Arthritis Information Basic Information Arthritis Studies Ibuprofen Chondroiten Glucosamine Traditional Treatments	Vibrant Life Home Web Family Of Three Chelation Formulas MSM Other VL Products The Wednesday Letter Frequently Asked Questions Testimonials	Arthritis Information Center Shopping Cart	Separate Search Page or search below
Navigation Help	MSM	Ingredients Technical	Write To Karl Loren	Table Of Contents

Arthritis Information  Center

Chondroitin

Results for your query:

Search all fields for: chondroitin on February 25, 1999

Published in 1966 through 1999

Only select references with abstracts available

Show references published in English only

Show references pertaining to humans

With an article type of: REVIEW

Documents: 1 to 100 of 130

Top

Record 1 from database: MEDLINE
Return To Top Of Menu

Title

The role of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease.

Author

Kelly GS

Address

 

Source

Altern Med Rev, 1998 Feb, 3:1, 27-39

Abstract

Successful treatment of osteoarthritis must effectively control pain, and should slow down or reverse progression of the disease. Biochemical and pharmacological data combined with animal and human studies demonstrate glucosamine sulfate is capable of satisfying these criteria. Glucosamine sulfate's primary biological role in halting or reversing joint degeneration appears to be directly due to its ability to act as an essential substrate for, and to stimulate the biosynthesis of, the glycosaminoglycans and the hyaluronic acid backbone needed for the formation of proteoglycans found in the structural matrix of joints. Chondroitin sulfates, whether they are absorbed intact or broken into their constituent components, similarly provide additional substrates for the formation of a healthy joint matrix. Evidence also supports the oral administration of chondroitin sulfates for joint disease, both as an agent to slowly reduce symptoms and to reduce the need for non-steroidal anti-inflammatory drugs. The combined use of glucosamine sulfate and chondroitin sulfates in the treatment of degenerative joint disease has become an extremely popular supplementation protocol in arthritic conditions of the joints. Although glucosamine sulfate and chondroitin sulfates are often administered together, there is no information available to demonstrate the combination produces better results than glucosamine sulfate alone.

Language of Publication

English

Unique Identifier

98262758

Return To Top Of Menu

MeSH Heading (Major)

Chondroitin Sulfates|CH/ME/*TU; Glucosamine|ME/*TU; Osteoarthritis|*DT

MeSH Heading

Drug Therapy, Combination; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1089-5159

Country of Publication

UNITED STATES

Record 2 from database: MEDLINE
Return To Top Of Menu

Title

Danaparoid. A review of its pharmacology and clinical use in the management of heparin-induced thrombocytopenia.

Author

Wilde MI; Markham A

Address

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Source

Drugs, 1997 Dec, 54:6, 903-24

Abstract

Danaparoid, a low molecular weight heparinoid consisting of a mixture of heparan, dermatan and chondroitin sulfates, has well established antithrombotic activity. The drug has a high antifactor Xa to antifactor IIa (thrombin) activity ratio, a low tendency to cause bleeding and minimal effects on the fibrinolytic system. Danaparoid has a low cross-reactivity rate with heparin-associated antiplatelet antibodies (0 to 20%; mean approximately 10%). This represents a significant advantage over low molecular weight heparins (LMWHs) as a potential replacement agent for unfractionated heparin (UFH) in patients with immune-mediated (type II) heparin-induced thrombocytopenia (HIT). In a worldwide compassionate-use programme involving a total of 667 patients with HIT to date, 93% of danaparoid treatment courses were considered to be successful. Thrombocytopenia resolved in 91% of episodes. In a multicentre randomised comparative trial of danaparoid and dextran in patients with HIT plus thrombosis (HITT), significantly more danaparoid than dextran recipients had resolution of thromboses, and an effective clinical response was achieved in significantly more danaparoid recipients. Results of a retrospective case-controlled study of danaparoid and ancrod in patients with HITT showed significantly fewer new or progressive thromboses with danaparoid. In the compassionate-use programme, danaparoid was associated with a mortality rate of 10.4% during treatment (up to 3.5 years) and 7.8% during the follow-up period (3 months). 14 of 114 deaths during the follow-up period were considered to be related to danaparoid therapy. A mortality rate of 23.5% was reported in patients accepted for but not treated with, danaparoid. Mortality rates with danaparoid, ancrod and dextran in the comparative studies were similar (7, 11 and 12%, respectively). Severe bleeding was reported in 3.1% of patients in the compassionate-use programme, persistent or recurrent thrombocytopenia in 2.6% and new thromboembolic events/extension of existing thrombosis in 1.7%. The incidence of bleeding was similar with danaparoid and dextran in a comparative trial. Although in vitro cross-reactivity does not always translate into clinical cross-reactivity, testing is currently recommended, when possible, before initiation of danaparoid therapy. Thus, danaparoid appears to be an effective and well tolerated replacement agent for UFH in many patients with HIT who require further anticoagulation. The drug has low cross-reactivity with HIT-associated antibodies. Further comparative trials are needed to confirm these promising findings.

Language of Publication

English

Unique Identifier

98083474

Return To Top Of Menu

MeSH Heading (Major)

Chondroitin Sulfates|AE/*PD/PK/*TU; Dermatan Sulfate|AE/*PD/PK/*TU; Heparitin Sulfate|AE/*PD/PK/*TU; Thrombocytopenia|CI/*DT/PP

MeSH Heading

Blood Coagulation|DE; Drug Combinations; Heparin|AE; Heparinoids|AE/PD/PK/TU; Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0012-6667

Country of Publication

NEW ZEALAND

Record 3 from database: MEDLINE
Return To Top Of Menu

Title

College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: the clinical use and laboratory monitoring of low-molecular-weight heparin, danaparoid, hirudin and related compounds, and argatroban.

Author

Laposata M; Green D; Van Cott EM; Barrowcliffe TW; Goodnight SH; Sosolik RC

Address

Division of Laboratory Medicine, Massachusetts General Hospital, Boston 02114, USA.

