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Biomedical subjects

A Ravid

Publications and source records attributed to A Ravid.

At least 55 records · Page 3Linked to original sources
PubMed1990

1,25-Dihydroxyvitamin D3 potentiates the decreased response of lymphocytes from atopic subjects to agents that increase intracellular cyclic adenosine monophosphate.

The inhibitory effect of prostaglandin E2, histamine, isobutylmethylxanthine, and 1,25-dihydroxyvitamin D3 (1,25-[OH]2D3) on the mitogenic stimulation of peripheral blood lymphocytes from normal and atopic subjects was studied. We found that lymphocytes from atopic patients were less susceptible to inhibition by the three agents that elevate intracellular cyclic adenosine monophosphate (cAMP) concentrations and by the active metabolite of vitamin D (inhibition of 27%, 14%, 12%, and 36% for the atopic patients as compared with 40%, 20%, 22%, and 46% for the normal donors, by the four agents, respectively; p less than 0.02). The inhibitory effect of the cAMP-elevating agents was potentiated by the addition of 1,25-(OH)2D3 to the lymphocyte cultures. The potentiation was more pronounced on lymphocytes from the atopic donors, increasing their responsiveness to levels comparable to levels of lymphocytes from normal donors. The synthetic corticosteroid, dexamethasone, had a similar potentiating effect on the inhibitory action of prostaglandin E2. In view of the beneficial action of beta-agonists, phosphodiesterase inhibitors, and corticosteroids in the treatment of allergy, the potentiating effect of 1,25-(OH)2D3 on the action of cAMP-elevating agents may be of therapeutic interest.

1-Methyl-3-isobutylxanthine↗
PubMed1990

1,25-dihydroxyvitamin D3 and agents that increase intracellular adenosine 3',5'-monophosphate synergistically inhibit the mitogenic stimulation of human lymphocytes.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3], like the immune response modulators prostaglandin E2 (PGE2) and histamine, inhibits mitogen-induced proliferation of human peripheral blood mononuclear cells. 1,25-(OH)2D3 acts synergistically with PGE2 and histamine to inhibit lymphocyte mitogenesis. This is apparent at a wide concentration range of 1,25-(OH)2D3 (3 X 10(-11)-10(-8) mol/L). Cholera toxin, forskolin, and isobutylmethylxanthine, which like PGE2 and histamine increase intracellular concentrations of cAMP, also act synergistically with 1,25-(OH)2D3 in this system. Culture of mitogen-stimulated adherent cell-depleted mononuclear cells with PGE2 increases the number of high affinity binding sites for 1,25-(OH)2D3. This finding may account for the synergistic interaction between the two agents.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Mononuclear cells from human neonates are partially resistant to the action of 1,25-dihydroxyvitamin D.

1,25-Dihydroxyvitamin D [1,25-(OH)2D] inhibits mitogen-induced proliferation of lymphocytes by a receptor-mediated mechanism. Peripheral blood lymphocytes may serve as a model for detecting hereditary defects in the response of classical target organs to 1,25-(OH)2D. Delayed bone mineralization and deficient intestinal calcium absorption are common in low birth weight formula-fed infants. The defect in calcium absorption exists despite normal or even elevated serum 1,25-(OH)2D levels, suggesting partial end-organ resistance to the hormone. We assessed the response to 1,25-(OH)2D of activated mononuclear cells obtained from cord blood of fullterm and preterm infants and from peripheral blood of adults. We found that the inhibitory effect of 1,25-(OH)2D on mitogen-induced [3H]thymidine incorporation was significantly less [mean, 34 +/- 8% (+/- SE)] in mononuclear cells from neonates (independent of gestational age) compared to mononuclear cells from adults (66 +/- 5%; P less than 0.001). This difference in the inhibitory effect was not due to a smaller number of high affinity receptors for 1,25-(OH)2D in activated cord blood lymphocytes. We conclude that the coupling between the receptors for 1,25-(OH)2D and the biological response in neonates is less efficient than that in adults.

Adult↗
PubMed1986

1,25-Dihydroxyvitamin D3 enhances prostaglandin E2 production by monocytes. A mechanism which partially accounts for the antiproliferative effect of 1,25(OH)2D3 on lymphocytes.

