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Biomedical subjects

A Morel

Publications and source records attributed to A Morel.

At least 55 records · Page 3Linked to original sources

Topography of visual cortex connections with frontal eye field in macaque: convergence and segregation of processing streams.

The primate visual system consists of at least two processing streams, one passing ventrally into temporal cortex that is responsible for object vision, and the other running dorsally into parietal cortex that is responsible for spatial vision. How information from these two streams is combined for perception and action is not understood. Visually guided eye movements require information about both feature identity and location, so we investigated the topographic organization of visual cortex connections with frontal eye field (FEF), the final stage of cortical processing for saccadic eye movements. Multiple anatomical tracers were placed either in parietal and temporal cortex or in different parts of FEF in individual macaque monkeys. Convergence from the dorsal and ventral processing streams occurred in lateral FEF but not in medial FEF. Certain extrastriate areas with retinotopic visual field organizations projected topographically onto FEF. The dorsal bank of the superior temporal sulcus projected to medial FEF; the ventral bank, to lateral FEF, and the fundus, throughout FEF. Thus, lateral FEF, which is responsible for generating short saccades, receives visual afferents from the foveal representation in retinotopically organized areas, from areas that represent central vision in inferotemporal cortex and from other areas having no retinotopic order. In contrast, medial FEF, which is responsible for generating longer saccades, is innervated by the peripheral representation of retinotopically organized areas, from areas that emphasize peripheral vision or are multimodal and from other areas that have no retinotopic order or are auditory.

Animals↗

Chronic neurogenic pain and the medial thalamotomy.

69 patients suffering from chronic therapy-resistant neurogenic pain of peripheral and/or central origin underwent a stereotactic medial thalamotomy. Medial thalamic unit recordings were performed peroperatively, allowing the physiological confirmation of the electrode location and the recognition of a specific physiopathology. Thanks to these recordings, a concept was developed, based on the presence of an imbalance between medial (nucleus centralis lateralis mainly) and lateral (nucleus ventroposterior) thalamic nuclei, resulting in an over-inhibition of both by the reticular thalamic nucleus, and then in a paradoxical activation of pain-related cortical areas. The medial thalamotomy, re-actualized by new technical, anatomical and physiological data, offers a 50-100% relief to 67% of all patients with peripheral as well as central neurogenic pain, on all body localizations, without producing neurological deficits and without risk for the development of iatrogenic pain.

Adult↗

Molecular analysis of vasopressin receptors in the rat nephron. Evidence for alternative splicing of the V2 receptor.

Expression and regulation of vasopressin V2 and V1a receptors were studied at the mRNA level in the rat kidney. Two V2 mRNA variants were identified and shown to arise from a single gene by alternative splicing using one donor and two different acceptor sites. The long (V2L) form encodes the adenylyl cyclase-coupled receptor. The short (V2S) form lacks the nucleotide sequence encoding the putative seventh transmembrane domain and undergoes a frame shift in its 3'end coding region; it is inactive on the cyclase pathway in transfected cells. Measurement of mRNAs, carried out by quantitative reverse transcription-polymerase chain reaction (RT-PCR) on microdissected nephrons, demonstrated that neither V2L, V2S nor V1A mRNAs are expressed in glomeruli and proximal tubules (< 100 mRNA copies/glomerulus or mm of tubular length), whereas they are present in the ascending limb of Henle's loop and in the collecting tubule. The V2L mRNA, which is always predominant in these structures, is expressed throughout the collecting tubule at 10 times higher levels (30,000 copies/mm) than in the thin and thick ascending limbs. The ratio of the V2S over V2L mRNA is constant (15%) in all nephron segments; hence high V2S levels are only observed in the collecting tubule. The V1A mRNA is slightly expressed in the thin ascending limb, absent in the thick ascending limb and reaches its maximum in the cortical collecting duct (4,000 copies/mm), before gradually decreasing to undetectable levels in the terminal collecting duct. Finally, in vivo administration of a vasopressin V2 agonist decreased by 50% V2L and V2S mRNAs, but did not alter the V1A mRNA level. We conclude that this study provides the quantitation, on a molar basis, of vasopressin receptor mRNAs in kidney tubules and demonstrates the occurrence of two V2 mRNA spliced variants which are similarly down-regulated.

Animals↗

Monitoring of pefloxacin serum concentrations in intensive care unit patients: comparison of a new immunoassay with high-performance liquid chromatography.

