Diclonal gammopathy in chronic cold agglutinin disease.

Serum from a patient with chronic cold agglutinin disease (CCAD) contained two paraproteins identified as IgM kappa and IgM lambda by immunoelectrophoresis and confirmed by immunofixation on high resolution agarose gel electrophoresis. The IgM kappa band was completely removed by incubation of the serum at 4 degrees with ficin-treated O Rh-positive red blood cells, and partially removed by incubation with cord cells, suggesting that it reacted with I antigen. The IgM lambda band was unaffected by these absorptions. Previous investigators have shown CCAD to be a monoclonal gammopathy, usually IgM kappa. The presence of both IgM kappa and IgM lambda paraproteins in this patient with the IgM kappa showing cold agglutinin activity is unique. The patient has a lymphoplasmacytic infiltrate in the bone marrow. These data suggest that CCAD may be part of a spectrum of disorders in which paraproteins are produced and are stimulated by factors unrelated to the target red blood cell antigens.

Interaction specificity of the anthracyclines with deoxyribonucleic acid.

The interaction specificity of salmon sperm DNA with various derivatives of daunorubicin has been studied. The results of binding, viscometric, 1H nuclear magnetic resonance (NMR), flow dichroism, DNA template inhibition, rates of dissociation, and circular dichroism studies are found to be consistent with an intercalation mode of binding of the anthracycline ring as has been shown by other investigators. Moreover, it is observed that (i) strength of binding, (ii) the ease of dissociation of DNA-anthracycline complexes, and (iii) the degree of inhibition of the DNA-dependent RNA polymerase are dependent on the presence of the amino sugar moiety of daunoseamine. The results are consistent with specific H bonding of the amino group of the sugar moiety with DNA as has been suggested earlier by Pigram et al. (Pigram, W.J., Fuller, W., and Hamilton, L.D. (1972), Nature (London), New Biol. 235, 17). Peptide derivatives substituted at the amino sugar function of daunorubicin lower the affinity of the drug to DNA and presumably interfere with the "full insertion" of the anthracycline drugs between base pairs of DNA. The significance of these findings in relation to the biological efficacy of daunorubicin and related derivatives as antileukemic agents is discussed.