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Biomedical subjects

S Mørk

Publications and source records attributed to S Mørk.

18 recordsLinked to original sources

Organ culture of a glioblastoma from a patient with an unusually long survival.

Multicellular tumor spheroids were directly initiated in vitro from the biopsy specimens of a patient who is alive and who has had no neurological changes in 7 years after the gross removal of a glioblastoma. The spheroids were studied alone and in confrontation with aggregates of fetal rat brain tissue. Both in the biopsy and in the tumor spheroids, a very high proportion of cells were proliferating, as flow cytometric deoxyribonucleic acid measurements showed that 40% of the cells in the biopsy specimens and in the tumor spheroids were in the S and G2M phases of the cell cycle. Despite this high proliferation rate, the volume of the spheroids decreased, indicating an even greater cell loss. Light and scanning electron microscopic studies also indicated cell death in the spheroids. This behavior may be related to the long-time survival.

Animals

The expression of CD59 in normal human nervous tissue.

The expression of CD59, a complement regulator of the formation and function of the terminal cytolytic membrane attack complex, was studied in human normal nervous tissue by immunohistochemical markers using two monoclonal antibodies 1F5 and MEM43. CD59 was present on Schwann cells, neurons and endothelial cells in the peripheral nervous system (PNS), and on Schwann cells in culture. In the central nervous system (CNS) CD59 was found predominantly on endothelial cells. There was also a diffuse staining of white and grey matter of the spinal cord and brain, presumably of microglia, oligodendrocytes, astrocytes and neurons, as these cells were CD59 positive in culture. Furthermore, CD59 was detected in the cerebrospinal fluid (CSF) of healthy individuals. CD59 in the PNS and CNS was glycosyl-phosphatidylinositol linked and had a molecular weight of 19,000-25,000. The presence of CD59 on various cells of the nervous system and in the CSF suggests that regulation of complement activation by this protein is important in neural host defence mechanisms.

Adult

HLA class II molecules (HLA-DR, -DP, -DQ) on cells in the human CNS studied in situ and in vitro.

Human leucocyte antigen (HLA) class II molecules expressed by antigen-presenting cells (APC) are major restriction elements in the interaction between APC and T cells of the CD4+ subtype. To explore the immune accessory function of cells in the central nervous system (CNS), we studied the expression of HLA-DR, -DP, and -DQ molecules on CNS cells in situ and in vitro. Reactive microglia and perivascular cells in multiple sclerosis lesions expressed all three HLA class II molecules, whereas microglia in the normal CNS expressed HLA-DR only. All three HLA class II molecules were up-regulated on cultured microglia after stimulation with interferon-gamma (IFN-gamma). Microglial stimulation of allogeneic CD4+ T cells in a mixed lymphocyte reaction (MLR) was effectively blocked using anti-HLA-DR monoclonal antibodies (mAb) but not using anti-HLA-DQ mAb. HLA class II-positive astrocytes and endothelial cells were not identified in normal or diseased CNS. Cultured astrocytes stimulated with IFN-gamma could, however, be induced to express HLA class II antigens of all subtypes, although great variability was observed between different donors. Our results indicate that although both microglia and astrocytes are capable of expressing all HLA class II subtypes in vitro, subtype expression differs between normal and pathological states in situ. Such selective expression may be associated with functional properties.

Adult

Mast cells in brains during experimental allergic encephalomyelitis in Lewis rats.

We studied the number of mast cells and their extent of degranulation in brains of Lewis rats with acute experimental allergic encephalomyelitis (EAE), activity induced with guinea pig spinal cord and Freund's complete adjuvant. Non-immunized controls and EAE rats were killed on days 10, 11, 12, and 16 post-immunization (p.i.). The percentage of degranulated mast cells was significantly increased in EAE brains. Signs of degranulation were observed as early as day 10 p.i. Clinical EAE signs appeared from day 10 p.i. A significant change in mast cell number was not observed. The percentage of degranulated cells was largest at day 16 p.i., at a time when the inflammation had reached the thalamus. This indicates that mast cell degranulation may occur as a result of the inflammation. Collectively, the data suggest that mast cells may play a role in the pathogenesis of EAE.

Animals

Interaction between human brain tumour biopsies and fetal rat brain tissue in vitro.