Serum quinolone concentrations are not routinely measured in clinical practice. However, in order to optimize quinolone treatment, monitoring of serum concentrations could sometimes be useful particularly in critically ill patients. A new enzyme-linked immunosorbent assay (ELISA) that permits direct determination of pefloxacin in serum is described. To validate this new assay, pefloxacin concentrations were measured in 314 serum samples from 74 intensive care unit patients treated with pefloxacin (400 mg i.v. twice daily). Reference concentrations were obtained by reverse phase high-performance liquid chromatography (HPLC) with spectrofluorometric detection. Results showed that concentrations measured by ELISA correlated very well with those by HPLC (r = 0.957; y = 1.03 and x -0.15). In this population, the concentrations found by ELISA varied between individuals (Cmin = 0.70-39 micrograms/ml; Cmax = 5.2-40 micrograms/ml). However, 86% of the measured Cmax and Cmin levels were adequate for optimal pefloxacin therapy. Only 11% of Cmin and 14% of Cmax were below the optimal values (i.e., 2 and 8 micrograms/ml, respectively). These results suggest that despite the large therapeutic index of pefloxacin, monitoring of its serum concentrations using a rapid ELISA technique may be useful for optimal antimicrobial treatment of certain intensive care unit patients.

Adolescent↗

[Implementation of an orodental prevention program in Auvergne: report after 1 year].

A pilot program in preventive dentistry has been carried out since 1992 in Auvergne (France). In this program, children of artisans and shopkeepers from 4 to 15 year-old have an annual dental consultation with the dentist of their choice. Dental care when related to dental caries prevention and treatment is free of charge. From September 1992 to September 1993, 48% of the 4 and 5 year-old children (n = 1040) to whom the program had been addressed went to the dentist for this consultation. Preventive dental treatments such as sealants and professional topical fluoride applications were rarely performed. However, a fluoride support was prescribed to 70% of the participants. Moreover, 75% of the children displaying caries at the time of the first consultation received appropriate curative dental treatments.

Adolescent↗

Tonotopic organization, architectonic fields, and connections of auditory cortex in macaque monkeys.

Microelectrode recordings were used to investigate the tonotopic organization of auditory cortex of macaque monkeys and guide the placement of injections of wheat germ agglutinin-horse radish peroxidase (WGA-HRP) and fluorescent dyes. Anatomical and physiological results were later related to histological distinctions in the same brains after sections were processed for cytoarchitecture, myeloarchitecture, acetylcholinesterase (AchE), or cytochrome oxidase (CO). The experiments produced several major findings. (1) Neurons throughout a broad expanse of cortex were highly responsive to pure tones, and best frequencies could be determined for neurons in arrays of recording sites. (2) The microelectrode recordings revealed two systematic representations of tone frequencies, the primary area (AI) and a primary-like rostral field (R) as previously described. The representation of high to low frequency tones in A1 was largely caudorostral along the plane of the sulcus. A reversal of the order of representation of frequencies occurred in R. (3) AI and R together were coextensive with a koniocellular, densely myelinated zone that expressed high levels of AchE and CO. These architectonic features were somewhat less pronounced in R than AI, but a clear border between the two areas was not apparent. (4) Cortex bordering AI and R was less responsive to tones, but when best frequencies for neurons could be determined, they matched those for adjoining parts of AI and R. (5) Architectonically distinct regions were apparent within some of the cortex bordering AI and R. (6) The major ipsilateral cortical connections of AI were with R and cortex immediately lateral and medial to AI. (7) Callosal connections of AI were predominantly with matched locations in the opposite AI, but they also included adjoining fields. (8) Neurons in the ventral (MGV), medial (MGM), and dorsal (MGD) nuclei of the medial geniculate complex projected to AI and cortex lateral to AI. (9) Injections in cortex responsive to high frequency tones labeled more dorsal parts of MGV than injections in cortex responsive to low frequency tones.

Acetylcholinesterase↗

Molecular cloning and expression of rat V1a and V2 arginine vasopressin receptors.

