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J Löhler

Publications and source records attributed to J Löhler.

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

Disseminated BK type polyomavirus infection in an AIDS patient associated with central nervous system disease.

A 27-year-old man with hemophilia type A and acquired immunodeficiency syndrome developed a subacute meningoencephalitis, associated with a normotensive internal hydrocephalus, 14 weeks before his death. From cerebrospinal fluid and brain autopsy material, a virus could be isolated and was classified by Southern blot analysis and restriction endonuclease reactions as the human polyomavirus BK. The postmortem findings of polyomavirus antigen and BK virus DNA in various cell types of the kidneys, lungs, and central nervous system strongly suggest that BK virus was the causative agent of a tubulointerstitial nephropathy, an interstitial desquamative pneumonitis, and a subacute meningoencephalitis with accentuation of the ventricular and meningeal surfaces of the brain. Besides distinctive cytopathic effects, the presence of intranuclear inclusions was a prominent histopathological feature. Therefore, the human polyomavirus BK should be regarded as a new candidate on the still growing list of opportunistic pathogens in acquired immunodeficiency syndrome.

AIDS-Related Opportunistic Infections↗
PubMed1992

The carbohydrate epitope 3-fucosyl-N-acetyllactosamine is developmentally regulated in the human cerebellum.

The carbohydrate epitope 3-fucosyl-N-acetyl-lactosamine (CD15) is involved, as a constituent of glycoconjugates, in cell-cell interactions and cell sorting during rodent CNS morphogenesis. The present study was designed to test whether CD15 is also involved in the development of the human CNS. Human cerebellar hemispheres and vermes from the 24th week of gestation (wg) to the 26th postnatal month (pnm) and from adults were investigated for CD15 immunoreactivity, using the monoclonal antibody MMA. Our findings establish that the carbohydrate moiety is developmentally regulated in neuronal and glial cells during their differentiation. First, the parallel fibers of granule cells are CD15+ during the epoch of synaptogenesis with Purkinje cell dendrites. Second, a subpopulation of neurons from the dentate nucleus is transiently CD15+ from the 32nd wg until the 15th pnm. Third, at the onset of myelination (around the 35th wg), CD15 immunoreactivity is discernible in the cytoplasm of young oligodendrocytes. Immunoreactivity on protoplasmic astrocytes of the inner granular layer and on fibrous astrocytes of the white matter progressively increases during fetal development. In addition, the CD15 epitope is persistently present on Bergmann glial processes and ependymal cells. Within the three subdivisions of the cerebellum, i.e., hemispheres, vermis, and flocculonodular lobe, the CD15 expression follows a different timing of morphogenesis. For example, diminution of immunoreactivity in the parallel fibers occurs first in the phylogenetically older flocculonodular lobe and vermis, and later in the phylogenetically younger hemispheres. This study shows that in the human cerebellum the distribution of CD15 undergoes marked developmental changes. This epitope may also act in cell-to-cell recognition, and perhaps could play a role in controlling CNS development.

Adult↗
PubMed1991

Entry of antivirally active T lymphocytes into the thymus of virus-infected mice.

The thymus has long been regarded as an immunologically "privileged site" by being shielded against the entry of exogenous Ag as well as protective elements of the immune system. After i.p. infection of mice, the lymphocytic choriomeningitis virus multiplied in this organ. Viral Ag was found predominantly in the epithelial-reticular cells of the medulla and to a lesser extent in such cells of the cortex. Beginning on day 7 after infection, the virus disappeared, a process that could be blocked by depleting the mice of peripheral T lymphocytes or of CD8+ cytotoxic T lymphocytes. Viral clearance was accelerated by i.v. injection of splenocytes from mice, which themselves were just eliminating the virus. CD8+ cells from CD8-congenic donor mice, most with blast morphology, were detected immunocytochemically in the thymus, predominantly in the medulla. A few CD8+ T lymphocytes from donors not previously infected were also demonstrated in the thymic tissue of infected mice. Our findings indicate that the lymphocytic choriomeningitis virus has access to the thymus and suggest that it is cleared by the antiviral activity of circulating cytotoxic T lymphocytes. Thus, just as other organs, the thymus appears to be subject to immune surveillance by mature T lymphocytes that have their origin in secondary lymphoid tissues.

Animals↗
PubMed1991

Toxoplasma encephalitis of immunocompetent and nude mice: immunohistochemical characterisation of Toxoplasma antigen, infiltrates and major histocompatibility complex gene products.

