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C Emond

Publications and source records attributed to C Emond.

At least 19 recordsLinked to original sources
PubMed2004

A genome wide linkage study of obesity as secondary effect of antipsychotics in multigenerational families of eastern Quebec affected by psychoses.

Antipsychotics can induce in schizophrenic (SZ) and bipolar disorder (BP) patients serious body weight changes that increase risk for noncompliance to medication, and risk for cardiovascular diseases and diabetes. A genetic origin for this susceptibility to weight changes has been hypothesized because only a proportion of treated patients are affected, the degree of affection differing also in rates and magnitudes. In a first genome scan on obesity under antipsychotics in SZ and BP, we analyzed 21 multigenerational kindreds (508 family members) including several patients treated for a minimum of 3 years mainly with haloperidol or chlopromazine. Obesity was defined from medical files and was shown to be 2.5 times more frequent in patients treated with antipsychotics than in untreated family members (30 vs 12%). The nine pedigrees that showed at least two occurrences of obesity under antipsychotics were submitted to model-based linkage analyses. We observed a suggestive linkage with a multipoint Lod score (MLS) of 2.74 at 12q24. This linkage finding vanished when we used as phenotypes, obesity unrelated to antipsychotics, and when we used SZ or BP. This suggests that this positive linkage result with obesity is specific to the use of antipsychotics. A potential candidate gene for this linkage is the pro-melanin-concentrating hormone (PMCH) gene located at less then 1 cM of the linkage. PMCH encodes a neuropeptide involved in the control of food intake, energy expenditure, and in anxiety/depression. This first genome scan targeting the obesity side effect of antipsychotics identified 12q24 as a susceptibility region.

Antipsychotic Agents↗
PubMed2000

Significant linkage for Tourette syndrome in a large French Canadian family.

Family and twin studies provide strong evidence that genetic factors are involved in the transmission of Gilles de la Tourette syndrome (TS) and related psychiatric disorders. To detect the underlying susceptibility gene(s) for TS, we performed linkage analysis in one large French Canadian family (127 members) from the Charlevoix region, in which 20 family members were definitely affected by TS and 20 others showed related tic disorders. Using model-based linkage analysis, we observed a LOD score of 3.24 on chromosome 11 (11q23). This result was obtained in a multipoint approach involving marker D11S1377, the marker for which significant linkage disequilibrium with TS recently has been detected in an Afrikaner population. Altogether, 25 markers were studied, and, for level of significance, we derived a criterion that took into account the multiple testing arising from the use of three phenotype definitions and three modes of inheritance, a procedure that yielded a LOD score of 3.18. Hence, even after adjustment for multiple testing, the present study shows statistically significant evidence for genetic linkage with TS.

Adult↗
PubMed1999

Distribution of uranium in rats implanted with depleted uranium pellets.

During the Persian Gulf War, soldiers were injured with depleted uranium (DU) fragments. To assess the potential health risks associated with chronic exposure to DU, Sprague Dawley rats were surgically implanted with DU pellets at 3 dose levels (low, medium and high). Biologically inert tantalum (Ta) pellets were used as controls. At 1 day and 6, 12, and 18 months after implantation, the rats were euthanized and tissue samples collected. Using kinetic phosphorimetry, uranium levels were measured. As early as 1 day after pellet implantation and at all subsequent sample times, the greatest concentrations of uranium were in the kidney and tibia. At all time points, uranium concentrations in kidney and bone (tibia and skull) were significantly greater in the high-dose rats than in the Ta-control group. By 18 months post-implantation, the uranium concentration in kidney and bone of low-dose animals was significantly different from that in the Ta controls. Significant concentrations of uranium were excreted in the urine throughout the 18 months of the study (224 +/- 32 ng U/ml urine in low-dose rats and 1010 +/- 87 ng U/ml urine in high-dose rats at 12 months). Many other tissues (muscle, spleen, liver, heart, lung, brain, lymph nodes, and testicles) contained significant concentrations of uranium in the implanted animals. From these results, we conclude that kidney and bone are the primary reservoirs for uranium redistributed from intramuscularly embedded fragments. The accumulations in brain, lymph nodes, and testicles suggest the potential for unanticipated physiological consequences of exposure to uranium through this route.

Animals↗
PubMed1999

Scintigraphic diagnosis of polysplenia in the adult.

