Robert L. Hunter

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.

Adjuvant Effect of Nonionic Block Polymer Surfactants in Humoral and Cellular Immunity

The adjuvant activities of four chemically similar, but physicochemically different nonionic surface-active agents called pluronic polyols F 68, L 31, L 101 and L 121 were studied. These four agents were tested in mice using an experimental model developed for studying the adjuvant activity of the cationic surface-active agent dimethyl dioctadecyl ammonium bromide (DDA). L 121 and DDA enhanced the primary antibody response to sheep red blood cells (SRBC) while F 68, L 31 and L 101 suppressed this response. The secondary humoral response to SRBC was enhanced by the polyol L 121 while the secondary response to dinitrophenylated bovine serum albumin (DNP22-BSA) was enhanced by both L 121 and L 101. DDA and the polyol L 101 were very effective adjuvants for induction of delayed-type hypersensitivity (DTH) to SRBC and DNP22-BSA after intracutaneous immunization of mice with a mixture of antigen and adjuvant. Since the four pluronic polyols were composed of identical chemical constituents, we proposed that difference in their activities as adjuvants were due to variation in their physicochemical properties. A correlation was found between a physicochemical parameter, the hydrophilelipophile balance (HLB), and the adjuvant activities of the pluronic polyols and several other types of nonionic surface-active agents. The agents which were strong adjuvants all had HLB values within a narrow range which classified them as spreading agents.

Studies on an oncofetal antigen, POA.

This paper describes the purification and partial characterization of a putative oncofetal antigen, POA, which appears to be associated with the pancreas. POA is a glycoprotein of molecular weight between 800,000 and 900,000 daltons. It is found in fetal pancreas and pancreas cancer tissue, but not in normal adult pancreas. It is clearly different from carcinoembryonic antigen, other known tumor associated antigens, acute phase reactants and normal serum proteins. A quantitative rocket immunoelectrophoresis assay was developed for POA. Its specificity was monitored routinely by double immuno‐diffusion against known fetal and adult standards. The assay was performed on sera from over 700 patients. The results demonstrate that POA is found in the sera of most individuals. However, by far the highest absolute levels and the highest frequency of elevated levels was found in sera of patients with carcinoma of the pancreas. Elevated levels of POA were also found in the serum of a proportion of patients with carcinomas of the lung, stomach, colon, biliary tract, and breast and in a few other individuals with benign conditions. The spectrum of patients who have elevated levels of POA in their serum is quite different from that found with CEA or other known tumor markers.

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.

Humoral and cellular responses to native antigen following oral and parenteral immunization with lipid-conjugated bovine serum albumin

Abstract Humoral and cellular immune responses of rabbits to bovine serum albumin (BSA) were measured following oral and parenteral immunization with either BSA or one of two dodecanoic acid conjugates of BSA. The first consisted of a mixture of lightly and heavily conjugated BSA-molecules (L-BSA-mix), while the second (L-BSA) was a homogeneous preparation of heavily conjugated BSA with more than 95% of the 60 available amino groups covalently bound to dodecanoic acid. Animals ingesting L-BSA-mix had a similar humoral immune response but enhanced cellular reactivity to BSA in comparison to animals ingesting the native antigen. No systemic immunologic responses to BSA were detected following ingestion of L-BSA in spite of the demonstration of circulating BSA antigenic groups. This lack of a detectable immune response after oral administration was not due to masking of antigenic sites by the lipid residues since both humoral and cellular immune responses to BSA were obtained in animals injected with L-BSA. Ingestion of L-BSA did not induce tolerance since a subsequent injection of BSA elicited a normal primary immune response. The differences in immunogenicity between BSA, L-BSA and L-BSA-mix following oral administration may be related to different modes of antigen recognition by the gut-associated lymphoid tissues.

Suppression of graft-versus-host disease and antibody formation by phytohemagglutinin: Examples of antigen competition

SUMMARY Phytohemagglutinin (PHA) has been used to suppress both graftversus- host disease and antibody formation in mice. However, PHA heated at 100 C for 30 min to destroy its in vitro mitogenicity and certain antigens produced quantitatively similar suppression. Consequently, the immunosuppressive effects of PHA demonstrated in our experiments were unrelated to its in vitro mitogenicity and are probably results of antigen competition

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.

Effects of Antilymphocyte Serum on the Localization of 125I-Labeled Flagella, Colloidal Carbon, and Titanium Dioxide in Splenic Lymphoid Follicles

Studies were undertaken in order to further define the effects of antilymphocyte serum (ALS) on the localization of antigen and colloidal particles in splenic lymphoid follicles.