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C Jacque

Publications and source records attributed to C Jacque.

At least 37 records · Page 2Linked to original sources

Migration patterns of donor astrocytes after reciprocal striatum-cerebellum transplantation into newborn hosts.

Fragments of striatum or cerebellum from E 25 rabbit embryo were implanted into either the striatum or the mesencephalon of newborn mice. Implanted rabbit astrocytes were selectively identified by monoclonal antibodies to the GFAP which are unable to combine with mouse GFAP. Previous investigations had shown that xenogenic astrocytes have the capacity to migrate in host CNS. The purpose of this study was to compare the patterns of migration of transplant-derived astroglial cells according to the topographic origin of the transplant and location of the grafting site. We found that the migration pattern of the grafted cells from any of both selected sites of implantation was independent from the topographic origin of the transplant. The routes as well as the distances of migration were similar after homo- or heterotopic transplantation. We conclude that astroglial cells or their precursors do not express information which would direct them to move specifically toward a defined region in the host brain according to the region of origin in the donor.

Animals

Host response during successful engraftment of fetal xenogenic astrocytes: predominance of microglia and macrophages.

Grafting of fetal rabbit brain fragments into the brains of newborn mice results in the successful establishment and migration of xenogenic astrocytes in the majority of recipients. This can be demonstrated by the use of Tp-GFAP1 monoclonal antibody which binds with rabbit, but not with murine glial fibrillary acidic protein. In the first phase, donor astrocytes are found in more than 80% of recipients 3 and 4 weeks after grafting. In the second phase, there is a decline and disappearance of donor astrocytes by the tenth week. We have recently demonstrated that the decline and disappearance of donor astrocytes was co-incident with infiltration of T cells into the brain, compatible with T-cell-mediated graft rejection. In the present studies, we wished to characterize the types of host cells responding during the period of graft success, in the first 4 weeks after transplantation. It was found that responses by microglia, macrophages, and astrocytes occurred promptly and were sustained throughout this period. Host responses occurred at the graft site and at sites of migration. Examination of sham transplanted control mice revealed responses by the same types of cells. No expression of donor Ia antigen was observed, and the expression of Ia antigen by the host was variable and of low magnitude. T cells were rarely present in transplanted brains during this period. Taken together with previous findings, the present studies demonstrate a clear difference in the host response in the brain at the time when xenogenic astrocytes migrate and survive compared to the period when they disappear.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Migration of xenogenic astrocytes in myelinated tracts: a novel probe for immune responses in white matter.

Experimental brain transplantation allows the study of the development of the immune response against brain antigens within the brain itself. This laboratory has developed a transplantation model in which rabbit embryo brain fragments are placed in the brains of newborn mice. The migration of xenogenic astrocytes is traced by a monoclonal antibody which combines with donor but not host glial fibrillary acidic protein. In the first 4 weeks after transplantation, the donor astrocytes successfully migrate, often within myelinated tracts. Following this period, T cells make their appearance and xenogenic astrocytes disappear by 10 weeks. The propensity for clearly identified foreign astrocytes to migrate in myelinated tracts coupled with a well-defined time course of host-vs-graft interaction suggested that the model could be used to study the immune response in white matter. The studies reported here provide sequential examples of the relationship between migration by foreign astrocytes in myelinated tracts and the development of the host immune response. Extensive migration in white matter tracts was first observed in the absence of any T cell response. Subsequently T cells were found at the transplantation site. Finally Ia was found to be expressed on blood vessels and microglia were strongly reactive in white matter that contained T cells but no foreign astrocytes. These observations support the suggestion that the model can be used to more precisely define cellular immune events that occur within white matter.

Animals

Developmental expression of myelin proteins by oligodendrocytes in the CNS of trout.

Using immunohistochemical techniques, the pattern of cytoplasmic staining and the temporal order of expression of 5 major myelin components of oligodendrocytes were studied in the developing central nervous system of trout. The two myelin glycoproteins, IP1 and IP2, in the cytoplasm of glial cells showed a granular pattern of immunostaining, whereas the 36K protein was homogeneously distributed. Analysis of freshly dissociated cells during early stages of myelinogenesis revealed a constant chronological sequence of expression of myelin proteins by the oligodendrocytes: glycoprotein IP2 was the first protein to appear during glial development together with the galactocerebroside GalC at stage 28 followed by the 36K at stage 30 and finally IP1 at stage 32. The deposition of myelin proteins into the nascent myelin sheath occurred in the same chronological order as their expression by oligodendrocytes. Moreover myelin basic protein, which was not detectable in glial cells, on tissue sections was found to appear in parallel with IP2.

