Two novel mutations in the gene for copper zinc superoxide dismutase in UK families with amyotrophic lateral sclerosis.
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Biomedical subjects
Publications and source records attributed to J Wilkinson.
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The case is described of a 36 year old woman who presented with a large left sided haemothorax. A thoracic computed tomographic (CT) scan suggested there was a bony outgrowth arising from the fourth rib. This was resected surgically and found to be an osteochondroma which was surrounded by blood clot. No definite site of bleeding was identified, but it is thought that the tumour may have traumatised the lung, the pericardiacophrenic artery, or the superior pulmonary vein, resulting in life threatening haemorrhage.
The aim of this research was to determine whether apolipoprotein[a] (apo[a]) is linked to apolipoprotein B (apoB) in human liver. Four ELISAs were developed: 1) a competition assay that measures apoB; 2) a competition assay that measures apo[a]; 3) a capture assay based on capture of apo[a] by a polyclonal antibody and detection of co-immobilized apoB using a monoclonal antibody; and 4) a capture assay based on capture of apo[a] using a polyclonal antibody and detection of immobilized apo[a] using a monoclonal antibody. Assays 2 and 4, therefore, measure apo[a] either free or in complex with other proteins, while assay 3 measures apo[a] associated with apoB. The levels of apo[a] ranged from 25 to 440 micrograms/g liver in nine individual liver samples. There was no significant difference between apo[a] levels in individual human liver samples measured using ELISA 1 or 3; however, it was not possible to detect apo[a]/apoB using assay 3. ApoB was present in human liver homogenates at levels ranging from 90 to 700 micrograms/g measured using assay 1. These results suggest, therefore, that apo[a] is not coupled to apoB in the liver and may be secreted in the free form to bind with low density lipoprotein (LDL) in the extracellular fluid or plasma.
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In the antibiotic era the ophthalmologist has become less familiar with the diagnosis of congenital syphilis. The recognition of this disease is crucial, as neurosyphilis or cardiovascular syphilis will develop in a substantial number of patients with latent congenital syphilis without the appropriate treatment. We describe eight patients aged 60 years or more who presented with refractive problems in whom congenital syphilis was subsequently diagnosed for the first time. One patient was found to have neurosyphilis and the highest VDRL result ever recorded by the London Public Health Laboratory. Seven patients required extensive antibiotic therapy, and three subsequently underwent successful ocular surgery. These cases illustrate the importance of recognizing this treatable disease.
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Injury to the subclavian artery or its branches is uncommon after blunt trauma. We report a case of blunt thoracic trauma resulting in avulsion of the right internal mammary artery from its origin on the subclavian artery. This presented as an atypical mediastinal hematoma in a patient with multiple injuries.
In order to identify drugs active against mutated ras oncogenes we have developed an in vitro assay employing two clones of the human fibrosarcoma cell-line, HT1080 which carries an N-ras gene mutated at codon 61. Clone, HT1080scc2, retains the transformed phenotype of the parental line, whilst the other, HT1081c, is a morphologically flat, non-tumourigenic, revertant with under-representation of the chromosome carrying the transforming N-ras allele. The clear implication of mutant ras in maintaining the transformed nature of HT1080scc2 was confirmed when these cells were microinjected with the pan ras neutralising antibody Y13-259, which resulted in the morphological detransformation of these cells to a phenotype resembling that of the HT10801c clone. A number of known anti-cancer drugs with modes of action unrelated to ras function were found to be equipotent against both clones. However, when compounds chosen on the grounds of their potential selective cytotoxic or differentiating activity were tested some interesting results were obtained. Thus 8-bromo cAMP affected some morphological detransformation of HT1080scc2 cells and reduced their colony forming potential. The IMP-dehydrogenase inhibitors, tiazafurin and mycophenolic acid also flattened the morphology of the transformed clone. Fumagillin, an antibiotic reported to exhibit selective activity against ras transformed cells showed very marked and selective cytostatic effects against HT1080scc2 cells with IC50 values as low as 1 x 10(-11) M.
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Epilation in the pig has been quantified following single exposures of X-rays in the range 1.0-25.0 Gy. The number of hairs in each field was determined by counting hairs from photographic negatives weekly for 10 weeks following irradiation, and the percentage hair loss was calculated for each individual field from an initial unirradiated control value. Hair loss was dose-dependent for exposures between 1.0 and 15.0 Gy and this response was linearly related to dose. No further increase in hair loss was observed for doses > or = 15.0 Gy, as 20-30% of the hairs remained. It was assumed that these hairs were not actively growing at the time of irradiation and did, therefore, not express damage. The ED50 for the loss of > or = 30% of hairs was 3.8 Gy whilst that for the loss of > or = 50% of hairs was 6.8 Gy and for the loss of > or = 67% of hairs was 12.5 Gy. There was +/- 7% hair loss per Gy exposure for doses between 0.0 and 15.0 Gy. Quantification of hair loss provided a more sensitive assay than the use of visual scoring systems. Hair loss was detectable within 4 weeks of irradiation. The system is simple, non-invasive and appears to have considerable potential for use as a biological dosimeter.