bluuebunny/crossref_metadata_2025 huggingface dataset:
The HP2 Survey
Authors: Hasenberger Birgit , Lombardi Marco , Alves João , Forbrich Jan , Hacar Alvaro , Lada Charles J.
Published: July 2018

Multi-wavelength observations in the sub-millimeter regime provide information on the distribution of both the dust column density and the effective dust temperature in molecular clouds. In this study, we created high-resolution and high-dynamic-range maps of the Pipe nebula region and explored the value of dust-temperature measurements in particular towards the dense cores embedded in the cloud. The maps are based on data from the Herschel and Planck satellites, and calibrated with a near-infrared extinction map based on 2MASS observations. We have considered a sample of previously defined cores and found that the majority of core regions contain at least one local temperature minimum. Moreover, we observed an anti-correlation between column density and temperature. The slope of this anti-correlation is dependent on the region boundaries and can be used as a metric to distinguish dense from diffuse areas in the cloud if systematic effects are addressed appropriately. Employing dust-temperature data thus allows us to draw conclusions on the thermodynamically dominant processes in this sample of cores: external heating by the interstellar radiation field and shielding by the surrounding medium. In addition, we have taken a first step towards a physically motivated core definition by recognising that the column–density–temperature anti-correlation is sensitive to the core boundaries. Dust-temperature maps therefore clearly contain valuable information about the physical state of the observed medium.
Probability distribution functions of gas surface density in M 33
Authors: Corbelli Edvige , Elmegreen Bruce G. , Braine Jonathan , Thilker David
Published: July 2018

Aims.We examine the interstellar medium (ISM) of M 33 to unveil fingerprints of self-gravitating gas clouds throughout the star-forming disk.

Methods.The probability distribution functions (PDFs) for atomic, molecular, and total gas surface densities are determined at a resolution of about 50 pc over regions that share coherent morphological properties and considering cloud samples at different evolutionary stages in the star formation cycle.

Results.Most of the total gas PDFs are well fit by log-normal functions whose width decreases radially outward. Because the HI velocity dispersion is approximately constant throughout the disk, the decrease in PDF width is consistent with a lower Mach number for the turbulent ISM at large galactocentric radii where a higher fraction of HI is in the warm phase. The atomic gas is found mostly at face-on column densities belowNHlim= 2.5 × 1021cm−2, with small radial variations ofNHlim. The molecular gas PDFs do not show strong deviations from log-normal functions in the central region where molecular fractions are high. Here the high pressure and rate of star formation shapes the PDF as a log-normal function, dispersing self-gravitating complexes with intense feedback at all column densities that are spatially resolved. Power-law PDFs for the molecules are found near and aboveNHlim, in the southern spiral arm and in a continuous dense filament extending at larger galactocentric radii. In the filament nearly half of the molecular gas departs from a log-normal PDF, and power laws are also observed in pre-star-forming molecular complexes. The slope of the power law is between −1 and −2. This slope, combined with maps showing where the different parts of the power law PDFs come from, suggests a power-law stratification of the density within molecular cloud complexes, in agreement with the dominance of self-gravity.
Orbital and atmospheric characterization of the planet within the gap of the PDS 70 transition disk
Authors: Müller A. , Keppler M. , Henning Th. , Samland M. , Chauvin G. , Beust H. , Maire A.-L. , Molaverdikhani K. , van Boekel R. , Benisty M. , Boccaletti A. , Bonnefoy M. , Cantalloube F. , Charnay B. , Baudino J.-L. , Gennaro M. , Long Z. C. , Cheetham A. , Desidera S. , Feldt M. , Fusco T. , Girard J. , Gratton R. , Hagelberg J. , Janson M. , Lagrange A.-M. , Langlois M. , Lazzoni C. , Ligi R. , Ménard F. , Mesa D. , Meyer M. , Mollière P. , Mordasini C. , Moulin T. , Pavlov A. , Pawellek N. , Quanz S. P. , Ramos J. , Rouan D. , Sissa E. , Stadler E. , Vigan A. , Wahhaj Z. , Weber L. , Zurlo A.
Published: July 2018

Context. The observation of planets in their formation stage is a crucial but very challenging step in understanding when, how, and where planets form. PDS 70 is a young pre-main sequence star surrounded by a transition disk, in the gap of which a planetary-mass companion has recently been discovered. This discovery represents the first robust direct detection of such a young planet, possibly still at the stage of formation.

Aims. We aim to characterize the orbital and atmospheric properties of PDS 70 b, which was first identified on May 2015 in the course of the SHINE survey with SPHERE, the extreme adaptive-optics instrument at the VLT.

Methods. We obtained new deep SPHERE/IRDIS imaging and SPHERE/IFS spectroscopic observations of PDS 70 b. The astrometric baseline now covers 6 yr, which allowed us to perform an orbital analysis. For the first time, we present spectrophotometry of the young planet which covers almost the entire near-infrared range (0.96–3.8 μm). We use different atmospheric models covering a large parameter space in temperature, log g, chemical composition, and cloud properties to characterize the properties of the atmosphere of PDS 70 b.

Results. PDS 70 b is most likely orbiting the star on a circular and disk coplanar orbit at ~22 au inside the gap of the disk. We find a range of models that can describe the spectrophotometric data reasonably well in the temperature range 1000–1600 K and log g no larger than 3.5 dex. The planet radius covers a relatively large range between 1.4 and 3.7 RJ with the larger radii being higher than expected from planet evolution models for the age of the planet of 5.4 Myr.