The experimental infection of immunocompetent and immunodeficient athymic mice with an avirulent encephalitogenic Toxoplasma strain (DX strain) was employed to study the ensuing encephalitic process by use of histological and immunocytochemical methods. In the acute phase of the infection Toxoplasma cysts and tachyzoites were accompanied by an infiltrate composed of macrophages, CD4+ and CD8+ T cells. In the chronic stage a granulomatous encephalitis developed. In contrast to immunocompetent NMRI mice, athymic nude NMRI mice died 3 weeks post-infection because of a generalized toxoplasmosis with predominant involvement of the brain. A salient feature of murine Toxoplasma encephalitis was up-regulation of class I and II major histocompatibility complex (MHC) gene products. Class I antigen was widely expressed on microglial cells and astrocytes. Class II antigen was only expressed on microglial cells despite a considerable astrogliosis. Our results indicate a differential expression of MHC-determined antigens on brain cells in acute and chronic murine Toxoplasma encephalitis.

Animals↗
PubMed1991

Production of random classes of immunoglobulins in brain tissue during persistent viral infection paralleled by secretion of interleukin-6 (IL-6) but not IL-4, IL-5, and gamma interferon.

The activities of cytokines were determined in cerebrospinal fluid (CSF) and serum of mice persistently or intracerebrally acutely infected with lymphocytic choriomeningitis (LCM) virus (LCMV). In contrast to CBA/J (LCMV carrier) mice that responded with low levels of LCMV-specific antibody, high-responder NMRI (carrier) mice showed antibody production by B cells outside of lymphoid organs. The B cells that had infiltrated the brains of LCMV carrier mice exhibited no preferential immunoglobulin isotype or subtype virus-specific antibody production. Phenotypic analysis of the brain infiltrates in virus carrier mice revealed dominance of CD4+ T cells in contrast to virtual absence of CD4+ and dominance of CD8+ in mice with acute LCM. In NMRI but not in CBA/J carrier mice, significant concentrations of interleukin-6 (IL-6) were detected in CSF and serum; IL-2, IL-4, IL-5, granulocyte-macrophage CSF (GM-CSF), and gamma interferon (IFN-gamma) were not elevated. In contrast, during acute, lethal LCM, IL-6 and IFN-gamma were found at high concentrations, and IL-4, IL-5, and GM-CSF were detectable in CSF and serum, but virus-specific antibody-producing cells were not (yet) detectable in the brain. Thus, distinct cytokine patterns are found in acute versus chronic LCMV infection of the brain: in LCM carrier mice, local random-class immunoglobulin production correlated with the absence of IL-2, IL-4, IL-5, and IFN-gamma but active secretion of IL-6.

Animals↗
PubMed1990

IFN-gamma production in tissues of mice during acute infection with lymphocytic choriomeningitis virus.

As shown by a single-cell solid-phase ELISA, splenocytes as well as liver lymphoid cells from unmanipulated specific-pathogen free mice synthesized and released IFN-gamma. Synthesis of this lymphokine could not be demonstrated either on the transcriptional level by Northern blotting or immunocytochemically. Thus, IFN-gamma is constitutively produced in mice, although in low quantities. During acute infection with lymphocytic choriomeningitis virus, IFN-gamma mRNA became detectable in spleen and brain but not in the liver. In spleens and livers of these mice, the numbers of cells synthesizing the lymphokine were increased and many were seen in foot tissue undergoing a delayed-type hypersensitivity reaction after intraplantar inoculation of the virus. In contrast, few IFN-gamma-producing cells were found in the inflammatory infiltrates of leptomeninges and choroid plexus after intracerebral infection.

Animals↗
PubMed1990

Virus-specific delayed-type hypersensitivity (DTH). Cells mediating lymphocytic choriomeningitis virus-specific DTH reaction in mice.

We had previously shown that the local lymphocytic choriomeningitis virus-induced delayed-type hypersensitivity (DTH) reaction in mice consists of two well delineated phases that are mediated by CD8+ and CD4+ T lymphocytes, respectively. These findings have been confirmed and extended by showing that the first CD8+ cell-dependent part of the response was enhanced by either the presence of CD4+ cells or systemic treatment with IL-2 and that it developed in the absence of detectable numbers of mononuclear phagocytes, whereas the later CD4+ cell part required monocytes or related elements. Furthermore, in the DTH reaction that was elicited with noninfectious viral Ag in mice previously immunized by infection, only the CD4+ cells participated. Thus, the two phases of the lymphocytic choriomeningitis-viral DTH reaction are principally different, which has to be taken into account when trying to assess the relevance of DTH during this virus infection.

Animals↗
PubMed1990

Changes in glial cell markers in recent and old demyelinated lesions in central pontine myelinolysis.

