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P Leroux

Publications and source records attributed to P Leroux.

At least 19 recordsLinked to original sources
PubMed1992

Somatostatin receptors are expressed by immature cerebellar granule cells: evidence for a direct inhibitory effect of somatostatin on neuroblast activity.

Somatostatin and somatostatin receptors are transiently expressed in the immature rat cerebellar cortex but virtually undetectable in the cerebellum of adults. Although somatostatin binding sites have been visualized during the postnatal period in the external granule cell layer, the type of cell that expresses somatostatin receptors has never been identified; thus, the potential function of somatostatin in the developing cerebellum remains unknown. In the present study, we have taken advantage of the possibility of obtaining a culture preparation that is greatly enriched in immature cerebellar granule cells to investigate the presence of somatostatin receptors and the effect of somatostatin on intracellular messengers on cerebellar neuroblasts in primary culture. Autoradiographic labeling revealed the occurrence of a high density of binding sites for radioiodinated Tyr-[D-Trp8]somatostatin-(1-14) on 1-day-old cultured immature granule cells. Saturation and competition studies showed the existence of a single class of high-affinity binding sites (Kd = 0.133 +/- 0.013 nM, Bmax = 3038 +/- 217 sites per cell). Somatostatin induced a dose-dependent inhibition of forskolin-evoked cAMP formation (ED50 = 10 nM), and this effect was prevented by preincubation of cultured immature granule cells with pertussis toxin. Somatostatin also caused a marked reduction of intracellular calcium concentration. These results show the presence of functionally active somatostatin receptors on immature granule cells. Our data suggest the possible involvement of somatostatin in the regulation of proliferation and/or migration of neuroblasts during the development of the cerebellar cortex.

Adenylyl Cyclases↗
PubMed1992

Somatostatin receptors in the human cerebellum during development.

The ontogeny of somatostatin receptors (SRIF-R) was studied in the human cerebellum from mid-gestation to the 15th month postnatal. The brains were collected 3-26 h after death, from 18 fetuses and infants, and from 4 adults aged from 48 to 82. SRIF-R were characterized by membrane-binding assay and their localization was determined by in vitro autoradiography. Both techniques were conducted with two radio-ligands: [125I-Tyr0, DTrp8]S14 and D-Phe-Cys-125I-Tyr-DTrp-Lys-Thr- ol (125I-SMS 204-090). Membrane-binding studies carried out with each radioligand showed the presence of a single population of saturable, high affinity binding sites. Neither were the Kd values for either ligand (assessed by Scatchard analysis) changed appreciably during development, mean Kd values being 0.36 +/- 0.04 nM and 0.56 +/- 0.11 nM for [125I-Tyr0,DTrp8]S14 and 125I-SMS 204-090, respectively. Although inter-individual fluctuations of the Bmax were observed, the concentration of SRIF-R in the cerebellum of fetuses and infants up to 8 months appeared to be at least 2- to 10-fold higher than in the adult cerebellum. No appreciable differences in the Bmax values were found using either radioligand. The highest density of SRIF-R was observed in the cerebellar cortex of fetuses, in particular in the external granule cell layer (EGC), where stem cells of the granule cells are generated and enter the differentiation process. A high density of SRIF-R also occurred in the internal granule cell layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Distribution of somatostatin receptors in the cat and monkey visual cortex demonstrated by in vitro receptor autoradiography.

