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Biomedical subjects

R R Rogers

Publications and source records attributed to R R Rogers.

At least 55 records · Page 3Linked to original sources

Immunological studies in mice following in utero exposure to NiCl2.

The effect that NiCl2 has on the development of immune function in mice was examined in the offspring of dams implanted with mini-osmotic pumps during pregnancy. Time bred C57BL/6J mice were implanted subcutaneously on day 5 of gestation with mini pumps which delivered a total dose of from 9.1 to 73.2 micrograms/g NiCl2. The pumps delivered NiCl2 to the dams through day 19 of gestation. At 8 -- 10 weeks of age the offspring of NiCl2-dosed dams were evaluated for immune function. No consistent significant alterations were observed between control and treated offspring for the following: lymphoid organ or body weights; the lymphoproliferative response to B or T lymphocyte mitogens; the lymphoproliferative response to allogeneic spleen cells in the mixed lymphocyte reaction; the development of syngeneic tumors; or the primary antibody response to sheep red blood cells. Natural killer (NK) cell activity was reduced in offspring exposed to NiCl2 in utero; however, the biological relevance of these reductions is questionable because of the failure to demonstrate an increased susceptibility to the B16-F10 syngeneic tumor. The results indicate that under the conditions and doses employed it appears that NiCl2. does not adversely affect the developing immune system of the mouse.

Animals↗

Immune function of young adult mice following in utero exposure to cyclophosphamide.

Long-lasting organic damage has been reported following in utero exposure to certain environmental or therapeutic agents. The sensitivity of the developing immune system to chemical insult during organogenesis or histogenesis was evaluated in mice employing the known immunosuppressive agent cyclophosphamide (CY). Experiments were conducted employing one of the following treatment regimens: (1) 1 microgram/g X d intravenously on d 9-12 or 14-17 of gestation; (2) 5 micrograms/g intravenously on 12 of gestation; (3) 1, 2.5, or 5 micrograms/g X d intraperitoneally on d 12 of gestation; or (4) 5, 10, or 20 micrograms/g intraperitoneally on d 17 of gestation. There were no surviving pups born to mothers administered CY by schedule 2; otherwise, numbers of surviving offspring were not affected by drug treatment, and no gross terata were observed. Employing this variety of exposure protocols, consistent enhancement or suppression of cell-mediated or humoral immune function was not observed in offspring of treated dams. Reduced body weight in 5- and 8-wk-old progeny was noted after exposure to 20 micrograms/g on gestational d 17. Increased in vitro B-lymphocyte blastogenic response to lipopolysaccharide occurred in 5-wk-old animals, and production of antibody to sheep erythrocytes was increased in 8-wk-old offspring exposed to CY at 20 micrograms/g on d 17 of gestation. The T-lymphocyte parameters were relatively unaffected by in utero exposure to CY, suggesting either that cell-mediated immune function was not affected by treatment or that homeostasis was restored prior to immunologic evaluation of offspring.

Animals↗

In vitro augmentation of natural killer cell activity by manganese chloride.

The in vitro cultivation of murine spleen cells with MnCl2 resulted in the enhancement of natural killer (NK) cell activity as measured in a 4-h 51Cr-release assay. Optimal enhancement of NK activity was observed at concentrations of 10-20 micrograms MnCl2/culture (72-144 microM Mn2+). Enhancement of NK activity by MnCl2 was not associated with any changes in the number or viability of cells following culture. The addition of antiasialo GM1 antibody and complement to spleen cell cultures completely abrogated the enhancement of NK activity by MnCl2. The enhancement of NK activity by MnCl2 in vitro was accompanied by interferon induction. The addition of rabbit antimouse interferon to spleen cells cultured with MnCl2 reduced NK activity. NK activity in cultures treated with MnCl2 was also reduced upon removal of plastic adherent cells. However, restoration of enhanced NK activity by addition of adherent cells to nonadherent cells in the presence of MnCl2 was not observed. Similar effects of NK activity were observed with polyinosinic-polycytidylic acid (Poly I X C), a known interferon inducer and NK enhancer. The results demonstrate that murine splenic NK activity is enhanced in vitro by MnCl2 and that this enhancement may be mediated by interferon induction. The results also suggest that in vitro enhancement of NK activity by MnCl2, as with Poly I X C, may require participation of an adherent cell population for NK augmentation.

Animals↗

Immune function in adult C57BL/6J mice following exposure to urethan pre- or postnatally.

