bluuebunny/crossref_metadata_2025_split huggingface dataset:
HAEMATOCRIT REDUCTION CONCOMITANT WITH ACUTE PHASE REACTANT RISE
Authors: Balnave K , Nelson S D , Moriarty A J 
Published: June 2019

The study aimed to investigate haematocrit variation as acute phase reactants rise in myocardial infarction.Serial measurements of haematocrit were undertaken in a cohort (N = 60) of patients over periods ranging from 6 to 28 days. Concurrent measurements of plasma fibrinogen were made by the method of Clauss. Patients with clinical or radiological evidence of heart failure were excluded as were patients with history or evidence of bleeding for any cause.Results showed a small initial transient rise in haematocrit above baseline of 3% within the first 12 hours post-infarction, followed by a mean decrease below baseline of the order of −16%. The decrease was maintained at the time of discharge from hospital (mean 9.5 days) at a level of −11%. In the single case where serial haematocrits were measured up to 28 days, haematocrit was still reduced by −12%. The maximum individual percentage decrease measured in any patient exceeded −30% and occurred at 3 days post-infarct. The decrease parallelled the rise in plasma fibrinogen but apart from the early post−infarct period, the correlation was poor because of the rise in other acute phase reactants subsequently.A postulated mechanism for the fall in haematocrit is that it reflects haemodilution. This is in part a physiological compensatory mechanism for the increasein colloid osmotic pressure that is attendant on the increase in acute phase reactants due to myocardial tissue destruction. The blood loss due to serial diagnostic phlebotomies cannot explain the magnitude of the decrease.
DO PLATELET INHIBITORS INCREASE OPERATIVE BLOOD LOSS?
Authors: Galvin DAJ , Meek A C , Pate P , McCollum C N 
Published: June 2019

Although platelet inhibitory therapy improves arterial graft patency, surgeons are anxious that preoperative administration may increase operative bleeding. We investigated the effect of platelet inhibitors on blood loss during femoral artery replacement in dogs.Thirty greyhounds were randomised to receive placebo, a thromboxane antagonist GR32191 25mg (Glaxo Group Research) or aspirin 150mg (ASA) plus dipyridamole 50mg (DPM) twice daily starting 48 hours prior to implanting a 6cm length of 6mm PTFE in the femoral artery using standardised incision, mobilisation and anastomosis with 6.0 prolene. All bleeding was collected in swabs which were then thoroughly washed in 2L heparinised saline. The erythrocytes were haemolysed by adding potassium cyanide and the haemoglobin concentration measured in a Coulter Haemoglobinometer (Coulter Electronics). Blood loss was calculated by comparison to 1:500 dilution of the same animal’s venous blood. The bleeding time of the arterial anastomosis was also recorded.The mean (± sem) blood loss was similar in all three groups tending to be slightly less with GR32191 and ASA ± DPM at 135125 and 115±121 mis respectively, compared to 152±129 mis on placebo (NS). Anastomosis bleeding time appeared to be prolonged at 390±131 secs by the thromboxane antagonist compared to 291±40 with placebo and 224±136 with ASA and DPM, but this difference did not achieve statistical significance. There was a significant correlation (r=0.53) between blood loss and anastomotic bleeding time (p<0.001).This method of measuring blood loss is easily applicable to patients and does not demonstrate any important tendency to increased bleeding with preoperative platelet inhibitors.
CHANGES IN THE COAGULATION AND FIBRINOLYTIC SYSTEM DURING PREGNANCY
Authors: Woodhams B J , Candotti G , Kernoff P B A 
Published: June 2019

Blood samples were collected from 17 volunteers between 8-14, 26-28 and 32-34 weeks of pregnancy. Control samples were collected from 12 non-pregnant female volunteers not using oral contraceptives. All samples were assayed for fibrinopeptide A (FPA), B beta 15-42 and for cross linked D-dimer fragments. A sample was collected for measurement of the in vitro rate of generation of fibrinopeptide A from whole blood (FPA-R).These results are consistent with an increased activation of coagulation (increased FPA and shortened FPA-R) during normal pregnancy, which is compensated for by a concomitant rise in fibrinolytic activity (increased D-dimer and B beta 15-42). In 2 patients who miscarried and 2 patients who developed hypertension during pregnancy changes indicative of a non compensated hypercoagulable state could be seen. The study shows that the progress of pregnancy is associated with increased activation of coagulation and a concomitant rise in fibrin(ogen) degradation products. This data shows that a combination of these tests may be capable of detecting changes in the haemostatic balance that occur before the onset of clinical signs of gynaecological problems.
SELECTED HEMOSTASIS PARAMETERS IN PREGNANCY AND HYPERTENSION
Authors: Saleh A A , Farag A M , Bottoms S F , Mammen E F , Hosni M , Ali A 
Published: June 2019