Somatostatin (SRIF, S14) receptors in the cat and monkey visual cortex were visualized by means of in vitro autoradiography with an iodinated agonist of SRIF, [125I-Tyr0,DTrp8]S14. The kinetics, performed on tissue sections, revealed an apparently single, saturable site (KD = 3.92 +/- 0.31 10(-10) M for the cat, and 3.82 +/- 0.28 10(-10) M for the monkey visual cortex) with pharmacological specificity for S14 and [DTrp]-substituted S14. Autoradiography, performed on frontal sections of the cat and monkey visual cortex, revealed a heterogeneous regional and laminar distribution of SRIF receptors. In cat areas 17, 18, and 19, SRIF receptors occur mainly in the supragranular layers, although small interareal and intra-areal differences are observed. The infragranular layers (V-VI) in area 19 contain a significantly higher proportion of SRIF receptors compared to both areas 17 and 18. In the antero- (AMLS) and posteromedial lateral suprasylvian area (PMLS), layers V and VI contain the highest proportion of SRIF receptors. This latter pattern is also observed in the area prostriata medially adjoining area 17 in the splenial sulcus. In the monkey visual cortex, areas 17 and 18 exhibit similar distribution patterns, SRIF receptors being primarily concentrated in layers V and VI. Neither in the cat nor the monkey visual cortex could we observe significant differences in SRIF receptor distribution between different retinotopic subdivisions within one area.

Animals↗
PubMed1991

Behaviour studies of the fungicide cymoxanil in two strains of the fungus Botrytis cinerea and in haemolymph of locust and lobster. I. In situ monitoring by internal surface reversed-phase high-performance liquid chromatography.

A method for following the metabolism of the fungicide cymoxanil in various biological media is described. By using a recently developed high-performance liquid chromatographic method, with an internal surface reversed-phase column, it is unnecessary to clean up the sample before analysis. Thus this technique makes monitoring in fungi as well as in arthropod haemolymph easier and faster.

Acetamides↗
PubMed1991

Ontogeny of somatostatin receptors in the rat somatosensory cortex.

The distribution and density of SRIF receptors (SRIF-R) were studied during development in the rat somatosensory cortex by in vitro autoradiography with monoiodinated [Tyr0-DTrp8]S14. In 16-day-old fetuses (E16), intense labeling was evident in the intermediate zone of the cortex while low concentrations of SRIF-R were detected in the marginal and ventricular zones. The highest density of SRIF-R was measured in the intermediate zone at E18. At this stage, labeling was also intense in the internal part of the developing cortical plate; in contrast, the concentration of binding sites associated with the marginal and ventricular zones remained relatively low. Profound modifications in the distribution of SRIF-R appeared at birth. In particular, a transient reduction of receptor density occurred in the cortical plate. During the first postnatal week, the density of receptors measured in the intermediate zone decreased gradually; conversely, high levels of SRIF-R were observed in the developing cortical layers (II to VI). At postpartum day 13 (P13), a stage which just precedes completion of cell migration in the parietal cortex, the most intensely labeled regions were layers V-VI and future layers II-III. From P13 to adulthood, the concentrations of SRIF-R decreased in all cortical layers (I to VI) and the pattern of distribution of receptors at P21 was similar to that observed in the adults.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1991

Transient expression of somatostatin receptors in the rat visual system during development.

The ontogeny of somatostatin receptors in the rat visual system was studied by auto-radiography, using [125I-Tyr0,DTrp8]S14 as a radioligand. The binding sites showed high affinity for somatostatin and somatostatin analogues, and were regulated by GTP as early as day 16 of fetal life (E16), indicating that they represent functional somatostatin receptors. The density of somatostatin receptors was quantified by computerized image-analysis of film autoradiograms, and by grain counting on emulsion-coated slides. During fetal life, somatostatin receptors were observed in the retina, optic nerve, optic chiasma, optic tract, and lateral geniculate nucleus. The highest densities of somatostatin receptors were measured from E16 to E18 in the retina and primary optic pathways. During the first postnatal days, the density of somatostatin receptors decreased dramatically in the retina. In both the optic pathways and dorsal lateral geniculate nucleus, somatostatin receptors gradually disappeared, and the levels of somatostatin receptors were almost undetectable at postnatal day 21 (P21). Conversely, the density of somatostatin receptors remained stable in the ventral lateral geniculate nucleus during the early postnatal life (P0-P7). The timing of expression and the localization of somatostatin receptors in the developing visual system suggest that the immature ganglion cells are responsible for the expression of these evanescent somatostatin receptors. After eye opening, the distribution patterns of somatostatin receptors in the retina and the lateral geniculate nucleus were similar to those observed in adults. In particular, from P14 onwards, somatostatin receptors were concentrated in the inner plexiform layer and, to a lesser extent, in the ganglion cell and photoreceptor layers. In the ventral lateral geniculate nucleus, a heterogeneous distribution of somatostatin receptors was noted, the highest densities being found in the intergeniculate leaflet and the medial zone limiting the parvo-magnocellular interface. The distribution of somatostatin receptors in the retina and the ventral lateral geniculate nucleus after the second postnatal week, together with the presence of somatostatin-like immunoreactive elements in these structures, provide support for the involvement of somatostatin as a neurotransmitter or neuromodulator in the visual system of the adult rat. Conversely, the transient expression of somatostatin receptors observed before maturation and complete organization of the optic pathways suggests that somatostatin plays a trophic role during development of the visual system.

