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Biomedical subjects

R Meyermann

Publications and source records attributed to R Meyermann.

At least 127 records · Page 7Linked to original sources
PubMed1987

Immune reactivity in the nervous system: modulation of T-lymphocyte activation by glial cells.

The vertebrate central nervous system (CNS) has been traditionally thought to be inaccessible for the passenger lymphocytes of the immune system. This does not seem to be the case: activated T-lymphocytes can readily cross the endothelial blood-brain barrier (BBB) and some glial cells, notably the astrocytes, seem to be programmed to act as most efficient and complex partners for antigen-specific T-lymphocytes. We used myelin basic protein (MBP) specific permanent rat T-lymphocyte lines as probes to assess the immune status of the CNS. These cells, upon activation in vitro, are able to transfer lethal, experimentally induced autoimmune-encephalomyelitis (EAE) to normal syngeneic recipients. Activated T-lymphocytes, but not resting ones, can break through the BBB irrespective of their antigen specificity. Immune surveillance of the CNS thus seems to be executed by activated T-lymphocytes. Having crossed the BBB, the activated T-cells interact with local glial cells by releasing factors, including interferon-gamma, which induced astrocytes to synthesize and express, on their membranes, class II major histocompatibility antigens (Ia determinants), which are critically required for immunogenic presentation of antigens to T-cells. Indeed, Ia-induced astrocytes of the CNS (and the Schwann cells of peripheral nerves) are efficient antigen presenter cells, which are able strongly to up-regulate antigen-reactive T-lymphocytes. In addition, it has recently been shown that at least some astrocytes are able to down-regulate immune cells. Some, but not all, astrocytes are capable of suppressing activation of T-cells. This suppression can be modulated by interferon-gamma, and is sensitive to irradiation. The question of whether suppression is mediated by direct cell-to-cell contact or via soluble mediators (e.g. apolipoprotein E) is under investigation. Astrocytes have been found to be most subtle regulators of immuno-competent T-cells. Most probably they are centrally involved in physiological immune reactivity of the CNS, and it will be tempting to learn how far glial cells are involved in transmitting regulatory signals between the immune and nervous systems.

Animals↗
PubMed1986

Induction of experimental allergic neuritis in the BN rat: P2 protein-specific T cells overcome resistance to actively induced disease.

T lymphocyte lines specific for the peripheral nerve myelin protein P2 were selected from the lymph nodes of Brown Norway (BN) rats immunized with bovine P2 protein in complete Freund's adjuvant. These T cells expressed the W3/25+, OX8-phenotype and responded specifically to bovine P2 protein, but not to PPD or bovine basic protein, in T cell proliferation assays. When injected i.v. into syngeneic recipients, BN P2-specific T cell lines induced both clinical and histologic signs of experimental allergic neuritis (EAN), overcoming the resistance of this rat strain to actively induced EAN. Although the histopathology of the disease was indistinguishable from that seen in T cell-mediated EAN in the Lewis rat, disease onset was considerably later, 7 to 8 days after cell transfer, as opposed to 4 days in Lewis. This lag phase between inoculation and disease onset could not be further reduced even by raising the cell dose to 50 X 10(6) cells/host. The fine specificity of the T cell response to P2 differs between Lewis- and BN-derived T cell lines. At least one neuritogenic epitope for each strain was present in the cyanogen bromide-derived peptide CB2 (residues 21-113), as shown by the ability of CB2-specific T cell lines derived from each strain to transfer EAN to the appropriate host strain. However, neuritogenic BN T lines fail to mount a response to the sequence 53-78 (SP4), which encompasses an epitope that is neuritogenic for Lewis rats. These results demonstrate that the resistance of BN rats to actively induced EAN is not due to the lack of appropriate P2-specific autoreactive T cell clones in the normal T repertoire. Furthermore, the results suggest that two distinct epitopes of P2 are responsible for EAN in Lewis and BN rats.

Animals↗
PubMed1986

Antigen presentation in the peripheral nervous system: Schwann cells present endogenous myelin autoantigens to lymphocytes.

