bluuebunny/crossref_metadata_2025_split huggingface dataset:
VENODILATION AND DEVELOPMENT OF DEEP VEIN THROMBOSIS IN TOTAL HIP AND KNEE REPLACEMENT PATIENTS
Authors: Stewart G J , Lachman J W , Alburger P D , Ziskin M C , Philips C M , Jensen K 
Published: August 2018

Postoperative deep vein thromboisis(DVT) is a frequent complication following total hip (THR) or knee (TKR)replacement but no test has been devised to identify specific patientswho will develop DVT. Because conventional prophylaxis does not significantly reduce the incidence of DVT, monitoring is widely used to detect evolving thrombosis. More intense anticoagulation (adjusted dose heparin,two step warfarin) may be effective but requires laboratory tests and carries increased risk of bleeding. Itwould be an economic and medical advantage to restrict prophylaxis and monitoring to patients who will develop DVT. Based on observations in a canine model of THR, we developed andtested a method that shows promise of being able toidentify, intraoperatively, patients who will develop DVT.In the canine model we found characteristic venous lesions (gaping tears through endothelium and basementmembrane, localized to confluences,selectively infiltrated with platelets and leukocytes). Incidence of lesions correlated with intraoperative venodilation, measured by a modified ultrasound scanner. Lesionsmight serve as sites for initiationand anchorage of thrombi. Diagnostic ultrasound was used to monitor cephalic vein diameter in 25 THR patients and 12 TKR patients. In THR patients, 1 of 9 patients with venodilation of 6-16% developed DVT. At 21-57% venodilation 12 of 12 THR patients developed thrombi. In the intermediate range of venodilation (19%,20%), 2 of 4 patients developedDVT. In 12 TKR patients, 10 had venodilation of 0-16% and none developedDVT in the non-operated leg. In patients with 22% and 55% venodilation,one did and one did not develop DVT in the non-operated leg (expectedfrcxn equal distribution between legs in THR patients).DVT in the operated leg did not correlate with venodilation. We suggest that in THR patients substances released at the operative site circulate briefly, causing venous dilation. In TKR patients the tourniquet prevented substances from being circulated, reducing venodilation and DVT in the non-operated leg. Proximitv of surgicalwound to calf veins and tourniquet pressure mav have contributed to DVT in the operated leg.
UNSTABLE ANGINA : DEFINITION
Authors: Julian D G 
Published: August 2018

A satisfactory definition of unstable angina continues to be elusive.Like stable angina, it is a clinicalsyndrome, and mustbe defined in those terms. In both cases, it is understood that myocardial ischaemiabut not infarction is responsible for the symptoms. For angina to earn the “unstable” label, theremust have been the recent development or deterioration of symptoms. Traditionally, “recent” has meant within the last month, but it has become increasingly clear thatthe time frame is of critical importance - the patient with a sudden irruption of severe chest pain in the last two days is likely to have a different pathology and prognosis from the individual who first developed exercise-induced pain two weeks ago, which has not worsened during this period. Likewise, the patient who hadhis last attack of pain one week agois very different from one who had his last attack one hour ago; indeed in the HINT study, there was a high incidence of myocardial infarction undetected on admission in the lattergroup (Br Heart J 1986;56:400-13).A problem that has hardly been addressed is “When does unstable angina stop being unstable?”. The answer must be when it either becomes stable (i.e. stops getting worse),or proceeds to myocardial infarctionor death.Most studies have shown that the vast majority of patients stablise quickly, often losing their symptoms completely. There is, however, a group of patients who fail to respond promptly to medical treatment, and it isthese patients who are most likely to go on to angiography, angioscopy, angioplasty, surgery, myocardial infarction or death. Thus, the enormously valuable information we have obtained from, for example, angiography and necropsy studies applies essentially only to this subset of unstableangina patients, albeit they are themost severe. Unfortunately, such studies tell us relatively little aboutthe more dynamic aspects of the disorder, such as the role of coronary vasomotion.It is only relatively recently that clinicians have appreciated that they have quite simple means of suspecting the mechanisms involved. Thus, the history of progressive exercise-induced angina on the one hand or angina only at rest on theother must tell us something of the underlying physiopathology. Likewise,the fact that the symptoms respond to rest, or beta-blockers, or calcium antagonists also provides evidenceas to causation.Thus, while all would agree that angina is “unstable” whenit has recently developed or worsened, it must bediscussed in subsetsdefined by their history and response to treatment.In this way, we may be able to assign a patient to a particular clinicalgroup, which will indicate that it is likely that he has a particular physiopathology, which inturn will suggest the most appropriate management.
EDRF AND RESISTANCE VESSELS
Authors: Griffith T M , Edwards D H , Davies R L , Harrison T J , Evans K L 
Published: August 2018

