Biomedical subjects
Publications and source records attributed to K Frese.
Immunohistology and special staining of plastic sections allow diagnosis and differentiation of subtypes of glomerulonephritis in dogs. Frequency and clinical importance of these forms of glomerulonephritis vary significantly. In cats, glomerulonephritis occurs frequently in FIV-positive cats but is rare in animals suffering from persistent FeLV infection or FIP.
The subcommissural organ (SCO)-Reissner's fiber (RF) complex of rats suffering from postnatal hydrocephalus was investigated immunocytochemically (peroxidase-antiperoxidase technique) by use of an anti-serum against bovine RF. Hydrocephalus was induced by injecting kaolin into the cisterna magna or by intracerebral infection with Borna disease virus. The kaolin-injected, hydrocephalic male rats were divided into two groups: (1) possessing an open communication between the fourth ventricle and the central canal of the spinal cord; (2) enduring an obliteration of this communication. In the latter group of rats the dilation of the ventricular cavities was far greater than in the former group. The Borna disease virus-infected female rats developed a severe hydrocephalus although in these animals all ventricular cavities and the central canal were in fully open communication. All rats belonging to the above-mentioned three groups displayed essentially the same alterations of their SCO-RF complex: (i) A reduction in the size of SCO and in the height of the ependymal secretory cells. (ii) A progressive disappearance of the immunoreactive hypendymal cells. (iii) The amount of AFRU-immunoreactive secretory material located in the rough endoplasmic reticulum was reduced. (iv) In contrast, the amount, location and immunoreactivity of the apical secretory granules did not undergo variations in comparison to sham-operated rats. (v) In the area of the SCO the layer of pre-RF material was thin or missing and a RF was not formed, and thus the central canal was also free of such secretory products. (vi) Clusters of AFRU-immunoreactive material were found attached to the wall of the Sylvian aqueduct.(ABSTRACT TRUNCATED AT 250 WORDS)
After intracerebral infection with Borna disease virus adult Lewis rats develop a virus-induced immunopathological reaction resulting in severe neurological symptoms and a non-purulent meningoencephalitis. The composition of inflammatory cells and major histocompatibility complex (MHC) class II antigen expression during the course of the infection was investigated using immunocytochemistry with a panel of monoclonal antibodies (mAb). Macrophages and lymphocytes of the T helper phenotype (CD4+) were dominant at all stages of infection, whereas T suppressor/cytotoxic lymphocytes (CD8+) were less frequent. B lymphocytes and plasma cells occurred mainly during later stages of the disease and marked parenchymal deposition of immunoglobulin developed. Beginning 10 days after infection massive expression of MHC class II antigen was noted up to the termination of experiments 70 days after infection. Besides lymphatic cells and macrophages, cells morphologically resembling microglia expressed this antigen. Furthermore, ependymal cells were found positive for MHC class II expression during infection whereas astrocytes remained negative. These findings are consistent with previous results which provide evidence for a delayed-type hypersensitivity reaction being operative in the pathogenesis of Borna disease.
After intracerebral inoculation of Borna disease virus (BDV). Lewis rats develop a persistent infection of the central nervous system which is pathohistologically represented by perivascular encephalitic lesions predominantly in the grey matter. In previous studies it has been shown that a cell-mediated immune response causes Borna disease (BD). In order to define further the immune cell responsible for this immunopathological disease, a BDV-specific T cell line, NM1, was established and cultured in vitro. Phenotypically this T cell line was characterized by cytofluorometry as CD4-positive (CD4+). Proliferation assays with syngeneic and allogeneic antigen-presenting cells, and blocking experiments with monoclonal antibodies, revealed major histocompatibility complex class II antigens to be restriction elements. After passive transfer of this virus-specific CD4+ T cell into immunosuppressed BDV-infected recipients, full-blown disease could be induced. Immunohistological examination of the cells involved in perivascular inflammatory infiltrates in BDV-infected rats and in recipients of the NM1 T cell line revealed a dominance of macrophages and CD4+ T cells. The presence of these cells in encephalitic lesions strongly suggests a delayed type of hypersensitivity reaction as the pathogenetic mechanism of BD.
