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Biomedical subjects

M Tardieu

Publications and source records attributed to M Tardieu.

At least 55 records · Page 3Linked to original sources
PubMed1999

Neuronal apoptosis does not correlate with dementia in HIV infection but is related to microglial activation and axonal damage.

To characterize the distribution of apoptotic neurons and their relationships with the stage of disease, a history of HIV-dementia, and the degree of productive HIV infection, microglial activation and axonal damage, we examined the brains of 40 patients. Samples of frontal and temporal cortex, basal ganglia and brain stem were taken post-mortem from 20 patients with AIDS (including three with HIV-dementia, and eight with cognitive disorders that did not fulfil the criteria for HIV-dementia), 10 HIV-positive asymptomatic cases and 10 seronegative controls. Neuronal apoptosis was demonstrated by in situ end labelling in 18 AIDS cases and two pre-AIDS cases; a single apoptotic neuron was present in the temporal cortex of a control. Semiquantitative evaluation showed that the severity of neuronal apoptosis in the cerebral cortex correlated with the presence of cerebral atrophy, but not with a history of HIV dementia. There was no global quantitative correlation between neuronal apoptosis and HIV encephalitis or microglial activation. However, there was some topographical correlation between these changes. In the basal ganglia, apoptotic neurons were much more abundant in the vicinity of multinucleated giant cells and/or p24 expressing cells. Microglial activation was constantly present in these areas. Axonal damage was identified using beta-amyloid-precursor protein (betaAPP) immunostaining in 17 AIDS and eight pre-AIDS brains. Although no global quantitative correlation could be established between axonal damage and neuronal apoptosis there was an obvious topographic correlation supporting the view that axonal damage, either secondary to local microglial activation or due to the intervention of systemic factors, may also contribute to neuronal apoptosis.

AIDS Dementia Complex↗
PubMed1999

HIV-1-related central nervous system diseases.

The frequency of HIV-1-related central nervous system diseases has been reduced by new combinations of antiviral agents, in part through the reduction of both viral load in blood and continuous penetration of virus into brain. This will probably not be sufficient to abolish any neurological risk. HIV-1-related dementia also depends on the intensity of glial cell activation in the central nervous system, which induces reactivation of latent infection in these cells with possible reinfection of the periphery, and on secretion of soluble inflammatory mediators acting on nearby neurones. The fact that only a small subgroup of patients suffers from neurological diseases also suggests a genetic component, at the level either of viral receptors or of the immune response.

AIDS Dementia Complex↗
PubMed1999

Persistent infection of human oligodendrocytic and neuroglial cell lines by human coronavirus 229E.

Human coronaviruses (HuCV) cause common colds. Previous reports suggest that these infectious agents may be neurotropic in humans, as they are for some mammals. With the long-term aim of providing experimental evidence for the neurotropism of HuCV and the establishment of persistent infections in the nervous system, we have evaluated the susceptibility of various human neural cell lines to acute and persistent infection by HuCV-229E. Viral antigen, infectious virus progeny and viral RNA were monitored during both acute and persistent infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK-N-SH, neuroglioma H4, and oligodendrocytic MO3.13 cell lines, were all susceptible to an acute infection by HuCV-229E. The CHME-5 immortalized fetal microglial cell line was not susceptible to infection by this virus. The MO3.13 and H4 cell lines also sustained a persistent viral infection, as monitored by detection of viral antigen and infectious virus progeny. Sequencing of the S1 gene from viral RNA after approximately 130 days of infection showed two point mutations, suggesting amino acid changes during persistent infection of MO3.13 cells but none for H4 cells. Thus, persistent in vitro infection did not generate important changes in the S1 portion of the viral spike protein, which was shown for murine coronaviruses to bear hypervariable domains and to interact with cellular receptor. These results are consistent with the potential persistence of HuCV-229E in cells of the human nervous system, such as oligodendrocytes and possibly neurons, and the virus's apparent genomic stability.

Astrocytoma↗
PubMed1999

Acute and persistent infection of human neural cell lines by human coronavirus OC43.

