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Biomedical subjects

G Dupuis

Publications and source records attributed to G Dupuis.

At least 55 records · Page 3Linked to original sources
PubMed1994

Porous balloon catheters for local delivery: assessment of vascular damage in a rabbit iliac angioplasty model.

OBJECTIVES: This experimental study assessed long-term vascular damage induced by the use of porous balloon catheters designed for local delivery. BACKGROUND: Local drug delivery using porous balloon catheters has emerged as a possible means by which compounds designed to prevent restenosis might be delivered locally at concentrations higher than achievable by systemic administration. There are, nonetheless, some concerns about the possibility of greater arterial trauma induced by the high pressure fluid jets from the delivery catheter itself, a complication that could provide additional stimulus for intimal hyperplasia. Because these concerns are based mainly on in vitro studies and on studies performed after acute experiments, further work is required to assess the long-term effects of this device on the arterial wall. METHODS: Local delivery of a saline solution was performed in 32 rabbits in one iliac artery, using an inflation pressure of 6 atm and a balloon/artery ratio of 1.3 to 1.5, followed by angioplasty in both iliac arteries. Vascular injury was assessed using tritiated thymidine incorporation at 4 days (12 rabbits) and planimetry at 30 days after the procedure (20 rabbits). RESULTS: Tritiated thymidine incorporation did not reveal any significant difference between the angioplasty group and the group with local delivery and angioplasty (117,921 +/- 18,853 vs. 140,652 +/- 23,125 cpm/mg protein, p = NS). Planimetry at 30 days was also similar in the two groups (neointimal area 0.11 +/- 0.02 vs. 0.13 +/- 0.02 mm2). CONCLUSIONS: In this model the use of porous balloon catheters before angioplasty did not lead to greater intimal hyperplasia than angioplasty alone. Further experimental investigation is required to determine whether this strategy could be used to prevent postangioplasty restenosis in humans.

Analysis of Variance↗
PubMed1994

Panic disorder, chest pain and coronary artery disease: literature review.

OBJECTIVE: To examine the association among panic disorder, atypical chest pain and coronary artery disease (CAD). This article's purpose is to inform cardiologists of the prevalence of psychiatric disorders, primarily panic disorder, among patients consulting for chest pain. Panic disorder is described. Treatment modalities are summarized, and social, financial and medical consequences of nondetection are underlined. DATA SOURCES: PSYCHLIT and MEDLINE searches under panic disorder and chest pain-related headings were conducted. DATA EXTRACTION: The search covered January 1973 to June 1993. Thirty-eight articles were studied. DATA SYNTHESIS: Panic disorder is present in 30% or more of chest pain patients with no or minimal CAD and may coexist with CAD. Panic disorder may often be unrecognized by physicians. Left untreated, risk for disease progression may be augmented, and social vocational disability as well as medical costs may increase. CONCLUSION: Physicians should attend to the panic symptomatology and, when in doubt, refer possible panic patients with or without CAD to a mental health professional for assessment and treatment. Future panic prevalence studies in cardiology patients should be prospective, attempt to increase sample size and use randomized protocols where experimenters are blind to chest pain and medical diagnoses. Studies should also focus on CAD patients with atypical chest pain refractory to optimal cardiac therapy.

Chest Pain↗
PubMed1993

Priming of human monocytes with leukotriene B4 enhances their sensitivity in IL-2-driven tumor necrosis factor-alpha production. Transcriptional and post-transcriptional up-regulation of IL-2 receptors.

Cytotoxic activity of monocytes may be mediated by their production of TNF-alpha, and IL-2 has been shown to induce TNF-alpha production in monocytes and alveolar macrophages. Unstimulated human monocytes constitutively express the beta-chain of the IL-2R (IL-2R beta), but little or no IL-2R alpha. When monocytes were pretreated with leukotriene (LT) B4, they responded to IL-2 with both enhanced production of TNF-alpha (two- to threefold) and, more strikingly, with augmented sensitivity (1000-fold) to IL-2. Treatment of monocytes with LTB4 induced IL-2R alpha gene transcription at 30 min and augmented expression of IL-2R alpha gene transcripts by 3 h, maximal at 10(-8) M LTB4. LTB4 induced increased shedding of the IL-2R alpha in the culture supernatants and a modest induction of IL-2R alpha protein expression on monocytes. On the other hand, although LTB4 could stimulate the cell membrane expression of IL-2R beta and the accumulation of IL-2R beta mRNA, LTB4 did not significantly affect IL-2R beta gene transcription. The augmented expression of IL-2R on monocytes was associated with augmented binding of 125I-labeled IL-2 to LTB4-pretreated monocytes. Our data present direct evidence that the inflammatory lipid mediator LTB4 can induce the expression of IL-2R alpha in human monocytes by activating IL-2R alpha gene transcription; it can also stimulate the expression of IL-2R beta, through post-transcriptional regulation; this augmented expression of both alpha- and beta-chains of the IL-2R is associated with enhanced sensitivity of monocytes to IL-2 in terms of TNF-alpha production and may be relevant to the proinflammatory actions of LTB4.

