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Biomedical subjects

C Leduc

Publications and source records attributed to C Leduc.

17 recordsLinked to original sources

p14ARF promotes RB accumulation through inhibition of its Tip60-dependent acetylation.

p14ARF is a tumour suppressor which plays a critical role in p53-dependent or -independent cell growth control. Several studies have recently provided evidence that p14ARF can also interfere either directly or indirectly with some components of the RB signalling pathway to mediate its antiproliferative activity. The aim of this study was to explore the existence of direct relationships between p14ARF and RB proteins. We show that p14ARF promotes the accumulation of a hypoacetylated RB protein, when it is upregulated in a model of stable-inducible clones or physiologically induced following cell exposure to cytotoxic agents. Looking for the mechanisms involved in this process, we demonstrate that the histone acetyl transferase Tip60 directly interacts with RB and stimulates its degradation by the proteasome through acetylation of its C-terminus. Furthermore, and consistent with p14ARF-induced RB accumulation, we provide evidence that p14ARF prevents Tip60-mediated RB acetylation, therefore precluding its proteasomal degradation. Overall, our results identify a novel mechanism by which p14ARF controls the RB pathway to trigger its antiproliferative function.

Acetylation↗

Plants used by the Cree Nation of Eeyou Istchee (Quebec, Canada) for the treatment of diabetes: A novel approach in quantitative ethnobotany.

In the last decade, the Cree Nation of Eeyou Istchee has witnessed a 150% increase in the prevalence of Type II Diabetes (T2D) for people aged over 20 years. Clinical intervention using conventional therapeutic methods has yielded only a limited success within this population. An ethnobotanical survey was carried out to identify potentially antidiabetic plant species used within the traditional pharmacopoeia of the Cree. Interviews were held with 34 Cree Elders using a list of 15 symptoms ranked according to their association to T2D. A total of 18 species were cited during the survey, spanning 9 plant families. Species were prioritized for pharmacological analysis according to a Syndromic Importance Value, based on their frequency of citation by informants and the number and specificity of symptoms for which they were used. Correspondence and clustering analyses were also performed to determine the specificity of association between species and symptoms and the symptom-based correlation between species. A data matrix and species ranking order generated from Cree-specific literature demonstrates significant similarity and correlation to our original matrix and ranking, respectively. This article demonstrates the applicability of various underutilized quantitative tools in ethnobotany, while taking a convincing preliminary step towards a therapy more in harmony with Cree culture and lifestyle.

Cluster Analysis↗

Contralateral effect of amitriptyline and bupivacaine for sciatic nerve block in an animal model of inflammation.

BACKGROUND: Using a carrageenan inflammation rat model, we evaluated two experimental approaches to prolong sciatic nerve block on contralateral hyperalgesia. Method. We performed ipsilateral sciatic nerve block on the inflamed hind paw with bupivacaine-loaded microspheres suspended in dexamethasone (bupivacaine 12.5 mg) and with amitriptyline (6.25 and 12.5 mg) as ultralong-acting local anaesthetics. Bupivacaine (1.25 mg) was used as long-acting local anaesthetic and saline was used as a control. The sixth group received amitriptyline 6.25 mg intraperitoneally (n=10 for each group). RESULTS: The duration of ipsilateral nerve block was 2 h for bupivacaine, 7 h for amitriptyline 6.25 mg, 11 h for amitriptyline 12.5 mg and 21 h for bupivacaine-loaded microspheres in suspension with dexamethasone. Whereas contralateral hyperalgesia was not observed during block produced by bupivacaine-loaded microspheres, contralateral hyperalgesia was observed with sciatic nerve block using amitriptyline. CONCLUSIONS: Because of the differential effect observed on the contralateral side, the mechanism underlying the prolongation of ipsilateral block with amitriptyline may not result only from a prolonged Na(+) channel blockade but might be explained by a local toxic effect or lack of systemic actions.

Amitriptyline↗

[Advantages of the in vivo HRT2 corneal confocal microscope for investigation of the ocular surface epithelia].

