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Biomedical subjects

J L McCoy

Publications and source records attributed to J L McCoy.

At least 55 records · Page 3Linked to original sources
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

Refractoriness to migration inhibitory factor of macrophages of LPS nonresponder mouse strains.

The responsiveness to macrophage migration inhibitory factor (MIF) of peritoneal exudate cells (PEC) from the LPS unresponsive C3H/HeJ and C57BL/10ScCR mice was assessed by the indirect agarose microdroplet macrophage migration inhibition assay. No migration inhibition with PEC from C3H/HeJ nor C57BL/10ScCR mice was detected, whereas PEC from both C3H/HeN and C57BL/10Sn mice were significantly inhibited by even a 1/32 dilution of MIF-containing supernatants. Responsiveness to MIF of C3H/HeJ PEC could, however, be induced. In vivo inoculations of Mycobacterium bovis, strain BCG, 7 days before in vitro assay rendered C3H/HeJ PEC responsive to MIF. The lack of responsiveness to MIF by C3H/HeJ PEC appeared related to some form of suppression, since a mixture of PEC from C3H/HeN mice with 10 to 15% PEC from C3H/HeJ mice resulted in undetectable migration inhibition at any MIF dilution. In contrast to the usual lack of responsiveness of their macrophage to MIF, C3H/HeJ mice were able to produce MIK in response to PPD as well as their counterpart C3H/HeN mice after BCG sensitization. These results demonstrate that macrophages from C3H/HeJ and C57BL/10ScCR mice are unable to be inhibited in their in vitro migration of MIF (possibly being directly or indirectly influenced by a suppressor cell), whereas lymphoid cells from at least one of these strains, the C3H/HeJ mice, can produce MIF in response to antigenic stimulation.

Animals↗
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↗
PubMed1978

Health status among low-income elderly persons: rural-urban differences.

This research compares the health status of low-income elderly persons in rural and urban areas. Using data from the Social Security Administration's 1973 national survey of low-income aged and disabled, the study demonstrates that the prevalence of many chronic disorders and impairments is significantly greater among the rural aged than for their cohorts in more urban areas. These differences persist after controls for age, sex, and race are introduced. No significant differences between rural and urban elderly were apparent in the utilization of health services. The determinants of chronic health status of the elderly have already occurred, by and large, and an explanation of disorders and impairments cannot be found by examining current sociodemographic status. Such an explanation is contained in the accumulated effects of years of residence in differing social, economic, and physical environments.

Aged↗
PubMed1977

Cell-mediated immunity against particulate and solubilized tumor-associated antigens of murine plasmacytomas detected by macrophage migration inhibition assays.

Cell-mediated immunity (CMI), as detected by the agarose microdroplet macrophage migration inhibition (MMI) assay, was investigated using peritoneal exudate cells (PEC) of BALB/c mice and several crude membrane (CM) and solubilized preparations of murine plasmacytomas. The MMI assay was quite sensitive and detected inhibition of macrophage migration as low as picogram quantities of CM, NP40 detergent- and papainsolubilized preparations (CS) of ADJ-PC5 and LPC-1 plasmacytomas. The data were highly reproducible from one experiment to the next with the same or different lots of the CM or solubilized extracts. Specificity studies demonstrated that ADJ-PC5 and LPC-1 plasmacytomas expressed cross-reactive tumor-associated antigens (TAA) as detected by MMI and confirmed by tumor challenge and Winn neutralization experiments. No cross-reactivity was observed with similar extracts prepared from an unrelated syngeneic simian virus 40 (SV40)-induced sarcoma. The inhibition of macrophage migration observed was mediated by culture supernatants generated from the mixture of plasmacytoma-immune spleen cells with antigens and then assayed in an indirect MMI assay on normal PEC. The agarose microdroplet MMI assay appeared to be a rapid and sensitive method to measure TAA recognition and to monitor TAA isolation and solubilization with minimum numbers of immune cells.

Animals↗
PubMed1977

The relative proliferation index as a more sensitive parameter for evaluating lymphoproliferative responses of cancer patients to mitogens and alloantigens.