Schwann cells (SC) isolated from neonatal rat sciatic nerves are shown to immunogenically present foreign and exogenous autoantigen to antigen-specific syngeneic T line cells in vitro. The antigen-presenting SC express Ia antigens on their membranes upon treatment with interferon gamma and contact with syngeneic T line cells. Monoclonal antibodies against Ia block specific antigen presentation, but not polyclonal mitogenic T cell activation. The antigen-presenting SC bind antibodies specific for astrocytic glial fibrillary acidic protein and may thus be related to the nonmyelinating glia cells of the peripheral nerve. Furthermore, SC isolated from 6-day-old rats activate rat myelin basic protein (MBP)-specific syngeneic T line cells in the absence of exogenous MBP. In contrast, they activate purified protein derivative of tuberculin (PPD)-specific T cells only in the presence of PPD. Since the MBP-specific T line cells are not activated by syngeneic professional antigen-presenting cells in the absence of MBP, endogenous MBP produced in the 6-day-old sciatic nerves appears to be presented by autochthonous SC to the autoreactive T cells.

Animals↗
PubMed1985

Morphologic study on experimental allergic neuritis mediated by T cell line specific for bovine P2 protein in Lewis rats.

Light and electron microscope studies were performed on experimental allergic neuritis (EAN) passively induced in Lewis rats by the intravenous injection of T line cells specific for bovine P2 protein. Histologic changes were almost entirely restricted to the peripheral nervous system, being most severe in the sciatic nerve and lumbosacral nerve roots, whereas the brachial nerve and cervical nerve roots were involved to a lesser extent. The lesions were composed of edema, cellular infiltrates, demyelination, and, subsequently, axonal degeneration. Infiltrated macrophages were observed actively stripping the myelin, and the Schwann cell cytoplasm of affected nerve fibers was pushed to the periphery without distinct evidence of degeneration. The first evidence of pathologic change was severe edema in the sciatic nerve 4 days postinoculation. This edema was demonstrated immunohistochemically by the presence of albumin and fibrinogen in the endoneurial space. Mast cell degranulation was observed in these edematous nerve lesions. The cellular infiltrates which formed perivascular cuffs were composed of not only mononuclear cells but also many granulocytes. In the central nervous system, meningeal cell infiltration was also observed in the spinal cord, and after 7 days postinoculation degeneration of the posterior column was also found. This latter observation is thought to represent degeneration due to axonal damage of lumbosacral posterior roots. These pathologic findings in a T cell-mediated model of EAN were essentially the same as those previously reported in conventionally induced EAN or human Guillain-Barré Syndrome. Thus, T cells specific for bovine P2 protein can induce typical EAN lesions in the Lewis rat. The further investigation of this transfer model of EAN will enable us to clarify the pathogenesis of EAN and Guillain-Barré syndrome.

Animals↗
PubMed1984

A permanent rat T cell line that mediates experimental allergic neuritis in the Lewis rat in vivo.

A rat T cell line of the "helper" phenotype (W3/25-positive, OX 8-negative) has been derived from Lewis rats inoculated with P2 protein isolated from bovine PNS myelin. The line LiP2/A is exquisitely specific for P2 protein, exhibiting no reactivity to bovine basic protein or to PPD. In addition to responding strongly to the intact P2 protein, the line cells show some response to a synthetic peptide containing the neuritogenic amino acid sequence of P2 protein (SP-B, residues 66-78). Intravenous inoculation of naive rats with as few as 10(4) activated LiP2/A cells leads to the onset of mild clinical signs of experimental allergic neuritis. Higher doses of cells lead to more severe clinical disease. Histologic examination of clinically ill animals confirmed the disease as EAN. The pathologic lesions were confined to the PNS and spared the central nervous system. The lesions consisted of marked perivascular cuffs and infiltrates of inflammatory cells associated with marked degenerative changes--demyelination and some axonal degeneration.

Animals↗
PubMed1982

Immunohistochemical identification of T-lymphocytes in the central nervous system of patients with multiple sclerosis and subacute sclerosing panencephalitis.

T-lymphocytes were identified in frozen brain sections derived from patients with chronic inflammatory disorders of the CNS by using a specific heteroantiserum and the unlabelled antibody enzyme method. Clusters of T-cells were found in post-mortem material of cases with multiple sclerosis (MS) and subacute sclerosing panencephalitis (SSPE). The results suggest that T-lymphocytes are involved in the pathogenesis of both MS and SSPE.