Source

Arch Pathol Lab Med, 1998 Sep, 122:9, 799-807

Abstract

OBJECTIVE: To review the role of the laboratory in monitoring therapy with low-molecular-weight heparin, danaparoid, hirudin, and argatroban, as reflected in the medical literature and the consensus opinion of recognized experts in the field. DATA SOURCES: Review of the medical literature and current clinical practice by a panel of 6 international experts in the field of anticoagulant therapy. DATA EXTRACTION AND SYNTHESIS: The experts made an extensive review of the published literature and prepared a draft manuscript, which included preliminary recommendations. The draft manuscript was circulated to participants in the College of American Pathologists Conference XXXI on Laboratory Monitoring of Anticoagulant Therapy prior to the conference. The manuscript and recommendations were then presented at the Conference for discussion. Recommendations were accepted if a consensus of the 26 experts attending the Conference was reached. The results of the discussion were used to revise the manuscript into its final form. CONCLUSIONS: This report reviews the mechanism of action and potential uses of these newer anticoagulant agents. General guidelines for monitoring these agents and 9 specific recommendations for laboratory monitoring of low-molecular-weight heparin and danaparoid are provided, along with citation of the appropriate supporting literature. Issues for which a consensus was not reached at the Conference are also discussed.

Language of Publication

English

Unique Identifier

98410853

Return To Top Of Menu

MeSH Heading (Major)

Anticoagulants|AD/*TU

MeSH Heading

Chondroitin Sulfates|AD/TU; Dermatan Sulfate|AD/TU; Drug Combinations; Drug Monitoring|MT; Heparin|AD/TU; Heparin, Low-Molecular-Weight|AD/TU; Heparitin Sulfate|AD/TU; Hirudin|AA/AD/TU; Human; Pathology, Clinical|MT; Pipecolic Acids|AD/TU; Thromboembolism|BL/DT

Publication Type

CONSENSUS DEVELOPMENT CONFERENCE; GUIDELINE; JOURNAL ARTICLE; PRACTICE GUIDELINE; REVIEW; REVIEW, TUTORIAL

ISSN

0003-9985

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (danaparoid); 0 (Anticoagulants); 0 (Drug Combinations); 0 (Heparin, Low-Molecular-Weight); 0 (Pipecolic Acids); 24967-94-0 (Dermatan Sulfate); 74863-84-6 (Argatroban); 8001-27-2 (Hirudin); 9005-49-6 (Heparin); 9007-28-7 (Chondroitin Sulfates); 9050-30-0 (Heparitin Sulfate)

 

Record 4 from database: MEDLINE
Return To Top Of Menu

Title

Danaparoid in the prevention of thromboembolic complications.

Author

Skoutakis VA

Address

National Pharmacotherapy Institute, Germantown, TN 38183, USA.

Source

Ann Pharmacother, 1997 Jul, 31:7-8, 876-87

Abstract

OBJECTIVE: To review the therapies used to prevent postoperative thromboembolic complications with a focus on the role of danaparoid, a new low-molecular-weight glycosaminoglycan. DATA SOURCES: A MEDLINE search was performed to identify pertinent English-language literature including studies, abstracts, and review articles. Key search terms included danaparoid, heparinoid, lomoparin, heparin, prophylaxis, thrombosis, embolism, thromboembolism, and thromboembolic and postoperative complications. The manufacturer of danaparoid was contracted for additional information related to this compound. STUDY SELECTION AND DATA EXTRACTION: All identified articles were reviewed for possible inclusion in this review. Comparisons primarily focused on data obtained from prospective, randomized, controlled, blind clinical trials. Another important consideration was the use of venography to determine the presence of deep venous thrombosis. DATA SYNTHESIS: Various therapies are available for the prevention of postoperative thromboembolic complications. Effective pharmacologic treatments currently available include adjusted-dose heparin, warfarin, aspirin, dextran, and low-molecular-weight heparins (LMWHs). Until recently, warfarin was considered the drug of choice for thromboprophylaxis in high-risk patients, including patients undergoing orthopedic surgical procedures. Because of their comparable efficacy and greater ease of use, LMWHs are gaining favor over warfarin in this patient population. In well-designed clinical trials involving patients undergoing elective total hip replacement or fractured hip surgery, danaparoid has demonstrated greater efficacy than other active treatments, including warfarin, dextran, aspirin, and heparin plus dihydroergotamine. While studies comparing danaparoid with LMWHs have not yet been published, danaparoid may be more useful in patients with heparin-associated thrombocytopenia. CONCLUSIONS: Danaparoid is an antithrombotic agent with characteristics that distinguish it from heparin and LMWHs. Based on the efficacy and safety data reviewed, danaparoid should be considered one of the drugs of choice for the prevention of thromboembolic complications in patients undergoing orthopedic hip procedures and the drug of choice for the management of any patient with heparin-induced thrombocytopenia who requires anticoagulant therapy.

Language of Publication

English

Unique Identifier

97363759

Return To Top Of Menu

MeSH Heading (Major)

Chondroitin Sulfates|CH/PD/*TU; Dermatan Sulfate|CH/PD/*TU; Heparin|CH/PD/*TU; Heparitin Sulfate|CH/PD/*TU; Postoperative Complications|*PC; Thromboembolism|*PC

MeSH Heading

Drug Combinations; Human; Randomized Controlled Trials

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1060-0280

Country of Publication

UNITED STATES

Record 5 from database: MEDLINE
Return To Top Of Menu

Title

A comparative review of the adverse effect profiles of heparins and heparinoids.

Author

Borris LC; Lassen MR

Address

Department of Orthopaedics, Aalborg Hospital, Denmark.

Source

Drug Saf, 1995 Jan, 12:1, 26-31

Abstract

On the basis of the results of the 11 studies reviewed, thromboprophylaxis with unfractionated heparin, low molecular weight (LMW) heparin or a heparinoid (danaparoid sodium; Org 10172) in patients undergoing total hip replacement did not show any important clinical differences with respect to the tolerability profiles of the different compounds. However, as a result of the great variability in the presentation and evaluation of blood losses and bleeding complications in these studies, it is mandatory to perform a direct comparison of the different compounds in question in a double-blind, prospective clinical study.

Language of Publication

English

Unique Identifier

95260439

Return To Top Of Menu

MeSH Heading (Major)

Chondroitin Sulfates|AD/*AE/TU; Dermatan Sulfate|AD/*AE/TU; Fibrinolytic Agents|AD/*AE/TU; Heparin|AD/*AE/TU; Heparinoids|AD/*AE/TU; Heparitin Sulfate|AD/*AE/TU

MeSH Heading

Comparative Study; Hemorrhage|CI; Hip Prosthesis; Human; Molecular Weight; Postoperative Complications|CI; Thrombocytopenia|CI; Thrombosis|PC; Wound Infection|CI

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0114-5916

Country of Publication

NEW ZEALAND

Record 6 from database: MEDLINE
Return To Top Of Menu

Title

Characterization of appican, the chondroitin sulfate proteoglycan form of the Alzheimer amyloid precursor protein.

