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R Qiu

Publications and source records attributed to R Qiu.

30 records · Page 2Linked to original sources
PubMed1994

Effects of lymphokines and mitogens on a histamine derivative-induced intracellular calcium mobilization and inositol phosphate production.

Histamine trifluoromethyl-toluidine derivative (HTMT), a novel immunosuppressive agent, stimulates H1, H2 and HTMT receptors in lymphocytes. HTMT receptors are different from the classical H1, H2 or H3 receptors. Stimulation of HTMT receptors results in increased intracellular concentrations of calcium ([Ca2+]i) and inositol phosphate (IP) in human peripheral blood lymphocytes. In the present study, we investigated the effects of lymphokines [interleukin-4 (IL-4), interleukin-2 (IL-2)] and other pharmacologic agents [lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA)] on HTMT-induced Ca2+ and IP responses in non-rosetted cells. HTMT caused enhanced [Ca2+]i and IP responses when the cells were pretreated with IL-4. The effects of IL-4 were concentration dependent and became maximal after the cells were incubated with IL-4 for 48 hr. Inhibitors of protein synthesis, but not of RNA synthesis, blocked the effects of IL-4 on HTMT-induced responses. LPS was more potent than IL-4 in augmenting CA2+ mobilization induced by HTMT. However, the effects of LPS were not altered by inhibitors of either protein synthesis or RNA transcription. This indicated that LPS may act differently than IL-4 on the HTMT response. IL-2 and PMA did not affect HTMT-induced [Ca2+]i and IP responses. The effects of IL-4 and LPS were agonist specific. They did not affect the Ca2+ mobilization induced by PAF. The data indicate that the response to HTMT can be regulated by IL-4 and LPS. Although the in vivo importance of these receptors is not yet clear, the receptor is likely a contributor to immune and/or inflammatory regulation.

Calcium↗
PubMed1994

A metastable state of high surface activity produced by sonication of phospholipids.

Sonication of phosphatidylcholine dispersions generates a metastable high energy assembly of molecules, the existence of which is revealed by its conspicuous surface activity. Freshly sonicated liposome dispersions release molecules to the air/water interface at rates sufficient to produce a close-packed monolayer within minutes. In contrast, monolayers at the surface of multilamellar and extruded vesicles take hours to form. The highly surface active species appears within the first few minutes of sonication, long before a major reduction in turbidity occurs, and accumulates over the course of a few hours of sonication. It disappears upon exhaustive sonication, extrusion, addition of extruded vesicles, or, more slowly, simply on standing. Tests for extraneous substances in the lipids before as well as after sonication revealed amounts of degradation products too small to represent the observed surfactant. Direct evidence that the metastable aggregate releases intact phospholipids was provided by a novel procedure to characterize monolayer composition by comparing surface tension with surface potential, both as a function of surface density. Centrifugation and gel filtration chromatography indicate that the surface activity is associated with a particle of diameter larger than a lysophosphatidylcholine micelle but not larger than limit sonicated vesicles. The metastable material appears to be lipid molecules in other than the normal stable vesicular state, perhaps an incompletely closed vesicle, one in which the inner and outer monolayers have not equilibrated, or possibly a micellar form.

Lipid Bilayers↗
PubMed1994

Fragmentation into small vesicles of dioleoylphosphatidylcholine bilayers during freezing and thawing.

Multilayered liposomes of some phosphatidylcholines progressively fragment into small vesicles when the electrolyte solution in which they are suspended is subjected to successive cycles of freezing and thawing. The fragmentation process, routinely monitored by absorbance measurements and verified by electron microscopy and dynamic light scattering, involves bilayer breakage and resealing. After 10 cycles of freezing and thawing in 0.1 M electrolyte solution, the result is a population of vesicles smaller than 200 nm diameter. Sucrose, a common cryoprotectant, completely inhibits fragmentation. Fragmentation is absolutely dependent upon the presence of an electrolyte. Those electrolytes most effective in promoting liposome fragmentation have large freezing point depressions and corresponding high solubilities at the freezing point. This, coupled with the observation that saturating concentrations of electrolyte are less effective than 0.1 M solutions indicates that an essential stage in the fragmentation process is osmotic extraction of water from the vesicles, i.e., ice formation in the external phase leads to a progressive increase in the electrolyte concentration of the residual external solution, which, in turn, dehydrates the vesicle. In addition, for maximal fragmentation, the minimum temperature must be at least as low as the solute eutectic temperature. Particular physical properties of the bilayer are also important, for dioleoyl and diphytanoyl derivatives are much more susceptible to fragmentation than are other phosphatidylcholines, and inclusion of 50 mol% cholesterol in dioleoylphosphatidylcholine completely inhibits membrane breakup. This system provides insight into mechanisms of freezing damage to membranes and may also offer a very simple and rapid assay for biological cryoprotectants.

