Proteinase-activated receptors regulate intestinal functions in a segment-dependent manner in rats.

Proteinases released e.g. during inflammatory or allergic responses affect gastrointestinal functions via proteinase-activated receptors such as PAR1 and PAR2.

Detection of cathepsin S cysteine protease in human brain tumour microdialysates in vivo.

Microdialysis enables the chemistry of extracellular fluid in body tissues to be measured. Extracellular proteases such as the cysteine protease, cathepsin S (CatS), are thought to facilitate astrocytoma invasion. Microdialysates obtained from human brain tumours in vivo were subjected to cathepsin S activity and ELISA assays.

Cathepsin S expression: An independent prognostic factor in glioblastoma tumours--A pilot study.

Cysteine proteinases have been implicated in astrocytoma invasion. We recently demonstrated that cathepsin S (CatS) expression is up-regulated in astrocytomas and provided evidence for a potential role in astrocytoma invasion (Flannery et al., Am J Path 2003;163(1):175-82).

Plasmacytoma: an unusual cause of a pituitary mass lesion. A case report and a review of the literature.

A sixty six year old female presented with headache and decreased hearing. Clinical examination confirmed the presence of impaired hearing on the left side. Visual fields were full to confrontation and corrected visual acuity was normal.

Cutaneous metastasis from glioblastoma.

A rare case of glioblastoma with isolated cutaneous metastasis adjacent to the scar site is described. Its pathogenesis and clinical significance are discussed.

Up-regulation of osteopontin and alphaBeta-crystallin in the normal-appearing white matter of multiple sclerosis: an immunohistochemical study utilizing tissue microarrays.

Tissue microarrays assembled from control and multiple sclerosis (MS) brain tissue have been used to assess the expression patterns and cellular distribution of two antigens, the proinflammatory cytokine osteopontin and the inducible heat shock protein alphaBeta-crystallin, which have previously been implicated in MS pathogenesis. Tissue cores were taken from paraffin-embedded donor blocks containing chronic active or chronic inactive plaques and normal-appearing white matter (NAWM) in seven MS cases, and white matter (WM) in five control cases. Expression patterns of both proteins were assessed against myelin density and microglial activation in the different tissue categories.

Tight junctional abnormality in multiple sclerosis white matter affects all calibres of vessel and is associated with blood-brain barrier leakage and active demyelination.

Blood-brain barrier (BBB) hyperpermeability in multiple sclerosis (MS) is associated with lesion pathogenesis and has been linked to pathology in microvascular tight junctions (TJs). This study quantifies the uneven distribution of TJ pathology and its association with BBB leakage. Frozen sections from plaque and normal-appearing white matter (NAWM) in 14 cases were studied together with white matter from six neurological and five normal controls.

Superficial siderosis of the central nervous system many years after neurosurgical procedures.

Recurrent haemorrhage into the subarachnoid space causes superficial siderosis, which clinically manifests as cerebellar ataxia, sensorineural hearing loss, and myelopathy. Two patients developed clinical, radiological, and biochemical evidence of superficial siderosis many years after surgery. One had two posterior fossa operations, a left temporal craniectomy, and radiotherapy for a presumed brain tumour before developing clinical evidence of superficial sidersosis 37 years later.

The clinical significance of cathepsin S expression in human astrocytomas.

Early local invasion by astrocytoma cells results in tumor recurrence even after apparent total surgical resection, leading to the poor prognosis associated with malignant astrocytomas. Proteolytic enzymes have been implicated in facilitating tumor cell invasion and the current study was designed to characterize the expression of the cysteine proteinase cathepsin S (CatS) in astrocytomas and examine its potential role in invasion. Immunohistochemical analysis of biopsies demonstrated that CatS was expressed in astrocytoma cells but absent from normal astrocytes, oligodendrocytes, neurones and endothelial cells.

CD83-positive dendritic cells are present in occasional perivascular cuffs in multiple sclerosis lesions.

Multiple sclerosis (MS) has a wide spectrum of clinical courses, characterized by multifocal central nervous system (CNS) damage, postulated to be mediated by CNS antigen-specific T cells. Dendritic cells (DC), the most potent antigen-presenting cell, play a pivotal role in the decision between T-cell activation or anergy. Monoclonal antibodies to CD1a (immature DC) and CD83 (mature DC) were used to screen lesions with evidence of recent demyelinating activity and chronic plaque and normal appearing white matter (NAWM) tissue sections from 12 MS cases by immunocytochemistry.

