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Selected AbstractsIs oxidative stress involved in the aetiology of pre-eclampsia?ACTA PAEDIATRICA, Issue 2001L Poston Pre-eclampsia is one of the major indications for elective premature delivery. Several lines of evidence suggest that pre-eclampsia is associated with a state of oxidative stress, offering hope of prevention by antioxidant supplementation. It was recently shown by the present authors that supplementation with vitamin C and E from early in pregnancy leads to a reduction in the incidence of the disease in "high-risk" women. [source] Activator of G-protein signaling in asymmetric cell divisions of the sea urchin embryoDEVELOPMENT GROWTH & DIFFERENTIATION, Issue 9 2006Ekaterina Voronina An asymmetric fourth cell division in the sea urchin embryo results in formation of daughter cells, macromeres and micromeres, with distinct sizes and fates. Several lines of functional evidence presented here, including pharmacological interference and dominant negative protein expression, indicate that heterotrimeric G protein Gi and its interaction partner, activator of G-protein signaling (AGS), are necessary for this asymmetric cell division. Inhibition of Gi signaling by pertussis toxin interferes with micromere formation and leads to defects in embryogenesis. AGS was isolated in a yeast two-hybrid screen with G,i as bait and was expressed in embryos localized to the cell cortex at the time of asymmetric divisions. Introduction of exogenous dominant-negative AGS protein, containing only G-protein regulatory (GPR) domains, selectively prevented the asymmetric division in normal micromere formation. These results support the growing evidence that AGS is a universal regulator of asymmetric cell divisions in embryos. [source] Reduced parietal and visual cortical activation during global processing in Williams syndromeDEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 6 2007Dean Mobbs BSc Several lines of investigation suggest that individuals with Williams syndrome (WS), a neurodevelopmental disorder of well-characterized genetic etiology, have selective impairments in integrating local image elements into global configurations. We compared global processing abilities in 10 clinically and genetically diagnosed participants with WS (eight females, two males; mean age 31y 10mo [SD 9y 7mo], range 15y 5mo-48y 4mo) with a typically developed (TD) age- and sex-matched comparison group (seven females, one male; mean age 35y 2mo [SD 10y 10mo], range 24y-54y 7mo) using functional magnetic resonance imaging (fMRI). Behavioral data showed participants with WS to be significantly less accurate (p<0.042) together with a non-significant trend to be slower than the TD comparison group while performing the global processing task. fMRI data showed participants with WS to possess reduced activation in the visual and parietal cortices. Participants with WS also showed relatively normal activation in the ventral occipitotemporal cortex, but elevated activation in several posterior thalamic nuclei. These preliminary results largely confirm previous research findings and neural models implicating neurodevelopmental abnormalities in extended subcortical and cortical visual systems in WS, most notably dorsal-stream pathways. [source] Adipocyte prolactin: regulation of release and putative functionsDIABETES OBESITY & METABOLISM, Issue 4 2007T. Brandebourg Pituitary-derived prolactin (PRL) is a well-known regulator of the lactating mammary gland. However, the recent discovery that human adipose tissue produces PRL as well as expresses the PRL receptor (PRLR) highlights a previously unappreciated action of PRL as a cytokine involved in adipose tissue function. Biologically active PRL is secreted by all adipose tissue depots examined: breast, visceral and subcutaneous. The expression of adipose PRL is regulated by a non-pituitary, alternative superdistal promoter. PRL expression and release increases during early pre-adipocyte differentiation and is stimulated by cyclic AMP activators, including , adrenergic receptor agonists. PRL release from subcutaneous adipose explants is attenuated during obesity, suggesting that adipose PRL production is altered by the metabolic state. Several lines of evidence indicate that PRL suppresses lipid storage as well as the release of adipokines such as adiponectin, interleukin-6 and possibly leptin. PRL has also been implicated in the regulation of adipogenesis. A newly developed PRL-secreting human adipocyte cell line, LS14, should allow comprehensive examination of the regulation and function of adipocyte-derived PRL. Collectively, these studies raise the prospect that PRL affects energy homeostasis through its action as an adipokine and is involved in the manifestation of insulin resistance. [source] How does the periapical inflammatory process compromise general health?ENDODONTIC TOPICS, Issue 1 2004Idikó. Several lines of evidence support the causative role of oral inflammatory lesions and certain systemic diseases, such as atherosclerosis and cardiovascular diseases, adverse pregnancy outcome and lung diseases. Properly executed epidemiologic studies identified increased odds ratios. Local or metastatic spread of oral microorganisms, local production of microbial or host-derived soluble regulatory molecules, that may initiate or sustain inflammatory events in remote tissues and organs and the presence of (a) common , extrinsic- or intrinsic-pathological mechanism(s) may result in or contribute to both local and systemic inflammation. A number of cross-sectional studies addressing a possible association between oral health and systemic diseases have also investigated the presence or the absence of periapical lesions. However, these studies cannot either confirm or refute a role of the periapical inflammatory lesion in the observed associations, since other variables of oral health might have exerted an inestimable influence on general health of the assessed population. The literature, dealing with patients with root canal infections and apical periodontitis as sole oral inflammatory lesions is extremely sparse. Our group has demonstrated