The influence of endothelium on vasomotionin resistance vessels was studied in an isolated, buffer-perfused rabbit ear preparation using novel microangiographic techniques and haemoglobin as a specific inhibitor of EDRF. In constricted preparations acetylcholine and Substance P, whose action is EDRF-dependent in large vessels, induceddilatation in vessels down to 25um in diameter which was inhibited by haemoglobin. Log (IC50>q) values calculated from diameter changes were the same in the central artery, GO, and its first three generations of branch vessels Gl, G2 and G3 (ie down to 7Oum) being -7.7 and -9.8 respectively. Consistent with this, almost identical valueswere derived from the pressure responses of the intact network. Such spatial homogeneity has not been found when the same vessels are studied in isolation. In contrast,constrictor responses to 5HT or histamine exhibited spatial heterogeneity (in the rank order G0>G1>G2>G3) which was exaggerated by inhibition of basal EDRF activity. Inerms of normalised diameter changes EDRF and its analogue GTN were equipotent in reversing these constrictor responses in GO to G3. Interms of hydraulic resistance however, dilator responses paralleled relative changesn resistance induced by the constrictor agents. EDRF and GTN thus appear more potentin vessels exhibiting high degrees of tone.In control preparations (i.e. in the absence of pharmacological constriction) basal EDRF activity was found to exert maximal influence in vessels in which calculatedshear stress and hydraulic resistance werehighest, and continuously inhibited myogenic tope in Gl and to a lesser extent G2 and G3. In the absence of haemoglobin, diameter and flow were related by the expression QÒaD4+b in GO, Gl and G2 over an 8-fold range of flow rates. In the high-flow limit this implies constancyof pressure gradient and pressure drop inthese vessels so that the energy expended in delivering a given volume of perfusate to the terminal elements of the bed would be effectively independent of flow rate, rather than directly proportional to it as in a rigid tube.Basal EDRF activity also conferred identical flow-related distensibility in G0 through G3 in control and partially constricted preparations over the samerange of flow rates. This implies independence of flow distribution from flowrate. Flow dependent release of EDRF may provide a mechanism which links network topography with vessel function, thus optimising perfusion characteristics.
GLA-CONTAINING PROTEINS FROM CALCIFIED HUMAN ATHEROSCLEROTIC PLAQUES
Authors: Van Haarlem L J M , Hemker H C , Soute B A M , Vermeer C 
Published: August 2018

Vitamin K-dependent carboxylase activity has been detected in human andbovine vessel wall. Studies comparingthe carboxylases from liver and vessel wall revealed that the enzyme systems may be regarded as isoenzymes withwidely different substrate specificities. The carboxylated product of vessel wall carboxylase has not yet been identified, but it seems plausible that it will be found amongst the Gla-containing proteins which are abundantly present in calcified atherosclerotic plaques (Gla= gammacarboxyglutamicacid, the abnormal amino acid formed by vitamin K-dependent carboxylase). Therefore we have started to characterize the protein constituents of hardened atherosclerotic plaques.The calcified areas from human aortae were solubilized in EDTA and the proteins extracted were partly purified by batch-wise adsorption onto QAE and elution with high salt. The crudeplaque-extract did not contain prothrombin, factor X or protein C. This excludes the possibility that Gla-containing coagulation factors are bound non-specifically from blood. Osteocalcin accounted for 20% of the total amount of protein-bound Gla-residues.Another Gla-containing protein waspurified from the crude plaque-extract by employing high performance liquid chromatography (HPLC). Gel filtration yielded a Gla-rich protein with anapparent Mr of 25 kD. In vitro boththe crude plaque-extract and the purified Gla-containing protein strongly inhibited the precipitation of calcium phosphate and calcium carbonate. A similar effect was not found with humanserum albumin nor with a thermallydecarboxylated plaque-extract. If also in vivo the Gla-containing proteinsproduced by vessel wall carboxylase prevent the precipitation of calcium salts remains to be investigated.
HIGH AND VERY HIGH DENSITY LIPOPROTEINS ADMINISTRATION INHIBITS PROGRESSION OF EXPERIMENTAL ATHEROSCLEROSIS IN THE RABBIT
Authors: Badimon J , Bodimon L , Fuster V 
Published: August 2018

