Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A monoclonal antibody, NDS 58, was produced by fusing the rat myeloma line Y3 Ag 1.2.3 with spleen cells from AS rats immunized with LEW thymocytes. The determinant recognized by this antibody is leucocyte-specific and present on all thymocytes, lymph node lymphocytes and some bone marrow cells. The strain distribution of NDS 58 was consistent with it being directed at the RT7a allele. Biochemical studies established that this antigen was carried on a cell surface glycoprotein with an apparent molecular weight on thymocytes of 190,000. This study confirms that the alloantigen originally designated Ly-1, and now termed RT7, is an allodeterminant of the LC molecule, and the controversy in this area, particularly with regard to the ART-1 alloantigen, is discussed.
 ...
PMID:A monoclonal alloantibody detecting a polymorphism of the rat leucocyte common (LC) antigen. 294 9

Erythropoietin (Epo) is a cytokine that controls the production of red blood cells (RBCs). Epo acts continuously on RBC precursors to prevent apoptosis, so it is important to maintain high levels of Epo activity when treating anemic patients. We describe here modified human Epo [Epo(NDS)] with mutations His32Gly, Cys33Pro, Trp88Cys and Pro90Ala that result in the rearrangement of the disulfide bonding pattern from Cys29-Cys33 to Cys29-Cys88 and that, in the context of an Fc-Epo(NDS) fusion protein, lead to significantly improved properties. Fc-Epo was secreted from NS/0 myeloma cells as about 35% high molecular weight aggregates, was unstable upon removal of N-linked oligosaccharides and showed poor pharmacokinetics and little efficacy in mice. In contrast, a corresponding Fc-Epo(NDS) was secreted almost exclusively as a unit dimer, was relatively stable to removal of N-linked oligosaccharides, had much improved pharmacokinetic properties and had a significantly improved effect on RBC production. These results indicate that rearrangement of the disulfide bonding pattern in a therapeutic protein can have a significant effect on pharmacokinetics and, potentially, the dosing schedule of a protein drug.
 ...
PMID:Improvement of Fc-erythropoietin structure and pharmacokinetics by modification at a disulfide bond. 1582 Sep 78