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H Lassmann

Publications and source records attributed to H Lassmann.

At least 73 records · Page 4Linked to original sources
PubMed1986

Presence of chromogranin A, B and C in bovine endocrine and nervous tissues: a comparative immunohistochemical study.

Antisera against chromogranin A, B and C were used to study the distribution of these acidic proteins in bovine endocrine and nervous tissues. The three chromogranins occur together in several endocrine organs (adrenal medulla, anterior pituitary, endocrine pancreas) and in sympathetic ganglion cells. In the posterior pituitary, only chromogranin C and in the intermediate lobe only A and C are found. The parathyroid gland contains only A, and enterochromaffin cells are immunoreactive for A and B. Cells of the thyroid gland and some cells of the anterior pituitary apparently do not contain any chromogranins. It is concluded that the three chromogranins are not always stored together and that they are not present in all endocrine cells. This distinct localization of the chromogranins indicates some special, although still undiscovered, function for these proteins.

Adrenal Medulla↗
PubMed1986

Recombinant interleukin 2 (IL-2) promotes T cell line-mediated neuroautoimmune disease.

Autoimmunity is dependent on a delicate balance of cellular interactions preventing activation of autoaggressive T cells. Possible side effects of therapeutically injected recombinant interleukins on latent or overt autoimmune disease are uncertain. Using a T cell transfer model of autoimmune central nervous system (CNS) disease, we investigated the in vivo effect of recombinant IL-2. We observed that recombinant IL-2 strongly promotes autoimmune disease.

Animals↗
PubMed1986

Molecular aspects of MAP-1 and MAP-2: microheterogeneity, in vitro localization and distribution in neuronal and nonneuronal cells.

We have studied various aspects of MAP-1 and MAP-2 from neuronal as well as nonneuronal sources. MAP-1 and MAP-2 polymerized from brain were resolved into a number of subcomponents upon electrophoresis on low percentage gels. Based on peptide mappings performed under a variety of different conditions, we conclude that the three major subcomponents of MAP-1 have very similar, though not identical structures. The two major MAP-2 subcomponents might have identical structure, because their peptide maps were hardly distinguishable. The apparent microheterogeneity of high Mr MAPs is not yet understood on a molecular basis. Proteolysis during isolation or a different degree of phosphorylation, however, seems to be an unlikely cause for microheterogeneity. When localized on microtubules polymerized in vitro by electron microscopy, both MAP-1 and MAP-2 polypeptides apparently form helical arrays on the polymer's surface with periodicities of 100 nm. In the presence of taxol, MAPs form irregular and bulky extensions. Both MAPs are found to be widespread in neuronal as well as nonneuronal cells. MAP-1- and MAP-2-related polypeptides, together with other high Mr proteins, such as plectin, were associated with microtubules polymerized by taxol from extracts of a nonneuronal cultured cell line. MAP-2 from cultured cells was found to be extremely sensitive to proteolysis, in particular in the presence of free Ca-ions. MAP-1 and MAP-2 generally were found associated with typical microtubule structures such as interphase and spindle microtubules and primary cilia. A differential distribution of MAP-1 and MAP-2 was clearly evident in neural tissues, where MAP-2 was restricted to cell bodies and dendrites, whereas MAP-1 was present also in axons. Moreover, a differential distribution of MAPs and tubulin was observed in de-and regenerating peripheral nerve, and in a few occasions, also with nonneuronal cells. A quite unexpected result was the identification of a protein in the extracellular matrix of cultured fibroblast cells, which has antigenic determinants in common with MAP-1 and MAP-2 from brain. As a whole, the data presented support a concept in which a family of structurally homologous, though not identical, high Mr polypeptides constitute the crosslinking elements between microtubules and various other cellular components. The structural diversity of these polypeptides might play a role in the development and dynamic changes in the cytoskeletal architecture.

Animals↗
PubMed1985

Kainic acid-induced seizures: dose-relationship of behavioural, neurochemical and histopathological changes.

Behavioural, neurochemical and histopathological changes induced by systemic injection of kainic acid were investigated at various doses of the neurotoxin (3, 6 and 10 mg/kg s.c.). There was a positive correlation between the dose of kainic acid and the extent of both the acute neurochemical changes 3 h after the injection (increases of 3,4-dihydroxyphenylacetic acid and 5-hydroxyindoleacetic acid levels and a decrease in noradrenaline levels in all brain regions investigated), the acute histopathological changes (shrinkage and condensation of nerve cells and brain oedema in the entire forebrain) and the extent of behavioural alterations (immobility, 'wet dog shakes' and limbic seizures). However, the slope of the dose-response curves was very steep. Late and irreversible alterations included losses of the enzyme markers glutamic acid decarboxylase and choline acetyltransferase and, histopathologically, incomplete parenchymal necrosis and haemorrhages. These changes, however, were restricted to a few brain regions, the most important being the hippocampus, amygdala, entorhinal and pyriform cortex, and olfactory bulb, and they were seen only in animals which had undergone severe convulsions. It is suggested that the irreversible brain lesions in this animal model of limbic (temporal lobe) epilepsy are not solely induced by a direct action of kainic acid, but may be caused--at least in part--by additional, secondary pathogenetic mechanisms.

