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  • Heparinase Production by Flavobacterium heparinum 

    Galliher, P.M.; Cooney, C.L.; Langer R.; Linhardt, Robert J. (1981)
    Heparinase production by Flavobacterium heparinum in complex protein digest medium, with heparin employed as the inducer, has been studied and improved. The maximum productivity of heparinase has been increased 156-fold ...
  • Mechanism of Diacyl Peroxide Decomposition 

    Linhardt, Robert J.; Murr, B.L.; Montgomery, E.; Osby J.; Sherbine, J. (1982)
    The presence of ion-pair intermediates in diacyl peroxide decomposition has been established. Various substituted (4-X·pOOiyl)phenylaoetyl Y·benzoyl peroxides and three corresponding 4·X-bemhydryl-4·nitrobenzolc carbonic ...
  • A System for Heparin Removal 

    Langer, R.; Linhardt, Robert J.; Klein, M.; Galliher, P.M.; Cooney C.L.; Flanagan, M.M. (1982)
    Extracorporeal medical machines rely on systemic heparinization to improve blood compatibility. However, heparin can lead to serious complications such as hemorrhaging. We propose a new approach to control heparin levels ...
  • Immobilized Heparinase: Productions, Purification, and Application In Extracorporeal Therapy 

    Langer, R.; Linhardt, Robert J.; Cooney, C.L.; Tapper, D.; Klein, M.D. (1982-01-01)
    There are nearly 20,000,000 perfusions involving extracorporeal medical machines performed each year (1,2). The artificial kidney is employed several times weekly by over 100,000 persons each year (1). Open-heart operations ...
  • Metachromatic Activity of Heparin and Heparin Fragments 

    Grant, Arthur C.; Linhardt, Robert J.; Fitzgerald, Gerald L.; Park, Janice J.; Langer, Robert (1984-02-15)
    Heparin of an average molecular weight of 13,000 was fractionated on the basis of size into five fractions of different weight-average molecular weight ranging from 8500 to 20,000. The heparin was also degraded using ...
  • The Regulation of Heparinase Production in Flavobacterium heparinum 

    Galliher, P.M.; Linhardt, Robert J.; Conway, L.J.; Langer, R.; Cooney, C.L. (1982)
    The effect of various carbon, nitrogen and sulfur sources on the production of heparinase by Flavobacterium heparinum in defined medium in the presence and absence of heparin as the inducer has been studied. Carbon catabolite ...
  • An Enzymatic System for Removing Heparin in Extracorporeal Therapy 

    Langer, Robert; Linhardt, Robert J.; Hoffberg, Steven; Larsen, Annette K.; Cooney, Charles L.; Tapper, David; Klein, Michael (1982-01-01)
    The need to fully heparinize patients undergoing extracorporeal therapy often leads to hemorrhagic complications. To enable heparinization of only the extracorporeal circuit, a blood filter containing immobilized heparinase ...
  • In Vivo Activity of Microbial Heparinase 

    Langer, R.; Linhardt, Robert J.; Larsen, A.K.; Cooney, C.L.; Tapper, D.; Klein, M. (1982)
    Heparin, prepared from mammalian intestinal mucosa, is the most widely used anticoagulant. It has been estimated, however, that the use of heparin leads to complications such as bleeding 8-33% of the time1. Of all prescription ...
  • A Colorimetric Assay for Chemical Heparin in Plasma 

    Klein, Michael D.; Drongowski, Robert A.; Linhardt, Robert J.; Langer, Robert S. (1982-07-15)
    A simple, rapid colorimetric assay for plasma heparin is presented. The assay employs the metachromasia of azure A when heparin is added. It is useful for 0 to 10 units/ml and does not depend on heparin's anticoagulant ...
  • Bioerodible Polyanhydrides For Controlled Drug Delivery 

    Rosen, H.; Chang, J.; Wenik, G.; Linhardt, Robert J.; Langer, R. (1983)
    Initial in vitro and in vivo (rat) studies using a poly(anhydride), poly[bis(p-carboxyphenoxy)methane], as a bioerodible matrix for controlled drug delivery are described. Drug delivery matrices fabricated from this material ...
  • Bioerodable Polyanhydrides for Controlled Drug Delivery 

    Linhardt, Robert J.; Rosen, H.B.; Langer, R. (1983)
    Initial in vitro and in vivo (rat) studies using a poly(anhydride), poly[bis(p-carboxyphenoxy)methane], as a bioerodible matrix for controlled drug delivery are described. Drug delivery matrices fabricated from this material ...
  • Mode of Action of Heparin Lyase On Heparin 

