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V Ter Meulen

Publications and source records attributed to V Ter Meulen.

At least 19 recordsLinked to original sources
PubMed2004

Modulation of simian immunodeficiency virus neuropathology by dopaminergic drugs.

Drug abuse and human immunodeficiency virus (HIV) infection seem to cause cumulative damage in the central nervous system (CNS). Elevated extracellular dopamine is thought to be a prime mediator of the reinforcing effects of addictive substances. To investigate the possible role of increased dopamine availability in the pathogenesis of HIV dementia, simian immunodeficiency virus (SIV)-infected monkeys were treated with dopaminergic drugs (selegiline or L-DOPA). Both substances increased intracerebral SIV expression, combined with aggravation of infection-related neuropathology and ultrastructural alterations of dendrites in dopaminergic areas (spongiform polioencephalopathy) in asymptomatic animals. Moreover, this treatment resulted in enhanced TNF-alpha expression in the brains of SIV-infected animals. These findings indicate a synergistic interaction between dopamine and SIV infection on microglia activation, leading to increased viral replication and production of neurotoxic substances. Our results suggest that increased dopamine availability through dopaminergic medication or addictive substances may potentiate HIV dementia.

Animals↗
PubMed1999

Measles virus-induced immunosuppression in vitro is associated with deregulation of G1 cell cycle control proteins.

Virus-induced immunosuppression is the major cause of the high morbidity/mortality rates associated with acute measles. It has been shown previously that mitogen-dependent proliferation of peripheral blood lymphocytes (PBL) was strongly impaired after contact with the measles virus (MV) glycoproteins F and H expressed on the surface of infected cells, cells transfected with the corresponding expression constructs or UV-inactivated MV (UV-MV). The state of unresponsiveness was not associated with the induction of apoptosis, and a significant proportion of PBL was found to be arrested in the G0/G1 phase of the cell cycle. It is now shown that cell cycle cessation, rather than complete arrest, is induced after MV glycoprotein contact. No obvious role was found for p53 in the induction of this unresponsiveness. With UV-MV as effector, downregulation of p27, an inhibitor of cyclin-dependent kinase (CDK)-cyclin complexes, was significantly delayed after mitogenic stimulation of human PBL. The activities of both CDK4/6-cyclin D and CDK2-cyclin E complexes for phosphorylation of exogenous substrates in vitro were strongly reduced. CDK4, CDK6, cyclins D3 and E and, to a minor extent, CDK2 failed to accumulate at the protein level after mitogenic stimulation in the presence of UV-MV. These data indicate that MV-induced proliferative unresponsiveness of PBL to mitogenic stimulation is associated with a drastic deregulation of the expression of cell cycle genes essential for the G1/S phase transition.

Adult↗
PubMed1996

Mapping amino acids of the measles virus hemagglutinin responsible for receptor (CD46) downregulation.

We compared the amino acid sequences of groups of receptor (CD46) downregulating and nondownregulating measles virus (MV) hemagglutinins (Hs) and identified seven group-specific differences as candidates for the mediation of the observed differential effects. Using site-directed mutagenesis, we mutated the chosen amino acids of the H of MV-strain WTF (WTF-H), a nondownregulating H, and Introduced the corresponding amino acids of Edmonston-H (Edm-H), a downregulating H. We identified four amino acids, 211G, 243R, 451V, and 481Y, which influenced the downregulative function when introduced into WTF-H. The double mutation 451V and 481Y in WTF-H led to a degree of CD46 downregulation comparable to that of Edm-H. Conversely, introducing amino acids 451E and 481N into Edm-H resulted in a loss of the downregulative function. These results indicate that these amino acids play a decisive role in the H-CD46 interaction.

Antigens, CD↗
PubMed1996

Image analysis detects lineage-specific morphologic markers in leukemic blast cells.