Lymphocyte proliferation (LP) assays were performed in microculture using the T-cell mitogens phytohemagglutinin (PHA) and concanavalin A (Con A); the T + B cell mitogens, pokeweed mitogen (PWM) and staphylococcal phage lysate (SPL); and a pool of allogeneic stimulating leukocytes in one-way mixed leukocyte cultures (MLC) in lung and breast cancer patients and normal individuals. The resultant data were expressed in three different ways: (1) as mean counts per minute (CPM) of tritiated thymidine incorporation; (2) as a stimulation index (SI) and (3) as a relative proliferation index (RPI). The RPI is defined as the ratio of net CPM (nCPM) in experimental cultures with stimulant (E) minus medium control cultures (C) of a test individual to the mean nCPM of three or more normal individuals examined in the same assay on the same day. These expressions were then compared for their ability to discriminate between LP responses in cancer patients and normal individuals. The RPI value and selected cut-off values gave the most sensitive measure for the determination of depressed proliferative responses. These analyses demonstrated that lung carcinoma patients were depressed to PHA (50%), MLC (47%), PWM (43%) and Con A (40%). To a lesser degree, breast carcinoma patients were also depressed to MLC (36%), PHA (31%), PWM (27%) and Con A (19%). Our data indicate that the use of the RPI in the analysis of LP response represents an improved method for detecting impaired response of lymphocytes to general mitogens and alloantigens which can consistently reveal immunosuppression in many cancer patients and may be useful for serial monitoring of individual patients.

Antigens, Bacterial↗
PubMed1977

Human cell-mediated immunity to tuberculin as assayed by the agarose micro-droplet leukocyte migration inhibition technique: comparison with the capillary tube assay.

Direct and indirect agarose microdroplet migration inhibition assays were performed with log dilutions (50--5 X 10(-8) microgram/ml) of soluble purified protein derivative (PPD) of tuberculin and leukocytes (4 X 10(5)/droplet) from PPD skin test positive or negative individuals. Some tests were run in parallel with the capillary tube method. Inhibition of migration of leukocytes from 9/11 PPD skin test positive donors studied was observed in direct tests when employing PPD doses ranging from 1--50 microgram/ml PPD. Inhibition of migration of leukocytes from some PPD skin reactive donors was obtained with as little as 5 X 10(-3)--5 X 10(-7) microgram/ml (i.e., 5 nanograms to 0.5 picograms). Some inhibition of leukocyte migration was seen with skin test negative donors (presumably toxicity) with the higher doses of PPD (50 microgram/ml), but generally little inhibition was observed with these donors at lower doses. Comparative experimetns of the agarose micromethod and the capillary tube technique indicated that the agarose assay was more sensitive in that it could detect reactivity with 2--4 logs lower antigen concentration. Indirect assays using supernatants of cultures of PPD triggered mononuclear cells and indicator granulocytes in agarose droplets demonstrating that a lymphokine (presumable leukocyte inhibitory factor) was being produced and suggested that cell-mediate immune (CMI) reactions were operative. The results indicate the usefulness of this technique in the sensitive-detection of CMI against such antigens as soluble PPD. The assay should prove useful in quantitative assessment of cell-mediated reactivity by using a wide range of antigen concentrations and the leukocytes from as little as 2--5 ml of blood.

Antigens↗
PubMed1977

Cell-mediated immune responses of breast cancer patients to autologous tumor-associated antigens.

Lymphocyte proliferation assays with autologous tumor material in mixed leukocyte-tumor interactions (MLTI) were employed to monitor tumor-associated cell-mediated immune responses of peripheral blood lymphocytes from patients with carcinoma of the breast. In addition, leukocyte migration inhibition (LMI) assays were employed to compare reactivity to autologous breast-tumor extracts versus allogeneic breast-tumor extracts. Positive lymphoproliferative responses to tumor-associated antigens (TAA) were observed in the MLTI assay with the use of either intact autologous tumor cells or crude extracts (in mug and ng quantities) in 12 of 34 (35%) breast cancer patients studied. Positive reactivity to tumor, but not to normal tissue of reactive patients, was observed in repeated assays. Finally, patients demonstrating positive MLTI responses to autologous tumor extracts likewise responded in LMI assays to these same autologus extracts as well as to allogeneic breast-tumor extracts, but not to non-breast-tumor extracts. Thus breast tumors appeared to possess common TAA among both male and female patients.

Antigens, Neoplasm↗
PubMed1977

Leukocyte migration inhibition in patients with Ewing's sarcoma by 3-M potassium chloride extracts of fresh and tissue-cultured Ewing's sarcomas.

Leukocyte migration inhibition (LMI) assays were performed to detect cell-mediated immune reactions against tumor-associated antigens (TAA) of Ewing's sarcoma. With the use of crude antigen preparations obtained by 3M KCl extractions of fresh Ewing's sarcoma or of tissue culture cells derived from a pleural effusion of a Ewing's sarcoma patient, assays were performed with leukocytes from these patients, patients with other cancers, and normal donors. The results demonstrated approximately 60% or greater positive LMI reactivity in Ewing's sarcoma patients, as compared to less than 10% reactivity of normal donors, with the use of extracts of either fresh or tissue-cultured Ewing's sarcoma cells. A lower proportion of positive reactivity was observed in patients with breast and lung cancer. Further specificity tests indicated that a smaller proportion of patients with Ewing's sarcoma had LMI reactivity with KCl extracts of tissue-cultured cells derived from breast cancer of fresh lung cancer cells than did patients with the homologous disease. The results indicate that many patients with Ewing's sarcoma have cell-mediated immunity toward TAA on Ewing's sarcomas. Inasmuch as all the LMI assay were performed with allogeneic extracts, the data also suggested that different Ewing's sarcomas possess common antigens and that some breast and lung cancers may share some TAA with Ewing's sarcoma.

