Biomedical subjects

J Montagne

Publications and source records attributed to J Montagne.

At least 19 recordsLinked to original sources

PubMed2001

Insulin signaling: lessons from the Drosophila tuberous sclerosis complex, a tumor suppressor.

The genes that encode the proteins composing the tuberous sclerosis complex (TSC) are tumor suppressors. Experiments in the model organism Drosophila melanogaster have provided insight into the identity of these genes and their functions in regulating cell size and proliferation. Montagne et al. describe the various genetic interactions that show TSC to be a regulator of the insulin signaling pathway and a regulator of progression through the cell cycle, which explains its effects on cell size and tissue and tumor growth.

Animals↗

PubMed2000

Putative cortical and thalamic inputs elicit convergent excitation in a population of GABAergic interneurons of the lateral amygdala.

Synaptic circuitry in the rat lateral amygdala (AL) was studied in brain slices using electrophysiological recordings. Electrical stimulation of external and internal capsules evoked an EPSC followed by a sequence of GABA(A) and GABA(B) receptor-mediated IPSC in principal neurons. Paired stimulation of either afferents resulted in a significant reduction ( approximately 45%) of the second GABA(A) receptor-mediated IPSC. A priming stimulation, consisting of a priming pulse to one pathway followed by a pulse to the other pathway, resulted in a strong depression of the second IPSC basically identical to that during paired stimulation. Paired- and primed-pulse depressions were largely relieved by 10 micrometer CGP 55845A, indicating regulation through presynaptic GABA(B) receptors. Furthermore, putative interneurons responded with EPSCs of constant latencies to minimal stimulation of both cortical and thalamic fibers, indicating convergent monosynaptic input. At higher stimulation strength, an approximately 15% reduction of EPSCs occurred in interneurons after paired and primed stimulation, which was not sensitive to CGP 55845A. These findings indicate that a rather homogeneous population of interneurons exists in the AL with respect to their afferent connectivity, in that they receive convergent input through putative thalamic and cortical fibers, both directly and indirectly (through principal neurons), and mediate inhibitory control of postsynaptic principal neurons. This symmetrically built GABAergic circuitry can be of functional significance, given the distinctive role of the two afferent input systems for the mediation of different components of fear responses and the importance of GABAergic mechanisms for limitation of excessive neuronal activity.

Afferent Pathways↗

PubMed2000

Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin.

The adaptation of growth in response to nutritional changes is essential for the proper development of all organisms. Here we describe the identification of the Drosophila homolog of the target of rapamycin (TOR), a candidate effector for nutritional sensing. Genetic and biochemical analyses indicate that dTOR impinges on the insulin signaling pathway by autonomously affecting growth through modulating the activity of dS6K. However, in contrast to other components in the insulin signaling pathway, partial loss of dTOR function preferentially reduces growth of the endoreplicating tissues. These results are consistent with dTOR residing on a parallel amino acid sensing pathway.

Amino Acids↗

PubMed2000

Genetic and molecular mechanisms of cell size control.

Since the discovery of the cell as the minimal indivisible living entity, scientists have tried to understand how all the various physiological aspects were assumed within this single functional unit. One fascinating question concerns the role of cell size and cell number in determining the overall size of an organism. During the past century, increasing knowledge in molecular genetics has allowed the characterization of a number of molecular events that influence the size of a cell. However, in spite of recent progress, precise molecular mechanisms governing cell size remain unclear. Although the existence of a master regulator is still possible, cell size may be primarily controlled by an interactive network linking gene expression with translational capacity and cell proliferation.

Animals↗

PubMed2000

Expression of the blistered/DSRF gene is controlled by different morphogens during Drosophila trachea and wing development.