Author

Pangalos MN; Shioi J; Efthimiopoulos S; Wu A; Robakis NK

Address

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.

Source

Neurodegeneration, 1996 Dec, 5:4, 445-51

Abstract

In this report we focus on the characterization of appican, the chondroitin sulfate proteoglycan form of amyloid precursor protein (APP), and the role that it and other proteoglycans may play in AD. Appican is expressed by certain transformed cell lines of neural origin, namely C6 cells and N2a neuroblastomas. It is detected in both human and rat brain and in primary cultures is expressed by astrocytes, but not neurons. The core protein of appican has been shown to be an alternatively spliced isoform of APP, lacking exon 15 of the APP gene, originally identified in leukocytes (L-APP). Splicing out of exon 15 results in the joining of exons 14 and 16, and formation of an Asp-Xaa-Ser-Gly consensus sequence for chondroitin sulfate chain attachment to serine 619 of L-APP, which lies 16 amino acids upstream of the A beta peptide sequence. Mutation of this serine residue to an alanine prevented chondroitin sulfate chain addition to the core protein. Levels of appican expression could be regulated by growth conditions independently of APP, suggesting that these molecules may serve distinct physiological roles within the cell. Morphological changes were also observed in both astrocytic and transformed cell cultures, that appeared to reflect changes in levels of appican expression. Preliminary data suggest that appican may be a strong cell adhesion molecule. Transfected C6 glioma cells overexpressing appican remained attached to tissue culture dishes markedly better than either C6 cells over-expressing exon-15 containing APP or WT C6 cells. Appican-enriched extracellular matrix (ECM) was also observed to serve as a much better substrate for attachment of N2a neuroblastomas, pheocromocytoma PC12 cells and primary astrocytes compared to APP enriched ECM.

Language of Publication

English

Unique Identifier

97179581

Return To Top Of Menu

MeSH Heading (Major)

Alzheimer Disease|*ME/PP; Amyloid beta-Protein Precursor|GE/ME/*PH; Proteochondroitin Sulfates|*PH; Proteoglycans|ME/*PH

MeSH Heading

Amino Acid Sequence; Animal; Chondroitin Sulfates|ME; Human; Molecular Sequence Data

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1055-8330

Country of Publication

ENGLAND

Record 7 from database: MEDLINE
Return To Top Of Menu

Title

Immunology of chondroitin/dermatan sulfate.

Author

Hascall VC; Midura RJ; Sorrell JM; Plaas AH

Address

Department of Biomedical Engineering, Cleveland Clinic Foundation, Ohio, USA.

Source

Adv Exp Med Biol, 1995, 376:, 205-16

Abstract

Variable substitutions and locations of the sulfate esters along the backbone of chondroitin/dermatan sulfate chains, combined with their carbohydrate structures, present topographies to immune systems which can be recognized as antigenic. This has led to the development of a number of monoclonal antibodies which recognize distinct epitopes in the native structures of these glycosaminoglycan chains. In some studies, the original chondroitin/dermatan sulfate proteoglycan was digested with chondroitinase enzymes before being used as an immunogen. in this case, the linkage oligosaccharides remaining bound to the core protein contain a modified (4,5-unsaturated) hexuronic acid derivative at their non-reducing ends as a result of the eliminase mechanism of the enzyme. This 'haptenic' structure is highly antigenic and has led to the development of a number of monoclonal antibodies which recognize this structure as part of their epitopes. Examples of the use of some of these monoclonal antibodies for localization of proteoglycan structures in tissue sections and on transblots are described. The precise structures are known for only a few of the native epitopes recognized by these monoclonal antibodies. Recent analytical methods have been developed for determining structures of chondroitin sulfate oligosaccharides. An example of the use of these methods to analyze the structures of the non-reducing termini of chondroitin/dermatan sulfate chains is discussed. The results show their potential value for quantifying the native epitope recognized by a monoclonal antibody, designated 3B3, which recognizes chains terminated by glucuronic acid-N-acetylgalactosamine-6-sulfate. Such methods should be useful for determining the epitope structures for other monoclonal antibodies in this class.

Language of Publication

English

Unique Identifier

96167365

Return To Top Of Menu

MeSH Heading (Major)

Antigens|*IM; Chondroitin Sulfates|CH/*IM; Dermatan Sulfate|CH/*IM

MeSH Heading

Antibodies, Monoclonal|IM; Antibody Specificity; Carbohydrate Sequence; Epitopes|AN; Human; Molecular Sequence Data; Molecular Structure

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0065-2598

Country of Publication

UNITED STATES

Record 8 from database: MEDLINE
Return To Top Of Menu

Title

Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface.

Author

Esmon CT

Address

Oklahoma Medical Research Foundation, Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.

Source

FASEB J, 1995 Jul, 9:10, 946-55

Abstract

The protein C anticoagulant system generates an "on demand" physiologic anticoagulant response. The pathway is initiated when thrombin binds to the endothelial cell thrombin binding protein, thrombomodulin. The complex exhibits dramatically altered macromolecular specificity. It rapidly cleaves the protein C zymogen to form the anticoagulant, activated protein C. Complex formation between thrombin and thrombomodulin also prevents thrombin, the enzyme responsible for clot formation and a potent platelet activator, from being able to clot fibrinogen or to activate platelets. Structural, kinetic, and competition studies suggest that thrombomodulin blocks these clotting reactions by masking the binding sites for fibrinogen and the platelet thrombin receptor. Stimulation of protein C activation appears to occur through conformational changes in the extended binding pocket of thrombin. This prevents repulsive interactions with protein C that exist when the free enzyme attempts to dock with this substrate. In addition to protein-protein interactions, thrombomodulin has a covalently associated chondroitin sulfate moiety. Chondroitin sulfate binds to a basic surface on thrombin that is also involved in heparin interaction. The chondroitin sulfate enhances the affinity of thrombin for thrombomodulin approximately 10- to 20-fold, making thrombomodulin a more potent inhibitor of coagulation, altering thrombin's conformation and specificity, and accelerating thrombin inhibition by the serpin, antithrombin. These properties make thrombomodulin a molecular switch ideally suited to trigger an anticoagulant response when too much thrombin is generated. The importance of the system is documented by the clinical observation that patients deficient in protein C often die of massive thrombotic complications that can be reversed or prevented by infusion of protein C.