Epidemiologic studies have shown an inverse relationship between HDL and coronary artery disease. We have previously demonstrated that in vivo administration of HDL-VHDL inhibits thedevelopment of atherosclerosis in cholesterol (cho)-fed rabbits. In the present study we have analyzed whether high levels of the physiological cholesterol acceptor, homologous HDL-VHDL,could inhibit the progression of established atherosclerotic lesions. Atherosclerosis was induced by feeding rabbits a 0.5% cho-rich diet for 2 months (140g/day). At that moment, a subgroup of animal (N=4) was sacrificed and their aortas showed 30 ± 8% of aortic atherosclerotic involvement. The remaining animals, kept on the same atherogenic diet, were randomly divided in two identical groups (N=7): a control and a treated group administered with 50 mg of HDL-VHDL a week for 4 weeks. HDL-VHDL fraction wasisolated from normal rabbit plasma byultracentrifugation at a density range of 1.063-1.25g/ml. The amount of HDL-VHDL administered was determined byits protein content according to Lowry"s technique. The 50mg of HDL-VHDL, measured as protein, contained1.4mg of total cholesterol, 1.43mg oftriglycerides and 0.6mg of phospholipids. At sacrifice, the treated group showed a marked decrease on the extent of aortic by fatty streaks (20 ± 6%X ± 1SE) as compared to(36% + 6) inthe control group (p < 0.05). Similar results were obtained in aortic wall lipid accumulation (See table, results expressed as X±1SEM; rag/gr dry aorta.)In conclusion, administration of HDL-VHDL induced a marked inhibition on the progression of atherosclerosis in cholesterol-fed rabbits.
HEPARIN STIMULATES FIBROBLAST GROWTH INDUCED BY PDGF
Authors: Dupuy E , Rohrlich P S , Tobelem G 
Published: August 2018

Heparin binds to smooth muscle cells and endothelial cells. It inhibits the proliferation of the smooth muscle cells and modulates the growth of endothelial cells. Fibroblasts which represent an other cell type belonging to the vascular wall could also have their growth modified by heparin. We have at first, demonstrated that 125I unfractionated heparin bigds to cultured human skin fibroblasts with a Kd of 1.16 10 M.A low molecular weight heparin fraction (PK 10169) competed (50 %)with I unfractionated heparin, but at aless extent than cold unfractionated heparin(90%).As it has been reported with endothelial and smooth muscle cells, about 30% of the bound unfractionated heparin was internalized bythe fibroblasts. Heparin alone at the concentration ranges from 0 to 10-5M has no effect on fibroblast proliferation measured by the H thymidine uptake. When the cellproliferation was induced by pure PDGF, heparin potentiated markedly the fibroblast growth.The effgct started at 10-8 M heparinand reached a plateau from 10-6 M to 10-5 M. Similar stimulationwas observed when the growth was induced by FGF or EGF. Low molecular weight heparin enhanced the fibroblast proliferation induced by PDGF but at a less extent than unfractionated heparin, chondroltin sulfate has no effect. When added during the cell culture growth withhuman serum (5%), unfractionated heparin increased by 48 the cell proliferation as measured bycell counting at the 6th day of the culture. PDGF did not modify the heparin binding on fibroblast cultures either at 4°C or 37°C and did not alter the process of heparin internalization. JDGF binding to the cultured fibroblast (Kd 10.1 ± 3.4 10-10 M)was not modified by the presence of heparin when studied at 4°C.In conclusion : i) cultured human fibroblasts bind and internalize heparin, ii) heparinand heparin fraction stimulate the fibroblastgrowth induced by PDGF, iii) since the binding of PDGF is not modified by bound heparin, the mechanism of stimulation remains unknown.
PLATELET-DERIVED GROWTH FACTORA-CHAIN GENE ACTIVATION AND GROWTH FACTOR PRODUCTION BY HUMAN AORTIC SMOOTH MUSCLE CELLS
Authors: Kanthou C , Parker C , Huber D E , Stroobant P , Kakkar V V , Pringle N , Richardson W 
Published: August 2018

