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Biomedical subjects

N Sommer

Publications and source records attributed to N Sommer.

At least 55 records · Page 3Linked to original sources
PubMed1992

Influence of gangliosides on experimental allergic neuritis.

The development of myelin-induced experimental allergic neuritis (EAN) in Lewis rats can be depressed and delayed by adding a ganglioside mixture (GM1, GD1a, GD1b, GT1b) to the immunization compound; however, gangliosides may enhance the induction of adjuvant arthritis. Antibodies against multiple gangliosides are produced in rats after immunization with gangliosides after addition of myelin, but only low titers can be detected in animals immunized with myelin and complete Freund's adjuvant alone. We conclude that this antibody production is not the result of peripheral nerve inflammation but depends rather from external applied gangliosides.

Animals↗
PubMed1992

Humoral CSF parameters in the differential diagnosis of hematologic CNS neoplasia.

Cerebrospinal fluid (CSF) and serum samples of 20 patients with central nervous system manifestations of hematological malignancies including primary cerebral lymphoma (n = 5) and disseminated non-Hodgkin lymphoma (n = 7) were examined for albumin, IgG, IgM, fibronectin, beta 2-microglobulin, interleukin-6, soluble interleukin-2 receptor, tumor necrosis factor alpha, and oligoclonal immunoglobulin bands. Although a broad range of abnormalities were detected, no reliable CSF parameter for the diagnosis of leptomeningeal spread from hematological neoplasias could be identified. An analysis of 61 repeat lumbar punctures added little to the findings of the first CSF examinations. Currently, immunochemical studies of CSF cell surface markers and early biopsy have probably more clinical value than the determination of the humoral CSF parameters included in this study. However, analysis of cytokine synthesis by single CSF cells using molecular biology techniques may improve the differential diagnosis of hematological neoplasia of the brain and spinal cord in the future.

Biomarkers, Tumor↗
PubMed1992

[Intrathecal immune response in meningeosis neoplastica: IgG, IgM, oligoclonal bands and cytokines].

Owing to improved systemic control of widespread malignancy, neurological complications have become a major outcome factor and determinant of life quality in oncological patients. While solitary cerebrospinal metastases are often amenable to surgical and radiological treatment, the management of diffuse leptomeningeal neoplasia, mostly using combined radiochemotherapy, is still very difficult. Immunomodulative approaches represent a therapeutic alternative with increasing potential. We have analysed the natural immune response to leptomeningeal tumor invasion in 43 Patients by assessing cerebrospinal fluid (CSF) levels of albumin, IgG, IgM, interleukins (IL) 1, 2, 4 and 6, soluble IL-2 receptor (sIL-2R), interferon gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), and the tumor markers, carcinoembryonic antigen (CEA) and alphafetoprotein (AFP). In most patients, either elevated IgG index, IgM index, CSF IL-6, or detection of CSF oligoclonal immunoglobulin bands indicated a host reaction against tumor cells. IL-1, IL-2, and IL-4 were never detected in CSF or serum. sIL-2R and IFN gamma were rarely detected and were not associated with specific malignancies. CSF TNF alpha was only detected in melanoma patients and may be a specific indicator of that neoplasm. No correlation was found between levels of the tumor markers, CEA and AFP, and parameters of the immune response such as IgG, IgM or IL-6. The demonstration of intrathecal immune activation in a majority of patients with leptomeningeal neoplasia may offer a new option for immunomodulative oncological therapy.

Biomarkers, Tumor↗
PubMed1991

Cerebrospinal fluid interleukins, immunoglobulins, and fibronectin in neuroborreliosis.

Intrathecal synthesis of IgM and IgG, oligoclonal immunoglobulin bands, and the levels of fibronectin, soluble interleukin 2 receptor, interleukin 6, and tumor necrosis factor alpha were investigated with the use of enzyme-linked immunosorbent assay in 46 paired cerebrospinal fluid and serum samples from 32 patients with meningopolyradiculoneuritis due to Borrelia burgdorferi (Lyme borreliosis stage 2). Cerebrospinal fluid and serum interleukin 6, although not specific for neuroborreliosis, were good indicators of disease activity, while the serum soluble interleukin 2 receptor level was only mildly elevated. Tumor necrosis factor alpha was never detected in cerebrospinal fluid or serum specimens, and cerebrospinal fluid IgM, IgM index, and cerebrospinal fluid IgM/cerebrospinal fluid IgG ratios were significantly higher than in all other neuroimmunologic disorders evaluated and may be valuable diagnostic indicators for neuroborreliosis. The estimation of intrathecally synthesized IgG and IgM fractions for the differential diagnosis of neuroimmunologic disorders did not add to IgG and IgM index calculations.

Antibody Formation↗
PubMed1991

Neurosarcoidosis without systemic sarcoidosis.

