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M D Peck

Publications and source records attributed to M D Peck.

At least 19 recordsLinked to original sources
PubMed2000

High-fat diets suppress CD3 and CD25 expression on the surface of murine lymphocytes.

To determine the effects of dietary fats on surface antigen expression, we tested the effects of amount and type of dietary fat on murine lymphocytes. Mice were fed diets with 12 en%, 23 en%, or 47 en% fat containing coconut, olive, safflower, or linseed oil. After 2 wk of ad libitum feeding, the mice were killed and splenic lymphocytes were harvested. Lymphocytes were incubated with fluorescent-tagged monoclonal antibodies and assayed for mean and total surface expression using flow cytometry. Our results show that high-fat (47 en%) diets suppress expression of CD3 and CD25 antigens. We also found that linseed-oil diets suppress expression of CD11a but enhance expression of CD25 antigens. Both CD3 and CD25 are critical for lymphocyte activation, and we conclude that immunosuppression associated with high-fat diets may be associated with suppression of these surface antigens.

Animals↗
PubMed2000

Dietary olive oil enhances murine lymphocyte calcium uptake.

BACKGROUND: Dietary lipids enhance immune function and improve outcome from injury or infection in animal models. We tested the hypothesis that amount, type, or both, of dietary lipid increases intracellular calcium concentration, a surrogate for lymphocyte activation. METHODS: Mice were fed 2 weeks on semipurified diets with 5% (by weight [w/w]), 10% (w/w), or 20% (w/w) dietary fat consisting of coconut, olive, safflower, or linseed oil. Changes in intracellular calcium concentration after mitogen stimulation of splenic lymphocytes was estimated by using flow cytometry. RESULTS: Olive oil diets increase intracellular calcium concentration after concanavalin A, lipopolysaccharide, and CD3 stimulation. On the other hand, linseed oil (which is high in omega-3 fatty acids, which have been shown in other studies to enhance immune function) depresses intracellular calcium levels. The amount of dietary fat had no effect on intracellular calcium. CONCLUSION: Olive oil merits further study in the application of nutritional pharmacology to immunomodulation of the critically injured, because it may enhance lymphocyte function.

Analysis of Variance↗
PubMed1996

Supplemental L-arginine HCl augments bacterial phagocytosis in human polymorphonuclear leukocytes.

That L-arginine (L-Arg) augments the host response to acute bacterial sepsis suggests that this amino acid intervenes early in the immune response, perhaps via the nitric oxide synthetase (NOS) pathway. The effect of L-Arg supplementation on in vitro phagocytosis of fluorescein-labeled, heat-killed Staphylococcus aureus by peripheral blood neutrophils (PMNs) from 12 normal human volunteers was studied. Separated PMNs were incubated for 2 h with labeled bacteria, with and without supplemental L-Arg, D-arginine, glycine, and/or the NOS inhibitors L-canavanine, aminoguanidine, or L-NG-nitroarginine methyl ester. PMNs were fixed and extracellular fluorescence quenched with crystal violet. By flow cytometry and confocal microscopy, L-Arg supplementation was shown to result in a highly significant increase in PMN bacterial phagocytosis, the maximal effect being seen with L-Arg 380 microM and falling off with higher concentrations. This augmentation was completely abrogated by NOS inhibitors in molar excess, but inhibitors alone did not suppress phagocytosis below that of unsupplemented controls. Neither D-arginine nor glycine affected phagocytosis; the L-Arg effect was stereospecific and not related to utilization of L-Arg as an energy source. L-Arg supplementation significantly enhances bacterial phagocytosis in human neutrophils, perhaps by effects on cytoskeletal phenomena, and this appears to be mediated through NOS activity. Phagocytosis by nonspecific immune cells which intervene early in the response to sepsis is critically important, and beneficial effects of L-Arg on the clinical course of sepsis may be due at least in part to augmentation of phagocyte function.

Arginine↗
PubMed1996

Involvement of CD44 and the cytoskeletal linker protein ankyrin in human neutrophil bacterial phagocytosis.