Patients with preeclampsia are believed to have a state of compensated DIC, and especially the differential diagnosis between preeclampsia and chronic hypertension with pregnancy can be difficult. Selected hemostasis parameters were analyzed in 50 women with preeclampsia (P), 50 matched normal pregnant women (N), 14 women with known hypertensionand pregnancy (CH) and 13 persons with known chronic hypertension and superimposed preeclampsia (CH + P). None of the patients had clinical evidence of DIC. Platelet counts, mean platelet volume, antithrombin III, α2 antiplasmin and fibrinogen activities and fibronectin were assayed. The following data wereThese data, together with higherlevels of fibrinopeptide A, platelet factor 4, 3 thromboglobulin and D-dimer in the P group suggests increased intravascular coagulation in preeclampsia. Fibronectin levels were markedly elevated only in the patient groups with preeclampsia. Discriminant function analysis of FN values between the groups revealed a78% diagnostic accuracy for Palone and 74% accuracy for CH + P
REDUCTION OF THE ANTICOAGULANT ACTIVITY OF PROTEIN C AND PROTEIN S DURING THE POSTOPERATIVE PERIOD
Authors: Vigano D'Angelo S , Gilardoni F , Seveso M P , Marassi A , Mari G , D'Angelo A 
Published: June 2019

Protein S circulates in plasma as free protein S and in complex with C4b-binding protein, an inhibitor of complement activation. Only free protein S functions as the cofactor for the anticoagulant and profibrinolytic effects of activated protein C. Since isolated reductions of protein C and protein S result in increased thrombotic risk, only measurement of both proteins permits comprehensive evaluation of the antithrombotic potential of the protein C system. No information is available on protein C and protein S functional levels during the postoperative period, an established prothrombotic condition. The plasma changes of protein C, protein S and C4b-binding protein were followed in 40 patients with no malignancy undergoing abdominal surgery. No significant change of protein C and protein S activi ty was observed following minor operations. After major surgery, protein C anticoagulant activity dropped to 80% of preoperative levels during the first postoperative week (p<0.00l). Significant increase of both total protein S antigen (110%, p< 0.01) and C4b-binding protein (130%, p<0.001) were observed after major surgery resulting in reduction of free protein S antigen to 86% of pre operative values (p<0.001). Protein S anticoagulant activity matched the changes of free protein S antigen.Albeit transient and moderate, the observed reductions of both protein C and protein S may act synergistically to cause significant impairment of the antithrombotic potential during the postoperative period. The effect of heparin prophylaxis on protein C and protein S postoperative levels is currently under investigation.
PHYSIOLOGICAL COAGULATION INHIBITORS (PROTEIN S, PROTEIN C AND ANTITHROMBIN III) IN NORMAL PREGNANCY AND IN SEVERAL HYPERTENSION STATES IN PREGNANCY
Authors: Gilabert J , Fernández J A , Espana F , Aznar J , Estellés A 
Published: June 2019

The protein C (PC) - protein S (PS) anticoagulant system and antithrorribin III (AT III) were evaluated in normal pregnancy (group A, n= 53), severe preeclampsia (group B, n= 15) and chronic hypertension with superinposed severe preeclampsia (group C, n= 18). Group A was classified according to the stage of pregnancy as 1st (n=9), 2nd (n=ll) and 3rd (n=33) trimester (tr). A control group comprised 21 normal, non-pregnant women who were non-users of oral contraceptives. In normal pregnancy a significant decrease in the level of free protein S was observed in the 2nd trimester of pregnancy and was sustained throughout the remaining months. The other coagulation inhibitors (protein C and AT III) undergo no significant changes during pregnancy and remain within the limits of normality. In cases of preeclampsia a significant decrease in protein C was observed. It was more evident in severe preeclarrpsia but was also found in chronic hypertension with superiirposed severe preeclanpsia when compared with the normal pregnancy group at similar gestational age. No statistically significant differences in protein S were found when the normal and pathological groups were compared. AT III decreased slightly in the severe preeclamptic group but the decrease was not significant.The decrease in protein C and AT III levels in severe preeclanpsia could be related with the microthrombotic state that these patients may present. However, protein S, which decreases during normal pregnancy, seems to play no role in preeclanpsia.
INHERITED DEFICIENCY OF FUNCTIONAL PROTEIN S IN A JAPANESE FAMILY
Authors: Nakamura K , Iijima K , Inoue N , Nishioka J , Suzuki K 
Published: June 2019