Partial removal of monocytes from human peripheral blood mononuclear cells, or the addition of indomethacin, reduced the antiproliferative effect of 1,25(OH)2D3 on mitogen-stimulated mononuclear cells. Addition of 1,25(OH)2D3 (1 nM) to mitogen-stimulated mononuclear cells caused a 2-4-fold increase in prostaglandin E2 production during the second day of culture. The inhibitory effect of 1,25(OH)2D3 on lymphocyte proliferation is greatly augmented up to 7-fold in the presence of prostaglandin E2. We conclude that monocytes are involved in the inhibitory effect of 1,25(OH)2D3 on the mitogenic stimulation of human lymphocytes and that their action is probably mediated by prostaglandins.

Calcitriol↗
PubMed1986

Oligozoospermia, asthenozoospermia, and sperm abnormalities in ex-addict to heroin, morphine, and hashish.

A 40-year-old male had been addicted to heroin, morphine, hashish, and other narcotics for 12 years. At examination, 2 years after abstinence from drugs, his semen analysis revealed oligozoospermia, asthenozoospermia, and morphologically abnormal spermatozoa such as "round-headed" and "kinked"--sperm with neck abnormalities and immature forms. There was no evidence of other morphological abnormalities or of the presence of morphologically normal sperm. A possible correlation is discussed between the long-lasting drug addiction and morphological sperm abnormality, endocrinological function, karyotype, and immunological status.

Adult↗
PubMed1985

Defective binding and function of 1,25-dihydroxyvitamin D3 receptors in peripheral mononuclear cells of patients with end-organ resistance to 1,25-dihydroxyvitamin D.

Lectin-induced DNA synthesis by peripheral mononuclear cells from 17 normal donors was inhibited (40-60%) by 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) at physiological concentrations (10(-10)-10(-9) M). The lymphocytes acquire specific receptors for 1,25(OH)2D3 upon activation by the lectins. This process precedes the inhibitory effect of 1,25(OH)2D3. We studied lymphocytes from six patients from four different kindreds with the syndrome of hereditary end-organ resistance to 1,25(OH)2D (the so-called vitamin D-dependent rickets type II). In five patients (three kindreds) peripheral blood mononuclear cells did not acquire receptors for 1,25(OH)2D3 upon phytohemagglutinin-induced activation. Moreover, in contrast to normal lymphocytes, the mitogenic stimulation of these patients' lymphocytes by phytohemagglutinin and concanavalin A was not inhibited by 1,25(OH)2D3. Activated lymphocytes of the sixth patient from a fourth kindred exhibited normal binding of [3H]1,25(OH)2D3 but the hormone failed to inhibit the mitogenic stimulation. A similar pattern of the vitamin D effector system was previously observed in fibroblasts cultured from skin biopsies of the same group of patients. The conclusions from these findings are: (a) the inhibition of mitogenic stimulation by 1,25(OH)2D3 is mediated by specific functional receptors to the hormone; and (b) the receptors for 1,25(OH)2D3 in mononuclear cells are probably controlled genetically by the same mechanisms as the effector system in well-characterized target organs of the hormone, such as intestine and kidney.

Adolescent↗
PubMed1984

1,25-Dihydroxyvitamin D3 inhibits selectively the mitogenic stimulation of mouse medullary thymocytes.

Mouse thymocytes were separated into cortical and medullary subpopulations by differential agglutination with peanut agglutinin. A high-affinity receptor for 1,25-dihydroxyvitamin D3 is present in medullary immunocompetent mouse thymocytes and is absent from cortical immature cells. 1,25-dihydroxyvitamin D3, at physiological concentrations, inhibits the mitogenic response of the medullary cells to phytohemagglutinin and interleukin-2, but has no effect on the cortical subpopulation. Other less active metabolites of vitamin D had little or no effect on medullary cell stimulation.

Animals↗
PubMed1983

Effect of polar organic compounds on leukemic cells. Butyrate-induced partial remission of acute myelogenous leukemia in a child.

