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J Trotter

Publications and source records attributed to J Trotter.

At least 55 records · Page 3Linked to original sources
PubMed1993

Astrocytes and neurons regulate the expression of the neural recognition molecule janusin by cultured oligodendrocytes.

Janusin (formerly designated J1-160/180) is an extracellular matrix glycoprotein highly homologous to tenascin, consisting of two major molecular forms of 160 and 180 kD expressed by oligodendrocytes and in myelin. Janusin expression is upregulated during myelination and in the adult it remains expressed at lower levels. It is also present at the node of Ranvier, where myelin, axon, and astrocytic process are in close contact. To gain an understanding of the regulatory mechanisms which may underlie expression of janusin, the differentiation stage-dependent expression of janusin was studied in cultures enriched in mouse oligodendrocytes and their precursor cells. Expression of janusin by these cells was highest on both A2B5+ and O4+/O1- oligodendroglial precursor cells and a subset of myelin associated glycoprotein-positive (MAG+) oligodendrocytes. Hardly any of the more differentiated O1+ or O10+ oligodendrocytes expressed janusin. Expression of janusin was influenced by co-culture with astrocytes or neurons. Astrocytes or astrocytic-conditioned culture supernatants elevated the expression of janusin by the more differentiated oligodendrocytes (O1+ or MAG+ cells), while its expression by oligodendroglial precursor cells was relatively unchanged. Platelet-derived growth factor, but not basic fibroblast growth factor, also elevated the expression of janusin by O1+ or O10+ oligodendrocytes. In contrast, co-culture with neurons originating from dorsal root ganglia or spinal cord decreased the expression of cell-bound janusin by oligodendrocytes and their precursor cells. These observations indicate that expression of janusin on these cells in culture is susceptible to opposing regulatory influences from astrocytes and neurons. Such influences may modulate the temporal and spatial distribution of janusin in the developing and adult central nervous system.

Animals↗
PubMed1993

The development of myelin-forming glia: studies with primary cell cultures and immortalized cell lines.

The myelin-forming glial cells, oligodendrocytes and Schwann cells, undergo a sequence of maturation steps from precursor cell to mature myelinating cell. This includes migration from their site of generation to the axons they will myelinate. The recognition and interaction with the axons prior to the formation of compact myelin involve the interplay of a range of cell surface receptors and adhesion molecules, some of which have been defined. Signal transduction by such adhesion molecules may play a role in the recognition event. The generation of a range of immortalized cell lines and clones of oligodendroglial precursor cells and the analysis of their in vitro and in vivo properties have demonstrated the ability of these lines to recognize axons. They are providing useful tools to investigate the molecular basis of glia-neuron interactions.

Animals↗
PubMed1992

Tcl-30, a new T cell-specific gene expressed in immature glucocorticoid-sensitive thymocytes.

Glucocorticoid treatment induces programmed cell death (apoptosis) in susceptible T lymphocytes. We have previously isolated and characterized 13 genes induced by agents that cause apoptosis in the murine thymoma cell line, WEHI-7TG. One of these genes, now designated Tcl-30, encodes a 2.4-kb mRNA that is specifically expressed in thymus. Sequence analysis of a full-length cDNA for Tcl-30 reveals a potential open reading frame of 454 amino acids that shares sequence identity to a human placental-specific protein of unknown function, PP11. The putative protein encoded by Tcl-30 also contains a cysteine-rich somatomedin B-like domain found in vitronectin, PP11, and the plasma cell membrane glycoprotein, PC-1. Subpopulations of murine thymocytes sorted on the basis of their expression of the CD4, CD8, and surface heat-stable Ag (HSA) were analyzed by an RNase protection assay to determine the expression of Tcl-30 as a function of T cell development. Tcl-30 was expressed exclusively in the HSA+ T cell populations (CD4-CD8-HSA+; CD4+CD8-HSA+; CD4-CD8+HSA+; and CD4+CD8+HSA+) and not in the HSA- single positive T cell populations (CD4+CD8- or CD4-CD8+) of the thymus or spleen. Therefore, we conclude that Tcl-30 expression is lost during T cell maturation and is absent at the most mature stages of T cell development. The function of Tcl-30 is unknown; however, the CD4+CD8+ double-positive subpopulation expressing Tcl-30 represents thymocytes destined to undergo massive intrathymic cell death. The possibility that Tcl-30 expression may define a population of T lymphocytes that is sensitive to glucocorticoid-mediated apoptosis is discussed.

