIL
Authors: Hoogasiam J , Fisher M , Levine P H , Weiner B W , Vaudreuil C H , Natale A , Johnson M 
Published: August 2018

Leukocytes appear to be important in the pathophysiology of atherogenesis. Fish oil derived, omega-3 fatty acids suppress atherogenesis in experimental atherosclerosis models and select human populations. We assessed the effect of dietary cod liver oil (CLO) supplementation for 6 weeks on human monocyte and polymorphonuclear leukocyte (PMN) inflammatory potential in healthy controls and patients with a purported autoimmune disorder, multiple sclerosis (MS) in whom monocytes appear to be chronically activated. Baseline and 6 week venous blood samples were obtained from 6 stable MS patients and 6 healthy controls. . Monocyte hydrogen peroxide (HO) production (pMoles/minute/Ix10 monocytes) was measured in a spectrophotofluorometer after stimulation with latex particles. Baseline H2O2 production was 1.551.60 (mean 1 S.D.) in the MS patients and 1.19± .49 in the controls. Post-CLO the values were 1.021.24 and 1.091.27 respectively, representing a significant decline with CLO supplementation in the MS group (P< .01). PMN chemiluminescence (counts x10 /5min/PMN) levels was assessed by a liquid scintillation counter after stimulation with latex particles. Baseline levels were 17.416.1 in the MS group and 17.814.8 in the controls Post-CLO the levels were 12.812.3 and 12.313.3; both signifi-antly lower than baseline (P < .05). PMN superoxide (0 —) levels (nMoles/20min/lxl0 PMN) were measured by the reduction of cyto-chrome-c after stimulation with zymosan. Baseline O2- levels were 21.0±5.8 in the MS group and 22.115.9 in the controls. Post-CLO the O2- levels declined to 8.210.7 and 7.811.5, both significantly lower than baseline (P< .O2-). These data demonstrate that CLO supplementation reduces the intensity of PMN and monocyte reactions to a standard stimulus as measured by toxic oxygen metabolite production, although the monocyte effects were only observed in a population (MS) with increased baseline activity levels.It has previously been assumed that omega-3 fatty acids might exert antiatherogenic effects via their inhibitory effects on platelet reactions. If leukocytes are important mediators of endothelial damage and/or cholesterol deposition in arterial walls, then our data suggest another mechanism by which fish oil may confer benefit in reducing the risk of arterial disease.
IMPAIREMENT OF PRIMARY HAEMOSTASIS BY LMW-HEPARINS
Authors: Borowska A , Lauri D , Maggi A , Dejana E , de Gaetano G , Pangrazzi J 
Published: August 2018

Low molecular weight (LMW) heparlns have been developed with the aim of reducing anticoagulant activity thereby minimizing the bleeding complications of conventional heparin. Unexpectedly, bleeding events were reported during treatment with some LMW-heparins, in clinical and experimental studies. We studied the effect of four different LMW-heparlns on primary haemostasis In male rats (CD COBS, Charles River) after l.v. administration of 0.75 mg/kg b.w. of the drugs. LMW heparin A was devoid of any activity on an experimental model of “template” bleeding time in rats (110.6±5.9 sec versus 108.7±4.1 control values) whereas LMW-heparins B, C and D prolonged the bleeding time to a different extent (228.7±19.9, 161.5±6.4 and 161.7±8.6 respectively). Pretreatment of animals with aspirin (100 mg/kg b.w. per o.s). resulted In a significant potentiation of the “template” bleeding time. In vitro platelet aggregation Induced by collagen (20 μg/ml) or by collagen in combination with ADP (5-10 μM) was strongly inhibited by LMW-heparln B, while LMW-heparln A showed no effect. LMW-heparins C and D exerted an Intermediate level of Inhibition of platelet aggregation. The same pattern of aggregating response was found when LMW-heparins A and B were given i.v. to rats (0.75 mg/kg b.w.) and platelet aggregation was studied “ex vivo” 15 min after drug administration.These data may help explain the impairment of primary haemostasis associated with some LMW-heparin preparations.
URINARY TRYPSIN INHIBITOR RELATED SUBSTANCE (UTIR) IN THE PLASMA AND TISSUES OF STOMACH CANCER
Authors: Nishino N , Tokura Y , Sakaguchi S , Takahashi S , Takada Y , Takada A 
Published: August 2018

Urinary trypsin inhibitor(UTI) is a single chain glycoprotein with molecular weight of 67,000. In SDS-PAGE a hand appeared at molecular weight of 48,000. Results of gel filtration indicate its molecular weight of 67,000, suggesting extensive changes in its conformation in SDS. Injection of UTI into rabbit did not result in the formation of anti-UTI antibody. Conjugation of rabbit serum albumin with UTI gave rise to antibody formation upon injection into rabbits. Anti-UTI did not cross-react with anti-inter(Xtrypsin inhibitor. A highly sensitive enzyme immunoassay of UTI was developed using β-D-galactosidase coupled to Fab' of anti-UTI. The inhibition of the hydrolysis of TAMe by trypsin was used for the functional assay of UTI. Functional assay of UTI showed a good correlation of UTI antigen (UTIR) to the UTI activity in the urine. UTIR levels in the plasma of the normal male volunteers were 198.0 ± 15.7 μg/ml, and did not change with increasing age. Cancer tissue of patients with stomach cancer showed higher UTIR than surrounding healthy tissue, and urine of such patients had higher UTI.In conclusion, UTIR were present in the plasma and tissue of normal persons, and UTI levels in the urine of cancer patients increased, and cancer tissues of patients with stomach cancer seem to have higher UTIR than that in sorrounding normal tissues.