A comparison of the distributions of eight peptides in spinal cord from normal controls and cases of motor neurone disease with special reference to Onuf's nucleus.

The distributions of 8 peptides were studied in the 4 major segmental levels (cervical, thoracic, lumbar, sacral) of the spinal cord in 52 neurologically normal cases. Similar regions from 36 cases of motor neurone disease (MND) were compared using the same procedures to determine possible changes in the distribution of peptides in areas associated with sensory, motor and autonomic function. In normal spinal cords, calcitonin gene-related peptide (CGRP)-, the C-flanking peptide of neuropeptide Y (CPON)-, enkephalin-, galanin-, neurokinin-like-, somatostatin- and vasoactive intestinal polypeptide (VIP)-immunoreactive fibres were abundant in the dorsal horn. Numerous somatostatin-immunoreactive cell bodies were also present. In the ventral horn, immunoreactive fibres were less abundant. Most motoneurones were closely apposed by fibres immunoreactive for enkephalin, neurokinin, somatostatin and thyrotrophin-releasing hormone (TRH). A subpopulation of motoneurones, most notable in lumbar segments, displayed CGRP immunoreactivity. In common with autonomic nuclei, Onuf's nucleus, which is thought to innervate perineal striated muscle and external urethral and anal sphincters, was densely innervated with CPON-, enkephalin-, and in particular somatostatin-immunoreactive fibres, thus suggesting Onuf's nucleus may have an autonomic component. In the diseased cords, there was a reduction in the area of the ventral horn and numbers of motoneurones as revealed by conventional histological staining and immunostaining of neurofilament triplet proteins. No changes in the distribution of peptides was noted in the dorsal horn or autonomic nuclei. By contrast, in the ventral horn, neurokinin-, enkephalin-, somatostatin- and TRH-immunoreactive fibres, which are normally found associated with motoneurones, were absent. Therefore, not only are motoneurones lost in MND, but also the fibres which innervate them. CGRP-immunoreactive motoneurones were not observed, a finding consistent with the proposed role of this peptide as a muscle-trophic factor. In contrast to the large motoneurone groups in the ventral horn, the neuronal integrity of Onuf's nucleus and the peptides associated with it were spared. These data further imply that Onuf's nucleus is not a typical motor nucleus and it is not purely somatic. The coincident loss of peptide immunoreactivity and motoneurones from the large motor nuclei and sparing of Onuf's nucleus and its peptide-containing constituents in the diseased state suggests that peptides contribute to maintenance of neural integrity.

Immunohistological diagnosis of primary brain lymphoma using monoclonal antibodies: confirmation of B-cell origin.

The antigenic characteristics of 20 primary cerebral lymphomas have been defined by their reactivity with a panel of monoclonal antibodies recognizing differentiation antigens of lymphocytes and other cell types. In 7 out of 20 cases (35%), immunohistological results were diagnostically crucial and this approach appeared almost to double the detection rate of brain lymphomas over a 10-year period. All 20 tumours were confirmed as B-cell neoplasms by the use of a monoclonal antibody (B-1) specific for B-lymphocytes, rather than by the demonstration of immunoglobulin production. Further immunophenotyping with antibody FMC7 indicated that the neoplastic B-cells had been 'arrested' at a relatively mature stage of differentiation. The importance of monoclonal antibody markers in the accurate diagnosis and characterization of primary cerebral lymphomas has now been established.

Immunohistological study of mononuclear cell infiltrate in malignant gliomas.

Sixty-five malignant gliomas (astrocytomas grade 3 and 4 and glioblastomas) were examined by means of immunoperoxidase staining on frozen tissue using various monoclonal antibodies directed against macrophages, lymphocytes and natural killer cells. Depending on the antibody used, the presence of macrophages in tumours ranged from 85%-100%. Many of the tumours contained substantial numbers of macrophages not only, as expected, in necrotic areas but also in intact tumour tissue. Eighty-nine percent of 39 tumours tested contained Fc receptor-bearing mononuclear cells in viable tumour. In 100% of 44 tumours tested for HLADR class 2 major histocompatibility complex antigen this antigen was detected in the macrophages. In 40% of these 44 cases, HLADR antigen was also present on the tumour cells. Eighty-eight percent of 53 tumours tested contained T cells in viable tumour and the majority of these cells were T cytotoxic/suppressor (T8). Twenty-four percent of 33 tumours contained no T helper/inducer (T4) lymphocytes and in the other 76% there were few positive cells. Only 9% of 21 tumours contained natural killer cells (NK). B cells were absent from 88% of 61 tumours and almost all of the remainder contained only a small number of B cells. The findings are discussed with reference to a possible host immune response to gliomas and relevant literature is reviewed.