Interactions between the genetic transfer-inhibiting systems finU and finV in polyplasmid complexes ofEscherichia coli K-12 cells

The inhibition of conjugative transfer of derepressed plasmids was appreciably increased in polyplasmid complexes ofEscherichia coli K-12 cells containing two repressed conjugative plasmids with the finV system of genetic transfer regulation, in comparison with the individual effects of each of the two plasmids. Combination of two plasmids with the finU system or of plasmids with the finU and finV systems did not result in such an increase of inhibitory activity. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N ^o 12, pp. 619–622, December, 1995 Presented by T. T. Berezov, Member of the Russian Academy of Medical Sciences     

Interleukin-6 production by astrocytes: Induction by the neurotransmitter norepinephrine

Astrocytes contribute to the immunocompetence of the central nervous system (CNS) via their expression of class II major histocompatibility complex (MHC) antigens and the production of inflammatory cytokines such as interleukin-1 beta (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). Of these cytokines, IL-6 is of particular interest because one of its many immune and inflammatory actions is the promotion of immunoglobulin synthesis, and it is thought that IL-6 expression within the brain exacerbates autoimmune diseases of the CNS, which are marked by local immunoglobulin production. Several stimuli induce astrocyte IL-6 expression, including such inducible endogenous factors as IL-1β and TNF-α. We have investigated the possibility that a constitutively present endogenous factor, the neurotransmitter norepinephrine (NE), can induce astrocyte IL-6 production. We report that NE induces both IL-6 mRNA and protein in primary neonatal rat astrocytes, with optimal induction at 10 μM. IL-6 protein induction by NE is comparable to that seen with IL-1β or TNF-α, and NE synergizes with these cytokines for a ten-fold enhanced effect. In contrast to astrocytes, microglia are relatively unresponsive to NE, IL-1β and TNF-α for IL-6 production. Experiments with the β-adrenergic receptor agonist isoproterenol, and α and β-adrenergic receptor antagonists (propranolol, phentolamine, atenolol, and yohimbine) indicate that β₂ and α₁-adrenergic receptors are involved in NE induction of astrocyte IL-6 expression. These results help to further the understanding of neuron-glial interactions, and the role of astrocytes and adrenergic activity in immune responses within the CNS.     

γ-Enolase and glial fibrillary acidic protein in nervous system tumors

Summary A large series of central and peripheral nervous system tumors was studied for the presence of glial fibrillary acidic protein (GFAP) and -enolase (neuron-specific enolase, NSE), using specific monoclonal antibodies (mAbs). Occurrence in and specificity of GFAP to glial and mixed tumors was confirmed and depended on the malignancy grade and features such as meningeal invasion. Using a well-characterized mAb, -enolase was demonstrated in neuronal, as well as in a whole range of non-neuronal tumors. This lack of specificity of -enolase prohibits its use as an exclusive neuronal marker. Nevertheless quantization or comparison with other types of enolases could still prove to be useful in well-defined situations. The advantages inherent to mAbs and a highly sensitive detection system turn GFAP stainings into a specific and readily reproducible technique.Supported in part by FGWO (grant no. 3.0019.86) and by the Geconcerteerde Actie (grant no. 84/89-68, Brain specific proteins)     

Simulation of space adaptation syndrome on earth

Summary The three Spacelab D-1 Scientist Astronauts were exposed to a 11/2 h 3 g centrifuge run in the supine position, resulting in a linear 3 g acceleration in the x-direction. They used their space experience to evaluate their readapting to normal gravity and compared their observations with Space Adaptation Syndrome. After the centrifuge runs, the vestibular visual system appeared to be modified in a very specific and reproducible manner. Readapting to the normal 1 g environment took at least 6 h. During this period there was a striking similarity to the astronaut's experience during adaptation to weightlessness in space. A series of vestibular tests were then performed, confirming these subjective findings.     

Assessment of dental health state utilities

The term "health state utility" implies the assigning of a numerical value to a state of health. Assessment of the success of health care procedures, using health state utilities, enables evaluation of available treatments and procedures in terms of differing health outcomes and therefore facilitates cost-benefit analyses. Although measurement of general health state utilities has become increasingly common in medicine using a variety of techniques, few attempts have as yet been made in dentistry to place valuations on different dental health states. The absence of tried and tested methods for measuring tooth quality make the benefits gained from preventive and restorative dental programmes difficult to quantify. The aim of this study was to assess the average utility values, held by a group of dentists and a group of members of the general public, for four different tooth states which it was hypothesised would have different values. These were 1) a decayed and painful posterior tooth; 2) a decayed and non-painful posterior tooth; 3) a posterior tooth which had been restored and would need further restorative treatment and 4) a permanently restored posterior tooth. A standard gamble questionnaire was used to elicit the utility values which were then substituted as "weightings" in a modified version of the "T-health" index (1). The results show that it is possible to assess dental health state utility values using the standard gamble method and that the average utility values of the dentists in the study were consistently higher than those of the general public.(ABSTRACT TRUNCATED AT 250 WORDS)     