that young adults with apical periodontitis exhibit certain biochemical changes, such as elevated levels of C-reactive protein and an increased whole blood chemiluminescence, which have been shown to elevate the risk for cardiovascular diseases. Future research will be required to determine whether and to what extent may endodontic diseases affect general health. [source] Multiple sclerosis complexity in selected populations: the challenge of Sardinia, insular Italy1EUROPEAN JOURNAL OF NEUROLOGY, Issue 4 2002S. Sotgiu Several lines of evidence indicate a genetic contribution to multiple sclerosis (MS) both in terms of predisposition to the disease and of immunological mechanisms which are known to play crucial roles in MS pathogenesis. The presence of high- and low-risk areas for MS in neighbouring regions supports the theory that MS predisposition is influenced by a complex interaction of genetic and environmental factors. Therefore, the use of genetically homogeneous and geographically isolated populations becomes an increasing requirement to reduce biasing biological variables. Sardinians fulfil these conditions well because of their different phylogeny from Europeans and the unique selective pressures which shaped their genome. Sardinians display amongst the highest MS prevalence rates world-wide and increasing MS incidence rates over time. Also, MS in Sardinia is linked to distinct human leucocyte antigen (HLA) alleles and associated to different patterns of cytokine production from lymphoid cells of different HLA subtypes. In this context, recent findings and future perspectives on the peculiarities of Sardinian MS concerning genetic, immunological and epidemiological aspects are presented. So far, our results indicate that variations at the level of territorial distribution and HLA-association are present which render MS heterogeneous even in this ethnically homogeneous population. [source] Intravenous heroin self-administration decreases GABA efflux in the ventral pallidum: an in vivo microdialysis study in ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2004Stéphanie Caillé Abstract Several lines of evidence suggest that opiate-induced disinhibition of the ventral pallidum participates in the mediation of opiate reward, though direct in vivo evidence to support this hypothesis has been lacking. The present experiment tested this hypothesis by investigating alterations in ventral pallidal amino acid efflux using in vivo microdialysis during ongoing intravenous heroin self-administration in rats. Concentrations of the inhibitory amino acid GABA in ventral pallidal dialysates were significantly reduced within the first 10 min of heroin self-administration (0.02 mg per infusion; FR-1), and remained ,,65% of presession baseline levels for the remainder of the 3-h self-administration session. Dialysate glutamate levels were unaltered during the first hour of heroin intake but significantly increased to a stable level of ,,120% presession values during the subsequent 2 h of self-administration. Thus, heroin self-administration is associated with both decreased GABA efflux and a late phase increase in glutamate efflux in the ventral pallidum. These observations are consistent with the hypothesis that heroin self-administration results in a disinhibition and/or excitation of the ventral pallidum. [source] Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2002Sangmi Chung Abstract Nurr1 is a transcription factor critical for the development of midbrain dopaminergic (DA) neurons. This study modified mouse embryonic stem (ES) cells to constitutively express Nurr1 under the elongation factor-1, promoter. The Nurr1-expression in ES cells lead to up-regulation of all DA neuronal markers tested, resulting in about a 4- to 5-fold increase in the proportion of DA neurons. In contrast, other neuronal and glial markers were not significantly changed by Nurr1 expression. It was also observed that there was an additional 4-fold increase in the number of DA neurons in Nurr1-expressing clones following treatment with Shh, FGF8 and ascorbic acid. Several lines of evidence suggest that these neurons may represent midbrain DA neuronal phenotypes; firstly, they coexpress midbrain DA markers such as aromatic l -amino acid decarboxylase, calretinin, and dopamine transporter, in addition to tyrosine hydroxylase and secondly, they do not coexpress other neurotransmitters such as GABA or serotonin. Finally, consistent with an increased number of DA neurons, the Nurr1 transduction enhanced the ability of these neurons to produce and release DA in response to membrane depolarization. This study demonstrates an efficient genetic manipulation of ES cells that facilitates differentiation to midbrain DA neurons, and it will serve as a framework of genetic engineering of ES cells by key transcription factor to regulate their cell fate. [source] PURGING THE GENOME WITH SEXUAL SELECTION: REDUCING MUTATION LOAD THROUGH SELECTION ON MALESEVOLUTION, Issue 3 2009Michael C. Whitlock Healthy males are likely to have higher mating success than unhealthy males because of differential expression of condition-dependent traits such as mate searching intensity, fighting ability, display vigor, and some types of exaggerated morphological characters. We therefore expect that most new mutations that are deleterious for overall fitness may also be deleterious for male mating success. From this perspective, sexual selection is not limited to influencing those genes directly involved in exaggerated morphological traits but rather affects most, if not all, genes in the genome. If true, sexual selection can be an important force acting to reduce the frequency of deleterious mutations and, as a result, mutation load. We review the literature and find various forms of indirect evidence that sexual selection helps to eliminate deleterious mutations. However, direct evidence is scant, and there are almost no data available to address a key issue: is selection in males stronger than selection in females? In addition, the total effect of sexual selection on mutation load is complicated by possible increases in mutation rate that may be attributable to sexual