PubMed Health⌕ Search

Biomedical subjects

J J Hauw

Publications and source records attributed to J J Hauw.

At least 19 recordsLinked to original sources
PubMed2005

Frontotemporal dementia, motor neuron disease and tauopathy: clinical and neuropathological study in a family.

We report a familial disorder occurring in three patients that presented as frontotemporal dementia (FTD). A neuropathological study was performed in a 58-year-old patient, who developed FTD 2 years prior to the onset of motor neuron disease (MND), and died at age 62. Lesions indicative of associated MND were observed: neuronal loss in the anterior horns of the spinal cord, Bunina bodies, axonal spheroids, degeneration of the pyramidal tracts, and of FTD: decreased neuronal density and laminar microvacuolation of layers II and III in the frontal and temporal cortex. Ubiquitin-only-immunoreactive changes were found in the spinal cord and medulla, but were absent from the temporal and frontal cortex. There were also widespread deposits of various neuronal and glial inclusions containing abnormally phosphorylated tau protein, the Western blotting pattern of which was characterized by two major bands of 64 and 69 kDa. There were no abnormalities of the entire coding sequences of microtubule-associated protein tau (MAPT) and copper-zinc superoxide dismutase (SOD(1)) genes. Our results suggest that FTD associated with MND can be caused by a larger spectrum of neuropathological lesions than commonly accepted.

Blotting, Western↗
PubMed2004

Compassionate use of quinacrine in Creutzfeldt-Jakob disease fails to show significant effects.

Quinacrine has been reported as an antiprion agent and proposed as an immediately applicable treatment for Creutzfeldt-Jakob disease (CJD). The authors report the results of an open compassionate procedure to which 32 CJD patients had access. In some genotypic subgroups, a slight but nonsignificant increase in survival was observed, likely due to biased inclusion of long-term surviving patients. There was no pathologic evidence of a beneficial effect of quinacrine treatment.

Brain↗
PubMed2003

Multiple sclerosis-associated retrovirus particles cause T lymphocyte-dependent death with brain hemorrhage in humanized SCID mice model.

A retroviral element (multiple sclerosis-associated retrovirus, MSRV) defining a family of genetically inherited endogenous retroviruses (human endogenous retrovirus type W, HERV-W) has been characterized in cell cultures from patients with multiple sclerosis. Recently, MSRV retroviral particles or the envelope recombinant protein were shown to display superantigen activity in vitro, but no animal model has yet been set up for studying the pathogenicity of this retrovirus. In the present study, the pathogenicity of different sources of MSRV retroviral particles has been evaluated in a hybrid animal model: severe combined immunodeficiency (SCID) mice grafted with human lymphocytes and injected intraperitoneally with MSRV virion or mock controls. MSRV-injected mice presented with acute neurological symptoms and died within 5 to 10 days post injection. Necropsy revealed disseminated and major brain hemorrhages, whereas control animals did not show abnormalities (P <.001). In ill animals, reverse transcriptase-polymerase chain reaction (RT-PCR) analyses showed circulating MSRV RNA in serum, whereas overexpression of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma was evidenced in spleen RNA. Neuropathological examination confirmed that hemorrhages occurred prior to death in multifocal areas of brain parenchyma and meninges. Further series addressed the question of immune-mediated pathogenicity, by inoculating virion to SCID mice grafted with total and T lymphocyte-depleted cells in parallel: dramatic and statistically significant reduction in the number of affected mice was observed in T-depleted series (P <.001). This in vivo study suggests that MSRV retroviral particles from MS cultures have potent immunopathogenic properties mediated by T cells compatible with the previously reported superantigen activity in vitro, which appear to be mediated by an overexpression of proinflammatory cytokines.

Animals↗
PubMed2003

[Usefulness of molecular genetic analysis of the PRNP gene in patients with cerebellar ataxia: a new case of fatal familial insomnia].

We report the fifth French case of fatal familial insomnia, characterized by a mutation at codon 178 of prion protein gene and by heterozygoty (Met/Val) at codon 129. The clinical picture included cerebellar ataxia, dysautonomia and frontal lobe syndrome. Prion protein gene analysis was performed in order to support a diagnosis of Creutzfeldt-Jakob disease and assert the diagnosis of fatal familial insomnia. Neuropathologic analysis showed unusual changes including severe neuronal loss in the inferior olive and the dentate nucleus, and absence of obvious lesions in the thalamus. Moreover, spongiform changes were moderate in the superior temporal cortex and the occipital cortex. There was no spongiform change in frontal cortex. Abnormal prion protein (PrP(res)) was mainly evidenced in the parietal cortex. Molecular genetic study of the PRNP gene should be performed in patients who present with a cerebellar ataxia of equivocal origin.

