S26 ribosomal protein RNA: an invariant control for gene regulation experiments in eucaryotic cells and tissues.
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Actins↗
Biomedical subjects
P Fort
Publications and source records attributed to P Fort.
Localization of ARHG, a member of the RAS homolog gene family, to 11p15.5-11p15.4 by fluorescence in situ hybridization.
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Chromosome Banding↗
Concerted evolution in the GAPDH family of retrotransposed pseudogenes.
In murine rodents the glyceraldehyde 3-phosphate dehydrogenase (GAPDH) multigene family includes more than 300 retroprocessed pseudogenes. Its single functional gene encodes GAPDH, an enzyme of glycolysis. Because of its manageable size, this family is a good model for the study of genome cohesion and evolution. By sequence comparison of several GAPDH pseudogenes in Rattus norvegicus and Mus musculus, we have obtained evidence that (i) the GAPDH family still generates new pseudogenes; we note in each species the beginning of a process of species-specific evolution since the pseudogenes of one genus on average cluster more with one another than they do with those of the other genus, and (ii) the GAPDH family contains diversified subfamilies. These findings suggest a certain level of transcription and transposition of the pseudogenes independent of the functional gene which may result from various mechanisms. The homogenization we observe may be due to the pseudogenes themselves (concerted evolution in a strict sense), which explains the occurrence of long-term homogenization of old sequences and subfamily groupings.
Animals↗
Characterization of late response genes sequentially expressed during renewed growth of fibroblastic cells.
Many proto-oncogenes are rapidly and transiently activated during the early stages of the cellular transition from a resting G0 state to the DNA synthesis (S) phase. To get better understanding of the gene complexity involved at later stages, we isolated, by cDNA cloning, and identified 17 genes that are activated sequentially during the period of time from proto-oncogene expression to the onset of DNA synthesis in the hamster CCL39 fibroblastic cell line. When protein synthesis is inhibited, induced expression of these genes is unaffected for 10 of them, enhanced for four, in a fashion similar to the immediate-early response genes, and inhibited for three, as observed for delayed early-response genes. In addition to rhoG, a new member of the ras homolog gene family (Vincent et al., 1992), cDNA sequencing indicated that six of them correspond to cytoskeletal proteins (alpha-tubulin, vascular alpha-actin and skeletal gamma-actin), extracellular matrix protein (thrombospondin), secreted protease (plasminogen activator inhibitor-1) and energy-linked transporter (mitochondrial proton/phosphate symporter). This overall survey shows that numerous differentially regulated gene activations are associated with the cell cycle progression, and suggests that proteins involved in cellular reshaping participate actively in the control of cellular growth.
Actins↗
Glycine-immunoreactive neurones in the cat brain stem reticular formation.
Using a specific glycine antiserum, we determined the localization of glycinergic neurones and fibres in the cat brain stem reticular formation. We visualized a large number of glycine-immunoreactive cell bodies and fibres in the medullary reticularis gigantocellularis, magnocellularis, paragigantocellularis lateralis and parvocellularis nuclei. The pontis oralis and caudalis and the raphe magnus nuclei also contained a large number of glycine-immunoreactive fibres but fewer neurones. Using a double staining method, we further observed glycine-immunoreactive boutons over (1) noradrenergic neurones in the locus coeruleus complex and the ventrolateral and dorsomedial medulla, (2) serotoninergic neurones in and outside the raphe nuclei and (3) cholinergic neurones in the pedunculopontine and laterodorsal tegmental nuclei. These results suggest that glycinergic neurones in the reticular formation may be involved in aspects of paradoxical sleep, including the general muscle atonia seen during this sleep state.
Animals↗
Role of catecholamines in the modafinil and amphetamine induced wakefulness, a comparative pharmacological study in the cat.
