Biomedical subjects

R A Du Pasquier

Publications and source records attributed to R A Du Pasquier.

7 recordsLinked to original sources

PubMed2006

Favourable outcome of progressive multifocal leucoencephalopathy in two patients with dermatomyositis.

Progressive multifocal leucoencephalopathy (PML), a demyelinating disease caused by the JC virus (JCV), occurs in immunosuppressed patients and carries a poor prognosis. A favourable outcome is reported in two patients with PML and dermatomyositis. Immunosuppressive drugs were stopped in patient 1 but could only be partially tapered in patient 2. The JCV-specific CD8+ T cell response was strong in patient 1 and weak in patient 2. Both were treated with cytosine-arabinoside, and patient 2 was also treated with mirtazapine, a 5HT2A receptor antagonist. Combination of these drugs might be helpful to treat HIV-negative patients with PML.

Adrenergic alpha-Antagonists↗

PubMed2004

Detection of JC virus-specific cytotoxic T lymphocytes in healthy individuals.

The polyomavirus JC (JCV) infects 85% of healthy individuals, and its reactivation in a limited number of immunosuppressed people causes progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. We hypothesized that JCV-specific cytotoxic T lymphocytes (CTLs) might control JCV replication in healthy individuals, blocking the evolution of PML. Using 51Cr release and tetramer staining assays, we show that 8 of 11 HLA-A*0201+ healthy subjects (73%) harbor detectable JCV-specific CD8+ CTLs that recognize one or two epitopes of JCV VP1 protein, the HLA-A*0201-restricted VP1p36 and VPp1100 epitopes. We determined that the frequency of JCV VP1 epitope-specific CTLs varied from less than 1/100,000 to 1/2,494 peripheral blood mononuclear cells. More individuals had JCV VP1-specific than cytomegalovirus-specific CTLs (8 of 11 subjects [73%] versus 2 of 10 subjects [20%], respectively). These results show that a CD8+-T-cell response against JCV is commonly found in immunocompetent people and suggest that these cells might protect against the development of PML.

Adult↗

PubMed2003

Productive infection of cerebellar granule cell neurons by JC virus in an HIV+ individual.

BACKGROUND: In the setting of severe immunosuppression, the polyomavirus JC (JCV) can cause a lytic infection of oligodendrocytes. This demyelinating disease of the CNS white matter (WM) is called progressive multifocal leukoencephalopathy (PML). JCV has a very narrow host-cell range and productive infection of neurons has never been demonstrated. Patient, methods, and results: An HIV-1-infected patient presented with signs of pyramidal tract and cerebellar dysfunction. Brain MRI revealed T2 hyperintensities in the WM of both frontal lobes and cerebellar atrophy. His disease progressed despite therapy and he died 6 months later. In addition to classic PML findings in the frontal lobe WM, autopsy revealed scattered foci of tissue destruction in the internal granule cell layer (IGCL) of the cerebellum. In these foci, enlarged granule cell neurons identified by the neuronal markers MAP-2 and NeuN reacted with antibodies specific for the polyomavirus VP1 capsid protein. Electron microscopy showed 40 nm viral particles, consistent with polyomaviruses, in these granule cell neurons. In addition, JCV DNA was detected by PCR after laser capture microdissection of cells from the areas of focal cell loss. Finally, in situ hybridization studies demonstrated that many granule cell neurons were infected with JCV but did not contain viral proteins. Sequence analysis of the JCV regulatory region from cerebellar virions showed a tandem repeat pattern also found in PML lesions of the frontal lobe WM. CONCLUSION: JCV can productively infect granule cell neurons of the IGCL of the cerebellum. This suggests a role for JCV infection of neurons in cerebellar atrophy occurring in HIV-infected individuals.

Acquired Immunodeficiency Syndrome↗

PubMed2003

The effect of aging on postural stability: a cross sectional and longitudinal study.

