myelin-basic-protein and Brain-Neoplasms

Topics: Animals; Brain Neoplasms; Genetic Therapy; Genetic Vectors; Glioma; Humans; Myelin Basic Protein; Promoter Regions, Genetic; Retroviridae

Retroviral vector is often used for gene therapy of malignant tumors. The main characteristic of this vector is that it integrates only into the genes of dividing and proliferating cells. Glioma cells proliferate actively, while surrounding normal brain cells rarely divide. Thus, we can expect the recombinant retrovirus modified to express cytotoxic genes to kill glioma cells selectively. However, this characteristic of specific toxicity to the dividing cells is also observed in many chemotherapeutic agents, and it is well known that they cause severe side effects, such as bone marrow suppression or diarrhea caused by simultaneous toxicity of the drugs to proliferating bone marrow cells or intestinal epithelial cells, respectively. We have cloned many genes which are specifically expressed in brain, and identified their promoter regions conferring tissue-specific expression. If we use the brain-specific promoters to regulate the expression of the toxic genes, these genes may not be expressed in the myeloid cells or intestinal epithelial cells, even if they were infected with the retrovirus. Therefore, we searched for brain-specific promoters which are also active in glioma cells to kill glioma cells specifically. Then, MBP promoter showed the strongest promoter activity in mouse glioma cells. These mouse glioma cells transduced with retrovirus containing the MBP promoter directing the herpes simplex virus type 1 thymidine kinase (HTK) gene were extremely sensitive to ganciclovir, even when transduced with the MBP promoter-HTK gene-containing retrovirus. And we could get complete remission in the mouse brain tumor models, which were transfected HTK genes in more than 25% glioma cells, with ganciclovir.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Brain Neoplasms; Genetic Therapy; Genetic Vectors; Glioma; Humans; Mice; Myelin Basic Protein; Promoter Regions, Genetic; Retroviridae

Topics: Adolescent; Adult; Brain Neoplasms; Cell Nucleus; Child; Child, Preschool; Cytoplasm; Diagnosis, Differential; Humans; Immunohistochemistry; Male; Microscopy, Electron; Middle Aged; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Oligodendroglioma; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

Myelin basic protein is a potential biomarker for the central nervous system diseases in which the myelin sheath is destroyed. Using pseudo-selected reaction monitoring and the method of standard additions, we have measured the myelin basic protein level in the cerebrospinal fluid of patients with neurotrauma (n = 6), chronic neurodegenerative diseases (n = 2) and brain cancer (n = 5). Myelin basic protein was detected only in four out of five cerebrospinal fluid samples of patients with brain cancer. The cerebrospinal fluid myelin basic protein level ranged from 3.7 to 8.8 ng ml

Topics: Adult; Aged; Brain Neoplasms; Female; Humans; Male; Mass Spectrometry; Middle Aged; Myelin Basic Protein; Proteomics

Neurofibromatosis type 1 (NF1) is a common neurogenetic disorder, in which affected individuals develop tumors of the nervous system. Children with NF1 are particularly prone to brain tumors (gliomas) involving the optic pathway that can result in impaired vision. Since tumor formation and expansion requires a cooperative tumor microenvironment, it is important to identify the cellular and acellular components associated with glioma development and growth. In this study, we used 3-D matrix assisted laser desorption ionization imaging mass spectrometry (MALDI IMS) to measure the distributions of multiple molecular species throughout optic nerve tissue in mice with and without glioma, and to explore their spatial relationships within the 3-D volume of the optic nerve and chiasm. 3-D IMS studies often involve extensive workflows due to the high volume of sections required to generate high quality 3-D images. Herein, we present a workflow for 3-D data acquisition and volume reconstruction using mouse optic nerve tissue. The resulting 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions.. The current work addresses a number of challenges in 3-D MALDI IMS, driven by the small size of the mouse optic nerve and the need to maintain consistency across multiple 2-D IMS experiments. The 3-D IMS data yield both molecular similarities and differences between glioma-bearing and wild-type (WT) tissues, including protein distributions localizing to different anatomical subregions, which could then be targeted for identification and related back to the biology observed in gliomas of the optic nerve.

Topics: Animals; Brain Neoplasms; Diazepam Binding Inhibitor; Fiducial Markers; Imaging, Three-Dimensional; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Imaging; Myelin Basic Protein; Neurofibromatosis 1; Optic Chiasm; Optic Nerve Glioma; Optic Nerve Neoplasms; Proteomics; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Topics: Autoantibodies; Biomarkers; Brain Neoplasms; Cerebrovascular Disorders; Enzyme-Linked Immunosorbent Assay; Globosides; Humans; Multiple Sclerosis; Myelin Basic Protein; Myelin P0 Protein; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating

The growth pattern of pilocytic astrocytoma (PAs) is unpredictable. Gene expression profiling has recently demonstrated an inverse relationship between myelin basic protein (MBP) expression and progression free survival (PFS) in PAs. We present here the pattern of expression of oligodendroglial differentiation markers (ODMs) in PAs by immunohistochemistry and their correlation with PI and PFS. Sixty-four cases of PA were reviewed and representative sections were stained for Ki-67 and ODMs, including MBP, platelet-derived growth factor receptor-alpha (PDGFR-alpha), Olig-1, and Olig-2. Sections were graded semi-quantitatively for intensity (I: 0-3+) and extent (E: 0-4+) of staining. PI was expressed as a percentage of Ki-67 positive cells. Immunoreactivity of MBP, PDGFR-alpha, Olig-1, and Olig-2 was observed in 84, 56, 97, and 75% of cases, respectively. There was a statistically significant inverse correlation between MBP expression and PI (r (2) = .696, p = .014). A positive correlation was observed between PDGFR-alpha and PI (r (2) = .727, p = .011). Further analysis showed a significant difference in PFS between low expressors [I + E score < or = 3] and high expressors (I + E score > or = 4) for PDGFR-alpha with p < .001. Notably, there was a significant difference in PFS between high expressors of MBP and high expressors of PDGFR-alpha with p < .001. These results suggest that expression of ODMs, especially MBP and PDGFR-alpha, may identify two clinical subsets of PA. In addition, we have shown the expression of 4 different ODMs in PAs, which may support the possibility that PAs arise from oligodendrocyte progenitor/precursor cells probably similar to the O2A progenitor cells in the mouse.

