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I Hussaini

Publications and source records attributed to I Hussaini.

7 recordsLinked to original sources
PubMed1991

An alpha 2-macroglobulin receptor-dependent mechanism for the plasma clearance of transforming growth factor-beta 1 in mice.

Radioiodinated transforming growth factor-beta 1 (TGF-beta 1) bound to the plasma proteinase inhibitor, alpha 2-macroglobulin (alpha 2M), as determined by chromatography on Superose-6 and native polyacrylamide gel electrophoresis. When alpha 2M conformational change was induced with methylamine, 125I-TGF-beta 1 binding significantly increased. Intravenously injected 125I-TGF-beta 1 cleared from the circulation of mice rapidly at first; however, intravascular radioactivity stabilized near 20% of the initial level. At necropsy, radioactivity was recovered predominantly in the liver (65%); however, the density of radioactivity (disintegrations per minute/g organ wt) was highest in the lungs. Markedly different results were obtained with purified 125I-TGF-beta 1-alpha 2M-methylamine complex. Clearance of the complex occurred as a first-order process with a t1/2 of 4 min. Greater than 90% of the radioactivity was recovered in the liver. The clearance and distribution of 125I-TGF-beta 1-alpha 2M-methylamine were equivalent to those observed with 125I-alpha 2M-methylamine and 125I-alpha 2M-trypsin. The latter two radioligands clear via specific alpha 2M receptors in the liver. Large molar excesses of alpha 2M-trypsin or alpha 2M-methylamine competed with 125I-TGF-beta 1-alpha 2M-methylamine for plasma clearance. Native alpha 2M, which does not bind to the alpha 2M receptor, did not compete. The receptor binding domain of alpha 2M-methylamine was blocked by chemical modification or enzyme treatment. The resulting alpha 2M preparations still bound 125I-TGF-beta 1; however, the complexes did not clear when injected intravenously in mice. The studies presented here demonstrate that alpha 2M can mediate the plasma clearance of a growth factor via the alpha 2M receptor system. We propose that alpha 2M, the alpha 2M receptor, and proteinases may function as a concerted system to regulate TGF-beta 1 activity and the activity of related factors in vivo.

Animals↗
PubMed1990

Further characterization of PAF receptor and novel antagonists.

To investigate the possible existence of subtypes of PAF receptors and antagonists, the relative activities of four typical competitive PAF antagonists, kadsurenone, BN 52021, WEB 2086 and L-659,989, were compared. Some differences in their inhibition of the specific binding of [3H]-PAF to human platelet and PMN membranes and PAF-induced platelet aggregation were observed. Synergism of the inhibition of platelet aggregation was indicated by combinations of suboptimal levels of two structurally unrelated antagonists, which suggested that the binding sites of these antagonists may not be identical. For 2,5-diaryl tetrahydrofurans, an unsymmetrical molecular configuration represented by the s,s-enantiomer of L-659,989 and its cyclopentane analogues is clearly preferred for optimal potency in vitro. The PAF-binding proteins from human platelet and bovine lung membranes have been solubilized and partially purified. As a research probe, L-662,025, which is an azido analogue of L-659,989, has been characterized as a photoactivable and irreversible PAF antagonist.

Animals↗
PubMed1988

Effect of fibrinopeptides A and B on human and rat platelet aggregation in vitro.

The effect of fibrinopeptides on platelet aggregation is reported. Fibrinopeptide A (minimal effective concentration, 0.65 microM) aggregated human (but not rat) platelets suspended in plasma and at lower concentrations (0.01-0.1 microM) potentiated platelet aggregation due to ADP and collagen in both species. Fibrinogen mimicked these effects of fibrinopeptide A. P-bromophenacyl bromide (100 microM), mepacrine (10 microM), indomethacin (10 microM) and dazoxiben (10 microM) inhibited human platelet aggregation induced by fibrinopeptide A and fibrinogen. In both species, fibrinopeptide B (0.65-6.5 microM) antagonised the platelet inhibitory effect of PGI2 and PGD2 but not adenosine. Antagonism was non-competitive in nature. The concentration of fibrinopeptide A required to potentiate platelet aggregation occurs naturally in the plasma of patients with thrombotic disease suggesting this effect may be of physiological significance during the formation of a thrombus. The novel action of fibrinopeptide B to reduce the platelet inhibitory effect of PGI2 and PGD2 may also contribute to the control of thrombus formation.

Adenosine Diphosphate↗
PubMed1988

Cardiovascular effects of fibrinopeptide B.

The effect of fibrinopeptide B (FpB) on isolated blood vessels and in the intact rat has been investigated. FpB contracted the rabbit superfused aorta preparation (EC50 = 7.5 nmol) and was some 20 times less potent than noradrenaline. Similarly, FpB (0.2-10 nmol) injected into the rat perfused kidney caused dose related, short-lived increases in perfusion pressure and potentiated the vasoconstrictor effect of injected noradrenaline. These effects were associated with increased efflux of PGE2 (but not TxB2) and were reduced but not abolished by indomethacin (10 microM). FpB injected intravenously into the urethane-anaesthetized rat exhibited vasoconstrictor activity (EC50 = 2.5 micrograms kg-1) but was less potent than noradrenaline (EC50 = 0.9 micrograms kg-1). The doses of FpB required to contract the rabbit isolated aorta and to constrict the vasculature of the rat kidney occur naturally in the bloodstream of patients with thrombotic disease. FpB released at the site of thrombus formation may play a part in regulating local blood vessel calibre.

Animals↗
PubMedDate not supplied

Prostanoids stimulate fibrinolysis in the rat.

Fibrinolysis was assessed in urethane-anaesthetized rats challenged by bolus intravenous injection of eicosanoids. A sensitive fibrin plate bioassay was used for this purpose. Classical prostanoids such as PGE2, PGI2, PGD2 and PGF2 alpha produced a dose-related increase in fibrinolysis in the rat which was first evident 15 min post-injection and remained increased until 75 min when experiments were concluded. 6 oxo PGE1, the stable enzymatic metabolite of PGI2, exhibited similar pro-fibrinolytic activity in the rat. The rank order of potency was PGE2 greater than 6 oxo PGE1 greater than PGD2 greater than PGF2 alpha. Neither saline nor Tris-HCl buffer stimulated fibrinolysis. Furthermore, the chemical hydrolysis product of PGI2, 6 oxo PGF1 alpha, and the enzymatic metabolite of PGE2, 15 oxo PGE2, were inactive at doses up to 50 micrograms/kg. LtC4 was also inactive at doses up to 25 micrograms/kg. None of the prostanoids used in this study stimulated fibrinolysis when applied directly to fibrin plates at doses up to 50 micrograms. Prostanoids may owe some of their clinical efficacy in cardiovascular disorders to stimulation of blood fibrinolytic activity.

Animals↗