Animals

Short-term post-grafting morphological alterations of glia from an adult brain transplant.

Fragments of corpus callosum from adult rabbit have been implanted into the brain of newborn mice. Previous studies had shown that under such conditions transplant-derived astroglial cells differentiate in the host and survive for at least 2 months. The present study was devised to clarify the fate of the differentiated astrocytes present in the adult transplant by using combined ultrastructural and immunohistochemical approaches. These mature cells are shown to degenerate and die within 2 days after the implantation. Therefore, we suggest that stem cells present in adult tissue would account for the surviving population of transplant-derived glial cells.

Animals

Glial fibrillary acidic protein and beta A4 protein deposits in temporal lobe of aging brain and senile dementia of the Alzheimer type: relation with the cognitive state and with quantitative studies of senile plaques and neurofibrillary tangles.

The aim of this study was to compare brain glial fibrillary acidic protein (GFAP) levels to the modifications of cognitive functions (Blessed test score [BTS]), the density of the main neuropathological lesions (senile plaques [SP] and neurofibrillary tangles [NFT]), and the density of the two main subtypes of beta A4 deposits (classic plaques and diffuse deposits) in a series of patients with normal aging and senile dementia of the Alzheimer type of various degrees of severity. GFAP levels (enzyme-linked immunosorbent assay [ELISA] technique) and the densities of changes were measured in the temporal lobe of 12 women over 75 years of age. Under these conditions, the ELISA assay could determine GFAP in brain homogenates (aqueous-Triton buffer soluble extract) in a range from 2.5 ng to 600 ng per assay. Least affected patients (with a BTS of 19 and over) all ranged below 60 micrograms/mg protein. Most affected patients (with a BTS under 6) ranged above 150 micrograms/mg protein. However, interindividual variations were wide. A significant correlation between the BTS and the amount of GFAP could be found only when using the non parametric test of Spearman. There was a significant positive correlation between the amount of GFAP and the density of 1) SP, 2) NFT both revealed by Bodian's silver stain, and 3) classic beta A4 plaques shown by immunocytochemistry. On the contrary, no correlation was observed with diffuse beta A4 deposits. One case with very large amounts of diffuse beta A4 deposits without SP or NFT showed no associated GFAP reactivity. This suggests that GFAP production is a critical event in the formation of classic SP.

Aged

Cerebrospinal myelin basic protein in multiple sclerosis. Identification of two groups of patients with acute exacerbation.

The myelin basic protein concentration in the cerebrospinal fluid (CSF) of 125 patients with multiple sclerosis was measured using a radioimmunoassay technique with a detection level of 200 pg/mL and was correlated with the clinical course of the disease. Myelin basic protein was detected in the CSF of some patients with an active progressive form of the disease and in the CSF obtained during exacerbations with the presence of signs or symptoms not previously experienced by the patient (26 of 29 cases were positive during the period of maximal symptoms). Myelin basic protein was not detected in any patient with an inactive or slowly progressive form of the disease, nor in any patient during exacerbations with only recurrence of old signs or symptoms. These results are consistent with the hypothesis that the two clinical forms of exacerbation defined above may be associated respectively with the absence or presence of an acute demyelination.

Humans

Absence of correlations between glutamine-synthetase activity and dysmyelination-associated modifications of astroglia in the brain of murine mutants.

Glutamine Synthetase (GS) activity was investigated in cerebellum (ce), cerebral cortex (cc), olfactory bulb (ob), and medulla oblongata (mo) of murine dysmyelinating mutants for correlations with modifications of astroglia associated with genetic dysmyelination. One of these mutants, jimpy, develops a strong gliosis throughout the CNS. The other three mutants: shiverer, mld, and quaking, exhibit various astrocytic responses to dysmyelination, but reduced gliosis if any. Comparison between CNS areas in control animals showed a higher GS activity in the olfactory bulb than in the cerebral cortex, medulla, and cerebellum. The developmental patterns of GS activity were similar in mutants and in controls in all four areas investigated. Data on Jimpy suggest that GS activity is not associated with reactive astrocytes.

