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P Price

Publications and source records attributed to P Price.

At least 271 records · Page 15Linked to original sources

Responses to polyvinyl pyrrolidone and pneumococcal polysaccharide in protein-deficient mice.

Indirect haemagglutination titres induced by polyvinyl pyrrolidone (PVP) or pneumococcal polysaccharide Type III (S111) were determined in mice maintained on a 4% albumin diet from weaning and normally-fed littermates. Responses to PVP, given intravenously (i.v.) or intraperitoneally (i.p.), were elevated by protein-deficiency at low antigen doses and increasingly depressed at high doses. Increases in the duration of protein-deficiency generally improved these responses. The persistence of tolerance was reduced by protein-deficiency and priming was evident in both groups when tolerance was broken. The low protein diet depressed responses to moderate doses of S111 given i.p. to C57Bl mice, but such responses were normal in BALB/c mice and in C57Bl mice injected i.v. High doses of S111 (i.p., i.v.) elicited poor responses in deficient mice. These findings are discussed in relation to previous studies using other antigens, with a view to elucidating mechanisms responsible for the effects of protein-deficiency.

Animals↗

The elevation of adoptive responses to sheep erythrocytes in protein-deficient mice.

Plaque-forming cell responses and antibody titres to sheep red cells (SRC) were elevated in normally-fed irradiated adult mice reconstituted with spleen cells from young mice which had received a 4% albumin diet, compared with those given cells from normally-fed littermates. This was independent of the dose of cells transferred (5 x 10(6)--4 x 10(7)), the day of assay (3--10) and the duration of protein-deficiency (1 or 3 weeks). It suggests that the depressed responses produced by protein-deficient (donor) mice reported in earlier papers resulted from an impairment of reticuloendothelial function or a shortage of protein reserves, not directly associated with the spleen. As protein-deficiency (of the donor) accelerated the initiation of the adoptive response and increased the cell yields of the recipients it is considered likely that an enhancement of cell proliferation during the first 3--5 days after transfer was responsible for the elevated responses.

Animals↗

The response of young chronically protein-deficient mice to multiple antigenic challenge.

Responses to two or more antigens given together or separated by an interval of up to four days were determined in young mice maintained from weaning on a 4% albumin diet, and compared with those of normally-fed controls. Simultaneous challenge with several antigens did not affect antibody production in mice of either dietary group ("Simultaneous Competition") and the responses of normal and protein-deficient mice to sheep or rat erythrocytes were similarly produced by the prior injection of horse or sheep cells ("Sequential Competition"). However, the low protein diet broadened the conditions under which primary and secondary injections of diphtheria toxoid impaired primary responses to tetanus toxoid. These findings are discussed in relation to mechanisms previously proposed to explain antigenic competition, with a view to explaining the effects of protein-deficiency on antibody production.

Adsorption↗

Correlation between hypomethylation of DNA and expression of globin genes in Friend erythroleukemia cells.

This report identifies L-ethionine as an inducer of differentiation in murine erythroleukemia cells. When Friend erythroleukemia cells are grown in the presence of 4mM L-ethionine, globin mRNA accumulates and in 4-5 days, 25-30% of the cells in the culture contain hemoglobin. Incubation of the cells with bromodeoxyuridine prevents both ethionine-induced accumulation of globin mRNA and erythroide differentiation. At the concentration where L-ethionine acts as an inducer of FL cell differentiation it inhibits methylation of DNA and tRNA in vivo but does not prevent macromolecular synthesis or cell division. To establish whether a link existed between inhibition of a specific methyltransferase and activation of globin synthesis in FL cells, we examined the degree of hypomethylation of DNA and tRNA from FL cells induced to differentiate with dimethylsulfoxide and butyrate. In contrast to the tRNA from ethionine-treated cells, tRNA from cells induced by butyrate or Me2SO cannot be methylated in vitro using homologous enzymes. DNA isolated from cells exposed to any of the three inducers, however, was significantly hypomethylated when compared with DNA from uninduced cells. These data suggest that methylation of DNA may play a role in the regulation of gene expression.

Cell Differentiation↗

Factors determining the effects of chronic protein-deficiency on antibody responses to sheep red blood cells and Brucella abortus vaccine in mice.