Aging↗
PubMed1990

Expression of somatostatin receptors is impaired in the cerebellum of developing Brattleboro rats.

Somatostatin (SRIF) receptors are expressed in the external granule cell layer of the rat cerebellum during early postnatal life. The aim of the present study was to investigate the distribution and biochemical characteristics of SRIF binding sites in the cerebellum of homozygous (vasopressin deficient) Brattleboro rats, which exhibit a selective impairment of their granule cell layer. This study has been conducted in 13-day-old rats by means of membrane-binding assay and autoradiography using [125I-Tyr0,DTrp8]S14 as a radioligand. In the cerebellum of homozygous Brattleboro rats, Scatchard plot analysis revealed the existence of a single class of SRIF receptors with similar Kd values as in Long-Evans or heterozygous Brattleboro rats (180-200 pM). Conversely, a marked reduction of the concentration of SRIF binding sites was observed in Brattleboro rats as compared to heterozygous or Long-Evans rats. In homozygous Brattleboro rats, autoradiographic studies revealed that the concentration of SRIF receptors was reduced in all lobules of the cerebellum as compared to Long-Evans. In addition, the magnitude of the decrease of receptor concentration was greater than the loss of granule cells observed in the homozygous Brattleboro rat. These results indicate that the expression of SRIF receptors by immature granule cells of the cerebellum is markedly reduced in Brattleboro rats. Whether the impairment of SRIF receptors in diabetes insipidus rats can directly be ascribed to vasopressin deficiency remains to be determined.

Animals↗
PubMed1990

Ultrastructural distribution of somatostatin-14 and -28 in rat adrenal cells.

Previous studies have shown that somatostatin modulates angiotensin-induced aldosterone secretion by adrenal glomerulosa cells. This effect is mediated through specific receptors which do not show any preference for somatostatin-14 (S14) or the N-extended form somatostatin-28 (S28). The study of the distribution of 125I-Tyr [Tyr0, DTrp8] S14- and 125I-Tyr [Leu8, DTrp22, Tyr25] S28-binding in frozen sections of the rat adrenal by autoradiography indicated that both peptides bind to similar loci. High concentrations of binding sites were observed in the zona glomerulosa, and low concentrations were detected in the medulla. At the ultrastructural level, immunocytochemistry after cryoultramicrotomy revealed endogenous S14- and S28-like immunoreactive material in zona glomerulosa and in medulla. In glomerulosa cells, immunoreactive material was localized at the plasma membrane level, in the cytoplasmic matrix, in the mitochondria, and in the nucleus. S14- and S28-like materials were detected in both epinephrine and norepinephrine-storing cells of the adrenal medulla. In these cells, the distribution of either immunoreactive product was similar; it was observed in cytoplasmic matrix, secretory granules and nucleus, but not at the plasma membrane level. In situ hybridization does not reveal somatostatin mRNA in zona glomerulosa or medulla. These results demonstrate that S14 and S28 bind to, and are taken up by zona glomerulosa and adrenal medullary cells, but are not produced by these cells.

