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Biomedical subjects

A F LoBuglio

Publications and source records attributed to A F LoBuglio.

At least 127 records · Page 7Linked to original sources
PubMed1978

Normal human monocytes inhibit tumor cell growth in vitro.

Normal human monocytes were evaluated in an in vitro assay of growth inhibition of tumor cells. Monocytes were isolated from the blood of 6 normal subjects by Ficoll-Hypaque separation and adherence to plastic microtest wells. Cervical carcinoma cells (HeLa) were added to the microwells to result in a ratio of 50 monocytes to one HeLa cell. Cultures were then incubated for 6 to 46 hr. Growth inhibition was evaluated by measuring the uptake of 3H-thymidine over a 4-hr pulse period after 2, 18, or 42 hr of monocyte-HeLa interaction. Inhibition of HeLa growth by monocytes was 23.8% +/- 8.6% over 6 hr, 22.0% +/- 8.9% over 22 hr. and 68.3% +/- 7.5% over 46 hr. Growth inhibition of HeLa cells was confirmed by direct enumeration of HeLa cells at the end of coincubation. Attachment of monocytes to the HeLa cells was confirmed by light and scanning electron micrographs. Granulocytes, lymphocytes, and other cell lines did not comparably inhibit HeLa growth and media replenishment did not ablate the effect. These data demonstrate that normal human monocytes can inhibit the growth of a malignant cell line in vitro in the absence of overt activation procedures.

Cell Division↗
PubMed1978

Skin test conversion following transfer factor. A double-blinded study of normal individuals.

The use of skin test conversion as a measure of change in cellular immune status is a fairly routine procedure despite considerable potential for variation in testing. This study is a double-blinded and randomized reassessment of this assay in the context of transfer factor (TF) activity. Thirty-three normal people with negative tuberculin skin tests received either dialyzable TF, column purified TF, hypoxanthine, or saline in a randomized and double-blinded fashion. Skin test reactivity to tuberculin and keyhole limpet hemocyanin (KLH) was read by three of the investigators. Nine of 20 recipients of TF and 7 of 13 controls demonstrated an increase in tuberculin reactivity after "transfer." Four reactions were greater than 10 mm. Fourteen of 20 recipients of TF and 7 of 13 controls demonstrated some reactivity to KLH on initial testing post-transfer. Control solutions were as effective as TF preparations in "causing" skin test conversion. These observations stress the importance of controlled and and blinded studies when serial skin test reactivity is used to evaluate cellular immune status in humans.

Clinical Trials as Topic↗
PubMed1978

Human monocyte antibody-dependent cell-mediated cytotoxicity to tumor cells.

Previous investigations of mononuclear cell antibody-dependent cell-mediated cytotoxicity (ADCC) toward tumor cells suggest that K lymphocytes and not monocytes are active in this cytotoxic reaction. This report, however, demonstrates that human monocytes are able to carry out ADCC toward three different human tumor cell lines (CEM T lymphoblasts, Raji bone marrow-derived (B) lymphoblasts, and HeLa cells). The cytolytic event was found to be temperature dependent and rapid, with most of the lysis occurring in the first 4 h of incubation. The extent of lysis was directly related to the number of monocytes (effector cells) and to the degree of antibody sensitization of the target cells. The antibody-dependent cell contact-mediated nature of the cytolytic event was confirmed by inhibition with competing nonspecific monomeric immunoglobulin and by the ability of monocytes in "innocent bystander" experiments to lyse antibody-coated targets but not nonantibody-coated target cells. Evidence that monocytes were clearly the effector cells in the monocyte preparations included the observation that preincubation of effector cells with opsonized zymosan particles abolished ADCC by monocytes, but had little effect on lymphocyte ADCC. Furthermore, no evidence for Fc receptor K lymphocyte contamination of the monocyte preparations was found using antibody-coated target cells that were selectively lysed by lymphocytes but not monocytes. We suggest that ADCC toward tumor cell targets may prove to be a useful assay of monocyte function in normal and disease states.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1977

Phytohemagglutinin skin tests in cancer patients.

