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J C Antoine

Publications and source records attributed to J C Antoine.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Biology of macrophages-Leishmania interactions].

Leishmania are trypanosomatidae which under their amastigote form behave as obligate intracellular parasites. At this stage, they multiply in macrophages of infected mammals (including man), within parasitophorous vacuoles (PV). These organelles of macrophage origin are part of the endocytic pathway. Study of their contents and membrane composition shows that they finally resemble lysosomes/prelysosomes. PV maintain a very acidic pH (< or = 5), and contain numerous functional lysosomal enzymes. They are limited by a membrane characterized by the presence of intrinsic and peripheral proteins described as being mainly associated with prelysosomal and/or lysosomal compartments (lamp-1, lamp-2, macrosialin, rab7p). Leishmania amastigotes appear to be acidophilic micro-organisms resistant to the action of lysosomal hydrolases and as such are fully adapted to the conditions encountered within prelysosomes/lysosomes. After stimulation of infected macrophages with interferon-gamma, we also note the presence of major histocompatibility complex (MHC) class II molecules in PV membrane but not that of MHC class I molecules. It is not yet known whether the PV-associated class II molecules play a role in the presentation of parasite antigens to protective specific T lymphocytes or whether parasites have developed strategies to inhibit or divert to their own advantage the antigen presentation process potentially detrimental to their survival. In any case, Leishmania-infected macrophages exhibit a deficiency in their capacity to present exogenous antigens in the context of MHC class II molecules. We are currently investigating whether this deficiency also extends to the presentation of parasite antigens.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Protozoan↗
PubMed1994

[Value of the detection of anti-nervous system autoantibodies in neurologic paraneoplastic syndromes].

In the last decade, anti-neurons autoantibodies have been found in serum and cerebro spinal fluid of patients suffering from neurological paraneoplastic syndrome. This discovery has made possible to improve the knowledge of these syndromes as well as to characterize some proteins specific to the nervous system, unknown until now. Paraneoplastic encephalomyelitis can manifest together with an ataxic sensitive neuropathy, a limbic encephalitis, a brainstem or cerebellum syndrome. This encephalomyelitis is almost always associated with a small cells lung cancer and auto-antibodies, called anti-Hu, which recognize all the neurons of the nervous system. Patients with paraneoplastic cerebellar degeneration present an antibody, called anti-Yo, directed against Purkinje cells. In this case, the tumor is a gynecologic cancer. Patients presenting with an opso-myoclonus and a breast cancer have an antineurons anti-body, called anti-Ri, which is absent when the opso-myoclonus is associated with a lung cancer or a neuroblastoma. These three antibodies are the most frequently found and the best studied, but others, rarer, have been described. The genes coding for the proteins recognized by these three antibodies have been cloned. These proteins seem to play a major role in the neuronal maturation and homeostasis. These antibodies prove to be irreplaceable tools to study the phenomenons subtending the neuronal degeneration and the cellular proliferation.

Autoantibodies↗
PubMed1994

Rheumatic heart disease and Sneddon's syndrome.

BACKGROUND: As the pathogenesis of Sneddon's syndrome is unknown, research for associated disease can facilitate our understanding. CASE DESCRIPTION: Of nine patients with Sneddon's syndrome, three had rheumatic heart disease (mitral valve stenosis, regurgitation, or both) due to rheumatic fever or Sydenham's chorea. Transient anticardiolipin antibodies or positive skin lupus band test were present. CONCLUSIONS: Sneddon's syndrome can have multiple causes. In some patients, rheumatic heart disease is a possible causal association.

Adult↗
PubMed1994

Distribution of MHC class I and of MHC class II molecules in macrophages infected with Leishmania amazonensis.