Amyloid↗
PubMed2002

Alpha-synuclein-immunoreactive deposits in human and animal prion diseases.

Prion related disorders are associated with the accumulation of a misfolded isoform (PrPsc) of the host-encoded prion protein, PrP. There is strong evidence for the involvement of unidentified co-factors in the PrP to PrPsc conversion process. In this study, we show alpha-synuclein-immunoreactive deposits in the central nervous system of various prion diseases (sporadic, iatrogenic and new variant Creutzfeldt-Jakob diseases, and experimental scrapie of hamsters). alpha-Synuclein accumulated close to PrPsc deposits but we did not observe strict colocalization of prion protein and alpha-synuclein immunoreactivities particularly in PrPsc plaques. alpha-Synuclein is thought to be a key player in some neurodegenerative disorders, is able to interact with amyloid structures and has known chaperone-like activities. Our results, in various prion diseases, suggest a role for alpha-synuclein in regulating PrPsc formation.

Animals↗
PubMed2002

MR spectroscopic pulvinar sign in a case of variant Creutzfeldt-Jakob disease.

We report MR spectroscopic findings in a patient hospitalized with biopsy-proven variant Creutzfeldt-Jakob (vCJD) disease. N-acetyl aspartate was markedly decreased in the postero-medial part of the thalami (pulvinar) but was not diminished in the parieto-occipital white matter and cortical grey matter. These observations, which are in accordance with the pathological findings in this disease, suggest that MR spectroscopy, a highly sensitive method for the detection of subtle brain metabolic dysfunction, could be of interest for the diagnosis, prognosis and therapeutic follow-up of vCJD.

Adult↗
PubMed2002

[Neuropathology of the cerebral vessels of centenarians].

Neuropathological study of brain and brain vessels was performed in two series of 12 and 20 centenarians, focusing on the prevalence of small vessel lesions, infarction, Alzheimer's changes and mental status. These are discussed as a function of vascular risk factors. In the first series (12 cases), there was no correlation between the severity of small vessel lesions: hyalinosis (12/12), mineralisation (10/12), amyloid angiopathy (9/12), vascular risk factors (high blood pressure or diabetes), Alzheimer's lesions. However, there was a tendency for an association between amyloid angiopathy and high density of neurofibrillary tangles. In the second series (20 cases), small infarcts and lacunes were found in 9/20 cases, neurofibrillary tangles and diffuse deposits of A beta peptide were constant, senile plaques were very frequent (19/20). Five patients were demented (one vascular dementia, one Alzheimer dementia, and 3 mixed dementias). These data indicate that: 1) Lesions of the walls of small cerebral vessels do not seem linked to the vascular risk factors observed at the end of the life of centenarians. 2) Cerebral infarcts and lacunes are frequent in these patients, and are responsible, at least in part, for a high proportion of the cognitive dysfunctions. The study of larger series is needed for a better understanding of relationships between vascular and degenerative lesions in the oldest old.

Aged↗
PubMed2001

Paradoxical phosphorylation of the serine 199 on tau proteins from young individuals.

The microtubule-associated tau proteins are abnormally aggregated in many tauopathies. Phosphorylation modulates the functions of tau. The serine 199 residue of tau is abnormally phosphorylated at early and late stages of Alzheimer's disease. The presence of the phosphorylated Ser199 was investigated in autopsy-derived and biopsy-derived brain tissue samples from non-demented individuals. A paradoxical expression was found in the hippocampus of the youngest ones, in granule cells of the dentate gyrus and in pyramidal cells of the Ammon's horn, which are particularly prone to neurodegeneration in several tauopathies. The rate of positive cells decreased with age. These data emphasize the importance of the phosphorylation of the Ser199 residue of tau in ageing and susceptibility to neurodegeneration.

Adolescent↗
PubMed2001

Adaptation of the bovine spongiform encephalopathy agent to primates and comparison with Creutzfeldt-- Jakob disease: implications for human health.

There is substantial scientific evidence to support the notion that bovine spongiform encephalopathy (BSE) has contaminated human beings, causing variant Creutzfeldt-Jakob disease (vCJD). This disease has raised concerns about the possibility of an iatrogenic secondary transmission to humans, because the biological properties of the primate-adapted BSE agent are unknown. We show that (i) BSE can be transmitted from primate to primate by intravenous route in 25 months, and (ii) an iatrogenic transmission of vCJD to humans could be readily recognized pathologically, whether it occurs by the central or peripheral route. Strain typing in mice demonstrates that the BSE agent adapts to macaques in the same way as it does to humans and confirms that the BSE agent is responsible for vCJD not only in the United Kingdom but also in France. The agent responsible for French iatrogenic growth hormone-linked CJD taken as a control is very different from vCJD but is similar to that found in one case of sporadic CJD and one sheep scrapie isolate. These data will be key in identifying the origin of human cases of prion disease, including accidental vCJD transmission, and could provide bases for vCJD risk assessment.

