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Biomedical subjects

J H Dean

Publications and source records attributed to J H Dean.

At least 91 records · Page 5Linked to original sources
PubMed1979

Increased monocyte-mediated cytostasis of lymphoid cell lines in breast and lung cancer patients.

Peripheral blood mononuclear cells of most normal adults and patients with breast or lung cancer were found to inhibit [3H] thymidine uptake by lymphoid cell lines in a growth inhibition assay. At effector:target cell ratios between 5:1 and 20:1, lung cancer patients and breast cancer patients, when compared to normal individuals, demonstrated significantly greater inhibition of [3H] thymidine uptake by a human lymphoid cell line (F-265). The effector cells were adherent and were probably monocytes. Sephadex G-10 column passage or adherence to plastic removed most growth-inhibitory activity. Adherent cells recovered from plastic flasks (88-94% monocytes) were strongly growth-inhibitory. Lung cancer patients receiving BCG immunotherapy were found to have an apparently increased activity compared to patients not treated with BCG. The possible mediation of the growth inhibition by release of prostaglandins was suggested by the reduced cytostatic effects in the presence of indomethacin. Growth-inhibitory activity was not species-restricted, since human effector cells and also effector cells from tumor-bearing mice were reactive against the human target cell and against a murine lymphoma line (RBL-5). Natural killer (NK) cells did not appear to contribute appreciably to the observed cytostasis, since the levels of their activities did not correlate, and human NK cells are non-adherent and have little reactivity against F-265 or RBL-5. The inhibition of [3H]thymidine uptake by target cells was demonstrated to be a good reflection of actual inhibition of proliferation, since incubation of adherent cells from cancer patients with F-265 resulted in similar degrees of reduction in the number of target cells and in [3H] thymidine uptake.

Animals↗
PubMed1979

Cytolytic activity of circulating human monocytes on transformed and untransformed human fibroblasts.

Monocytes from the peripheral blood of 10 normal adult human donors were tested for their cytolytic activity on untransformed or SV40-transformed, early passage, human fibroblasts. Two pairs of human fibroblast lines (2303 and SV40-2303, 2931 and SV40-2931) were used and lysis was assessed in terms of release of [3H]thymidine from prelabelled target cells over a 72-h incubation period. High levels of cytolytic activity were consistently observed on transformed fibroblasts at attacker to target cell (A:T) ratios ranging from 5:1 to 40:1. Low, but significant, lysis of untransformed cells was observed only with two donors at the highest (40:1) A:T ratio tested. With all donors, the cytolytic activity on transformed lines was significantly greater than on untransformed fibroblasts. Thus natural human monocyte-mediated cytotoxicity is preferentially expressed on transformed, as compared to untransformed, cells although sparing of the latter is not absolute.

Adult↗
PubMed1979

Assessment of immunobiological effects induced by chemicals, drugs or food additives. I. Tier testing and screening approach.

The indications of immunologic dysfunction following low level exposure of rodents or even man to certain chemicals and drugs have raised concern regarding methodology and approaches for routine assessment of immunobiological effects. The immunogiological effect observed may either indicate impaired immunopotentiation or hypersensitization. The assays selected for testing should be relevant to the human experience and adaptable to certain practical considerations such as cost, reproducibility of data, ease of performance and application to routine toxicology studies. Using these considerations, a tier approach was proposed consisting of assays for screening for immunologic effects (Tier I) and assays to help define the mechanisms responsible for the immunobiological effects observed (Tier II). A tier of assays was also proposed for measuring the sensitization potential of certain compounds. Certain assays from the screening tier were assembled into a hypothetical and practical test battery to screen for immunological effects of a chemical with potential immunosuppressive properties. Information provided by this test battery should provide a reasonable and sensitive data base from which a standard of evaluation could be made regarding the safety of the test (1) compound.

Animals↗
PubMed1979

Immunologic abnormalities in melanoma-prone families.

Sixty members of 4 families prone to cutaneous malignant melanoma (CMM) and a genetically determined precursor nevus syndrome underwent extensive immunologic evaluation. The most consistent finding was a diminished in vitro response to pooled alloantigens in the one-way mixed leukocyte culture (MLC) and a tendency to low T-lymphocyte and B-lymphocyte levels. When compared to controls, low B-lymphocyte levels and reduced MLC responses were found not only in family members with CMM and/or precursor nevi but also in unaffected blood relatives and spouses. The genesis of the immune dysfunction and its possible relationship to melanoma pathogenesis remain to be clarified.

B-Lymphocytes↗
PubMed1978

Demonstration of specific cell-mediated anti-tumor immunity in lung cancer to autologous tissue extracts.

Cell-mediated immunity (CMI) of lung cancer patients to autologous tumor antigens was assessed by mixed lymphocyte tumor interactions (MLTI) as measured in a microculture (200 microliter) lymphocyte proliferation (LP) assay. Positive lymphoproleferative responses were observed with cryopreserved intact mitomycin-C-treated autologous tumor cells (8/12 or 67% patients reactive) and with hypotonic membrane extracts (HMP) of tumor cells (28/40 or 70%). Good correlation was found between reactivity to tumor cells and extracts in parallel testing. In contrast, HMP of autologous normal lung tissue elicited very little LP reactivity, with only one patient giving a weak response by the SI criterion and low level of n cpm. Upon repeat testing, many patients gave reproducibly positive LP responses to tumor HMP. Patients at all clinical stages of disease and with different histologic tumor types had a similar proportion of HMP reactivity. Most reactive patients responded to a broad range of protein concentrations of tumor HMP, and LP responses were frequently elicited with 1 microgram or less of HMP. Thus, HMP appear to afford a convenient source of reactive tumor antigen for assessing anti-tumor immunity.