The Drosophila serum response factor (DSRF) is expressed in the precursors of the terminal tracheal cells and in the future intervein territories of the third instar wing imaginal disc. Dissection of the DSRF regulatory region reveals that a single enhancer element, which is under the control of the fibroblast growth factor (FGF)-receptor signalling pathway, is sufficient to induce DSRF expression in the terminal tracheal cells. In contrast, two separate enhancers direct expression in distinct intervein sectors of the wing imaginal disc. One element is active in the central intervein sector and is induced by the Hedgehog signalling pathway. The other element is under the control of Decapentaplegic and is active in two separate territories, which roughly correspond to the intervein sectors flanking the central sector. Hence, each of the three characterized enhancers constitutes a molecular link between a specific territory induced by a morphogen signal and the localized expression of a gene required for the final differentiation of this territory.

Animals↗

PubMed1999

Drosophila S6 kinase: a regulator of cell size.

Cell proliferation requires cell growth; that is, cells only divide after they reach a critical size. However, the mechanisms by which cells grow and maintain their appropriate size have remained elusive. Drosophila deficient in the S6 kinase gene (dS6K) exhibited an extreme delay in development and a severe reduction in body size. These flies had smaller cells rather than fewer cells. The effect was cell-autonomous, displayed throughout larval development, and distinct from that of ribosomal protein mutants (Minutes). Thus, the dS6K gene product regulates cell size in a cell-autonomous manner without impinging on cell number.

Animals↗

PubMed1998

A case of perforated cystic duplication of the transverse colon.

A 7-year-old girl presented with an abdominal cystic mass close to the pancreas. US and CT could not identify its origin. The diagnosis of duplication of the transverse colon was made at surgery. This location is rare. The differential diagnosis in this case included a pancreatic cystadenoma, a pseudocyst or a mesenteric cyst.

Child↗

PubMed1996

The Drosophila Serum Response Factor gene is required for the formation of intervein tissue of the wing and is allelic to blistered.

The adult Drosophila wing is formed by an epithelial sheet, which differentiates into two non-neural tissues, vein or intervein. A large number of genes, many of them encoding components of an EGF-receptor signaling pathway, have previously been shown to be required for differentiation of vein tissue. Much less is known about the molecular control of intervein differentiation. Here we report that the Drosophila homolog of the mammalian Serum Response Factor gene (DSRF), which encodes a MADS-box containing transcriptional regulator, is expressed in the future intervein tissue of wing imaginal discs. In adult flies carrying only one functional copy of the DSRF gene, additional vein tissue develops in the wing, indicating that DSRF is required to spatially restrict the formation of veins. In mitotic clones lacking DSRF, intervein tissue fails to differentiate and becomes vein-like in appearance. Genetic and molecular evidence demonstrates that DSRF is encoded by the blistered locus, which produces ectopic veins and blistered wings when mutant. Our results show that DSRF plays a dual role during wing differentiation. It acts in a dosage-dependent [correction of dosage-dependant] manner to suppress the formation of wing veins and is required cell-autonomously to promote the development of intervein cells. We propose that DSRF acts at a key step between regulatory genes that define the early positional values in the developing wing disc and the subsequent localized expression of intervein-specific structural genes.

Alleles↗

PubMed1995

Characterization of a transcriptional attenuator within the 5' R region of the human T cell leukemia virus type 1.

Several regulatory sequences have been characterized in the HTLV-I promoter. We report here identification of a sequence element downstream of the transcriptional start site within the first 52 nucleotides of the 5' R region, which acts negatively on the activity of the HTLV-I promoter. Determination of the half-lives of the RNAs either including or lacking this sequence element showed that the observed effect intervenes at the transcriptional level. This negative element does not affect basal activity of the HTLV-I TATA box, but down-regulates transcription induced by strong activators. Thus, we propose that this so-called negative regulatory sequence functions as an attenuator of transcription.

Actins↗

PubMed1994

The Drosophila SRF homolog is expressed in a subset of tracheal cells and maps within a genomic region required for tracheal development.

