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Biomedical subjects

M Imbert

Publications and source records attributed to M Imbert.

At least 19 recordsLinked to original sources
PubMed2003

New mechanisms of AML1 gene alteration in hematological malignancies.

The human AML1 gene (also named CBFA2 or RUNX1), located in the 21q22 chromosomal band, encodes for one of the two subunits forming a heterodimeric transcription factor, the human core binding factor (CBF). AML1 protein contains a highly evolutionary conserved domain of 128 amino acids called runt domain, responsible for both heterodimerization with the beta subunit of CBF and for DNA binding. AML1 is normally expressed in all hematopoietic lineages and acts to regulate the expression of various genes specific to hematopoiesis playing a pivotal role in myeloid differentiation. AML1 is one of the genes most frequently deregulated in leukemia through different mechanisms including translocation, mutation and amplification. Translocations lead to the formation of fusion genes encoding for chimerical proteins such as AML1-ETO which induces leukemogenesis. Recently, new mechanisms of AML1 deregulation by point mutations or amplification have been reported. To our knowledge, 51 patients (among 805 studied) with AML1 point mutations have been described. Forty of them have acute myeloid leukemia (AML) most often M0 AML. In this subtype of AML, the frequency of AML1 mutation is significantly higher; 21.5% of patients mutated (34/158). Mutations have also been found with lower frequency in other FAB subtype AML (6 cases), in myeloproliferative disorders (6 cases), in myelodysplastic syndrome (3 cases) and rarely in acute lymphoblastic leukemia (1 case). AML1 gene amplification has been found essentially in childhood ALL (12 cases) and more rarely in myeloid malignancies (4 cases). Here, we reviewed all these cases of AML1 point mutations and amplification and focused on the mechanisms of AML1 deregulation induced by these alterations.

Acute Disease↗
PubMed2002

The effect of hypertonic saline dextran solutions on hypoxic pulmonary vasoconstriction in anaesthetised piglets.

Hypoxic pulmonary vasoconstriction (HPV) is a regulatory mechanism by which blood is diverted from poorly ventilated to better ventilated areas of the lung. The aim of the present study was to assess the extent to which hypertonic saline dextran and dextran solutions modify the magnitude of HPV during isovolumic haemodilution in intact acutely instrumented piglets. Eighteen large white piglets were anesthetised and assigned to two groups. Mean pulmonary arterial pressure (PAP) and cardiac output (Q), systemic arterial pressure and left arterial pressure (LAP) were measured. A decrease in Q was obtained by reducing venous return. This enabled measurement of transpulmonary pressures (mean PAP minus LAP) at four levels of Q in hyperoxia (inspiratory oxygen fraction (FiO2)=0.4) then in hypoxia (Fi,O2=0.1) in the two groups before blood soustraction (10 mL x kg(-1)) and after loading with sodium chloride (NaCl) 7.5% and dextran 6% or with dextran 6% alone. Dextran alone led to a decrease in mean PAP-LAP/Q values, and NaCl with dextran was associated with a significant shift of mean PAP-LAP/Q plots to higher pressures in hypoxia. Hypertonic saline dextran solution, as replacement fluid in isovolaemic haemodilution increased the magnitude of hypoxic pulmonary vasoconstriction, whereas dextran solution reduced it.

Anesthesia, Inhalation↗
PubMed2001

Occurrence of two superoxide dismutases in Aeromonas hydrophila: molecular cloning and differential expression of the sodA and sodB genes.

Aeromonas spp., considered as emerging opportunistic pathogens, belong to the family Vibrionaceae. Among the criteria currently used for their classification is the presence of a single FeSOD (iron-containing superoxide dismutase), which distinguishes them from Enterobacteriacea. In this paper the cloning of the sodA and sodB genes encoding two different SODs in Aeromonas hydrophila ATCC 7966 is reported. The sodB gene encoded an FeSOD (196 amino acids, 21.5 kDa), was constitutively expressed and showed 75% homology with the E. coli FeSOD. The sodA gene encoded a protein of 206 amino acids (22.5 kDa) with MnSOD (manganese-containing SOD) activity and showed 55% homology with the Escherichia coli MnSOD. The MnSOD of A. hydrophila was detected only during the stationary phase of growth under high aeration or when induced by lack of iron. Nevertheless, paraquat had no detectable effect on its production. The amino-terminal part of the Mn-containing protein contained a putative signal sequence which could permit a periplasmic localization.

