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Biomedical subjects

A L Rubin

Publications and source records attributed to A L Rubin.

At least 91 records · Page 5Linked to original sources
PubMed1983

Cellular and growth factor requirements for activation of human T lymphocytes by neuraminidase and galactose oxidase-treated lymphoid cells.

Proliferation of peripheral blood mononuclear leukocytes (PBL) can be stimulated by irradiated autologous PBL that have been treated with neuraminidase and galactose oxidase (NAGO). We determined the types of cells that stimulate and respond by isolating populations of cells enriched for macrophages, B lymphocytes, and T lymphocytes. With PBL as responding cells, proliferation was stimulated by irradiated, NAGO-treated cells with the following hierarchy: macrophage greater than PBL greater than B cells greater than T cells. Irradiated NAGO-treated macrophages and PBL induced proliferation of isolated T cells greater than or equal to the proliferation they stimulated in PBL, indicating that T cells are the predominant responding cell type. Irradiated, NAGO-treated B cells or T cells were weak stimulators of isolated T cell proliferation when compared to their ability to stimulate PBL. The ability of irradiated NAGO-treated B cells or T cells to stimulate isolated T cell proliferation was greatly enhanced by the addition of untreated macrophages or by the addition of conditioned media from mitogen-activated PBL. Biologic, biochemical, and biophysical characterization of the conditioned media revealed it contained both lymphocyte polypeptide growth factors, interleukin 1 and interleukin 2. Semipurified preparations of either of these growth factors were capable of enhancing T cell proliferation stimulated by irradiated NAGO-treated B or T cells. These data indicate T cell proliferation induced by irradiated, NAGO-treated cells requires the aldehyde-bearing cells for the induction of soluble growth factor production and for the induction of putative membrane receptors for these growth factors.

Adult↗
PubMed1983

Inhibition of phorbol ester-mediated interleukin-2 production by cellular differentiating agents.

Lymphocyte proliferation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) is inhibited by agents known to induce differentiation in murine erythroleukemia cells and other cell lines. In the present study, we determined the cellular targets for the action of TPA among murine thymocyte subpopulations, the phase of blastogenesis that is activated by the tumor promoter, and the phase that is inhibited by the differentiating agents. Mouse thymocytes were fractionated into populations bearing receptors for peanut agglutinin (PNA; PNA-positive cells) and populations lacking such receptors (PNA-negative cells). TPA is comitogenic for lectin-treated, unfractionated thymocytes and PNA-negative thymocytes but not for PNA-positive thymocytes. PNA-negative cells, a minor population in unfractionated thymocytes, are therefore the cellular targets for the comitogenic activity of TPA. TPA induces the production of interleukin-2 (IL-2) in lectin-treated PNA-negative populations but not in PNA-positive cells. The differentiating agents inhibit TPA-mediated proliferation of unfractionated and PNA-negative, lectin-treated thymocytes. In contrast, IL-2-mediated proliferation of lectin-treated thymocyte subpopulations is resistant to inhibition by these agents. Inhibition appears to be related to decreased production of IL-2, since the differentiating agents inhibit IL-2 production by both PNA-negative thymocytes and by a human leukemic cell line.

Animals↗
PubMed1983

The advantage of measurement of intact PTH in the prediction of clinical response and calcium metabolism after subtotal parathyroidectomy for renal osteodystrophy.

As previously reported, the circulating half-life of carboxyterminal PTH is greatly prolonged in renal failure (mean t1/2 33.20 +/- 10.18 hrs), while intact PTH is much less affected (t1/2 less than one hour). Preoperative intact PTH levels were strongly predictive of clinical response to subtotal parathyroidectomy, and may help to differentiate the nature of metabolic bone disease in symptomatic dialysis patients. Intact PTH levels showed strong correlation with postoperative calcium metabolism, allowing prediction of extent of postoperative hypocalcemia. Carboxyterminal PTH levels, influenced by renal function as well as by functional parathyroid state, were poorly predictive of response to parathyroidectomy and not correlated with postoperative calcium metabolism.

Adult↗
PubMed1982

Hydroxyl radical scavengers inhibit lymphocyte mitogenesis.

