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Biomedical subjects

G Stoll

Publications and source records attributed to G Stoll.

At least 73 records · Page 4Linked to original sources
PubMed1994

Peripheral myelin protein-22 expression in Charcot-Marie-Tooth disease type 1a sural nerve biopsies.

Peripheral myelin protein-22 (PMP22) is expressed in myelinating Schwann cells and shows significant homology to murine growth arrest-specific gene gas3. Charcot-Marie-Tooth disease type 1a (CMT1a) is a common hereditary demyelinating neuropathy. Recently it was demonstrated that the gene for PMP22 is duplicated in CMT1a patients. A gene dosage mechanism has been postulated to cause CMT1a. According to this hypothesis, the increase in copy number of PMP22 gene would lead to an elevated expression of PMP22 and thereby cause the demyelinating phenotype of CMT1a. In the present communication we analyzed PMP22 mRNA and protein expression in sural nerve biopsies from CMT1a patients and normal controls. We show that PMP22 mRNA expression in CMT1a is not uniform. We found both elevated as well as normal PMP22 mRNA levels in patients. Interestingly, the highest PMP22 mRNA level was found in the least affected patient. In contrast to the mRNA levels, PMP22 was clearly reduced in all CMT1a patients as shown by immunohistochemistry. Thus the CMT1a phenotype may not be strictly correlated with increased PMP22 mRNA and protein expression. Possible roles of PMP22 in the pathogenesis of CMT1a are discussed.

Biopsy↗
PubMed1994

Local immune responses in the rat cerebral cortex after middle cerebral artery occlusion.

This study describes local immune responses in cerebral ischemia induced by permanent occlusion of the middle cerebral artery (MCAO) in the rat. The temporal and spatial pattern of leukocyte infiltration was characterized immunocytochemically using monoclonal antibodies against CD5, a pan T cell marker, against CD4 and CD8 for subtyping of T lymphocytes, and ED1, a marker for macrophages. CD5+ T cells were present in some animals on the pial surface at day 1 and with increasing numbers mainly at the edges of the infarcts at days 3 and 7. By day 14 their number had significantly decreased. Subtyping of T lymphocytes revealed that CD4+ helper/inducer T cells were rare, while CD8+ lymphocytes were abundant. Moreover, CD8+ lymphocytes outnumbered CD5+ T cells indicating the presence of CD5-/CD8+ natural killer (NK) cells. ED1+ macrophages primarily infiltrated the core of the infarct starting on day 1. Infiltrating leukocytes expressed leukocyte function associated antigen-1 and MHC class I and II antigens. Early after infarction, increased expression of the intercellular adhesion molecule-1 was found on vessels and leukocytes. In conclusion, this study shows that lymphocytes enter the nervous system not only in autoimmune diseases, but also in response to primarily 'non-immune' neuronal damage such as stroke.

Animals↗
PubMed1994

Serum and cerebrospinal fluid levels of soluble intercellular adhesion molecule 1 (sICAM-1) in patients with HIV-1 associated neurological diseases.

We measured levels of soluble intercellular adhesion molecule 1 (sICAM-1) in paired serum and CSF samples of 110 HIV-1-positive patients with and without neurological symptoms and 40 HIV-negative non-immune neurological controls, and in sera of 26 asymptomatic HIV-1-positive patients. Serum sICAM-1 levels in asymptomatic HIV-1-positive patients were significantly increased in comparison to HIV-negative controls. Moreover, they were significantly higher in HIV-1-positive patients with AIDS-defining diseases than in the asymptomatic HIV-1-positive group. In subgroups of patients with neurological disease, the highest serum values were found in HIV encephalopathy. CSF levels of sICAM-1 were elevated only in HIV-1-positive patients with neurological disease mainly due to passive diffusion through a defective blood-brain barrier. An sICAM-1 index was calculated as a measure for intrathecal production of sICAM-1 but showed no significant differences between patients with and without neurological involvement. However, increased levels of the sICAM-1 index were found in some patients with opportunistic CNS infection of bacterial or fungal origin. Serum and CSF levels of sICAM-1 correlated with neopterin levels, a marker of interferon-gamma-mediated macrophage activation and CSF sICAM-1 levels were inversely correlated to numbers of CD4+ T cells. Elevated serum sICAM-1 levels already in asymptomatic HIV-1-positive individuals add to the evidence for an early immune activation in HIV infection. With the further increase of serum and CSF s-ICAM-1 in patients with AIDS-defining diseases sICAM-1 could serve as a new surrogate marker similar to neopterin.

AIDS Dementia Complex↗
PubMed1994

Deficiency of both protein C and protein S in a family with ischemic strokes in young adults.

