Skin-reactive soluble antigen from intestinal cancer-cell-membranes and relationship to carcinoembryonic antigens.
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Biomedical subjects
Publications and source records attributed to P Gold.
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A radioimmunoassay has been developed for determining the serum levels of carcinoembryonic antigen of the human digestive system in patients with cancer of the colon and rectum. The assay is simple to perform and has a high degree of reproducibility and specificity. The test detects a concentration of 2.5 ng of carcinoembryonic antigen per ml of serum and this has provided the first demonstration of a circulating tumor-specific antigen in the sera of cancer patients.
A procedure has been described for the purification of the carcinoembryonic antigens (CEA) of the human digestive system. Tumor tissue extraction in 0.6 M perchloric acid followed by paper block electrophoresis and column chromatography on Sephadex G-200 resulted in highly purified CEA preparations as determined by both immunological and physicochemical criteria. The properties and composition of five different purified CEA preparations derived from digestive system cancer metastases were examined. The findings demonstrated a high degree of uniformity amongst these samples. Sedimentation coefficients ranged from 6.9 to 8S. Each sample showed the presence of 14 different amino acid residues and six different carbohydrate constituents (four of which could be quantitated with the amount of material available for analyis). Studies of a purified CEA preparation from a primary hepatoma yielded results which, in some respects, differed from those obtained with the CEA samples of metastatic tumor origin. The implications of these variations were discussed with regard to the probable presence of non-CEA components in the hepatoma preparation. Of primary importance was the observation that the few normal adult digestive system tissues tested failed to show the presence of constituents similar to the CEA. This finding would seem to indicate that, in the adult, the carcinoembryonic antigens of the human digestive system are qualitatively tumor-specific and are not dectectable in comparable normal tissues.
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A wide variety of human adult and fetal tissues were studied by immune-diffusion techniques in agar gel to determine whether they contained the tumor-specific antigen(s) previously found in coionic cancers. In the adult tissues it was demonstrated that identical antigens were present in all tested specimens of malignant tumors of the entodermally derived epithelium of the gastrointestinal tract and pancreas, but were absent from all other tested adult tissues. The common antigenic constituents, therefore, represent system-specific cancer antigens of the human digestive system. System-specific cancer antigens have not previously been demonstrated in humans. Experiments with fetal tissues demonstrated that identical antigens were also present in fetal gut, liver, and pancreas between 2 and 6 months of gestation. These components were named "carcinoembryonic" antigens of the human digestive system. On the basis of the present findings and the recent work regarding control of the expression of genetic potentialities in various types of cells, it was concluded that the carcinoembryonic antigens represent cellular constituents which are repressed during the course of differentiation of the normal digestive system epithelium and reappear in the corresponding malignant cells by a process of derepressive-dedifferentiation.
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Levels of plasma ACTH in relation to dexamethasone administration were evaluated in 16 medication-free patients with a major depressive episode and 39 normal controls. Depressed patients had significantly higher levels of plasma ACTH than controls both at 4:00 p.m. predexamethasone and 4:00 p.m. postdexamethasone. The significance of this finding is discussed.
A substantial body of data suggests that excessive cortisol secretion in depression may result from a dysregulation at several sites within the hypothalamic-pituitary-adrenocortical (HPA) axis. These alterations in regulatory mechanisms are thought to be the result of a hypothalamic 'overdrive' of corticotropin-releasing hormone (CRH). Previous studies have demonstrated a diminished adrenocorticotropin (ACTH) secretory response, as well as a heightened adrenocortical responsiveness after ovine-CRH administration in depressed patients. In the present investigation, we examined pituitary and adrenocortical responsiveness after an ovine-CRH stimulation test before and during clinical recovery in seven depressed patients. Cumulative ACTH responses increased significantly during clinical recovery (P = 0.014). Paradoxically, maximum and peak cortisol responses increased after recovery, suggesting that heightened adrenocortical responsiveness to ACTH during depression may take longer to 'normalize' than abnormal pituitary responsiveness to ovine-CRH stimulation.
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