This report outlines the morphologic classification of acute myeloid (AML: French-American-British FAB classification: M1) and lymphoid (ALL) leukemia by automatic image analysis and the correlation to immunologic and cytochemical classification. The investigation was carried out on Romanowsky-Giemsa stained bone marrow (n = 15) and blood smears (n = 10) from 25 patients with primary acute leukemia. The cases had been classified as of myeloid or lymphoid origin by three hematologic centers using immunochemistry or cytochemistry, but the specimens were submitted to the authors' laboratory without the diagnosis. The nuclear and cytoplasmic pattern of the blast cells were analyzed by a high resolution image analysis system and the measured and calculated cell features were sorted by means of a classifier program (CART). The image analysis classification was then compared with the immunophenotypical and cytochemical classification. Blood blast cells showed nuclear features that were significantly correlated to a myeloid or lymphoid immunophenotype. In contrast, bone marrow blast cells displayed overlapping and therefore nondiscriminating nuclear features. However, by generating a learning data set using the immunophenotypes the classifier program found specific cytoplasmic features that eventually permitted a differentiation into myeloid or lymphoid subtypes. In summary, the authors suggest that high resolution image analysis of leukemic blast cells detect nuclear and cytoplasmic features that are associated with the immunophenotype and therefore with the lineage determination of the cell. With this new objective and reproducible approach of morphologic cell analysis, it might not only be possible to classify blast cells with minimal cellular differentiation, but furthermore to discover prognostic features because the remarkable difference in classification quality between blood and bone marrow blast cells reported in this study, might be of biologic relevance and requires further investigation.

Adolescent↗
PubMed1993

Differential induction of cytokines by primary and persistent measles virus infections in human glial cells.

The effect of measles virus (MV) infection on mRNA expression and protein synthesis of cytokines in human malignant glioma cell lines (D-54 and U-251) was investigated. Primary MV infections led in both cell lines to the induction of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interferon-beta (IFN-beta), and tumor necrosis factor-alpha (TNF-alpha). In contrast, persistently infected astrocytoma lines continually produced IL-6 (two out of 12 lines high levels) and IFN-beta, whereas only 1 out of 12 lines synthesized TNF-alpha and none IL-1 beta. The pathways for induction of IL-1 beta and TNF-alpha expression were not suppressed by the persistent MV infection, since IL-1 beta and TNF-alpha could be induced by external stimuli like diacylglycerol analog plus calcium ionophore. Interestingly, persistently infected astrocytoma cells synthesized considerably higher levels of IL-1 beta and TNF-alpha than uninfected cells after additional external induction. These results suggest that in the central nervous system (CNS) of SSPE patients a percentage of persistently infected astrocytes may continually synthesize IL-6 and IFN-beta, and in the presence of additional external stimuli, as possibly provided by activated lymphocytes, might overexpress the inflammatory cytokines IL-1 beta and TNF-alpha. This may be of pathogenetic significance in CNS diseases associated with persistent MV infections.

Animals↗
PubMed1992

HIV-1 gp120 receptor on CD4-negative brain cells activates a tyrosine kinase.

Human immunodeficiency virus (HIV-1) infection in the human brain leads to characteristic neuropathological changes, which may result indirectly from interactions of the envelope glycoprotein gp120 with neurons and/or glial cells. We therefore investigated the binding of recombinant gp120 (rgp120) to human neural cells and its effect on intracellular signalling. Here we present evidence that rgp120, besides binding to galactocerebroside or galactosyl-sulfatide, specifically binds to a protein receptor of a relative molecular mass of approximately 180,000 Da (180 kDa) present on the CD4-negative glioma cells D-54, but not on Molt4 T lymphocytes. Binding of rgp120 to this receptor rapidly induced a tyrosine-specific protein kinase activity leading to tyrosine phosphorylation of 130- and 115-kDa proteins. The concentration of intracellular calcium was not affected by rgp120 in these cells. Our data suggest a novel signal transducing HIV-1 gp120 receptor on CD4-negative glial cells, which may contribute to the neuropathological changes observed in HIV-1-infected brains.

Brain↗
PubMed1991

Expression of measles virus RNA in peripheral blood mononuclear cells of patients with measles, SSPE, and autoimmune diseases.