Agents that are known to be scavengers of hydroxyl radicals inhibit lymphocyte mitogenesis induced by phorbol myristate acetate (PMA) to a greater extent than they inhibit mitogenesis induced by concanavalin A or phytohemagglutinin. These agents include dimethyl sulfoxide, benzoate, thiourea, dimethylurea, tetramethylurea, L-tryptophan, mannitol, and several other alcohols. Their inhibitory effect is not associated with cytotoxicity. The hydroxyl radical scavengers do not inhibit PMA-dependent amino acid transport in T cells or PMA-induced superoxide production by monocytes. Thus, they do not inhibit the primary interaction of PMA with responding cells. Treatment of peripheral blood mononuclear cells with PMA increased cellular guanylate cyclase in most experiments, and dimethyl sulfoxide tended to inhibit this increase. In addition to inhibition of PMA-induced mitogenesis, hydroxyl radical scavengers markedly inhibited the activity of lymphocyte activating factor (interleukin 1). The differential inhibition of lymphocyte mitogenesis induced by different mitogens appears to be related to the differential macrophage requirements of the mitogens. The data suggest that hydroxyl radicals may be involved in mediating the triggering signal for lymphocyte activation. Some of the hydroxyl radical scavengers are inducers of cellular differentiation,. nd it is possible that their differentiating activity is related to their ability to scavenge free radicals.

Benzoates↗
PubMed1982

Immunosuppressive properties of polar organic compounds that induce cellular differentiation in Friend erythroleukemia cells.

We studied the effect of several polar organic compounds, known to induce erythroid differentiation in Friend leukemia (FL) cells, on in vitro human lymphocyte responses and on skin graft survival in mice. The short chain fatty acids, butyric acid (BA), propionic acid (PA), valeric acid, and the polar organic solvents, dimethyl sulfoxide, dimethylformamide, and dimethylacetamide, all mediated significant inhibition of alloantigen-induced proliferation and generation of cytotoxic T lymphocytes (CTLs) in human primary and secondary mixed lymphocyte culture (MLC) reactions. Hexamethylenebisacetemide, another potent inducer of differentiation in FL cells, also mediated significant suppression. Inhibition of MLC with polar organic compounds was accomplished at concentrations known to induce differentiation in FL cells and that are not cytotoxic to peripheral blood mononuclear cells. In distinct contrast, agents that are structurally related to BA, but that do not induce differentiation in FL cells, such as caproic acid, beta-OHBA, gamma-amino BA, and isobutyric acid, did not exhibit immunosuppressive properties. Pokeweed mitogen-driven polyclonal B cell activation was also suppressed by agents that induce erythroid differentiation in FL cells. In addition to potent in vitro immunosuppressive properties, supplementation of drinking water with BA or PA resulted in prolongation of full-thickness skin grafts in DBA/2 (H-2d) to C57BL/6 (H-2b) donor-recipient combinations. Our findings indicate that polar organic compounds that induce differentiation in FL cells are potent immunosuppressive agents.

3-Hydroxybutyric Acid↗
PubMed1982

Enhanced kidney graft survival with retroplacental source gamma-globulin. Results of a 5-year prospective study at a single center.

We examined the possibility that retroplacental source gamma-globulin (RPGG), with its content of anti-HLA antibodies, would improve cadaver kidney graft survival rates. In a 5-year controlled prospective study of 208 transplants, we found that the addition of RPGG to a standard immunosuppressive drug regimen (azathioprine and prednisone) resulted in significant improvement of the cumulative survival rate (CSR) of first and second grafts. At 2 years, the overall CSR of first grafts increased from a control value of 37% +/- 6 to 52% +/- 6 (P = 0.037). Among second graft recipients, the CSR increased from a value of 19% +/- 8 to 50% +/- 10 (P = 0.014). This improvement in graft survival was seen as early as 3 months after surgery and was sustained through 3 years without added recipient morbidity or mortality. When recipient populations were stratified for various factors, those groupings remonstrative of an intact or active humoral immune response capacity were found to have the highest survival rates in the study; 2-year graft CSRs of 70% +/- 6 and 65% +/- 10 were found in recipients with preformed antibody resulting from blood transfusions (P - 0.003) and cytomegalovirus infectivity (P = 0.0006), respectively. These findings indicate that the improved graft survival seen in this study may have resulted from a recipient's immunological response to challenge with RPGG.

