Blood-group antigens NN and Me-Vg were obtained as homogeneous substances from human red cells and meconium, respectively, and fully characterized chemically and biologically. For the first time a homogeneous erythrocyte membrane component of such high blood-group activity is described. Both substances induce anti-N specific antibodies in rabbits. They are also highly potent myxovirus receptors. The N and myxovirus specificities of the erythrocyte antigen are destroyed by sialidases and by proteases. Human N specificity is also destroyed by galactose oxidase. Specificities are carried by sialyl, sialylgalactopyranosyl, and P-galactopyranosyl structures. Both antigens are glycoproteins containing sialic acid, galactose, galactosamine, glucosamine, and mannose as the main carbohydrates. The Me-Vg antigen in addition contains a T here are at least 14 human blood-group systems with over 60 blood-group antigens (cf. Race and Sanger, 1962; Wiener, 1963) whose mosaic structures are believed to be the products of one or more genes and their allelomorphs. Until recently chemical knowledge was confined to members of the two closely related ABH(0) and Lewis systems (Kabat, 1956;Morgan, 1960; Watkins, 1966). Most of this chemical information is based on studies, not of red cells, but of the abundant water-soluble substances in secretions which are similar in serological specificity to the ABH(0) and Lewis structures on human erythrocytes.The first conclusive chemical evidence on the second human blood-group system to be discovered, the M N system (Landsteiner and Levine, 1928; cf. Wiener, 1%3), was provided by Springer and Ansell (1958) and independently, shortly thereafter, by Makela and ~ __.________ ment is maintained by the Susan Rebecca Stone Fund for Immunochemistry. t On leave from Fukushima Medical College, Fukushimashi, 3254 Japan.large amount of fucose. Components migrating on paper chromatograms like N,O-diacetylneuraminic acid have been identified in these antigens. This is the first account of these substances in products of human origin. The peptide part amounts to 44% in the NN antigen and to 13 % in the Me-Vg antigen. Threonine and serine are prominent in both glycoproteins; the concentration of aromatic amino acids is low. Tryptophan and cystine are absent. Alkali degradation studies show that the threonine and serine are involved in the peptide-carbohydrate linkage; galactosamine and galactose are the carbohydrates destroyed by alkali in the NN antigen and glucosamine in addition in the antigen from meconium. Haptenic structures in which sialic acid and galactose predominate have been isolated by enzymatic and mild acid hydrolysis.Cantell (1958), who showed that strains of type A and B influenza viruses inactivated the M and N antigens of human erythrocytes. Since then glycoproteins of varying purity and with different degrees of blood-group M and N activity together with ABH(0) activity isolated from human erythrocyte stroma have been described (Baranowski et a[. Klenk and Uhlenbruck, 1960; Stalder and ...

For nearly 20 yrs, we used T/Tn antigen vaccine in safe, specific, effective, long-term intradermal vaccination against recurrence of advanced breast carcinoma. Treatment is ad infinitum. All 18 breast carcinoma patients treated, pTNM Stages IV (6), III (6), and II (6), survived > 5 yrs postoperatively; 10 survived > 10 to > 18 yrs; of the latter, three patients each are Stages III and IV. Five additional 5 yr survivors have not yet reached 10 yrs. The probability that our survival results are due to chance, with NCI "1991 Standard PDQ Data" as control, for all three stages taken together is: 5-yr survival: p < 1 x 10(-8); 10-yr survival: p < 1 x 10(-5). There were no untoward side effects. The vaccination area presented as a delayed-type hypersensitivity reaction, but at variance with the PPD reaction, with significant inflammation, increase of helper T lymphocytes and decrease of the T suppressor/cytotoxic cell ratio.

Interest in anti-Thomsen-Friedenreich (T) antibodies has increased because of their significance in detection of and their possible interaction with human adenocarcinoma. The origin of anti-T, which all humans possess, has not been ascertained. We determined here that anti-T and -Tn agglutinins could readily be induced via the physiological intestinal route by an enteric bacterium, E. coli O86, which possesses T and Tn activities. One dose of live E. coli O86 given in the drinking water to germfree chicks, who had no anti-T and -Tn antibodies, resulted, in all birds, in formation of saline agglutinating anti-T and -Tn antibodies as well as those detectable only by indirect agglutination. Antibody specificity was confirmed by adsorption on and elution from homologous human erythrocytes and for anti-T also by haemagglutination inhibition. In contrast, control chicks raised under ordinary conditions did have anti-T and -Tn prior to feeding E. coli O86. In humans, six diarrhoeic and five healthy infants and the majority of 13 adults investigated were fed killed rather than live E. coli O86. All infants, but one, suffering from diarrhoea showed a significant increase (greater than or equal to 4-fold) in anti-T and/or anti-Tn antibodies; in some, these antibodies were elicited de novo. All four adults with intestinal lesions had a significant increase of anti-T and/or -Tn subsequent to ingestion of E. coli O86, as did five of nine healthy adults, but to a lesser extent. These findings support the immune nature of demonstrable levels of anti-T and -Tn.

Studies of the reactivity of the various anti-human blood group N reagents with isolated human blood group M and N antigens and smaller molecules revealed besides the expected interaction with N antigens that M antigens inhibited all rabbit anti-N sera, Viciu grumineu extract and most human anti-N sera. Mild acid hydrolysis of M antigens, which released sialic acid only, led to a large increase or de novo appearance of this inhibitory capacity. The partially hydrolyzed M antigens became temporarily indistinguishable from N antigens, indicating that the product of the N gene is the immediate precursor of the product of the M gene and that the allele to the M gene is an amorph. In the NM biosynthetic pathway, the Viciu-reactive structure seems to precede the N-specific molecule.Uncovering of N-specific structures paralleled the appearance of terminal B-D-galactopyranosyl structures; their exposure to B-galactosidase resulted in destruction of N specificity. Galactose and some B-D-galactopyranosyl derivatives inhibited the N erythrocyte agglutination by some anti-N sera. Ganglioside I and 'asialoganglioside' were inhibitors of anti-N reagents and anti-ganglioside serum reacted preferentially with human blood group N antigens.The M and N agglutinogens are the two main factors of the second human blood group system [I 1, 121. They are thought to result from the action of two allelomorphic genes [7,12, 391. The first known antibodies against specific determinants of the N antigen were produced in rabbits by LANDSTEINER and LEVINE [Ill. These early workers noted that anti-N sera agglutinated homozygous M erythrocytes in addition to their much stronger reaction with N red cells; this phenomenon was thought to be a cross-reaction akin l