selection. Finally, sexual selection affects population fitness not only through mutation load but also through sexual conflict, making it difficult to empirically measure how sexual selection affects load. Several lines of enquiry are suggested to better fill large gaps in our understanding of sexual selection and its effect on genetic load. [source] EVOLUTION OF SUBTERRANEAN DIVING BEETLES (COLEOPTERA: DYTISCIDAE HYDROPORINI, BIDESSINI) IN THE ARID ZONE OF AUSTRALIAEVOLUTION, Issue 12 2003Remko Leys Abstract Calcrete aquifers in arid inland Australia have recently been found to contain the world's most diverse assemblage of subterranean diving beetles (Coleoptera: Dytiscidae). In this study we test whether the adaptive shift hypothesis (ASH) or the climatic relict hypothesis (CRH) is the most likely mode of evolution for the Australian subterranean diving beetles by using a phylogeny based on two sequenced fragments of mitochondrial genes (CO1 and 16S-tRNA-ND1) and linearized using a relaxed molecular clock method. Most individual calcrete aquifers contain an assemblage of diving beetle species of distantly related lineages and/or a single pair of sister species that significantly differ in size and morphology. Evolutionary transitions from surface to subterranean life took place in a relatively small time frame between nine and four million years ago. Most of the variation in divergence times of the sympatric sister species is explained by the variation in latitude of the localities, which correlates with the onset of aridity from the north to the south and with an aridity maximum in the Early Pliocene (five mya). We conclude that individual calcrete aquifers were colonized by several distantly related diving beetle lineages. Several lines of evidence from molecular clock analyses support the CRH, indicating that all evolutionary transitions took place during the Late Miocene and Early Pliocene as a result of aridification. [source] Bifidobacterium longum lysate, a new ingredient for reactive skinEXPERIMENTAL DERMATOLOGY, Issue 8 2010Audrey Guéniche Please cite this paper as: Bifidobacterium longum lysate, a new ingredient for reactive skin. Experimental Dermatology 2010; 19: e1,e8. Abstract:, Reactive skin is characterized by marked sensitivity to physical (heat, cold, wind) or chemical (topically applied products) stimuli and by the impairment of the skin barrier's ability to repair itself. Several lines of evidence suggest that beyond their capacity to positively influence the composition of intestinal microbiota, some probiotic bacteria can modulate the immune system both at local and systemic levels, thereby improving immune defense mechanisms and/or down-regulating immune disorders such as allergies and intestinal inflammation. Several recent human clinical trials clearly suggest that probiotic supplementation might be beneficial to the skin. Using a probiotic lysate, Bifidobacterium longum sp. extract (BL), we demonstrated first in vitro, and then in a clinical trial, that this non-replicating bacteria form applied to the skin was able to improve sensitive skin. The effect of BL were evaluated first on two different models. Using ex vivo human skin explant model we found a statistically significant improvement versus placebo in various parameters associated with inflammation such as a decrease in vasodilation, oedema, mast cell degranulation and TNF-alpha release. Moreover, using nerve cell cultures in vitro, we showed that after 6 h of incubation in culture medium (0.3,1%), the probiotic lysate significantly inhibited capsaicin-induced CGRP release by neurones. Then, a topical cream containing the active extract was tested in a randomized, double-blind, placebo-controlled trial. Sixty-six female volunteers with reactive skin were randomly given either the cream with the bacterial extract at 10% (n = 33) or the control cream (n = 33). The volunteers applied the cream to the face, arms and legs twice a day for two months. Skin sensitivity was assessed by stinging test (lactic acid) and skin barrier recovery was evaluated by measuring trans-epidermal water loss following barrier disruption induced by repeated tape-stripping at D1, D29 and D57. The results demonstrated that the volunteers who applied the cream with bacterial extract had a significant decrease in skin sensitivity at the end of the treatment. Moreover, the treatment led to increase skin resistance against physical and chemical aggression compared to the group of volunteers who applied the control cream. Notably, the number of strippings required to disrupt skin barrier function was significantly increased for volunteers treated with the active cream. Clinical and self-assessment scores revealed a significant decrease in skin dryness after 29 days for volunteers treated with the cream containing the 10% bacterial extract. Since in vitro studies demonstrated that, on one hand, isolate sensitive neurones release less CGRP under capsaicin stimulation in the presence of the bacterial extract and, on the other hand, increased skin resistance in volunteers applying the test cream, we speculate that this new ingredient may decrease skin sensitivity by reducing neurone reactivity and neurone accessibility. The results of this studies demonstrate that this specific bacterial extract has a beneficial effect on reactive skin. These findings suggest that new approaches, based on a bacteria lysate, could be developed for the treatment and/or prevention of symptoms related to reactive skin. [source] Definition of the residues required for the interaction between glycine-extended gastrin and transferrin in vitroFEBS JOURNAL, Issue 17 2009Suzana Kovac Transferrin is the main iron transport protein found in the circulation, and the level of transferrin saturation in the blood is an important indicator of iron status. The peptides amidated gastrin(17) (Gamide) and glycine-extended gastrin(17) (Ggly) are well known for their roles in controlling acid secretion and as growth factors in the gastrointestinal tract. Several lines of evidence, including the facts that transferrin binds gastrin, that gastrins bind ferric ions, and that the level of expression