Conclusions. This study provides a comprehensive data set on the orbital motion of PDS 70 b, indicating a circular orbit and a motion coplanar with the disk. The first detailed spectral energy distribution of PDS 70 b indicates a temperature typical of young giant planets. The detailed atmospheric analysis indicates that a circumplanetary disk may contribute to the total planetflux.
Natural rarity places clownfish colour morphs at risk of targeted and opportunistic exploitation in a marine aquarium fishery
Authors: Militz Thane A. , Foale Simon , Kinch Jeff , Southgate Paul C.
Published: July 2018

As fish stocks become depleted, exploitation eventually fails to be cost-efficient. However, species or morphs of species can suffer from continual exploitation if their rarity results in increased value, justifying the cost-efficiency of targeted or opportunistic exploitation. The trade in coral reef fishes for public and private aquaria is an industry in which naturally rare species and rare morphs of species command high prices. Here we investigate the relationship between price and the natural prevalence of colour morphs of two highly demanded clownfish species using a localised case study. The export prices for colour morphs increased with decreasing prevalence of occurrence (y = 4.60x−0.51, R2 = 0.43), but price increase was inversely less than the observed reduction in prevalence. This renders rare colour morphs (i.e., those at relatively low prevalence) at risk of opportunistic exploitation. Using ecological data, we also demonstrate how this increased value can subject rare colour morphs with aggregated distributions to targeted exploitation. These findings are discussed in relation to the broader marine aquarium trade, identifying taxa potentially at risk from exploitation motivated by rarity and addressing potential management strategies.
Bilan de la surveillance épidémiologique des travailleurs du cycle électronucléaire en France
Authors: Samson E. , Leuraud K. , Rage E. , Caër-Lorho S. , Ancelet S. , Cléro E. , Bouet S. , Hoffmann S. , Fournier L. , Belloni M. , Jovanovic I. , Bah T. , Davesne E. , Blanchardon E. , Challeton-de Vathaire C. , Laurier D. , Laurent O.
Published: July 2018

À ce jour, les normes internationales de radioprotection sont essentiellement basées sur les connaissances des effets sanitaires des rayonnements ionisants issues des études de cohortes de survivants des bombardements atomiques d’Hiroshima et de Nagasaki, qui ont subi des irradiations par voie externe à forts débits de doses. Or, les expositions aux rayonnements ionisants survenant en population générale et chez certains travailleurs correspondent généralement à de faibles doses, cumulées de manière prolongée dans le temps. Ces expositions peuvent avoir lieu par irradiation externe mais aussi par contamination interne. Les études épidémiologiques chez les travailleurs du nucléaire permettent notamment de mieux caractériser les effets de ces conditions d’expositions. Elles permettent ainsi d’évaluer l’adéquation des normes de radioprotection pour protéger les travailleurs, mais également la population générale adulte, contre les risques de cancer. Par ailleurs, elles permettent d’aborder de nouveaux questionnements de recherche en radioprotection, comme les potentiels effets non cancéreux. Enfin, ces études fournissent un bilan de santé général des populations de travailleurs du nucléaire. Cet article propose une vue d’ensemble des recherches épidémiologiques menées par l’Institut de Radioprotection et de Sûreté Nucléaire (IRSN) chez les travailleurs du cycle électronucléaire en France. Il dresse également quelques perspectives de développements possibles de ces recherches.
Atropisomerism in the 2,3,4,5-Tetrahydro-1H-1,5-benzodiazepine Nucleus: Effects of Central Chirality at C3 on the N-Mesylation Reaction
Authors: Tabata Hidetsugu , Takahashi Hideyo , Natsugari Hideaki , Tsuji Yuka , Yoneda Tetsuya , Tasaka Tomohiko , Oshitari Tetsuta
Published: July 2018

The mesylation reaction of the 1,3-dimethyl-2,3,4,5-tetra­hydro-1H-1,5-benzodiazepine nucleus was investigated in detail. Two diastereomers (A and B) of 5-mesyl-1,3-dimethyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepines, originating from chirality at C3 and at the Ar–N(SO2) axis were formed, among which isomers of the derivative with a methyl group at C6 (R = CH3) were separable at room temperature. A and B had chair-like and boat-like conformations, respectively, in which the C3-methyl group adopts a pseudoequatorial arrangement. Furthermore, A and B were shown to be the thermodynamically and ­kinetically controlled products, respectively.
Capturing Waste Heat Energy with Charge-Transfer Organic Thermoelectrics
Authors: Dimitrov Vladimir , Woodward Simon
Published: July 2018

Electrically conducting organic salts, known for over 60 years, have recently demonstrated new abilities to convert waste heat directly into electrical power via the thermoelectric effect. Multiple opportunities are emerging for new structure–property relationships and for new materials to be obtained through synthetic organic chemistry. This review highlights key aspects of this field, which is complementary to current efforts based on polymeric, nanostructured or inorganic thermoelectric materials and indicates opportunities whereby mainstream organic chemists can contribute.

