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Biomedical subjects

R R Watson

Publications and source records attributed to R R Watson.

At least 199 records · Page 11Linked to original sources

Thymosin treatment: serum corticosterone and lymphocyte mitogenesis in moderately and severely protein-malnourished mice.

The present studies were performed to determine the levels of serum corticosterone (SC) and the proliferation of lymphocytes in response to phytohemagglutinin (PHA) in mice that were injected with thymosin fraction V and fed low protein diets. We found that protein-malnourished mice had consistently higher SC values than the control animals. This result confirms the existence of nutritional stress, which stimulates the adrenal glands increasing the release of corticosteroid hormones. No changes were observed in the SC level in controls whether or not thymosin was injected. However, in mice fed a protein-deficient diet, there was a significant decrease in SC levels after thymosin treatment, as compared to those of groups not treated with thymosin. Additionally, the thymosin effect on the SC levels was correlated with the cell-mediated immune changes. A significant increase in both PHA and lipopolysaccharide-induced lymphocyte transformation was observed in spleen cells from malnourished mice treated with thymosin fraction V. Thus, stress-induced glucocorticoid immunosuppression was demonstrated in malnourished mice. Our results suggest that components of thymosin fraction V may be involved in the mechanism of the restoration of lymphocyte transformation that was suppressed by glucocorticoid in protein-malnourished mice.

Adrenal Glands↗

Effect of moderate malnutrition on immediate hypersensitivity and immunoglobulin E levels in asthmatic children.

Dermal reactions and IgE levels were compared in 51 asthmatic Colombian children identified on the basis of anthropometric measurements as nutritionally normal (25) or mildly (16) or moderately (10) undernourished. Twenty-five nonatopic children served as controls. Total serum IgE concentrations were significantly elevated in the asthmatic group as a whole. Moderately malnourished (grade II) asthmatic children had more than twice as much serum IgE as normal or mildly malnourished (grade I) asthmatic subjects and seven times more than nonatopic children. Intestinal parasitism did not appear to contribute to these differences in IgE levels. Serum levels of IgA and IgD were similarly elevated in grade II asthmatics. Concentrations of serum IgG, IgM, and C3 and C4 complement were unaffected by nutritional or allergic status. Eosinophilia in nasal mucus was significantly reduced in grade I and grade II malnourished asthmatic children. Among asthmatics, the most frequent dermal reactions were to mite antigens (96%), house dust (67%), and grass pollens (35%). Significant levels of specific IgE were detected by the RAST to two species of mites in nearly all atopic children. There was no apparent influence of nutritional status on the distribution of reactivity or specific IgE assay. The clinical significance of hyperimmunoglobulin E in atopic, moderately malnourished children remains to be elucidated.

Adolescent↗

Dietary stress and development of resistance ot Listeria monocytogenes in mice.

The native and acquired cell-mediated immune resistance against Listeria monocytogenes steadily developed in young mice after weaning and reached maximum activity at 6 and 12 weeks of age, respectively. Mice fed a high fat (20% corn oil) diet from 3 weeks of age had a significantly more rapid development of resistance against L. monocytogenes. Mice fed the high fat diet beginning at 6 and 12 weeks of age had significantly lower native preimmune resistance against L. monocytogenes after 3 weeks on the diet. On the other hand, 3-week-old mice fed a low protein (4% casein) diet had a significantly retarded development of native and acquired resistance against L. monocytogenes. However, mice consuming the low protein diet at 6, 12 or 24 weeks of age did not exhibit an impairment in this resistance. Therefore age at which the dietary stress, either low protein or high fat, was initiated had an important effect on native and acquired resistance of mice against L. monocytogenes.

Aging↗

Alteration of cell-mediated immunity to Listeria monocytogenes in protein-malnourished mice treated with thymosin fraction V.

