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Biomedical subjects

E H Perkins

Publications and source records attributed to E H Perkins.

At least 19 recordsLinked to original sources
PubMed1990

Biological heterogeneity and radiation sensitivity of in vitro propagated lung metastatic lines originated from a transplantable squamous cell carcinoma of BALB/c mouse.

Seven cell lines established from a diethylnitrosamine (DEN)-induced forestomach carcinoma (DEN3) of a BALB/c mouse and its six pulmonary metastatic foci were used to study the biological and functional diversity of tumor cells. DEN3 is a highly tumorigenic line capable of forming lung metastases readily. Six metastatic nodules were isolated from the lungs of syngeneic mice and six cell lines were established. The cell lines differed in characteristics such as tumorigenicity, metastatic capability, and in vivo and in vitro growth properties. Radiation sensitivity of these cell lines was examined by exposure, at near confluency stage of in vitro growth, to doses of 2.5 to 50 Gray (Gy) X-rays (1 Gy = 100 rads). Shortly after exposure (approximately 5 min), the cells were harvested and 10(5) cells were cultured or inoculated into syngeneic mice, or both. Growth of three of the six cell lines tested was prohibited by 5 Gy. However, some populations from the other cell lines were able to survive 5 or 10 Gy. Progenies of the cells that survived primary radiation exposure after several in vitro passages were able to withstand another exposure of the same magnitude but not a higher dose. The X-rayed survivor cells also maintained their tumorigenic potential.

Animals↗
PubMed1983

The proliferative capacities of popliteal lymph node lymphocytes and of their functionally distinct T-cell subpopulations from young-adult and old mice.

Young adult and old mice were immunized by footpad injection of dinitrophenyl-conjugated bovine gamma-globulin (DNP-BGG) in complete Freund's adjuvant. A comparison of lymph node weight and total number of nucleated cells per lymph node as a function of time after antigen injection demonstrated a significantly greater absolute increase in lymph node weight and peak number of nucleated cells per lymph node in young-adult than in old animals. However, as judged by this increase in total nucleated cells, other than being delayed in old mice, the magnitude of these in situ proliferative responses appeared comparable for young-adult and old mice. That is, the antigen-stimulated to non-stimulated cell ratio did not differ significantly between young-adult and old animals. This was because lymph nodes from old animals prior to antigen injection always weighed less and had fewer numbers of nucleated cells compared with young-adult animals. Therefore, the in vitro cellular proliferative response of three T-cell-enriched lymphocyte subpopulations from young-adult and old mice was further characterized. This was done by measuring [3H]thymidine incorporation following antigen- (DNP-BGG)- or mitogen-[phytohemagglutinin (PHA) or Concanavalin A (Con A)]-induced proliferation and assessing their quantitative and/or qualitative requirements for macrophages. In contrast to the markedly reduced proliferation of the two T-cell subpopulations from popliteal lymph nodes which respond to PHA and Con A in old animals primed 21-days earlier with DNP-BGG, antigen-induced in vitro cellular proliferation of the small T-cell subset in old mice specifically responsive to the immunizing antigen DNP-BGG always responded as well as, if not better than, cells from young-adult mice.

Age Factors↗
PubMed1982

Restoration of impaired immune functions in aging animals. VI. Differential potentiating effect of 2-mercaptoethanol on young and old murine spleen cells.

The differential effect of 2-mercaptoethanol (2-ME) on spleen and bone marrow cells of young and old mice was determined in vitro. Both the ability of spleen cells to proliferate and to generate Ig-secreting cells and the capacity of bone marrow cells to generate myeloid colonies were assessed. All three activities assessed in both young and old mice were enhanced by the presence of 2-ME, but a differential effect with respect to age was noted in only one. This was the polyclonal activating antibody response to bacterial lipopolysaccharide (LPS) in which 2-ME enhanced young spleen cells to a greater extent than old spleen cells, although their mitogenic responses to LPS were enhanced to the same extent. The ability of 2-ME to enhance old spleen B cells to proliferate but not differentiate in their response to LPS would suggest that aging alters certain subpopulations of spleen cells, some of which are sensitive and others insensitive to the potentiation effects of 2-ME. The enhancing action of 2-ME on the proliferative activity of LPS-stimulated young spleen cells was reduced drastically by decreasing the number of T cells by prior treatment of spleen cells with anti-T cell reagent. The proliferative activity was then brought back to normal pretreatment level by adding enriched T cells. Therefore it would appear that regulatory T cells are the target of the enhancing action of 2-ME. The failure of old spleen cells to respond vigorously to the polyclonal activating action of LPS and 2-ME individually and in combination would indicate that age-related alterations may be taking place in the B cells and/or the regulatory cells. Young-old spleen cell mixture study indicates that there are regulatory cells in old spleen cells which can inhibit B cell differentiation but not B cell proliferation.

Adjuvants, Immunologic↗
PubMed1981

Temporal advancement of diethylnitrosamine carcinogenesis in aging mice.

Female BALB/c mice were given diethylnitrosamine (DEN) in their drinking water beginning at 2.5, 9.5, and 17 months of age (cumulative dose approximately 300 to 400 mg/kg body weight) or were untreated. Median times of death for the treatment groups were 193, 168, and 125 days, respectively, after cessation of DEN treatment and were significantly different (p less than .01). Induced tumors in the three respective age groups were of squamous forestomach (88, 87, and 84%), vascular tumors of the liver (11, 13, and 16%), and adenomas of the lung (65, 56, and 54%). Controls had no forestomach or liver tumors and relatively low incidences of lung tumors. The fact that aging mice have similar incidences and types of tumors of the same size and in the same tissues, but at an earlier time, shows that (1) DEN is carcinogenic in aging BALB/c mice; (2) age at treatment does not alter the tumor-susceptible tissue nor types of tumors after DEN treatment; (3) tumor incidences are not affected by age at time of treatment; (4) mice die earlier with induced tumors with increasing age at time of treatment; (5) age-matched non-DEN-treated mice die from different diseases (leukemias) than do DEN-treated mice (stomach and liver tumors). These observations may be related, in part, to an identified age-dependent decrease in immunocompetency or to other age-related changes, such as vascular or hormonal, which could explain temporal advancement in the tumorigenic process.