Adaptation, Biological↗
PubMed2001

Outcome of patients with HIV-1-related cognitive impairment on highly active antiretroviral therapy.

OBJECTIVE: To examine the impact of highly active antiretroviral therapy (HAART) on the outcome of HIV-1-related cognitive impairments using a neuropsychological (NP) battery to assess separately the psychomotor, executive function and memory fields. DESIGN: A longitudinal study of HIV-1-infected patients based on serial NP tests in a Paris University Hospital. METHODS: A group of 91 HIV-1-infected patients, of whom 47 were already taking HAART at their first NP examination, were initially categorized as cognitively impaired (n = 53) or non-impaired (n = 38) and underwent one to six serial NP batteries (mean follow-up 12.3+/-8.3 months). Generalized estimating equations (GEE) were used to evaluate performance in a given NP test according to the number of days on HAART. RESULTS: Despite a 25% mortality rate among patients who had cognitive impairment at their first NP examination, GEE showed a positive relationship between the duration of HAART and cognitive performance. Performance in psychomotor tests (e.g. Purdue Pegboard dominant hand) improved continuously during the study period, while memory test performance (e.g. Grober and Buschke free recall) tended to reach a plateau. CONCLUSIONS: HAART improves subcortical cognitive functions during the first year of treatment. Distinct neuropathological mechanisms appear to underlie psychomotor and memory dysfunctions in AIDS.

Adult↗
PubMed2001

Autometallographic tracing of bismuth in human brain autopsies.

For decades, drugs containing bismuth have been used to treat gastrointestinal disorders. Although a variety of adverse effects, including neurological syndromes, have been recorded, the biological/toxicological effects of bismuth ions are far from disclosed. Until recently, only quantitative assessments were possible, but resent research has made histochemical tracing of bismuth possible. The technique involves silver enhancement of bismuth crystallites by autometallography (AMG). In the present study, the localization of bismuth was traced by AMG in sections of paraffin-embedded brain tissue obtained by autopsy from 6 patients suffering from bismuth intoxication in a period ranging from 1975 through 1977. Tissue was analyzed at light and electron microscopical levels, and the presence of bismuth further confirmed by proton-induced x-ray emission (PIXE). Clinical data and bismuth concentrations in blood, cerebellum, and thalamus were measured by atomic absorption spectrophotometry (AAS) and are reported here. Histochemical analyses demonstrate that bismuth accumulated in neurons and glia cells in the brain regions examined (neocortex, cerebellum, thalamus, hippocampus). Cerebellar blood vessels stained most intensely. The PIXE and AAS data correlated with the histochemical staining patterns and intensities. At the ultrastructural level, bismuth was found to accumulate intracellularly in lysosomes and extracellularly in the basement membranes of some vessels.

Aged↗
PubMed2001

[Autopsy].

The disappearance of autopsies is of concern in Neurology for three reasons: in some cases, such as degenerative diseases, the predictive value of clinical diagnosis is still poor; autopsy is, for Neurology, an important piece of the public health watch; the modern post-genomic research needs tissue samples that cannot be obtained by other means for ethical reasons. The main rules of autopsy in France, including the pitfalls of legislation, are recalled. The prerequisites for a renewing of autopsy, the modifications that are required, the procedure to explain its importance in the hospital, among neurologists, and in the society are considered.

Autopsy↗
PubMed2001

[The different varieties of autopsy. Proposal for a renewed medical and scientific autopsy].

Five main varieties of autopsies can be distinguished in France: the forensic pathology autopsy, medical and scientific autopsies, the "gift of corpse to the University", and the sanitary autopsy. The main rules and the shortcomings of French regulations ant its implementation are recalled. The disappearance of medical and scientific autopsies is of concern for three reasons: in some cases, the predictive value of clinical diagnosis is still poor and the proportion of unexpected findings that may have modified the patient therapy (20/25%) has remained unchanged for many years; autopsy is an important piece of the health watch, i.e. of public welfare; the modern post-genomic research needs tissue samples that often cannot be obtained by other means for ethical reasons. Numerous patients associations campaign for making easier the gift of organs for research purpose. The prerequisites for a renewing of autopsy, the modifications of regulations and practices that are required, the procedures to explain its importance in the hospital, among medical doctors and care givers, and in the society are considered.

Autopsy↗