1 What Are Thermoelectrics? And Why Use Them?

2 Current Organic and Hybrid Thermoelectrics

3 Unique Materials from Tetrathiotetracenes

4 Synthesis of Tetrathiotetracenes

5 Materials and Device Applications

6 Future Perspectives
The Acid-Catalyzed 2-O-Alkylation of Substituted 2-Hydroxy-1,4-naphthoquinones by Alcohols: Versatile Preparative Synthesis of Spinochrome D and Its 6-Alkoxy Derivatives
Authors: Polonik Sergey , Sabutskii Yuri , Denisenko Vladimir
Published: July 2018

A series of substituted 2-alkoxy-1,4-naphthoquinone derivatives were obtained by acid-catalyzed condensation of substituted 2-hydroxy-1,4-naphthoquinones with propan-1-ol, butan-1-ol, or pentan-1-ol in good yields. Based on this reaction a versatile preparative synthesis of spinochrome D was developed.
Nucleophilic Phosphine-Promoted Domino Reaction of Dialkyl Acetylenedicarboxylates and 3-Arylamino-1-methyl-1H-pyrrole-2,5-diones
Authors: Han Ying , Yan Chao-Guo , Liu Chang-Zhou , Zhang Yuan-Yuan , Sun Jing
Published: July 2018

The three-component reaction of triphenylphosphine, dimethyl acetylenedicarboxylate and 3-arylamino-1-methyl-1H-pyrrole-2,5-diones in CH2Cl2 at room temperature resulted in functionalized 3-(triphenyl-λ5-phosphanylidene)succinates in nearly quantitative yields. However, tri(n-butyl)phosphine promoted reaction of dialkyl acetylenedicarboxylates and 3-arylamino-1-methyl-1H-pyrrole-2,5-diones in CH2Cl2 afforded functionalized pyrrolo[3,4-b]pyridine-4-carboxylates in satisfactory yields.
Plasma Measurement of D-Dimer as Diagnostic Aid in Suspected Venous Thromboembolism: An Overview
Authors: Bounameaux H , de Moerloose P , Perrier A , Reber G
Published: July 2018

This paper reviews the published experience with plasma measurement of D-dimer (DD), a specific degradation product of crosslinked fibrin, in the diagnostic approach of venous thromboembolism (VTE). Pooling 11 studies (with weighting of the figures according to sample size) with a total of 1337 patients clinically suspected of deep venous thrombosis (DVT) (prevalence of DVT 35%) disclosed an average weighted sensitivity of 96.8% (95% CI: 95.2–98.4) and specificity of 35.2% (95% Cl: 32.0–38.4) for the presence of DVT when the ELISA technique was used. In 908 patients suspected of pulmonary embolism (PE) from 9 trials (prevalence of PE 38%), the ELISA technique was associated with a weighted sensitivity of 96.8% (95% Cl: 95.0–98.6) and specificity of 45.1% (95% Cl: 40.8–49.4) for the disease. Figures obtained with latex assays were definitely lower, precluding their use in the diagnostic approach of VTE.

These results show that a low concentration of plasma DD measured by the ELISA technique (usually less than 500 μg/1) might be used to rule out VTE in clinically suspected patients. Increased plasma concentrations are of no utility because of the low specificity of this test result.

The clinical usefulness of the DD ELISA test should now be assessed in management trials under routine conditions, in the frame of clinical decision-making diagnostic processes. Lastly, the promising data obtained in a small number of asymptomatic, postoperative patients at risk of VTE deserve confirmation before the test can be recommended for initial screening in thrombo-prophylactic trials.
Comparison of Subcutaneous Unfractionated Heparin with a Low Molecular Weight Heparin (Fragmin®) in Patients with Venous Thromboembolism and Contraindications to Coumarin
Authors: Monreal M , Lafoz E , Olive A , del Rio L , Vedia C
Published: July 2018

Intravenous heparin followed by oral anticoagulant therapy (e. g. with coumarin) is still the most widely used treatment for deep venous thromboembolism. Self-administered subcutaneous injections of heparin have been thought of as a promising alternative to coumarin, but the high doses required for ongoing prophylaxis have raised concerns about the possible development of bone disease. Certainly, long-term heparin therapy has been reported to cause osteoporosis in both laboratory animals and humans.

This study aimed to compare the efficacy and safety of unfractionated (UF) heparin with that of a low molecular weight heparin (Fragmin®, Kabi Pharmacia) in the prevention of recurrent deep venous thrombosis (DVT) and pulmonary embolism (PE) in a consecutive series of patients with contraindications to coumarin therapy. The patients comprised 40 men and 40 women, aged between 19 and 92 years (mean age, 68 years). They had all previously been diagnosed as having acute DVT and had been treated with conventional doses of heparin while in hospital. All patients had at least one of the following conditions: recent blood loss (either spontaneous or during admission while receiving heparin therapy); active gastroduodenal ulcer disease; psychological or physical inability or unwillingness to understand and accept the need for regular laboratory monitoring during coumarin treatment; chronic alcoholism; dementia; pregnancy; recent neurosurgery, and pericardial effusion; or were over 80 years of age. They were randomly allocated to receive either UF heparin, 10,000 IU s.c. b.d., or Fragmin®, 5000 IU anti-Factor Xa s. c. b. d., for a period of 3-6 months.

Two patients taking UF heparin were readmitted to hospital 2 and 3 months after discharge, owing to symptomatic, scintigraphically proven recurrent PE. No patients receiving Fragmin® had recurrent PE. There were 10 reports of minor bleeding: six in patients receiving UF heparin and four in patients on Fragmin®. Furthermore, there were seven cases of spinal fracture: six in patients on UF heparin, and one in a patient taking Fragmin®.