Protein C and protein S deficiencies increase the risk of venous thrombosis and pulmonary embolism, but their role in arterial thrombosis or embolism is controversial. We describe cerebral ischemia in two young women in a family with inherited deficiencies of both proteins C and S and provide evidence that a combined deficiency of proteins C and S may be a high risk factor for ischemic stroke in young adults.

Adult↗
PubMed1993

Expression of NGF-receptors during immune-mediated and lysolecithin-induced demyelination of the peripheral nervous system.

Nerve growth factor receptor, expressed in Schwann cells during early development of the PNS, is rarely found in the normal mature PNS. Following nerve transection nerve growth factor receptor is re-expressed at high levels in the Schwann cells of the denervated nerve fibres. In this study we asked if demyelination caused by an immune-mediated process or by physical destruction of myelin is associated with expression of nerve growth factor receptor, and if so, what cells are positive. We examined spinal roots and sciatic nerves from rats with experimental autoimmune neuritis and sciatic nerves from rats with focal demyelination produced by local application of lysolecithin. Both in 1 micron serial cryosections and in immunostained teased nerve fibres we found that the Schwann cells that were associated with demyelinated internodes expressed nerve growth factor receptor. Immunoreactivity for nerve growth factor receptor appeared first in a perinuclear ring, probably corresponding to the Golgi complex. In completely demyelinated internodes the postmitotic Schwann cells ensheathing the axons expressed nerve growth factor receptor on their plasmalemma. Neighbouring Schwann cells with intact myelin sheaths remained nerve growth factor receptor negative. In contrast, Schwann cells of neighbouring unmyelinated fibres expressed prominent nerve growth factor receptor immunoreactivity. These data further indicate that expression of nerve growth factor receptor by Schwann cells does not require axonal degeneration, but can be stimulated by some factor associated with acute demyelination.

Animals↗
PubMed1993

Tumor necrosis factor-alpha in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system.

This study reports on the immunocytochemical localization of tumor necrosis factor-alpha (TNF alpha) in immune-mediated demyelination and Wallerian degeneration of the rat peripheral nervous system (PNS) using teased nerve fiber preparations. In experimental autoimmune neuritis induced by active immunization (EAN) or by adoptive transfer of autoreactive T cells (AT-EAN), macrophages passing blood vessels as well as macrophages adherent to nerve fibers were TNF alpha-positive. Large post-phagocytic macrophages at later stages of demyelination were TNF alpha-negative. Intraperitoneal application of an anti-TNF alpha antibody to EAN rats significantly reduced the degree of inflammatory demyelination, suggesting a pathogenic role for TNF alpha. After nerve transection only macrophages located within degenerating nerve fibers were TNF alpha-positive, while those entering and leaving nerves were negative. TNF alpha produced by macrophages seems to be involved in immune-mediated demyelination and non-immune myelin degradation after axotomy. While interferon-gamma (IFN gamma) is present in EAN nerves and may act as a local stimulus for TNF expression, the nature of this signal in Wallerian degeneration in the absence of IFN gamma is unknown.

Animals↗
PubMed1993

Serum and CSF levels of soluble intercellular adhesion molecule-1 (ICAM-1) in inflammatory neurologic diseases.

Intercellular adhesion molecule-1 (ICAM-1), a cell surface receptor important for cellular interactions in immune responses, especially leukocyte trafficking into inflamed tissue, is released in a soluble form (sICAM-1) into the extracellular space. In this study, we measured sICAM-1 in paired serum and CSF samples from patients with inflammatory diseases of the nervous system (IND) and calculated a sICAM-1 index as a measure of the intrathecal release of ICAM-1. In comparison with noninflammatory neurologic disease (NIND) controls, we found increased sICAM-1 index levels in viral meningoencephalitis, bacterial meningitis and, to a lesser degree, multiple sclerosis but not in Guillain-Barré syndrome. Serial examination of viral meningoencephalitis patients in most cases showed a decrease of sICAM-1 index in parallel with falling cell counts and clinical improvement. Except for those in bacterial meningitis, sICAM-1 serum levels of IND patients were not significantly different from those of NIND controls. The increased intrathecal release of sICAM-1 in viral meningoencephalitis and bacterial meningitis most likely reflects activation of macrophages and lymphocytes and provides evidence for a strong local immune response that itself, in addition to the infectious agent, may damage nervous tissue.

Cell Adhesion Molecules↗
PubMed1993

Localization of interferon-gamma and Ia-antigen in T cell line-mediated experimental autoimmune encephalomyelitis.

This study reports the cellular localization of interferon-gamma (IFN-gamma) and MHC class II antigen (Ia) in the spinal cord of rats with experimental autoimmune encephalomyelitis induced by adoptive transfer of myelin basic protein-specific T cells. Numerous IFN-gamma-positive cells, stained with two different monoclonal antibodies against IFN-gamma, were present from days 3 to 7 after cell transfer. Their number was greatly reduced on day 10. A subpopulation of T cells was IFN-gamma positive. Moreover, a large number of ED1-positive macrophages contained IFN-gamma immunoreactivity. The transient presence of immune cells containing IFN-gamma immunoreactivity in experimental autoimmune encephalomyelitis suggests a pathogenic role of this cytokine in immune-mediated demyelination of the central nervous system.

