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Biomedical subjects

P Remy

Publications and source records attributed to P Remy.

At least 37 records · Page 2Linked to original sources
PubMed2000

[18 F]-dopa PET study in patients with juvenile-onset PD and parkin gene mutations.

+Parkin gene mutations cause a form of early-onset autosomal recessive PD with neuronal loss in the substantia nigra and no Lewy bodies. The authors present a PET [18F]-dopa study of one familial and two sporadic cases with juvenile-onset PD resulting from parkin gene mutations. They found a profound decrease of [18F]-dopa uptake, representing 28% of putamen and 44% of caudate nucleus control subject values. PD caused by parkin gene mutations is distinct from idiopathic PD on molecular grounds but has similar clinical and PET findings.

Adult↗
PubMed2000

Comparison of clinical data sets acquired on different tomographs using 6-18F-L-dopa.

Longitudinal positron emission tomography (PET) studies of 6-18F-L-dopa uptake in the striatum are used to assess the progression of Parkinson's disease or the survival of neuronal cells grafted in parkinsonian patients. These studies are performed over several years, and data analysis may suffer from the change from old tomographs to new machines with better sensitivity and spatial resolution. Furthermore, such studies on parkinsonian patients may be accomplished in either 2D or 3D acquisition mode. The aforementioned improvements offer great benefits for the study of neurodegenerative diseases, especially those affecting the striatum. However, direct comparison of data is not straightforward owing to variation in scanner characteristics. In this study, we assessed the feasibility of comparing the 6-18F-L-dopa striatal uptake values (Kc) measured in two groups of healthy subjects using two tomographs of different generations. We re-studied and compared acquisitions performed on 14 healthy subjects using 6-18F-L-dopa. Half of these studies had been performed in 2D acquisition mode using an ECAT 953B. The other half had been performed in 3D acquisition mode using an ECAT EXACT HR+. Different reconstruction protocols were used and the Kc values obtained were statistically compared. The results showed that lowering the transverse spatial resolution of images obtained with the scanner having the better spatial resolution, so that it more closely matched that of the other machine, allowed similar KC values to be obtained in healthy subjects. This study shows that quantitative results of 6-18F-L-dopa scans can be matched between different scanners with different intrinsic resolutions. This can be accomplished using adequate modifications of the reconstruction parameters. Such modifications can be used to help in the longitudinal monitoring of parkinsonian patients using different tomographs.

Adult↗
PubMed2000

Temporal lobe dysfunction in childhood autism: a PET study. Positron emission tomography.

OBJECTIVE: The nature of the underlying brain dysfunction of childhood autism, a life-long severe developmental disorder, is not well understood. Although researchers using functional brain imaging have attempted to contribute to this debate, previous studies have failed to report consistent localized neocortical brain dysfunction. The authors reasoned that early methods may have been insensitive to such dysfunction, which may now be detectable with improved technology. METHOD: To test this hypothesis, regional cerebral blood flow was measured with positron emission tomography (PET) in 21 children with primary autism and in 10 nonautistic children with idiopathic mental retardation. Autistic and comparison groups were similar in average age and developmental quotients. The authors first searched for focal brain dysfunction in the autistic group by using a voxel-based whole brain analysis and then assessed the sensitivity of the method to detect the abnormality in individual children. An extension study was then performed in an additional group of 12 autistic children. RESULTS: The first autistic group had a highly significant hypoperfusion in both temporal lobes centered in associative auditory and adjacent multimodal cortex, which was detected in 76% of autistic children. Virtually identical results were found in the second autistic group in the extension study. CONCLUSIONS: PET and voxel-based image analysis revealed a localized dysfunction of the temporal lobes in school-aged children with idiopathic autism. Further studies will clarify the relationships between these temporal abnormalities and the perceptive, cognitive, and emotional developmental abnormalities characteristic of this disorder.

Adolescent↗
PubMed1999

Functional anatomy of neuropsychological deficits after severe traumatic brain injury.