of gastrins positively correlates with transferrin saturation, suggest the possible involvement of the transferrin,gastrin interaction in iron homeostasis. In the present work, the interaction between gastrins and transferrin has been characterized by surface plasmon resonance and covalent crosslinking. First, an interaction between iron-free apo-transferrin and Gamide or Ggly was observed. The fact that no interaction was observed in the presence of the chelator EDTA suggested that the gastrin,ferric ion complex was the interacting species. Moreover, removal of ferric ions with EDTA reduced the stability of the complex between apo-transferrin and gastrins, and no interaction was observed between Gamide or Ggly and diferric transferrin. Second, some or all of glutamates at positions 8,10 of the Ggly molecule, together with the C-terminal domain, were necessary for the interaction with apo-transferrin. Third, monoferric transferrin mutants incapable of binding iron in either the N-terminal or C-terminal lobe still bound Ggly. These findings are consistent with the hypothesis that gastrin peptides bind to nonligand residues within the open cleft in each lobe of transferrin and are involved in iron loading of transferrin in vivo. Structured digital abstract ,,MINT-7212832, MINT-7212849: Apo-transferrin (uniprotkb:P02787) and Gamide (uniprotkb:P01350) bind (MI:0407) by surface plasmon resonance (MI:0107) ,,MINT-7212881, MINT-7212909: Ggly (uniprotkb:P01350) and Apo-transferrin (uniprotkb:P02787) bind (MI:0407) by cross-linking studies (MI:0030) ,,MINT-7212864: Apo-transferrin (uniprotkb:P02787) and Ggly (uniprotkb:P01350) bind (MI:0407) by competition binding (MI:0405) [source] Association study between kynurenine 3-monooxygenase gene and schizophrenia in the Japanese populationGENES, BRAIN AND BEHAVIOR, Issue 4 2006N. Aoyama Several lines of evidence suggest that metabolic changes in the kynurenic acid (KYNA) pathway are related to the etiology of schizophrenia. The inhibitor of kynurenine 3-monooxygenase (KMO) is known to increase KYNA levels, and the KMO gene is located in the chromosome region associated with schizophrenia, 1q42-q44. Single-marker and haplotype analyses for 6-tag single nucleotide polymorphisms (SNPs) of KMO were performed (cases = 465, controls = 440). Significant association of rs2275163 with schizophrenia was observed by single-marker comparisons (P = 0.032) and haplotype analysis including this SNP (P = 0.0049). Significant association of rs2275163 and haplotype was not replicated using a second, independent set of samples (cases = 480, controls = 448) (P = 0.706 and P = 0.689, respectively). These results suggest that the KMO is unlikely to be related to the development of schizophrenia in Japanese. [source] Permeability of the continental crust: dynamic variations inferred from seismicity and metamorphismGEOFLUIDS (ELECTRONIC), Issue 1-2 2010S. E. INGEBRITSEN Geofluids (2010) 10, 193,205 Abstract The variation of permeability with depth can be probed indirectly by various means, including hydrologic models that use geothermal data as constraints and the progress of metamorphic reactions driven by fluid flow. Geothermal and metamorphic data combine to indicate that mean permeability (k) of tectonically active continental crust decreases with depth (z) according to log k , ,14,3.2 log z, where k is in m2 and z in km. Other independently derived, crustal-scale k,z relations are generally similar to this power-law curve. Yet there is also substantial evidence for local-to-regional-scale, transient, permeability-generation events that entail permeabilities much higher than these mean k,z relations would suggest. Compilation of such data yields a fit to these elevated, transient values of log k , ,11.5,3.2 log z, suggesting a functional form similar to that of tectonically active crust, but shifted to higher permeability at a given depth. In addition, it seems possible that, in the absence of active prograde metamorphism, permeability in the deeper crust will decay toward values below the mean k,z curves. Several lines of evidence suggest geologically rapid (years to 103 years) decay of high-permeability transients toward background values. Crustal-scale k,z curves may reflect a dynamic competition between permeability creation by processes such as fluid sourcing and rock failure, and permeability destruction by processes such as compaction, hydrothermal alteration, and retrograde metamorphism. [source] Seismic constraints on the three-dimensional geometry of low-angle intracrustal reflectors in the Southern Iberia Abyssal PlainGEOPHYSICAL JOURNAL INTERNATIONAL, Issue 2 2008S. M. Dean SUMMARY Several lines of evidence suggest that simple shear rifting of the continental crust, in the form of low-angle detachment faulting, occurred during the final stages of continental breakup between West Iberia and the Grand Banks. The primary evidence for such faulting is the occurrence of low-angle, high amplitude reflectors within the basement adjacent to the ocean,continent transition zone. Here we present a series of intersecting, depth migrated seismic reflection profiles that image one such reflector, the H-reflector, located on the southern edge of Galicia Bank. ,H' lies beneath several boreholes drilled during ODP Legs 149 and 173, in a region where the oceanward extent of extended continental crust steps at least 150 km westward from its location in the southern Iberia Abyssal Plain to its location off the relatively shallow Galicia Bank. In our profiles ,H' appears to define a surface that extends over a region of at least 200 km2 and that dips down ,19° to the north, towards Galicia Bank. The profiles show that a close affinity exists between ,H' and the most seaward continental crust. Based on geophysical data and ODP drilling results, we infer that the basement above ,H' is composed of continental crust deformed by extensional faults into a series of wedge-shaped blocks and thin slivers. These basement wedges have a complex 3-D geometry. ,H' rises to the basement surface on a number of the seismic profiles and appears to define locally the oceanward extent of continental fault