Biomedical subjects

C Hébert

Publications and source records attributed to C Hébert.

At least 37 records · Page 2Linked to original sources

PubMed2001

Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects.

Duloxetine is a dual inhibitor of norepinephrine (NE) and serotonin (5-HT) uptake. Initial trials conducted in depressed patients using regimens of 20 mg/day or less did not convincingly demonstrate its efficacy as an antidepressant. The aim of this study was to assess the effects of duloxetine on the 5-HT and NE reuptake processes in healthy human volunteers. Twenty-seven healthy young males without a history of psychiatric disorder were randomly assigned to four groups, each group receiving one of the following daily drug regimens: placebo, clomipramine (a potent 5-HT/NE reuptake blocker) 100 mg/day, duloxetine 20 mg/day, or duloxetine 60 mg/day. In order to assess the NE reuptake process, the pressor response to intravenous tyramine (4 and 6 mg) was measured. Determination of the whole blood 5-HT content was used to evaluate the 5-HT reuptake blockade. These measurements were performed at baseline and repeated after 7 and 14 days of drug intake. Both duloxetine, at doses of 20 to 60 mg/day, and clomipramine significantly interfered with the 5-HT reuptake process, as demonstrated by marked decreases in blood 5-HT concentrations. However, the same doses of duloxetine, unlike clomipramine, failed to impede the usual increase in blood pressure that follows a tyramine intravenous infusion, indicating that clomipramine but not duloxetine blocked NE reuptake. At doses tested in a population of healthy volunteers, duloxetine acted as a selective 5-HT reuptake inhibitor, having no clear effect on the NE reuptake process. Nevertheless, given that the highest dose of duloxetine increased supine systolic blood pressure, it is possible that it represents the threshold regimen for NE reuptake inhibition.

Adolescent↗

PubMed2000

Central serotonin system in Dystonia musculorum mutant mice: biochemical, autoradiographic and immunocytochemical data.

The autosomal recessive mutation dystonia musculorum (dt(J)/dt(J)) causes degenerative alterations of peripheral and central sensory pathways that lead to ataxia. To investigate possible changes in the central serotonin system of these mice, HPLC measurements of 5-hydroxytryptophan, 5-hydroxy-tryptamine (serotonin; 5-HT), and 5-HT metabolites were obtained from 22 brain regions and the spinal cord of wild type and dt(J)/dt(J) mutant mice. Also, 5-HT transporters were quantified by [(3)H]citalopram autoradiography in 72 brain regions, subregions, and nuclei, and the 5-HT innervation visualized by immunocytochemistry throughout the brain and spinal cord. In all brain regions measured for indoleamine content, there were no significant differences between the two genotypes. In the spinal cord, an increased tissue concentration of 5-HT (+34%), 5-hydroxyindole-3-acetic acid (+33%), 5-hydroxytryptophol (+21%), and 5-hydroxytryptophan (+45%) in dt(J)/dt(J) actually corresponded to the same total amount of each of these indoleamines in the entire spinal cord, when taking into account its reduced size in the mutants. Quantification of the binding to 5-HT transporters showed increases in the medial geniculate nucleus (+14%), medial (+24%) and lateral (+18%) hypothalamus, interpeduncular (+13%), vestibular (+22%), and deep cerebellar nuclei (+37%) of dt(J)/dt mice, and decreases in the ventral tegmental area (-13%), median and linear raphe nuclei (-20%), as well as in the solitary complex (-35%). There were no apparent differences in the distribution of 5-HT-immunostained fibers in these and other regions of brain and in the spinal cord of dt(J)/dt(J) compared to wild type mice. The bulk of these results indicates a relative sparing of the central 5-HT system in the dt(J)/dt(J) mice, even though alterations in 5-HT transporters could justify attempts at improving the sensorimotor dysfunction by administration of serotoninergic agents in these mice.

5-Hydroxytryptophan↗

PubMed2000

Dopamine D(1) and D(2) receptors in the forebrain of dystonia musculorum mutant mice: an autoradiographic survey in relation to dopamine contents.