Seventeen adult cats were chronically implanted with electrodes for polygraphic recordings in order to assess the role of catecholamines in the arousal effects of oral administrations of modafinil, a presumed noradrenergic agonist, and amphetamine, a well-known catecholamine-releasing agent. Whereas both modafinil (1, 2.5 and 5 mg/kg) and amphetamine (0.25, 0.5 and 1 mg/kg) caused a significant and dose-dependent increase in wakefulness and brain temperature, amphetamine, but not modafinil, elicited marked signs of behavioral excitation. Pretreatments with alpha-methyl-DL-p-tyrosine methyl ester (50 mg/kg, i.p.), an inhibitor of catecholamine synthesis, almost completely prevented the effects of amphetamine (0.25 and 1 mg/kg), but only slightly reduced the duration of the waking effect of modafinil (2.5 and 5 mg/kg). Pretreatments with phentolamine (10 mg/kg, i.p.), prazosin (1.5 mg/kg, per os) and propranolol (5 mg/kg, i.p.), an alpha-, alpha 1- and beta-receptor antagonist, respectively, attenuated significantly the arousal effect of modafinil (1 mg/kg, the same as below) but not of amphetamine (0.25 mg/kg, the same as below). Intraperitoneal injections of haloperidol (0.5 mg/kg), a dopamine-receptor antagonist, blocked significantly the arousal of amphetamine but not of modafinil. The effects of both modafinil and amphetamine were enhanced by a pretreatment with yohimbine (1 mg/kg, i.p.), an alpha 2-receptor antagonist. These results suggest that the arousal effect of modafinil does not depend on the availability of the endogenous catecholamines but results from an enhancement of alpha 1- and beta-receptor activity and that the waking and behavioral effects of amphetamine may be mainly due to an increase in dopamine release.
Amphetamine↗
The relationship between beta-endorphin and the growth hormone (GH) response to GH releasing hormone in prepubertal children.
Endogenous opioids are thought to participate in the regulation of growth hormone (GH) release through the mediation of growth hormone releasing hormone (GHRH). This study was intended to investigate whether the endogenous opioid beta-endorphin could modulate the GH response to GHRH and if this hypothesis could be demonstrated in children with familial short stature with or without constitutional growth delay. Seventeen children (6 female and 11 male) with stature below the fifth percentile were studied to rule out disorders in growth hormone dynamics. All had normal growth velocities, had appropriate predicted heights for their families and had normal GH levels on standard testing. Eight were prepubertal and 9 were Tanner II. All were given 0.1 mcgm/kg (1-44)hpGHRH-NH2 IV. Blood for growth hormone was obtained at 0, 15, 30, 45, 60, 90 and 120 minutes. Blood for beta-endorphin and cortisol was obtained at 0 and 60 minutes. The basal beta-endorphin level significantly correlated with the peak GH level (r = 0.868, p less than 0.05) in the prepubertal group only. In the same group of children, the degree of the negative feedback on the beta-endorphin level correlated significantly with the rise in GH level (r = 0.912, p less than 0.01). However, there was no correlation between the basal beta-endorphin and the peak GH level nor between the rise in GH level and the change in beta-endorphin in the pubertal children. These data are compatible with the hypothesis that beta-endorphin levels affect the GH response to GHRH in prepubertal children, but have no discernible effect on the GH response to GHRH in pubertal children.
Adolescent↗
Macrophage-released interleukin-1 in patients with type 1 diabetes mellitus.
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Adolescent↗
Growth-regulated expression of rhoG, a new member of the ras homolog gene family.
Cellular transition from the resting state to DNA synthesis involves master switches genes encoding transcriptional factors (e.g., fos, jun, and egr genes), whose targets remain to be fully characterized. To isolate coding sequences specifically accumulated in late G1, a differential screening was performed on a cDNA library prepared from hamster lung fibroblasts stimulated for 5 h with serum. One of the positive clones which displayed a sevenfold induction, turned out to code for a protein sharing homology to Ras-like products. Cloning and sequence analysis of the human homolog revealed that this putative new small GTPase, referred to as rhoG, is more closely related to the rac, CDC42, and TC10 members of the rho (ras homolog) gene family and might have diverged very early during evolution. rhoG mRNA accumulates in proportion to the mitogenic strength of various purified growth factors used for the stimulation, as a consequence of transcriptional activation. G1-specific RNA accumulation is impaired upon addition of antimitogenic cyclic AMP and is enhanced when protein synthesis is inhibited, mainly as a result of RNA stabilization. rhoG mRNA expression is observed in a wide variety of human organs but reaches a particularly high level in lung and placental tissues.
