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J P Brion

Publications and source records attributed to J P Brion.

At least 19 recordsLinked to original sources
PubMed2005

Hospital-wide prospective mandatory surveillance of invasive aspergillosis in a French teaching hospital (2000-2002).

A multidisciplinary working group devoted to epidemiological surveillance of invasive aspergillosis (IA) was created in January 2000 in Grenoble University Hospital. This article presents the results of a three-year IA surveillance. The multidisciplinary working group surveyed all hospitalized patients, and the mycology laboratory detected most suspected IA cases. Cases were reviewed monthly by the Aspergillosis Committee, and were classified according to international consensus criteria. Possible nosocomial acquisition was determined. Among the 490 alerts, 74 IA cases were observed: six proven cases (8%), 36 (49%) probable cases and 32 (43%) possible cases. The incidence was 4.4 (95% CI 3.4-5.4) IA/100 000 patient-days. Among the proven and probable IA cases, we observed 10 nosocomial cases and six cases of undetermined origin. No cases were noted in the protected rooms in the haematology unit. Only one cluster of cases (three nosocomial cases) was detected in the haematology unit. Forty-three percent of cases (N=32) were hospitalized in the haematology unit, and all other cases were hospitalized elsewhere. This three-year survey found a high rate of non-nosocomial IA cases and a high frequency of IA cases hospitalized in units other than haematology. Thus, this study shows the importance of IA surveillance in haematology units and all high-risk units.

Aspergillosis↗
PubMed2005

Disseminated toxoplasmosis with pulmonary involvement after heart transplantation.

We report a case of pulmonary toxoplasmosis after heart transplant despite the prophylactic anti-toxoplasmic treatment that was given but was not sufficient to prevent toxoplasmosis. However, the patient survived thanks to early diagnosis confirmed by polymerase chain reaction on blood and by serological techniques, and early treatment.

Adult↗
PubMed2004

Expression of tau mRNA and soluble tau isoforms in affected and non-affected brain areas in Alzheimer's disease.

In Alzheimer's disease (AD), selective expression of tau isoforms might underlie the susceptibility of different brain areas to develop neurofibrillary tangles and this pattern might change in the disease. In this study, we have analyzed in control subjects and in sporadic AD patients the pattern of expression of tau mRNA and tau proteins in areas unaffected (cerebellar cortex, white matter), moderately affected (occipital striate cortex, thalamus, caudate nucleus, and putamen) or strongly affected by neurofibrillary tangles (temporal and frontal associative cortex). After RT-PCR amplification, five products corresponding to the tau mRNAs containing exons 2 and 3, exon 2, without exons 2 or 3, with exon 10 and without exon 10 were identified. In control subjects, these five PCR products were present in all areas except in white matter, where transcripts with exons 2 or exons 2 and 3 were not identified. In AD patients, the same pattern of transcripts was observed in different areas, regardless of the presence of neurofibrillary lesions. After dephosphorylation of soluble tau proteins, the six tau isoforms were identified in the same areas by immunoblotting, including in the white matter, suggesting that most tau isoforms with exons 2 and 3 are transported along axons. The relative expression of 0N3R isoforms was higher in the temporal cortex than in the cerebellar cortex, both in control and AD subjects. The qualitative pattern of expression was identical in subjects with or without an APOE4 allele. Our results suggest that splicing regulation of the tau gene and the relative expression of tau isoforms are not significantly changed in sporadic cases of the disease, although differential expression of tau isoforms in temporal cortex might underlie this brain area susceptibility to neurofibrillary tangles formation.

Aged↗
PubMed2004

Paraneoplastic acute diffuse encephalitis revealing Hodgkin's disease.

Paraneoplastic neurological syndromes are associated with various cancers. Cerebellar and limbic paraneoplastic manifestations are known to be associated with Hodgkin's disease (HD), but reports of diffuse encephalitis associated with HD are very rare. We report a case of acute severe diffuse encephalitis revealing a HD. Clinical presentation, cerebro-spinal fluid modifications and magnetic resonance imagery data are described. The treatment associated specific chemotherapy and plasma exchange. The neurological status improved dramatically within the first days of treatment, with parallel neoplasm regression. This case stresses the fact that encephalopathy can be the first sign of an undiagnosed extra-cerebral neoplasm.

Adolescent↗
PubMed2004

A case of arthritis caused by cytomegalovirus after kidney transplantation.