Abnormal endothelial tight junctions in active lesions and normal-appearing white matter in multiple sclerosis.

Blood-brain barrier (BBB) breakdown, demonstrable in vivo by enhanced MRI is characteristic of new and expanding inflammatory lesions in relapsing-remitting and chronic progressive multiple sclerosis (MS). Subtle leakage may also occur in primary progressive MS. However, the anatomical route(s) of BBB leakage have not been demonstrated.

Pathological abnormalities in the normal-appearing white matter in multiple sclerosis.

In established cases of multiple sclerosis (MS), the normal-appearing white matter (NAWM), as defined for magnetic resonance imaging (MRI), is abnormal in the majority of cases. The clinical significance of these NAWM abnormalities is the subject of debate, but there is strong correlation with degree and progression of disability. New lesions form in NAWM before blood-brain barrier breakdown, as evidenced by gadolinium enhancement.

Immunohistochemical evaluation of the post-translational processing of chromogranin A in human pituitary adenomas.

Chromogranin A (CgA), pancreastatin (PST), intervening-peptide (IP) and WE-14 antisera were employed to investigate the proteolysis of CgA in 50 pituitary adenomas. All non-functioning (NF) pituitary tumours (n = 28) exhibited CgA immunoreactivity. PST, IP and WE-14 immunostaining was observed in 85%, 89% and 67%, respectively.

Discordant repeat size and phenotype in Kennedy syndrome.

Previous reports in the literature have described correlation of increasing repeat length with severity of the phenotype, in Kennedy syndrome. We describe male siblings with different repeat lengths, with lack of expression of the phenotype in the sibling with the longer repeat length. The phenotype was identical to motor neurone disease.

Expression of bcl-2 oncoprotein in pituitary tumours: comparison with c-myc.

Aims/background: Whereas the control of hormone secretion from pituitary adenomas has been studied in considerable detail, the molecular events underlying the development of these tumours are still poorly understood. Abnormalities of some oncogenes and tumour suppressor genes have been previously reported to occur at very low frequencies. The aim of the present study was to assess the possible expression of the bcl-2 oncoprotein and to compare it with that of c-myc in pituitary adenomas.

Deficiency of respiratory chain complex I is a common cause of Leigh disease.

We reviewed the clinical features and etiologies of Leigh disease in 66 patients from 60 pedigrees. Biochemical or molecular defects were identified in 50% of all pedigrees, and in 74% of the 19 pedigrees with pathologically proved Leigh disease. Isolated deficiency of respiratory chain complex I was found in 7 patients, though the complex was only assayed in 25 patients, making this the second most common biochemical abnormality after complex IV deficiency.

Focal myositis of the floor of mouth: report of two cases and review of the literature.

Focal myositis is an uncommon inflammatory myopathy of unknown cause affecting skeletal muscle. It may be mistaken on clinical evaluation for a malignant neoplasm. We describe two cases, both involving the mylohyoid muscle of the floor of the mouth.

Desmin myopathy with cardiomyopathy.

We report a case of abnormal desmin accumulation within the muscle of a 30-year-old female with a 2-year history of cardiomyopathy and axial muscle weakness. Serum creatine kinase was normal. A quadriceps muscle biopsy revealed pink hyaline inclusions, which stained for acid phosphatase and with PAS and were present in both fibre types.

A clinicopathological review of spinal ependymomas in Northern Ireland.

Of eighty-three tumours of ependymal origin diagnosed in the twenty years 1969-1988 in Northern Ireland, fifteen were located within the spine. Two were in children, 13 in young adults with a mean age of 33 years. 70% presented with back pain and 60% had weakness of the lower limbs.

Cutaneous remnants of the vitellointestinal duct: a clinico-pathological study of 19 cases.

The presence of cutaneous vitellointestinal duct remnants was confirmed histologically in 19 cases in the period 1970-1984. These lesions occurred mostly in males (16 males, 3 females), and 80% in children under the age of five years. One case was identified in an adult, suggesting that these lesions may in some cases cause little inconvenience, and that their true incidence is underestimated.