Showing papers by "Université de Montréal published in 1984"

The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation. A study 10 years after aortocoronary bypass surgery.

Abstract: We examined 82 patients 10 years after saphenous-vein aortocoronary bypass surgery to determine their angiographic status and to relate those findings to the risk factors for coronary-artery disease. Of 132 grafts shown to be patent 1 year after surgery, only 50 were unaffected at 10 years. The remainder were narrowed (43) or occluded (39). Disease progression in coronary arteries without grafts was also frequent, both in vessels that were normal (15 of 32) and in those with minor stenosis (25 of 53). New lesions did not develop in 15 patients, whereas they did in 67--in the grafts, the native vessels, or both. There was no significant difference between the two groups in the incidence of hypertension, diabetes, or smoking, whereas plasma levels of very-low-density lipoproteins (VLDLs) and low-density lipoproteins (LDLs) were higher, and high-density lipoprotein (HDL) levels were lower in those with new disease than in those without. Univariate analysis showed that plasma cholesterol and triglyceride levels were significantly higher at the time of surgery and at the 10-year examination in those with new lesions. Multivariate analysis indicated that among the lipoprotein indexes, levels of HDL cholesterol and plasma LDL apoprotein B best distinguished the two groups. The findings indicate that atherosclerosis in these patients was a progressive disease, frequently affecting both the grafts and the native vessels, and that the course of such disease may be related to the plasma lipoprotein levels.

Protein A-gold electron microscopic immunocytochemistry: Methods, applications, and limitations

Abstract: The postembedding protein A-gold immunocytochemical approach has been introduced as an alternative to other techniques for the ultrastructural localization of antigenic sites. The present review deals with the development, the theoretical background, and technical approach of the protein A-gold method as well as the different modifications introduced in order to enhance the resolution of the results and to perform double labelings on the same section. Various examples demonstrate the reliability and the wide range of application of this technique. In addition, some problems, pitfalls, and limitations particular to this method are reported.

On the evolutionary descent of organisms and organelles: a global phylogeny based on a highly conserved structural core in small subunit ribosomal RNA

Abstract: To probe the earliest evolutionary events attending the origin of the five known genome types (archaebacterial, eubacterial, nuclear, mitochondrial and plastid), we have analyzed sequences corresponding to a ubiquitous, highly conserved core of secondary structure in small subunit rRNA. Our results support (i) the existence of three primary lineages (archaebacterial, eubacterial, and nuclear), (ii) a specific eubacterial ancestry for plastids and mitochondria (plant, animal, fungal), and (iii) an endosymbiotic, evolutionary origin of the two types of organelle from within distinct groups of eubacteria (blue-green algae (cyanobacteria) in the case of plastids, nonphotosynthetic aerobic bacteria in the case of mitochondria). In addition, our analysis suggests (iv) a biphyletic origin of mitochondria, with animal and fungal mitochondria branching together but separately from plant mitochondria, and (v) a monophyletic origin of plastids. The method described here provides a powerful and generally applicable molecular taxonomic approach towards a global phylogeny encompassing all organisms and organelles.

Empirical analysis of zooplankton filtering and feeding rates1

Abstract: Multiple regression analysis of published zooplankton filtering and feeding rates yielded separate regression equations for cladocerans, marine Calanoid copepods, and all zooplankton. Ingestion rate was found to increase significantly with animal size, food concentration, and temperature. Filtering rate also increased with animal size and temperature, but declined as food concentration increased. The analysis suggests a difference in particle size preference between cladocerans and copepods. Experimental conditions such as crowding and duration also significantly affected filtering and feeding rates. The regression models allow examination of differences and similarities among zooplankton taxa, functional response, particle size selection, energy allocation, and threshold food concentration. The statistical models describe suspension feeding more precisely than either average literature values or verbal descriptions of trend. The results also suggest possible mechanisms of feeding limitation and provide a heuristic framework for the design of experimental analyses of zooplankton feeding in marine and freshwater systems.

