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Biomedical subjects

L Tremblay

Publications and source records attributed to L Tremblay.

At least 73 records · Page 4Linked to original sources

Purification and characterization of metabolically active capillaries of the blood-brain barrier.

Microvessels were isolated from bovine and rat cerebral cortex by simple procedures involving mechanical homogenization, differential and density-gradient centrifugation, and chromatography on a column of glass beads. The preparations were composed of short capillaries with a diameter of 1-10 microns. Both purifications were monitored by assaying the activity of the marker enzyme gamma-glutamyl transpeptidase (gamma-GTase). The final bovine and rat preparations were enriched 20- and 14-fold over the homogenate respectively. gamma-GTase activity was measured in different fractions after bovine and rat membranes were solubilized with 0.5% and 0.3% Triton X-100 respectively. Measurement of 5'-nucleotidase and acetylcholinesterase activities indicated very low levels of contamination of the microvessel preparations by glial cells and neurons. The integrity of the capillary membranes was confirmed by the assay of a cytosolic marker enzyme, lactate dehydrogenase. Viability of the microvessels was demonstrated by the presence of detectable levels of adenylates and by tissue respiration induced by glucose and succinate. Comparison of the proteins of homogenized bovine and rat brain cortex with those of purified capillaries separated by SDS/PAGE revealed enrichment of at least three predominant proteins of 14, 16 and 18 kDa in the capillary preparations. It is concluded that these methods allow rapid isolation of small blood vessels of the blood-brain barrier which are suitable for metabolic and structural studies in vitro.

Acetylcholinesterase↗

Abnormal spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism.

The goal of the study was to determine abnormalities in the spontaneous activity of globus pallidus neurons at the output of the basal ganglia, in cynomolgus monkeys rendered parkinsonian by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In parkinsonian compared to intact monkeys, the mean spontaneous firing rate of the neurons of the internal segment of the globus pallidus (GPi) increased but that of the prevailing neuronal population in the external segment (GPe) inversely decreased. Correspondingly, the mean modal interval between spikes shortened, suggesting increased excitation, in both the GPi and GPe. However, the mean proportion of intervals longer than 100 ms increased in the GPe but remained unchanged in the GPi, suggesting increased inhibition only in the GPe. In the two populations, bursting activities and the mean variability of firing rate increased. Concurrently, a small and distinct neuronal population located in the GPe and another located at the periphery of both the GPi and GPe displayed minor changes, which were however different from those observed in the GPi and in the prevailing neuronal population of the GPe. The intensity of changes varied with time and severity of nigral lesion. In severe parkinsonism, the neuronal activity at the output of the basal ganglia (GPi) is excessive.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Effects of dopamine agonists on the spontaneous activity of globus pallidus neurons in monkeys with MPTP-induced parkinsonism.

The mixed (D1 and D2) dopamine agonist apomorphine was injected (10-200 micrograms/kg, s.c.) to cynomolgus monkeys before and after they were rendered parkinsonian by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Motor behavior was examined together with corresponding neuronal activity in the external (GPe) and internal (GPi) segments of the globus pallidus, including a small population of neurons localized within the GPe and displaying a characteristic discharge at low frequency with bursts (LFB), and border (Bor) neurons localized at the periphery of the pallidal segments. In the intact animal strong but not weak doses of the drug induced generalized agitation without apparent neuronal effects. In 1 parkinsonian animal that showed some recuperation of normal behavioral and pallidal activity, weak doses induced agitation and partly reduced the signs of parkinsonism, again without apparent neuronal effects. The same results were obtained before day 21 after MPTP in a parkinsonian monkey that did not recuperate. After day 21, however, the drug acted at a shorter latency, completely abolished the signs of parkinsonism, induced dyskinesia, increasing with repetition of injections, and clear neuronal effects. The same results were obtained from the start in another monkey in which recordings were begun 398 days after MPTP. Nearly all GPi neurons decreased their firing rate following apomorphine. The reverse was true of the predominant neuronal population in the GPe. In both cases, the intensity of the changes in firing rate varied much between neurons following the same dose of apomorphine. When the changes in firing rate were moderate or null, abnormal bursting firing patterns were normalized. Both LFB and Bor neurons decreased their firing rate following apomorphine; LFB neurons being extremely sensitive. The selective D2 agonist RU-24213 induced behavioral and neuronal effects identical to those of apomorphine.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

The immune response to the HPA-1a antigen: association with HLA-DRw52a.