PURPOSE: To show the advantages of the in vivo HRT2 confocal microscope corneal module for studying the superficial and peripheral corneal and conjunctival epithelia. MATERIAL AND METHODS: We examined 15 patients whose superficial cornea was healthy and ten patients with keratoconjunctivitis sicca and/or rosacea. Some conjunctival imprints where taken on patients with superficial ocular disease and examined by immunofluorescence. RESULTS: We found superficial corneal epithelial cells, corneoconjunctival Langerhans and dendritic cells, goblet cells, limbic epithelial junction, new blood vessels, as well as deeper corneal structures such as Bowman's membrane, keratocytes, corneal nerves, and endothelium. We also observed pathological corneal epithelium in keratoconjunctivitis sicca and substantial inflammatory and vascular changes in rosacea. In two cases of stem cell deficiency associated with rosacea, we observed goblet cells in the corneal epithelium. An interesting anatomical-clinical parallelism between in vivo confocal microscopy images and those obtained by ex vivo immunofluorescence was observed. DISCUSSION: Central corneal pictures after explorations by in vivo HRT2 confocal microscopy are similar to those obtained with standard confocal microscopy. But conjunctiva, peripheral cornea and limbus are better examined at the surface and at medium depth with the HRT2. Diagnosis and therapy of superficial corneoconjunctival and limbal diseases are therefore made easier in vivo.

Conjunctiva↗

Evidence for spinodal decomposition in nuclear multifragmentation.

Multifragmentation of a "fused system" was observed for central collisions between 32 MeV/nucleon 129Xe and (nat)Sn. Most of the resulting charged products were well identified due to the high performances of the INDRA 4pi array. Experimental higher-order charge correlations for fragments show a weak but nonambiguous enhancement of events with nearly equal-sized fragments. Supported by dynamical calculations in which spinodal decomposition is simulated, this observed enhancement is interpreted as a "fossil" signal of spinodal instabilities in finite nuclear systems.

Journal Article↗

Production of "neometalloenzymes" by de novo biosynthesis. New ELISA method for their characterization.

Several approaches known for producing "neometalloenzymes" are classified into two categories: protein engineering using antibodies as starting materials and "de novo" biosynthesis of metal-binding antibodies with potential catalytic metal-binding structure. This latter approach is chosen in this study. Polyclonal anti-zinc-iminodiacetate [IDA-Zn(II)] antibodies are produced in rabbits and mice. Because of the absolute need for the unequivocal screening of the hapten [IDA-Zn(II)] specific antibodies, a new ELISA method was developed using a biheaded polyethylene glycol with biotin on one end and the hapten on the other end. The parameters for optimizing the immunization and the ELISA technique are discussed and the method is validated with rabbit and mice sera.

Animals↗

Role of endovaginal sonography in the diagnosis and management of ectopic pregnancy.

Although diagnostic laparoscopy is still considered the standard reference in the diagnosis of ectopic pregnancy (EP), use of high-resolution endovaginal sonography, in conjunction with qualitative serum assays of the beta subunit of human chorionic gonadotropin (beta-hCG), allows detection of earlier and smaller EPs. The most common endovaginal sonographic finding of EP (89%-100% of cases) is an extraovarian, round or elongated, solid tubal mass. A tubal ring (an extrauterine saclike structure) is the second most common finding (40%-68% of cases). Pelvic fluid may be present, but it is a nonspecific finding. An EP may have a pseudosac, which can be distinguished sonographically from the true gestational sac of an intrauterine pregnancy. Color Doppler techniques can complement endovaginal sonographic findings, but they should be performed only after a thorough real-time evaluation of the adnexal region. Current therapeutic options for EP include expectant management (ie, close follow-up), medical treatment (usually injections of methotrexate), and surgery. Accurate diagnosis with endovaginal sonography is the prerequisite to nonsurgical management, since surgery is the logical treatment if laparoscopy is used for diagnosis.