Amino Acid Sequence↗
PubMed1992

The differentiation of glial cell progenitor populations following transplantation into non-repairing central nervous system glial lesions in adult animals.

The non-repairing nature of the locally x-irradiated ethidium bromide (EB)-induced demyelinating white matter lesion has been further validated by showing that injections of two cultures which promote host remyelination of EB lesions in normal tissue do not do so in x-irradiated lesions. The behaviour of an oncogene-immortalized glial cell line and a growth-factor-expanded glial progenitor population have been examined following transplantation into the non-repairing EB lesion. Our studies indicate that the selected glial cell populations were each capable of establishing glial environments around demyelinated axons. Extensive oligodendrocyte remyelination with little astrocytic presence was observed in lesions transplanted with growth-factor-expanded optic nerve progenitors, while less extensive oligodendrocyte remyelination with the establishment of astrocyte-like cells was found in lesions transplanted with ts A58-SV40T immortalized glial cells. Prolonged expansion of both populations resulted in a loss of differentiation to normal glial phenotypes.

Animals↗
PubMed1992

Extranodal Ki-1 lymphoma in a renal transplant patient.

THe Ki-1 (CD 30) antigen has been identified as a marker of a subset of large cell anaplastic non-Hodgkin's lymphoma that may have a more favourable prognosis. We describe an immunosuppressed renal transplant patient who developed primary extranodal large cell anaplastic Ki-1 lymphoma of T-cell phenotype confined to the sigmoid colon. The patient was treated with local resection of the sigmoid colon and reduction of immunosuppression and at two year follow-up remains free of recurrence. It is recognised that long term immunosuppression in post transplant patients increases the risk of certain malignancies. Localised gut lymphoma may be amenable to local resection as a curative procedure.

Colonic Neoplasms↗
PubMed1992

Thyroid involvement in multiple myeloma.

Involvement of the thyroid gland by plasma cell neoplasms is a rare occurrence. Two modes of presentation are described; firstly as part of disseminated myeloma and secondly, as an isolated plasma cell neoplasm of the thyroid as the only evidence of disease. We wish to describe two cases of thyroid involvement as part of disseminated disease.

Aged↗
PubMed1991

Autoantigen-induced self lysis of human myelin basic protein-specific T lymphocytes.

Cytotoxic T cells reactive with myelin basic protein (MBP) may be isolated from most human subjects. Since activated T cells express major histocompatibility complex (MHC) class II antigens, we assessed whether MBP-specific, CD4+ T cells could present MBP or synthetic MBP peptides to themselves and whether this provoked self lysis. We examined two MBP-specific cell lines and eight T cell clones recognizing four different MBP epitopes. All T cell populations presented MBP as well as synthetic peptides to themselves eliciting self lysis of the T cell clones. CD4+ T cell populations recognizing another central nervous system (CNS) protein, proteolipid protein (PLP), or the recall antigen, Candida, did not exhibit this antigen-induced, autocytolytic activity. However, activated, PLP-reactive T cells were susceptible to lysis by cytotoxic MBP-specific T cells in the presence of MBP. These results suggest that antigen-induced self lysis of activated human T cells might limit an autoimmune response within a target organ independent of other immunoregulatory mechanisms.

Autoantigens↗
PubMed1991

Physiological properties of oligodendrocytes during development.

The electrical properties of oligodendrocytes during their development in cell culture were analyzed by combining two techniques: cell identification with cell-type and stage-specific antibodies and the patch-clamp technique. The transition from the bipotential precursor cell, which can still develop into astrocytes and oligodendrocytes, into an oligodendrocyte results in a marked change in the ion channel pattern. During this developmental transition, voltage-activated Na+ and several types of K+ currents disappear, whereas a comparatively passive, inwardly rectifying K+ current becomes dominant. GABAA receptor-mediated Cl- currents and a pH-activated Na+ current are down-regulated at this transition but are still present at all developmental stages. In contrast, electrical coupling develops only in oligodendrocytes. This change in the channel repertoire could reflect the transition of a cell in a mobile, mitotic, plastic state (the glial precursor) to a more differentiated specialized state (the oligodendrocyte).

