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Interplay between extracellular -SH groups and Ca2+ in their mitogenic action on murine lymphocytes: the role of SiO2.

Murine spleen lymphocytes, cultured under serum-free conditions and stimulated with concanavalin A (Con A), showed an increased demand for supplemental concentrations of Ca2+ when 2-mercaptoethanol (2-ME) or L-cysteine were also present in the culture medium. The requirement for additional Ca2+ ions was particularly evident at high cell concentrations. The addition of SiO2 (Aerosil 200), in concentrations depending on the original level of Ca2+ in the culture medium, could substitute for the increased demand on calcium ions. This dependency of SiO2 effects on calcium levels in the medium was also evident when supraoptimal, i.e. inhibitory concentrations of silica were tested. Results of experiments with 45Ca suggest that silica particles may act as intercellular carriers of calcium. In contrast to spleen lymphocytes, Con A-stimulated thymus cells exhibited neither a need for an increase in the concentration of Ca2+ nor a dependency on the presence of 2-ME in the medium.

Animals↗

Interplay between the human TCR/CD3 epsilon and the B-cell antigen receptor associated Ig-beta (B29).

T and B lymphocytes are characterized by the surface expression of highly variable antigen receptors called the T-cell (TCR) and B-cell (BCR) receptor. In both B and T cells, binding of antigen to their respective surface receptors results in transmembrane signaling which leads either to programmed cell death or to proliferation and differentiation. The human and murine TCR consist of the highly variable TCR alpha and beta or gamma and delta chains recognizing antigen and the non-covalently associated invariable CD3 complex (gamma, delta, epsilon) and zeta. The antigen-recognizing surface membrane-bound immunoglobulin (Ig) molecules on the surface of human and murine B cells are non-covalently associated with a heterodimeric protein complex of Ig-alpha (MB-1) and Ig-beta (B29). Like the CD3 complex associated with TCR the Ig-associated proteins are predicted to regulate the assembly and transport of the Ig complex to the cell surface and to couple membrane-bound Ig to intracellular signal transduction pathways. To gain more insight into structure/function relationships between CD3 proteins and Ig-alpha and Ig-beta, we transiently co-transfected pairs of expression vectors encoding either TCR/CD3 chains on the one hand and Ig-alpha or Ig-beta on the other into Cos cells. Thus we found a very strong interaction between CD3 epsilon and Ig-beta mediated by the extracellular domains. Experiments in which we could stain Jurkat T cells with soluble Ig-beta but not Ig-alpha protein indicated the recognition of CD3 epsilon by Ig-beta even in the context of the whole TCR/CD3 complex.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The interplay of learning and anxiety in the elevated plus-maze.

In naive rats benzodiazepines have clear anxiolytic effects in the elevated plus-maze, but in rats with previous plus-maze experience benzodiazepines are ineffective. This phenomenon does not depend on the drug state on trial 1 or on the inter-trial interval and generalises across mazes of different material; it is dependent on experience of the open arm. The phenomenon of "one-trial tolerance" to the anxiolytic effect of benzodiazepines is not seen in other animal tests; and there is no equivalent phenomenon of "one-trial withdrawal" or of tolerance to anxiogenic effects in the plus-maze. The phenomenon is not seen in unhandled rats, in rats given longer trials in the plus-maze, or in those given an amnesic treatment on trial 1. It is suggested that during the first 5 min in the elevated plus-maze the rats are acquiring a fear of heights and it is this phobic anxiety state that is measured during the second 5-min trial. Thus the nature of the anxiety generated by the maze is different on trials 1 and 2. The results of a factor analysis study confirm this conclusion.

Animals↗

The differences shown by C57BL/6 and DBA/2 inbred mice in detecting spatial novelty are subserved by a different hippocampal and parietal cortex interplay.

