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Biomedical subjects

J A Stratton

Publications and source records attributed to J A Stratton.

At least 37 records · Page 2Linked to original sources
PubMed1983

In vivo antineoplastic activity of various biological response modifiers for tumors of the ovary and breast.

Fourteen pharmacologic agents reported to have biological activities which are directly or indirectly antineoplastic, were assayed for their ability to inhibit the growth of a mouse neoplasia (M5076) and a rat mammary adenocarcinoma (13762) implanted beneath the renal capsule of the host. Ascorbic acid, cimetidine hydrochloride. Corynebacterium parvum, dimethylsulfoxide, naloxone hydrochloride, indomethacin, muramyl-dipeptide, Protein A from Staphylococcus aureus, theophylline, tilorone (analog R11, 877DA), tuftsin diacetate and sodium ibuprofen were completely inactive as antineoplastic agents for these 2 tumors. In fact, theophylline and dimethylsulfoxide seemed to enhance the formation of 13762 metastases. Blue tongue virus and polyinocinic-polycytidylic acid were marginally effective antineoplastic agents for 13762. Polyinocinic-polycytidylic acid was an excellent antineoplastic agent for M5076; this agent not only prevented the growth of M5076, it was oncolytic.

Adjuvants, Immunologic↗
PubMed1983

Accurate predictions of tumor growth in vivo: the subrenal capsule implant site.

An assay system with exquisite predictive qualities is described for four animal tumors: two rat mammary adenocarcinomas, R3230 Ac and 13762; a mouse papillary mammary carcinoma, MXT; and the mouse reticulum cell sarcoma M5076. The tumors were implanted beneath the renal capsule of syngeneic hosts (BDF1 mice or Fischer 344 rats). This site is readily accessible, well-protected, and provides a rich vascular bed, thus controlling many of the variables involved in neoplastic growth. The growth of each implant was recorded as a function of time and/or the initial tumor size. The absolute growth of each of the tumors could be predicted accurately from a simple linear regression analysis of time (i.e., number of days post-implant). Even more accurate predictions of tumor growth were obtained when both variables (days post-implant and initial implant size) were evaluated by multiple regression analysis. The subrenal capsule tumor implant site provides a superior model system to investigate the effects of biological response modifiers and other immunological manipulations on tumor growth in intact normal immunocompetent animals.

Animals↗
PubMed1982

Effect of immunomodulating factors present in ascitic fluids and sera from cancer patients on the responses of cultured mononuclear cells from normal subjects.

Ascitic fluids and sera from patients with malignant tumors were tested for their ability to modulate the mitogen-induced blastogenic responses of normal subjects' peripheral blood mononuclear cells in vitro. The addition of either ascitic fluid or serum to cultures of normal blood cells greatly enhanced the blastogenic response of cells to phytohemagglutinin P, and markedly depressed the responses to concanavalin A and succinyl-concanavalin A. The blastogenic response of the cells to pokeweed mitogen was unaffected by the addition of serum and depressed by the addition of ascitic fluid. Autologous normal serum also enhanced the response to phytohemagglutinin P but had no effect on the response to the other mitogens. These activities were concentration-dependent and heat-stable (56 degrees C, 60 min) and could be detected even if the ascitic fluid or serum was added as late as the second day of culture. Cells that had been preincubated with serum or ascitic fluid and washed well before culturing with the mitogens responded in the same manner as cells cultured in the presence of serum or ascitic fluid. The mitogen-induced blastogenic responses of mononuclear cells were not affected by the addition of autologous cells that had been preincubated with either serum or ascitic fluid, washed, and treated with mitomycin C. Indomethacin (2 X 10(-7)M) did not prevent the ascitic fluid-mediated depression of blastogenic responses of normal cells. The ascitic fluid and serum of these cancer patients appeared to contain a specific immunoinhibiting substance which exerted its effects by a direct action on the responding mononuclear cells and not by the induction of suppressor cells.