In order to characterize measles virus (MV) infection in peripheral blood mononuclear cells (PBMCs), RNA was isolated from PBMCs after PHA-stimulation for 72 hr of 9 patients with acute measles, 16 patients with subacute sclerosing panencephalitis (SSPE), 13 patients with various autoimmune diseases, and 16 healthy control donors. The RNA obtained was screened for the presence of MV N (nucleocapsid) gene specific transcripts of either positive or negative orientation in a S1 nuclease protection assay. The sensitivity of this assay allowed us to detect one infected cell in 20,000 PBMCs or 0.1 to 0.05 copies of MV-specific RNA per cell. Using single-stranded DNA or RNA probes expression of MV genomic RNA of negative polarity could be detected in only one case of acute measles and one healthy control donor. Conversely, N-specific transcripts of positive polarity, indicating active transcription, could only be detected in patients with acute measles. In addition, in infected PBMCs and in a persistently MV-infected B cell line positive stranded N-specific transcripts containing leader usually present at very low frequency have been found in relatively increased amounts in comparison with transcripts lacking leader. Whereas the ratio of these RNA species during lytic infection with MV in Vero cells is about 1:50, the ratio found here ranges from 1:3 to 1:10. This altered ratio indicates a specific regulation of MV specific transcription in cells of lymphoid origin that has not been found in any other cell system analyzed.

Animals↗
PubMed1986

Accumulated measles virus mutations in a case of subacute sclerosing panencephalitis: interrupted matrix protein reading frame and transcription alteration.

Subacute sclerosing panencephalitis (SSPE) is a fatal disease affecting the human central nervous system several years after acute measles infection. Measles virus (MV) genomes replicating in SSPE brains do not give rise to budding particles and present various defects in gene expression, mostly concerning the matrix (M) protein. For one SSPE case (K), shown previously to be devoid of M protein expression, we examined here in detail the features involved in this defect. In the brain of patient K the normal, monocistronic MV M mRNA was completely substituted by a bicistronic RNA containing the coding sequence of the preceding phosphoprotein (P) gene in addition to the M coding sequence. Analysis of the P-M intercistronic region by direct cDNA sequencing showed that the consensus sequence at this RNA processing site was unaltered but revealed several distant point mutations. cDNA cloning and sequencing of the entire M coding region established that one of the point mutations leads to a stop codon at triplet 12 of the M reading frame. It is unknown whether this defect, explaining by itself the lack of M protein, is related also to the block of M mRNA formation. In addition we note that as much as 1% of the nucleotides differed between two overlapping clones from the same brain. This high sequence variability could possibly account for the diversity of defects observed in MV gene expression in SSPE brains and may be a general phenomenon associated with RNA virus persistence.

Amino Acid Sequence↗
PubMed1984

Cloning of DNA corresponding to four different measles virus genomic regions.

Hybrid plasmids containing sequences corresponding to four different regions of the measles virus genome inserted in pBR322 were obtained by use of polyadenylated 50 S viral RNA as template for reverse transcription. One class of plasmids contains inserts corresponding to the 3' terminal region of the virus genome. The sequence of one of these inserts (605 nucleotides) partially overlaps with the cloned cDNA sequence corresponding to a part of the nucleocapsid protein (N) mRNA (M. Gorecki and S. Rozenblatt (1980). Proc. Natl. Acad. Sci. USA 77, 3686-3690). This insert region shows only one long open reading frame defining the N-terminal part of the nucleocapsid protein. The nucleocapsid protein mRNA starts at about 60 nucleotides from the genome end as revealed by nuclease S1 mapping. Three other classes of plasmid clones contain inserts derived from unidentified regions of the viral genome; they hybridize with viral mRNA species less abundant than those from which cDNA clones have been isolated so far (S. Rozenblatt, C. Gesang, V. Lavie, and F. S. Neumann (1982) J. Virol. 42, 790-797.

Amino Acid Sequence↗
PubMed1984

Detection and identification of virus-specific, oligoclonal IgG in unconcentrated cerebrospinal fluid by immunoblot technique.