Vasopressin, one of the first characterized neuropeptides, has a wide spectrum of biological action, acting on distinct tissues. Indeed, it is involved in water retention, glucose metabolism, blood pressure and its implication in the CNS has also been described. This diversity of effects on mammalian tissues is mediated by distinct G protein-coupled receptors, acting via distinct second messenger pathways. This receptor family has been subtyped by pharmacological studies, as V1a receptor whose action is mediated by intracellular calcium mobilization, and V2 receptor which is linked to adenylyl cyclase. Since so many essential functions were ensured by vasopressin, molecular characterization of its receptors became soon a great challenge. This prompted us to isolate the cDNA of AVP V1a receptor as the first member of this family, by expression cloning. Intracellular calcium mobilization was therefore assayed after rat liver mRNA injection into Xenopus oocytes. A single clone, encoding a functional AVP receptor corresponding to the V1a subtype was finally characterized as a G protein-coupled receptor. Furthermore, we used homology cloning strategy in order to clone the AVP V2 subtype from a rat kidney cDNA library. A putative receptor clone was finally characterized as the rat V2 receptor cDNA by binding and cAMP increase experiments, on transfected cells.

Amino Acid Sequence↗

Thalamus and neurogenic pain: physiological, anatomical and clinical data.

Microelectrode recordings in the medial thalamus of 45 neurogenic pain patients undergoing medial thalamotomy revealed that most units (316/318) did not respond to somatosensory stimuli, and that half exhibited low-threshold calcium spike bursts. After medial thalamotomy, 67% of the patients reached a 50 to 100% pain relief, without somatosensory deficits. Colocalization of bursting activities and of the most efficient therapeutic lesions in the central lateral nucleus suggests a key role of this structure in neurogenic pain. We propose that neurogenic pain is due to an imbalance between central lateral and ventroposterior nuclei, resulting in an overinhibition of both by the thalamic reticular nucleus.

Follow-Up Studies↗

Connections of visual areas of the upper temporal lobe of owl monkeys: the MT crescent and dorsal and ventral subdivisions of FST.

An oval of cortex of moderately dense myelination just ventral to the middle temporal visual area (MT) with input from MT has been referred to as the fundal area of the superior temporal sulcus (FST). Injections of the tracer WGA-HRP into dorsal (FSTD) and ventral (FSTv) halves of FST revealed that only FSTD has connections with MT. FSTv has connections instead with small patches of cortex that string together like beads to form a ring or crescent (MTc) around most of MT. The patches in MTc stain densely for myelin or cytochrome oxidase, and they are embedded in a less densely stained matrix. The connections of FSTD associate the area with the dorsal stream of processing directed toward posterior parietal cortex and important in spatial aspects of vision. Thus, FSTD has direct connections with ventral posterior parietal cortex (VPP), and connections with MT, the medial superior temporal (MST), and dorsomedial (DM) visual areas, all areas that relay to posterior parietal cortex. In contrast, FSTv does not appear to have connections with either VPP or MST, and only sparse connections with DM. Rather, major connections of FSTv are with inferior temporal cortex. Thus, FSTv is more associated with the ventral stream of processing related to object vision. However, both FSTv and FSTD have connections with area 18 or V-II, the dorsolateral visual area, the frontal eye field, and a frontal visual area. Interhemispheric connections of FSTD include FSTD, MT, and MST, while interhemispheric connections of FSTv include FSTv and MTc.

Animals↗

Cloning and characterization of a vasopressin V2 receptor and possible link to nephrogenic diabetes insipidus.

The antidiuretic effect of arginine vasopressin (AVP) is mediated by renal-type (V2) receptors linked to adenylyl cyclase. We report here the cloning of the rat kidney V2 AVP receptor complementary DNA that encodes a 370-amino-acid protein with a transmembrane topography characteristic of G protein-coupled receptors, and with similarity to the V1a (hepatic) AVP receptor in its seven membrane-spanning domains. Expression of the cloned cDNA in mammalian cells showed specific ligand binding and activity characteristic of the native V2 AVP receptor. The receptor messenger RNA is detected only in the kidney. The human V2 receptor gene has been localized to the long arm of the X chromosome close to the locus for nephrogenic diabetes insipidus, an X-linked recessive disorder characterized by renal resistance to the antidiuretic action of AVP.

Adenylyl Cyclases↗

Molecular cloning and expression of a rat V1a arginine vasopressin receptor.

The neurohypophyseal hormone arginine vasopressin has diverse actions, including the inhibition of diuresis, contraction of smooth muscle, stimulation of liver glycogenolysis and modulation of adrenocorticotropic hormone release from the pituitary. Arginine vasopressin receptors are G protein-coupled and have been divided into at least three types; the V1a (vascular/hepatic) and V1b (anterior pituitary) receptors which act through phosphatidylinositol hydrolysis to mobilize intracellular Ca2+, and the V2 (kidney) receptor which is coupled to adenylate cyclase. We report here the cloning of a complementary DNA encoding the hepatic V1a arginine vasopressin receptor. The liver cDNA encodes a protein with seven putative transmembrane domains, which binds arginine vasopressin and related compounds with affinities similar to the native rat V1a receptor. The messenger RNA corresponding to the cDNA is distributed in rat tissues known to contain V1a receptors.