Chorionic Gonadotropin, beta Subunit, Human↗

Non-specific adherence of oxide particles as a means of quantifying protein adsorption on surfaces.

This paper reports quantification of a method for measuring amounts of protein adsorbed to a surface; the method is especially useful for revealing macroscopic spatial patterns of adsorption. The experiments tested the effectiveness of iron oxide suspensions adsorbed onto the adsorbed protein to indicate, in separate trials, the amount of either human plasma fibrinogen or human serum albumin (HSA) present on glass slides. Corresponding trials, using radioactively labeled proteins, were performed to calibrate the amount of either albumin or fibrinogen adsorbed onto similar slides out of solutions of varying bulk concentrations. The oxide deposits were quantified using a scanner and an image analysis program. The isotherms produced from the collected data indicate a continuous, monotonic correlation between light absorbed by adherent oxide and surface concentration of protein. The same correlation applies to albumin and fibrinogen when surface concentrations are expressed in weight units. These results confirm that patterns of oxide deposition correspond to patterns of protein deposition and show clearly how qualitative observations, such as those previously reported, can be made quantitative with scanning and digital image analysis.

Adsorption↗

Adsorption of proteins out of plasma onto glass from a separated flow.

Perturbations in the adsorption of plasma proteins caused by flow separation were studied quantitatively. An instrument was constructed that causes flow to separate over approximately half the width of a standard microscope slide and the pattern of protein deposition in and near the separated flow was observed by staining the slide with black iron oxide. The slide was mounted at the edge of a Couette flow field established between two concentric cylinders, the outer of which was rotating. The slide was located on the stationary, inner cylinder just downstream of a rectangular bar that causes the flow to separate. After exposure to dilute plasma injected upstream of the bar, the slide was removed and stained with oxide suspension. The resulting, visible pattern was scanned through a video camera and analyzed to yield relative values of stain density that could be quantified. The oxide patterns suggest that proteins were deposited onto the slide less rapidly in and just downstream of the separated flow region than farther downstream. At a shear rate of 6.61 s-1, corresponding to a velocity of 1.32 cm s-1 0.2 cm above the point of flow separation, overall amounts of adsorbed proteins increased with exposure time in the range 3-30 min with the exception of a period from 10 to 11 min when all data show a temporary decrease. In calibration experiments, oxide failed to adhere to slides exposed to purified albumin but adhered copiously to slides exposed to purified fibrinogen. These results suggest that the oxide patterns following plasma exposure are attributable primarily to fibrinogen and that the temporary decrease in the separated flow experiments is attributable to the displacement of fibrinogen by a less stainable protein, conjecturally high molecular weight kininogen and factor XII. This study yields quantitative information confirming earlier findings that were less controlled and non-quantitative. It confirms the hypothesis that the sequence of protein deposition from dilute plasma to glass surfaces is delayed in regions of separated flow.

Adsorption↗

Assessment of laryngeal cancer: CT scan versus endoscopy.

In order to assess the value of the systematic use of CT scan in the workup for laryngeal cancer, a retrospective study was conducted on 66 consecutive previously untreated cases of laryngeal cancer. Endoscopic and CT scan findings were systematically compared. The areas of particular difficulty in CT scan assessment are described. CT scan alone understaged laryngeal cancers in 10.6% of cases, all of them being superficial spreading tumors within the larynx or in the juxtalaryngeal areas. CT scan worsened the staging in 22.7% of cases, all of them being deep invasions overlooked by endoscopy. CT was most useful in lesions initially classified as T2 and T3, which included all those reclassified by CT. None of the T1 lesions was upgraded after CT, and systematic use of CT for this stage is not warranted. CT scan workup changed the therapeutic attitude in 10 of the 66 patients (15.1%), causing a switch to conservative surgery in seven patients and total laryngectomy with radiotherapy for the three others. CT was also valuable in choosing the most suitable technique for conservation surgery.

Carcinoma, Squamous Cell↗

Retinoid treatment of human psoriatic fibroblasts induces an increase in cyclic AMP-dependent protein kinase activity.

