Fasting insulin and left ventricular mass in hypertensives and normotensive controls.

The mechanism by which increased left ventricular (LV) mass leads to increased coronary heart disease morbidity and mortality is unknown. We evaluated the relation between fasting insulin and echocardiographic LV mass in hypertensives off medication and normotensive controls, controlling the analyses for blood pressure (BP) and body mass index (BMI). Fasting insulin (p = 0.0217) was the most significant predictor of LV mass in hypertensives, while BMI (p = 0.0265) and diastolic BP (p = 0.0159) were the only significant predictors of LV mass in controls. The relation between fasting insulin and LV mass was not confounded by obesity in hypertensives, but obesity and fasting insulin may interact to predict LV mass.     

Evidence that the enhancement of dopamine function by repeated electroconvulsive shock requires concomitant activation of D1-like and D2-like dopamine receptors

In this study, the behavioural response to dopamine D₁-like receptor agonists (SKF 38393, SKF 81297 and SKF 77434) and D₂-like receptor agonists (quinpirole and RU 24213), administered alone and in combination to rats treated repeatedly with electroconvulsive shock (five ECS over 10 days) or sham, was tested. Agonist-induced behaviour was monitored by automated activity meters and direct observation using a checklist scoring method. Repeated ECS (compared to sham controls) had no significant effect on the behavioural response to SKF 38393 (7.5 mg/kg SC), SKF 81297 (0.2 mg/kg SC), SKF 77434 (0.1 mg/kg SC), quinpirole (0.1 and 0.25 mg/kg SC) or RU 24213 (0.3 mg/kg SC), when administered alone. In contrast, repeated ECS markedly increased locomotion (activity counts and scores) induced by the non-selective dopamine agonist apomorphine (0.5 mg/kg SC) and by co-administration of a D₁-like agonist plus a D₂-like agonist [SKF 38393 (7.5 mg/kg SC) plus quinpirole (0.25 mg/kg SC), SKF 81297 (0.2 mg/kg SC) plus quinpirole (0.1 mg/kg SC), and SKF 77434 (0.1 mg/ kg SC) plus RU 24213 (0.3 mg/kg SC)]. This ECS-induced enhancement of dopamine-mediated behaviour was observed for up to 3 weeks after cessation of ECS treatment. In addition, ECS also enhanced the locomotor response to intra-accumbens SKF 38393 plus quinpirole (0.4 and 1.0 μg/side, respectively). These results provide evidence that the enhancement of dopamine function by repeated ECS requires concomitant stimulation of both D₁-like and D₂-like receptors, and that this effect is long-lasting. Received: 24 January 1997 /Final version: 5 March 1997     

Restoring and preserving trust in biomedical research.

Recent media depictions of the dangers of biomedical research have fueled public and regulatory scrutiny of academic research institutions. The authors argue that if these institutions are to preserve the trust that the public has historically bestowed upon them, they must go beyond mere compliance with regulatory mandates. Several steps are suggested that institutions can take to strengthen and supplement ongoing compliance efforts, steps the authors believe will bolster the public's confidence in the integrity of academic research institutions. These steps grow out of the authors' analysis of three key components of institutional trustworthiness: (1) shared goals between research institutions and the communities they serve, (2) robust institutional oversight of research activities, and (3) training programs that build professional character. The authors' recommendations include the use of research advisory councils to assure the public that research goals reflect community interests, more collaborative relationships between institutional review boards and members of investigative teams, and educational programs that emphasize the importance of professional integrity in biomedical research. These efforts will help preserve public confidence that an institution's research priorities are appropriate and that the research it conducts is ethical. Preserving this public trust is central to the long-term success of biomedical research and the institutions in which such research takes place.     

Heat shock protein hsp72 induction in cortical and striatal astrocytes and neurons following infarction

Transient global and transient focal ischemia induced the 72 kDa heat shock protein (hsp72) in neurons in cortex, striatum, and other regions known to be injured during transient ischemia. A novel finding was the induction of hsp72 in islands (cylinders in three dimensions) of cells composed of astrocytes around the perimeter and neurons in the interior. Since histology showed pale staining in these regions, it is proposed that these islands represent areas of focal infarction in the distribution of small cortical and lenticulostriate arteries. Although the factors responsible for hsp72 induction during ischemia and infarction are unknown, these results suggest differences in mechanisms of hsp72 induction in astrocytes compared to neurons.     

Features of MotA proton channel structure revealed by tryptophan-scanning mutagenesis.

The MotA protein of Escherichia coli is a component of the flagellar motors that functions in transmembrane proton conduction. Here, we report several features of MotA structure revealed by use of a mutagenesis-based approach. Single tryptophan residues were introduced at many positions within the four hydrophobic segments of MotA, and the effects on function were measured. Function was disrupted according to a periodic pattern that implies that the membrane-spanning segments are alpha-helices and that identifies the lipid-facing parts of each helix. The results support a hypothesis for MotA structure and mechanism in which water molecules form most of the proton-conducting pathway. The success of this approach in studying MotA suggests that it could be useful in structure-function studies of other integral membrane proteins.