Search PubMed⌕ Search

Biomedical subjects

R Tanguay

Publications and source records attributed to R Tanguay.

At least 19 recordsLinked to original sources

Adenovirus-mediated gene therapy in a mouse model of hereditary tyrosinemia type I.

Mice lacking the enzyme fumarylacetoacetate hydrolase (FAH) have symptoms similar to humans with the disease hereditary tyrosinemia type I (HT1). FAH-deficient mice were injected with a first-generation adenoviral vector expressing the human FAH gene and followed for up to 9 months. Nontreated FAH mutant control mice died within 6 weeks from fulminant liver failure, whereas FAH adenovirus-infected animals survived until sacrifice at 2-9 months. Nine of 13 virus-treated animals developed hepatocellular cancer. Immunohistochemical analysis revealed a mosaic of FAH-deficient and FAH-positive cells in all animals and liver function tests were improved compared to controls. Even mice harvested 9 months after viral infection had > 50% FAH-positive cells. These results demonstrate the strong selective advantage of FAH-expressing cells in an FAH-deficient liver but also illustrate the danger of carcinomas arising from FAH-deficient hepatocytes in HT1.

Adenoviridae↗

The effect of catecholamine precursor L-dopa on sleep bruxism: a controlled clinical trial.

The putative role of the dopaminergic system in sleep bruxism (SB) was studied in a double-blind clinical trial by using low doses of short-term L-dopa in combination with benserazide. We recorded 10 patients with SB in our sleep laboratory for 3 consecutive nights. The first night was for habituation to the laboratory environment. During the second and the third nights, the patients received two doses of either L-dopa or a placebo in a crossover fashion: the first dose 1 h before bedtime and the second, 4 h after the first one. The order of administration was reversed in half the patients. The efficacy of L-dopa was analyzed by using multilevel models. L-Dopa resulted in a significant decrease in the average number of bruxism episodes per hour of sleep, as well as in a significant reduction in the average value of the root-mean-square (RMS) electromyography (EMG) level per bruxism burst. This indicates that L-dopa exerts an attenuating effect on SB. In addition, L-dopa caused a reduction in the variance in RMS values, which suggests that L-dopa normalizes the EMG activity patterns associated with SB.

Adult↗

Effects of food texture and sample thickness on mandibular movement and hardness assessment during biting in man.

This study was designed to investigate the relationship among jaw movements, physical characteristics of food, and sensory perception of hardness in man. Vertical movements of the mandible were recorded with an infrared tracking device in humans during biting on two test foods, carrot and cheese. Samples of standard length (2 cm) and width (2 cm) were prepared in three different thicknesses (0.5, 1.0, and 1.5 cm). Nine subjects were asked to perform two types of bite with their incisor teeth. In the first, they cut through the food, then stopped and spat out the pieces (bite alone); in the second, biting was followed by mastication and swallowing (bite+chew). The 12 conditions (thickness x3, food x2, and bite x2) were presented in a random order within each block, and blocks were repeated five times (60 trials per subject). Subjects also estimated the hardness of the samples twice for each condition on visual analogue scales (VAS) 100 mm long. The duration, vertical amplitude, and maximum vertical velocity of the mandible during biting were calculated by computer for the three phases of the movements (opening, and fast and slow closing). Multilevel statistical models were used for data analysis. The estimated hardness scores associated with the first bite of thin carrot (59.0 VAS units) was significantly greater than for cheese (16.8 VAS units). The type of bite had no significant effect on these scores, but the estimate of hardness was significantly greater for the thickest sample (+13.3 VAS units). Food type had its strongest effect on the slow-closing phase. In particular, the peak velocity that followed the fracturing of the food sample was much greater for carrot than for cheese (thin, 34.1 mm.s-1 vs. 26.6 mm.s-1), and the difference between foods increased with thickness. The amplitude of opening was significantly greater for the thickest sample than for the other two. There were no significant relationships between VAS scores and the movement parameters. These results suggest that, when humans bite food: (1) changing the thickness of food has a greater effect on movement parameters than changing from soft to hard food, (2) the parameters of biting change little if biting is followed by mastication, (3) hardness perception is dependent on the thickness of food, (4) hardness perception is not different when food is removed from the mouth than when it is chewed and swallowed, and (5) there is no relationship between any of the parameters of movement that change with food type and the perceived hardness of food.

Adult↗

Pain perception in idiopathic cervical dystonia (spasmodic torticollis).