We recently showed a deficiency of cyclic AMP (cAMP)-dependent protein kinases in psoriatic cells. In this work the effects of retinoids on cAMP-dependent protein kinases of fibroblasts from 7 normal subjects and 7 psoriatic patients were studied. The levels of RI and RII (two forms of the cAMP-dependent protein kinases) present in control and retinoic acid-treated cells were quantitated by photoaffinity labeling with [8-azido-32P]cAMP. In psoriatic fibroblasts the levels of RII are decreased or undetectable compared with those of normal fibroblasts both in the cytosolic and membrane fractions. The amount of RI was normal in the cytosol of fibroblasts of 5 out of 7 patients and decreased in 2 patients. Membrane-associated levels of RI were decreased in 5 patients and normal in 2 patients. Retinoic acid treatment induces an increase in the amount of RI and RII regulatory subunits when they are deficient in the cytosolic and membrane fractions of psoriatic fibroblasts. Retinoic acid had no effect on RI and RII in normal fibroblasts. In addition, with in vitro retinoic acid treatment the cAMP-dependent protein kinase activity, measured in the fibroblasts of 4 psoriatic patients, was increased in the cytosol in 2 patients and in the membranes in all 4 patients. In these studies, comparable results were obtained with fibroblasts cultured from involved and uninvolved skin. This in vitro effect of retinoids on cAMP-dependent protein kinases in psoriatic fibroblasts may help to explain some of the in vivo therapeutic effects of retinoids.

Fibroblasts↗

Sex differences in the changing anatomic distribution of colorectal carcinoma.

The anatomic site distribution of large bowel cancer was studied in 2079 patients between 1967 and 1980. To measure the trend in the localization of the carcinomas, the slope of the regression line of the proportions at each site over the years was computed. The large bowel was divided into five segments: cecum, ascending colon and hepatic flexure, transverse and descending colon, sigmoid and rectosigmoid junction, and rectum. A significant decrease in the proportions of cancer in the sigmoid for both sexes (slope parallel b = -0.89; P less than 0.001) and an increase of cecal cancer (b = 0.54; P less than 0.004) was observed. Sex-specific results indicated the diminishing proportion of sigmoid cancer in men (b = -1.04; P less than 0.004) with an increase in transverse and descending colon cancer proportions (b = 0.52; P = 0.012). In women, a negative slope of -0.74 was not significant for sigmoid cancer, but cancer of the cecum showed an increase in proportions (b = 0.80; P = 0.01). The age distribution indicated a significant decrease in proportion of men older than 80 years and of women in the age group of 40 to 49 years and an increase in women older than 80 years. However, age adjustment did not change any of the previous conclusions. The observed sex differences in the changing distribution within the large bowel over a 14-year period cannot be explained by the improvement of diagnostic tools in the last years. In view of these findings, it is important to evaluate the possible sex-related bias in the application of screening and preventive measures as well as the changes in the ecologic features of the large intestine.

Adult↗

[Interference of liquemine with plasma somatomedin activity].

Experimental conditions for preparation of plasma and the interference of the heparin (liquemine) on the somatomedin bioassay were studied. Results showed the significant inhibitory effect of liquemine, increasing with the delay before centrifugation, on the interpretation of the results of the assay.

Adult↗

Acute epiglottitis in children: management of 27 consecutive cases with nasotracheal intubation, with special emphasis on anaesthetic considerations.

Twenty-seven consecutive cases of acute epiglottitis in children were treated by nasotracheal intubation during a 25-month period. The duration of intubation averaged 44.2 hours. No mortality or morbidity occurred. Mean hospitalization was 4.5 days. Anaesthetic techniques are discussed. Ketamine is a somewhat controversial choice for these patients as it can enhance excitement, restlessness, and accidental extubation. This study reconfirms the ease of maintaining an assured airway by nasotracheal intubation in cases of acute epiglottitis.

Age Factors↗