Brain tissue from 187 animals of different species was investigated by means of fluorescent antibody test, peroxidase anti-peroxidase technique, mouse inoculation test and cell culture technique for a diagnosis of rabies. With peroxidase anti-peroxidase technique the rabies specific reaction comprised inclusion bodies and a granular staining of the cytoplasm of affected cells. A specific positive reaction was found only in neurons, in which perikaryon as well as cell processes were affected. Fluorescent antibody test and peroxidase anti-peroxidase technique detected 98% each, mouse inoculation test 95% and cell culture technique 81% of the rabies positive animals. In conclusion, peroxidase anti-peroxidase technique allows a highly reliable diagnosis of rabies when only formalin-fixed and paraffin-embedded material is available. Histopathological alterations comprising Negri bodies, inflammatory and degenerative lesions were encountered in 53% of the rabies positive brains.
Borna disease virus (BDV) infection, naturally occurring in horses and sheep induces a mononuclear retinitis and meningoencephalitis in adult Lewis rats. In the pathogenesis a virus-specific cell mediated immune reaction presumably of delayed hypersensitivity type is operative. Corresponding to the encephalitic lesions a progressive retinitis with loss of the first and second retinal neuron develops. The inflammatory response is characterized by predominance of macrophages in the early phase of infection followed by distinct plasmacellular infiltration. Immunosuppressed and immuno-incompetent rats do not develop retinal lesions after intracerebral inoculation. Thus similar as in the brain probably virus specific immunopathological reactions play a crucial role in the pathogenesis of BDV-induced retinitis in Lewis rats.
Neuroaxonal dystrophy and minimal diffuse degenerative myelopathy was diagnosed in two female full sibling, 1- and 2-year-old, Haflinger horses. Both animals developed slowly progressive ataxia from the age of 4 months. Clinical signs, which were more prominent in the hind legs, included hypermetria and dysmetria. Histological examination revealed neuroaxonal dystrophy characterized by spheroid formation, vacuolation, astrogliosis and lipofuscin pigment deposition in macrophages and neuronal perikarya. These changes were restricted to the gracilis and cuneate nuclei, nucleus of the solitary tract, nucleus intermediomedialis in the sacral and the seventh segment of the cervical spinal cord and Stilling-Clarke's column in both horses and the medial vestibular nucleus in the older horse. Both diseased Haflingers had significantly reduced serum alpha- and gamma-tocopherol values. No significant alteration in serum total lipid concentrations and serum selenium values were observed. It is likely that the condition has a familial hereditary basis. It is unclear whether there is a link between the observed neuroaxonal dystrophy and vitamin E deficiency and further investigations are warranted.
In rats persistently infected with Borna disease virus (BDV), severe neurologic disorders and occasional death are the consequences of a T cell-mediated immunopathologic reaction in the brain. It is shown here that the pathologic alterations in the brain and as a result, Borna Disease (BD) can be prevented if animals are treated with the immunosuppressive drug cyclosporine A (CSA) under the following optimal conditions: greater than or equal to 25 mg/kg/day of CSA, started before infection and given for 4 wk. Rats treated with lower doses of CSA, for shorter periods or after infection displayed encephalitic lesions and developed BD. When CSA treatment was begun even as early as 1 day after infection, encephalitis and disease were not influenced. Immune spleen cells passively transferred into CSA-treated rats induced the disease in the recipients, whereas lymphoid cells from CSA-treated rats did not induce BD in infected cyclophosphamide-treated recipients. Antibodies were not involved in BD because rats treated with CSA revealed an inhibition of the synthesis of virus-specific antibodies for all regimens of treatment used (whether successful in preventing BD or not). After i.v. challenge of CSA-treated healthy rats with BDV, antiviral antibodies at low titers could be induced in some animals; however, no encephalitis or disease symptoms could be observed at any time after infection. The same was true for rats reinfected intracerebrally with BDV after discontinuation of CSA. These results support the hypothesis that unresponsiveness and even tolerance can be induced by CSA in the presence of the foreign Ag, demonstrating the beneficial effect of this immunosuppressive drug during a persistent viral infection.
