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Selected AbstractsFrequency, function and CLA expression of CD4+CD25+FOXP3+ regulatory T cells in bullous pemphigoidEXPERIMENTAL DERMATOLOGY, Issue 1 2007Anne Rensing-Ehl Abstract:, Bullous pemphigoid (BP) is an autoimmune blistering skin disease associated with autoantibodies to collagen XVII and tissue-separation along the dermo-epidermal junction. We addressed the question whether the loss of tolerance in BP patients is associated with a reduction and/or functional impairment of CD4+CD25+FOXP3+ regulatory T cells, which are essential for the active maintenance of self tolerance. The relative and absolute frequency of CD4+CD25+ and CD4+CD25high regulatory T cells in the peripheral blood of newly diagnosed, untreated patients was similar to that of healthy controls. Interestingly, more than 50% of circulating CD4+CD25high regulatory T cells from both patients as well as healthy controls expressed cutaneous lymphocyte-associated antigen. Considerable numbers of FOXP3+ cells were detected in lesional skin of patients. CD4+CD25+ regulatory T cells of patients were functionally intact as assessed by their ability to suppress allogeneic as well as antigen-specific T-cell proliferation. These data argue against a general defect of CD4+CD25+FOXP3+ regulatory T cells in patients with BP. [source] Sensitization to 26 fragrances to be labelled according to current European regulationCONTACT DERMATITIS, Issue 1 2007Results of the IVDK, review of the literature To study the frequency of sensitization to 26 fragrances to be labelled according to current European regulation. During 4 periods of 6 months, from 1 January 2003 to 31 December 2004, 26 fragrances were patch tested additionally to the standard series in a total of 21 325 patients; the number of patients tested with each of the fragrances ranged from 1658 to 4238. Hydroxymethylpentylcyclohexene carboxaldehyde (HMPCC) was tested throughout all periods. The following frequencies of sensitization (rates in %, standardized for sex and age) were observed: tree moss (2.4%), HMPCC (2.3), oak moss (2.0), hydroxycitronellal (1.3), isoeugenol (1.1), cinnamic aldehyde (1.0), farnesol (0.9), cinnamic alcohol (0.6), citral (0.6), citronellol (0.5), geraniol (0.4), eugenol (0.4), coumarin (0.4), lilial (0.3), amyl-cinnamic alcohol (0.3), benzyl cinnamate (0.3), benzyl alcohol (0.3), linalool (0.2), methylheptin carbonate (0.2), amyl-cinnamic aldehyde (0.1), hexyl-cinnamic aldehyde (0.1), limonene (0.1), benzyl salicylate (0.1), ,-methylionon (0.1), benzyl benzoate (0.0), anisyl alcohol (0.0). 1) Substances with higher sensitization frequencies were characterized by a considerable number of ,++/+++' reactions. 2) Substances with low sensitization frequencies were characterized by a high number of doubtful/irritant and a low number of stronger (++/+++) reactions. 3) There are obviously fragrances among the 26 which are, with regard to contact allergy, of great, others of minor, and some of no importance at all. [source] Restoring satisfactory status in ThinPrep Pap test specimens with too few squamous cells and containing microscopic red blood cellsDIAGNOSTIC CYTOPATHOLOGY, Issue 10 2008Ph.D., Yijun Pang M.D. Abstract Treatment of specimens that contain excessive blood can effectively reduce the unsatisfactory rate; however, a considerable number of unsatisfactory specimens remain. We evaluated the effectiveness of reprocessing unsatisfactory specimens that had too few squamous cells and contained microscopic red blood cells (TFSQRBC). Out of the 688 unsatisfactory specimens at microscopic screening, 197 (28.63%) were TFSQRBC that were reprocessed by treatment of glacial acetic acid (GAA). Red blood cells were observed clogging the pores in the filter of the ThinPrep device. After reprocessing, 129 (68.48%) yielded a satisfactory diagnosis, which accounted for a reduction of the unsatisfactory rate by 18.25%. In the restored satisfactory specimens, abnormal diagnoses of 1 high-grade squamous intraepithelial lesion (HSIL) (0.78%), 3 atypical glandular cells (AGC) (2.33%), and 13 atypical squamous cells of undetermined significance (ASCUS) (10.08%) were made. The abnormal diagnoses in this group of patients were significantly higher than that in the general population screened. Reprocessing unsatisfactory ThinPrep® (TP) specimens of TFSQRBC can reduce the unsatisfactory rate of the TP Pap test significantly and is a cost-effective measure. The initially unsatisfactory specimens are more likely to represent cases with an abnormal diagnosis, which also justifies the effort of reprocessing this group of specimens. Adjustment of the pore size on the ThinPrep filter device may reduce the interference of red blood cells. Diagn. Cytopathol. 2008;36:696,700. © 2008 Wiley-Liss, Inc. [source] High local species richness of parasitic wasps (Hymenoptera: Ichneumonidae; Pimplinae and Rhyssinae) from the lowland rainforests of Peruvian AmazoniaECOLOGICAL ENTOMOLOGY, Issue 6 2004Ilari E. Sääksjärvi Abstract., 1. The parasitic wasp family Ichneumonidae (Hymenoptera) is of great interest because it has been claimed that its species richness does not increase with decreasing latitude. 2. No extensive studies of the family have been conducted in South American localities. 3. Arthropods were sampled using 27 Malaise traps in the Allpahuayo,Mishana National Reserve (56 000 ha) in the north-eastern Peruvian Amazonian lowland rainforest. The total duration of the sampling programme was 185 Malaise trap months. 4. Altogether, 88 species were collected. This is one of the highest local pimpline and rhyssine species numbers ever recorded. A comparison with results from Mesoamerica revealed that at equal numbers of individuals sampled, the number of Pimplinae and Rhyssinae species in Peruvian Amazonia is at least twofold compared with lowland locations in Mesoamerica and somewhat higher than in the most species-rich Costa Rican higher altitude localities. 