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Biomedical subjects

G Stoll

Publications and source records attributed to G Stoll.

At least 91 records · Page 5Linked to original sources
PubMed1990

Macrophage responses in inflammatory demyelinating neuropathies.

Macrophages are prominent participants in inflammatory demyelinating neuropathies. To provide a different means of evaluating macrophage behavior, we used immunostaining of teased nerve fibers and endoneurial blood vessels. We assessed the frequency with which macrophages were seen in inflammatory demyelinating neuropathies, their relationship to normal and demyelinating fibers, and their expression of major histocompatibility Class II markers (Ia antigen). In 6 patients with chronic inflammatory neuropathy and 1 with Guillain-Barré syndrome, we found regularly that macrophages were adherent to teased blood vessels. Cells presumed to be entering the nerve were elongated, often with a polarized appearance suggesting motility, and were Ia-positive. After entry into nerve, the Ia-positive macrophages were adherent to both normal and demyelinating fibers. They often retained their Ia positivity after penetrating into the nerve fiber and removing myelin. Foamy macrophages, judged to be postphagocytic, were Ia-negative. The foamy macrophages found adhering to blood vessels were presumed to be leaving the nerve. This pattern of entry as Ia-positive prephagocytic cells and evolution to Ia-negative foamy macrophages was compared with other experimental and human neuropathies.

Demyelinating Diseases↗
PubMed1990

Macrophages but not Schwann cells express Ia antigen in experimental autoimmune neuritis.

This study was designed to identify which cells express major histocompatibility complex class II (Ia) antigen in experimental autoimmune neuritis and may therefore be antigen presenters. Serial 1-micron-thick cryosections of ventral roots of animals with experimental autoimmune neuritis were labeled with Ox6 antibody against rat Ia, the ED1 antibody to identify monocytes/macrophages and an antiserum against S100, a marker for Schwann cells. Ia-positive cells were predominantly present before overt clinical signs and demyelination (day 12). At later stages when many axons were demyelinated, their number was markedly reduced. Few Ia-positive cells that had extending long processes, which over some distance were in immediate contact with several myelin sheaths, were scattered in normal-appearing nerve roots at these later time points. Most of the Ia-positive cells could be identified as ED1-positive lean monocytes/macrophages, but in contrast most phagocytic macrophages in advanced stages of myelin degradation no longer expressed Ia. Ia-positive structures were invariably negative for S100 at early and late stages of experimental autoimmune neuritis, indicating that Schwann cells did not express identifiable Ia antigen. These findings contrast with reports of expression of major histocompatibility complex class II antigens by Schwann cells in human neuropathies. Furthermore they do not support the notion that aberrant Ia expression by Schwann cells plays a major pathogenic role in experimental autoimmune disease of the peripheral nervous system.

Animals↗
PubMed1990

The characterization of Ia expression during Sindbis virus encephalitis in normal and athymic nude mice.

To characterize the expression of Ia systemically and locally on mononuclear cells during acute viral encephalitis, weanling mice were inoculated intracerebrally with Sindbis virus (SV), an alphavirus. Peripheral blood mononuclear cells, splenocytes and perivascular inflammatory cells in frozen brain sections were examined immunocytochemically for the presence of Ia. Ia expression increased in the spleen, blood and brain during SV encephalitis. The majority of the cells in the central nervous system (CNS) expressing Ia were perivascular mononuclear cells but Ia was also found on stellate parenchymal cells. Using one micrometer cryopreserved serial sections we identified these parenchymal cells as macrophages and microglia but not astrocytes. We also identified rare Ia-positive cells resembling endothelial cells. Frozen brain sections of SV-infected T cell-deficient nu/nu mice were also examined for Ia expression. The number and percentage of Ia-positive cells in perivascular inflammatory cells were markedly decreased compared to normal mice and Ia-positive stellate parenchymal cells were less numerous. This suggests that immunocompetent T cells are necessary for "normal" infiltration of inflammatory cells and for Ia expression in the CNS during SV encephalitis.

Animals↗
PubMed1989

Oligodendrocytes but not astrocytes express apolipoprotein E after injury of rat optic nerve.