Perceived velocity of moving chromatic gratings

Abstract: Equiluminous red-green sine-wave gratings were drifted at a uniform rate in the bottom half of a 10-deg field. In the top half of the display was a sinusoidal-luminance grating of the same spatial frequency and 95% contrast that drifted in the opposite direction. Observers, while fixating a point in the display center, adjusted the speed of this upper comparison grating so that it appeared to match the velocity of the chromatic grating below. At low spatial frequencies, equiluminous gratings were appreciably slowed and sometimes stopped even though the individual bars of the grating could be easily resolved. The amount of slowing was proportionally greatest for gratings with slow drift rates. Blue-yellow sine-wave gratings showed similar effects. When luminance contrast was held constant, increasing chrominance modulation caused further decreases in apparent velocity, ruling out the possibility that the slowing was simply due to decreased luminance contrast. Perceived velocity appears to be a weighted average of luminance and chrominance velocity information.

Routing with time windows by column generation

Abstract: Consider a set of trips where each trip is specified a priori by a place of origin, a destination, a duration, a cost, and a time interval within which the trip must begin. The trips may include visits to one or more specific points. Our problem is to determine the number of vehicles required, together with their routes and schedules, so that each trip begins within its given time interval, while the fixed costs related to the number of vehicles, and the travel costs between trips, are minimized. The problem is a generalization of the m-traveling salesman problem. We use column generation on a set partitioning problem solved by simplex and branch-and-bound; columns are generated by a shortest path algorithm with time windows on the nodes. Numerical results for several school bus transportation problems with up to 151 trips are discussed.

Expression of a bacterial gene in plants by using a viral vector

Abstract: Several properties of the cauliflower mosaic virus (CaMV) indicate that it could provide a useful vector for gene transfer in higher plants: (1) it has a relatively small double-stranded genome that can be easily manipulated in vitro1–3; (2) cloned viral DNA is infectious when rubbed onto healthy leaves4,5; (3) virus spreads throughout the plant and can be found in most cells at high copy number. Two regions of the CaMV genome—open reading frames (ORFs) II and VII—do not seem to be essential for infection, as both can be either deleted or expanded by small inserts of foreign DNA6–8. No functional genes have yet been introduced into these ORFs. Here we report the replacement of CaMV ORF II by the R67 plasmid-encoded dihydrofolate reductase (DHFR) gene; this gene (dhfr) confers resistance to methotrexate in Escherichia coli. The chimaeric viral DNA can be stably propagated in turnip plants and the dhfr gene is expressed, producing a functional enzyme.

Immunocytochemical localization of atrial natriuretic factor in the heart and salivary glands

Abstract: Antibodies produced in the mouse by repeated intraperitoneal injections of partly purified atrial natriuretic factor (low molecular weight peptide (LMWP) and high molecular weight peptide (HMWP)) have been used to localize these factors by immunohistochemistry (immunofluorescence and immunoperoxidase method) and by immunocytochemistry (protein A-gold technique) in the heart of rats and of a variety of animal species including man and in the rat salivary glands. Immunofluorescence and the immunoperoxidase method gave identical results: in the rat, atrial cardiocytes gave a positive reaction at both nuclear poles while ventricular cardiocytes were consistently negative. The cardiocytes of the right atrial appendage were more intensely reactive than those localized in the left appendage. A decreasing gradient of intensity was observed from the subpericardial to the subendocardial cardiocytes. The cardiocytes of the interatrial septum were only lightly granulated. Sodium deficiency and thirst (deprivation of drinking water for 5 days) produced, as already shown at the ultrastructural level, a marked increase in the reactivity of all cardiocytes from both atria with the same gradient of intensity as in control animals. Cross-reactivity of intragranular peptides with the rat antibodies allowed visualization of specific granules in a variety of animal species (mouse, guinea pig, rabbit, rat, dog) and in human atrial appendages. No reaction could be elicited in the frog atrium and ventricle although, in this species, specific granules have been shown to be present by electron microscopy in all cardiac chambers. With the protein A-gold technique, at the ultrastructural level, single labeling (use of one antibody on one face of a fine section) or double labeling (use of two antibodies on the two faces of a fine section) showed that the two peptides are localized simultaneously in all three types (A, B and D) of specific granules. In the rat salivary glands, immunofluorescence and the immunoperoxidase method showed reactivity exclusively in the acinar cells. The reaction was most intense in the acinar cells of the parotid gland. In the sublingual gland, only the serous cells, sometimes forming abortive “demi-lunes”, were reactive. In the submaxillary gland, the reaction was weaker and distributed seemingly haphazardly in the gland. The most constantly reactive cells were localized near the capsule while many cells did not contain visible reaction product.