5. Non-parametric methods of estimating species richness were applied. These suggest that additional sampling would yield a considerable number of new Pimplinae and/or Rhyssinae species. [source] Predicting competition coefficients for plant mixtures: reciprocity, transitivity and correlations with life-history traitsECOLOGY LETTERS, Issue 4 2001R.P. Freckleton There are few empirical or theoretical predictions of how per capita or per individual competition coefficients for pairs of plant species should relate to each other. In contrast, there are a considerable number of general hypotheses that predict competitive ability as a function of a range of ecological traits, together with a suite of increasingly sophisticated models for competitive interactions between plant species. We re-analyse a data set on competition between all pairwise combinations of seven species and show that competition coefficients relate strongly to differences between the maximum sizes, root allocation, emergence time and seed size of species. Regressions suggest that the best predictor of competition coefficients is the difference in the maximum size of species and that correlations of the other traits with the competition coefficients occur through effects on the maximum size. We also explore the patterns of association between coefficients across the competition matrix. We find significant evidence for coefficient reciprocity (inverse relationships between the interspecific coefficients for species pairs) and transitivity (numerically predictable hierarchies of competition between species) across competition matrices. These results therefore suggest simple null models for plant community structure when there is competition for resources. [source] Generalizability of Cognitive Interview-Based Measures Across Cultural GroupsEDUCATIONAL MEASUREMENT: ISSUES AND PRACTICE, Issue 2 2009Guillermo Solano-Flores We addressed the challenge of scoring cognitive interviews in research involving multiple cultural groups. We interviewed 123 fourth- and fifth-grade students from three cultural groups to probe how they related a mathematics item to their personal lives. Item meaningfulness,the tendency of students to relate the content and/or context of an item to activities in which they are actors,was scored from interview transcriptions with a procedure similar to the scoring of constructed-response tasks. Generalizability theory analyses revealed a small amount of score variation due to the main and interaction effect of rater but a sizeable magnitude of measurement error due to the interaction of person and question (context). Students from different groups tended to draw on different sets of contexts of their personal lives to make sense of the item. In spite of individual and potential cultural communication style differences, cognitive interviews can be reliably scored by well-trained raters with the same kind of rigor used in the scoring of constructed-response tasks. However, to make valid generalizations of cognitive interview-based measures, a considerable number of interview questions may be needed. Information obtained with cognitive interviews for a given cultural group may not be generalizable to other groups. [source] Playing texts against each other in the multimodal English classroomENGLISH IN EDUCATION, Issue 2 2005Richard Beach Abstract This article explores the way adolescents and adults are experimenting with the multimodal affordances of contemporary intertextual practices. Drawing on a considerable number of recent research studies, we outline how young people and young adults are consistently engaging with the opportunities of the digital environment. We explore the recent history of multimodality, examining how we can help students move from simply using intertextuality for their own enjoyment, to a far more critical and informed position. This critical position, we feel, is especially powerful when students engage in intercontextuality and when they investigate issues of identity through the affordances of multimodal texts. Drawing on the research studies, we offer a number of ways in which English teachers can utilize the potential of their students' capability with the new technologies. [source] Eating-disordered patients with and without self-injurious behaviours: a comparison of psychopathological featuresEUROPEAN EATING DISORDERS REVIEW, Issue 5 2003Laurence Claes Objective: A considerable number of eating-disordered patients also display all kinds of self-injurious behaviours (SIB), which might be viewed as an indicator of psychopathological severity. Method: To test this hypothesis in 70 females admitted to a specialized treatment programme for eating disorders, a wide spectrum of psychopathological features was studied by means of self-reporting questionnaires: clinical symptomatology, personality disorders, aggression regulation, trauma history, dissociation and body experience. A comparison was made between patients with (n,=,27) and without SIB (n,=,43), as well as between patients with one (n,=,13) versus more types (n,=,14) of SIB. Results: In general, patients with SIB reported significantly more complaints or signs of anxiety, depression, hostility, cluster B personality disorders, feelings of anger, traumatic experiences, dissociation and negative appreciation of body size. The presence of more than one type of SIB was linked to a more pronounced clinical symptomatology and trauma history. . Copyright © 2003 John Wiley & Sons, Ltd and Eating Disorders Association. [source] The maintenance of specific aspects of neuronal function and behavior is dependent on programmed cell death of adult-generated neurons in the dentate gyrusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2009Woon Ryoung Kim Abstract A considerable number of new neurons are generated daily in the dentate gyrus (DG) of the adult hippocampus, but only a subset of these survive, as many adult-generated neurons undergo programmed cell death (PCD). However, the significance of PCD in the adult brain for the functionality of DG circuits is not known. Here, we examined the electrophysiological and behavioral characteristics of Bax -knockout (Bax -KO) mice in which PCD of post-mitotic neurons is prevented. The continuous increase in DG cell numbers in Bax -KO mice resulted in the