THE DISTRIBUTION AND ROLE OF MICROTUBULES AND FILAMENTS IN THE NEOPLASTIC ASTROCYTES OF EXPERIMENTAL GLIOMAS

The distribution and role of microtubules and filaments in the neoplastic astrocytes of experimental gliomas Neoplasms of the nervous system were induced transplacentally by giving N-ethyl-N-nitrosourea (ENU) to pregnant rats on the 15th day of gestation. Astrocytomas and mixed gliomas with a significant astrocytic component were selected in order to study the distribution of microtubules and filaments in neoplastic fibrillary astrocytes. Electron microscopy of these gliomas revealed a population of pleomorphic astrocytes at various stages of differentiation. Poorly differentiated neoplastic astrocytes showed many microtubules but few filaments. In moderately differentiated cells there was a decrease in the number of microtubules with a concurrent increase of filaments. In well differentiated neoplastic astrocytes filaments dominated the cytoplasm forming thick, tightly packed bundles at the periphery of the cells and in the large processes, while occasional microtubules were intermingled with shorter and looser bundles of filaments. Thus, neoplastic fibrillary astrocytes in ENU-induced gliomas simulate the various stages in the differentiation of normal fibrillary astrocytes. This suggests that the ratio of microtubules to filaments may be one of the more discriminating criteria by which the degree of differentiation of neoplastic astrocytes can be established.     

GLIAL FIBRILLARY ACIDIC PROTEIN IN HUMAN GLIOMAS

The presence of GFA protein, an astrocyte specific antigen, was investigated in surgical biopsies of ninety-five gliomas using an immunoperoxidase detection method. In some cases electron microscopy was added and also in one tumour immunoelectron microscopy. The results were correlated with the histological classification and grading of the tumours. In astrocytomas, the number of GFA positive cells decreased with increasing malignancy. Some malignant oligodendrogliomas surprisingly showed GFA in oligodendroglial and gemistocytic tumour cells. Thus, transition from oligodendroglial into astrocytic tumour cells seems to occur. In the mixed astrocytoma/oligodendrogliomas, theoli godendroglioma areas were negative. Subependymomas were strongly GFA positive, whereas ependymomas and medulloblastomas were negative. The presence or absence of GFA seems to contribute a 'hard' criterion for classifying gliomas and may be helpful in grading them according to the degree of malignancy.     

AXONAL AND DORSAL ROOT GANGLION CELL CHANGES IN EXPERIMENTAL ALLERGIC NEURITIS

King R.H.M., Thomas P.K. & Pollard J.D. (1977) Neuropathology and Applied Neurobiology 3, 471486 Axonal and dorsal root ganglion cell changes in experimental allergic neuritis Observations have been made on experimental allergic neuritis in guinea pigs induced by the inoculation of rabbit sciatic nerve combined with Freund's adjuvant. Axonal lesions were observed most often in the later stages of the acute disease and in animals with a chronic relapsing course. They consisted of axonal interruption and regeneration, and ‘reactive’ axonal changes in demyelinated and remyelinated fibres, and in fibres of normal appearance that may have possessed lesions at some other point along their course. Abnormalities were not detected in anterior horn cells. Loss of dorsal root ganglion cells was rare, but invasion of the cells by lymphocytes which were present within large intracellular vacuoles, was at times conspicuous. The axonal and dorsal root ganglion cell changes may represent a ‘bystander’ effect in a cell-mediated delayed hypersensitivity reaction.     

EXPERIMENTAL INTRACEREBRAL HAEMATOMA IN THE RAT: SEQUENTIAL LIGHT MICROSCOPICAL CHANGES

In a small animal model of controlled intracerebral haemorrhage, changes within the haematoma and surrounding tissues were examined by light microscopy in toluidine blue stained semithin sections. Groups of animals were killed at 2, 6, 15, 24 and 48 hours, 2, 4, 8 and 14 days, and 3 months survival. Sequential changes in neurons, glia and leucocytes, together with the gradual absorption of the blood clot and its replacement by an astrocytic scar are described.     

THE DEVELOPMENT AND ULTRASTRUCTURE OF THE MICROVASCULATURE IN MALIGNANT GLIOMAS

The development and ultrastructure of the microvasculature in malignant gliomas The ultrastructural features of the small blood vessels in sixteen gliomas and in their zones of infiltration were compared with normal cerebral capillaries. Extensive new blood vessel formation was seen both in the zones of infiltration and within the main tumour. Immature capillaries in the former had a relatively simple structure with a slit-like lumen containing no blood cells; they resembled capillary buds seen in normal repair tissue and in brain adjacent to a cerebral metastasis. Near areas of necrosis and in pleomorphic regions of gliomas, endothelial cells formed complex, compound immature capillaries with many rudimentary lumina. These appearances are discussed in relation both to the production of tumour angiogenesis factors by gliomas and to the occurrence of gliosarcomas. There was a transition in the structure of the mature capillaries through the zone of tumour infiltration; the vessels gradually changed from normal structure to resemble the capillaries in the main tumour. The endothelial cells became thinner and developed villous processes on the luminal surfaces. Perivascular spaces developed with separation of the glial and capillary basement membranes. Perivascular glial or tumour cell end-feet were seen even in anaplastic gliomas, but in most tumours they formed an incomplete layer around the vessels. The differences between capillary structure in gliomas and in normal brain are discussed in relation to the alteration in the blood-brain barrier observed in gliomas.     