Amino Acid Sequence↗

Subdivisions and connections of auditory cortex in owl monkeys.

The organization and connections of auditory cortex in owl monkeys, Aotus trivirgatus, were investigated by combining microelectrode mapping methods with studies of architecture and connections in the same animals. In most experiments, portions of auditory cortex were first explored with microelectrodes, neurons were characterized as responsive or not to auditory stimuli, and best frequencies were determined whenever possible. Most recordings were in cortex previously designated as primary (A-I) and rostral (R) auditory fields (Imig et al. J Comp Neurol 171:111, '77) and in a newly defined rostrotemporal field (RT) located rostral to R. Injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) and fluorescent tracers were placed in electrophysiologically identified locations of A-I, R, and RT; the posterolateral (PL) and anterolateral (AL) divisions of a narrow belt of auditory cortex lateral and adjacent to A-I and R; cortex of the superior temporal gyrus lateral and rostrolateral to PL and AL; and regions of prefrontal cortex that receive inputs from auditory cortex. There were several major findings: 1. Best frequencies were most clearly determined for neurons within a densely myelinated strip of cortex on the lower bank and lip of the lateral sulcus. We divided this strip into three fields, A-I, R, and RT, although an alternative interpretation that A-I and R are parts of a single field remains tenable. In some cases, isofrequency contours appeared to continue uninterrupted across fields A-I and R, with lower frequencies represented laterally and higher frequencies represented deeper in the sulcus. In other cases, there was a tendency for high frequencies to be represented caudally and medially, and low frequencies laterally in A-I and rostrally in R, with partial discontinuity in the isofrequency contours. A reversal of the tonotopic gradient appeared in RT with a common low-frequency representation at the caudal border with R, and progressively higher frequencies encountered rostrally. Of the three fields, A-I appears slightly more myelinated than R, and RT slightly less than R. The distinctiveness of the three fields is further demonstrated by the patterns of connections. In particular, A-I and RT are both interconnected with R, but not with each other. Connections between A-I and R are between tonotopically matched locations. 2. A narrow 2-3 mm wide band of cortex lateral to A-I, R, and RT was also responsive to auditory stimuli, but typically neurons were more difficult to activate, and best frequencies were more difficult to determine. No distinctions in myeloarchitecture or CO activity were obvious.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic Stimulation↗

Segregated thalamocortical pathways to inferior parietal and inferotemporal cortex in macaque monkey.

Inferior parietal and inferotemporal cortex, which process different aspects of visual information through largely segregated pathways from the visual cortex, both receive thalamic afferents from the pulvinar complex. We examined the topography of pulvinar projections to these two cortical regions by placing multiple injections of different tracers (fluorescent dyes, horseradish peroxidase) in the inferotemporal and inferior parietal cortex of macaque monkeys. The patterns of label observed after injections in inferotemporal gyrus indicate that area TEO and the ventral part of area V4 receive a major input from the ventral part of the lateral pulvinar (PuLv) while area TE has strong connections with the caudal pole of the medial pulvinar (PuM) and only minor connections with PuLv. In contrast, injections in the caudal inferior parietal cortex demonstrate that area PGc, on the lateral surface of the inferior parietal gyrus, and area POa, in the ventral bank of intraparietal sulcus, receive strong projections from PuM and the adjacent fringe of the dorsal part of the lateral pulvinar (PuLd). Paired injections of two different tracers in the inferotemporal and inferior parietal cortex of the same hemisphere revealed a nearly complete segregation of the two populations of labeled neurons in the pulvinar, with only a small region of overlap in PuM, close to the PuM/PuLd border. These results demonstrate a clear separation of the thalamic afferents to the inferior parietal and inferotemporal cortex which parallels the separation of prestriate afferents to these two cortical territories (Morel & Bullier, 1990).

Afferent Pathways↗

Biochemical and pharmacological characterization of serotonin-O-carboxymethylglycyl[125I]iodotyrosinamide, a new radioiodinated probe for 5-HT1B and 5-HT1D binding sites.

