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P Remy

Publications and source records attributed to P Remy.

At least 55 records · Page 3Linked to original sources

X-twi is expressed prior to gastrulation in presumptive neurectodermal and mesodermal cells in dorsalized and ventralized Xenopus laevis embryos.

Early X-twi expression has been now investigated from egg laying to the early neurulation stages in Xenopus embryos, using both in situ hydridization and the more sensitive techniques of RT-PCR. We show that in unfertilized eggs, a decreasing gradient of X-twi transcript distribution is observed from animal to vegetative caps. X-twi RNA can be weakly detected at stages prior to gastrulation, and with increased intensity from stage 8 onwards. At blastula, X-twi transcripts are located towards the animal pole, and as gastrulation begins, they are detected in the developing axial mesoderm and then they accumulate in the sensorial layer of the neurectoderm, the mesodermal layer and in neural crest cells up to late neurula stages. We show, in addition, that in lithium-chloride- and UV-treated Xenopus embryos (that are respectively both "anteriorized/dorsalized" and in "posteriorized/ventralized"), X-twi RNA is detected in cells in similar positions to those that express X-twi in normal embryos. As a whole, our results show that X-twi is expressed even when regionalization of the mesoderm is disturbed and raises the question of a putative function of X-twi prior to gastrulation.

Animals↗

Ets-1 and Ets-2 proto-oncogenes exhibit differential and restricted expression patterns during Xenopus laevis oogenesis and embryogenesis.

Xenopus XI-ets-1 and XI-ets-2 are maternally expressed. From late oogenesis to early embryogenesis their transcripts are localized to the animal pole and the intermediate zone, suggesting a function in the differentiation of animal blastomeres and future mesoderm. Their presence at the level of germ plasm suggests also a role in the differentiation of the germinal lineage. Both zygotic genes are expressed ubiquitously beginning at MBT, and then restricted to a circumblastoporal collar. In neurula and tailbud stages, ets-1 and ets-2 transcripts are detected in neural crest cells and their derivatives. Specific transcription can also be observed for ets-1 in the hemangioblastic precursors, in endothelial cells of the forming heart and blood vessels. Ets-2 is itself specifically expressed in the putative pronephros and in the forming pronephric tubules and extending pronephric duct. Like another member of the ets-gene family (XI-fli), both genes are transcribed in regions of the embryo undergoing important morphogenetic modifications, especially in migrating cells and/or along their migration pathways. We postulate that these genes orchestrate modifications of cellular adhesion. Changes in the expression of cadherins and integrins repertories would be consistent with such a role and could account for the phenotypes we reported earlier for XI-fli overexpression. Such a role would be critical for tumor cell dissemination, in addition to the one already ascribed to ets-1 in the expression of proteases specific for the extracellular matrix.

Animals↗

Transcription of XLPOU3, a brain-specific gene, during Xenopus laevis early embryogenesis.

XLPOU3 is a member of the Xenopus POU domain family of genes, encoding a class of homeodomain-containing transcription factors implicated in cell differentiation during development. Here we describe the isolation and characterisation of XLPOU3b, an allelic genomic counterpart of the XLPOU3 cDNA previously described (Baltzinger et al. (1992) Nucleic Acids Res. 20, 1993), and the spatio-temporal transcription patterns of this gene during development, as determined by Northern blotting and whole-mount in situ hybridisation. Like other genes encoding POU domains of class III, XLPOU3b is intronless. XLPOU3 and XLPOU3b proteins share 82% amino acid identity with the mammalian N-Oct-3/Brn-2 proteins. XLPOU3 mRNA, which is first detected at the neurula stage, is expressed in the developing brain and spinal cord. In addition, XLPOU3 transcription is observed in a restricted region of the auditory vesicle during development. The results suggest that XLPOU3 may participate in patterning the central nervous system during early Xenopus development.

Age Factors↗

Long-term outcome of unilaterally transplanted parkinsonian patients. I. Clinical approach.

