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B Shore

Publications and source records attributed to B Shore.

14 recordsLinked to original sources

Surface exposure of apolipoproteins in high density lipoproteins. I. Reactivities with agarose-immobilized proteases.

The exposure of apolipoproteins at the surface of human plasma high density lipoproteins (HDL) was assessed by their accessibility to agarose-immobilized forms of trypsin and chymotrypsin. Proteolysis of lipid-free apolipoproteins and the lipoprotein subfractions HDL2 (d = 1.08--1.125 g/ml) and HDL3 (d = 1.125--1.195 g/ml) that differ in lipid-to-protein ratio was compared by polyacrylamide gel electrophoresis and isoelectric focusing of the apolipoproteins and peptide fragments and by quantitation of the various carboxyl-terminal groups formed. Gel filtration of the proteolyzed lipoproteins on Sephadex G-150 column indicated that more than 90% of the apolipoproteins and peptides remain associated with lipoprotein complexes. Proteolysis of lipoproteins occurred more slowly and with less fragmentation of the lipoproteins and apolipoproteins than proteolysis of thelipid-free apolipoproteins or the proteolysis of lipoproteins by soluble proteases reported by other investigators. The difference in lipid content of HDL2 and HDL3 made little difference in their proteolysis. Proteolysis of the lipoproteins by agarose-trypsin was more rapid at 37 degrees C than at 22 degrees C, but the proteolytic products were similar and differed from the products from the lipid free proteins. Peptide fragments from lipoproteins were larger than those from lipid-free proteins, which suggests masking of potentially cleavable groups by lipid. The amounts (mol/g protein) of new carboxyl-terminal tyrosine and phenylalanine released by agarose -chymotrypsin were much greater from the lipid-free proteins, but about 3/4 of the tryptophan residues were inacessible in both lipoproteins and lipid-free proteins. In agarose-trypsin digestion, lysine residues were slightly more masked than arginine in the absence of lipids and much more so in the lipoproteins. However, in the lipoproteins apoA-II, which contains lysine but no arginine, was cleaved more rapidly and extensively by agarose-trypsin than apoA-I.

Amino Acids

Rabbits as a model for the study of hyperlipoproteinemia and atherosclerosis.

Lipoproteins of normal and cholesteremic plasma were compared in New Zealand White (hyperresponder) and Dutch Belt (hyporesponder) rabbits. Three major differences were observed between the strains: (1) New Zealand White rabbits developed much higher plasma levels of very low, intermediate, and low density lipoproteins after cholesterol feeding; (2) Dutch Belt rabbits, normal and cholesteremic, had higher ratios of the more dense high density lipoproteins HDL3 (d 1.125-1.20 g/ml) to the less dense HDL2 (d 1.081-1.125 g/ml); (3) cholesteremic Dutch Belt rabbits had higher plasma levels of the more dense HDL3 subfraction than did cholesteremic New Zealand White rabbits. Cholesteremic very low density lipoproteins of both strains are large particles of beta electrophoretic mobility that are rich in cholesteryl esters and an arginine-rich apolipoprotein(s). The intermediate and low density lipoprotein fractions were similarly altered in composition, although the proportion of arginine-rich protein to total protein was ledd than in the very low density fraction. Although the high density lipoproteins were greatly decreased in concentration in cholesteremic plasma, no major changes in their apolipoproteins were seen in either strain of rabbits. The major high density apolipoprotein of rabbits occurs in two electrophoretically separable forms and is similar to human apo A-I. Six minor apolipoproteins were isolated from the high density lipoproteins; some of these occur also in other density fractions.

Adenosine Triphosphatases

Biological considerations of tumor-specific and virus-associated antigens of human breast cancers.

In vivo and in vitro studies bearing on tumor-specific and viral-associated antigenicity of human breast carcinomas were reviewed with particular attention to the following clinical considerations: (a) breast carcinomas arise in a nonrandom fashion; (b) in situ carcinomas precede invasive breast carcinomas; (c) invasive breast carcinomas behave in a heterogeneous fashion. Microscopically demonstrable lymphoreticuloendothelial responses, skin window tests, and leukocyte migration tests all indicate that tumor-specific antigenicity develops in assoication with the early phases of mammary carcinogenesis. Such antigenicity is maximally expressed in in situ carcinomas without associated invasive breast cancer and minimally in invasive breast cancers with metastases. Immunogenic breast cancer tissues commonly contain a protein component the antigenic and physicochemical properties of which are similar to those of a protein component of murine mammary tumor virus. Advances in our understanding and control of human mammary carcinogenesis and biological behavior are dependent on the clinicopathological characterization of individual patients and their breast tissues as well as on the analytical procedures used.