PURPOSE: The authors describe an adult patient with low index of suspicion for polysplenia. The diagnostic contribution of various investigative modalities is considered, and the key role of scintigraphy is specifically highlighted. RESULTS: CT scan findings revealed multiple abdominal and retroperitoneal masses. Needle biopsy of a flank mass was nonspecific. Tc-99m sulfur colloid liver spleen scintigraphy and Tc-99m heat-denatured RBC scans showed the presence of polysplenia. CONCLUSIONS: Multiple spleens can be mistaken for abdominal neoplasms on CT. Biopsy results may not always be helpful. In patients in whom there is such a diagnostic dilemma, Tc-99m heat-denatured RBC scans can successfully establish the definitive diagnosis of polysplenia.

Abdominal Neoplasms↗
PubMed1998

Lung cancer in women compared with men: stage, treatment, and survival.

BACKGROUND: In cardiac disease there appears to be a difference in the treatment of men and women, and thus an advantage in survival in men. This study aimed to determine whether these differences exist in lung cancer. METHODS: We undertook a retrospective cohort study in a university hospital. The study population consisted of 104 consecutive women and 104 consecutive men with newly diagnosed lung cancer between March 1988 and June 1990. The following information was collected: sex, age, presenting symptoms, investigations, histology, stage, treatment, and survival. RESULTS: The location of the tumor, presenting symptoms, investigations, and stages were similar in men and women. There was a difference in the distribution of the various histologic types of lung cancer: Small cell lung cancer was more frequent in women (25% versus 11.5% in men) and squamous cell carcinoma more frequent in men (38% in women versus 51% in men). The overall survival was similar among the two sexes, but there was a survival advantage in women when adjusted for stage. CONCLUSIONS: There was a higher incidence of small cell carcinoma in women and squamous cell carcinoma in men. There was evidence of a difference in the survival rate of lung cancer in favor of women according to stage.

Bias↗
PubMed1998

Urinary and serum mutagenicity studies with rats implanted with depleted uranium or tantalum pellets.

During the 1991 Persian Gulf War several US military personnel were wounded by shrapnel fragments consisting of depleted uranium. These fragments were treated as conventional shrapnel and were not surgically removed to spare excessive tissue damage. Uranium bioassays conducted over a year after the initial uranium injury indicated a significant increase in urine uranium levels above natural background levels. The potential mutagenic effects of depleted uranium are unknown. To assess the potential mutagenic effects of long-term exposure to internalized depleted uranium, Sprague-Dawley rats were implanted with depleted uranium and their urine and serum were evaluated for mutagenic potential at various times after pellet implantation using the Ames Salmonella reversion assay. Tantalum, an inert metal widely used in prosthetic devices was used for comparison. Enhancement of mutagenic activity in Salmonella typhimurium strain TA98 and the Ames II mixed strains (TA7001-7006) was observed in urine samples from animals implanted with depleted uranium pellets. In contrast, urine samples from animals implanted with tantalum did not show a significant enhancement of mutagenic activity in these strains. In depleted uranium-implanted animals, urine mutagenicity increased in a dose- and time-dependent manner demonstrating a strong positive correlation with urine uranium levels (r = 0.995, P < 0.001). There was no mutagenic enhancement of any bacterial strain detected in the sera of animals implanted with either depleted uranium or tantalum pellets. The results suggest that uranium content in the urine is correlated with urine mutagenicity and that urinary mutagenicity might be used as a biomarker to detect exposure to internalized uranium.

Animals↗
PubMed1996

The distribution of protein kinase C in human leukocytes is altered in microgravity.

Protein kinase C (PKC) is an ubiquitous enzyme that mediates intracellular signal transduction in eukaryotes. Jurkat and U937 cells were exposed to microgravity during a Space Shuttle flight and stimulated with a radiolabeled phorbol ester (3H-PDBu) that specifically activates and labels several PKC isoforms. Both the total amount of 3H-PDBu labeling per cell and the relative distribution of labeling between subcellular compartments were altered in microgravity compared to onboard and ground 1 g control samples. The amount of total phorbol ester labeling per cell was increased approximately twofold in microgravity samples when compared with onboard 1 g samples for both cell lines. The subcellular distribution of PKC in the cytosol and nuclear fractions appeared to be correlated with the applied acceleration. In both cell types the relative amount of phorbol ester labeling in the nuclear fraction decreased with applied acceleration, whereas the labeling in cytosolic fraction increased with g level. No significant differences were observed between labeling levels in the membrane fraction in both cell types. Interleukin-1beta synthesis by U937 cells was markedly decreased in microgravity when compared to the onboard 1 g control, suggesting that the observed alterations in PKC distribution may have functional consequences. The results may have important implications for the effect of gravity on cellular signal transduction.