Dystonia musculorum (dt(J)/dt(J)) mutant mice suffer from a degeneration of spinocerebellar tracts as well as a dystrophy of peripheral sensory tracts. This neurological mutant has been proposed as an animal model of human cerebellar ataxia, in particular of the Friedreich's type; thus, it was deemed of interest to examine the endogenous contents of dopamine (DA) and metabolites as well as the distribution of DA receptors of the D(1) and D(2) subtypes, in order to delimit the biochemical characteristics of this pathological disorder, and determine an eventual dopaminergic dysfunction in this mutant. Tissue DA and its major metabolites 3, 4-dihydroxyphenylacetic acid, homovanillic acid and 3-methoxytyramine were measured by HPLC coupled to electrochemical detection in six cortical regions, in four divisions of rostral neostriatum and two halves of caudal neostriatum, as well as in olfactory bulb, nucleus accumbens, septum, amygdala, hippocampus, thalamus, hypothalamus, brainstem, cerebellum, substantia nigra, and ventral tegmental area. The only significant difference between dt(J)/dt(J) mice and wild-type controls was an increase in hypothalamic DA contents (+47%). Quantitative autoradiography with [(3)H]SCH23390 and [(3)H]raclopride, to label D(1) and D(2) receptors, respectively, revealed only moderate changes in receptor densities in a few localized regions. In dt(J)/dt(J) mutants, D(1) receptor numbers were found to be higher in thalamus (+27%) as well as in the medio-dorsal (+16%) and in the latero-dorsal (+16%) quadrants of rostral neostriatum, while D(2) receptor densities were greater in the medio-ventral (+32%) and the latero-dorsal (+17%) quadrants. The present results indicate an overall conservation of dopaminergic functions, albeit the few localized sites of increased D(1) and D(2) receptor densities, and that are seemingly independent of the DA innervation pattern, as revealed by the tissue measurements of DA and metabolites. They also rule out a major pathology linked to deficits in DA neurotransmission, and validate this mutant as an animal model of human cerebellar ataxia, probably of the Friedreich type.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Hydrography and population genetic structure in brook charr (Salvelinus fontinalis, Mitchill) from eastern Canada.

Despite the abundance of studies of genetic diversity in freshwater fishes, few have specifically addressed the role of habitat structure in partitioning genetic variance within and among populations. In this study, we analysed the variability of six microsatellite loci among 24 brook charr population samples in order to correlate hydrographic structure with genetic organization. These populations originated from three Canadian National parks (Kouchibouguac, Fundy and Forillon) that showed distinct hydrographic structure. Considering the general characteristics of these habitats, we formulated specific hypotheses in regard to genetic structure, which were principally based on the potential for gene flow and population size associated with each habitat. The hierarchical analysis of molecular variance and the genetic distances computed among populations revealed that habitat structure analyses constitute an important, but insufficient, predictor of genetic structure. We discuss the importance of habitat complexity on genetic structure in the context of management and conservation.

Alleles↗

PubMed1999

Serotonin innervation of Lurcher mutant mice: basic data and manipulation with a combination of amantadine, thiamine and L-tryptophan.

The Lurcher (Lc/+) mutant mouse is characterized by a considerable atrophy of the cerebellum due to a massive loss of cerebellar Purkinje and granule cells, as well as of neurons from the inferior olivary nucleus. In this study the effects of a therapeutic combination of amantadine, thiamine and L-tryptophan on the serotonin (5-HT) innervation was assessed in Lurcher mice by autoradiography, using [3H]citalopram to label 5-HT transporters. In wild type mice as well as in both saline-treated and drug-treated Lurcher mutants, [3H]citalopram binding remained unchanged in forebrain and brainstem regions. In the cerebellum, labelling of deep cerebellar nuclei (CBnuc) was about twofold higher than in the cortex (CBctx). In saline-treated Lurcher mutants compared to wild type mice, the densities of [3H]citalopram were 98% higher in CBctx, and 180% higher in CBnuc. In CBctx of drug-treated Lurcher mutants, transporter densities were 89% higher than in the wild type, but did not differ from the saline-treated Lurcher. In the CBnuc of the drug-treated Lurcher mutants, [3H]citalopram binding was 50% higher than in the saline-treated Lurcher group, and 320% higher than in wild type mice. The results show that 5-HT transporters, already upregulated in the CBnuc of Lurcher mutant mice, can be further increased by a pharmacological treatment, possibly altering the availability of 5-HT in some of its target areas.

