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Biomedical subjects

A F LoBuglio

Publications and source records attributed to A F LoBuglio.

At least 145 records · Page 8Linked to original sources

Effects of corticosteroid therapy on human monocyte function.

Since high-dose corticosteroid therapy appears to impair cellular defense mechanisms, this study examined its effect on human monocyte function. Fifteen normal volunteers were studied before and after a three-day course of prednisone therapy (50 mg every 12 hours for six doses). A transient period of monocytopenia occurred during the first few hours of therapy. Monocyte killing of Staphylococcus aureus was reduced in nine subjects from 5.6 plus or minus 0.2 (plus or minus S.E.) X 10-6 organisms before to 1.3 plus or minus 0.4 x 10-6 organisms at completion of therapy (p less than 0.01). Similary, killing of Candida tropicalis four subjects fell from 9.3 plus or minus 0.6 to 0.6 plus or minus 0.3 x 10-6 organisma (p less than 0.01). Bactericidal activity returned to normal levels 48 hours after the last dose of prednisone. These same monocyte preparations had normal or increased chemotactic response, phagocytic rate of cryptococci, hexosemonophosphate-shunt response to phagocytosis and ultrastructural characteristics. This impairment of bactericidal and fungicidal activity during prednisone therapy may contribute to the infectious complications seen in patients receiving comparable doses of corticosteroids.

Adult↗

Transfer factor: Potential for therapy of malignant diseases.

Transfer factor (TF) is a low molecular weight nonantigenic extract of leukocytes that is capable of transferring cell-mediated immunity from an immune individual to a nonimmune individual. Reports of efficacy of transfer factor in immunodeficiency states and chronic infectious diseases, as well as its lack of toxicity, have spurred clinical trials of TF therapy in human malignant diseases. Variables such as donor and patient selection, dose of TF, and use of concurrent therapy have not been explored. Preliminary reports suggest that TF may find a role as adjuvant therapy in human malignant neoplasms.

Humans↗

Leukemic reticuloendotheliosis. A study of the origin of the malignant cell.

A highly pure preparation of neoplastic cells from the spleen of a patient with leukemic reticuloendotheliosis was studied for function, membrane characteristics and glucose metabolism. Glass adherence and phagocytosis of small particles (latex and carbon black) were demonstrated with phase contrast microscopy. Staphylocidal activity was similar to that of normal monocytes. Immunofluorescent assays revealed nonspecific uptake of antiserums to immunoglobulins G (IgG), M (IgM), A (IgA) and kappa and kappa and lambda light chains. Rosette assays indicated the presence of receptors for IgG on the surface of all cells but no receptors for complement (C3) or sheep red blood cells. Glucose metabolic studies revealed a pattern that differed from that of normal monocytes or lymphocytes with intermediate values for glycolysis, low hexose monophosphate shunt activity and high Krebs cycle activity. Increments in tritiated (3H)-thymidine uptake and glucose metabolism in response to phytohemagglutinin stimulation were minimal (5 per cent of normal lymphocyte values) and no response was noted with pokeweed mitogen stimulation. These findings suggest that the leukemic reticuloendotheliosis cell most closely resembles cells of the monocyte-histiocyte series.

Cell Separation↗

Phytohemagglutinin (PHA) skin test in patients with sarcoidosis.

A group of 17 patients with histologically confirmed sarcoidosis were examined for the presence of anergy and the intracutaneous response to 2 mug of purified phytohemagglutinin (PHA); lymphocytes of 15 of these patients were studied for in vitro blastic response to PHA-M. Although 8 of the patients were anergic and 8 had impaired in vitro response to PHA, all patients showed a normal response to intradermal injection of PHA. It was concluded that patients with sarcoidosis have an intact intradermal response to PHA, suggesting that the anergy seen in this disease results from impaired initiation of the delayed hypersensitivity reaction and not from impaired mononuclear cell responsiveness. The PHA skin test may be a useful adjunct in the evaluation of anergic patients.

Humans↗

Phytomitogen- and antigen-induced blast transformation of feline lymphocytes.