Inbred C57BL/6 (C57) and DBA/2 (DBA) mice with hippocampus, posterior parietal cortex or sham lesions were placed in an open-field containing five objects and their reactivity to the displacement (spatial novelty) or the substitution (object novelty) of some of these objects was examined. C57 mice reacted to spatial novelty by exploring more the displaced than the non-displaced objects while DBA mice did not show any consistent reaction. In the highly reactive C57 strain, the peak of exploratory responses directed towards the displaced objects was completely abolished by hippocampal and posterior parietal cortex lesions. In the non-reactive DBA strain, hippocampal lesions induced an aspecific decreased interest towards the two categories of objects while posterior parietal cortex lesions did not produce any behavioral modification. The high reactivity of C57 mice to spatial change appears to be subserved by the conjunctive participation of the hippocampus and the posterior parietal cortex. Conversely, the deficit shown by DBA mice in that situation seems to be related to: (i) a poorly functional hippocampus; and (ii) the non-involvement of the posterior parietal cortes. The present data suggest that the participation of the posterior parietal cortes to the detection of spatial novelty may depend on the degree of functionality of the hippocampus.

Animals↗

The interplay of microbes and their hosts.

Microbes and their hosts exert considerable evolutionary pressure on one another. This brief report of a recent meeting describes the strategies and tactics, and highlights some of the key molecules involved in the complex host-parasite relationship.

Animals↗

The thymus in pregnancy: the interplay of neural, endocrine and immune influences.

This article discusses the dramatic events that accompany thymic involution during pregnancy, and traces the possible immune, neural and endocrine interactions that may occur. Ann Clarke and Marion Kendall present accumulating evidence that activity, not inactivity, is a feature of the thymus at this time. Whilst the cortex shrinks, the medulla enlarges and rearranges to create a microenvironment containing increased numbers of mature thymocytes. It is suggested that these recently derived T cells may contribute to the unique populations of cells with suppressive function that appear during pregnancy, and thereby contribute to the immune suppression of the mother to paternal and fetal antigens. In addition, the pregnancy-associated cortical involution of the thymus may reflect the deletion of clones with potential reactivity to paternal and/or fetal antigens.

Animals↗

Cycles within cycles: the interplay between differentiation and cell division in Trypanosoma brucei.

The life cycle o f the African trypanosome is divided between the mammal and the tsetse. Those life cycle stages which traverse between these two hosts appear to be pre-adopted for survival in their new habitat They are also non-dividing. Here, Keith Matthews and Keith Gull discuss how and why trypanosomes might enmesh the control o f their cell cycle with their regulation o f the transition between different life cycle forms.

Journal Article↗

Coagulase-negative staphylococci: interplay of epidemiology and bench research.

Coagulase-negative staphylococci (CNS) are major nosocomial pathogens in patients with prostheses and indwelling devices such as central venous catheters. For Staphylococcus epidermidis the unique association with foreign-body infections appears to be due in part to a capsular polysaccharide adhesin that mediates attachment to silicon elastomer and other biomedical materials. In addition, staphylococcal "slime" may promote persistent colonization of indwelling devices and protect staphylococci from clearance by host defense mechanisms. Given these research findings, it seemed reasonable to assume that nosocomial CNS bacteremia in neonatal intensive care units might be associated with the use of indwelling vascular lines, as had been suggested by other investigators. We found that CNS cause the majority of nosocomial bacteremias in our neonatal intensive care units and that low birth weight and length of stay are major independent risk factors for these infections. In addition, we confirmed the association of central venous lines with CNS bacteremia but were surprised to find that intravenous administration of lipid emulsion was an even greater risk factor. These observations have brought our work back to the laboratory, where a rabbit model of CNS catheter infection is being studied to explore the relationship between lipid emulsion and catheter colonization and bacteremia.

Birth Weight↗

The interplay of traditional therapies in south Thailand.

