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Possible Relevance (possible + relevance)
Selected AbstractsTryptamine induces cell death with ultrastructural features of autophagy in neurons and glia: Possible relevance for neurodegenerative disordersTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 9 2006Federico Herrera Abstract Tryptamine derivatives are a family of biogenic amines that have been suggested to be modulators of brain function at physiological concentrations. However, pharmacological concentrations of these amines display amphetamine-like properties, and they seem to play a role in brain disorders. Amphetamines induce autophagy in nerve cells, and this type of cell death has also been involved in neurodegenerative diseases. In the present work, we clearly demonstrate for the very first time that high concentrations of tryptamine (0.1,1 mM) induce autophagy in HT22 and SK-N-SH nerve cell lines and in primary cultures of astrocytes, glial cells being less sensitive than neurons. Ultrastructural cell morphology shows all of the typical hallmarks of autophagy. There is no nuclear chromatin condensation, endoplasmic reticulum and mitochondria are swollen, and a great number of double-membraned autophagosomes and residual bodies can be shown in the cytoplasm. Autophagosomes and residual bodies contain mitochondria, membranes, and vesicles and remain unabridged until the cell membrane is disrupted and the cell dies. The same results have been found when cells were incubated with high concentrations of 5-methoxytryptamine (0.1,1 mM). Our results establish a possible link between the role of tryptamine derivatives in brain disorders and the presence of autophagic cell death in these kinds of disorders. Anat Rec Part A, 288A:1026,1030, 2006. © 2006 Wiley-Liss, Inc. [source] Decreased glucocorticoid receptor mRNA and dysfunction of HPA axis in rats after removal of the cholinergic innervation to hippocampus.EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2002Jung-Soo Han Abstract Excess exposure to glucocorticoids can have deleterious effects on physiology and cognition. Glucocorticoids acting via receptors located in hippocampal neurons contribute to negative feedback after stress by terminating the further release of glucocorticoids. The current study investigated the effects of selective immunolesions of septo-hippocampal cholinergic neurons on hippocampal corticosterone receptor mRNA and on hypothalamic-pituitary-adrenal (HPA) activity. As evaluated by in situ hybridization, hippocampal glucocorticoid receptor (GR) mRNA, but not mineralocorticoid receptor (MR) mRNA, was significantly decreased in lesioned rats compared to controls. In a companion study, the peak corticosterone response to one hour of restraint stress did not differ between lesion and control groups but the post-stress decline of corticosterone was more protracted in the lesioned rats. These findings are discussed in terms of their possible relevance to ageing as age-related degeneration of the basal forebrain cholinergic system may contribute to the commonly observed dysfunction of the HPA axis in older animals. [source] Effects of ,-aminoisobutyric acid on leptin production and lipid homeostasis: mechanisms and possible relevance for the prevention of obesityFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2010Karima Begriche Abstract ,-Aminoisobutyric acid (BAIBA) is a catabolite of thymine and antiretroviral thymine analogues AZT and d4T. We recently discovered that this ,-amino acid is able to enhance fatty acid oxidation and reduce body weight in mice through an increased production of leptin by the white adipose tissue (WAT). Furthermore, BAIBA could have favourable effects on nonalcoholic steatohepatitis in a leptin-independent manner. In the present review, we shall recall the circumstances that led us to discover the effects of BAIBA on body fat mass and lipid homeostasis. In addition, we put forward several hypothetical mechanisms whereby BAIBA could enhance leptin secretion by WAT and present some anti-inflammatory effects in the liver. We also discuss in this review (i) the deleterious impacts caused by the absence of, or low leptin expression on lipid homeostasis and body weight in humans and animals and (ii) recent data from other investigators suggesting that increasing leptin levels and/or responsiveness may be indeed an attractive pharmacological strategy in order to prevent (and/or treat) obesity, at least in some individuals. [source] Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophreniaGENES, BRAIN AND BEHAVIOR, Issue 5 2005K. K. Szumlinski Homer proteins are involved in the functional assembly of postsynaptic density proteins at glutamatergic synapses and are implicated in learning, memory and drug addiction. Here, we report that Homer1 -knockout (Homer1 -KO) mice exhibit behavioral and neurochemical abnormalities that are consistent with the animal models of schizophrenia. Relative to wild-type mice, Homer1 -KO mice exhibited deficits in radial arm maze performance, impaired prepulse inhibition, enhanced ,behavioral despair', increased anxiety in a novel objects test, enhanced reactivity to novel environments, decreased instrumental responding for sucrose and enhanced MK-801- and methamphetamine-stimulated motor behavior. No-net-flux in vivo