An immunohistochemical study was performed to compare glial reactions in recent and old lesions of central pontine myelinolysis (CPM). Regions of demyelination and destruction of oligodendrocytes, showed reduced immunoreactivity of myelin basic protein (MBP), myelin-associated glycoprotein (MAG), transferrin, and carbonic anhydrase C (CA C). In addition, labeling of glial fibrillary acidic protein (GFAP) and S-100 protein revealed distinct dystrophic alterations of the astroglia. Remarkably, immunolabeling of GFAP was drastically reduced in astrocytic cytoplasm within freshly demyelinated lesions. Immunostaining of vimentin revealed a differential intracytoplasmic decoration of hypertrophic and dystrophic astrocytes in recent and old CPM lesions. Immunolabeling of desmin failed to stain glial cells. Monoclonal antibodies against HNK-1 exhibited greatly increased immunoreactivity both of persisting oligodendrocytes and of reactive fibrillary astrocytes in old CPM foci. In freshly demyelinated lesions, enhanced immunoreactivity of the X-hapten (3-fucosyl-N-acetyllactosamine) was prominent in astroglia and oligodendrocytes. Simultaneously, reactive astrocytes revealed intracytoplasmic labeling of laminin. Quantitation of GFAP+ astroglia in fresh CPM and control cases revealed an increase in the number of astrocytes within the demyelinated foci and in the surrounding non-demyelinated pontine tissue of CPM cases. The occurrence of astroglial alterations in the demyelinated foci of CPM could be interpreted as "astroglial dystrophy" which may represent a pathogenic factor in CPM. Furthermore, it is possible that changes of the glial microenvironment may influence the astroglia to revert transiently back to an immature phenotype as indicated by the enhanced expression of the X-hapten and HNK-1, and the de novo synthesis of vimentin and laminin.

Adult↗
PubMed1990

[Hematopoietic stem cells (CFU-S) in retrovirus-induced murine malignant histiocytosis].

The murine malignant histiocytosis sarcoma virus (MHSV) is a replication-defective murine retrovirus which contains a ras-oncogen. Upon intravenous infection of normal adult NIH-mice a rapidly fatal systemic proliferation of transformed mononuclear phagocytes develops. We have investigated the involvement of other mature hematopoietic lineages and of hematopoietic stem cells during the course of the disease. The erythroid lineage is affected by a profound anemia which is temporarily accompanied by an increase of erythroid precursors in bone marrow and spleen and a final ablation of erythroid stem cells. A granulopenia occurs with a concurrent decrease of granulocytic precursors and stem cells. The platelets fall to very low levels early during the disease despite of an increase of megakaryocytes and megakaryocytic stem cells. Multipotential stem cells show temporarily a slight increase followed by an almost total terminal ablation. The results show that MHSV has distinct effects on other hematopoietic lineages apart from its transforming properties.

Animals↗
PubMed1988

Immunopathological reactions in viral infections of the central nervous system.

Viral infections of the central nervous system (CNS), as of any other organ, evoke humoral and cellular immune responses which enable the host to eliminate the pathogen. However, effective responses may themselves produce tissue damage sometimes exceeding that caused by the virus itself. The relative contribution of the various immunopathological mechanisms in human viral encephalitides remains mostly ill defined. Most of our understanding of the immunopathogenesis in viral CNS infections comes from studies on experimentally infected animals. The prototype model of a virus-induced, cell-mediated, immunopathological CNS disease is the neurological illness of mice that follows intracerebral inoculation with lymphocytic choriomeningitis virus. Virus-specific cytotoxic T cells are crucial to the pathogenesis but death of the animals only results when these cells are targeted into functionally essential brain structures like the circumventricular organs or the medulla oblongata and cervical spinal cord.

Animals↗
PubMed1987

Mechanism of recovery from acute virus infection. IV. Questionable role of mononuclear phagocytes in the clearance of lymphocytic choriomeningitis virus from spleens of mice.

After intravenous infection of mice with 10(3) infectious units (IU) the WE strain lymphocytic choriomeningitis (LCM) virus multiplied in the spleens (as in all other major organs), reaching more than 10(8) IU/g of tissue on days 4 to 5. Subsequently, the virus was quickly eliminated, being below detectability usually by day 10. During the time of virus clearance, the mononuclear phagocytes (MNP) of the spleen were activated as revealed by suppression of growth of Listeria monocytogenes and increase of cell-associated hydrolytic enzymes. In athymic nude mice, in whom the MNP system is assumed to be permanently activated, the virus replicated slightly but reproducibly less than in their euthymic counterparts. However, when the MNP were activated by Corynebacterium parvum, virus in spleens attained higher concentrations than in mice not so treated, and the rate of elimination was not altered. In mice whose MNP had been damaged by injection of dextran sulfate 500, the spleen virus titers were also increased, but the subsequent immune elimination was slightly delayed. Activation of spleen MNP was not evident at the time virus was rapidly cleared as a result of transfusion of LCM-immune T lymphocytes. Adoptive immunization was as successful in mice that had been pretreated with gamma-rays or cyclophosphamide, suggesting that replicating cells or their descendants, in particular monocytes, did not participate measurably in the process of elimination. Pretreatments of recipients with dextran sulfate 500 reduced the efficacy of transfused LCM-immune T lymphocytes, but this compound probably directly affected the cells. We interpret these findings to mean that the LCM virus in the mouse's spleen is controlled by a mechanism in which MNP do not play an essential role.

