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Biomedical subjects

H Lassmann

Publications and source records attributed to H Lassmann.

At least 199 records · Page 11Linked to original sources
PubMed1990

Intrathecal application of interferon gamma. Progressive appearance of MHC antigens within the rat nervous system.

Intrathecal injection of interferon-gamma induced a significant increase of the number of class I and class II major histocompatibility complex (MHC)-expressing cells within the rat nervous system. A progressive appearance of MHC-antigen-positive cells was found by light- and electron microscopic immune histology. The first level comprised cells that constitutively expressed MHC antigens in normal animals (meningeal and endoneural monocytes, some perivascular dendritic cells, and few parenchymal microglia cells, especially in the lumbar spinal cord and in the cerebellar white matter). The second level represented cells readily expressing MHC antigens after stimulation with interferon-gamma (all perivascular, dendritic cells, and microglia). The third level included ependymal cells, astrocytes, and Schwann cells. After stimulation with interferon-gamma, these neuroectodermal cells expressed MHC antigens inconsistently, usually in a low density and patchy distribution. The progressive appearance of MHC antigens may be reflected by the variances of lesional patterns found in experimental allergic encephalomyelitis of different histologic severity.

Animals↗
PubMed1990

Some mechanisms of brain edema studied in a kainic acid model.

Kainic acid (KA) is a potent neuroexcitatory drug widely used in the experimental study of seizure activity. Subcutaneous injection of KA into rats (10 mg/kg in saline 10 mg/ml; pH 7.0) induced longlasting status epilepticus followed by damage of CNS tissue in the entorhinal/pyriform cortex and in the hippocampus. The studies covered by this report demonstrated the formation of cytotoxic brain edema characterized by massive swelling of perineuronal and perivascular astroglia with microcirculation disturbance after KA injection, resulting in parenchymal necrosis of the affected region; furthermore perivenous hemorrhages and necroses corresponding to herniation lesions of the brain appear. Tracer studies with Na-fluorescein, Evans blue, albumin, and horseradish peroxidase revealed only a mild increase in the permeability of cerebral vessels, topographically unrelated to areas of brain edema. Treatment of brain edema with dexamethasone did not influence the incidence and severity of edematous brain damage. Treatment with mannitol, however, completely prevented the lesion in 54% of animals injected with KA. The present results indicate that brain edema plays an important role in the pathogenesis of epileptic brain damage following systemic KA intoxication. It is suggested that in this model brain edema develops due to massive ionic imbalance caused by KA induced persistent neuronal excitation. In addition the model demonstrates the possible pathogenetic role of selective astrocytic swelling in the production of local hippocampal ischemia followed by herniation and its sequels. Such pathology originating from astrocytes probably may occur also in closed brain injury.

Animals↗
PubMed1989

Limbic seizures without brain damage after injection of low doses of kainic acid into the amygdala of freely moving rats.

Kainic acid (KA, 8-15 ng) was injected into the amygdala of conscious freely moving rats via chronically implanted fused silica cannulas. At 15-25 min after the injection, most rats suffered a limbic seizure attack of short duration, consisting of mastication, forelimb clonus, and raising on hind limbs, behaviorally indistinguishable from kindled seizures. Typically, the attack was followed by stereotypies, intense exploration, and by 1 or 2 more attacks. About 60 min after the injection, most rats appeared normal again and histopathological changes in their brains did not exceed those seen in vehicle-injected rats. In 3 cases, however, recurrent seizures culminated in behavioral status epilepticus 60-90 min after the injection. The status epilepticus was stopped by i.p. injection of diazepam (10 mg/kg) after a duration of 10 min (1 case) and 30 min (2 cases), respectively. After 10 min status epilepticus, we observed marginal neuronal damage with slight gliosis in both hippocampi (CA3 and CA1); after 30 min, hippocampal histopathology was more pronounced, with additional necrosis of the ipsilateral piriform cortex. After 0.8 microgram KA, a hundredfold higher dose, the incidence of limbic seizures during the first 40 min was not significantly higher (9/12) than after the lower KA doses (13/19). However, a significantly higher proportion of rats exhibited long-lasting seizure activity, associated with confluent destruction of CA3 pyramidal cells and additional seizure-related brain damage. Our results show that limbic motor seizures do not inevitably lead to histopathological changes in the brain, provided they do not culminate in a state of permanent seizure activity.