Amino Acid Sequence↗
Alterations in spontaneous growth hormone (GH) secretion and the response to GH-releasing hormone in children with nonorganic nutritional dwarfing.
The effects of suboptimal nutrition on the spontaneous overnight GH secretion (SGHS) and the GH response to GHRH were studied. Sixteen patients with nonorganic nutritional dwarfing (ND) were compared with 25 healthy short children with familial short stature with or without constitutional growth delay (FC). The effects of puberty were also assessed. All patients underwent an overnight study to assess SGHS with serum GH levels sampled every 20 min for 12 h, and a GHRH stimulation test was administered. Pubertal ND children had a blunted SGHS with a mean overnight GH level of 4.9 +/- 1.1 micrograms/L, significantly less than the level of 6.2 +/- 1.8 micrograms/L of the pubertal FC children (P less than 0.05). Also, prepubertal ND patients had an area under the curve in GH secretion after GHRH which was greater than that of the pubertal ND patients (2483 +/- 1581 vs. 1600 +/- 1056, P less than 0.05). The peak GH response to GHRH in the prepubertal ND patients was also higher than that of the pubertal ND patients (51.8 +/- 22.1 micrograms/L vs. 22.5 +/- 15.4 micrograms/L, P less than 0.05). This study shows that the SGHS is attenuated in ND patients during puberty but their GH response to GHRH is increased before adolescence. These abnormalities may represent compensatory mechanisms to energy restriction and may increase our understanding of the poor growth seen in ND patients.
Adolescent↗
Sustained improvement in growth velocity and recovery from suboptimal growth hormone (GH) secretion after treatment with human pituitary GH-releasing hormone-(1-44)-NH2.
The sustained effect of human pancreatic GH-releasing hormone [hpGHRH-(1-44)-NH2] on growth rate and GH secretory patterns was studied in 14 patients (10 males and 4 females; aged 10-16 yr; all Tanner stage I or II). Nine children had inadequate spontaneous GH secretion (ISGHS), while 5 had classic GH deficiency. Seven of 9 patients with ISGHS and 1 of 5 patients with GH deficiency were given 2 sc injections/day of 5 micrograms/kg GHRH for 2-3 months; the others received 5 pulses of GHRH (5 micrograms/kg BW.pulse) for 6 nights a week for 2-13 months, given every 3 h. Six of the nine ISGHS patients increased their growth velocity in response to GHRH therapy. These same six patients maintained an increased growth velocity for up to 24 months after GHRH was discontinued. The remaining three ISGHS patients did not show a significant growth response to GHRH administration. Neither a temporary nor a sustained growth response was correlated with spontaneous overnight GH secretion in these patients. In contrast, three of five classical GH deficiency patients exhibited increased growth velocity while undergoing GHRH therapy, but growth returned to preintervention rates upon discontinuation of treatment. The other two of the five classic GH deficiency patients failed to demonstrate any growth response to GHRH treatment. The increased growth velocity that was sustained for long intervals even after discontinuation of GHRH in ISGHS patients may indicate restoration of normal regulation of the hypothalamic-pituitary GH secretion axis.
Child↗
Is there compensated hypothyroidism in infancy?
The state-mandated newborn thyroid screening program may uncover infants who exhibit normal thyroxine (T4) levels with various degrees of hyperthyrotropinemia. To elucidate further the thyroid status, the basal metabolic rate (BMR) of 10 infants (7 boys, 3 girls; aged 9 to 63 days) was studied by indirect calorimetry. They were clinically euthyroid and healthy with no evidence of overt biochemical hypothyroidism (low T4, high thyroid-stimulating hormone [TSH]). Confirmatory testing indicated that all infants had normal serum T4 levels for age (mean +/- SD: 10.3 +/- 3.2 micrograms/dL). However, serum TSH levels varied from 2.3 to 99.2 microU/mL. In 4 infants (2 boys, 2 girls) the BMR was low (38.1 +/- 4.1 kcal/kg per day), while the other 6 patients (5 boys, 1 girl) demonstrated BMRs within the normal range (49.6 +/- 1.9 kcal/kg per day, P less than .001). The serum TSH levels were above 7.0 microU/mL among those infants with a low BMR, whereas the serum TSH levels were always below 6.0 microU/mL among the normometabolic infants. All infants who had a low BMR received thyroid therapy and promptly became normometabolic (BMR: 48.7 +/- 1.0 kcal/kg per day) with suppression of TSH levels (3.2 +/- 1.3 microU/mL) within 3 weeks of therapy, while their serum T4 levels remained within the normal range. The observed normalization of BMR in parallel to reduction of TSH levels following thyroid replacement therapy strongly suggests that these patients demonstrated a hypometabolic state, despite normal serum T4 levels. Therefore, the assessment of BMR may help define subclinical hypothyroidism in infancy in conjunction with a close monitoring of TSH concentration.