AIMS OF THE STUDY: Only a good knowledge of the effects of age on postural stability allows differentiating between physiological aging and pathologies leading to its impairment. The aims of this study were to define the posturographic parameters which best reflected the effects of aging on postural stability and to determine the slope of postural stability impairment related to aging. PATIENTS AND METHODS: Postural stability of 50 normal volunteers aged 25-83 years (55.4) was studied with one Kistler force plate. Subjects were asked to stand for 30 s on two-legged stance, eyes open then closed. The center of pressure displacement (COPd) and velocities (COPv), in the antero-posterior (x) and the medio-lateral (z) axis, the sway axis, and the integral of COP displacement vs. time were computed. Eleven subjects were retested at 3 and 6 months to estimate the reliability of posturographic measurements. In addition, 28 subjects aged 25-83 years (60.2) were retested 2.2 years after their first posturographic assessment. RESULTS: COPxv best reflected postural stability impairment with aging. Closure of the eyes increased the variance of the results. This change was higher in subjects more than 60 years old: 0.019-0.157 cm2 s(-2) than in younger ones: 0.011-0.043 cm2 s(-2). Retesting at 3 and 6 months showed a reliability of 79%. According to the cross-sectional part of the study, the slope of postural stability impairment with aging was estimated at 0.0038 cm/s/year. These results were confirmed by the longitudinal part of the study, which showed that COPxv increased from 0.66-0.75 cm/s/year (P = 0.0001) (slope = 0.0041 cm/s/year). CONCLUSION: (1) Measurement of COPxv, on two-legged stance, is a simple and reliable way to assess postural stability. (2) Thanks to both a cross sectional and a longitudinal study, the rate of postural stability impairment due to aging was precisely estimated, which will be useful to help distinguishing between the part of postural stability impairment attributable to aging from the one due to neuro-degenerative diseases.

Adult↗

PubMed2001

JCV-specific cellular immune response correlates with a favorable clinical outcome in HIV-infected individuals with progressive multifocal leukoencephalopathy.

Most immunosuppressed individuals who develop progressive multifocal leukoencephalopathy (PML) have a rapid fatal outcome, whereas some become long-term survivors. We explored the impact of the cellular immune response against JC virus (JCV) on the clinical outcome of 7 HIV+ and 3 HIV- individuals with PML. Of the 4 HIV+/PML survivors, all had detectable cytotoxic T lymphocytes (CTL) specific for JCV T or VP 1 proteins compared to none of the 3 HIV+/PML progressors tested. Of the 3 HIV-/PML patients, 1 was recently diagnosed with PML and showed evidence of neurologic improvement without any treatment. This patient had CTL specific for the VP1 protein of JCV. The other 2 HIV-/PML survivors were stable 3-8 years after the diagnosis of PML. They did not have any detectable CTL against JCV. These findings suggest that JCV-specific immune response is associated with favorable outcome in HIV+ individuals with PML. The lack of detectable JCV-specific CTL in 2 HIV-/PML survivors might indicate a burnt-out disease without sufficient antigenic stimulation to maintain the cellular immune response. The detection of JCV-specific CTL in an HIV- patient recently diagnosed with PML, who was showing evidence of neurological improvement without any treatment, indicates that this finding may be used as a favorable prognostic marker of disease evolution in the clinical management of patients with PML. As the quest for an effective treatment of PML continues, JCV-specific cellular immune response deserves further attention because it appears to play a crucial role in the prevention of disease progression.

AIDS-Related Opportunistic Infections↗

PubMed2001

JC virus-specific cytotoxic T lymphocytes in individuals with progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by a reactivation of the polyomavirus JC (JCV) within a setting of immunosuppression. The nature of the immune response that contains replication of this virus is unknown. We have explored JCV-specific cellular immune responses in patients with PML and control subjects. JCV antigen-stimulated peripheral blood mononuclear cells (PBMC) of four human immunodeficiency virus (HIV)-infected patients who were survivors of PML and one HIV-uninfected patient recently diagnosed with PML lysed autologous B-lymphoblastoid cell lines expressing either the JCV T regulatory protein or the VP1 major capsid protein. This lysis was mediated by CD8(+) T lymphocytes and was major histocompatibility complex class I restricted. These cells were therefore cytotoxic T lymphocytes (CTL). JCV-specific CTL could not be detected in PBMC of three HIV-infected PML patients who had progressive neurologic disease and an eventual fatal outcome. These data suggest that the JCV-specific cellular immune response may play a crucial role in the containment of PML. This finding may also prove useful as a favorable prognostic marker in the clinical management of these patients.

Antigens, Polyomavirus Transforming↗

PubMed2000

Monocular central dazzle after thalamic infarcts.

The authors observed a patient after he had ischemic strokes in both paramedian thalamic regions, which were more marked on the left side. Symptoms included dysphasia, vertical binocular diplopia, right-sided hemianopia, and a right-sided sensory and motor deficit, sparing the face. However, the most disturbing phenomenon was a painless, left monocular dazzle, which was the presenting symptom and also the only persisting symptom. This report shows that a thalamic lesion may be at the origin of central dazzle, and to the authors' knowledge, it is the first clinical observation of its monocular occurrence. It is conceivable that this dazzle was due to optic-trigeminal summation.

Brain Infarction↗