Topics: Adolescent; Adult; Antigens, Differentiation; Astrocytoma; Basic Helix-Loop-Helix Transcription Factors; Biomarkers, Tumor; Brain Neoplasms; Cell Differentiation; Child; Child, Preschool; Female; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Infant; Ki-67 Antigen; Male; Myelin Basic Protein; Nerve Tissue Proteins; Oligodendrocyte Transcription Factor 2; Oligodendroglia; Receptor, Platelet-Derived Growth Factor alpha; Retrospective Studies; Survival Analysis

Tumor stem cells (TSCs) possess the ability of chemoresistance. This study was to isolate and identify TSCs from human glioma cell line U87.. After U87 cells were grown as monolayer attached at the bottom of flasks in the medium containing serum, neural stem cell culture medium containing 5 ng/ml vincristine was added to obtain the first generation of tumorosphere. Then, the first generation of tumorosphere was dissociated into single cell suspension and seeded in the neural stem cell culture medium to obtain the second generation of tumorosphere. The morphology of the first and the second generations of tumorosphere was observed by light and scanning electron microscopy, respectively. The expression of nestin, glial fibrillary acidic protein (GFAP), beta-tubulin III and myelin basic protein (MBP) in the second generation of tumorosphere and differentiated cells were determined by immunofluorescence assay and confocal laser scanning microscopy.. The first and second generations of tumorosphere were obtained successfully. Cells inside the second generation of tumorosphere with a few protrusions attached with each other tightly. The expression of nestin, a stem cell marker, was detected in the second generation of tumorosphere. The expression of nestin, GFAP, beta-tubulin III, MBP was detected in the differentiated cells derived from the second generation of tumorosphere.. Tumor stem cells with the capacity of self-renewal and multipotency exist in U87 cells. Selective culture of tumor cells with treatment of vincristine might be a simple and practical method for isolation of TSCs.

Topics: Brain Neoplasms; Cell Differentiation; Cell Line, Tumor; Cell Separation; Glial Fibrillary Acidic Protein; Glioma; Humans; Intermediate Filament Proteins; Myelin Basic Protein; Neoplastic Stem Cells; Nerve Tissue Proteins; Nestin; Tubulin; Vincristine

The classification of human gliomas is currently based solely on neuropathological criteria. Prognostic and therapeutic parameters are dependent upon whether the tumors are deemed to be of astrocytic or oligodendroglial in origin. We sought to identify molecular reagents that might provide a more objective parameter to assist in the classification of these tumors. In order to identify mRNA transcripts for genes normally transcribed exclusively by oligodendrocytes. Northern blot analysis was carried out on RNA samples from 138 human gliomas. Transcripts encoding the myelin basic protein (MBP) were found in an equally high percentage of tumors that by neuropathological criteria were either astrocytic or oligodendroglial. In contrast, proteolipid protein (PLP) and cyclic nucleotide phosphodiesterase (CNP) mRNA molecules were found significantly more often in oligodendrogliomas than in astrocytomas. The strongest association with histological typing was found with the transcript for the myelin galactolipid biosynthetic enzyme UDP-galactose: ceramide galactosytransferase (CGT), which was about twice as frequently detected in tumors of oligodendroglial type. Results of glycolipid analyses were previously reported on a subset of the tumors studied herein. Statistical analyses of both molecular and biochemical data on this subset of astrocytomas, oligoastrocytomas, and oligodendrogliomas were performed to determine if a panel of markers could be used to separate astrocytic and oligodendroglial tumors. The presence of asialo GM1 (GA1) and the absence of paragloboside occurred most frequently in oligodendrogliomas. Ceramide monohexoside (CMH) levels correlated highly with the expression of mRNA for 4 myelin proteins: CGT, MBP, CNP, and PLP. The best combination of 2 markers of oligodendroglial tumors was CGT and GA1; the best combination of 3 markers was the presence of CGT, GA1, and the absence of paragloboside. We conclude that this combination of markers could be useful in distinguishing between astrocytic and oligodendroglial tumors.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; Cerebrosides; G(M1) Ganglioside; Galactosyltransferases; Glycolipids; Humans; Myelin Basic Protein; Myelin Proteolipid Protein; N-Acylsphingosine Galactosyltransferase; Oligodendroglioma; RNA; Survival Rate

To assess the concentrations of S-100 protein, myelin basic protein (MBP), and lactate, and the (CSF)/serum albumin ratio (Qalb) during intracranial neurosurgical procedures.. Samples of CSF from 91 patients with various CNS diseases were obtained by aspiration of cisternal CSF at the beginning of surgery (before starting surgical manipulation of the brain) and concentrations of S-100 protein, MBP, and lactate, and Qalb were determined. At the same time blood was sampled for determination of serum S-100 protein concentration. Patients were divided into three groups according to the aetiology of their CNS disease (intracranial haemorrhage, n=11; benign intracranial mass lesion, n=52; malignant neoplastic disease, n=28). Radiological and intraoperative characteristics were documented.. In each of these three groups median values of all four CSF variables measured were raised. The occurrence of brain oedema and a midline shift correlated significantly with raised concentrations of MBP and Qalb. Breaching of the arachnoid layer, documented at surgery for benign lesions, correlated with higher concentrations of MBP, lactate, CSF S-100 protein, and Qalb.. Intraoperative values of S-100 protein, MBP, lactate, and Qalb are increased in patients with intracranial haemorrhage, benign intracranial mass lesion, and malignant neoplastic disease. Breaching of the arachnoid layer and oedema is associated with higher concentrations of some of the aforementioned proteins. These biochemical data can serve as a basis for further research into CSF specific proteins.

Topics: Adolescent; Adult; Aged; Albumins; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Infant; Intracranial Hemorrhages; Intraoperative Care; Lactic Acid; Male; Middle Aged; Myelin Basic Protein; Reference Values; S100 Proteins

Malignant gliomas (MGs), lethal human central nervous system (CNS) neoplasms, contain tumor infiltrating lymphocytes (TIL). Although MHC class II molecules are frequently detected on MG cells, suggesting that they may be capable of antigen (Ag) presentation to CD4(+) T cells, deficiencies in CD4(+) T-cell activation are associated with these nonimmunogenic tumors. We evaluated regulation of the MHC class II transactivator (CIITA), the key intermediate that controls class II expression, in MG cells and tested whether MG cells could process native Ag. After interferon-gamma (IFN-gamma) stimulation, MG cells upregulated CIITA and class II molecules. IFN-gamma-inducible CIITA expression in MG cells, as well as primary human astrocytes, was directed by two CIITA promoters, pIV, the promoter for IFN-gamma-inducible CIITA expression in nonprofessional antigen-presenting cells (APC), and pIII, the promoter that directs constitutive CIITA expression in B cells. Both pIII and pIV directed CIITA transcription in vivo in MGs and ex vivo in IFN-gamma-activated primary MG cultures. We also demonstrate for the first time that MG cells can process native Ag for presentation to CD4(+) MHC class II-restricted Th1 cells, indicating that MG cells can serve as nonprofessional APC. CIITA may be a key target to modulate MHC class II expression, which could augment immunogenicity, Ag presentation, and CD4(+) T-cell activation in MG therapy.