readjustment of afferent and efferent synaptic connections, represented by age-dependent reductions in the dendritic arborization of DG neurons and in the synaptic contact ratio of mossy fibers with CA3 dendritic spines. These neuroanatomical changes were associated with reductions in synaptic transmission and reduced performance in a contextual fear memory task in 6-month-old Bax -KO mice. These results suggest that the elimination of excess DG neurons via Bax -dependent PCD in the adult brain is required for the normal organization and function of the hippocampus. [source] Neural selectivity for hue and saturation of colour in the primary visual cortex of the monkeyEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2000Akitoshi Hanazawa Abstract In the inferior temporal (IT) cortex of monkeys, which has been shown to play a critical role in colour discrimination, there are neurons sensitive to a narrow range of hues and saturation. By contrast, neurons in the retina and the parvocellular layer of the lateral geniculate nucleus (pLGN) encode colours in a way that does not provide explicit representation of hue or saturation, and the process by which hue- and saturation-selectivity is elaborated remains unknown. We therefore tested the colour-selectivity of neurons in the primary visual cortex (V1) and compared it with those of pLGN and IT neurons. Quantitative analysis was performed using a standard set of colours, systematically distributed within the CIE (Commission Internationale de l'Eclairage)-xy chromaticity diagram. Selectivity for hue and saturation was characterized by analysing response contours reflecting the overall distribution of responses across the chromaticity diagram. We found that the response contours of almost all pLGN neurons were linear and broadly tuned for hue. Many V1 neurons behaved similarly; nonetheless, a considerable number of V1 neurons had clearly curved response contours and were selective for a narrow range of hues or saturation. The relative frequencies of neurons exhibiting various selectivities for hue and saturation were remarkably similar in the V1 and IT cortex, but were clearly different in the pLGN. Thus, V1 apparently plays a very important role in the conversion of colour signals necessary for generating the elaborate colour selectivity observed in the IT cortex. [source] Transcriptional profiling of Francisella tularensis infected peripheral blood mononuclear cells: a predictive tool for tularemiaFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 1 2008Chrysanthi Paranavitana Abstract In this study, we analyzed temporal gene expression patterns in human peripheral blood mononuclear cells (PBMCs) infected with the Francisella tularensis live vaccine strain from 1 to 24 h utilizing a whole human Affymetrix® gene chip. We found that a considerable number of induced genes had similar expression patterns and functions as reported previously for gene expression profiling in patients with ulceroglandular tularemia. Among the six uniquely regulated genes reported for tularemia patients as being part of the alarm signal gene cluster, five, namely caspase 1, PSME2, TAP-1, GBP1, and GCH1, were induced in vitro. We also detected four out of the seven potential biomarkers reported in tularemia patients, namely TNFAIP6 at 4 h and STAT1, TNFSF10, and SECTM1 at 16 and 24 h. These observations underscore the value of using microarray expression profiling as an in vitro tool to identify potential biomarkers for human infection and disease. Our results indicate the potential involvement of several host pathways/processes in Francisella infection, notably those involved in calcium, zinc ion binding, PPAR signaling, and lipid metabolism, which further refines the current knowledge of F. tularensis infection and its effects on the human host. Ultimately, this study provides support for utilizing in vitro microarray gene expression profiling in human PBMCs to identify biomarkers of infection and predict in vivo immune responses to infectious agents. [source] Genome-wide DNA methylation profile of tissue-dependent and differentially methylated regions (T-DMRs) residing in mouse pluripotent stem cellsGENES TO CELLS, Issue 6 2010Shinya Sato DNA methylation profile, consisting of tissue-dependent and differentially methylated regions (T-DMRs), has elucidated tissue-specific gene function in mouse tissues. Here, we identified and profiled thousands of T-DMRs in embryonic stem cells (ESCs), embryonic germ cells (EGCs) and induced pluripotent stem cells (iPSCs). T-DMRs of ESCs compared with somatic tissues well illustrated gene function of ESCs, by hypomethylation at genes associated with CpG islands and nuclear events including transcriptional regulation network of ESCs, and by hypermethylation at genes for tissue-specific function. These T-DMRs in EGCs and iPSCs showed DNA methylation similar to ESCs. iPSCs, however, showed hypomethylation at a considerable number of T-DMRs that were hypermethylated in ESCs, suggesting existence of traceable progenitor epigenetic information. Thus, DNA methylation profile of T-DMRs contributes to the mechanism of pluripotency, and can be a feasible solution for identification and evaluation of the pluripotent cells. [source] Gross SDHB deletions in patients with paraganglioma detected by multiplex PCR: A possible hot spot?GENES, CHROMOSOMES AND CANCER, Issue 3 2006Alberto Cascón Pheochromocytoma and paraganglioma are rare neuroendocrine tumors that arise in the adrenal medulla and the extra-adrenal paraganglia, respectively. Inheritance of these tumors is mainly a result of mutations affecting the VHL, RET, NF1, and SDH genes. Germ-line mutations of the SDH genes have been found to account for nearly 10% of apparently sporadic cases. Nevertheless, alterations other than point mutations have not yet been well characterized. In this study, we investigated the frequency of gross SDH deletions in 24 patients who tested negative for point mutations and had at least one of the recommended features for genetic testing. For this purpose, we used a technique that is easy to implement in the lab to specifically detect gross deletions