Animals↗
PubMed1991

Replication timing control can be maintained in extrachromosomally amplified genes.

Extrachromosomal elements are common early intermediates of gene amplification in vivo and in cell culture. The time at which several extrachromosomal elements replicate was compared with that of the corresponding amplified or unamplified chromosomal sequences. The replication timing analysis employed a retroactive synchrony method in which fluorescence-activated cell sorting was used to obtain cells at different stages of the cell cycle. Extrachromosomally amplified Syrian hamster CAD genes (CAD is an acronym for the single gene which encodes the trifunctional protein which catalyzes the first three steps of uridine biosynthesis) replicated in a narrow window of early S-phase which was approximately the same as that of chromosomally amplified CAD genes. Similarly, extrachromosomally amplified mouse adenosine deaminase genes replicated at a discrete time in early S-phase which approximated the replication time of the unamplified adenosine deaminase gene. In contrast, the multicopy extrachromosomal Epstein-Barr virus genome replicated within a narrow window in late S-phase in latently infected human Rajii cells. The data indicate that localization within a chromosome is not required for the maintenance of replication timing control.

Adenosine Deaminase↗
PubMed1991

Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin-associated glycoprotein.

We studied a series of 64 patients with sensory +/- motor peripheral neuropathies by comparing clinical and physiologic features to serum antibody reactivity against compounds containing sulfated carbohydrate moieties. We determined antibody reactivity by an enzyme-linked immunosorbent assay (ELISA) using purified glycolipids and glycoproteins as antigens, and we used high-performance thin-layer chromatography and Western blotting to test the specificity of results. Twelve patients with high titers of IgM antibodies directed against the myelin-associated glycoprotein (MAG) had sensory-motor polyneuropathies with physiologic evidence of demyelination. IgM antibody reactivity to MAG was associated with an IgM serum M protein in five patients. Eight other patients, most with sensory greater than motor polyneuropathies, had high titers of antibody reactivity to sulfatide but not of IgM to MAG. Two had an associated IgM paraprotein. None of the patients with selective serum antisulfatide activity had predominantly demyelinating features on physiologic testing. We conclude that (1) high ELISA titers of antibodies to MAG may be more common than previously suspected in patients with chronic demyelinating sensory-motor neuropathies, and (2) the presence of high titers of antisulfatide antibodies in serum may provide clues to the pathogenesis of otherwise idiopathic, axonal, predominantly sensory neuropathies.

Adult↗
PubMed1990

Cultured glial precursor cells from mouse cortex express two types of calcium currents.

Glial precursor cells of the oligodendrocyte lineage express two types of Ca2+ channels which can be distinguished by their peak activation. Ca2+ currents were recorded using the patch-clamp technique in the whole cell configuration and were found to be similar to the low and the high voltage activated Ca2+ channel described in neurons. While the majority of precursor cells expressed only one of the two current types respectively, in 30% of cells both types of current could be identified. These Ca2+ channels might play an important role in signal transduction during target recognition of the developing glial cell.

Animals↗
PubMed1990

Phenotypic analysis of the early events during repopulation of the thymus by the bone marrow prothymocyte.

The phenotype of the donor thymocytes present in the thymus of irradiated mice injected intravenously with CD3-depleted total bone marrow cells has been studied by three-color flow cytometry during the time period 6-16 days postinjection. Donor cells could first be reliably detected at Day 6 after reconstitution. Donor and host cells maintain their relative proportions over the first few days, after which time the proportion of donor cells derived from the bone marrow increases. At Days 6 and 7 after reconstitution, Pgp-1+, IL-2R- cells predominate, although a minority of Pgp-1+, IL-2R+ cells is also seen. Few cells are Pgp-1-, IL-2R+. Over the next 3 days, the relative proportion of Pgp-1+, IL-2R- cells declines rapidly and the relative proportion of Pgp-1+, IL-2R+ cells and then of Pgp-1-, IL-2R+ cells peaks and declines. The absolute number of all three populations, however, increases exponentially until Day 14. Most donor cells present at Days 6-7 after reconstitution are L3T4-, Lyt-2-. Over the next 2 days, the majority of donor-derived cells express low, but significant, levels of both L3T4 and Lyt-2. L3T4+, Lyt-2+ cells expressing levels of cell surface antigen characteristic of the cognate population found in the adult first appear at Day 10 after reconstitution. These L3T4+, Lyt-2+ donor cells increase in proportion to reach 70-80% of donor-derived cells after Day 14 of reconstitution. The host thymocyte population, on the other hand, contains few Pgp-1+ or IL-2R+ cells even at 7 days after irradiation and is predominantly L3T4+, Lyt-2+ by Day 8. This observation suggests that the host cells are derived from a more mature precursor than the bone marrow prothymocyte or the earliest intrathymic progenitors.