Apolipoprotein E (apoE), a lipid-binding glycoprotein involved in transport and metabolism of phospholipids and cholesterol, is synthesized and secreted at elevated rates following transection of mature rat peripheral and central nerves. In the peripheral nervous system (PNS) infiltrating macrophages express apoE during Wallerian degeneration. Following injury of the optic nerve (ON) apoE synthesis is significantly stimulated but the apoE-expressing cells have thus far not been identified. This study used 1 micron and thin cryosections to identify the cellular source of apoE in transected ON. Serial 1 micron frozen sections were stained by avidin-biotin-peroxidase complex immunocytochemistry by using a specific antiserum to apoE and by antibodies that identify different cell types: glial fibrillary acidic protein (GFAP) for astrocytes, 2',3'-cyclic nucleotide-3' phosphodiesterase (CNP) for oligodendrocytes, and ED1 for macrophages. In normal ON both astrocytes and oligodendrocytes were apoE-positive. One week after ON transection oligodendrocytes accounted for the majority of apoE-positive cells, while apoE immunoreactivity had disappeared from astroglial cell bodies and processes. In contrast to the PNS only a few ED1/apoE-positive macrophages were present in ON 7 days after transection. By using immunogold-labeled ultrathin cryosections apoE could be localized in the Golgi apparatus of oligodendrocytes, indicating synthesis by these cells. Our data suggest that oligodendrocyte-derived apoE protein may participate in the redistribution of myelin lipids after CNS injury.

Animals↗
PubMed1989

Wallerian degeneration in the peripheral nervous system: participation of both Schwann cells and macrophages in myelin degradation.

This study examined the role of Schwann cells and hematogenous macrophages in myelin degradation and Ia antigen expression during Wallerian degeneration of rodent sciatic nerve. To identify and distinguish between macrophages and Schwann cells we used, in addition to electron microscopy, immunocytochemical staining of teased nerve fibres and 1 microns thick cryosections. Before the appearance of adherent macrophages the myelin sheath fragmented into ovoids, small whorls of myelin debris appeared within Schwann cell cytoplasm and the Schwann cell displayed numerous lipid droplets. However, at least in large fibres most myelin degradation and removal was accomplished or assisted by macrophages, identified by their expression of the ED1 marker. These cells began entering the nerve from blood vessels by day 2, migrated to degenerating nerve fibres and adhered to nerve fibres in the regions of the ovoids. There they penetrated the Schwann cell basal lamina to occupy an intratubal position and phagocytose myelin. During Wallerian degeneration a subpopulation of ED1-positive monocytes/macrophages expressed Ia antigen; Schwann cells were Ia-negative. Ia expression by monocytes/macrophages appeared to be a transient event and was not seen in post-phagocytic macrophages, as indicated by the fact that ED1-positive phagocytes with large vacuoles were Ia-negative. Our data show that both Schwann cells and macrophages play important roles in degrading and removing myelin during Wallerian degeneration. The expression of Ia antigen during Wallerian degeneration indicates that Ia expression need not necessarily reflect specific immune events but in some instances can represent a nonspecific response to PNS damage.

Acrylamide↗
PubMed1989

Macrophage function during Wallerian degeneration of rat optic nerve: clearance of degenerating myelin and Ia expression.

This study examined Wallerian degeneration (WD) of rat optic nerve (ON) with 2 goals: to determine which cell types are involved in myelin degradation and clearance and to evaluate the extent to which Ia antigen, a product of the immune response genes, is expressed. We examined immunostained 1-micron and ultrathin cryosections of rat ON at 1, 8, and 16 weeks after nerve transection. Serial 1-micron cryosections were stained with monoclonal antibodies to rat Ia antigen (Ox6) and with antibodies that identify astrocytes (GFAP) and monocytes/macrophages (ED1). In normal ON, ED1-positive cells were not found. A few ED1-positive monocytes/macrophages were present in the transected ON at one week. Macrophages were prominent throughout the ON at 8 weeks; by 16 weeks their number was decreasing. These cells contained myelin debris in various stages of digestion. GFAP-positive astrocytes did not contain myelin debris in their cytoplasm. At all 3 times a subpopulation of the ED1-positive monocytes/macrophages expressed Ia antigen. Ia antigen was not detected in endothelial cells or GFAP-positive astrocytes. In ultrathin cryosections stained by immunogold procedures, Ia immunoreactivity was found exclusively in cells containing multiple vacuoles and myelin debris and lacking intermediate filaments. The same cell type was labeled by ED1 antibodies. Our results indicate that macrophages remove the vast majority of debris during Wallerian degeneration in the CNS; a proportion of these macrophages concomitantly express Ia antigen. These results suggest that the Ia expression by macrophages observed in other CNS disorders does not necessarily reflect specific local immune events, but in some instances can represent a nonspecific response to CNS damage.