Cytomegalovirus (CMV) is the leading cause of infectious complications after organ transplantation. We report the case of a 55-year-old renal transplant recipient who presented with CMV infection 2 months after transplantation. During oral ganciclovir treatment (5 weeks after interruption of intravenous ganciclovir), he experienced a sharp pain in the right shoulder. Examination was normal, but CMV antigenemia remained positive with 30 cells/300,000. He underwent a shoulder puncture, which confirmed the presence of CMV in the articular fluid after evaluation by polymerase chain reaction gene amplification. The patient recovered from his arthritis of the shoulder, and antigenemia became negative after 3 weeks of parenteral ganciclovir. We describe a CMV arthritis that occurred despite a curative treatment for CMV disease, and comment on the pathogenesis of this infection, the pharmalogical failure, and dosing or treatment duration.

Arthritis↗
PubMed2004

Funiculitis due to Schistosoma haematobium: uncommon diagnosis using parasitologic analysis of semen.

Schistosomal funiculitis is one of the rare localizations of longstanding chronic infection with schistosomiasis. We report a case of a 24-year-old-man who experienced iliac fossa pain and weight loss eight years after his last trip to Mali. Clinical diagnosis of lesions in the genitourinary tract due to schistosomiasis and biologic analysis are required to diagnose this uncommon localization of schistosomiasis.

Adult↗
PubMed2003

Mutant presenilin 1 proteins induce cell death and reduce tau-dependent processes outgrowth.

The expression of familial Alzheimer's disease mutants of presenilin-1 (PS1) proteins has been observed to induce cell death in cellular systems. To investigate how this phenomenon might be associated to alterations of the microtubule network, we have studied the effect of wild-type and mutant (C263R, P264L and delta9) PS1 proteins expression on the formation of microtubule-dependent processes outgrowth and the association of PS1 to the insoluble cytoskeletal fraction in a cell line expressing the tau microtubule-associated protein. Expression of wild-type and mutant PS1 was associated with increased cell death, most marked for the P264L and delta9 mutants. The three PS1 mutants induced a significant reduction of the length of cell processes. These effects were not associated to a change in tau phosphorylation. However, the mutant PS1 proteins increased the proportion of insoluble tau in the cytoskeletal fraction and they were concentrated in the same fraction. These results suggest that PS1 proteins interact with the microtubule network, affect its organization and that this phenomenon, more marked for the PS1 mutants, might play a role in the cell dysfunction induced by mutant PS1 proteins.

Animals↗
PubMed2002

Increased tau phosphorylation but absence of formation of neurofibrillary tangles in mice double transgenic for human tau and Alzheimer mutant (M146L) presenilin-1.

Neurofibrillary tangles, composed of tau proteins, are a key lesion observed in sporadic forms of Alzheimer's disease and in familial forms associated with mutations of presenilin-1 (PS1). We have generated a double transgenic mouse line expressing a human tau isoform and a mutated form of PS1 (M146L) in neurons. Increased expression of the PS1 holoprotein was observed in the tau/PS1 transgenic mice and the proteolytic fragments of PS1 did not appear to be modified. A somatodendritic accumulation of the transgenic tau and an increase in tau phosphorylation were observed in both tau- and tau/PS1 transgenic mice. Neurofibrillary tangles were not observed in animals analyzed up to 17 months. Immunoprecipitation of tau from brain homogenates demonstrated its binding with active glycogen synthase kinase-3beta in control, tau- and tau/PS1 transgenic lines. These results suggest that overexpression of this Alzheimer mutant PS1 in vivo is not by itself sufficient to induce the formation of neurofibrillary tangles, even in neurons co-expressing and accumulating a human tau isoform.

Alzheimer Disease↗
PubMed2001

Presenilin 1 independently regulates beta-catenin stability and transcriptional activity.