We conclude that fixed doses of both UFH and Fragmin® appear to be quite effective and safe for use in patients with a high risk of bleeding. In our experience, however, UF heparin is associated with an unacceptably high incidence of spinal fracture.
Blood Fibrinolysis and the Response to Desmopressin in Glomerulonephritis
Authors: Brommer E J P , Van den Wall Bake A W L , Dooijewaard G , Potter van Loon B J , Emeis J J , Weening J J
Published: July 2018

Fibrinolytic parameters and von Willebrand factor (VWF) antigen were measured in 22 patients with glomerulonephritis (GN) who underwent renal biopsy after desmopressin (DDAVP) infusion. Blood was collected immediately before and after DDAVP infusion, after one week, and 3–6 months later. The main abnormalities on admission were the following: the mean baseline levels of t-PA antigen and VWF were significantly higher in GN patients than in 22 healthy controls; the median t-PA activity and the mean scu-PA level were significantly lower than normal . The t-PA response to DDAVP was impaired in 7 patients (32%), the response of VWF in 9 patients (41%), and the u-PA: Ag response in 11 patients (50%). When the patients were stratified according to creatinine clearance rate, significant differences between the subgroups with severely and moderately impaired renal function were noted: the baseline levels of PAI activity and VWF were higher in patients with severe renal failure and the VWF response to DDAVP was significantly lower. The response of u-PA (not of t-PA or VWF) to DDAVP appeared to correlate with urine flow during the first 24 h, suggesting the dependence of u-PA release on intact nephrons. A series of 18 patients with adult-type polycystic kidney disease (APKD) with creatinine clearance rates in the same abnormal range as the GN patients, had lower mean PAI and a significantly higher mean scu-PA level. Normalization of scu-PA and t-PA:Ag levels during follow-up despite impaired renal function in GN, and the absence of depressed scu-PA levels in APKD suggest that the fibrinolytic abnormalities are independent of the impaired renal function per se, but associated with the acute stage of nephritis.
Antiplatelet Effects of Ticlopidine Are Reduced in Experimental Hypercholesterolemia
Authors: Hohlfeld Thomas , Scharnowski Frank , Braun Marina , Schrör Karsten
Published: July 2018

This study determines the antiplatelet effects of oral ticlopidine (100 mg/kg × day) in experimental hypercholesterolemia. Rabbits were fed either a standard diet or a cholesterol-enriched diet (0.5% for 3 months, 1% for 1 month). In normocholesterolemic controls ADP-, but not collagen-induced platelet aggregation was inhibited by ticlopidine treatment. This was accompanied by a significantly enhanced inhibition of ADP-induced platelet aggregation and stimulation of cyclic AMP accumulation by iloprost. Hypercholesterolemia considerably attenuated the inhibition of ADP-induced aggregation by ticlopidine but did not change its effect on the iloprost-induced inhibition of platelet function and cyclic AMP formation. ADP-induced platelet-derived Llnumbuxane formation was considerably greater in hypercholesterolemic rabbits and not reduced by ticlopidine. Ticlopidine did also not significantly influence the extent and severity of atherosclerotic plaque formation although a tendency for improvement was observed in a subgroup of animals. The data suggest that hypercholesterolemia attenuates the inhibitory effect of ticlopidine on A DP-induced platelet aggregation. This might be related to the stimulation of thromboxane formation by ADP in hypercholesterolemia. The maintained protection from ADP-induced inhibition of cAMP accumulation suggests a minor role of this mechanism in the progression of hypercholesterolemia-induced vessel disease in this model.
Attenuating Effect of Antithrombin III on the Fibrinolytic Activation and Microvascular Derangement in Rat Gastric Mucosa
Authors: Kurose Iwao , Miura Soichiro , Fukumura Dai , Suzuki Masayuki , Nagata Hiroshi , Sekizuka Eiichi , Morishita Tetsuo , Tsuchiya Masaharu
Published: July 2018

The roles for the fibrinolytic activation and disorder of coagulation in formation of gastric ulcer induced by microvascular derangement were investigated. The rat stomach was exposed and repeated electrical stimuli (RES) were applied on the small arterial wall close to the lesser curvature to induce mucosal microcirculatory disturbances. The level of tissue-type plasminogen activator (t-PA), a key enzyme for fibrinolytic activity, in the regional blood of the stomach was significantly elevated immediately after RES. At 5 min after RES, the leakage of FITC-labeled albumin and thrombus formation in the mucosal microvasculature were visually demonstrated by using an intravital microscopic system. At 30 min, hemorrhagic erosions and linear ulcers were observed in the gastric mucosa. Pretreatment with human anti-thrombin-III (AT-III) in the range of 0.1–10 U/kg dose-dependently attenuated both the fibrinolytic activation and microvascular alteration promoted by RES. Human AT-III also prevented RES-induced gastric mucosal injury. Thrombin inhibitory activity in the gastric vein decreased (69.0 ± 2.1%) just after RES, and further reduced at 30 min (47.7 ± 5.3%). The present study suggests a hypothesis that human AT-III has a preventive effect on the gastric mucosal hemorrhagic changes via attenuating the fibrinolytic activation and subsequent microcirculatory disturbances.
Prevalence and Induction of Circulating Antibodies against Recombinant Staphylokinase
Authors: Declerck P J , Vanderschueren S , Billiet J , Moreau H , Collen D
Published: July 2018

Streptokinase (SK) is a routinely used thrombolytic agent but it is immunogenic and allergenic; staphylokinase (STA) is a potential alternative agent which is under early clinical evaluation. The comparative prevalence of antibodies against recombinant STA (STAR) and against SK was studied in healthy subjects and their induction with intravenous administration in small groups of patients.