Macrophages, being apparently the only cells that in vivo allow the growth of the intracellular pathogen Leishmania, are likely candidates to present antigens to Leishmania-specific CD4+ and CD8+ T lymphocytes, known to be involved in the resolution or in the development of lesions induced by these parasites, and recognizing processed antigens bound to MHC class I and MHC class II molecules, respectively. In the present study, we analysed by confocal microscopy and by immunoelectron microscopy the subcellular distribution of both MHC class I and class II molecules in mouse (Balb/c and C57BL/6 strains) bone marrow-derived macrophages infected for 12 to 48 hours with Leishmania amazonensis amastigotes and activated with gamma interferon to determine the intracellular sites where Leishmania antigens and MHC molecules meet and can possibly interact. Double labelings with anti-MHC molecule antibodies and with either propidium iodide or an anti-amastigote antibody allowed localization of MHC molecules with regard to the endocytic compartments housing Leishmania amastigotes, organelles known as the parasitophorous vacuoles (PV) and which most likely contain the highest concentration of parasite antigens in the host cell. Both uninfected and infected macrophages from Balb/c mice expressed the MHC class I molecules H-2Kd and H-2Dd on their cell surface but no significant amount of these molecules could be detected in the PV, which indicates that, if infected macrophages play a role in the induction of Leishmania-specific CD8+ T lymphocytes, PV are probably not loading compartments for MHC class I molecules. In contrast, MHC class II molecules were found to be associated with the PV membranes as shown previously with microscopic techniques at lower resolution (Antoine et al. Infect. Immun. 59, 764-775, 1991). In addition, we show here that, 48 hours after infection of Balb/c macrophages, in about 90% of PV containing MHC class II molecules, the latter were mainly or solely localized at the attachment zone of amastigotes to PV membranes. This peculiar distribution, especially well demonstrated using confocal microscopy, was confirmed by subcellular fluorescence cytometry of infected macrophages stained for the MHC class II molecules. The following data agree with the idea that PV-associated MHC class II molecules establish specific interactions with plasma membrane components of amastigotes. First, the polarized localization of class II appeared specific to these molecules, since the distribution of the lysosomal glycoproteins Igp110 and Igp120, of the macrosialin (a macrophage-specific marker of endocytic compartments) and of the GTP-binding protein rab7p, shown here as being PV membrane components, was homogeneous.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Leishmania donovani-infected macrophages: characterization of the parasitophorous vacuole and potential role of this organelle in antigen presentation.

Leishmania donovani amastigotes, the etiological agents of visceral leishmaniasis, are obligate intracellular parasites residing in membrane-bound compartments of macrophages called parasitophorous vacuoles (PV). The study of these organelles is of paramount importance to understanding how these parasites resist the microbicidal mechanisms of macrophages and how they escape the immune response of their hosts. Confocal microscopy of mouse bone marrow-derived macrophages infected with L. donovani amastigotes and stained for various prelysosomal/lysosomal markers and for major histocompatibility complex (MHC) molecules was used to define PV with respect to the endocytic compartments of the host cells and to address the issue of their potential role in antigen processing and presentation. Forty-eight hours after infection, many PV contained cathepsins B, D, H and L and they were all surrounded by a membrane enriched for the lysosomal glycoprotein lgp120/lamp 1 but apparently devoid of the cation-independent mannose 6-phosphate receptor, a membrane protein generally absent from the lysosomes. These data suggested that PV acquire within 48 hours the characteristics of a lysosomal compartment. However, both macrosialin and the GTP-binding protein rab7p (specific markers of the prelysosomal compartment) were found to be highly expressed in/on PV membrane. Thus, at this stage, PV appear to exhibit both lysosomal and prelysosomal features. Infected macrophages activated with IFN-gamma before or after infection showed PV strongly stained for MHC class II molecules but not for MHC class I molecules. This suggests that, if infected macrophages can act as antigen-presenting cells for class I-restricted CD8+ T lymphocytes, Leishmania antigens must exit the PV. MHC class II molecules reached the PV progressively, indicating that they were not plasma membrane-bound molecules trapped during internalization of the parasites. The redistribution of class II observed in infected cells did not alter their quantitative expression on the plasma membrane at least during the first 48 hours following the phagocytosis of the parasites. The invariant chains, which are transiently associated with class II molecules during their intracellular transport and which mask their peptide-binding sites, did not reach PV or were rapidly degraded in these sites, suggesting that PV-associated class II are able to bind peptides. This last assumption is strengthened by the fact that class II located in PV could bind conformational antibodies that preferentially recognize class II with tightly associated peptides.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

[Myxoma of the left atrium with neurologic manifestations: 8 cases].