Animals↗
PubMed1988

Antibodies to calcium/phospholipid binding protein (calelectrin) recognize neurons, astrocytes and Schwann cells in the nervous system of rat.

We report on the identification of proteins Mr 32 kDa, 34 kDa, 68 kDa in rat brain or sciatic nerve which cross-react (by immunoblotting) with antibodies to purified Ca2+/phospholipid binding protein calelectrin from Torpedo marmorata. Immunocytochemical staining revealed that anti-calelectrin antibodies labeled cell bodies and processes of cortical neurons and astrocytes in the central nervous system (CNS). In sciatic nerve, calelectrin-like immunoreactivity was expressed in the cytoplasm of Schwann cells of adult as well as newborn rat. Additional staining occurred at periaxonal sites in mature nerve. The localization of calelectrin-related proteins in distinct cell types of the mammalian nervous system suggests a cell-specific role of this new group of proteins in Ca2+-mediated membrane processes involved in neural function.

Animals↗
PubMed1988

The role of macrophages and eicosanoids in the pathogenesis of experimental allergic neuritis. Serial clinical, electrophysiological, biochemical and morphological observations.

Experimental allergic neuritis (EAN) can be prevented or ameliorated by global blockade of macrophages. How these cells damage peripheral nervous tissue in this autoimmune demyelinating polyneuropathy is not fully understood. Since macrophages exert a number of their inflammatory actions by the release of arachidonic acid-derived eicosanoids, we investigated the possible role of these mediators in the pathogenesis of EAN. Lewis rats with myelin-induced EAN were treated before and after onset of clinical signs. Administration of corticosteroids or of the cyclo-oxygenase inhibitors indomethacin and BW755c before the onset of neurological signs suppressed the disease, as judged by clinical assessment, serial electrophysiological testing and histological examination, while initiation of drug treatment on day 13 postimmunization still markedly attenuated the course of EAN. The selective lipoxygenase blocker nafazatrom had only a slight effect. Determination of the production by macrophages ex vivo of eicosanoids corroborated the predicted site of action of the pharmacological compounds applied. We infer that macrophage-derived proinflammatory arachidonic acid metabolites significantly contribute to functional and tissue damage in EAN. Our results may be relevant to future pharmacological treatment of the acute Guillain-Barré syndrome.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1986

Macrophages in the peripheral nervous system and astroglia in the central nervous system of rat commonly express apolipoprotein E during development but differ in their response to injury.

Macrophages have been identified by immunocytochemical methods in rat sciatic nerve neonatal development expressing significant amounts of apolipoprotein E (apo E). In contrast, in mature peripheral nerve apo E appears to be associated with the basal lamina. Following sciatic nerve crush apo E-immunoreactive macrophages reappear in the denervated distal stump within 3 days. In the optic nerve and spinal cord of newborn rat apo E is associated with the astroglia. During maturation of the central nervous system the number of apo E-immunoreactive astrocytes significantly increases, but as a specific response to injury this protein rapidly disappears from the astroglial cell bodies.

Aging↗
PubMed1986

Conduction failure and nerve conduction slowing in experimental allergic neuritis induced by P2-specific T-cell lines.

P2-specific T cells (LiP2/A) mediate experimental allergic neuritis (EAN) in the Lewis rat after adoptive transfer to naive recipients. After a latent period of 4 days, injection of 2 X 10(6) line cells induced fulminant paraplegia and complete conduction failure in the peripheral nerves and roots, resembling acute axonal breakdown. Injection with 10(6) cells caused milder clinical signs, nerve conduction failure, and conduction slowing. Clinical and electrophysiological recovery from adoptively transferred EAN was nearly complete and its time course was inversely correlated to the initial severity of EAN. These findings suggest that EAN induced by the P2-specific T-cell line can lead to a profound and rapidly evolving nerve dysfunction in a dose-dependent fashion.

Animals↗
PubMed1986

Normal myelination of regenerating peripheral nerve sprouts despite circulating antibodies to galactocerebroside in rabbits.

Rabbits were immunized with galactocerebroside and a crush lesion was created in the tibial nerve before the onset of experimental allergic neuritis. Normal regeneration and myelination of distal peripheral nerve sprouts occurred and was identical to that of controls, although circulating antigalactocerebroside antibodies were present and nerve roots showed typical signs of beginning experimental allergic neuritis.