A semiautomated microassay of blast transformation of feline lymphocytes was developed and used in a study of the response of normal cats to phytomitogen- and antigen-induced stimulation. Peripheral blood lymphocytes were isolated from defibrinated blood by ficolldiatrizoate gradient centrifugation and incubated at a concentration of 1 X 10(5) cells/culture. Blast transformation was measured by the incorporation of tritiated thymidine, to which the cells were exposed during the last 18 hours of incubation. Phytomitogens induced maximal transformation after 3 days' incubation. Greatest stimulation produced by 10 mug of concanavalin A (38- to 183-fold) followed by 4 mug of pokeweek mitogen (nine- to 51-fold), and finally phytohemagglutinin-P (three- to sixfold). Three of 4 cats sensitized to keyhole limpet hemocyanin responded when exposed to 50 mug of keyhole limpet hemocyanin in vitro, maximal transformation occurring after 4 days' incubation. Lymphocyte blast tranformation provides a convenient technique to assess lymphocyte function serially during experimentally induced immunologic alterations in the cat.

Animals↗

Immunologic specificity of transfer factor.

This study examined the immunologic specificity of transfer factor using a chromatographically purified transfer factor preparation. The specificity of transfer was examined utilizing immunity to keyhole limpet hemocyanin (KLH) and tuberculin. Transfer factor prepared from a donor immune to KLH successfully transferred KLH skin test reactivity to 10 out of 10 recipients. In contrast, comparable amounts of transfer factor from two donors not immune to KLH failed to transfer immunity to KLH in 11 recipients despite evidence for successful transfer of tuberculin reactivity. Unlike prior studies with a variety of antigens, the immunity to KLH in recipients of KLH immune transfer factor appeared comparable to that of the donor since both could be elicited with the same skin test antigen dose. These observations indicate that transfer factor can initiate a specific immune response to an antigen not previously encountered by the recipient and that in certain circumstances this immune response can be comparable to that of the donor. These observations on specificity and potency of transfer factor have important implications for the clinical use of this material.

Antibody Specificity↗

Effects of corticosteroids on human monocyte function.

This report examined the effect of corticosteroids in vitro on human peripheral blood monocytes, essential cells in both immune and nonimmune cellular defense mechanisms. Monocyte chemotaxis in response to sera, Escherichia coli filtrate, and lymphokine chemotactic factor was markedly reduced (P < 0.01) by hydrocortisone succinate (HCS) at 16 mug/ml. Methylprednisolone succinate and unesterified hydrocortisone produced similar impairment of monocyte chemotaxis while two drugs which unmodified do not enter cells, hydrocortisone phosphate (HCP) and cortisone acetate, had no effect on chemotaxis. HCS also significantly impaired monocyte random migration at 16 mug/ml. Monocyte bactericidal activity was reduced by HCS at 16 mug/ml (P < 0.01)) but was not affected by HCP even at 120 mug/ml. In comparison, HCS did not alter granulocyte chemotaxis even at 500 mug/ml, and bactericidal activity was reduced at 16 mug/ml (P < 0.01). Monocyte phagocytosis of cryptococci was reduced only 20% (P < 0.05) at 120 mug/ml. HCS at 120 mug/ml did not alter monocyte base-line or postphagocytic hexosemonophosphate shunt activity, viability by trypan blue exclusion, adherence to tissue culture flasks, or surface binding of IgG globulin. These corticosteroid-induced defects in monocyte function may contribute to reduced cellular defense during corticosteroid therapy.

Adrenal Cortex Hormones↗

Human blood monocytes: stimulators of granulocyte and mononuclear colony formation in vitro.

Human blood monocytes in a feeder layer or by use for conditioning medium produced a colony-stimulating factor capable of stimulating the in vitro growth of colonies of granulocytes and mononuclear cells from human and murine marrow. Lymphocytes and neutrophils did not stimulate colony formation, and medium conditioned by neutrophils was inhibitory. This suggests that the monocyte may control granulocyte proliferation and maturation.

Animals↗