BACKGROUND: Neurobehavioral disorders after severe traumatic brain injury (TBI) are poorly correlated with focal lesions detected by structural neuroimaging techniques such as CT scan or MRI. OBJECTIVE: To explore the relationships between regional cerebral glucose metabolism at rest, as measured by PET, and neurobehavioral status after severe TBI at the subacute stage. METHODS: Thirteen patients without focal structural lesion on MRI were studied. Neuropsychological assessment included tests of memory, attention and speed of information processing, and executive functions, and a global neurobehavioral assessment. Regional cerebral glucose metabolism at rest was measured with (18F)-fluorodeoxyglucose and PET. RESULTS: A close link was found between cognitive and behavioral disorders and decreased cortical metabolism in prefrontal and cingulate cortex. Tests of memory and executive functions significantly correlated with regional metabolism in the mesial and lateral prefrontal cortex and the cingulate gyrus. Behavioral disorders correlated significantly with mesial prefrontal and cingulate metabolisms. CONCLUSION: These results suggest a predominant role of prefrontal and cingulate dysfunction in cognitive and behavioral disorders of patients with severe traumatic brain injury, even in the absence of focal structural lesion of the brain. Further cognitive functional activation research using PET or functional MRI might help clarify the relative contributions of both areas to dysfunction.

Adolescent↗
PubMed1999

Upregulation of human heme oxygenase gene expression by Ets-family proteins.

Overexpression of human heme oxygenase-1 has been shown to have the potential to promote EC proliferation and angiogenesis. Since Ets-family proteins have been shown to play an important role in angiogenesis, we investigated the presence of ETS binding sites (EBS), GGAA/T, and ETS protein contributing to human HO-1 gene expression. Several chloramphenicol acetyltransferase constructs were examined in order to analyze the effect of ETS family proteins on the transduction of HO-1 in Xenopus oocytes and in microvessel endothelial cells. Heme oxygenase promoter activity was up-regulated by FLI-1ERGETS-1 protein(s). Chloramphenicol acetyltransferase (CAT) assays demonstrated that the promoter region (-1500 to +19) contains positive and negative control elements and that all three members of the ETS protein family were responsible for the up-regulation of HHO-1. Electrophoretic mobility shift assays (EMSA), performed with nuclear extracts from endothelial cells overexpressing HHO-1 gene, and specific HHO-1 oligonucleotides probes containing putative EBS resulted in a specific and marked bandshift. Synergistic binding was observed in EMSA between AP-1 on the one hand, FLI-1, ERG, and ETS-1 protein on the other. Moreover, 5'-deletion analysis demonstrated the existence of a negative control element of HHO-1 expression located between positions -1500 and -120 on the HHO-1 promoter. The presence of regulatory sequences for transcription factors such as ETS-1, FLI-1, or ERG, whose activity is associated with cell proliferation, endothelial cell differentiation, and matrix metalloproteinase transduction, may be an indication of the important role that HO-1 may play in coronary collateral circulation, tumor growth, angiogenesis, and hemoglobin-induced endothelial cell injuries.

Animals↗
PubMed1999

Dopaminergic dysfunction in midbrain dystonia: anatomoclinical study using 3-dimensional magnetic resonance imaging and fluorodopa F 18 positron emission tomography.

OBJECTIVE: To determine the role of damage to neuronal systems, especially the dopaminergic system, in patients with symptomatic dystonia and mesencephalic lesions. DESIGN: Stereotaxic magnetic resonance imaging analysis and positron emission tomography after the administration of fluorodopa F 18. PATIENTS: Of a group of 48 patients with unilateral dystonia following a stroke, 7 patients with a well-defined midbrain lesion were selected. RESULTS: All patients had unilateral dystonic posture of an upper extremity and cerebellar dysmetria or hypotonia. Cerebellar tremor was present in 1 patient. Two patients had resting and postural tremor, which showed a marked improvement with treatment with levodopa. In patients with dystonia only, dopaminergic lesions were mostly confined to the ventromesial mesencephalon and red nucleus area, including the substantia nigra and nigrostriatal and cerebellothalamic fibers. Dystonia was severe and did not resolve with time in patients with lesions involving the nigrostriatal pathway, and the degree of dopaminergic denervation revealed by positron emission tomography was correlated with the severity of dystonia. In patients with resting and postural tremor, lesions of the dopaminergic structures were larger and located more laterally and dorsally in the pars compacta, the perirubral and retrorubral areas, and extending to the central tegmental tract. CONCLUSIONS: Dopaminergic dysfunction plays a role in the occurrence and severity of midbrain dystonia, and additional lesions to dopaminergic neurons in the perirubral and retrorubral areas result in tremor that responds to levodopa treatment.

Adolescent↗
PubMed1999

Xl erg: expression pattern and overexpression during development plead for a role in endothelial cell differentiation.

