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D Michel

Publications and source records attributed to D Michel.

At least 91 records · Page 5Linked to original sources

Clusterin/ApoJ expression is associated with neuronal apoptosis in the olfactory mucosa of the adult mouse.

The molecular events orchestrating neuronal degeneration and regeneration remain poorly understood. Attempts at identifying genes specifically expressed during these processes, have constantly led to the (re)isolation of the clusterin/ApoJ gene, whose expression is highly reactive to injury in a wide variety of tissues. To get insight into the function of clusterin in neuron loss, we have assessed in detail the clusterin gene expression in an experimental model of neurodegeneration, using the peripheral olfactory system of adult mouse. The sensory neurons of olfactory nasal mucosa can be massively induced to degenerate in vivo, by surgical removal of their only synaptic target: the olfactory bulb. We have previously shown that this neuron loss results from a near-synchronized induction of apoptosis genetic programs. We present here evidence that clusterin gene expression is tightly correlated to the onset of neuronal apoptoses in lesioned olfactory mucosae. The simultaneous preparation of DNA and RNA from the same tissue samples reveals that a strong clusterin mRNA accumulation coincides with the wave of nucleosome-sized DNA fragmentation. However, double detection of apoptotic nuclei by the TUNEL method and of clusterin messengers by in situ hybridization revealed that the clusterin gene expression is not induced in dying neurons, but in the glial sheath surrounding the axon bundles of degenerating olfactory neurons. Clusterin immunocytochemistry reveals that the clusterin protein accumulates not only in these producing cells, but also in the olfactory epithelium, suggesting the possibility of clusterin internalization by cells located at a distance from the synthesis loci. In view of this localization and of the activities of the clusterin protein reported so far, possible functions of clusterin in nervous plasticity are discussed.

Age Factors↗

[Neurolupus with dementia manifestations. 2 cases].

Manifestations of dementia occurred in two young patients with disseminated lupus erythematosus who had no signs of focalized neurological deficit. In case 1 followed for 8 years, a probably autonomous and familial psychiatric syndrome was complicated during a lupus flare-up by a prolonged dementia syndrome which regressed to a large extent. In the second patient with moderate dementia and familial hearing loss, severe mental deterioration suddenly occurred with long-term degradation of the cognitive capacity. In both of these cases with neurolupus, the frontal clinical signs, the neuropsychological deficits evidenced at testing, and the lesions demonstrated at CT scan and magnetic resonance imaging favored a frontal and/or frontobasal type dementia. Treatment with cyclophosphamide was effective in case 1 after failure of corticosteroid therapy.

Adult↗

The UL97 gene product of human cytomegalovirus is an early-late protein with a nuclear localization but is not a nucleoside kinase.

The temporal expression of the UL97 gene product during human cytomegalovirus (HCMV) infection of human foreskin fibroblasts (HFF) and subcellular localization of this protein were analyzed by using a polyclonal antiserum raised against a truncated UL97 protein of 47 kDa. The UL97 protein was detectable 16 h after infection by Western blot (immunoblot) analysis. Since only reduced UL97 expression occurred in the presence of two inhibitors of DNA replication, phosphonoacetic acid and ganciclovir, we conclude that UL97 is an early-late gene, requiring DNA replication for maximum expression. By indirect immunofluorescence, the protein could be visualized in the nuclei of virus-infected HFF 22 h after infection. Nuclear localization of the UL97 protein was also detected in thymidine kinase-deficient 143B cells infected with a recombinant vaccinia virus containing the entire UL97 open reading frame (ORF), as well as in HFF transiently expressing the entire UL97 ORF under the control of HCMV major immediate-early promoter. However, transiently expressed 5'-terminal deletion mutants of the UL97 ORF in addition showed a cytoplasmic localization of the UL97 protein, confirming the presence of a nuclear localization site in the N-terminal region of the protein. Our high-pressure liquid chromatography analyses confirmed the ganciclovir phosphorylation by the UL97 protein, but no specific phosphorylation of natural nucleosides was observed, indicating that the UL97 protein is not a nucleoside kinase. During plaque purification of recombinant UL97-deficient HCMV, this virus was growth defective; hence, we presume that UL97 may be essential for the viral life cycle.