Cholesterol↗
PubMed1990

Effects of histamine-trifluoromethyl-toluidide derivative (HTMT) on intracellular calcium in human lymphocytes.

We have studied the effects of histamine trifluoromethyl-toluidide derivatives on calcium mobilization in human peripheral blood lymphocytes using spectrofluorometric analysis. HTMT (compound 1) induced two phases of increase in intracellular calcium concentration--a rapid intracellular calcium concentration peak (10-60 sec), partial recovery (1-3 min) and a sustained moderate elevation that persisted for more than 5 min. The EC50 value was 1.9 X 10(-5) M. Pretreatment of lymphocytes with the agonist resulted in receptor desensitization that recovered after 15 min when the cells were drug free. The presence of extracellular ethylene glycol bis(beta-aminoethyl ether)N,N'-tetraacetic acid did not abrogate the early phase of the calcium rise, suggesting that the calcium appearing in the cytosol during the early phase was derived from intracellular stores. The increase in intracellular calcium concentration by this compound was competitively antagonized by high concentrations of histamine but not by classic histamine receptor antagonists (H1, H2 or H3). Other cyclic AMP elevating agents, with the exception of prostaglandin E2, did not affect the increase in calcium levels induced by compound 1. Compound 1 caused phosphatidylinositol metabolism resulting in inositol phosphate production, suggesting that inositol triphosphate may be the second messenger for the mobilization of intracellular Ca2+ by compound 1. The data imply a specific binding site for histamine trifluoromethyl toluidide derivative on lymphocytes that is different than the classic H1, H2 or H3 receptors.

Calcium↗
PubMed1989

Protective effects of histamine H1 and H2 antagonists, adenosine and hydrocortisone on cardiac anaphylaxis.

Cardiac anaphylaxis was elicited in isolated working guinea pig hearts in the presence of the histamine receptor antagonists pyrilamine and cimetidine, adenosine or hydrocortisone. Histamine antagonists partially inhibited the occurrence of arrhythmias during cardiac anaphylaxis, but did not significantly antagonize the decrease in cardiac function. Adenosine used in combination with pyrilamine and cimetidine manifested an apparent anti-arrhythmic effect, however, the attenuation of cardiac function was still present. In the presence of hydrocortisone plus histamine antagonists, cardiac anaphylaxis, as expressed by arrhythmias and a decrease in cardiac function, was significantly inhibited. The results suggest that when histamine receptor antagonists are used in combination with hydrocortisone, a good protective effect on cardiac anaphylaxis can be achieved.

Adenosine↗
PubMed1989

Dissociation of cimetidine effects on inotropic and chronotropic action in cardiac anaphylaxis.

The changes of heart rate (HR) and dP/dtmax elicited by challenging the sensitized heart and by a bolus injection of histamine in the presence of cimetidine were observed. The results showed that cimetidine did not completely inhibit the positive chronotropic effect in cardiac anaphylaxis. The increase in HR elicited by exogenous histamine on sensitized heart was completely abolished. Cimetidine inhibited the positive inotropic and chronotropic effect of histamine on normal heart in a dose-dependent manner. It is suggested either an H2 receptor subtype or concomitant with the release of histamine, other mediators eliciting positive chronotropism in cardiac anaphylaxis may exist.

Anaphylaxis↗
PubMedDate not supplied

Cyclic AMP is not a direct regulator of calcium flux and hydrolysis of phosphoinositides in human lymphocytes.