The Drosophila homolog of the vertebrate serum response factor (SRF) was isolated by low stringency hybridization. Nucleotide sequence analysis revealed that the Drosophila SRF homolog (DSRF) codes for a protein that displays 93% sequence identity with human SRF in the MADS domain, the region required for DNA binding, dimerization and interaction with accessory factors. The DSRF gene is expressed during several phases of embryonic development. In the egg, both the RNA and the protein are maternal in origin and slowly decrease in amount during gastrulation. After germ band retraction, high levels of zygotic expression are observed in a distinct subset of peripheral tracheal cells distributed throughout the embryo. Many of these cells are at the tip of tracheal branches and are in direct contact with the target tissues. The DSRF gene was mapped to position 60C on the second chromosome, and overlapping deficiencies which remove the gene were identified. Analysis of tracheal development in embryos carrying these deletions revealed a degeneration of most of the major branches of the tracheal system. Although the initial migration of tracheal cells was not affected in those deficient embryos, many tracheal cells appeared not to maintain their correct position and continued to migrate. Thus, the DSRF gene might play a role in the proper formation and maintenance of the trachea.

Amino Acid Sequence↗

PubMed1993

The transcriptionally active factors mediating the effect of the HTLV-I Tax transactivator on the IL-2R alpha kappa B enhancer include the product of the c-rel proto-oncogene.

The transactivator HTLV-I Tax activates the promoter of the gene coding for the interleukin 2 alpha-chain receptor (IL-2R alpha) via a kappa B site that can bind several protein species of the rel family. Tax1 strongly activates the enhancer activity of this motif, in both epithelial HeLa and lymphoid Jurkat cells. This activation was not observed in undifferentiated embryocarcinoma F9 cells. Overexpression of the p50, p65 and Rel proteins in these cells showed that significant activation of the IL-2R alpha kappa B site was observed only with Rel and Rel plus p65. Moreover, whereas both Tax and phorbol 12-myristate 13-acetate (PMA) are able to efficiently induce the binding of NF-kappa B to the IL-2R alpha kappa B site, PMA is functionally inactive. Using the DNA affinity precipitation assay, we observed that Tax1 is able to efficiently induce the binding of Rel, whereas PMA is not. This established a clear difference between both stimuli, indicating that Rel is the functionally active factor. We conclude from these results that the functional activity of members of the rel family is regulated by their interaction with DNA and that Rel can be a potent transcriptional activator on specific kappa B sites.

Base Sequence↗

PubMed1992

[Ioversol 300: clinical study in pediatric intravenous urography].

The efficacy and safety of Optiray (Ioversol), a new low osmolar non ionic contrast agent, were evaluated in an open trial for pediatric intravenous urography. At a concentration of 30% iodine, Optiray had a good diagnostic efficacy and was found to be well tolerated.

Adolescent↗

PubMed1990

Single unit activity at ventromedial medulla level in the awake, freely moving rat: effects of noxious heat and light tactile stimuli onto convergent neurons.

In this study, we recorded single unit activity at the ventromedial medulla (VMM) level in the awake, freely moving rat. In agreement with previous work under the same conditions, we found a vast majority of neurons which possess heterosensory and heterosegmental inputs ('convergent'). These units are activated either by auditory or mechanical innocuous and noxious stimuli applied all over the body surface. The activation threshold of these neurons is very low since light stimulation such as air puff produce intense bursts. In addition to this highly represented neuronal class, we also find another consistent VMM group of neurons which fire in relation to precise or generalized body movements. The main result of the present work is that, in addition to auditory and mechanical inputs, a relatively high proportion of VMM convergent neurons are activated by noxious heat pulses between 43 and 51 degrees C. In this range, it was possible to obtain stimulus-response functions with 2 degrees C steps only when a skin twitch reflex produced by the heat was present, also encoding the temperature intensity. In comparison to the VMM activations produced by an intense noxious heat pulse such as 51 degrees C, either auditory or controlled light touch stimuli induced a more robust response in terms of maximum frequency of discharge. Differential properties of VMM neurons in relation to innocuous and noxious information were also found using repetitive stimulation: although a strong and fast habituation of the 51 degrees C responses was observed, this phenomenon was not present for light touch induced activations. We propose that these differential properties might reflect separate pathways reaching the VMM, the one carrying innocuous information possibly relayed through the dorsal column nuclei. Although obtaining stimulus-response functions might implicate the VMM convergent neurons in the sensory-discriminative aspect of pain, their massive heterosensory and heterosegmental inputs favor a role in more general processes such as alertness or stress. Also, due to massive convergent properties, the involvement of this neuronal class in specific bulbospinal descending control systems of nociceptive information is questionable, Finally, our results obtained in the awake, freely moving rat strongly differ from the anesthetized preparation in that we found neither nociceptive specific units nor neurons inhibited by noxious peripheral stimulations largely described in this approach.

