W R Timperley

Enolase isoenzymes in the cerebrospinal fluid of patients with diseases of the nervous system.

Alpha and gamma enolase isoenzymes have been studied in 212 patients with a variety of neurological diseases. The results show that these proteins are sensitive markers of tissue damage which enable a distinction to be made between the involvement of glial and neuronal components.

Levels of enolase and other enzymes in the cerebrospinal fluid as indices of pathological change

The activities of enolase, aldolase, pyruvate kinase, lactate dehydrogenase and creatine phosphokinase were measured in cerebrospinal fluid of 121 patients presenting with a range of disorders of the central nervous system. The results from 41 patients undergoing myelography were used as controls. An assessment was made of the relative merits of these five enzymes as markers of brain damage with special reference to brain tumours. Enolase was the most sensitive marker of pathological change and was the only enzyme raised in the CSF of patients with low grade astrocytomas.

The potential role of myofibroblasts in the obliteration of arteriovenous malformations after radiosurgery.

OBJECTIVES To examine the structural changes in arteriovenous malformations (AVMs) after stereotactic radiosurgery and to identify the cytoskeletal antigen phenotype of the proliferating cells to gain information about the possible mechanism of obliteration. METHODS We conducted immunohistochemical and electromicroscopic investigations of surgical material that was removed from seven patients. The patients were harboring cerebral AVMs that had been previously treated with gamma knife irradiation, and they experienced subsequent bleeding 10 to 52 months after treatment. RESULTS Light microscopy revealed spindle-shaped cell proliferation in the connective tissue stroma and in the subendothelial region of the vessels. The ultrastructural and immunohistochemical characteristics of these spindle cells were identical to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Whereas in nonirradiated specimens of AVMs, similar cells expressed vimentin and desmin positivity, in irradiated cases, alpha-smooth muscle actin activity was also observed. CONCLUSION In view of the contractile activity of myofibroblasts, the proliferation generated by irradiation and the transformation of the resting cells into an activated form could be relevant to the shrinking process and eventual occlusion of AVMs after radiosurgery.

An Immunohistochemical Study of Glial and Neuronal Markers in Primary Neoplasms of the Central Nervous System

SummaryParaffin-embedded tissues from 56 primary neoplasms of the central nervous system and seven cases of non-neoplastic reactive astrocytosis were examined by immunoperoxidase techniques on serial sections using monoclonal antibodies to glial fibrillary acidic protein (GFAP) and the 68 kDa neurofilament subunit and monospecific polyclonal antibodies to α-and γ-enolase. γ-Enolase was present in all neoplasms of neuronal origin, but was also present in anaplastic gliomas (particularly in giant cells), in some well-differentiated astrocytomas and reactive astrocytes. The cells containing γ-enolase in these cases appeared morphologically identical to those containing α-enolase and GFAP in adjacent serial sections. No relationship was found between γ-enolase immunoreactivity and cellular anaplasia in the gliomas studied. Subependymal neoplasms from patients with tuberose sclerosis exhibited evidence of both astrocytic and neuronal differentiation, sometimes in morphologically distinct cell populations, consistent with their suggested origin from a primitive cell line.

Multiple intraspinal and intracranial epidermoids and lipomata following gunshot injury.

This case report describes the presence of numerous intradural spinal and cranial epidermoids and lipomata, as an incidental finding, 14 years after a spinal gunshot injury. The aetiological factors operating in the development of such tumours are discussed with reference to the general literature and to this case.

Mdm2 and the p53 pathway in human pituitary adenomas.

Studies on pituitary tumours have failed to identify mutations in the tumour suppressor gene p53 suggesting that the protein identified is wild type. p21WAF−1 is a downstream effector of p53 which promotes growth arrest. Mdm2 (mouse double minute) is a protein induced by wild type p53 and forms an autoregulatory feedback loop suppressing wild type p53 activity. The purpose of this study was to examine a group of pituitary tumours for expression of p53 and its two downstream effector proteins p21WAF−1 and mdm2 and to compare this with their radiological invasive status and proliferative potential as assessed by Ki‐67 expression.

