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Biomedical subjects

W I Cox

Publications and source records attributed to W I Cox.

28 records · Page 2Linked to original sources

Dietary nucleotide effects upon immune function in infants.

Nucleotide (NT) nitrogen, a component of nonprotein nitrogen, accounts for approximately 0.1% to 0.15% of the total nitrogen content of human milk. The results of studies in animals indicate that dietary NTs may be required for maintenance of normal immune function. Thirty-seven healthy term infants were either breast-fed (n = 9) or fed SMA formula supplemented with 33 mg of NTs per liter (n = 13, NT+) or standard SMA formula (n = 15; NT-). At 2 months of age, natural killer cell percent cytotoxicity was significantly higher in the breast-fed and NT+ groups compared with the NT- group (41.7 +/- 4.7, 32.2 +/- 3.4, 21.7 +/- 2.2%, respectively). Interleukin-2 production by stimulated mononuclear cells was higher in the NT+ compared with the NT- group at 2 months of age (0.90 +/- 0.28 U/mL, 0.27 +/- 0.11 U/mL, respectively); neither formula-fed group differed significantly from the breast-fed group. Rate of growth and incidence and severity of infections did not differ significantly among dietary groups. Nucleotides may be a component of human milk that contributes to the enhanced immunity of the breast-fed infant.

Breast Feeding↗

Dimethyl sulfoxide-induced inhibition of the immunosuppressive activity of cultured Friend erythroleukemia cells.

Two Friend leukemia virus-induced tumor cell lines lost their immunosuppressive properties in vitro when treated with dimethyl sulfoxide (DMSO), a known cellular differentiation agent. Incubation of the cell lines, GM 979 and GM 86, with DMSO for 4 days or longer, inhibited their ability to suppress the antibody forming capacity of normal murine spleen cells immunized in vitro with sheep red blood cells. Suppression of the inhibitory capability of the tumor cell lines by DMSO was time dependent. Three days incubation caused only slight, if any, inhibition, while a shorter period of treatment had no effect. Inhibition of the immunosuppressive properties of the tumor cell lines was not due to a decrease in tumor cell viability. The development of previously reported metabolic alterations in the treated cells, such as increased hemoglobin synthesis and other physicochemical alterations, paralleled cellular differentiation, and loss of immunosuppressive properties.

Animals↗

Mechanism of glucocorticoid action on murine natural killer cell activity.

With the use of an in vitro model system, the mode of action of glucocorticoids on murine natural killer (NK) cell-mediated cytotoxicity of tumor cells was investigated. Of the steroids tested, only the glucocorticoids notably suppressed NK activity. Glucocorticoids were not toxic to the NK effector cell since inhibitors of protein synthesis protected NK activity from the suppressive action of glucocorticoids. Glucocorticoid-treated C57BL/6J spleen cells, although suppressed in NK activity, were unable to suppress the NK activity of normal syngeneic spleen cell cultures. Similarly, the supernatants of glucocorticoid-treated cultures were also unable to suppress normal NK activity. Thus a role for suppressor cell activity or soluble suppressive factors was excluded. Results of analyses of the NK activity of Percoll-fractionated glucocorticoid-treated C3H/HeN (nu/nu) spleen cells at the single-cell level demonstrated that NK effector cells could efficiently bind to YAC-1 lymphoma cells but were incapable of inducing cytolysis. Moreover, the production of NK cytotoxicity factor(s) in tumor cell-stimulated nude mouse spleen cell cultures was severely depressed after glucocorticoid treatment. The results of these studies suggest that glucocorticoids suppress murine NK activity by acting directly on the NK effector cells, possibly by inhibiting the formation or release of specific effector molecules that are cytotoxic to NK-sensitive tumor cells.

Animals↗

Direct suppression of natural killer activity in human peripheral blood leukocyte cultures by glucocorticoids and its modulation by interferon.

In vitro treatment of human peripheral blood leukocytes for 18 to 24 hr with physiological concentrations of glucocorticoids resulted in a marked decrease (up to 90%) in natural killer (NK) activity. The effect on NK activity was both dose and time dependent and was specific for glucocorticoids. Glucocorticoids had no effect when added directly to the 4-hr 51Cr release cytotoxicity assay, nor did they alter the susceptibility of K562 cells to NK-mediated cytolysis. Glucocorticoid-induced inhibition occurred in Percoll-fractionated peripheral blood leukocytes enriched for NK activity. Viabilities of steroid-treated and untreated cultures were similar. Mixing experiments failed to demonstrate the involvement of suppressor activity in the inhibition. Purified cloned human leukocyte interferon subtype A and inducers of interferon enhanced NK activity in the presence of glucocorticoid, although the levels of enhancement were lower than those produced by these agents in the absence of the steroid. Thus, glucocorticoids appear to suppress human NK activity by interacting directly with the NK effector cell, and our results obtained with physiological concentrations of these steroids suggest that they may play an important role in regulating NK activity in vivo. Additionally, these findings suggest a possible means for overriding this immunosuppressive side effect of glucocorticoid therapy by simultaneous treatment with interferon.

Adult↗

Dietary nucleotide effects upon murine natural killer cell activity and macrophage activation.

Weanling mice fed chow or chow plus water supplemented with 3.5 mg of nucleotides per 100 ml of water for 6 weeks exhibited increased natural killer cell (NK) activity and lower macrophage activation compared to mice fed chow plus nonsupplemented water. In a dose-response study, NK activity, macrophage activation and spleen weight (as a percentage of body weight) were higher in mice fed up to 0.035% w/w nucleotides, however macrophage activation was decreased by feeding over 0.35% w/w compared to those receiving basal purified diet (BPD). Nucleotides in human milk may affect the immune response in breast-fed infants.

Animals↗