A family with a history of severe recurrent venous thromboembolic disease in some of the members was studied over three generations. In the propositus, a 36-year-old Japanese man, assays for the coagulation, anticoagulation and fibrinolytic factors including fibrinogen, plasminogen, antithrombin III and protein C associated with inherited venous thrombotic disease were normal. While markedly decreased protein S, a cofactor of activated protein C, was revealed. The functional protein S activity in plasma was lower than 5% of normal. The same laboratory data were shown in his paternal uncle and two sisters who had recurrent thrombotic episodes, and his asymptomatic father as well. The mean protein S antigen was 38%(range 22-52%) by the conventional Laurell rocket immunoelectrophoresis. But by the crossed immunoelectrophoresis and the Laurell rocket electrophoresis using the PEG 8000 precipitation method, the free form protein S was undetectable in their plasma(Table). Thus, a significant coincidence between the antigenic free protein S levels and the functional protein S activities was clarified.It is suggested that the recurrent, thrombotic disease family is due to an inherited deficiency of protein S, larly of free form and functional protein S.
PROTEIN C : ROUEN - A NEW HEREDITARY PROTEIN C ABNORMALITY WITH LOW ANTICOAGULANT BUT NORMAL AMIDOLYTIC ACTIVITIES
Authors: Borg J Y , Vasse M , Monconduit M 
Published: June 2019

During the last three years, we could detect hereditary quantitative protein C (PC) deficiency in 43 patients belonging to 18 families. In those defects type I without oral anticoagulant treatment, the values of PC measured either by an ELISA method (PC:Ag) or by a chronometric functional assay were very closed and well correlated. (Results expressed in % of normal pooled plasmas PC:Ag m=44,l %, SD = 15,3 ; PC : activity m = 49,5, SD = 13,5 - correlation r = 0,82). In a 32 year#old man with a severe thrombo-embolic disease and in 11 related people, we could diagnose a hereditary qualitative PC deficiency type II, because of a discrepancy between normal PC:Ag levels (m = 105 %, SD = 20,3, range = 78-143) and low PC anticoagulant activities (m = 46 %, SD = 9,5, range = 30-60). FunctionalpC studies included assays, with or without preliminary adsorption on baryum citrate or aluminium hydroxide, with various PC activators (thrombin, PROTAC venom), in chronometric and amidolytic assays.(Normal protein S levelswere first tested).As shown by those results, PC activity is normal in amidolytic assays even after preliminary adsorption whatever the activation is. On the contrary, the PC anticoagulant activity is reduced in any technique. We can conclude that the activation is normal. Crossed immunoelectrophoresis (CIE) with or without calcium showed normal migration as compared to controls. Normal adsorption on insoluble salts and normal Ca-binding in CIE allow us to say that the abnormal PC is not completely acarboxylated. As amidolytic assays (normal in patients) do not assess the ability of activated PC to interact with protein S (PS) and phospholipids via calcium, 3 hypothesis can explain the functional abnormality:- abnormal binding to PS- abnormal binding to phospholipids due to partially carboxylated glutamic acids (which would be sufficient to promote adsorption)- defective inhibition of Va and Villa because a conformational change allowing only hydrolysis of little synthetic peptides.
AMIDOLYTIC DETERMINATION OF ANTI-ACTIVATED PROTEIN C ACTIVITY IN PLASMA
Authors: Nicham F , Martinoli J L 
Published: June 2019