The hemagglutinin of influenza (fowl plague) virus was expressed in larvae of Heliothis virescens by using recombinant Autographa californica nuclear polyhedrosis virus (AcNPV) as a vector. Animals were infected with the recombinant virus either by parenteral injection or by feeding. For oral uptake, recombinant virus occluded in polyhedra obtained from cultured Spodoptera frugiperda cells after coinfection with authentic AcNPV was used. Immunohistological analyses of infected animals revealed that the hemagglutinin was expressed only in those tissues that are also permissive for the replication of authentic AcNPV. These tissues included hypodermis, fat body, and tracheal matrix. After oral infection, hemagglutinin was also detected in individual gut cells. The amount of hemagglutinin synthesized in larvae after parenteral infection was 0.3% of the total protein, compared with 5% obtained in cultured insect cells. The hemagglutinin was transported to the cell surface and expressed in polarized cells only at the apical plasma membrane. It was processed by posttranslational proteolysis into the cleavage products HA1 and HA2. Oligosaccharides were attached by N-glycosidic linkages and were smaller than those found on hemagglutinin obtained from vertebrate cells. Hemagglutinin from larvae expressed receptor binding and cell fusion activities, but quantitation of the hemolytic capacity revealed that it was only about half as active as hemagglutinin from vertebrate or insect cell cultures. Chickens immunized with larval tissues containing hemagglutinin were protected from infection with fowl plague virus. These observations demonstrate that live insects are able to produce a recombinant membrane protein of vertebrate origin in biologically active form.
In this study it has been shown that infection of mother rats by Borna disease virus (BDV) from infected newborns led to a fatal disease. This differed both in clinical symptoms and in histological alterations from the form of the disease which occurred after intracerebral (i.c.) infection. Both parameters were, however, similar to those seen after experimental intranasal (i.n.) infection of adult rats. Detailed immunohistological studies showed clearly that after experimental i.n. infection, the infecting virus migrates intraaxonally from the neuroreceptors in the olfactory epithelium into the brain. It is therefore suggested that i.n. transmission is an important route of natural BDV infection.
Pathogenic properties of influenza A viruses introduced into embryonated chicken eggs via the allantoic cavity, the amniotic cavity or the yolk sac were studied using viruses with cleavable or non-cleavable haemagglutinin (HA), or reassortants derived from the highly pathogenic fowl plague virus (FPV) which has a cleavable HA. The various organs, membranes and fluids were analysed for virus yields, and by immunohistochemistry for production of viral nucleoprotein. Virus replication in primary tissue cultures derived from various embryonic organs was also studied. Some of the reassortants, which were previously found to be non-pathogenic for chickens and were temperature-sensitive (ts) at 40 degrees C, multiplied at 37 degrees C to the same extent as the highly pathogenic FPV. The spread of other non-pathogenic reassortants in the embryo was restricted. For example, 81/Ho was able to multiply to a reasonable extent only in the chorioallantoic and the allantoamniotic membranes. After inoculation of the A/PR/8/34 strain containing a non-cleavable HA into the amniotic cavity, virus multipled only in the inner epithelial layer of the amnion, in superficial epidermal cells and in superficial epithelia of the oropharyngeal cavities, the nasal and paranasal sinuses and the oesophagus. Kidneys were free of virus antigen, although the virus multiplied to high titres in primary tissue cultures derived from embryonic kidneys. Thus influenza A viruses can be non-pathogenic for chickens because they are ts and unable to multiply at the body temperature of chickens (41 degrees C), or because their spread in the animal is impaired per se.
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Homozygous athymic nude rats (rnu/rnu) infected intracerebrally with Borna disease virus produced relatively high titres of infectious virus in the central nervous system. However, no clinical signs of disease or pathological alterations could be found during a 100 day observation period. In contrast, heterozygous euthymic albino littermates (rnu/+), which were used as controls, reacted in a similar manner to immunocompetent Lewis rats. They developed behavioural alterations which coincided with encephalitis and retinitis. The results obtained confirm our previous concept that the genesis of Borna disease, at least in rats, is attributed to a cellular immune response.
A pigmented choroidal tumor was diagnosed in a 13-month-old male beagle. The tumor was observed ophthalmoscopically over a period of seven years. Light and electron microscopical features are those of a benign melanocytic tumor with marked histological similarities to uveal nevus in man.
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There are age-dependent differences in the tissue distribution of Borna disease (BD) virus in rats infected intracerebrally. While in adult rats BD virus replication is restricted to neural cells, in neonatally infected rats infectious virus or viral antigens were found in the cells of most organs. The possibility that differences in the immune status between newborn and adult animals are responsible for different tissue susceptibility could be excluded.
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Borna virus replicated persistently in the brains of rats, causing frenzied and apathetic behavioral states in sequence but no mortality. The transient frenzied behavior was caused by an immune-mediated, cytolytic, encephalitic response that was unexpectedly self-limiting. Cessation of active pathological processes coincided with the onset of the passive phase of the disease. This study thus demonstrates suppression of virus-specific inflammation despite continuous viral replication and describes a new mechanism by which chronic encephalitis may become established.