Animals↗
PubMed1987

Antiviral antibody-producing cells in parenchymatous organs during persistent virus infection.

In mice persistently infected with lymphocytic choriomeningitis virus (LCMV), the parenchymatous organs contain infiltrates of mononuclear cells, the sizes and numbers of which vary between strains and become more numerous and extensive when the animals grow older. Histologically, these were found to possess a tissue-like structure, and by use of immunohistologic procedures they were shown to contain plasma cells secreting IgM and IgG. Cells of kidneys, livers, brains, and spleens of LCMV carrier mice were dispersed by digestion with trypsin, leukocytes were separated by density gradient centrifugation, and numbers of cells producing antibodies against LCMV were determined by use of a solid-phase immunoenzymatic technique. In all these organs, cells producing LCMV-specific IgM and IgG antibodies were demonstrated, the latter more numerous than the former. Their numbers correlated with numbers and extent of the lymphoid cell infiltrates. The blood of the same mice was essentially free of antiviral antibody-forming cell. The proportion of cells producing LCMV-specific antibodies to all cells producing Ig of any specificity varied between organs, being lowest in spleen, intermediate in liver and kidney, and highest in the brain, where in individual mice up to 90% of all active cells produced virus-specific antibodies. The LCMV carrier mouse should prove to be a useful animal model to investigate antibody production in parenchymatous organs during persistent virus infections.

Aging↗
PubMed1987

Expression of 3-fucosyl-N-acetyllactosamine on glia cells and its putative role in cell adhesion.

Mouse monoclonal antibodies from five clones (MMA, 1G10, VIM C6, MC-1 and Tü9), elicited to human myeloid cells and reactive with the 3-fucosyl-N-acetyllactosamine sequence (also termed X-determinant), cross-react with glia cells from human and rat brain. In brain cell cultures from neonatal rats both astrocytes and oligodendrocytes express the X-determinant during the first period of the culture as shown by immunofluorescence tests. While the astrocytes, which exhibit signs of adhesion, permanently express the X-determinant, the oligodendrocytes lose the epitope nearly completely during culture. The oligodendrocytes preferentially grow on top of the astrocytic layer. After about 8-10 days of culture, numerous X-determinant-positive astrocytic membranes show oligodendrocyte-shaped negative print images underneath the galactocerebroside-positive oligodendrocytes. At this time, the oligodendrocytes are relatively firmly attached to the astrocytic layer. Since participation of the X-determinant in the compaction of the mouse 8-32 cell stage is being discussed, we conclude from our observations that the X-determinant may also play a role in the astrocyte-astrocyte and astrocyte-oligodendrocyte adhesion. It may represent the functionally active carbohydrate moiety of a heterotypic cell adhesion molecule of glia cells.

Animals↗
PubMed1987

Murine retrovirus-induced malignant histiocytosis, an experimental model for the disease in humans.

The hematopoietic disregulation in adult mice induced by the malignant histiocytosis sarcoma virus (MHSV) and the Harvey murine sarcoma virus (Ha-MuSV), which both possess c-Ha-ras-related oncogenic sequences, was investigated. Spleen focus formation induced by MHSV and Ha-MuSV was not restricted by the Fv-2 resistance locus in congenic DDD and C57BL/6 mice, unlike leukemogenesis induced by Friend virus, Rauscher virus, and the myeloproliferative sarcoma virus (MPSV). C57BL/6 mice were much more resistant to MHSV and Ha-MuSV-induced spleen focus formation than DDD mice regardless of their Fv-2 state. Infection of DDD mice with MHSV caused a systemic histiocytic neoplasia, best described as murine malignant histiocytosis. Transformed histiocytic cells proliferated excessively in the bone marrow, spleen, and lymph nodes and, in the final stages of the disease, in all major parenchymal organs. The Ha-MuSV caused a strikingly different benign histiocytic tumor in DDD mice and, unlike MHSV, did not induce a rapid, progressive splenomegaly in C57BL/6 mice. Infection of DDD mice with MHSV induced a rapid and synchronized depletion of early and late erythroid precursor cell pools. In MHSV-infected C57BL/6 mice comparable changes were observed with dissimilar kinetics. Macrophage colony-forming cells of MHSV-infected mice were increased in number and proliferated independently of stimulating growth factors. The disease induced by MHSV in mice can thus serve as a model for malignant histiocytosis in humans.

Animals↗