Topics: Adult; Antigen Presentation; Antigen-Presenting Cells; Antigens, Surface; Astrocytes; Autoantigens; Base Sequence; Brain Neoplasms; CD4-Positive T-Lymphocytes; Exons; Female; Gene Expression Regulation, Neoplastic; Glioma; Histocompatibility Antigens Class II; Humans; Immunohistochemistry; Interferon-gamma; Male; Middle Aged; Molecular Sequence Data; Myelin Basic Protein; Nuclear Proteins; Promoter Regions, Genetic; RNA, Messenger; Trans-Activators; Tumor Cells, Cultured

The transduction of Bax protein, which is up-regulated in radiation- and chemotherapy-induced apoptosis, augments the cytotoxicity of radiotherapy and chemotherapy for cancers. The cytotoxicity of Bax overexpression is caused primarily by mitochondrial dysfunction, which is also involved in the apoptosis triggered by caspase-8. In this study, we transduced the Bax gene in combination with caspase-8 gene to evaluate whether or not this approach induces effective cytotoxicity in glioma cells. In terms of cancer gene therapy, it is critically important to induce cytotoxic genes in a cancer-specific manner. Therefore, we used the myelin basic protein promoter to drive cytotoxic genes. The expression level controlled by the myelin basic protein promoter was relatively low in gliomas. In U251 and U-373 MG glioma cells, adenovirus-mediated transduction of the Bax gene combined with caspase-8 gene induced enhanced apoptosis and cell death as determined by morphological analysis and assay for dead cells, hypodiploid cells, and DNA fragmentation (terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end labeling method). This therapeutic modality would be useful to induce a specific and enhanced cytotoxic effect for gliomas.

Topics: Adenoviridae; bcl-2-Associated X Protein; Brain Neoplasms; Caspase 8; Caspase 9; Caspases; Cell Death; Cell Separation; DNA Fragmentation; DNA, Complementary; Flow Cytometry; Gene Transfer Techniques; Glioma; Humans; Immunoblotting; Lac Operon; Microscopy, Electron; Mitochondria; Myelin Basic Protein; Promoter Regions, Genetic; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-bcl-2; Transduction, Genetic; Tumor Cells, Cultured

Caspase-8 is a member of the family of caspases, which are involved in the execution of apoptosis. To investigate whether caspase-8 can be used for gene therapy of gliomas, we transduced A-172 and U251 glioma cells with the caspase-8 gene via an adenoviral vector (Adv) controlled by the chicken beta-actin (CA) promoter (Advcaspase-8), and found that a similar level of caspase-8 protein induced A-172 cells to undergo necrotic cell death and U251 cells to undergo apoptotic cell death. Neither Bcl-XL nor Bcl-2, which play important roles in antiapoptotic mechanisms in gliomas, protected glioma cells from apoptosis induced by overexpression of caspase-8. Injection of Adv-caspase-8 suppressed the in vivo growth of U251 xenografts, in which apoptotic cell death remarkably increased as revealed by TUNEL analysis. Finally, we assessed whether gene therapy with a tissue-specific promoter, the myelin basic protein (MBP) promoter, is applicable to gliomas. Adv for caspase-8 controlled by the MBP promoter induced drastic apoptosis in U251 and U-373MG glioma cells, whereas it did not induce apoptosis in human endothelial cells, fibroblasts, and nerve growth factor-treated PC12 cells. These results indicate that Adv for caspase-8 effectively induced cell death in gliomas, and that this approach may be a useful modality for gene therapy of gliomas.

Topics: Actins; Adenoviridae; Animals; Apoptosis; Brain Neoplasms; Caspase 8; Caspase 9; Caspases; Cell Separation; Diploidy; DNA Fragmentation; Endothelium; Fibroblasts; Flow Cytometry; Genetic Therapy; Genetic Vectors; Glioma; Humans; In Situ Nick-End Labeling; Mice; Mice, Inbred BALB C; Mice, Nude; Microscopy, Electron; Myelin Basic Protein; Necrosis; Neoplasm Transplantation; Neoplasms, Experimental; Nerve Growth Factor; PC12 Cells; Promoter Regions, Genetic; Rats; Transduction, Genetic

Many of the strategies developed in the last few years to treat cancer by gene therapy are based on putative killer-suicide genes whose products convert a prodrug into a toxic compound. When the therapy is applied to humans, a vector carrying the killer gene is first inoculated into the tumor of the patient, who 1 week later receives the corresponding prodrug that will selectively kill the cells able to process it to its toxic derivative. A strategy that obviates the need for a prodrug to destroy the cancer cells would be preferable because the patient would only need one treatment instead of two consecutive ones. In the following study, we describe the construction of retroviral vectors in which a reporter or a toxin gene (either the Pseudomonas exotoxin or the Ricinus communis toxin, ricin) is placed under the control of the thyroid hormone (T3) regulatable promoter of the rat myelin basic protein (MBPp). We demonstrate that the expression of these genes under the control of MBPp is regulated by T3 in vitro and in vivo. In vitro, the MBPp is switched off when T3 is removed from the serum of the culture medium, allowing the production of retroviruses carrying the toxic gene. In vivo, the toxin gene bearing retroviruses is capable of eradicating experimentally induced brain tumors in Wistar rats. The gene therapy strategy described here does not require the use of a prodrug to destroy the neoplastic cells.

Topics: Animals; Brain Neoplasms; Female; Fluorescent Antibody Technique; Genes, Reporter; Genetic Therapy; Genetic Vectors; Glioblastoma; Magnetic Resonance Imaging; Mice; Mice, Inbred BALB C; Mice, SCID; Myelin Basic Protein; Neoplasm Transplantation; Plasmids; Promoter Regions, Genetic; Rats; Rats, Wistar; Retroviridae; Ricin; Thyroid Hormones; Toxins, Biological; Transfection

Topics: Animals; Brain Neoplasms; Cell Differentiation; Cell Survival; Female; Fluorescent Antibody Technique, Indirect; Glial Fibrillary Acidic Protein; Glioblastoma; Humans; Male; Mice; Mice, Nude; Myelin Basic Protein; Neoplasm Transplantation; Neoplasms, Experimental; Transplantation, Heterologous; Tumor Cells, Cultured

Developments in transgenic technology have greatly enhanced our ability to understand the functions of various genes in animal models and relevant human diseases. The tetracycline (tet)-regulated transactivation system for inducing gene expression allowed us to control the expression of exogenous genes in a temporal and quantitative way. The ability to manipulate a cell-specific promoter enabled us to express one particular protein in a single type of cell. The combination of a tetracycline system and a tissue-specific promoter has led us to the development of an innovative gene expression system, which is able to express genes in a cell type-specific and time- and level-controllable fashion. An oligodendrocyte-specific myelin basic protein (MBP) gene promoter controls the reversed tet-inducible transactivator. The green fluorescent protein (GFP) gene was placed under the control of the human cytomegalovirus (CMV) basic promoter in tandem with seven tet-responsive elements (TRE), binding sites for the activated transactivator. Upon the addition of doxycycline (DOX, a tetracycline derivative), tet transactivators became activated and bound to one or more TRE, leading to the activation of the CMV promoter and the expression of GFP in oligodendrocytes. We have successfully expressed GFP and luciferase at high levels in oligodendrocytes in a time- and dose-dependent fashion. In the absence of DOX, there was almost no GFP expression in oligodendroglial cultures. Graded levels of GFP expression were observed after induction with DOX (0.5 to 12.5 microg/ml). Our data indicate that this inducible gene expression system is useful for the study of gene function in vivo and for the development of transgenic animal models relevant to human diseases such as multiple sclerosis.

