Search PubMedSearch

Biomedical subjects

H Nyland

Publications and source records attributed to H Nyland.

At least 19 recordsLinked to original sources

[Multiple sclerosis].

Multiple sclerosis is a chronic inflammatory disease of the central nervous system which affects young and middle-aged adults. The clinical symptoms and course vary considerably; most patients experience a relapsing-remittent course which may become secondary progressive, a benign course with a favourable prognosis is seen in 30-40%. 10-15% experience a primary progressive course, with a less favourable prognosis. Magnetic resonance imaging, MRI, has become the most important paraclinic investigation and MRI with paramagnetic contrast enhancement reveals "subclinical" disease activity. Demyelination is caused by phagocytosis of microglial cells which appear to be activated by cytokines produced by T helper cells. A delayed type autoimmune response to myelin antigens is probably involved, initiated by a viral infection. Immunosuppressive treatment, corticosteroids and interferons have been shown to affect the MRI behaviour, and reduce the frequency of relapse. The effect on the natural course of the disease has been less convincing and no treatment will reverse long standing neurological dysfunction.

Adrenal Cortex Hormones

Prognostic factors for survival in multiple sclerosis: a longitudinal, population based study in Møre and Romsdal, Norway.

A longitudinal, population based study of life expectancy in multiple sclerosis was performed in the county of Møre and Romsdal, Norway during the period 1950-84. A total of 251 patients with multiple sclerosis (110 men, 141 women, mean age at onset of disease 33.6 years) were included. The mean follow up time was 18.1 years. At the end of the study period 70 patients had died. Fifty four (77.1%) of these had multiple sclerosis as the underlying or contributing cause of death on the death certificates. Young age at onset, initial remitting clinical course, and the presence of sensory symptoms at onset were significantly associated with longer survival.

Adolescent

Reactive microglia in multiple sclerosis lesions have an increased expression of receptors for the Fc part of IgG.

Receptors for the Fc part of IgG, FcRI (CD64), FcRII (CD32), and FcRIII (CD16) were studied by indirect immunoperoxidase staining of cryostat sections from normal and multiple sclerosis (MS) brains. Microglia in the parenchyma of normal white matter had a dendritic morphology, and were weakly stained by monoclonal antibodies (mAbs) to FcRI, FcRII, and FcRIII. In active MS lesions reactive microglia were strongly stained by the mAbs 32.2 (FcRI), IV-3 (FcRII), and 3G8 (FcRIII). Perivascular macrophages were stained by all anti-FcR mAbs in both normal white matter and in MS lesions, whereas endothelial cells were stained by the anti-FcRIII mAb only. The FcR on microglia and perivascular macrophages may be of functional importance in antibody-dependent cell-mediated cytotoxicity (ADCC), phagocytosis, and local immunoregulation. FcR on endothelium may be of importance in binding and transportation of immune complexes into the CNS. FcR mediated functions may consequently be highly relevant to the pathogenesis of MS.

Adult

Detection of MHC class II-antigens on macrophages and microglia, but not on astrocytes and endothelia in active multiple sclerosis lesions.

Tissue sections of brains from patients with multiple sclerosis (MS) and from control individuals were immunostained with MHC class II and glial or vascular endothelial cell antibodies and analyzed by confocal microscopy. MHC class II was abundant in and around actively demyelinating MS lesions and was detected on microglia, phagocytic macrophages, and perivascular macrophages. Astrocytes and vascular endothelial cells were MHC class II-negative. Changes in the size and shape of MHC class II-positive cells associated with MS lesions suggest that microglia transform into phagocytic macrophages, and that they are actively involved in demyelination. Many MHC class II-positive perivascular macrophages within MS lesions contained abundant intracellular MHC class II immunoreactivity; these cells may be involved in antigen presentation and in T cell activation.

Adolescent

Fc receptor for IgG (FcR) on rat microglia.

