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R Meyermann

Publications and source records attributed to R Meyermann.

At least 109 records · Page 6Linked to original sources
PubMed1992

Cloning of a novel TGF-beta related cytokine, the vgr, from rat brain: cloning of and comparison to homologous human cytokines.

Here we describe cloning of a TGF-beta related cytokine from a rat brain cDNA library. This novel cytokine, the vgr (vegetal related), is homologous to the vegetal (Vg1) gene of Xenopus (DL Weeks and DA Melton, Cell, 51:861-867, 1987). In rat brain mRNA a single 3.5 kb RNA could be detected by Northern blot analysis. Thus, this new cytokine is constitutively expressed in the central nervous system. A monoclonal antibody reactive with a synthetic peptide of vgr revealed a faint vgr-like immunoreactivity throughout the CNS, with more pronounced staining of hippocampal neurons, ependymal cells, cells of the choroid plexus, and hypophysis. Using the rat cDNA, two homologous human cytokine cDNAs encoding the human vgr and op-1 were cloned.

Animals↗
PubMed1992

Immunohistochemical co-localization of glycogen phosphorylase with the astroglial markers glial fibrillary acidic protein and S-100 protein in rat brain sections.

Immunofluorescence double-labelling and immunoenzyme double-staining methods were used to examine the location of glycogen phosphorylase brain isozyme with the astrocyte markers glial fibrillary acidic protein (GFAP) and S-100 protein in formaldehyde-fixed, paraffin-embedded slices from adult rat brain. Astrocytes in the cerebellum and the hippocampus, which express GFAP or S-100 protein immunoreactivity, show glycogen phosphorylase immunoreactivity. Regional intensity and intracellular distribution of the three antigens vary characteristically. In ependymal cells, glycogen phosphorylase immunoreactivity is co-localized with S-100 protein immunoreactivity, but not with GFAP immunoreactivity. These findings confirm that glycogen phosphorylase in the rat brain is exclusively localized in astrocytes and ependymal cells. All astrocytes, as far as they express GFAP or S-100 protein, do contain glycogen phosphorylase.

Animals↗
PubMed1991

The multidrug-resistance gene MDR1 is expressed in human glial tumors.

The most consistantly reported alteration of multidrug-resistant carcinoma cells is the overexpression of a membrane glycoprotein, termed P-glycoprotein. In this study we examined whether the strong intrinsic chemotherapy resistance of glial tumors might be related to the expression of the MDR1 gene which codes for P-glycoprotein. Fourteen glial tumors were examined immunohistochemically using the monoclonal antibody C219. In addition, RNA samples of 11 of these tumors were analysed using a sensitive Northern blot assay. P-glycoprotein is expressed in all 14 glial tumors; the number of stained tumor cells, however, varied considerably ranging from 0.3% to 15%. There was no correlation between the number of MDR1-positive cells and the histological malignancy. Varying amounts of MDR1 mRNA were detectable in 7 from 11 examined tumors. The results of our study show that the MDR1 gene is expressed in human glial tumors and suggest that the multidrug transporter may contribute to the clinical non-responsiveness of these tumors to chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Spontaneous multidrug transport in human glioma cells is regulated by transforming growth factors type beta.

The multidrug transporting cell membrane molecule P-glycoprotein can be spontaneously expressed in human glioma cells. Transcripts of mdr genes were detected in glial tumor cells by polymerase chain reaction and Northern blotting, expression of P-glycoprotein was analyzed by immunocytochemistry and functional activity by cytofluorometry of fluorescent probe transport. In vitro treatment of glioma cells with vincristine induced coordinate over-expression of both mdr1 and mdr3 genes associated with very high P-glycoprotein-mediated multidrug transport, resistant to the inhibitory activity of chemosensitizers like verapamil. The physiological modulators of multidrug transport are as yet unknown. We therefore initiated a screening program to analyze the effects of cytokines on multidrug transport. We observed, that transforming growth factors (TGF)-beta 1, -beta 2, and -beta 1.2-but not the related bone morphogenetic protein (BMP) 2--inhibited multidrug transport. Interestingly, BMP 2 antagonized the TGF-beta induced inhibition of multidrug transport.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Chronic relapsing experimental allergic neuritis induced by repeated transfer of P2-protein reactive T cell lines.