Chronic protein-deficiency in weanling mice caused variable suppression of the humoral plaque-forming cell (PFC) responses to sheep erythrocytes. This was most prominent at high antigen doses and did not increase when mice were maintained on the diets for longer periods. Antibody responses produced by deficient mice were often short-lived and involved high levels of IgM. Total PFC counts were depressed slightly more than were circulating antibodies. Antibody responses to Brucella abortus were slightly decreased by protein-deficiency at high antigen doses but were normal or elevated at lower doses, the proportion of IgM produced was increased and the splenomegaly response to B. abortus was severely depressed. These results suggest that the depression of antibody production by protein-deficiency is not simply due to an impairment of helper T cell function, but a reduction in the availability or effectiveness of macrophage and regulatory or suppressor T cells may be important.

Animals↗

The response of protein-deficient mice to tetanus toxoid. Effects of antigen dose, adjuvants, period of deprivation and age on antibody production.

The effects of a 4% albumin diet initiated at weaning on primary and secondary responses to AIPO4-adsorbed and soluble tetanus toxoid (TT) were studied in C57BL mice. Responses of both groups were directly proportional to the dose of antigen over most of the range tested, but at very low doses protein-deficient mice produced higher primary titres than normal mice. In the primary response AIPO4-adsorption of the antigen essentially increased the effective dose irrespective of the diet, but after secondary challenge responses to soluble TT were more severely affected by the diet. Normal secondary titres to AIPO4-adsorbed TT were achieved when deficient mice were given high doses of antigen. Diet also affected the relative proportions of IgG and IgM produced in most responses. Gram-negative bacterial vaccines and lipopolysaccharide increased antibody production in both groups of mice. The low protein diet produced less dramatic effects when initiated at the time of inoculation or later, and mice maintained for longer on the diet produced more nearly normal titres. Mechanisms which may explain these findings are discussed.

Age Factors↗

The effects of tumour extract on macrophage proliferation in lymph-nodes.

Injection of a soluble tumour extract induces mitosis in sinus macrophages of the draining lymph-node. This is not abolished by irradiation; the stimulus also induces monocytosis somewhat later. These findings make it likely that the stimulus induces mitosis in the resident lymph-node macrophage population.

Animals↗

Influence of dietary protein restriction on immune competence. II. Effect on lymphoid tissue.

Weanling mice fed a 4 percent diet showed a generalized loss of lymphoid tissue which was greater than the loss of total body weight. This effect was greatest in the thymus greater than spleen greater than mesenteric lymph node. Cell loss was most pronounced during the 1st week on diets, then remained at stable levels for 3 weeks and showed a gradual rise thereafter. The effect was shown to be mediated partly by a cessation of growth in lymphoid organs due to the low protein intake and, secondly, an adrenal corticosteroid induced lympholysis which actually reduced cell numbers. Recirculating T cells and resident B cells were amongst the least affected cells whereas stem cells, non-migratory T cells and other reticuloendothelial cells were most depressed in numbers. At no stage was the germinal centre forming capacity of the mesenteric node lost although cell recruitment to antigenically stimulated nodes was diminished. During nutritional repletion the spleen, thymus and mesenteric node all showed different and characteristic regrowth. The spleen was most active initially and rapidly reconstituted haemopoietic cells and B cells. This was followed by the thymus which showed a delayed reinitiation of its normal growth kinetics which had been interrupted by the diet. The evidence suggested that full rehabilitation of the immune apparatus took place even after 2 months of nutritional deprivation.

Adrenal Cortex Hormones↗

The effects of nutritional rehabilitation on antibody production in protein-deficient mice.

The transfer of chronically protein-deficient mice to an optimal diet a few days before immunization with sheep erythrocytes, tetanus toxoid or Brucella abortus vaccine either failed to increase antibody production above the level produced by deficient mice, or suppressed the responses to below those produced by deficient mice or normally-fed controls. Transfer to high protein diet on the day of immunization or feeding deficient mice the normal diet for just 2 days at the time of injection produced higher titres than did transfer a few days before immunization. Secondary responses to TT were affected by transfer to the normal diet at priming, rather than at rechallenge. Some mechanisms which may explain these findings and their implications for immunization schedules in malnourished humans are discussed.

Agglutination Tests↗