affecting SDHB, SDHC, and SDHD. We identified 3 heterozygous SDHB deletions (3/24) in 3 independent cases with paraganglioma: 1 whole SDHB deletion and 2 deletions exclusively affecting exon 1. These latter mutations match the unique gross deletion previously reported, indicating this region could be a hot spot for gross SDHB deletions. It seems likely that these alterations can account for a considerable number of both familial and apparently sporadic paraganglioma cases. Although this is the first report describing the presence of gross deletions in patients with apparently sporadic paragangliomas, the extra-adrenal location of the tumor seems to constitute a determining factor for whether to include these patients in genetic testing for gross deletions in the SDHB gene. © 2005 Wiley-Liss, Inc. [source] ,Rescue' Therapy with Rifabutin after Multiple Helicobacter pylori Treatment FailuresHELICOBACTER, Issue 2 2003Javier P. Gisbert abstract Aim. Eradication therapy with proton pump inhibitor, clarithromycin and amoxicillin is extensively used, although it fails in a considerable number of cases. A ,rescue' therapy with a quadruple combination of omeprazole, bismuth, tetracycline and metronidazole (or ranitidine bismuth citrate with these same antibiotics) has been recommended, but it still fails in approximately 20% of cases. Our aim was to evaluate the efficacy and tolerability of a rifabutin-based regimen in patients with two consecutive H. pylori eradication failures. Patients and Methods. Design: Prospective multicenter study. Patients: Consecutive patients in whom a first eradication trial with omeprazole, clarithromycin and amoxicillin and a second trial with omeprazole, bismuth, tetracycline and metronidazole (three patients) or ranitidine bismuth citrate with these same antibiotics (11 patients) had failed were included. Intervention: A third eradication regimen with rifabutin (150 mg bid), amoxicillin (1 g bid) and omeprazole (20 mg bid) was prescribed for 14 days. All drugs were administered together after breakfast and dinner. Compliance with therapy was determined from the interrogatory and the recovery of empty envelopes of medications. Outcome: H. pylori eradication was defined as a negative 13C-urea breath test 8 weeks after completing therapy. Results. Fourteen patients have been included. Mean age ± SD was 42 ± 11 years, 41% males, peptic ulcer (57%), functional dyspepsia (43%). All patients took all the medications and completed the study protocol. Per-protocol and intention-to-treat eradication was achieved in 11/14 patients (79%; 95% confidence interval = 49,95%). Adverse effects were reported in five patients (36%), and included: abdominal pain (three patients), nausea and vomiting (one patient), and oral candidiasis (one patient); no patient abandoned the treatment due to adverse effects. Conclusion. Rifabutin-based rescue therapy constitutes an encouraging strategy after multiple previous eradication failures with key antibiotics such as amoxicillin, clarithromycin, metronidazole and tetracycline. [source] Neuropsychiatric dysfunction in patients with chronic hepatitis and liver cirrhosisHEPATOLOGY RESEARCH, Issue 11 2008Kojiro Michitaka Aim:, The aim of this study is to clarify the cerebral functions in patients with chronic hepatitis (CH) as well as those with liver cirrhosis (LC). Methods:, We studied 58 patients with CH (20 in fibrosis stage F1, 20 in F2, 18 in F3), 77 with LC (46 rated as Child,Pugh class A, 24 as B, 7 as C), and 20 healthy volunteers (HV). Computer-aided quantitative neuropsychiatric function test systems, including eight neuropsychiatric tests were performed. Results:, Subjects with results over the cut-off value for healthy subjects ranged from 11.1,28.6% in CH and 19.5,36.4% in LC. The percentages with abnormality in at least one test in CH and LC were 72.4% and 80.6%, respectively, which were significantly higher than that in the HV group (35.0%) (P = 0.003, P = 0.0003, respectively). Among CH subjects, those with three or more abnormal results in the F1, F2 and F3 subgroups were 15.0%, 20.0% and 38.9%, respectively. Among LC subjects, those with three or more abnormal results in the Child,Pugh class A, B and C subgroups comprised 30.4%, 50.0% and 57.1%, respectively. The rate in the CH F3 subgroup (P = 0.011) and in all three LC subgroups (P = 0.023, P = 0.001, P = 0.002, respectively) were significantly higher than that in the HV group. Conclusion:, The percentage of patients with neuropsychiatric function impairment was high in both LC and CH, especially in stage F3. Neuropsychiatric dysfunction may initiate in CH in a considerable number of patients. [source] Roles of informal workplace trainers in different organizational contexts: Empirical evidence from Australian companiesHUMAN RESOURCE DEVELOPMENT QUARTERLY, Issue 2 2006Rob F. Poell Informal workplace trainers help employees learn what they need to know and do in order to get their job done. Little is known about the actions of informal workplace trainers, who may be colleagues or supervisors. This study provides an empirical basis for actions undertaken by informal workplace trainers. A total of 350 Australian enterprises were interviewed by telephone. Actions of informal workplace trainers were measured using a list of thirty-two statements based on prior qualitative research. Three factors were found to describe core role dimensions: support, structure, and performance. Also, three types of informal workplace trainer appeared: some had a passive indifferent role conception, a considerable number had a restricted role conception, and many had a broad, active role conception. Relationships of role dimensions and role conceptions with organizational context variables and characteristics of informal workplace trainers were tested as well. The study proposes several directions for further research. [source] Determining controller benefits via probabilistic optimizationINTERNATIONAL JOURNAL OF ADAPTIVE CONTROL AND SIGNAL PROCESSING, Issue 7-9 2003Y. Zhou Abstract For the most part, process control research has focussed on the synthesis and tuning of controllers, which has