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Biomedical subjects

J Dubé

Publications and source records attributed to J Dubé.

At least 19 recordsLinked to original sources

Prostaglandin E(2) increases cyclic AMP and inhibits endothelin-1 production/secretion by guinea-pig tracheal epithelial cells through EP(4) receptors.

Prostaglandin E(2) (PGE(2)) increased adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation in tracheal epithelial cells and concomitantly decreased the production/secretion of immunoreactive endothelin (irET). Naturally occurring prostanoids and selective and non-selective EP receptor agonists showed the following rank order of potency in stimulating cyclic AMP generation by epithelial cells: PGE(2) (EP-selective)>16,16-dimethyl PGE(2) (EP-selective)>11-deoxy PGE(2) (EP-selective)>>>iloprost (IP/EP(1)/EP(3)-selective), butaprost (EP(2)-selective), PGD(2) (DP-selective), PGF(2alpha) (FP-selective). The lack of responsiveness of the latter prostanoids indicated that the prostanoid receptor present in these cells is not of the DP, FP, IP, EP(1), EP(2) or EP(3) subtype. Pre-incubating the cells with the selective TP/EP(4)-receptor antagonists AH23848B and AH22921X antagonized the PGE(2)-evoked cyclic AMP generation. This suggested that EP(4) receptors mediate PGE(2) effects. However, in addition to any antagonistic effects at EP(4)-receptors, both compounds, to a different extent, modified cyclic AMP metabolism. The selective EP(1), DP and EP(2) receptor antagonist (AH6809) failed to inhibit PGE(2)-evoked cyclic AMP generation which confirmed that the EP(2) receptor subtype did not contribute to the change in cyclic AMP formation in these cells. The PGE(2)-induced inhibition of irET production by guinea-pig tracheal epithelial cells was due to cyclic AMP generation and activation of the cyclic AMP-dependent protein kinase since this effect was reverted by the cyclic AMP antagonist Rp-cAMPS. These results provide the first evidence supporting the existence of a functional prostaglandin E(2) receptor that shares the pharmacological features of the EP(4)-receptor subtype in guinea-pig tracheal epithelial cells. These receptors modulate cyclic AMP formation as well as ET-1 production/secretion in these cells.

Adenosine↗

Adenosine induces cyclic-AMP formation and inhibits endothelin-1 production/secretion in guinea-pig tracheal epithelial cells through A(2B) adenosine receptors.

1. The adenosine receptor subtype mediating adenosine 3' : 5'-cyclic monophosphate (cyclic AMP) formation and the effect of its activation on endothelin-1 (ET-1) secretion were studied in primary cultures of tracheal epithelial cells. 2. Adenosine analogues showed the following rank order of potency (pD(2) value) and intrinsic activity on the generation of cyclic AMP by tracheal epithelial cells: 5'-N-ethylcarboxyamidoadenosine (NECA, A(1)/A(2A)/A(2B), pD(2): 5.44+/-0.16)>adenosine (ADO, non selective, pD(2): 4.99+/-0. 09; 71+/-9% of NECA response) >/=2-Cl-adenosine (2CADO, non selective, pD(2): 4.72+/-0.14; 65+/-9% of NECA response)>>>CGS21680 (A(2A); inactive at up to 100 microM). 3. Cyclic AMP formation stimulated by NECA in guinea-pig tracheal epithelial cells was inhibited by adenosine receptor antagonist with the following order of apparent affinity (pA(2) value): Xanthine amine congeners (XAC, A(2A)/A(2B), 7.89+/-0.22)>CGS15943 (A(2A)/A(2B), 7.24+/-0. 26)>ZM241385 (A(2A), 6.69+/-0.14)>DPCPX (A(1), 6.51+/-0. 14)>3n-propylxanthine (weak A(2B), 4.30+/-0.10). This rank order of potency is typical for A(2B)-adenosine receptor. 4. Adenosine decreased basal and LPS-stimulated irET production in a concentration-dependent manner. Moreover, NECA but not CGS21680 inhibited LPS-induced irET production. 5. The inhibitory effect of NECA on LPS-induced irET production was reversed by XAC (pA(2)=8.84+/-0. 12) and DPCPX (pA(2)=8.10+/-0.22). 6. These results suggested that adenosine increased cyclic AMP formation and inhibited irET production/secretion by guinea-pig tracheal epithelial cells through the activation of a functional adenosine receptor that is most likely the A(2B) subtype. This adenosine receptor may be involved in the regulation of the level of ET-1 production/secretion by guinea-pig tracheal epithelial cells in physiological as well as in pathophysiological conditions.