Action Potentials↗

PubMed1990

Tax1 induction of the HTLV-I 21 bp enhancer requires cooperation between two cellular DNA-binding proteins.

Activation of the HTLV-I promoter by the viral Tax1 transactivator is mediated by a 21 bp sequence motif imperfectly repeated three times and composed of three exactly conserved domains (A, B and C from 5' to 3'). We show here that the Tax1 response requires the integrity of the B domain and of at least one of the flanking A or C domains. We have identified three cellular proteins which bind specifically to the 21 bp motif. One of these is the already well-characterized transcription factor ATF. The other two, namely HEB1 and HEB2, are specific for the 21 bp motif. HEB1 can bind to either domain A or C, but binding of ATF and HEB2 is determined by domain B. However, neither domain B alone, nor ATF/CREB binding sites respond significantly to Tax1. We therefore propose that Tax1 induction of the 21 bp enhancer element requires interaction with the two different cellular proteins identified in this study: HEB1 and HEB2, rather than binding of the ATF factor.

Base Sequence↗

PubMed1990

A single-unit recording system, contact thermal probe and electromechanical stimulator for studying cellular mechanisms related to nociception at brain stem level of awake, freely moving rats.

The purpose of this paper is to describe a simple, light-weight (3 g) device bearing a fine platinum-irridium Teflon-coated wire (50 microns) used to record single-unit activity extracellularly at brain stem level in the totally conscious freely moving rat. The up and down movements of the electrode through a guide cannula are insured by a small nut and a spring; the distance between the electrode and the end of the guide cannula is measured with a nut index. The system is directly connected to an amplifier (no FET or preamplifier) and allows for long term recordings necessary for a complete neuronal characterization and pharmacological experiments. The device is easy to make, entirely recoverable, and can be implanted from an animal to another. Further improvements are possible such as tungsten microelectrodes and telemetric or microinjection systems. In order to study some neuronal brain stem mechanisms involved in nociception, we have also designed a contact thermal probe and an electromechanical stimulator. The thermode is stuck to the shaved skin on the back of the rat, allowing heat pulses up to 51 degrees C to be applied. The mechanical stimulator is used manually and delivers reproducible innocuous stimuli to the skin. The fact that both types of stimulations are driven electrically enables the elaboration of cumulated peristimulus histograms which will reflect the neuronal activities in response to the application of noxious and non noxious stimuli.

Action Potentials↗

PubMed1989

Electrophysiological properties of ventromedial medulla neurons in response to noxious and non-noxious stimuli in the awake, freely moving rat: a single-unit study.