microdialysis revealed a decrease in extracellular glutamate content in the nucleus accumbens and an increase in the prefrontal cortex. Moreover, in Homer1 -KO mice, cocaine did not stimulate a rise in frontal cortex extracellular glutamate levels, suggesting hypofrontality. These behavioral and neurochemical data derived from Homer1 mutant mice are consistent with the recent association of schizophrenia with a single-nucleotide polymorphism in the Homer1 gene and suggest that the regulation of extracellular levels of glutamate within limbo-corticostriatal structures by Homer1 gene products may be involved in the pathogenesis of this neuropsychiatric disorder. [source] A review of the possible relevance of inositol and the phosphatidylinositol second messenger system (PI-cycle) to psychiatric disorders,focus on magnetic resonance spectroscopy (MRS) studiesHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2005Hyeonjin Kim Abstract Myo -inositol is an important part of the phosphatidylinositol second messenger system (PI-cycle). Abnormalities in nerve cell myo -inositol levels and/or PI-cycle regulation has been suggested as being involved in the pathophysiology and/or treatment of many psychiatric disorders including bipolar disorder, major depressive disorder, panic disorder, obsessive-compulsive disorder, eating disorders and schizophrenia. This review examines the metabolism and biochemical importance of myo -inositol and the PI-cycle. It relates this to the current in vivo evidence for myo -inositol and PI-cycle involvement in these psychiatric disorders, particularly focusing upon the magnetic resonance spectroscopy (MRS) findings in patient studies to date. From this review it is concluded that while the evidence suggests probable relevance to the pathophysiology and/or treatment of bipolar disorder, there is much less support for a significant role for the PI-cycle or myo -inositol in any other psychiatric disorder. More definitive investigation is required before PI-cycle dysfunction can be considered specific to bipolar disorder. Copyright © 2005 John Wiley & Sons, Ltd. [source] Vascular endothelial growth factor (VEGF) expression in oral tissues: possible relevance to angiogenesis, tumour progression and field cancerisationJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 8 2001J. Carlile Abstract: The aim of this study was to assess whether vascular endothelial growth factor (VEGF) expression in oral tissues is associated with angiogenesis, disease progression or field cancerisation. Vascularity and VEGF immunoreactivity were quantified in 68 archival specimens including normal oral mucosa (NOM), dysplasia (DYS) and squamous cell carcinoma (SCC). Vascularity increased significantly with disease progression; it was also higher in NOM adjacent to SCC than in NOM from healthy tissue, suggesting an association with field cancerisation. VEGF expression in epithelial cells was evaluated using two antibodies and three indices. VEGF indices and vascularity were not directly correlated. The expression of VEGF was similar in all DYS and NOM specimens, whether or not adjacent to a concurrent lesion. A comparison of SCC with NOM or DYS led to opposite results, depending on the VEGF antibody and index used. We conclude that VEGF expression in the oral mucosa may play a physiological role, but does not appear to be associated with angiogenesis, field cancerisation or transition to dysplasia. Further studies concerned with tumour development require examining specific VEGF isoforms and standardisation of the methodology. [source] Structural characterization of cyclic kallidin analogues in DMSO by nuclear magnetic resonance and molecular dynamicsJOURNAL OF PEPTIDE SCIENCE, Issue 1 2005Elisabetta Schievano Abstract The conformational properties in DMSO of two head-to-tail cyclic analogues of kallidin ([Lys0]-bradykinin, KL) as well as those of the corresponding linear peptides were studied by NMR and molecular dynamics (MD) simulations. The modifications in the sequence were introduced at position 6, resulting in the four peptides, [Tyr6]-KL (YKL), [Trp6]-KL (WKL), cyclo-([Tyr6]-KL) (YCKL) and cyclo-([Trp6]-KL) (WCKL). The linear WKL analogue was significantly more potent than kallidin on rat duodenum preparations, whereas YKL was significantly less potent. Both cyclic peptides, YCKL and WCKL displayed similar activity, lower than that of the linear analogues and also of cyclo-KL. The two linear analogues display high conformational flexibility in DMSO. In the predominant conformer, for both peptides, all three X-Pro bonds adopt a trans configuration. Three out of four conformers present in YCKL and WCKL were completely assigned. The configurations at the X-Pro bonds are the same for the two analogues. All cyclic conformers show a cis configuration in at least one X-Pro bond and always opposite configuration for the two consecutive X-Pro bonds. The NOE-restrained MD calculations resulted in the detection of several elements of secondary structure in each of the conformers. Such elements are described and their possible relevance to biological activity is discussed. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source] Anomalous variations in low-degree helioseismic mode frequenciesMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 2 2006R. Howe ABSTRACT We compare changes in the frequencies of solar acoustic modes with degree between 0 and 2, as derived from Global Oscillation Network Group (GONG), Birmingham Solar Oscillations Network (BiSON) and Michelson Doppler Imager (MDI) spectra obtained between 1995 and 2003. We find that, after the solar-activity dependence has been removed from the frequencies, there remain variations that appear to be significant, and are often well correlated between the different data sets. We consider possible explanations for these fluctuations, and conclude that they are likely to be related to the stochastic excitation of the modes. The existence of such fluctuations has possible relevance to the analysis of other low-degree acoustic mode spectra such as those from solar-type stars. [source] Surface trapping and leakage of low-frequency g modes in rotating early-type stars , I. Qualitative analysisMONTHLY NOTICES OF THE ROYAL ASTRONOMICAL SOCIETY, Issue 1 2000R. H. D. Townsend A qualitative study of the surface trapping of low-frequency non-radial g modes in rotating early-type stars is undertaken within the Cowling, adiabatic and traditional approximations. A dispersion relation describing the local character of waves in a rotating star is derived; this dispersion relation is then used to construct propagation diagrams for a 7-M, stellar model, which show the location and extent of wave trapping zones inside the star. It is demonstrated that, at frequencies below a cut-off, waves cannot be fully trapped within the star, and will leak through the surface. Expressions for the cut-off frequency are derived in both the non-rotating and rotating cases; it is found from these expressions that the cut-off frequency increases with the rotation rate for all but prograde sectoral modes. While waves below the cut-off cannot be reflected at the stellar surface, the presence of a sub-surface convective region in the stellar model, owing to He ii ionization, means that they can become partially trapped within the star. The energy leakage associated with such waves, which are assigned the moniker virtual modes owing to their discrete eigenfrequencies, means that stability analyses which disregard their existence (by assuming perfect reflection at the stellar surface) may be in error. The results are of possible relevance to the 53 Per and SPB classes of variable star, which exhibit pulsation frequencies of the same order of magnitude as the cut-off frequencies found for the stellar model. It is suggested that observations either of an upper limit on variability periods (corresponding to the cut-off), or of line-profile variations owing to virtual modes, may permit asteroseismological studies of the outer layers of these systems. [source] The pathogenesis of cell death in Parkinson's disease , 2007MOVEMENT DISORDERS, Issue S17 2007C. Warren Olanow MD Abstract A number of factors have been implicated in the pathogenesis of cell death in Parkinson's disease (PD). These include oxidative stress, mitochondrial dysfunction, inflammation, excitotoxicity, and apoptosis. While the precise pathogenic mechanism leading to neurodegeneration in PD is not known, there is considerable evidence suggesting that cell death occurs by way of a signal-mediated apoptotic process. PD is also characterized by intracellular proteinaceous inclusions or Lewy bodies. Proteolytic stress arises as a consequence of the excessive production of misfolded proteins, which exceed the capacity of the ubiquitin-proteasome system to degrade them. Recent genetic and laboratory studies support the possible relevance of proteolytic stress to both familial and sporadic forms of PD. Postmortem studies have shown that in the SNc of sporadic PD patients there are reduced levels of the alpha subunit of the 20S proteasome and reduced proteolytic enzyme activities. A determination as to the precise cause of cell death in PD, and the identification of specific targets for the development of drugs that might modify disease progression is one of the most critical goals in PD research. It is anticipated that over the next few years there will be a flurry of scientific activity examining the mechanism of cell death and putative neuroprotective interventions. © 2007 Movement Disorder Society [source] Structures at high pressure from random searchingPHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 3 2009C. J. Pickard Abstract An approach to searching for the structures of crystals is described. We choose an ensemble of "random" starting structures and relax them, often constraining the starting structures and/or relaxation to bias the search in some manner. The methodology is illustrated by applications to high-pressure phases of group IV hydrides, especially silane (SiH4), and to solid hydrogen, using first-principles density-functional-theory methods. We discuss the issue of possible decomposition of group IV hydrides into their constituent elements under pressure. A new molecular-hydrogen structure is described whose enthalpy is calculated to be slightly lower than all other known structures in the pressure range 75,108 GPa, and we mention its possible relevance to phase II of hydrogen. (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Distinct Expression Pattern of Cytokines in Semen of Men with Genital Infection and