Kynurenine aminotransferase activity in human liver: identity with human hepatic C-S lyase activity and a physiological role for this enzyme

The C-S lyase enzymes are responsible for the generation of mutagenic and cytotoxic metabolites via aberrant drug-metabolising pathways in mammalian tissues. We have examined human hepatic cytosolic, mitochondrial and microsomal fractions for evidence of C-S lyase activity. The cytosolic enzyme was purified using fast protein liquid chromatography over FFQ Sepharose, Mono P and Superose 12. An homogeneous protein (monitored by SDS-PAGE) was obtained following purification, and an 11-fold increase in C-S lyase specific activity was observed. The molecular weight of the enzyme was found to be 37 kDa in denaturing conditions, 82.3 kDa in non-denaturing conditions, and the C-S lyase activity was shown to co-purify with kynurenine aminotransferase activity when the transaminase activity of the enzyme was examined with kynurenine as the substrate.     

Quality of Life in Progressive Ovarian Cancer

When ovarian cancer progresses, goals change from cure to prolongation of life with the best possible quality for the patient. Criteria for futility must be established to guide the transition from active to palliative management. Pain control can be achieved by following established WHO guidelines. Continued education of the medical community, legislators, and the public is needed to assure pain control for the cancer patient. Limited surgery or radiation can be used to control symptoms from locally progressive disease. Other symptoms to be actively controlled include nausea and vomiting, nutrition, hydration, and fatigue. Support services, including home services, psychological counseling, and nutritional support need funding for both home and hospital settings. Quality of life assessment must be as specific as possible and address the patient's concerns by self-assessment techniques. Funding must be provided to develop specific quality of life tools and to then apply them clinically, both as part of research protocols and to assess success of palliative care.     

Use of the objective structured clinical examination for assessment of vocational trainees for general practice

General practice training schemes currently have no structured methods of assessment and most rely on a variety of subjective ratings of performance. In West Cumbria the `objective structured clinical examination' has been used to assess training performance in areas covered by small group teaching during the preceding terms. Consultation skills, interpretation of clinical data and a number of aspects of practice management were tested. The examination was conducted in the local postgraduate centre and assessed 20 trainees. Each trainee received feedback of his performance on each problem set and also an overall comparison with his peers.

This method of assessment appeared to be well received by trainees and was practicable within the limited resources available. In addition, the variety of problems set allowed for a broad range of trainees' performances to be assessed.

     

The stability and chemical stress relaxation of peroxide cured polyurethane elastomers

The chemical stress relaxation of two polyurethane elastomers Genthane S and Adiprene CM has been studied in air and in nitrogen in the temperature range 60 to 150°C. Both continuous and intermittent stress relaxation measurements were made on well characterized samples covering a range of crosslink densities. Scission and crosslinking reactions were observed for both the polyester based Genthane S and the polyether based Adiprene CM. The degradation of Genthane S is largely non oxidative and the scission reaction involves the main chain. The behaviour of Adiprene CM under nitrogen broadly resembles that of Genthane S; it differs from Genthane S in that it also undergoes an oxidative reaction. Activation energies for the scission and crosslinking processes were evaluated from kinetic analysis. Pretreatment of the elastomers with isocyanates inhibits both of these reactions. A mechanism involving the urethane group is proposed to account for the degradation behaviour and the role of water in this respect is discussed briefly.     

A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C

Background: There is increasing interest in the influence of host genetic factors on hepatic fibrosis, and whether genetic markers can reliably identify subjects at risk of developing severe disease. We hypothesised that hepatitis C virus (HCV) infected subjects with progressive fibrosis, classified using strict criteria based on histology at biopsy in addition to disease duration would be more likely to inherit several genetic polymorphisms associated with disease progression compared with subjects with a low rate of disease progression. Methods: We examined polymorphisms in eight genes that have been reported to have an association with hepatic fibrosis. Results: Associations between polymorphisms in six genes and more rapidly progressing fibrosis were observed, with individual adjusted odds ratios ranging from 2.1 to 4.5. The relationship between rapidly progressing fibrosis and possession of ⩾3, ⩾4, or ⩾5 progression associated alleles was determined and the adjusted odds ratios increased with increasing number of progression associated alleles (9.1, 15.5, and 24.1, respectively). Using logistic regression analysis, a predictive equation was developed and tested using a second cohort of patients with rapidly progressing fibrosis. The predictive equation correctly classified 80% of patients in this second cohort. Conclusions: This approach may allow determination of a genetic profile predictive of rapid disease progression in HCV and identify patients warranting more aggressive therapeutic management.