Evaluation of platelet hypersensitivity in experimentally induced canine nephrotic syndrome /

Bibliographic Details
Main Author: Relford, Roberta Lynn, 1957-
Other Authors: Adams, L. Gary (degree committee member.), Lees, George E. (degree committee member.), Smith, Roger (degree committee member.)
Format: Thesis Book
Language:English
Published: 1993.
Subjects:
Online Access:ProQuest, Abstract
Link to OAKTrust copy
Description
Abstract:Platelets from three dogs with experimentally induced nephrotic syndrome (NS) were evaluated for hypersensitivity to [gamma]-thrombin. Cationic bovine serum albumin (cBSA) was used to experimentally induce glomerulonephritis in five, mixed breed, male dogs. The dogs were hyperimmunized with a single subcutaneous injection of cBSA emulsified in Complete Freund's Adjuvant, rested for two weeks, and then daily IV injections of cBSA were begun. In general, 20 mg cBSA was given for four consecutive days then the dogs were rested for 3 days. This protocol was followed for 3 weeks increasing the dose by 25 mg weekly, after which time cBSA injections were given daily until day 46. A maximum dose of 120 mg was given to dogs weighing 20 kg and 200 mg to dogs weighing > 20 kg. All dogs developed mild to massive proteinuria with inactive urine sediment. Three of the five dogs met our criteria for NS (UP:C [greater than or equal to] 5.0, serum albumin [less than or equal to] 2.5 g/dl, and serum cholesterol > 250 mg/dl) and remained nephrotic for 28-109 days after cBSA injections were stopped. Platelets activation was quantitated in whole blood using a flow cytometer prior to and after establishment of NS in dogs. Platelet activation was defined as the percent of platelets that reacted with an activation-dependant monoclonal antibody. A flow cytometric assay was developed to measure the binding of the antibody RR799 on the surface of platelets. RR799, a murine, IgM, monoclonal antibody was produced that showed increased reactivity with thrombin stimulated platelets when compared to resting platelets. Immunoblot analysis revealed RR799 reacted with a 43,000 Kd protein. Platelet activation was evaluated by incubating whole blood with 0.0, 0.5, 1.0, 2.0, 3.0, 4.0, and 5.0 μl of 1 μmol [gamma]-thrombin. Percent platelet activation was significantly increased in nephrotic dogs when compared to pre-nephrotic samples at the 2.0, 3.0, 4.0, and 5.0 μl doses.
Item Description:Vita.
"Major subject: Veterinary Pathology."
Physical Description:ix, 214 leaves : illustrations ; 28 cm
Bibliography:Includes bibliographical references.