Adrenal Glands↗
PubMed1990

Pharmacological characterization of somatostatin receptors in the rat cerebellum during development.

Somatostatin (SRIF) receptors (SRIF-Rs) are transiently expressed in a germinative lamina of the rat cerebellum, the external granule cell layer. The appearance of SRIF-Rs coincides with the expression of SRIF-like immunoreactivity in the cerebellum. However, the cellular location of SRIF-Rs does not overlap with the distribution of SRIF-like immunoreactivity, with the latter being restricted to ascending fibers arising from the brainstem, to perikarya within the white matter, and to some Purkinje cells. The characterization of SRIF-Rs in the immature (13-day-old) rat cerebellum was conducted by means of binding experiments in membrane-enriched preparations and autoradiography, using two radioligands, [125I-Tyr0,D-Trp8]SRIF-14 [( 125I-Tyr0,D-Trp8]S14) and 125I-SMS 204-090. The pharmacological profile of cerebellar SRIF-Rs was compared with that of adult cortical SRIF-Rs. Saturation studies performed in 13-day-old rat cerebellum showed that the KD values for [125I-Tyr0,D-Trp8]S14 and 125I-SMS 204-090 binding were 0.35 +/- 0.04 and 0.39 +/- 0.01 nM, respectively. The corresponding Bmax values were 52.7 +/- 4.8 and 49.9 +/- 5.3 fmol/mg of protein, a result indicating that radioligands with high specific radioactivity (2,000 Ci/mmol) bind to a single class of high-affinity sites (SS1). Competition studies showed that different D-Trp-substituted analogs displaced [125I-Tyr0,D-Trp8]S14 binding with Hill coefficients less than 1, a finding indicating the existence of different subtypes of binding sites. When [Tyr0,D-Trp8]S14 was used as a competitor, two sites were resolved by Scatchard analysis in both 13-day-old cerebellum and adult cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Distribution of somatostatin receptors in the brain of the frog Rana ridibunda: correlation with the localization of somatostatin-containing neurons.

The biochemical characterization and anatomical distribution of somatostatin binding sites were examined in the brain of the frog Rana ridibunda, and the distribution of the receptors was compared with the location of somatostatin immunoreactive neurons. The pharmacological profile of somatostatin receptors was determined in the frog brain by means of an iodinated superagonist of somatostatin, [125I-Tyr0,DTrp8]S-14. Membrane-enriched preparations from frog brain homogenates were shown to contain high-affinity receptors (KD = 0.78 +/- 0.34 nM; Bmax = 103 + 12.7 fmoles/mg protein) with pharmacological specificity for [DTrp] substituted S14 and S28 analogs. The distribution of somatostatin-binding sites was studied by autoradiography on coronal sections of frog brain. Various densities of somatostatin receptors were detected in discrete areas of the brain. The highest concentration of binding sites was observed in the olfactory bulb, in the pallium, and in the superficial tectum. Moderate binding was observed in the striatum, amygdaloid complex, preoptic area, and cerebellum. Immunocytochemical studies of the distribution of somatostatin-28 (S28) related peptides were also conducted in the frog brain. Two antisera that recognize distinct epitopes of the somatostatin molecule have been used for immunohistochemical mapping of the peptide. Antiserum SS9 recognizes both S28 and somatostatin-14 (S14) and allowed the labelling of perikarya. Antiserum S320 recognizes the N-terminal fragment (1-12) resulting from enzymatic cleavage of S28. This latter antiserum, which does not cross-react with S28, stained mainly neuronal processes. At the infundibular level, however, both antisera stained cell bodies and fibers. Immunoreactive somatostatin-related peptides were detected in many areas of the frog brain. In the diencephalon, a heavy accumulation of perikarya and fibers was seen in the preoptic nucleus, the dorsal and ventral infundibular nuclei, and the median eminence. Immunoreactive perikarya were also observed in the telencephalon, especially in the pallium and in thalamic nuclei. Immunostained processes were detected in many telencephalic areas and in the tectum. There was good correlation between the distribution of somatostatin-immunoreactive elements and the location of somatostatin-binding sites in several areas of the brain, in particular in the median pallium, the tectum, and the interpeduncular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

Ontogeny of somatostatin receptors in the rat brain: biochemical and autoradiographic study.

