Memories of James Bertram Collip.
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Biomedical subjects
Publications and source records attributed to R L Noble.
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In view of the findings of Moon, Simpson, and Evans (Science, 116:331,1952) that the hypophysectomized rat was refractory to the carcinogenic effect of methyl-cholanthrene, similar experiments have been conducted but using the more powerful carcinogen 9,10-dimethyl-1,2-benzanthracene. The results of 2 separate experiments were as follows: All animals received 5 mg in sesame oil of the carcinogen intramuscularly. In the control animals, 15 showed discrete sarcoma out of 21 animals in 4-5 months. In the hypophysectomized animals only 3 showed comparable sarcoma, but in 7 there was marked abnormal proliferation of fibroblasts suggestive of malignant change. 9 animals were negative, although serial sections were not made. In addition to these findings it was noted that in control animals 6 mammary tumors developed in tissue adjacent to the injection site. 4 of these were of a malignant nature. In the hypophysectomized group no mammary changes were observed. Although these findings are somewhat in accord with the original observations it is believed that the change is quantitative rather than qualitative. Unfortunately, the hypophysectomized animals survived only 3-4 months, and the findings are suggestive that the malignant process occurs but more slowly in the absence of the normal pituitary function. The changes in mammary tissue would seem more clearcut, but are being repeated on a larger series of animals.
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Hormonal responsiveness should be considered in terms of at least three homeostatic constraint mechanisms. Observations on the induction of specific responses in rat prostate reveal that certain of these are controlled differentially, and also that immature cells can be modified by low levels of androgen. The conditioning effect of low levels of steroid is further demonstrated by the benefits of fractional hormone-replacement therapy in controlling and delaying tumor progression. A revised approach to endocrine therapy of cancer should be seriously considered. This would entail the fractional replacement of hormone after ablative surgery.
Excellent results have been obtained for the Fmoc solid-phase syntheses of peptides using the activating reagent 2-(1H-benzotriazol-1-yl)-1,1,3,3,-tetramethyluronium hexafluorophosphate (HBTU). Activation occurs very rapidly in N,N-dimethylformamide and N-methyl-pyrrolidone, optimal solvents for peptide-resin solvation. It has been observed that complete coupling reactions occur in only 10-30 min. Residues such as Arg, Ile, Leu and Val, which often require double coupling by other activation methods, react with high efficiency by single coupling when HBTU is used. The Fmoc/HBTU chemistry has recently been applied to the peptide synthesizers. The incorporation of trityl side-chain protection for Fmoc-Asn and Fmoc-Gln further enhances coupling efficiencies in difficult sequences.