Antigens, Neoplasm↗
PubMed1977

Migration inhibition by an agarose microdroplet assay: monitoring of tumor-associated antigens on a simian virus 40-induced sarcoma.

Macrophage migration inhibition assays, with a direct agarose microdroplet method, were used to monitor TAA activity of preparations of SV-40-induced mKSA cells. These preparations included cell-free crude membranes, papain-solubilized and NP40 detergent-solubilized membrane extracts from mKSA tumor cells. The assay was extremely sensitive and could detect migration inhibition reactivity with all three types of antigenic preparations with concentrations as low at 250 ng protein/ml. The reactivities were quite reproducible from experiment to experiment using the same or different lots of these antigen preparations, and the reactivities were specific in that peritoneal exudate cells from BALB/c mice, immunized with antigenically unrelated but syngeneic plasmacytomas, were not inhibited by these antigens. The results demonstrated the usefulness of this assay in rapidly detecting small concentrations of partially purified TAA preparations by using small number of immune cells.

Animals↗
PubMed1976

Immunological monitoring and immunotherapy in carcinoma of the lung.

One hundred and seven patients with carcinoma of the lung underwent immunologic testing, and 62 of these patients were randomized to an immunotherapy protocol comparing the effects of Pasteur strain BCG, either alone or combined with allogeneic tumor cells, to the effects of no immunotherapy. Patients with residual disease left at the time of surgery or with metastatic disease at the time of diagnosis showed no increase in survival as a result of this form of immunotherapy. An insufficient number of patients with less advanced disease, in whom we would expect the most beneficial effect, have been entered in this study. In general, we were unable to document substantial effects of immunotherapy on the immunologic parameters tested. Only in recall antigen skin testing was there a statistically significant increase in reactivity in the immunotherapy groups. Tests of general immune status appeared to have a predictive value in monitoring lung cancer patients. Anergic patients had a poorer prognosis than did patients who demonstrated skin test reactivity. Patients with normal percentages of lymphocytes (T cells) forming rosettes with sheep erythrocytes at 29 degrees C were generally normal in other tests of immune competence. In serial studies of rosette formation, all patients who developed recurrent disease had a pattern of depressed or falling rosette values, and these abnormalities occurred an average of 3.1 months prior to clinical detection of recurrence. Patients with large-cell anaplastic carcinoma were found to have a significantly higher incidence of depressed rosette levels than the other histologic types. Both large and small-cell anaplastic patients had significantly depressed lymphocyte proliferation by mitogens and allogeneic cells. Although lung cancer patients have been described as immunologically depressed, they are capable of recognizing tumor-associated antigens. When tested in leukocyte migration inhibition assays with tumor-associated antigens, the majority of the patients in our study were found to be reactive. The use of a 3 M KCl extract of pleural effusion cells from a patient with pulmonary adenocarcinoma has given good reactivity and specificity in lung cancer patients of all histologic types. In addition, these patients have been shown to respond in a mixed lymphocyte/tumor interaction to tumor-associated antigens (Dean, 1976b).

Adenocarcinoma↗
PubMed1976

Cryopreservation of human lymphocyte function as measured by in vitro assays.

Methods are described by which cryopreserved cells can be utilized in a number of in vitro assays. On a per cell basis, nearly total recovery of function can be demonstrated for lymphocyte transformation (mitogens, antigens and MLC) and rosette-forming cells. Excellent recovery of mononuclear cell production of leukocyte migration inhibitory factor was also observed. Highly reproducible activity was recovered on a per lymphocyte basis in lymphocyte cytotoxicity but with a definite decrement in the percentage recovery. Both for longitudinal studies of immune function and for standardization of these assays in one or more laboratories such cryopreserved cells are ofimmense value and should be widely utilized.

Blood Specimen Collection↗
PubMed1976

Lymphocytes forming rosettes with sheep erythrocytes in metastatic pleural effusions.

Percentages of lymphocytes forming rosettes with sheep erythrocytes at 29 degrees C were determined in 10 cancer patients with metastases to the pleural cavity. Compared with normal controls, the patients showed a decreased proportion of rosette-forming cells (RFC) in the peripheral blood. The same patients had elevated levels of RFC in their metastatic pleural effusions. However, 2 patients with benign diseases had normal levels of RFC in their peripheral blood and pleural transudates. These observations suggested that in cancer patients some T-cells might migrate from the peripheral blood and accumulate in sites of tumor infiltration such as the pleural cavity.

Adult↗