Anti-activated protein C (anti-APC) potency of plasma was studied using purified bovine activated protein C (Bovine APC) and the chromogenic peptide substrate CBS 65.25. The choice of bovine instead of human APC was justified by a better sensitivity (Km = 0.14 and 0.42 mM respectively). Inhibition was shown to be dramatically enhanced by the presence of Heparin and calcium. No significant difference occurred for pH values up to 8.2 for both inhibition and hydrolysis reactions.In the final test, O.l ml of 1:5 diluted plasma (Tris buffer saline, pH 8.4, containing 5 U/ml of Heparin) were incubated at 37°C with 0.2 ml of Bovine APC (0.125 U/ml). After 10 minutes of inhibition, 0.2 ml of CBS 65.25 (1.5 mM/1) were added to the mixture and the change in absorbance was recorded at 405 nm for 2 minutes. In these conditions linearity of the dose-response curve was ensured from O up to 130 % of activity (normal plasma pool being assigned to 100 %) ; day to day precision was 1.9 %. When a normal plasma was overloaded with different purified inhibitors such as antithrombin III, cl-esterase inactivator, alpha 2 macroglobulin, the measured anti-APC activities were not affected at all. It could be concluded that this test measures protein C inhibitor described by Suzuki.Levels in 23 normal individuals averaged 97.7 %, giving a normal range of 77 - 118 %. Levels were below normal in 6 of 10 patients after surgery (54.1 +/- 4.8 %), in 18 of 19 patients with liver disease (49.5 +/- 9.6 %) and in 4 of 18 coumarin treated patients (54.9 +/- 6.5 %). In 9 of 10 patients previou sly characterized as type I protein C deficient, a statistically significant increase in anti-APC activity was observed (mean 110.7 +/- 7.7 %).The use of a chromogenic peptide substrate has led to a sensitive and fast assay for anti-APC activity in plasma. That could be of interest in clinical investigations and knowledge of regulatory mechanisms in thrombotic disorders.
The Synthesis of Factor V in Tissue Culture and Isolated Organ Perfusion
Authors: Giddings J. C. , Shaw E. , Tuddenham E. G. D. , Bloom A. L. 
Published: June 2019

Human foetal tissues were maintained in tissue culture and the presence of factor V detected by an indirect immunofluorescence technique. Established monolayer cultures of human foetal liver cells showed positive immunofluorescence when treated with rabbit anti human factor V serum and fluorescein isothiocyanate conjugated with anti rabbit immunoglobulin. Parallel liver cultures containing cycloheximide did not show positive fluorescence when stained by the same technique.Hepatic factor V synthesis was also investigated by an ex-vivo organ perfusion method using adult rat livers. Factor V synthesis was most clearly demonstrated utilising leucocyte-and platelet-poor perfusate. Factor V synthesis was totally inhibited by cycloheximide and was inhibited by actinomycin D after an initial delay. Factor V synthesis was not inhibited by Warfarin.The results indicate that factor V is synthesised in the liver by a mechanism similar to that of other plasma proteins and is not dependant on vitamin K for its activity.
Immunological Method for the Detection of the Carrier of Haemophilia B.
Authors: Matsuoka M. , Ito M. , Sakuragawa N. , Takahashi K. 
Published: June 2019

Both the immunoassay and bioassay were performed on factor IX activity of haemophilia B patient. Their values were compared with each other.The immunoassay by neutralization was performed as follows: antibody to factor IX was obtained by immunization of purified factor IX to rabbit which was isolated by the technique of DEAE-Sephadex column chromatography using eluate from BaS04 which absorbed factor IX of normal human plasma.In approximately 90% of the cases of definite carriers of haemophilia B, the activity of factor IX by bioassay was observed to be lower than that of factor VIII of haemophilia A carrier. The factor IX activity was observed to be at the same level as factor IX antigen by immunoassay in almost all of the cases, but in the cases of the mother of haemophilia B, and the North Carolina type of haemophilia B the factor IX antigen was much greater than that of activity by bioassay. The same results were obtained by the above mentioned methods using inhibitor substance arising from severe haemophilia B patient.It was suggested that the immunoassay method is useful in detecting the carrier of haemophilia B and North Carolina type of haemophilia B.
Fibrinogen Biosynthesis
Authors: Blombach B. , Redman C. , Kudryk B. 
Published: June 2019

A mixture of 3H-labeled amino acids was injected into dogs. Blood was collected at specific time intervals and fibrinogen from each corresponding plasma fraction was isolated by affinity chromatography. After reduction and alkylation, the fibrinogen chains were separated either by CM-cellulose chromatography or preparative SDS-gel electrophoresis. In one dog whose fibrinogen level was approximately 8 mg/ml, it was found that both the γ and B β chains had lower radioactivity when compared to the Aα chain, at least in the early times of appearance in blood. When this experiment was repeated in another dog whose fibrinogen level was 2 mg/ml and non-labeled amino acids were given as “chaser”, the radioactivity in the γ and Bβ chain did not reach the same value as that in the Aα chain, even after a three hour period. The significance of these findings with respect to rate of synthesis, secretion and assembly of the polypeptide chains will be discussed.Experiments were also performed using dog liver slices incubated with radioactive amino acids. Labeled, fibrinogen-related, material from detergent-solubilized rough endoplasmic reticulum (HER) could be recovered either by affinity chromatography or immunoprecipitation. Fractions were also isolated from smooth endoplasmic reticulum and Golgi. Analysis of the material isolated from BEB suggests that it may not consist of all three chains but rather one or possibly two of them to be either in degraded (during isolation procedures) or precursor form.(Supported by N.I.H. grants HL 09011–11 and AM 13620.)
Observations on Fragment D Species Arising During Hydrolysis of Crosslinked Human Fibrin
Authors: Mosesson M. W. , Finlayson J. S. 
Published: June 2019