Cell-mediated immune reactivity, measured by lymphocyte responsiveness to phytohemagglutinin, was higher in both young or aged mice fed a 4% casein diet compared with age-matched controls. Treatment in vivo with bovine thymosin fraction V decreased the responsiveness to phytohemagglutinin of lymphocytes from mice fed either the control or moderately protein-deficient diets when compared with mice treated in vivo with saline. Resistance against Listeria monocytogenes, known to be a cell-mediated immune function, was impaired in young and aged mice which were fed the low-protein diet. Treatment with thymosin was able to significantly improve the cell-mediated immune resistance to L. monocytogenes of moderately protein-malnourished mice. Thymosin treatment impaired the resistance to L. monocytogenes of young or aged mice fed the control diet. The splenic natural killer cell cytotoxicity of protein-malnourished mice was impaired compared with that of mice fed the control diet. Treatment with thymosin did not restore the natural killer cell cytotoxic activity in protein-malnourished mice, but did enhance that activity in control mice.

Aging↗

Resistance to L1210 mouse leukemia cells in moderately protein-malnourished BALB/c mice treated in vivo with thymosin fraction V.

Moderate protein malnutrition retarded the i.p. proliferation of L1210 mouse leukemia cells in BALB/c mice. The increased resistance against leukemia cell growth in protein-malnourished mice was correlated with increased in vitro mitogenic responsiveness of spleen lymphocytes to phytohemagglutinin and increased levels of serum corticosterone but could not be correlated with altered development of splenic lymphocyte-mediated cytotoxicity. The increased resistance against leukemia cells in well-fed mice treated with thymosin alone could not be correlated with an increase in any of these parameters. Treatment with Thymosin Fraction V further increased the resistance of protein-malnourished mice to i.p. leukemia cell growth. The increased resistance of these mice to tumor cell growth was correlated with increased splenic lymphocyte mitogenic responsiveness to phytohemagglutinin, elevated serum corticosterone levels, and a slight increase in lymphocyte-mediated cytotoxicity 14 days after tumor challenge. For 7 days after the last treatment, protein-malnourished mice had reduced serum corticosterone levels. Nevertheless, the serum corticosterone levels were still higher than normal in these mice.

Animals↗

Effect of renutrition on humoral and cell-mediated immunity in severely malnourished children.

Forty-three Colombian children suffering from either kwashiorkor (21), combined protein-calorie malnutrition (11), or maramus (11) were hospitalized and provided a high protein, high calorie diet for 4 to 5 wk. Improvement in clinical and nutritional status was accompanied by significant increases in levels of serum immunoglobulins G and M and C3 complement and by significant decreases in serum immunoglobulin A concentrations, especially in infants with kwashiorkor. Skin test reactions to purified protein derivative and candidin improved during renutrition. Lymphocyte blastogenesis after stimulation in vitro with phytohemagglutinin and pokeweed mitogen increased rapidly during hospitalization. After 1 yr posttreatment, cell-mediated immune responses, both in vivo and in vitro, had diminished. These results indicate that some aspects of the immune response are affected to a different degree in kwashiorkor, maramus, and combined malnutrition. Short-term nutritional rehabilitation has a differential effect on the long-term restoration of various aspects of immunity.

Antibody Formation↗

Immune components of the intestinal mucosae of ageing and protein deficient mice.

The studies were designed to investigate the effect of ageing and low protein (4%) diet on antibody-dependent cell-mediated cytotoxicity (ADCC) and IgA concentration in the intestine. Both ADCC activity and IgA concentration were shown to reach mature levels at 17 weeks old. The effect of ageing was greater on ADCC activity which showed a drastic drop in activity at 75 weeks old than IgA which had only a slight decline in concentration at this age. The low protein diet has a greater suppressive effect on IgA concentration than on ADCC activity. As the duration of feeding low protein to the young mice increased, greater decline in IgA concentration in the intestine was observed. There was, however, no significant difference from the normal mice in ADCC activity and IgA concentration of aged and adult mice given short term (8 weeks) low protein diet.

Aging↗

Effect of vitamin E on cell-mediated immune responses and serum corticosterone in young and maturing mice.