Adenosine↗

Synergistic action of endothelin (ET)-1 on the activation of bronchial fibroblast isolated from normal and asthmatic subjects.

Bronchial subepithelial fibrosis is an histological characteristic of asthma. Cytokines and other mediators, such as PDGF-BB, TGF-beta1 and ET-1 found in the asthmatic submucosa can potentially activate a repair process that leads to fibroblast proliferation and collagen synthesis. The mechanisms of modulation of the repair process leading to extracellular matrix deposition are still to be documented. In this study, we assessed the in vitro proliferation and collagen synthesis of bronchial fibroblasts isolated from normal and asthmatic subjects in response to ET-1, platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-beta1 alone or in combination, in the presence or absence of dexamethasone. The combination of ET-1 with one of the other two growth factors, or the triple combination, significantly increased DNA synthesis and collagen production of bronchial fibroblasts isolated from both normal and asthmatic subjects, but the same growth factors used separately had no significant effect on the same parameters. These results suggest that the simultaneous presence of ET-1, PDGF-BB and TGF-beta1 in both normal and asthmatic subjects is necessary to activate bronchial fibroblast proliferation and collagen synthesis. As these mediators are present in the submucosa of the asthmatic bronchi, they could be responsible, at least in part, for the accumulation of collagen in the mucosa.

Analysis of Variance↗

Stroke-like episodes in autosomal recessive cytochrome oxidase deficiency.

Stroke-like episodes, defined as periods of acute localized neurological dysfunction during which brain imagery suggests cerebral ischemia but vascular anatomy is normal, occurred in 3 patients with autosomal recessive Saguenay-Lac St-Jean (SLSJ) cytochrome oxidase (COX) deficiency. The patients developed focal neurological deterioration and frontal hypodensities on cerebral computerized tomography (CT). Arteriography, performed in 1 patient during an acute episode, showed normal vascular anatomy. Nevertheless, capillary shunting was evident both in regions that appeared abnormal on the initial cerebral CT study and in regions that appeared normal but subsequently developed Leigh disease. Stroke-like episodes did not exacerbate systemic acidosis, and acidotic decompensations occurred independently of stroke-like episodes. In conclusion, stroke-like episodes occur in autosomal recessively inherited congenital lactic acidoses as well as in those caused by mitochondrial DNA mutations. In some cases, acute localized neurovascular changes occur in regions that subsequently develop Leigh disease.

Brain↗

In vitro procollagen synthesis and proliferative phenotype of bronchial fibroblasts from normal and asthmatic subjects.

Asthma is characterized histologically by a bronchial subepithelial fibrosis. Cytokines and other mediators released in the asthmatic chronic inflammatory microenvironment can activate the repair process that leads to fibroblast proliferation and collagen synthesis. To our knowledge, there are no data regarding the effect of a chronic inflammatory microenvironment on the phenotype of human bronchial fibroblasts. In the present study, we address this issue by comparing bronchial fibroblasts isolated from normal and asthmatic subjects in terms of: (a) proliferation over cell passage; (b) in vitro lifespan; (c) proliferative response to transforming growth factor-beta 1, platelet-derived growth factor-BB, dexamethasone, and retinoic acid; and (d) base-line synthesis of procollagens I and III. Bronchial fibroblasts from asthmatic subjects demonstrated lower DNA synthesis with cell passage than bronchial fibroblasts from normals. The in vitro lifespan of asthmatic bronchial fibroblasts was lower than in those from normal subjects and was significantly correlated with airway responsiveness. Platelet-derived growth factor-BB and dexamethasone increased 3H-thymidine incorporation in asthmatic bronchial fibroblasts without having any significant effect on normal fibroblast proliferation. Transforming growth factor-beta 1 and retinoic acid had no significant effect on bronchial fibroblast proliferation. Base-line procollagens I and III synthesis measurements showed no differences between normal and asthmatic fibroblasts. Taken together, these results indicate that the chronic inflammatory microenvironment found in asthma can modulate some aspects of bronchial fibroblast phenotype.