Amygdala↗
PubMed1989

Induction of stress protein HSP70 in nerve cells after status epilepticus in the rat.

The accumulation of the stress protein HSP70 was found to be an excellent marker for prolonged seizure related metabolic activity of neurons. After kainic acid (KA) induced status epilepticus we observed HSP70 immunoreactivity in the hippocampal CA4 and CA1 sectors, the subiculum, the basolateral and the lateral nuclei of the amygdala, the mediodorsal nucleus of the thalamus, the caudal part of the striatum, the claustrum and in neurons of certain neocortical areas. HSP70-positive nerve cells appeared normal in conventional histological stains. Conversely, degenerating neurons (e.g. in the hippocampal CA3 sector) remained unlabeled.

Animals↗
PubMed1989

Accumulation of abnormally phosphorylated tau precedes the formation of neurofibrillary tangles in Alzheimer's disease.

The intraneuronal accumulation of paired helical filaments in the form of neurofibrillary tangles is one hallmark of the brain pathology in Alzheimer's disease. At certain predilection sites, a small number of similar lesions are also present in the brains of the majority of aged non-demented individuals. As suggested by several studies before, these abnormal cytoskeletal structures contain determinants of microtubule-associated protein tau and ubiquitin. The present study uses a morphological classification of neurofibrillary tangles into different stages of maturation, as suggested by Alzheimer in 1911, and shows by quantitative immunocytochemistry that early stages of neurofibrillary degeneration contain abnormally phosphorylated tau. Immunoreactivity for the altered tau is seen not only in tangles but also in the cytoplasm of some nerve cells lacking neurofibrillary tangles. Similar numbers of such immunoreactive neurons without tangles are present in age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls. In contrast, incorporation of an epitope, recognized by a monoclonal antibody (3-39) raised to paired helical filaments, which is directed against a determinant residing in the 50-65 amino acid residue region of ubiquitin occurs late in the process of tangle maturation and is most pronounced in extracellular 'ghost tangles'. It is suggested that the accumulation of abnormally phosphorylated tau is one of the earliest cytoskeletal changes in the process of tangle formation. Exposure of certain ubiquitin epitopes in the pathological fibers may reflect an unsuccessful attempt of proteolytic degradation.

Adult↗
PubMed1989

Molecular mimicry and Lyme borreliosis: a shared antigenic determinant between Borrelia burgdorferi and human tissue.

The pathogenesis of chronic manifestations in Lyme borreliosis, a disease induced by Borrelia burgdorferi, is at present unresolved. By testing monoclonal antibodies directed against various borrelia antigens, we found an antigenic determinant shared by the 41 kDa flagella protein and human tissue, especially prominent on myelinated fibers of human peripheral nerve, on nerve cells and axons of the central nervous system, as well as on certain epithelial cells (including joint synovia) and on heart muscle cells. Immune reactions against such a shared antigen could play a pathogenetic role in chronic organ manifestations of Lyme borreliosis.

Antibodies, Monoclonal↗
PubMed1989

Hepatic encephalopathy in thioacetamide-induced acute liver failure in rats: characterization of an improved model and study of amino acid-ergic neurotransmission.

An imbalance of excitatory and inhibitory amino acid-ergic neurotransmission has been suggested to play a role in the pathogenesis of hepatic encephalopathy. For further evaluation of this hypothesis, several parameters of amino acid-ergic neurotransmission were studied in rats with acute liver failure induced by the administration of 300 mg per kg thioacetamide by gavage on two consecutive days. By appropriate supportive care, hypoglycemia, renal failure and hypothermia were avoided. Rats were monitored clinically and neurologically. Hepatic encephalopathy evolved in four distinct, easily recognizable stages. Light and electron microscopic examination of brains of rats with hepatic encephalopathy revealed only a slight swelling of nuclei of neurons and astrocytes without signs of neuronal degeneration or brain edema. In rats with hepatic encephalopathy, the concentrations of GABA, glutamate and taurine were decreased in the cerebral cortex, the hippocampus and the striatum, whereas those of aspartate and glycine were unchanged or increased. GABAA and benzodiazepine receptors were studied as parameters for the postsynaptic GABAA-benzodiazepine receptor complex, glutamic acid decarboxylase as parameter for presynaptic GABA-ergic neurons and stimulation of benzodiazepine binding by GABA as a parameter for a GABA-mediated postsynaptic event. None of these parameters was different in hepatic encephalopathy as compared to controls. Similarly, Ca++/Cl(-)-dependent and -independent glutamate receptors as parameters for glutamatergic neurons were unchanged in rats with hepatic encephalopathy. Thus, in rats with thioacetamide-induced liver failure and hepatic encephalopathy, changes of the concentrations of neurotransmitter amino acids occur in the brain. Other neurochemical parameters, however, failed to identify alterations of GABA-ergic or glutamatergic neurotransmission in hepatic encephalopathy.