The leukocyte CD44 and CD45 cell surface receptors are associated via the linker proteins ankyrin and fodrin with the cytoskeleton, which itself is important in immune cell functions such as adherence, chemotaxis, and phagocytosis. The effects of rat antihuman CD44 and CD45 monoclonal antibodies on phagocytosis of fluoresceinated heat-killed Staphylococcus aureus 502A by normal human neutrophils (PMNs) during 2 hr incubation in RPMI-1640 was studied via flow cytometry and confocal microscopy. Flow cytometry was performed using an excitation wavelength of 488 nm, fluorescence being measured at 515-560 nm on 50,000 PMNs per sample. Confocal microscopy was performed on samples after further incubation with rhodamine-conjugated antiankyrin. Anti-CD44 resulted in an increase of 27-31% compared to control (P = 0.004) in the proportion of PMNs fluorescing, an increase of 17-24% (P = 0.001) in mean intracellular fluorescence per PMN, and an increase in total PMN fluorescence of 50-58% compared to control (P < 0.001). In contrast, anti-CD45 had little effect on phagocytosis. Colchicine (a microtubule-disrupting agent) enhanced, whereas cytochalasin-D (a microfilament inhibitor) inhibited bacterial phagocytosis; cytochalasin-D completely abrogated the effect of anti-CD44 on this PMN function. Hyaluronic acid augmented phagocytosis by an increment similar to that observed with anti-CD44. Two-color flow cytometry and confocal microscopy demonstrated that ankyrin always colocalized with ingested fluorescein isothiocyanate (FITC)-labeled bacteria. These data strongly suggest that CD44 is involved in bacterial phagocytosis, provide further evidence of CD44 receptor linkage to cytoskeletal elements in human leukocytes, and suggest that ankyrin has a significant role in the transport of phagosomes.

Ankyrins↗
PubMed1996

Association of murine splenocyte CD3 complex to the cytoskeleton: absence of modulation by exogenous fatty acids.

The cytoplasmic regions of the CD3 complex are presumably involved in signal transduction following ligand-receptor binding. We investigated the effects of incubating either stearic or oleic acid on the association of murine lymphocyte CD3 complex with the cytoskeleton. Both cytochalasin D, an inhibitor of microfilament formation, and W7, an inhibitor of calmodulin, inhibited capping of CD3. The association of CD3 with the cytoskeleton was confirmed by confocal laser scanning microscopy studies, which showed co-localization of the cross-linked CD3 receptors and the membrane attachment proteins ankyrin and fodrin. Although exogenous oleic acid increased plasma membrane fluidity, neither expression nor capping of CD3 receptors was increased. Nonetheless, oleic acid did increase uptake of tritiated thymidine after binding of anti-CD3 antibodies. Lymphoproliferation was progressively inhibited by both cytochalasin D and W7, confirming the importance of intact cytoskeleton for cellular activation.

Animals↗
PubMed1996

Fatty acid unsaturation increases expression and capping of murine lymphocyte CD44 and CD45.

We studied the effect of incubating murine lymphocytes with cis-unsaturated fatty acids on expression and capping of CD44 and CD45. Lymphocytes were incubated with stearic (18:0) or oleic (18:1 omega-9) acid bound to bovine serum albumin (BSA). After incubation with rat anti-CD44 or anti-CD45 monoclonal antibodies and then with fluorescent-labeled anti-rat antibody, mean fluorescence intensity (FI) was measured by using flow cytometry. Capping was measured after warning and fixation in paraformaldehyde. Steady-state fluorescence anisotropy (rs) was measured after the cells had been incubated with trimethylammoniumdiphenylhexatriene. Incubation with oleic acid, but not stearic acid or BSA alone, was associated with an increase in FI of CD44. Expression of CD45, however, was increased by both stearic and oleic acids to the same degree over BSA controls. CD44 and CD45 capping were both increased by incubation with oleic acid. Rs was decreased in cells incubated with oleic acid, suggesting an increase in membrane fluidity. We conclude that incubation with oleic acid increases expression of CD44 and increases capping of both CD44 and CD45. These findings were confirmed in feeding experiments, in which rs was reduced and CD44 capping increased by polyunsaturated fatty acid diets.

Animals↗
PubMed1995

High doses of dietary arginine during repletion impair weight gain and increase infectious mortality in protein-malnourished mice.