Cervical spinal pain is frequently found in conjunction with idiopathic cervical dystonia (ICD), a focal dystonia characterized by sustained deviation of the head. Since the perception of noxious stimuli has never been studied in ICD, we performed a controlled study to obtain more insight into the psychophysics of dystonia-related muscle pain by evaluating pressure-induced pain levels. In nine ICD patients and five gender- and age-matched asymptomatic control subjects, pain-pressure thresholds (PPTs) were determined in the sternocleidomastoid and upper trapezius muscles, both at resting activity and at maximal voluntary contraction (MVC). The masseter muscles served as non-pathological control regions. To determine the accuracy of PPT values, pain intensity and unpleasantness were rated at threshold on 100-mm visual analogue scales. Four replication measurements were obtained. The data were analyzed by multilevel procedures. For all muscles under investigation, average PPTs of the ICD patients were about two times lower than those of the control subjects (P < 0.001-0.0005) and showed a smaller intra-subject variance. Further, average PPTs at MVC were about two times higher than those at resting activity (P < 0.005). These results provide psychophysical evidence to suggest that, at controlled levels of muscle contraction, the threshold of pain perception is decreased in ICD. In addition, ICD patients seem to be better able to establish their own PPTs than control subjects, which might be due to a different setting of the discriminative aspect of pain in ICD. Surprisingly, lower intensity and unpleasantness scores were found in ICD patients with coinciding painful and deviated sides than in ICD patients for whom the painful side was opposite to the deviated one (P < 0.05). This finding might be of clinical importance for defining functional disability and predicting treatment outcome.

Adult↗

Hepatocytes corrected by gene therapy are selected in vivo in a murine model of hereditary tyrosinaemia type I.

Current strategies for hepatic gene therapy are either quantitatively inefficient or suffer from lack of permanent gene expression. We have utilized an animal model of hereditary tyrosinaemia type I (HT1), a recessive liver disease caused by deficiency of fumarylacetoacetate hydrolase (FAH), to determine whether in vivo selection of corrected hepatocytes could improve the efficiency of liver gene transfer. As few as 1,000 transplanted wild-type hepatocytes were able to repopulate mutant liver, demonstrating their strong competitive growth advantage. Mutant hepatocytes corrected in situ by retroviral gene transfer were also positively selected. In mutant animals treated by multiple retrovirus injections >90% of hepatocytes became FAH positive and liver function was restored to normal. Our results demonstrate that in vivo selection is a useful strategy for hepatic gene therapy and may lead to effective treatment of human HT1 by retroviral gene transfer.

Amino Acid Metabolism, Inborn Errors↗

Multiparametric analysis of waterline contamination in dental units.

Microbial contamination of dental unit waterlines is thought to be the result of biofilm formation within the small-bore tubing used for these conduits. Systematic sampling of 121 dental units located at the dental school of Université de Montréal showed that none of the waterlines was spared from bacterial contamination. Multilevel statistical analyses showed significant differences between samples taken at the beginning of the day and samples taken after a 2-min purge. Differences were also found between water from the turbine and the air/water syringe. Random variation occurred mainly between measurements (80%) and to a lesser extent between dental units (20%). In other analyses, it was observed to take less than 5 days before initial bacterial counts reached a plateau of 2 x 10(5) CFU/ml in newly installed waterlines. Sphyngomonas paucimobilis, Acinetobacter calcoaceticus, Methylobacterium mesophilicum, and Pseudomonas aeruginosa were the predominant isolates. P. aeruginosa showed a nonrandom distribution in dental unit waterlines, since 89.5% of the all the isolates were located in only three of the nine clinics tested. Dental units contaminated by P. aeruginosa showed significantly higher total bacterial counts than the others. By comparison, P. aeruginosa was never isolated in tap water remote from or near the contaminated dental unit waterlines. In conclusion, dental unit waterlines should be considered an aquatic ecosystem in which opportunistic pathogens successfully colonize synthetic surfaces, increasing the concentration of the pathogens in water to potentially dangerous levels. The clinical significance of these findings in relation to routine dental procedures is discussed.

Acinetobacter calcoaceticus↗

Evaluation of three transporter ligands as quantitative markers of serotonin innervation density in rat brain.

Direct counting of axon terminals (varicosities) labeled by uptake/storage of a tritiated monoamine provides a means to test radioligands of the corresponding membrane transporter as quantitative markers of regional monoamine innervation density in brain tissue. In autoradiographs from alternate rat brain slices, counts of [3H]5-HT-labeled axon terminals were matched with densitometric measurements of the specific binding of tritiated cyanoimipramine (CYI), citalopram (CITAL), and 6-nitroquipazine (6-NTQ), under conditions of hypo-, normo-, or hyper-5-HT innervation of the neostriatum. A total of 267 pairs of data were subjected to a multilevel analysis (iterative generalized least square procedure). With all three ligands, there was a linear relationship between the density of 5-HT innervation and the density of specific binding and no change in the slope of the regression lines as a function of 5-HT innervation density. Thus, none of these ligands gave any sign of down- or up-regulation of the 5-HT transporter consequent to 5-HT hypo- or hyper-innervation. The regression lines for CYI and CITAL were not significantly different from one another and crossed the ordinate near zero, whereas the regression line for 6-NTQ was less steep and had a higher intercept with the ordinate. In addition, the dispersion of values around the regression line (residuals) was lower with CYI and CITAL than 6-NTQ. It was concluded that both CYI and CITAL may serve as quantitative markers of 5-HT innervation density, at least in vitro, whereas 6-NTQ demonstrates a certain lack of specificity and sensitivity. Further work will be needed to assess the potential of CYI and CITAL for positron emission tomographic studies of living brain. Such empirical testing should also be applicable for screening radioligands of the dopamine or the noradrenaline transporters.