Antigens, Neoplasm

Cellular hypersensitivity of gp55 of RIII-murine mammary tumor virus and gp55-like protein of human breast cancers.

Previous studies suggested that immunogenic breast cancer tissues contained a component(s) that is antigenically similar to some component of murine mammary tumor virus (MuMTV) and resembles the glycoprotein, M.W. 55,000 (gp55), of RIII-MuMTV in molecular weight and charge density. This investigation measured in vitro cellular hypersensitivity responses of breast cancer patients to RIII mouse milk, purified RIII-gp55, C3H-MuMTV, autologous and homologous breast cancer tissues, gp50 of A-MuMTV, and preparations of Rauscher leukemia virus and Mason-Pfizer monkey virus. Particular attention was paid to cross-reactivity between gp55 and the other targets. The data indicate that responsiveness to C3H-MuMTV and RIII milk are linearly correlated with responsiveness to gp55. A preferential relationship was demonstrable between responses to gp55 and to those breast cancer tissues containing a gp55-like protein component (S-p50). The critical role of a gp55-like protein as the antigen responded to by breast cancer patients' in leukocytes was also suggested by the ability of anti-gp55 antiserum to decrease leukocyte responsiveness to RIII-gp55, C3H-MuMTV, and breast cancer tissues. In vitro cellular hypersensitivity against RIII-gp55 was preferentially found in prognostically favorable cases with immunogenic lesions. Further studies are needed to test the possibility that gp55 might be of value in the immunodiagnosis of early breast cancer, the monitoring of prognostically significant cellular hypersensitivity, and the induction of such hypersensitivity (immunoprophylaxis).

Animals

Prognostically significant protein components of human breast cancer tissues.

Cryostat sections of clinicopathologically characterized breast cancer tissues were eluted with phosphate-buffered 0.9% sodium chloride solution, pH 7.2. The proteins were then characterized by polyacrylamide gel electrophoresis with and without prior treatment with sodium dodecyl sulfate. Approximately 65% of the brease cancer tissue eluates contained a prominent protein fraction with a molecular weight of 47,000 to 55,000 (p50). No such component was found in 15 of 17 eluates of benign breast tissue. Charge density studies disclosed that the p50 component included three populations of proteins that could be characterized according to the migration relative to gp55 derived from RIII murine mammary tumor virus, namely, fast (F-p50), intermediate (I-p50), and slow (S-p50). Prognostically favorable pathological characteristics, i.e., stage, nuclear grade, and lymphoreticuloendothelial responses, were proportionately most frequently found among S-p50 bbreast cancers and were least frequently found among F-p50 breast cancers. It appears that the S-p50 component acts in vivo as a prognostically significant immunogen. Further knowledge of the relationship between protein characteristics and clinicopathological features of human breast cancers would contribute to our understanding of mammary carcinogenesis and biological behavior.

Breast Neoplasms

Prognostically favorable immunogens of human breast cancer tissue: antigenic similarity to murine mammary tumor virus.

A leukocyte migration procedure was utilized to test cellular hypersensitivity of breast cancer patients' leukocytes to autologous and homologous breast cancer tissues and to murine milk containing murine mammary tumor virus (MuMTV). The in vitro responsiveness of the leukocytes and the antigenicity of breast cancer tissues were compared with in vivo prognostically favorable lymphoreticuloendothelial (L-RE) responses seen microscopically at the time of mastectomy and with the results of skin window tests of cellular hypersensitivity. The data suggest that immunogens appear in the in situ phase of the disease and provoke prognostically favorable L-RE responses. These immunogens possess antigenic similarity to some component(s) of MuMTV. Progression of the disease is associated with or preceded by a loss of tissue immunogenicity and/or diminished specific cellular hypersensitivity. The findings are pertinent to investigations of human mammary carcinogenesis and immunoprophylaxis.

Animals