A cohort of 8 patients with myxoma of the left atria and neurological manifestations is reported. Cerebral ischaemia, sometimes responsible for epileptic seizures, led to the discover of the myxoma (5 cases) or recurrence after exeresis (1 case) with imaging evidence of cerebral infarction in 5 cases. The first manifestation was a retinal embolism and temporary ischaemia in 1 case and pulmonary embolism with regressive cerebral ischaemia in another case with bilateral myxoma. Some clinical particularities should be underlined including exercise-induced neurological defect (3 cases), systemic embolism associated with cerebral infarction (3 cases), migraine headache as the initial manifestation (1 case) preceding by a pseudolupic syndrome suggesting the possibility of cerebral vasculitis or infectious endocarditis (1 case). The prognosis depends on the risk of recurrent atrial tumour formation (1 case). Metastases are rare. Multiple cerebral aneurysms (3 cases) did not lead to haemorrhagic complications.

Adult↗
PubMed1994

High resolution two-dimensional polyacrylamide gel electrophoresis using Immobilines. Application to the study of brain proteins.

Cytoplasmic soluble proteins of unknown origin but which could be associated with the development and maturation of the central nervous system are recognized by antibodies found in serum of patients with a paraneoplastic neurological syndrome. The associated antigens are of great interest in understanding these neurological pathologies. To study these antigens we describe and criticize a two dimensional polyacrylamide gel electrophoresis (2D-PAGE), using immobilized pH gradient (IPG) in first dimension. Proteins from brain complex mixtures were separated by this technique in order to identify and characterize (molecular weight, p-isoelectric point, sequencing) a protein of interest. Results prove the high reproducibility and the good resolution of the technique. Without applying enrichment method prior to 2D-PAGE, any proteins are not sequenceable after transblotting to PVDF (polyvinylidene difluoride) membrane and Coomassie blue staining. In these cases the meaning to reach the wanted aim, i.e. sequencing, was discussed.

Animals↗
PubMed1993

Antigen presentation capacity of murine macrophages infected with Leishmania amazonensis amastigotes.

Leishmania-infected M phi are potential candidates for the presentation of parasite Ag to Leishmania-specific CD4+ T lymphocytes. To assess whether infected cells could function as APC, we examined the ability of bone marrow-derived M phi infected with Leishmania amazonensis amastigotes to stimulate various CD4+, l-Ad- or l-Ed-restricted T-cell hybridomas specific for the bacteriophage lambda repressor cl protein, the human chorionic gonadotropin or OVA. A reduced capacity of infected M phi to present native Ag to most T-cell hybridomas tested was noted that was probably a result of a lower expression on their plasma membrane of stimulatory [la-peptide] complexes. Neither a reduced Ag uptake nor an altered Ag processing appeared to be at the origin of the partial inability of infected M phi to present Ag. As regards the level of plasma membrane la expression, no quantitative difference could be detected between uninfected and infected M phi. Moreover, after fixation with paraformaldehyde, the ability of plasma membrane la molecules to bind immunogenic peptides was apparently not reduced in infected M phi. So, these cells most likely expressed functional la molecules on their cell surface. Interestingly, infected M phi and M phi infected then cured by a treatment with a leishmanicidal compound were similarly impaired in their capacity to present native Ag or peptides to the hybridomas, and no recovery was noted even 24 h after the leishmanicidal treatment. Furthermore, infected M phi and M phi incubated with heat-killed amastigotes or with an amastigote homogenate exhibited similar inhibitions of Ag presentation. Taken together, these results suggest that the functional failure of infected M phi to present exogenous Ag could be because either of interferences with the events leading to the meeting of la molecules with peptides derived from these exogenous Ag or to a competition for binding to la molecules between these peptides and parasite molecules.