5-Hydroxytryptophan↗

PubMed1999

Effects of antipsychotic drugs on dopamine and serotonin contents and metabolites, dopamine and serotonin transporters, and serotonin1A receptors.

The effects of neuroleptics have been attributed to dopamine (DA) receptor blockade; however, other neurotransmitters, in particular serotonin (5-HT), have also been implicated. In this study, we examined the effects of clozapine and haloperidol on the distribution of DA and 5-HT transporters, on endogenous DA, 5-HT and their major metabolites, and on 5-HT1A receptors. Adult male Sprague-Dawley rats were treated with either haloperidol (1 mg/kg/day, i.p.), clozapine (20 mg/kg/day, i.p.) or saline for 21 days, and following 3 days of withdrawal, the brains were removed. Tissue levels of DA and 5-HT and their metabolites were measured by high-performance liquid chromatography in 16 brain regions, while quantitative autoradiography with [125I]RTI-121, [3H]citalopram and [3H]8-OH-DPAT was employed to label DA transporters, 5-HT transporters and 5-HT1A receptors, respectively. After haloperidol, densities of 5-HT transporters were increased in the dorsal insular cortex and in the ventral half of caudal neostriatum, while 5-HT1A receptors augmented in cingulate cortex but decreased in the entorhinal area. After clozapine, [3H]citalopram labelling was increased in ventral hippocampus, ventral caudal neostriatum and nucleus raphe dorsalis, but decreased in medio-dorsal and latero-dorsal neostriatum as well as in substantia nigra. Binding of [3H]8-OH-DPAT following clozapine was decreased in frontal, parietal, temporal and entorhinal cortices but increased in the CA3 division of Ammon's horn. The changes in 5-HT transporters in nucleus raphe dorsalis and substantia nigra, as well as the 5-HT1A receptor down-regulations caused by clozapine but not by haloperidol, may explain effects obtained with clozapine and other atypical neuroleptics. There were no modifications in densities of DA transporters, nor of tissue DA levels, after the chronic neuroleptic treatments. The results are in line with previous suggestions that a certain degree of tolerance to neuroleptics develops, in spite of profound D1 and D2 receptor changes that persist during the entire chronic treatment with these psychotropic agents.

Animals↗

PubMed1999

Regional brain distribution of noradrenaline uptake sites, and of alpha1-alpha2- and beta-adrenergic receptors in PCD mutant mice: a quantitative autoradiographic study.

The mouse "Purkinje cell degeneration" (pcd) is characterized by a primary loss of Purkinje cells, as well as by retrograde and secondary partial degeneration of cerebellar granule cells and inferior olivary neurons; this neurological mutant can be considered as an animal model of human degenerative ataxia. To determine the consequences of this cerebellar pathology on the noradrenergic system, noradrenaline transporters as well as alpha1-, alpha2- and beta-adrenergic receptors were evaluated by quantitative ligand binding autoradiography in adult control and pcd mice using, respectively, [3H]nisoxetine, [3H]prazosin, [3H]idazoxan and [3H]CGP12177. In cerebellar cortex and deep nuclei of pcd mutants, [3H]nisoxetine labelling of noradrenaline transporters was higher than in control mice. However, when binding densities were corrected by surface area, they remained unchanged in the cerebellar cortex but associated with 25% and 40% lower levels of labelling of alpha1 and beta receptors, as well as a very important increase (275%) of alpha2 receptors. In deep cerebellar nuclei, surface corrections did not reveal any changes either in transporter or in receptor densities. Higher densities of [3H]nisoxetine labelling were found in several regions related with the cerebellum, namely inferior olive, inferior colliculus, vestibular, reticular, pontine, raphe and red nuclei, as well as in primary motor and sensory cerebral cortex; they may reflect an increased noradrenergic innervation related to motor adjustments for the cerebellar dysfunction. Increased [3H]nisoxetine labelling was also measured in vegetative brainstem regions and in dorsal hypothalamus, implying altered autonomic functions and possible compensation in pcd mutants. Other changes found in extracerebellar regions affected by the mutation, such as thalamus and the olfactory system implicated both noradrenaline transporters and adrenergic receptors. In contrast to the important alterations of the noradrenergic system in cerebellar cortex, the lack of receptor changes in deep cerebellar nuclei suggests that local adaptations may be sufficient to minimize the consequence of the cerebellar atrophy on motor control. An intense labelling by [3H]idazoxan of the inner third of the molecular layer was a novel, albeit unexplained finding, and could represent a postsynaptic subset of alpha2-adrenergic receptors.

