bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE FIBRINOLYTIC, FACTOR VIII:C, VON WILLEBRAND FACTOR AND HEMODYNAMIC RESPONSES TO DDAVP IN PATIENTS WITH HEREDITARY NEPHROGENIC DIABETES INSIPIDUS
Authors: BRINK K , DERKX F , BROMMER E , STIBBE J , KOLSTEE H , SCHALEKAMP M 
Published: August 2018

The pressor response of vasopressin (AVP) is mediated by a calcium-dependent mechanism (VI-receptor), whereas its antidiuretic effect depends on c-ANP (V2-receptor). DDAVP (1-desamino-8-D-arginine vasopressin) is a synthetic V2 analog of AVP. AVP and DDAVP also increase FVIII:C vWF:Ag and tissue-type plasminogen activator (t-PA) in plasma. The mechanism by which AVP and DDAVP elevate these factors is unclear. Patients with X-linked nephrogenic diabetes insipidus (NDI) are resistant to the V2-mediated antidiuretic action of AVP and DDAVP. We therefore have studied the effect of DDAVP (0.4 ug/kg iv infusion in 10 min) in 2 brothers with NDI, their mother and an unrelated patient.In control subjects (n=12) FVIII:C rose 122 (6) % ,mean (SEM), vWF:Ag 104 (4) % and t-PA 115 (7) % over basal levels. This rise was associated with a fall in diascolic blood pressure -11 (3) mmHg and an increase in heart rate from 62 (4) to 91 (5) bpm. Plasma noradrenaline rose from 262 (34) to 590 (84) pg/ml and renin from 16 (3) to 42 (6) uU/ml. Ten out of 12 controls showed facial flusning. The patients with NDI had normal basal FVIII:C, vWF:Ag and t-PA levels. Plasma noradrenaline and renin were within the nor mam range. Tne patients with NDI were also resistant to the stimulatory effect of DDAVP on the release of FVIII:C, vWF:Ag and t-PA. They also showed no change in blood pressure, nearc rate, plasma noradrenaline and renin and had no facial flushing. The carrier had normal responses to DDAVP.Tne increase in FVII:C, vWF:Ag and t-PA and the hemodynamic responses after DDAVP infusion probably appear to depend on extrarenal V2-receptor activation. DDAVP cannot be used in identifying carriers in families at risk.
AIDS 1987
Authors: Desmyter J 
Published: August 2018

AIDS virus (HIV) transmission by transfusions and blood products has been essentially halted in industrialized countries which haye introduced systematic anti-HIV screening of donations in 1985. New anti-HIV screening assays, based in part on the replacement of disrupted HIV virions by defined DNA recombinant HIV antigens, have improved specificity; sensitivity has been improved as to dectect seroconversion at an earlier stage. Confirmatory assays and (self-)exclusion of risk groups from blood donation do remain mandatory. HIVAg can be detected in some infections before antibody conversion, and HIVAg is more likely to be found in those anti-HIV positives who proceed to disease. However, there is no justification so far for routine parallel HIVAg and anti-HIV screening. There is continued uncertainty how many HIV carriers have not (yet) developed antibody, but their numbers may have been overestimated. Studies to determine how many HIV transmitters have escaped blood bank detection, and why, need to be undertaken in spite of formidable logistic difficulties.The risk of developing AIDS is now estimated at 25-50 % within 10 years after the infectious contact. It is not clear whether the risk should be estimated differently in different groups or persons. In cities in Central Africa, 5-20 % of men and women are confirmed anti-HIV positives. At least 75 % of this HIV carrier rate is due to heterosexual transmission. Heterosexual transmission has been slower in Western countries, but factors precluding slow evolution to high figures by the same route outside Africa have not been identified. Therefore, countries have no choice in advocating behaviour changes in the general population, and not only in the classical risk groups. Initial hesitations toward extended voluntary and confidential screening are dwindling. Well-conceived confidential screening may be the only way to avoid strong-armed government intervention. The latter is certain to be divisive, and is likely to be counterproductive on balance.An efficacious vaccine remains remote, but an antiviral which prolongs life by at least several months in AIDS patients, but not all of them, is now available. Zidovudine (AZT), however, is toxic and mere prolongation of life without cure will impose an additional burden on AIDS economics.A novel virus (HIV-2) has been identified and is already widespread in West-Africans. It causes AIDS, but the present ratio of AIDS cases in those infected seems lower than with HIV(-l); this feature may be transient. HIV-2 antibodies are either detected or missed by anti-HIV-1 screens; if found, they can be distinguished from anti-HIV-1 only by special confirmatory technique. New screening assays showing equal sensitivity for HIV-1 and HIV-2 in a single test should be devised. At present, HIV-2 is very rare in Western countries compared to HIV-1.
DIRECTED MUTAGENESIS IN THE STUDY OF THE REQUIREMENTS FOR FACTOR VIII ACTIVITY IN VITRO AND IN VIVO
Authors: Kaufman Randal J , Pittman Debra D , Wasley Louise C , Foster W Barry , Amphlett Godfrey W , Giles Alan R 
Published: August 2018