Chronic relapsing experimental allergic neuritis (crEAN) was induced by repeated transfers of P2-protein reactive T lymphocyte lines. Clinically, each intravenous transfer of P2-reactive T cells induced a relapse of the disease with weight loss and flaccid paresis of the hindlimbs followed by recovery. After multiple transfers, recovery from disease was incomplete, leading to increasing neurological deficit during the remissions. The pathology of the lesions during exacerbations was characterized by massive inflammation in the peripheral nervous system, associated with extensive endoneurial oedema, nerve fibre destruction and wallerian degeneration. Selective primary demyelination and remyelination was found in the minority of affected nerve fibres. No onion bulbs were present in chronic lesions. In the central nervous system partial degeneration of the posterior columns reflected the extent of wallerian degeneration in the peripheral nerves and spinal roots. In addition, during stages of active disease some T lymphocytes and upregulation of Ia antigen expression were found in the spinal cord.

Animals↗
PubMed1991

Interaction of T lymphocytes with cerebral endothelial cells in vitro.

As a prerequisite of inflammatory lesion formation in (auto-)immune disease of the central nervous system, lymphocytes have to interact with brain endothelia. In recent years much progress has been made towards a better understanding of mechanisms and factors involved in organ specific homing of lymphocytes. Many lines of evidence indicate that T lymphocytes recognizing antigens which are exclusively beyond the blood-brain barrier cross this barrier only when they are in an activated state, irrespective of their antigen specificity. Antigen presentation by blood-brain barrier endothelia, however, may play a role in later stages of florid inflammation.

Animals↗
PubMed1991

Experimental allergic encephalomyelitis-prophylactic and therapeutic treatment with the cyclooxygenase inhibitor piroxicam (Feldene).

Prophylactic administration of Piroxicam (Feldene), a reversible inhibitor of prostaglandin biosynthesis, significantly reduced the occurrence of paralytic signs and the amount of antibodies against myelin basic protein in the model of mild acute experimental allergic encephalomyelitis in the Lewis rat. Mononuclear infiltration of the central nervous system remained unaffected. A therapeutic intervention with piroxicam, however, increased paresis and CNS pathology. Immunohistochemical studies revealed an increased proportion of ED1-positive macrophages and monocytes in the infiltrates of the spinal cord in animals treated with piroxicam. Possible reasons for the different effects of the prophylactic and therapeutic treatment are discussed in the study.

Administration, Oral↗
PubMed1991

TGF-beta 1, beta 2, beta 1.2 and the bone morphogenetic protein BMP2: members of the transforming growth factor type beta supergene family with different morphogenetic effects on rat astrocyte cultures.

The transforming growth factors type beta (TGF-beta) are immunoregulatory cytokines with pronounced effects on tissue homeostasis and repair. We observed that TGF-beta 1, TGF-beta 2, and the heterodimeric TGF-beta 1.2 induced astrocyte hyperplasia and strongly affected monolayer formation. After confluent growth, astrocytes are contact inhibited and form a dense monolayer. Addition of TGF-beta induced migration of cells to local centers, the formation of foci, followed by detachment of these aggregates from the cell culture surface. This effect was unique and could neither be induced by BMP2, a member of the decapentaplegic subfamily of type beta transforming growth factors nor by other cytokines or interleukins. Thus TGF-beta secreted by activated leukocytes might be a local regulator of astrocyte function during regenerative processes in inflammatory demyelinating brain disease.

Animals↗
PubMed1990

Diseases of the vertebral arteries.

Case reports and postmortem neuropathological findings of a wide spectrum of diseases affecting the vertebral arteries, in particular vasculitis, traumatic lesions, degenerative changes and congenital abnormalities, are discussed.

Adult↗
PubMed1990

Experimental autoimmune encephalomyelitis in the maturing central nervous system. Transfer of myelin basic protein-specific T line lymphocytes to neonatal Lewis rats.