The invasiveness of human intracranial tumours was studied in an organ culture system. Biopsies from six glioblastomas, four astrocytomas, two mixed gliomas, one ependymoma, four meningiomas and two carcinoma metastases were cut into fragments of 0.5 mm diameter, and placed in agar overlay tissue culture. The tumour specimens formed spheroids which were co-cultured with cell aggregates or fragments from fetal rat brain for up to 10 days in vitro. The invasiveness of the glioblastoma spheroids was characterised by a gradual destruction of normal brain tissue by tumour cells, followed by replacement of normal tissue by these cells. Co-cultures from two glioblastomas showed lesions in the normal brain tissue in areas removed from the tumour cells. Tumour spheroids from four glioblastomas totally destroyed the normal brain tissue without any change in the original tumour spheroid configuration. The low-grade gliomas were less invasive than the glioblastomas. The meningiomas and the metastases were non-invasive. This organ culture assay appeared to reflect the in situ invasive behaviour of the brain tumours examined. It is suggested that it may be used for evaluating the aggressiveness of individual brain tumours with the specific aim of correlating clinical data with the biological character of the tumour.

Adolescent

Mast cells and multiple sclerosis: a light and electron microscopic study of mast cells in multiple sclerosis emphasizing staining procedures.

In the brains of 7 patients with multiple sclerosis, mast cells were observed within the demyelinated plaques, in the border zone of the plaques as well as in seemingly normal white matter. The cells were mostly located in close connection with small vessels. The routine staining with toluidine blue for the demonstration of mast cells is not adequate as compared with staining of similar sections in pinacyanol erythrosine. Mast cells may be a hitherto underestimated contributor to the demyelinating process of multiple sclerosis.

Brain

Tumor characteristics in colorectal cancer and their relationship to treatment and prognosis.

Two hundred sixty one patients with adenocarcinoma of the colon and rectum were studied with respect to histopathologic and macroscopic tumor characteristics. Nonmetastatic disease was associated significantly with well-differentiated tumors, tumors with pronounced inflammation, and polypoid adenocarcinomas. There was a higher proportion of poorly-differentiated tumors in the right colon. Inflammatory changes were uncommon in rectal lesions; these tumors were more often polypoid than in other locations. Survival was significantly influenced by tumor differentiation, degree of inflammation, macroscopic appearance, and tumor size. Well-differentiated adenocarcinomas, less than 2 cm in diameter, and well-differentiated polypoid adenocarcinomas, less than 4 cm in diameter, were all found in patients with Dukes' stage A tumors. Such patients may be candidates for local excision if the tumor is located in the distal part of the rectum.

Adenocarcinoma

Metastasizing neuroectodermal tumour.

This report describes a medulloblastoma with extracranial metastases in a 24-year-old man. Postoperatively, 60Co irradiation was given and clinical recovery was good. Cervical lymph node metastases developed 2.5 years later. The patient received cytostatic treatment and a second course of radiation therapy with 60Co and lived for 6 years after the onset of symptoms, finally dying with signs of bronchopneumonia. The possible routes of spread are discussed.

Adult

Immunological characterization of sural nerve biopsies from patients with Guillain-Barré syndrome.

Among eight sural nerve biopsies from patients with the Guillain-Barré syndrome (GBS), demyelination was observed in five and endoneural mononuclear cell infiltrates in three. Receptors for the activated third component of complement (C3b) were detected within the nerve fascicles. The receptor activity was reduced in five biopsies, and in vivo deposition of C3 within the endoneurium occurred in four. Immunoglobulins were found in four biopsies and appeared to be localized along the myelin sheaths. Both T and B lymphocytes could be detected in the mononuclear cell infiltrates, but the relative proportions of these cells could not be determined. Macrophages present in two biopsies were found to possess IgG Fc receptors. The results indicate that the complement receptors may play a role in the binding of complement-containing complexes in the nerve during the GBS disease process.

Adult

Encephalitis induced in rabbits by staphylococcal lipoteichoic acid.

