Manipulation of aggressive behavior in adult DBA/2/Bg and C57BL/10/Bg male mice implanted with testosterone in silastic tubing

Adult DBA/2/Bg and C57BL/10/Bg male mice were orchidectomized and implanted subcutaneously with one of two doses of testosterone (T) in Silastic tubing. Steroid doses which resulted in significant atrophy and hypertrophy of accessory sex tissues were determined for each strain. Relative to sham-castrated vehicle-implanted controls, both hypophysiological and hyperphysiological implants caused augmentation of aggression in C57BL/10/Bg males. In DBA/2/Bg mice, the hypophysiological dose reduced and the hyperphysiological implant increased aggression scores. The results demonstrate that agonistic behavior in male mice is influenced by the titer of circulating T and emphasize the importance of genetic variance in the study of hormones and behavior.     

The complete primary structure of mouse 20S proteasomes

 The proteasome is a large multicatalytic proteinase that plays a role in the generation of peptides for presentation by major histocompatibility complex class I molecules. The 20S proteolytic core of mammalian proteasomes is assembled from a group of 17 protein subunits that generate a distinctive pattern of spots upon two-dimensional gel electrophoresis. The genes for most of these subunits have been cloned from humans and rats. We isolated cDNA clones for the mouse orthologues of ten of the subunits [PSMA1 (C2), PSMA2 (C3), PSMA3 (C8), PSMA4 (C9), PSMA5 (ZETA), PSMA6 (IOTA), PSMA7 (C6-I), PSMB2 (C7-I), PSMB3 (C10-II), and PSMB5 (X)] to complete the cloning of all of the mouse subunits. Using antisera raised against these subunits or their orthologues, we verified the identity of these proteins by two-dimensional NEPHGE-PAGE. Received: 8 March 1999 / Accepted: 8 April 1999     

The mitochondrion of Plasmodium falciparum visualized by rhodamine 123 fluorescence

Rhodamine 123 (Rh123) has been used to probe the functional status of the mitochondrion present within the asexual, intraerythrocytic stages of the malarial parasite Plasmodium falciparum. This cationic fluorescent dye accumulates specifically in negatively charged cellular compartments, such as mitochondria. Using epifluorescence microscopy the development of what appears to be a single mitochondrion has been followed through the intraerythrocytic cycle. Mitochondrial development progresses from a fine thread-like organelle that becomes longer and eventually branched. Each daughter merozoite receives a branch or piece of the parent organelle. Cytoplasmic Rh123 accumulation was also observed, indicating that there exists a transmembrane potential across the outer plasma and parasitophorous vacuolar membranes of the parasite. The effects of uncouplers (protonophores), ionophores, and inhibitors were examined by monitoring Rh123 accumulation and retention. Our results demonstrate that the mitochondrion of P. falciparum actively maintains a high transmembrane potential, the function of which is as yet undefined.     

Chlorophyll breakdown in senescent leaves: demonstration of Mg-dechelatase activity

The action of Mg-dechelatase was brought to light by incubating senescent rape cotyledons or chloroplasts under conditions which prevented the oxidative cleavage of chlorophyll-porphyrin. The accumulation of chlorophyllide and pheophorbide taking place under such conditions was considered as a measure of apparent activities of chlorophyllase and dechelatase, respectively. In excised cotyledons metal chelators such as 2,2'-dipyridyl and o -phenanthroline caused a marked accumulation of pheophorbide a , without affecting the apparent activity of chlorophyllase. Treatment of cotyledons with an inhibitor of cytoplasmic protein synthesis d -2-(4-methyl-2,6-dinitroanilino)-N-methyl-propionamide ( d -MDMP) caused a reduced accumulation of pheophorbide a in the presence of dipyridyl, suggesting that the appearance and maintenance of Mg-dechelatase activity in senescent cotyledons requires continuous cytoplasmic protein synthesis. In isolated senescent chloroplasts (gerontoplasts) the cleavage of chlorophyll-porphyrin requires the supplementation with glucose-6-phosphate (Glc6P). Upon the incubation of gerontoplasts in the absence of Glc6P, a conspicuous accumulation of pheophorbide a occurred. Much smaller pools of pheophorbide a were produced when porphyrin cleavage was allowed in the presence of Glc6P. These phenomena were not observed in pre-senescent chloroplasts. In contrast to the apparent Mg-dechelatase activity, chlorophyllase activity did not change in a senescent-specific fashion. The lysis of gerontoplasts by freezing and thawing caused an enhancement of apparent chlorophyllase activity whereas the activity of Mg-dechelatase was lower than in the intact organelles. In the pre-senescent chloroplasts, lysis evoked a small apparent Mg-dechelatase activity, suggesting that in a latent form this enzyme may be present even before the onset of foliar senescence.     

