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Biomedical subjects

R A Phillips

Publications and source records attributed to R A Phillips.

At least 217 records · Page 12Linked to original sources
PubMed1976

Requirement for non-T cells in the generation of cytotoxic T lymphocytes in vitro. I. Use of nude mice as source of non-T cells.

The ability of small numbers of LN cells to produce cytotoxic lymphocytes on in vitro culture with allogeneic stimulator cells is greatly augmented by the addition of spleen cells from athymic nude mice. The possibility that the synergism is a result of improved culture conditions or a "feeder effect" is excluded. All cytotoxic cells found in these cultures are shown to be T cells and to arise from precursors contained in the LN-cell component. The nude spleen cell component appears to be providing a required non-T cell which has been lost from the LN component through dilution. Synergism between the two components can occur whether they are syngeneic or allogeneic provided that both can recognize the same alloantigens in the stimulator population.

Animals↗
PubMed1976

The use of oral BCG in the treatment or metastatic malignant melanoma.

This study assess the effects of oral BCG, as a single agent, on tumor progression and on cell-mediated immune function in patients with metastatic malignant melanoma. Thirty patients were studied including 22 with measurable metastatic lesions and 8 with no detectable disease, following treatment of metastases by surgery, radiotherapy, or 5-(3, 3-dimethyl-1 -triazeno)-imidazole-4-carboxamide (DTIC; DIC). Oral BCG was given in doses of 120--240 mg, 1--3 times per week for periods ranging from 9 to 80 weeks and to total doses of from 1.2 to 20.1 gm. Patients were assessed by direct measurements of tumor mass, PPD skin test and in vitro blastogenic responses to PPD PHA. Of the 22 patient with measureable disease, 19 showed tumor progression and none showed regression of any lesion. Of the 8 without apparent disease, 5 remained stable and 3 had tumor recurrence. Of the total group of 30 patients, 8 showed some increased sensitivity to skin testing with PPD. Of 19 tested, 3 showed an increased PPD response in vitro, while 3 showed a decreased response. Six of 20 tested showed an increased PHA response in vitro. Oral BCG alone was not effective as an antitumor agent in patients with metastatic malignant melanoma.

Adult↗
PubMed1976

Characterization of cells that suppress the cytotoxic activity of T lymphocytes. I. Quantitative measurement of inhibitor cells.

Target cell lysis by sensitized cytolytic T lymphocytes (CTL) may be conveniently quantitated by 51Cr release. By fitting to the formula, P (% specfic release) = 100 (1-e-Nat) one obtains alpha, the relative frequency of CTL in N lymphoid cells. Using a microassay and murine sarcoma target cells, we observed an unexpected decrease in lysis whenever effectors obtained from a graft-vs-host reaction were tested at high concentrations. This inhibition was not observed with CTL generated by an MLC reaction. Inhibition could not be explained by nonspecific mechanical 'crowding', reutilization of released isotope, suppression of release from dead target cells, or the particular strain combination and target used. By modifying the formula to allow suppression of CTL by a stochastic cell-cell interaction with suppessor cell, we found that P = 100 (1-e-Nate-Ngamma) adequately fitted the data, where Ngamma is proportional to inhibitor content. An 18- to 24-hr incubation at 37 degrees C but not 4 degrees C allowed selective depletion or enrichment of inhibitors; in mixing experiments, both parameters Nalpha t and Ngamma behaved stoichiometrically as independent cellular properties. The inhibitor was resistant to concentrations of anti-T cell (RAMG) serum + complement which killed -TL. A similar inhibitor arose in vivo during an anti-tumour allograft response. The ability to quantitate CTL and inhibitor activities from titration curves provides a technique for studying the identity and mechanism of suppressor cells acting at the effector stage of cell-mediated immunity.

Animals↗
PubMed1976

Appearance of functional lymphocytes in fetal liver.