Benzodiazepines antagonize cholecystokinin-induced activation of rat hippocampal neurones.

Abstract: Cholecystokinin (CCK) is a neuropeptide present in the mammalian central nervous system (CNS)1. In all species studied so far, the highest concentrations of this neuropeptide have been found in the cerebral cortex, the amygdala and the hippocampus2–5. Five molecular forms of CCK having 39, 33, 13, 8 and 4 amino acid residues have been identified in the CNS, the sulphated octapeptide (CCK8) being the most abundant form detected2,6–8. Specific CCK binding sites have been demonstrated in the rat, guinea pig and human brain9,10. CCK8, applied by microiontophoresis to deep cortical neurones and hippocampal pyramidal neurones, has a powerful excitatory effect, whereas the nonsulphated CCK octapeptide has no such effect on these neurones11–16. Low doses of benzodiazepines depress the spontaneous activity of hippocampal pyramidal neurones17–20. We report here that benzodiazepines at very low doses antagonize selectively the CCK8-induced activation of rat hippocampal pyramidal neurones. This antagonistic action might be involved in the anxiolytic effect of these drugs.

Enzyme-gold electron microscopic cytochemistry: A new affinity approach for the ultrastructural localization of macromolecules

Abstract: The enzyme-gold postembedding approach has been introduced recently in the field of cytochemistry for the ultrastructural localization of macromolecules. This technique is based on the affinity properties existing between an enzyme and its substrate. The possibility of detecting substrate molecules by applying enzyme-gold complexes has been established. The present review deals with the development and the technical approach of this method. Various applications are reported for the demonstration of the reliability of the technique that yields results of high specificity and resolution. In addition, some technical problems and limitations particular to this method are reported and discussed.

Platelet function after cigarette smoking in relation to nicotine and carbon monoxide.

Abstract: In two sets of experiments involving 10 smokers, we followed the acute effect of inhaling smoke from cigarettes with five different nicotine yields (0.07 to 1.44 mg) on platelet function in relation to blood levels of carboxyhemoglobin and nicotine. Blood was drawn from fasted subjects who had not smoked for 10 hr before and after smoking one cigarette. Depending on the cigarette, the increase in platelet aggregation to thrombin, adenosine diphosphate, collagen, and epinephrine 10 min after smoking ranged from 0% to approximately 80% for the cigarettes with the higher nicotine yields. Blood nicotine levels increased from 112% to 644%. Clotting activity of platelet-rich plasma (PRP) and platelets rose by 16% with the cigarettes with the highest nicotine contents. Platelet activity correlated with blood nicotine levels but not with carboxyhemoglobin levels. Nicotine diluted in saline solution and added in vitro to PRP from six other subjects 2 min before the aggregation or clotting test at levels after smoking (10 and 20 ng/ml) induced a rise in platelet reactivity of the same order as that after smoking cigarettes. Data suggest that in some cigarettes, nornicotine and substances contained in tar may contribute to the effect of cigarette smoking on platelets.

Etiology of Parkinson's disease: a research strategy

Abstract: In this essay I present a new "global approach hypothesis" to explain the pathophysiology of Parkinson's disease: "Susceptibility to Parkinsonism is genetically determined and is reflected in all cells. I propose that idiopathic Parkinson's disease is the combined result of a generalized cell aging process accelerated, in susceptible individuals, by a variety of often repetitive trigger factors. These factors have in common the fact that they cause a transient increase in turnover within catecholamine producing neurons, centrally as well as peripherally. This results in accumulation within these neurons of free radicals. When the level of the toxic substances, in quantity or in time of exposure, exceeds the scavenging capacity of the cell, damage to organelles and to membranes results, leading to the formation of Lewy bodies through an autoimmune reaction to damaged filaments and to cell death, particularly in the pigmented neurons of the brainstem. The progressive cell depletion leads to a compensatory increase in catecholamine turnover in the remaining pigmented cells, and an ever-accelerating degenerative process. The resulting neurotransmitter imbalance in the basal ganglia explains the symptoms of Parkinson's disease". In the light of this hypothesis, our research objectives should be (1) to delineate the limits of true Parkinson's disease from all phenocopies; (2) to identify individuals susceptible to parkinsonism and the most common trigger factors; (3) to reduce the metabolic effects of unavoidable trigger factors and (4) to protect susceptible individuals by increasing the functional availability of free radical trapping agents.