The regulatory effects of adenosine 3',5'-cyclic monophosphate (cAMP) on Ca2+ flux and phosphatidylinositol (PI) turnover in human lymphocytes were studied. cAMP did not affect the intracellular accumulation of Ca2+ induced by phytohemagglutinin (PHA) and histamine-trifluoromethyl toluidide derivative (HTMT) in peripheral blood lymphocytes (PBL). In addition, cAMP also did not alter Ca2+ flux induced by PHA, anti-CD3, or PAF in T cells, or by anti-IgM and HTMT in non-rosetted cells. Similarly, cAMP did not inhibit IP accumulation induced by HTMT in PBL, anti-CD3 in T cells, and by anti-IgM or HTMT in non-rosetted cells. The only exception was the synthesis of IP induced by PHA in T cells that was inhibited by cAMP. Furthermore, prolonged treatment of T cells with cholera toxin inhibited Ca2+ accumulation in response to CD3. The degree of inhibition of Ca2+ and IP responses was not proportional to the levels of intracellular cAMP generated.

Antibodies, Anti-Idiotypic↗
PubMedDate not supplied

A histamine derivative increases intracellular calcium mobilization and oxidative metabolism in HL-60 cells.

Past work in our laboratory has shown that a derivative of histamine, histamine-trifluoromethyl-toluidide (HTMT), has surprising tissue specificity on lymphocytes and can produce remarkable immunosuppression. This study focuses on the effects of HTMT on Ca2+ mobilization and oxidative metabolism in undifferentiated and DMSO-differentiated HL-60 cells. HTMT caused two phases of increases in intracellular calcium concentrations ([Ca2+]i) in HL-60 cells. The responses were dose dependent, with similar EC50 values (1.7 x 10(-5) M for undifferentiated and 1.5 x 10(-5) M for differentiated cells). The increase in [Ca2+]i in differentiated cells was much greater than in undifferentiated cells. The maximum responses were observed after the undifferentiated cells were incubated with DMSO for 7 days. The increase in [Ca2+]i induced by HTMT in both types of cells was competitively antagonized by high concentrations of histamine but not by classic histamine receptor antagonists (H1, H2, or H3). The inhibitory effects of histamine on [Ca2+]i accumulation in differentiated cells were partially reversed by histamine H2 receptor antagonist ranitidine, whereas in undifferentiated cells, the effects of histamine on Ca2+ mobilization were not affected by ranitidine. Other cAMP elevating agents did not inhibit increases in [Ca2+]i in undifferentiated cells but did affect [Ca2+]i in differentiated cells. The enhanced response in [Ca2+]i mobilization after differentiation of HL-60 cells appeared to be the result of an increase in the expression/function of receptors for HTMT. One interesting feature of this regulation was the fact that cAMP per se did not regulate HTMT induced Ca2+ mobilization in undifferentiated cells but inhibited the mobilization in differentiated cells. HTMT caused the generation of reactive oxygen species in both undifferentiated and differentiated HL-60 cells as measured by chemoluminescence and the levels of generation correlated with the mobilization of [Ca2+]i. In addition, the EC50s for the HTMT induced calcium mobilization and the generation of reactive oxygen species were similar, as was the case for histamine induced inhibition (Ki) in both cell types. The data imply a second messenger role for Ca2+ in HTMT induced neutrophil activation.

Binding Sites↗
PubMedDate not supplied

ACTH-receptor deficient mutants of the Y1 mouse adrenocortical tumor cell line.

Two mutant clones (Y6 and OS3) derived from the ACTH-responsive Y1 mouse adrenocortical tumor cell line fail to respond to ACTH with increased adenylyl cyclase activity and, as a consequence, are resistant to the steroidogenic effects of the hormone. As determined from Northern blot and RNase protection assays, ACTH resistance in these mutants results from the failure to accumulate ACTH receptor transcripts. The ACTH receptor gene appears to be present in these mutants as determined by Southern blot hybridization analysis and can be activated following the growth of the mutant cells as tumors in mice, suggesting that the ACTH receptor gene is modified in a reversible manner. When mutant cells are transformed with a gene encoding the mouse beta 2-adrenergic receptor they respond to beta-adrenergic agonists with increased adenylyl cyclase activity in a manner that is indistinguishable from a similarly transformed parent Y1 cell line. These results suggest that the adenylyl cyclase system in the mutants is otherwise intact and that the failure to express ACTH receptor transcripts limits the responsiveness of these clones to the hormone.

Adenylyl Cyclases↗