provided a plethora of techniques that can address virtually any application. With each new control technique, a steady stream of ,successful' application results are generated and reported. Recently, a considerable number of control researchers have turned their attention to assessing the performance of installed control systems and to the diagnosis of controller performance problems. Despite successes in the areas of controller synthesis, tuning and performance analysis, almost no research has addressed the fundamental issue of determining whether the economic performance gains that are expected accrue from a proposed process control project are sufficient to justify its execution. The work presented here proposes an optimization-based technique for calculating the expected economic performance of a given control system; a method, which is analogous to analysis of variance, for determining the expected economic benefit that will arise from a particular controller improvement effort; and a sensitivity analysis approach for determining the effect of specific assumptions on control system improvement decisions. Copyright © 2003 John Wiley & Sons, Ltd. [source] Problem solving therapy for the depression-executive dysfunction syndrome of late lifeINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 8 2008George S. Alexopoulos Abstract Background The ,depression executive dysfunction syndrome' afflicts a considerable number of depressed elderly patients and may be resistant to conventional pharmacotherapy. Non-pharmacological approaches addressing their behavioral deficits may reduce disability and experienced stress and improve depression. Methods This paper focuses on problem solving therapy (PST) because it targets concrete problems that can be understood by patients with executive dysfunction and trains patients to address them using an easy to comprehend structured approach. Results We suggest that PST is a suitable treatment for patients with the depression-executive dysfunction syndrome because it has been found effective in uncomplicated geriatric major depression and in other psychiatric disorders accompanied by severe executive dysfunction. Furthermore, PST can address specific clinical features of depressed patients with executive dysfunction, especially when modified to address difficulties with affect regulation, initiation and perseveration. Conclusions A preliminary study suggests that appropriately modified PST improves problem solving skills, depression and disability in elderly patients with the depression-executive dysfunction syndrome of late life. If these findings are confirmed, PST may become a therapeutic option for a large group of depressed elderly patients likely to be drug resistant. Copyright © 2008 John Wiley & Sons, Ltd. [source] Evolutionary analysis of fructose 2,6-bisphosphate metabolismIUBMB LIFE, Issue 3 2006Paul A. M. Michels Abstract Fructose 2,6-bisphosphate is a potent metabolic regulator in eukaryotic organisms; it affects the activity of key enzymes of the glycolytic and gluconeogenic pathways. The enzymes responsible for its synthesis and hydrolysis, 6-phosphofructo-2-kinase (PFK-2) and fructose-2,6-bisphosphatase (FBPase-2) are present in representatives of all major eukaryotic taxa. Results from a bioinformatics analysis of genome databases suggest that very early in evolution, in a common ancestor of all extant eukaryotes, distinct genes encoding PFK-2 and FBPase-2, or related enzymes with broader substrate specificity, fused resulting in a bifunctional enzyme both domains of which had, or later acquired, specificity for fructose 2,6-bisphosphate. Subsequently, in different phylogenetic lineages duplications of the gene of the bifunctional enzyme occurred, allowing the development of distinct isoenzymes for expression in different tissues, at specific developmental stages or under different nutritional conditions. Independently in different lineages of many unicellular eukaryotes one of the domains of the different PFK-2/FBPase-2 isoforms has undergone substitutions of critical catalytic residues, or deletions rendering some enzymes monofunctional. In a considerable number of other unicellular eukaryotes, mainly parasitic organisms, the enzyme seems to have been lost altogether. Besides the catalytic core, the PFK-2/FBPase-2 has often N- and C-terminal extensions which show little sequence conservation. The N-terminal extension in particular can vary considerably in length, and seems to have acquired motifs which, in a lineage-specific manner, may be responsible for regulation of catalytic activities, by phosphorylation or ligand binding, or for mediating protein-protein interactions. IUBMB Life, 58: 133 - 141, 2006 [source] Heparin and Heparan Sulfate BiosynthesisIUBMB LIFE, Issue 4 2002Kazuyuki Sugahara Abstract Heparan sulfate is one of the most informationally rich biopolymers in Nature. Its simple sugar backbone is variously modified to different degrees depending on the cellular conditions. Thus, it matures to have an enormously complicated structure, which most likely exhibits a considerable number of unique overlapping sequences with peculiar sulfation profiles. Such sequences are recognized by specific complementary proteins, which form a huge group of "heparin-binding proteins," and the sugar sequences in turn support unique functions of the respective proteins through specific interactions. The heparan sulfate sequences are not directly encoded by genes, but are created by elaborate biosynthetic mechanisms, which ensure the generation of these indispensable sequences. In heparan sulfate biosynthesis, the tetrasaccharide sequence (GlcA-Gal-Gal-Xyl-), designated the protein linkage region, is first assembled on a specific Ser residue at the glycosaminoglycan attachment site of a core protein. A heparan sulfate chain is then polymerized on this fragment by alternate additions of GlcNAc and GlcA through the actions of glycosyltransferases with overlapping specificities encoded by the tumor suppressor EXT family genes. Then follow various modifications by N -deacetylation and N -sulfation of glucosamine, C5-epimerization of GlcA and