Topics: Animals; Anti-Bacterial Agents; Brain Neoplasms; Dose-Response Relationship, Drug; Doxycycline; Gene Expression Regulation, Neoplastic; Green Fluorescent Proteins; Humans; Kinetics; Luminescent Proteins; Myelin Basic Protein; Oligodendroglia; Oligodendroglioma; Promoter Regions, Genetic; Rats; Recombinant Proteins; Time Factors; Transcription, Genetic; Transfection

Intracranial nervous-system tumours were diagnosed in three of 1092 bovine necropsy specimens submitted to the Department of Veterinary Pathology, Obihiro University between April 1983 and March 1996. A fourth case was a referral from the Department of Veterinary Pathology, Rakuno Gakuen University. Histopathological examination revealed four types of tumour: intracranial malignant peripheral nerve sheath tumour (MPNST), choroid plexus papilloma, differentiated fibrillary astrocytoma and anaplastic (malignant) astrocytoma. Immunohistochemically, the intracranial MPNST was strongly positive for S-100 protein and vimentin, and in places weakly positive for glial fibrillary acid protein (GFAP). The choroid plexus papilloma was strongly positive for epithelial membrane antigen (EMA), keratin, S-100 protein and vimentin, and positive for GFAP in places. The cytoplasm and fibrous component in the differentiated fibrillary astrocytoma were strongly positive for S-100 protein and GFAP. The anaplastic (malignant) astrocytoma was strongly positive for vimentin, S-100 protein and keratin in the cytoplasm and fibrous processes, and weakly positive for GFAP and EMA in places. Myelin basic protein (MBP) and synaptophysin showed a weak positive reaction in the marginal areas of the tumour.

Topics: Animals; Astrocytoma; Brain Neoplasms; Cattle; Cattle Diseases; Glial Fibrillary Acidic Protein; Glioblastoma; Glioma; Immunohistochemistry; Keratins; Mucin-1; Myelin Basic Protein; Nerve Sheath Neoplasms; S100 Proteins; Vimentin

We examined the expression of glial- and neuronal-specific mRNAs within human gliomas using in situ hybridization. We found that low-grade astrocytomas contained a high number of proteolipid protein (PLP) mRNA-positive cells and that the number of PLP-stained cells decreased markedly with increasing tumor grade. Interestingly, the ratio of PLP mRNA-stained cells:myelin basic protein (MBP) mRNA-stained cells in normal white matter and low-grade astrocytoma was about 2:1 but approached 1:1 with increasing tumor grade. This parameter appeared to be a good indicator of tumor infiltration in astrocytomas, so we tested this in the analysis of other gliomas. Unlike astrocytomas, oligodendrogliomas were found consistently to contain few PLP mRNA- or MBP mRNA-expressing cells. In contrast, gemistocytic astrocytomas, typically highly invasive tumors, contained high numbers of PLP-positive cells and a ratio of PLP mRNA:MBP mRNA-stained cells of about 1.5:1, similar to low-grade astrocytomas. Nonradioactive in situ hybridization also enabled the morphological identification of specific cells. For example, gemistocytic astrocytes, which were found to be strongly vimentin mRNA positive, contained little glial fibrillary acidic protein mRNA and did not stain for PLP or MBP mRNAs. Neuronal mRNAs, such as neurofilament 68, were observed in small numbers of entrapped neurons within gliomas but were uninformative with respect to predicting tumor grade. Our results suggest that oligodendrocytes survive low-grade tumor infiltration and that glial tumor cells, unlike cell lines derived from them, do not express oligodendrocyte or neuronal mRNAs. In addition, the expression of mRNAs for the two major myelin protein genes, PLP and MBP, could be used to predict the grade and extent of tumor infiltration in astrocytomas.

Topics: Astrocytoma; Brain Neoplasms; Gene Expression Regulation, Neoplastic; Glial Fibrillary Acidic Protein; Glioma; Humans; In Situ Hybridization; Keratins; Myelin Basic Protein; Myelin Proteolipid Protein; Neurofilament Proteins; Neuroglia; Neurons; Oligodendroglia; Oligodendroglioma; RNA, Messenger; RNA, Neoplasm; Vimentin

Pathological differentiation of oligodendroglioma and mixed oligoastrocytoma from astrocytoma is difficult, relying on morphological characteristics due to the lack of reliable immunohistochemical stains. Oligodendrocytes, the presumed cell of origin of oligodendrogliomas, highly express the genes encoding myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the expression of these genes to determine whether they might be useful molecular markers of oligodendrocytic tumors. MBP and PLP were highly expressed in all oligodendrogliomas and minimally expressed in glioblastomas multiforme. MBP was highly expressed in mixed oligoastrocytomas, whereas PLP expression was minimal. The association between tumor classification and expression of the MBP and PLP genes was statistically significant. Expression of these genes may serve as a useful molecular marker for some subtypes of human gliomas.

Topics: Adult; Aged; Biomarkers, Tumor; Brain Neoplasms; Female; Gene Expression Regulation, Neoplastic; Glioblastoma; Glioma; Humans; Male; Middle Aged; Myelin Basic Protein; Myelin Proteolipid Protein; Oligodendroglia; Oligodendroglioma; Reverse Transcriptase Polymerase Chain Reaction; Survival Analysis; Time Factors

Myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with brain tumors and other neurological diseases was measured before, during and after various treatments such as surgery, chemotherapy and irradiation. We assessed the significance of changes in the MBP levels during the course of treatment, and speculate on what the elevated level of MBP in brain tumor patients indicates. In meningeal dissemination of malignant tumors, meningeal carcinomatosis from cancer of the systemic organ showed the highest level of MBP followed by meningeal gliomatosis and meningeal lymphoma. Meningeal carcinomatosis and meningeal lymphoma, which have responded to chemotherapy, showed normal levels of MBP after chemotherapy. Six of eight patients with newly diagnosed malignant glioma showed moderate to high levels of MBP (range 4.6-35.5ng/ml) just before intraarterial chemotherapy with VP-16 and CDDP. The level increased in five patients during the course of chemotherapy and then decreased in relation to the degree of tumor reduction by chemotherapy. In the solid type of metastatic brain tumor, five of seven patients with multiple tumors showed high levels of MBP and these levels also returned to normal after treatment in four patients. As for the influence of irradiation, levels of MBP did not increase after irradiation except in three patients who developed radiation necrosis, local extensive edema or atrophic change. In other brain tumors, levels of MBP were high in a patient with a large meningioma with very extensive edema and during an unstable postoperative condition after total removal of a large craniopharyngioma.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Brain Diseases; Brain Neoplasms; Female; Humans; Male; Middle Aged; Myelin Basic Protein; Prognosis