Animals↗

Poly(A) binds to initiation factors and increases cap-dependent translation in vitro.

Both the 5' cap (m7GpppN) and the 3' poly(A) tail of eukaryotic mRNAs are important regulators of translation efficiency in vivo. Their function, however, is markedly reduced in in vitro translation systems derived from either rabbit reticulocytes or wheat germ. The impact of exogenous poly(A) on cap-dependent translation was examined in vitro. The translation of uncapped mRNA was preferentially repressed in the presence of exogenous poly(A). As a result, translation became increasingly cap-dependent with the increase in exogenous poly(A). The translation in wheat germ lysate was stimulated by the addition of purified eukaryotic initiation factor (eIF)-4B or eIF-4F; however, addition of poly(A) prevented this eIF-4B- or eIF-4F-mediated stimulation. Addition of eIF-4F or eIF-4B, alone, was not sufficient to restore translation in lysate to which poly(A) had been added. Restoration, however, was observed when eIF-4F, eIF-4B, and eIF-4A were added in combination. These data suggest that 1) exogenous poly(A) may bind to and sequester factors required for translation and 2) that capped messages compete with poly(A) more efficiently for these factors than do uncapped mRNAs. Gel shift analysis of purified initiation factors isolated from wheat germ confirmed that eIF-4B and eIF-4F do in fact form complexes with poly(A) in vitro.

Animals↗

Within-subject comparisons of implant-supported mandibular prostheses: psychometric evaluation.

In a within-subject cross-over clinical trial, psychometric and functional measurements were taken while 15 completely edentulous subjects wore mandibular fixed prostheses and long-bar removable implant-supported prostheses. In this paper, the results of a psychometric assessment are presented. Eight subjects first received the fixed bridge and seven the removable type. After having worn a prosthesis for a minimum of two months, subjects responded to psychometric scales that measured their perceptions of various factors associated with prostheses. They also chewed test foods while masticatory activity was recorded. The prostheses were then changed and the procedures repeated. At the end of the study, patients were asked to choose the prosthesis that they wished to keep. Patients assigned significantly higher scores, on visual analogue scales, to both types of implant-supported prostheses than to their original conventional prostheses for all factors tested, including general satisfaction. However, no statistically significant differences between the two implant-supported prostheses were detected except for the difficulty of chewing carrot, apple, and sausage. For these foods, the fixed prostheses were rated higher. Subjects' responses to category scales were consistent with their responses to the visual analogue scales. These results suggest that, although patients find the fixed bridge to be significantly better for chewing harder foods, there is no difference in their general satisfaction with the two types of prostheses.

Adaptation, Psychological↗

Within-subject comparisons of implant-supported mandibular prostheses: evaluation of masticatory function.

In the past, fixed prostheses were believed to be more efficient implant-supported devices than removable types for edentulous patients. However, this hypothesis was never properly tested. Therefore, a within-subject crossover clinical trial was designed in which 145 completely edentulous subjects were tested wearing implant-supported mandibular fixed prostheses and long-bar overdentures. Eight subjects received the fixed appliance first and seven the removable type. The patients' perceptions of various characteristics of the implant-supported prostheses were measured after a minimum of two months' adaptation. Mandibular movements and jaw muscle electromyographic activity were recorded while the patients chewed five standard-sized test foods: bread, apple, hard cheese, sausage, and raw carrot. The prostheses were then changed, worn for the same period of adaptation, and the procedures repeated. There were three test sessions per prosthesis, and each included five trials per food. The measurements were repeated three times at one-week intervals. Mastication time was found to be shorter for three foods (bread, cheese, and sausage) when subjects wore the long-bar overdenture. The vertical amplitude of the masticatory strokes was significantly less with the overdenture for all foods except carrot. Cycle duration was significantly longer with the overdenture for sausage and carrot. Contrary to what might be expected, the long-bar overdenture appears to be no less efficient than the fixed prosthesis. Furthermore, these data suggest that patients are capable of adapting their masticatory movements to the characteristics of the two prostheses.

Adult↗

A phylogenetically conserved sequence within viral 3' untranslated RNA pseudoknots regulates translation.