The spontaneous and evoked activities of ventromedial medulla (VMM) neurons have been recorded in the chronic, awake, freely moving rat. The vast majority of neurons located at the level of the nucleus raphé magnus exhibited an irregular and variable (2-16 Hz) spontaneous activity and were activated by either cutaneous or auditory stimuli. Within this convergent neuronal class the neurons were activated by either cutaneous noxious and non-noxious inputs. The threshold for cutaneous activation was likely very low since a majority of units responded to air puffs, but the application of controlled brushing and pin-prick revealed that the VMM convergent neurons responded more for the noxious mechanical stimulation. Similar findings were found with pinch application. For both innocuous and noxious stimuli, the cutaneous receptive field was extremely extensive (almost all of the body); however, the application of the controlled brushing showed that for this innocuous stimulation, the most sensitive regions were the tail, back, snout and vibrissae and, to a lesser extent, the flank and paws. Preliminary experiments indicated that both the spontaneous and evoked activities of VMM convergent neurons were inhibited during stressful manipulations such as scruff lifting or defense reactions. These data contrast with other studies on VMM single unit recordings in anesthetized rats since the majority of these studies did not emphasize the VMM convergent group; in addition, with one exception, we did not find neurons exclusively driven by noxious inputs. Without excluding a role of the VMM convergent group in pain descending control systems, we proposed that this neuronal class is perhaps also involved in pain transmission or in general processess such as alertness and stress. Experiments are proposed in order to precisely determine the involvement of the VMM convergent neurons in alertness versus sensory discriminative aspects of nociception in the awake, freely moving rat.

Action Potentials↗

PubMed1986

Changes of fatty acid composition of phospholipids and lipid structural order in rat liver mitochondrial membrane subsequent to galactosamine intoxication. Effect of clofibrate.

Since it has been earlier reported that D-galactosamine induces an inhibition of palmitoylcarnitine transferase I and a depletion of mitochondrial phospholipids which were both prevented by clofibrate, an evaluation of the effects of these drugs on mitochondrial fatty acid composition was made. Galactosamine does not alter the fatty acid pattern of these fatty acids whereas clofibrate induces a 2-fold increase in monounsaturated/saturated fatty acids ratio and a 10-fold decrease of the 20:4 (n - 6)/20:3 (n - 6) ratio in phosphatidylcholine. These alterations suggest an increase of delta 9-desaturation and a decrease of delta 5-desaturation. To determine whether the drug-induced changes in mitochondrial phospholipids has an effect on the physical properties of the membrane, the lipid structural order of mitochondrial preparations was studied using the lipophilic probes DPH and TMA-DPH. Mitochondrial isolated either from galactosamine- or clofibrate-treated rats showed a decrease in fluorescence polarization, indicating an overall decrease in lipid structural order. This alteration is more drastic when both drugs are administered. This phenomenon suggests drastic changes in the bulk phase of inner mitochondrial membrane lipids after treatments and could explain the altered kinetic properties of palmitoylcarnitine transferase I.

Animals↗

PubMed1986

Preventive effect of clofibrate on carnitine palmitoyltransferase I inhibition and mitochondrial membrane phospholipid depletion induced by galactosamine.

We have previously reported that a D-galactosamine injection induces a decrease of carnitine palmitoyltransferase I activity correlated with a depletion of total phospholipid content in the mitochondrial membrane. The impact of a short-term clofibrate treatment on these membrane alterations is investigated, i.e., the kinetic properties of carnitine palmitoyltransferase I, including its sensitivity to malonyl-CoA and mitochondrial membrane content of the various phospholipids. A 4-day clofibrate treatment increases by 42% the apparent Km value of carnitine palmitoyltransferase I for palmitoyl-CoA, while the sensitivity of the enzyme to malonyl-CoA appears slightly decreased. Simultaneously, the cardiolipin content is increased by 70% in the mitochondrial membrane, whereas the phosphatidylethanolamine and phosphatidylcholine contents remain almost unaffected. This 4-day clofibrate treatment prevents the inhibition of carnitine palmitoyltransferase I activity subsequent to galactosamine administration but induces an increase in the apparent Km value for palmitoyl-CoA and a decrease of the sensitivity of the enzyme to malonyl-CoA. The contents of phospholipids which are decreased by galactosamine (phosphatidylcholine, -21%; phosphatidylethanolamine, -29%; cardiolipin, -40%) regain the control values when galactosamine administration is preceded by a clofibrate treatment. The data suggest that the clofibrate treatment counteracts the inhibition of activity of carnitine palmitoyltransferase I through the maintenance of mitochondrial membrane integrity.

Acyltransferases↗