The ontogeny of somatostatin receptors in the rat brain has been studied by both membrane binding assays and in vitro receptor autoradiographic techniques. High levels of somatostatin binding sites were detected in brain of 15-day-old fetuses (E15). The pharmacological characterization of somatostatin binding sites and the regulatory effect of GTP on somatostatin binding at E15 suggest that somatostatin recognition sites correspond to authentic receptors. The values of maximal binding showed important variations throughout pre- and postnatal development. Globally, a marked increase in the total binding capacity was observed between E15 and postnatal day 8 (P8), with a transient fall at birth and P1. After P8, the concentration of somatostatin receptors progressively decreased and the weaning imposed at P21 accentuated the decline of receptor concentration. Although the density of somatostatin binding sites varied considerably, KD values did not change during brain development. Autoradiographic studies showed marked differences in the distribution of somatostatin receptors during ontogenesis. In the cortex, the cortical plate and the subplate zone appeared to contain high densities of binding sites from E15 to P1. However, the cortical layer which exhibited the higher labelling was the intermediate zone, located just beneath the subplate zone. On the contrary, the germinal epithelium bordering the lateral ventricle appeared virtually devoid of somatostatin binding sites. This laminar distribution of binding sites in the cortex disappeared from P4 to P8, in coincidence with the evolution of the underlying histological organization. At these stages, a homogeneous distribution was observed in almost all cortical layers, contrasting with the distribution of somatostatin receptors in the adult, which was restricted to layers IV-VI. In the cerebellar cortex, autoradiographic labelling was first seen at E15. After birth, the density of somatostatin receptors increased dramatically between P4 and P13, while, at P23, the labelling vanished in most lobes of the cerebellum. Taken together, these results show the early appearance of somatostatin receptors in the rat brain. The high density of somatostatin receptors observed in proliferative or pre-migratory areas suggests that somatostatin may be an important factor involved in the organization of the central nervous system.

Aging↗
PubMed1989

Methotrexate diffusion from acrylic cement. Local chemotherapy for bone tumours.

We investigated the possible use of acrylic cement containing chemotherapeutic drugs in the treatment of malignant lesions in bone. The diffusion of methotrexate (MTX) from methylpolymethacrylate implants was studied in vitro: polymerisation of the cement did not destroy the drug; liberation began immediately and about 10% was released by 18 hours. Some release continued for as long as six months. In vivo experiments on rats with induced osteosarcoma showed that MTX in cement had both local and general effects which were dependent on the dosage. A series of 17 large dogs with spontaneous osteosarcoma were then treated by local resection and cement containing MTX. General chemotherapeutic effects were detectable from 2 hours to 5 days, survival was increased and local recurrence was reduced, but there were four cases of delayed wound healing. Preliminary studies in human patients confirm the possibility that this method of local chemotherapy could be a useful addition to the treatment of malignant tumours of bone.

Animals↗
PubMed1989

Studies on type II collagen induced arthritis in rats: an experimental model of peripheral and axial ossifying enthesopathy.