Presenilin 1 (PS1) regulates beta-catenin stability; however, published data regarding the direction of the effect are contradictory. We examined the effects of wild-type and mutant forms of PS1 on the membrane, cytoplasmic, nuclear, and signaling pools of endogenous and exogenous beta-catenin by immunofluorescence microscopy, subcellular fractionation, and in a transcription assay. We found that PS1 destabilizes the cytoplasmic and nuclear pools of beta-catenin when stabilized by Wnt or Dvl but not when stabilized at lower levels of the Wnt pathway. The PS1 mutants examined were less able to reduce the stability of beta-catenin. PS1 also inhibited the transcriptional activity of endogenous beta-catenin, and the PS1 mutants were again less inhibitory at the level of Dvl but showed a different pattern of inhibition toward transcription below Dvl. The transcriptional activity of exogenously expressed wild-type beta-catenin and two mutants, DeltaN89beta-catenin and DeltaSTbeta-catenin, were also inhibited by wild-type and mutant PS1. We conclude that PS1 negatively regulates the stability and transcriptional activity of beta-catenin at different levels in the Wnt pathway, that the effect on transcriptional activity appears to be independent of the GSK-3beta mediated degradation of beta-catenin, and that mutations in PS1 differentially affect the stability and transcriptional activity of beta-catenin.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Increase of adenomatous polyposis coli immunoreactivity is a marker of reactive astrocytes in Alzheimer's disease and in other pathological conditions.

Mutations in the adenomatous polyposis coli (APC) tumor suppressor gene are responsible for colon cancer in familial adenomatous polyposis coli and in many sporadic colorectal tumors. The product of the APC gene is also essential for normal development and is expressed in the adult brain. We have investigated the immunocytochemical localization of APC in the temporal cortex and hippocampus of normal human brain, in Alzheimer's disease (AD) and in several other neuropathological conditions. APC was expressed in neuronal cell bodies and dendrites both in control subjects and in patients with different diseases. In addition, a high APC expression was observed in a proportion of fibrillary and glial fibrillary acidic protein-positive astrocytes in AD. Furthermore, in AD the proportion of APC-positive astrocytes was higher in astrocytes associated with beta-amyloid (Abeta) deposits in senile plaques than in astrocytes not associated to Abeta deposits. APC-positive astrocytes were also observed in control cases, in diffuse Lewy body disease, in Creutzfeldt-Jacob disease, in HIV encephalitis and around cerebral infarcts. Tumoral astrocytes in pilocytic astrocytoma and in glioblastoma were also strongly APC positive. APC was not detected in cultured astroglial cells. These results indicate that APC expression is upregulated in astrocytes following their activation by several types of pathological insults and is a newly identified molecular characteristic of the reactive phenotype of astrocytes, possibly related to the control of cell proliferation. In addition, it also suggests that Abeta, and/or the inflammatory process associated with Abeta deposits, is responsible for a preferential increase of APC expression in astrocytes in AD.

Adenomatous Polyposis Coli Protein↗
PubMed2001

Sites of phosphorylation in tau and factors affecting their regulation.

The microtubule-associated protein, tau, is the principal component of paired helical filaments (PHFs) in Alzheimer's disease. PHF-tau is highly phosphorylated and a total of 25 sites of phosphorylation have so far been identified. Many of these sites are serine or threonine residues that are immediately followed in the sequence by proline residues, and hence are candidate phosphorylation sites for proline-directed kinases. In vitro, glycogen synthase kinase-3 (GSK-3), extracellular signal-related kinase-1 and -2, and mitogen-activated protein kinases, p38 kinase and c-jun N-terminal kinase, all phosphorylate many of these sites, although with different efficiencies for particular sites. Phosphorylation studies in transfected cells and neurons show that GSK-3 phosphorylates tau more extensively than do these other proline-directed kinases. Mutations in tau have been shown to affect in vitro phosphorylation of tau by GSK-3. The Arg406-->Trp (R406W) tau mutation also affects tau phosphorylation in cells.

Alzheimer Disease↗
PubMed2001

Neurofibrillary tangles and tau phosphorylation.