During ontogeny of the mouse, cells bearing surface Ig first appear at approximately 16 days of gestation. To characterize B cell differentiation during embryogenesis further, we have measured several functional activities of B cells and their precursors. B cell function was measured in two assays, response to sheep red blood cells in a transplantation assay, and response in vitro to a B cell mitogen. By both assays, B function is first detectable at 16 days, the same time that Ig-positive cells appear. The immediate precursors of B cells, PB cells,3 can also be measured by a transplantation assay. This activity is first detectable in fetal liver at 13 days. The yolk sac at 13 days does not contain significant PB activity even though both fetal liver and yolk sac contain pluripotent stem cells, spleen colony-forming units, at that time. Tese data are consistent with the hypothesis that the development of B lymphocytes occurrs early in ontogeny and that the fetal liver may provide the inductive stimulus for B cell maturation.

Animals↗
PubMed1976

Reduction of the in vitro cytotoxic lymphocyte response produced by in vivo exposure to semiallogeneic cells: recruitment or active suppression?

Twenty-four hours after intravenous injection of (C57BL/6 X DBA/2)F1 hygrid lymphoid cells into C57BL/6 mice, the in vitro cytotoxic lymphocyte (CL) response of the C57BL/6 spleen and LN cells against DBA/2 alloantigens can be greatly reduced. The reduction is specific for the foreign alloantigens injected; is reduced by irradiating the cells before injection; develops significantly within 10 min of injection, thereafter increasing with a time constant of about 2 hr; varies with the number and origin of cells injected; can be induced byseveral subpopulations of injected cells within one tissue; varies with the host organ tested (e.g., injection of 10(4) semiallogeneic LN cells can reduce hose LN response more than 100-fold and have no effect on host spleen); and (for the LN response) is largely reversed by treatment with anti-H-2 antibody plus complement specific for the injected cells. The reduction appears to be induced by grafted cells entering host lymphoid organs rather than, e.g., host cells being specifically recruited to go elsewhere. When cocultured with normal cells, lymphoid cells from mice injected as above do not reduce the in vitro CL response of the normal cells but do if left in vivo for 7 days before testing. If left 1 day in vivo, followed by 4 days culture in vitro with the same alloantigen, they strongly reduce the normal cell response. The reduction is increased by both the in vivo and in vitro exposure. The grafted cells, once in the host lymphoid tissue, appear to activate a host suppressor mechanism which develops in vitro and reduces the CL response.

Animals↗
PubMed1975

B-lymphocyte subpopulations in the mouse. Organ distribution and ontogeny of immunoglobulin-synthesizing and of mitogen-sensitive cells.

The first fetal cells synthesizing Ig can be demonstrated at day 10 of gesta tion, well before cells with detectable surface-bound Ig have been found. These early Ig-synthesizing cells are exclusively large cells. The first small cells synthesizing Ig appear at day 15-16 of gestation, a time when cells. with detectable surface-bound Ig have been found in fetal liver. Ig synthesis of liver cells declines 2 days after birth, presumably reflecting a change in cellular composition of the liver, whereas spleen cells, on a per cell basis, synthesize Ig at a constant rate from birth to adult life. At the time that the first small Ig-synthesizing cells are detected and surface-bound Ig has been found on fetal liver cells, such small fetal liver cells can be stimulated by LPS in serum-containing media to generate 19S IgM secreting PFC. Three to four days after birth, cells develop in the small fraction of spleen which can be stimulated in serum-free media by either LPS or PPD to PFC development. Thus we can distinguish three types of B-lymphocytes as they appear sequentially during ontogeny: I. Large, Ig-producing cells, not susceptible to polyclonal activation to PFC development by either LPS or PPD. II. Small, Ig-producing cells, susceptible to LPS-stimulation in serum-containing media; and III. Small, Ig-producing cells, susceptible to LPC- and PPD-stimulation in serum-free media.

Animals↗
PubMed1975

Recognition of traffic signals viewed through colored filters.

Experiments were carried out to provide an empirical basis for setting color standards for sunglasses. Nineteen individuals, ten with anomalous color vision, viewed traffic signals through a series of color filters. Limits on the apparent color shift for the amber and green signals as well as for D65 are presented on a 1931 CIE chromaticity diagram. Limits on the reduction in the apparent luminosity for each of the three signals are given in terms of the minimum transmittance of the lens for each signal.