Adrenergic alpha-Antagonists↗

PubMed1999

Distribution of dopamine, its metabolites, and D1 and D2 receptors in heterozygous and homozygous weaver mutant mice.

In weaver mice, besides a postnatal cerebellar developmental anomaly probably caused by alterations of an inwardly rectifying K+ channel, there is a progressive loss of mesencephalic dopaminergic neurons. To further evaluate this deficit, endogenous dopamine and its metabolites were measured in 22 brain regions from heterozygous (wv/+) and homozygous (wv/wv) mutants, and compared to wild type (+/+) mice. In both wv/+ and wv/wv mutants there were profound dopamine depletions in all regions; these changes were accompanied by decreases in metabolites but with an increase of turnover indexes. Dopamine D1 and D2 receptors were examined by autoradiography, and their distribution was conserved. The results show that the dopaminergic deficit is widespread to all areas of innervation, and is probably compensated for by an increased turnover. Abnormal developmental growth signals, or aberrant cellular responses, may result in defective neurite formation of the midbrain dopaminergic neurons, leading to their postnatal death.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1998

Two recent developments in XMCD.

This paper reports on two new technical developments concerning sample environments for X-ray magnetic circular dichroism (XMCD). The first measurements under high pressures of up to 30 GPa are described. The difficulties of combining the techniques of high pressure and XMCD are commented on. The second development involves the use of a fast-switching magnetic field. A new superconducting device is used to perform XMCD measurements on paramagnetic compounds in magnetic fields of up to 6 T. The small amplitude of the XMCD signal imposes, for a given signal-to-noise ratio, a noise less than a few 10(-5). The signal-to-noise ratio is improved by the use of a series of acquisitions, switching the magnetic field between each acquisition. A very fast switching mechanism has been built based on mechanical rotation of a superconducting coil, with the sample kept in place inside the coil. The XMCD signals at the L(II,III)-edges of paramagnetic rare-earth compounds have been measured at 4.5 K in fields of up to 6 T with a switching time of 11 s.

Journal Article↗

PubMed1998

Distribution of dopamine transporters in basal ganglia of cerebellar ataxic mice by [125I]RTI-121 quantitative autoradiography.

Dopamine (DA) uptake sites, or transporters, were examined with [125I]RTI-121 in mutant mice that exhibit motor control deficits, namely weaver, lurcher and dystonia musculorum. In lurcher mice, the distribution of [125I]RTI-121 binding was similar to controls, except for a decrease in the subthalamic nucleus. For dystonia musculorum mice, the labelling presented no differences between controls and mutants, except for decreases in the dorsal half of caudal neostriatum and in the ventral tegmental area. Moreover, in this mutant the left rostral neostriatum DA transporters were reduced, when compared to the right counterpart. In weaver heterozygote (wv/+) mice, the distribution and density gradients of [125I]RTI-121 labelling were similar as in their controls, except in caudal neostriatum, where binding was slightly higher. In contrast, the weaver homozygote (wv/wv) showed important decreases in labelling of the dorsal quadrant of rostral neostriatum as well as of the dorsal half of caudal neostriatum, where the reductions of binding densities were of 65% to 70%, respectively. There were also slight decreases in [125I]RTI-121 binding in olfactory tubercles as well as in subthalamic nucleus, but only in wv/wv mice. In substantia nigra pars compacta and ventral tegmental area of wv/wv mice the labelling was lower; however, while the 60% decrease in labelling in substantia nigra was highly significant, the 30% reduction in ventral tegmental area did not attain statistical significance. In summary, in the ataxic neurological mutant mice studied, important reductions of DA transporters were documented only for the weaver mice, the cerebellar mutant presenting, besides its cerebellar pathology, a known degeneration of mesencephalic dopaminergic neurons. The results rule out major alterations of the central DA systems in lurcher and dystonia musculorum, and are compatible with the hypothesis that the dopaminergic abnormalities of weaver mutants are not secondary to cerebellar atrophy, but may be a direct consequence of the abnormal weaver gene expressed by DA neurons leading to their apoptotic death.