Neurofibrillary tangles (NFTs) are a characteristic neuropathological lesion of Alzheimer's disease (AD). They are composed of a highly-phosphorylated form of the microtubule-associated protein tau. We are investigating the relationship between NFTs and microtubule stability and how tau phosphorylation and function is affected in transgenic models and by co-expression with beta-amyloid precursor protein and presenilins. In most NFT-bearing neurons, we observed a strong reduction in acetylated alpha-tubulin immunoreactivity (a marker of stable microtubules) and a reduction of the in situ hybridization signal for tubulin mRNA. In transfected cells, mutated tau forms (corresponding to tau mutations identified in familial forms of frontotemporal dementias linked to chromosome 17) were less efficient in their ability to sustain microtubule growth. These observations are consistent with the hypothesis that destabilization of the microtubule network is an important mechanism of cell dysfunction in Alzheimer's disease. The glycogen synthase kinase-3 beta (GSK-3 beta) generates many phosphorylated sites on tau. We performed a neuroanatomical study of GSK-3 beta distribution showing that developmental evolution of GSK-3 beta compartmentalization in neurons paralleled that of phosphorylated tau. Studies on transfected cells and on cultured neurons showed that GSK-3 beta activity controls tau phosphorylation and tau functional interaction with microtubules. Tau phosphorylation was not affected in neurons overexpressing beta-amyloid precursor protein. Transgenic mice expressing a human tau isoform and double transgenic animals for tau and mutated presenilin 1 have been generated; a somatodendritic accumulation of phosphorylated transgenic tau proteins, as observed in the pretangle stage in AD, has been observed but NFTs were not found, suggesting that additional factors might be necessary to induce their formation.

Alzheimer Disease↗
PubMed2000

The function of the microtubule-associated protein tau is variably modulated by graded changes in glycogen synthase kinase-3beta activity.

The microtubule-associated protein tau favors microtubule nucleation and stabilization and plays a role in the elongation of axons. We have investigated the ability of glycogen synthase kinase-3beta (GSK-3beta) to control tau-induced processes outgrowth. Tau-transfected Chinese hamster ovary (CHO) cells developed processes containing microtubule bundles after cytochalasin treatment, but a significant reduction in the number of cells harboring processes was observed in tau/GSK-3beta-co-transfected cells. Lithium, an inhibitor of GSK-3beta, counteracted in a dose-dependent manner this inhibitory effect of GSK-3beta. These findings suggest that GSK-3beta modulates in a graded manner the ability of tau to control the microtubule-dependent induction of cell processes.

Animals↗
PubMed2000

[Malignant non-Hodgkins B lymphoma related to Epstein-Barr virus and chronic natural killer lymphocytosis in a immunocompromised patient].

INTRODUCTION: Immunocompromised patients are at high risk of Epstein-Barr virus (EBV)-related lymphoproliferative disorders. The lymphoproliferation affects B, T, and natural killer (NK) cells. EXEGESIS: We report the case of a woman suffering from systemic lupus erythematous. She developed an opportunistic pneumonia while immunodepressed during long-term corticotherapy aimed at curing her auto-immune disease. Chronic lymphocytosis was also diagnosed at this time. Several months later, non-Hodgkin's lymphoma was diagnosed. Genomic amplification of the Epstein-Barr virus in the patient's blood and positive EBV latent membrane protein 1 on the lymph nodes provided evidence for a strong correlation between EBV reactivation and lymphoma. CONCLUSION: Two distinct lymphoid diseases occurred during the immunosuppressive therapy for the auto-immune disease. PCR monitoring of Epstein-Barr virus allows for early screening of lymphoproliferative disorders in immunocompromised patients, leading to earlier and more efficient treatment.

Aged↗
PubMed1999

Lithium reduces tau phosphorylation: effects in living cells and in neurons at therapeutic concentrations.

BACKGROUND: The mechanism of action of lithium remains to be determined satisfactorily. Recent studies suggested a possible role in inhibiting glycogen synthase kinase-3 (GSK-3), previously shown to phosphorylate the protein tau. Tau is expressed mainly in neurons, where it functions to stabilize microtubules in a phosphorylation-dependent manner. METHODS: Neurons and transfected non-neuronal cells were treated with lithium and the phosphorylation of tau at multiple epitopes examined by western blotting and by immunocytochemistry. Using green fluorescent protein as a tag we examined the effects of lithium on phosphorylated tau in living cells. RESULTS: Lithium reversibly reduced tau phosphorylation at therapeutic concentrations, and even at high concentrations did not alter neuronal morphology. Green fluorescent protein tagged-tau when phosphorylated by GSK-3 was diffusely distributed; treatment with lithium resulted in association with microtubules and then bundle formation. Removing lithium allowed observation of the dissolution of bundles and gradual dissociation of tau from microtubules in living cells. CONCLUSIONS: Lithium may have multiple effects in brain, but at least one action is demonstrated to be a relative inhibition of GSK-3-induced tau phosphorylation. These results carry implications for future studies of the actions of mood-stabilizing drugs and indeed of the molecular mechanisms of affective disorders.

Animals↗