Receptor for IgG (FcR) was demonstrated on rat microglia in vivo and in vitro by immunohistochemical staining with immune complexes of horseradish peroxidase (HRP) and rabbit IgG anti-HRP. Astrocytes, oligodendrocytes and neurons did not express FcR. Microglia in culture also showed FcR-mediated agglutination and phagocytosis of IgG-sensitized erythrocytes. A radiolabelled cDNA probe for rat FcRIII hybridized with a 1.4-kb RNA band in Northern blots prepared from total RNA from rat brain. FcRIII mRNA-positive cells in rat brain, presumably microglia, were demonstrated by in situ hybridization. FcR participates in the initiation of cytotoxic responses and of phagocytosis by microglia and is therefore likely to be important in mediating immune reactions in the brain.

Animals

Fc receptors for IgG on cultured human microglia mediate cytotoxicity and phagocytosis of antibody-coated targets.

We have utilized surgically resected human central nervous system (CNS) tissue to determine the expression and functions of Fc receptors (Fc gamma R) on individual cell types found within the CNS. We observed all three classes of Fc gamma R on microglial cells in situ and in vitro, but not on astrocytes or oligodendrocytes. Incubation of cultured microglia with immune complexes (antibody-coated red blood cells) induced phagocytosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and oxidative bursts. We also found that microglia have the capability to produce T cell stimulatory soluble mediators after Fc gamma R crosslinking. These functional responses were enhanced by pretreatment of the microglia with interferon-gamma (IFN-gamma). Our results implicate microglial effector responses triggered by interaction of Fc gamma R with opsonized antigens as potential mediators of tissue injury within the CNS. Such injury may be particularly applicable to multiple sclerosis, an inflammatory demyelinating disease characterized by intrathecal production of immunoglobulins and cytokines.

Adult

Phenotypic differences between human monocytes/macrophages and microglial cells studied in situ and in vitro.

This report describes a phenotypic differentiation pattern conceived to distinguish invading monocytes from resident microglia in frozen and formalin-fixed human CNS. Phagocytic cells in normal and diseased CNS (multiple sclerosis and encephalitis) were studied immunohistochemically with a panel of antibodies, and phenotypic characteristics were compared with cultured monocytes/macrophages and microglia. Monocytes/macrophages were positive for the markers non-specific esterase, myeloperoxidase, L1, lysozyme, RFD7, and CD14, whereas microglia were negative for the same markers. Both populations of cells were positive for CD11c and CD68. Our results indicate that invading monocytes/macrophages mainly have a perivascular location in active multiple sclerosis lesions, whereas invading monocytes/macrophages also infiltrate the parenchyma in acute inflammatory CNS diseases such as in encephalitis.

Acute Disease

Sequelae one year after meningococcal disease.

Of 99 consecutive patients with meningococcal disease, 6 died during the acute stage. The 93 survivors were examined one year after hospitalization. 21 (40%) of the adults and 6 (15%) of the children had definite sequelae, and an additional 27% and 11% possible sequelae. 6 adults (12%) and 1 child (2%) had definite neurological sequelae. Electroencephalography (EEG) abnormalities were observed in 7 adults (14%) and 2 children (5%). Epileptogenic activity was present in 3 of these, but none had experienced seizures. 8 adults (19%) and 5 children (14%) had sensorineural hearing loss or impaired vestibular function. Cerebral computerized tomography (CT) scan showed definite and possible abnormalities in 1 (3%) and 6 (18%), respectively, of the 34 patients tested. Neuropsychological tests were performed in 9 patients, 2 of these showed definite impairment. The frequency of neurological abnormalities was higher than in many previous studies, probably reflecting the more comprehensive examinations performed in the present study. However, only 3 patients had serious sequelae. The results suggest that the occurrence of sequelae after meningococcal disease is related to the severity of the acute disease. This may explain the higher rate of sequelae in adults, who have a higher proportion of seriously ill patients. The presence of meningitis is not required for the occurrence of neurological sequelae.

Adolescent

Autoantibodies to myelin basic protein are not present in the serum and CSF of MS patients.