Acetamides↗
PubMed1989

Immunohistochemical localisation of terminal complement component C9 in experimental allergic encephalomyelitis.

The deposition of terminal complement component C9 within the central nervous system (CNS) has been studied immunohistochemically in three models of experimental allergic encephalomyelitis (EAE) in the rat; inflammatory EAE induced by the passive transfer of myelin basic protein-specific T cells (tEAE), antibody-mediated, demyelinating tEAE and a subacute/chronic model induced by active immunisation with guinea pig spinal cord tissue in adjuvant. Two distinct patterns of C9 reactivity were observed, a diffuse staining of the tissue adjacent to inflammatory lesions, similar to that seen for other extra-vasculated serum proteins, and also granular, sometimes fibrillar C9 deposits around some inflammed vessels and in areas of active demyelination. The latter staining pattern was most pronounced in animals with acute antibody-mediated demyelinating tEAE, in which extensive, but transient, subpial and perivascular granular deposits of C9 were associated with regions of acute demyelination. A similar pattern of granular C9 reactivity was also associated with demyelinating lesions in animals with actively induced chronic progressive EAE. However, these C9 deposits were not observed in rats with purely inflammatory, clinically mild tEAE, although C9 deposition was occasionally observed around a small number of inflammed vessels in animals with hyperacute, lethal tEAE. These observations demonstrate that deposition of C9, the major component of the cytolytic membrane attack complex, in EAE is related to myelin injury rather than CNS inflammation.

Animals↗
PubMed1989

Vacuolar myelopathy with multinucleated giant cells in the acquired immune deficiency syndrome (AIDS). Light and electron microscopic distribution of human immunodeficiency virus (HIV) antigens.

Vacuolar myelopathy (VM) is a frequent neurological complication of the acquired immune deficiency syndrome (AIDS). A suspected connection between VM and human immunodeficiency virus (HIV) has been based only on HIV isolation from affected spinal cord tissue. We report here an AIDS patient dying after 14 months of progressive dementia, including 3 months of spinal signs and symptoms. At autopsy, the brain revealed moderate diffuse damage of the white matter compatible with HIV-induced progressive diffuse leukoencephalopathy. The spinal cord showed VM mainly in the lateral and the posterior columns. Mono- and multinucleated macrophages were localized within intramyelinic and periaxonal vacuoles. Light and electron microscopic immunocytochemistry revealed the presence of HIV antigens restricted to mono- and multinucleated macrophages within the spongy lesions. Productive HIV infection is documented for the first time within VM lesions of this case. Therefore, VM should be included among HIV-induced lesions of the central nervous system. The intimate relation of infected macrophages to vacuolar myelinopathy could suggest secretion of a myelinotoxic factor by macrophages productively infected by HIV. Immune electron microscopy appears as promising tool to detect HIV in tissue even when the density of virus may be low.

AIDS Dementia Complex↗
PubMed1989

Manufacture and use of fused silica cannulas for intracerebral injections in freely moving rats.

This report describes in detail the assembly and use of miniature cannulas for intracerebral injections in freely moving rats. Guide and injection cannulas were prepared from polyimid-coated fused silica capillaries as routinely in use for gas chromatography, in this way avoiding the permanent contact of stainless-steel with brain tissue. The outer diameter of the guide capillary measured 300 microns, that of the injection capillary 170 microns. In spite of their fragile appearance, the capillaries were robust and easy to handle. In the same animal, up to 20 consecutive injections were possible. In the course of 2 years 204 cannulas directed to the amygdala or the lateral ventricle were implanted, and only in 8 rats (4%) the inner capillary broke and plugged the guide cannula, making injections impossible. Histological examination of brains implanted for up to 2 months demonstrated only blunt scar formation along the cannula's track. No changes in transmitter levels (biogenic amines, amino acids) could be detected in chronically implanted rat brains except for a slight increase in serotonergic activity in the contralateral piriform cortex. Intra-amygdaloid injection of 0.32 microliters 0.9% saline resulted in a mild and transient reduction of GABA levels in both piriform cortices, without any detectable persistent histopathological consequences.