Animals↗
PubMed1993

Posterior uveitis, paraneoplastic encephalomyelitis and auto-antibodies reacting with developmental protein of brain and retina.

We report a 68-year-old woman who presented with posterior uveitis, cerebellar ataxia, dysautonomia, peripheral neuropathy and undifferentiated carcinoma. Autopsy showed slight brain inflammatory changes and severe Purkinje cell degeneration. By immunocytochemistry, the serum and CSF contained antibodies that reacted with the cytoplasm of cells in the brain and retina of rat. Some neurons and glial cells were stained. However, the most labelled cells were immature cells of the subventricular layers of the dentate gyrus, olfactory bulb and lateral ventricles. In rat retina, the plexiform layers and cells of the inner granular layer were stained. E15 rat embryo showed diffuse staining of post-mitotic cells and process in the central and peripheral nervous system. With the patient's IgG, various bands of 45, 60, 70 and 135 kDa apparent molecular weight were demonstrated on immunoblots of adult human, adult and E15 embryonic rat brain and rat and bovine retina. Eluates of tissue bound IgG labelled the same bands.

Aged↗
PubMed1993

[Fatal peripheral neuropathy with predominant motor involvement associated with anti-MAG IgM monoclonal gammapathy].

A 75 year old woman died of predominantly motor peripheral neuropathy with amyotrophy and fasciculations progressing to tetraplegia and death within 19 months. There was a mild distal sensory loss. At electrophysiology, the pattern was initially demyelinating and later became axonal. Nerve biopsy disclosed severe myelinated and unmyelinated fiber loss with wallerian degeneration. The remaining fibers had demyelination widening of the external myelin lamellae and intense hypermyelination. Serum contained an anti-MAG monoclonal IgM reacting with SGPG. Two siblings without monoclonal gammopathy had died of definite amyotrophic lateral sclerosis. This family association is discussed.

Aged↗
PubMed1992

[Autoantibodies in paraneoplastic polioencephalomyelitis: 8 cases].

Antibodies directed against the central nervous system were looked for by indirect immunohistochemistry in the sera of 8 patients with paraneoplastic neurological syndrome (group 1), 21 cancer patients without neurological signs, 23 patients with miscellaneous neurological diseases and 63 normal subjects (groups 2 to 4). Four patients in group 1 had very high titres of antibodies. In 2 patients with small-cell lung carcinoma associated with sensory neuropathy the antibody recognized the cytoplasm and nucleus of all neurons. A 37 Kd protein was recognized by Western blot. A woman with cancer of the ovary and cerebellar syndrome exhibited an antibody against Purkinje's cell cytoplasm with a band of about 50-55 Kd at Western blot. In a woman with chronic uveitis and cerebellar atrophy with disappearance of Purkinje's cells the antibody (in blood and CSF) recognized certain layers of the retina as well as glial cells and cells present in the subependymal areas of the brain. Two bands of 46 and 59 Kd were revealed by Western blot. Immunoglobulins were detected in the cytoplasm of white matter cells in the cerebellum and brain stem. Among the other groups, one patient with lung cancer had a moderate titre of neuronal antinuclear antibody. The Western blot test was negative. The relevance of these antibodies for the diagnosis and treatment is discussed.

Aged↗
PubMed1992

[Sacral perineural cysts. Contribution of magnetic resonance imaging].

In a 41-year old woman complaining of episodic bilateral sciatic pain, MRI showed large sacral cysts developed in the pelvis. The fact that these cysts communicated with the subarachnoidal spaces was not clearly demonstrated by CT. The mechanism underlying the development of this perineural variety of extradural cysts is discussed.

Adult↗