Myelin basic protein (MBP) is one of the main constituents of the CNS myelin sheaths, and an autoimmune response directed against MBP may be crucial in the demyelination process in patients with multiple sclerosis (MS). In this study sera and cerebrospinal fluid (CSF) from 25 MS patients, 25 patients with other neurological diseases and 16 healthy controls were examined for antibodies against MBP by using radio immunoblot, western blot, radio immunoassay and enzyme-linked immunosorbent assay. No evidence for the presence of antibodies to MBP was found in sera or CSFs in either the MS patients, or in the control groups tested.

Adult

Serum antibodies from MS patients do not recognize HTLV-I, HIV-1, HIV-2 and SIV.

A retroviral aetiology has been proposed for multiple sclerosis (MS). Although there is as yet no definitive evidence of viral involvement, there have been preliminary reports of antiretroviral antibody detection in sera from MS patients. Such sera have, for example, been found to react with HTLV-I. We here describe investigations involving various immunological techniques which attempt to confirm the virus-specific nature of these antibodies against a range of human and macaque retroviruses. Sera from 25 MS patients, 25 patients with non-associated neurological diseases and 16 patients with non-neurological conditions were tested by immunoblotting methods using lysates of HIV-1-, HIV-2-, HTLV-I- and SIV-infected cells as antigens. None of the sera reacted against any of these retroviral antigens but each serum demonstrated a distinctive and reproducible reaction pattern against cellular components of the cells in which the viruses were propagated. Further examination of the sera was carried out by ELISA using synthetic oligopeptides covering the HIV-1 Gag p24 protein as antigens. None of the sera reacted with the peptides. Our results suggest that in some MS patients the repeated seropositivity to HTLV-I may be due to the reaction with host cell proteins.

Adult

A histopathologic and immunocytochemical study of the spinal cord in amateur and professional divers.

To clarify the influence of diving activity on the central nervous system, we studied 10 amateur and 10 professional deceased divers with emphasis on the presence of subacute or chronic pathologic changes in the spinal cord. Of the 10 professional divers (median age 38 yr; range 29-52; median experience in excess of 13 yr), 7 were experienced saturation divers. Five had dived to a maximum depth of 150 meters of seawater, the 2 others to 300 and 500 msw, respectively. Five of the professional divers had experienced decompression sickness. The experience of the amateur divers (median age 29 yr; range 17-51) varied from a few dives to many years of recreational diving. The spinal cords were formalin-fixated and routinely processed for neuropathologic examination, which included light microscopy after immunostaining for glial fibrillary acidic protein and monocyte-macrophage-microglial markers. The microscopic examination did not reveal previous spinal cord damage. Thus, diving activity, saturation diving to extreme depths included, does not in itself seem to lead to necrosis, degeneration, or scar formation in the human spinal cord.

Adolescent

Yersinia enterocolitica infection--an unrecognized cause of acute and chronic neurological disease? A 10-year follow-up study on 458 hospitalized patients.

The purpose of the present study was to obtain further information about nervous system involvement associated with Yersinia enterocolitica infection. During the period 1974-1983, the infection was diagnosed by antibody response (agglutination titer or ELISA) and/or isolation of the microorganism in 458 hospitalized patients. 2 patients presented with acute symptoms of the peripheral nervous system, and 6 with symptoms of the central nervous system. The 458 patients were followed for 4-14 years (until 1987). During the follow-up period another 6 patients developed chronic neurological conditions; 4 with peripheral symptoms, and 2 with central symptoms. 11 of the 14 patients experienced persistent complaints. In 1991 (10-17 years after the diagnosis of yersiniosis), 6 patients still had significant antibody response (ELISA). The possibility that the immunologically competent Yersinia enterocolitica might have initiated the chronic neurological disease in these patients should not be disregarded.

Acute Disease

Organic solvents and multiple sclerosis: a case-control study.

A case-control study of multiple sclerosis (MS) has been carried out in western Norway. The study included 93% of the patients who had clinical onset of MS in the county of Hordaland during the years 1976-86 (N = 155) and 200 controls, marginally matched for age, sex and residence. There was no statistically significant difference between MS patients and controls with regard to exposure to organic solvents, exposure to the combination organic solvents and welding or to organic solvents and other chemical compounds.

Adult

Infections in childhood and adolescence in multiple sclerosis. A case-control study.

