Deep brain stimulation in Parkinson's disease: opposite effects of stimulation in the pallidum.
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Antiparkinson Agents↗
Biomedical subjects
D Dormont
Publications and source records attributed to D Dormont.
Search for a nuclear localization signal in the prion protein.
Spongiform transmissible encephalopathies are neurodegenerative diseases characterized by the accumulation, in infected brains, of a pathological form of a normal host-encoded protein called PrP. Previous data have shown that PrP could interact with cytosolic factors, including nuclear molecules, emphasizing the possible function of such interactions. Moreover, in infected cells, PrP is observed not only at the plasma membrane but also in the nuclear compartment. The N-terminal extremity of the mature PrP has been thought to harbor a nuclear localization signal reminiscent of the nuclear localization signal of the simian virus 40 large T antigen. By designing a fusion protein between the putative nuclear localization signal of PrP and the green fluorescent protein, we have shown that the N-terminal sequence of PrP is not efficient in targeting the protein in the nuclear compartment. This implies new insights regarding the way by which PrP could, however, reach the nuclear compartment.
Amino Acid Sequence↗
Distribution and submicroscopic immunogold localization of cellular prion protein (PrPc) in extracerebral tissues.
In transmissible spongiform encephalopathies (TSE), such as scrapie in animals and Creutzfeldt-Jakob disease in humans, the central event is the conversion of a host-encoded amyloidogenic protein (PrPc) into an abnormal isoform (PrPsc) that accumulates as amyloid in TSE brain. PrPc is a membrane sialoglycoprotein synthesized in the central nervous system and elsewhere. We have examined the ultrastructural localization of PrPc in numerous hamster and some human extracerebral tissues, by means of a post-embedding electron-microscopic method combined with immunogold labeling. In stomach, intestine, lung, and kidney from hamsters, and in stomach, kidney, and spleen from humans, immunogold labeling specific for PrPc is observed on various cellular substructures related to secretory pathways: Golgi apparatus, secretory globules, and plasma membrane. In mucous epithelial cells of stomach and intestine, PrPc appears to be concentrated in secretory globules, suggesting a role for PrPc in the secretory function of the digestive tract. The secretory aspect of PrPc may be a key to understanding the physiopathological mechanisms underlying TSE.
Animals↗
[Pseudotumorous presentation of neuro-Behçet: role of the withdrawal of colchicine?].
BACKGROUND: Neurological involvement occurs in 10 to 28% of patients with Behçet's disease. CASE REPORT: We report a case of neurological pseudotumoral presentation of Behçet's in a patient with a long standing disease treated with low dose of prednisone and colchicine (1 mg/day), 2 months after withdrawal of colchicine. CONCLUSION: Neurological manifestations during Behçet disease can be secondary to direct central nervous system involvement (encephalitis, encephalomyelitis) or vascular angitis (essentially cerebral venous thrombosis and, rarely, intracranial aneurysms). Neurological pseudotumoral presentation is rarely reported.
Anti-Inflammatory Agents↗
[Unconventional transmissible agents: risk of transmission by blood].
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Animals↗
CD80 expression is decreased in hyperplastic lymph nodes of HIV+ patients.
A centrofollicular hyperplasia is present within secondary lymphoid organs during all the asymptomatic phase of the HIV disease. Although this hyperplasia has been well characterized by histological studies, the nature of the phenotypic alterations in B cell populations occurring within HIV+ lymphoid organs remains to be established. By immunohistochemistry, we thus investigated whether a particular germinal center (GC) B cell population was increased during HIV-induced hyperplasia and whether any phenotypic change was specific to HIV-1 infection. As compared to normal tonsils (three cases) and HIV- hyperplastic lymph nodes (eight patients), we observed a loss of GC polarization in all HIV+ sections (11 patients), with no more delineation between dark and light zones, as shown by Ki67, CD10, CD77, CD95 and CD86 staining. In contrast to CD86 expression which remained as intensive in HIV+ as in HIV- lymph nodes, CD80 staining was strongly decreased in GC of HIV+ lymph nodes but not in their extrafollicular zones. The loss of CD80 expression from CD19+ B cells was also observed by cytometric analysis of cell suspensions of three HIV+ patients. Although we found no evidence of an increase in a particular GC B cell subset in HIV-1-induced hyperplasia, the strong GC disorganization observed may induce impaired cell-cell interactions and thus participate in the loss of CD80 antigen. In contrast to HIV- situations where CD80 and CD86 was similarly expressed on B cells, the lower level of CD80 expression in HIV+ GC may favor Th2 T cell responses through CD86-CD28 interactions.