Animals↗

PubMed1998

Regional distribution of 5-HT transporters in the brain of wild type and 'Purkinje cell degeneration' mutant mice: a quantitative autoradiographic study with [3H]citalopram.

The neurological mutant 'Purkinje cell degeneration' (pcd) is characterized by a primary degeneration of Purkinje cells, as well as by retrograde and secondary partial degeneration of cerebellar granule cells and inferior olivary neurons, and can be considered as an animal model of human degenerative ataxias. The serotonin (5-HT) innervation was examined in wild type and pcd mice, by quantifying 5-HT uptake sites, or transporters, using [3H]citalopram binding autoradiography. In both wild type and pcd mutants, the highest densities of 5-HT transporters were in mesencephalic and rostral pontine regions, in limbic structures, in hypothalamus and in discrete thalamic divisions, while the lowest labelling was found in cerebellum and brainstem reticular formation. In pcd mice, although [3H]citalopram labelling was higher in cerebellar cortex and deep cerebellar nuclei, when binding densities were corrected for surface area, the up-regulation of 5-HT transporters was present only in deep cerebellar nuclei. Also, higher labelling was found in nuclei raphe dorsalis and medialis, in ventral divisions of rostral neostriatum, caudal neostriatum, rostral globus pallidus, posteromedial amygdaloid nucleus, septum, olfactory tubercles, vertical limb of Broca's diagonal band, periventricular, latero-ventral and medio-ventral thalamic nuclei, medial geniculate nucleus, anterior hypothalamus and entorhinal cortex. The results indicate a relative integrity of the 5-HT innervation, but with a reorganization of serotoninergic terminals in the cerebellum, in particular in the deep cerebellar nuclei. This suggests that in progressive cerebellar degeneration, as found in the pcd mutant, the modified 5-HT system may still participate in motor functions by exerting an overall modulation of excitatory amino acid neurotransmission, but the availability of 5-HT may be altered in defined brain targets, as is the case for other spontaneous cerebellar mutants, in particular for the 'Lurcher' mutant mouse, a model of human olivopontocerebellar atrophy.

Animals↗

PubMed1998

Neuroleptics and dopamine transporters.

The effects of neuroleptic treatments on dopamine transporters and on dopamine receptors was investigated in the forebrain of adult rats treated for 21 days with either haloperidol, clozapine or saline. The dopamine D1 receptors, labeled with [3H]SCH23390, increased in nucleus accumbens, latero-dorsal rostral neostriatum and substantia nigra, after clozapine but not haloperidol. The dopamine D2 receptors, studied with [3H]raclopride, increased in nucleus accumbens and in dorso-lateral, ventro-medial and dorso-medial quadrants of the rostral neostriatum after either haloperidol or clozapine treatments, and also in latero-ventral rostral neostriatum but only after haloperidol. Haloperidol also up-regulated D2 receptors in rostral and caudal neostriatum, but clozapine produced a more uneven increase, especially in caudal neostriatum. In contrast, the densities of dopamine uptake sites, or transporters, labeled with [125I]RTI-121, remained unchanged after both neuroleptic treatments. The observation that dopamine transporters are resistant to treatments that modify D1 and D2 receptors indicates that these uptake sites can probably be ruled out as the target of neuroleptic drugs, and that dopamine receptor up-regulations can indeed occur independently of the densities of nerve endings at the terminal fields of innervation.

Animals↗

PubMed1997

Effects of a chronic lithium treatment on central dopamine neurotransporters.

The objectives of this study were to characterize the effects of a chronic lithium (Li+) treatment on dopamine (DA) uptake sites, as well as on the levels of mRNA encoding for these transporters, and to determine the eventual reversibility of the treatment. Quantitative autoradiography was carried out on sections from rat brain using 3beta-(4-[125I]iodophenyl)tropane-2beta-carboxylic acid isopropyl ester ([125I]RT1-121) to label DA transporters, and mRNA levels were measured by in situ hybridization. Following chronic Li+ treatment (28 days), the labelling to DA transporters increased (60-90%) in all sections of the rostral and caudal neostriatum, whereas no alteration was observed in the other regions studied, namely the substantia nigra, the ventral tegmental area, and the dorsal raphe nucleus. These effects were reversed completely following a withdrawal period of 2 days without Li+. Also, there were no modifications in the labelling of DA transporters after only 2 days of Li+ treatment. In addition, we measured the levels of mRNA encoding for DA transporters in the substantia nigra and the ventral tegmental area; however, no alterations were observed following a chronic Li+ treatment, and thus the hypothesis of an increased synthesis is not supported. This could mean that the Li+ treatment modified the affinity of DA transporters for the radioligand, possibly a consequence of conformational changes induced by the disruption of the nerve terminal membrane environment; however, a modification in the number of transporters could not be ruled out. The results of this study further support the hypothesis of the implication of central dopaminergic transmission in the pathology and treatment of affective disorders.