Animals↗
PubMed1989

An antigenic profile of Lewy bodies: immunocytochemical indication for protein phosphorylation and ubiquitination.

An antigenic profile of subcortical and cortical Lewy bodies was determined in the presence or absence of neurofibrillary tangles in the same brain using antisera and monoclonal antibodies to various cytoskeletal elements as well as to determinants not present in the normal cytoskeleton. The cores of many Lewy bodies were strongly reactive with a monoclonal antibody to paired helical filaments which has been shown to recognize ubiquitin. This antibody also stained Marinesco bodies in the same tissue sections. Two monoclonal antibodies to phosphorylated epitopes of neurofilament proteins (SM I 31, SM I 34) stained the peripheries of about 40% of all discernable Lewy bodies on untreated paraffin sections. Reactivity with a monoclonal antibody to neurofilaments (SM I 33) appeared only after pretreatment of the sections with phosphatase. Lewy bodies did not bind antibodies to tau protein. Our results show that, as previously shown for neurofibrillary tangles, Lewy bodies also contain ubiquitin. The uncovering of neurofilament epitopes by treatment with phosphatase indicates that abnormal phosphorylation of cytoskeletal elements may play a role in the pathogenesis of the Lewy body.

Aged↗
PubMed1989

Differential ultrastructural localization of myelin basic protein, myelin/oligodendroglial glycoprotein, and 2',3'-cyclic nucleotide 3'-phosphodiesterase in the CNS of adult rats.

In a light and electron microscopic immunocytochemical study we have examined the distribution of myelin basic protein (MBP), 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), and myelin/oligodendroglial glycoprotein (MOG) within CNS myelin sheaths and oligodendrocytes of adult Sprague-Dawley rats. Ultrastructural immunocytochemistry allowed quantitative analysis of antigen density in different myelin and oligodendrocyte zones: MBP was detectable in high density over the whole myelin sheath, but not in regions of loops, somata, or the oligodendrocyte plasma membrane. CNP reactivity was highest at the myelin/axon interface, and found in lower concentration over the outer lamellae of myelin sheaths, at the cytoplasmic face of oligodendrocyte membranes, and throughout the compact myelin. MOG was preferentially detected at the extracellular surface of myelin sheaths and oligodendrocytes and in only low amounts in the lamellae of compacted myelin and the myelin/axon border zone. Our studies, thus, indicate further the presence of different molecular domains in compact myelin, which may be functionally relevant for the integrity and maintenance of the myelin sheath.

Animals↗
PubMed1989

Demyelination in brain cell aggregate cultures, induced by a monoclonal antibody against the myelin/oligodendrocyte glycoprotein (MOG).

Previous work has shown that aggregate cultures prepared from fetal rat telencephalon and grown in a chemically defined medium offer a useful model to study developmental processes such as myelin synthesis. Since compact myelin is formed in these cultures, we investigated the possibility to use this culture system to study demyelinating mechanisms. In particular, we examined the effect of a monoclonal antibody (8-18C5) directed against the myelin/oligodendrocyte glycoprotein (MOG). We found that addition of anti-MOG antibodies and complement to aggregate cultures led to a highly significant decrease in myelin basic protein (MBP) content and 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNP) specific activity. These results indicate that, in our culture system, anti-MOG antibodies have a strong demyelinating effect.

Animals↗
PubMed1989

Tau and ubiquitin immunoreactivity at different stages of formation of Alzheimer neurofibrillary tangles.

In his original 1911 publication Alois Alzheimer classified neurofibrillary tangles (ANT) into three morphologically defined subgroups according to their stage of maturation. The present study shows that changes in the morphological appearance of ANT during their maturation process are accompanied by changes in their antigenic profile. As shown by several immunocytochemical studies these abnormal phosphorylated microtubule-associated protein tau and of ubiquitin. In this study, immunoreactivity for the altered tau is not only seen in a subset of tangles but also in the cytoplasm of some nerve cells lacking ANT, which we believe to be at a stage of neuronal alteration preceding the formation of compact tangles (Stage 0 tangles). Similar numbers of Stage 0 tangles are present in the brains of age-matched non-demented individuals as in Alzheimer cases, but are absent in young controls lacking ANT. In extracellular "ghost tangles", the ultimate stage of neurofibrillary degeneration, immunoreactivity for tau is accessible to antibodies only when tissue sections are pretreated with formic acid to uncover the binding sites. In contrast to tau, presence/accessibility of an epitope residing on residues 50-65 of ubiquitin recognized by a monoclonal antibody raised to paired helical filaments (3-39) increases during the maturation of ANT and is most pronounced in "ghost tangles". Appearance/uncovering of the 3-39 epitope and masking of tau reactivity during tangle maturation may reflect degradation or conformational changes in the pathological filaments due to their aging and the final loss of their parent nerve cells.