Antibodies to the HPA-1a antigen can elicit a condition in the new-born known as neonatal alloimmune thrombocytopenia (NAITP). Retrospective and prospective studies have shown that there is a strong correlation between the presence of HLA-DR3, HLA-DRw52 in the mother and the antibody response to HPA-1a. HLA Class II molecules play an important role in the initiation of the immune response and it has been postulated that HPA-1a antibody production could be determined by the presence of a specific HLA Class II molecule at the surface of the antigen-presenting cell. Thirty-one HPA-1a negative women with HPA-1a antibodies (responders) and nine HPA-1a negative women without HPA-1a antibodies (non-responders) were recruited. They were studied using serological HLA Class I and Class II typing and RFLP analysis with a DR beta probe. We found that all responders had the HLA-DRw52a sub-specificity confirming recently published data. Moreover, two of the nine non-responders were also found to be HLA-DRw52a. These results suggest that the HLA-DRw52a molecule is necessary for HPA-1a antibody responsiveness but not sufficient. The results also indicate that in HPA-1a negative women the absence of HLA-DRw52a is associated with a very low risk of being antibody producers and hence, is associated with a very low risk for NAITP in their new-borns.

Antigens, Human Platelet↗

Responses of pallidal neurons to striatal stimulation in intact waking monkeys.

Extracellular single-unit activity was recorded from neurons of the internal and external pallidal segments, and from 'border cells' at the periphery of the segments, in 3 waking cynomolgus monkeys during electrical stimulation of 3 sites bilaterally in the striatum: one in the caudate nucleus and two in the putamen. Nearly 90% of each of the 3 types of neurons responded to at least one ipsilateral stimulation site. Contralateral stimulation was much less effective, except for border neurons. Neurons responding exclusively to caudate stimulation were located in a dorsomedial zone of the pallidum, those responding exclusively to putamen were in a larger ventrolateral zone, and those responding to both nuclei were in an intermediate zone, larger at rostral than at caudal levels. The great majority of responses consisted of an initial inhibition, at a mean latency of 14 ms, followed by excitation, at a mean latency of 35 ms. Later components of weaker magnitude, often comprising inhibition, occurred in only 30% of the cases. Only border neurons displayed an initial excitation preceding the early inhibition. The responses were not different in the internal and external pallidal segments, except for the slightly more frequent occurrence of excitation in the latter segment. The early inhibition was always displayed by neurons located in the center of the pallidal zone of influence of each striatal stimulation site, and was ended and often curtailed by excitation. At the periphery of the zone, excitation occurred alone or as the initial component of responses. This topological arrangement suggests that excitation is used, temporally, to control the magnitude of the central striatopallidal inhibitory signal and, spatially, to focus and contrast it onto a restricted number of pallidal neurons.

Action Potentials↗

Responses of pallidal neurons to striatal stimulation in monkeys with MPTP-induced parkinsonism.

