Familial childhood onset neuropathy and cirrhosis with the 4977bp mitochondrial DNA deletion.

The common 4977 base pair mitochondrial deletion has been identified in association with a number of distinct clinical phenotypes. These include the Kearns-Sayre syndrome, the Pearson marrow-pancreas syndrome, and chronic progressive external ophthalmoplegia. We report the clinical and pathological findings in two siblings in whom the 4977 base pair mitochondrial DNA deletion was identified in muscle-derived mitochondrial DNA. One sibling manifested early onset liver and renal failure, and both developed prominent peripheral sensorimotor neuropathy. These clinical findings have not been previously described in association with the 4977bp mtDNA deletion and thus represent a further expansion of the spectrum of mitochondrial disease.

Mitochondrial encephalopathy with lactic acidosis and stroke-like episodes (MELAS) in a Donegal kindred--clinical features and molecular genetic analysis.

A 19 year old female with a background history of migraine, sensorineural deafness and recent personality change developed a parieto-occipital cerebral infarct. Investigations revealed altered lactate to pyruvate ratios, ragged red fibres in muscle and an A-G point mutation at position 3243 in mitochondrial DNA. Subsequent clinical and molecular genetic analysis of 14 family members in three generations identified 12 affected individuals, two of whom were asymptomatic. Maternal inheritance was confirmed. MEALS is an important but under recognised cause of stroke and seizures in the young. There is insufficient data available to determine if the treatment of asymptomatic individuals retards the onset or reduces the severity of stroke.

Chronic encephalitis associated with epilepsy: immunohistochemical and ultrastructural studies.

Chronic encephalitis has been recognized as a cause of epilepsy since the work of Rasmussen et al. in the late 1950s. Despite this, few immunohistochemical studies of the affected brain tissue have been attempted. We have studied specimens of brain tissue from seven patients with this condition who underwent therapeutic multilobar cortical resection or hemispherectomy. Immunohistochemical studies were carried out using antibodies to glial fibrillary acidic protein (GFAP), proliferating cell nuclear antigen (PCNA, PC10), T lymphocytes (UCHL-1), B lymphocytes (L26), macrophages and microglia (HAM-56), and major histocompatibility complex molecules (LN3 and beta 2-microglobulin). Additionally, the results of preliminary immunohistochemical and ultrastructural investigation of possible immune complex deposition in blood vessel walls of affected brain tissue are presented. The pattern of GFAP immunoreactivity suggested a patchy and/or laminar disease process in most patients. GFAP immunoreactive cells were especially prominent around microvessels in some cases, suggesting an abnormality and perivascular collections of inflammatory cells, seen to a variable extent in all cases, contained abundant cells immunolabelled with UCHL-1, LN3 and beta 2-microglobulin. L26-labelled B lymphocytes were extremely sparse. Anti-PCNA frequently labelled microvascular endothelial cells, rare pericytes and occasional cells with microglial/macrophage morphology. The data suggest that chronic encephalitis found in patients with epilepsy results from patchy but widespread parenchymal brain injury, in the course of which cells of both microglial and lymphocyte series accumulate or proliferate within brain.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA ploidy in squamous oesophageal carcinoma.

The role of DNA ploidy in the management of oesophageal carcinoma is unclear. Most studies have employed flow cytometry (FC) for DNA analysis but some have used image analysis (IA) of tissue sections. In this study aneuploidy rates in stage IIa squamous tumours were determined by both FC and IA of cell suspensions and results were compared with outcome in two patient subgroups. Group 1 (n = 15) were patients who died from tumour recurrence within 1 year of surgery while Group 2 (n = 21) were patients who survived tumour free for at least 1 year. Aneuploidy rates differed significantly between techniques; 29 of 36 tumours (81%) were aneuploid by IA compared with 19 of 34 (56%) by FC (P < 0.05). Aneuploidy rates differed significantly between groups 1 and 2 as determined by FC (79%) versus 40%) (P < 0.05) but not by IA (93% versus 71%) (P = ns). Euploid status was a good prognostic indicator; 6 of 7 (86%) patients with euploid tumours by IA and 12 of 15 (80%) by FC (P < 0.05) survived more than 1 year. The sensitivity and specificity of euploidy was 93% and 28.6% for IA compared with 78.6% and 60% for FC. Since 33 (92%) of these tumours exhibited a marked peritumoral desmoplastic or chronic inflammatory reaction IA, being more sensitive to subtle nuclear change, may be a more appropriate technique than FC for evaluation of the role of ploidy in such tumours.

DNA quantification of squamous cell carcinoma of the oesophagus by flow cytometry and cytophotometric image analysis using formalin fixed paraffin embedded tissue.

This is the first comparative study of DNA quantification of oesophageal squamous cell carcinoma by flow cytometry (FCM) and image cytometry (ICM) using formalin fixed paraffin embedded tissue. The potential advantages of ICM include the identification of a reliable control cell population; avoidance of non-tumour stromal and inflammatory cell nuclei, nuclear fragments, degenerate cell nuclei and doublets, triplets etc., which are not possible with FCM using archival tissue. Twenty-eight cases, all of the same stage (stage 2a) and similar grade (well or moderately differentiated) were analysed. The cases were separated into two groups, those that had succumbed to tumour in less than 18 months (group A) and those that were tumour free at least 18 months post-resection (group B). Using ICM all 28 tumours yielded interpretable histograms by comparison to 25 of 28 using FCM. Aneuploidy was identified in 100% of cases in group A using ICM (in comparison to 73% by FCM) and in 73% of group B using ICM (in comparison to 44% by FCM). Any tumour aneuploid by FCM was also aneuploid by ICM. Nine cases aneuploid by ICM were euploid by FCM. The mean 5C exceeding rate (% of cells whose nuclei contain a DNA mass equivalent to > 5 sets of 23 chromosomes) was 21% in group A and 14% in group B (P < 0.01). Euploidy was confined to tumours of those patients disease free for more than 18 months. The conclusions of this study are that: firstly, ICM is superior in its yield of interpretable histograms to FCM using formalin fixed paraffin embedded tissue; secondly, ICM is more sensitive in the identification of aneuploid stemlines than FCM; and thirdly, euploid tumours (as detected by ICM) appear to have a better prognosis than aneuploid tumours of similar stage and grade.