Animals

Are anti-brain antibodies in multiple sclerosis directed to myelin basic protein? Studies employing the Shiverer mouse mutant.

The dysmyelinating mouse mutant Shiverer has a severe and relatively selective deficiency of myelin basic protein (MBP) in the central and peripheral nervous system. Nevertheless, Shiverer brain and control-mouse brain showed similar antigenic titers when tested by a complement fixation assay against a panel of 14 multiple sclerosis (MS) sera and 6 MS CSF samples known to represent several specificities of antibrain antibodies. By analogy with experimental allergic encephalomyelitis, a sensitization to MBP has been proposed in MS. Our results, however, show that antibodies to other CNS antigens are quantitatively more important in this disease.

Animals

Immunohistochemical localization of myelin basic protein in the developing optic system of trout.

Immunofluorescent localization of basic protein (BP) in the CNS of trout was performed using a heterologous antiserum raised against human BP. Bright specific fluorescence was confined to the myelin sheath of axons in most regions of the brain, whereas neuronal pericarya and dendrites as well as glial cells were entirely negative. In the tectum immunofluorescence was characteristically distributed in two rows of horizontally aligned patches, most evidently reflecting the orderly array of myelinated fiber bundles in the stratum opticum and stratum album. During development of the retino-tectal pathway, the appearance of BP followed a distinct rostro-caudal gradient firstly reaching the anterior ventral border of the tectum by larval stage 34. Furthermore, on cross sections through the optic nerve a specifically organized pattern of myelin formation was revealed by immunohistochemistry, which strikingly coincided with the pattern of fiber outgrowth.

Animals

Double ligand ELISA technique for the estimation of antibodies to brain tissue antigens in patients with neurological disorders.

A double ligand enzyme-linked immunosorbent assay (ELISA) has been developed to detect antibodies against brain tissue antigens in the sera of patients with neurological diseases. The sera were tested on human white matter homogenate. The technique consists of successive incubations with the human serum to be tested, rabbit immunoglobulin G (IgG) to human immunoglobulins (Ig), alkaline phosphate-labeled protein A and alkaline phosphatase substrate. This procedure has the advantage of increased sensitivity compared to the classical ELISA. Application of this procedure to the sera of patients with neurological diseases showed that the unspecific binding is very low and the results are reliable. Moreover the test allows the detection of antibodies to chemically different antigenic structures that can occur in a variety of neurological diseases.

Adolescent

Immunocytochemical characterization of pulmonary histiocytosis X cells in lung biopsies.

Morphologic and immunohistochemical studies were made of open lung biopsies from 9 patients with pulmonary histiocytosis X (HX) and 12 patients with other conditions, and of skin biopsies from patients with cutaneous sarcoidosis, Chester-Erdheim disease, and eruptive histiocytoma. The monoclonal antibody OKT6 was detected with the use of goat anti-mouse IgG labeled with fluorescein (FITC) for light microscopy, and sheep antimouse Fab'2 fragment of IgG labeled with horseradish peroxidase (HRP) for immunoelectron microscopy. The presence of S-100 protein was revealed by an antibody prepared against bovine S-100 protein, using sheep anti-rabbit IgG labeled with FITC for light microscopy and with HRP for immunoelectron microscopy. OKT6 antibody and S-100 protein were detected simultaneously by double labeling with FITC and rhodamine. In all patients with pulmonary HX, the major cellular components (HX cells) of the granulomas showed labeling of the plasma membranes by OKT6 and of the cytoplasm by the anti S-100 protein antibody. The double-labeling technique demonstrated that the same cells carried both reactivities. Immunoelectron microscopy showed that the reactive cells had all the structural characteristics of Langerhans cells, including Langerhans cell granules. Cells reacting with OKT6 showed discrete internal labeling in some of the Langerhans granules, especially those in continuity with the plasma membranes. However, internal labeling of Langerhans granules was not demonstrated in preparations for the localization of S-100 protein. Control samples of sarcoid lesions and other pulmonary lesions unrelated to HX did not show any reactivity except in Langerhans cells; a skin lesion from a patient with eruptive histiocytoma contained OKT6-positive cells which did not have Langerhans granules.