Factor VIII is a high molecular weight plasma glycoprotein that functions in the blood clotting cascade as the cofactor for factor DCa proteolytic activation of factor X. Factor VIII does not function proteolytically in this reaction hut itself can be proteolytically activated by other coagulation enzymes such as factor Xa and thrombin. In the plasma, factor VIII exists as a 200 kDa amino-terminal fragment in a metal ion stabilized complex with a 76 kDa carboxy-terminal fragment. The isolation of the cENA for human factor VIII provided the deduced primary amino acid sequence of factor VIIT and revealed three distinct structural domains: 1) a triplicated A domain of 330 amino acids which has homology to ceruloplasmin, a plasma copper binding protein, 2) a duplicated C domain of 150 amino acids, and 3) a unique B domain of 980 amino acids. These domains are arranged as shown below. We have previously reported the B domain is dispensible far cofactor activity in vitro (Toole et al. 1986 Proc. Natl. Acad 5939). The in vivo efficacy of factor VIII molecules harboring the B domain deletion was tested by purification of the wildtype and modified forms and infusion into factor VIII deficient, hemophilic, dogs. The wildtype and the deleted forms of recombinant derived factor VIII exhibited very similar survival curves (Tl/2 = 13 hrs) and the cuticle bleeding times suggested that both preparations appeared functionally equivalent. Sepharose 4B chromatography indicated that both factor VIII molecules were capable of binding canine plasma vWF.Further studies have addressed what cleavages are necessary for activation of factor VIII. The position of the thrombin, factor Xa, and activated protein C (AFC) cleavage sites within factor VIII are presented below, site-directed ENA medicated mutagenesis has been performed to modify the arginine at the amino side of each cleavagesite to an soleucine. In all cases this modification resulted in molecules that were resistant to cleavage by thrombin at the modified site. Modification of the thrombin cleavage sites at 336 and 740 and modification of the factor Xa cleavage site at 1721 resulted in no loss of cofactor activity. Modification of the thrombin cleavage site at either 372 or 1689 destroyed oofactor activity. Modification of the thrombin cleavage site at 336 resulted in a factor VIII having an increased activity, possibly due to resistance to inactivation. These results suggest the requirement of cleavage at residues 372 and 1689 for cofactor activity.
THE INTERACTION BETWEEN FACTOR VIII AND VON WILLEBRAND FACTOR
Authors: Koedam Joost A , Hamer Rob J , Beeser-Visser Nel H , Tjoen San Etienne Jap , Schippers Kees , Sixma Jan J 
Published: August 2018

