Search PubMed⌕ Search

Biomedical subjects

J Brostoff

Publications and source records attributed to J Brostoff.

At least 91 records · Page 5Linked to original sources
PubMed1984

Anergy in sarcoidosis: the role of interleukin-1 and prostaglandins in the depressed in vitro lymphocyte response.

We have shown that peripheral blood monocytes from patients with sarcoidosis release reduced amounts of interleukin-1 (IL-1) when compared with normals. In part, this defect explains the relative in vitro unresponsiveness of T lymphocytes from patients with sarcoidosis as measured by mitogen- or antigen-induced lymphocyte transformation. The addition of supernatants containing pre-formed IL-1 partially restored this defect. This enhancement was found to be additive to the previously described effect of indomethacin, an inhibitor of prostaglandin synthesis. Thus, it would appear that the activated peripheral blood monocytes found in sarcoidosis not only cause reduced lymphocyte proliferation by acting as suppressor cells but are also unable to act as accessory cells in producing IL-1.

Adult↗
PubMed1983

Inhibition of human natural killer cell activity by prostaglandin D2.

We have studied the effect of prostaglandin (PG) D2 on human natural killer (NK) cell activity using 51Cr-labelled K562 target cells. PGD2 caused a dose dependant inhibition of NK cell activity, producing maximal, non-toxic inhibition at a concentration of 1 X 10(-6) M. This inhibition was not due to interference with effector:target cell binding (E:TCB) and was seen using Percoll-enriched NK cells. A time dependent inhibition of NK cell activity was seen when dibutyryl cyclic AMP (DiBcAMP) and PGD2 were added in parallel to the NK cell assay suggesting that PGD2 directly inhibits NK cell activity via the adenylate cyclase system which modulates the killing process.

Adult↗
PubMed1983

The role of prostaglandins in the modulation of histamine suppression of mitogen responses in atopic and normal subjects.

We have shown that lymphocytes from atopics are more sensitive to histamine-induced suppression of mitogen transformation than are cells from normal subjects. Recent reports have suggested that histamine suppression may act via prostaglandin synthesis. We have investigated this and found that indomethacin partially reversed the histamine suppression seen in atopics, but not that in normals. This effect was seen even when the direct enhancing effect of indomethacin was taken into account. The direct effect of indomethacin on mitogen-induced transformation was similar in both normal and atopic cultures, which suggests that these results are not due to the presence of PG producing cells in atopic cultures, but rather that histamine modulates the function of these cells. It was found that a specific H2 agonist, but not an H1 agonist could partially mimic the effect of histamine this system.

Adolescent↗
PubMed1983

Studies of the allergens of Olea europea pollen.

Allergens of Olea europea have been prepared by isoelectrofocusing and tested by RAST, RAST inhibition and skin tests. The major allergen was found to be an acidic protein of pI 6, consisting of two polypeptide chains of molecular weight 15000 and 17000 daltons, possibly non-covalently associated into a dimer. Most other allergens were acidic proteins, but basic proteins were also observed with allergenic activity. The RAST inhibition studies show a considerable degree of allergic cross-reactivity between the isoelectrofocusing fractions.

Allergens↗
PubMed1983

Intrinsic and extrinsic asthma, a shared lymphocyte abnormality.

We have examined in vitro cell-mediated lymphocyte responses to Concanavalin A, (Con. A), and the effects of histamine and indomethacin upon these responses, in normal subjects, and patients with extrinsic and intrinsic asthma, and chronic bronchitis. Lymphocytes from both intrinsic and extrinsic asthmatics are particularly sensitive to histamine-induced suppression of their response to Con. A, and this increased sensitivity was reversed by indomethacin. In these respects, lymphocytes from intrinsic and extrinsic asthmatics behave in an identical fashion, but differ significantly from lymphocytes from both normal subjects and patients with fixed airways obstruction (chronic bronchitis). It is suggested that there is a common immunological mechanism in extrinsic asthma and intrinsic asthma.

Adult↗
PubMed1983

An antiglobulin: IgG anti-IgE. Occurrence and specificity.

An IgG type of antibody directed against IgE has been studied in serum from healthy and allergic individuals. The technique used is based on a solid phase paper radioimmunoassay in which the discs were sensitized with purified IgE myeloma. After incubation with patient's serum, 125I anti-human IgG was added. The anti-IgE antibodies were partially blocked by endogenous IgE, indicating the presence of IgE-containing immune complexes in the serum. Heating of serum at 56 degrees C disrupted the immune complexes, thereby increasing the detectable levels of IgG anti-IgE. Significantly raised levels of anti-IgE antibodies were found in patients suffering from atopic disorders in comparison with the controls.

Antibodies, Anti-Idiotypic↗
PubMed1983

The lack of effect of histamine--protein conjugates on human lymphocyte responses to concanavalin A and histamine.