multiple O -sulfations of the component sugars. Recent studies have achieved purification of several, and molecular cloning of most, of the enzymes responsible for these reactions. Some of these enzymes are bifunctional. The availability of cDNA probes has facilitated elucidation of the crystal structures for two of the biosynthetic enzymes, demonstration of their intracellular location, and their occurrence in complexes to achieve rapid and efficient synthesis of complex sugar sequences. Genomic structure and transcript analysis have shown the existence of multiple isoforms for most of the sulfotransferases. Many aspects of the heparan sulfate biosynthetic scheme are shared by the structural analog heparin, which is synthesized in mast cells and some other mammalian cells and is several-fold higher degree of polymerization and more extensive modification than heparan sulfate. [source] Studies on codon usage in Thermoplasma acidophilum and its possible implications on the occurrences of lateral gene transferJOURNAL OF BASIC MICROBIOLOGY, Issue 5 2005S. K. Gupta Codon usage studies have been carried out on the coding sequences of Thermoplasma acidophilum, which is an archaeon and grows at very low pH and high temperature. Overall codon usage data analysis indicates that all the four bases are almost equifrequent at the third position of codons, which is expected (since genomic GC % of this genome is about 46%). However, multivariate statistical analysis indicates that there are two major trends in the codon usage variation among the genes in this organism. In the first major trend it is observed that genes having G and C ending codons are clustered at one end while, A and T ending ones are clustered at the other end. We have also found a significant positive correlation between the expressivities of genes and GC contents at the synonymous third codon positions. In the second major trend, it is seen that the genes are clustered into three distinct parts. A comparative analyses of codon usage data of T. acidophilum and Sulfolobus solfataricus reveals that one of the three clusters of genes of T. acidophilum is very similar to a considerable number of S. solfataricus genes, suggesting possible occurrences of lateral gene transfer between these two microorganisms as reported by earlier workers. (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Antisense applications for biological controlJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2006Wei-Hua Pan Abstract Although Nature's antisense approaches are clearly impressive, this Perspectives article focuses on the experimental uses of antisense reagents (ASRs) for control of biological processes. ASRs comprise antisense oligonucleotides (ASOs), and their catalytically active counterparts ribozymes and DNAzymes, as well as small interfering RNAs (siRNAs). ASOs and ribozymes/DNAzymes target RNA molecules on the basis of Watson-Crick base pairing in sequence-specific manner. ASOs generally result in destruction of the target RNA by RNase-H mediated mechanisms, although they may also sterically block translation, also resulting in loss of protein production. Ribozymes and DNAzymes cleave target RNAs after base pairing via their antisense flanking arms. siRNAs, which contain both sense and antisense regions from a target RNA, can mediate target RNA destruction via RNAi and the RISC, although they can also function at the transcriptional level. A considerable number of ASRs (mostly ASOs) have progressed into clinical trials, although most have relatively long histories in Phase I/II settings. Clinical trial results are surprisingly difficult to find, although few ASRs appear to have yet established efficacy in Phase III levels. Evolution of ASRs has included: (a) Modifications to ASOs to render them nuclease resistant, with analogous modifications to siRNAs being developed; and (b) Development of strategies to select optimal sites for targeting. Perhaps the biggest barrier to effective therapies with ASRs is the "Delivery Problem." Various liposomal vehicles have been used for systemic delivery with some success, and recent modifications appear to enhance systemic delivery, at least to liver. Various nanoparticle formulations are now being developed which may also enhance delivery. Going forward, topical applications of ASRs would seem to have the best chances for success. In summary, modifications to ASRs to enhance stability, improve targeting, and incremental improvements in delivery vehicles continue to make ASRs attractive as molecular therapeutics, but their advance toward the bedside has been agonizingly slow. J. Cell. Biochem. 98: 14,35, 2006. © 2006 Wiley-Liss, Inc. [source] What determines the management of anxiety disorders and its improvement?JOURNAL OF EVALUATION IN CLINICAL PRACTICE, Issue 2 2008Mirrian Smolders MSc Introduction, Although anxiety disorders are highly prevalent, lack of correct diagnosis and related concerns about treatment are serious clinical problems. Several factors affect, positively or negatively, management of anxiety and its improvement. A literature review and thematic analysis was executed to obtain an overview of the types of determinants of anxiety care and its improvement. Methods, Literature was identified from electronic database searching (January 1995,March 2006), contact with authors of studies, and searching of websites of organizations concerned with mental health. By using a template analysis approach, a set of strong themes relating to determinants of anxiety care and its improvement was identified. Results, The 15 eligible studies identified 43 factors that impeded or facilitated optimal anxiety care and its improvement. Individual characteristics of both patients (n = 13) and professionals (n = 6) were most frequently reported as determinants of anxiety care and its improvement. A considerable number of factors were related to the organizational context (n = 12), such as practice type and location. Some factors related to the social context (n = 4), the economic context (n = 2), or to the innovation itself (n = 6) were identified. Conclusion, The findings show that there is a multitude