Animals↗
PubMed1993

Macrophages and endothelial cells express intercellular adhesion molecule-1 in immune-mediated demyelination but not in Wallerian degeneration of the rat peripheral nervous system.

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) plays an important role in immune responses, especially in T cell/endothelial cell and T cell/macrophage interactions. This study reports the cellular localization of ICAM-1 during immune-mediated demyelination of the peripheral nervous system induced by adoptive transfer of P2 specific T cells. EXPERIMENTAL DESIGN: Cryosections 1 micron thick of ventral roots of rats with experimental autoimmune neuritis were labeled with a monoclonal antibody against rat ICAM-1. RESULTS: Numerous ICAM-1 positive cells were present before and shortly after the onset of clinical disease from days 4 to 6 after cell transfer. By day 8, their number had greatly decreased. ICAM-1 positive infiltrating cells could be identified as ED1 positive macrophages. Moreover, endothelial cells expressed ICAM-1. Schwann cells and T cells were ICAM-1 negative. While at early stages of experimental autoimmune neuritis, ICAM-1 and Ia colocalized on macrophages but not endothelial cells, Ia persisted for a longer period in nerve roots than ICAM-1. After nerve transection, macrophages entering the distal stump and endothelial cells did not express ICAM-1. CONCLUSIONS: The presence of ICAM-1 immunoreactivity in peripheral nerve indicates an underlying immune-mediated process. Among other cytokines interferon-gamma, which is transiently expressed in nerves during immune-mediated demyelination but not after nerve transection, could be one mediator that induces ICAM-1 in immune-mediated demyelination of the peripheral nervous system.

Animals↗
PubMed1992

Inflammatory mediators in demyelinating disorders of the CNS and PNS.

Work in both experimental models and human disorders of the central and peripheral nervous system has delineated multiple effector mechanisms that operate to produce inflammatory demyelination. The role of various soluble inflammatory mediators generated and released by both blood-borne and resident cells in this process will be reviewed. Cytokines such as interleukin (IL)-1, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha are pivotal in orchestrating immune and inflammatory cell-cell interactions and represent potentially noxious molecules to the myelin sheath, Schwann cells, and/or oligodendrocytes. Arachidonic acid metabolites, synthesized by and liberated from astrocytes, microglial cells and macrophages, are intimately involved in the inflammatory process by enhancing vascular permeability, providing chemotactic signals and modulating inflammatory cell activities. Reactive oxygen species can damage myelin by lipid peroxidation and may be cytotoxic to myelin-producing cells. They are released from macrophages and microglial cells in response to inflammatory cytokines. Activation of complement yields a number of inflammatory mediators and results in the assembly of the membrane attack complex that inserts into the myelin sheath-creating pores. Activated complement may contribute both to functional disturbance of neural impulse propagation, and to full-blown demyelination. Proteases, abundantly present at inflammatory foci, can degrade myelin. Vasoactive amines may play an important role in breaching of the blood-brain/blood-nerve barrier. The importance of nitric oxide metabolites in inflammatory demyelination merits investigation. A better understanding of the multiple effector mechanisms operating in inflammatory demyelination may help to devise more efficacious antigen non-specific therapy.

Animals↗
PubMed1992

Transient cellular expression of gamma-interferon in myelin-induced and T-cell line-mediated experimental autoimmune neuritis.

This study reports the cellular localization of gamma-interferon (gamma-IFN) in nerve roots during the course of experimental autoimmune neuritis induced either by active immunization (EAN) or adoptive transfer of P2-specific T-cells (AT-EAN). One micrometre thick cryosections of ventral roots of EAN and AT-EAN animals were labelled with the monoclonal antibodies DB-1 and DB-12 recognizing different epitopes of rat gamma-IFN. In EAN numerous gamma-IFN-positive cells were present before overt clinical signs and demyelination (days 11-13 after immunization). Concomitantly, raised gamma-IFN levels were measured in the serum of these animals. However, systemically increased gamma-IFN serum levels were not specific for a neuritogenic T-cell response. At subsequent stages when many axons were demyelinated (day 16 and later) gamma-IFN-positive cells had disappeared and gamma-IFN serum levels returned to normal value. gamma-Interferon positive cells could be identified as W3/13 positive T-cells and polymorphonuclear leukocytes. Additionally, a considerable number of ED1-positive macrophages showed gamma-IFN immunoreactivity. The majority of macrophages and all Schwann cells were gamma-IFN negative. Similar results were obtained in AT-EAN 4 d and 6 d following cell transfer. After nerve transection no gamma-IFN-positive cells were found in the distal stumps. The localization of gamma-IFN in nerve roots indicates an important role of this lymphokine in acute immune-mediated demyelination. gamma-Interferon most likely locally affects macrophage functions such as migration, major histocompatibility complex (MHC) class II antigen (Ia) expression, and production of cytotoxic molecules in nerves, and thereby contributes to myelin damage.