Five patients with Parkinson's disease, unilaterally transplanted with foetal mesencephalic cells into putamen (n=1) or putamen and caudate (n=4), were followed throughout a period of 15-36 months after surgery, according to the recommendations of the core assessment programme for intracerebral transplantations (CAPIT). All these patients exhibited an increase in the fluorodopa uptake in the grafted putamen, which was most significant in the first and last patient of the series. Long-term bilateral improvement of skilled hand movements was observed, starting between the third and sixth month after grafting, and confirmed by the statistical analysis of CAPIT timed tests. A mild to moderate effect on the amount of 'off' time and 'on-off' fluctuations was observed, whereas, apart from one case, no other clear effect on gait, walking and speech was found. One patient included in the study, already suffering slight cognitive impairment, clearly exhibited progression of a dementia process after surgery. Daily living activities were clearly improved in only one of the other four patients. At the end of the study period, all patients needed L-dopa therapy at a similar or higher dose than before grafting, but, in most of them, other dopaminergic drugs were reduced or stopped. All patients exhibited bilateral dyskinesias before grafting that were greatly decreased in intensity a few months after surgery. Delayed asymmetrical dyskinesias, occurring on the side displaying the better motor improvement, i.e. contralateral to the graft, were observed in three patients. These results suggest that neural transplants may influence two central mechanisms involved in motor function and the onset of dyskinesias. These effects are likely to occur through complex interactions with the post-synaptic dopaminergic receptors. The occurrence of dyskinesias might simply reflect increased presynaptic storage and release of dopamine. Alternatively, it might, in part, represent some other long-term deleterious effect of the graft. Since PET-scan data indicate that the reinnervation obtained is sub-optimal, it will be of interest to obtain a larger and denser reinnervation of the host striatum and to try, thereafter, to reduce the dose of L-dopa.

Aged↗

Recovery from nonfluent aphasia after melodic intonation therapy: a PET study.

We examined mechanisms of recovery from aphasia in seven nonfluent aphasic patients, who were successfully treated with melodic intonation therapy (MIT) after a lengthy absence of spontaneous recovery. We measured changes in relative cerebral blood flow (CBF) with positron emission tomography (PET) during hearing and repetition of simple words, and during repetition of MIT-loaded words. Without MIT, language tasks abnormally activated right hemisphere regions, homotopic to those activated in the normal subject, and deactivated left hemisphere language zones. In contrast, repeating words with MIT reactivated Broca's area and the left prefrontal cortex, while deactivating the counterpart of Wernicke's area in the right hemisphere. The recovery process induced by MIT in these patients probably coincides with this reactivation of left prefrontal structures. In contrast, the right hemisphere regions abnormally activated during simple language tasks seem to be associated with the initial persistence of the aphasia. This study supports the idea that abnormal activation patterns in the lesioned brain are not necessarily related to the recovery process.

Adult↗

Overexpression of the Xenopus Xl-fli gene during early embryogenesis leads to anomalies in head and heart development and erythroid differentiation.

The product of the Xl-fli gene, a Xenopus laevis transcription factor of the ets family, specifically expressed in several lineage of migratory cells during Xenopus development (Meyer et al., Int. J. Dev. Biol. 39: 909-919, 1995) was overproduced during Xenopus embryogenesis, upon microinjection of a synthetic transcript in the fertilized egg or in the early embryo. This results in anomalies of the antero-posterior and dorso-ventral polarities, and in tissue differentiation, particularly in the eye- and head cartilage development, as well as erythroid differentiation (absence of erythrocyte differentiation in the circulating blood, often accompanied by ectopic localization of mature erythrocytes, leading to important hemangiomas). Cytological examination reveals at gastrulation the existence of abnormal cells separating the different embryonic layers, suggesting modifications of the cellular adhesion properties. The possible involvement of the fli gene in controlling the dissemination of migratory cells is discussed.

Animals↗

Clinical correlates of [18F]fluorodopa uptake in five grafted parkinsonian patients.

To assess the efficacy of fetal mesencephalic grafts in Parkinson's disease, it is important to know if the grafted cells survive and are functional. Positron emission tomography (PET) and [18F]fluorodopa ([18F]dopa) have been used to demonstrate the survival of the grafted cells, but the relationship of [18F]dopa uptake changes in the grafted striatum to motor function remains unclear. We investigated this question with 16 serial PET scans in 5 severe parkinsonian patients unilaterally grafted in whom we found a significant and progressive increase of the [18F]dopa uptake in the grafted putamen. The number of patients was too small to assess the sensitivity of [18F]dopa PET scans in individual patients. Yet, by analyzing the 16 serial PET scans we found a correlation between the [18F]dopa uptake (Ki) in the grafted putamen and the percentage of daily time spent "on," suggesting that Ki changes have a functional meaning. In addition, the Ki values were correlated with the contralateral finger dexterity to the same extent in both the grafted and nongrafted putamen. These results indicate that [18F]dopa uptake reflects the motor function of the opposite side of the body, similarly in the grafted and ungrafted putamen, at least in terms of these tasks. Finally, extrapolating from these correlations offers the suggestion that clinical optimal results of the graft could be achieved if the graft brings the Ki values in the putamen to about two standard deviations of mean control values.

Brain↗

Striatal dopaminergic denervation in pallidopyramidal disease demonstrated by positron emission tomography.