Bäcklund transformations for nonlinear sigma models with values in Riemannian symmetric spaces

Abstract: This work deals with Backlund transformations for the principal SL(n, ℂ) sigma model together with all reduced models with values in Riemannian symmetric spaces. First, the dressing method of Zakharov, Mikhailov, and Shabat is shown, for the case of a meromorphic dressing matrix, to be equivalent to a Backlund transformation for an associated, linearly extended system. Comparison of this multi-Backlund transformation with the composition of ordinary ones leads to a new proof of the permutability theorem. A new method of solution for such multi-Backlund transformations (MBT) is developed, by the introduction of a “soliton correlation matrix” which satisfies a Riccati system equivalent to the MBT. Using the geometric structure of this system, a linearization is achieved, leading to a nonlinear superposition formula expressing the solution explicitly in terms of solutions of a single Backlund transformation through purely linear algebraic relations. A systematic study of all reductions of the system by involutive automorphisms is made, thereby defining the multi-Backlund transformations and their solution for all Riemannian symmetric spaces.

Gross energy cost of horizontal treadmill and track running.

Abstract: The gross energy cost of treadmill and track running is re-investigated from data published in the literature. An average equation, weighted for the number of subjects in each study, was found: VO2 (ml/kg/min) = 2.209 + 3.163 speed (km/h) for 130 subjects (trained and untrained males and females) and 10 treadmill studies. On the track, wind resistance as predicted by Pugh (1970) was added to the treadmill cost of running and yielded the following equation for adults of average weight and height: VO2 = 2.209 + 3.163 speed + 0.000525542 speed3. Between 8 and 25 km/h, the following linear equation: VO2 = 3.5 speed (or met = km/h) was very close to the cubic equation. This linear equation for track running is, however, different from the treadmill linear equation, particularly for speeds over 15 km/h. This equation is also slightly different from the one published by Pugh (1970) for track running from 7 trained subjects only.

On auxotrophy for pyrimidines of respiration‐deficient chick embryo cells

Abstract: Chick embryo cells treated with chloramphenicol are inherently resistant to the growth-inhibitory effect of the drug when cultured in the presence of tryptose phosphate broth. The cells were found to be auxotrophic for pyrimidines and the presence in the broth of compounds of pyrimidine origin is demonstrated by chromatographic procedures and mass spectral analyses. They are in the form of ribonucleosides, ribonucleotides and pyrimidine-containing oligoribonucleotides. To understand the mechanism responsible for pyrimidine auxotrophy, the activity of enzymes involved in the pyrimidine biosynthetic pathway was determined. Measurement of the conversion of dihydroorotic acid to orotic acid in cell-free extracts revealed that chloramphenicol-treated chick embryo cells are deficient in dihydroorotate dehydrogenase activity. The data in vitro are supported by studies on the nutritional requirements of the respiration-deficient cells and by the incorporation in vivo of labelled dihydroorotic acid into the acid-insoluble fraction of the cells. Although the activity of the dehydrogenase in vitro is decreased by 95%, the enzyme is present in chloramphenicol-treated cells and its activity is unmasked by the artificial electron acceptor menadione. A study of the activity of other enzymes of the pyrimidine biosynthetic pathway demonstrated that their activity is comparable to that in control cells. The present results indicate that auxotrophy for pyrimidines results from the inhibition of the flow of electrons along the mitochondrial electron transport chain.

The intermediate filament cytoskeleton of myofibroblasts: an immunofluorescence and ultrastructural study.

