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Biomedical subjects

R L O'Brien

Publications and source records attributed to R L O'Brien.

At least 55 records · Page 3Linked to original sources
PubMed1988

B cells expressing Ig transgenes respond to a T-dependent antigen only in the presence of Ia-compatible T cells.

We sought a quicker and easier method for the isolation of B cells enriched for a given Ag specificity. Here, we report our results using transgenic mice bearing mu- and kappa-transgenes that encode an IgR against the hapten phosphorylcholine. Splenic B cells from such mice had a high percentage of phosphorylcholine-binding cells and differentiated in vitro in response to T cell hybridomas in an Ag-specific, Ia-restricted manner. Supernatants from such in vitro cultures could not transfer helper activity, nor could the T cell be replaced in other ways tried when using a classical T-dependent Ag. These results support the model of a cognate interaction between T and B cell, and we present evidence that the interaction may consist of two or more steps.

Animals↗
PubMed1985

A patient selection profile for the use of speech prostheses in adult dysarthria.

This paper deals with the decision making process involved in patient selection for the use of speech prostheses in adult dysarthria. A candidacy profile is presented and explained. Assessment of all components of dysarthria, including resonance, articulation, phonation, respiration, and prosody, is stressed along with motivational and medical considerations.

Adolescent↗
PubMed1985

Further characterization of low density mononuclear cells: FACS-assisted analysis of human MLR stimulators.

Previously, we reported that all of the potent stimulators of the allogeneic mixed leukocyte reaction (MLR) are contained in a heterogeneous low density fraction of human peripheral blood mononuclear (PBM) cells. We have further characterized human MLR stimulators by staining them with highly specific monoclonal antibodies, and then analyzing and separating them with the fluorescence-activated cell sorter. These studies revealed two populations of low density cells with potent allogeneic stimulatory activity. One population is a monocyte subset that reacts with anti-OKM1, MO.2, and expresses C3b as well as Fc-IgG receptors. The second population exhibits even greater stimulatory capacity and does not express any of these monocyte markers. Moreover, these cells are not phagocytic and do not react with alpha-naphthyl esterase. They comprise approximately 10% of the low density fraction or 0.5% of PBM. These cells are most likely lymphoid dendritic cells, described in various species as potent MLR stimulators. In contrast to the allogeneic MLR, only the low density cell type exhibiting dendritic cell characteristics induced a potent autologous MLR.

Antibodies, Monoclonal↗
PubMed1984

Early mitogen-induced metabolic events essential to proliferation of human T lymphocytes: dependence of specific events on the influence of adherent accessory cells.

Adherent accessory cells (AC) are required for the proliferative response of T lymphocytes to antigens and various mitogens. A current model of AC-T cell cooperation is that commitment to growth of mitogen activated T lymphocytes occurs via sequential action of IL 1 and IL 2. Initial mitogen action on T lymphocytes in the presence of AC is followed by a sequence of metabolic changes which culminate in DNA replication and mitosis. Many of these early events are critical to DNA replication. We studied several of these mitogen-induced events in experiments designed to define the specific influence of AC on T cell metabolism before initiation of DNA replication. By using human peripheral T lymphocytes depleted of AC to the extent that the proliferative response is essentially ablated, we found that the sequence of early events is divided into two phases: an early activated state in which certain events are stimulated directly by mitogen and independently of AC, and an AC-dependent state in which other events occur in mitogen-treated lymphocytes only in the presence of the numbers of AC necessary to support the proliferative response. We partially support the proliferative response. We partially characterized the nature of the metabolic activation that pulse neuraminidase-galactose oxidase treatment induces in lymphocytes in the presence and functional absence of AC. Stimulated uptake of [3H] uridine and [3H]-leucine into cellular precursor pools and incorporation into macromolecules apparently requires the presence of AC, but stimulated influx of both [3H]3-O-methyl glucose and [3H]alpha-amino isobutyric acid are independent of the presence of AC. These data suggest that stimulated influx of glucose and a certain class of essential amino acids are events of the early activated state, whereas increased RNA and protein synthesis are events of the AC-dependent state. All of these events are critical to the T cell's commitment of DNA replication and mitosis. The early activated state is consistent with AC-T cell cooperation via IL 2. It is possible that IL 2 mediates passage of IL 2 receptor-bearing T cells from the early activated state to the AC-dependent state, which then leads directly to DNA replication and mitosis.

3-O-Methylglucose↗
PubMed1983

Low-density mononuclear cells. Potent stimulators of the human MLR.

