Adjuvant-like effects of lithium on peripheral blood mononuclear cells.
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Biomedical subjects
Publications and source records attributed to R S Holzman.
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During an eight month period in 1978, a large number of infants in a special care nursery at Bellevue Hospital, New York City, were found to carry a Staphylococcus aureus which was resistant to gentamicin. The records of 43 newborn infants who were admitted during this period of high prevalence were analyzed retrospectively for factors that might favor acquisition of gentamicin sensitive or resistant strains. It was found that neither sex nor administration of gentamicin or kanamycin played a significant role. Duration of stay was a major determinant of colonization, but there was no significant difference between the median stay of infants colonized with gentamicin sensitive or resistant strains. A life table analysis showed no difference in the rate at which gentamicin sensitive or resistant strains were acquired. As a group, staphylococci were acquired at the same rate as Gram negative rods and less rapidly than S. epidermidis. A review of all nosocomial staphylococcal infections recognized in the unit during 1977 and 1978 did not support a concern that there might be greater risk of serious infections during the months when gentamicin resistant strains of S. aureus were prevalent. Both sensitive and resistant strains appeared to be similar in virulence. Indeed, in this infant population, there were no differences in behavior between gentamicin resistant and sensitive strains of S. aureus.
Three cases of generalized exfoliative staphylococcal scalded skin syndrome (SSSS) were encountered during a 25-day period in a nursery for premature infants. A single strain of Staphylococcus aureus, phage type 42E/54/75 (group 3), was recovered from each of the three infants and from no others. Two of the three isolates were tested and both produced epidermolytic toxin (ET). Most cases of SSSS have been associated with phage group 2 strains. To our knowledge, this is the first report of a nursery outbreak caused by a phage group 3 staphylococcus. It illustrates that ET production and not phage type distinguishes S aureus strains that are associated with SSSS.
In two previously well nonsmokers fatal pneumonia developed with extensive abscess formation. Legionnaires' bacillus was the only pathogen isolated. These cases indicate that Legionnaires' bacillus is capable of causing extensive necrosis of the lung.
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We studied the in vitro effects of levamisole on phagocytosis by macrophages and on proliferation of lymphocytes obtained from human peripheral blood. It was observed that levamisole directly stimulated phagocytosis in a lymphocyte-free system. Enhancement was optimal at a concentration that inhibited antigen- or mitogen-induced stimulation of sensitive lymphocytes. Lower concentrations of levamisole enhanced the proliferative lymphocyte response.
We have studied in vitro the effects of leukocyte dialysates containing transfer factor on the formation of sheep cell rosettes by human lymphocytes. Dialysate had no effect on the toral rosettes, but increased the number of rapidly forming ("active") rosettes. This was due to an increased affinity of the lymphocytes for the sheep red cell. Trypsin-treated lymphocytes regained the ability to form rosettes more rapidly when cultured with leukocyte dialysates than with control media. These experiments suggest that leukocyte dialysate acts to increase the number or arrangement of sheep cell receptors on the lymphocyte surface.
In a patient with only meningitis, a septate hypha was seen in a Langhans giant cell, and the rarely pathogenic Aspergillus oryzae was cultured from the cerebrospinal fluid. Serologic results confirmed the diagnosis. The patient responded to therapy with amphotericin B and flucytosine.
After our initial report tha leukocyte dialysates containing transfer factor augment the thymidine incorporation of antigen-stimulated lymphocytes, we have adapted the system to microleukocyte cultures. This modification permits both (a) the simultaneous assay of a single dialysate on the cells of multiple individuals, and (b) the assay of multiple dialysates on the cells of a single individual. The data thus secured, demonstrate that dialysates from both skin-test-positive and -negative donors produced similar degrees of augmentation whether the data are expressed as an arithmetic difference or as a ratio. When expressed as an arithmetic difference, the amount of augmentation is increased in proportion to the level of thymidine incorporation of the assay cells when they were stimulated by antigen alone. When expressed as a ratio, however, the degree of augmentation is independent of the response of the assay cells. An analysis of the ability of dialysates to engage previously uncommitted lymphocytes and thus to augment thymidine incorporation, revealed that precommitted cells were required. In these experiments, antigen-reactive cells were deleted from populations of peripheral blood lymphocytes by incubation with purified protein derivative of tuberculin, diphtheria toxoid, or streptokinase-streptodornase in the presence of [3H]thymidine of high specific activity. This deletion depressed or abolished the effect of dialysate on the residual population when it was recultured with the same antigen, but the effect on the response of the remaining lymphocytes to other antigens was unaltered. In this study, leukocyte dialysate appeared to augment nonspecifically the thymidine incorporation of an antigen-specific precommitted clone of lymphocytes. The relationship of these adjuvant effects on peripheral blood lymphocytes in vitro to the specific and nonspecific activities of transfer factor in vivo remains to be elucidated.
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Nonspecific enhancers of resistance may include (1) viral interference, (2) interferon, (3) interferon inducers, (4) bacterial interference, (5) bacterial products such as Coley's "toxins," endotoxins, or staphylococcal, BCG, and Corynebacterium parvum vaccines, (6) transfer factor, and (7) well-defined chemicals such as dinitrochlorbenzene, levamisole, and vitamin C. These are discussed only as they have been applied to man to learn whether or not they have enhanced his ability to resist infections and growth of tumors. Preliminary studies suggest that a variety of relatively safe and effective nonspecific enhancers may soon be available for clinical use.
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