A transplantable mouse fibrosarcoma, HSDM 1 , produces a potent bone resorption-stimulating factor. The factor can be extracted from the tumor tissue and harvested from the medium of clonal strains of HSDM 1 tumor cells growing in monolayer culture. It has several chemical and biological properties of a prostaglandin. Using radioimmunoassay techniques, we have shown that HSDM 1 cells synthesize and secrete large quantities of prostaglandin E 2 (PGE 2 ). The specific bone resorption-stimulating activity of the HSDM 1 factor extracted from the tumor is high and approximately equal to that of PGE 2 as measured in a bone tissue culture system in vitro. Indomethacin, a potent inhibitor of PGE 2 synthesis in HSDM 1 cells, also inhibits production by the cells of the bone resorption-stimulating factor, and has no detectable nonspecific effects on the bone culture assay system. Mice bearing the HSDM 1 tumor have higher levels of both calcium and PGE 2 in serum than control mice. We conclude that PGE 2 is the bone resorption-stimulating factor produced by HSDM 1 tumor cells, and that secretion of PGE 2 by the tumor in vivo accounts for the relative hypercalcemia observed in tumor-bearing animals. The HSDM 1 tumor cell system constitutes a new model for studying the pathogenesis of hypercalcemia associated with certain malignant tumors.

Tropocollagen preparations from carp, buffalo fish, rats, calves, sheep, and humans have been studied by electron microscopy and serologic methods. Tropocollagens from each species appeared identical by electron microscopy but they were readily distinguished (except between sheep and calves) by C'-fixation tests with rabbit antisera against the various tropocollagens. Tests with calf tropocollagen antiserum showed no distinction between tropocollagen isolated from different tissues nor between individuals of the same or different strains. The major immunogenic sites in native tropocollagen are the telopeptides, and these are present on both α1- and α2-chains. The C'-fixing activity was lost with heat denaturation of the tropocollagen, but could be recovered in a concentration-dependent process on cooling. The fact that pure and enzyme-treated collagen can provoke serologic reaction implies that collagenous sutures and prostheses used in surgery may lead to sensitization and rejection, a fact which may merit clinical concern.

Hemoglobin, its chains, and myoglobin enhance the antibiotic activity of colicine K. These proteins also interact with colicine K and other O antigens to alter their serological activity. The hemoglobin proteins did not alter the serological activities of three Pneumococcus polysaccharides or T4 bacteriophage DNA antigens but did alter the antigenic activity of fetuin. Interaction of hemoglobin and colicine K resulted in a retardation of colicine K antibiotic moiety as measured by gel filtration but did not affect the gel filtration properties of the lipopolysaccharide moiety.

1. Immunochemical cross-reactivity, but not identity, has been demonstrated between bovine parathyroid hormone and an antigen in biologically active extracts of human parathyroid tissue by quantitative C' fixation and C' fixation inhibition. 2. An antigen that fixes C' with rabbit antibody to bovine parathyroid hormone has been found in urea extracts of six human non-parathyroid neoplasms associated with a hypercalcemic syndrome mimicking primary hyperparathyroidism. Comparable extracts of control tissues and other tumors were serologically negative. 3. It is concluded that the tumor antigen is parathyroid hormone or a very closely related protein, and that its production by these neoplasms was the cause of the hypercalcemic syndrome in these six patients.

High density serum lipoprotein underwent serologic and physicochemical alterations on aging during storage at 0°C. for 1 month, as judged by decrease of diffusion coefficient and increase of C' fixation. Ultracentrifugation, dialysis, and high concentrations of sodium chloride did not cause these changes. A protein sedimenting at density 1.24 in the ultracentrifuge reacted with antiserum to high density lipoprotein. Probably it was the protein portion of α lipoprotein dissociated from the lipide during ultracentrifugation. Although the antiserum to high density lipoprotein did not react with low density lipoprotein prepared from normal serum, it reacted with similarly prepared lipoproteins from the serum of a patient with biliary cirrhosis.

The following human low density lipoproteins were prepared: ß-lipoproteins of densities greater than 1.040 (A, B,C) a ß-lipoprotein of – S 1·063 = 5 (D), a lipoprotein of – S 1·063 = 19 (E), and a lipoprotein of – S 1·063 = 70 (F). Data are presented which show the immunochemical homogeneity of the D lipoprotein rabbit-anti-D lipoprotein system. Cross-reactions between antibody to A and D lipoproteins and the above lipoproteins have been demonstrated by quantitative precipitation, quanitative complement fixation, and single and double diffusion in agar. The antigenic similarities appear to be associated with the protein portions of the molecule. The antisera produced did not differentiate the low density lipoprotein classes.