Adult↗
Neutralizing antibodies and complement-mediated, antibody-dependent enhancement (C'-ADE) of human immunodeficiency virus infection in its vertical transmission.
PROBLEM: Mother-to-child transmission is a major route for the spread of human immunodeficiency virus (HIV) worldwide. Our understanding of its mechanisms and parameters is still limited. Among the factors possibly involved in virus passage determination are the level and quality of antiviral humoral response. METHOD OF STUDY: Anti-HIV-1/Lai neutralizing activity in sera from 35 mother-infant pairs (in which 13 transmission cases occurred) was investigated, as was the complement-mediated antibody-dependent enhancement capacity of the same sera. RESULTS: Neutralization titers of 640 or more were found only in four mothers of uninfected children, but this result was not significant. No significant link was obtained with the occurrence of complement-mediated, antibody-dependent enhancement. CONCLUSIONS: As suggested by a synthesis of the literature, vertical transmission of HIV is probably the result of multiple active and/or stochastic parameters in the mother, the fetal structures, and the viral population. The precise definition of cellular mechanisms involved in in utero infection would help to better define which immune activity in the mother should be more carefully considered.
Cohort Studies↗
Diffusion-weighted magnetic resonance imaging in a case of cerebral venous thrombosis.
BACKGROUND: Diffusion-weighted imaging (DWI) is the most sensitive MR sequence in acute arterial ischemic stroke but has not yet been evaluated in venous cerebral ischemia. We describe a patient with DWI performed at the acute phase of a venous ischemic stroke. CASE DESCRIPTION: A rapid cerebral MRI including DWI and fast fluid-attenuated inversion recovery (FLAIR) sequences was performed at the acute phase of a venous stroke confirmed by conventional angiography. DWI showed a slight decrease in apparent diffusion coefficient values 3 hours after onset (0.53+/-0.07x10(-3) mm2/s) and was normal 48 hours later (0.064+/-0.15x10(-3) mm2/s). Fast FLAIR sequences showed large left frontoparietal hyperintensities. The lack of a clear decrease in apparent diffusion coefficient values associated with marked FLAIR abnormalities may suggest prominent or early associated vasogenic edema. Physiopathological differences between arterial and venous ischemia may explain the different type of DWI FLAIR abnormalities during the acute phase as well as the better recovery of neurological deficit in venous stroke than in arterial ischemic stroke. CONCLUSIONS: In the context of an acute stroke, the contrast between marked FLAIR and subtle DWI abnormalities on MRI may reflect the venous mechanism of cerebral ischemia.
Brain↗
[What is your diagnosis? Hypertrophic olivary degeneration].
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Adult↗
Loss of digitations of the hippocampal head on high-resolution fast spin-echo MR: a sign of mesial temporal sclerosis.
PURPOSE: The purpose of our study was to determine the significance of the loss of visualization of digitations in the hippocampal head on high-resolution fast spin-echo MR images in the diagnosis of mesial temporal sclerosis (MTS). METHODS: MR examinations of 193 patients with intractable epilepsy were evaluated retrospectively for atrophy and/or T2 signal changes of the hippocampi. On the basis of these two criteria, MTS was diagnosed in 63 hippocampi. Twenty-four patients had surgery, and MTS was confirmed in all cases. A control group included 60 hippocampi in patients with frontal seizures but no MR-detectable abnormalities. In a second step, visibility of digitations in the hippocampal head was evaluated in the two groups of subjects. RESULTS: In the group of 63 hippocampi in which MTS was diagnosed, digitations were not visible in 51 cases, poorly visible in eight, and sharply visible in four. Twenty-two of 24 hippocampi in which MTS was confirmed histologically had no MR-visible digitations. In the control group, digitations were sharply visible in 55 cases and poorly visible in five. Statistical analysis showed a significant difference in the visualization of digitations between hippocampi with MTS and those in the control group. CONCLUSION: With a sensitivity of 92% and a specificity of 100%, the finding of complete loss of digitations in the hippocampal head may be used as a major diagnostic criterion to establish the MR diagnosis of MTS. This morphologic sign may also be useful in the diagnosis of bilateral MTS or to validate the MR diagnosis of MTS when there is no obvious atrophy or changes in signal intensity.
Adolescent↗
Are the brains of monozygotic twins similar? A three-dimensional MR study.