Cell Nucleus↗
PubMed1995

In vivo and in vitro homologous desensitization of rat glomerular bradykinin B2 receptors.

We investigated the effects of bradykinin on glomerular bradykinin B2 receptor functions and parameters in vivo, after intrarenal infusion of bradykinin, and in vitro, after incubation of isolated rat glomeruli with bradykinin. Bradykinin transiently increased renal plasma flow whereas a second challenge was ineffective. Scatchard analysis demonstrated the presence of two populations of bradykinin binding sites whose densities were similarly decreased by about 40% after intrarenal bradykinin infusion. This decrease was not altered by an acid wash suggesting internalization of the radiolabelled ligand. The effect of bradykinin was prevented by a bradykinin B2 receptor antagonist. Pre-exposure of isolated rat glomeruli to bradykinin mimicked the in vivo results because there was a reduction in bradykinin-induced prostaglandin E2 and prostaglandin F2 alpha release. Rapid recovery was observed 15 min after washing out the bradykinin. Our results directly demonstrate a negative homologous down-regulation of B2 glomerular bradykinin receptor density under both in vivo and in vitro conditions, an effect which involves a rapid sequestration of the receptor.

Animals↗
PubMed1995

[Endoscopic YAG laser and palliative therapy of cancer of the esophagus].

In our institution, the YAG laser has been used to treat 110 patients with inoperable esophageal carcinoma. Therapy was palliative as patients presented metastases (41.8%), advanced systemic disease (22.7%), extensive local disease (18.2%) or recurrent carcinoma (10%). The study group included 92 men (mean age 68.4 years) and 18 women (mean age 67.0 years); 47.3% of the patients had received no previous treatment while 52.7% had been treated previously with either radiotherapy, chemotherapy, surgery, stents or dilatation. The majority of lesions were adenocarcinomas (57.3%) with squamous cell carcinomas in 37.3%; 66.3% of cancers were located in the distal third of the esophagus. The patients received a mean of 2.4 laser treatments with 4883 joules per treatment on average. The rate of major complications was 2.7% and the rate of mortality 1.8%. The median survival for the group was 4.5 months. No significant difference was found in the length of survival according to the histology of the tumour (p = 0.35), the presence of metastases (p = 0.24) and the association of other treatment modalities with the laser (p = 0.06). Functional results were considered good to excellent in 82.1% of cases. In conclusion, the YAG laser does not influence overall survival of inoperable patients, but this therapy is effective and safe and is presently the treatment of choice for these patients.

Adenocarcinoma↗
PubMed1994

Spontaneous primary and secondary pneumothorax: a 10-year study of management alternatives.

OBJECTIVE: To study the outcome of conservative and surgical management of spontaneous pneumothorax. DESIGN: Retrospective study between January 1980 and December 1990, with a mean follow-up of 6.5 years. SETTING: A tertiary-care university hospital with a referral thoracic surgical unit. PATIENTS: All patients seen in the study period with spontaneous pneumothorax. Those with traumatic, iatrogenic or ventilator-associated pneumothoraces were excluded. There were 366 consecutive patients who had 508 episodes of spontaneous pneumothorax. Two hundred and thirty-nine patients had primary spontaneous pneumothorax (group 1); 127 had secondary spontaneous pneumothorax (group 2). INTERVENTIONS: Tube thoracostomy, apical resection with either pleurectomy or pleural abrasion. MAIN OUTCOME MEASURES: Recurrence and outcome after surgical management relative to recurrence, complications, operative technique and mean hospital stay were evaluated by clinical review and questionnaire by an independent observer. RESULTS: No significant differences were noted between the two groups with respect to the incidence of recurrent spontaneous pneumothorax after the first or second episode, and no significant differences were noted between the two operative techniques with respect to recurrence, complications, operative technique or death rate. However the mean hospital stay was doubled for group 2 patients (9.9 versus 4.3 days). CONCLUSIONS: Conservative treatment, including tube thoracostomy, was effective for primary and secondary spontaneous pneumothorax. Open surgery was effective in preventing recurrence in 95% of cases in both groups.

Adult↗
PubMed1993

Evidence for existence of two distinct bradykinin receptors on rat mesangial cells.

