Search PubMed⌕ Search

Biomedical subjects

M R Jarvis

Publications and source records attributed to M R Jarvis.

25 records · Page 2Linked to original sources

Determination of dissociation constants and ligand specificity of detergent solubilized surface membrane immunoglobulin A from MOPC-315.

Surface membrane immunoglobulin from MOPC-315 plasmacytoma cells (smM315) was isolated by nonionic detergent lysis of radioiodinated cells and affinity chromatography on Dnp-aminohexyl-Sepharose 4B. Verification of the solubilized molecule as an integral membrane protein, distinct from secreted MOPC-315 IgA (M315) was accomplished by NaDodSO4-PAGE, charge-shift electrophoresis and molecular sieve gel filtration with NP-40 and deoxycholate. smM315 was compared to reduced and alkylated monomeric secreted immunoglobulins from MOPC-315, MOPC-460, and XRPC-25 by quantitative affinity chromatography (QAC) using two differently substituted Dnp-aminohexyl-Sepharose 4B resins. Unique patterns of cross-reactivity of all secreted myeloma proteins were independently established with a competitive hapten inhibition assay using 125I-Dnp26BSA as the precipitating probe. After derivation with dinitrobenzylsulfonate, Dnp-aminohexyl-Sepharose 4B was modified with succinic anhydride which, with the inclusion of 0.03% Doc in a PBS and 0.1% NP-40 buffer, prevented nonhapten specific protein-matrix interactions during QAC. Dissociation constants determined by QAC for three ligands, (dinitrophenyl-glycine, trinitrophenyl-amino-caproate and tetramethylrhodamine) were essentially the same for smM315 and M315. Both of the other nitrophenyl binding IgA myelomas had distinct and significant differences in dissociation constants. Thus, for a differentiated antibody secreting cell which has undergone a heavy chain class switch, such as MOPC-315, the cell surface immunoglobulin has an identical ligand binding active-site as the secreted immunoglobulin.

Animals↗

Consequences of avidity in lymphocyte receptor-multivalent antigen binding in affinity maturation.

A mathematical model proposed by Crothers & Metzger (Immunochemistry 9, 341-357, 1972), describing the influence of multiple site interactions on the effective antigen binding property of antibodies was used to assess the possible role of lymphocyte receptor affinity in antibody affinity maturation. The model proposed that observed association constants (KobsS) were primarily dependent on the number of allowed active site-antigen interactions (n), the density and orientation of antigenic sites and the intrinsic association constant (K1) of an univalent antibody active site interacting with an univalent antigen. Because of the inherent uncertainty involved in the estimation of lymphocyte membrane structure and molecular parameters necessary to utilize other mathematical models, the Crothers and Metzger model was applied to the case of surface membrane bound immunoglobulin (smIg) on B-lymphocytes interacting with polyvalent antigens as a simple and direct concept. Consideration of red blood cells, dinitrophenyl16 guinea-pig albumin, and fluorescyl220 keyhole limpet hemocyanin as model antigens revealed that Kobs was many orders of magnitude higher than K1 when only a few interactions were allowed. A dissociation rate of several hours for release of polyvalent antigen from cooperating smIg was calculated for receptors with a K1 as low as 10(3) M-1. Assuming prolonged antigen contact as necessary to activate lymphocytes, cells bearing low-affinity receptors are functionally indistinguishable from those carrying higher-affinity smIg in their ability to retain antigen. The presumed role for antigen-driven selection of lymphocytes bearing increasingly higher-affinity smIg, which results in antibody affinity maturation, must be reexamined if the K1 of smIg does not confer a selective advantage to lymphocytes for retaining antigen.

Animals↗

ECT-induced interictal delirium in patients with a history of a CVA.

Earlier works have documented a high incidence of affective disorders in patients with a history of a cerebrovascular accident (CVA). In general, electroconvulsive therapy (ECT) has been reported to be effective in treating depressed patients with a history of CVA. Recent works have shown that preexisting structural brain changes may predispose patients to develop interictal ECT-induced delirium. However, the incidence of ECT-induced interictal delirium in patients with a history of CVA has not been directly studied. In this pilot study, the authors examined the incidence of ECT-induced interictal delirium in 14 depressed CVA patients compared with 14 elderly depressed controls (without a history of CVA). Interestingly, the overall incidence of delirium was identical in both groups (28.5%). However, consistent with previous works, some patients who had had a recent CVA involving the caudate nucleus appeared more likely to develop delirium. Thirteen of the 14 depressed CVA patients (92%) showed a moderate to significant improvement in their depressive symptoms from ECT. None of the patients developed significant cardiac complications during ECT.

Aged↗