Adolescent↗
PubMed1982

[Microsurgical blood vessel sutures using the so-called fibrin adhesive].

Since the development of microvascular surgery by Jacobson and Suarez, adaptation of vessel ends of less than 1 mm diameter has been performed by means of 8-10 interrupted sutures. Even the finest suture material, however, produces a foreign body reaction. In addition, necrosis of the media can be seen after insertion of interrupted sutures. After the initial demonstration in 1940 that divided nerves could be successfully rejoined by means of factors from the blood coagulation system, this technique was introduced to microsurgery in 1977. The present investigation was carried out on 50 end-to-end anastomoses in rat common carotid arteries. Subsequently, the healing process was studied by light and electron microscopy. The adhesive used was fibrinogen cryoprecipitate (Fibrinkleber-Human-Immuno), which polymerises after simultaneous application of thrombin. Electron microscopy shows no basic difference between the healing after this technique and the healing process after trauma to the vessel wall. This method, however, prevents regional necrosis of the vessel wall and reduces intimal thickening. The condition of the intimal lining appears better than in sutured anastomoses. The question, whether this change is due only to the absence of sutures or due also to application of fibrinogen, cannot be answered, however.

Animals↗
PubMed1979

Neurochemical and morphological studies of bulk isolated rat brain cells. II. Preparation of viable cerebral neurons which retain synaptic complexes.

The bulk isolation from rat cerebral cortex of viable neurons retaining synaptic complexes is described. The basis of this procedure is to dissociate the neurons in situ from the surrounding glial cells. The glial structures that are normally adjacent to the neuronal cell body and to the proximal parts of the neuronal processes are largely destroyed by perfusion of the brain under special conditions. The most important of these conditions was found to be a hyperosmolar concentration of hexoses in the perfusion medium. In addition, the presence of collagenase and hyaluronidase in the perfusion medium and specific perfusate flow characteristics were required to produce the structural changes throughout the brain tissue. When the perfused brain was further dissociated into a cell suspension by mincing and sieving, isolated neurons were obtained, the majority of which retained the proximal parts of their processes. A novel feature of these neurons was the retention of synaptic boutons on the plasma membrane. Presynaptic terminals with mitochondria and vesicles as well as pre- and postsynaptic membranes and densities were observed on the isolated neurons. The neurons were fractionated to 90--95% purity using discontinuous Ficoll density gradient centrifugation with a liquid fluorocarbon as cushion. Highly purified, viable cerebral neurons retaining synaptic complexes are thus available in bulk for neurobiological studies.

Animals↗
PubMed1979

Demyelinating encephalomyelitis induced by a long-term corona virus infection in rats. A preliminary report.

About 30% of weanling rats inoculated with JHM virus developed a subacute demyelinating encephalomyelitis (SDE) 3 weeks after inoculation (a.i.). From the remaining animals, 5% displayed overt neurological signs 3, 6, and 8 months a.i. Animals with and without clinical signs 6-8 months a.i. were morphologically examined. Fresh demyelinating lesions could be demonstrated in paralyzed animals. Viral antigen was demonstrated and infectious JHM virus could be recovered from one animal which developed clinical signs at 3 months a.i. In one animal with clinical onset of 8 months a.i. completely remyelinated areas as well as recent demyelinating lesions were observed, suggesting a recurrence of the disease process. Remyelinated areas were also found in 40% of clinically silent animals. The morphology of the late onset of the demyelination was similar to that occurring in SDE. Remyelination consisted of both CNS and PNS-type. This animal model offers the possibility to investigate the virus-host relationship which is responsible for the induction of a demyelinating process after a long incubation period.

Animals↗
PubMed1978

Corona virus induced subacute demyelinating encephalomyelitis in rats: a morphological analysis.