We measured the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF) of patients with various kinds of tumors, including malignant tumors, using radioimmunoassay. The CSF had been obtained by lumbar puncture through an Ommaya reservoir or a shunt device placed in the lateral ventricle. The level of MBP was high (> 4 ng/ml) in the patients with meningeal dissemination of malignant tumors, but in those who showed a good response to chemotherapy and/or radiation, it decreased or returned to the normal level, with improvement on the computed tomography and magnetic resonance imaging, cytological, general CSF, and neurological findings. Of seven malignant gliomas without CSF dissemination, six showed an elevated level of MBP before selective intra-arterial chemotherapy with a combination of etoposide and cisplatin administered via a microcatheter placed at A1, M1, P1-P2, and the basilar top. All CSF specimens obtained during the period of the intra-arterial chemotherapy showed an abnormally high (> 4 ng/ml) level of MBP that exceeded the prechemotherapy level. The MBP level decreased or returned to normal in the patients with a good response to chemotherapy after intra-arterial chemotherapy. In some patients with multiple metastatic brain tumors, the MBP level was elevated before treatment and returned to normal after treatment (surgical removal, chemotherapy, and/or irradiation) in all except one. Thus, there was a clear correlation between the timing of treatment and changes in imaging studies and MBP levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Astrocytoma; Biomarkers, Tumor; Brain Damage, Chronic; Brain Neoplasms; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Cranial Irradiation; Etoposide; Female; Follow-Up Studies; Glioblastoma; Humans; Infusions, Intra-Arterial; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Male; Meningeal Neoplasms; Meningioma; Middle Aged; Myelin Basic Protein; Treatment Outcome

We have taken a transgenic approach in an effort to specifically transform oligodendrocytes, the myelinating glial cells of the central nervous system (CNS). Transgenic mice were generated with a DNA construct that contained the activated neu oncogene under the transcriptional control of the myelin basic protein (MBP) gene. The MBP/c-neu transgenic animals have experienced a low incidence of brain tumors that express molecular markers specific to oligodendrocytes, providing a mouse model to study the formation and progression of oligodendrocyte tumors. A tumor from a transgenic animal has been dispersed in culture, and transformed cells that express properties of oligodendrocytes and astrocytes have been maintained. The degree to which these cells express phenotypic characteristic of oligodendrocytes or astrocytes is influenced by culture conditions. These transformed cells should serve as a valuable resource with which to study various molecular and biochemical aspects of the myelination process, as well as the lineage interrelationship of CNS glial cells.

Topics: Animals; Astrocytes; Base Sequence; Biomarkers; Biomarkers, Tumor; Brain Neoplasms; Cell Differentiation; Cell Transformation, Neoplastic; Gene Expression Regulation; Genes, Synthetic; Glioblastoma; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Transgenic; Molecular Sequence Data; Myelin Basic Protein; Neoplasm Proteins; Nerve Tissue Proteins; Oligodendroglia; Oncogenes; Organ Specificity; Phenotype; Promoter Regions, Genetic; Proto-Oncogene Proteins; Receptor, ErbB-2; Recombinant Fusion Proteins; Tumor Cells, Cultured

We have studied paraffin-embedded specimens of 17 rat granular cell brain tumors (GCBT) from four long-term drug safety carcinogenicity studies by peroxidase-antiperoxidase (PAP) immunohistochemistry with either polyvalent or monoclonal antibodies against glial fibrillary acidic protein (GFAP), S-100 protein (S-100), Leu-7 epitopes, vimentin (VIM), keratin, desmin, and myelin basic protein. We have found that 9 of the 17 GCBT contained GFAP-positive, S-100-positive, and VIM-positive astrocytes, while GFAP-positive and VIM-positive granular cells were observed in 5 of these 9 tumors. Our findings indicate that astroglial cells are involved in rat GCBT and suggest that an astrocytic origin should be considered for these neoplasms.

Topics: Animals; Antibodies; Antibodies, Monoclonal; Antigens, Differentiation; Brain Neoplasms; CD57 Antigens; Desmin; Female; Glial Fibrillary Acidic Protein; Granular Cell Tumor; Immunohistochemistry; Keratins; Male; Myelin Basic Protein; Rats; Rats, Inbred Strains; S100 Proteins; Vimentin

Two cases of TS associated with brain tumors had severe psychomotor retardation and early onset of long-term intractable convulsions, compared with cases without tumors. In one case, the tumor was partially cystic and progressed rapidly. Immunohistochemical studies of neuron specific enolase, glial fibrillary acidic protein and myelin basic protein revealed differences in positivity between cell types and between cases. These results suggested that the origin of the tumor cells could be variably differentiated cells.

Topics: Adolescent; Adult; Astrocytoma; Brain Neoplasms; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Myelin Basic Protein; Phosphopyruvate Hydratase; Staining and Labeling; Tomography, X-Ray Computed; Tuberous Sclerosis

35 intracranial tumours, 18 gliomas, 12 meningiomas, one neurilemmoma (neurinoma), one malignant melanoma and two metastases were successfully grown in-vitro and were submitted to immunocytochemical reactions, including cytokeratin, glial fibrillary acid protein (GFAP), vimentin, fibronectin, S-100 protein, neurofilament proteins, neuron-specific enolase (NSE) and basic myelin protein (MBP). Cytokeratin in metastases, GFAP and vimentin in gliomas, vimentin in meningiomas were consistently positive. S-100 protein was weakly and partially positive in gliomas, meningiomas, the neurilemmoma and malignant melanoma. Positive demonstration of fibronectin within cells was interpreted as a consequence of phagocytosis, except in meningiomas where fibronectin expression next to cell membranes seemed genuine. All other tested markers proved negative. The most important result seems to be that cells expressed markers irrespective of cellular shape and cytological morphology. It can be concluded that the cellular population as a whole consisted of tumour cells during the short time under observation and that supportive cell contamination during this early growth period was negligible.