Administration of urethan (URE or ethyl carbamate) to mice results in the development of a variety of tumors, and, in certain strains of mice, marked suppression of the immune response. Perinatal exposure of mice to URE has been found to result in increased tumor induction compared to exposure of adult animals. In the present study, the effects of perinatal exposure to URE on the development of immunocompetence was investigated. Pregnant mice were injected with total doses of either 0.5 or 1.0 mg URE/g of body weight over days 7-16 of gestation or pups of nontreated dams were administered a total dose of 2.0 mg URE/g of body weight over postpartum days 5-14. Postnatal exposure to URE suppressed NK (natural killer) cell activity but left intact other measured parameters of the host defense system. Prenatal exposure, on the other hand, resulted in elevated leukocyte counts and a trend toward increased spleen and thymus size in offspring of treated mothers. Humoral immune function, as measured by the IgM response to sheep erythrocytes, was suppressed in pups from dams injected with a total of 1.0 mg/g URE. These results indicate that marked differences in immunopharmacologic effects may be observed if chemical exposure occurs at different times during the ontogeny of the immune system.

Animals↗

Immunologic effects of nickel. II. Suppression of natural killer cell activity.

A single intramuscular injection of nickel chloride (18.3 mg/kg) caused a significant reduction in murine splenic natural killer (NK) cell activity. This reduction in NK activity was not associated with a significant reduction in spleen cellularity nor in the production of suppressor cells. In a 4-hr 51Cr-release assay, NK cell activity was suppressed in both CBA/J and C57BL/6J mice. Administration of the nickel dose (i.e., 18.3 mg/kg total) over a 2-week period also caused a significant reduction in NK cell activity. In an in vivo NK assay, the clearance of [125I]iododeoxyuridine-labeled YAC-1 tumor cells from the lungs of nickel-treated mice was significantly reduced compared with saline injected controls. Another in vivo correlate of nickel-induced NK suppression was observed in mice injected with the B16-F10 melanoma. Mice given a single intramuscular injection of NiCl2 (18.3 mg/kg) developed significantly greater numbers of lung tumors than saline controls. The results indicate that NiCl2 is a potent suppressor of NK cell activity.

Animals↗

Manganese chloride enhances natural cell-mediated immune effector cell function: effects on macrophages.

A single intramuscular injection of MnC12 in mice caused an increase in macrophage functional activity. Spleen cell antibody-dependent cell-mediated cytotoxicity against both chicken erythrocytes and P815 tumor cell targets was enhanced 24 h following a single injection of MnC12. Enhanced antibody-dependent cell-mediated cytotoxicity activity following MnC12 treatment was not associated with a change in spleen cellularities compared with saline-injected mice. Resident peritoneal macrophages from mice injected intramuscularly with MnC12 displayed enhanced phagocytic activity for chicken erythrocytes in the presence or absence of opsonizing antibody. Enhanced cytolytic activity against P815 mastocytoma target cells and enhanced cytostatic activity against MBL-2 lymphoma target cells was also observed for nonelicited resident peritoneal macrophages from mice injected intramuscularly with MnC12. There were no differences in the cellularity or relative number of adherent cells obtained from the peritoneal cavity of saline or MnC12-injected mice. These enhanced macrophage functions were associated with the induction of increased interferon levels in mice injected with MnC12.

Adjuvants, Immunologic↗

Evaluation of immune function in mice exposed to Ordram.

The potential effects that the thiocarbamate herbicide Ordram has on the immune system of mice was evaluated following 12 days of acute dosing by oral gavage. Dosages of Ordram ranging from 20 to 320 mg/kg/day had no consistent significant effects on a variety of immune parameters investigated. The immune parameters measured were the following: body and lymphoid organ weights; splenic natural killer (NK) cell activity; lymphoproliferative responses to B and T lymphocyte mitogens and allogeneic spleen cells in a one-way mixed lymphocyte reaction; and delayed-type hypersensitivity and antibody responses to sheep red blood cells (SRBC). The effects that the immunosuppressant cyclophosphamide has on these immune parameters was also examined. The results indicate that Ordram does not appear to affect key parameters of the immune system of mice under the conditions of exposure employed.

Administration, Oral↗

Evaluation of the immunotoxic potential of chlordecone with comparison to cyclophosphamide.