Adult↗

Peripherally inserted central catheters in infants and children.

PURPOSE: To determine prospectively the feasibility, complications, and mid- and long-term advantages of peripheral insertion of central catheters in infants and children. MATERIALS AND METHODS: During a 15-month period between March 1995 and June 1996, a total of 285 catheter placement attempts were made to peripherally insert central catheters in 183 pediatric patients (89 boys, 94 girls). Phlebographic guidance was used, and the catheters were inserted below the elbow in 99% of cases. Catheter insertion was indicated for prolonged antibiotic therapy in 108 patients (158 catheter placement attempts), hematologic or oncologic care in 24 patients (40 attempts), total parenteral nutrition in 16 patients (46 attempts), and venous access for fluid or blood in 35 patients (41 attempts). The success rate and complications were recorded along with the indication, patient age, and duration of catheter placement. RESULTS: One hundred fifty-two of 158 (96%) catheter placement attempts were successful in outpatients (n = 108), 124 of 127 (98%) in hospitalized patients (n = 75), and 70 of 73 (96%) in patients aged less than 1 year. Infection and pericatheter venous thrombosis were the main complications and were seen in 17 of 276 (6%) and one of 276 (0.3%) catheter placement attempts, respectively. Catheter occlusion occurred in 23 of 276 (8%) catheter placement attempts. CONCLUSION: Peripheral insertion of central catheters was highly feasible in infants and children with this protocol. Such catheters were well tolerated in the pediatric population with a low frequency of complications.

Catheterization, Central Venous↗

Morphologic and functional properties of bronchial cells isolated from normal and asthmatic subjects.

Recent advances in biomedical sciences have led to the development of various methods for the evaluation of the physiopathology of respiratory diseases. This study reports morphologic and functional features of cells isolated by a new method from bronchial biopsies of normal and asthmatic subjects. Both epithelial and fibroblastic cells were isolated from the same biopsies using collagenase. The cells were cultured for several passages and stored frozen. Two selective culture media were used in order to obtain pure epithelial and fibroblastic cell populations. Immunofluorescence analysis of intermediate filaments, keratins, and vimentin confirmed the type of the isolated cells. The proportions of alpha-actin-expressing cells varied among the fibroblastic cell populations isolated from normal and asthmatic subjects. Interestingly, the population containing high numbers of alpha-actin-expressing cells and presenting the fastest collagen contraction kinetic was isolated from bronchial biopsies of an asthmatic subject. Moreover, the fibroblastic cells that showed the best contractile properties 24 h after their seeding in floating collagen gels were isolated from bronchial biopsies of asthmatic patients having PC20 values below 1 mg/ml. On the basis of these data, we propose a new approach to isolate, culture and characterize human bronchial cells in vitro.

Adult↗

Lower airways remodeling in nonasthmatic subjects with allergic rhinitis.

We analyzed by immunohistochemistry the distribution of types I, II, III, IV, V, and VII collagens, laminin, and fibronectin in the bronchial biopsy specimens of nonasthmatic subjects with seasonal allergic rhinitis (n = 8) and compared these results with those found in mild stable allergic asthmatics (n = 6) and normal controls (n = 5). The content of type I and III collagens was increased in rhinitic subjects compared with controls. These collagens were focally deposited in the reticular basement membrane area. Three subjects with allergic rhinitis had no fibronectin deposition in their basement membrane, as in controls, whereas the other five had a focal fibronectin deposition. In asthmatic patients, type I and III collagens and fibronectin were more abundant and more uniformly distributed underneath the basement membrane than they were in rhinitic subjects. Expression of type II, IV, V, and VII collagens and laminin were similar in the three groups. Electron microscopic and immunohistochemical analyses of bronchial mucosa showed a network of myofibroblasts beneath the epithelium in rhinitis as in asthma subjects. These data show that the irregularly distributed subepithelial fibrosis observed in subjects with allergic rhinitis results from the deposition of type I and III collagens and fibronectin, probably produced by bronchial myofibroblasts. These results suggest the presence of an active structural remodeling in the lower airways of allergic rhinitic subjects that is similar in nature to that seen in asthma, although less marked.