Topics: Biomarkers, Tumor; Brain Neoplasms; Fibronectins; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunohistochemistry; Intermediate Filament Proteins; Melanoma; Meningioma; Myelin Basic Protein; Neurilemmoma; Phosphopyruvate Hydratase; S100 Proteins; Vimentin

Subependymal giant cell astrocytomas associated with tuberous sclerosis were studied with immunostains for glial fibrillary acidic protein (GFAP), myelin basic protein (MBP) and neuron-specific enolase (NSE). Tumor tissue was composed of three forms of cells; polygonal, ovoid and fusiform. A polygonal form was large in size and contained a vesicular nucleus, a distinct nucleolus and scarce Nissl granules resembling a nerve cell. An ovoid cell was similar to a gemistocytic astrocyte. Glial fibers stained with PTAH were observed to surround the tumor cell cluster. Immunocytochemically the polygonal cells were GFAP-and NSE-positive, the ovoid cells were GFAP-, MBP- and NSE-positive, and the fusiform cells were sometimes GFAP- and NSE-positive. The origin of tumor cells remains controversial, either glial or neuronal. This tumor occurs commonly in the subependymal region where germinal matrix cells appear at the early developmental stage. These results suggest that subependymal giant cell astrocytoma could have the totipotential to differentiate to astrocytic, oligodendrocytic as well as neuronal cells.

Topics: Astrocytoma; Brain Neoplasms; Cell Transformation, Neoplastic; Child; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Male; Myelin Basic Protein; Phosphopyruvate Hydratase; Tuberous Sclerosis

The present study was undertaken to evaluate the utility of pathologic features and specific immunohistochemical studies in estimating the prognosis of oligodendroglioma. The pathological diagnosis of an oligodendroglioma was made on HE stained-sections according to WHO classification. Sixteen oligodendrogliomas, twelve mixed oligoastrocytomas and ten anaplastic oligodendrogliomas were immunotested by the peroxidase-antiperoxidase (PAP) method with anti-GFAP serum, anti-S-100 serum and anti-MBP (Myelin basic protein) serum and by the avidin biotin peroxidase-complex (ABC) method with anti-vimentin serum and ant-Leu 7 monoclonal antibody. GFAP positive cells were interpreted as reactive astrocytes, neoplastic astrocytes and neoplastic oligodendrocytes, S-100 positive cells were interpreted as reactive astrocytes and neoplastic astrocytes. Leu 7 positive cells were found in only one case of anaplastic oligodendroglioma. Anti-Leu 7 could not be considered as a specific marker for oligodendroglioma. Of the anaplastic oligodendroglioma 60% displayed MBP positively and 70% displayed vimentin positively. NSE positive cells were found in a few anaplastic oligodendrogliomas. The present study has not so far uncovered any marker that is restricted to oligodendrogliomas. However GFAP may be useful to assess the extent of reactive astrocytes and neoplastic astrocytes in the oligodendroglioma or mixed oligoastrocytoma. MBP and vimentin will help to determine the malignancy of oligodendroglioma.

Topics: Adult; Aged; Biomarkers, Tumor; Brain Neoplasms; Child; Female; Glial Fibrillary Acidic Protein; Glioma; Humans; Immunohistochemistry; Male; Middle Aged; Myelin Basic Protein; Oligodendroglioma; Phosphopyruvate Hydratase; Prognosis; S100 Proteins; Vimentin

To search for a marker for oligodendroglioma, immunohistochemical analysis of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) were performed on tissues from 38 oligodendrogliomas. MBP was detected in 14 such tumors, positive cells being characterized by having rather rich cytoplasm containing a large nucleus and a prominent nucleolus. They seemed to be relatively poorly differentiated cells corresponding to oligodendroglioma grade II in the WHO classification, and appeared to have some cytological resemblance to immature oligodendrocytes in the newborn brain. Mature grade I tumor cells with a small dark nucleus and a perinuclear halo, and grade III anaplastic cells were MBP-negative. GFAP-positive cells were also found in tumors containing MBP-positive cells. A double immunostain for MBP and GFAP demonstrated that some tumor cells were simultaneously stained with both. Presumably the oligodendroglioma cells that showed such dual immunostaining would intrinsically express a myelin-forming glial phenotype. MBP may be applicable as a marker for oligodendrogliomas.

Topics: Biomarkers, Tumor; Brain Neoplasms; Glial Fibrillary Acidic Protein; Humans; Immune Sera; Immunohistochemistry; Myelin Basic Protein; Oligodendroglioma

Topics: Adolescent; Adult; Aged; Astrocytoma; Brain; Brain Chemistry; Brain Neoplasms; Child; Child, Preschool; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Immunohistochemistry; Infant; Infant, Newborn; Middle Aged; Myelin Basic Protein; Phosphopyruvate Hydratase

The histologic feature of oligodendroglioma is constituted by the monotonously arranged sheets of tumor cells intersected with delicate vascular stroma. The shape of the tumor cells is usually uniform and occasionally rather pleomorphic. In order to clarify biological characteristics of the tumor cells at level of cell differentiation, immunohistochemical stains for myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) with PAP method were performed on 13 oligodendrogliomas obtained by surgical removal. The cells stained positive with MBP immunostain were encountered in 5 tumors and their incidence was ranging from 1% to more than 30% of all tumor cells. The MBP-positive cells were characterized by having a large clear nucleus with a prominent nucleolus and relatively abundant cytoplasm, that seemed to mimic myelin-forming glia appearing in normal developing brain. The cells with poor cytoplasm or surrounded by a perinuclear halo were MBP-negative, and the pleomorphic cells in majority of anaplastic oligodendrogliomas were also negative. On the other hand, with GFAP stain the positive cells were observed in 8 tumors. It is still controversial to interpret the occurrence of GFAP-positive cells in oligodendrogliomas. In this study the GFAP-positive cells were morphologically identical to the MBP-positive cells, so that both MBP and GFAP are supposed to exist in the same tumor cells. It is assumed that some of oligodendroglioma cells which showed such immunostainabilities could possess an intrinsic character to express a phenotype of myelin-forming glia. Possibly, MBP substance is applicable as one of immunohistochemical markers for oligodendroglioma cells to indicate a certain cell differentiation.

Topics: Adult; Aged; Brain Neoplasms; Female; Glial Fibrillary Acidic Protein; Humans; Immunologic Techniques; In Vitro Techniques; Male; Middle Aged; Myelin Basic Protein; Neoplasm Proteins; Oligodendroglioma; Staining and Labeling

In patients with intracranial tumors (ICT) and acute cerebral infarctions (CI), both necrosis and reversible changes occur in central nervous system (CNS) tissue. The damaged CNS cells release specific substances into the cerebrospinal fluid (CFS). Radioimmunoassay (RIA)-determined myelin basic protein (MBP) and RIA-determined creatine kinase BB (CK-BB) are markers of damage to CNS specific structures. The elevated CSF level of MBP is considered a marker of myelin damage and the increased concentration of CSF CK-BB may be of combined neuronal and astrocytic origin. CSF was collected from 57 patients with the diagnosis of CI (n = 30) and ICT (n = 27) and the concentration of MBP and CK-BB were measured by RIA. Our study shows increased CSF levels of MBP and CK-BB in patients with CI and patients with ICT. We have also found a linear correlation between MBP and CK-BB in both CI and ICT, and for a given CK-BB level, MBP was significantly higher in patients with ICT than in patients with CI. These facts suggest that lesion markers behave differently in the different pathologic processes affecting the CNS.