Animals↗
PubMed1990

Changes in the relative abundance of type I and type II lck mRNA transcripts suggest differential promoter usage during T-cell development.

The lck gene, which encodes the lymphoid cell-specific tyrosine protein kinase p56lck, is expressed from two widely separated promoters. The proximal promoter gives rise to a type I lck transcript, and the distal promoter gives rise to a type II transcript. We found that the ratio of the two transcripts changed during T-cell maturation. Type I lck mRNA was twofold more abundant than the type II transcript in early fetal thymocytes. In the adult, the type I and type II lck mRNAs were present in approximately equal amounts in immature thymocytes expressing the heat-stable antigen. In contrast, there was five- to ninefold more type II lck than type I lck mRNA in more mature thymocytes that did not express the heat-stable antigen and in splenic T cells. This change in relative transcript abundance probably reflects activation of the distal promoter and inactivation of the proximal promoter during T-cell maturation in the thymus. It is possible that the two promoters are regulated by different trans-acting factors whose expression is regulated during T-cell maturation.

Animals↗
PubMed1989

Cells positive for the O4 surface antigen isolated by cell sorting are able to differentiate into astrocytes or oligodendrocytes.

Cells expressing the surface antigen O4 were isolated as pure populations from cultures of murine brain or cerebellum using fluorescence activated cell sorting. When these O4-positive cells were further cultured in the presence of fetal calf serum (FCS) many cells expressed both O4 and the astrocyte marker glial fibrillary acidic protein (GFAP) after 4 days of culture. Cells not exposed to FCS expressed O4, but never GFAP. GFAP-positive cells in the presence of fetal calf serum very rarely expressed the myelin associated glycoprotein (MAG) or O1, both of which are expressed on more differentiated oligodendrocytes, and never expressed O10 that is characteristic of even more mature oligodendrocytes. These results show that glial cells expressing O4, but not MAG, O1, O10 or GFAP are bipotential precursor cells able to differentiate into astrocytes or oligodendrocytes depending on the culture conditions and suggest that bipotentiality of glial precursor cells is retained up to a later developmental stage than that of the O2A progenitor cell.

Animals↗
PubMed1989

Differentiation-regulated loss of the polysialylated embryonic form and expression of the different polypeptides of the neural cell adhesion molecule by cultured oligodendrocytes and myelin.

The expression of the neural cell adhesion molecule (N-CAM) on cultured murine oligodendrocytes, their precursors, and myelin was examined by indirect immunofluorescence, biosynthetic radiolabeling followed by immunoprecipitation and Western blot analysis, using antibodies specific for various forms of the molecule. In all culture systems studied, whether the oligodendrocytes were cultured as an enriched fraction containing precursor cells or in the presence of astrocytes and neurons, a similar differentiation-stage-related expression of N-CAM was seen. At early developmental stages many tetanus toxin receptor- and A2B5 antigen-positive putative oligodendrocyte precursors with bipolar morphology were seen and found to express N-CAM in its embryonic form. Of the 04 antigen-positive immature oligodendrocytes with few slender processes most expressed N-CAM, but few the embryonic form of N-CAM. The more mature 01 or 010 antigen-positive oligodendrocytes were found to express exclusively the adult form of N-CAM. Oligodendrocytes synthesized the 120 and 140 kD forms of N-CAM (N-CAM 120 and N-CAM 140), but not N-CAM 180, although with differentiation, N-CAM 120 predominated in oligodendrocytes and also in pure myelin. N-CAM 120 could be released from oligodendrocytes and myelin by phosphatidylinositol-specific phospholipase C, suggesting that in both oligodendrocytes and myelin N-CAM 120 is inserted into the membrane by covalent linkage to phosphatidylinositol.

Animals↗