Self monitoring of blood glucose concentrations by non-insulin dependent diabetic patients.
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Biomedical subjects
Publications and source records attributed to R Tattersall.
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L-asparaginase from Erwinia provides an alternative to the enzyme from E. coli for the effective treatment of acute lymphoblastic leukaemia. A procedure was required for the large-scale partial purification of the recombinant Erwinia enzyme cloned and expressed in Erwinia. Enzyme was extracted from Erwinia at high pH and extraneous protein precipitated at low pH. S-Sepharose FF was selected as the medium of choice for the chromatography step since it was adequate for the high flow rates required (linear flow rate 315 cm h-1) and the methylsulphonate functional groups exploited the high pI of the enzyme by allowing binding of L-asparaginase at pH 4.8 while most of the other proteins passed through the column. The useful capacity of the matrix was up to 34 mg enzyme/ml matrix at a linear flow rate of 95 cm h-1 and 15.4 mg enzyme/ml matrix at a linear flow rate of 315 cm h-1. Weakly bound protein was removed by a wash at pH 6.0. The L-asparaginase was eluted by a wash at pH 6.8 (linear flow rate 95 cm h-1) and was substantially pure, only requiring polishing steps to be suitable for use as a parenteral agent. The purity of the protein was complemented by a 92% recovery of active enzyme from this cation-exchange matrix.
OBJECTIVE: To determine the course of brittle diabetes. DESIGN: 12 year follow up of patients identified in 1977-9 as having brittle diabetes; retrospective review of the case notes. SETTING: Nottingham health district. SUBJECTS: 25 brittle diabetic patients were identified in 1979-9; 11 (five men) had three or more admissions with ketoacidosis between June 1977 and 1979 and 14 (eight men) had three or more attendances at the accident and emergency department with hypoglycaemia in 1978. Two controls from our diabetic register were matched to each patient for age, sex, and duration of diabetes. MAIN OUTCOME MEASURES: Frequency of ketoacidosis and severe hypoglycaemia in the 12 years after ascertainment; diabetic control and complications in 1988-90; retrospective attribution of the cause of brittleness. RESULTS: Patients with recurrent ketoacidosis had had a median (range) of 28 (8-67) episodes. One man died of a cerebral tumour but five of the surviving nine patients had not been admitted in the past two years, although diabetic control remained poor (median haemoglobin A1 concentration 14%). Seven patients had pure hypoglycaemic brittleness, and five had also had eight or more admissions with ketoacidosis (mixed brittleness). Two died of uraemia within a year after ascertainment and two others in hypoglycaemic coma seven and 12 years later. Brittle diabetes was in most cases related to a specific situation, usually unhappiness at home or school. CONCLUSIONS: Brittle diabetes is often episodic and almost always related to stressful life circumstances. Once the underlying cause is removed it tends to improve. Recurrent hypoglycaemic brittleness of psychological origin has a poor prognosis.
The free energies of formation of the peptide bond between carbobenzoxy-glycine and L-phenylalanine amide in aqueous solution at temperatures up to 60 degree C were calculated from experimentally determined equilibrium constants. The reaction was catalyzed by a thermophylic enzyme. The thermodynamic energy barrier to peptide bond formation was found to decrease with increasing temperature: the standard free energy of peptide bond formation did appear to become negative in the region of 60 degrees C. The possible significance of these results for peptide bond formation under prebiotic conditions is discussed.
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