Vasoproliferative activity has been demonstrated in extracts of retinas from human, bovine, and feline sources. These retinal extracts are capable of stimulating (a) proliferation and thymidine uptake of bovine vascular endothelial cells in culture and (b) neovascularization on the chick chorioallantoic membrane. Extracts of skeletal muscle, cardiac muscle, and liver lack similar stimulatory activity. The activity is nondialyzable, stable at 56 degrees C, and inactivated at 100 degrees C. Retinal extracts stimulate the proliferation of corneal fibroblasts but have no effect on the proliferation of vascular smooth muscle cells. Indirect evidence suggests the liberation of a vasoproliferative factor from retina in several ocular disorders. The data in this report represent the first direct demonstration of vasoproliferative activity from mammalian retina.

Bovine retinas contain a factor that stimulates proliferation of aortic endothelial cells in culture as well as neovascularization on the chicken chorioallantoic membrane. The stimulatory activity has been partially purified from a balanced salt solution extract of bovine retinas. The stability of the activity to acid pH was utilized as the first step in purification. The acidtreated material was subjected to ion-exchange chromatography on DEAE Bio-Gel A. The material thatwas eluted with 0.

values calculated from known bond moments and ring conformations.A dipole moment of 1.87 D. has been reported13 for tetrahydrothiophene. If one takes the CSC angle in this compound as loo", the observed moment can be considered as the vector sum of two CS bond moments of 0.935/cos 50", or 1.46 D.Bond angles and bond lengths in 1,2-dithiolane-4carboxylic acid have been determined by Foss and TjomslandZ1 based on X-ray diffraction studies. Based upon their data, the average angle between the valence bonds of each sulfur atom is 94.6" and the value of the dihedral angle between the CSS plane and the SSC plane is 26.6'. Then, by assuming the angular conformation of the 1,2-dithiolane ring in 2,3-dithiaspiro [4,5]decane to be the same as in the corresponding carboxylic acid, neglecting any small contribution of the cyclohexane ring, and taking 1.46 D. as the C-S bond moment, the calculated moment of 2,3-dithiaspiro-[4S]decane is 2.82 D., in good agreement with the observed moment of 2.85 D.The moments of the selenium-containing compounds cannot be treated so precisely because of lack of information about the C-Se-Se bond angles. However, monoselenides usually have moments only slightly smaller than monosulfides,22 and it is, therefore, not (21) 0. Foss and 0. Tjomsland, Acra Chem. Scand., 12, 1810 (1958). (22) For exainp.e, the moment of diphenyl sulfide is quoted as 1.5 D., that of diphenyl se:enide 1.4 D.: R. J. W. Le Fevre, "Dipole Moments,"Methuen and Co., Ltd., London, 1963, pp 134,135. unexpected to find that the dithiolanes and diselenolanes have similar moments or that the moment of the thiaselenenates, in the absence of a significant degree of polarization, is again similar to those of its iso-Turning now to the carboxylic acids, 1,2-dithiolane-4carboxylic acid (I) can be treated as containing a planar ring with a moment of 2.85 D. The contribution of the carboxyl group in I is taken from the observed moment of cyclopentanecarboxylic acid (1.70 D.) and the angle of the C-COOH bond to the plane of the ring is assumed to be one-half the normal tetrahedral angle of 110". The angle of the carboxyl moment to the C-COOH bond is taken as 74°.23Hydrogen bonding of the carboxylic hydrogen to the disulfide bond would restrict rotation of the carboxyl group and result in a molecule with conformation Ia, having a calculated dipole moment of 1.4 D. Conversely, conformation Ib, resulting from interaction of the S-S bond with the carbonyl oxygen, would produce a moment of 4.1 D. The moments observed for the free acids as well as for the methyl ester of 1,2-dithiolane-4-carboxylic acid are in surprisingly good agreement with the moment calculated assuming unrestricted rotation of the carboxyl group, 3.1 D. This further substantiates the contention that little, if any, interaction occurs between the carboxyl group and the disulfide bond. logs.Abstract: The mechanism of the oxidation reaction resulting from treatment of an alcohol with dimethyl sulfoxide and dicyclohexylcarbodiimide in the presence of a proton source has be...

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2,4-Dinitrophenylhydrazone.-Compound VI, 34 mg, was refluxed 5 min with 30 mg of 2,4-dinitrophenylhydrazine in 4 ml of methanol containing 0.1 ml of 6 N HC1. After cooling to room temperature the reaction mixture was centrifuged. The precipitate was crystallized from methanol, yield 27 mg, mp 138-1410.