D-Glucaric (8accharFc) acid, the naturally occurring dicarboxylic acid aualogue of D-glucose, can support the growth of a variety of microorganisms (den Dooren de Jong, 1926), particularly grcherlchia coli and related enteric bacteria (Kay, 1926). Initial studies on the intermediary metabolism of D glucarate shoved that when 3. coli is grown In glucarate or galactarate, both resting-cell suspensions and cell-free axtracts from this culture can convert 1 mole of glucarate to 1 mole of pyruvate and unidentified products in the presence of areenfte (Blumenthal and Campbell, 1958). Later the first step in this conversion was shown to involve dehydration by D-glucarate dehydrase (Blumenthal, 1960), resulting in a yield of both 2-lceto-J-deoxy-and 4-deoxy-5-keto-D-glucarate, the latter compound being the major product (Fish and Blumenthal, 1961). We now have evidence that two additional eusymee take part in the conversion of 1 mole of D-glucarate to 1 mole each of pyruvate and glycerate. These enzymes, which have bean partially purified from E.-coli extracts, are ketodeoqglucarate aldolase (Fish and Blumenthal, 1963) and tartronate seuialdehyde reductase (D-glycerate 3-dehydrogeuaee). The entire sequence for the catabolism of D-glucarate is showu in Pig. 1. gvidence substantiating this mechanism has been gained through stoichiometric analysis (Table 1) of reactions employing the partially purified 9. & enzymes.

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The three components of the toxin of Bacillus anthracis, edema factor (EF), protective antigen (PA), and lethal factor (LF), were purified 197-, 156-, and 1,025fold, with 38, 78, and 11% recovery, respectively. Each purified component was serologically active, distinct, and free from the other components. The purified EF produced edema when mixed with PA, and the purified PA was an active immunogen. The components did not appear to be simple proteins by spectrophotometric analysis. As they were purified, the pH range in which they were most stable narrowed, centering between pH 7.4 and 7.8. Heat readily destroyed the biological activity of the components but not their serological activity. The rat lethality test showed that, with a constant amount of LF and an increasing amount of PA, the time to death reached a minimum and then was extended. When an increasing amount of LF was added to a constant amount of PA, the time to death became shorter as more LF was added. The biological, immunological, and serological properties of the components were shown to vary independently with storage and extent of purification so that serological activity was not always directly correlated with biological activity. Evidence is presented that the components can exist in different molecular configurations or as aggregates, and that this property is influenced by the state of component purity and by the environment.

AKR/J mice, 80-90% of which ordinarily die of spontaneous lymphocytic leukemias by 12 months of age, were significantly protected from developing leukemia in the initial experiment by a single course of treatment with AKR serotype-specific antibodies made in goats and processed as immune gamma globulin (IgG). In experiment 1, IgG was given on the day of birth and on four additional days, and finished on day 14. This schedule resulted in suppression of over 4 logarithms of normal virogene expressions up to 25 days of age and led to partial viral suppression for over 200 days of age. At 365 days of age, 20 of 24 (83.3%) control animals were dead of leukemia whereas six of 30 (20%) treated animals had died of leukemia. In a second experiment, only four inoculations of IgG were given from birth to 20 days, after which they were given three inoculations of radiation-killed vaccine specific for AKR-Gross leukemia virus and one injection of murine sarcoma virus-Gross leukemia virus 10 days later. This combined immunization procedure provided significant virus suppression up to 288 days of age. At 300 days of age, 30 of the 50 (60%) controls had died of leukemia while only 1 of 24 (4.2%) of the immunized mice developed fatal leukemia; the significance of protection for each of the experiments was P << 0.001. We conclude that these data establish in classical fashion with type-specific immunosuppression the determining role of type-C endogenous virogenes in leukemogenesis and, at the same time, also establish the feasibility of nearly total prevention of leukemia in AKR mice.In this communication we report two experiments, both resulting in highly significant prevention of spontaneous leukemia in AKR/J mice. In the first experiment, several injections of virus-specific antisera prepared as immune gamma globulin (IgG) were given shortly after birth and continued to the 14th and 20th days of age, after which the control and immunized mice (starting at 170 days of age) were observed twice daily for development of the leukemia and/or thymic lymphomas which normally account for nearly all deaths in AKR mice by 12 months of age.

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