blocks. [source] Cardiovascular Tolerability and Safety of Triptans: A Review of Clinical DataHEADACHE, Issue 2004David W. Dodick MD Triptans are not widely used in clinical practice despite their well-established efficacy, endorsement by the US Headache Consortium, and the demonstrable need to employ effective intervention to reduce migraine-associated disability. Although the relatively restricted use of triptans may be attributed to several factors, research suggests that prescribers' concerns about cardiovascular safety prominently figure in limiting their use. This article reviews clinical data,including results of clinical trials, postmarketing studies and surveillance, and pharmacodynamic studies,relevant to assessing the cardiovascular safety profile of the triptans. These data demonstrate that triptans are generally well tolerated. Chest symptoms occurring during use of triptans are usually nonserious and usually not attributed to ischemia. Incidence of triptan-associated serious cardiovascular adverse events in both clinical trials and clinical practice appears to be extremely low. When they do occur, serious cardiovascular events have most often been reported in patients at significant cardiovascular risk or in those with overt cardiovascular disease. Adverse cardiovascular events also have occurred, however, in patients without evidence of cardiovascular disease. Several lines of evidence suggest that nonischemic mechanisms are responsible for sumatriptan-associated chest symptoms, although the mechanism of chest symptoms has not been determined to date. Importantly, most of the clinical trials and clinical practice data on triptans are derived from patients without known cardiovascular disease. Therefore, the conclusions of this review cannot be extended to patients with cardiovascular disease. The cardiovascular safety profile of triptans favors their use in the absence of contraindications. [source] The role of genetic testing in soft tissue sarcomaHISTOPATHOLOGY, Issue 1 2006C R Antonescu Soft tissue tumours represent a heterogeneous group of mesenchymal lesions and their classification continues to evolve as a result of incorporating advances in cytogenetic and molecular techniques. In the last decade traditional diagnostic approaches were supplemented with a significant number of reliable molecular diagnostic tools, detecting tumour type-specific genetic alterations. In addition, the successful application of some of these techniques to formalin-fixed paraffin-embedded tissue made it possible to subject a broader range of clinical material to molecular analysis. Thus, molecular genetics has already become an integral part of the work-up in some tumours, such as paediatric small blue round cell tumours, which demonstrate characteristic translocations. Several lines of evidence suggest that sarcomas can be divided into two major genetic groups: (i) sarcomas with specific genetic alterations and usually simple karyotypes, such as reciprocal chromosomal translocations (e.g. FUS-DDIT3 in myxoid liposarcoma) and specific oncogenic mutations (e.g. KIT mutation in gastrointestinal stromal tumours); and (i) sarcomas with non-specific genetic alterations and complex unbalanced karyotypes. Some of these genetic abnormalities, including chromosomal numerical changes, translocations, gene amplifications or large deletions can be apparent at the cytogenetic level (karyotyping, fluoresence in situ hybridization), while others, such as small deletions, insertions or point mutations, require molecular genetic techniques (polymerase chain reaction and sequence analysis). This review focuses on the applicability of genetic testing in the diagnosis and prognosis of soft tissue sarcomas, and gives a realistic appraisal of the ancillary role of molecular techniques, including its advantages and limitations. [source] Presence of nanobacteria in psammoma bodies of ovarian cancer: evidence for pathogenetic role in intratumoral biomineralizationHISTOPATHOLOGY, Issue 6 2004G Hudelist Aims:, The presence of laminated, calcified extracellular debris known as psammoma bodies is a well-known histomorphological feature of ovarian adenocarcinomas and other human malignancies. Biomineralization has recently been found to be associated with a group of extremely small Gram-negative bacteria capable of precipitating calcium salts. The aim of the present study was to evaluate a possible pathogenic link between the development of psammoma bodies and nanobacteria infection. Material and results:, Immunohistochemical staining and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to analyse nanobacterial protein and gene expression in eight psammona body-containing adenocarcinomas and in 10 malignant ovarian tumours without signs of biomineralization. Nanobacterial proteins were detected in eight out of eight (100%) psammoma-positive tumour samples. Conversely, none of the 10 psammoma-negative tissues (0%) was positive for nanobacterial antigens. Furthermore, nanobacterial mRNA was detectable in all of the four tissues (100%) that contained psammoma bodies, but was absent in all 10 ovarian cystadenocarcinomas (0%) that were psammoma negative. Conclusions:, We found a 100% concordance between the expression of nanobacteria and the presence of psammoma bodies in malignant ovarian tumours. Several lines of evidence suggest the involvement of these organisms in the process of biomineralization. We therefore conclude that nanobacterial infection of malignant ovarian tissue contributes to mechanisms leading to the formation of calcified deposits known as psammoma bodies. [source] Mutations in the holocarboxylase synthetase gene HLCS,HUMAN MUTATION, Issue 4 2005Yoichi Suzuki Abstract Holocarboxylase synthetase (HLCS) deficiency is an autosomal recessive disorder. HLCS is an enzyme that catalyzes biotin incorporation into carboxylases and histones. Since the first report of the cDNA sequence, 30 mutations in the HLCS gene have been reported. Mutations occur throughout the entire coding region except exons 6 and 10. The types of mutations are one single amino acid deletion, five single nucleotide insertions/deletions, 22 missense mutations, and