Complement-derived polypeptide C3adesArg as a mediator of inflammation at the blood-brain barrier in a new experimental cat model

Summary The effect of the complement-derived polypeptide C3adesArg as a mediator of inflammation in the central nervous system was examined. Twenty-five anesthetized cats received 4 mg of this polypeptide by intraventricular injection, 20 cats who served as controls received saline. Cerebrospinal fluid (CSF) was sampled 3 h after intraventricular injection and the brains were removed. For assessment of the permeability of the blood-brain barrier the CSF penetration of four antibiotics, which were given intravenously, was measured. Five control animals were employed for each antibiotic (tobramycin, ampicillin, imipenem, fosfomycin), whereas six C3adesArg-treated animals were used for each antibiotic and seven for tobramycin. Besides CSF levels of glucose, the prostanoids 6-keto-prostaglandin F₁, thromboxane B₂ and prostaglandin E₂ were measured. The morphological examinations in the CSF sediments and histological brain sections in the C3adesArg-treated animals disclosed a distinct inflammation with leptomeningeal and perivascular infiltration of polymorphonuclear granulocytes compared to normal findings in the controls. The CSF/serum ratios of all of the antibiotics were markedly elevated compared to controls, indicating a blood-brain barrier disruption. The levels of all prostanoids were significantly higher in the treatment group than in the control group, whereas the glucose levels were lower. These findings are in accordance with a granulocytic meningitis as seen in some infections at the acute stage. It is concluded that C3adesArg acts as a mediator of inflammation in the central nervous system.     

Humoral and cellular effects of the K+-channel activator cromakalim in man

Summary The effect of cromakalim, a K⁺-channel activator, on the plasma renin-angiotensin-aldosterone system, catecholamines and -atrial natriuretic peptide, and on the intraerythrocyte concentration and transmembrane fluxes of Na⁺ and K⁺ has been investigated in 18 normal male subjects, in a double-blind parallel study. After a run-in period on placebo for 1 week, the subjects were treated either with placebo (n=6) or cromakalim (n=12) for 1 week.Plasma renin activity was significantly increased during cromakalim. No effect of cromakalim on plasma angiotensin II, aldosterone, adrenaline, noradrenaline and -atrial natriuretic peptide was demonstrated. The intra-erythrocyte K⁺ concentration was decreased during cromakalim administration and Ca²⁺-dependent K⁺-channels in red blood cells were increased.     

Lactic dehydrogenase virus (LDV) impairs the antigen-presenting capacity of macrophages yet fails to affect their phagocytic activity

The effect of acute infection of mice with lactic dehydrogenase virus (LDV) on two major functions of peritoneal macrophages was tested. Using a macrophage-dependent T cell proliferative assay to test the antigen-presenting capacity of LDV-infected macrophages we found that LDV impairs the capacity of antigen-presenting cells to trigger memory T lymphocytes. Endocytosis of antigen by LDV-infected macrophages was similar to that of uninfected cells. In addition, the proportion of intracellular antigen versus membrane-bound antigen in LDV-infected cells were similar to that observed in uninfected mice. It appears therefore, that the impaired immunogenic effect of LDV-infected macrophages results from reduced immunogenicity of the membrane-bound antigen.Testing the phagocytic activity of peritoneal macrophages we found that the uptake of radiolabeled antibody-coated sheep erythrocytes or bacteria (E. coli) by infected cells was similar to that by uninfected macrophages. In addition, LDV failed to affect the ability of peritoneal macrophages in a nitroblue tetrazolium reduction reaction which serves as an alternative parameter for measuring phagocytic activity. Our results support the assumption that LDV, which probably propagates in the cells of the reticuloendothelial system, impairs some of the immunogenic functions of macrophages and thereby affects macrophage-dependent immune responses.     

Computer simulations and the use of radiolabelled sulphur colloid to measure the efficiency of the mononuclear phagocyte system

Technique are described whereby the clearance of the radiolabelled blood borne colloid can be continuously and reproducibly measured non-invasively from the same animal in vivo or from the isolated perfused intact liver in vitro. Using these techniques, the rate of removal of radiolabelled sulphur colloid by the mononuclear phagocytes in vivo and in vitro was shown to be biexponential. The pattern of clearance of colloid and the factors contributing to this were analysed with the aid of a computer program which mimicked the in vitro liver perfusion.