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Biomedical subjects

R Alam

Publications and source records attributed to R Alam.

105 records · Page 6Linked to original sources

Multiple sclerosis: increased expression of interleukin-2 receptors on lymphocytes.

The percentage of interleukin-2-receptor-positive peripheral blood lymphocytes in MS patients was significantly higher in acute relapse than in remission or in controls. After stimulation by phytohemagglutinin, the expression of interleukin-2 receptor on peripheral blood lymphocytes of MS patients was within the range of healthy controls, implying no general impairment of receptor expression. These results confirm other evidence that there is a small population of activated T lymphocytes in acute relapse of MS.

Adult↗

Bacterial antigens stimulate the production of histamine releasing factor (HRF) by lymphocytes from intrinsic asthmatic patients.

Lymphocyte from 12 intrinsic asthmatic patients and 10 healthy controls were studied for their capability to produce histamine releasing factor (HRF) in vitro. Spontaneous HRF production was measured by culturing the lymphocytes alone for 20 h. In another set of experiments lymphocytes were first preincubated separately with phytohaemagglutinin, antigens of Haemophilus influenzae, Streptococcus viridans, Staphylococcus sp. and Neisseria catarrhalis for 4 h then carefully washed three times and cultured alone for an additional 16 h. Cell-free supernatant was assayed for histamine releasing activity using basophils from healthy donors. It was observed that lymphocytes from intrinsic asthmatic patients spontaneously produced HRF. The production of this lymphokine was enhanced following preincubation of lymphocytes with phytohaemagglutinin or bacterial antigens. Results of skin test with bacterial antigens did not correlate with the magnitude of the production of HRF by lymphocytes. At gel chromatography over Sephadex G-75 bacterial antigen-stimulated lymphocyte supernatant revealed two peaks of HRF activity in the molecular weight ranges 35,000-50,000 and 3,000-7,000.

Adult↗

Enhancement of cholesteryl ester metabolism in cultured human monocyte-derived macrophages by verapamil.

The effect of the Ca2+ entry blocker, verapamil, on the biosynthesis of cholesterol and the metabolism of low-density lipoprotein (LDL) was studied in cultured human monocyte-derived macrophages. Addition of verapamil (50 microM) of monocyte-derived macrophages enhanced 125I-LDL and 125I-labelled acetyl-LDL binding and internalization, and increased [2-14C]acetate incorporation into cholesterol. Since higher levels of LDL and modified lipoproteins may be implicated in atherogenesis, the more efficient processing of these lipoproteins by monocyte-derived macrophages in the presence of Ca2+ blocker warrants further assessment for its potential as an antiatherogenic agent.

Cholesterol↗

Action of the human lymphokine histamine releasing factor on mouse peritoneal mast cells.

Histamine releasing factor (HRF)--a human lymphokine--has been shown previously to release histamine from basophils in vitro. In this paper we show that HRF acted across the species barrier and released histamine from mouse peritoneal mast cells. This response was dose-dependent. Mast cells from both sensitized and non-sensitized mice were equally susceptible to the action of HRF. We observed synergistic action of HRF with specific allergen (ovalbumin) or HRF with anti-IgE antibody in releasing histamine from mast cells. Preincubation of mast cells with calcium ion chelating agent ethylenediaminetetraacetic acid (EDTA) or disodium cromoglycate induces only a small inhibition of histamine release caused by HRF. We conclude that histamine release from mouse peritoneal mast cells can serve as an in vitro test for the assay of human HRF.

Allergens↗

A mononuclear cell-derived histamine releasing factor in asthmatic patients. II. Activity in vivo.

In an attempt to study the role of lymphokines in asthma, lymphocytes from asthmatic patients were stimulated in vitro with skin test-positive allergen (dust mite) or with non-specific mitogen-phytohaemagglutinin for 4 h, then washed carefully and cultured alone for 16 h. Cell-free supernatants were subsequently collected and applied in the basophil histamine release test in vitro and in bronchial provocation test and skin prick test in vivo. Supernatant of non-stimulated lymphocytes from asthmatic patients released significant amounts of histamine from basophils. Stimulation of lymphocytes with specific allergen or phytohaemagglutinin augmented the supernatant-induced histamine release. Lymphocyte supernatants from the majority of patients also induced bronchoconstriction and elicited skin wheal and flare reaction in vivo.

Asthma↗

A lymphocyte-derived histamine-releasing factor in asthmatic patients. III. Further studies.