Oligo-Terato-AsthenozoospermiaAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2002Ioannis Matalliotakis PROBLEM: The objective of this study was to evaluate the possible relevance of cytokines in seminal plasma (SP) of patients with accessory gland infection and oligo-terato-asthenozoospermia. METHOD OF STUDY: Semen samples were obtained by masturbation from 90 men and were examined for the presence of interleukin (IL)-2, IL-6, IL-8, IL-11 and soluble CD23 (sCD23) by enzyme-linked immunosorbent assay. Five groups were included: (1) fertile men (n=20), (2) infertile men with varicocele and oligo-terato-asthenozoospermia (V-OTA, n=20), (3) infertile men with genital infection and OTA (INF-OTA, n=20), (4) infertile men with idiopathic testicular lesion and OTA (ITL-OTA, n=20) and (5) infertile men with azoospermia (AZOO, n=10). RESULTS: We found that the mean level of IL-2 was higher in SP from infertile men compared with SP from fertile men (P < 0.05). Mean levels of IL-6, IL-8, IL-11 in SP of INF-OTA were higher than that of all other groups (P < 0.05, P < 0.05, P < 0.001, respectively). However, no significant differences could be detected between other groups. A significant increase was noted in sCD23 levels in SP from men with ITL-OTA compared with all other groups (P < 0.01). We have not observed any correlations between IL-2, IL-6, IL-8, IL-11 and sCD23 levels in SP and semen parameters. Spearman's correlation coefficient revealed that there was a significant association between IL-6, IL-8, IL-11 levels in men with INF-OTA. CONCLUSION: The measurement of each cytokine separately in the SP of men with INF-OTA, in spite of the existing significant differences, does not have a diagnostic value in male infertility. However, a combined determination of IL-6, IL-8, IL-11 in the SP of men with genital infection and oligo-terato-asthenozoospermia may provide clinically useful information for the diagnosis of male accessory gland infection. [source] Myocardium distribution of sertindole and its metabolite dehydrosertindole in guinea-pigsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 4 2006Mireille Canal-Raffin Abstract Sertindole, like other atypical antipsychotics, has been shown to increase the action potential duration and QT interval in a concentration dependent manner, in in vitro electrophysiological studies. However, this does not always translate into increased duration of the QT interval, increased risk of torsade de pointes or sudden death in clinical practice. The reasons for these apparent discrepancies are unclear and many studies have underscored the importance of the interpretation of in vitro electrophysiological data in the context of other pharmacodynamic (e.g. cardiac ion channels target, receptor affinity) and pharmacokinetic parameters (total plasma drug concentration and drug distribution). To address the possible relevance of the concentrations used in experimental studies, the myocardium distribution of sertindole and its metabolite was determined after single and repeated intraperitoneal administration to guinea-pigs. The data suggest that the plasma concentration appears to predict the concentration in the myocardium and that the myocardium concentrations of sertindole are 3.1 times higher than plasma concentrations. Using these data, the relevance of in vitro electrophysiological studies to clinical plasma concentrations has been appraised. Copyright © 2006 John Wiley & Sons, Ltd. [source] Electrospray-ionization mass spectrometry as a tool for fast screening of protein structural propertiesBIOTECHNOLOGY JOURNAL, Issue 1 2009Rita Grandori Abstract Since the early 1990s, electrospray-ionization mass spectrometry (ESI-MS) has encountered growing interest as a complementary tool to established biochemical and biophysical methods for investigating protein structure and conformation. Nowadays, applications of ESI-MS to protein investigation span from the area of analytical biochemistry to that of structural biology. This review focuses on applications of this technique to the analysis of protein conformational properties and molecular interactions, underscoring their possible relevance for molecular biotechnology, although representing a still very young field. An introductive section presents the major issues related to theoretical and technical aspects of ESI-MS under non-denaturing conditions. Examples from our work and from the literature illustrate which kind of information can be obtained concerning key issues in biotechnology such as stability and aggregation of proteins under both near-native and challenging conditions, and interactions with other proteins, ligands and cofactors. [source] Haplotypes of the interleukin-4 receptor , chain gene associate with susceptibility to and severity of atopic asthmaCLINICAL & EXPERIMENTAL ALLERGY, Issue 10 2004A.