We analyzed the effects of myelin basic protein (MBP)-specific encephalitogenic T line cells in neonatal syngeneic recipients before and after formation of central nervous system myelin. Lewis rat pups (postnatal days 0, 1, 2, 4, 8) were injected intraperitoneally with MBP-specific T cell line in doses which cause clinical and histologic changes of experimental autoimmune encephalomyelitis (EAE) in adult rats. We correlated the susceptibility to transferred EAE with the developmental appearance of MBP as demonstrated by immunohistochemical staining. MBP was barely demonstrable until postnatal day 2 but became definitely apparent on postnatal day 4. All newborn rats that were injected on postnatal day 0, 1, 2 failed to develop any apparent clinical signs, but histologically some recipients displayed slight inflammatory cell infiltration of the meninges and subpial lesions limited to the lower spinal cord. In striking contrast, rats that were injected on postnatal day 4 or 8, developed clinical signs and, in particular, many of the older recipients became moribund. Histologically, these animals displayed marked inflammatory cell infiltrations and white matter destruction within the spinal cord. Clinical and histologic severity clearly increased with the recipient's age. Histologically, there were some differences between adult rat EAE and newborn rat EAE. In contrast to adult rat EAE which displayed grey and white matter involvement with marked perivascular mononuclear cell infiltrations, newborn rat EAE typically showed very severe changes with edema formation selectively in the white matter and the cellular infiltrates were dominated by polymorphonuclear cells and macrophages. Newborn T line-mediated EAE thus strikingly resembles hyperacute EAE induced in immunocompromised (irradiated) recipients.

Animals↗
PubMed1989

Resistance to experimental autoimmune encephalomyelitis induced by neonatal tolerization to myelin basic protein: clonal elimination vs. regulation of autoaggressive lymphocytes.

The target autoantigen of experimental autoimmune encephalomyelitis (EAE), myelin basic protein (MBP), appears late in ontogeny. In the rat MBP is expressed first on days 2-3 post partum, at a development stage, when self tolerance to most other autoantigens has already developed. To shed light on the cellular mechanisms that lead to immunological self tolerance to MBP, we treated neonatal rats with high doses of MBP before ontogenetic appearance of this autoantigen. We found that high doses are required to confer MBP-specific tolerance lasting until the adult life. Neonatally tolerized, adult rats are completely resistant to induction of EAE by injection of MBP in complete Freund's adjuvant (CFA). Upon MBP CFA challenge, these animals develop a limited humoral response to MBP, but are completely unreactive to MBP on the T cell level. The function of antigen-presenting cells is unchanged by neonatal tolerization, and there is no evidence for the induction of suppressive mechanisms. Transfers of large numbers of tolerized lymphocytes to normal hosts fails to interfere with EAE inducibility. Moreover, neonatally tolerized lymphocytes do not reduce MBP reactivity of primed lymph node cells or T line cells in vitro. Finally, neonatally tolerized rats are susceptible to EAE transferred by activated primed lymphocytes or by in vitro-activated MBP-specific T line cells. The apparent deletion of MBP-specific T lymphocytes in neonatally tolerized rats is in striking contrast to the physiological self tolerance to MBP, which is characterized by the presence of MBP-specific clones in the normal immune repertoire.

Animals↗
PubMed1989

T cell vaccination in monoclonal antibody-induced hyperacute experimental allergic encephalomyelitis.

Demyelinating inflammatory disease of the central nervous system-(CNS) can be a multifactorial process mediated by cellular and antibody-mediated immune processes. In rats, hyperacute disease progression and severe demyelination can be induced in experimental allergic encephalomyelitis (EAE)-diseased animals by injection of a monoclonal antibody, 8-18C5, specific for an oligodendrocyte cell surface glycoprotein. Here we demonstrate that this antibody-induced hyperacute EAE can be prevented by 'vaccination' with myelin basic protein (MBP)-specific T cells. Thus, the 8-18C5 antibody-mediated disease process is critically dependent on inflammatory processes induced by T lymphocytes and T cell vaccination is highly effective in preventing the development of demyelinating CNS lesions.

Acute Disease↗
PubMed1989

Synthesis, inactivation, and localization of extracellular and intracellular Escherichia coli hemolysins.