Aeromonas↗
PubMed2000

Effects of sevoflurane on hypoxic pulmonary vasoconstriction in anaesthetized piglets.

In vitro, halogenated agents reduce the pulmonary vasoconstrictor response to alveolar hypoxia in isolated perfused lungs. However, studies in intact animals have been less convincing. The aim of the present study was to assess the effect of sevoflurane on hypoxic pulmonary vasoconstriction (HPV) in anaesthetized piglets using the pressure/cardiac index relationship (P/Q). Ten large white piglets were anaesthetized and mechanically ventilated, alternately in hyperoxia (FIO2 = 0.4) and hypoxia (FIO2 = 0.12). Multipoint plots of pulmonary arterial pressure (PAP) or differences between PAP and left atrial pressure (LAP) against Q were generated by gradual inflation of a balloon introduced into the inferior vena cava. P/Q relationships were established in hyperoxia and hypoxia at baseline, and then with sevoflurane. In hypoxia, pressure gradients (PAP-LAP) increased at every level of Q, thus demonstrating active pulmonary vasoconstriction. Sevoflurane at 1 MAC did not affect these P/Q relationships in hyperoxia or hypoxia as compared with baseline. Sevoflurane at a clinically relevant concentration (1 MAC) has no significant effect on HPV in anaesthetized piglets.

Anesthesia, Inhalation↗
PubMed1999

Effect of light on germinating spores of Streptomyces viridosporus.

Our study showed that the effect of light on germinating spores of Streptomyces was variable: some species were indifferent, whereas others, such as Streptomyces viridosporus, displayed a marked inhibition of CFU numbers on growth medium. A special study with S. viridosporus showed that light only had an impact during the first few hours of spore incubation. The effects of scavengers of toxic forms of oxygen and of photosensitizers, along with the oxidative stress of illuminated spores evidenced by the superoxide dismutase levels, suggested that light and oxygen had a combined action.

Colony Count, Microbial↗
PubMed1998

On the iron requirement of lactobacilli grown in chemically defined medium.

The iron requirement of four strains of lactobacilli (L. acidophilus, L. delbrueckii subsp. bulgaricus, L. plantarum, and L. pentosus) was studied in a synthetic medium under aerobic or anaerobic conditions. Effects of iron salt and iron-chelated compounds were tested on bacterial growth in manganese-free or -supplemented media. No significant growth stimulation was observed in any condition. These results support the absolute manganese requirement for optimum growth of lactobacilli and the needless incorporation of iron in growth media.

Aerobiosis↗
PubMed1998

The cell cycle gene SKP1 is regulated by light in postnatal rat brain.