two nonsense mutations. The only intronic mutation identified thus far is c.1519+5G>A (also designated IVS10+5G>A), which causes a splice error. Several lines of evidence suggest that c.1519+5G>A is a founder mutation in Scandinavian patients. Prevalence of this mutation is about 10 times higher in the Faroe Islands than in the rest of the world. The mutations p.L237P and c.780delG are predominant only in Japanese patients. These are probably founder mutations in this population. Mutations p.R508W and p.V550M are identified in several ethic groups and accompanied with various haplotypes, suggesting that these are recurrent mutations. There is a good relationship between clinical biotin responsiveness and the residual activity of HLCS. A combination of a null mutation and a point mutation that shows less than a few percent of the normal activity results in neonatal onset. Patients who have mutant HLCS with higher residual activity develop symptom after the neonatal period and show a good clinical response to biotin therapy. Hum Mutat 26(4), 285,290, 2005. © 2005 Wiley-Liss, Inc. [source] The p38 mitogen-activated protein kinase regulates interleukin-1,-induced IL-8 expression via an effect on the IL-8 promoter in intestinal epithelial cellsIMMUNOLOGY, Issue 4 2003Kuljit Parhar Summary Several lines of evidence implicate the p38 mitogen-activated protein kinase (p38 MAPK) in the proinflammatory response to bacterial agents and cytokines. Equally, the transcription factor, nuclear factor (NF)-,B, is recognized to be a critical determinant of the inflammatory response in intestinal epithelial cells (IECs). However, the precise inter-relationship between the activation of p38 MAPK and activation of the transcription factor NF-,B in the intestinal epithelial cell (IEC) system, remains unknown. Here we show that interleukin (IL)-1, activates all three MAPKs in Caco-2 cells. The production of IL-8 and monocyte chemotactic protein 1 (MCP-1) was attenuated by 50% when these cells were preincubated with the p38 MAPK inhibitor, SB 203580. Further investigation of the NF-,B signalling system revealed that the inhibitory effect was independent of the phosphorylation and degradation of I,B,, the binding partner of NF-,B. This effect was also independent of the DNA binding of the p65 Rel A subunit, as well as transactivation, determined by an NF-,B luciferase construct, using both SB 203580 and dominant,negative p38 MAPK. Evaluation of IL-8 and MCP-1 RNA messages by reverse transcription,polymerase chain reaction (RT,PCR) revealed that the inhibitory effect of SB 203580 was associated with a reduction in this parameter. Using an IL-8,luciferase promoter construct, an effect of p38 upon its activation by both pharmacological and dominant,negative p38 construct co-transfection was demonstrated. It is concluded that p38 MAPK influences the expression of chemokines in intestinal epithelial cells, through an effect upon the activation of the chemokine promoter, and does not directly involve the activation of the transcription factor NF-,B. [source] The role of monitored natural recovery in sediment remediationINTEGRATED ENVIRONMENTAL ASSESSMENT AND MANAGEMENT, Issue 1 2006Victor S Magar Abstract The long-term goal of monitored natural recovery (MNR) is to achieve ecological recovery of biological endpoints in order to protect human and ecological health. Insofar as ecological recovery is affected by surface-sediment-contaminant concentrations, the primary recovery processes for MNR are natural sediment burial and contaminant transformation and weathering to less toxic forms. This paper discusses the overall approach for effective implementation of MNR for contaminated sediment sites. Several lines of evidence that may be used to demonstrate natural recovery processes are summarized, including documentation of source control; evidence of contaminant burial; measurement of surface sediment mixing depths and the active sediment benthic layer; measurement of sediment stability; contaminant transformation and weathering; modeling sediment transport, contaminant transport, and ecological recovery; measuring ecological recovery and long-term risk reduction; knowledge of future plans for use and development of the site; and watershed and institutional controls. In general, some form of natural recovery is expected and should be included as part of a remedy at virtually all contaminated sediment sites. Further, MNR investigations and an understanding of natural recovery processes provide cost-effective information and support the evaluation of more aggressive remedies such as capping, dredging, and the use of novel amendments. The risk of dredging or capping may be greater than the risk of leaving sediments in place at sites where capping or dredging offer little long-term environmental gain but pose significant short-term risks for workers, local communities, and the environment. [source] Cola-induced hypokalaemia: pathophysiological mechanisms and clinical implicationsINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2009V. Tsimihodimos Summary Background/Aims: The consumption of soft drinks has increased considerably during the last decades. Among them, the cola-based preparations are possibly the refreshments with the largest sales worldwide. In addition to the possible detrimental effects of moderate, chronic cola consumption, it has been proposed that the consumption of large amounts of cola-based soft drinks may result in severe hypokalaemia. Methods: In this review, we discuss the clinical significance of these disturbances and summarise the pathophysiological mechanism that may underlie the development of this rare, but potentially severe, side effect. Results/Conclusion: Several lines of evidence suggest that the chronic consumption of large amounts of cola soft drinks may adversely affect potassium homeostasis and result in potentially severe conditions such as hypokalaemic myopathy. [source] Isotretinoin and the controversy of psychiatric adverse effectsINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2006Jamison E. Strahan MD Isotretinoin is a synthetic oral retinoid that has great efficacy against