Aging↗
PubMed1980

Cooperation of murine F T and parental B lymphocytes in rejection of a xenogeneic tumour: adaptive differentiation of B lymphocytes?

The primary humoral immune response to rat Yoshida ascites sarcoma (YAS) grown in mice was used to study thymus-dependent (T) and bone marrow-derived (B) lymphocyte cooperation. It was shown that B6D2F1 T lymphocytes that do not cooperate with parental B lymphocytes enabled parental B lymphocytes from B6 leads to B6D2F1 radiation chimaeras to reject the tumour. However, when the bone marrow cells from B6 leads to B6D2F1 chimaeras were used to reconstitute parental B6 mice, these B6 leads to B6D2F1 leads to B6 mice lost their tolerance to D2 transplantation antigens, and their B lymphocytes were not able to cooperate with B6D2F1 T lymphocytes. In our search for the reasons for the failure of F1 T cells to be effective in parental and P leads to F1 leads to P TIR mice, rejection of F1 T cells was excluded because : (i) immune reactivity in TIR mice was found to be either absent or minimal; (ii) parental TIR mice did not produce any detectable cytotoxic antibodies after an intravenous injection of F1 splenic T cells; and (iii) YAS rejection was not induced at very high doses of F1 T cells. However, in a cell transfer system we were able to demonstrate that injection of spleen cells from parental TIR mice could thwart the successful cooperation of transferred F1 T cells with host B cells. Collectively, these data suggest that the changes of the collaborative potential of parental B cells as achieved in the F1 environment could be ascribed to 'adaptive' differentiation of B lymphocytes. It appears that the differentiation process that has rendered nonsyngeneic chimaeric cells able to cooperate was independent of the exogenous antigen.

Animals↗
PubMed1980

Immunodepression, a noncontributor to radiation-induced leukemogenesis of the RFM mouse.

Following a single acute exposure to 300 R of X-rays at 6 weeks old, approximately 65% of female RFM mice die of thymic lymphoma during the first year of life. In contrast, nonirradiated animals do not die of this neoplasm during this same period. To determine if immediate immunological restoration is of significance in interrupting the inductive process, we injected 50 X 10(6) syngeneic spleen or bone marrow cells into these animals immediately following X-irradiation. Restoration of immunocompetence as measured by both humoral and cell-mediated parameters was more rapid in spleen cell-reconstituted animals than in bone marrow-treated animals; however, spleen cells failed to protect the mice against the irradiation-induced thymic lymphomas. In contrast, although there was no significant difference in the immunological recovery of bone marrow-reconstituted animals and animals that received only irradiation, mortality was dramatically reduced as a result of marrow injection. Therefore, although immunodepression is an inherent component, it cannot be considered as a critical obligatory requirement in the pathogenesis of radiation-induced thymic lymphomas of RFM mice.

Animals↗
PubMed1979

A positive correlation between declining immune competence and early mortality associated with diethylnitrosamine carcinogenesis in aging mice.

The effect of age (2.5, 9.5, and 17 months) at time of treatment upon diethylnitrosamine (DEN) carcinogenesis and immune competence has been assessed in female BALB/c mice. Median times of death were 193, 168, and 125 days, respectively, after termination of DEN treatment. Immune competence as a measure by both cell-mediated and humoral immune parameters immediately after DEN treatment was not significantly different among treated and age-matched non-treated control animals. In contrast, a significant age-related decline in immune competence was seen in both DEN-treated and non-treated controls, thereby demonstrating a direct and positive correlation between the natural age-related decrease in immune competence and cancer-induced advanced mortality.

Aging↗
PubMed1977

Age-related changes in T cell function.

A comparison was made of the abilities of carrier (BGG)-primed T cell populations from young (4-month old), middle-aged (14- and 19-month old) and old (31- and 34-month old) mice to collaborate with hapten (DNP)-primed B cells from young mice in a cell-transfer system. The plaque-forming cell responses to 2,4-dinitrophenol (DNP) were measured by a modification of the Jerne plaque assay. The DNP-specific antibody-forming cell responses of old T cell/young B cell combinations were significantly lower than those of young T cell/young B cell combinations, both in the number of T cells needed for peak response and in the size of that response. These data indicate that the primed T cell populations of old mice are deficient by a factor of 6 in their ability to initiate B cell proliferation and differentiation into antibody-forming cells.

Aging↗
PubMed1972

Model approach to immunological rejuvenation of the aged.

Reconstitution of a damaged or exhausted immune system by injection of genetically compatible immunocompetent cells (immunologic rejuvenation) is a promising approach for restoration of immune activity. By using this model, spleen cells from young-adult mice, previously immunized with Salmonella typhimurium, were transferred to either young-adult or old, syngeneic recipients before or after storage at -196 C. The susceptibility of recipient mice was then determined by challenging them at increasing time intervals after reconstitution with lethal doses of the virulent organisms. The findings, although preliminary in nature, demonstrate that (i) immunological rejuvenation of mice is possible with immunocompetent cells from specifically immunized donors; (ii) prolonged "takes" of these cells can occur even in nonirradiated recipient mice, and (iii) storage at -196 C does not impair their protective capacity.

Aged↗