There is considerable evidence for the beneficial effects of dietary arginine, a conditionally-essential amino acid that enhances anabolism and T-cell function. However, the safety and efficacy of higher doses of arginine supplementation following infection have not been investigated completely. These issues were explored therefore, in a murine model of malnutrition and infection. Severe protein malnutrition was induced by feeding mice for 6 weeks on an isoenergetic diet containing only 10 g protein/kg. Mice were then allowed to consume diets with normal amounts of protein (200 g/kg) with 50 g/kg provided as amino acid mixtures of glycine and arginine in which the arginine content ranged from 0 to 50 g/kg. During the repletion period a significant weight gain was noted in the groups fed on diets with either 10 or 20 g arginine/kg, but not in the group fed on the diet with 50 g arginine/kg, compared with the diet with 0 g arginine/kg. Mortality rates after infection with Salmonella typhimurium were not decreased by the addition of 10 or 20 g arginine/kg to the diet, and were in fact worsened by supplementation with 50 g arginine/kg. The results of the present study showed that not only are the beneficial effects of arginine supplementation after infection lost when high doses are administered, but also that these high doses become toxic. Mice fed on higher doses showed significant impairment of weight gain and an increase in mortality rates.

Animals↗
PubMed1994

Omega-3 polyunsaturated fatty acids: benefit or harm during sepsis?

omega-3 polyunsaturated fatty acids (PUFAs) are potent modulators of the immune response. Their inclusion in enteral diets may benefit surgical patients recovering from injury or infection. Caution should be used when supplementing omega-3 PUFAs, particularly when fish oil is used as the source. The long-chain, highly polyunsaturated fatty acids in fish oil are prone to autoxidation, and can potentially damage cells by forming free radicals. In addition, fish oil may impair the hemostatic response by inhibiting platelet aggregation. Finally, the biochemical and biological end points for the use of omega-3 PUFAs have not been clearly established. Thus, although omega-3 PUFAs offer tremendous potential as immunomodulators, they also offer potential toxicities, and we must employ them in our clinical practice with this understanding.

Eicosanoids↗
PubMed1993

The esterified plasma fatty acid profile is altered in early HIV-1 infection.

Previous studies have shown that alterations in micronutrient utilization occur in patients with Acquired Immune Deficiency Syndrome. In this study, total plasma fatty acid composition was measured in 36 homosexual men infected with the Human Immunodeficiency Virus 1 (HIV-1) and in 17 HIV-1 seronegative homosexual men in order to evaluate differences associated with early HIV-1 infection. Immunologic assessment included CD4 cell number count and lymphocyte blastogenesis in response to the mitogens phytohemagglutinin (PHA) and pokeweed (PWM). The mean total amount of omega 6 polyunsaturated fatty acids (18:2 and 20:4) was significantly lower in the HIV-1 seropositive subjects (38 +/- 8.1% SD) as compared to HIV-1 seronegative subjects (43 +/- 4.2%; P = 0.0027). This was also reflected in a higher level of total saturated fatty acids (16:0 and 18:0) in HIV-1 seropositive subjects (30 +/- 2.2% vs. 26 +/- 2.8%; P = 0.0001). The ratio of linoleic to arachidonic acid (18:2 to 20:4) was higher in the HIV-1 seropositive group (6.76 +/- 4.88) compared to the HIV-1 seronegative group (4.86 +/- 1.37; P = 0.0213). The response to PHA in seropositive subjects correlated inversely with total plasma omega 6 fatty acids (r = -0.36; P = 0.027), and directly with the 18:2 to 20:4 ratio (r = 0.33; P = 0.046). CD4 cell counts and the response to PWM did not correlate with plasma fatty acid levels in HIV-1 seropositive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Composition of fat in enteral diets can influence outcome in experimental peritonitis.