Both the 68-base 5' leader (omega) and the 205-base 3' untranslated region (UTR) of tobacco mosaic virus (TMV) promote efficient translation. A 35-base region within omega is necessary and sufficient for the regulation. Within the 3' UTR, a 52-base region, composed of two RNA pseudoknots, is required for regulation. These pseudoknots are phylogenetically conserved among seven viruses from two different viral groups and one satellite virus. The pseudoknots contained significant conservation at the secondary and tertiary levels and at several positions at the primary sequence level. Mutational analysis of the sequences determined that the primary sequence in several conserved positions, particularly within the third pseudoknot, was essential for function. The higher-order structure of the pseudoknots was also required. Both the leader and the pseudoknot region were specifically recognized by, and competed for, the same proteins in extracts made from carrot cell suspension cells and wheat germ. Binding of the proteins is much stronger to omega than the pseudoknot region. Synergism was observed between the TMV 3' UTR and the cap and to a lesser extent between omega and the 3' UTR. The functional synergism and the protein binding data suggest that the cap, TMV 5' leader, and 3' UTR interact to establish an efficient level of translation.

Base Sequence↗

Power and sample size calculations for clinical trials of myofascial pain of jaw muscles.

When a clinical trial is planned, the approximate number of subjects needed for significant differences between/among groups to be detected must be estimated. Sample-size calculations provide the investigator with this information. This paper discusses the choice of outcome measures and describes the steps used to estimate the numbers of subjects necessary for a study that compares treatments for patients with chronic myofascial pain of jaw muscles. Within- and between-subject variances were estimated for the chosen variables, the subjects' pain ratings on visual analogue scales. Sample sizes were then calculated for theoretical differences between groups by pre-treatment means and overall standard deviations (Cohen, 1977). The results of this analysis can be used by other researchers when planning studies involving these types of patients.

Adolescent↗

Radiopacity of glass ionomer dental materials.

The radiopacity of glass ionomer dental materials is quite variable. The use of a poorly radiopaque material as a base under other restorative materials can mislead the dentist to a diagnosis of recurrent decay. This study investigates the radiopacity of these materials and proposes a minimal radiopacity under which a material should not be used as a base or liner. All base, liner, and core formulations of glass ionomer under investigation were more radiopaque than dentin. All restorative and luting formulations of glass ionomer under investigation were less radiopaque than dentin and therefore should be avoided as bases or liners.

Analysis of Variance↗

Mandibular growth prediction: mean growth increments versus mathematical models.

The aim of this study was to compare growth predictions obtained by adding mean annual velocities with predictions derived from a polynomial model of the population's growth curve. Given the child's previous measures at 11, 12 and/or 13 years of age, the cephalometric distance sella-gnathion at 15 years was estimated. Based on a sample of 223 boys and girls, the root mean square error decreased from 0.28 cm (males) and 0.18 cm (females) at 11 years, to 0.19 cm (males) and 0.12 cm (females) at 13 years. Root mean square errors were similar between methods, which was due to high correlations between measures across ages. Significantly, predictions based on mean increments were biased. They often over or underestimate growth for children who are larger and smaller than average. The observed bias was due to expected changes of variance associated with growth, which unconditional methods of prediction cannot control for. Predictions derived from growth models are conditional upon the child's size and are, therefore, unbiased.

Adolescent↗

Modeling longitudinal mandibular growth: percentiles for gnathion from 6 to 15 years of age in girls.

Growth of the cephalometric landmark gnathion is modeled mathematically with multilevel statistical techniques. The findings, pertaining to a mixed longitudinal sample (N = 772) of 105 girls, 6 to 15 years of age, provide the most accurate descriptions of longitudinal mandibular growth presently available. Polar, rather than rectangular, coordinates are used to better distinguish between the amount and direction of growth. The velocity curve for sella-gnathion includes growth spurts during childhood (7.5 years) and adolescence (12.7 years). Growth direction of gnathion changes regularly throughout the age range, indicating a relative increase of vertical over horizontal growth. These reference standards serve as a basis for comparing and better understanding abnormal growth patterns.

Adolescent↗

Pubertal growth of the cephalometric point gnathion: multilevel models for boys and girls.

Two-level polynomial models are used to summarize the amount Sella-Gnathion (S-Gn) and direction Nasion-Sella-Gnathion (N-S-Gn) of growth changes for the cephalometric landmark gnathion. Growth descriptions pertain to a mixed longitudinal sample of 209 French-Canadian children 10-15 years of age. The boy's growth curve attains mean minimum prepubertal velocity at 10.8 years and maximum pubertal velocity at 14.1 years. The girl's curve follows a cubic pattern, attaining maximum pubertal velocity at 12.1 years. Boys are larger than girls throughout the age range. Variation between-subjects increases with age in a curvilinear fashion. Growth direction of gnathion is more horizontally directed for girls than boys. Small but significant changes in growth direction occur between 10 and 15 years of age.

Adolescent↗