Animals↗
PubMed1991

Serum interleukin-2 concentrations in Guillain-Barré syndrome and chronic idiopathic demyelinating polyradiculoneuropathy: comparison with other neurological diseases of presumed immunopathogenesis.

Serum concentrations of the cytokine interleukin-2 (IL-2) were quantitated by enzyme-linked immunosorbent assay in 42 patients with Guillain-Barré syndrome, 15 patients with chronic idiopathic demyelinating polyradiculoneuropathy, 37 patients with other neuropathies, 54 patients with other noninflammatory, nondemyelinating neurological disorders, and 26 healthy control subjects. We found markedly increased serum levels of IL-2 in patients with Guillain-Barré syndrome and to a much lesser extent, in patients with chronic idiopathic demyelinating polyradiculoneuropathy. Increased serum concentrations of IL-2 in patients with Guillain-Barré syndrome returned to normal in parallel with recovery from the disease. These findings suggest ongoing T-cell proliferation in patients with Guillain-Barré syndrome and some patients with chronic idiopathic demyelinating polyradiculoneuropathy. IL-2 levels were also raised in patients with active multiple sclerosis, myasthenia gravis, and herpes simplex encephalitis, and some patients with polymyositis, invoking T cells in the pathogenesis of these diseases.

Autoimmune Diseases↗
PubMed1991

Presence of the terminal complement complex (C5b-9) precedes myelin degradation in immune-mediated demyelination of the rat peripheral nervous system.

In this study, the terminal complement complex C5b-9 (TCC) was localized by immunocytochemistry at different clinical stages of experimental autoimmune neuritis. Deposits of TCC were found on the surface of Schwann cells and their myelin sheaths, and to some extent in the extracellular space at predilective sites of impending demyelination before onset of clinical signs and for a short period thereafter. Additionally, TCC was deposited on the surface of W3/13 positive leukocytes. No TCC immunoreactivity was seen in the distal stump of transected sciatic nerves 1 to 15 days after axotomy. The early and transient deposition of TCC on Schwann cells and myelin sheaths in experimental autoimmune neuritis before overt demyelination suggests that complement activation plays a pathogenic role in the initiation of immune-mediated myelin damage. The lack of TCC immunoreactivity after nerve transection excludes a nonspecific activation process. The signals involved in local TCC formation in demyelinating peripheral nervous system disorders have yet to be explored.

Animals↗
PubMed1991

Acute posterior multifocal placoid pigment epitheliopathy with cerebral involvement.

In a patient with angiographically proven cerebral vasculitis five months after acute posterior multifocal placoid pigment epitheliopathy (APMPPE) neurological symptoms promptly responded to steroid treatment. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis. Magnetic resonance imaging (MRI) revealed multifocal white matter lesions in the hemispheres and the brain stem suggesting a diffuse subcortical vasculitis.

Cerebral Arterial Diseases↗
PubMed1991

Encephalo-myelo-radiculo-ganglionitis presenting as pandysautonomia.

A 68-year-old man developed pandysautonomia with severe orthostatic dysfunction, fixed heart rate, low serum levels of norepinephrine and epinephrine, absent sympathetic skin responses, and pupillary abnormalities. CSF protein was 92 mg/dl. In spite of a good recovery following corticosteroid administration, a relapse occurred, with accompanying sensory symptoms confined to both arms. Fatal sudden cardiac arrest occurred after 4 months. Autopsy revealed numerous lymphocytic infiltrates, predominantly in autonomic and sensory ganglia and, to a lesser extent, in the nerve roots, spinal cord, and brainstem without evidence for an underlying tumor. This case provides histopathologic evidence for an inflammatory etiology of panautonomic neuropathy in some patients.

Aged↗
PubMed1990

Rat astrocytes express interferon-gamma immunoreactivity in normal optic nerve and after nerve transection.

Astrocytes are pivotal components of immune reactions in the CNS. We further support this notion by the localization of the lymphokine interferon-gamma (IFN-gamma), which plays an important role during immune responses, to astrocytes in rat optic nerve (ON). Astrocytes identified by glial fibrillary acidic protein immunoreactivity were IFN-gamma positive in normal and transected ON while oligodendrocytes did not express IFN-gamma immunoreactivity. These findings indicate that astrocytes can generate important signals which orchestrate immunoinflammatory responses in the brain.

Animals↗