Aged↗
PubMed1988

Experimental allergic encephalomyelitis: the balance between encephalitogenic T lymphocytes and demyelinating antibodies determines size and structure of demyelinated lesions.

The effect of a circulating monoclonal antibody recognizing an antigen located on the surface of myelin sheaths (myelin/oligodendroglia glycoprotein, MOG) on clinical and histopathological expression of experimental allergic encephalomyelitis (EAE) was tested in a model of EAE passively transferred by monospecific T lymphocytes. Intravenous injection of anti-MOG antibody at the onset of the disease massively augmented clinical impairment as well as primary demyelination. The structure of the CNS lesions depended on the balance between encephalitogenic T cells and anti-MOG antibody: when EAE was induced with high numbers of T cells, circulating anti-MOG antibody resulted in ubiquitous perivenous demyelination in the spinal cord and medulla oblongata. On the contrary, focal confluent demyelinated lesions were observed in animals injected with low numbers of T cells (even as few as 10(4] and anti-MOG antibody. Our studies, thus, indicate that the formation of inflammatory demyelinating lesions may be due to a synergistic action of cellular and humoral immune mechanisms.

Animals↗
PubMed1988

Expression of the VEP13 antigen (CD16) on native human alveolar macrophages and cultured blood monocytes.

Human alveolar macrophages (AM phi) from thirteen patients, who were suffering from various lung diseases were harvested by bronchoalveolar lavage. Peripheral blood monocytes from eight healthy donors were isolated by Ficoll-Hypaque gradient centrifugation and adherence to plastic surface. To detect the VEP13 antigen (CD16) on these cells, a rosette assay employing ox erythrocytes coated by the CrCl3 method with purified VEP13 monoclonal antibody (Eo-VEP13) was used. A mean of 31.3% of freshly isolated AM phi and 3.9% of blood monocytes formed Eo-VEP13 rosettes. Monocytes cultured for 3 or 6 days in the presence of a supernatant from mouse L929 cells, which had been shown previously to improve long-term viability of human monocytes in culture, showed 12.5% and 25.3% Eo-VEP13 rosettes, respectively. No significant increase in VEP13 antigen expression was noted by culturing monocytes without L929 cell supernatant. The factor in L929 supernatant that induces VEP13 antigen expression has not been identified. Tunicamycin at 10 micrograms/ml inhibited significantly VEP13 antigen expression on monocytes. In contrast, IgG rosette formation was not reduced by tunicamycin. Our data show that subpopulations of native human AM phi and peripheral blood monocytes cultured in presence of a supernatant of L929 fibroblasts containing mainly murine CSF may express the CD16 antigen, which is normally found on large granular lymphocytes (LGL). Suppression by tunicamycin indicates that Fc receptor glycosylation takes place during a later differentiation step of mononuclear phagocytes.

Antibodies, Monoclonal↗
PubMed1988

Augmentation of demyelination in rat acute allergic encephalomyelitis by circulating mouse monoclonal antibodies directed against a myelin/oligodendrocyte glycoprotein.

In this study the authors have developed a model with which can be studied directly the influence of circulating anti-myelin antibody on the clinical and pathologic course of inflammatory T-cell-mediated experimental allergic encephalomyelitis (EAE) in the rat. EAE was induced by passive transfer of either myelin basic protein (MBP)-activated spleen cells derived from sensitized donors or long-term-cultured MBP-specific T-cell lines. At the onset of the disease, monoclonal antibodies against a myelin/oligodendrocyte glycoprotein (MOG) were injected intravenously. This antigen is exposed on the surface of central nervous system myelin and oligodendrocytes. Intravenous injection of the antibody in the course of T-cell-mediated transfer EAE augmented the severity and duration of clinical signs and resulted in the formation of large, confluent demyelinated plaques.

Animals↗