Amino Acid Sequence↗

Chronic inflammatory demyelinating polyneuropathy associated with carcinoma.

The association of chronic inflammatory demyelinating polyneuropathy (CIDP) and carcinoma has rarely been reported and its relevance is debated. Thirty three consecutive patients with probable or definite CIDP (idiopathic or associated with M protein) were investigated. Three patients with definite CIDP had a concomitant carcinoma. One had an IgM paraprotein. Steroids and intravenous immunoglobulins were effective.

Aged↗

Demyelinating peripheral neuropathy with Creutzfeldt-Jakob disease and mutation at codon 200 of the prion protein gene.

We performed a study of the distribution of PrP27-30, the proteinase-K-resistant form of prion protein, in the central and peripheral nervous system of a patient with a Glu200Lys mutation of the prion protein gene, cerebellar ataxia, subcortical dementia, rigidity, and demyelinating peripheral neuropathy. In the CNS, there was neuron loss and spongy degeneration, principally in the cerebellum, and with progressively lower density in the caudate nucleus, thalamus, temporal cortex, frontal cortex, and brainstem. Evaluation of the expression of PrP27-30 by Western blot showed that its distribution correlated with the intensity of the lesions in these regions. In contrast, we did not detect PrP27-30 in the peripheral nervous system where lesions consisted of demyelination, and remyelination that predominated in the proximal nerve trunks and roots.

Base Sequence↗

SGPG in ALS.

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Amyotrophic Lateral Sclerosis↗

Are somatosensory evoked potential recording and magnetic resonance imaging useful for evaluating the risk of neurologic compromise in rheumatoid arthritis patients with atlantoaxial subluxation?

The objective of this study was to determine whether early somatosensory evoked potential recording and/or magnetic resonance imaging are helpful for evaluating and monitoring the risk of neurologic compromise in rheumatoid arthritis patients. Thirty-seven patients with definite rheumatoid arthritis were studied, including 18 with atlantoaxial subluxation. A physical examination, roentgenograms of the cervical spine, early somatosensory evoked potential recording at all four limbs and magnetic resonance imaging of the cervical spine were done in each case. Alterations in somatosensory evoked potentials and magnetic resonance imaging evidence of compression of the medulla oblongata or spinal cord were found in similar proportions of patients with and without atlantoaxial subluxation. These results support the view that physical findings and changes on plain films of the cervical spine are the most reliable data for evaluating and monitoring the risk of neurologic damage in patients with atlantoaxial subluxation. Somatosensory evoked potential studies and magnetic resonance imaging should be reserved for those cases in which physical and roentgenographic data cannot be collected in a satisfactory manner and for patients who are included in study protocols that require accurate evaluation of lesions.

Adolescent↗

Insertion mutations at the maize Opaque2 locus induced by transposable element families Ac, En/Spm and Bg.

Eight independently isolated unstable alleles of the Opaque2 (O2) locus were analysed genetically and at the DNA level. The whole series of mutations was isolated from a maize strain carrying a wild-type O2 allele and the transposable element Activator (Ac) at the wx-m7 allele. Previous work with another unstable allele of the same series has shown that it was indeed caused by the insertion of an Ac element. Unexpectedly, the remaining eight mutations were not caused by the designated Ac element, but by other insertions that are structurally similar or identical to one of two different autonomous transposable elements. Six mutations were caused by the insertion of a transposable element of the Enhancer/Suppressor-Mutator (En/Spm) family. Two mutations were the result of the insertion of a transposable element of the Bergamo (Bg) family. Genetic tests carried out with plants carrying the unstable mutations demonstrated that all were caused by the insertion of an autonomous transposable element.

Alleles↗

Detrusor-sphincteric dyssynergia in humans with spinal cord lesions may be caused by a loss of stable phase relations between and within oscillatory firing neuronal networks of the sacral micturition center.