Antibodies, Monoclonal

Tamm-Horsfall protein, a kidney marker is expressed on brain sulfogalactosylceramide-positive astroglial structures.

The Tamm-Horsfall (TH) glycoprotein and the acidic glycosphingolipid sulfogalactosylceramide (SGC) have a strictly superimposable localization on kidney tissue sections. The fact that SGC is a prevalent glycolipid in mammalian brain, prompted us to look for the presence of TH in the rat central nervous system (CNS). An antiserum raised against human TH was found to react with rat CNS homogenate in the complement fixation assay. This anti-TH antiserum recognized a rat CNS protein having an identical electrophoretical mobility on SDS polyacrylamide gel electrophoresis (PAGE). Indirect immunofluorescence on rat brain tissue sections allowed us to localize this brain TH cross-reacting material to ependymal cells and astrocytic processes such as the Bergmann fibers or astrocytic feet in contact with either the blood vessels or the meninges. All these astroglial structures are also SGC-positive. Since TH and SGC in the kidney are localized on a membrane that possesses an electrogenic Cl-pump, we propose that the astroglial structures which contain these two molecules are also the site of a Cl-transport system.

Animals

Cell-free synthesis of myelin basic proteins in normal and dysmyelinating mutant mice.

Total polyribosomes were isolated from the brains of 16-20 day C57BL/6 mice, four neurological mutants (qk/qk, shi/shi, mld/mld, and jp/Y), and four heterozygote or littermate controls (qk/+, shil/+, mld, and jp littermates) and translated in a homologous, cell-free system. No differences were observed among the nine genotypes in either the yield of polysomes (32.2 +/- 0.6 A260/g brain) or in the incorporation of [35S]methionine into trichloroacetic acid-precipitable protein. However, when the four myelin basic proteins (BPs) were isolated from the translation mixtures little incorporation of [35S]methionine into the BPs was noted in those assays directed by polysomes from mld/mld or from shi/shi animals. Compared with C57BL/6 polysomes, mld littermate and shi/+ polysomes incorporated approximately half the levels of label into the four BPs while qk/+ and qk/qk incorporated normal and close-to-normal levels. Polysomes from jp littermates and jp/Y brains synthesized 66% and less than 15% of the levels of the 14K BP compared with C57BL/6 polysomes. Incorporation of label into the other three BPs was normal with jp littermate polysomes and about half the control levels with jp/Y polysomes. The data indicate that shi/shi and mld/mld mutants either produce altered BPs not recognized by our antibody or synthesize very low levels of BP. The data provide additional support for the notion that the qk/qk mutant synthesizes much higher levels of MBP than are incorporated into myelin. They also indicate that in the jimpy mutant the synthesis of the four BPs is affected to differing extents; thus, the mutant cannot be easily characterized as either an "assembly" or "synthesis" defect.

Animals

[Recent data on Schwann cells].

Because of the role they play in the physiopathology of peripheral neuropathies, Schwann cells have been the subject of numerous studies for some ten years. Schwann cells originate in the ectoderm. They migrate along the myelinated and the unmyelinated axons of peripheral nerves, and lie on a basal lamina. They are responsible for the myelination of peripheral nerves; whether the Schwann cell does or does not form a myelin sheath is determined by the type of axon with which it associates. Recent techniques, such as chimaeric quail-chick embryos, biochemical analysis of human peripheral nerve biopsies, Schwann-cell cultures, nerve grafts, mouse mutants, have permitted some progress. The biochemical composition of peripheral myelin is almost completely known. In vitro, Schwann cells can synthesize myelin-specific molecules. Interactions between axons, Schwann-cells and extra-cellular space have been observed.

Animals

Survival and differentiation of oligodendrocytes from neural tissue transplanted into new-born mouse brain.

Fragments of new-born mouse central nervous system have been transplanted into new-born mice host brains, under conditions in which the myelin synthesized by the oligodendrocytes included in the graft, could be distinguished from the host myelin. The work demonstrates that transplanted oligodendrocytes survive in the host brain, migrate out of the graft and synthesize myelin. No sign of rejection was observed during the time of the experiment.

Animals