Abstract: The intermediate filament cytoskeleton of stromal myofibroblasts from a series of twenty-eight infiltrating ductal breast carcinomas was examined by transmission electron microscopy (TEM) and indirect immunofluorescence (IF), the latter using antibodies to desmin, vimentin and prekeratin. Three cases of fibromatoses, selected as an additional source of myofibroblasts, were processed in the same manner. Stromal myofibroblasts from invasive ductal breast carcinomas rich in actin and readily identified by IF, were most numerous in the "young" edematous mesenchyme, areas corresponding to early stromal invasion or the peripheral invasive cellular front. Within the central sclerotic zone wherein clusters of neoplastic epithelial cells were surrounded by abundant collagen, most stromal cells corresponded by TEM to fibroblasts. In like fashion, myofibroblasts were most numerous in cellular, poorly collagenized portions of fibromatoses. By IF the only detectable intermediate filament protein of myofibroblasts in these two settings was vimentin. Since the appearance of stromal myofibroblasts appears to be associated with stromal invasion by malignant epithelium, their development by modulation of pre-existent periductal fibroblasts is postulated. With the exception of vascular smooth muscle cells and endothelial cells, the only periductal mesenchymal cells shown to contain vimentin were fibroblasts. The lack of desmin in myofibroblasts constitutes evidence against an origin from vascular smooth muscle cells. Because the molecular markers (intermediate filament proteins) of stromal cell differentiation presented quantitative but not qualitative modifications, the transformation of fibroblasts into myofibroblasts is quite likely, suggesting that myofibroblasts may be more closely related to fibroblasts than to smooth muscle cells.

Effects of the two antidepressant drugs mianserin and indalpine on the serotonergic system: Single-cell studies in the rat

Abstract: Several antidepressant treatments enhance serotonergic neurotransmission. The present electrophysiological studies were undertaken to assess the effect of mianserin and indalpine, two antidepressant drugs with different pharmacological profiles, on serotonergic neurotransmission. In a first series of experiments, the responsiveness of hippocampal pyramidal neurons to microiontophoretic applications of serotonin (5-HT), norepinephrine (NE) and γ-aminobutyric acid (GABA) was assessed following mianserin, imipramine (5 mg/kg/day IP) or saline administration for 14 days. At 48 h after the last dose of mianserin, responsiveness to 5-HT was increased whereas that to NE and GABA was not modified. The degree of sensitization to 5-HT was the same as that produced by imipramine. Acute IV administration of mianserin (up to 10 mg/kg) did not decrease the firing rate of dorsal raphe 5-HT neurons. In a second series of experiments, long-term administration of indalpine (5 mg/kg/day IP for 14 days) did not modify the responsiveness of hippocampal pyramidal neurons to microiontophoretically applied 5-HT, NE and GABA whereas imipramine treatment (5 mg/kg/day IP) increased selectively their sensitivity to 5-HT when compared to indalpine-treated rats. In keeping with its potent reuptake-blocking property, acute IV indalpine produced a marked decrease in the firing rate of dorsal raphe 5-HT neurons (ED50 0.33 mg/kg). The firing rate of dorsal raphe 5-HT neurons was assessed following 2-, 7- and 14-day treatments with indalpine (5 mg/day IP). After 2 days, the firing rate of 5-HT neurons was greatly reduced, after 7 days it had recovered partially and after 14 days it had returned to normal. At this point, the responsiveness of 5-HT neurons to IV LSD, an agonist of the 5-HT autoreceptor, and to microiontophoretically-applied 5-HT was decreased twofold, indicating desensitization of the autoreceptor. In conclusion, it is proposed that long-term treatment with mianserin, as with tricyclic antidepressant drugs and electroconvulsive shocks, increases 5-HT neurotransmission via sensitization of postsynaptic neurons to 5-HT whereas long-term treatment with indalpine, as with zimelidine, results in the same final effect via its presynaptic effect on 5-HT neurons presumably by blocking 5-HT reuptake. These data further support the notion that enhancing 5-HT neurotransmission might have an antidepressant effect.

A long-term longitudinal study of anticentromere antibodies

Abstract: A longitudinal retrospective study of 37 patients previously tested for anticentromere antibodies (ACA) in 1982 was carried out. No ACA were found in stored sera from 22 ACA-negative patients including 1 patient with CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasia). All ACA-positive patients, with 1 exception, were found to have ACA in their sera over prolonged periods of time. One patient developed ACA for the first time when the third feature of the CREST syndrome (Raynaud's phenomenon) was noted. Anticentromere antibodies were IgG, and no consistent change in titer over time was found.