An animal model of protracted acute peritonitis was used to study the effects on survival of different amounts and types of dietary fat. Guinea pigs (n = 132) were provided with gastrostomies and allowed to recover. Intraperitoneal osmotic pumps were then placed, allowing for effusion of viable bacteria during the next week. Three days after pump implantation, the animals were randomized to receive one of nine diets, differing only in fat content (3.5%, 14%, or 56% of total calories) and fat composition (100% Microlipid [primarily safflower oil, rich in linoleic acid], 100% MaxEPA [fish oil containing 35% omega-three fatty acids], or a 50:50 mixture of both oils). At the end of 2 weeks, survival rates were compared. Among all types of fat used, the level of fat did not affect outcome, with survival rates of 13% (6 of 45) at the low level of fat used, 30% (13 of 44) at the medium level, and 26% (11 of 43) at the high level (P greater than 0.10). However fat composition significantly influenced survival across all levels of fat, with a 39% (17 of 44) survival rate in the groups given equal amounts of Microlipid and MaxEPA, compared either to 21% (9 of 44) for the 100% Microlipid groups, or to 9% (4 of 44) for the 100% MaxEPA groups (p less than 0.05). A second experiment was performed with 58 animals fed five different mixtures of fats, all at 14% of total calories. Diets were made with fat ratios of 100:0, 75:25, 50:50, 25:75, and 0:100 Microlipid to MaxEPA. The survival rate in the 50:50 group was 83% (10 of 12), which is significantly higher than the survival rates with any of the others (p less than 0.05). It is concluded that the amount of fat in the diet does not strongly influence outcome in this model. However an equal mixture of safflower and fish oils significantly improves survival rates compared to diets made with single-oil preparations.

Acute Disease↗
PubMed1990

The process of microbial translocation.

The process of microbial translocation was studied using Candida albicans, Escherichia coli, or endotoxin instilled into Thiry-Vella loops of thermally injured guinea pigs and rats. Translocation of C. albicans occurred by direct penetration of enterocytes by a unique process different from classical phagocytosis. Translocation between enterocytes was not observed. Internalization was associated with a disturbance of the plasma membrane and brush border, but most internalized organisms were not surrounded by a plasma membrane. Passage of the candida into the lamina propria appeared to be associated with disruption of the basal membrane with extrusion of cytoplasm of the cell and candida. Organisms in the lamina propria were commonly phagocytized by macrophages but also were found free in lymphatics and blood vessels. Translocation of E. coli and endotoxin also occurred directly through enterocytes rather than between them, but translocated endotoxin diffused through the lamina propria and muscular wall of the bowel wall by passing between rather than through the myocytes. These descriptive phenomena provide new insight into the role of the enterocyte and intestinal immune cells in the translocation process.

Animals↗
PubMed1990

The effect of dietary fatty acids on response to Pseudomonas infection in burned mice.

Since fatty acids influence prostaglandin synthesis, and since both fatty acids and prostaglandins modulate immune function, we investigated the hypothesis that manipulation of dietary fats would affect survival after infection in a murine burn model. Mice were fed for 2 to 3 weeks with diets containing different types and amounts of fat. They were then subjected to a 20% flame burn and infected with Pseudomonas aeruginosa. Survival in the group fed 40% of total calories as fish oil had significantly higher mortality than those fed safflower oil. This difference was not noted at lower fat levels. Similar groups of animals were sacrificed the day after injection. Splenic macrophage production of PGE2 was significantly lower in the fish-oil group, but production of LTB4 and TXB2 were not affected. In vitro tests of T- and B-cell function were not different amongst groups. We conclude that manipulation of dietary fats can alter outcome in this murine model of infection after thermal injury.

Animals↗
PubMed1990

The effect of free radical scavengers on outcome after infection in burned mice.

Thermal injury generates free radicals from various cellular populations, and modulation of free radical activity with scavengers may improve outcome. Balb/c mice were infected with Ps. aeruginosa the day after burn injury and mortality rates observed. Tocopherol was given by gavage daily for 4 days starting 2 days before burn. Survival was improved in the groups receiving 25 and 250 IU/kg compared to control. In other groups, tocopherol was given after burn, but mortality rates were not changed. Treatment with the oxygen radical scavengers ascorbic acid, and a combination of superoxide dismutase and catalase had no effect on mortality. We conclude that ascorbic acid, superoxide dismutase, and catalase do not appear to benefit survival after thermal injury and infection in this murine model. Tocopherol given in high doses of at least 25 IU/kg by gavage preceding injury and continued thereafter for 2 days did improve survival, but this benefit was not seen if tocopherol was not started until after injury.