Factor VIII (FVIII) circulates in plasma as a non-covalent complex with von Willebrand factor (VWF), a large multimeric adhesive glycoprotein. VWF serves as a carrier for FVIII and is thought to stabilize FVIII. The interaction between the two proteins was studied by binding purified human 125I-FVIII to VWF which was coated on a solid matrix. Experiments employing isolated heavy and light chains of FVIII and monoclonal antibodies indicated that binding occurred through the carboxyterminal 80kDa light chain of factor VIII. Treatment of VWF-bound 125I-FVIII with thrombin resulted in the release of a light chain-derived 70kDa fragment and a heavy chain-derived 50kDa fragment. A 42kDa heavy chain-derived fragment was found in the fraction which remained bound to VWF. Treatment with factor Xa (FXa) resulted in the release of 63, 50, 45, and 42kDa fragments. No phospholipids were required for proteolysis of FVIII by either of these enzymes. In solution, the activation of FVIII by FXa, but not by thrombin, was inhibited by VWF. Neither activation, nor cleavage or release from VWF were observed when FVIII was incubated with factor IXa. Activation of FVIII was parallelled by its release from VWF. We conclude that the thrombin-activated form of FVIII consists of a complex between the 70kDa and 50kDa fragments. Inactivation of FVIII by activated protein C (APC) was inhibited when FVIII was complexed to VWF. This protective effect of VWF was abolished upon activation of FVIII and its subsequent release from VWF.In order to locate the binding site for FVIII on the VWF molecule, we digested VWF with Staphylococcal V8 protease (Sp). Digestion products were isolated with Mono Q ion-exchange chromatography and identified as Spl (39 kDa), SpII dimers (220 kDa) and Spill dimers (a triplet ranging from 210-280 kDa) by their molecular weight and chromatographic behaviour (J.-P. Girma et al.. Biochemistry 1986, 25:3156-3163). Purified VWF or digestion products were spotted on nitrocellulose paper, followed by blocking with an albumin solution. Binding of FVIII was studied by incubating the filters with 125I-FVIII, followed by autoradiography. Fifty ng of VWF was sufficient in order to detect FVIII binding. No binding was observed to partially reduced dimeric undigested VWF. Of the isolated digestion products, only the SpIII dimer was able to bind 125I-FVIII. After Western blotting of VWF-fragments from SDS-polyacrylamide gels, 125I-FVIII bound only to the bands which represented SpIII. Therefore, the domain on VWF responsible for the binding of FVIII seems to be located on its aminoterminal SpIII fragment. The integrity of internal disulfide bonds and dimerisation of VWF are required for FVIII binding.
CHANGES IN PGE2 AND TXB2 FORMATION BY PLATELETS OF ATHEROSCLEROTIC RABBITS
Authors: Laekeman G M , Van Hoydonck A , Van Diest M , Herman A G 
Published: August 2018

The synthesis of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were studied in groups of 9 rabbits fed a normal diet or a diet containing 0.3 % of cholesterol. After 16 weeks, a platelet rich suspension containing 300.000 platelets/mm3 was prepared. Portions were incubated at 37°C with arachidonic acid (AA). Biosynthesis of PGE2, TXA2 and TXB2 was evaluated by the bioassay cascade system (rabbit coeliac and mesenteric artery and rat fundus strip) and by radioimmunoassay (RIA) :No significant differences were recorded for TXB2 after 1 or 10 minutes incubationA small portion of blood without EDTA was allowed to clot at 37°C during 1 hour. TXB2 was measured in the serum by RIA. The mean ± SEM obtained for the atherosclerotic rabbits (82.70 ± 9.28 ng/ml) was significantly higher than the one for the normal group (42.66 ± 11.45 ng/ml) (P < 0.02, n = 9 for both groups. From these results it can be concluded that platelets of atherosclerotic rabbits apparently synthetize less PGE2 when incubated with AA, and more TXB2 during a standardized clotting process
EFFICACY OF INTRAVENOUS PENTOXIFYLLINE IN THE MANAGEMENT OF PATIENTS WITH CRITICAL LEG ISCHEMIA
Authors: Zahavi J , Schafer R , Zelikos-ki A , Firsteter E , Zahavi M , Avrahami E 
Published: August 2018

The xantine derivative pentoxifylline (P) can promote blood flow in the macro-and-micro circulation of ischemic tissues by improvement of red cell rigidity and by enhancing PGI2 release from the vascular endothelium. 35 patients (mean age 71±1.2 1SE years) suffering from critical leg ischemia due to advanced peripheral vascular disease (PVD) were treated by continuous I.V. drip of P (mean dose 22.2 g. during a mean period of 22.2 days). 19 patients were diabetics and 16 non-diabetics. Severity of PVD was assessed by the walking distance (WD), the presence of ischemic rest pain (IRP), leg ulcers or gangrene (doccumented photographically), hemodynamic evaluation using Doppler auscultation andby an arteriography of the lower limbs. The most common lesion on arteriography was occlusion or severe stenosis of the superficial femoral artery. All the patients suffered from IRP, 20 of them from leg ulcers and or gangrene. Following treatment of the diabetics, the WD was considerably improved (p≺0.01) in 7patients, the IRP disappeared in 11 and was milder in another 4 patients. Leg ulcers were healed in 5.out of 11 patients and gangrene subsided in 2 out of 9 patients. It was partially healed in another3 patients. Thus only in 4 patients the leg ischemia was worse and required bellow-knee amputation. In the non-diabetics, WD was improved considerably in 12 patients, the IRP disappeared in 11 and was milder in another 4 ' patients. Gangrene subsided in 2 out of 4 patients andwasimproved in the remaining 2 patients. None of these patients underwent amputation. The resting ankle pressure index(on Doppler auscultation) values were similar in the 2 groups and were increased after treatment (p≺0.01).Our results indicate that P ia a useful drug in the management of patients with advanced PVD and critical leg ischemia particularly in non-diabetics. It should be considered in inoperable patients in whom leg amputation is imminent. P can induce both subjective and objective improvement in the WD and the hemodynamicprofile of these patients and promote the blood flow in the microcicul-ation of the ischemic tissues in the lower limbs.
LIPOXYGENASE PRODUCTS CHANGES IN ‘IN VITRO’ AND ‘IN VIVO’ ASPIRINISED PLATELETS UNDER THE INFLUENCE OF PAF AND EPINEPHRINE
Authors: Makris P E , Papadopoulos A , Tsakiris D A 
Published: August 2018