Can we learn from the pathogenetic strategies of group A hemolytic streptococci how tissues are injured and organs fail in post-infectious and inflammatory sequelae?

The purpose of this review-hypothesis is to discuss the literature which had proposed the concept that the mechanisms by which infectious and inflammatory processes induce cell and tissue injury, in vivo, might paradoxically involve a deleterious synergistic 'cross-talk', among microbial- and host-derived pro-inflammatory agonists. This argument is based on studies of the mechanisms of tissue damage caused by catalase-negative group A hemolytic streptococci and also on a large body of evidence describing synergistic interactions among a multiplicity of agonists leading to cell and tissue damage in inflammatory and infectious processes. A very rapid cell damage (necrosis), accompanied by the release of large amounts of arachidonic acid and metabolites, could be induced when subtoxic amounts of oxidants (superoxide, oxidants generated by xanthine-xanthine oxidase, HOCl, NO), synergized with subtoxic amounts of a large series of membrane-perforating agents (streptococcal and other bacterial-derived hemolysins, phospholipases A2 and C, lysophosphatides, cationic proteins, fatty acids, xenobiotics, the attack complex of complement and certain cytokines). Subtoxic amounts of proteinases (elastase, cathepsin G, plasmin, trypsin) very dramatically further enhanced cell damage induced by combinations between oxidants and the membrane perforators. Thus, irrespective of the source of agonists, whether derived from microorganisms or from the hosts, a triad comprised of an oxidant, a membrane perforator, and a proteinase constitutes a potent cytolytic cocktail the activity of which may be further enhanced by certain cytokines. The role played by non-biodegradable microbial cell wall components (lipopolysaccharide, lipoteichoic acid, peptidoglycan) released following polycation- and antibiotic-induced bacteriolysis in the activation of macrophages to release oxidants, cytolytic cytokines and NO is also discussed in relation to the pathophysiology of granulomatous inflammation and sepsis. The recent failures to prevent septic shock by the administration of only single antagonists is disconcerting. It suggests, however, that since tissue damage in post-infectious syndromes is caused by synergistic interactions among a multiplicity of agents, only cocktails of appropriate antagonists, if administered at the early phase of infection and to patients at high risk, might prevent the development of post-infectious syndromes.     

Neurochemical investigation of an endogenous model of the "hyperkinetic syndrome" in a hybrid dog.

A telomian-beagle hybrid has been recently proposed as a possible model for the hyperkinetic syndrome. They resemble hyperkinetic children in their poor ability to respond with the appropriate behavior in an inhibitory training test. Two groups of hybrids could be differentiated, the behavior of one of which improved with amphetamine (“Responders”) and of the other did not (“Non responders”). In the present study, the levels of HVA, 5-HIAA, MOPEG-SO were measured in CSF and the levels of NA, DA, HVA, DOPAC⁴, 5-HIAA were assayed in brain tissues from different regions, taken under basal conditions from beagles and telomian-beagle hybrids. Responder hybrids had lower levels of NA, DA, HVA in brain and low HVA in CSF. Therefore, they can be distinguished biochemically as well as behaviorally from non-responder hybrids and beagles and may prove to be useful as models for study of the mechanism and the therapy of this syndrome.