It was suggested that type II collagen induced arthritis in rats may be considered an experimental model for rheumatoid arthritis (RA) because of clinical, histological, and immunological similarities. However, some features separate it from RA. We studied 40 inbred female Wistar Furth rats. Two weeks after immunization with native human type II collagen, they had polyarthritis which progressed to ankylosis associated with ossifying enthesopathy and periosteal new bone formation. Inflammatory nodules of the tail appeared after 2 months, with radiological and histopathological aspects of multistage spondylodiscitis. Our findings suggest that collagen induced arthritis may be a relevant model of peripheral and axial ossifying enthesopathy.

Animals↗
PubMed1988

Transient expression of somatostatin receptors in the rat cerebellum during development.

Somatostatin and somatostatin receptors have not been identified in adult rat cerebellum. In contrast, during the development, somatostatin-containing neurons have been visualized in the deep layers of the cerebellum. The present study shows that during ontogenesis, somatostatin receptors are present in close association with the external granule cell layer of the cerebellum. No correlation was found between the location of immunoreactive somatostatin and the distribution of somatostatin receptors. The disappearance of somatostatin receptors, from postnatal day 13 to 23, was concomitant with the involution of the external germinal layer.

Age Factors↗
PubMed1988

Displaceable somatostatin binding sites in the gray matter and pyramidal paths of the human developing spinal cord.

The binding of the somatostatin analogue, 125I-iodo-Tyr-[Tyr0,D-Trp8]S14, to the foetal (18- and 24-week-old) and infant (newborn and 17-month-old) spinal cord was examined using in vitro autoradiography. Somatostatin binding sites were detected at cervical, thoracic and lumbosacral levels in foetal as well as in infant spinal cord. The radiolabelling was localized over the grey especially in the superficial layers of the dorsal horn including the substantia gelatinosa and the marginal zone. In foetal and newborn spinal cord, the direct and crossed pyramidal paths exhibited a substantial binding of the ligand. A similar labelling was not observed in the pyramidal paths of a 17-month-old child or in anencephalic newborn spinal cord or previously described in adult. These results emphasize the early presence of somatostatin binding sites during the ontogeny of the human spinal cord. Further, the transient appearance of somatostatin binding sites in the pyramidal paths, prior the myelination, raises the question whether somatostatin receptors could be involved in the maturation of certain normal paths.

Aging↗
PubMed1988

Intra and juxtavagal paraganglia: a topographical, histochemical, and ultrastructural study in the human.

The topographical, ultrastructural, and histochemical features of 23 human vagal paraganglia were analyzed. Nineteen of the 23 paraganglia were found in previously unreported sites; 18 of the 19 were in the cervical part of the nerve, between the carotid bifurcation and the superior thoraco-cervical inlet, and one paraganglion was located in the retrothyroidal part of the left inferior laryngeal nerve. The results of ultrastructural studies (2 cases), the histochemical and formaldehyde-induced-fluorescence studies (3 cases), and specific acetylcholinesterase activity (one case) demonstrate that these structures fulfill many of the modern criteria for paraganglionic tissue. In addition to paraganglia, single, isolated neurons or true micro-ganglia were always found along the trunk and branches of the vagus nerve when multiple sections were examined.

Adolescent↗
PubMed1988

Role of prostaglandins in bone resorption in a synchronized remodeling sequence in the rat.

The role of prostaglandins (PGs) in physiological remodeling has not yet been defined. The present study was undertaken to determine whether they intervene during the activation phase in a highly reproducible and synchronized model of bone remodeling. Indomethacin was employed to inhibit PG synthesis. This treatment throughout the entire activation period (4 days in this model) inhibited osteoclastic resorption completely. By modifying the treatment procedure, it appeared that PGs were operative mainly between the second and third day of activation. PGs did not seem to act on precursor recruitment, since off-bone osteoclasts (putatively inactive cells) were numerous in the treated groups. PGs might also be involved in osteoclast activity as the mean interface between osteoclasts and bone surface was reduced in the treated groups. However, indomethacin was unable to inhibit the remodeling sequence durably since a 6-day treatment resulted in a high profile of resorption. This suggests that factors other than PGs were responsible for activating resorption.

Animals↗