Adenocarcinoma↗
PubMed1978

Brief communication: technical modifications of the human agarose microdroplet leukocyte migration inhibition assay.

Direct leukocyte migration inhibition assays using the capillary tube technique can be used to demonstrate cell-mediated immunity in vitro. Unfortunately, the cumbersome nature of this technique makes it time consuming and difficult to perform. Similar results have been obtained using the direct agarose microdroplet leukocyte migration inhibition assay. In this paper, modifications of the agarose technique are outlined which insure standardization of droplets and ease of performance of the assay. Additionally a technique is described to reduce the time required for calculation of results.

Cell Migration Inhibition↗
PubMed1978

Conditions for generating and assaying human leukocyte inhibitory factor (LIF) induced by purified protein derivative (PPD).

This report examines a variety of experimental conditions for the production of human leukocyte inhibitory factor (LIF). The data indicate that the production of LIF as measured in the indirect capillary-tube migration inhibition assay using human polymorphonuclear indicator cells accurately reflects delayed hypersensitivity to purified protein derivative (PPD) as detected by skin-test reactivity. Mononuclear cells and semipurified lymphocytes separated from whole blood by sedimentation in Ficoll-Hypaque were able to generate LIF in response to PPD. The quantity of cells responsible for LIF production were standardized and as little as 1 x 10(6) mononuclear cells were required for detectable LIF production. LIF produced by mononuclear cells required only temporary exposure to PPD, thus eliminating the necessity for a control to which antigen was added at the end of culture to antigen-free supernatants. In addition, the removal of antigen after a brief exposure helps to avoid the possible toxic effect of some antigens on the migrating polymorphonuclear leukocytes (PMNL) population. LIF production did not require extraneous serum protein (i.e., fetal bovine serum). Further, kinetic studies indicated that LIF was detected as early as 8 hr following a 2 hr-exposure to PPD and that even a 1 hr-exposure was sufficient to generate measurable detectable quantities of LIF. After 48 hr of culture, supernatants were found to contain considerable amounts of LIF, with reactivity at dilutions as high as 1:40.

Cell Migration Inhibition↗
PubMed1978

Immunogenetic determinants of familial acute lymphocytic leukemia.

Acute lymphocytic leukemia developed almost simultaneously in two adolescent brothers, and another brother and both parents had rheumatoid arthritis. Laboratory studies uncovered no evidence for an underlying immunodeficiency state in the family. Immunogenetic evaluation showed the leukemic siblings to be HLA- and mixed-leukocyte-culture identical and homozygous for a recessively inherited locus dictating the presence of antigens on the surface of B-cells. This Ia antigen, as detected by sera from mothers of leukemic children, appeared to be mapped within the major histocompatibility region and may be a human analogue to murine immune-response antigens associated with susceptibility to leukemia.

Adolescent↗
PubMed1978

Restorative effects of levamisole on cell-mediated immune responses following chemotherapy with aniline mustard in mice bearing ADJ-PC5 plasmacytoma.

Restorative effects of levamisole on general and tumor-associated cell-mediated immune responses were investigated following aniline mustard (AM) chemotherapy of BALB/c mice bearing ADJ-PC5 plasmacytoma. Total eradication of tumor following AM chemotherapy resulted in severe depression of lymphoproliferative (LP) responses which recovered after a prolonged period of 4-6 weeks. During this time, spleen cells from these treated mice were shown to be generally depressed to T- and B-cell mitogens. Levamisole, an anthelmintic drug capable of enhancing depressed immune responses in mice and in man, was employed following AM chemotherapy in an attempt to restore immunocompetency. Administration of levamisole following AM had a significant effect on the ability of mice to resist rechallenge with ADJ-PC5 tumor and in tumor cell neutralization. The enhanced resistance to tumor cell challenge appeared to be associated with a faster recovery of the general T-cell immunocompetence as demonstrated in the LP assays among the mice receiving chemotherapy followed by adjuvant therapy. Levamisole, when administered alone to tumor-bearing mice, did not appear to possess a direct antitumor effect. In addition, levamisole did not potentiate cellular immunity to higher than normal levels in nonimmunodepressed mice. These results demonstrate the efficacy of levamisole as a restorative agent of the general and tumor-associated immunocompetency in the immunodepressed host.

Aniline Mustard↗
PubMed1978

Cellular immunity to solubilized tumor antigens of a methylcholanthrene-induced sarcoma with a migration inhibition assay.

BALB/c mice immunized with Nonidet P-40 (NP-40) crude solubilized (CS) extracts of a syngenetic methylcholanthrene-induced BALB/c sarcoma (Meth A) were challenged with viable Meth A cells to determine the ability of the solubilized preparations to induce transplantation rejection. Animals resisting such challenge were then used in agarose microdroplet macrophage migration inhibition (MMI) and tumor cell neutralization (Winn) assays to evaluate the antigenic specificity of these CS extracts. Spleen cells from those animals that rejected Meth A after immunization with the NP-40-solubilized preparations effectively neutralized the tumor-producing capacity of Meth A tumor cells as determined in Winn assays. MMI assays were quite sensitive and detected migration inhibition of peritoneal exudate (PE) cells from immunized mice with extract concentrations as low as picogram quantities. Specificity studies demonstrated that Meth A expressed no antigenic cross-reactivity with similarly prepared extracts of an unrelated SV40-induced sarcoma (mKSA), nor with a mineral oil-induced plasmacytoma (ADJ-PC5) of BALB/c mice. Inhibition of PE cell migration was mediated by culture supernatants (presumably migration inhibition factor [MIF]) generated from a mixture of immune spleen cells and mitomycin C (MMC)-treated Meth A cells as assayed in an indirect MMI test.

Animals↗