Human coronaviruses (HuCV) are recognized respiratory pathogens. Data accumulated by different laboratories suggest their neurotropic potential. For example, primary cultures of human astrocytes and microglia were shown to be susceptible to an infection by the OC43 strain of HuCV (A. Bonavia, N. Arbour, V. W. Yong, and P. J. Talbot, J. Virol. 71:800-806, 1997). We speculate that the neurotropism of HuCV will lead to persistence within the central nervous system, as was observed for murine coronaviruses. As a first step in the verification of our hypothesis, we have characterized the susceptibility of various human neural cell lines to infection by HuCV-OC43. Viral antigen, infectious virus progeny, and viral RNA were monitored during both acute and persistent infections. The astrocytoma cell lines U-87 MG, U-373 MG, and GL-15, as well as neuroblastoma SK-N-SH, neuroglioma H4, oligodendrocytic MO3.13, and the CHME-5 immortalized fetal microglial cell lines, were all susceptible to an acute infection by HuCV-OC43. Viral antigen and RNA and release of infectious virions were observed during persistent HuCV-OC43 infections ( approximately 130 days of culture) of U-87 MG, U-373 MG, MO3.13, and H4 cell lines. Nucleotide sequences of RNA encoding the putatively hypervariable viral S1 gene fragment obtained after 130 days of culture were compared to that of initial virus input. Point mutations leading to amino acid changes were observed in all persistently infected cell lines. Moreover, an in-frame deletion was also observed in persistently infected H4 cells. Some point mutations were observed in some molecular clones but not all, suggesting evolution of the viral population and the emergence of viral quasispecies during persistent infection of H4, U-87 MG, and MO3.13 cell lines. These results are consistent with the potential persistence of HuCV-OC43 in cells of the human nervous system, accompanied by the production of infectious virions and molecular variation of viral genomic RNA.

Cell Line↗
PubMed1999

Differences in kinetics of human cytomegalovirus cell-free viral release after in vitro infection of human microglial cells, astrocytes and monocyte-derived macrophages.

Microglial cells and astrocytes isolated from human embryonic proencephalon were compared to monocyte-derived macrophages (MDM) for their ability to replicate human cytomegalovirus (HCMV) in vitro. A specific cytopathic effect was observed in microglial cells and astrocytes, but not in MDM. A high percentage of glial cells but a low percentage of MDM expressed immediate-early and late viral antigens. The ability of HCMV-infected microglial cells and astrocytes to release viral particles in their supernatants was significantly higher than that of infected MDM. Human microglial cells and astrocytes at an early stage of development are highly susceptible to HCMV infection.

Antigens, Viral↗
PubMed1999

[Accurate use of imaging in ankle sprain].

Imaging ankle trauma has two goals: to evaluate bone lesions and to appreciate the capsulo-ligamentous tears. Concerning bone lesions, Ottawa's criteria specify the clinical characteristics to perform radiography in the emergency conditions. These recommendations negate the need for nearly 30% of unnecessary radiographs initially performed. Four views of the tarsis have been selected: anteroposterior, lateral, internal rotation, external oblique. Immediate screening of the ligament is very accurately performed with ultrasound, which depicts the number of bundle concerned and the extent of the lesions. This requires an experienced operator and a high quality sonograph. Stress radiography should not be performed anymore as sensitivity is around 50%. Arthrography and CT arthrography are very accurate when performed immediately but are more expensive. This report highlights the complementary role of radiography and ultrasound to evaluate ankle sprain.

Ankle Injuries↗
PubMed1998

Identification and molecular characterization of a small 11q23.3 de novo duplication in a patient with Rett syndrome manifestations.

We report on an interstitial duplication of the long arm of chromosome 11 [46XX,dup(11) (q23.3)] in a girl with atypical Rett syndrome (RS). This case was discovered during a systematic cytogenetic study of RS. Fluorescent in situ hybridization including total chromosome painting and use of regional specific YAC, cosmid and plasmid probes, was used to confirm the chromosome 11q involvement and to identify the landmarks of the smallest 11q duplication reported to date. The findings are compared to cases of trisomy 11q reported previously, all of which have a larger duplication and different clinical manifestations. Surprisingly, mental retardation and behavior disorders are less severe in these cases.

Adult↗
PubMed1998

Excessive production of tumour necrosis factor alpha by peripheral blood mononuclear cells in X-linked adrenoleukodystrophy.