Extracellular single unit activity was recorded from neurons of the internal (GPi) and external (GPe) pallidal segments, and from 'border cells' (Bor) which are part of the nucleus basalis, in 2 cynomolgus monkeys rendered parkinsonian by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). Cell counts showed that at least 90% of the nigral neurons of the compacta-type were degenerated. Electrical stimulation was applied to 3 sites bilaterally in the striatum: one in the caudate nucleus and 2 in the putamen. The results were compared to those obtained in intact monkeys. In the parkinsonians, more neurons of the 3 types responded to ipsilateral stimulation. The difference was even greater for contralateral responses, except in the case of Bor neurons. Greater proportions of the 3 types of neurons also responded to 2 and 3 sites and showed convergent responses to both the caudate nucleus and the putamen. The magnitude of the responses was larger. These results are in accordance with the excessive and unselective responses of the same neurons to passive limb movement, obtained in the same animals and described previously. The electrical stimulation allowed more detailed analyses of the responses. The major change in the responses of GPi and Bor neurons was the more frequent and larger late inhibitions, whereas the excitations were larger in GPe neurons. Long lasting oscillatory responses occurred frequently in the parkinsonians, mainly in GPi, and at frequencies close to the tremor displayed by the animals. Responses beginning with early inhibition were displayed by neurons located in the center of the pallidal zone of influence of each striatal stimulation site, as in intact animals, but in the GPi of the parkinsonians they were less frequently curtailed by excitation. Moreover, in the parkinsonians, the zones of influence were larger in both GPi and GPe, mainly because of the expansion of their periphery, where responses began with excitation and had lower thresholds than in intact animals. The dopamine agonist apomorphine normalized the responses in the parkinsonians. Thus, both the temporal and spatial magnitudes of inhibitions and excitations are abnormal at the output of the basal ganglia in parkinsonism.

Action Potentials↗

Isolation and characterization of iso-rANP, a new natriuretic peptide from rat atria.

Using a specific radioimmunoassay we have isolated and sequenced a new 45-amino acid peptide from rat atria which exhibits similar physiological and pharmacological properties to rat atrial natriuretic peptide (rANP). We have termed the new peptide iso-rANP, because of its functional and structural similarities to rANP. Amino acid sequence differences show that iso-rANP is genetically distinct from rANP. Iso-rANP has a single disulfide bond between residues 23-39 and this portion of the peptide shows substantial homology to rANP and to porcine brain natriuretic peptide (BNP). Little homology is evident at the N- and C-termini of iso-rANP and ANP. Iso-rANP is equipotent with rANP in eliciting diuresis, natriuresis and hypotension in the bioassay rat.

Amino Acid Sequence↗

Abnormal influences of passive limb movement on the activity of globus pallidus neurons in parkinsonian monkeys.

Extracellular single unit activity was recorded in the globus pallidus of waking Macaca fascicularis during passive limb movement. The main upper and lower limb joints were investigated bilaterally. The animals were either intact or rendered parkinsonian by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell counts showed that at least 90% of nigral neurons of the compacta-type were degenerated in the parkinsonian animals. In the intact animals, only 17% of the pallidal neurons responded to the natural stimulus. As already reported by others, the responses were typically related to movement about a single contralateral joint and in only one direction. In the parkinsonian animals, however, more neurons responded, often more vigorously, to the same stimulation. In many of these neurons the responses were elicited by movement about more than one joint of both upper and lower limbs or ipsi-and contralateral sides and in more than one direction. The increase in number and magnitude and loss of specificity of responses were much greater in the internal pallidal segment, where the number of responding neurons quadrupled. These results suggest that dopaminergic mechanisms regulate gain and selectivity in the basal ganglia. In animals with decreased dopaminergic functions, the excessive and unselective motor responses may explain all 3 major signs of parkinsonism: rigidity, tremor and akinesia.

Animals↗

The relationship between callosal variation and lateralization in mice is genotype-dependent.

The relation between morphological variation of the corpus callosum and variation in the degree of paw preference was investigated in 129/J and BALB/cCF mice. A positive relationship explaining 24% of the variance of paw preference was found in 129/J mice; no such relationship exists in BALB/cCF mice. It is suggested that, since the genetic dissimilarity between these two inbred strains is comparable in magnitude with the genetic dissimilarity between unrelated human subjects, genetic variation may have been an uncontrolled source of heterogeneity in previous human neuropsychological studies.

Animals↗

Sex biases in mental health scales: do women tend to report less serious symptoms and confide more than men?