Language of Publication

English

Unique Identifier

95340068

Return To Top Of Menu

MeSH Heading (Major)

Blood Coagulation|*; Proteins|*ME; Thrombomodulin|*PH

MeSH Heading

Chondroitin Sulfates|ME; Comparative Study; Fibrinogen|ME; Human; Platelet Activation; Protein C|ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Thrombin|ME

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0892-6638

Country of Publication

UNITED STATES

Record 9 from database: MEDLINE
Return To Top Of Menu

Title

CD44 in inflammation and metastasis.

Author

Lesley J; Hyman R; English N; Catterall JB; Turner GA

Address

Department of Cancer Biology, The Salk Institute, San Diego, California 92186, USA.

Source

Glycoconj J, 1997 Aug, 14:5, 611-22

Abstract

CD44 is a major cell surface receptor for the glycosaminoglycan, hyaluronan (HA). CD44 binds HA specifically, although certain chondroitin-sulfate containing proteoglycans may also be recognized. CD44 binding of HA is regulated by the cells in which it is expressed. Thus, CD44 expression alone does not correlate with HA binding activity. CD44 is subject to a wide array of post-translational carbohydrate modifications, including N-linked, O-linked and glycosaminoglycan side chain additions. These modifications, which differ in different cell types and cell activation states, can have profound effects on HA binding function and are the main mechanism of regulating CD44 function that has been described to date. Some glycosaminoglycan modifications also affect ligand binding specificity, allowing CD44 to interact with proteins of the extracellular matrix, such as fibronectin and collagen, and to sequester heparin binding growth factors. It is not yet established whether the HA binding function of CD44 is responsible for its proposed involvement in inflammation. It has been shown, however, that CD44/HA interactions can mediate leukocyte rolling on endothelial and tissue substrates and that CD44-mediated recognition of HA can contribute to leukocyte activation. Changes in CD44 expression (mainly up-regulation, occasionally down-regulation, and frequently alteration in the pattern of isoforms expressed) are associated with a wide variety of cancers and the degree to which they spread; however, in other cancers, the CD44 pattern remains unchanged. Increased expression of CD44 is associated with increased binding to HA and increased metastatic potential in some experimental tumor systems; however, in other systems increased HA binding and metastatic potential are not correlated. CD44 may contribute to malignancy through changes in the regulation of HA recognition, the recognition of new ligands and/or other new biological functions of CD44 that remain to be discovered.

Language of Publication

English

Unique Identifier

97442145

Return To Top Of Menu

MeSH Heading (Major)

Antigens, CD44|*PH; Inflammation|*PP; Neoplasm Metastasis|*PP; Neoplasms|PA/*PP

MeSH Heading

Animal; Antigens, CD|PH; Chondroitin Sulfates|ME; Human; Hyaluronic Acid|ME; Proteoglycans|CH/ME; Support, Non-U.S. Gov't; Support, U.S. Gov't, P.H.S.; Variation (Genetics)

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0282-0080

Country of Publication

ENGLAND

Record 10 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

Pathogenesis and therapy of neuropathies associated with monoclonal gammopathies.

Author

Latov N

Address

Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

Source

Ann Neurol, 1995 May, 37 Suppl 1:, S32-42

Abstract

Approximately 10% of patients with peripheral neuropathy of otherwise unknown etiology have an associated monoclonal gammopathy. Both the neuropathies and the monoclonal gammopathies in these patients are heterogeneous, but several distinct clinical syndromes that may respond to specific therapies can be recognized. It is important to recognize these syndromes because monoclonal gammopathies also occur in 1% of the normal adult population, and in some cases, monoclonal gammopathies are coincidental and unrelated to the neuropathy. In patients with IgM monoclonal gammopathies, IgM M proteins frequently have autoantibody activity and are implicated in the pathogenesis of the neuropathy. IgM M proteins that bind to myelin-associated glycoprotein (MAG) have been shown to cause demyelinating peripheral neuropathy; anti-GM1 antibody activity is associated with predominantly motor neuropathy, and anti-sulfatide or chondroitin sulfate antibodies are associated with sensory neuropathy. The IgM monoclonal gammopathies may be malignant or nonmalignant, and polyclonal antibodies with the same specificities are associated with similar clinical presentations in the absence of monoclonal gammopathy. IgG or IgA monoclonal gammopathies are associated with neuropathy in patients with osteosclerotic myeloma or the POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy myeloma, and skin changes). Amyloidosis or cryoglobulinemic neuropathies can occur with either IgM or IgG and IgA monoclonal gammopathies. Therapeutic intervention depends on the specific clinical syndrome but is generally directed at removing the autoantibodies, reducing the number of monoclonal B cells, and interfering with the effector mechanisms.

Language of Publication

English

Unique Identifier

97122966

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Autoimmune Diseases|*ET/IM/TH; Paraproteinemias|*CO/EP/IM/TH; Peripheral Nervous System Diseases|EP/*ET/IM/TH

MeSH Heading

Adult; Aged; Amyloidosis|ET/IM/TH; Antibody Specificity; Antineoplastic Agents|TU; Autoantibodies|IM; Autoantigens|IM; Chondroitin Sulfates|IM; Gangliosides|IM; Human; IgA|IM; IgG|IM; IgM|IM; Immunoglobulins, Intravenous|TU; Middle Age; Myelin-Associated Glycoprotein|IM; Paraneoplastic Syndromes|ET/IM/TH; Paraproteins|AN/IM; Plasmapheresis; Sulfatides|IM

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, ACADEMIC

ISSN

0364-5134

Country of Publication

UNITED STATES

Record 11 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

MHC class II antigen processing: biology of invariant chain.

Author

Sant AJ; Miller J

Address

Department of Pathology, University of Chicago, Illinois 60637.

Source

Curr Opin Immunol, 1994 Feb, 6:1, 57-63

Abstract

The invariant chain (Ii) has been shown to play a critical role in the assembly, intracellular transport and function of MHC class II molecules. Recent studies suggest that these distinct activities can in many cases be attributed to distinct isoforms of Ii or to specific regions within it. Thus, regulation of Ii synthesis, post-transcriptional events, and post-translational modification has the potential to dramatically modulate immune responses.

Language of Publication

English

Unique Identifier

94226733

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Antigen Presentation|*IM; Histocompatibility Antigens Class II|*IM/ME

MeSH Heading

Animal; Chondroitin Sulfates|PH; Endocytosis|IM; Human; Peptides|IM; Protein Binding; Protein Processing, Post-Translational

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0952-7915

Country of Publication

ENGLAND

Record 12 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

Effects of cryopreservation upon vein function in vivo.