Animals↗
PubMed1990

Future prospects for adjunctive therapy: pharmacologic and nutritional approaches to immune system modulation.

An increasingly large number of dietary components have been found to alter immune system function and, therefore, may be considered to have a pharmacologic effect (pharmacologic nutrition). Those dietary factors which have already been shown to influence outcome by producing a pharmacologic effect rather than correcting or preventing a simple deficiency include proteins (both type and amount), arginine, glutamine, omega-6 and omega-3 fatty acids, short-chain fatty acids, the metals iron and zinc, and the vitamins E, C, and A. Therapeutic outcome has already been influenced by dietary therapy (pharmacologic nutrition) in patients after burn injury or who have vascular diseases, and in experimental animals for the prevention of gut origin sepsis, the prevention and treatment of infection, prevention and development of secondary lesions in autoimmune diseases, augmentation of immunosuppression in transplantation, and in the treatment of cancer. Nutritional therapy using disease-specific formulations or supplements is an old idea now undergoing rapid evolution to increasing importance for successful therapeutic outcome.

Animals↗
PubMed1989

Dietary iron and recovery from peritonitis in guinea pigs.

Ninety female Hartley guinea pigs underwent gastrostomy placement. One week later they underwent implantation of an osmotic pump, which allowed constant delivery of bacteria into the peritoneal cavity. Three days after pump implantation the animals were begun on enteral diets differing only in iron content (the None [no Fe], Low [1 X RDA], and High [10 X RDA] groups). When survivors were killed no differences were found in body, carcass, or organ weights among the three groups. Serum Fe and percent Fe-binding sites occupied were significantly lower in the None group although total Fe-binding capacity was similar. Mortality was not statistically different (p = 0.29): 18/32 in the None group (56%), 14/24 in the Low group (58%), and 25/34 in the High group (73%). We conclude that although deprivation of dietary sources of Fe does affect available circulating Fe, diet-induced hypoferremia does not alter mortality rates from bacterial peritonitis in the guinea pig.

Animals↗
PubMed1989

A new model for studying nutrition in peritonitis. The adverse effect of overfeeding.

In guinea pigs fed ad libitum, controlled intraperitoneal infusion of bacteria by an implanted 7-day osmotic pump resulted in peritonitis or abscess formation with a 50% survival 14-18 days after pump implantation. Administration of 125 kcal/kg/day of a diet found to be optimal for burned guinea pigs by continuous pump controlled feedings via a previously placed gastrostomy was well-tolerated, with a 62.5% mortality by Day 17. Administration of only 100 kcal/kg/day caused weight loss of approximately 17% after 16 days, but fewer animals died (42.8%, p = NS). Feeding either 150 kcal/kg/day or 175 kcal/kg/day caused death in all 25 animals (p less than 0.001) and their survival time was slightly shortened (p = NS) when compared with animals receiving 100 or 125 kcal/kg/day. This is the first animal model of peritonitis that permits incisive dissection of the relative influences of dietary composition on outcome, because survival can be extended to 2 weeks or more in the presence of continuing sepsis.

Animals↗
PubMed1989

Low protein diets improve survival from peritonitis in guinea pigs.

Enteral diets with different protein content were tested to determine their effect on outcome in a model of protracted bacterial peritonitis. Hartley guinea pigs were provided with gastrostomies, and 1 week later, osmotic pumps were implanted into the peritoneal cavity to allow for continuous release of live bacteria over the course of 1 week. Three days after pump implantation, the animals began receiving isocaloric enteral diets that contained 5%, 10%, 15%, or 20% of total calories as protein. After 2 weeks of observation, the survivors were killed. All animals lost weight during the 2-weeks period, but there was no difference in weight lost. Nitrogen balance correlated with dietary protein. The mortality rate was significantly higher in the groups that received 15% and 20% of total calories compared with the group that received 5% (p less than 0.05). Although dietary protein in the 5% group was insufficient for meeting the nutritional needs of the animal, survival was best in this group. Possible explanations are that protein restriction in this model may either augment host defence or impair bacterial virulence.

Animals↗