The ets gene family encodes transcription factors related to the proto-oncogene c-ets-1 and involved in cell proliferation, differentiation, and oncogenic transformation. We have characterized the Xenopus homologue of the human erg gene, an ets-related-gene, and its expression has been examined throughout early embryonic development. Xl erg encodes at least two proteins, resulting from alternative splicing events. The transcripts are restricted to the forming endocardium, the endothelial cells of the blood vessels and to the neural crest-derived mesenchyme cells of the pharyngial arches. When Xl ERG is expressed ectopically in Xenopus embryos by microinjection of synthetic mRNA, multiple developmental defects are observed. Dorsally injected embryos have their AP axis shortened and present severe defects in eye and somite morphogenesis. Ventrally injected embryos show a posteriorization of the cells having received the message together with ectopic endothelial cell differentiation as revealed by the accumulation of X-msr transcripts. In both cases, accumulation of erythrocytes in structures not connected with the blood circulatory system can be observed. Our data suggest that Xl erg may be involved in cell motility and in the development of the circulatory system.

Alternative Splicing↗
PubMed1999

Correlation of viral RNA, alanine aminotransferase, and histopathology in hepatitis C virus-associated hepatitis.

BACKGROUND: Hepatitis C virus (HCV) infection is usually monitored by the level of alanine aminotransferase (ALT) and histopathological changes in liver biopsy specimens. However, accumulating data indicate these parameters are not always correlated with disease progression or the response of HCV infection to therapy. MATERIALS AND METHODS: Using the Amplicor PCR Monitor Test Kit (Roche Diagnostic Systems, Branchburg, NJ), HCV RNA level was measured in 38 patients with positive anti-HCV antibodies and in 21 of those patients after interferon treatment. The grade and stage of histological changes on hematoxylin and eosin-stained sections of liver biopsy specimens were evaluated on a scale of 1 to 4. In each case, the HCV RNA level was compared with the histological grade or stage and level of ALT and statistically analyzed by Student's t-test. RESULTS: ALT level did not correlate with pretreatment and posttreatment levels of HCV RNA or histopathological changes. However, there was a statistically significant correlation between HCV RNA and histological grade (P,.05). CONCLUSION: HCV RNA measurement is a better means of determining and monitoring HCV infection than either ALT level or histopathological characteristics and may provide insight into hepatic injury caused by HCV infection even without an invasive liver biopsy.

Adult↗
PubMed1999

Negative regulation of human heme oxygenase in microvessel endothelial cells by dexamethasone.

Heme oxygenase-1 (HO-1) is a stress protein, and its induction has been suggested to participate in defense mechanisms against agents that promote oxidative injury such as endotoxins and heme. We have shown that the inflammatory cytokines, interleukin-6 (IL-6) and heme-induced HO-1 gene expression, were suppressed by dexamethasone (Dex) in a sustained manner. We examined the mechanism by which the anti-inflammatory agent, Dex, inhibits IL-6 and heme-induced HO-1 expression in rabbit coronary endothelial cells. Endothelial cells treated with heme (10 microM) and IL-6 (25 ng/ml), increased HO-1 mRNA 15- and 60-fold, respectively. The activity of HO was increased 3-fold after such treatment. Although Dex failed to inhibit heme-mediated HO-1 mRNA and HO activity, it was able to reverse IL-6-stimulated HO activity. Several human HO-1 promoter-drive chloramphenicol acetyltransferase (CAT) constructs were examined to analyze IL-6 and Dex-mediated modulation of the HO-1 gene in endothelial cells. CAT assays revealed that the HO-1 promoter region between -180 and -1500 might contain a Dex-mediated negative regulator. Gel mobility shift assays using nuclear extracts from IL-6-treated endothelial cells showed a binding to the synthetic 21 base pairs of the HO-1 sequence that contains the putative STAT3 sequence. STAT3-specific probe inhibited nuclear binding protein to the putative HO-1-STAT3 sequence. This suggests that IL-6 induction of human HO-1 is mediated via the JAK-STAT pathway and that Dex inhibition of gene expression is carried out by activation of a transcriptional protein in competition with the STAT3 binding site.

Acute-Phase Proteins↗
PubMed1999

Primary somatosensory cortex activation is not altered in patients with ventroposterior thalamic lesions: a PET study.