Rabbits were immunized with staphylococcal lipoteichoic acid (LTA) in Freund's adjuvant. After four injections (six weeks) the rabbits showed decreased activity and unsteadiness of the head. Two weeks after the sixth injection (ten weeks), two of five rabbits developed clinical signs of encephalitis with nystagmus, ataxia, general weakness, decreased activity, and dragging of the hind legs. The other three animals showed only mild symptoms. Neuropathological examination showed inflammatory infiltrates containing small lymphocytes and some plasma cells in the leptomeninges and within the perivascular spaces of the brain.

Animals

Creutzfeldt-Jakob disease. Infection of infancy or childhood?

A 51-year-old man who died of Creutzfeldt-Jakob disease (CJD), had transient dyskinesias with intention myoclonus and exaggerated startle reaction in early life. This may suggest a link between myoclonic encephalopathy of infants and CJD, and an incubation period of more than 40 years of the transmissible agent of CJD.

Creutzfeldt-Jakob Syndrome

Malignant glioma and sensorimotor neuropathy.

A case of sensorimotor neuropathy in a male with malignant glioma is reported. The symptoms of peripheral motor and sensory disturbances preceeded those of the intracranial tumor. The history, clinical findings, electrophysiological and histopathological results are presented, as well as immunological data. A possible causal relationship between glioma and peripheral neuropathy is discussed.

Brain Neoplasms

[Clinical and neuroradiological findings in gliomatosis of the brain with special reference to magnetic resonance tomography].

We present three cases of GC, one belonging to the brainstem, and two belonging to the hemisphere type. Two cases were investigated by MRI. Tumour infiltration, while yielding only vague CT findings, was well demonstrated in MR studies where extensive hyperintense lesions were found in T2- and proton density images. In patients studied by MR these were localized within the white matter and corpus callosum. No enhancement was seen after administration of Gd- DTPA. These findings may strongly indicate the presence of gliomatosis cerebri, when clinical and laboratory data exclude inflammatory or neurodegenerative disease. Despite the good delineation of white matter changes stereotactic biopsy remains necessary to confirm the diagnosis of gliomatosis cerebri pathohistologically.

Adolescent

Heterogeneity and selection of neoplastic neurogenic rat cells in vivo and in vitro.

Analysis of chromosome numbers and flow cytometric measurements of relative DNA content have been performed on four neoplastic neurogenic rat cell lines obtained from fetal BD IX-rat brain cells exposed to N-ethyl-N-nitrosourea (EtNU) in vivo, which sequentially underwent neoplastic transformation in cell culture. In vitro, the cell lines showed varying degrees of ploidy (ranging from near-diploid to near-hexaploid values) and chromosome aberrations. When grown in vivo as solid tumours in BD IX-rats and in thymus deficient nude mice, or in intraperitoneal diffusion chambers in rats, the near diploid cell lines were stable. In the lines with higher ploidies the proportion of cells with near-diploid values increased. Upon retransfer to cell culture, the cell lines gradually changed to the original in vitro pattern. However, in some cases an elevated near-diploid fraction persisted during culture after retransfer. Despite the selection of malignant cells with different ploidy in vivo and in vitro, their ultrastructural morphology remained unchanged. Thus, in this system, near-diploid cells are favoured under conditions of in vivo growth.

Animals

Invasive pattern and phenotypic properties of malignant neurogenic rats cells in vivo and in vitro.

Twelve malignant neurogenic rat cell lines induced by the carcinogen ethylnitrosourea (EtNU) have been investigated for invasiveness in an in vitro three-dimensional culture system. The histological pattern of invasiveness into embryonic chick heart fragments has been compared to the morphology in subcutaneous and intracerebral solid tumours as well as to other phenotypic properties of the cells. In all the cell lines invasiveness was seen both in vivo and in vitro. The site of in vivo transplantation seemed to influence the tumour-host tissue interface, since intracerebral tumours were more sharply delimited than subcutaneous tumours and primary EtNU-induced CNS tumours. The histological patterns in vivo (glioma versus neurinoma-like) were in most cases similar to invasive growth in vitro. The pattern of invasiveness did not correlate to other phenotypic properties of the cells (e.g. ploidy, doubling time, latency for tumour formation and surface microarchitecture). A rat fibroblastic cell line, RE-E was non-tumourigenic in rats and non-invasive in culture, but formed small subcutaneous tumours in nude mice.

Animals