We aimed to investigate the changes of lipoxygenase products in platelets and the simultaneous behaviour of ‘in vivo’ or ‘in vitro’ aspirinised platelets, stimulated by two agonists, PAF and epinephrine (EPI). 12 healthy were included. 6 received 20mg of aspirin (ASA) per os for 7 days (group A), and in 6 (group B) platelets were aspirinised ‘in vitro’ (5 or lOmin incubation at 37°C with ASA 1M). In group A blood was drawn once at the beginning and once at the end of the trial, while in group B just ome. First, platelet aggregation was studied using two agonists simultaneously (0.6 ¼M EPI and 20 nM PAF). We incubated then all platelet samples with 0.5 M of the substance BW755C (kind offer of Dr Moncada) far 3 min at 37°C. Second we measured PL0 products according to Takayama et al (1980), in platelets with or without ASA, and in platelets with ASA and after treatment with BW755C, always after addition of both agonists. Our results showed: a) Irreversible aggregation was slightly enhanced by the simultaneous addition of PAF and EPI in both groups and in non-aspirinised platelets. After ASA treatment, each agonist alone did not induce irreversible aggregation, whereas their combination overcame this inhibition, a fact not noticed under BW755C (a known PLO inhibitor). b) PLO products were measured in nmol TBRS/10 platelets:Our results agree with Cerletti et al (1986) and confirm that the two agonists combined are capable of overcoming the inhibition caused by ASA, possibly by activating the PLO pathway (Cerletti et al, 1986). Respectively the quantitative determination of PLO products (about which we did not notice any other report insofar) confirm the above assumption, since inhibition by BW755C coincides with the steep fall of PLOlevels, which for group A is statisticallysignificant (p≺0.01, paired t-test) and for group B entirely significant (p ≺0.001).
POST-OPERATTVE CHANGES IN PROIEINASE INHIBITORS IN NORMAL AND IMPAIRED WOUND HEALING
Authors: Reitz M , Sauer H , Witzke G , Neher M 
Published: August 2018

Tissue trauma after surgery activates blood coagulation. This results in a change and in the consumption of important inhibitors.We investigated the oonoentraticn of antithrorfoin III (AT III), ∝ 1-antitrypsin (∝l-AT), ∝ 2- macrogloublin (∝ 2-M) and Cl-inactivator (Cl-INH) in the blood plasma by means ofradial iirmunodiffusicn in 16 patients before surgery, after surgery and cn the 1st, 3rd and 7th days after surgery. In 11 patients normal wound healing wasobserved (group A), while in 5 patients amplicationsoccurred (group B). AT III: Fall in concentration upto the 3rd day after surgery, then a rise in concentration. In the patients with impaired wound healing there was a particularly marked reduction in AT III cn the 3rd day.∝ 1-AT: Fall in concentration after surgery, followed by a rise in concentration. In impaired wound healing a lower mean value was determined on the 3rd day after surgery than in normal wound healing. ∝ 2-M: Fall in concentration up to the 3rd day after surgery, followed by a slight increase in concentration. No striking difference between the normal group and the group with complications. Cl-INH: Fall in concentration after surgery, followed by arise in concentration; in the patients with impaired wound healing there was adelayed rise in concentration.
Induction of plasminogen activator inhibitor (PAI) by lipopolysaccharide (LPS)
Authors: DOSNE A M , DUBOR F , CHEDID L 
Published: August 2018