A technique is described which allows the detection of virus-specific oligoclonal IgG in unconcentrated cerebrospinal fluid (CSF) from patients with virus infections of the central nervous system. CSF is isoelectrically focused in agarose gels and immunoglobulins are blotted to nitrocellulose filters, passively loaded with either anti-human IgG or viral antigen. Transferred total IgG, as well as virus-specific IgG, is identified by the use of peroxidase-labelled anti-human IgG and 4-chloro-1-naphthol as a precipitating peroxidase substrate. Application of this assay in cases of SSPE, mumps meningitis and herpes simplex encephalitis demonstrates sensitivity and possible suitability of this technique for use in diagnosis of virus infections of the CNS.

Adolescent↗
PubMed1983

Comparison of lytic and persistent measles virus matrix proteins by competition radioimmunoassay.

Measles virus matrix (M) proteins were compared by competitive monoclonal antibody-binding studies. Three strains of measles and of subacute sclerosing panencephalitis viruses were found to be identical in this way. The matrix protein formed by Edmonston strain virus during a persistent infection could be distinguished from that made in the lytic virus infection. It is concluded that structural alterations in the M peptide can occur during persistence.

Antibodies, Monoclonal↗
PubMed1981

Coronavirus JHM: characterization of intracellular viral RNA.

After infection of Sac(-) cells with the murine coronavirus JHM the synthesis of seven major and two minor RNA species was induced. These RNAs were polyadenylated and single-stranded. Their mol. wt. were estimated by electrophoresis in agarose gels containing methylmercury hydroxide. The values for the major species were 6.67 x 10(6) for RNA of genome size (RNA 1), 3.42 x 10(6) for RNA 2, 2.76 x 10(6) for RNA 3, 1.35 x 10(6) for RNA 4, 1.19 x 10(6) for RNA 5, 0.93 x 10(6) for RNA 6 and 0.62 x 10(6) for RNA 7. The minor species have a size of 4.7 x 10(6) (RNA a) and 1.5 x 10(6) (RNA b). The same number of species were found by electrophoresis after denaturation with glyoxal-dimethyl sulphoxide. No gross difference in number of RNAs and the amount of each species was found between total cytoplasmic RNA, polyadenylated cytoplasmic RNA and RNA extracted from pelleted polysomes.

Coronaviridae↗
PubMed1979

Morphology and morphogenesis of a new paramyxovirus (PMV 107).

The morphology of the virions and nucleocapsids of paramyxovirus 107 (PVM 107) and the replication of the virus were investigated by electron microscopy. The virions and nucleocapsids exhibited the same structural properties as other paramyxoviruses. Nuclecapsids were found in the nucleus and cytoplasm of infected bovine embryonic lung (BEL) cell cultures. A similar situation has been described for the morbilliviruses measles, SSPE, distemper and rinderpest. Alignment of nucleocapsids beneath the plasma membrane and budding of PMV 107 in the productive BEL cell infections were also similar to the morbillivirus-infected cells. In a line of monkey cells (CV1) persistently infected with PMV 107 only cytoplasmic nucleocapsids could be demonstrated. On the basis of its morphology and morphogenesis it is suggested that PMV 107 should be classified as a paramyxovirus. Since nucleocapsids could also be found in the nucleus of infected BEL cells the morphogenesis of PMV 107 closely resembles that of viruses of the morbillivirus group.

Animals↗
PubMed1976

A rapid method for the quantitative study of RNA from canine distemper virus infected cells.

Centrifugation through CsCl was used to isolate 32P-labelled RNA in a one-step purification procedure. The method is suitable for quantitative as well as preparative studies and appears to have considerable advantages over conventional methods of RNA extraction. We have used this procedure to investigate the RNA synthesized in Vero cells infected with canine distemper virus (CDV). We show that the combination of CsCl centrifugation and affinity chromatography on poly-U Sepharose provides a rapid method for isolating messenger RNA from virus infected cells.

Cell Line↗