The immunotoxic potential of chlordecone was evaluated in male Fischer-344 rats following 10 d of acute dosing by oral gavage. These results were compared with those obtained following a comparable dosing regimen with the known immunosuppressive drug cyclophosphamide. Significant changes in ratios of spleen and thymus to body weight, blastogenic responsiveness of lymphocytes to concanavalin A, and natural killer (NK) cell activity against allogeneic W/Fu-G1 rat lymphoma target cells and xenogeneic YAC-1 mouse lymphoma target cells were observed only at the highest chlordecone dosage (10 mg/kg . d). A significant decrement in body weight also occurred at this dosage which suggests that the observed changes in the immune parameters measured were most likely due to the overt toxicity of chlordecone. In contrast, rats dosed over 10 d by oral gavage with cyclophosphamide showed significant decreases in spleen and thymus to body weight ratios at a dosage as low as 1.5 mg/kg . d. Body weight decrements were observed only at dosages of 12 mg/kg . d or greater. At dosages of 1.5 mg/kg . d or greater, cyclophosphamide caused a significant decrease in the total leukocyte and absolute lymphocyte counts in peripheral blood, and a decrease in the lymphoproliferative responses to both T- and B-lymphocyte mitogens. Significant suppression of NK cell activity was observed at dosages of 6 mg/kg . d or greater. These results suggest that T and B lymphocytes are more sensitive than are NK lymphocytes to the immunosuppressive effects of cyclophosphamide. The results of these two studies indicate that the failure to detect chlordecone-induced immunotoxic effects in the absence of overt toxicity is not due to the possible insensitivity of the parameters examined. Instead, since cyclophosphamide affected all of the parameters tested, these results indicate that the endpoints examined here are capable of detecting immunotoxicity with sufficient sensitivity to permit distinction between probable indirect immunosuppression due to overt toxicity and subtle, direct impairment of the immune system.

Animals↗

Immunologic effects of nickel: I. Suppression of cellular and humoral immunity.

The effects of nickel chloride on the cellular and humoral immune responses of mice were studied. A single intramuscular injection of nickel chloride (18.3 mg/kg) caused a significant involution of the thymus within 2 days following treatment. Significant reductions in the in vitro mitogen-stimulated response of lymphocytes from nickel chloride-treated mice (24 hr following a single injection of 18.3 or 36.6 mg/kg) were observed for the T-cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A), and the B- and T-cell mitogen pokeweed mitogen (PWM) but not the B-cell mitogen lipopolysaccharide (LPS). Theta-positive but not Ig-positive spleen cells were significantly reduced in nickel-treated mice compared with controls. Significant suppression of the primary antibody response to the T-cell dependent antigen sheep red blood cells was observed following a single injection of 18.3 mg/kg NiCl2. Natural killer (NK) cell activity was significantly suppressed following a single injection of 18.3 mg/kg NiCl2. The administration of NiCl2 (18.3 mg/kg) also decreased the amount of endotoxin required to kill 50% of treated mice, although this was not statistically significant. In all cases the immunosuppressive effects of NiCl2 were found to be transient with responses returning to normal within a few days. No alteration in the response of mice immunized with the T-cell independent antigen polyvinylpyrrolidone was observed following treatment with nickel. Furthermore, the phagocytic capacity of resident peritoneal macrophages from nickel-treated mice was not significantly different from saline-injected mice. The results indicate that NiCl2 predominantly affects T-cell mediated immune responses and natural killer cells.

Animals↗

Women's satisfaction with partners' penile implant. Inflatable vs noninflatable prosthesis.

We evaluated 49 women whose sexual partners were organically impotent and subsequently received either an inflatable or noninflatable penile prosthesis. The women comprised three groups, based on the type of prostheses their partners had received: inflatable (n = 34), noninflatable (n = 11), and a double implant group (n = 4). The comparisons made were (1) dimensions of sexual satisfaction, (2) emotional stability, (3) satisfaction with the prosthesis, and (4) relationship changes. Two special questionnaires and the Derogatis Sexual Functioning Inventory were utilized in this evaluation. Women in the inflatable prosthesis group were found to be significantly more satisfied with the quality of their sexual relations and with their partner's prosthesis than were the women in the noninflatable prosthesis group. There apparently is a general advantage to women whose partners have received an inflatable prosthesis compared with the noninflatable alternatives.

Adult↗

Indices of fatness and serum cholesterol at age eight years in relation to feeding and growth during early infancy.

During the early months of life, gains in length and weight are more rapid by formula-fed than by breast-fed infants and we and others have speculated that the greater gains of the formula-fed infants are the result of greater food intake. If overfeeding during early infancy resulted in establishment of habits of overeating, or if, for any other reason, diet-induced fatness in infancy persisted into childhood, we might be able to demonstrate differences in fatness in childhood related to mode of feeding (breast or bottle) during infancy. We therefore examined at age 8 years 469 children born in 1966-1971 who had been studied intensely in our unit from 8 to 112 days of age. At age 8 years there were no differences in indices of fatness related to mode of feeding during infancy. Serum concentrations of cholesterol at age 8 years were also of interest because of reports from animal studies that differences in feeding during early life may be responsible for subsequent differences in cholesterol homeostasis. Cholesterol concentrations at age 8 years did not demonstrate significant differences related to mode of feeding during infancy. It is possible, however, that age 8 years is too early for an effect to be demonstrated.

Adipose Tissue↗

Manganese chloride enhances murine cell-mediated cytotoxicity: effects on natural killer cells.