Enzyme-linked immunosorbent assays, using microtiter plates coated with STAR or SK and calibration with affinospecific human antibodies, revealed 2.1 to 65 μg/ml (median 11 μg/ml) anti-STAR antibodies and 0.9 to 370 μg/ml (median 18 μg/ml) anti-SK antibodies (p <0.001 vs anti-STAR antibodies) in plasma from 100 blood donors, with corresponding values of 0.6 to 100 μg/ml (median 7.1 μg/ml) and 0.4 to 120 μg/ml (median 7.3 μg/ml), respectively, in 104 patients with angina pectoris. Three out of 17 patients with Staphylococcus aureus bacteremia had significantly increased anti-STAR antibody levels (150, 75 and 75 μg/ml), and STAR neutralizing activities (2.2, 3.6 and 4.1 μg STAR neutralized per ml plasma, respectively). In 6 patients with acute myocardial infarction, given 10 mg STAR intravenously over 30 min, median anti-STAR antibody levels were 3.5 μg/ml at baseline, 2.9 μg/ml at 6 to 8 days and 1.2 μg/ml at 2 to 9 weeks, with median corresponding titers of STAR neutralizing activity at 2 to 9 weeks of 42 μg/ml plasma. Conversely, in 5 patients treated with 1,500,000 units SK over 60 min, median anti-SK antibodies increased from 2.9 μg/ml at baseline to 360 μg/ml at 5 to 10 days, with corresponding median SK neutralizing activities of 13 μg/ml. Antibodies against STAR did not cross-react with SK and vice versa.

Plasma from human subjects contains low levels of circulating antibodies against recombinant staphylokinase, and intravenous administration of this compound boosts antibody titers. These antibodies do however not cross-react with streptokinase, whereby the use of these two immunogenic thrombolytic agents would not be mutually exclusive.
Expression and Characterization of Clustered Charge-to-Alanine Mutants of Low Mr Single-Chain Urokinase-Type Plasminogen Activator
Authors: Ueshima S , Holvoet P , Lijnen H R , Nelles L , Seghers V , Collen D
Published: July 2018

In an effort to modify the fibrinolytic and/or pharmacokinetic properties of recombinant low M
r single-chain urokinase-type plasminogen activator (rscu-PA-32k), mutants were prepared by site-directed mutagenesis of clusters of charged amino acids with the highest solvent accessibility. The following mutants of rscu-PA-32k were prepared: LUK-2 (Lys 212, Glu 213 and Asp 214 to Ala), LUK-3 (Lys 243 and Asp 244 to Ala), LUK-4 (Arg 262, Lys 264, Glu 265 and Arg 267 to Ala), LUK-5 (Lys 300, Glu 301 and Asp 305 to Ala) and LUK-6 (Arg 400, Lys 404, Glu 405 and Glu 406 to Ala).

The rscu-PA 32k moictic3 were expressed in High Five Ttichoplasiani cells, and purified to humugciicily from the conditioned cell culture medium, with recoveries of 0.8 to 3.7 mg/1. The specific fibrinolytic activities (220,000 to 300,000 IU/mg), the rates of plasminogen activation by the single-chain moieties and the rates of conversion In lwo chain moieties by plasmin were comparable for mutant and wild-type rscu PA 32k moieties, with the exception of LUK-5 which was virtually inactive. Equi-effective lysis (50% in 2 h) of 60 pi 125I-fibrin labeled plasma clots submerged in 0.5 ml normal human plasma was obtained with 0.7 to 0.8 μg/ml of wild-type or mutant rscu-PA-3?.k, except with LUK-5 (no significant lysis with 16 pg/ml). Following bolus injection in hamsters, all rscu-PA-32k moieties had a comparably rapid plasma clearance (1.3 to 2.7 ml/min), as a result of a short initial half-life (1.4 to 2.5 min). In hamsters with pulmonary embolism, continuous intravenous infusion over 60 min at a dose of 1 mg/kg, resulted in 53 to 72% clot lysis with the mutants, but only 23% with LUK-5, as compared to 36% for wild-type rscu-PA-32k.

These data indicate that clustered charge-to-alanine mutants of rscu-PA-32k, designed to eliminate charged regions with the highest solvent accessibility, do not have significantly improved functional, fibrinolytic or pharmacokinetic properties.
Immunofluorescence Study on Thrombolysis with Special Reference to the Patterns of Distribution and the Contents of Fibrin, Plasminogen, α2-Macroglobulin and Urokinase in Artificial Thrombi
Authors: Hisano Shuusuke
Published: July 2018

By the immunofluorescence technique, fibrin, plasminogen and α2-macroglobulin demonstrated a similar basic pattern of distribution in the artificial thrombi, rimming the platelet aggregates in the white part and forming a network structure in the red part. The content of plasminogen seemed to be higher in the red part than in the white part. After superfusion with urokinase solution, urokinase was found in a similar pattern of distribution to that of fibrin. The content of urokinase seemed to be higher in the red part, especially in its outer area, than in the white part. It is concluded that urokinase diffused into the artificial thrombi can convert plasminogen, trapped onto fibrin threads to plasmin. Poor lysibility of the white part might be due to thick strands of fibrin, a low content of plasminogen and a low diffusibility of plasminogen activator, in addition to the antifibrinolytic activity of platelets.
Biochemical Changes Noted during Intermittent Administration of Streptokinase
Authors: Verstraete M , Vermylen J , Schetz J
Published: July 2018

An intermittent dosage scheme of streptokinase (standard initial dose 600,000 units SK infused over 30 min and repeated injections of 250,000 units SK at 24 hr intervals) was applied during 4 days in 9 patients with chronic obliterative arterial disease and in 8 patients with venous occlusion.