ABO Blood-Group System↗
PubMed1982

Abrogation of proliferation and generation of cytotoxic T cells in human mixed lymphocyte culture reactions by modification of the cell surface with mitogenic oxidizing agents.

Multiple lectins with specificity for cell surface glyco-proteins inhibit cellular and humoral immune responses and induce transplantation tolerance. Because cell surface glycoproteins play a significant role in various immune events involving cell to cell interactions and because the mixed lymphocyte culture (MLC) reaction is a prototype of immune phenomenon involving cell to cell interactions as well as an in vitro analogue of graft-destructive immune events, the effect of modification of the cell surface with oxidizing mitogens was investigated. Treatment of responder or stimulator cells with neuraminidase and galactose oxidase (NAGO) or with sodium periodate (IO-4) resulted in marked suppression of alloantigen-induced proliferation and in vitro generation of primary cytotoxic T cells (CTLs) in human MLCs. A prominent coupling of mitogen-induced proliferation to abrogation of MLC was consistently observed with modification of stimulator or responder cell surface with either NAGO or IO-4. The possibility that destruction of receptor sites and/or stimulatory units was responsible for the suppression of MLCs was excluded by restoring both proliferation and generation of primary CTLs by reduction of mitogen-oxidized cell surfaces with sodium borohydride. The ability of polyclonal activators to inhibit antigen-specific responses might be useful in abrogating unfavorable alloimmune responses.

Adult↗
PubMed1981

The insect brain (Na+ + K+)-ATPase. Binding of ouabain in the hawk moth, Manduca sexta.

(1) A quantitative study has been made of the binding of ouabain to the (Na+ + K+)-ATPase in homogenates prepared from brain tissue of the hawk moth, Manduca sexta. The results have been compared to those obtained in bovine brain microsomes. (2) The insect brain (Na+ + K+)-ATPase will bind ouabain either in the presence of Mg2+ and Pi, ('Mg2+, Pi' conditions) or in the presence of Na+, Mg2+, and an adenine nucleotide ('nucleotide' conditions) as is the case for the bovine brain (Na+ + K+)-ATPase. The binding conditions did not alter the total number of receptor sites measured at high ouabain concentrations in either tissue. (3) Potassium ion decreases the affinity (increases the KD) of ouabain to the M. sexta brain (Na+ + K+)-ATPase under both binding conditions. However, ouabain binding is more sensitive to K+ inhibition under the nucleotide conditions. In bovine brain ouabain binding is equally sensitive to K+ inhibition under both conditions. (4) The enzyme-ouabain complex has a rate of dissociation that is 10-fold faster in the M. sexta preparation than in the bovine brain preparation. Because of this, the M. sexta (Na+ + K+)-ATPase has a higher KD for ouabain binding and is less sensitive to inhibition by ouabain than the bovine brain enzyme. (5) This data supports the hypothesis that two different conformational states of the M. sexta (Na+ + K+)-ATPase can bind ouabain.

Animals↗
PubMed1981

Mitogenic and co-mitogenic properties of hemin.

We report here that hemin, an agent known to induce cellular differentiation in Friend erythroleukemia cells, induces mitogenesis in human T cells and enhances mitogenic responses to supraoptimal concentrations of Con A. Mitogenesis induced by suboptimal or optimal concentrations of Con A is not affected by concentrations of hemin that markedly potentiate responses to supraoptimal amounts of Con A. Maximum mitogenic responses are reached 4 to 5 days after initiation of the cultures. The mitogenic response is macrophage dependent, whereas enhancement of responses to supraoptimal concentrations of Con A is not. Indeed, a greater degree of enhancement is observed after removal of adherent cells. Responses to other mitogens (phytohemagglutinin, wheat germ agglutinin, and sodium periodate) are also enhanced by hemin. Compounds that are metabolically or structurally related to hemin are neither mitogenic nor co-mitogenic. Protoporphyrin IX, which is nonmitogenic, is rendered mitogenic by the chemical insertion of iron to form hemin. Hemin does not affect Con A binding to lymphocytes. These findings indicate that hemin is a macrophage-dependent T cell mitogen with the unusual and remarkable property of overcoming the inhibition of mitogenesis induced by high concentrations of Con A. Since hemin has a limited number of metabolic effects, it provides a useful probe for determination of molecular events associated with lymphocyte activation.

Adult↗