Adult↗

Renovascular hypertension in children: curability predicted with negative intrarenal Doppler US results.

PURPOSE: To assess whether intrarenal Doppler ultrasound (US) enables prediction of the outcome of renovascular hypertension in a pediatric population. MATERIALS AND METHODS: A prospective study of 29 children with renin-mediated hypertension was performed. In these patients, intrarenal Doppler US was performed before angiography. Doppler US and angiographic findings were compared with patient outcome with respect to treatment required and blood pressure (BP) status after therapy. Cure was defined as a normal BP without medication. RESULTS: Intrarenal Doppler US was positive in 15 patients (52%), group 1, and negative in 14 patients (48%), group 2. In 10 patients (67%) in group 1, the severity of the vascular lesion precluded permanent cure. Cure was achieved in all patients in group 2, except for patients with neurofibromatosis. Thus, there was a statistically significant association (P < .05) between cure and a negative Doppler US result. CONCLUSION: In children with renovascular hypertension, a negative Doppler US result enables the prediction that a cure is more likely to be achieved with endovascular therapy or surgery.

Angioplasty, Balloon↗

Hyperammonemia-hyperornithinemia-homocitrullinuria syndrome: neurologic, ophthalmologic, and neuropsychologic examination of six patients.

We report the clinical, electrophysiologic, ophthalmologic, and neuropsychologic features of six patients with hyperammonemia-hyperornithinemia-homocitrullinuria syndrome, an inborn error of ornithine metabolism. Pyramidal signs, decreased vibration sense, bucco-facio-lingual dyspraxia, and learning difficulties or subnormal intelligence were found in the majority. Anomalies of peripheral nerve conduction velocity and of evoked potentials were common, and one patient had markedly abnormal white matter images on cranial magnetic resonance imaging. One patient had retinal depigmentation and chorioretinal thinning. The clinical severity varied greatly among patients; in general, the three younger patients had less neurologic and intellectual impairment than did the three older patients. Only two of our patients have had episodes of symptomatic hyperammonemia. We conclude that hyperammonemia-hyperornithinemia-homocitrullinuria syndrome can be associated with widespread manifestations in the central and peripheral nervous systems. Although the control of hyperammonemia is an essential element in the treatment of these patients, the relationship of hyperammonemia to the chronic neuropsychologic problems of these patients is unclear.

Adolescent↗

Blood banking-induced senescent modifications on red blood cells.

In the past few years significant progress has been made in the extension of storage time for red blood cells (RBCs). Albeit this, membrane still undergoes damage during conservation under blood bank conditions, reducing red cell viability following transfusion. Consequently in this study, we evaluated the presence of senescence indices (appearing on RBCs during in vivo aging) on blood bank stored RBCs, more precisely the 4.1a/4.1b ratio and the binding of autologous immunoglobulins. Although not significant, a slight increase (0.995 +/- 0.070 to 1.008 +/- 0.058) was observed in the 4.1a/4.1b ratio during the first three weeks of storage. A rapid and significant (p less than 0.001) increase in the number of cell-bound IgGs (91 +/- 22 to 913 +/- 92), following incubation with purified autologous IgGs, was observed in the first days of storage. Thus, following transfusion, binding of autologous IgGs to stored RBCs could influence post-transfusion viability.

Acids↗

Sodium-phosphate cotransport and vascular reactivity.

Inorganic phosphate (PO4) alters vascular reactivity in vivo as well as in vitro. In the latter condition, low PO4 reduces, while high PO4 augments reactivity. We used phosphonoformate (PFA), a phosphaturic compound, binding the renal Na-PO4 co-transporter, to examine the existence of such a transport mechanism in selected vascular smooth muscles (VSM). Strips of aorta (A), mesenteric artery (MA), and vein (MV) were obtained from normal rabbits. All tissues were either superfused in normal PO4 (Group 1: 3 mg/dL), then in modified low PO4 (Group 2: 0 mg/dL) or high PO4 (Group 3: 9 mg/dL) Ringer's solutions. The effect of angiotensin II (AII: 10-11 to 10-8M) was tested on each tissue preparation, and contraction values obtained in the presence of PFA (18.5 micrograms/ml:0.018 ml/min) were compared to control responses in the absence of the drug. In Group 1, the contractions of A were reduced by 23% during PFA, for higher doses of AII only, compared to controls (p less than 0.01). Similarly, the contractions of MA in the presence of PFA were reduced at higher doses of AII, by 22% (p less than 0.01). Finally, the contractions of MV were reduced by 75% (p less than 0.01) for all doses of AII. In Group 2, there was no difference in vascular tissue contraction between controls and PFA, whereas in Group 3, the reduction in A, MA, and MV contractions in PFA-treated tissues were approximately twice as extensive as in Group 1 (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

