A mixture of 4 g. (0.032 mole) of II and 2.65 g. (0.035 mole) of chloroacetonitrile in 20 ml. of benzene was refluxed for 90 min. The separated hydrochloride was collected, the base liberated with 10% sodium hydroxide, extracted with ether and distilled.3-/3-Aminoethyl-8-methyl-3,8-diazabicyclo [3.2.1] octane (XXIV) .-To a stirred suspension of 2.3 g. (0.06 mole) of lithium aluminum hydride in 150 ml. of dry tetrahydrofuran at 0°, 3.2 g. (0.0197 mole) of XXIII diluted with 10 ml. of tetrahydrofuran was added. The reaction mixture was refluxed for 3 hr., cooled to -5°and cautiously decomposed with 8 ml. of water. After stirring for 1 hr. at room temperature, the inorganic material was filtered and thoroughly washed with tetrahydrofuran. Tin; filtrate was dried over sodium sulfate, the solvent evaporated and the residue distilled.3-Guanidinoethyl-8-methyl-3,8-diazabicyclo[3.2.1] octane (XXV) .-A stirred mixture of 2.2 g. (0.013 mole) of XXIV, 4.8 g.(0.020 mole) of S-ethylisothiuronium bromide and 30 ml. of chloroform was refluxed for 5 hr., under an efficient hood. A viscous oil separated and solidified on cooling. The chloroform solution was decanted and stored. The solid crop (4 g.) after washing with ether was crystallized twice from isopropyl alcohol (200 ml.)to give 1.7 g. (35%) of the dihydrobromide of XXV, m.p. 230-233°. The chloroform solution was evaporated and the oily residue was crystallized from isopropyl alcohol to give 1.7 g. (45%) of XXV monohydrobromide. 8-Methyl-3-nitroso-3,8-diazabicyclo [3.2.1] octane (XXVI).-To a stirred solution at 0°of 7.3 g. (0.058 mole) of II in 29 ml. of 2 N hydrochloric acid, was added dropwise a solution of 4.5 g. (0.065 mole) of sodium nitrite in 10 ml. of water. The reaction mixture was kept, at room temperature for 2 hr., cooled, made alkaline with 50%. sodium hydroxide solution and extracted with ether. The extract was dried over sodium sulfate, the solvent evaporated and the residue distilled.
TWO FIQURESI n 1952, an experiment was started concerned with the effects of x-radiation upon cell (division on regenerating rat livers. Groups of rats were partially hepatectomized and then irradiated a certain number of hours after the operations. Each group was sacrificed at 12-hour intervals following irradiation and the livers subsequently sectioned, stained, and examined. The average number of mitoses per unit volume of liver parenchyma, as compared with that of the non-irradiated controls, was used as the criterion of radiation effect. Initially, the partial hepatectomies, and, therefore, the radiation, were performed a t different hours of the day, so arranged that killing and autopsy were always carried out in the morning. To test the reliability of this procedure, two groups of animals, to be sacriiiced at the same time after radiation, were hepatectomized at reciprocal hours of the day -one group at 9 : 00-10 : 00 A.M., the other at 9 : 00-10 : 00 P.M.Except for the time difference, the general schedule followed was identical for both groups. It was noted at once that there was a wide gulf f;eparating the mean values recorded for each group. These results suggested the possibility that a diurnal periodicity in mitotic activity was responsible for thc discrepancy, and the experiment was redesigned so that all operations were carried out at the same hours, all time being reckoned thereafter from this Rhode Island.
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