THE HORMONE DEPENDENCE OF EXPERIMENTALLY INDUCED GLIOMAS IN THE RAT

Pellets of 3,4-benzpyrene were implanted into the brains of groups of male and female rats. Animals from each of these groups were castrated or ovariectomized, and of these animals half the males and half the females received subcutaneous implants of testosterone. The position of the carcinogenic pellet in the brain was carefully controlled so that it impinged on the subependymal plate of the left lateral ventricle. A high proportion of glial tumours were produced in normal animals and it was found that deaths from cerebral tumour occurred earlier in males. Castration significantly reduced the time-related tumour incidence, and this was not reversed by testosterone. In ovariectomized females tuinour incidence was unmodified by testosterone and deaths from glioma apparently occurred later than in hormonally normal females. The implications from these results are that glial tumours are not dependent on testosterone as previously suggested. Alternative mechanisms for the sex differentiation incidence are discussed.     

PEROXIDASE ACTIVITY IN THE PAROTID GLAND IN JUVENILE NEURONAL CEROID-LIPOFUSCINOSIS

The parotid gland of a 17 year old boy who died from juvenile type of neuronal ceroid-lipofuscinosis contained autofluorescent lipopigments in epithelial and mesenchymal cells that showed the typical curvilinear and fingerprint profiles; these were not mixed with his secretory granules of the epithelial cells. Determination of p-phenylenediamine-mediated peroxidase in this tissue under various conditions yieded normal total enzyme activity and isoenzyme pattern. From these findings it is concluded that the pathological changes in this inherited disease cannot be related to a peroxidase deficiency.     

VASCULAR PERMEABILITY IN TRANSPLANTABLE MURINE GLIOMAS: MORPHOLOGICAL CORRELATION WITH TRACER STUDIES

Invasive astrocytomas were produced in mice by intracerebral injection of a cell line obtained from a spontaneous murine astrocytoma. These tumours grew in the cerebral hemispheres and, in many cases, extended through the needle hole in the skull to give rise to large extracranial tumours. On injection of the tracers, Evans' blue or horseradish peroxidase (HRP), into the femoral vein, differences were noted in the vascular permeability of the intracerebral and extracranial tumours; the latter alone being stained. Ultrastructurally, small amounts of HRP were localized on the luminal membranes of the vascular endothelium in intracerebral tumours, while in extracranial neoplasms, the tracer was present in the widened extracellular space and in the cytoplasm of macrophages and neoplastic cells. Accordingly, endothelial fenestrations, open junctions and irregular vessels with hypertrophic endothelia were seen exclusively in extracranial neoplasms. These anomalies in the vasculature of intracerebral and extracranial components of VMDk P 497 tumours may have important implications in chemotherapeutic studies using this glioma model.     

THE MITOCHONDRIAL DERANGEMENTS IN NEURONAL DEGENER ATION AND NEURODEGENERATIVE DISEASES

There are diverse concepts on the pathogenesis of neuronal degeneration and the neurodegenerative diseases. Among them there are different factors which might influence the initiation of neuronal degeneration as well as the pathogenesis of neurodegenerative diseases, such as Alzheimer′s disease, Parkinson′s disease, motor neuron disease, and so on.     

人脑胶质瘤中p16,p15基因分子的病理学研究

目的:探讨p16、p15基因改变、蛋白表达与脑胶质瘤组织病理的相互关系。方法:应用PCR、银染PCR-SSCP及免疫组化技术检测68例脑胶质瘤中p16、p15基因变化和蛋白表达情况。结果:显示脑胶质瘤中p16、p15基因缺失和P16蛋白丢失主要见于Ⅱ~Ⅳ级肿瘤中,而PCR-SSCP分析未见p16、p15基因点突变。结论:表明脑胶质瘤中p16、p15基因改变是以缺失为主,该基因功能的丧失促进了肿瘤细胞由良性向恶性的演进过程;P16蛋白表达状态可作为判断脑胶质瘤恶性程度及预后的指标。     

INTRACELLULAR SERUM PROTEINS IN CEREBRAL GLIOMAS AND METASTATIC TUMOURS: AN IMMUNOPEROXIDASE STUDY

An immunoperoxidase technique was used to compare the presence of serum proteins in tumour cells in twenty cerebral gliomas and four intracerebral metastatic carcinomas, with the serum protein content of reactive astrocytes around four cerebral infarcts. Rabbit antiserum to human immunoglobulins and albumen was applied to paraffin sections of tumour biopsies and of infarcts from postmortem brains. All the reactive astrocytes surrounding infarcts stained positively for immunoglobulins and albumen. In the gliomas, a continuous range of staining was observed in plump astrocytic tumour cells varying from strongly positive to unstained. Very few poorly-differentiated glioma cells stained for serum proteins; metastatic tumour cells, areas of capillary endothelial proliferation, and spindle cells in gliosarcomas remained unstained. These results suggest that the astrocytic function of serum protein uptake from the extracellular fluid is often lost in poorly-differentiated glioma cells, but is retained to a variable degree by those tumour cells which histologically resemble reactive astrocytes.     

VISUALIZING NEURONAL STRUCTURES IN THE HUMAN BRAIN VIA DIFFUSION TENSOR MRI

Acquisition, analysis, and visualization of diffusion tensor magnetic resonance imaging (DT-MRI) is still an evolving technology. This article reviews the fundamentals of the data acquisition process and the pipeline leading to visual results that are interpretable by physicians in their clinical practice. The limitations of common approaches for visualizing the retrieved data are discussed and a new statistical method is presented to assess the reliability of the acquired tensor field. A novel visualization method is proposed which is discussed in light of neurophysiological considerations of the perception of colored patterns. It is argued that this method is more accurate for medical data while providing a nearly optimal visual stimulus. The method is evaluated on a patient study with a brain tumor.