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Biomedical subjects

N P Cummings

Publications and source records attributed to N P Cummings.

10 recordsLinked to original sources
PubMed1985

Oxidative metabolic response and microbicidal activity of human milk macrophages: effect of lipopolysaccharide and muramyl dipeptide.

Mouse macrophages can be primed by exposure in vitro to the bacterial products lipopolysaccharide and muramyl dipeptide (MDP) or in vivo by injection of MDP, so that they produce more of the bactericidal agent superoxide anion (O2-) when stimulated by phagocytosis or by contact with phorbol myristate acetate (PMA). Because little is known about the physiology of human tissue macrophages, we examined release of O2- by milk macrophages obtained from 45 normal women for the ability to undergo priming for greater O2- release. In samples from the same individuals, PMA-stimulated O2- release was similar from colostrum (0 to 3 days postpartum) or from transitional milk (5 to 8 days). Release of O2- by milk macrophages was almost identical to that by blood monocytes from the same women. Milk macrophages phagocytized and killed Candida albicans relatively effectively. Incubation with lipopolysaccharide activated the macrophages in that they were primed for greater PMA-stimulated O2- release. Incubation with the adjuvant MDP or its analog 6-O-(2-tetradecylhexadecanoyl)-MDP did not prime, but incubation with a second analog, 6-O-(stearoyl)-MDP, primed the macrophage for greater O2- release. These results indicated that human tissue macrophages can be primed for greater oxidative response by exposure to bacterial products. Potential exists for the therapeutic use of such immunomodulating agents in the enhancement of host defense.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Combination drug therapy in children with exercise-induced bronchospasm.

Fifty-three children with moderately severe asthma were studied to determine the capacity of drugs to block exercise-induced bronchospasm (EIB). All 53 children demonstrated EIB (as defined by a 20% fall in FEV1 or 30% fall in FEF25-75) while receiving therapeutic theophylline (serum level 10-20 micrograms/ml). EIB was completely blocked in 47 children by an inhaled metaproterenol 10 minutes prior to exercise, in addition to the theophylline. In six children, EIB was only partially blocked when either metaproterenol or cromolyn was added to the theophylline, but was completely blocked when all three drugs were used. A small group of children may benefit from combination therapy for EIB.

Adolescent↗
PubMed1983

Human macrophages may normally be "primed" for a strong oxygen radical response.

Human blood monocytes, peritoneal macrophages and milk macrophages, when initially isolated, displayed a vigorous release of superoxide anion (0-2), following stimulation with phorbol myristate acetate (PMA). This result contrasts with behavior of mouse peritoneal macrophages, which produce a weak 0-2 response, unless the macrophages are activated by infection or are elicted by injection of inflammatory agents. Treatment of mouse cells in vitro with bacterial products such as lipopolysaccharide (LPS) or muramyl dipeptide (MDP) also "primes" them for a high 0-2 response. Exposure of human macrophages to LPS or MDP for 16 h failed to enhance their 0-2 response. Thus the human cells appeared to be already "primed" for a vigorous oxygen radical response. In this respect, human cells resembled mouse peritoneal macrophages that have been "activated" by infection. These results suggest that MDP or other macrophage "activators" may offer less protection against infection in normal humans than they do in mice.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1983

Failure of children with asthma to respond to daily aspirin therapy.

Adverse reactions to aspirin in asthmatic patients have been widely described in the past. In contrast to this more frequent complication, several authors have published reports suggesting that aspirin and other nonsteroidal anti-inflammatory drugs can improve asthma. We studied the effect of long-term aspirin administration in children with moderately severe asthma. Ten children who showed no immediate effect of aspirin challenge (either adverse or beneficial) were placed in a 9 wk, double-blind crossover study, receiving aspirin (10 gr twice daily) or placebo for 4 wk, then a 1 wk washout period, followed by aspirin or placebo for 4 wk. There was no difference between aspirin and placebo periods in number of wheezing episodes, frequency of additional bronchodilator or prednisone use, or daily spirometric measurements. Serum thromboxane B2 levels were significantly reduced during aspirin therapy (p less than 0.001), indicating that the patients had complied with the aspirin therapy. Thus long-term administration of aspirin to asthmatics who show no immediate beneficial or adverse response to aspirin challenge appeared not to influence the clinical course of asthma. In addition, inhibition of the platelet prostaglandin cyclooxygenase pathway in these patients did not modify the clinical course of their asthma.

Adolescent↗
PubMed1980

Activation of macrophages for enhanced release of superoxide anion and greater killing of Candida albicans by injection of muramyl dipeptide.

The adjuvant muramyl dipeptide (MDP) has been shown to affect a number of macrophage functions in vitro. We studied the effect of subcutaneous injection of MDP into mice. Cultured peritoneal macrophages from treated mice displayed increased spreading, total cell protein, and specific activity of beta-glucosaminidase a constituent of macrophage lysosomes, and of lactate dehydrogenase. Generation of superoxide anion (O2-) by MDP-treated macrophages stimulated by contact with phorbol myristate acetate was enhanced by over fivefold to levels achieved by macrophages from bacillus Calmette-Guérin-infected mice. The enhancement in stimulated O2- release was noted by 1 h after injection of MDP, peaked by 3 h, and remained high for at least 48 h. Priming for enhancement of O2- release by MDP was similar in athymic nude mice and in normal littermates, suggesting that mature T lymphocytes are not involved in this MDP effect. Priming for enhanced stimulated O2- release, and morphologic and enzymic changes, were not achieved by injection of the D-D stereoisomer of MDP. Phagocytosis of Candida albicans was only slightly greater by macrophages from mice give MDP, but MDP-stimulated cells killed two times more C. albicans in vitro than did cells from untreated animals. When MDP was given 18 h before, simultaneously with, or 24 h after lethal infectious challenge with C. albicans, treated mice were protected compared with controls. These results suggest that injection of MDP effectively and rapidly activates macrophages in the recipient animal. This agent should serve as an important probe of macrophage physiology and, perhaps ultimately, as a means of enhancing host defense in humans.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1980

Lipophilic derivative of muramyl dipeptide is more active than muramyl dipeptide in priming macrophages to release superoxide anion.

Mouse peritoneal macrophages, when treated with a lipophilic derivative of muramyl dipeptide either in vitro or in vivo by intraperitoneal injection, showed a more than fivefold increase in their ability to generate superoxide anion after stimulation of the macrophages with phorbol myristate acetate. This response was more than twice that observed with the parent molecule, muramyl dipeptide (MDP). Unlike MDP, which has a systemic effect, the lipophilic derivative, [B30]-MDP, did not alter the response of peritoneal macrophages when given subcutaneously in the flank, suggesting that [B30]-MDP remains localized at the site of injection. The enhanced effect of [B30]-MDP over MDP appeared to be due to the inherent lipophilicity of the molecule, and was probably not due to either stimulation of T lymphocytes or activation of the alternative pathway of complement.

Acetylmuramyl-Alanyl-Isoglutamine↗