of barriers and facilitators to optimal anxiety care and its improvement. Some determinants are modifiable, and thus responsive to interventions. Examples are collaboration within and between organizations, financial resources and assignment of both an opinion leader and responsible staff. The quality of anxiety care can be improved by systematically designing innovation strategies which are tailored to a selection of the determinants identified in this study. [source] Forecasting market impact costs and identifying expensive tradesJOURNAL OF FORECASTING, Issue 1 2008Jacob A. Bikker Abstract Often, a relatively small group of trades causes the major part of the trading costs on an investment portfolio. Consequently, reducing the trading costs of comparatively few expensive trades would already result in substantial savings on total trading costs. Since trading costs depend to some extent on steering variables, investors can try to lower trading costs by carefully controlling these factors. As a first step in this direction, this paper focuses on the identification of expensive trades before actual trading takes place. However, forecasting market impact costs appears notoriously difficult and traditional methods fail. Therefore, we propose two alternative methods to form expectations about future trading costs. Applied to the equity trades of the world's second largest pension fund, both methods succeed in filtering out a considerable number of trades with high trading costs and substantially outperform no-skill prediction methods. Copyright © 2008 John Wiley & Sons, Ltd. [source] Vitreous Fluid and/or Urine Glucose Concentrations in 1335 Civil Aviation Accident Pilot Fatalities,JOURNAL OF FORENSIC SCIENCES, Issue 3 2009Arvind K. Chaturvedi Ph.D. Abstract:, During aviation accident investigations, vitreous fluid and urine samples from pilot fatalities are analyzed for glucose and blood for hemoglobin A1c (HbA1c) to monitor diabetic pilots and to discover other pilots with undiagnosed/unreported diabetes. The prevalence of elevated glucose concentrations in fatally injured pilots was evaluated by searching the Civil Aerospace Medical Institute's Toxicology Database for the period 1998,2005. Out of 1335 pilots involving 363 vitreous fluid, 365 urine, and 607 vitreous fluid and urine analyses, 43 pilots had elevated glucose in vitreous fluid (>125 mg/dL) and/or in urine (>100 mg/dL). Of the 20 pilots whose blood samples were analyzed, nine had >6% HbA1c,four were known diabetics, and five were unknown diabetics. Urinary glucose levels were elevated in all 13 known hyperglycemic pilots. A considerable number of pilots (30 of 43) had elevated glucose and HbA1c (5 of 20), suggesting undiagnosed/unreported diabetic conditions. [source] Management of skin toxicity during radiation therapy: A review of the evidenceJOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2010S Kumar Summary Acute skin toxicity occurs in the majority of the patients undergoing radical radiotherapy. While a variety of topical agents and dressing are used to ameliorate side effects, there is minimal evidence to support their use. The aims of this study were to systematically review evidence on acute skin toxicity management and to assess the current practices in ANZ. A systematic review of the literature was conducted on studies published between 1980 and 2008. A meta-analysis was performed on articles on clinical trials reporting grade II or greater toxicity. Analyses were divided into breast (the most common site) and other sites. A survey of Radiation Oncology departments across ANZ was conducted to identify patterns of practices and compare these with the published evidence. Twenty-nine articles were reviewed. Only seven articles demonstrated statistically significant results for management of side-effects. These were for topical corticosteroids, hyaluronic acid, sucralfate, calendula, Cavilon cream (3M, St Paul, Minnesota, USA) and silver leaf dressing. Meta-analysis demonstrated statistical significance for the prophylactic use of topical agents in the management acute toxicity. The survey of departments had a low response rate but demonstrated variation in skin care practices across ANZ. A considerable number of these practices were based only on anecdotal evidence. Lack of evidence in the literature for the care of radiation skin reactions was associated with variation in practice. Only a limited number of studies have demonstrated a significant benefit of specific topical agents. There is a need for objective and prospective recording of skin toxicity to collect meaningful comparative data on which to base recommendations for practice. [source] Five years survival in metastatic non-small cell lung cancer patients treated with chemotherapy alone or chemotherapy and melatonin: a randomized trialJOURNAL OF PINEAL RESEARCH, Issue 1 2003P. Lissoni Abstract: Numerous experimental data have documented the oncostatic properties of melatonin. In addition to its potential direct antitumor activity, melatonin has proved to modulate the effects of cancer chemotherapy, by enhancing its therapeutic efficacy and reducing its toxicity. The increase in chemotherapeutic efficacy by melatonin may depend on two main mechanisms, namely prevention of chemotherapy-induced lymphocyte damage and its antioxidant effect, which has been proved to amplify cytotoxic actions of the chemotherapeutic agents against cancer cells. However, the clinical results available at present with melatonin and chemotherapy in the treatment of human neoplasms are generally limited to the evaluation of 1-year survival in patients with very advanced disease. Thus, the present study was performed to assess the 5-year survival results in metastatic non-small cell lung cancer patients obtained with a chemotherapeutic regimen consisting of cisplatin and etoposide, with or without the concomitant administration of melatonin (20 mg/day orally in the evening). The study included 100 consecutive patients who were randomized to receive chemotherapy alone or chemotherapy and melatonin. Both the overall tumor regression rate and the 5-year survival results were