During the early postnatal phase of high neuronal plasticity, an altered visual input leads to great modifications of visual cortex organization [Y. Frégnac, M. Imbert, Development of neuronal selectivity in primary visual cortex of cat, Physiol. Rev., 64 (1984) 375-434; D.H. Hubel, T.N. Wiesel, S. LeVay, Plasticity of ocular dominance columns in monkey striate cortex, Philos. Trans. R. Soc. London, Ser. B, 278 (1977) 377-409.]. We used refined differential screening of an organized cDNA library to identify the genes that may participate in this plasticity. We isolated a candidate plasticity gene encoding for a 163 aa protein that is closely related to the human and yeast Skp1p, a key factor in cell cycle progression [C. Baï, K. Hofman, L. Ma, M. Goebl, J.W. Harper, S.J. Elledge, SKP1 connects cell cycle regulators to the ubiquitin proteolysis machinery through a novel motif, the F-box, Cell, 86 (1996) 263-274; C. Connelly, P. Hieter, Budding yeast SKP1 encodes an evolutionary conserved kinetochore protein required for cell cycle progression, Cell, 86 (1996) 275-285; H. Zhang, R. Kobayashi, K. Galaktionov, D. Beach, p19Skp1 and p45Skp2 are essential elements of the cyclin A-CDK2 S phase kinase, Cell, 82 (1995) 915-925.]. Northern blot analysis showed that the expression of SKP1 (Skp1p gene) dramatically decreased after 2 h of light stimulation in the visual cortex of young dark-reared rats. This down regulation lasted at least 72 h. It was specific for the critical period as we did not observe any significant regulation of SKP1 mRNA by light in adult dark-reared rat brain. The down regulation was observed in the superior colliculus but also in the frontal cortex and in the hippocampus. The fact that this down regulation was not restricted to the visual system, suggested that it could be produced by dark rearing-induced hormonal changes. The significance of SKP1 expression in the brain and its regulation are discussed.

Animals↗
PubMed1998

Scanning direction and line bisection: a study of normal subjects and unilateral neglect patients with opposite reading habits.

Sixty normal dextrals (30 left-to-right and 30 right-to-left readers) and two left unilateral neglect patient with opposite reading habits performed a passive line bisection task. In order to study the effect of scanning direction on performance, subjects had to stop a mark moving on the to-be-bisected line either from the left to the right or in the opposite direction. Results showed that the position of the subjective middle was dependent upon the scanning direction of the line for all the subjects. A leftward deviation appeared for left to right scanning, whereas a rightward shift occurred when the mark moved from the right to the left. These results emphasize the role of scanning direction in space organization and are discussed with respect to the explanatory hypotheses of unilateral neglect.

Adolescent↗
PubMed1998

Diagnosis, classification, and cytogenetics of myelodysplastic syndromes.

BACKGROUND AND OBJECTIVE: The diagnosis of myelodysplastic syndromes (MDS) is essentially morphological and based on the presence of dysplastic features in the peripheral blood and bone marrow. The French-American-British (FAB) Cooperative Group proposed a classification based on easily obtainable laboratory information. In spite of some limitations, the FAB criteria have been useful for a long time. Currently, the recognition of other distinct morphological MDS subgroups such as hypocellular MDS and MDS with myelofibrosis, the increasing incidence of MDS in children as well as that of therapy-related MDS, and the finding of specific chromosomal alterations associated with different morphological features, reveal the insufficiency of this classification. The aim of the present review is to examine some new aspects of the diagnosis, classification, and cytogenetics of MDS. EVIDENCE AND INFORMATION SOURCES: The authors of this review have been actively working and contributing original papers on MDS for the last 15 years. They also organized or participated in the Fourth International Symposium on MDS (Barcelona, April 24-27, 1997). In addition, the present review critically examines relevant articles and abstracts published in journals covered by the Science Citation Index and Medline. STATE OF THE ART AND PERSPECTIVES: Most of investigators working on MDS tend to integrate morphology and cytogenetics in the diagnosis and classification of these disorders. FAB criteria remain useful particularly for patients with not available cytogenetic study. Refractory cytopenia with multilineage dysplasia should be considered as a new MDS subtype. Some authors propose considering all patients with more than 20% of blast cells in peripheral blood or bone marrow as having acute leukemia. Chronic myelomonocytic leukemia with myeloproliferative features may be included among chronic myeloproliferative disorders. MDS with myelofibrosis is recognized as a new MDS subtype. Therapy-related MDS (t-MDS) should be classified according to the involved agents. Finally, besides including chromosomal abnormalities in the diagnosis (e.g., RAEB with trisomy 8), several cytogenetic abnormalities such as deletion 5q and deletion 17q, associated to specific clinical-morphological features, should be of help to identify new MDS syndromes.

Cytogenetics↗
PubMed1997

N-methyl-D-aspartate subunit R1 involvement in the postnatal organization of the primary visual cortex of Callithrix jacchus.