Animals↗
PubMed1986

Relation of clinical, serological, morphological, and electrophysiological findings in galactocerebroside-induced experimental allergic neuritis.

Rabbits were immunised repeatedly with bovine brain galactocerebroside. Almost all animals developed overt polyradiculoneuropathy. Circulating IgG antibodies to galactocerebroside in the serum and deposits of IgG in the spinal roots were detectable weeks before definite clinical, morphological, and electrophysiological alterations occurred. The levels of IgG antibody titres to galactocerebroside did not correlate with the severity of the clinical disease and of nerve conduction slowing. Remyelination and a virtually complete recovery of nerve dysfunction occurred although circulating antibodies to galactocerebroside were still present.

Animals↗
PubMed1985

Pitch shift of pure and complex tones induced by masking noise.

Psychoacoustic experiments were performed to measure the pitch-shift effects of pure and complex tones resulting from the addition of a masking noise to the tonal stimuli. Harmonic residue tones with either two or three harmonics and a fundamental frequency of 200 Hz were chosen as test tones. The pitch shifts of virtual and spectral pitches of the residue tones were measured as a function of the intensity of a low-pass noise with 600-Hz cutoff frequency. The SPL of this noise varied between 30 and 70 dB. In another experiment, the pitch shifts of single pure tones corresponding to the frequencies and SPLs of the harmonics of the residue tones were measured using the same masking noise. The results from five subjects for the harmonic residue tones show only a weak dependence of pitch shift on masking noise intensity. This dependence exists for both spectral and virtual pitches. In the case of single pure tones, pitch shift depends more distinctly on noise intensity. Pitch shifts of up to 5% were found in the range of noise intensity investigated. The magnitude of pitch shift shows pronounced interindividual differences, but the direction of the shift effect is always the same. In all cases pitch increases with higher masking noise levels.

Adult↗
PubMed1985

Human monoclonal anti-MAG antibody and anti-Leu 7 recognise shared antigenic determinants in peripheral nerve and spinal cord.

Anti-Leu 7 monoclonal antibody (MAB), a marker of natural killer cells, and a human MAB to myelin-associated glycoprotein (MAG) from a patient with a demyelinating neuropathy specifically stained Schmidt-Lanterman incisures, paranodal and periaxonal regions in peripheral nerve myelin by immunocytochemistry on thin plastic sections, while compact myelin was labelled in paraffin-embedded material. Preabsorption studies indicated that the antigen recognised was a MAG epitope shared by MAG and Leu 7. In spinal cord both MABS bound to oligodendrocytes and a subclass of anterior horn cells. Our findings support the hypothesis that shared antigens between the nervous and the immune systems do exist in situ, which may be important in the pathogenesis of demyelinating neuropathies with monoclonal gammopathies.

Animals↗
PubMed1985

Passive transfer studies in demyelinating neuropathy with IgM monoclonal antibodies to myelin-associated glycoprotein.

Serum or IgM fraction from two patients with a demyelinating neuropathy and IgM monoclonal antibodies to myelin-associated glycoprotein were injected in three different animal species. There were no clinical, electrophysiological or morphological signs of demyelination in either chronic or acute passive transfer experiments. These results suggest that the pathogenesis of this human demyelinating neuropathy may be more complex than has been assumed.

Animals↗
PubMed1984

Control of peptide release from cells of the intermediate lobe of the rat pituitary.

When rats were injected with 6-hydroxydopamine the catecholaminergic nerve terminals in their intermediate lobes exhibited distinct signs of degeneration. Morphometric examination of the Golgi apparatus in cells of the intermediate lobe of these rats showed significant enlargement of Golgi cisternae. The release of adrenocorticotropin, beta-endorphin/lipotropin and alpha-melanotropin from intermediate-lobe cells in vitro was measured by radioimmunoassay. The high basal peptide release was inhibited by dopamine and stimulated by methyl-isobutyl-xanthine. In contrast, gamma-aminobutyric acid, serotonin, histamine and noradrenaline, or corticotropin-releasing hormone, rat hypothalamic extract and vasopressin had no or only very weak effects. These observations indicate that the synthetic apparatus of intermediate-lobe cells is constantly depressed by dopaminergic nerves. We were not able to stimulate peptide release from intermediate-lobe cells by use of the above-mentioned endogenous agents.

Adrenocorticotropic Hormone↗