PURPOSE: The role of genetic mechanisms and the influence of environmental events in human brain development have been difficult to evaluate. The purpose of this study was to compare the cerebral cortical morphology and midline structures of monozygotic twin pairs using MR imaging. METHODS: Six observers, blinded to twin pairings, evaluated the 3-D renderings of the cortical surface and midline structures from MR images of seven monozygotic twin pairs. A morphometric analysis of the corpus callosum and of the distance between the anterior and posterior commissures was also performed. RESULTS: Despite surprising anatomic differences, the brains of the twin pairs were similar enough to enable the observers to distinguish twin pairs from unrelated subjects. Five of six observers correctly identified the brains of all seven twin pairs; the remaining observer failed to make a correct match in only one of seven pairs. Three of six observers identified the midline sagittal images of the related twins in all seven pairs, and the other three identified the related midline sagittal images in five of seven pairs. The results were statistically significant. CONCLUSION: Although the observed differences in morphologic characteristics between twins necessarily reflect nongenetic influences, the cortical patterns and midline structures of monozygotic twins probably are genetically similar.
Adult↗
[Astrocytes and lentivirus infection in an experimental models of macaque infected with SIVmac251].
The present study demonstrates the susceptibility of astrocytes to infection with SIVmac251. Indeed, primary cultures of astrocytes derived from simian adult brains, can be infected in vitro with the SIVmac251. Results show that SIVmac251 establishes a persistent infection in primary astroglial cultures and that viral replication can be reactivated by TNF-alpha, GM-CSF, IFN-gamma. Viral proteins as Nef, Rev, Vpx and occasionally gp120/160 are evidenced by immunocytochemistry. In vivo SIVmac251 and/or HIV-2 infected astrocytes have been isolated from brains of macaques following ex vivo primary cultures. The whole of these results demonstrated that, in this model, SIV establishes a persistent state of infection of astrocytes, that viral replication can be reactivated by cytokines and moreover suggest strongly an in vivo infection of astrocytes in the brain of these infected macaques.
Animals↗
[Biology of non-conventional transmissible agents or prions].
Transmissible subacute spongiform encephalopathies (TSE) are a group of human and animal diseases which includes Creutzfeldt-Jakob disease, Gerstmann-Straüssler-Scheinker syndrome (GSS), Kuru, fatal familial insomnia (FFI), scrapie in sheep and goat, mink and feline transmissible encephalopathy, chronic wasting disease, and bovine spongiforme encephalopathy (BSE). TSE are transmissible among individuals of the same species and some of different species. These diseases stem from a specific category of agents that have biological and physiochemical characteristics unlike other micro-organisms; they are known as transmissible spongiform encephalopathy agent (TSA), prions, or virinos. So far, despite considerable progress made in the molecular biology toward the understanding of neurological injury, the nature of the TSA/prions remains unknown. TSE are characterised by the pathognomic accumulation, within the central nervous system of the infected individual, of a normal protein from the host organism, the PrP (prion protein). Differences between the PrP isolated from normal individuals (PrP-c) and PrP isolated from infected individuals (PrP-res) have been investigated. There are no differences in the sequence in amino acids, and the secondary structure seems identical, but since normal PrP is totally degraded by proteinase K pathological PrP resists to enzymatic digestion. One can therefore describe two PrP isoforms: a normal isoform, the PrP-c (c for cellular), sensitive to proteinase K and present in the normal individual and in the infected patients or animals: and a pathological isoform, the PrP-res, resistant to proteinase K and present in amount proportional to the infectivity in the brains of infected individuals. The presence of TSA/prions is detectable in the spleens of infected animals early after inoculation; it is then present in the CNS following a period not exceeding a half of the total length of the experimental disease. In the CNS, PrP-res is the origin of spongiosis and gliosis that are observed in infected individuals. A double causality, "infectious" and genetic, of these diseases can be derived from the various ideas currently accepted. Indeed the genetic basis of some familial forms has now been confirmed and transmissibility has been proven in natural situations such as the outbreak of CJD among children treated with extractive growth hormone and the recent surge of a new disease decimating British cattle, the bovine spongiform subacute encephalopathy, or mad cow disease. In TSE affected individuals, PrP has a key role in the incubation time and in the species barrier.
Animals↗
Techniques for quantification of cytokine mRNAs.