Phytohemagglutinin (PHA) stimulates blastic transformation of normal lymphocytes in vitro and when injected intradermally produces a skin response histologically similar to a delayed hypersensitivity reaction. We investigated the skin test responses to PHA, mumps, candida, and varidase (SK-SD) and the PHA-induced lymphocyte transformation in patients with malignant neoplasms. Increased incidence of anergy to recall antigens and unresponsiveness to PHA skin testing was observed in patients with lymphoreticular malignancies but not in those with solid tumors. There was a direct correlation between skin test reactivity to at least one recall antigen and/or PHA and survival in lymphoma patients. This was true of both short and long terms survival in Hodgkin's disease and of survival at least through 42 months in non-Hodgkin's lymphomas. In vitro stimulation of lymphocytes with PHA did not correlate with PHA skin test reactivity. We conclude that PHA skin testing is a useful adjunct in the evaluation of patients with lymphoreticular malignancies.

Adult↗
PubMed1977

Immune response to L2 guinea pig leukemia-specific antigens.

Strain 2 guinea pigs were immunized with the LE-L2C cell line and challenged with either LE-L2C or BZ-L2C, a subline of L2C leukemia deficient in la gene product and C3 receptor. The LE-L2C-immune animals were completely protected from a challenge of 5 X 10(6) cells (100 times the lethal dose) of either cell line, and the delayed skin test responses for both lines of injected cells were equivalent. Thus established in vivo immune recognition of the leukemia antigen was similar for both cell lines. After repeated immunization of strain 2 animals with BZ-L2C cells, animals were challenged with 3 X 10(5) viable cells; 9 of 13 animals survived. A subsequent 5 x 10 (6) challenge lowered survival to 8 of the 13 animals. The skin test response to BZ-L2C developed slowly during the immunization period, but survivors of the viable cell challenge exhibited good responses to skin testing with BZ-L2C or LE-L2C leukemic cells. Thus the BZ-L2C cell line possesses a leukemia-specific antigen, but the immunogenicity of this mutant line is decreased when compared to that of the LE-L2C line.

Animals↗
PubMed1977

Evidence for hydroxyl radical generation by human Monocytes.

A number of highly reactive oxygen species have been implicated in the oxygen-dependent mechanisms involved in bactericidal activity of phagocytic leukocytes. Hydrogen peroxide and superoxide, two agents known to occur during phagocytosis, are thought to interact to generate hydroxyl radical, singlet oxygen, and other potentially reactive molecules. Using an assay system of ethylene generation from methional, cell preparations of human monocytes were demonstrated to generate hydroxyl radical or a similar agent during phagocytosis of zymosan particles. The generation of ethylene was impaired by agents which reduce superoxide or hydrogen peroxide concentrations as well as by agents reported to be hydroxyl radical scavengers. The ethylene generation did not appear to be dependent on myeloperoxidase in that azide enhanced ethylene generation. Monocytes from a patient with chronic granulomatous disease failed to generate ethylene during phagocytosis. This assay technique may be useful in exploring the metabolic events integral to the bactericidal and inflammatory activity of phagocytic leukocytes.

Benzoates↗
PubMed1976

Transfer factor: a potential agent for cancer therapy.

This review has attempted to describe the characteristics of transfer factor which make it a very attractive potential agent for immunotherapy. Preliminary observations suggest that it may be capable of modifying resistance to a variety of diseases including cancer but considerable progress in basic knowledge regarding this agent is crucial to its successful application in clinical disease states. Fortunately, a sizable number of interested and dedicated investigators are exploring these difficult problems and their success may lead to new approaches in immunotherapy.

Animals↗
PubMed1976

Sarcoid lymphocytes: B- and T-cell quantitation.