Cells, Cultured↗
PubMed1993

Effects of modulators of cytosolic Ca2+ on phytohemagglutin-dependent Ca2+ response and interleukin-2 production in Jurkat cells.

We have previously reported the presence, in Jurkat T cells, of outward K+ currents and inward currents that have been attributed to Ca2+ channels. Here, we have studied the effects of dimethyl 1,4-dihydro-2,6-dimethyl-4-(2-nitrophenyl)-3,5-pyridine-dicarboxylate (nifedipine) and 4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-2,6-dimethyl-5- methoxy-carbonylpyridine-3-carboxylate (PN200-110), two dihydropyridines (DHPs) known to inhibit voltage-dependent Ca2+ channel activity in different types of cells, and two inhibitors of internal Ca2+ release (muscle cells), ryanodine and 3,4,5-trimethoxybenzoic acid 8-(diethylamino)octyl ester (TMB-8), on the Phaseolus vulgaris phytohemagglutinin (PHA)-dependent responses in Jurkat T lymphocytes. Our results show that nifedipine and PN200-110 inhibit the PHA-dependent production of interleukin-2 except when 12-O-tetradecanoyl-13-O-acetyl phorbol is added to the cultures. Ryanodine and TMB-8 are not inhibitors. The PHA-dependent Ca2+ response is significantly reduced when the cells are preincubated in the presence of the DHPs. Under these conditions, ryanodine has only a small inhibitory effect and TMB-8 has no effect. In contrast, only ryanodine (50 microM) decreases the PHA-dependent cytosolic release of Ca2+i when the cells are bathed in a medium containing a low concentration of Ca2+ (60 nM). The inhibitory effects of nifedipine and PN200-110 may result from the binding of these DHPs to specific receptor sites as revealed by studies using [3H]PN200-110 (KD = 8.5 +/- 3.1 nM; 2300 +/- 500 apparent binding sites/cell). Photoaffinity labeling studies using [3H]azidopine as a probe showed specific incorporation of label into three glycoproteins of molecular mass (+/- SD) 170 +/- 13, 110 +/- 25, and 60 +/- 17 kd as analyzed by electrophoresis under reducing conditions.

Affinity Labels↗
PubMed1993

Microtubules are not an essential component of phytohemagglutinin-dependent signal transduction in Jurkat T lymphocytes.

We have used two disruptors of the cytoskeleton microtubular network (colchicine and vinblastine) to investigate the role of microtubules in Phaseolus vulgaris phytohemagglutinin (PHA) signal transduction in Jurkat T cells. Both drugs decreased but did not abolish the PHA-dependent Ca2+ response of Jurkat cells. Neither colchicine nor vinblastine had any major effects on the PHA-dependent turnover of the mono-, di-, tri-, and tetra-substituted phosphorylated derivatives of D-myo-inositol or the cellular distribution of protein kinase C (PKC) activity. However, both microtubule disruptors increased interleukin-2 (IL-2) production. Whereas vinblastine enhanced IL-2 production approximately twofold at all the concentrations tested (0.1, 1.0, and 10 microM), colchicine did so only at a 10 microM concentration. When a combination of PHA and 12-O-tetradecanoyl-13-O-acetyl phorbol (TPA) was used, a small increase in IL-2 production was observed only in the presence of vinblastine (10 microM). In contrast to recent reports that microfilaments may be involved in the regulation of signal transduction, our data suggest that this is not the case for microtubules in PHA-dependent signal transduction in Jurkat T cells.

Animals↗
PubMed1992

Dual regulation of the n type K+ channel in Jurkat T lymphocytes by protein kinases A and C.

We have measured the activity of the n type K+ channel present in human (Jurkat) T lymphocytes using the patch clamp technique in the whole-cell configuration. We report that protein kinase A (PKA) and protein kinase C (PKC) modulate, in a dual manner, the K+ conductance in these cells. Activation of PKA decreases the amplitude of the current, as previously reported (Bastin, B., Payet, M. D., and Dupuis, G. (1990) Cell. Immunol. 128, 385-399), and this is also the case for 12-O-tetradecanoylphorbol-13-acetate-dependent activation of PKC. In contrast, inhibitors of PKC (H7, staurosporine, polymixin B, and anti-PKC antibody) increase the current amplitude. Of importance, down-regulation of PKC or its inhibition prevented the PKA-dependent inhibition of the K+ channels. Addition of alkaline phosphatase via the patch pipette increased the K+ conductance under basal conditions and reversed the inhibition produced by PKA. The dual modulation of K+ channels in Jurkat T cells is in agreement with the presence of consensus sequences in the primary structure of the n type K+ channel.