BACKGROUND AND PURPOSE: We know remarkably little about the mechanisms underlying cortical activation. Such mechanisms might be better understood by studying the effect of well-localized lesions on the cortical activations in simple paradigms. METHODS: We used H(2)(15)O and positron emission tomography to measure regional cerebral blood flow (rCBF) at rest and during hand vibration in 7 patients with unilateral thalamic lesion involving the ventroposterior (VP) somatosensory thalamic relay nuclei. We compared the results with those obtained in 6 patients with thalamic lesions sparing the VP nuclei and 6 healthy controls. RESULTS: The patients with VP lesions had a selective hypoperfusion at rest in the ipsilesional primary sensorimotor cortex (SM1). This hypoperfusion was significantly correlated with the degree of contralateral somatosensory deficit. This abnormality may reflect the deafferentation of SM1 from its somatosensory thalamic input. Despite this deafferentation, the ipsilesional SM1 was normally activated by the vibration of the hypoesthetic hand. CONCLUSIONS: The fact that a lesion of the somatosensory thalamic relay nuclei alters the rCBF at rest in SM1 but not its activation by hand vibration indicates that the mechanism of cortical activation is complex, even in the case of simple sensory stimulation. In addition, a dissociation may occur between obvious neurological deficits and apparently normal activation patterns, which suggests that activation studies should be interpreted cautiously in patients with focal brain lesions.

Adult↗
PubMed1999

Somatosensory cortical activations are suppressed in patients with tactile extinction: a PET study.

OBJECTIVE: To investigate whether tactile extinction alters the cortical somatosensory activations induced by hand vibration. BACKGROUND: Tactile extinction occurs mainly after right-brain lesions and consists of the inability to perceive a contralesional cutaneous stimulation when a similar stimulus is applied to the mirror region of the ipsilesional hemibody. The pathophysiology of tactile extinction is poorly understood, but it is considered to be a deficit of selective attention of somatosensory stimuli. Although other theories have been proposed, our understanding of the pathophysiology of tactile extinction may benefit from functional imaging studies. METHODS: We selected three patients with pure tactile extinction and a mainly subcortical right-brain lesion that spared the primary sensorimotor cortex (SM1). We used PET to investigate the responses to unilateral and bilateral hand vibration in SM1 and the secondary somatosensory cortical area (SII). RESULTS: During bilateral hand vibration, activation was normal in the left SM1, suppressed in the right SM1, and markedly decreased in both SII, which was consistent with the extinction of the left-hand stimulus. During unilateral left-hand vibration, the activation of the right SM1 was still markedly impaired, but the activation of both SII was normal. CONCLUSIONS: We found marked changes in the activation of cortical somatosensory areas induced by hand vibration in patients with tactile extinction. The role of selective attention in cortical activation is also examined.

Aged↗
PubMed1999

[Mechanisms of aphasia recovery and brain imaging].

Aphasia recovery may depend on right hemisphere or non-lesioned left hemisphere structures, pre-morbid brain language organization, and de novo learning of language. Here we review the brain imaging evidence supporting these different hypotheses. CT-scan studies have investigated the prognosis value of size and site of left hemisphere lesions. The size of the lesion is a global but not an individual predictor of the initial severity and subsequent recovery of aphasia. Studies on the site of the lesion have given different results for verbal expression and comprehension. There is no consensus on a single critical site for recovery of verbal expression in non-fluent aphasia, which may depend on sub-cortical more than cortical extend of the lesion. Conversely the extend of the lesion in the superior temporal gyrus emerges as a critical negative factor for comprehension recovery. Rest measurements of brain metabolism have consistently shown that aphasia severity depends much more on the degree of dysfunction of language-related areas in the left hemisphere than on the site of the lesion it-self. This suggests that aphasia recovery may depend on metabolic dysfunction recovery in peri-lesional structures. More recently, activation studies have shown consistent right hemisphere activation during language tasks in aphasic subjects, but their role in recovery remains debated. It is likely limited, and may depend on atypical pre-morbid language lateralization. Left hemisphere activations are also found in aphasic patients. They are often relocalized in peri-lesional areas, and emerge in most studies as the main factor of aphasia recovery.

Aphasia↗
PubMed1998

Gene transfer of human heme oxygenase into coronary endothelial cells potentially promotes angiogenesis.