Natural killer (NK) cell activity of mice given a single injection of manganese chloride (MnCl2) was significantly enhanced as measured in a 4-hr in vitro 51Cr release assay. Enhanced activity persisted for several days after injection. This cytotoxic activity was associated with nonadherent spleen cells and was completely eliminated by injecting MnCl2-treated mice with anti-asialo GM1 serum. Manganese-enhanced natural cytotoxicity was observed in several mouse strains with differing NK cell reactivity (CBA/J, C57BL/6, A/J, C3H/HeJ, and C57BL/6 beige mice) and with several tumor target cells with differing sensitivity to NK cytolysis (YAC-1, RBL-5, EL-4, and P815). The growth of B16-F10 melanoma lung tumors was inhibited in mice injected with MnCl2 one day before tumor challenge. Manganese chloride enhancement of NK cell activity appeared to be mediated by interferon (IFN). Low levels of IFN were detected in the serum of mice as early as 4 hr after MnCl2 injection. Rabbit anti-mouse IFN alpha, beta but not anti-mouse IFN gamma completely eliminated the MnCl2-enhanced NK cell activity in the spleens of mice. The observed enhancement of NK cell activity by MnCl2 is similar to that reported for more complex molecules that act by inducing IFN production.

Animals↗

Microwaves (2,450 MHz) suppress murine natural killer cell activity.

The effect of 2,450-MHz CW microwaves on natural killer (NK) cell activity and lymphocyte responsiveness to mitogen stimulation was studied in mice. Groups of mice were irradiated at power densities of 5, 15, or 30 mW/cm2 (SAR = 3.5, 10.5, and 21 W/kg respectively) for 1.5 h on 2 or 9 consecutive days. NK cell activity was determined using an in vitro 51Cr release cytotoxicity assay and an in vivo tumor-cell clearance assay. No consistent change was observed in the mitogen response of spleen cells from sham compared with irradiated mice. A significant suppression of NK cell activity measured in vitro was observed for mice irradiated at 30 mW/cm2, but not at 15 or 5 mW/cm2. A significant suppression of NK cell activity, as determined using the in vivo tumor clearance assay, was also observed at 30 mW/cm2. NK cell activity, as determined using the in vitro assay, returned to normal within 24 h following the last irradiation. Treatment of mice with hydrocortisone caused suppression of NK cell activity measured in vitro and in vivo. Paradoxically, peritoneal macrophage phagocytosis was enhanced following irradiation at 30 mW/cm2, the power density at which NK activity was suppressed. The possible role that microwave heating plays in producing these effects is discussed.

Animals↗

Augmentation of murine natural killer cell activity by manganese chloride.

Natural killer (NK) cell activity of spleen cells from male CBA/J mice was augmented by a single parenteral injection of MnCl2 administered 1 day prior to testing by in vitro and in vivo isotope release assays. Increased cytotoxic activity was observed in vitro against both NK-sensitive (YAC-1) and NK-resistant (EL-4) target cells. NK activity was also enhanced in normally low (A/J) and intermediately (C57Bl/6J) reactive strains of mice. Augmentation of NK activity by MnCl2 was accompanied by an increase in circulating interferon (IFN) levels.

Animals↗

Assessment of immune function development in mice irradiated in utero with 2450-MHz microwaves.

Groups of time-bred pregnant mice were irradiated with 2450-MHz microwaves at an incident power density of 28 mW/cm2 for 100 min daily from day 6 to day 18 of pregnancy. The average specific absorption rate (SAR) was 16.5 W/kg. Two experiments were performed under these conditions. At 3 and 6 weeks of age the mice were assessed for development of the primary immune response to sheep erythrocytes, in vitro mitogen-stimulated lymphocyte proliferation, and natural killer (NK) cell activity. No consistent significant difference in the primary immune response, in the mitogen response, or in the NK cell activity was observed between irradiated and sham-irradiated mice.

Animals↗

Microwave radiation (2450-MHz) potentiates the lethal effect of endotoxin in mice.

Groups of male CBA/J mice were injected with Salmonella typhimurium lipopolysaccharide (LPS) and irradiated with 2450 MHz (CW) microwaves. The 50% lethal dose (LD50) of LPS was determined for mice irradiated at 30, 20, 10 and 5 mW/cm2 immediately following injection. The average specific absorption rate was approximately 0.6 W/kg per 1 mW/cm2 incident power. An equal number of animals served as sham-irradiated controls for each power density. The mice were placed individually in small containers and were maintained at 22 degrees C and 50% relative humidity during a 2 hour irradiation period. Following irradiation the mice were returned to their home cages and were observed for 48 hr. A significant decrease in the LPS dose required to kill 50% of the mice was observed at power densities of 20 and 30 mW/cm2. High ambient temperature (37 degrees C) also potentiated the lethal effect of endotoxin. Microwave irradiation prior to LPS injection, however, did not affect the lethal action of LPS.

Animals↗