Biomedical subjects

B H Devens

Publications and source records attributed to B H Devens.

21 records · Page 2Linked to original sources

PubMed1984

Induction of murine fibrosarcomas by low dose treatment with 3-methylcholanthrene followed by promotion with 12-O-tetradecanoyl-phorbol-13-acetate.

Repeated application of the tumor promoter 12-O-tetradecanoyl phorbol-13-acetate (TPA) to the skin of mice previously treated with an initiating dose of the carcinogen 7,12-dimethylbenz[a] anthracene has been shown to lead to an increased incidence of papilloma. The studies presented here describe a modified murine two-stage carcinogenesis model in which a single subcutaneous administration of the carcinogen 3-methylcholanthrene (3-MC) is followed by multiple applications of TPA administered subcutaneously or intraperitoneally. TPA was observed to act as a promoter under these conditions when given either subcutaneously or intraperitoneally. When a carcinogenic dose of 3-MC was administered (0.5 mg/mouse) followed by regular treatment with TPA (10 micrograms/mouse) the percent of tumor-bearing mice increased and the length of time until tumors developed significantly shortened. At a subcarcinogenic dose of 3-MC (0.025 mg/mouse), repeated treatment with TPA led to tumor development whereas no tumors were observed in mice not treated with TPA. All tumors were found to be fibrosarcomas. Thus, TPA is capable of acting as a systemic promoter of mesenchymally derived tumors.

Animals↗

PubMed1984

Production of human-human hybridomas secreting antibody to sheep erythrocytes after in vitro immunization.

This report describes the formation of human hybridomas after in vitro immunization of tonsillar lymphocytes and fusion of the stimulated lymphocytes with a human lymphoblastoid cell line, WI-L279HF2. Lymphocytes were stimulated in vitro with sheep erythrocytes (SRBC) and polyclonal activators (PCA). By varying the duration of in vitro immunization before fusion and varying the PCA concentrations, the optimal conditions for cell fusion, hybrid cell growth, nonspecific immunoglobulin (Ig) secretion, and secretion of antibody to SRBC were determined. Lymphocytes cultured allogeneically at 5 X 10(6) cells per well in 24-well plates with SRBC and PCA (PWM, 1/10,000 dilution or LPS, 5 micrograms/ml) fused with the greatest efficiency. PWM-stimulated cultures fused on day 6 of in vitro stimulation yielded the greatest number of wells containing Ig-secreting hybridomas, whereas LPS-stimulated cultures produced more wells with hybridomas secreting Ig when fused on day 7 of stimulation. In vitro stimulation conducted in tissue culture flasks produced fewer wells with hybrid cell growth and Ig secretion. A fusion ratio of 1:1 (lymphocyte:WI-L2729HF2) yielded the most hybrid formation. Ig levels in wells with hybrid cell growth varied greatly, from less than 10 ng/ml up to 30 micrograms/ml. Ig of IgG, IgA, and IgM isotypes were produced. The addition of lymphocyte conditioned medium to in vitro immunization cultures does not improve the yield of Ig-secreting hybridomas. Hybrid cells secreting antibody to SRBC were cloned and analyzed for HLA specificities and chromosome numbers. Additionally hybridoma cells were formed after in vitro stimulation of peripheral blood lymphocytes (PBL) of normal individuals by fusion of the stimulated lymphocytes with WI-L2-729HF2. Hybridoma formation with PBL was less successful, but hybridoma cells secreting antibody to SRBC after in vitro stimulation were isolated.

Animals↗

PubMed1983

Influence of dietary restriction and aging on natural killer cell activity in mice.

Natural killer cells (NK) are believed to defend against tumor growth. Because rodents subjected to dietary restriction without malnutrition live longer and develop spontaneous tumors less often or later in life than unrestricted controls, we measured NK activity in restricted and in unrestricted mice. An age-related decline in NK responses to YAC-1 tumor target cells was detected in both groups. NK responses for control mice were highest in 2- to 3-mo-old mice, sharply reduced in middle-age mice (14 to 15 mo), and slightly reduced further in old mice (30 to 33 mo). At all ages the response of restricted mice was less than that of controls. However, after injection with Poly I:C (which increases NK activity), old restricted mice showed NK cytolysis not different from young mice on either diet, and substantially higher responses than old unrestricted mice. In addition, restricted mice showed increased in vitro generation of cytotoxic T lymphocytes (CTL) to YAC-1 and P815 compared with age-matched controls. Restricted mice may better resist cancer via an NK system very responsive to induction signals coupled with a CTL system more effective than that of unrestricted controls.

Aging↗