A high vitamin E diet altered cell-mediated immune responses of maturing BALB/c mice. Serum corticosterone concentrations in these animals were also determined because of the pharmacological effect the glucocorticoid hormone has on immune systems. Mice receiving high vitamin E diet (twenty times higher than the vitamin E concentration in control diet) showed significant increase in antibody-dependent cellular cytotoxicity (ADCC) activity within a week after initiation of the diet. Adult levels of spleen and intestinal ADCC activities were reached at a much younger age in these high vitamin E-treated animals. In addition, there was a good correlation between increase in spleen and intestinal ADCC activities and the significantly lower than control concentration of serum corticosterone in these mice. However, after prolonged consumption of high vitamin E diet, decrease in ADCC activity was observed in these mice. No significant differences in PHA-induced spleen lymphocytes [3H]-thymidine incorporation, along with a decrease in serum corticosterone levels, were observed in mice given either high vitamin E or the control diets throughout most study periods.

Animals↗

Modifications of cell-mediated immune responses by moderate dietary protein stress in immunologically immature and mature BALB/c mice.

Female BALB/c mice at 5, 6 (immature) and 35 weeks of age (mature) were placed on isocaloric control (20% protein) or experimental (4% protein) diets. Cell-mediated immune responses [theta-bearing cell percentages, phytohemagglutinin (PHA) induced mitogenesis, mixed lymphocyte reaction (MLR) and antibody-dependent lymphocyte-mediated cytotoxicity (ADLMC)] of splenic lymphocytes were measured. A significant decline in percentages of theta-bearing cells, PHA and MLR responses occurred as early as two weeks for the immature mice on the restricted diet and continued for up to 8 weeks. In mature mice, protein restriction did not influence theta-bearing cell percentages, but did suppress PHA and MLR responses between 7 and 13 weeks. A significant suppression of ADLMC responses were also noted at 16 weeks. These results indicate that developing cellular immune systems of immature BALB/c mice are more sensitive to moderate protein restriction (i.e. immunosuppression occurs after a shorter interval) than those of mature mice. They suggest that moderate protein malnutrition retards but does not prevent immunological maturation.

Aging↗

Effect of moderate chronic protein deficiency on rat salivary components.

Chronic protein insufficiency was achieved in rats with an 8% protein diet initiated at weaning. The total activity and activity per milliliter of the principal salivary protein, amylase, were significantly decreased at day 66. The amount of total protein per milliliter of saliva and total protein in stimulated saliva collected during 30 minutes was decreased in the malnourished rats. The levels of immunoglobulin G (IgG) and aminopeptidase in saliva were not affected by dietary status. Prolonged malnutrition on the low-protein, high-starch diet resulted in an apparent stimulation or induction of salivary amylase and protein secretion by day 110. Total protein collected and milligram of protein per milliliter of saliva were very similar in the malnourished and control rats at day 110. Salivary amylase activity in the malnourished rats was significantly greater than in the saliva of controls. The initial decrease in the principal salivary protein, amylase, and in total protein followed by a significant increase with prolonged stimulation by low-protein and high-starch diets suggests that early protein deficiency retards synthesis of amylase and that a high-starch diet may induce salivary amylase production.

Aging↗

Effects of age on cellular immune responses in BALB/cJ mice: increase in antibody-dependent T lymphocyte mediated cytotoxicity.

Two in vitro cell-mediated immune (CMI) responses of splenic lymphocytes of BALB/cJ mice of various ages (1.25, 2.5, 4, 10.5 and 30 months) were examined. These were the antibody-dependent lymphocyte-mediated cytotoxicity (ADLMC) responses, mediated by the K cell subclass to T lymphocytes, and phytohemagglutinin (PHA) induced mitogenesis, mediated by the theta positive T lymphocytes. ADLMC responses increased with age, culminated at 10.5 months, then slowly declined. Lymphocytes of young mice (2.5 or 4 months of age) were significantly more responsive to PHA than lymphocytes of mature (10.5 months) or aged adults (30 months) (p less than 0.01), indicating progressive suppression of this type of CMI response with age, as observed previously. The difference in time of maturation and extent of suppression of ADLMC and PHA responses was not influenced by changes in numbers of specific effector cells, since percentages of these did not change with age (as measured by immunofluorescence and rosetting techniques). The increase with age of ADLMC responses may be due to deregulation of earlier suppressor activity which allows the K cell to be fully responsive, but other mechanisms may be involved.

Aging↗