severe, recalcitrant, nodulocystic acne. Since its introduction to the market, it has been associated with a variety of adverse psychiatric effects, including depression, psychosis, mood swings, violent behavior, suicide, and suicide attempts. A MEDLINE review was performed to compile all case reports, case series, adverse drug event reportings, and prospective and retrospective studies relating psychiatric adverse events to isotretinoin. In addition, literature linking a biological mechanism for psychiatric adverse events to retinoid signaling pathways was also reviewed. Although a variety of anecdotal and epidemiologic studies are available, the overall lack of concrete scientific data limits any conclusion that can be drawn about a causal relationship between istotretinoin and psychiatric adverse events. Several lines of evidence link retinoid signaling to theorized psychiatric pathogenesis, but are limited in their applicability to adult neurophysiology. [source] Association of 5-HTT gene polymorphism, platelet MAO activity, and drive for thinness in a population-based sample of adolescent girlsINTERNATIONAL JOURNAL OF EATING DISORDERS, Issue 5 2008Kirsti Akkermann MSc Abstract Objective: Several lines of evidence suggest that alterations in serotonergic activity contribute to the pathophysiology of abnormal eating behaviors. Since platelet monoamine oxidase (MAO) activity and the 5-HT transporter gene promoter polymorphism (5-HTTLPR) have been associated with eating disorders, the knowledge from a population-based sample may provide useful information which changes in 5-HT function observed in eating disorders represent trait vs. state effects. Method: The sample was based on both cohorts of the Estonian Children Personality, Behavior and Health Study (ECPBHS). The current study was conducted during the second follow-up where altogether 82% from the original sample was recruited. EDI-2 subscales,Drive for Thinness and Bulimia,were used to determine eating attitudes and behaviors. Platelet MAO activity was measured and the participants were genotyped for the 5-HTTLPR. Results: Allelic variation of 5-HTTLPR or platelet MAO activity were not independently associated with drive for thinness or binge eating, but girls homozygous for the 5-HTTLPR long allele and with high platelet MAO activity, both considered indicators of a higher capacity 5-HT system, exhibited higher scores of drive for thinness. Conclusion: The results suggest that drive for thinness is the highest in girls with the presence of two markers of higher serotonergic capacity. © 2008 by Wiley Periodicals, Inc. Int J Eat Disord 2008 [source] Promoter polymorphism of the IL-18 gene is associated with atopic asthma in Tunisian childrenINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2008J. Lachheb Summary Several lines of evidence point to a relevant role of IL-18 in the process of asthma. Some studies suggest that the polymorphism in the gene of IL-18 can be involved in many inflammatory and atopic diseases such as asthma. The aim of our study is to estimate the frequency of the IL-18- 607 C/A (rs 1946518) promoter polymorphism in Tunisian children with asthma. We investigated whether the presence of this polymorphism -607 C/A was associated with asthma or atopy and whether this polymorphism influenced the severity of asthma in affected children. We examined also the relationship between the IL-18 gene polymorphism and the serum total IgE level. The IL-18/-607 C/A polymorphism was analysed by polymerase chain reaction and restriction fragment-length polymorphism (PCR-RFLP) analysis. A total of 105 asthma patients and 112 controls as part of the whole children population were studied in a case-control study. Among the 105 children with asthma, 40 were also studied for linkage analyses with their respective parents. We noted that the A allele was associated with statistically significant increases in the risk of asthma in the case-control study (odd ratio (OR) = 1.55, 95% confidence interval (CI) 1.03,2.33. Moreover, the A allele was also associated with atopic asthma (P = 0.008), but not with asthma severity. The transmission disequilibrium test (TDT) analysis in this family study did not suggest a preferential transmission of the IL-18/ -607 C/A polymorphism to affected children. There is no correlation between the IgE level and the IL-18 - 607 C/A promoter polymorphism. Our data indicate that IL-18 - 607 C/A promoter polymorphism is associated with susceptibility to developing asthma in Tunisian population. [source] CADISP-genetics: an International project searching for genetic risk factors of cervical artery dissectionsINTERNATIONAL JOURNAL OF STROKE, Issue 3 2009S. Debette Background Cervical artery dissection (CAD) is a frequent cause of ischemic stroke, and occasionally death, in young adults. Several lines of evidence suggest a genetic predisposition to CAD. However, previous genetic studies have been inconclusive mainly due to insufficient numbers of patients. Our hypothesis is that CAD is a multifactorial disease caused by yet largely unidentified genetic variants and environmental factors, which may interact. Our aim is to identify genetic variants associated with an increased risk of CAD and possibly gene,environment interactions. Methods We organized a multinational European network, Cervical Artery Dissection and Ischemic Stroke Patients (CADISP), which aims at increasing our knowledge of the pathophysiological mechanisms of this disease in a large group of patients. Within this network, we are aiming to perform a de novo genetic association analysis using both a genome-wide and a candidate gene approach. For this purpose, DNA from approximately 1100 patients with CAD, and 2000 healthy controls is being collected. In addition, detailed clinical, laboratory, diagnostic, therapeutic, and outcome data are being collected from all participants applying predefined criteria and definitions in a standardized way. We are expecting to reach the above numbers of subjects by early 2009. Conclusions We present the strategy of a collaborative project searching for the genetic risk factors of CAD. The CADISP network will provide detailed and