Alkaline Phosphatase↗
PubMed1992

Q fever endocarditis: diagnostic approaches and monitoring of therapeutic effects.

The scope of current diagnostic methods for Q fever endocarditis includes serology, direct demonstration of Coxiella burnetii in the resected heart valve tissue, and animal inoculation studies. Illustrated by a clinical case report, the different methods are presented and discussed. Serology represents the primary method, using the techniques of complement fixation, indirect immunofluorescence, and enzyme-linked immunosorbent assay (ELISA). The latter two techniques allow the detection of immunoglobulins G, M, and A to the phase I and II antigens of C. burnetii. After cardiac surgery, we visualized C. burnetii on smears and specifically stained it on histologic sections of the resected heart valve by light and electron microscopic immunohistochemistry. In addition, seroconversion in animals after inoculation with valve specimens confirmed the presence of C. burnetii in the heart valve. The antibody titers determined by ELISA correlated well with the patient's clinical course during the treatment period. Therefore it is suggested that its usefulness for monitoring the efficacy of antimicrobial agents in patients with Q fever endocarditis should be further evaluated.

Endocarditis, Bacterial↗
PubMed1991

Human PAF receptor gene expression: induction during HL-60 cell differentiation.

Platelet-activating factor is a potent lipid mediator of inflammation and immune regulation. Its numerous biological activities are mediated through specific receptors on the plasma membranes of responsive cells. The expression of such receptors may be modulated by various agents, including those responsible for cell differentiation. Here, we demonstrate that differentiation of the human promyelocytic leukemia cell line HL-60 by 1 alpha,25(OH)2 vitamin D3 towards the macrophage phenotype is associated with induction of PAF receptor gene expression: PAF receptor mRNA accumulation correlates with the induction and development of specific PAF responsiveness as assayed by [Ca2+]i fluxes. Our studies suggest that PAF responsiveness parallels macrophage differentiation and that PAF receptor expression can be regulated at the transcriptional level.

Blotting, Northern↗
PubMed1991

[The diagnosis of Lyme borreliosis. Apropos of a neurological case].

The clinical diagnosis of Lyme borreliosis is easily established in the initial phase of the illness. Erythema chronicum migrans is pathognomonic of this infection. However, during further complications (neurological, cardiac or articular) the diagnosis is chiefly based on laboratory results. The detection of specific antibodies to B. burgdorferi is one of the effective means of confirming the diagnosis. Culture or isolation of this bacteria is not routinely performed due to its very low yield. In this article a case of serologically proved neuro-borreliosis is described and the methods of diagnosis are discussed. Intrathecal synthesis of antibodies observed in the cerebrospinal fluid of this patient and the specificity of serologic tests confirmed by Western-blot provide the diagnosis. However, the absence of locally synthesized antibodies in the cerebrospinal fluid is not sufficient to rule out neuro-borreliosis.

Aged↗
PubMed1991

Spectrofluorimetric and image recordings of spontaneous and lectin-induced cytosolic calcium oscillations in Jurkat T cells.

Intracellular variations in Ca2+ concentrations have been measured in single Jurkat T lymphocyte variants (77 6.8 and E6.1) using Fura-2 as a probe. Under basal conditions, the cytosolic Ca2+ level is stable but some cells show spontaneous Ca2+ oscillations (frequency, 0.30 +/- 0.06 Hz). These oscillations are sensitive to the external concentration of Ca2+ since they can no longer be observed when the bathing solution is replaced (superfusion) with a Ca(2+)-free medium or when a Ca2+ chelator (EGTA) is added. Various changes in the cytosolic concentration of Ca2+ ([Ca2+]i) can be observed when the cells are exposed to the mitogenic lectin phytohemagglutinin (PHA, 80 nM). For instance, in the case of non-oscillating cells, the lectin induces either a rapid increase in [Ca2+]i that is followed by a sustained response (plateau) or it triggers Ca2+ spikes. In the case of experiments done in Ca(2+)-free medium, only the initial spike was observed. In the case of spontaneously oscillating cells, PHA induces a rapid increase in [Ca2+]i that is followed by a plateau where oscillations are absent. In every case, the PHA-dependent Ca2+ response is abrogated in a Ca(2+)-free medium. Computer simulations based on the model of Goldbeter et al. [27] show that the various Ca2+ responses of Jurkat cells are related to the cytosolic level of free Ca2+. Video imaging analyses show that the cellular Ca2+ responses are not homogeneous whether the observations are made in spontaneously oscillating Jurkat cells or when they are exposed to PHA.