Heme oxygenase (HO-1) is a stress protein that has been suggested to participate in defense mechanisms against agents that induce oxidative injury such as hemoglobin/heme, hypoxia-ischemia and cytokines. Overexpression of HO-1 in endothelial cells (EC) might, therefore, protect against oxidative stress produced under these pathological conditions, by generation of CO, a vasodilator, and bilirubin, which has antioxidant properties that enhance blood vessel formation to counteract hypoxia-induced injury. A plasmid containing the cytomegalovirus promoter (pCMV) neomycin human HO-1 gene complexed to cationic liposomes, lipofectin, was used to transfect rabbit coronary microvessel EC. Cells transfected with human HO-1 gene demonstrated a twofold increase in HO activity and maintained a similar phenotype as in the nontransfected cells. Cell number in transfected cells with human HO-1 gene increased by about 45%, as compared to nontransfected or those transfected with control pCMV. Transfected and nontransfected EC revealed a similar response to basic fibroblast growth factor (bFGF) in capillary formation. However, transfected cells with the human HO-1 gene exhibited a twofold increase in blood vessel formation. The angiogenic response of EC to overexpression of HO-1 gene provides direct evidence that the inductive form of HO-1 following injury represents an important tissue adaptive mechanism for moderating the severity of cell damage produced in inflammatory reaction sites of hemorrhage, thrombosis and hypoxic-ischemia. Thus, HO-1 may participate in the regulation of EC activation, proliferation and angiogenesis.

Animals↗
PubMed1998

MRI-stereotactical approach for neural grafting in basal ganglia disorders.

Optimization of the procedures for neural grafting is a timely issue, as this technique has proven beneficial for a few patients with late-stage Parkinson's disease in pilot studies and therefore may expand to become a more widely available therapeutic. In this research, one major issue is that of the placement of the cell deposits in the right target areas within the striatum. Although it is widely accepted that these suitable regions are the sensorimotor regions of the putamen, reliable delineation of these areas using classical stereotactical mapping techniques remains difficult. Along the course of a 5-year-long clinical transplantation program, we have developed an original procedure based on magnetic resonance imaging of the striatum on parasagittal views. This technique allowed us to identify precisely, and reproducibly in each patient, three subregions of the putamen (precommissural, commissural, and postcommissural) to be implanted. On the basis of the literature defining the sensorimotor putaminal regions in nonhuman primates, it was subsequently possible to extrapolate and localize these regions in each patient, thus providing a basis for the placement of cell deposits. Examples taken from our series of grafted patients demonstrate the value of this procedure that, in addition, minimizes interference of interindividual variability in the interpretation of clinical results.

Basal Ganglia↗
PubMed1998

Validation of the three-dimensional acquisition mode in positron emission tomography for the quantitation of [18F]fluoro-DOPA uptake in the human striata.

Three-dimensional (3D) positron emission tomography (PET) is attractive for [18F]fluoro-DOPA studies, since the sensitivity improvement is maximal for radioactive sources located in central planes, which is usually the case for the human striata. However, the image quantitation in that mode must be assessed because of the nearly threefold increase in scattered coincidences. We report the results of [18F]fluoro-DOPA studies performed on six normal volunteers. Each one was scanned in the 3D and two-dimensional (2D) modes on the same tomograph. The quantitation in the 3D and 2D modes was compared for a Patlak graphical analysis with the occipital counts as the input function (Ki) and a striatooccipital ratio analysis. We find that, in 3D PET, a scatter correction is required to preserve the same quantitation as in 2D PET. When the 3D data sets are corrected for scatter, the quantitation of the [18F]fluoro-DOPA uptake, using the Patlak analysis, is similar in the 2D and 3D acquisition modes. Conversely, analysis of the striatooccipital ratio leads to higher values in 3D PET because of a better in-plane resolution. Finally, using the 3D mode, the dose injected to the subjects can be reduced by a factor greater than 1.5 without any loss in accuracy compared to the 2D mode.

Adult↗
PubMed1998

The avian fli gene is specifically expressed during embryogenesis in a subset of neural crest cells giving rise to mesenchyme.

The ets-family of transcription factors is involved in the development of endothelial and hematopoietic cells. Among these genes, fliwas shown to be responsible for erythroblastomas and Ewing's sarcomas. Its involvement in Ewing's sarcoma, a putative neurectodermal tumor, as well as the in situ hybridization studies performed in mice and Xenopus suggested a role in neural crest development. We cloned quail fli cDNA in order to analyze in more detail its expression in neural crest cells, which have been extensively studied in avian species. Fli gene maps on chicken chromosome 1 to band q31->q33. Two RNAs are transcribed, most likely arising from two different promoters. The analysis of its expression in neural crest cells reveals that it is expressed rather late, when the neural crest cells reach their target. Among the various lineages derived from the crest, it is restricted to the mesenchymal one. It is maintained at later stages in the cartilage of neural crest but also of mesodermal origin. In addition, fli is expressed in several mesoderm-derived cells: endothelial cells as well as intermediate and splanchnopleural mesoderm.

Amino Acid Sequence↗