It has been demonstrated that the primary visual cortex is highly sensitive to manipulations of the visual environment during a specific, early, postdevelopmental period: the critical period. Pharmacological studies have shown that N-methyl-D-aspartate (NMDA) receptors are involved in the plasticity of the visual cortex just as they are involved in the induction of long-term potentiation (LTP), another activity-dependent form of plasticity. The setting up of synaptic connectivity in the neocortex may rely on LTP-like mechanisms. By using immunohistochemistry techniques, we tested the hypothesis of the role of subunit R1 of NMDA (NMDAR1) receptors in the thalamocortical afferent segregation into ocular-dominance columns in the New World monkey, Callithrix jacchus. We employed early and short (2 weeks) monocular-deprivation periods at different ages of postnatal development (17, 46, 67, 107, and 188 postnatal days). We observed heterogeneous distribution of NMDAR1 in the layer IVC receiving the thalamic inputs if the deprivation was realized between the ages of 46 and 107 days. Layers IVCalpha and IVCbeta were involved differently as a function of the deprivation age. The striped pattern lost its differential intensity with the postnatal age. These results are compared with the ocular-dominance pattern evolution described in other works on this primate. They provide evidence of the NMDAR1 role in the modular organization, within time limits, during the postnatal development of the primary visual cortex.

Aging↗
PubMed1997

Expression of SKP1 mRNA and protein in rat brain during postnatal development.

We previously isolated the cell cycle element SKP1 as a candidate plasticity gene in the rat visual cortex. Here, we studied the expression and localization of SKP1 mRNA and protein in rat brain. We found a high level of expression for the SKP1 gene in the cortex at different postnatal ages. SKP1 mRNA levels remained stable from P2 (postnatal day 2) to adulthood. SKP1 mRNA expression was also detected in several other brain areas. Skp1p (SKP1 protein) immunohistochemistry showed nuclear staining in a large majority of neurones. The pyramidal cells in the hippocampus, as well as cortical cells were stained. The presence of Skp1p in post-mitotic neurones suggests that this protein is involved in processes other than the cell cycles other target proteins and functions in neurones are currently under investigation.

Animals↗
PubMed1997

Length representation in normal and neglect subjects with opposite reading habits studied through a line extension task.

In the first part of this paper, 45 French (left-to-right readers) and 30 Israeli (right-to-left readers) normal dextrals were given half a line and requested to construct the missing other with the same length (either the left one or the right one). Using this line extension task, a significant effect of reading habits on the performance was found, with no significant bias for Israeli subjects, and a significant underconstruction when building the left half from the right one for French subjects. In the second part, two patients with opposite reading habits (one French, one Israeli) suffering from left unilateral neglect were submitted to the same protocol. Both patients were found to under-construct the right half of the line from the left given half, and to over-construct the left half from the right given one, hence reproducing the well-known line bisection bias. Results are discussed with regard to enhancement and activation hypotheses, and current theories of the neglect syndrome.

Adult↗
PubMed1997

A new c-kit mutation in a case of aggressive mast cell disease.

Systemic mast cell disease (SMCD) is a disorder characterized by a mast cell proliferation in various tissues. Mast cells express the c-kit proto-oncogene. A few cases of c-kit mutations have been described in SMCD. We report an aggressive SMCD in a patient who presented with a bone marrow infiltration by abnormal mast cells. Molecular studies of mast cell DNA and RNA revealed a new c-kit heterozygous mutation (Asp820Gly). This mutation leads to a drastic amino-acid change and is located close to the highly oncogenic Asp816Val. These findings suggest that the Asp820Gly has a potential role in c-kit activation.

Adult↗
PubMed1996

Prenatal lesioning of vestibular organ by aminoglycosides.

The effects of gentamicin administrated to gravid mice on the vestibular hair cells of their offspring were investigated. Scanning electron microscopy showed the effect to be dose-dependent and age-dependent, and there was a different sensitivity to toxicity for each of the three types of vestibular receptors. The destructive action of gentamicin on the vestibule before birth provides a mechanism to study the influence of the vestibular system on the central nervous system throughout its development.