Animals↗

PubMed1997

Effects of chronic neuroleptic treatments on dopamine D1 and D2 receptors: homogenate binding and autoradiographic studies.

The antipsychotic effects of neuroleptics are believed to be mediated via dopamine D2 receptor blockade; however, the anatomical and pharmacological targets of these drugs remain somewhat controversial. The purpose of this study was to examine the effects of chronic clozapine (CLZ) and haloperidol (HAL) treatments on the densities of DA D1 and D2 receptors. Adult male Sprague-Dawley rats (300-350 g) were treated for 21 days with either HAL (1 mg/kg/day, i.p.), CLZ (20 mg/kg/day, i.p.) or saline. Three days after ending the treatments, the brains were removed and used for biochemical assays of tissue DA and metabolites as well as for receptor studies. DA D1 and D2 receptors were labelled with [3H]SCH23390 and [3H]raclopride, respectively, and measured in the neostriatum by binding studies, and in autoradiograms of forebrain sections by quantitative densitometry. The autoradiographic measurements revealed significant increases in the densities of D2 receptors in nucleus accumbens, in the medio-ventral, latero-dorsal and latero-ventral quadrants of the rostral neostriatum, in caudal neostriatum and in globus pallidus of both HAL-(28-44%) and CLZ-treated (15-85%) animals. The HAL-induced up-regulation of D2 receptors in rostral and caudal neostriatum was homogenous, but CLZ produced a more uneven increase, with the highest absolute densities measured in latero-dorsal neostriatum, as well as with changes in the medio-dorsal rostral neostriatum. For D1 receptors, only CLZ and not HAL, produced significant increases in five regions, namely nucleus accumbens (43%) latero-dorsal rostral neostriatum (16%), caudal neostriatum (30%), globus pallidus (67%) and substantia nigra (12%). The observation that CLZ, contrary to HAL, also has an effect on D1 receptor densities may explain the greater therapeutic and selective efficacy with fewer side-effects of this agent, in comparison to other neuroleptics.

Animals↗

PubMed1997

Dexmedetomidine inhibits osmotic water permeability in the rat cortical collecting duct.

The purpose of this study was to determine whether the selective alpha-2 agonist dexmedetomidine inhibits basic transport properties in the rat cortical collecting duct (CCD). Sprague-Dawley rat CCDs were isolated and perfused to allow measurement of osmotic water permeability (Pf), transepithelial voltage (Vt) and resistance (Rt). Arginine vasopressin (AVP) increases Pf, hyperpolarizes Vt and decreases Rt in the CCD via stimulation of adenylyl cyclase. Dexmedetomidine at 100 nM added to the basolateral side of the CCD reduced AVP-stimulated Pf by 95% to 100%, and the alpha-2 antagonist atipamezole reversed the inhibition. In the presence of the protein kinase C inhibitor staurosporine, dexmedetomidine reduced AVP-stimulated Pf by 70% to 75% compared with the complete inhibition without staurosporine. When Pf was increased by the use of the non-hydrolyzable analog of cAMP, 8-chlorophenylthio-cAMP, in lieu of AVP, dexmedetomidine inhibited Pf by approximately 35%. This demonstrated alpha-2-mediated inhibition of Pf despite the presence of constant cellular cAMP levels. Dexmedetomidine reversed AVP-induced effects on Vt and Rt, indicating inhibition of Na+ transport. Results confirm an alpha-2-mediated mechanism that reduces Na+ and water transport in the CCD and suggest that a cellular messenger other than cAMP is involved. This messenger could be protein kinase C.