We have studied the effect of depleting human peripheral blood lymphocytes (PBL) on plates coated with histamine-rabbit serum albumin (H-RSA) or control (E-RSA) conjugates, on the concanavalin A (Con A) response and the histamine suppression of Con A responses. Low H10-RSA-substituted conjugate depletion had little effect on [3H]-thymidine incorporation of Con A-stimulated cells compared to control (E10-RSA) conjugates and unseparated cells, but significantly increased unstimulated cell counts, therefore reducing stimulation index (SI). Highly histamine-substituted (H30-RSA) and control (E30-RSA) conjugates decreased SI in a similar way, but also decreased the [3H]-thymidine incorporation of Con A-stimulated cells. Histamine suppression of Con A responses was reduced by both E10- and H10-RSA-coated plates at suboptimal but not optimal mitogen concentrations. The induction of Con A-induced suppressor cells was unaffected by prior depletion of cells on H10- or E10-RSA conjugate-coated plates. Addition of H10- and E10-RSA to Con A cultures had a slight enhancing effect on transformation, but no effect on histamine suppression of the Con A response. Thus, whilst it is clear from other studies in vitro that functional histamine receptors are present on suppressor T cells, the results presented here show that histamine-protein conjugates do not specifically bind to histamine receptor-bearing human peripheral blood suppressor T lymphocytes.

Concanavalin A↗
PubMed1983

Modulation of human natural killer cell activity by pharmacological mediators.

We have studied the effects of various pharmacological mediators on human NK cell activity. Prostaglandin E2 (PGE2) inhibits NK cell activity in a dose-dependent fashion, whereas PGF2 alpha has no significant effect over the same concentration range. Histamine at high doses (10(-4) M) induced a small but significant inhibition of NK cell activity which was mimicked by both H1 and H2 specific histamine receptor agonists. Inhibition of endogenous prostaglandin production by indomethacin did not alter NK cell activity. Inhibition of NK activity by cAMP but not cGMP analogues, together with other data presented suggests that the mechanism of PGE2-induced inhibition of NK cell activity is not due to impairment of effector cell movement or effector: target cell interaction, but through the adenylate cyclase system which modulates the killing process.

Bucladesine↗
PubMed1982

Prostaglandin E2-mediated enhancement of human plasma cell differentiation.

Addition of prostaglandin E2 (PGE2) to blood mononuclear cell cultures containing pokeweed mitogen (PWM) enhances plasma cell (PC) differentiation measured by intracytoplasmic immunoglobulin 7 days later. T-cell mitogenesis to concanavalin A is inhibited using the same concentrations of PGE2. PGE2 failed to enhance the PC differentiation of lymphocytes from patients with systemic lupus erythematosus (SLE). Indomethacin, on the other hand, either had no effect or suppressed PC differentiation. The data is discussed in terms of the effect of PGE2 on human suppressor T-cell function.

Adult↗
PubMed1982

Effect of histamine, H1 and H2 agonists on E-rosette formation in normal and atopic subjects.

The effect of histamine on the capacity of human peripheral blood lymphocytes to form E rosettes was studied in normal and atopic subjects. Histamine had little effect on E-rosette formation (E-RF) in atopic subjects, but significantly inhibited E-RF in normal subjects in a dose-dependent fashion. To investigate this phenomenon further, specific histamine type 1 and 2 receptor agonists were used in the rosette assay. The H1 receptor agonist caused significant inhibition of E-RF in both normal subjects and atopics, whereas the H2 agonist produced significant inhibition of E-RF in normal but not atopic subjects. The results indicate a histamine type 2 receptor dysfunction in a subpopulation of atopic peripheral blood T lymphocytes.

Animals↗
PubMed1981

Evidence of diminished suppressor T cell activity in patients with atopy and SLE.

The T cell mitogen concanavalin A (Con A) was added to lymphocytes pre-cultured for 24 hours in vitro in tissue culture medium. Delayed addition of the mitogen resulted in an enhanced lymphocyte activation measured by incorporation of radioactive precursors of DNA. T cells isolated by rosetting with sheep erythrocytes also exhibited this enhancement. In a limited study, lymphocytes from both atopic patients and those with systemic lupus erythematosus (SLE) showed little or no enhanced responsiveness to Con A. The possibility that some patients with atopy and SLE possess defective suppressor T cells is discussed in the light of these data.

Adult↗
PubMed1981

Effect of prostaglandins and cyclic nucleotides on growth and immunoglobulin secretion of two IgE myeloma cell lines.

The effect of various mediators on the growth and secretion of IgE by two human myeloma cell lines derived originally from the same tumour was tested. It was found that the growth of U266 was unaffected by PGE2, but IgE secretion was blocked. PGF2 alpha, whilst inhibiting growth, had little effect on IgE secretion. With the second cell line, U266 BL, it was found that none of the agents tested could modulate the secretion of IgE, though cell growth was blocked by PGE2. Prostaglandins act by modulating cyclic nucleotides, the E series increasing the level of cAMP and the F series causing a rise in cGMP. Our findings with prostaglandins could be mimicked by the relevant cyclic nucleotide. Possible explanations for these differences are discussed.

Cell Division↗