Four monoclonal antibodies against carcinoembryonic antigen (CEA) have been selected from 32 hybrids that produce antibodies against this antigen, by the criteria of high affinity for CEA and low cross-reactivity with granulocyte glycoprotein(s). The specificity of tumor localization in vivo of the four MAb, and their F(ab')2 and Fab fragments was compared in nude mice bearing grafts of a serially transplanted, CEA-producing, human colon carcinoma. The distribution of radiolabeled MAb and their fragments after intravenous injection was analyzed by direct measurement of radioactivity in tumor and normal organs, as well as by whole-body scanning and by autoradiography of tumor sections. Paired labeling experiments, in which 131I-labeled antibody or fragments and 125I-labeled control IgG are injected simultaneously, were undertaken to determine the relative tumor uptakes of each labeled protein. The tumor antibody uptake divided by that of control IgG defines the specificity index of localization. Tumor antibody uptakes (as compared with the whole mouse), ranging between 7 and 15, and specificity indices ranging between 3.4 and 6.8, were obtained with the four intact MAb at day 4-5 after injection. With F(ab')2 fragments of the four MAb, at day 3, the tumor antibody uptakes ranged between 12 and 24 and the specificity indices between 5.3 and 8.2. With the Fab fragments prepared from the two most promising MAb, the antibody uptakes reached values of 34 and 82 at day 2-3 and the specificity indices were as high as 12 and 19. The scanning results paralleled those obtained by direct measurement of radioactivity. With intact MAb, tumor grafts of 0.5-1 g gave very contrasted positive scans 3 d after injection. Using MAb fragments, tumors of smaller size were detectable earlier. The best results were obtained with Fab fragments of MAb 35, which gave clear detections of tumors weighing only 0.1 g as early as 48 h after injection. Autoradiographs of tumor sections from mice injected with 125I-labeled MAb demonstrated that the radioactivity was localized in the tumor tissues and not in the stromal connective tissue of mouse origin. The highest radioactivity concentration was localized in areas known to contain CEA such as the pseudolumen of glands and the apical side of carcinoma cells. The penetration of radioactivity in the central part of tumor nodules and the pseudolumen appeared to be increased with the use of MAb fragments.

In a retrospective study of 119 patients, followed for 1 to 30 years after treatment of a papillary carcinoma of the thyroid, the authors searched for possible prognostic factors of the risk of recurrence. Microcarcinomas, anaplastic tumors and Hürthle cell carcinomas were excluded from the study. In a univariate analysis, age (greater than 45 years), sex (male), loss of histologic differentiation, size (greater than 3 cm), presence of carcinomatous lymphangitis, extrathyroid extension, and presence of metastasis at diagnosis were associated with a higher recurrence rate; type of growth and multifocality were not significant. In a multivariate analysis (logistic regression), age, size, and carcinomatous lymphangitis were significant predictors for women, whereas metastasis at diagnosis and cystic growth were significant for men.

Forty-three cases of large cell anaplastic thyroid carcinoma were examined with various antisera. Four histological patterns were identified: spindle cell, giant cell, trabecular and squamous. In 38 cases the epithelial origin was demonstrated with various epithelial markers: 11 cases stained positively for thyroglobulin, 19 for T3 and/or T4, 35 for fat globule membrane antigens, 28 for keratin, 29 for lactoferrin, and one for calcitonin. Five cases were negative for all epithelial markers but could not be characterized further since, except for vimentin, they did not have mesenchymal markers. The immunohistochemical proof of the epithelial nature of anaplastic thyroid tumours is given by staining with anti-keratin and anti-fat globule membrane antigen. In addition the detection of lactoferrin seems useful, but not that of thyroglobulin which was present in only 4% of the spindle cell tumours and in 32-56% of the other histological types. Thirty carcinomas were positive for vimentin; the co-expression of vimentin and epithelial markers seems frequent in thyroid anaplastic carcinomas.

Glucose and lipid metabolism were studied in 12 patients with hyperthyroid Graves' disease for 3 h during an oral glucose tolerance test (100 g) by continuous indirect calorimetry. In the postabsorptive state, glucose oxidation was not different from that in normal subjects, but lipid oxidation was significantly increased. Impaired glucose tolerance was found, but total glucose oxidation increased after the glucose load to 47.1 +/- 2.0 (+/- SEM) vs. 33.4 +/- 1.4 g/3 h in the control group (P less than 0.001). Total glucose oxidation corresponded, in hyperthyroid patients, to the highest rate obtained with progressively increasing insulin and glucose administration in normal man. Glucose storage was clearly lower in hyperthyroid patients. After treatment in 7 patients, glucose tolerance improved significantly, and the metabolic patterns almost normalized. In the 12 hyperthyroid patients and the 7 patients after treatment (n = 19), a correlation was found between total serum T3 concentration and both basal lipid oxidation and suprabasal glucose oxidation. It is concluded that the decrease in glucose tolerance in hyperthyroidism cannot be explained by an alteration in glucose oxidation, but, rather, by a defect in nonoxidative glucose uptake in the periphery.