It has been shown that, under culture conditions, human endothelial cells synthetize plasminogen activator inhibitor (PAI) which neutralize urokinase and tissue plasminogen activator.Treatment of human endothelial cells with LPS (50 ngto 10 μg/ml) from S. enteritidis resulted in a dose-dependent increase in PAI production.Fibrinoenzymographic analysis showed that incubation of supernatantfrom LPS-treated cells with urokinase of low and high mol. w. (33.000 and 55.000) led to disappearance of the two urokinase lytic bands and formation of high mol. w. complexes (Mr 93.000 and 107.000). The mol. w. of the urokinase binding factor was calculated to be near 50.000. Polymyxin B and colimycin could suppress this effect of LPS. Injection of LPS (30 ng-30 yg/kg in the rat led to a considerable decrease in the fibrinolytic activity of plasma euglobulins which clot lysis time was prolonged from 55 up to morethan 240 min. This hypofibrinolytic state was associated with PAI detected in euglobulins and in plasma.Large complexes (Mr 80.000-105.000) were formed between exogenous urokinase of low and high mol. w. mixed with post LPS plasma or euglobulins. Polymyxin B and Colimycin could prevent the hypofibrinolytic response to low doses of LPS. These results suggest thatPAI generation in endotoxemia could be due in part to the direct effect of LPS on endothelium.
WINE CONSUMMATION AND PLATELET AGGREGATION
Authors: Seigneur M , Bonnet J , Dorian B , Hourdille P , Gouverneur G , Larrue J , Crockett R , Boisseau M , Ribereau-Gayon P , Bricaud H 
Published: August 2018

To compare the effects of ethanol and wine on factors inducing thrombosis, 16 healthy male volunteers had to drink3 kinds of beverage according to the following regimen :Ethanol reference is hydroethanolic solution at PH and ethanolic titre of wine.White wine is the reference of all wine cofactors excepting phenolics.Red wine is the reference all wine cofactors.At the beginning and at the end of each period, aggregation was measured with ADP 2 umole, Adrenaline 0,75 mg/1, Arachidonic Acid 0,5 mg/1.Results show statistically significant hyperaggregation with the 3 aggregation inductors during the ethanol period, no variation during white wine period and statistically significant hypoaggre-gation with adrenaline and ADP during red wine period.In contrast of ethanol, red wine seems to induce antiaggregant properties that could explain low incidency of CAD in countries of south of Europa.
Expanding Human Computer Interaction Methods to Understand User Needs in the Design Process of Personal Health Systems
Authors: Siek Katie 
Published: August 2018

Objectives: To review innovative human computer interaction methods researchers utilize to identify stakeholders' needs that inform the design of personal health systems outside of clinical environments.
Methods: A selective review of recent literature.
Results: Summaries of exemplar needs analysis papers showing how researchers utilize novel methods to surface the lived experiences of users.
Conclusions: The medical informatics community is encouraged to ensure that we are designing health technology for all individuals - including underrepresented and underserved populations — by investigating the complex needs of target users. This paper summarizes the novel ways researchers have explored target populations via social media and engaged populations as part of the design team. Medical informaticians should continue investigating the soundness of these methods by comparing the design outcomes with currently utilized user-centered methods and to report on unintended consequences
The Omics Revolution Continues: The Maturation of High-Throughput Biological Data Sources
Authors: Mathé Ewy , Hays John , Stover Daniel , Chen James 
Published: August 2018

Objective: The aim is to provide a comprehensive review of state-of-the art omics approaches, including proteomics, metabolomics, cell-free DNA, and patient cohort matching algorithms in precision oncology.
Methods: In the past several years, the cancer informatics revolution has been the beneficiary of a data explosion. Different complementary omics technologies have begun coming into their own to provide a more nuanced view of the patient-tumor interaction beyond that of DNA alterations. A combined approach is beneficial to the patient as nearly all new cancer therapeutics are designed with an omics biomarker in mind. Proteomics and metabolomics provide us with a means of assaying in real-time the response of the tumor to treatment. Circulating cell-free DNA may allow us to better understand tumor heterogeneity and interactions with the host genome.
Results: Integration of increasingly available omics data increases our ability to segment patients into smaller and smaller cohorts, thereby prompting a shift in our thinking about how to use these omics data. With large repositories of patient omics-outcomes data being generated, patient cohort matching algorithms have become a dominant player.
Conclusions: The continued promise of precision oncology is to select patients who are most likely to benefit from treatment and to avoid toxicity for those who will not. The increased public availability of omics and outcomes data in patients, along with improved computational methods and resources, are making precision oncology a reality.