A case-control study on multiple sclerosis was conducted in Western Norway during the years 1986-1988. Included were 155 persons with multiple sclerosis and 200 controls, marginally matched according to age, sex and area of residence. The mean age at measles infection was for the cases 6.6 years and for the controls 5.7 years (p = 0.06). The cases had more frequently experienced bronchitis and/or pneumonia in the age group 11-15 years (OR = 3.20, 95% confidence interval 0.96-10.63). Tonsillectomies were reported more frequently by the cases. The odds ratio was especially high for those treated at age 0-6 years (OR = 3.44, 95% confidence interval 1.63-7.27). The results are consistent with the idea of MS as an age-dependent, host-immune response to infection during childhood or adolescence.

Adolescent

An immunohistochemical study of mononuclear cells in meningiomas.

A consecutive series of 34 meningiomas were re-examined as to subtype and presence of nuclear atypia, mitotic figures, areas of high cellularity and necrosis. Meningioma cells were epithelial membrane antigen (EMA) positive in 31 out of the 34 tumours. The presence of mononuclear cells and macrophages was assessed by immunohistochemistry using the monoclonal antibodies L26 (CD20, B cell marker), DF-T1 (CD43, T cell marker), KP1 (CD68, macrophage marker) and MAC387 (monocytes). L26 positive B cells were observed infrequently. CD43 positive mononuclear cells were infiltrating the parenchyma as individual cells and as groups of cells in 29 (87% of the tumours). CD68 positive macrophages were seen in 19 (59% of the tumours), as scattered single cells or groups of cells. There was a statistically significant association between the number of CD68 positive cells (necrotic areas excluded) and microscopic features of aggressiveness, i.e. high cellularity as well as the combination of nuclear atypia and frequent mitotic figures. MAC387 stained only a few cells; the immunopositive cells were present mainly within and around vessels. Meningioma cells displayed a diffuse immunopositivity for L26 (CD20) in 29 out of 34 meningiomas, but did not stain with macrophage markers. Mast cells were found in 9 out of 32 tumours; when present they were significantly more prevalent in the syncytial subtype. Thus, mononuclear cell infiltrates in meningiomas are mainly composed of T cells and macrophages, indicating an immune system surveillance and response to the tumour cells. The functional and prognostic significance of the presence of CD68 positive cells, macrophages, deserve further study in the search for more reliable histological criteria to predict recurrence and biological aggressiveness in meningiomas.

Adult

Early prognostic factors for disability in multiple sclerosis, a European multicenter study.

The effects of initial clinical variables on short-term prognosis are analyzed in a cross-sectional study of 574 multiple sclerosis patients from 7 centers in 5 European countries. Patients with a primary progressive course had a 2.3 higher mean disability score (EDSS) than the primary remittent group after a mean duration of disease of 6.6 years. High age at onset was associated with a primary progressive course, and was also related to increased risk of a rapid shift to a secondary progressive course. Among the remittent patients without a secondary progressive course a high age at onset was significantly correlated to a higher disability score. In the whole remittent group the presence of pyramidal and cerebellar symptoms at onset predicted both a high disability score and a rapid shift to a secondary progression, while the effect was reverse for sensory and visual symptoms. No difference between the sexes was found.

Adult

An immunogenetic heterogeneity in multiple sclerosis.

Two clinical forms of multiple sclerosis (MS), primarily chronic progressive MS (PCP MS) and relapsing/remitting MS (R/R MS) have been shown to differ in several respects. The results of genomic HLA class II typing with restriction fragment length polymorphism analysis of 62 MS patients from Western Norway, 42 with R/R MS and 20 PCP MS, are reported on here. As in previous studies of Swedish patients, the haplotype DRw17(3), DQw2 was found to be five times more common in R/R MS than in PCP MS. This finding supports the hypothesis that R/R and PCP MS are immunogenetically separate entities. In contrast with a previous investigation of Norwegian MS patients, no association of MS with glutamine at position 34 of the HLA-DQ alpha chain or with defined sequences of the HLA-DQB1 gene was found.

Adult