(1) Single-fibre action potentials (APs) were recorded with 2 pairs of wire electrodes from lower sacral nerve roots during surgery in patients with spinal cord lesions and in a brain-dead human. Conduction velocity distribution histograms were constructed for afferent and efferent fibres, nerve fibre groups were identified and simultaneous impulse patterns of alpha and gamma-motoneurons and secondary muscle spindle afferents (SP2) were constructed. Temporal relations between afferent and efferent APs were analysed by interspike interval (II) and phase relation changes. (2) In a paraplegic with hyperreflexia of the bladder, urinary bladder stretch (S1) and tension receptor afferents (ST) fired already when the bladder was empty, and showed a several times higher bladder afferent activity increase upon retrograde bladder filling than observed in the brain-dead individual. Two alpha 2-motoneurons (FR) innervating the external bladder sphincter were already oscillatory firing to generate high activity levels when the bladder was empty. They showed activity levels with no bladder filling, comparable to those measured at a bladder filling of 600 ml in the brain-dead individual. A bladder storage volume of 600 ml was thus lost in the paraplegic, due to a too high bladder afferent input to the sacral micturition center, secondary to inflammation and hypertrophy of the detrusor. (3) In a brain-dead human, 2 phase relations existed per oscillation period of 160 ms between the APs of a sphincteric oscillatory firing alpha 2-motoneuron, a dynamic fusimotor and a secondary muscle spindle afferent fibre. Following stimulation of mainly somatic afferent fibres, the phase relations changed only little. (4) In a paraplegic with dyssynergia of the urinary bladder also 2 phase relations existed per oscillation period of 110 ms in a functional unit between the APs of a sphincteric alpha-motoneuron, a fusimotor and a secondary spindle afferent fibre. The phase relations changed with time following stimulation of mainly somatic afferents. A second functional unit organized by phase-related interactions was phase related to the first functional unit. (5) Following painful bladder catheter pulling, the parasympathetic division was transiently activated several times in the paraplegic. At times of activation of the parasympathetic division, 3 broad phase relations occurred within and between the two functional units, indicating that the parasympathetic division in the sacral micturition and defecation center channeled an additional input to the somatic oscillatory firing neuronal networks driving motoneurons which innervate the external bladder and/or anal sphincters.

Action Potentials↗

The expression of the avian clusterin gene can be driven by two alternative promoters with distinct regulatory elements.

Clusterin cDNA has been isolated as a copy of a mRNA overexpressed in a wide variety of biological disorders, including tissue regression, brain injuries and oncogenic cell transformation. While the molecular cloning of the rat and the human clusterin genes has revealed a high degree of conservation of the genomic organization between mammals, the avian locus described here illustrates several divergent features. The avian gene has the particularity to be transcribed from at least two different promoters, both of which are active in transient expression assays using the quail QT6 transformed cell line. The detection of the two clusterin mRNA species by reverse-transcription-mediated PCR reveals a coordinated initiation of transcription from both promoters in all organs tested. In possible relation to the bipartite organization of the avian regulatory region, the putative cis-elements described in the unique mammalian promoters appear divided among the two avian promoters. In addition, the sequence comparison of avian and mammalian regulatory sequences has allowed the identification of a conserved putative cis-element which appears to be the target for specific DNA-binding factors.

Amino Acid Sequence↗

[Specialized memory consultation and management of dementia syndrome].

The specialized memory consultation is based on two successive examinations: one by a neurologist, the other by a psychologist, using standardized batteries of tests. In 200 consecutive subjects with 63.8 years mean age, the authors observe dementia syndromes (39%), age related disorders of memory (6.5%), psychiatric disorders (28.5%), disorders after brain injury or neurosurgery (18.5%) and medical neurological pathologies (5.5%). Patients are addressed by practician in 34.5%. In the group of 78 patients with dementia syndrome were studied the delay before consultation, familial story, memory complaints of patients and family and diagnosis. In subjects with memory complaints a psychometric evaluation performed by a team of specialists seems to be a mean of refining the diagnosis and to improve a personalized management.

Aging↗

Transposon tagging of the maize Glossy2 locus with the transposable element En/Spm.

