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Biomedical subjects

R L Hunter

Publications and source records attributed to R L Hunter.

At least 109 records · Page 6Linked to original sources

Prognostic significance of immunological tests in lung cancer.

We performed a battery of tests on peripheral blood samples from 94 patients with lung cancer to determine the extent to which immunological depression was due to abnormal lymphocyte function, as compared to changes in the number of lymphoid cells in the peripheral blood or in the efficiency of purification of cells in Ficoll-Hypaque gradients in preparation for testing. The percentage of lymphocytes in the gradient-derived cell suspension (%LG) was the most informative test. It decreased significantly with advancing stage of cancer and could predict survival of patients with uniform stage. The %LG correlated with survival better than any other test when multivariate analyses of all test combinations were performed. Low values of %LG reflected both the depressed lymphocyte counts and the altered buoyant density of the leucocytes of many patients with advanced cancer. A large proportion of the depression in other immune function tests was statistically attributed to changes in %LG. We concluded that this simple measurement provides valuable information about patients with lung cancer.

Carcinoma, Bronchogenic↗

Studies on stimulation of cell-mediated cytotoxicity by skin test antigens. I. Candida antigen stimulation of cell-mediated cytotoxicity in vitro correlated with the skin test response to candida antigen in vivo.

The magnitude of the skin test response in a group of normal volunteers to intradermal Candida antigen correlated closely with the level of cytolytic activity stimulated by Candida antigen in vitro in the peripheral blood lymphocytes from those same individuals. The cytolytic activity stimulated by Candida antigen was cell mediated, and cold target inhibition studies demonstrated that Candida antigen-stimulated effector cells were capable of cross-species (i.e., nonspecific) killing. Analysis of the Candida antigen-induced effector cell population for various cell markers did not enable absolute identification of the cell responsible for the killing. The findings in this study indicate that the stimulation of cell-mediated cytolysis by Candida antigen may be related to the delayed-type hypersensitivity response produced by the same antigen.

Animals↗

The relationship between cytotoxicity and prognostically significant histologic changes in lymph nodes from patients with cancer of the breast.

Axillary lymph nodes obtained from 37 patients with cancer of the breast were used in a microcytotoxicity assay against a human mammary cancer cell line, ALAB. Cell suspensions made from 60 individual lymph nodes and 51 lymph node pools were tested. Each lymph node was graded for the extent of the histologic changes of sinus histiocytosis (SH), paracortical hyperplasia (PCH), and germinal center hyperplasia (GCH). High levels of cytotoxicity correlated significantly with the presence of SH and PCH. When multiple lymph nodes of individual patients were pooled and tested, a high intensity of GCH correlated with a low degree of cytototoxicity. The cytotoxic activity of pooled lymph nodes from different axillary regions was studied in 20 patients. In 7 of these patients, low axillary lymph node cells were more cytotoxic than high axillary node cells. The reverse was found for 7 patients, and there was no difference in cytotoxicity between axillary regions in 6. Cytotoxic lymph node pools had high SH and low GCH whether they were obtained from the low or high region. Noncytotoxic lymph node pools from the high axillary region had a low intensity of all three histologic reactions. In contrast, noncytotoxic lymph node pools from the low axillary regions had high intensities of SH, PCH, and GCH. These results suggest that germinal center hyperplasia in the lymph nodes nearest an advancing tumor is associated with a local suppression of cytotoxic cell activity.

Adult↗

Prediction of survival in gynecological cancer based on immunological tests.

Patients with advanced cancer have a depressed immunological function. We performed a battery of tests on peripheral blood samples from 42 patients with gynecological cancer to determine the extent to which this depression was due to abnormal lymphocyte function, as compared to changes in the number of lymphoid cells in the peripheral blood or in the efficiency of purification of cells in Ficoll:Hypaque gradients in preparation for testing. The percentage of lymphocytes in the gradient-derived cell suspension (% LG) and the absolute lymphocyte count were more informative than mitogen stimulation, mixed leukocyte culture, and T- and B-cell measurements. Both values decreased significantly with the advancing stage of cancer, and we were able to predict survival of patients with uniform stage of disease. The % LG correlated with survival better than did any other test when multivariate analyses of all test combinations were performed. Low values of % LG reflected both the depressed lymphocyte counts and the altered buoyant density of the leukocytes of many patients with advanced cancer. A large portion of the depression in other immune function tests was statistically attributed to changes in % LG and the lymphocyte counts. We concluded that these two simple measurements provide valuable information about patients with gynecological cancer.

Female↗

Prediction of survival in head and neck cancer based on leukocyte sedimentation in Ficoll-Hypaque gradients.

A battery of immunologic tests were performed on 42 patients with recurrent cancer of the head and neck whose median survival time was 6.8 months. Two tests correlated with survival: total white blood cell (WBC) count and the percentage of lymphoid cells (%LG) in the Ficoll-Hypaque gradient separated leukocyte fraction of blood. Patients with abnormally low values of %LB had a poor prognosis, as did patients who had greater than 8000 WBC count. Of the variation in %LG, 43% was due to the differences in differential WBC counts among the patients, with the remaining variation attributed to changes in the buoyant densities of the leukocytes. These data suggest that further study of the factors effecting buoyant density of cells may be clinically useful.

Cell Count↗

Lymphocyte stimulation by yeast phase Histoplasma capsulatum in presumed ocular histoplasmosis syndrome.