Adrenergic alpha-2 Receptor Agonists↗

PubMed1994

Neutralizing monoclonal antibodies to human IL-8 receptor A map to the NH2-terminal region of the receptor.

mAbs against human IL-8 receptor A (IL-8R-A) were generated by immunizing mice with either: 1) peptides corresponding to various extracellular domains of IL-8R-A or 2) transfected 293 cells expressing IL-8R-A (293-71 cells). Among the seven peptides used for immunization, only the peptide corresponding to residues 2-19 of IL-8R-A produced Abs capable of recognizing native IL-8R-A on 293-71 cells. We screened for hybridomas secreting mAbs capable of binding strongly to peptide 2-19 in an ELISA and capable of recognizing native IL-8R-A in flow cytometry experiments with 293-71 cells. Two clones secreting mAbs capable of recognizing native IL-8R-A were selected for further characterization. None of these mAbs were able to block the binding of 125I-IL-8 to 293-71 cells. We also screened hybridomas derived from mice immunized with the intact receptor expressed on transfected 293-71 cells and identified several clones secreting mAbs capable of recognizing native IL-8R-A in flow cytometry experiments. Two of these mAbs were capable of blocking the binding of 125I-IL-8 to 293-71 cells. The epitopes, recognized by these blocking mAbs and by the other nonblocking mAbs derived from the peptide immunization, mapped to the NH2-terminal region of IL-8R-A using an ELISA against synthetic peptides: the two blocking mAbs mapped to residues 2-14 of IL-8R-A, whereas the nonblocking mAbs mapped to residues 2-11. Furthermore, flow cytometry analysis of IL-8 receptor mutants showed that Asp6 plays an important role in the binding of the blocking mAbs but not in the binding of the nonblocking mAbs. Conversely, a mutation of Asp11 to Lys disrupts the binding of one of the nonblocking mAbs (4C8) but has no effect on recognition by others. Analysis of the affinity of these mAbs for IL-8R-A demonstrated that blocking mAbs have affinities at least sevenfold higher than the nonblocking mAbs.

Amino Acid Sequence↗

PubMed1994

Frost tolerance and bud dormancy of container-grown yellow birch, red oak and sugar maple seedlings.

Container-grown seedlings of red oak (Quercus rubra L.), sugar maple (Acer saccharum Marsh.) and yellow birch (Betula alleghaniensis Britton) in their first year of growth were overwintered outdoors. Tolerance of roots and stems to freezing was compared from late summer to the following spring. Mitotic activity in the apical bud was related more closely to air temperature than to bud dormancy as defined by days to bud break. In all species, stem hardening was observed before days to bud break reached a maximum. Dormancy release (days to bud break equal to zero) of yellow birch coincided with loss of stem hardening in the spring. Roots hardened more slowly, had a lower frost tolerance than stems in fall and winter, and dehardened earlier than stems in the spring. There were differences in stem and root hardiness among the species, with yellow birch being the most tolerant, followed by sugar maple and red oak. Primarily because of root sensitivity to frost, winter was a critical period for all three species, but particularly for red oak.

Journal Article↗

PubMed1993

Experiences of student and practicing physical therapists with inappropriate patient sexual behavior.

BACKGROUND AND PURPOSE: The objectives of this study were (1) to describe the extent to which practicing physical therapists and physical therapy students have reported experiencing inappropriate patient sexual behavior (IPSB), (2) to document the consequences of IPSB, and (3) to identify the strategies the subjects have used to manage IPSB. SUBJECTS AND METHODS: A survey questionnaire was sent to 118 physical therapists and 87 physical therapy students. Completed questionnaires were returned by 74.1% of the subjects (over 70% in each group). RESULTS: The majority of respondents (80.9%) reported having encountered some level of IPSB. Although almost half of the physical therapists and one third of the third- and fourth-year students reported experiencing severe IPSB, including forceful sexual touching and deliberate sexual exposure, only 20% of the respondents perceived that they had been "sexually barassed." Most of the respondents were satisfied with the way in which they handled the IPSB; however, almost 90% considered that in-service and undergraduate education would be desirable. CONCLUSION AND DISCUSSION: It is concluded that this problem should be addressed by further study with a broader sample and by inclusion of these issues in education programs for students and physical therapists.

Adult↗