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J M Duffy

Publications and source records attributed to J M Duffy.

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The detection, quantification and partial characterisation of cathepsin B-like activity in human pathological synovial fluids.

In this study, the levels of the cysteine proteinase--cathepsin B were measured in diseased synovial fluids using a steady state fluorometric assay. Cathepsin B-like activity was shown to be present in all the samples analysed, with the rheumatoid arthritic synovial fluids possessing significantly higher concentrations (mean value ca. 416 mg/l) than the osteoarthritic fluids (mean value ca. 142.4 mg/l). In addition, upon treatment with pepsin, all of the rheumatoid arthritis samples were shown to possess additional cathepsin B-like activity, suggesting the presence of a reservoir of latent precursor molecules. By utilising a recently developed biotinylated affinity label for cathepsin B-like proteinases and sheep anti-(human cathepsin B) antibodies, used in combination with SDS-PAGE and Western blotting, the rheumatoid arthritic synovial cathepsin B was shown to exist in two forms with apparent molecular masses of M(r) 29,000 and 42,000. We propose that the former is a functionally active proteinase, whereas the latter is a pepsin activatable proform which, when cleaved by this aspartyl proteinase, is converted into a catalytically competent species of M(r) 20,000.

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1H-nuclear magnetic resonance studies of human synovial fluid in arthritic disease states as an aid to confirming metabolic activity in the synovial cavity.

1. A 1H-n.m.r. method was used to measure concentrations of valine, alanine, lactate, acetate, hyaluronan and lipids in synovial fluid obtained, during the normal course of examination from the knee joints of patients attending rheumatology and orthopaedic clinics. Fluid was available from 16 patients with osteoarthritis, 18 patients with rheumatoid arthritis, four patients with meniscal tear and one patient each with systemic lupus erythematosis, mono-arthritis, synovitis and loose bodies. Four normal specimens were obtained for comparison. 2. Valine, alanine and acetate levels all showed a normal Gaussian distribution, reflecting the distributions within the serum of the sample population. 3. Lactate concentrations divided into two distinct patterns. At concentrations below 2.5 mmol/l the lactate levels showed a Gaussian distribution, reflecting the distribution in normal serum. The normal synovial fluid specimens belong to this distribution. Above 2.5-3.0 mmol/l, lactate levels were asymmetric in distribution with a long tail at higher concentrations. These high levels of lactate can be explained by the generation of lactate through anaerobic metabolism within the synovial cavity. This metabolic process is triggered by a general inflammatory condition such as in rheumatoid arthritis. 4. The distribution of n.m.r.-observable lipid concentrations in rheumatoid arthritis and osteoarthritis each shows a normal distribution and the mean concentration is significantly higher in rheumatoid arthritis. 5. An increased n.m.r.-observable hyaluronan concentration is associated with an inflammatory situation. 6. It is concluded that raised levels of lactate and n.m.r.-observable hyaluronan and lipids are useful markers to aid the clinical distinction between rheumatoid arthritis and osteoarthritis.(ABSTRACT TRUNCATED AT 250 WORDS)

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Farmer's hip.

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Agricultural Workers' Diseases↗

Aphasia, apraxia, and agnosia in the diagnosis of dementia.

The association of aphasia, apraxia and agnosia with cortical but not subcortical dementias, is a widely held belief. The purpose of the present study was to determine the frequency of aphasia, apraxia, and agnosia in groups of cortical and subcortical dementia patients, and to assess the diagnostic utility of these symptoms. Subjects were 64 patients with subcortical dementias (Parkinson's disease and normal pressure hydrocephalus) and 192 patients with cortical dementia (probable Alzheimer's disease) matched for sex, age, and Mini-Mental State Examination score. Each patient was evaluated for the presence of aphasia, apraxia, and agnosia. Results indicated that only aphasia was reported significantly more often in cortical dementia patients than in subcortical dementia patients. The presence of either of these three symptoms has very low diagnostic sensitivity, specificity, and total predictive value. The severity of the patient's dementia was predicted whether the patient had aphasia or apraxia; type of dementia had no predictive value. These data led to the conclusion that cortical and subcortical dementias cannot be reliably dissociated on the basis of aphasia, apraxia, or agnosia.

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