-M. Hytönen Summary Background Development of asthma is likely to depend on a complex interaction between environmental and genetic factors. Several groups have suggested the gene of the IL-4 receptor , chain (IL4R) as a candidate gene for the development of asthma, although association with single polymorphisms has shown contradicting results. Objective We chose to analyse IL4R gene haplotypes and assess their possible relevance in susceptibility to asthma and to certain clinical phenotypes. Methods IL4R gene haplotypes were analysed, based on the three markers C-3223T, Q551R and I50V, using the expectation,maximization algorithm, in 170 atopic asthma patients and 350 controls, all adult Swedish Caucasians. Results Our data showed significantly higher levels of soluble IL-4R (sIL-4R) in asthma patients compared with controls (P<0.0001). Furthermore, we showed a significant association between the IL4R haplotype containing the alleles T-3223, V50 and R551 (TVR) of the IL4R gene, and susceptibility to atopic asthma, with a frequency of 6.5% in the patients compared with 1% in the controls (P<0.0005). A subgroup of patients with heterozygous or homozygous state for the T-3223, V50 and R551 alleles, also had lower levels of sIL-4R in their circulation compared with patients with homozygous state in the C-3223, I50 and Q551 alleles (P<0.05) and showed less severe asthma according to lung function test (P<0.05). Analysis of single markers showed the T-3223 IL4R allele to associate with lower serum levels of sIL-4 receptor (P<0.0001) and patients carrying the T allele also had more symptoms of active asthma (wheezing, P<0.01; coughing, P<0.05 and breathing difficulties, P<0.01). Conclusion Our data suggest that asthmatic patients with low levels of sIL-4 receptor may represent a genetically distinct subgroup of atopic asthma. TVR haplotype analyses confirm the importance of IL4R as a candidate gene for susceptibility to asthma. This finding may have implications for the understanding of the pathogenesis of asthma and possibly for the development of more specific therapies. [source] Which children should we patch test?CLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 1 2007P. E. Beattie Summary Background., Allergic contact dermatitis (ACD) in childhood was considered rare until recently. However, reports are increasing, which may reflect an increased incidence and/or more frequent patch testing of children. It is also likely that allergen exposure in children has changed with time. Aims., To determine the most common contact allergens and the rate of positive patch-test reactions among children with suspected contact allergy. Methods., We carried out a retrospective case study of 114 children (66 girls and 48 boys) aged from 3 to 15 years (median 11.5) patch tested over a 3-year period. Indications for patch testing included uncontrolled or deteriorating atopic dermatitis, localized dermatitis or a history of reacting to a specific allergen. Results., Of 110 children for whom we had notes, 83 (75%) had a history of atopy. Positive reactions that were of current, past or possible relevance were seen in 61 children (54%); in 58 (52%) of 111 tested with the standard series (SS) and in 6 (10%) of 60 tested with the medicament series. None of the children patch tested to the corticosteroid (n = 47), shoe (n = 15), fragrance (n = 12), cosmetic (n = 10) or rubber (n = 5) series had a positive reaction. However, 11 (10%) reacted to rubber allergens within the SS and one of five to their own shoes. The lowest rate of relevant positive reactions was among those with deteriorating atopic dermatitis (22%) and facial (33%) or perioral dermatitis (40%), and the highest rate amongst those with eyelid (86%) or hand (71%) dermatitis. Nickel was the most common allergen (20%) in line with previous reports (82% female), followed by rubber chemicals (10%), fragrance (7.2%), cobalt (5.4%) and lanolin (wool alcohol) (4.5%). Conclusions., The reported incidence of ACD among children, in particular nickel and rubber allergy, appears to be increasing, which may relate to changing fashions and hobbies. Contact allergy should be considered in all children with dermatitis, particularly with eyelid or hand dermatitis, and patch testing carried out more frequently. [source] Starting with complex primitives pays off: complicate locally, simplify globallyCOGNITIVE SCIENCE - A MULTIDISCIPLINARY JOURNAL, Issue 5 2004Aravind K. Joshi Abstract In setting up a formal system to specify a grammar formalism, the conventional (mathematical) wisdom is to start with primitives (basic primitive structures) as simple as possible, and then introduce various operations for constructing more complex structures. An alternate approach is to start with complex (more complicated) primitives, which directly capture some crucial linguistic properties and then introduce some general operations for composing these complex structures. These two approaches provide different domains of locality, i.e., domains over which various types of linguistic dependencies can be specified. The latter approach, characterized as complicate locally, simplify globally (CLSG), pushes non-local dependencies to become local, i.e., they arise in the basic primitive structures to start with. The CLSG approach has led to some new insights into syntactic description, semantic composition, language generation, statistical processing, and psycholinguistic phenomena, all these with possible relevance to the cognitive architecture of language. In this paper, we will describe these results in an introductory manner making use of the framework of lexicalized tree-adjoining grammar (LTAG), a key example of the CLSG approach, thereby describing the interplay between formal analysis on the one hand and linguistic and processing issues on the other hand. [source] | ||||||||||||||||