Peripheral blood lymphocytes from atopic asthmatic patients cultured overnight (16 hours) produced a novel lymphokine-histamine releasing factor (HRF) in the culture supernatant. Activity of this lymphokine has been tested in the basophil histamine release test. Supernatant from unstimulated lymphocytes released 29% histamine from basophils. A short incubation of lymphocytes with skin test-positive allergens (grass, mite) enhanced the generation of HRF. Skin test-negative allergens had no effect. HRF appeared in the supernatant as early as four hours after the start of the culture and its production level remained high even at 48 hours. Gel-filtration with Sephadex G-75 revealed an apparent molecular weight for HRF in the range of 10,000 to 15,000. HRF is relatively heat stable at 56 degrees C.

Allergens↗

A mononuclear cell derived histamine releasing factor (HRF) in asthmatic patients. Histamine release from basophils in vitro.

Mononuclear cells from asthmatic patients produced a histamine releasing factor (HRF). Mononuclear cells produced this factor in culture spontaneously but significantly much more following specific allergen stimulation. This factor released histamine from both sensitized and unsensitized basophils in vitro. Mononuclear cells from healthy subjects produced HRF only after nonspecific mitogen/phytohemagglutinin stimulation. Asthmatic patients on immunotherapy with essential benefits failed to produce HRF.

Adult↗

The interleukin-5/receptor interaction activates Lyn and Jak2 tyrosine kinases and propagates signals via the Ras-Raf-1-MAP kinase and the Jak-STAT pathways in eosinophils.

We have shown that the interaction of interleukin (IL)-5 with the receptor activates Lyn tyrosine kinase within 1 min and Jak2 tyrosine kinase within 1-3 min. IL-5 also stimulates GTP binding to p21ras. The signal is subsequently propagated through the activation of Raf-1, MEK, and MAP kinases as shown by their increased autophosphorylation in vitro and phosphorylation in situ. Jak2 kinase has been shown to phosphorylate STAT nuclear proteins. The activation of STAT nuclear factors was studied by electrophoretic mobility shift assay using a gamma activation site (GAS) probe. We found that IL-5 induces two GAS-binding proteins in eosinophils, one of which is STAT1. We conclude that IL-5 induced signals are propagated through two distinct pathways: (1) Lyn-->Ras-->Raf-1-->MEK-->MAP kinase and (2) Jak2-->STAT1.

Calcium-Calmodulin-Dependent Protein Kinases↗

Scavenger activity in monocyte-derived macrophages from atherothrombotic strokes.

Foam cells are lipid-laden macrophages derived primarily from circulating mononuclear cells and are a characteristic feature of atheromatous lesions. The exact role of these foam cells in the pathogenesis of atherosclerotic lesions remains uncertain, but one potential function is to take-up and process excess interstitial arterial lipoproteins, suggested by their extraordinary ability to engulf enormous quantities of modified low density lipoproteins by the so-called "scavenging pathway." To test this possibility, monocytes from 15 atherothrombotic brain infarct patients and age and sex matched controls were isolated and cultured for 7-8 days in 20% normal serum. The monocyte-derived macrophages were investigated for their ability to bind, internalize and degrade both native and modified (acetylated) LDL labelled with 125Iodine. While native LDL was metabolized similarly, stroke macrophages displayed significantly reduced ability to scavenge modified LDL. These findings suggest that insufficient processing of interstitial arterial cholesterol by monocyte-derived macrophages may contribute to the aggravation of atheroma formation. This inadequacy is likely further compromised by reduced levels of serum high density lipoprotein since the absence of a cholesterol-acceptor will promote the slow but continued accumulation of lipids and the formation of foam cells.

Cells, Cultured↗

Histamine releasing lymphokines: a new approach to some old problems.

Studies carried out in recent years reveal that some endogenous substances can degranulate mast cells and basophils. Lymphokines produced in vitro by T lymphocytes in presence of an antigen or a mitogen, which are capable of provoking histamine liberation in basophils and mast cells have been described. Lastly the mechanisms for histamine release not mediated by IgE in bronchial asthma and which can be mediated by these factors, is discussed.

Animals↗

Complement in allergen-induced bronchospasm in house-dust RAST negative asthmatic patients.

We studied a group of asthmatic patients with aspirin intolerance who were RAST-negative for house-dust and Dermatophagoides-pteronyssinus despite having positive skin tests and positive inhalation tests to these allergens. Total haemolytic activity (CH50), C3, C4 and C3PA were measured after allergen-induced bronchospasm in these patients and also in a group of RAST-positive asthmatic patients taken as a control group. We did not find any change in complement level after allergen-induced bronchospasm in both groups of patients.

Allergens↗