Extra- and intracellular Escherichia coli hemolysin expressed by two cloned hly determinants, both under the control of the activator element hlyR, were analyzed. One determinant carried all four hly genes (hlyC, hlyA, hlyB, and hlyD), whereas the other carried only the two genes (hlyC and hlyA) required for synthesis of active hemolysin but not those essential for its secretion. It was shown that the total amounts of HlyA protein and of hemolytic activity are similar in both cases in logarithmically growing cultures. The E. coli strain carrying the complete hly determinant released most hemolysin into the media and accumulated very little HlyA intracellularly. The active extracellular hemolysin (HlyA*) was inactivated in the stationary phase without degradation of the HlyA protein. In contrast, the hemolysin which accumulated intracellularly in the E. coli strain carrying hlyA and hlyC only was proteolytically degraded at the end of the logarithmic growth phase. Immunogold labeling indicates that active intracellular HlyA bound preferentially to the inner membrane, whereas that part of the extracellular HlyA which remained cell-bound was located exclusively at the cell surface. It was shown by fluorescence-activated cell sorter analysis that active extra- and intracellular HlyA* bound with similar efficiency to erythrocytes, whereas hemolytically inactive HlyA protein did not bind to these target cells.

Biological Transport↗
PubMed1988

The peplomer protein E2 of coronavirus JHM as a determinant of neurovirulence: definition of critical epitopes by variant analysis.

We selected murine coronavirus JHM variants specifically changed in defined antigenic sites of the peplomer protein E2. Variants were isolated from the supernatants of monoclonal antibody hybridoma cell cultures which continued to secrete neutralizing antibodies after being infected with JHM. Comparative antigenic analysis and biological tests were performed in order to refine an operational epitope map and to characterize functional domains important for pathogenicity. The reaction patterns (neutralization, inhibition of cell fusion, immunofluorescence and binding in ELISA) between the variant viruses and the panel of monoclonal antibodies were very similar. Four groups of variants were characterized each of which revealed distinct changes affecting one defined antigenic site. These observations indicated that at least four independently mutable antigenic sites were associated with domains involved in cell fusion, neutralization and pathogenicity (E2-Aa, -Ab, -Ba and -Bb). JHM variants with alterations in the E2-Aa, -Ab or -Bb sites were similar to wild-type virus. These variants caused acute hepatitis and encephalomyelitis in mice. In contrast, JHM variants with changes in site E2-Ba had a strong propensity to induce chronic disease accompanied by demyelination persisting for several months.

Animals↗
PubMed1987

Ultrastructural immunocytochemistry of glia cells. Double labeling studies using LR White embedding and colloidal gold.

The introduction of acrylate resins (Lowicryl K4M, LR White) into electronmicroscopic immunocytochemistry applied to embedded tissue (post-embedding method) has improved the localization of antigens because of a satisfactory preservation of both ultrastructure and antigenicity of tissues. Here we describe a method that allows double staining of intracellular and membranous determinants in ultrathin sections of nervous tissue and cultures of peripheral nervous system cells. Ultrathin sections of the rat central nervous system fixed on uncoated grids were stained first for MBP selectively on the one face, then the opposite face was stained for GFAP using monoclonal antibodies and indirect immunogold staining method (IGS). Cultured Schwann cells induced to express major histocompatibility complex (MHC) class II antigens were stained for class II antigens by pre-embedding method then followed by post-embedding IGS for the other intracytoplasmic antigens.

Acrylates↗
PubMed1987

No disturbance of myelination in the central nervous system by selective 3H beta-irradiation.

The effect of a selective irradiation of myelin by 3H beta-particles was studied by light and electron microscopic methods in guinea pig spinal cord. The animals were injected with [3H]leucine shortly after birth when the rate of myelin biosynthesis is high and sacrificed 130 days later. In spinal cord the radioactivity was mainly preserved in myelin because the half life of myelin proteins is much higher than that of most other CNS proteins. As a consequence the irradiation dose in the white matter was much higher than in the gray matter. In myelin internally irradiated by 3H beta-particles within 130 days at a dose of 10 Gy no alterations could be detected either by morphological or by morphometric methods.

Animals↗