The large vestibular aqueduct syndrome and sensorineural hearing loss in the pediatric population.

Sensorineural hearing loss, associated with a dilated vestibular aqueduct, is often described as progressive. Since 1982, computed tomography of the mastoids has become part of the routine investigation of deaf children at Sainte-Justine Hospital. Using clinical, audiometric and radiological material from 130 patients with sensorineural hearing loss, we identified 18 patients with enlarged vestibular aqueducts. The large vestibular aqueduct population was then compared to the normal vestibular aqueduct patients in regard to the degree and evolution of the sensorineural hearing loss. Progression of hearing loss was noted in 46% of patients in the presence of large vestibular aqueducts as compared to 35% in the absence of this anomaly. Normal radiographic findings did not exclude the possibility of further hearing loss.

Child↗

[The role of conjugal relations in the abuse and neglect of children: towards an ecological study].

The phenomenon of child abuse and neglect has always existed in Western society. Yet, it is only recently that clinicians and researchers have taken a serious look at these problems. This ever growing interest has come about from not only the stunning number of cases identified each year, but also by the extent and gravity of consequences observed among children. Several professionals interested by the issue have put forward a great number of etiological factors to try to explain abuse and neglect within the family unit. However, when assessing the proposed theoretical models (psychiatric/psychological, sociological, systemic), it appears that certain simple factors can play a large role, for instance the history behind parental development, the quality of marital relations, the child-parent relation, the stress and the extent of the social network, but none of these can clearly differentiate abusive families from non abusive families. It seems however that these different explicative factors would be even more valuable if they were considered in interaction rather than taken individually. Inspired by the ecological framework proposed by Bronfenbrenner (1977, 1979), Belsky (1980, 1984) as well as Cicchetti and Rizley (1981) have also developed a model that simultaneously takes into account all of these factors and their interaction.

Adult↗

Epstein-Barr virus polymorphic B-cell lymphoma associated with leukemia and with congenital immunodeficiencies.

Polymorphic B-cell lymphoma seen in four patients with congenital immunodeficiencies and in two patients with leukemia receiving chemotherapy was associated with the Epstein-Barr virus (EBV). The tumors had characteristic histologic features: they were polymorphic consisting of a mixture of lymphoblasts and differentiated cells including plasma cells, and areas of hemorrhagic necrosis were prominent. The tumors were either polyclonal, monoclonal, or multiclonal. Patients with congenital immunodeficiencies who developed these tumors died despite radiotherapy, corticosteroids plus acyclovir, or a combination of intravenous (IV) immunoglobulins and alpha 2 interferon. Patients with leukemia recovered when immunosuppressive drugs were discontinued and leukemia has not recurred over a period of 2 and 4 years, respectively, in the two patients.

Antineoplastic Agents↗

Reduced pituitary volume in children with short stature: clinical and radiological correlates.

A retrospective evaluation of 80 cases of growth retardation evaluated at the Hôpital Sainte-Justine of Montreal has revealed that 20 of them (25%; 15 boys and 5 girls) had a reduction of pituitary volume as revealed by high-resolution CT scanning of the pituitary gland. Of these patients, 8 had complete growth hormone (GH) deficiency, as evaluated by arginine infusion and L-Dopa-propranolol testing and nocturnal blood sampling, and 3 had GH neurosecretory dysfunction. Five patients had combined or multiple hormonal deficiencies. A statistically significant correlation was found between nocturnal plasma GH values and pituitary volumes. From this study it can be concluded that reduced pituitary volume is a frequent finding in growth-retarded children with hypopituitarism.

Adolescent↗