Discernible among the diversity of folk-medical practitioners of Songkhla, Thailand, are three prominent therapeutic traditions: those of the herbalists, folk psychotherapists, and supernaturalists. Most curers describe themselves as specialists in one or another of these modes, but at the same time, many also recognize multiple levels of causation and multi-modal treatment alternatives for any specific affliction. Accordingly, they liberally apply their own therapeutic orientation to afflictions ordinarily diagnosed as calling for treatment in modes other than their own. To treat afflictions normally outside their own domain, they call on metaphorical principles to render their traditional techniques and paraphernalia applicable to a greater variety of illnesses. In this way they strive to attract a wider variety of clientele in the increasingly competitive environment created by the expansion of modern medical facilities. An analysis of this system contributes to our understanding of therapeutic pluralism in these times of rapid culture change.

Cross-Cultural Comparison↗

The interplay between X-ray crystallography, neutron diffraction, image reconstruction, organo-metallic chemistry and biochemistry in structural studies of ribosomes.

Crystals of ribosomes, their complexes with components of protein biosynthesis, their natural, mutated and modified subunits, have been subjected to X-ray and neutron crystallographic analyses. Electron microscopy and 3-dimensional image reconstruction, supported by biochemistry, genetic, functional and organo-metallic studies were employed for facilitating phasing of the crystallographic data. For example, a monofunctional multi heavy-atom cluster (undecagold) was designed for covalent and quantitative binding to ribosomes. The modified particles were crystallized isomorphously with the native ones. Their difference-Patterson maps contain indications for the usefulness of these derivatives for subsequent phasing. Models of the ribosome and its large subunit were reconstructed from tilt series of 2-dimensional sheets. The comparison of the various reconstructed images enabled an initial assessment of the reliability of these models and led to tentative assignments of several functional features. These include the presumed sites for binding mRNA and for codon-anticodon interactions, the path taken by the nascent protein chain and the mode for tRNA binding to ribosomes. These assignments assisted in the design of biologically meaningful crystal systems. The reconstructed models are being used to identify structural features in initial density maps derived from X-ray and neutron diffraction data.

Crystallography↗

Vitellogenin hormonal control in the green frog, Rana esculenta. Interplay between estradiol and pituitary hormones.

1. The effect of estradiol and pituitary hormones on the titre of serum vitellogenin has been studied in Rana esculenta by rocket immunoelectrophoresis. 2. Hepatic synthesis of vitellogenin depends on physiological doses of estradiol. 3. Gonadotrophins enhance the uptake, presumably by acting directly on the oocyte plasma membrane. 4. In addition, our data support direct pituitary intervention on liver synthesis and/or release of vitellogenin. 5. Hormonal response, as evaluated by vitellogenin serum titres, tends to increase from November to July. This could be the expression of a modification, throughout the sexual cycle, of liver sensitivity to the hormones.

Animals↗

Cell motility: an interplay between local and non-local measurement.

The bending motions of an ATP-activated actin filament and a flagellar axoneme of starfish spermatozoon exhibit a one-to-many correspondence between the displacement of the medium and the force actualized in the medium, demonstrating sharp contrast to the one-to-one correspondence in classical mechanics. Uniqueness of the actualized forces is lacking. Cell motility suggests the absence of a completely specifiable boundary condition that would unambiguously control the dynamics of generating mechanical forces in motile cells. The one-to-many relationship between the displacement of the medium and the force actualized in the medium necessitates a materialistic capacity for making choices on the part of molecules and cells in transforming future possibilities into actualized reality, the latter of which again serves as the source of the further future possibilities.

Animals↗

Interplay between expressed non-NMDA receptors and endogenous calcium-activated chloride currents in Xenopus laevis oocytes.

Current-voltage (I-V) relationships of glutamate receptors activated by the non-NMDA receptor agonist, kainate (KA), were determined in Xenopus laevis oocytes injected with either calf or chick brain mRNA. In most injected oocytes (n = 44; 84%), I-V plots to 80 microM KA exhibited inward rectification; however, in some oocytes (n = 7; 16%), the KA-evoked membrane current showed only slight outward rectification. A comparison between the resting membrane properties of injected oocytes with the KA-evoked currents revealed that weak outward rectification was often observed in oocytes possessing predominant voltage-activated calcium-dependent chloride currents (ICl(Ca)). In these oocytes, replacement of extracellular calcium (2 mM Ca2+) with magnesium ions (Mg2+), or the addition of the chloride channel blocker, anthracene-9-carboxylic acid (500 microM to 1 mM A9C), reduced ICl(Ca) and also altered the nature of the KA I-V plot revealing inward rectification. It is proposed that the responses mediated by expressed non-NMDA receptors may be influenced by the activation of endogenous calcium-dependent membrane currents in Xenopus laevis oocytes.