The many contributory factors leading to the development of cardiovascular disease are currently thought to induce a common pathological change involving smooth muscle cells, which migrate from the vessel wall, proliferate,accumulate at the sites of endothelial cell damage, and then secrete connective tissue proteins and lipids which contribute to the plaque which results in the occlusion of the vessel. According to the recently modified hypothesis of Ross (1), a key event in the development of atheroma may be the abnormal release of a number of growth modulatory polypeptides,including platelet-derived growth factor (PDGF), which can potentially originate from platelets, endothelial cells, monocytes or macrophages, and smooth muscle cells themselves.We have isolated smooth muscle cell lines from 25 samples of human aorta, using digestion with collagenase and elastase. With DNA synthesis and Northern blot techniques, we examined them for both the production of PDGF-like proteins, and for the possible activation of the PDGF A-chain and B-chain genes. Severallines secreted a growth factor and were stillviable after culture for 57 days in serum-free medium. Parallel experiments using Northernblot analysis revealed the activation of the PDGF A-chain gene in all lines examined with no detectable B-chain gene transcripts.These data raise the possibility that vascular damage may activate the gene encoding the A-chain of PDGF in adjacent smooth muscle cells. Such cells might then become capable ofautonomous growth, in an analogous manner tocells transformed by Simian Sarcoma Virus, whose sis oncogene encodes the B-chain of PDGF.
A SPECIFIC THROMBOXANE A2 ANTAGONIST, GR32191, REDUCES PLATELET DEPOSITION IN PTFE GRAFTS
Authors: McCollum C N , Harper R A , Lane I F , Meek A C 
Published: August 2018

Platelet inhibitory therapy improves patency in arterial grafts but when aspirin is given over 20% of patients discontinue therapy. We evaluated a specific Thromboxane A2 antagonist (GR32191 - Glaxo Group Research) on graft platelet uptake and pseudo-intimal hyperplasia in a canine model.Thirty greyhounds were randomised to orally administered placebo, GR32191 25mg, or aspirin150mg (ASA) plus dipyridamole 50mg (DPM) 12 hourly, commencing 48 hours prior to implantation of a 6cm length of 6mm-PTFE in the femoral artery. Autologous 111In-platelete were infused on the fifth postoperative day and platelet uptake measured by probe and ratemeter with the daily rise in graft radioactivity over reference expressed as Thrombogenicity Index (TI). Drugs were continued to 8 weeks when 111In-platelets were again infused and graft uptake measured on the excised graft and expressed as a ratio to blood. Percentage luminal stenosis was measured by grid microscopy.GR32191 significantly reduced luminal stenosis and graft platelet uptake compared to placebo and although TI appeared lower with both platelet inhibitory regimens this did not achieve statistical significance (p<0.1>0.05). Thromboxane A2 antagonists reducethrombus formation on artificial surfaces andbeing specific may have less undesirable effects.
LOCALIZATION CF FIBRIN POLYMERIZATION SITES BY PHOTQAFFINITY LABELING
Authors: Kuyas C , Sigrist H , Straub P W 
Published: August 2018

Fibrin polymerization is competitively inhibited by the te-trapeptide GlyProArgPro. This peptide corresponds to the N-terminal sequence of the fibrin α-polypeptide chain, which is exposed upon release of fibrinopeptide A by thrombin. A binding site for GlyProArgPro was suggested to be located in the C-terminal end of the 411 amino acids containing γ-chain (Varadi and Scheraga, Biochemistry, 25, 519, 1986). In order to characterize the polymerization domain, GlyProArgProLys-azidoazobenzene, a photoactivable derivative of GlyProArgPro was synthesized. Photoaffinity label was bound to fibrinogen in the dark and photolysis was carried out at 0°C. After reduction and S-carboxymethy-lation of the photoaffinity labeled fibrinogen, the polypeptide chains (Aα, Bβ,γ ) were separated by ion-exchange chromatography. Photolabel binding was monitored imnunologically with anti-azo-benzene antibodies (ELISA, Western blot). Selective labeling of the γ-chain was observed. Labeled γ-chains were further digested with CNBr, and the resulting fragments were separated by reversed phase HPIC, immunologically characterized and identified by Edman degradation. GlyProArgProLys-azidoazobenzene was incorporated in the 18 kD CNBr-fragment (γ95-264). The CNBr-fragments arising from C-terminal end of the γ-chain were not labeled.Our results indicate that the binding site of GlyProArgPro is localized exclusively on γ-chain, within the sequence γ95-264.
FACTOR VII-PHOSPHOLIPID COMPLEX IN MALE SURVIVIRS OF ACUTE MYCORDIAL INFARCTION
Authors: Arnesen H , Dalaker K , Smith P , Prydz H 
Published: August 2018

