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Dark-cycle, night administration of the pineal hormone melatonin in drinking water to aging mice (15 months of age) prolongs survival of BALB/c females from 23.8 to 28.1 months and preserves aspects of their youthful state. Similar results were seen in New Zealand Black females beginning at 5 months and C57BL/6 males beginning at 19 months. As melatonin is produced in circadian fashion from the pineal, we grafted pineals from young 3- to 4-month-old donors into the thymus of 20-month-old syngeneic C57BL/6 male recipients, and a 12% increase in survival was induced. Prolongation of survival was also seen on pineal transplant to the thymus in C57BL/6, BALB/cJ, and hybrid female mice at 16, 19, and 22 months. In all studies, the endogenous pineal of grafted mice was left in situ. Pineal grafted aged mice display a remarkable maintenance of thymic structure and cellularity. Preservation of T-cell-mediated function, despite age, as measured by response to oxazolone is seen. Other evidence suggests that melatonin and/or pineal-related factors could produce their effects through an influence on thyroid function. These data indicate that pineal influences have a place in the physiologic regulation of aging.

Ethylbis(2,2-dimethyl-1-aziridinyl)phosphinate (AB-163) was used to treat 27 patients in a phase I trial. The limiting toxicity on a weekly schedule of IV administration involved nausea and vomiting associated with a variety of cholinergic side effects, including possible seizures. A starting dose of 300–400 mg/M2/week is suggested for a Phase II trial. One partial response in a patient with squamous-cell carcinoma of the cervix metastatic to the lungs was seen.

Twenty-five patients with a variety of solid tumors were treated with hydrazine sulfate. Hydrazine was given orally in the form of 60 mg capsules from one to four times daily. No patient had a 50% reduction of tumor size. Subjective benefit was seen in three patients but it was of brief duration.

Pyran copolymer, administered with sheep red blood cells to mice, enhances the early rate of appearance of antibody-forming spleen cells. Although the cytotoxicity and pyrogenicity of pyran and bacterial endotoxins are similar, pyran, in contrast to endotoxin, does not trigger a nonspecific initiation of antibody formation; it only enhances specific responses. The major effect of pyran appears to be on macrophages.

The decrease of the molecular size of poly(I·C) to less than 106decreases its ability to induce interferon, protect mice against virus, or enhance the immune response. Immune adjuvant activity appeared more sensitive to molecular weight than the other protective activities. The composition of the complex—the molecular size of the individual homopolymers when one was large and the other small—did not affect antiviral activity; the activity of a complex made from large poly(I) and small poly(C) was similar to one made from small poly(I) and large poly(C). Molecular size of the complex did not profoundly alter the side effects of poly(I·C). At 2 mg/kg, none of the complexes markedly altered phagocytic function. Only the largest complex sensitized the mouse to endotoxin. However, all of the complexes studied profoundly inhibited drug metabolism by the liver microsomal enzymes between 24 and 72 hr after their inoculation. Decreasing the molecular weight did not alter this inhibition.