H. Gideon Wells

An immunological and chemical study of the alcohol-soluble proteins of cereals.

The prolamines, or alcohol-soluble proteins, are the characteristic proteins of cereal grains. These proteins were isolated from wheat, Triticum vulgare, durum, Triticum durum, emmer, Triticum dicoccum, spelt, Triticum spelta, einkorn, Triticum monococcum, rye, Secale cereale, oats, Avena sativa, barley, Hordeum vulgare, corn, Zea mays, kafir, Andropogon sorghum, teosinte, Euchlaena mexicana Schrad., and sorghum, Sorghum vulgare, and subjected to chemical and immunological study. The chemical study included the nitrogen distribution by the Van Slyke method, the free amino nitrogen, the free carboxyl groups, the true ammonia nitrogen, the cystine and tryptophane content, and the acid and alkali binding at various hydrogen ion concentrations and at different temperatures. This study showed certain similarities of chemical composition among the prolamines, as a class, as contrasted with the composition and behavior of such proteins as casein and fibrin. The chemical evidence suggested that the prolamines studied might be grouped into a “wheat group”, which would include the proteins isolated from the genus Triticum, and a “corn group” including those isolated from maize, teosinte, kafir, and sorghum. The genetic behavior of these groups has been extensively studied by plant blreeders, although relatively more work has been done upon the wheat group. Sakamura, 1 Kihara, 2 and Sax 3 have shown that T. monoccum is characterized by having 7 chromosomes, that T. dicoccum and T. durum have 14 chromosomes, and T. vulgare and T . spelta have 21 chromosomes.

The purines and purine metabolism of tumors, and the chemical relations of primary and secondary tumors

The purines of both benign and malignant tumors are the same as those found in normal tissues, and they exist in much the same relative proportions, The proportion of the total nitrogen of tumors which is constituted by the purine nitrogen is less than would be exspected from the histological evidence of the amount of nuclear material contained in the tumors. Tumors seem to contain much the same purine enzymes as the normal tissues. Thus, guanase seems universally present in tumors derived from human tissues, and adenase is missing, although autolyzing tumors can disintegrate their nucleic acid (nuclease) and change the adenine radicals of the nucleic acid into hypoxanthine, presumably by way of adenosine and inosine (Amberg and Jones). Secondary tumors growing in the human liver do not acquire the enzyme, xanthine-oxidase, which is a characteristic enzyme of this organ. The liver tissue between the cancer nodules seems to oxidize purines less actively than normal liver tissue. In view of the peculiarities of the distribution of purine enzymes in different species, we have examined a number of tumors of the domestic animals, obtained from the Chicago Stock Yards. The results of these investigations will appear in an early number of the Journal of experimental medicine.

The purine enzymes of the anthropoids and marsupials

Previous studies have shown that the human organism contains no enzymes which will destroy uric acid in vitro, in which respect man differs from all other mammals hitherto investigated. This corresponds with the repeated observations, especially of Wiechowski, that man alone of all domestic mammals excretes uric acid rather than allantoin as the chief end product of purine metabolism. These facts have been especially emphasized of late by Andrew Hunter. One of us found that even the monkey has no demonstrable uricolytic enzymes in its tissues. Wiechowski made the interesting observation that the chimpanzee, like man, excretes only uric acid and little or no allantoin, while Hunter and Givens reported that monkeys resembled the other mammals in excreting chiefly allantoin, corresponding with our observations on the purine enzymes of the monkey. We have recently, through the kindness of Dr. W. T. Hornaday of the New York Zoölogical Society, come into possession of two fresh bodies of anthropoids—–a male chimpanzee and a female orang-utan. Examination of their tissues shows that, like man, they do not possess the uricolytic enzyme, uricase, demonstrable in vitro. They also resemble adult man in having guanase but no demonstrable adenase. Hence it seems that the anthropoids stand with men in constituting, in respect to uricolytic power, an exception to all other known mammals; the monkeys resemble the other lower mammals in possessing uricase, and hence in this property the anthropoids stand closer to man than to the monkeys, as they are also said to do in serological reactions. We have found a marsupial, the opossum, to have uricase, xanthine oxidase, guanase but no adenase. In respect to uric acid destruction our results agree perfectly with the urinary analyses of Hunter and others.

Observations on uricolysis, with particular reference to the "uric acid infarcts" of the newborn

Mendel and Mitchell demonstrated that in the embryo pig the enzymes concerned with purin metabolism appear at different stages of development, the uricolytic power not appearing until after birth and being feeble during the first months of extra-uterine life. If the same late development of uricolytic power were present in the human fetus it would explain the occurrence of deposits of urates in the kidneys of newborn infants. Schittenhelm and Schmidt alone have studied uricolysis by infantile and fetal tissues, and have claimed to get active uricolysis. This result is questionable, because later work by Kunzel and Schittenhelm indicate absence of uricolysis by adult tissues. We have found no evidence whatever of uricolytic activity on the part of fetal tissues at any stage of development, nor of adult tissues. The latter observation is in harmony with the negative results obtained by Wiechowski in experiments in vitro and in vivo, and indicates that the human body has little if any power to destroy uric acid. The statements in the older literature that allantoin is found in the urine of pregnant women has been disputed by Wiechowski, and our failure to demonstrate uricolysis by human placenta as well as other fetal or adult human tissues points in the same direction. Additional observations are the demonstration of active uricolysis by the liver of the guinea pig, absence of uricolysis by spleen, bone marrow and probably the leucocytes of the dog, and the apparent absence of inhibitory power of dog serum upon uricolysis by dog liver.