Animals↗
PubMed1985

Immunocytochemical study of myelin-associated glycoprotein (MAG), basic protein (BP), and glial fibrillary acidic protein (GFAP) in chronic relapsing experimental allergic encephalomyelitis (EAE).

Chronic relapsing experimental allergic encephalomyelitis (EAE) lesions that resemble those seen in multiple sclerosis (MS) were produced in young Hartley and strain 13 guinea pigs (Lassmann and Wisniewski 1979). To study distributions of myelin-associated glycoprotein (MAG), myelin basic protein (MBP), and glial fibrillary acidic protein (GFAP) in these lesions, paraffin and semithin epon sections of CNS from eight of these guinea pigs were immuno-stained with antisera to these proteins according to the peroxidase-antiperoxidase (PAP) method. In lesions with active myelin sheath breakdown, changes in anti-MAG and anti-BP immunoreactivity corresponded closely. Abnormal and/or decreased anti-MAG staining did not extend beyond margins of lesions into surrounding areas containing myelin sheaths stained normally by anti-BP and by histological stains for myelin. GFAP-stained astrocyte processes were more numerous and much larger in more chronic lesions. Anti-MAG and anti-BP both stained regenerating myelin sheaths which were very numerous in both paraffin and epon sections. In the latter, anti-MAG also stained some myelin-forming oligodendroglia. The results are additional evidence suggesting that in chronic relapsing EAE, myelin sheaths are the primary target. Oligodendroglia appear to be relatively unaffected and remyelinate most of the demyelinated axons.

Animals↗
PubMed1985

Immunological studies on the distribution of chromogranin A and B in endocrine and nervous tissues.

Bovine chromaffin granules contain two major families of acidic proteins, chromogranins A and B. The occurrence of these proteins in endocrine and nervous tissue was investigated by immunoblotting (one- and two-dimensional), and by immunohistochemistry. Immunoblotting revealed that in anterior hypophysis and in splenic nerve from ox, immunologically crossreacting proteins are present which in two-dimensional electrophoresis migrate to the same position as adrenal chromogranins A and B. Smaller proteins derived from chromogranin B by endogenous proteolysis were much less prominent in these tissues when compared with adrenal medulla. Immunohistochemistry performed in rat and bovine tissues established that chromogranin B is present in all cells of the adrenal medulla. It is also found in the anterior hypophysis, the endocrine pancreas, in enterochromaffin and in sympathetic ganglion cells, but e.g. is absent from posterior hypophysis and exocrine tissues. It is concluded that chromogranins A and B have a widespread distribution in endocrine and nervous tissue. Proteolytic processing of chromogranin B in the storage organelles of hypophysis and splenic nerves is apparently slower than that in chromaffin granules. The widespread distribution of the chromogranins resembling that of neuropeptides is a clear indication for some special, yet to be discovered, function.

Adrenal Medulla↗
PubMed1984

Ultracytochemical distribution of myelin basic protein after injection into the cerebrospinal fluid. Evidence for transport through the blood-brain barrier and binding to the luminal surface of cerebral veins.

Distribution of myelin basic protein (MBP) in the central nervous system (CNS) following injection into the cerebrospinal fluid (CSF) was studied by different qualitative and quantitative immunelectron -microscopic techniques. Endogenous MBP was present in myelin sheaths in injected as well as in control animals. After injection of exogenous MBP into CSF this protein was present in the subarachnoid space, on the surface of meningeal cells, on the surface of collagen fibers, in the basement membrane of the glia limitans, in vessel walls, and in the extracellular space of spinal roots. In meningeal veins, endothelial vesicles filled with peroxidase reaction product were found on the abluminal side of endothelial cells, in the endothelial cytoplasm and sometimes opening into the vascularllumen . In addition patchy staining of the luminal surface of endothelial cells was noted, indicating binding of antigen at this location. Quantitative immunelectron microscopy (an indirect technique with rabbit anti-MBP serum as primary layer and gold-labeled anti-rabbit IgG as secondary layer) revealed highly significant MBP binding on the luminal surface of endothelial cells after injection of this antigen into the CSF. The present results indicate that MBP, when liberated in CNS is transported through the blood-brain barrier and presented on the luminal surface of endothelial cells of the cerebral and meningeal veins. This observation may be important in interpretation of pathogenesis of initial inflammatory infiltrates in experimental allergic encephalitis (EAE).

