Receptor binding of an apolipoprotein E-rich subfraction of high density lipoprotein to rat and human brain membranes.

During nerve cell degeneration, cholesterol released from the degrading cells is conserved through the formation of a cholesterol-apolipoprotein (apo) E complex which is subsequently taken up by regenerating nerve cells. The aim of the present project was to identify the physiologically relevant lipoprotein receptor for this lipoprotein complex which has remained elusive. HDL was separated into apo E-rich and apo E-poor subfractions and labelled with [14C]-sucrose. Labelled apo E-rich HDL bound to rat brain membranes in a time- and ligand concentration-dependent manner and was a saturable process. Essentially no binding occurred with [14C]-apo E-poor HDL or with free apo E. Binding was partially inhibited by low density lipoprotein (LDL) and by alpha 2-macroglobulin. These results provide new evidence that native apoE-rich HDL particles resembling those present in the brain bind to rat brain membranes and that the binding may be due, at least in part, to the LDL receptor and to the LDL-receptor related protein. Evidence was also provided for the presence of a receptor which binds [14C]-sucrose human apoE-rich HDL in human brain. Characterisation of the receptor which mediates the uptake of cholesterol from HDL-like complexes by brain cells is important in understanding the role of apoE in the central nervous system and of the alterations which occur in disorders such as Alzheimer's disease.

Very early onset multiple sclerosis.

The authors report two cases of multiple sclerosis occurring in very young children. Age at onset in one child was 13 months; he had the primary progressive form of the condition and died at nine years. Age at onset of the other child was two years; he has the classical relapsing-remitting form and is well at 15 years. These children illustrate the broad clinical spectrum of the condition even in very-early-onset disease.

Primary low-grade hepatic B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)-type.

We describe the clinical, histological, and immunohistochemical features of four cases of primary low-grade B-cell lymphoma of the liver. The lymphomas were first seen as a solitary nodule in two patients and as two nodules in the third patient. These were found incidentally in an otherwise normal liver during abdominal surgery for other causes. In the fourth patient, several up to 2 cm nodules of lymphoma were found in a liver removed before transplant for chronic active hepatitis and cirrhosis. There was no evidence of lymphoma elsewhere in any of the patients. One patient has remained well, without evidence of lymphoma, 1 year after resection, one died intraoperatively, one is lost to follow-up, and the transplanted patient died 1 year after transplant from complications without evidence of recurrent lymphoma. The histology was typical of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT)-type with centrocyte-like cells surrounding reactive B-cell follicles and forming lymphoepithelial lesions with bile ducts. Primary hepatic lymphomas are rare, and most reported cases have been high-grade B-cell lesions. The liver should be added to the list of extranodal sites where low-grade MALT lymphoma may occur.

Cutaneous cryptococcal infection without immunodeficiency.

A case of cutaneous cryptococcosis (encapsulated strain) in a 67-year-old female, with no evidence of immune suppression (normal cell surface marker analysis and mitogen proliferation studies) and which responded to treatment with oral fluconazole is reported. To date her clinical progress remains satisfactory after 12 months of follow-up.

Differences in the fatty acid composition of the grey and white matter of different regions of the brains of patients with Alzheimer's disease and control subjects.

In the present study, a comparison was made of the fatty acid composition of the grey and white matter of the frontal, parietal and parahippocampal regions of post-mortem brains of patients who had died with Alzheimer's disease (n = 15) and control postmortem subjects (n = 10). Diagnosis of Alzheimer-type disease was based on the presence of senile plaques and neurofibrillary tangles in post-mortem sections. Several highly significant and specific differences were observed between the two groups. Adrenic acid (22:4 n-6) was three to four times higher in the grey matter but lower in the white matter in each of the three regions in the Alzheimer brains than in the control group. These alterations were compensated by reciprocal changes in 18:0 in the grey matter and 16:1 fatty acids in the white matter. There was no significant difference in the proportion of other fatty acids, including those of the n-6 and n-3 series, in either the grey or the white matter of any of the three regions of the two groups, except for a higher proportion of 22:6 n-3 in the parietal white matter in the Alzheimer patients. There was no significant relationship between the levels of the individual fatty acids and age at death. It is suggested that the alterations in the fatty acid composition observed in the brains of Alzheimer patients may be caused by an aberration in the system by which essential fatty acids are transported into the brain.

Adenomatosis of minor salivary glands. Report of a case.

An account is given of a patient who had multiple canalicular adenomas in the upper lip and adjacent oral mucosa. A few months after these had been excised, several more tumors of the same type developed. Microscopic examination also revealed numerous tiny foci of adenomatous proliferation within otherwise normal salivary gland lobules. We suggest that this phenomenon represents a field neoplastic change although it appears to be benign.

Post-mortem proton magnetic resonance spectrometric measures of brain regions in patients with a pathological diagnosis of Alzheimer's disease and multi-infarct dementia.

In-vitro spectrometric measures were made of spin-lattice (T1) and spin-spin (T2) relaxation times of samples of grey and white matter from the brains of 15 patients with a pathological diagnosis of Alzheimer's disease, 5 with multi-infarct dementia, and 11 non-demented subjects. Relaxation times were significantly greater in the parietal white matter and temporal white matter of patients with Alzheimer's disease compared with that of the other subjects. This was associated with an increase in tissue water content. These findings confirm measures obtained in some imaging studies.

Malignant glandular triton tumor.

A case of left brachial plexus-related malignant peripheral nerve sheath tumor showing neoplastic, glandular, and rhabdomyoblastic elements in a 39-year-old Chinese man is reported. The authors suggested that this tumor be termed a malignant glandular triton tumor in view of the presence of the adenocarcinomatous component. The patient had extensive local recurrence comprising mainly the Schwann spindle cells within a year after complete piecemeal removal and died 15 months later after the initial presentation. The natural behavior of this tumor, as in other reported cases of malignant triton tumor, is extremely aggressive, unlike malignant schwannoma or glandular malignant schwannoma. The histogenesis of this tumor is likely to be from primitive neural crest cells, Schwann's cell precursors, or metaplastic malignant Schwann's cells.

Cystadenocarcinoma of the appendix testis.

We report an example of what we believe to be an adenocarcinoma of the appendix testis. This very rare neoplasm arose in a patient on long term treatment with oestrogens which may be implicated as an aetiological factor.

Multimodal imaging in Alzheimer's disease. The relationship between MRI, SPECT, cognitive and pathological changes.

Patients with a clinical diagnosis of Alzheimer's disease were studied using MRI, SPECT, and psychometric tests. Significant correlations between focal perfusion deficits and focal cognitive deficits were found. Significant correlations between regional relaxation time of white matter and psychometric tests of diffuse and focal categories were also found. Pathological examination confirmed Alzheimer's disease as the only diagnosis.

JC virus genomes in progressive multifocal leukoencephalopathy: detection using a sensitive non-radioisotopic in situ hybridization method.

JC virus genomes have been localized in formalin-fixed, paraffin-embedded brain tissues of two cases of known progressive multifocal leukoencephalopathy by in situ hybridization utilizing a biotinylated JC virus DNA probe. A three-stage immunoperoxidase system with gold-silver amplification of the diaminobenzidine substrate was used to visualize biotinylated nucleic acid hybrids. Dot-blot quantification of this visualization system indicates that subpicogramme amounts of biotinylated DNA can be detected. Optimal detection of the virus genomes in the brain tissues required a microwave irradiation step prior to hybridization. JC virus genomes were observed in the nuclei of enlarged oligodendrocytes and of some bizarre astrocytes. No other cell types were found to harbour the genomes.