Author

Brockbank KG

Address

CryoLife, Inc., Marietta, Georgia 30067.

Source

Cryobiology, 1994 Feb, 31:1, 71-81

Abstract

This review covers experimental and clinical experiences with transplantation of allogeneic veins processed by slow rate cooling with 2.5% (W/V) chondroitin sulfate and 1 M dimethylsulfoxide. These results are contrasted with the results obtained using dimethylsulfoxide alone. The short-term patency of experimental autologous (100%) and allogeneic (70-100%) cryopreserved veins may be attributed to the combination of "no-touch" procurement techniques employing the smooth muscle relaxant papaverine, the chondroitin sulfate preservation method, and recipient therapy. Explanted autografts retain many cell and tissue functions. In contrast, explanted allografts demonstrate short-term loss of endothelial cells and smooth muscle function, both of which subsequently return. Clinically there have been positive short-term correlations between good initial runoff from the graft site and 1-year patency (68-74%) and limb salvage (94%) rates. In contrast, grafts with poor initial runoff, composite grafts, or grafts requiring secondary reconstruction resulted in lower 1-year patency (40-44%) and limb salvage (64%) rates. More experience, larger study groups, and longer follow-up are necessary to evaluate the clinical performance of chondroitin sulfate-preserved grafts. In the meantime, chondroitin sulfate-preserved veins are reserved for coronary artery bypass or peripheral bypass patients in the absence of suitable autologous vessels.

Language of Publication

English

Unique Identifier

94208279

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Cryopreservation|*MT; Veins|*/IM/PP/TR

MeSH Heading

Animal; Chondroitin Sulfates; Cryoprotective Agents; Dimethyl Sulfoxide; Human; Immunosuppression; Platelet Aggregation Inhibitors|PD; Thrombophlebitis|PC; Transplantation, Autologous; Transplantation, Homologous

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0011-2240

Country of Publication

UNITED STATES

Record 13 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

Update on chemonucleolysis.

Author

Brown MD

Address

Department of the Orthopaedics and Rehabilitation, University of Miami School of Medicine, Florida, USA.

Source

Spine, 1996 Dec, 21:24 Suppl, 62S-68S

Abstract

A review of the world medical literature on chemonucleolysis with an emphasis on recent studies, meta-analyses, and the history of the procedure in North America from a regulatory, social, and medicolegal perspective was performed to determine the current status of chemonucleolysis in the management of disc displacement. The world literature supports the use of chymopapain for chemonucleolysis as a safe and effective alternative to surgical disc excision. The efficacy of chymopapain has been shown by prospective, randomized, placebo-controlled, double-blind trials with a minimum 10-year follow-up period. The safety of chymopapain injection compared with surgery has been demonstrated in meta-analyses and in extensive post-marketing surveillance in the United States and Europe. Clinical studies with collagenase and laboratory studies with chondroitinase ABC have shown that chemonucleolysis can be performed with enzymes other than chymopapain. Clinical trials have been performed with collagenase for chemonucleolysis, but all of the results have not been published. Preclinical research with chondroitinase ABC has demonstrated its usefulness for chemonucleolysis in the animal model, but human trials have not begun.

Language of Publication

English

Unique Identifier

97266574

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Chymopapain|*TU; Intervertebral Disk Chemolysis|*; Intervertebral Disk Displacement|*DT/SU

MeSH Heading

Animal; Chondroitin Lyases|TU; Collagenases|TU; Comparative Study; Human; Meta-Analysis; Randomized Controlled Trials

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0362-2436

Country of Publication

UNITED STATES

Record 14 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

New antithrombotic agents for the prevention and treatment of deep vein thrombosis.

Author

Boneu B

Address

Laboratoire de Recherche sur l'HÆemostase et la Thrombose Toulouse, France.

Source

Haemostasis, 1996 Oct, 26 Suppl 4:, 368-78

Abstract

Besides low molecular weight heparins (LMWHs) a number of new antithrombotic agents have been evaluated mainly in the prevention of deep vein thrombosis (DVT) and, to a lesser extent, in the treatment of established DVT. They include the Pentasaccharide, a synthetic ultra LMWH, Dermatan Sulphate, a glycosaminoglycan which activates heparin cofactor II, Orgaran, a mixture of Heparan and of Dermatan Sulphate, Hirulog and Hirudin, two direct thrombin inhibitors. The efficacy and safety of these compounds have been studied in comparison with a placebo or with unfractionated heparin but not with LMWH which is considered as a gold standard for these clinical indications. It is thus difficult at present to appreciate the advantages of these new antithrombotic agents over conventional LMWH therapy.

Language of Publication

English

Unique Identifier

97133746

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Fibrinolytic Agents|*TU; Pulmonary Embolism|DT/*PC; Thrombophlebitis|DT/*PC

MeSH Heading

Anticoagulants|TU; Antithrombin III|CH/ME; Binding Sites; Chondroitin Sulfates|TU; Clinical Trials; Dermatan Sulfate|TU; Drug Screening; Factor Xa|AI; Heparin|CH/ME/TU; Heparin, Low-Molecular-Weight|TU; Heparitin Sulfate|TU; Human; Multicenter Studies; Oligosaccharides|TU; Postoperative Complications|PC; Recurrence; Thrombin|AI

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0301-0147

Country of Publication

SWITZERLAND

Record 15 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

Cell surface chondroitin sulfate proteoglycans in tumor cell adhesion, motility and invasion.

Author

Iida J; Meijne AM; Knutson JR; Furcht LT; McCarthy JB

Address

University of Minnesota, Department of Laboratory Medicine and Pathology, Minneapolis, USA.

Source

Semin Cancer Biol, 1996 Jun, 7:3, 155-62

Abstract

Tumor cell invasion and metastasis is highly dependent on dynamic changes in the adhesion and migration of transformed and malignant cells. As with normal cell adhesion, the adhesion of tumor cells influences their cytoskeletal organization, activation of signal transduction pathways within the cell, and nuclear events leading to changes in mRNA transcription and protein synthesis. Furthermore, as tumor cells invade the circulation, they adhere to activated endothelial cells at sites within the vasculature during arrest and extravasation. Studies in the area of tumor cell adhesion and migration have demonstrated that the recognition of extracellular matrix ligands, or adhesion promoting ligands expressed on neighboring cells (i.e. counter-receptors), involves complex molecular recognition mechanisms. The complexity arises, in part, from the multiple recognition sites that are present within adhesion promoting ligands. Some of these structures within ECM components act by binding integrins, whereas others bind additional receptors such as cell surface proteoglycans. In this sense, adhesion promoting ligands may be considered as informational arrays, that function to modulate cell phenotype by engaging specific combinations of adhesion receptors on the cell surface. Understanding the mechanism(s) by which these receptor 'cluster' modify cell adhesion, motility and growth may lead to novel therapeutic strategies to control tumor cell invasion and metastasis formation. This review will highlight the role that cell surface chondroitin sulfate proteoglycans may play in modulating tumor cell adhesion, migration and invasion, with an emphasis on the relationship between cell surface chondroitin sulfate proteoglycans and integrins.