Previous studies have suggested that cytokine production may play a role in the cerebral demyelination and phenotypical variations of X-linked adrenoleukodystrophy (ALD). At initial evaluation, the serum titre of tumour necrosis factor alpha (TNFalpha) but not interleukin IL-1alpha, IL-1beta, IL-6, IL-4 and interferon INF-gamma of 12 ALD patients with cerebral demyelination, was higher than that of controls and of six ALD patients without cerebral demyelination. However, TNFalpha was not detected in the cerebrospinal fluid of the same patients with cerebral demyelination. In a serial study of 15 patients over 2-5 years, the level of serum TNFalpha paralleled the progression of demyelination. Peripheral blood mononuclear cells from 15 symptomatic ALD patients, irrespective of their clinical phenotype, produced higher levels of TNFalpha than controls after in vitro stimulation by lipopolysaccharide. The production of other cytokines was normal. Abnormal production of TNFalpha was observed in two of six asymptomatic ALD patients but was absent in both of two bone marrow transplanted ALD patients. These data suggest that monocytes of ALD patients have an intrinsic alteration in the regulatory pathway of TNFalpha production.

Adolescent↗
PubMed1998

Neuropathogenesis of HIV-1 infection. Outstanding questions.

Significant progress in understanding and treating acquired immunodeficiency syndrome (AIDS) has been made over the last 5 years. Current multi drug therapies prolong patients' lives and reduce the incidence of neurobehavioural symptoms. However, the impact of therapy on human immunodeficiency virus type one (HIV-1), the causative agent of AIDS, in the brain, is unknown. Some patients develop dementia in spite of the multi drug therapies and others develop subtle neurobehavioural changes that diminish the quality of their prolonged lives. Thus, HIV-1 infection of the central nervous system remains an important clinical concern. Although much is known about neuropathology of HIV-1 infection, major questions about neuropathogenesis remain. How does HIV-1 reach the brain? Is it present in neurons and glial cells? What is the biological and therapeutic significance of neurotropism of HIV-1? What causes neuronal damage and loss? And, is CNS a reservoir of HIV-1? More research in vivo and in situ in humans and in animals, is needed to answer these outstanding questions. Specific experiments addressing these questions are proposed.

AIDS Dementia Complex↗
PubMed1998

[Waiting for the end of poliomyelitis. Setting of the last phase of the eradication program. National Commission for the Certification of the Eradication of Poliomyelitis].

The worldwide eradication of poliomyelitis is expected within a few years. A reinforcement of epidemiological, clinical and viral supervision is necessary. Besides a sustained immunization effort, particular attention is required from all clinicians concerning the cases of non-traumatic acute flacid palsy that they may observe. In these cases it is asked to clinicians to perform a search for enterovirus in stool and spinal fluid, and a poliomyelitis serology.

Cerebrospinal Fluid↗
PubMed1998

[Neurogenic bladder in children with acute transverse myelopathy].

BACKGROUND: Neurogenic sphincter dysfunction may result from acute transverse myelopathy. The aim of this paper is to study the course of such a dysfunction and to propose management techniques. PATIENTS AND METHODS: The files of 21 children admitted at the mean age of 8 years 5 months (2 to 14 years, 8 months) for acute transverse myelopathy were retrospectively studied. RESULTS: Bladder sphincter dysfunction occurred in the first days of disease in 85% of these patients. Abnormal perception of micturition was one of the most constant and specific symptoms. Anorectal function was also impaired. Complete regressive course was noted in 38% of patients, minor sequellae in 39% and major sequellae beyond 6 months of course in 23%. None upper tract deterioration was noted after 3 years of course. Factors of favorable prognosis were early motor function recovery (especially recommencement of walking before 20 days) and early management of bladder dysfunction (inability to void had better prognosis than urinary incontinence). CONCLUSION: Early systematic bladder drainage in case of inability to void might be essential for improved prognosis.

Acute Disease↗
PubMed1998

Childhood dermatomyositis: clinical course of 36 patients treated with low doses of corticosteroids.

Thirty-six patients with juvenile dermatomyositis, seen consecutively between 1983 and 1996 and treated initially with low doses of corticosteroids (prednisolone 1 mg/kg/day), were studied retrospectively to evaluate their long-term evolution and to identify factors predictive of the functional outcome. After a mean follow-up of 4.9 years, 28 (78%) of the patients were well without functional impairment; five patients had inactive disease but with persisting disabilities; and three patients had active disease despite several years of treatment. Fifteen children (42%) developed dystrophic calcifications which, in five of these patients, interfered with functions. These patients treated for juvenile dermatomyositis with a low dose corticosteroid regimen had an evolution identical to that of the published series of patients treated with higher doses and probably had a better quality of life. The best predictors of good functional recovery and minimal calcinosis were early treatment after the onset of symptoms and low creatine kinase serum level at the time of diagnosis.

Adolescent↗
PubMed1998

Transient cerebral arteriopathy: a disorder recognized by serial angiograms in children with stroke.