significantly higher in patients concomitantly treated with melatonin. In particular, no patient treated with chemotherapy alone was alive after 2 years, whereas a 5-year survival was achieved in three of 49 (6%) patients treated with chemotherapy and melatonin. Moreover, chemotherapy was better tolerated in patients treated with melatonin. This study confirms, in a considerable number of patients and for a long follow-up period, the possibility to improve the efficacy of chemotherapy in terms of both survival and quality of life by a concomitant administration of melatonin. This suggests a new biochemotherapeutic strategy in the treatment of human neoplasms. [source] Acne's relationship with psychiatric and psychological morbidity: results of a school-based cohort study of adolescentsJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 1 2010PJ Magin Abstract Background, There is a considerable number of studies linking acne with psychological and psychiatric morbidities, although this literature is not entirely consistent and is largely cross-sectional in methodology. Objective, This study aims to establish the relationship of acne and psychological and psychiatric morbidity in adolescents in a community setting and, via a longitudinal methodology, provide evidence for causality in the relationship. Methods, The study was a 12-month cohort study. Two hundred and forty-four students in Years 8, 9 and 11 (ages 14,17) at four Australian high schools were assessed at baseline 6 months and 12 months. Presence and severity of acne were assessed, along with a number of psychological and psychiatric morbidities and personality traits (depression, anxiety, overall psychiatric morbidity, self-consciousness, neuroticism and introversion/extraversion) and other demographic variables. Results, Of the 244 participating students, 209 (86%) completed all three rounds of data collection. A further 26 (11%) completed two rounds. The study failed to demonstrate an association of the presence of acne or of acne severity with the examined measures of psychological and psychiatric morbidity, and no evidence for an effect of acne in their causation. Conclusion, The relationship of acne and psychological morbidities found in previous health care settings was not found in this community sample. This may be due to differences between community and clinical acne populations. Other possible reasons for this finding are attenuation of psychological morbidity in subjects in this study by successful acne treatment, and the role of personality traits in the complex relationship between acne and psychological morbidities. It is suggested that this relationship would be best investigated by means of longer-term cohort studies enlisting subjects at an zearly age, prior to the onset of acne. [source] Novel MPZ Mutation In A Sporadic CMT PatientJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 1 2001E Bellone Mutations in the gene for the major structural protein component of peripheral nerve myelin, myelin protein zero (MPZ), are associated with some forms of hereditary neuropathies such as Charcot-Marie-Tooth disease type 1B (CMT1B), Dejerine-Sottas syndrome (DSS) and congenital hypomyelinating neuropathy (CHN). The common pathological characteristics of these allelic disorders are severe demyelination and remyelination of peripheral nerves. Recently, MPZ mutations were also found in patients with the axonal form of CMT neuropathy (CMT2). We studied a patient with negative familiar history and clinical and electrophysiological features of Charcot-Marie-Tooth disease: distal muscle weakness and atrophy, foot deformities (pes cavus), and severely reduced nerve conduction velocities in the motor and sensory nerves. The sural nerve biopsy showed marked loss of myelinated fibers, few onion bulbs, and a high percentage of fibers showing excessive myelin outfoldings. DNA analysis excluded CMT1A duplication by Southern blot and by pulsed field gel electrophoresis methods. SSCP analysis of all six exons of MPZ revealed a shift band in exon 2 in the patient's DNA. No such difference was detected in normal controls. Direct sequencing disclosed a G , A transition at nucleotide position 181. This base substitution predicts the replacement of aspartic acid with asparagine at codon 61. A mutation at the same codon (but different amino acid replacement) was recently identified in a family with the axonal type of CMT, in which the disease was autosomal dominantly inherited. This finding provides further confirmation of the role of MPZ gene in peripheral neuropathies and suggests that MPZ coding region mutations may account for a considerable number of CMT cases which do not involve DNA duplication on 17p11.2-p12. This research was partially supported by a MURST and an Ateneo grant to FA, by a Ministero della Sanità grant to PM. Our laboratory is a member of the European Charcot-Marie-Tooth Consortium co-ordinated by Prof. Christine Van Broeckhoven. [source] A scratch circle origin for the medusoid fossil KullingiaLETHAIA, Issue 4 2002SÖREN JENSEN Kullingia is considered a key taxon in demonstrating the presence of terminal Proterozoic-early Cambrian chondrophorine hydrozoans. However, Kullingia concentrica from the Lower Cambrian of northern Sweden possesses several features that show that it is not a body fossil but that it was formed by current or wave-induced rotation of an anchored tubular organism, possibly a sabelliditid. A scratch circle interpretation applies also to several other reports of Lower Cambrian Kullingia, including Kullingia delicata from the Chapel Island Formation of Newfoundland. Given the considerable number of problematic fossils that have been interpreted as chondrophorines, it is difficult to put an age on the oldest fossil chondrophorines, but it may be as late as the Devonian. Overall, scratch circles appear to be rarely preserved. The occurrence of these scratch circles in Lower Paleozoic storm deposits is probably related to low levels of bioturbation that enhanced both the likelihood of formation and preservation of these structures. [source] | ||||||||||||||||||||||||||||||||||||||||||||||