Language of Publication

English

Unique Identifier

96369295

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Cell Adhesion|*PH; Cell Movement|*PH; Chondroitin|*BI; Proteoglycans|*BI

MeSH Heading

Human

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

1044-579X

Country of Publication

UNITED STATES

Record 16 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

Heparinoid anticoagulation and topical fibrin sealant in heparin-induced thrombocytopenia.

Author

Jackson MR; Danby CA; Alving BM

Address

Department of Surgery, Walter Reed Army Medical Center, Washington, DC, USA.

Source

Ann Thorac Surg, 1997 Dec, 64:6, 1815-7

Abstract

The development of heparin-induced thrombocytopenia in patients who require systemic anticoagulation for cardiac and vascular operations poses a therapeutic dilemma because no alternative anticoagulants are generally available. Heparinoid (Org 10172) has been used as an alternative anticoagulant under protocol or on a compassionate use basis, and has recently been approved by the Food and Drug Administration. There is, however, no heparinoid antagonist to reverse the anticoagulation. This report describes the combined use of heparinoid anticoagulation and adjunctive fibrin sealant for topical hemostasis in a patient with heparin-induced thrombocytopenia. Recommendations for perioperative monitoring of heparinoid anticoagulation are provided.

Language of Publication

English

Unique Identifier

98097082

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Anticoagulants|*TU; Chondroitin Sulfates|*TU; Coronary Artery Bypass|*; Dermatan Sulfate|*TU; Fibrin Tissue Adhesive|*TU; Heparin|*AE; Heparinoids|*TU; Heparitin Sulfate|*TU; Thrombocytopenia|*CI

MeSH Heading

Case Report; Human; Male; Middle Age

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW OF REPORTED CASES

ISSN

0003-4975

Country of Publication

UNITED STATES

Record 17 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

Glycosaminoglycans: structure and interaction.

Author

Chakrabarti B; Park JW

Address

 

Source

CRC Crit Rev Biochem, 1980, 8:3, 225-313

Abstract

In the last few years, there has been considerable progress in the studies on glycosaminoglycans, a group of acidic polysaccharides present in the intercellular matrix of connective tissue. X-ray diffraction studies have indicated that these polymers can exist in the condensed phase in some helical form. Chiroptical and hydrodynamic measurements have provided significant information regarding the molecular conformation in solution and other physicochemical properties of the polymers. Studies related to the interaction properties of glycosaminoglycans with polypeptides, metal ions, and other molecules are numerous. This review covers mainly the results and their interpretations of both published and as yet unpublished material of the 1970s, but certain previous data are also included. A present-day concept regarding the structure and interaction properties of these molecules on the basis of various physicochemical measurements is presented. The biosynthesis and metabolism of glycosaminoglycans, and the structure of proteoglycans and glycoproteins, are not discussed.

Language of Publication

English

Unique Identifier

81023329

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Glycosaminoglycans|*

MeSH Heading

Animal; Cations; Chemistry; Chemistry, Physical; Chondroitin; Chondroitin Sulfates; Circular Dichroism; Dermatan Sulfate; Heparin; Heparitin Sulfate; Human; Hyaluronic Acid; Hydrogen-Ion Concentration; Keratan Sulfate; Macromolecular Systems; Metals|ME; Models, Molecular; Molecular Conformation; Spectrum Analysis; Support, U.S. Gov't, Non-P.H.S.; Support, U.S. Gov't, P.H.S.; Tissue Distribution; X-Ray Diffraction

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0045-6411

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Cations); 0 (Glycosaminoglycans); 0 (Macromolecular Systems); 0 (Metals); 24967-94-0 (Dermatan Sulfate); 9004-61-9 (Hyaluronic Acid); 9005-49-6 (Heparin); 9007-27-6 (Chondroitin); 9007-28-7 (Chondroitin Sulfates); 9050-30-0 (Heparitin Sulfate); 9056-36-4 (Keratan Sulfate)

Record 18 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10

Title

Mechanisms for the anticoagulant effect of heparin and related polysaccharides.

Author

Ofosu FA

Address

Canadian Red Cross Society, Blood Transfusion Service, Hamilton, Ontario.

Source

Nouv Rev Fr Hematol, 1988, 30:3, 155-60

Abstract

The anticoagulant actions of heparin and related polysaccharides can best be addressed by answering the following 2 questions: to what extent do unfractionated heparin, low molecular weight heparins, dermatan sulfate and heparan sulfate inhibit the activation of prothrombin in plasma depleted of antithrombin III and heparin cofactor II? What roles do antithrombin III and heparin cofactor II play in the expression of the overall anticoagulant effects of heparin, low molecular weight heparins, dermatan sulfate and heparan sulfate? Since only heparin can, but only weakly at best, inhibit the activation of prothrombin in plasma depleted of both antithrombin III and heparin cofactor II, it is obvious that the anticoagulant effects of heparin, low molecular weight heparins, dermatan sulfate and heparan sulfate are mediated primarily by their catalytic effects on the antiprotease actions of antithrombin III (heparin, low molecular weight heparins and heparan sulfate) and heparin cofactor II (dermatan sulfate). The catalytic efficiencies of various glycosaminoglycans (GAGs) on the inhibition of thrombin by undiluted plasma follow in the order of the ability of each GAG to inhibit the intrinsic pathway activation of prothrombin. The reasons for this observation probably follow from the effects of GAGs on the 2 positive amplification reactions of thrombin during blood coagulation. Factor VIIIa and factor Va, which directly or indirectly contribute to the rapid formation of prothrombinase, arise from the limited proteolysis of factor VIII and factor V by thrombin and/or factor Xa. On depletion of thrombin by enhanced formation of thrombin-antithrombin III or thrombin-heparin cofactor II, factor Xa provides the only mechanism by which factor VIII and factor V activation in plasma will proceed.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

88335518

Return To Top Of Menu
Return To Menu Position #10

MeSH Heading (Major)

Anticoagulants|*; Chondroitin|*AA; Dermatan Sulfate|*PD; Glycosaminoglycans|*PD; Heparin|*PD; Heparitin Sulfate|*PD

MeSH Heading

Antithrombin III|AI; Human; Support, Non-U.S. Gov't; Thrombin|AI

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0029-4810

Country of Publication

GERMANY, WEST

CAS Registry/EC Number

EC 3.4.21.5 (Thrombin); 0 (Anticoagulants); 0 (Glycosaminoglycans); 24967-94-0 (Dermatan Sulfate); 9000-94-6 (Antithrombin III); 9005-49-6 (Heparin); 9007-27-6 (Chondroitin); 9050-30-0 (Heparitin Sulfate)

 

Record 19 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10
Return To Menu Position #20

Title

Mucosal mast cells in the rat and in man.