Basal Metabolism↗
Anatomical and electrophysiological evidence for a glycinergic inhibitory innervation of the rat locus coeruleus.
Using a highly specific antiserum to glycine and a very sensitive immunohistochemical technique with streptavidin-horseradish peroxidase, we visualized for the first time a dense plexus of glycine varicose fibers in the locus ceruleus (LC) of the rat. We further demonstrated that iontophoretically applied glycine inhibits the spontaneous LC noradrenergic cell discharge and that this inhibition is blocked by co-iontophoresis of strychnine. These anatomical and electrophysiological results indicate that the rat locus ceruleus receives an inhibitory glycinergic input.
Animals↗
Immunohistochemical evidence for the presence of type B monoamine oxidase in histamine-containing neurons in the posterior hypothalamus of cats.
Using a double immunostaining method, we demonstrated that type B monoamine oxidase (MAO-B) immunoreactivity was present in virtually all histamine (HA)-immunoreactive neurons in the posterior hypothalamus of the cat. Not all MAO-B-positive neurons, however, displayed HA immunoreactivity: a minor group of neurons immunoreactive for MAO-B alone was observed in the area dorsolateral to the caudal arcuate nucleus. The results suggest that the degradation of tele-methylhistamine might occur within the intraneuronal structures of histaminergic neurons.
Animals↗
Worldwide migration of amplified insecticide resistance genes in mosquitoes.
In Culex pipiens, overproduction of nonspecific esterases is a common mechanism of resistance to organophosphate insecticides. The esterases are attributed to closely linked loci named A and B according to substrate preference, and overproduction of all esterases B is due to gene amplification. Distribution of electrophoretically distinct variants of overproduced esterases A and B is geographically restricted, with the exception of esterases A2 and B2, always found together throughout at least three continents. To determine whether this situation is due to migration or to a high mutation rate, esterase B structural genes and their flanking regions were compared by sequence and/or restriction fragment length polymorphism analysis. Whereas structural genes were similar, flanking regions of electrophoretically dissimilar esterases B varied considerably. In contrast, flanking sequences of esterases B2 from different geographical locations (Africa, Asia, North America) were identical. These results suggest that amplified esterase B2 genes originated from an initial event that has subsequently spread organophosphate insecticide resistance by migration.
Amino Acid Sequence↗
Excess weight and precocious pubarche in children: alterations of the adrenocortical hormones.
In this paper we assess the qualitative and quantitative differences in adrenal function before and after adrenocorticotropic hormone (ACTH) stimulation between normal weight and overweight precocious pubarche (PP) patients. Twelve of the 22 PP patients had a normal body weight for height with linear growth and bone ages (BAs) that were appropriate for chronological age. The remaining 10 PP patients had body weights which were greater than 120% of ideal weight for height and body mass indices (BMIs), which were more than 125% of the ideal for age and sex. In six overweight patients, linear growth was accelerated and BAs were advanced beyond chronological age. All patients underwent an ACTH stimulation test where they received an intravenous bolus of 250 micrograms Cortrosyn. Blood samples were obtained at 0' and 60' for 17-OHProgesterone (17-OHP), 17-OHPregnenolone (17-OHPG), dehydroepiandrosterone (DHEA), androstenedione (A-dione), and cortisol levels. Results of the baseline and stimulated adrenal hormones in the normal weight children were found to be within reference range for normal Tanner I children. In contrast, two of the 10 overweight children were suspected of having congenital adrenal hyperplasia [one with 21-hydroxylase (21-OHase) deficiency, another with 3-betahydroxysteroid (3 beta ol) deficiency]. These two children were indistinguishable in their linear growth rate and degree of skeletal maturation from the other overweight children. In both patients the BA/chronological age and BA/height age (HA) ratios were within two standard deviations of the mean for the overweight patients.(ABSTRACT TRUNCATED AT 250 WORDS)
17-alpha-Hydroxypregnenolone↗
Iontophoretic application of unconjugated cholera toxin B subunit (CTb) combined with immunohistochemistry of neurochemical substances: a method for transmitter identification of retrogradely labeled neurons.