Histopathological changes in cerebral arteriovenous malformations following Gamma Knife radiosurgery.

Histological, immunohistochemical and electron microscopic investigations were carried out in a series of surgical pathology material that was removed from 7 patients. They were harboring cerebral arteriovenous malformations (AVMs) that had been previously treated with Leksell Gamma Knife radiosurgery, and presented subsequent bleeding 10-52 months after treatment. Light microscopic studies revealed a spindle cell proliferation in the connective tissue stroma and in the subendothelial region of the irradiated AVM vessels. The histological, immunohistochemical and ultrastructural characteristics of the spindle cell population in the Leksell Gamma Knife-treated AVMs are similar to those designated as myofibroblasts in wound healing processes and pathological fibromatoses. Considering that similar cell modifications have not been demonstrated in control, nonirradiated AVM specimens, these myofibroblasts might contribute to the shrinking process and final occlusion of AVMs after radiosurgery.

Immunolocalisation of cytokeratins in the normal and neoplastic human pituitary gland.

Cytokeratins were studied by immunocytochemical techniques at light and electron microscopy on 12 normal pituitary glands, 30 pituitary adenomas and three craniopharyngiomas. The results are presented in relation to clinical and biochemical features and new information on the subcellular localisation of cytokeratins in pituitary cells is discussed.

Cryostat section assay of oestrogen and progesterone receptors in meningiomas: a clinicopathological study.

Oestrogen receptors and progesterone receptors were measured in the cytosols from cryostat sections of 45 meningiomas from 40 patients (12 men, 28 women) using an isoelectric focusing technique. Near fascimile adjacent sections from the same tissue blocks were stained and examined to determine the histological subtype of the neoplasms. Appreciable levels of progesterone receptor (greater than 10 fmol/mg cytosol protein) were present in 24 (53.3%) of of the neoplasms, but no clinically important oestrogen receptor was detected in any of the tumours. Competitive binding studies on control tissue confirmed the specificity of the assay procedures. No correlation was found between progesterone receptor state and the age, sex, or menopausal state of the patients, or the histological subtype and site of the neoplasms. Four of the patients studied had multiple intracranial neoplasms, which in two were of differing progesterone receptor state. The presence of specific progesterone receptor in meningioma cytosols raises the possibility of hormonal manipulation in the treatment of this group of neoplasms.

Meningiomas, dicentric chromosomes, gliomas, and telomerase activity

Lack of telomere maintenance during cell replication leads to telomere erosion and loss of function. This can result in telomere associations which probably cause the dicentric chromosomes seen in some tumour cells. One mechanism of telomere maintenance in dividing cells is the action of telomerase, a ribonucleoprotein enzyme that adds TTAGGG repeats onto telomeres and compensates for their shortening during cell division. Over 90 per cent of extracranial malignant neoplasms have been found to have telomerase activity. This study sought to determine if there was a relationship between absence of telomerase activity and presence of dicentric chromosomes in meningiomas and to what extent the other main group of central nervous system tumours, the gliomas, expressed telomerase activity. Telomerase activity was measured on 25 meningiomas and 29 gliomas. Four of the meningiomas were atypical variants and 11 were positive for dicentric chromosomes. Twenty‐five of 29 gliomas were glioblastoma multiforme tumours. Measures were taken to ensure absence of false positives due to primer‐dimer interaction and false negatives due to protein degradation or the presence of Taq polymerase inhibitors. All 25 meningiomas and the four low‐grade gliomas (WHO grade II) were telomerase activity‐negative. Seven (28 per cent) of the 25 glioblastoma multiforme tumours showed telomerase activity. The absence of telomerase activity in meningiomas and the high frequency of telomere associations support the hypothesis that these tumours are benign, transformed but pre‐crisis. The relatively low frequency of telomerase activity in the malignant glioblastoma multiforme suggests that most of these tumours may have other mechanisms of telomere maintenance and that the potentially therapeutic telomerase inhibitors will not be of great value in the future management of the majority of patients suffering from these tumours. Copyright