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Biomedical subjects

F F Richards

Publications and source records attributed to F F Richards.

At least 73 records · Page 4Linked to original sources
PubMed1973

Tumor induction by immunologically activated murine leukemia virus.

A graft-vs.-host reaction (GVHR) was induced in young male CAF(I) and CB6F(1) mice by the administration of BALB/cJ spleen cells. A proportion of such mice subsequently developed lymphoreticular rumors. Cell-free extracts (CFEs) prepared from the reticular tissues of CAF(1) mice killed at intervals after the induction of the GVHR were tested for their capacity to produce the same tumors in a litter of syngeneic mice inoculated at birth. 12 of 29 (41.4%) such extracts were positive, causing lymphoreticular tumors in one or more littermate recipients. The positive CFEs came from donors killed at all stages of the GVHR, from tumor-bearing mice as well as from non-tumor-bearing mice. However, whereas less than 30% of CFEs from mice killed within 12 mo of GVHR induction were oncogenic, the incidence of oncogenic extracts from mice killed 12-15 mo after GVHR induction rose to 75%. None of the CFEs prepared from nine normal uninjected male CAF(1) mice killed between the ages of 8 and 18 mo transmitted tumors to recipients. CFEs prepared from CAF(1) mice with the GVHR were tested for infectious murine leukemia virus (MuLV) using the XC assay and also for complement-fixing (CF) group-specific MuLV antigen. Substantial titers of B-tropic MuLV and CF antigen were detected in at least half the extracts from mice killed 11-14 mo after GVHR induction. During the first few months of GVHR induction, MuLV titers were low and CF antigen was absent. Neither infectious MuLV nor CF antigen were detected in CFEs prepared from normal control mice. Serially passed CFEs originating from a CB6F(1) GVHR-induced RCN caused similar tumors in successive generations of syngeneic recipient mice. These lymphoreticular tumors were shown to contain infectious MuLV, CF MuLV antigen, and C-type particles. These data together provide evidence that MuLV is activated during the GVHR and that it is responsible for the eventual development of lymphoreticular tumors.

Animals↗
PubMed1973

Antibodies with multiple binding functions. Induction of single immunoglobin species by structurally dissimilar haptens.

Anti-hapten sera prepared in rabbits contain individual immunoglobulin species capable of binding several pairs of structurally diverse haptens A and B. (A = inosine, uridine, menadione, vitamin K(1), ribonuclease; B = 2,4-dinitrophenyl). In antisera against hapten A subjected to isoelectric focusing, there are many anti-A immunoglobulin species, but only a small proportion of these bind both A and B. When rabbits are primed with haptens A coupled to a carrier and then challenged with hapten B-carrier complex, there is an early restricted response of those species that bind both A and B. Later, immunoglobulins appear which bind B, but not A. These results suggest that multiple-binding antibodies exist in antisera against hapten and that such multiple binding is functional; i.e., that when two diverse haptens A and B bind to an immunoglobulin, both haptens may stimulate the cell-surface receptor to induce production of this immunoglobulin. Such phenomena may also provide a molecular basis for maturation of the immune response.

Animals↗
PubMed1972

Contact regions for dinitrophenyl and menadione haptens in an immunoglobulin binding more than one antigen.

Protein 460 is a mouse myeloma gamma A(2) protein that competitively binds two small haptens, 2,4-epsilon-dinitrophenyl-L-lysine (Dnp-Lys) and 2-methyl-1:4-naphthaquinone thioglycollate (MenTG), to the antibody-combining region. The intact protein has a relatively inaccessible sulfhydryl group on each heavy chain. When it is substituted with a bulky reagent the binding affinity for MenTG decreases, while the binding of Dnp-Lys remains the same. Guanidine.HCl selectively reduces binding of Dnp-Lys; dimethylsulfoxide selectively reduces binding of MenTG. Papain digestion of protein 460 followed by column chromatography gave two fractions: one contained both binding activities and the other contained the sulfhydryl group. The affinity for Dnp-Lys of the first fraction is the same as that of the whole molecule, while affinity for MenTG is decreased. Since selective alteration of one or the other binding activity can occur in different ways, it seems likely that even though the haptens compete with each other, there is some spatial separation between the groups of contact amino-acid residues involved in the binding of these two haptens. These findings do not support the hypothesis that an immunoglobulin molecule carries combining sites complementary only to a single hapten or to a structurally related series of haptens, but rather suggests that the antibody-combining site may be a polyfunctional region capable of binding several structurally dissimilar haptens. We discuss a mechanism whereby polyfunctional combining sites can give rise to an antibody population (immune serum) that has a high degree of specificity to a single hapten.

Alkylation↗