Gonadal steroids have paradoxical effects on brain oxytocin receptors

Specific brain receptors for oxytocin have been described in several mammalian species. The distribution of these receptors differs greatly across species and in the rat, receptor binding in specific brain regions appears to depend upon gonadal steroids. This study used in vitro receptor autoradiography to examine the effects of testosterone on oxytocin receptor binding in the mouse forebrain. Three groups of male mice were compared: castrates treated with blank capsules, castrates treated with testosterone filled capsules, and intact males. Irrespective of steroid treatment, the distribution of oxytocin receptors in mouse forebrain differed markedly from patterns previously described in the rat. In addition to these species differences in receptor distribution, testosterone had effects in the mouse which differed from the induction of receptors previously reported in the rat. In the mouse ventromedial nucleus of the hypothalamus, binding in the untreated castrate males was approximately double that observed in either the intact or the testosterone-treated castrates. In other regions of the mouse brain, such as the intermediate zone of the lateral septum, binding to oxytocin receptors was increased with testosterone treatment. These results suggest that the brain oxytocin receptor varies across species not only in its distribution but also in its regional regulation by gonadal steroids. These apparently paradoxical changes in oxytocin receptor binding may result from either direct or indirect effects of gonadal steroids in mouse brain.     

Molecular mechanisms in the control of limb regeneration: the role of homeobox genes

The Ca2+ sensitivity of cardiac myofibrillar force production can be decreased by acidosis or inorganic phosphate (P(i)) and increased by caffeine. To investigate whether the source of tissue influences the potency of these agents, we compared the actions of acidosis (change of pH from 7.0 to 6.2), P(i) and caffeine (both 20 mM) on force production of skinned cardiac muscles from adult ventricle, adult atrium and neonate ventricle of the rat. Maximum Ca(2+)-activated force was reduced by all three interventions and the responses of the different muscle types to a given intervention were similar. Acidosis reduced myofibrillar Ca2+ sensitivity by 1.09 and 1.04 pCa units in adult ventricle and atrium, respectively, and P(i) reduced it by 0.19 and 0.22 pCa units. However, each effect was only one-third as great in the neonate ventricle, which showed falls of 0.33 pCa units for acidosis and 0.06 for P(i). In contrast, caffeine raised the Ca2+ sensitivity by the same amount (approximately 0.4 pCa units) in all three muscle types. The differential effect between adult and neonate seen with both acidosis and P(i) suggests some similarity in the mechanisms by which these factors decrease Ca2+ sensitivity. In contrast, the equal effects of caffeine on neonate and adult suggests that caffeine acts by a completely different mechanism. The lower pH- and P(i)-sensitivity of the neonatal ventricle can help to explain why neonatal and adult myocardium exhibit differential force responses to ischaemia (or hypoxia alone).     

Some Thoughts on the Evolution of Work Teams in Organizations

In this time of flat, team-based and technology-enabled organizations the effectiveness of communication and team leadership practices will be more important than ever before. Therefore, we believe that some of the earlier, time-tested classic works on group dynamics and leadership are worthy of re-reading. We are particularly impressed by how relevant one of the oldest classics, Benne and Sheats' (1948) article on functional roles of group members, remains to this day.     

Role of newly synthesized cholesterol or its metabolites on the regulation of bile acid biosynthesis after short-term biliary diversion in the rat

Cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in the bile acid biosynthetic pathway, is thought to be regulated by hydrophobic bile acids through negative feedback control. The role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase is more controversial, in part because of incomplete understanding of the relationship between the pathways of cholesterol synthesis and degradation. The main objective of this study was to define the interaction between these two pathways in an experimental model in which the supply of newly synthesized cholesterol was interrupted by sustained infusion of mevinolin (lovastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) or accelerated by a continuous infusion of mevalonate, a cholesterol precursor. The study was carried out in rats subjected to short-term bile fistula. In one set of experiments, rats were treated postoperatively with mevinolin (5 mg/kg loading dose followed by 2 mg/kg/hr infusion), mevalonate (180 mumol/hr infusion) or both for up to 96 hr. In a separate set of experiments, rats were infused intraduodenally with taurocholate (36 mumol/100 gm/hr for up to 96 hr). We determined cholesterol 7 alpha-hydroxylase- and HMG-CoA reductase specific activities at those time intervals, whereas bile acid synthesis rates were determined throughout the study. Compared with rats not subjected to surgery, rats with short-term biliary diversion had increases in cholesterol 7 alpha-hydroxylase activity of 259% and 827% at 48 and 96 hr, respectively. The increase in bile acid biosynthesis was less pronounced. Continuous infusion of mevinolin completely prevented increases in cholesterol 7 alpha-hydroxylase specific activity and bile acid biosynthesis at both time intervals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Imaging of hippocampal and neocortical neural activity following intravenous cocaine administration in freely behaving cats

We examined spatial-temporal patterns of neural activity, as inferred from 700 nm light reflectance, from the dorsal hippocampus and surrounding neocortex in seven freely behaving cats following 1.5, 2.5, 3.5 and 5.0 mg/kg intravenous cocaine administration. Images were acquired using a new technique which gathered reflected light from cortical and subcortical structures. Cardiac and respiratory patterning, collected simultaneously with optical images, revealed increased rates and diminished variation after intravenous cocaine administration. Cocaine increased reflectance correlates of hippocampal neural activity in a dose-dependent fashion over a 120 min period, with a lengthening time-to-peak effect (22-76 min). The largest dose resulted in an initial decrease, followed by the greatest enhancement in neuronal activity. Correlates of neural activation in the neocortex displayed an inverse dose-response curve to that found in the hippocampus; the time-to-peak effect was shorter (6-43 min) and the maximal change was reduced. Regional patches and bands of activation occurred during the period of the cocaine response, and were more pronounced in the hippocampus than the neocortex. Procaine, administered in a similar dose, slightly increased neural activity for 10 min in both the hippocampus and neocortex, and elicited a small increase in respiration. Cocaine induces a pronounced enhancement of neural activation in the neocortex and dorsal hippocampus; the time course of activation in the hippocampus parallels an increased respiratory pattern and outlasts the neocortical response. We speculate that hippocampal activation may be related to the profound respiratory acceleration found in response to cocaine.     

Receptor editing in self-reactive bone marrow B cells

A central paradigm of immunology is clonal selection: lymphocytes displaying clonally distributed antigen receptors are generated and subsequently selected by antigen for growth or elimination. Here we show that in mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Transgenic bone marrow B cells encountering membrane-bound Kb or Kk proteins modify their receptors by expressing the V(D)J recombinase activator genes and assembling endogenously encoded immunoglobulin light chain variable genes. This (auto)antigen-directed change in the specificity of newly generated lymphocytes is termed receptor editing.     

Stability of proximal femoral grafts in canine hip arthroplasty

In a canine model, the fixation stability of a prosthesis and proximal bone graft composite were measured relative to the distal femur. One group had the prosthesis graft composite cemented into the distal femur. The second group had the prosthesis graft composite press fit into the distal femur for biologic ingrowth. Displacements of the proximal femoral grafts relative to the host bone in each group were measured after ex vivo (acute with graft) implantation and 4 months after implantation. A third group with no osteotomy (acute intact) simulated perfect graft to host bone union. Relative displacements representing 6 degrees freedom (translation and rotation) were calculated from the displacement values measured by 9 eddy current transducers. Measurements of displacement were used to test the hypothesis that distal press fit fixation equals distal cement fixation at 4 months after implantation. In all cases the measured translations and rotations of the graft to implant construct were small and of a magnitude that should encourage bone ingrowth (< 0.05 mm and < 0.1 degree, respectively). The stability of the press fit group at 4 months was not significantly different from the cemented group in axial and transverse displacement during axial and transverse loading, respectively. There was no difference in stabilities at 4 months between distal press fit and cemented fixation in hip replacements requiring a proximal femoral graft.