Women report more symptoms than men in mental health surveys. The evidence shows that psychometric biases cannot explain this significant difference. This study attempts to explore other factors that could bias the results--for example, that women are likely to report less serious symptoms than men or are less apprehensive in reporting symptoms because they have a higher tendency to report symptoms than men. A random sample of 213 women and 222 men, all married and between the age of 25 and 40, were interviewed at home in two districts of Montreal (Canada) and given the Health Opinion Survey (HOS). As has been usually found, women scored higher than men on the HOS. A variety of scales assessed the seriousness of the symptoms and the results did not indicate any sex difference in this regard. Moreover, there was no correlation between the mental health and the Jourard Self-Confidence Scale. Finally, women did not confide more about their symptoms than men, contrary to the prevalent opinion according to which they are more likely to do so. Sex differences on mental health scales do not, therefore, appear to be related to the type of bias assessed in this survey.

Adult↗

Sympathetic control of motility, fluid transport, and transmural potential difference in the rabbit ileum.

Both intestinal motility and intestinal fluid and electrolyte transport are influenced by the sympathetic nervous system. The aim of this study is to examine the relationship between the sympathetically induced inhibition of spontaneous contractile activity and epithelial function, monitoring simultaneously motility, fluid transport, and transmural potential difference (PD) in the rabbit ileum. Experiments were performed in vitro to eliminate any possible indirect effects on intestinal function caused by alterations in intestinal blood flow. Perivascular nerve stimulation induced an inhibition of spontaneous motility, a fall in transmural PD (toward more lumen positive), and an enhanced fluid absorption. The sympathetically induced inhibition of motility was abolished by the beta-adrenoceptor antagonist, propranolol, whereas the subsequent administration of phentolamine, the alpha-adrenoceptor antagonist, was required to abolish the fall in transmural PD. Thus the sympathetic nervous system is capable of simultaneously influencing intestinal motility and fluid and electrolyte function. However, separate but parallel neural mechanisms control the smooth muscle and epithelial responses; the inhibition of motility is beta-mediated, while alpha-receptors alter fluid and electrolyte transport.

Animals↗

Gas chromatographic/mass spectrometric analysis of 19-nortestosterone urinary metabolites in man.

A sensitive and highly specific method based on capillary column gas chromatography/mass spectrometry has been developed for the detection of 19-nortestosterone (17 beta-hydroxy-4-estren-3-one) metabolites in urine. After intramuscular administration of 19-nortestosterone decanoate to man, urine samples were collected during several days and treated with Helix pomatia digestive juice. The free steroids were extracted and converted into O-methyl-oxime-trimethylsilyl or the trimethylsilyl ether derivatives and analysed by capillary column gas chromatography/mass spectrometry (GC/MS). Three isomeric metabolites were detected and identified as 3 alpha-hydroxy-5 alpha-extran-17-one (19-norandrosterone), 3 alpha-hydroxy-5 beta-estran-17-one (19-noretiocholanolone) and 3 beta-hydroxy-5 alpha-estran-17-one (19-norepiandrosterone). Packed column GC/MS was also employed in the selected ion monitoring mode for the specific detection of 19-norandrosterone, the most abundant urinary metabolite of 19-nortestosterone. These gas chromatographic/mass spectrometric methods are highly specific tests which can be used on a routine basis for the confirmation of 19-nortestosterone administration to athletes as well as for therapeutic monitoring following administration of the drug.

Estranes↗

Proximal airway pressure monitoring in the neonatal ICU.

The static and dynamic responses of diaphragm-type pressure manometers currently used with manual ventilation in the neonatal ICU were determined at different pressures and frequencies. Using a precalibrated transducer attached to a closed-loop system, the manometer peak pressure was adjusted to 15, 20, 25, and 30 cm H2O, first for static measurements and then again while the frequency was increased from 20 to 200 breath/min in increments of 20. Most manometers with inlet flow-restricting devices built into the manometer or attached to the connection system in a ventilator significantly underestimated the delivered pressure as the peak inflation pressure and frequency were increased. In those manometers without inlet flow restrictors the correlation between transducer pressure and observed manometer pressure was close. Diaphragm-type pressure manometers with inlet flow-restricting devices may substantially underestimate the delivered proximal airway pressure when incorporated into neonatal manual ventilation equipment.

Humans↗