Topics: Adolescent; Adult; Aged; Brain Neoplasms; Cerebrovascular Disorders; Child; Child, Preschool; Creatine Kinase; Female; Humans; Isoenzymes; Male; Middle Aged; Myelin Basic Protein

Seventy-four canine neuroectodermal tumors were examined immunocytochemically for the presence of glial fibrillary acidic protein (GFAP). Eleven oligodendrogliomas were examined for the presence of myelin basic protein (MBP) and myelin-associated glycoprotein (MAG). Twenty-three tumors, including ten astrocytomas, one ependymoma, two glioblastomas, one case of gliomatosis, and nine poorly differentiated gliomas were positive for GFAP. Two astrocytomas, eleven oligodendrogliomas, eight ependymomas, four choroid plexus papillomas, two medulloblastomas, one glioblastoma, nine poorly differentiated gliomas, six cases of gliomatosis, and three unclassified tumors were GFAP-negative. In six tumors (including four that were classified as astrocytoma) GFAP staining was equivocal. All oligodendrogliomas were MBP-negative but three expressed MAG. It was concluded that many canine gliomas are not only morphologically but also immunocytochemically similar to human gliomas, but that a larger proportion of canine neuroectodermal growths are undifferentiated tumors.

Topics: Animals; Brain Neoplasms; Dog Diseases; Dogs; Glial Fibrillary Acidic Protein; Histocytochemistry; Immunochemistry; Myelin Basic Protein; Myelin Proteins; Myelin-Associated Glycoprotein; Neoplasms, Germ Cell and Embryonal

In brain tumors and other neurological diseases cell-mediated immune reactions to fetal brain tissue antigens (FBA), normal tissue antigen of adult brain (NTA) and tumor-associated antigens of different brain tumors (TAA) have been analysed. The detection of sensitized lymphocytes using the MEM-(macrophage-electrophoretic-mobility-) test revealed general tumor-related results applying the FBA, in some extent a cross reactivity and partly no kind of reaction. A phase-specific reactivity to normal brain antigens could not be found, only cases of multiple sclerosis produced restrictive results employing the NTA. By testing tumor-associated brain antigens different reaction types were seen: The common TAA caused a tumor-characteristic reaction; the histo-specific TAA predominantly presented a organotypic form of reaction, confined a histo-specific reaction pattern; in some cases there were found inadequate, non-corresponding reactions as well as unreactivity. With regard to different types of reaction the problems of heterogeneity of the brain tumors and the cellular immune response--i.e. a heterogeneity of 1. or 2. order--were discussed including further factors concerning several special conditions in the nervous system.

Topics: Antigens, Neoplasm; Brain; Brain Neoplasms; Epitopes; Histocompatibility Antigens Class II; Humans; Immunity, Cellular; Lymphocytes; Meningeal Neoplasms; Meningioma; Multiple Sclerosis; Myelin Basic Protein

Patients admitted to the neurosurgical wards for the management of nervous system tumours, subarachnoid and intracerebral haemorrhage, head injury, spinal and peripheral nerve lesions, and other miscellaneous neurosurgical conditions, were studied by assay of serum immunoreactivity for myelin basic protein. Of 171 patients, 70% proved to have elevated myelin basic protein activity. In cerebral cases the extent of brain damage assessed by clinical methods appeared to correlate with the appearance of elevated serum myelin basic protein. In spinal and peripheral nerve cases no similar elevation of myelin basic protein was observed.

Topics: Adolescent; Adult; Brain Diseases; Brain Neoplasms; Child; Child, Preschool; Female; Humans; Infant; Male; Middle Aged; Myelin Basic Protein; Nervous System Diseases; Peripheral Nervous System Diseases; Postoperative Complications; Prognosis; Radioimmunoassay; Spinal Cord Diseases

In 44 patients undergoing neurosurgical procedures for intracranial tumors, subarachnoid hemorrhage, or spinal and peripheral nerve lesions, serum myelin basic protein (MBP) immunoreactivity was measured preoperatively and serially in the first 10 postoperative days. The double-antibody radioimmunoassay method was used, with a detection limit of 2.5 ng/ml in serum. Clinical evaluation was carried out at admission and on successive days during the period of neurosurgical management; outcome was assessed later. In the early postoperative phase, there was a fall in MBP immunoreactivity in all groups of patients. In the groups with intracranial tumor and subarachnoid hemorrhage, there was a subsequent rise in MBP immunoreactivity before the end of the 10-day period, which was not found in the group with spinal and peripheral nerve lesions.

Topics: Adenoma; Brain Neoplasms; Central Nervous System Diseases; Female; Glioma; Humans; Male; Meningioma; Middle Aged; Myelin Basic Protein; Radioimmunoassay; Spinal Cord Diseases; Spinal Diseases; Subarachnoid Hemorrhage

Forty three patients, admitted to the department of Neurological Surgery for management of central nervous system tumours, were studied pre-operatively for serum myelin basic protein immunoreactivity as a marker of central nervous system lesion and for circulating immunoglobulins and complement (C3) levels. Myelin basic protein concentration did not appear to correlate with tumour type or grade. Serum immunoglobulin levels were found to be within the normal range but the mean IgM level was significantly higher in the glioma group when compared with meningiomas.

Topics: Adult; Brain Neoplasms; Complement C3; Female; Humans; Immunoglobulins; Male; Myelin Basic Protein; Radioimmunoassay; Spinal Cord Neoplasms

Myelin basic protein (BP) is a specific constituent of the myelin sheath. This structural protein cannot be detected in the cerebrospinal fluid (CSF) unless myelin is acutely degraded. In order to detect active demyelinating diseases, BP was measured in CSF samples of radioimmunoassay. The assay is specific and sensitive to as little as 1.5 to 2.5 ng/ml BP. A moderate non-parallelism between the standard curve and various dilutions of CSF samples indicates that in CSF BP is present in an altered state. Over 1000 CSF samples have been measured in a double-blind study, in which 100 patients were selected and their clinical records evaluated. Twenty-eight patients without demyelinating disease had BP levels lower than 2.5 ng/ml. 72 patients had values higher than 2.5 ng/ml. Among them, the most frequent causes of demyelination were multiple sclerosis (19 cases), brain tumors (22 cases) and cerebral or spinal vascular accidents (12 cases). During a single acute demyelinating episode, BP levels revert to background levels within a few days. In contrast to immunological anomalies observed in the CSF, the presence of BP is concomitant with the breakdown of myelin. The size and location of the lesion influence the level of BP in the CSF. Thus, the assay is useful for the detection of active demyelination in the central nervous system and in following the course of the disease, although normal values do not rule out the presence of demyelinating lesions. For the time being, therefore, this assay should be restricted to specialized neurological centers and selected patients.

