Thermal inactivation and chaperonin-mediated renaturation of mitochondrial aspartate aminotransferase.

Mitochondrial aspartate aminotransferase is inactivated irreversibly on heating. The inactivated protein aggregates, but aggregation is prevented by the presence of the chaperonin 60 from Escherichia coli (GroEL). The chaperonin increases the rate of thermal inactivation in the temperature range 55-65 degrees C but not at lower temperatures. It has previously been shown [Twomey and Doonan (1997) Biochim. Biophys. Acta 1342, 37-44] that the enzyme switches to a modified, but catalytically active, conformation at approx. 55-60 degrees C and the present results show that this conformation is recognized by and binds to GroEL. The thermally inactivated protein can be released from GroEL in an active form by the addition of chaperonin 10 from E. coli (GroES)/ATP, showing that inactivation is not the result of irreversible chemical changes. These results suggest that the irreversibility of thermal inactivation is due to the formation of an altered conformation with a high kinetic barrier to refolding rather than to any covalent changes. In the absence of chaperonin the unfolded molecules aggregate but this is a consequence, rather than the cause, of irreversible inactivation.

Acute adrenal insufficiency: hemodynamic and echocardiographic characteristics.

A patient with high output circulatory failure due to acute secondary adrenal insufficiency is described. The hemodynamic similarities and echocardiographic differences between volume expanded cortisol deficiency and septic shock are identified.

Vulnerability to childhood problems and family social background.

The relationship between family social background and risks of problems in the areas of health, education, behaviour and offending was examined in a birth cohort of New Zealand children studied to the age of 11 years. The analysis showed the presence of small consistent correlations between family social background and individual outcomes on a range of childhood measures. These correlations ranged from 0.12 to 0.31 with a median value of 0.18. The association between family social background and childhood outcomes was modelled using LISREL modelling methods which assumed that this association was mediated by common non-observed vulnerability processes. This analysis suggested that while variations in family social background act as relatively weak determinants of specific problem outcomes, these factors had a relatively strong influence on the child's generalized vulnerability to a wide range of childhood problems. The implications of these results for research into social background and childhood are discussed.

Hyperkalemic electromechanical dissociation.

Two patients with hyperkalemic electromechanical dissociation are described. Electrocardiograms at the time of the cardiac arrests demonstrated normal appearing QRS complexes. Both patients responded to intravenous calcium chloride administration with prompt restoration of normal blood pressure. Implications of these observations with respect to current advanced cardiac life support guidelines are discussed.

The relationships between neuroticism and depressive symptoms.

A structural equation model designed to estimate the reciprocal associations which may exist between mental state and personality trait variables is presented. This model is applied to measures of neuroticism and depression obtained for a sample of over 1000 women studied over a two year period. The fitted model suggests that while measures of neuroticism are contaminated by the effects of short term mental state on the reporting of personality, there is still a fairly substantial relationship between trait neuroticism (corrected for the effects of mental state contamination) and reports of depressive symptoms.

The Christchurch Child Development Study: a review of epidemiological findings.

The Christchurch Child Development Study is a longitudinal study of a birth cohort of 1265 New Zealand children who have been studied over an 11-year period using data from multiple sources including parental interview, medical records, teacher questionnaires and direct testing of children. The article provides a review of the major lines of epidemiological research examined in the Study. These include: breast feeding and child health; parental smoking and child health; the effects of low level lead exposure; childhood asthma; nocturnal bladder control; the effects of early hospital admission; the distribution of child health services; and the consequences of private medical insurance. In addition a number of general topics (sample attrition, measurement error, individual differences and causal inference) relating to longitudinal designs are discussed briefly. It is concluded that the longitudinal design is a powerful and cost-effective method of gathering data for general paediatric epidemiological purposes but that research in this area would benefit from an increased use of emerging methods of statistical modelling.

Neonatal circumcision and penile problems: an 8-year longitudinal study.

The prevalence of penile problems was examined in a birth cohort of more than 500 New Zealand children studied from birth to 8 years of age. By 8 years, circumcised children had a rate of 11.1 problems per 100 children, and uncircumcised children had a rate of 18.8 per 100. The majority of these problems were for penile inflammation including balanitis, meatitis, and inflammation of the prepuce. However, the relationship between risks of penile problems and circumcision status varied with the child's age. During infancy, circumcised children had a significantly higher risk of problems than uncircumcised children, but after infancy the rate of penile problems was significantly higher among the uncircumcised. These associations were not changed when the results were adjusted statistically for the effects of a series of potentially confounding social and perinatal factors.

Acute oxalate nephropathy after massive ascorbic acid administration.

A single 45-g dose of intravenous ascorbic acid, a metabolic precursor of oxalate, was administered to a patient as adjuvant therapy for primary amyloidosis and the nephrotic syndrome. Acute oliguric renal failure occurred. Postmortem histopathologic examination of renal tissue revealed extensive intratubular deposition of crystalline material, which was confirmed as calcium oxalate by a microincineration technique. There were no extrarenal deposits of calcium oxalate. Plasma oxalate and ascorbic acid concentrations were increased. We conclude that therapy with high-dose ascorbic acid is a potential cause of oxalate nephropathy.