Evidence for the presence of pro-oxytocin/neurophysin-converting enzyme in the human ovary

The activity of pro-oxytocin/neurophysin (pro-OT/Np)-processing enzymes was determined in human granulosa cells, follicular fluids and purified secretory granules of corpora lutea. We detected the presence of an endoprotease which releases OT-Gly10-Lys11-Arg12 on cleavage of the synthetic pro-OT/Np(1-20) peptide after the dibasic Lys11-Arg12 doublet. This endoprotease was inhibited by EDTA, but was not affected by phenylmethanesulfonyl fluoride and pepstatin. Enzymatic activity was markedly reduced by replacement of L-Arg by D-Arg in the basic amino acid doublet of the substrate. The molecular weight of this enzyme was estimated to be 60 kDa. These features closely resembled those of the endoprotease identified in the bovine pituitary. The endoprotease is a metalloenzyme, specific for the Lys-Arg doublet. We also detected a carboxypeptidasic activity, inhibited by guanidinoethane-mercaptosuccinic acid. In the light of our previous detection of the processing intermediates, OT-Gly-Lys-Arg, OT-Gly-Lys and OT-Gly, in human ovary, these observations are in favour of a pro-OT/Np-processing pathway in the human ovary comparable with that in the bovine ovary. Moreover, these results confirm that oxytocin post-translational processing occurs in the human ovary and strongly suggest that pro-OT/Np is synthesized locally.     

Abrasive wear in filled elastomers

The abrasive wear of rubbers is strongly affected by the filler particles dispersed in the elastomer matrix. The fillers are incorporated usually for the purposes of mechanical reinforcement and improving the conductivity of the neat resins. It is found that the wear rates of the filled silicone rubbers increase slowly with filler concentration until a critical volume fraction,v _c, is reached, at which point they increase very rapidly with increasing filler concentration. This behaviour appeared to be universal in all the filled silicones we studied, regardless of the type of filler and silicone rubber used. However the magnitude of the critical filler fraction,v _c, can be changed significantly with the filler shape, resin cross-linking density and filler surface treatments. No reasonable relationship could be found between this wear behaviour and the mechanical properties measured in a macroscopic manner. Experimental evidence suggests that the incipient cracks that lead to wear losses may start within the thin layers of highly stressed material, the damage zones, surrounding the rigid particles. A simple model taking into account the stress concentration induced by the rigid fillers shows excellent correlation between the wear rate and the damage zones volume. With this new model, the observed wear behaviours can be explained satisfactorily.     

Loss of heterozygosity and overexpression of the p53 gene in ovarian carcinoma

Eight anticonvulsant drugs-including clonazepam, diazepam and phenobarbital-were tested for their effects on GABA-stimulated chloride uptake in rat cerebral cortical microsacs (unfiltered synaptoneurosomes). "Mid" and "high" therapeutic concentrations were screened, and, if significant enhancement was found, full concentration-response tests were done. In the initial screens, enhancement of GABA-stimulated uptake was found only with phenobarbital, clonazepam and diazepam. In subsequent concentration-response tests, the effects of phenobarbital were found to occur throughout the range of normal, anticonvulsant concentrations, whereas the effects of clonazepam and diazepam were observed only above the concentrations normally used for the chronic control of seizures or anxiety. These data suggest that phenobarbital's anticonvulsant effects are mediated via the GABAA receptor complex, but that the low-dose effects of the benzodiazepines may be mediated via some other mechanism.     

In vivo fluorescence microscopy for the assessment of microvascular reperfusion injury in small bowel transplants in rats

With the use of in vivo fluorescence microscopy we have analyzed microvascular reperfusion injury of small bowel isograft transplants in rats. Following 1 hr cold storage in University of Wisconsin solution, the small bowel was transplanted heterotopically, and the intestinal microcirculation was quantitatively analyzed 20-60 min after onset of reperfusion. The intestinal grafts' capillary perfusion of both the mucosa and the circular and longitudinal muscles was not found altered when compared with the intestinal capillary perfusion of sham-operated controls. In contrast, leukocyte-endothelial cell interaction, including leukocyte rolling (40 +/- 5%) and sticking (280 +/- 100 mm-2) in submucosal postcapillary venules, was significantly increased when compared with nontransplanted controls (12 +/- 8% and 20 +/- 10 mm-2, P < 0.01 and P < 0.05, respectively). Leukocyte-endothelial cell interaction was associated with a marked alteration of lymphatic capillary drainage, as indicated by the low functional density of lymphatic microvessels of 10.2 +/- 6.1 cm-1 (P < 0.01 vs. sham-operated controls (39.2 +/- 6.1 cm-1)). From these results we propose that leukocyte-endothelial cell interaction, not capillary "no-reflow," is the primary step in the manifestation of microvascular reperfusion injury following a short period of cold ischemia in small bowel grafts.     

Phosphofructokinase from mantle tissue of Mytilus galloprovincialis. Purification and effects of phosphorylation on the enzymatic activity

Phosphofructokinase purified from mantle tissue of the sea mussel Mytilus galloprovincialis, was phosphorylated "in vitro" by the catalytic subunit of cyclic AMP-dependent protein kinase. The incorporation of phosphate gave rise to an activation of the enzyme by increasing its affinity for fructose-6-phosphate, by decreasing its sensitivity to the inhibition by ATP and by enhancing the effect of allosteric activators (5'-AMP and fructose-2,6-bisphosphate). In addition, the effects of phosphorylation on the catalytic activity are pH-dependent.     

Introduction to the special section on contemporary issues in human sexuality: research and practice

Critical issues in human sexuality have changed markedly during the past decade and so have the contributions of psychology to the evaluation and treatment of sexual behavior problems. Some of the greatest challenges facing psychologists today include the increasing emphasis on medical interventions for the male sexual disorders and the relative decline of traditional behavioral sex therapies, the recalcitrance of sexual desire disorders, the prevention of "unsafe" sexual behavior, and the limited understanding of female sexuality. This overview introduces a series of 5 articles that examine these selected critical issues in human sexuality. Guidelines for clinical practice and directions for future research are highlighted.     

The myth of Eve: molecular biology and human origins

It has been proposed that modern humans descended from a single woman, the "mitochondrial Eve" who lived in Africa 100,000 to 200,000 years ago. The human immune system DRB1 genes are extremely polymorphic, with gene lineages that coalesce into an ancestor who lived around 60 million years ago, a time before the divergence of the apes from the Old World monkeys. The theory of gene coalescence suggests that, throughout the last 60 million years, human ancestral populations had an effective size of 100,000 individuals or greater. Molecular evolution data favor the African origin of modern humans, but the weight of the evidence is against a population bottleneck before their emergence. The mitochondrial Eve hypothesis emanates from a confusion between gene genealogies and individual genealogies.