Adult↗
PubMed1982

Depressed mononuclear cell function in advanced neoplastic disease.

The ascites fluids from 9 patients with invasive gynecologic neoplasms were examined to determine the immunocompetence of the mononuclear ascites cells and the immunoregulatory properties of the cell-free ascitic fluid. Blood mononuclear cells (from 5 patients) were also tested. The mononuclear cells from the cancer patients responded poorly to stimulation with polyclonal mitogens; only the blood mononuclear cell response to pokeweed mitogen was not significantly less than that of normal subjects. The addition of autologous serum or cell-free ascitic fluid to the cell cultures enhanced the response of the cells to phytohemagglutinin and pokeweed mitogen, had little effect on the response to concanavalin-A, and greatly depressed the response to succinyl-concanavalin-A. We found no evidence for the presence of suppressor cells in the ascites cell populations. The data are consistent with the thesis that the depressed immune responses are the result of malnutrition associated with advanced malignant disease.

Ascitic Fluid↗
PubMed1982

Recovery of lymphocyte function after radiation therapy for cancer in relationship to prognosis.

The number and functional abilities of lymphocytes from patients with either breast cancer or cervical cancer were assessed before, during and after radiation therapy given to treat the disease and the patients were followed for several years. Radiation depleted both T and B cells and depressed the responses to PHA and Con-A in all patients groups. The response to mitogens in the weeks immediately following radiation therapy was greater in patients whose disease did not recur and was depressed for a much longer time in patients whose disease recurred within the next few years. This difference was most clearly reflected in the ratio of mitogen response to the number of T-cells. The relationship of responsive to non-responsive or suppressor lymphocytes in the weeks following radiation therapy may be a clue to prognosis.

Adult↗
PubMed1981

The immunoinhibitory activities of the lung lavage materials and sera from patients with pulmonary alveolar proteinosis (PAP).

Pulmonary alveolar proteinosis (PAP) is a diffuse pulmonary disease of unknown etiology, characterized by the accumulation of large amounts of amorphous phospholipid containing material in the alveolar spaces. Lavaging the lungs with large amounts of saline to remove the accumulated material results in marked clinical improvement and often complete remission. We have examined theperiperal blood and lung lavage material from 6 PAP patients in an attempt to detect abnormalities of the normal immune response. The complete blood counts and the numbers of T and B lymphocytes and monocytes were normal: the lavage fluids contained large numbers of macrophages, most of which were engorged with the amorphous material, and varying numbers of lymphocytes and polymorphonuclear leukocytes. The lavage material inhibited the blastogenic response of mononuclear cells to mitogens: 3HTdR incorporation in response to stimulation with concanavalin-A and Pokeweed mitogen was inhibited in both allogeneic and autologous cells, while response to phytohemagglutinin stimulation was inhibited only in autologous cells. The sera of the PAP patients inhibited 3HTdR incorporation in response to all three mitogens. Neither the lavage material nor the sera inhibited E-rosette formation, nor were they cytotoxic to allogeneic mononuclear cells. Thus while the peripheral blood monoculear cells from patients with PAP appeared to respond normally in vitro, the sera and lavage material contained substances which inhibited the in vitro response of mononuclear cells toi mitogens by interfering with normal monocyte-lymphocyte interactions. The inhibiting material does not appear to be immunoglobulin.

Adult↗
PubMed1980

Breast milk lymphocyte response to K1 antigen of Escherichia coli.