Various methods are currently used to monitor cytokine mRNA expression levels in clinical samples. In instances where sample size is limited (e.g. biopsies), amplification procedures such as reverse transcription followed by polymerase chain reaction amplification appear to be the only ones that are currently useful. This paper provides a review of such techniques for the detection and quantitation of cytokine message in clinical samples, and compares semiquantitative and competitive techniques in terms of sensitivity, reproducibility, feasibility and costs.
Animals↗
[Dementia and memory: morphologic imagery with MRI].
Modern imaging techniques, and notably magnetic resonance imaging (MRI) enable an increasingly precise exploration of primary degenerative dementias. The main contribution of imaging is to demonstrate lesion localizations which confirm the degenerative nature of the observed disorders, contributing to an understanding of the correlation between clinical signs and causal lesions. The development of techniques quantifying cerebral volume which can be applied to an analysis of small structures such as the hippocampus coupled with a better understanding of primary degenerative dementias allow more specific study of the atrophy than could be obtained with a global assessment of ventricular dilatation. More recently, the development of MRI methods studying brain perfusion open the way for noninvasive exploration of perfusion anomalies in these patients.
Dementia↗
[Influence of irradiation on the risk of HIV virus transmission by bone allograft].
PURPOSE: The purpose of this study was to determine, when assuming the worst case scenario of bone contamination, the sterility assurance level in bone transplantation treated by irradiation and after donor screening. MATERIAL AND METHODS: The virus: We employed the HIV-1, LAV-1 as our reference strain, which has always been cultured on normal human cells (and has therefore never been in contact with cell lines). To test viral virulence, we used a very sensitive cell line: MT2 cell line, a T lymphoblastoid cell line which is HTLV-I positive and is sensitive to HIV-1/LAV-1 infection. It was maintained in RPMI 1640 culture medium containing 10 per cent heat-inactivated fetal calf serum (Boehringer Mannheim), 2 mM L-glutamine (Boehringer Mannheim) and 1 per cent antibiotics (PSN 100 x, Gibco). Cell concentration was 100,000 cells per milliliter. Irradiation was performed using an accelerator delivering electrons of 6.2 MeV providing several tens of kilograys in a few seconds. The dose delivered was checked by placing alanine dosimeters at the site of the HIV aliquots. Alanine is a solid amino acid which, when irradiated, gives rise to free radicals; these were counted using electron paramagnetic resonance (relative standard deviation of less than 1 per cent). RESULTS: 25 kilograys irradiation of 316,227 TCID50/ml at -80 degrees C led to a considerable titer reduction (3 logs) with 316 TCID50/ml remaining. According to the technique's sensitivity (100 TCID50/ml) and to the sensitivity with which the dose of irradiation can be measured (less than 1 per cent), the D10 value with "99 per cent confidence limits" was between 8.3 kilograys and 7.2 kilograys. Assuming the worst characteristics of irradiation, we have chosen 8.3 kilograys as the D10 value for -80 degrees C. DISCUSSION: Considering a mean level of contamination of 30 TCID50 per milliliter of plasma during the asympomatic phase of infection, the reduction of the transmission risk of HIV by a femoral head allograft was calculated in the best case to be only 5 per cent when performed at 25 kilograys. Irradiation cannot be considered as a process able to achieve sterility of the graft and has to be associated to an extensive screening. However irradiation associated with appropriate screening of donors decreases the risk of transmission of the disease under one out of one million in femoral allograft implantation.
Bone Transplantation↗
[Outcome of patients treated with intra-peritoneal immunochemotherapy for ovarian cancer].
OBJECTIVE: The aim of this study is to show that i.p. chemotherapy improves the evolution of the patients with an ovarian cancer, as the risk of a small number of complications due to this route of administration. METHODS: 85 patients (11 stage Ic, 4 IIc and 70 stage III) were treated from 1980 to 1993 (median of follow up > 77 months) by a cisplatin based immunochemotherapy administered intraperitoneally, by a needle. RESULTS: Median overall survival exceeds, 72 months (60 months for stage III). Out of 41 relapses, 11 took place after 48 months of follow up. Delayed general complications consisted of 2 chronic nephotoxicities due to CDDP and one leukemia. Local complications are dominated by serous adherences (5 cases of plastic peritonitis). Secondary cytoreductions turned out to be beneficial in this series in spite of relapse diagnosis of them being carried out to late. CONCLUSION: Classic imagery remains disappointing for the exploration of the pelvic abdominal region. Paclitaxel by i.p. way seems very promising, which should launch once again interest in secondary debulking surgery.
Adjuvants, Immunologic↗