We investigated the possible presence of bradykinin (BK) B1 receptor on rat mesangial cells (MC) by binding studies and by the effect of the B1 agonist des-Arg9-BK on intracellular calcium concentration ([Ca2+]i) and DNA synthesis in comparison with the effects of BK. Binding studies demonstrated specific, saturable binding for des-Arg9-[3H]BK inhibited by B1 but not by B2 antagonists. Scatchard analysis revealed a single class of B1 binding site with a maximum density of 15 fmol/mg protein and an affinity of 8.7 +/- 2.4 nM. Saturation and competition studies of 125I-[Tyr0]BK demonstrated the presence of two classes of B2 binding sites [dissociation constant (Kd) = 0.1 and 4 nM, respectively]. On fura-2-loaded adherent MC, both des-Arg9-BK and BK induced a biphasic increase (a transient enhancement followed by a sustained phase) in [Ca2+]i, both in primary culture and in cloned MC. Both the transient and sustained phases of [Ca2+]i induced by des-Arg9-BK were dose dependent, whereas BK induced a transient dose-dependent rise in [Ca2+]i, but the sustained phase remained constant. The increases in [Ca2+]i induced by des-Arg9-BK and BK were specifically abolished by B1 and B2 receptor antagonists, respectively, and showed homologous but not heterologous desensitization. Des-Arg9-BK and BK induced a significant proliferation (tested by cell counting and [3H]thymidine incorporation) of quiescent MC. Furthermore, the effects of des-Arg9-BK and BK were additive on Ca2+ mobilization but not on mitogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Protective effect of cicletanine on hypertension-induced decreases in the renal kallikrein-kinin and prostaglandin systems in stroke-prone spontaneously hypertensive rats.

We investigated the effect of two oral (p.o.) doses of cicletanine (5 and 30 mg/kg/day) for 4 weeks on urinary excretion (UKE), renal concentration (RKC) of kallikrein, and prostaglandin E2 (PGE2) and 6-keto-PGF1 alpha urinary excretion of stroke-prone (SP) spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) rats submitted to a high sodium intake (1%). Both doses of cicletanine induced a significant antihypertensive effect in treated SHR as compared with hypertensive untreated controls (HC). After 4-week treatment, a significant difference in mortality was observed between normotensive controls (NC) (0%) and HC (84%). Both doses of cicletanine reduced the mortality of hypertensive animals (8% SHR with 5 mg and 24% SHR with 30 mg vs. 84% in HC). Whereas UKE and RKC were decreased in HC during the progression of untreated hypertension from week 1 to week 4, both doses of cicletanine administration significantly prevented this decrease. Consistently with maintenance of UKE during the course of hypertension, the level of tissue kallikrein was higher in hypertensive cicletanine-treated than in untreated SHR. This increased RKC was associated with a significantly higher rate of kallikrein biosynthesis. The increased level of the urinary excretion and tissue concentration of PGE2 and 6-keto-PGF1 alpha in cicletanine-treated SHR as compared with untreated animals was also of interest. This protective effect on PG excretion correlated with that on kallikrein excretion. The results confirm the efficiency of cicletatine as an antihypertensive treatment. The antihypertensive action includes protective effects on potential vasodepressor kallikrein-kinin and prostaglandin systems.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Signal transduction pathways of BK2 receptor in the renal glomerulus and mesangial cells: a mini review.

Using binding techniques we identified specific B2 kinin binding sites showing a pharmacological profile similar in glomeruli and in mesangial cell. Scatchard analysis revealed two classes of binding sites: a very-high-affinity site (Kd = 0.44 nM) and a high affinity site (Kd = 6.3 nM). Activation of the BK receptor of mesangial cells is associated with i) a transient dose-dependent increase in inositol 1,4,5 Triphosphate, ii) a biphasic rise in cytosolic free calcium, iii) a progressive secretion of PGE2, iv) an inhibition of the PGE2-stimulated increase of cAMP formation. All these effects were prevented by B2 antagonists. This multiple signal transduction pathway could suggest either heterogeneity in the BK receptor of the mesangial cell or different biological responses to be identified. Taken together, the results indicate that BK, at least in cultured cells, acts as a contractile effector, however, the physiological significance of a kinin receptor in the glomerulus remains to be elucidated.

Animals↗
PubMed1992

Characterization of two different affinity B2-kinin binding sites in rat glomeruli.