Pallidopyramidal disease is a rare disease of young patients in which they manifest a parkinsonian syndrome and pyramidal signs. Pallidopyramidal disease has been attributed to a degeneration of the pallidum and the pyramidal tract, although only 1 patient has been studied postmortem. In the present report, [18F]fluorodopa positron emission tomography in 2 patients showed a marked dopaminergic denervation of the striatum, suggesting that this disease corresponds more to a nigropallidopyramidal dysfunction.

Adolescent↗

Factors associated with Pneumocystis carinii pneumonia in Wegener's granulomatosis.

OBJECTIVE: To determine the factors associated with the occurrence of Pneumocystis carinii pneumonia (PCP) in Wegener's granulomatosis (WG). METHODS: We retrospectively compared a group of 12 patients with WG and PCP (PCP group), with 32 WG patients without PCP followed over the same period in the same centres (control group). RESULTS: The mean delay of onset of PCP after the start of the immunosuppressive therapy was 127 (SD 128) days. Before treatment, the clinical and biological features of the two groups were similar, except for the mean lymphocyte count which was lower in the PCP group than in the control group (1060/mm3 v 1426/mm3; p = 0.04). During treatment, both groups were lymphopenic. There was a significant difference between the lowest absolute lymphocyte count in each group (244/mm3 in the PCP group v 738/mm3 in the control group; p = 0.001). During the first three months of treatment, the lymphocyte count was less than 600/mm3 at least once in 10 of the 12 patients in the PCP group and in 11 of the 32 patients in the control group (p < 0.01). The mean cumulative dose of cyclophosphamide was greater in the PCP group than in the control group at the end of both the second (1.55 mg/kg/day v 0.99 mg/kg/day; p = 0.05) and the third (1.67 mg/kg/day v 0.97 mg/kg/day; p = 0.03) months. However, in multivariate analysis, the only two factors independently and significantly associated with the occurrence of PCP were the pretreatment lymphocyte count (p = 0.018) and the lymphocyte count three months after the start of the immunosuppressive treatment (p = 0.014). CONCLUSIONS: The severity of lymphocytopenia before and during immunosuppressive treatment is the factor best associated with PCP in WG.

Female↗

Delayed maturation of the frontal cortex in childhood autism.

OBJECTIVE: The authors investigated the metabolic maturation of the frontal cortex in pre-school autistic children. METHOD: Regional cerebral blood flow (CBF) in five children with primary autism diagnosed according to the DSM-III-R criteria was studied longitudinally. Regional CBF in each of the autistic children was measured with single photon emission computed tomography twice during their development: at the age of 3-4 years and 3 years later. At each stage, the autistic children were compared to an age-matched comparison group of five nonautistic children with normal development. RESULTS: A transient frontal hypoperfusion was found in the autistic children at ages 3-4 years; this corresponded to the pattern of perfusion observed in much younger normal children. By the ages of 6-7, the autistic children's frontal perfusion had attained normal values. CONCLUSIONS: Since CBF patterns in children are related to maturational changes in brain function, these results indicate a delayed frontal maturation in childhood autism. Such a delayed brain maturational process is consistent with the clinical data and cognitive performance of autistic children.

Adolescent↗

Peduncular 'rubral' tremor and dopaminergic denervation: a PET study.

Lesions causing so-called rubral tremors frequently involve the substantia nigra or the nigrostriatal fibers, suggesting dopaminergic denervation as possibly contributory. We examined this hypothesis using PET and [18F]-fluorodopa in six patients with a contralateral tremor following a peduncular lesion. The denervation revealed by PET was even more marked than in severe parkinsonian patients. All patients showed partial to complete improvement with levodopa therapy. PET evaluation of D2-receptors with [76Br]bromolisuride showed no asymmetry of the D2 binding despite the important asymmetry of 18F-fluorodopa uptake. Our results indicate an important involvement of the nigral dopaminergic system in peduncular tremors that appears to be independent of postsynaptic dopamine receptors.

Adult↗

Low-dose angiotensin-converting-enzyme inhibitor captopril to reduce proteinuria in adult idiopathic membranous nephropathy: a prospective study of long-term treatment.