The Glossy2 (Gl2) locus of maize is required for the formation of the epicuticular wax layer of young plants. gl2 mutant seedlings can be visually identified because of their glossy leaf surface which is different from the dull surface of wild-type seedlings. The Gl2 locus was isolated by transposon tagging. Seven unstable mutations, gl2-m2 to gl2-m8, were induced in a parental strain carrying an active transposable Activator (Ac) element in the unstable wx-m7 allele. Genetic tests on the gl2-m2 allele indicated that it was not caused by the Ac element but by the insertion of the transposable element Enhancer/Suppressor-Mutator (En/Spm). A Sa/l restriction fragment segregating with the mutant phenotype was identified, by Southern analysis, using sequences from the En/Spm element as a probe. Part of the fragment was cloned and was shown to carry part of the unstable gl2-m2 allele. These gl2 sequences were used to identify a genomic fragment carrying the wild-type allele and to isolate its corresponding cDNA sequence. The predicted Glossy2 protein consists of 426 amino acids. No similar amino acid sequence was found in protein data banks and the biochemical function of the Gl2 gene product is still unknown. The wild-type Gl2 transcript is found predominantly in juvenile leaves. The transcript level in the leaves of seedlings homozygous for a stable recessive gl2-ref allele is hardly detectable.

Alleles↗

Intestinal cytomegalovirus disease in immunocompromised patients may be ruled out by search for cytomegalovirus DNA in stool samples.

Cytomegalovirus (CMV) PCR from stool specimens was adopted as a diagnostic tool for patients with suspected CMV colitis. After being established, the method was evaluated in 17 AIDS patients and 19 other immunocompromised patients by comparison of PCR results with clinical, histological, and microbiological or virological data. CMV PCR was positive in 4 symptomatic patients with proven CMV colitis and negative in 15 of 16 patients without characteristic histopathology. Neither CMV immunoglobulin G seropositivity nor intestinal symptoms alone were significantly associated with positive PCR results, but severe active systemic CMV infection may lead to a positive PCR. Absence of CMV DNA in stool samples may prove useful in ruling out CMV related colitis.

Acquired Immunodeficiency Syndrome↗

Limbic encephalitis and immunological perturbations in two patients with thymoma.

Two patients with clinical and radiological evidence of limbic encephalitis associated with an invasive lymphoepithelial thymoma who improved after thymectomy and radiotherapy are reported. The serum of both patients and the CSF of one of them contained different types of antibodies that immunoreacted with human and rat brain and newborn rat thymus. After treatment of the tumour, the antibody titres decreased. Similar antibodies were not found in various controls. Two out of 16 patients with thymoma, myasthenia gravis, and no CNS involvement had low titres of antibodies reacting with the brain. It is suggested that in some patients with thymoma, an autoimmune reaction involving antigens common to the brain and thymus is possibly misdirected against the CNS.

Aged↗

RNA-dependent DNA binding activity of the Pur factor, potentially involved in DNA replication and gene transcription.

The PUR element is a polypurine polypyrimidine motif that can stimulate transcription, encountered in the 5' regions of various genes and in the vicinity of several DNA replication initiation zones. We demonstrate that the PUR complex formation between the purine-rich strand of PUR and nuclear extracts can be prevented by pretreatment of nuclear extracts with RNA-damaging agents such as UV light or RNase A. A biochemical affinity method reveals that small RNA molecules copurify with the Pur factor. Moreover, the PUR binding activity of RNA-depleted nuclear extracts can be restored by addition of phenol-extracted RNAs. This work adds a new member in the emerging class of ribonucleoprotein particles as regulatory factors of the genetic expression.

Animals↗

[Antifungal activity in vitro of Scutellaria baicalensis Georgi upon cutaneous and ungual pathogenic fungi].

The root of Scutellaria baicalensis Georgi (Lamiaceae) is one of the traditional drugs commonly used in the Far East. The extracts obtained by the successive exhaustion in chloroform and in ethyl acetat present clear fungistatic activities in vitro against to some cutaneous and ungual pathogenic fungi, and particularly upon strains of Candida albicans, Cryptococcus neoformans and Pityrosporum ovale. For each of these, its minimum inhibitory concentration is determined. The ethyl acetat extract appears the most interesting because of its efficiency and of its stability. An antifungal substance is found out as the baicalein.

Antifungal Agents↗