Calcium↗
PubMed1990

Effects of modulators of adenylyl cyclase on interleukin-2 production, cytosolic Ca2+ elevation, and K+ channel activity in Jurkat T cells.

We have studied the effects of prostaglandin E2 (PGE2) and cholera toxin, two modulators of adenylyl cyclase, and 8-bromo cAMP (8-BrcAMP) on various parameters of lymphocyte activation using the human T cell line Jurkat. Our results show that PGE2 and cholera toxin inhibit, in a dose-related manner, the phytohemagglutinin (PHA)-dependent production of interleukin 2 by these cells. The data are consistent with the interpretation that the inhibition is due to an intracellular increase in cAMP, since the metabolically stable 8-BrcAMP analog produced the same inhibitory effect. However, PGE2 or 8-BrcAMP did not interfere with the PHA-induced elevation in the cytosolic concentration of Ca2+, suggesting that changes in the intracellular concentration of cAMP does not affect the internal release or the influx of Ca2+. In contrast, cholera toxin prevented the Ca2+ response of Jurkat cells to PHA. We studied the effects of PGE2, cholera toxin, and 8-BrcAMP on the amplitude of the K+ outward current using the patch clamp technique in the whole cell configuration. Results showed that PGE2, 8-BrcAMP, and cholera toxin inhibited K+ channel activity. For instance, the amplitude of the outward K+ current was reduced to 43 +/- 19%, 50 +/- 26%, and 46 +/- 16% of control values in the case of cells perfused in the presence of PGE2, 8-BrcAMP, and cholera toxin, respectively. Blocking K+ channels with tetraethylammonium ions did not prevent the characteristic Jurkat Ca2+ response to PHA. Our observations that cAMP inhibits K+ channel activity in a T cell line provide an additional explanation for its reported inhibition of lymphocyte activation. Increasing the intracellular concentration of cAMP may result in reduction of K+ movements and in negative modulation of signal transduction via G-proteins as previously suggested. These two effects could act in synergy to impair signal transduction.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1990

Increase in histone poly (ADP-ribosylation) in mitogen-activated lymphoid cells.

Poly (ADP-ribosylated) histones appear to be intermediates in nuclear processes that involve DNA strand breaks. We have studied histone ADP-ribosylation in cellular lysates from activated human lymphoid cells in culture. Modified histones differing in the number of ADP-ribose groups gave separate bands upon two-dimensional gel electrophoresis. Cellular lysates from control cells contained histones modified with 1 to 15 ADP-ribose groups. Stimulation of the cells during culture with phytohemagglutinin (PHA) or a phorbol ester (TPA) as well as combinations of these two reagents led to a significant increase in the upper limit number of ADP-ribose groups attached to histones in the presence of divalent metal ions. Hyper (ADP-ribosylated) H2B carrying at least 32 ADP-ribose groups gave a distinctly characteristic pattern on two-dimensional gels showing that highly ordered enzymatic steps are followed for its synthesis. Moreover, it was found that PHA and/or TPA induces branching of the poly (ADP-ribose) on H2B. The increase in histone poly (ADP-ribosylation) following lymphocyte activation was less dramatic during incubation of cellular lysates in the absence of divalent metal ions. The increased histone modification observed in this study may result from an increase in cell proliferation during activation of lymphoid cells. The finding that the number of ADP-ribose groups on H4 equals or exceeds by one the number of acetyl groups suggests that the two modifications may share common functions.

Calcimycin↗
PubMed1990

[Hyalinizing trabecular adenoma of the thyroid gland. Histologic and immunohistochemical study. Report of 2 cases].