We have applied purification strategies similar to those used to purify murine dendritic cells to human peripheral blood in an attempt to enrich for stimulators of the human mixed lymphocyte reaction (MLR). Equilibrium density centrifugation of peripheral blood mononuclear cells yields a population of low density cells that are potent stimulators of a human MLR. The stimulator cells are Dr+, nonlymphocytic, and weakly adherent. Strongly adherent monocytes, also present in the low-density cell population, do not stimulate a human MLR. This contrasts with other human MLR studies that ascribe stimulatory activity to adherent monocytes, and it indicates functional and morphological heterogeneity among monocytes.

Cell Separation↗
PubMed1980

Characterization of responding cells in oxidative mitogen stimulation. III. Presence of I-A- and I-J, E, C-subregion gene products on the surface of required cells.

Ia antigens coded by genes of the murine major histocompatibility complex are expressed on the surface of a population of cells critical to the proliferative response of murine spleen cells to the oxidative mitogen neuraminidase/galactose oxidase. By selective depletion with antiserum and complement, Ia antigens coded (or determined) by the I-A and I-J, E, C subregions of the Ir region can be detected on the surface of cells required for the response. In addition, I-A-subregion products have a functional significance in cellular activation which can be demonstrated by blocking experiments with anti-Ia serum in the absence of complement.

Animals↗
PubMed1980

Characterization of responding cells in oxidative mitogen stimulation. I. Ia+ cells and Ly-1+2+ cells are required for the proliferative response.

Addition of anti-Ia sera to cultures of mouse spleen cells stimulated with oxidative mitogens, neuraminidase/galactose oxidase (NaGO) or sodium periodate (NaIO4), inhibits the subsequent proliferative response 30 to 70%. Anti-H-2K or D sera were not specifically inhibitory. Similar inhibition was seen when cells were pretreated with anti-Ia sera and washed before exposure to the mitogenic enzymes. Treatment with anti-Ia serum and complement depletes greater than 89% of the NaGO and the NaIO4 responses but 2% or less of the phytohemagglutinin (PHA) response. The response to NaGO was sensitive to depletion with anti-Thy-1 serum, rabbit anti-mouse brain serum, anti-Ly-1, or anti-Ly-2 serum. Mixtures of Ly-1 and Ly-2-depleted populations did not restore responsiveness. Thus both an Ia+ cell and an Ly-1+2+ T cell are required for [3H]TdR incorporation in response to NaGO treatment.

Animals↗
PubMed1980

Characterization of responding cells in oxidative mitogen stimulation. II. Identification of an Ia-bearing adherent accessory cell.

Treatment of murine lymph node or spleen cells with anti-Ia serum and complement (C), depletes the subsequent proliferative response of the residual cells to the oxidative mitogen galactose oxidase (NaGO). Restoration of the mitogenic response could be achieved by the addition of adherent accessory cells prepared by a variety of techniques. Loosely adherent dendritic cells were the most efficient population of restoring cells. Treatment of adherent cells with anti-Ia serum and C removed their capacity for restoration. Restoration of the oxidative mitogen response to lymph node cells depeleted of adherent cells by passage over nylon wool and Sephadex columns was similar to restoration of Ia- depleted lymphocyte populations. Further NaGO-induced lymphocyte transformation requires an Ly-1+2+ T lymphocyte and an Ia-positive adherent accessory cell.

Animals↗
PubMed1978

Surface proteolytic activity in cell interactions: activation of human peripheral lymphocytes in contact with mitogen-treated glass-adherent leukocytes.

The transformation of lymphocytes by mitogens or by periodate treatment requires the presence of glass-adherent leukocytes. We have demonstrated that contact with periodate-treated adherent cells transforms human peripheral T lymphocytes. Using a new method to estimate proteolytic activity released by cells or available at cell surfaces, we found marked stimulation of cell surface-associated enzyme activity on glass-adherent cells treated by NaIO4 or by Con A. The expression of this enzymatic stimulation required contact with substrate, just as the transformation of untreated T cells required contact with treated adherent cells. Therefore, we propose that cell-cell interaction leads to an efficient mode of stimulation, which may be mediated by or initiated by surface-associated proteases of adherent cells.

Cell Adhesion↗
PubMed1977

Human B lymphocytes in giemsa stained preparations.

A mixed antiglobulin procedure has been developed to provide simultaneous study of cell surface immunoglobulin and detailed cytological features in Giemsa stained preparations. The percentage of surface immunoglobulin bearing lymphocytes, monocytes and granulocytes changed dramatically when lymphocytes were incubated at 37 degrees C, or following sheep erythrocyte rosette enrichment procedures.

Animals↗