Thirty percent of weanling rats infected with JHM murine corona virus developed a subacute demyelinating encephalomyelitis approximately 3 weeks after intracerebral inoculation. Small demyelinating foci were located in the deep cerebral white matter and large, sharply demarcated demyelinating lesions were detectabll preserved in the demyelinating plaques in areas where the lesions extended to the gray matter. Perivascular cuffings, consisting of plasma cells and mononuclear cells, were frequently found. Viral antigen was found mostly in the white matter and in glial cells, leaving neurons unstained. Electron microscopic studies of the early lesions of white matter disclosed two different kinds of cell degeneration which developed prior to the myelin disruption and mononuclear cell infiltration. One was a small pyknotic cell, which is thought to be an oligodendrocyte and the other is a ballooned cell containing abundant microtubules. Virus particles could be demonstrated only in the latter cell type. Discussion about astrocytes as well as oligodendrocytes was made in relation to the initial stage of demyelination caused by virus infection. This animal model may be useful in the analysis of the mechanisms leading to demyelination in subacute or chronic infections.

Animals↗
PubMed1976

Ultrastructural findings after microsurgical interventions on the carotid artery of the rat.

For 10 years, it has been known that operations on vessels 1 mm in diameter are possible. The application of microvascular techniques to neurosurgery demands microscopic and ultrastructural examinations of the effects of such interventions on small vessels. Histological examinations can help to provide answers to questions concerning operating technique, ultrastructural examinations give information on the indications for operation. Since these questions have not been studied previously, preliminary examinations on easily accessible vessels are necessary. For this purpose, the common carotid artery of the rat was chosen. Histological and ultrastructural examinations were carried out on end-to-end anastomoses of these vessels. The ultrastructural findings are described and compared with anatomical findings in normal and abnormal vessels in the rat.

Animals↗
PubMed1976

Comparative evaluation of various histological techniques for the rapid diagnosis of brain tumours.

Intraoperative procedures for the rapid histological diagnosis of space occupying intracranial processes are required. These currently include three major techniques: 1. crush preparations; 2. frozen sections with prefixation, and 3. frozen sections without prefixation. We have compared these techniques, using identical tissue material. While frozen sections of samples subjected to rapid fixation produce the best specimens, crush preparations are preferred wherever a well equipped laboratory is not available.

Astrocytoma↗
PubMed1975

Sporadic bovine meningo-encephalitis-isolation of a paramyxovirus.

Isolation of a viral agent (107) directly from brain explants of a 15-month-old heifer with symptoms of a sporadic encephalomyelitis is described. The virus shares properties with the paramyxovirus family. It grows in a variety of cell cultures from different species, and induces nuclear and cytoplasmic inclusion bodies in infected cells. Nucleocapsids measuring 17 nm in diameter were found in the nucleus and cytoplasm of these cells when studied electron microscopically, thus indicating a close relationship of the agent to the measles-distemper-rinderpest group. No infectious virus was released from infected cells, although alignment of nucleocapsids was observed beneath the cell membrane, and no hemagglutinating activity could be detected with the methods employed. The 107 agent was compared serologically with parainfluenza viruses type 1, 2 and 3, simian virus 5, mumps and Newcastle disease virus (NDV), two bovine respiratory syncytial viruses and measles/subacute sclerosing panencephalitis, distemper and rinderpest viruses, always using 107 virus infected CV1 cells and antiserum of the different viruses in indirect FA tests. Positive FA reactions were observed only with two sera obtained from SSPE patients with high antibody titer to SSPE virus, and with one rabbit-anti-rinderpest serum. The titers of these sera to 107 virus, however, were significantly lower than those against homologous viruses. Five out of 9 sera from randomly selected healthy cattle showed antibody titers between 1:10 and 1:80 to 107 virus in FA tests. The significance of these results is discussed with respect to the epidemiology of SSPE in children and its possible implication with rinderpest in Europe.

Animals↗
PubMed1975

[The importance of the histological structure of the superficial temporal artery for the functioning of the arterial extra-intracranian anastomosis].

After extra-intracranial anastomosis one could find a considerable dilatation of the superficial temporal artery in a relatively short period of time. This vessel as well as other arteries of the circulatory system were examined histologically. On the basis of a large amount of autopsy material the atherosclerotic changes of the different vessels were correlated. Thus it turned out that the superficial temporal artery revealed another type of atherosclerotic changes. A type which exhibited hardly any calcification, but shows an increase of elastic fibers which make dilatation of the vessel possible despite of its thickened wall and primarily narrowed lumen.

Adult↗