Each dose of streptokinase produced an immediate fall in plasminogen to 17 % (SEM 5.1) of the initial value, the level then rose to 50 % (SEM 5.4) within 24 hr. Lowered levels of antiplasmin and fibrinogen (both less than 40% of the initial values) were maintained. This safe level of fibrinogen was maintained despite brief but high peaks of plasmin activity after each injection of SK. A parallel increase of the thrombin time and the fibrin(ogen) degradation products was obtained following each infusion. No bleeding was observed. The relative therapeutic effect of intermittent infusions of streptokinase has still to be compared with the continuous administration of streptokinase in controlled clinical trials.
Clinical and Laboratory Aspects of Disseminated Intravascular Coagulation (DIC): A Study of 118 Cases
Authors: Siegal Tali , Seligsohn Uri , Aghai Esther , Modan Michaela
Published: July 2018

The medical records of 118 cases who met laboratory criteria of DIC were studied. The most frequent etiologies were: Generalized infection (39.8%), trauma (16.9%), malignancy (6.8%) and surgical cases (6.8%). The main clinical manifestations which appeared to be related solely to DIC were (in a decreasing order of frequency): Bleeding (64.4%), renal dysfunction (24.6%), liver dysfunction (18.6%), respiratory dysfunction (16.1%), shock (14.4%), thromboembolic phenomena (6.8%) and central nervous system involvement (1.7%). In 26 patients none of these manifestations were observed. In patients with infection, liver and renal dysfunction were frequent and respiratory dysfunction rare, whereas in trauma cases, liver and renal dysfunctions were rare and respiratory dysfunction frequent. This variability indicates that the clinical manifestations are affected not only by the process of intravascular coagulation but also by the underlying clinical disorders.

The most impaired coagulation tests were prothrombin time, partial thromboplastin time, platelet count and thrombin time. The degree of abnormality of these coagulation tests was found to be related to the extensiveness of organ involvement.

The mortality (overall 54.7%) increased independently with age, with the number of clinical manifestations and with the degree of abnormality of the above-mentioned four most impaired coagulation tests. In addition, older patients were more likely to have an increased number of clinical manifestations and more impaired coagulation tests. Mortality was similar in the various etiologies except for trauma patients in whom it was lower (30%).
Ultrastructural Changes of the Tissue Thromboplastin after Intravenous Injection in Rabbits
Authors: Hasegawa Hiroshi , Nagata Hiroshi , Murao Makoto
Published: July 2018

Attempts were made to demonstrate ultrastructural changes of the tissue thromboplastin after intravenous injection, as a model experiment on the pulmonary microthrombi formation induced by the tissue thromboplastin circulating from venous return.

Concentrically arranged membrane structures of the injected thromboplastin disappeared in extremely short time after the injection of the thromboplastin in rabbits. The long sheet membrane of the injected thromboplastin was frequently seen as adhered to the vascular endothelium or to the surface of blood corpuscles. Furthermore, fibrin fibres were formed in contact with the long sheet membrane of the thromboplastin. Membrane structures were not found anywhere in the control rabbits.
Factor XI (PTA) Deficiency in an English-American Kindred
Authors: Zacharski Leo R , French E Elizabeth
Published: July 2018

2 sisters of English-American descent had a mild bleeding syndrome due to marked deficiency (less than 1 % activity) of factor XI. This defect was transmitted in an autosomal recessive manner. Although factor XI deficiency was previously thought to occur largely, if not exclusively in Jews, extensive review of geneologic records and analysis of family names failed to disclose Jewish ancestry. These findings, together with the existence of several definite and presumed consanguineous English-American ancestors, the fact that family members had resided in a restricted geographic area for many generations, and analysis of English and Jewish immigration patterns lead to the conclusion that this defect is not likely to be of Jewish derivation. Should this mutation have occurred in the distant past it is conceivable that the gene pool for this defect is substantial, particularly in certain areas in New England.
Spontaneous Platelet Aggregation in Cerebrovascular Disease
Authors: Ten Cate J W , Vos J , Oosterhuis H , Prenger D , Jenkins C S P
Published: July 2018

50 patients from a group of 130 patients with transient ischaemic attacks or cerebral infarction were found to demonstrate in vitro spontaneous platelet aggregation (SPA) while 80 normal subjects tested never showed this phenomenon.

The following additional findings point towards a possible platelet abnormality:

1. Platelets from 10 patients with SPA when isolated and resuspended in normal plasma still demonstrated SPA while isolated normal platelets resuspended in patient’s plasma did not.

2. Platelets demonstrating SPA showed an increased aggregation tendency upon incubation with ADP while normal platelets developed the expected refractory state.

SPA was found to be dependant upon the presence of divalent cations and could further be inhibited by phentolamine and adenosine. Aspirin effectively abolished SPA in 50 patients and relieved the clinical symptoms of patients with recurrent complaints of transient blindness and paraesthesia.
Platelet Function in Hyperbetalipoproteinemia
Authors: Colman Robert W
Published: July 2018

Individuals with familial hyperbetalipoproteinemia are at increased risk of premature atherosclerosis and thrombosis. Although there is controversy whether platelet survival is shortened or normal in this disease, several in vitro tests of platelet function are abnormal including a decreased threshold concentration for stimulation of aggregation by ADP, epinephrine and collagen and increased release of nucleotides to the same agents. These functional changes are accompanied by an increase of cholesterol to phospholipid ratio in the platelet membrane and in low density lipoprotein in individuals with type Ha hyperlipoproteinemia. Clofibrate and halofenate reverse some of the abnormalities in vitro and the former drug, when administered for 6 weeks to patients with type II a hyperlipoproteinemia decreases platelet sensitivity to ADP and epinephrine. The platelet hypersensitivity to aggregating agents can be reproduced in vitro by increasing the cholesterol to phospholipid rather in normal platelets. These artificially hypersensitive platelets can be returned to normal by halofenate in vitro. Incorporation of cholesterol into platelet membranes increases the basal level of the membrane associated enzyme adenylate cyclase. However, the enzyme no longer responds to stimulation by prostaglandin E1 and this is associated with relative resistance of the platelet to inhibition by this pharmacologic agent. These functional alterations produced by cholesterol enrichment of platelet membranes occur is parallel with an increase in platelet membrane microviscosity suggesting that the more rigid membrane can alter the behavior of membrane associated enzymes and receptors. A correlation appears to exist between the ability of certain drugs to induce phase separation in model membranes and the potency in inhibitory platelet aggregation.
The von Willebrand Pig as a Model for Atherosclerosis Research
Authors: Fuster V , Bowie E J W
Published: July 2018