Hyalinizing trabecular adenoma of the thyroid gland is an uncommon neoplasm that was recently described by Carney et al. (1987). It is important to recognize this tumor, considered benign, as it may mimic papillary carcinoma, medullary carcinoma or paraganglioma. We present two cases with histological and immunohistochemical criteria and discuss the diagnostic problems. Grossly, this small tumor is yellow tan and well circumscribed. The epithelial cells, polygonal or elongated and sharply outlined, have an eosinophilic or clear cytoplasm. The nuclei are oval or elongated, with often non-visible nucleoli. Grooved nuclei are quite frequent. Mitotic figures are very uncommon. The cells are arranged in clusters or trabeculae or pseudofollicles containing colloid material. Characteristically the cells, arranged shoulder to shoulder, can show a palisade pattern. The fibrovascular stroma appears hyaline, pseudoamyloid (Congo red staining is negative). The tumor cells show intense staining for thyroglobulin and no staining for thyrocalcitonin. Immunoreactivity for cytokeratin, vimentin, protein S100, NSE is positive but staining is negative for EMA and desmin. In one case, the tumor cells show little positivity for chromogranin A. The variable patterns of this tumor can lead to diagnostic problems. We can exclude the diagnosis of papillary carcinoma as this tumor lacks any true papillary architecture. We reject the diagnosis of medullary carcinoma because of its thyroglobulin and calcitonin immunoreactivity. Paraganglioma never shows immunoreactivity for thyroglobulin. Very often the surrounding thyroid tissue shows focal thyroiditis. The association of the tumor with Hashimoto's thyroiditis can be explained by an autoimmune process.

Adenoma↗
PubMed1989

Characterization of Ca2+ and K+ currents in the human Jurkat T cell line: effects of phytohaemagglutinin.

1. Inward and outward currents were recorded in the human Jurkat T cell line using the whole-cell configuration of the patch-clamp technique. 2. The transient outward current was activated at membrane potentials positive to -60 mV. The activation time constant-voltage relationship decreased from 17 ms to 2 ms for membrane potentials ranging from -40 to +40 mV. The inactivation phase could be fitted by a single-exponential function and the inactivation time constant decreased from 250 ms to 150 ms for membrane potentials ranging from -20 to +100 mV. 3. The steady-state inactivation-voltage relationship showed a mid-point potential of -32 +/- 2.6 mV, and the slope factor was 10.8 +/- 1.8 mv (n = 3). 4. The calcium ionophore A23187 provoked a decrease in the amplitude of the outward current, suggesting a dependence of this current on the cytosolic concentration of Ca2+. 5. The K+ outward current was blocked by tetraethylammonium (TEA, Michaelis-Menten constant (Km), 6 mM) and by the calcium channel blockers Ni2+, Co2+, Mn2+ and Cd2+. 6. Forty per cent (n = 120) of the patched Jurkat cells displayed an inward current. In a physiological medium containing Ca2+ (2.2 mM), the inward current threshold voltage was -60 mV, the maximum current was observed at -40 mV and the zero current voltage was positive to +20 mV. At negative membrane potentials, the time required to reach 50% of the maximum amplitude was 60 ms and grew shorter with increasing depolarization, reaching a value of 5 ms at -5 mV. The inactivation of the inward current was very slow and the time constant varied from 1200 ms at -35 mV to approximately 250 ms for potentials positive to -10 mV. 7. The current availability had a value of one for potentials negative to -50 mV and zero for potentials positive to -15 mV. The mid-point potential was -31 +/- 3.4 mV and the slope factor was 3.3 +/- 0.2 mV (n = 3). 8. The inward channels were permeable to Sr2+, but were blocked by classical Ca2+ channel inhibitors such as Co2+, Mn2+ and Ni2+. 9. Phaseolus vulgaris phytohaemagglutinin (PHA), an inducer of interleukin-2 production in Jurkat cells, increased the inward current amplitude by 32 +/- 20% (n = 4). This increase was concomitant with a decrease (45 +/- 12%) in the amplitude of the outward current, but only when the current was carried by Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Calcium Channels↗
PubMed1989

[Efficacy and tolerability of cefuroxime-axetil in infections of the upper respiratory tract. Comparative study with cefadroxil].

Cefuroxime-axetil is the first oral broad spectrum cephalosporin to be naturally stable in the presence of bêta-lactamases. The aim of this randomized trial was to evaluate the efficacy and safety of cefuroxime-axetil (250 mg twice daily after meal) with cefadroxil (1 g twice daily during meal) for the treatment of upper respiratory tract infection. In this study 150 patients were enrolled. Before treatment, the two groups were comparable. Clinical success was achieved for 94.3% of the patients treated with cefuroxime-axetil versus 90.4% for cefadroxil. Statistical significance was reached (p less than 0.05) concerning the number of days with facial pain for sinusitis (3 days for the cefuroxime-axetil treated group versus 4 days), the rate of normal tympanum at the second examination (58.3% vs 20% respectively) for otitis, and the number of day with painful dysphagia for tonsillitis (2.6 vs 3.8 days respectively). Cefuroxime-axetil was safe (a few advers events occurred, almost all gastro-intestinal). Cefuroxime-axetil is a safe and effective treatment of upper respiratory tract infections.

Adolescent↗