Author

Enerbäck L

Address

 

Source

Int Arch Allergy Appl Immunol, 1987, 82:3-4, 249-55

Abstract

The proteoglycan structure of mucosal mast cells (MMC) of the two species has been analyzed with histochemical in situ techniques. The findings indicate that human MMC, like human mast cells of several other sites, contain a heparin proteoglycan, unlike rat MMC which lack heparin but contain an oversulphated chondroitin sulphate. However, the dye-binding of the human MMC proteoglycan, like that of the rat, is highly susceptible to blocking by formaldehyde. Human MMC also exhibit a lower critical electrolyte concentration (CEC) of dye-binding than mast cells of other connective tissue sites, suggesting a relatively lower charge density and/or molecular weight of the glycosaminoglycan of the MMC. These findings thus suggest that the human MMC like those of the rat have a distinctive proteoglycan structure. Recent findings of another group indicate that the human MMC like those of the rat have also a distinctive proteinase composition. Finally, the mast cell response of the nasal mucosa during birch pollen allergy shows fundamental similarities to the nematode response of the rat intestinal mucosa. During both conditions mast cells are redistributed from the lamina propria into the epithelium, probably as a result of migration of mast cells or mast cell precursors. Taken together, these findings suggest the existence of a distinctive MMC phenotype also in man.

Language of Publication

English

Unique Identifier

87193224

Return To Top Of Menu
Return To Menu Position #10
Return To Menu Position #20

MeSH Heading (Major)

Chondroitin|*AA; Chondroitin Sulfates|*AN; Heparin|*AA/AN; Mast Cells|*AN; Mucous Membrane|*CY; Proteoglycans|*AN; Rats|*AH

MeSH Heading

Animal; Comparative Study; Cystitis|PA; Hay Fever|PA; Human; Intestinal Diseases, Parasitic|PA; Organ Specificity; Peptide Hydrolases|AN; Phenotype; Species Specificity; Staining; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW

ISSN

0020-5915

Country of Publication

SWITZERLAND

CAS Registry/EC Number

EC 3.4 (Peptide Hydrolases); 0 (heparin proteoglycan); 0 (Proteoglycans); 9005-49-6 (Heparin); 9007-27-6 (Chondroitin); 9007-28-7 (Chondroitin Sulfates)

 

Record 20 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10
Return To Menu Position #20

Title

Viscoelastic agents.

Author

Larson RS; Lindstrom RL; Skelnik DL

Address

Department of Ophthalmology, University of Minnesota School of Medicine, Minneapolis.

Source

CLAO J, 1989 Apr-Jun, 15:2, 151-60

Abstract

Viscoelastic materials possess a unique set of properties that result from their chemical structure. These properties enable them to protect the corneal endothelium and epithelium from mechanical trauma and to maintain an intraocular space, such as the anterior or vitreous chambers, even in the face of an open incision. Hence viscoelastic materials have been successfully applied to many areas of ophthalmic surgery, most notably anterior segment surgery, with few complications. There are currently three commercially available viscoelastic preparations, and several new preparations are in various stages of development.

Language of Publication

English

Unique Identifier

89249770

Return To Top Of Menu
Return To Menu Position #10
Return To Menu Position #20

MeSH Heading (Major)

Acrylic Resins|*TU; Chondroitin|*TU; Eye|PH/*SU; Hyaluronic Acid|*TU; Methylcellulose|*AA/TU

MeSH Heading

Anterior Eye Segment|PH/SU; Chemistry; Drug Combinations|TU; Endothelium, Corneal|PH; Human; Intraocular Pressure

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0733-8902

Country of Publication

UNITED STATES

CAS Registry/EC Number

0 (Acrylic Resins); 0 (Drug Combinations); 123352-36-3 (Viscoat); 9003-05-8 (polyacrylamide); 9004-61-9 (Hyaluronic Acid); 9004-65-3 (hydroxypropyl methylcellulose); 9004-67-5 (Methylcellulose); 9007-27-6 (Chondroitin)

 

Record 21 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10
Return To Menu Position #20

Title

Keratan sulphate--a 'reserve' polysaccharide?

Author

Scott JE

Address

Manchester University, U.K.

Source

Eur J Clin Chem Clin Biochem, 1994 Apr, 32:4, 217-23

Abstract

The early history of keratan sulphate and its proteoglycans is briefly described. Studies were overlooked that could have had a profound influence on later work. Early methods of writing the structures of keratan and chondroitin sulphates obscured the fundamental relationships between them. Both are now seen to be based on the same polymer backbone poly(Gal beta 1:4 Glc beta 1-3). Confusion over the complicated sulphation patterns in keratan sulphate was clarified by the domain structure idea by the group of Helmut Greiling. Keratan sulphate is characteristic of avascular tissues (cartilages, intervertebral discs, corneal stromas) that get their oxygen supplies by diffusion. Stockwell's early idea that the distribution of keratan sulphate in cartilages was a response to the poor supply of oxygen has been generalised, to the hypothesis that keratan sulphate is a functional substitute for chondroitin sulphate under conditions of oxygen lack. The keratan:chondroitin sulphate ratios in discs, corneas of different species, and changes therein with age can be explained on this basis. The biochemical controlling step is probably the NAD:NADH ratio. Keratan sulphate may thus be a 'reserve' polysaccharide, able to do the job of chondroitin sulphate in adverse conditions of oxygen supply. Keratan and chondroitin/dermatan sulphates have similar functions in corneal stroma, and probably in the other connective tissues in which they are found. They swell the collagenous matrix, keeping the fibrils apart. Even more importantly, they probably act as tissue organisers, orienting the fibrils vis-a-vis each other via specific interactions of their proteoglycan protein cores with the fibrils.(ABSTRACT TRUNCATED AT 250 WORDS)

Language of Publication

English

Unique Identifier

94312496

Return To Top Of Menu
Return To Menu Position #10
Return To Menu Position #20

MeSH Heading (Major)

Keratan Sulfate|*CH/*PH; Polysaccharides|*PH

MeSH Heading

Animal; Carbohydrate Sequence; Human; Molecular Sequence Data; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0939-4974

Country of Publication

GERMANY

Record 22 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #10
Return To Menu Position #20

Title

Structure-function relationships of the thrombin-thrombomodulin interaction.