In order to evaluate a possible role played by platelets in the development of atherosclerosis, the aortas of 11 control pigs and 11 homozygous von Willebrand (vWd) pigs were examined for spontaneous atherosclerosis. Of the 11 normal pigs, 6 showed multiple atherosclerotic plaques with an intimal thickening of 63 to 130 μm. In contrast, none of the von Willebrand pigs had multiple plaques and only one showed a single lesion of more than 2 mm in diameter.

In a prospective study 5 control pigs and 5 vWd pigs were given a high (2%) cholesterol diet from the age of 3 to 9 months. All of the controls developed atherosclerotic plaques. In 4 of the pigs the plaques exceeded 13% of the aortic surface with an intimal thickening of 50 to 390 pm. In contrast, only one of the vWd pigs developed atherosclerotic plaques which only involved 7% of the aortic surface. Most of the vWd pigs, however, developed non-atherosclerotic flat fatty lesions. These findings may be related to the imp aired platelet arterial wall interaction in vWd. The vWd pigs seem to be an ideal model for atherosclerosis research.
β-Thromboglobulin and Deep Vein Thrombosis
Authors: Smith R C , Duncanson Jeanette , Ruckley C V , Webber R G , Allan N C , Dawes Joan , Bolton A E , Hunter W M , Pepper D S , Cash J D
Published: July 2018

The measurement of plasma β-thromboglobulin as a potential diagnostic test for venous thrombosis has been investigated in 16 normal volunteers, 24 patients presenting with deep vein thrombosis (DVT) or pulmonary embolism and 46 patients screened by 125 I fibrinogen test (IFT) for post-operative DVT. The normal mean was 33 ng/ml (range 15-117 ng/ml). Of the 24 patients with clinical thrombotic disease 22 presented with DVT confirmed by phlebogram or IFT and 2 presented with embolism confirmed by lung scan. At the time of first presentation 12 out of 24 had βTG values greater than 70 ng/ml. All except 3 of this group of 24 patients had values of greater than 70 ng/ml at some stage during a subsequent week of daily sampling. DVT was detected in 13 out of 46 screened post-operative patients. There was a rise in βTG observed within 24 hr of the IFT becoming positive but the mean rise did not reach significance at the 5% level.

An association between DVT and high βTG values has been confirmed. However, its clinical value cannot yet be fully elucidated until factors, probably related to blood sampling and clearance, are further investigated.
Platelet Metal Levels in Normal Subjects Determined by Atomic Absorption Spectrophotometry
Authors: Baker Richmond J , McNeil John J , Lander Harry
Published: July 2018

A method has been developed for the estimation of iron, copper, zinc, calcium and magnesium in human platelets using atomic absorption spectrophotometry. Fe and Cu are either absent or present in very low concentration approaching the limit of detection: Zn, Ca and Mg are readily detectable. EDTA is preferable to ACD(A) or heparin as the anticoagulant for collection in that the platelet yield is reliable: however, slightly low results for Ca and Mg are obtained. Corrections for residual plasma and contaminating red cells are essential. Plasma and platelet metal levels in 33 normal subjects are reported together with the findings in four studies undertaken on platelets obtained from subjects with polycythemia vera.
Relationships of Adenine Nucleotide Metabolism to Platelet-Collagen Adhesion
Authors: Morin Robert J , Chen Albert F T
Published: July 2018

Adhesion of platelets to collagen fibrils in a stirred system was inhibited by preincubation of platelets with combinations of 2-deoxy-D-glucose and oligomycin or antimycin. The inhibition of adhesion was associated with a decrease in metabolic ATP to 6% of control levels. Without metabolic inhibitors, platelets adherent to collagen fibrils were found to have catabolized approximately 57% of their metabolic ATP, and converted a major part of this to IMP. Storage pool ATP and ADP contents were also diminished in the adherent platelets. Pretreatment with imipramine resulted in 76% inhibition of the release reaction, but only 5% inhibition of adhesion. Imipramine-treated platelets that were adherent to collagen showed significant depletion of metabolic ATP, but markedly diminished conversion of ATP to IMP as compared to control adherent platelets. Inhibition of deamination of platelet AMP by coformycin or erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) did not inhibit adhesion, although platelets adherent to collagen after treatment with these agents showed depletion of metabolic ATP. These studies suggest that adhesion is an energy dependent process, occurring independently of release, and not associated with conversion of ATP to IMP. The energy dependent portions of the adhesion process are probably disc to sphere transformation and pseudopod formation, the ATP threshold requirement is relatively low, and the ATP utilized can probably be regenerated during the adhesion process via glycolysis and oxidative phosphorylation.
Quantitation of Radio-Labelled Vitamin K1 and Vitamin K1 Epoxide in Plasma by High Pressure Liquid Chromatography
Authors: Bjornsson Thorir D , Swezey Sarah E , Meffin Peter J , Blaschke Terrence F
Published: July 2018