Animals↗
PubMed1983

[NK cells and the nervous system].

Light- and electron-microscopic studies of human, mouse, rat and guinea pig tissue subjected to PAP and ABC immune reactions revealed, that a monoclonal antibody against human natural killer cells (LEU 7) reacted also specifically with neural elements. In man, not only NK cells, but also myelin sheaths, oligodendrocytes, neurones, astroglial and ependymal cells as well as some enterochromaffin cells were labelled. Similar results, with the exception of negative ependymal cells, were obtained in the laboratory animals investigated. Controls and experiments using another monoclonal antibody against human natural killer cells (VEP 13) were negative. The presence of an antigen shared by human natural killer cells and neural elements could be of importance for the pathogenesis of demyelinating disorders.

Animals↗
PubMed1983

Chronic relapsing experimental allergic encephalomyelitis: its value as an experimental model for multiple sclerosis.

Comparison of the pathohistology of chronic relapsing experimental allergic encephalomyelitis (CR-EAE) and multiple sclerosis (MS) reveals a close similarity. Thus, CR-EAE appears to be a valuable model for the study of pathogenetic factors leading to the formation of MS lesions, although the induction of the disease may be different (active sensitization with CNS antigens and adjuvant in CR-EAE versus unknown etiology in MS). CR-EAE furthermore mimicks the pathohistological patterns of other related human inflammatory demyelinating diseases (i.e., acute perivenous leukoencephalomyelitis and acute hemorrhagic leukoencephalomyelitis). The expression of an acute, predominantly inflammatory versus chronic inflammatory demyelinating disease in this model depends upon the time interval between sensitization and sampling of the animals. Recent evidence is discussed that a cooperation between cellular and humoral immune mechanisms, directed against multiple CNS antigens, is responsible for the formation of large demyelinated plaques in EAE and MS.

Animals↗
PubMed1983

Kainic acid induced seizures: neurochemical and histopathological changes.

Behavioural, histopathological and neurochemical changes induced by systemic injection of kainic acid (10 mg/kg, s.c.) were investigated in rats. The most pronounced behavioural changes were strong immobility ("catatonia"), increased incidence of "wet dog shakes", and long-lasting generalized tonic-clonic convulsions. The behavioural symptoms were fast in their onset and lasted for several hours. Two distinct phases of histopathological and neurochemical changes were observed. (1) Early partially reversible changes were seen up to 3 h after kainic acid injection. They consisted of shrinkage and pyknosis of neuronal perikarya together with swelling of dendrites and axon terminals. These changes were accompanied by generalized signs of edema throughout the whole brain. Neurochemically, there was a marked decrease in noradrenaline levels (up to 70%) and an increase in levels of 5-hydroxyindoleacetic acid, 3,4-dihydroxyphenylacetic acid and homovanillic acid (up to 200%) in all analysed brain regions, suggesting a strongly increased firing rate of aminergic neurones during the period of generalized seizures. These histological and neurochemical changes were found in all the brain regions examined; they were greatly reduced or only sporadically seen after 1-3 days, when the animals had recovered from the seizures. (2) Late irreversible changes developed 24 h and later following kainic acid injection. They consisted of incomplete tissue necrosis with loss of nerve cells and oligodendrocytes, demyelination, astroglial scar formation, small perivenous hemorrhages and extensive vascular sprouting. The changes were restricted to the pyriform cortex, amygdala, hippocampus (most pronounced in the CA1 sector), gyrus olfactorius lateralis, bulbus olfactorius and tuberculum olfactorium. Neurochemically, a selective decrease was seen in choline acetyltransferase activity (40%) of the amygdala/pyriform cortex area, and of glutamate decarboxylase activity in the dorsal hippocampus (45%) and amygdala/pyriform cortex (55%). No such changes were found in the frontal cortex and the striatum/pallidum. Since at these later time periods the widespread early changes in monoamine metabolism were mostly normalized, loss of acetylcholine and gamma-aminobutyric acid neurons in the affected brain regions represented a selective neurochemical change typical for this stage of kainic acid action. The observed neurochemical and histopathological changes may be directly related to the excitotoxic and convulsive properties of kainic acid. However, brain edema resulting in herniation damage of the basal portions of the brain in addition to disturbances of microcirculation and +

Amygdala↗
PubMed1982

Antibodies-restricted heterogeneity in serum and cerebrospinal fluid of chronic relapsing experimental allergic encephalomyelitis.