Animals↗

Interplay between calcium and activated cGMP phosphodiesterase from retinal rod outer segments.

Hypotonic extraction of bovine retinal rod outer segments after bleaching in isotonic buffer yielded an extract exhibiting activated cGMP phosphodiesterase properties. Since this extract was virtually devoid of other proteins involved in the rod outer segment cGMP enzymatic cascade, it was used to study phosphodiesterase catalytic activity. The hypotonic extract required Mg2+ in the range 0.1-1.0 mM for optimal cGMP hydrolysis. At these Mg2+ concentrations hydrolysis could be effectively inhibited by Ca2+ at concentrations which might be attainable in rod outer segments. Since higher Ca2+ concentrations were required to give a chosen degree of inhibition at higher Mg2+ concentrations, this inhibition was probably due to competition by Ca2+ for Mg2+ binding site(s) on the phosphodiesterase catalytic unit. Other divalent cations were also able to inhibit cGMP hydrolysis, many of them (especially those with ionic radii close to that of magnesium) more effectively than calcium. It is suggested that Ca2+ may play a role in phototransduction by participating in the control of photoreceptor sensitivity, and that this is achieved by modulating rod outer segment cGMP hydrolysis.

3',5'-Cyclic-GMP Phosphodiesterases↗

Retention of misonidazole in normal and malignant tissues: interplay of hypoxia and reductases.

Tritiated misonidazole (MISO) was injected intravenously (iv) into mice bearing five different tumors. At 24 hr the tumors were removed for analysis of bound MISO, and at the same time three normal tissues were removed (liver, labial gland, and esophagus). The labial gland and esophagus were selected as representatives of sebaceous and stratified squamous tissues, respectively, tissues that in many parts of the body retain high levels of MISO. The tumors used were early transplant generations of spontaneous mouse tumors of mammary gland, lung, and liver. The levels (mean +/- SEM) of MISO at 24 hr for the five tumors and three normal tissues, expressed as percentage of the injected dose per gram of tissue were: A110 (0.03 +/- 0.007), A114 (0.103 +/- 0.04), A150 (0.09 +/- 0.005), A167 (0.037 +/- 0.012), A168 (0.122 +/- 0.0016), esophagus (0.507 +/- 0.09), labial gland (0.125 +/- 0.013), liver (0.11 +/- 0.004). Histochemical examination of the normal tissues showed reductase activity in all three. In the esophagus and labial gland, inhibition of the reaction by dicumarol indicated the likely presence of the reductase DT-diaphorase which, by 2-electron transfer, can be expected to reduce MISO to a reactive, locally-binding metabolite, even in the presence of oxygen.

Animals↗

Interplay of novobiocin-resistant and -sensitive DNA gyrase activities in self-protection of the novobiocin producer, Streptomyces sphaeroides.

The novobiocin (Nb)-producing organism, Streptomyces sphaeroides, possesses two gyrB genes: gyrBS and gyrBR (encoding the DNA gyrase B subunit-the normal target for Nb) whose products differ in their response to the drug. Novobiocin-sensitive gyrase is the predominant form of the enzyme in this strain and is produced constitutively but at variable levels, whereas Nb-resistant gyrase appears when growth takes place in the presence of the drug. The promoter isolated from the Nb-resistance determinant responds sharply to changes in DNA topology, being activated when the (negative) superhelical density is reduced and vice versa when the supercoiling of DNA is increased. Thus, resistance to Nb in S. sphaeroides is induced by a reduction in DNA supercoiling due to the action of autogenous drug on the sensitive gyrase.

Blotting, Southern↗