In this report, we demonstrate that cholera-toxin B subunit (CTb) is a very sensitive retrograde tracer in the central nervous system when recognized by streptavidin-peroxidase immunohistochemistry. We further show that: (1) injection of a small volume of CTb gives rise to small sharply defined injection sites limited to the cell group of interest associated with the labeling of all the known afferent projections, (2) CTb is taken up, and anterogradely as well as retrogradely transported in damaged but not intact fibers of passage, (3) CTb can be applied iontophoretically, allowing us to study the afferents to small cell groups without any evidence of tissue necrosis in the sites and therefore without artefactual labeling due to uptake by damaged fibers of passage, (4) the use of 4% paraformaldehyde fixative ideally suited for the preservation of most neural antigens, the addition of a 48 h colchicine treatment and the development of a double immunohistochemical method allow the biochemical characterization of the cell of origin of particular pathways in the CNS, (5) CTb is also anterogradely transported with an extensive filling of axons and axon terminals and thereby opens up the possibility of identifying simultaneously the afferents as well as the efferents of the group of cells studied and finally (6) the very long conservation of the preparation, the possibility of counterstaining it and of making camera lucida drawings allow easy and precise localization of the retrogradely labeled cells.
Afferent Pathways↗
Nuclei of origin of monoaminergic, peptidergic, and cholinergic afferents to the cat trigeminal motor nucleus: a double-labeling study with cholera-toxin as a retrograde tracer.
The aim of the present study was to determine the brainstem afferents and the location of neurons giving rise to monoaminergic, cholinergic, and peptidergic inputs to the cat trigeminal motor nucleus (TMN). This was done in colchicine treated animals by using a very sensitive double immunostaining technique with unconjugated cholera-toxin B subunit (CT) as a retrograde tracer. After CT injections in the TMN, retrogradely labeled neurons were most frequently seen bilaterally in the nuclei reticularis parvicellularis and dorsalis of the medulla oblongata, the alaminar spinal trigeminal nucleus (magnocellular division), and the adjacent pontine juxtatrigeminal region and in the ipsilateral mesencephalic trigeminal nucleus. We further observed that inputs to the TMN arise from the medial medullary reticular formation (the nuclei retricularis magnocellularis and gigantocellularis), the principal bilateral sensory trigeminal nucleus, and the dorsolateral pontine tegmentum. In addition, the present study demonstrated that the TMN received 1) serotonergic afferents, mainly from the nuclei raphe obscurus, pallidus, and dorsalis; 2) catecholaminergic afferent projections originating exclusively in the dorsolateral pontine tegmentum, including the Kölliker-Fuse, parabrachialis lateralis, and locus subcoeruleus nuclei; further, that 3) methionin-enkephalin-like inputs were located principally in the medial medullary reticular formation (nuclei reticularis magnocellularis and gigantocellularis and nucleus paragigantocellularis lateralis), in the caudal raphe nuclei (Rpa and Rob) and the dorsolateral pontine tegmentum; 4) substance P-like immunoreactive neurons projecting to the TMN were present in the caudal raphe and Edinger-Westphal nuclei; and 5) cholinergic afferents originated in the whole extent of the nuclei reticularis parvicellularis and dorsalis including an area located ventral to the nucleus of the solitary tract at the level of the obex. In the light of these anatomical data, the present report discusses the possible physiological involvement of TMN inputs in the generation of the trigeminal jaw-closer muscular atonia occurring during the periods of paradoxical sleep in the cat.
Afferent Pathways↗