We have recently characterized a bradykinin (BK) receptor in rat renal mesangial cells (1). Activation of this receptor is associated with PGE2 release and IP3 formation suggesting involvement in cell contraction which can be linked to the control of the glomerular filtration rate (2). Whether this mesangial BK receptor is the unique glomerular BK receptor remains to be elucidated. In an attempt to answer to this question, we performed binding studies using decapsulated isolated glomeruli. Scatchard analysis of the binding data obtained with this preparation revealed the presence of two distinct B2-kinin binding sites. However, a consistent difference was observed in both the affinity and the density. We further investigated the pharmacological binding profile after an initial step of solubilization. Several experiments were performed to establish optimal conditions of solubilization. For this, different detergents such as Triton X-100, CHAPS and n-octyl beta-D glucopyranoside were tested at various concentrations, durations and temperatures of incubation. The binding was performed with two different [125I]-Tyr0-BK concentrations (0.5 and 7 nM) with either untreated decapsulated glomeruli or solubilized preparation for 45 minutes at +4 degrees C in the binding buffer containing a mixture of protease inhibitors. The greatest binding was achieved after treating glomeruli with 25 mM n-octyl beta-D glucopyranoside for 60 minutes at +4 degrees C under constant shaking. Two B2-kinin receptors of different affinities were detected. The same binding characteristics were obtained both in the 12,000 x g and 100,000 x g supernatant.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Direct effects of bradykinin on glomerular filtration and proximal tubule reabsorption in rat kidney.

Intrarenal infusion of a low dose of bradykinin devoid of extrarenal action exerts direct vasodilator and diuretic effects on rat kidney. It does not significantly alter glomerular filtration rate and absolute proximal reabsorption but increases the delivery of fluid from the proximal tubule evaluated by the clearance of lithium. None of these effects are observed in kidneys infused with both bradykinin and a specific bradykinin antagonist.

Animals↗
PubMed1991

Re-evaluation of the role of dopamine in intracranial self-stimulation using in vivo microdialysis.

Rats were implanted with an electrode-microdialysis assembly in order to test the hypothesis that the reward signal elicited by medial forebrain bundle stimulation is relayed by the meso-accumbens dopamine cells. We first obtained the strength-duration function of self-stimulation, that is, a family of behaviorally equivalent stimuli (pulse intensity and pulse duration pairs yielding a constant self-stimulation rate). We then collected the self-stimulation-bound intra-accumbens dopamine for several pairs of intensity and duration, selected from within the strength-duration function. Our reasoning was that if the reward signal travels along the meso-accumbens dopaminergic neurons, the release of dopamine should not depend on the stimulus parameters because behaviorally equivalent stimuli should produce a constant output in all neural stages carrying the reward signal. The results showed that short duration/high intensity pulses induced considerably larger increases in dopamine levels than long duration/low intensity pulses, despite the fact that these stimuli maintained a constant self-stimulation rate. Among the interpretations envisaged, the most parsimonious one seems to be that the MFB rewarding signal is not relayed exclusively by meso-accumbens dopaminergic cells and that the latter may play a permissive-facilitator role at some transmission stage of the reward signal.

Animals↗
PubMed1991

Bradykinin stimulates production of inositol (1,4,5) trisphosphate in cultured mesangial cells of the rat via a BK2-kinin receptor.

1. Using [125I-Tyr0]-BK, as radiolabelled ligand, and various agonists and antagonists of bradykinin (BK) we identified a single class of specific BK2-binding sites in mesangial cell membranes (Bmax = 73 fmol mg-1 protein and Kd = 3.7 nM). 2. Following the addition of 0.1 microM BK, inositol (1,4,5) trisphosphate (IP3) formation increased within 20 s from a basal level of 64 to a maximal value of 175 pmol mg-1 protein. 3. Incubation in a Ca(2+)-free medium did not change IP3 production but a 5 min preincubation with 1 mM EGTA completely prevented the BK-induced IP3 formation, suggesting that IP3 formation is partly dependent on extracellular calcium. 4. The BK2 antagonist D-Arg-Hyp3-D-Phe7-BK (10 microM) but not the BK1 antagonist (des-Arg9-Leu8-BK) abolished IP3 production in response to 0.1 microM BK. Pretreatment of mesangial cells with pertussis toxin was without effect on BK-induced IP3 formation, whereas phorbol 12-myristate 13-acetate significantly enhanced (by 25%) BK-induced IP3 formation. 5. The present data demonstrate that inositol phosphate breakdown in rat mesangial cells can be mediated via activation of a BK2-kinin receptor and is under negative control of protein-kinase C.

Analgesics↗