Automobile Driving↗
PubMed1975

Development of B lymphocytes-1,2.

A rough outline of the development pathway of stem cells to B lymphocytes in mammals is beginning to emerge. The stem cell is most probably either identical to or closely related to the spleen colony-forming unit or hemopoietic stem cell. The stem cell appears not to be specificity-restricted and to lack Ig surface receptors. Whether part of B-cell development in mammals takes place in a specialized lymphoid environment, analogous to the bursa of Fabricius in birds, is still unresolved. The bone marrow does not form such an environment. The bone marrow and spleen, but not the lymph nodes, of mice contain a nondividing B-cell precursor population at an intermediate stage of development between the stem cell and B cell. This population has Ig surface receptors and is specificity-restricted. It cannot be initiated into differentiating into antibody-producing cells. However, under appropriate conditions it can give rise to functional B cells within 3 days. Newly-formed B cells (designated B1) are physically different from mature B cells (designated B2) and appear to be a dividing population of cells differentiating from the B-cell precursor to B2 nondividing cell populations.

Animals↗
PubMed1973

Inhibition of the immune response by 7S antibody mechanism and site of action.

A cell culture system was used to investigate the mechanism of action of the feedback inhibition caused by specific 7S antibody. It was found that preincubation of spleen cells with specific 7S antibody led to a marked reduction in the in vitro response of the treated spleen cells to the antigen used to prepare the antibody. The inhibition was not caused by a carry-over of free antibody nor by the release of 7S antibody from the cells. Rather, the preincubation appeared to specifically inactivate one of the cells required for initiation of an in vitro response. Since the suppression could be reversed by addition of untreated cells, it was possible to characterize the properties of the reconstituting cell. This cell is identified as the nonlymphoid accessory cell (A cell) by several criteria. (a) Suppression can be demonstrated only in assay systems requiring functional A cells. (b) The most active sources for reconstitution are also good sources for A cells. (c) The sedimentation velocity of the reconstituting cell is identical with that for A cells. (d) Like A cells, the reconstituting cell is resistant to high doses of ionizing radiation. (e) The reconstituting ability is not affected by anti-theta antibody. Of the three cells required for the initiation of an immune response, A cells, bone marrow-derived cells, and thymus-derived cells, the data are only compatible with the reconstituting cell being an A cell. Additional experiments suggest that the Fc portion of 7S antibody binds to the surface of A cells. Thus, fluorescein isothiocyanate-labeled 7S antibody binds specifically to cells with properties similar to those described above, and F(ab')(2) fragments, lacking Fc portion, are unable to cause immunosuppression when they are preincubated with spleen cells. It is possible that this binding is related to the specific suppression caused by 7S antibody molecules.

Animals↗
PubMed1973

Restriction of specificity in the precursors of bone marrow-associated lymphocytes.

Previous work has shown that the immediate precursor of B lymphocytes (PB cell) has many properties that distinguish it from both B lymphoctes and hemopoietic stem cells. Size, density, tissue distribution, and sensitivity to cytotoxic antisera differ for each type of cell. The work described here was designed to study three aspects of the differentiation of PB cells. First, since PB cells probably have immunoglobulin surface receptors, fluorescein-labeled anti-immunoglobulin antiserum was used in an attempt to investigate directly the physical properties of PB cells. The use of this labeled antiserum revealed a population of cells with properties similar to the PB cells defined by the functional assays. Second, the differentiative potential of PB cells was studied by comparing the size of the total population of PB cells, as determined with fluorescein-labeled anti-immunoglobulin antiserum, to the size of the population of PB cells responding in a functional assay with a specific antigen. The cells responding in the functional assay represent only 0.1% of the total population of PB cells. This observation suggests that PB cells are not pluripotent stem cells of the immune system. Finally, the kinetics of the differentiation of PB cells to B lymphocytes was studied. The differentiation to mature lymphocytes involves at least one intermediate stage in which cells larger than mature B cells are active in a functional assay for B cells. These large B cells are present in irradiated mice soon after transplantation of PB cells, but by 20 days the majority of the B cells are typical small lymphocytes.

Animals↗