A convenient, accurate and reproducible high pressure liquid chromatographic method for the quantitation of radio-labelled vitamin K1 and vitamin K1 epoxide in plasma is described. The method involves the determination of total ether extractable radioactivity, and a chromatographic separation to determine the relative quantities of radio-labelled vitamin K1 and vitamin K1 epoxide. The method is useful over a wide range of ratios of the two compounds, and has a coefficient of variation of approximately 5%.
Comparison of Reagents for Determining the Activated Partial Thromboplastin Time
Authors: Hoffmann J J M L , Meulendijk P N
Published: July 2018

Six commercially available reagents for the determination of the activated partial thromboplastin time have been evaluated and compared with respect to their sensitivity to the coagulation factors VIII, IX and XI and to their response to heparin. Some variation was observed among the reagents regarding their sensitivity to factor XI and even greater differences were obtained with factors VIII and IX. It was also clear that none of the reagents was sensitive to the same extent to the factors tested. The sensitivity to heparin shows considerable variation, in terms of time as well as mode of response to increasing heparin levels. In four reagents this response is linear, it is logarithmic in one and the remaining one is yet again different.

It seems unlikely that any standardization of the APTT determination is at present possible with the reagents studied.
Blood Platelets as a Possible Source of Creatine Kinase in Rat Plasma and Serum
Authors: Shibata Sachiko , Kobayashi Bonro
Published: July 2018

The creatine kinase (CK) activity in rat plasma was found to be correlated with that in serum or platelets. Rat serum contained higher activity not only of CK but also of lactate dehydrogenase than the corresponding plasma. The plasma CK activity decreased with increasing age of rats. Only the brain-type isoenzyme of CK was found in plasma, serum and platelets. Contamination of brain-type with muscle-type isoenzyme was detected in rather exceptional cases in which the activity was high among old rats. These results suggest the possible contribution of blood platelets to the CK activity of circulating plasma as well as to the activity in serum in rats.
Ultrastructural Studies on the Surface Coat of Human Platelet Aggregated by Polylysine and Dextran
Authors: Taketomi Y , Kuramoto A
Published: July 2018

Positively charged macromolecule, polylysine (mol. wt. 15,000; 23,000; 180,000) could induce the platelet aggregation in low concentration but high concentration was required in the case of neutral macromolecule, dextran (mol. wt. 40,000; 250,000; 2,000,000). The larger molecules of polylysine and dextran were more effective in inducing platelet aggregation. In the dextran-induced aggregation, positively charged Thorotrast particles on the cell surface did not decrease significantly. On the other hand, the surface membranes of platelets aggregated by polylysine were essentially devoid of bound particles. Heparin in hibited the poly lysine-induced platelet aggregation but not the dextran-induced aggregation. These findings suggested that polylysine induced aggregation more effectively than dextran by reducing the negative surface charge and giving stronger adsorption force on cell surface.

In platelet-rich plasma, polylysine elicited the release reaction of 14C-serotonin but dextran did not. Possible mechanism by which polylysine could elicit the release reaction is the formation of more tightly packed platelet aggregate than that by dextran in the presence of the low calcium ion concentration in citrated platelet-rich plasma. Average distance between plasma membranes of aggregated platelets, however, did not vary with the degrees of polymerization of these macromolecules.
Meseclazone, 5-Chlorosalicylic Acid and Acetylsalicvlic Acid
Authors: Diamantis William , Kohlhepp William C , Haertlein Barbara , Melton John , Sofia R Duane
Published: July 2018

Meseclazone and its major metabolite, 5-chlorosalicylic acid (5-CSA) have been shown to possess anti-inflammatory, analgesic and antipyretic activity. The comparative effects of these compounds on platelet aggregation were evaluated in vitro and ex vitro with acetylsalicylic acid (ASA). in vitro, meseclazone and ASA exhibited almost identical inhibitory potency of secondary phase ADP aggregation while 5-CSA was less effective. Moreover, collagen aggregation was inhibited by all three agents: ASA > meseclazone > 5- CSA. Thrombin-induced aggregation was inhibited to approximately the same extent by 5- CSA and ASA while meseclazone was inactive. The in vitro effects on the release-inducing aggregants were confirmed by ex vitro experiments in rats. These demonstrated that ASA and meseclazone inhibited collagen-induced aggregation 1 and 4 hr after oral administration although ASA was three to four times more active. ASA, but not meseclazone, was still effective 24 hr after administration. Bleeding times in rats 1 and 4 hr following oral administration of meseclazone and ASA were not altered. It is concluded that meseclazone and/or 5-CSA inhibit in vitro and ex vitro platelet aggregation initiated by the release reaction similar to ASA and other non-steroidal anti-inflammatory drugs.
In Vivo Platelet Kinetics in 31 Diabetic Patients
Authors: Dassin E , Najean Y , Poirier O , Passa Ph , Bensoussan D
Published: July 2018

In vivo platelet survival was estimated, in 31 diabetic patients, using 51Cr-labelled autologous platelets. A mathematical analysis attempted to measure the “potential” life span (senescence process) and the degree of a superimposed aleatory destruction (consumption process).

The potential platelet life span in diabetics did not differ from normal values. However, excessive consumption was observed in one third of the studied cases, without correlation with the age of the patients, the clinical duration of diabetes, and the degree of vascular impairment. Thus, platelet kinetic studies did not provide presently useful indications, in a particular patient, regarding the prognosis of the vascular disease, and the justification of anti-aggregant therapy.