Repeated clinical evaluation and cerebral arteriography during the evolution of ischemic strokes of idiopathic origin allowed us to characterize a transient cerebral arteriopathy. We retrospectively studied the clinical characteristics, course, and neuroimaging features of this disorder in nine children. Of 34 children with ischemic strokes seen consecutively between 1984 and 1995, 9 (26%) were diagnosed as having transient attack of the cerebral arterial wall, termed transient cerebral arteriopathy. All of these patients had previously been in good health. The mean age at the time of the first stroke was 6 years (range, 2 9/12 years to 13 4/12 years). All children presented with acute hemiplegia. A recurrence of the stroke took place 3 months at the latest after the initial infarct in three children (mean clinical follow-up 2 7/12 years). Cerebral imaging in all the patients showed small subcortical infarcts located in basal ganglia or internal capsule. Arteriography revealed multifocal lesions of the arterial wall (focal stenosis or segmental narrowing), mostly located in the initial parts of basal arteries of the carotid system. Longitudinal arteriographic follow-up showed initial worsening of these arterial lesions (n = 5) for a maximum duration of 7 months followed by complete regression (n = 2), improvement (n = 5), or stabilization of the lesions (n = 2). Five patients had a complete clinical recovery. Further studies are necessary to confirm a presumed inflammatory cause of this arteriopathy.

Acute Disease↗
PubMed1998

Congenital muscular dystrophy and cerebellar atrophy.

Two siblings and two other unrelated patients had congenital muscular weakness and dystrophic changes but normal immunocytochemical stainings for merosin, dystrophin, and dystrophin-related proteins on muscle biopsy. All had marked ataxia and cerebellar atrophy or hypoplasia. Cerebral white matter and cortical organization appeared normal.

Atrophy↗
PubMed1998

Induction of human immunodeficiency virus type 1 replication in human glial cells after proinflammatory cytokines stimulation: effect of IFNgamma, IL1beta, and TNFalpha on differentiation and chemokine production in glial cells.

Although evidence for human immunodeficiency virus 1 (HIV-1) presence in the central nervous system (CNS) of infected patients is well established, the intensity of viral replication within the brain is not usually known. In vitro, human embryonic microglial cells internalized HIV-1 through a CD4-dependent pathway but were not permissive to viral replication. We observed that HIV replication was induced when CNS cell cultures were stimulated for 14 days by a combination of proinflammatory cytokines including IFNgamma, IL1beta, and TNFalpha. After long-term cytokine stimulation, morphologically differentiated glial cells appeared, in which HIV-1 tat antigen was detected after infection. Thus, variations in the stage of maturation/activation of CNS cells under inflammatory conditions probably play a major role in facilitating massive production of HIV-1. We then studied the effect of prolonged cytokine stimulation on the secretion of inflammatory mediators by glial cells. An early increased secretion of prostaglandin F2alpha and chemokines (RANTES>>MIP-1alpha>>MIP-1beta) was observed, due to both microglia and astrocytes. In contrast to persistent PGF2alpha production, an extinction of RANTES and MIP-1beta but not of MIP-1alpha secretion occurred during the 14 days of stimulation and was inversely correlated with the ability of glial cells to replicate HIV-1. The study of the secretory factors produced in response to a persistent inflammation could provide a better understanding of the modulation of HIV replication in glial cells.

Cell Differentiation↗
PubMed1998

[Productive replication of human cytomegalovirus in primary microglial cells].

Human cytomegalovirus (HCMV) infection can result in neurological symptoms. In vitro replication of the HCMV was studied in primary cultures of microglial cells from the central nervous systems (CNS) of human embryos. The microglial cells were infected with various amounts of either the AD169 laboratory HCMV strain or a clinical HCMV isolate. A specific cytopathic effect occurred within 24 h and persisted for two months. Immunocytochemical tests for immediate early and late viral antigens done one and three days after the infection demonstrated that 60% to 80% of the microglial cells were infected and that 3% to 8% were the site of viral DNA replication. Kinetic studies showed accumulation of viral particles in the supernatant during the first two weeks after the infection. Prestimulation of the cells by PMA 24 h before the infection was associated with increased release of viral particles and with an increased percentage of cells expressing late viral antigens. The microglial cells of the human embryonic CNS are fully permissive targets for the HCMV. The in vitro HCMV model used in this study may prove useful for investigating the pathophysiology of HCMV encephalitis, in particular after mother-to-fetus transmission of the virus.

Antigens, Viral↗