Evidence has been presented by several investigators that functional capacity of the kidney in the premature and young infant is lower than in older children and adults. Schoenthal (1) using urea clearance, McCance and Young (2) urea and inulin clearances, Barnett (3) inulin clearance, and
Immunological and biochemical studies of spontaneously metastasizing and nonmetastasizing rat mammary carcinomas and, their plasma membranes indicated that: (i) all spontaneously metastasizing tumors have little or no demonstrable glycocalyx, while all nonmetastasizing tumors have a thick glycocalyx; (ii) there is a direct relationship between the glycocalyx and immunogenicity, and an inverse relationship with the metastasizing capacity of tumor cells, properties which can be quantitated by levels of the plasma membrane marker enzyme 5'-nucleotidase (EC 3.1.3.5; 5'-ribonucleotide phosphohydrolase) activity; (iii) the absence of glycocalyx from the metastasizing tumor cell surface seems to result from its dissociation from plasma membranes, for solubilized cell surface antigen is readily found in the'blood of metastasizing tumor bearing rats, while there was no detectable tumor cell surface antigen in the blood of the nonmetastasizing tumor hosts tested; (iv) both metastasizing and nonmetastasizing mammary tumors appear to have a common soluble cell surface' antigen; (v) in addition to this common antigen, there is another membrane-bound antigen in the nonmetastasizing, immunogenic tumor cell surface which presumably is the tuinor specific transplantation antigen; and (vi) this antigen is immunobiologically unique, but seems to be immunochemically related to the common soluble antigen. It is postulated that the lack of an immunogenic coat and/or the presence of solubilized tumor cell surface antigen in the blood may provide an immune escape mechanism for tumor cells by interfering with cell-mediated immune response of tumor hosts, leading to their dissemination.In an earlier report one of us (U.K.) (1) described the induction of spontaneously metastasizing mammary carcinomas (MT) in a highly inbred strain of W/Fu female rats by feeding 3-methylcholanthrene in splenectomized, thymectomized, or both splenectomized and thymectomized hosts, and subsequently subjecting the developing tumors to "immunoselection" in vivo. Such tunmors maintained their metastasizing capacity in normal syngeneic rats generation after transplantation generation, indicating that the metastasizing capacity is an intrinsic property of tumor cells. It was further demonstrated that the metastasizing tumor cells were nonimmunogenic while the ordinary methylcholanthrene-induced nonmetastasizing mammary carcinomas in normal female rats were highly immunogenic, as tested by immunization of the hosts with an equal number of radiation-killed tumor cells, followed by a challenge with a counted number of live tumor cells.In order to study the relationship between tumor cell immunogenicity and metastasizing capacity, two spontaneously metastasizing, non-or weakly-immunogenic mammary carcinomas (SAIT-2A and TMT-50), induced in the manner described above, and a spontaneously metastasizing mammary carcinoma induced with 7,12-dimethylbenz(a)-anthracene in a BCG (bacille Calmette-Guerin) inoculated rat (BCG-MT) were selected. They were matched accord...
Antibodies were raised in rabbits against pure ligandin. Employing the fluorescent antibody procedure, an antigen identical to ligandin was shown to be uniformly distributed in the hepatic cells of both normal rat liver and in early and late 3′-methyl-4-dimethylaminoazobenzene (3′-Me-DAB)-treated liver. Ligandin was absent in liver carcinomas induced by this azocarcinogen. The results obtained with the fluorescent antibody procedure were confirmed by the immunoquantitation of ligandin in the cytosols prepared from normal rat liver, early and late 3′-Me-DAB-treated liver, mixtures of both late 3′-Me-DAB-treated liver and liver carcinomas, and liver carcinomas. Riboflavin-deficient diets lowered significantly the hepatic ligandin content.
THE manner by which carcinogenic agents induce neoplastic growths is unknown in spite of the large amount of work which has been carried out on the chemistry of carcinogenesis. Epidermis was chosen as the tissue of choice for the work reported here for reasons given previously (Carruthers, 1950). Various stages in the malignant process such as methylcholanthrene-induced hyperplastic epidermis, papillomas and squamous-cell carcinomas were investigated. These phases were studied because large changes were sought in the present study particularly since the various degrees of intermediate and late epidermal hyperplasia show little, if any, significant chemical alterations (Carruthers, 1950). Also the recent studies of Rudall (1952) on the structural (urea extractable) proteins of beef snout epidermis offer some background for the proposed work. The structural proteins of epidermis may play a role in the adhesiveness of squamous cells (Rudall, 1952) and alterations in such proteins may account for the invasiveness and metastasis of skin carcinomas. In addition to the urea extractable protein (Carruthers, Woernley, Baumler and Kress, 1955) Croton oil treated epidermis served as a control since a huge number of normal mice would have to be sacrificed to yield sufficient epidermis from which to extract the proteins in large enough quantities for characterization. Croton oil treated epidermis shows a relatively benign hyperplasia since numerous applications of this material are necessary to elicit a good carcinogenic response in many mice (Roe, 1956). The epidermis was removed from the dermis at 50°C. (Baumberger, Suntzeff and Cowdry, 1942). Papillomas from many mice were pooled and then stored at 0-4°in 95 per cent alcohol until the amount was ample for extraction of the various proteins. Methylcholanthrene induced squamous-cell carcinomas were pooled from some 15 to 20 mice, and a small piece from each cancer was fixed and stained for histological examination. The remainder was cleaned of necrotic and connective tissue and placed in 95 per cent alcohol. The urea extract-
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