    Lindhardt, Robert J.; Fitzgerald, Gerald L.; Cooney, Charles L.; Langer, Robert (1982-04-03)
    Heparinase (heparin lyase, EC 4.2.2.7) prepared from Flavobacterium heparinum was used to digest heparin. The products of digestion were examined with a viscosometric assay at various stages of the reaction to measure their ...
  • An Immobilized Microbial Heparinase for Blood Deheparinization 

    Linhardt, R. J.; Cooney, C. L.; Tapper, D.; Zannetos, C. A.; Larsen, A. K.; Langer, R. (1984-02-01)
    A new medical application of an immobilized microbial enzyme is described. Extracorporeal devices require systemic heparin administration to prevent thrombus formation; however, the use of heparin often leads to serious ...
  • Small Heparin Fragments Regulate the Amplification Pathway of Complement 

    Sharath, Murali D.; Merchant, Zohar M.; Kim, Yeong S.; Rice, Kevin G.; Linhardt, Robert J.; Weiler, John M. (1985-01-01)
    Heparin is a highly sulfated, polydisperse and heterogenepus glycosaminoglycan which has been well characterized for its ability to regulate multiple sites in the complement cascade. Although previous studies demonstrated ...
  • Angiogenesis Inhibition and Tumor Regression Caused by Heparin or a Heparin Fragment in the Presence of Cortisone 

    Folkman, Judah; Langer, Robert; Linhardt, Robert J.; Haudenschild, Christian; Taylor, Stephanie (1983-01-01)
    Heparin or a heparin fragment administered with cortisone inhibited angiogenesis, caused regression of large tumor masses, and prevented metastases. Oral administration of heparin resulted in the release of non-anticoagulant ...
  • Heparinase: In Vivo Activity and Immunogenicity in Rabbits 

    Klein, M.D.; Drongowski, R.A.; Linhardt, Robert J.; Cooney, C.L.; Langer, R.S. (1983)
    Anticoagulation with heparin is required during extracorporeal circulation for hemodialysis and cardiopulmonary bypass as well as during vascular surgery. Reversal of anticoagulation with protamine may be associated with ...
  • Polymer Based Drug Delivery: Magnetic Modulation and Bioerodible Systems 

    Edelmen, E.; Linhardt, Robert J.; Bobeck, H.; Kost, J.; Rosen, H.B.; Langer, R. (1984)
    Polymer based drug, delivery systems have been considered for many applications to supplement standard means of medical therapeutics. Currently nitroglycerin, scopolamine, progesterone, and pilocarpine [1] are being ...
  • The Effect of Extracorporeal Enzymatic Deheparinization on the Formed Blood Components 

    Larsen, Annette K.; Linhardt, Robert J.; Tapper, David; Klein, Michael; Langer, Robert (1984-01-01)
    A stirred blood filter containing an immobilized enzyme, heparinase, has been used to neutralize heparin's anticoagulant activity at the outflow of an extracorporeal circuit in dogs. The hematocrit and red blood cell count ...
  • A Dose Escalation Study or Org 10172 (Low Molecular Weight Heparinoid) in Stroke 

    Biller, J.; Massey, E.W.; Marler, J.R.; Adams, H.P.; Davis, J.N.; Bruno, A.; Henriksen, R.A.; Linhardt, Robert J.; Goldstein, L.B.; Alberts, M.; Kisker, C.T.; Toffol, G.J.; Greenberg, C.S.; Banwart, K.J.; Bertels, C.; Beck, D.W.; Walker, M.; Maganani, H.N. (1989-01-01)
    An intravenous infusion of a low molecular weight heparinoid, with a reduced risk of hemorrhage, may be an alternative to heparin in the management of acute ischemic stroke. To evaluate this hypothesis, we studied the ...
  • High-Performance Liquid Chromatographic Separation of Heparin Derived Oligosaccharides 

    Rice, K.G.; Kim, Y.S.; Grant, A.C.; Merchant, Z.M.; Linhardt, Robert J. (1985-11-01)
    Heparin has been enzymatically depolymerized with heparinase (heparin lyase (EC 4.2.2.7)) and then separated into di-, tetra-, hexa-, octa-, and decasaccharide mixtures by low-pressure gel-permeation chromatography (GPC). ...

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