novel data on environmental risk factors and genetic susceptibility to CAD. [source] LPS-Induced Inhibition of Osteogenesis Is TNF-, Dependent in a Murine Tooth Extraction Model,,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2009Nobuyoshi Tomomatsu Abstract TNF-, is a major etiologic factor of inflammatory bone diseases such as periodontitis and rheumatoid arthritis. In addition, patients with metabolic diseases such as chronic heart disease and diabetes have significantly increased plasma levels of TNF-,. Several lines of evidence show inhibition of osteoblastogenesis by TNF-, in vitro. Therefore, bone formation and osteogenesis in these patients might be inhibited because of TNF-,. However, little is known about the inhibitory role of TNF-, in bone formation/osteogenesis in vivo. The purpose of this study was to investigate the role of TNF-, in osteogenesis using a murine tooth extraction model. Lipopolysaccharide (LPS) was injected subcutaneously into the calvariae of either wildtype (WT) or TNF-,,deficient (KO) mice. The left incisor was extracted 4 days after LPS injection. The measuring area was established as the tooth socket under the mesial root of the first molar. A significant increase in serum TNF-, levels after LPS injection was observed in WT mice. The BMD of the tooth socket was significantly decreased by LPS injection 21 days after extraction in WT but not in KO mice. Histomorphometric analysis showed a significant decrease in the mineral apposition rate after LPS injection, which appeared at an early stage in WT but not in KO mice. Injection of a peptide that blocked the TNF-, signaling pathway by preventing transmission of the NF-,B signal recovered the inhibition of osteogenesis observed after LPS injection. In conclusion, TNF-, might play a major role in LPS-induced inhibition of osteogenesis under inflammatory conditions. [source] Indirect modulation of dopamine D2 receptors as potential pharmacotherapy for schizophrenia: III.JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2002Retinoids Present antipsychotic drugs, whose clinical activity correlates with direct binding to dopamine D2 or other receptors, alleviate some of the symptoms of schizophrenia, but not all and not completely in many patients. In continuation of our overview of potential novel antipsychotic pharmacotherapy that would be based upon indirect modulation of dopamine or other neurotransmitter functioning, we focus in this article on the postulated use of retinoid analogs as novel antipsychotic agents. Several lines of evidence can be viewed as implicating retinoid dysregulation in schizophrenia, either as a causative or contributory factor. It has been proposed that using retinoid analogs to alter the downstream expression of dopamine D2 receptors might represent a novel approach to the treatment of the disease or amelioration of symptoms when used either as monotherapy or as adjunct pharmacotherapy to dopamine D2 receptor antagonists. [source] Ant nest location, soil nutrients and nutrient uptake by ant-associated plants: does extrafloral nectar attract ant nests and thereby enhance plant nutrition?JOURNAL OF ECOLOGY, Issue 3 2010Diane Wagner Summary 1. As central place foragers, ants accumulate organic debris near their nests. Consequently, soil nutrient stocks are often enriched near the nest site. We investigated the hypothesis that plant-derived food sources, such as extrafloral nectar (EFN), can encourage soil-dwelling ant colonies to nest near the plant, thereby inadvertently providing the plant with an additional source of mineral nutrients. The study focused on a population of Acacia constricta, a North American shrub bearing EFNs. 2. Several lines of evidence supported the notion that food rewards drew ant nests close to A. constricta plants. Firstly, ant species that visit EFNs nested significantly closer to A. constricta plants than would be expected by chance, whereas this was not the case for two ant species that do not visit EFNs. Secondly, A. constricta plants with an ant nest occurring naturally underneath the canopy had greater foliar volume, more EFNs per leaf and more EFNs per cm of leaf rachis than plants lacking an ant nest under the canopy. Thirdly, experimental supplementation of the nectar resources on acacias led to the establishment of significantly more new nests near the plant, relative to controls. However, nectar supplementation did not affect acacia seed production within the year of the study. 3. Soil from the nests of three, EFN-visiting ant species contained higher average stocks of most mineral nutrients than nearby soils outside the influence of the nest. 4. To test whether A. constricta can assimilate the nutrients in ant nests, we fed 15N-labelled food to Dorymyrmex sp. (smithi complex) workers nesting near acacias. Twenty-four days later, the leaves of acacias with an experimentally fed ant colony under the canopy contained significantly higher 15N and %N than acacias without a nest under the canopy, indicating that acacias assimilated and benefited from nutrients derived from ants. 5.Synthesis. The results indicate that nectar resources can attract the nests of some ant species, and that plants may benefit from access to soil nutrients derived from ant nests. Our data support the hypothesis that EFNs may confer nutritive, as well as protective, benefits. [source] VOTING, INEQUALITY AND REDISTRIBUTIONJOURNAL OF ECONOMIC SURVEYS, Issue 1 2007Rainald Borck Abstract This paper surveys models of voting on redistribution. Under reasonable assumptions, the baseline model produces an equilibrium with the extent of redistributive taxation chosen by the median income earner. If the median is poorer than average, redistribution is from rich to poor, and increasing inequality increases redistribution. However, under different assumptions about the economic environment, redistribution may not be simply rich to poor, and inequality need not increase redistribution. Several lines of argument are presented, in particular, political participation, public provision of private goods, public pensions, and tax avoidance or evasion. [source] | |||||||||||||||||||||||||||||||||||||||||||