Bone-marrow-derived B lymphocytes and thymus-dependent T lymphocytes were quantitated in a group of 38 patients with histologically confirmed sarcoidosis. B lymphocytes were identified by detecting surface immunoglobulins (Ig, IgG, IgM, and IgA) and complement receptors. T lymphocytes were identified by E-rosette assay. The untreated patients with both limited and disseminated disease had lymphopenia, reduced T-cell number, and low E/Ig cell ratios. Absolute numbers of circulating E-rosette lymphocytes did not show any correlation with cutaneous anergy. The numbers of Ig-bearing lymphocytes or the sum of the numbers of IgG, IgM, and IgA(GMA)-bearing lymphocytes were elevated in patients with disseminated disease, whereas the numbers of complement receptor lymphocytes were normal in all groups. It is proposed that this discrepancy of results on B-lymphocyte subpopulations might be explained by the presence of antibody or extrinsic antigen-antibody complexes bound to lymphocytes, as supported by elevated GMA/Ig ratios. The numbers of circulating B lymphocytes, as detected by any of three markers employed in this study, showed no correlation with the levels of serum immunoglobulins. The mechanisms of T-cell depletion and increase of immunoglobulin-bearing cells remain to be determined.

B-Lymphocytes↗
PubMed1976

Sarcoid lymphocytes: spontaneous transformation and release of macrophage migration inhibition activity.

A group of 26 untreated patients with histologically confirmed sarcoidosis were studied. Multiple immunologic parameters were defined, including spontaneous morphologic lymphoblastic transformation, spontaneous production of macrophage inhibitory factor activity, 8-day cell culture lymphocyte count, phytohemagglutinin-induced lymphoblastic transformation, and cutaneous reactivity to a battery of recall antigens. The in vitro impairment of phytohemagglutinin-induced lymphoblastic transformation occurred only in patients with more disseminated disease (Group II). Cutaneous anergy did not correlate either with the degree of in vitro phytohemagglutinin-induced lymphoblastic transformation or with the extent and known duration of disease. The in vitro occurrence of enhanced spontaneous morphologic lymphoblastic transformation and spontaneous release of macrophage inhibitory factor activity were demonstrated, but these did not always occur in the same lymphocyte cultures and appeared to be independent parameters of immunologic activity. In conclusion, it is suggested that, contrary to the previously held view of general depression of delayed hypersensitivity in sarcoidosis, the immune apparatus of patients with sarcoidosis may be hyperreactive. Further, it proposed that determination of the macrophage migration index may prove valuable in evaluating the activity of the disease.

Adult↗
PubMed1976

Immune function of successfully treated lymphoma patients.

Immunologic function was evaluated in 12 patients with Hodgkin's disease and 5 patients with lymphocytic lymphoma who had been successfully treated with either chemotherapy, radiation therapy, or both of these modalities 3-42 mo previously. Only two of the patients were found to have total anergy to a battery of six recall skin test antigens and all were responsive to skin testing with phytohemagglutinin. However, 10 of 16 patients were unable to develop delayed cutaneous hypersensitivity to either of the neoantigens dinitrochlorobenzene or keyhole limpet hemocyanin. Four other patients developed reactivity to only one of these neoantigens for a total of 14 of 16 (88%) of the patients demonstrating some impairment in neoantigen response. Total lymphocyte, T-lymphocyte, B-lymphocyte, and null cell numbers, as well as serum immunoglobulins were quantitatively normal. Monocyte numbers, chemotaxis, and Fc receptor activity were normal. Monocyte staphylocidal activity at 60 min was modestly depressed and candidacidal activity was depressed in those receiving both chemotherapy and radiation therapy. Spontaneous (unstimulated) lymphocyte [3H]thymidine incorporation was low in the patients as a group and lymphoblastic transformation to specific antigens was impaired in 11 of 17 patients who had positive skin test reactions to the same antigen. Highly significant suppression of lymphoblastic transformation was noted after stimulation by the mitogens phytohemagglutinin, pokeweed, and concanavalin-A. The greatest impairment of mitogen response was seen in those patients receiving both chemotherapy and radiation therapy. These data demonstrate specific impairments of neoantigen processing, lymphocyte function, and to a lesser extent monocyte function in successfully treated patients with lymphoma. These impairments may contribute to the increased incidence of infections and second primary malignancies in these patients.

Adolescent↗