We measured skin reactions serum antibody, and lymphocyte stimulation to Histoplasma antigens in a series of patients with presumed ocular histoplasmosis syndrome and in controls. The most sensitive test, lymphocyte stimulation to H. capsulatum sonicate, also correlated with severity of the disease. Lymphocyte stimulation to Histoplasma may be a useful adjunct to the monitoring of presumed ocular histoplasmosis syndrome.

Antibodies, Fungal↗

Induction of cell-mediated immunity to chemically modified antigens in guinea pigs. II. The interaction between lipid-conjugated antigens, macrophages, and T lymphocytes.

Protein antigens covalently conjugated with lipid groups (dodecanoic acid) have previously been shown to stimulate strong delayed-type hypersensitivity (DTH) without the aid of adjuvants. The present experiments show that lipid-conjugated bovine serum albumin (L-BSA) is taken up in vitro by macrophages (Mpsi) 25- to 50-fold more than unconjugated BSA or aminidated BSA, neither of which induces DTH. Macrophages that take up 125I-labeled L-BSA in vitro stimulate DTH even more efficiently, when injected into syngeneic guinea pigs, than does soluble L-BSA. Tracer studies on the fate of radiolabeled BSA and L-BSA showed that much more L-BSA than BSA was retained by draining lymph nodes. Autoradiography demonstrated that 125I-L-BSA is rapidly taken up by Mpsi in the medullary sinuses of the lymph nodes. Some of this antigen is then transported into the paracortex, a region in which T lymphocytes predominate. The capacity of lipophilic antigens to stimulate cell-mediated immune responses may be caused by their increased uptake by Mpsi, resulting in more efficient presentation to immunocompetent T lymphocytes. The anatomical site of this Mpsi-T cell interaction may be within the sinusoids or paracortex of the draining lymph nodes.

Animals↗

Induction of cell-mediated immunity to chemically modified antigens in guinea pigs. I. Characterization of the immune response to lipid-conjugated protein antigens.

Bovine serum albumin (BSA) conjugated with a lipid, dodecanoic acid, is capable of inducing strong delayed-type hypersensitivity (DTH) in guinea pigs. This paper reports experiments on the nature and specificity of this hypersensitivity. The response to lipid-conjugated BSA (L-BSA) was found to be classical DTH, as evidenced by its ability to be transferred passively by immune cells, but not by serum. In addition, special histologic examination of skin test sites demonstrated the characteristics of DTH rather than cutaneous basophil hypersensitivity. Similar results were obtained when lipid-conjugated purified protein derivative of tubercle bacilli (L-PPD) was used. The increased immunogenicity of L-BSA was not caused by the presence of protein aggregates, but seemed to be related to the hydrophobic nature of the conjugated side chains. A series of cross-reacting serum albumins was used for a study of the specificity of the antibody and DTH responses to BSA. It was found that the degree of enhancement of immunogenicity for DTH caused by lipid conjugation varied for different antigenic determinants on BSA.

Animals↗

Survival with mammary cancer related to the interaction of germinal center hyperplasia and sinus histiocytosis in axillary and internal mammary lymph nodes.

In a review of the histologic sections of axillary and internal mammary lymph nodes removed during surgery for invasive ductal carcinoma of the breast, we found that 16 of 17 patients in whom sinus histiocytosis was the dominant lymphoid proliferative reaction are alive with no evidence of cancer 5 or more years after operation. In contrast, 5 of 6 patients in whom germinal center hyperplasia was the only significant reaction found died of cancer in less than 5 years. Patients with both sinus histiocytosis and germinal center hyperplasia in significant amounts had survival that was intermediate; 17 of 25 of these patients are currently alive and apparently free of cancer. In addition, 5 of 6 patients in whom no evidence was found of any lymphoid proliferative reaction and 3 of 3 patients with diffuse cortical hyperplasia in their axillary lymph nodes died of cancer in less than 5 years. Germinal center hyperplasia was associated with nodal metastases anatomically in individual lymph nodes and statistically in the series of cases. The internal mammary lymph nodes of most cases showed less proliferative reaction to tumor than the axillary lymph nodes. The pattern of proliferative reactions in lymph nodes and its correlation with survival after surgery suggest that different immune reactions may either suppress or enhance the growth of carcinoma of the breast.

Axilla↗

Immunization with a lipid-conjugated membrane antigen to suppress growth of a fibrosarcoma induced by simian virus 40.

The covalent conjugation of fatty acid to a tumor cell membrane preparation transformed it from an antigen that enhanced tumor growth to one that suppressed it. A crude cell membrane preparation was made by sequential hypertonic and hypotonic salt extraction of tumor cells from a fibrosarcoma induced in hamsters by simian virus 40. The membranes were chemically conjugated with dodecanoic anhydride in 0.5 M carbonate buffer (pH 9.0). Injection of unmodified membranes 10 days before transplantation of live tumor cells produced clear-cut enhancement of the tumor growth rate. In contrast, injection of lipid-conjugated membranes in a similar dose and protocol suppressed tumor growth. The lymphoid proliferative reactions to the tumor cells as demonstrated by the histology of both the tumor and regional lymph nodes were consistent with the hypothesis that unmodified membranes stimulated the production of antibody which participated in the enhancement of tumor growth, and that lipid-conjugated membranes stimulated the production of cell-mediated immunity which suppressed this growth.

Animals↗