Topics: Adult; Brain Diseases; Brain Neoplasms; Central Nervous System Diseases; Child; Demyelinating Diseases; Female; Humans; Male; Meningoencephalitis; Multiple Sclerosis; Myelin Basic Protein; Radioimmunoassay

Topics: Brain Neoplasms; Electrophoresis; Glioma; Humans; Lymphocytes; Macrophages; Myelin Basic Protein; Neoplasm Proteins; Stomach Neoplasms

Topics: Animals; Brain; Brain Neoplasms; Cell Line; Encephalomyelitis, Autoimmune, Experimental; Female; Freund's Adjuvant; Glioblastoma; Guinea Pigs; Humans; Immunization; Macaca fascicularis; Male; Myelin Basic Protein; Neoplasm Proteins

Myelin basic protein in spinal fluid was measured with a radioimmunoassay method after surgery of brain tumors and posttraumatic brains in thirteen cases. Three cases were studied daily for up to three weeks. Immediately after the operation the values were high but then successively returned to normal. Repeated measurement of the myelin basic protein in spinal fluid seem to be useful for assessing the healing rate of brain tissue after surgery for brain tumors and after other brain damage.

Topics: Adult; Aged; Brain Diseases; Brain Neoplasms; Contusions; Ependymoma; Female; Glioma; Hematoma; Humans; Male; Meningioma; Middle Aged; Myelin Basic Protein; Postoperative Period; Skull Fractures

The diagnosis of multiple sclerosis is still a clinical one, and depends on the occurrence of neurological symptoms due to lesions at two or more necessarily distinct sites in the white matter of the central nervous system. Up to now there exists no specific laboratory test for the diagnosis of multiple sclerosis. The cerebrospinal fluid-profile strongly supporting the diagnosis of multiple sclerosis consists of: cell count slightly elevated, total protein concentration normal or slightly elevated, in the electrophoresis distinct immunreaction without disturbance of the blood-brain-barrier, i.e. significant increase of gammaglobulins and IgG, oligoclonal pattern of the gammaglobulin subfractions. Newly developed diagnosistic possibilities are based on the determination of myelin basic protein, determination of the different glycerophosphatides and on the measurement of the activity of lipid hydrolyzing enzymes. Disturbances of lipid metabolism play an important role in the course of demyelination. Therapy of multiple sclerosis by steroids and immunsuppression will be discussed.

Topics: Adrenal Cortex Hormones; Brain Neoplasms; Cerebellar Neoplasms; Diagnosis, Differential; gamma-Globulins; Humans; Hydrocortisone; Immunoglobulin G; Multiple Sclerosis; Muscle Relaxants, Central; Myelin Basic Protein

Topics: Brain Neoplasms; Humans; Immunity, Cellular; Immunization; Lymphocytes; Lymphokines; Meningoencephalitis; Multiple Sclerosis; Myelin Basic Protein; Nervous System Diseases

Serum levels of myelin basic protein (M.B.P.), a nervous-system-specific protein, were measured in 157 patients after head injury and related both to the type of brain damage and to the clinical outcome assessed three months after injury. Mean concentrations of M.B.P. in patients with severe intracerebral damage, with or without associated extracerebral haematoma, were significantly raised at the time of admission and remained high for two weeks after injury. In patients with extracerebral haematoma not associated with severe intracerebral damage mean M.B.P. values rose four to six days after injury and were significantly raised only in patients with poor eventual outcome. Mean serum-M.B.P. concentrations in patients with a good outcome after injury were similar to those in controls. In patients with a poor outcome the mean M.B.P. levels between two and six days after injury were significantly higher than in those with a good outcome. The assay of serum-M.B.P. may be valuable in assessment of severity of brain damage in patients after head injury and in prediction of outcome.

Topics: Blood-Brain Barrier; Brain Diseases; Brain Injuries; Brain Neoplasms; Cerebrovascular Disorders; Craniocerebral Trauma; Hematoma; Humans; Myelin Basic Protein; Prognosis

Lymphocyte sensitization to myelin basic protein (encephalitogenic factor, EF) was determined in 193 children by measuring the electrophoretic mobility of indicator particles which had been incubated with the supernatant of the lymphocyte-antigen (EF) mixture. A significant decrease in electrophoretic migration time was found in 77 of 85 children with malignant tumours localized in brain, abdomen and extremities, in 36 of 38 children with acute lymphoblastic leukaemia (all except one in hematological remission), and in all 17 patients with lymphoma, in contrast to only 1 of 10 healthy children and 14 of 48 patients with non-malignant disorders. 10 of these 14 "false positive" patients, however, had auto-immune diseases. Thus, with false negative and false positive rates of less than 10%, this test could be of diagnostic help in patients with suspected malignant or auto-immune disease. Two examples of preoperative application of the EM-test are demonstrated.

Topics: Abdominal Neoplasms; Adolescent; Age Factors; Autoimmune Diseases; Brain Neoplasms; Cell Movement; Child; Electrophoresis; Humans; Leukemia, Lymphoid; Lymphocytes; Lymphoma; Myelin Basic Protein; Neoplasms

The effect of low concentrations of bovine encephalitogenic protein on the migration of human peripheral leukocytes in agarose was studied. A concentration of 0.3 mug/ml of the protein stimulated the migration of cells from many donors, including some healthy subjects. An indirect technique suggested that the migration enhancement is due to the production of soluble factor, possibly corresponding to the leukocyte migration enhancement factor described by others. The frequency of subjects whose cells could be stimulated and the recorded degree of stimulation tended to be higher in a group of patients with multiple sclerosis than in a group of healthy subjects. When the effect of some of the main peptide fragments of the protein was studied on cells that were stimulated by the intact protein, one or more of these peptides sometimes induced the opposite effect: a migration inhibition. There is, apparently, a complex balance between enhancing and inhibiting factors acting on leukocyte migration in vitro; and the character of the antigen seems to be one important factor.

Topics: Amyotrophic Lateral Sclerosis; Brain Neoplasms; Cell Migration Inhibition; Cell Movement; Glioma; HLA Antigens; Humans; Infarction; Leukocytes; Lymphocyte Activation; Meningioma; Multiple Sclerosis; Myelin Basic Protein; Peptides; Stimulation, Chemical

Topics: Amyotrophic Lateral Sclerosis; Antigens, Viral; Brain; Brain Neoplasms; Cell Migration Inhibition; Female; Gastrointestinal Neoplasms; Glioma; Humans; Immunity, Cellular; Infarction; Leukocytes; Lung Neoplasms; Meningioma; Methods; Multiple Sclerosis; Myelin Basic Protein; Peptides; Polysaccharides