Author

Sadler JE; Lentz SR; Sheehan JP; Tsiang M; Wu Q

Address

Howard Hughes Medical Institute, Washington University School of Medicine, St. Louis, Mo.

Source

Haemostasis, 1993 Mar, 23 Suppl 1:, 183-93

Abstract

Thrombomodulin is an anticoagulant protein cofactor that modulates the substrate specificity of thrombin and promotes the cleavage of protein C. The structure-function relationships of the thrombin-thrombomodulin interaction have been explored by recombinant DNA and protein chemistry methods. Thrombomodulin binds to thrombin at an anion-binding exosite on the carboxyl-terminal side of the substrate binding cleft. This interaction interferes with the recognition and cleavage of fibrinogen, factor V, and the platelet thrombin receptor. Binding to thrombomodulin also protects thrombin from inhibition by heparin cofactor II. The major thrombin binding site on thrombomodulin consists of EGF-like domains 5 and 6. In addition, EGF-like domain 4 is required for thrombomodulin to accelerate the activation of protein C. Some thrombomodulin molecules contain a chondroitin sulfate moiety attached to a Ser/Thr-rich domain adjacent to the cell membrane. This modification is not required for the cofactor activity of thrombomodulin, but appears to contribute to 'direct anticoagulant' activity--the ability of thrombomodulin to inhibit fibrinogen clotting, factor V activation, and platelet activation. The chondroitin sulfate moiety of thrombomodulin also can affect the rate of thrombin inhibition by antithrombin III, possibly by competing with heparin for the heparin binding site on thrombin. Detailed understanding of these interactions could lead to new strategies for the treatment of bleeding or thrombotic disorders.

Language of Publication

English

Unique Identifier

93266145

Return To Top Of Menu
Return To Menu Position #10
Return To Menu Position #20

MeSH Heading (Major)

Receptors, Cell Surface|*ME; Thrombin|*ME

MeSH Heading

Amino Acid Sequence; Animal; Binding Sites; Blood Coagulation; Chondroitin Sulfates|ME; Human; Ligands; Molecular Sequence Data; Peptide Fragments|CS/ME; Protein Binding; Protein Conformation; Recombinant Fusion Proteins|ME; Structure-Activity Relationship; Support, U.S. Gov't, P.H.S.

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0301-0147

Country of Publication

SWITZERLAND

CAS Registry/EC Number

EC 3.4.21.5 (Thrombin); 0 (Ligands); 0 (Peptide Fragments); 0 (Receptors, Cell Surface); 0 (Receptors, Thrombin); 0 (Recombinant Fusion Proteins); 9007-28-7 (Chondroitin Sulfates)

Record 23 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #20

Title

The structure, function and turnover of aggrecan, the large aggregating proteoglycan from cartilage.

Author

Hardingham TE; Fosang AJ; Dudhia J

Address

Kennedy Institute of Rheumatology, Hammersmith, London, UK.

Source

Eur J Clin Chem Clin Biochem, 1994 Apr, 32:4, 249-57

Abstract

Aggrecan, the large aggregating proteoglycan from cartilage contains chondroitin sulphate and keratan sulphate attached to a multidomain protein core. It aggregates by binding to hyaluronan and this is further stabilised by a separate globular link protein. There are two structurally related N-terminal globular domains, G1 and G2, of which only G1 and not G2 is involved in aggregation. The interglobular domain joining G1 and G2 contains proteinase sensitive sequences which appear to be the key site for cleavage during aggrecan turnover. Much of the keratan sulphate and all of the chondroitin sulphate is attached to the long extended glycosaminoglycan attachment region. The function of the C-terminal G3 domain is unknown. It contains a mammalian type C lectin and complement regulatory protein motifs. These may have interactive properties that contribute to matrix organisation. There is also an alternatively spliced form with an epidermal growth factor-like motif. The carbohydrate composition of aggrecan varies with cartilage source, development and age and is heterogeneous in each sample. There is evidence of a close control of chondroitin sulphate synthesis that determines chain length and disaccharide composition and which change during development and in pathology. Monoclonal antibodies that recognise specific sequences within chondroitin sulphate chains enable some of these changes in fine structure to be detected. Progressive digestion of chains with chondroitinase AC II has provided evidence of a pattern of sulphation, with 6-sulphated disaccharides more abundant towards the protein core, although the disaccharide next to the linkage region is predominantly non-sulphated.

Language of Publication

English

Unique Identifier

94312499

Return To Top Of Menu
Return To Menu Position #20

MeSH Heading (Major)

Cartilage|CH/ME/*PH; Proteoglycans|CH/ME/*PH

MeSH Heading

Amino Acid Sequence; Animal; Human; Molecular Sequence Data; Proteochondroitin Sulfates|CH/ME/PH; Structure-Activity Relationship; Support, Non-U.S. Gov't

Publication Type

JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL

ISSN

0939-4974

Country of Publication

GERMANY

Record 24 from database: MEDLINE
Return To Top Of Menu
Return To Menu Position #20

Title

Mapping of proteoglycans in atherosclerotic lesions.

Author

Völker W; Schmidt A; Oortmann W; Broszey T; Faber V; Buddecke E

Address

University of Münster, Federal Republic of Germany.

Source

Eur Heart J, 1990 Aug, 11 Suppl E:, 29-40

Abstract

The involvement of sulphated glycosaminoglycans in atherosclerotic changes have been studied in human and rat arteries, and biochemical experiments have revealed that a significant increase in the contents of chondroitin sulphate/dermatan sulphate and cholesterol, but loss of heparan sulphate, occurs in human atherosclerotic arterial tissues. Electron micrographs have revealed that extracellular deposits of lipid are predominantly present in areas rich in chondroitin sulphate proteoglycans but not in areas rich in collagen bundles and dermatan sulphate proteoglycans. The different types of proteoglycans have been distinguished in situ by the cuprolinic blue staining method and enzymatic degradation experiments, and their topohistochemical distributi