There is a lack of radioactive probes, particularly radioiodinated probes, for the direct labeling of serotonin-1B (5-HT1B) and serotonin-1D (5-HT1D) binding sites. Serotonin-O-carboxymethylglycyltyrosinamide (S-CM-GTNH2) was shown previously to be specific for these two subtypes; we, therefore, linked a 125I to its tyrosine residue. Biochemical and pharmacological properties of S-CM-G[125I]TNH2-binding sites were studied by quantitative autoradiography on rat and guinea pig brain sections. S-CM-G[125I]TNH2 binding is saturable and reversible with a KD value of 1.3 nM in the rat and 6.4 nM in the guinea pig. Binding is heterogeneous, paralleling the anatomical distribution of 5-HT1B sites in the rat and of 5-HT1D sites in the guinea pig. The binding of 0.02 nM S-CM-G[125I]TNH2 was inhibited by low concentrations of 5-HT, S-CM-GTNH2, CGS 12066 B, 5-methoxytryptamine, and tryptamine in both species. Propranolol inhibited the radioligand binding with a greater affinity in the rat than in the guinea pig. Conversely, 8-hydroxy-2-(di-n-propylamino)tetralin inhibited S-CM-G[125I]TNH2 binding with a greater affinity in the guinea pig than in the rat. Other competitors, specific for 5-HT1C, 5-HT2, 5-HT3, and adrenergic receptors, inhibited S-CM-G[125I]TNH2 binding in rat and guinea pig substantia nigra and in other labeled structures known to contain these receptors, but only at high concentrations. S-CM-G[125I]TNH2 is then a useful new probe for the direct study of 5-HT1B and 5-HT1D binding sites.

Animals↗

A new 5-hydroxy-indole derivative with preferential affinity for 5-HT1B binding sites.

The affinities of several 5-hydroxy-indole derivatives for serotonin-1 (5-HT1) binding site subtypes, labeled with 2 nM [3H]5-HT, were assessed by quantitative autoradiography on rat brain sections. The results obtained with known ligands, namely 5-hydroxytryptamine (5-HT), 5-methoxytryptamine (5-Me-OT), 5-methoxy-N,N- dimethyl-tryptamine (5-Me-ODMT), 5-hydroxy-N,N-dimethyl-tryptamine (bufotenine) and 8-hydroxy-2-[di-N-propylamino]tetralin (8-OH-DPAT) demonstrate the reliability and the advantages of this technique for pharmacological studies. Novel serotonin derivatives were synthesized by carboxymethylation of the hydroxyl group. One of those new ligands, serotonin-O-carboxy-methyl- glycyl-tyrosinamide (S-CM-GTNH2), inhibited 2 nM [3H]5-HT binding to the substantia nigra with an IC50 of 22.4 nM, a value which is 22 times lower than that found in the dentate gyrus and choroid plexus. This demonstrates the preferential affinity of S-CM-GTNH2 for 5-HT1B versus 5-HT1A and 5-HT1C binding sites. S-CM-GTNH2 contains a tyrosine residue, which may be useful for the synthesis of a radioactive iodinated molecule and for the preparation of 'long-lasting ligands' linked through peptide bonds with a protein. These derivatives could be of great interest for ultrastructural and behavioral studies relevant to 5-HT1B sites.

Animals↗

A study of human jaw movements deduced from scratches on occlusal wear facets.

In a previous investigation, scratches on tooth wear facets provided information about functional movements of the mandible in the occlusal range. Depending on the type of facet observed, two or three main directions were found. The aim now was to answer two questions: (1) how long does it take for a newly formed scratch to disappear? and (2) do the observed orientations of the scratches change over a long period of time? Eleven wear facets from lower first molars were analysed in four subjects with good natural dentition. Scratches recorded on cellulose replicas were observed under an interference microscope. The same wear facets were recorded one, two, three and six months later. From the photographs of the replicas, a sample of scratches was selected at random and their direction was measured. In the first part of the study, scratches absent at the time of the first observation appeared one month later; 87% of the new scratches had disappeared after one month. Ninety-six percent of the same group of scratches had disappeared after two months. In the second part of the study the angle made by each scratch with the sagittal plane was recorded. It was found that: (1) jaw movements in their occlusal phase can take any possible direction and (2) the distribution of the observed scratches was not random; preferential orientations exist and those present on the working facets are different from those on the non-working facets. Similar orientations were identified 6 months later.

Adult↗