The finding of coagulation factor VII-phospholipid complex in plasma of some men at high risk for cardiovascular disease has previously been reported (1). Factor VII present in such complexes is markedly activated, and this activitation is reversible upon treatment with phospholipase C.We report here on the presence of this activated form of factor VII in 100 male survivors of acute myocardial infarction The subjects were recruited from 475 patients in the placebo group of the prospective double-blind Warfarin Re-Infarction Study (WARIS).Two age groups were defined:55 years or younger, and older than 55. In each age group the 25 patients with the highest or lowest conventional risk factor scores (total cholestrol, systolic blood pressure, and smoking habits) were selected. The amount of factor Vll-phospholipid complex was estimated as factor VII activity before and after treatment with phospholipase C.The factor VII-phospholipid complex was found to be responsible for 29% (mean value) of the total factor VII activity in the whole material. The level of this activated form of factor VII did not correlate with age or level of conventional risk factor score, but showed a highly significant positive correlation with serum triglycerides in all the subgroups, as well as in the total material (r=0,88, p<0.0001).Presence of the factor VII-phospholipid complex contributes to the procoagulant state in hypertriglyceridemia, and its measurement may constitute an additional screening method for men at risk for cardiovascular disease.
Ref.:	(1) Dalaker K., Hjermann I, and Prydz H.
Br J Haematol 1985,61,315
EFFECT OF DIFFERENT HEPARINS ON THROMBOLYSIS WITH t-PA AND scu-PA IN RABBITS WITH EXPERIMENTAL THROMBOSIS
Authors: Juhan-Vague I , Stassen J M , Alessi M C , Kieckens L , Collen D 
Published: August 2018

Infusion of heparin or low-Mr heparin fractions in animals with experimental thrombosis or in patients with thromboembolic disease may result in a significant reduction of the thrombus size, without being associated with measurable changes in the blood fibrinolytic parameters.We measured the effect of clinical grade heparin (Hep) and of two low-Mr heparin fragments (CY216 and CY222 from Choay, Paris, France) on thrombolysis with t-PA and with scu-PA in a rabbit jugular vein thrombosis model (Collen et al., J. Clin. Invest. 71, 368, 1983). After thrombus formation, t-PA (0.25 mg/kg) or scu-PA (0.5 mg/kg) were infused over 4 hours. The heparins were administered at hourly intervals at the start and during the infusion as bolus injections of the following amounts (expressed in anti-Xa units): Hep: 70 (A) or 200 (B); CY216: 30 (A) or 90 (B); CY222: 50 (A) or 150 (B). Results were (mean ± SEM): It is concluded that at sufficiently high doses, heparin and to a larger extent the two low-Mr heparin fractions CY216 and CY222, potentiate thrombolysis by rt-PA and scu-PA in this animal model of thrombosis.
PGI2 AND PGE1 INHIBIT SMOOTH MUSCLE CELL PROLIFERATION MITOTIC ACTIVITY AND EXTRACELLULAR MATRIX FORMATION
Authors: Sinzinger H , Zidek T , Fitscha P , Wagner O , Rogatti Waltraud 
Published: August 2018

Earlier findings that activated smooth muscle cells (SMC) generate more PGI2 indicate a pathophysiological role of PG's in SMC-proliferation. In a rabbit experiment enhanced mitotic activity (MA) induced by ACTH or desoxycorticosterone acetate(DCS) is significantly depressed by both PGI2 and El.most effective.Similarly, a decrease in collagen and glycosamino-glycan-formation canbe noted. PGI2 is able to inhibit quite selectively liberation of platelet derived growthfactor (PDGF). PDGF itself stimulates vascular PGI2-generation,inhibiting further PGDF-relese long-1lasting intermittent alternating PGI2/PGE1 therfore be of optional effect concerning the local vascular SMC-action