An animal model which might help to study multiple sclerosis has long been sought. With chronic relapsing experimental allergic encephalitis (EAE), the search seems to have brought hope and evidence of comparable pathology whether concerned with clinical or neuropathological results, but no study of the cerebrospinal fluid (CSF) electrophoretic pattern has been made so far. A new sensitive method enables to study the CSF proteins: unconcentrated CSF proteins after agar gel electrophoresis are stained with silver reagents. The silver technique allows to follow the evolution of the inflammatory reaction in chronic relapsing EAE as well as in the acute form of EAE. This technique provides an additional approach to the study of EAE and an argument in favor of chronic relapsing EAE in guinea pigs as a model for multiple sclerosis.

Animals↗
PubMed1981

Relapsing experimental allergic encephalomyelitis induced with isolated myelin and with myelin basic protein plus myelin lipids.

To test the ability of different spinal cord fractions to reproduce the clinicopathological features of relapsing experimental allergic encephalomyelitis (R-EAE), groups of young guinea pigs were inoculated with: (1) spinal cord myelin; (2) delipidated myelin; (3) reconstituted myelin and (4) MBP plus myelin lipids. The four sets of antigens induced acute EAE in most of the animals tested. During an observation period of 18 months, only one clinical relapse was observed in animals sensitized with myelin and with MBP plus myelin lipids. Extensive CNS demyelination was found in relapsing animals injected with myelin. No demyelinated lesions were observed in non-relapsing animals. By contrast, half of the surviving guinea pigs injected with MBP plus myelin lipids had demyelinated lesions, irrespective of whether they relapsed or not. The inability of the spinal cord myelin fractions to fully reproduce the R-EAE model suggest that other non-myelin antigens may be involved in the pathogenesis of multiple relapses.

Animals↗
PubMed1981

Myelin proteins, glycoproteins, and myelin-related enzymes in experimental demyelination of the rabbit optic nerve: sequence of events.

Wallerian degeneration of the rabbit optic nerve was investigated by the technique of retinal ablation which precludes edema, hemorrhage, or macrophage infiltration. After 8 days of degeneration, marked degradation of axons and some myelin abnormalities appeared in the optic nerve, optic chiasma, and optic tract. Myelin lesions were maximal 32 days after retinal destruction. The amount of material stained with a myelin dye decreased drastically between 32 and 90 days after the operation. Biochemical parameters gave the following sequence of events. The concentration of the major periodic acid--Schiff staining glycoproteins was decreased after 2 days, and 6 days later the presence of cholesterol esters was detected in the optic tissue. After 16 days of Wallerian degeneration, the specific activity of 2',3'-cyclic nucleotide 3'-phosphodiesterase not associated with myelin decreased, indicating a possible de-differentiation of oligodendrocytes. Degradation of myelin basic protein became significant at 32 days and the amount of myelin isolated decreased later. The loss of myelin basic protein coincided with a reduction of myelin periodicity as measured in purified fractions by electron microscopy. These results show that secondary myelin destruction in the absence of edema, hemorrhage, or macrophages is a very slow process, and in this situation myelin undergoes a selective and sequential loss of its constituents.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1979

Chronic relapsing experimental allergic encephalomyelitis: effect of age at the time of sensitization on clinical course and pathology.

Experimental allergic encephalomyelitis was induced by sensitization with guinea pig spinal cord in complete Freund's adjuvant with increased content of myobacterium in Hartley guinea pigs between the first and 28th day after birth. The animals either died during acute EAE or showed chronic progressive, chronic relapsing or chronic EAE with delayed onset. In animals immunized between the 1 and 13 day after birth, predominatly ordinary and chronic progressive EAE was noted, whereas animals sensitized between the 14th and 23rd day frequently suffered from hyperacute or chronic relapsing EAE. Immunization on the 24th day led to very high mortality in acute EAE. The relation of the pathohistologic alterations to different types of human inflammatory demyelinative disease is discussed.

Age Factors↗
PubMed1979

Chronic relapsing experimental allergic encephalomyelitis: morphological sequence of myelin degradation.

Myelin degradation in chronic relapsing experimental allergic encephalomyelitis was studied using light microscopic histochemistry and electron microscopy. In the earliest stages, a large number of myelin stripping macrophages were found. The Luxol fast blue positive degradation products were then gradually transformed into PAS positive material. No sudanophilic stage of myelin degradation was found in this model. In electron microscopy, the Luxol fast blue positive material was identified as uniformly layered lipid inclusions with a periodicity of 4.0--4.5 nm. During further digestion, this material was transformed into polymorph structured material, consisting of lamellar leaflets with a diameter of 7--10 nm, curved cylindrical profiles and granular osmiophilic material.

Animals↗