Aminoglycosides↗
PubMed1996

[Cytology of acute leukemia].

Cytological analysis of peripheral blood and bone marrow films is a quick and simple method for diagnosis of acute leukemia. In association with cytochemistry techniques it allows the rapid identification and subsequent classification of most types of acute myeloid leukemias. Although morphological analysis can suggest the diagnosis of an acute lymphoblastic leukemia, it is necessary to have the corroborating evidence of immunological markers for confirmation. In addition, ultrastructural studies contribute to the identification of rare forms of acute myeloid leukemias (minimally differentiated, megakaryoblastic). Cytological studies have also proven useful for the follow-up activities of confirming complete remission and detecting relapses.

Acute Disease↗
PubMed1996

Neural processing of stereopsis as a function of viewing distance in primate visual cortical area V1.

1. The influence of viewing distance on disparity selectivity was investigated in area V1 of behaving monkeys. While the animals performed a fixation task, cortical cells were recorded extracellularly in the foveal representation of the visual field. Disparity selectivity was assessed by using static random dot stereograms (RDSs) through red/green filters flashed over the central fixation target. To determine the influence of the viewing distance, a color video monitor was positioned at fixed distances of 20, 40, or 80 cm. The same RDSs with the same angular size of dots were used at the three distances. 2. Disparity sensitivity was tested on 139 cells, of which 78 were analyzed at two or more distances and the rest (61) at a single distance. When disparity selectivity was analyzed at a given distance, about half the cells were found to be selective at 40 or 80 cm, but only a third at 20 cm. Near cells were > or = 1.5 times more common than far cells at all three distances. The latency distribution of the responses of disparity-selective (DS) cells was similar at all three distances, with a mean distribution centered around 60 ms. 3. Changing the viewing distance drastically affected the neural activity of the V1 neurons. The visual responsiveness of 60 of 78 cells (77%) was significantly changed. Disparity selectivity could be present at a given distance and absent at other(s), with often a loss of visual response. This emergence of disparity coding was the strongest effect (28 of 78 or 36%) and occurred more frequently from short to long distances. Among the cells that remained disparity insensitive at all recorded distances (31 of 78 or 40%), about half also showed modulations of the amplitude of the visual response. For cells that remained DS at all recorded distances (13 of 78 or 17%), changing the viewing distance also affected the sharpness (or magnitude) of disparity coding in terms of level of visual responsiveness and those changes were often combined with variations in tuning width. In only two cells did the peak of selectivity type change. Finally, the activity of four DS cells was not affected at all by the viewing distance. 4. Another effect concerned the level of ongoing activity (OA), defined as being the neural activity in darkness preceding the flash of the visual stimulus while the monkey was fixating the small bright target. Changing the viewing distance resulted in significant changes in OA level for more than half of the cells (41 of 78 or 53%). The most common effect was an increase in OA level at the shorter distance. The modulations of both visual responsiveness and OA could occur simultaneously, although they often had opposite signs. Indeed, the two effects were statistically independent of each other, i.e., modulations of visual responses were not related to the level of excitability of the neurons. 5. Control experiments were performed that showed that the effects of changing the viewing distance were not due to the retinal patterns in that the modulations of visual responsiveness were independent of the dot density. Seventeen cells were also tested for a possible effect of vergence by the use of prisms. When there was an effect of distance, it could be closely or partially reproduced by using prisms. These controls, together with the effects observed on OA, strongly suggest that the modulations of neural activity of the V1 neurons by the viewing distance are extraretinal in origin, probably proprioceptive. 6. The modulation of visual responsiveness by the viewing distance in the primary visual cortex indicates that integration of information from both retinal and extraretinal sources can occur early in the visual processing pathway for cortical representation of three-dimensional space. A functional scheme of three-dimensional cortical circuitry is discussed that shows cortical areas where disparity selectivity and modulations of visual activity by the angle of gaze have been described so far.

Animals↗