Polar organic compounds, such as dimethylsulfoxide and butyric acid, are known to induce differentiation in Friend erythroleukemia cells as well as in other cell types. It has been found that many of the compounds that induce cellular differentiation, inhibit 3H-thymidine incorporation and induce cell damage when incubated with leukemic cells from patients with acute or chronic myelogenous or acute lymphocytic leukemia. These effects are time and dose dependent. Among the compounds tested, butyrate was the most potent. Parenteral administration of butyrate (500 mg/kg/day) for ten days to a child with acute myelogenous leukemia in relapse, and resistant to conventional therapy, resulted in elimination of myeloblasts from the peripheral blood, an increase in mature myeloid cells and a reduction in 3H-thymidine uptake by the patient's peripheral blood cells. Bone marrow myeloblasts were reduced from 70-80% to 20% following the course of intravenous butyrate. No impairment of liver or renal function and no coagulation abnormalities were observed during butyrate treatment. Organic agents that induce cell differentiation may provide additional reagents for the clinical management of selected cases of leukemia.

Adult↗
PubMed1983

On the mechanisms of inhibition of lymphocyte mitogenesis by high conA concentrations.

ConA at high concentrations inhibits lymphocyte mitogenesis. Previous studies have shown that inhibitory conA concentrations do not inhibit the acquisition of responsiveness to interleukin-2 (IL-2) when excessive conA is removed. To analyse further the problem of high-dose inhibition by conA, we determined whether inhibition of mitogenesis is related to inhibition of IL-2 production or, alternatively, whether factor production is intact, but the cells are rendered incapable of responding to the factor. ConA stimulates IL2 production at concentrations that are inhibitory to mitogenesis of human lymphocytes. IL-2 was assayed both in a murine cytotoxic T cell line and human memory cells. The response of IL-2-dependent cells to Il-2-containing medium was, on the other hand, inhibited by conA in a dose-dependent fashion. One mechanism whereby high conA concentrations inhibit mitogenesis is by rendering cells resistant to IL-2, possibly via extensive cross-linking of cell surface sites.

Animals↗
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↗
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↗
PubMed1979

Involvement of gangliosides in lymphocyte stimulation.

N4-Dinitrophenyl-L-2,4-diaminobutyric acid hydrazide was attached covalently to the aldehyde groups produced by periodate oxidate of bovine brain gangliosides and it was incorporated into mature thymocytes. High concentrations of antibodies to dinitrophenyl (DNP) or lower concentrations followed by protein A agglutinated the cells and stimulated DNA synthesis. Incubation of the thymocytes containing DNP-modified ganglioside with rabbit anti-DNP and fluorescein-labeled anti-rabbit IgG resulted in the formation of uniform rings on the cell surface, which subsequently developed into patches and caps. These results indicate that gangliosides may play a primary role in the lymphocyte activation process.

Agglutination↗
PubMed1978

Cooperativity of lectin binding to lymphocytes, and its relevance to mitogenic stimulation.

The relationship between the binding patterns of soybean agglutinin, peanut agglutinin (both in their native (unaggregated) form and in their polymerized form), and of Phaseolus vulgaris leucoagglutinin, to neuraminidase-treated lymphocytes from different sources, and the mitogenic activity of these lectins, was studied. In all cases investigated, binding of a lectin to lymphocytes which resulted in stimulation was a positive cooperative process. Our findings support the assumption that clustering of receptors and conformational changes in membrane structure are prerequisites for mitogenic stimulation.

Animals↗
PubMed1978

Grafting of triggering sites onto lymphocytes: requirement of multivalency in the stimulation of dinitrophenyl-modified thymocytes by anti-dinitrophenyl antibody.

N4-Dinitrophenyl-L-2,4,-diaminobutyric acid hydrazide was coupled to aldehyde groups generated by periodate oxidation of sialyl residues on thymocytes. Anti-2,4-dinitrophenyl(Dnp)antibody was found to stimulate mature, hydrocortisone-resistant thymocytes, while it had no mitogenic effect on the immature thymocytes. In order to study the involvement of different regions of the antibody molecule in the triggering process of stimulation, the mitogenicity of various antibody fragments was also assessed. The divalent F(ab')2 was found to be a superior mitogen compared to the intact antibody when added to Dnp-conjugated thymocytes. The monovalent Fab' and Fab fragments have no mitogenic activity indicating that cross-linkage may be a prerequisite for stimulation.

Animals↗