Neurosarcoidosis is a well-recognised complication of systemic sarcoidosis but diagnosis may be difficult if there is no clear evidence of an extracerebral manifestation of the disease. We present the case of a 42-year-old woman with clinical features characteristic of cerebral sarcoidosis including tetraparesis, diabetes insipidus, diencephalic hyperphagia, personality changes, and memory loss. Diagnosis was supported by cerebrospinal fluid (CSF) findings and magnetic resonance imaging (MRI): CSF showed mild lymphocytic pleocytosis, intrathecal production of IgG without oligoclonal bands, and a raised level of lysozyme. MRI revealed multiple contrast-enhanced granulomas at the base of the brain with partial involvement of diencephalic and mesencephalic structures and parts of the spinal cord. There was no evidence of systemic manifestation of sarcoidosis. Administration of corticosteroids led to improvement of the symptoms.

Adult↗
PubMed1991

Comparative analysis of cytokine patterns in immunological, infectious, and oncological neurological disorders.

Interleukins (IL) 1, 2, 4, 6 and soluble IL-2 receptor (sIL-2R), interferon-gamma (IFN-gamma), and tumor necrosis factor-alpha (TNF-alpha) were measured in CSF and serum from patients with relapsing-remitting and chronic multiple sclerosis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, HIV infection, bacterial meningitis, viral encephalitis, meningeal carcinomatosis, hematologic meningeal malignancies, and disseminated melanoma. Our findings suggest that monitoring of disease activity in neuroimmunologic disorders by means of IL-1 beta, IL-2, sIL-2R, or IL-4 determination will not prove useful. IL-6, on the other hand, indicates relapse in multiple sclerosis and active disease in Guillain-Barré syndrome and meningeal carcinomatosis. High CSF TNF-alpha in metastatic melanoma and frequent detection in CSF of the multifunctional B-cell growth factor, IL-6 (27/30) and oligoclonal immunoglobulin bands (33%) in meningeal carcinomatosis confirm an intrathecal immune response in disseminated leptomeningeal neoplasia which might be amenable to therapeutic immunomodulation.

Cytokines↗
PubMed1991

Acetylcholine receptor-reactive T lymphocytes from healthy subjects and myasthenia gravis patients.

Peripheral blood lymphocytes from 23 of 114 (20%) myasthenia gravis (MG) patients showed positive T-cell proliferative responses to native acetylcholine receptor (AChR) purified from the electric fish Torpedo, compared with two of 25 (8%) healthy or other neurologic disease controls. Responsiveness appeared to fluctuate seasonally. Long-term T-cell lines and clones could be selected as readily from the two healthy responders as from the MG cases and showed similar culture behavior, CD4+ phenotype, and HLA class II restrictions. One clone from a control cross-reacted with recombinant human AChR alpha chain (r37-429A) and with the synthetic peptide 125-143(S-S) from its sequence. Both these human antigens stimulated primary proliferative responses at substantially higher frequencies (26 to 59%) than native xeno-AChR--in both patients and controls--demonstrating that truly autoreactive T cells are not inevitably deleted during normal T-cell development.

Animals↗
PubMed1990

Myasthenic thymus and thymoma are selectively enriched in acetylcholine receptor-reactive T cells.

We compared T-cell proliferative responses to acetylcholine receptor (AChR) and to purified protein derivative (PPD) (of tuberculin) of hyperplastic thymus, thymoma, and blood cells from patients with myasthenia gravis (MG). Hyperplastic MG thymus cells gave significantly higher and more consistent responses to AChR than parallel cultures of autologous blood cells, whereas responses to PPD showed an opposite trend. Thus there was a preferential localization of AChR-reactive T cells in the hyperplastic MG thymus. Furthermore, there was a strong correlation between blood and thymus cell responses to PPD (but not to AChR), arguing that the hyperplastic MG thymus contains a sample of sensitized peripheral T cells. By contrast, both AChR- and PPD-responsive T cells were almost undetectable in thymus from nonmyasthenic patients, which is evidently much less receptive to circulating T cells. Cells from MG thymomas showed the highest stimulations by AChR but did not consistently react to PPD. However, the uninvolved thymus adjacent to these thymomas behaved almost identically to the hyperplastic samples described above. Our interpretation is that AChR-specific T cells are initially sensitized in the MG thymoma but are selectively trapped in the hyperplastic thymus after being primed elsewhere.

Cell Division↗
PubMed1990

Central pontine myelinolysis associated with low potassium levels in alcoholism.

Two patients with chronic alcohol abuse and central pontine myelinolysis are described. One developed a Korsakoff syndrome 2 days before admission to our hospital and the other showed signs of a incipient delirium without Korsakoff syndrome. Diagnosis of incipient central pontine myelinolysis was based on acute brain-stem dysfunction, serum electrolyte disturbances, malnutrition with vitamin B1 (thiamine), B6 (pyridoxine) and B12 (cyanocobalamin) deficiency in combination with typical neuroradiological findings. Hypokalaemia but no disturbance in serum sodium levels was found in both patients. After correction of hypokalaemia and vitamin deficiency the patients showed complete recovery of neurological and neuropsychological function. The findings are interpreted as suggesting that disturbances in serum potassium levels as well as rapid correction of hyponatraemia may be associated with pontine swelling and dysfunction which, if undetected, leads to central pontine myelinolysis.