The objective of this trial was to determine the long-term antiproteinuric effect of a low-dose of the angiotensin-converting-enzyme inhibitor (ACEI) captopril in patients with idiopathic membranous nephropathy (IMN), stable renal function, and no indicators of poor long-term prognosis. Fourteen adult IMN outpatients (median age 53 years) with a median duration of disease of 3 years received 12.5 mg of captopril twice a day for 12 months in a prospective trial. The effects of therapy were evaluated on the basis of plasma creatinine, 24-h proteinuria, the proteinuria selectivity index, albuminaemia, and serum IgG levels. Data were compared by means of the non-parametric paired Wilcoxon test. Three patients withdrew from the trial. Renal function remained stable in the 11 who completed the study. A clear decrease in proteinuria was observed after 1 month of therapy, which persisted with time and was associated with a trend towards a further long-term decrease. An increase in serum albumin was only observed after 6 months of therapy, again with a trend towards an increase over time. Serum IgG levels increased during therapy. This study together with data from the literature suggests a potential long-term benefit of angiotensin-converting-enzyme inhibitors in moderately proteinuric IMN. Prospective trials comparing low-dose and high-dose ACEI to no treatment or a placebo in non-severe IMN are now required.

Adult↗

Whole-mount in situ hybridization reveals the expression of the Xl-Fli gene in several lineages of migrating cells in Xenopus embryos.

The expression of the Xl-Fli gene, which belongs to the ets family of transcription factors, was studied by whole-mount in situ hybridization during Xenopus embryogenesis. Digoxigenin-labeled antisense RNA probes were synthesized by in vitro transcription and used in the hybridization reaction. In addition to expression in territories invaded by neural crest cells reported earlier (Meyer et al., 1993), we observed Xl-Fli gene expression in a number of regions affected by important cellular migrations and/or epithelium<==>mesenchyme transitions: in the endothelial cells of the heart, in blood vessels, along the pronephric duct migration pathway and at the level of hypophysis. The possibility that the FLI protein is involved in the expression of guidance cues and/or modification of the cellular adhesion properties is discussed. A screening of a promoter library with a consensus sequence, bound by the FLI protein with a high affinity, revealed the presence of putative FLI response elements in a number of genes encoding adhesion molecules or components of the extra-cellular matrix.

Animals↗

High-dose immunoglobulin therapy for severe IgA nephropathy and Henoch-Schönlein purpura.

OBJECTIVE: To determine if polyvalent IgG is promising therapy for severe IgG nephropathy. DESIGN: Open prospective cohort study. SETTING: Referral nephrology unit. PATIENTS: 11 adult patients with severe IgA nephropathy (9 who had idiopathic disease and 2 who had Henoch-Schönlein purpura) and indicators of poor prognosis. INTERVENTION: Patients were given high-dose immunoglobulins (2 g/kg each month) for 3 successive months, followed by intramuscular immunoglobulins (preparation content, 16.5%; 0.35 mL/kg every 15 days) for another 6 months. MEASUREMENTS: Histologic changes were analyzed by comparing pre- and post-therapy renal biopsy specimens blindly, using an activity index (14-point scale), a sclerosis index (10-point scale), and a semiquantitative immunofluorescence test of immune deposits. Proteinuria, hematuria, leukocyturia, enzymuria, and global renal function (creatinine and polyfructosan clearances) were evaluated before and after intervention. RESULTS: Proteinuria (median level before intervention, 5.20 g/d; median level after intervention, 2.25 g/d), hematuria, and leukocyturia decreased substantially. The decrease in glomerular filtration rate was greatly slowed or stopped (median rate of decline in glomerular filtration before, -3.78 mL/min per month; after, 0 mL/min per month). The histologic index of activity (median index before, 5; after, 2) and the staining intensity of glomerular IgA and C3 deposits also decreased. Immunoglobulin therapy was well tolerated. CONCLUSIONS: Immunoglobulin therapy may be effective in treating severe IgA nephropathy and protecting renal function. However, prospective controlled trials must confirm these preliminary results.

Adolescent↗

Movement- and task-related activations of motor cortical areas: a positron emission tomographic study.

Using repeated measurements of regional cerebral blood flow with positron emission tomography, we investigated the regional cortical activations induced in 10 normal subjects, by two different finger motor tasks, i.e., a repeated flexion-extension of all fingers and a repeated flexion-extension of the middle finger. The all-finger movement only activated the primary sensorimotor cortex (SM) and the supplementary motor area (SMA) contralateral to the movement. However, the activation of the SMA was clearly task related during this motor task, because it was only observed when the movement was triggered by an auditory cue but not when it was self-paced. The middle finger movement was performed during self-paced conditions. It induced a much more complex pattern of activation than the all-finger movement, characterized by a high degree of SM and SMA activation contralateral to the side of the movement, as well as a slight ipsilateral activation of these areas. We suggest that this pattern of cortical activation may reflect the process of individuating finger movement or the early stages of motor learning of this unusual and technically difficult movement. Our data also confirm that the SM activation is closely linked to the intrinsic parameters of the movement; while the SMA may be activated by different aspects of the movement realization and preparation.

Adult↗