A covalently linked bimolecular form of plasmic Fragment D has been identified by several investigators in digests of F. XIIIa-crosslinked (xlinked) fibrin (f). Peptides containing xlinks between α chains separate from the clot matrix prior to release of D ; therefore, such multimolecular core fragments must be joined by xlinked remnants of γ chain dimers. This observation has been interpreted as evidence for the so-called ‘mono-meric D’ fibrinogen structural model (Marder et al. J. Biol. Chem. 244, 2111 1969,). For this interpretation to be unambiguous, virtually all xlinked γ regions must retain their continuity with the D moiety at the time of its release from the clot. The studies to be reported did not support that presumption, and thus the observation by itself is consistent as well with the ‘dimeric D’ structural model (Mosesson et al. J. Biol. Chem. 1973, 248, 7913).Human f was xlinked by F. XIIIa to achieve at least complete γ dimerization. Following syneresis, clots were transferred to EDTA-containing buffers (pH 8.6), plasmin was added, and samples of the buffer solution were examined by dodecyl sulfate gel electrophoresis. Monomolecular species of D were generated as were derivatives corresponding to multi-molecular xlinked forms of D. Ultimately, although xlinked sites are themselves refractory to plasmic hydrolysis, all xlinked forms of D were degraded to species indistinguishable from those arising in digests of fibrinogen or non-xlinked f. These results indicate that intermolecular connections created by introduction of xlinks between γ chains are severed during the plasmin-catalyzed formation of D fragments. This event may prove to be a requirement for the release of D from clot matrix.(Supported by NHLI grant HL-11409.)
Early Endothelial Injury
Authors: Lough J. , Moore S. 
Published: June 2019

A variety of blood constituents were injected into an isolated segment of rabbit aorta to determine which elements might be involved in early endothelial injury. Test materials consisted of platelet rich plasma (P. R. P.) alone; P. B. P. plus adenosine diphosphate (A. D. P.); P. R. P. plus tendon extract; P. B. P. plus thrombin; ultrasonicated P. R. P. alone; platepoor plasma (P. P. P.) alone and thrombin in saline. Each experimental mixture was left in the aorta for 15 minutes, followed by reflow for 20 min. The vessel was then flex by glutaraldehyde perfusion. Thick sections of the entire circumference of the aorta were taken for phase contrast microscopy and representative areas were selected for electron microscopy. In control experiments and with sonicated P. R. P. and P. R. P. plus tendon extract, the endothelium was normal. With P. R. P. alone, P. P. P. alone and with P. R. P. plus A. D. P. there were occasional subendothelial vesicles. When P. R. P. plus thrombin and P. P. P. plus thrombin were injected separately to form a thrombus or when thrombin in saline was used, there was extensive subendothelial vesiculation with focal ulceration and adherence of thrombus to endothelium. Severe injury was associated with the presence of thrombin initiating the polymerization of fibrinogen to fibrin. Electron micrographs demonstrate the earliest lesion as a disruption of the superficial fibrillary elastica with separation of overlying endothelium.Additional Key Words: Plasminogen activation, turbulent flow, atherosclerosis, encrustation.
Mechanism of Collagen: Glucosyl-transferase and its Relation to Platelet: Collagen Adhesion
Authors: Smith D. F. , Kosow D. P. , Jamieson G. A. 
Published: June 2019

Elucidation of the enzymatic mechanism of collagen: glucosyltransferase is essential to an understanding of its role in platelet function. A soluble form of the enzyme has been purified 100-fold and a sensitive new assay system developed. Studies with effectors such as UDP, ADP and ristocetin under steady state conditions have shown that only two of the possible sequential mechanisms are consistent with the kinetic data. Inhibition by UDP and ADP is competitive with UDPG but non-competitive with galactosylhydroxylysine. They would not, therefore, be expected to inhibit the formation of an enzyme-substrate complex with collagen. Under physiological conditions, their presence would be expected to increase the affinity of the cell surface enzyme for its acceptor on collagen in the case of the ordered mechanism, or not to affect it in the case of the random mechanism. These data are consistent with the potentiation of collagen-induced aggregation by ADP, and the lack of effect of UDP on the adherence of platelets to collagen.(Supported, in part, by USPHS.)