Adult↗
PubMed1990

Increased intrathecal synthesis of fibronectin in bacterial and carcinomatous meningitis.

Immunoreactive fibronectin (Fn) was quantified in paired cerebrospinal fluid (CSF) and serum samples from patients with bacterial meningitis (n = 46), tick-borne encephalitis (TBE) (n = 6), HIV infection (n = 6), Guillain-Barré syndrome (n = 5), carcinomatous meningitis (n = 11), multiple sclerosis (n = 15), disk disease (n = 11), and controls (n = 28). A highly significant elevation of CSF Fn was found in bacterial meningitis, TBE, and carcinomatous meningitis. There were no significant differences in serum Fn between any of the groups. An Fn index to estimate the rate of intrathecal Fn synthesis reached the highest value in bacterial meningitis. Our findings suggest that CSF Fn may be an indicator of adequate host reaction and tissue repair. For diagnostic purposes, the determination of CSF Fn probably does not add much to routine CSF laboratory tests.

Albumins↗
PubMed1989

T-cell reactivity in myasthenia gravis.

In a proliferation assay, peripheral blood lymphocytes (PBL) from a relatively small proportion of myasthenia gravis (MG) patients and from controls responded to Torpedo acetylcholine receptor (T-AChR), which shows approximately 75% homology with the human AChR. Over 50% of MG patients responded to recombinant human AChR alpha-subunit (r37-437) however, compared with 9% of controls. A proportion of MG PBL respond to synthetic peptides of the extracellular portion of the human alpha-subunit, but only MG patients (18%) responded to the juxta-membrane sequence p257-269. MG T-cell lines raised against native T-AChR failed to respond to the synthetic peptides. These results underline the need to use human AChR sequences to test relevant T-cell reactivity in MG. T-cell lines raised from three MG patients to human alpha-subunit r37-437 have shown Stimulation Index (SI) values of 3.5-22. Three clones derived from one of these had SI values of 100-500. Preliminary testing of responsiveness in one of these clones showed reactivity to several recombinant polypeptides including r37-437 and r37-181, as in the parent line. The epitope(s) within this latter sequence have not yet been identified, but the experimental approach used here should make it possible to define critical T-cell epitopes in MG, and to determine their functional relevance by investigating the ability of AChR-reactive T-cell clones to provide specific help in anti-AChR antibody production.

Animals↗
PubMed1989

Variable corticosteroid sensitivity of thymic cortex and medullary peripheral-type lymphoid tissue in myasthenia gravis patients: structural and functional effects.

The thymus has been studied in myasthenia gravis patients to assess the effects of previous immunosuppression on total yields of cell suspension, immunohistology and culture responses. The reduction in cell yields by pretreatment with corticosteroid was very variable. In 16 of 32 cases, cortical, medullary and total cell numbers were all greatly reduced ('depleted cases'), whereas in the others, they were within or near the typical range for untreated myasthenics. Cortical thymocytes were even more depleted than precursor thymic blasts. Thus the interpatient differences in sensitivity to corticosteroid recently described for mature T cells also affected immature cortical thymocytes and their differentiating medullary progeny. In the medulla, mature (CD3+) T lymphocytes and germinal centres were enriched by the loss of cortex and appeared relatively healthy, but somewhat depopulated. Concomitantly, in-vitro T-cell responses to acetylcholine receptor (AChR) and production of anti-AChR antibody and total IgG by thymic cells were usually well within the typical range (assessed per 10(6) cells). Moreover, the total productivity of the entire thymus was reduced almost entirely by the cellular depopulation rather than by decreased function per surviving cell. Thus the main actions of this alternate day therapy with corticosteroids were apparently on total peripheral cell numbers, and perhaps on activated cells and effector mechanisms too, and its thymic effects were inessential.

Adolescent↗
PubMed1988

A juxta-membrane epitope on the human acetylcholine receptor recognized by T cells in myasthenia gravis.

T cell proliferative responses to synthetic peptides taken from the human nicotinic acetylcholine receptor (AChR) alpha-chain sequence, or to whole AChR purified from electric fish (Torpedo marmorata), have been studied, using blood, thymus, and lymph node cells, from 34 patients with myasthenia gravis (MG) and 17 controls mostly with other neurological diseases. Peptides were selected because they contained amino acid motifs that recur in most defined T cell epitopes. Peptide 257-269 (from the extracellular loop of the AChR alpha-chain between the second and third trans-membrane domains) stimulated cells from six patients and no controls. Peptides from region 125-143 (from the main extracellular 1-210 stretch), which is thought to be an important T cell epitope in rats, provoked responses in 26% of patients and 41% of controls. Two patients responded both to these peptides and to peptide 257-269, thereby implying some heterogeneity of their reacting T cells. Whereas the initial blood T cell samples sometimes responded both to Torpedo AChR and to the 125-143 peptides, T cell lines selected with either antigen subsequently showed no response to the other. This observation suggests that it may be essential to use human AChR sequences for studying truly autoreactive T cells in MG. Finally, no strong association was found between any of the responses to peptides and the HLA types of the responding individuals.

Adult↗