Comparison milk and blood lymphocyte blastogenic responses to the K1 antigen of Escherichia coli and lipopolysaccharide (LPS) from E. coli O127,B8 were examined in 16 postpartum women by [3H]thymidine uptake. Rabbit hemolysincoated sheep erythrocyte monolayers were used to deplete macrophages from milk lymphocyte preparations and to enrich for T lymphocytes in order to make milk preparations more comparable to blood preparations. Response was defined as a stimulation index of greater than or equal to 2.0. There was no evidence of selective response to K1 antigen by milk lymphocytes, since both blood and milk lymphocytes responded in four women and neither blood nor milk lymphocytes responded in nine. Milk lymphocytes alone responded to K1 in one woman, whereas blood lymphocytes alone responded in two women. Additional nonpaired milk or blood cultures were available from three women. None of these responded to K1 antigen. Corresponding lymphocyte cultures were stimulated with LPS. A positive K1 response was always accompanied by an LPS response, and the LPS response correlated with the K1 response in 17 of 19 women. Stool cultures examined with an antiserum agar showed no correlation between the presence of K1 E. coli in the stool and milk or blood lymphocyte response to K1 antigen. In the system used here, no selectivity of response of breast milk lymphocytes to K1 antigen was noted.

Antigens, Bacterial↗
PubMed1979

The protection of primates against soman poisoning by pretreatment with pyridostigmine.

The effectiveness of pyridostigmine pretreatment against soman poisoning has been determined in rhesus monkeys and marmosets receiving atropine therapy. Pretreatment with the maximum sign-free dose (200 microgram kg-1, i.v.) raised the subcutaneous LD50 of soman by a factor of 28 in rhesus monkeys and 15 in marmosets. The protection afforded by a quarter of the sign-free dose of pyridostigmine was not significantly less. These levels of protection are higher than any reported in non-primate species.

Animals↗
PubMed1976

Structural aspects of immune recognition of lysozymes. III. T cell specificity restriction and its consequences for antibody specificity.

We have studied the relationship between the determinants encountered by T cells on an antigenic molecule and the specificities of the antibodies eventually produced by the B cells with which these T cells cooperate. The number of epitopes on the hen lysozyme (HEL) molecule available to T cell receptors was functionally limited by inducing T cell tolerance to HEL in rabbits. Highly cross-reactive lysozymes were then used to challenge the HEL-unresponsive rabbits. Only T cells which recognize new epitopes on the challenge lysozymes could act as helpers in generating an anti-lysozyme response. Amino acid differences between Japanese quail lysozyme (JEL) and HEL are segregated within a single quadrant of this small antigen molecule. HEL-tolerant rabbits challenged with JEL produced antibodies which were totally cross-reactive with the tolerogen HEL. This result is in contrast to the result obtained in nontolerant rabbits which produced antibodies to JEL which were only 50-70% cross-reactive with HEL. We conclude that T cells restricted to the JEL-unique epitopes were only capable of cooperating with B cells specific for common epitopes shared between JEL and the tolerogen HEL. Turkey lysozyme (TEL), on the other hand, bears different amino acids which are distributed over several regions on the surface of the molecule. Any one HEL-tolerant rabbit developed a restricted response to TEL; in some rabbits the anti-TEL was highly HEL cross-reactive, while in others little cross-reactivity with HEL was observed. Each of four HEL-tolerant rabbits injected with the minimally altered bob-white quail lysozyme possessed the reactive T cells necessary to mount a limited response to this challenge lysozyme, suggesting a diverse library of T cell specificities. Recognition of the small differences between the challenge lysozymes and the T cells of these tolerant rabbits to make a fine discrimination between minimally changed epitopes.

Animals↗
PubMed1975

A comparison of the acute effects of radiation therapy, including or excluding the thymus, on the lymphocyte subpopulations of cancer patients.

Radiation therapy to either mediastinum or pelvis causes a rapid decrease in circulating lymphocytes of both B and T types and in addition an impairment in the function of the remaining lyphocytes, as measured by their ability to proliferate in response to mitogens. The acute depression is short-lived. Substantial recovery is apparent within 3 wk after cessation of therapy; however, most patients show a modest, chronic depression in both numbers and functional capacities of circulating lymphocytes. T cells are somewhat more sensitive than B cells, but both are affected. Irradiation of the thymus per se seems to have little influence on the acute changes which occur, as patients receiving pelvic and mediastinal (including thymic) radiotherapy show a similiar degree of lymphopenia and depression of lymphocyte responsiveness.

Animals↗