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Selected AbstractsLeft-asymmetric expression of Galanin in the linear heart tube of the mouse embryo is independent of the nodal co-receptor gene crypticDEVELOPMENTAL DYNAMICS, Issue 12 2008Axel Schweickert Abstract Only very few left/right asymmetrically expressed genes are known in the mammalian embryo. In a screen for novel factors we identified the gene encoding the neuropeptide Galanin in mouse. At embryonic day (E) 8.5 asymmetric mRNA transcription was found in the left half of the linear heart tube. During heart looping and morphogenesis expression became restricted to the atrio-ventricular (AV) canal, followed by specific staining of the AV-node and AV-rings in the four-chambered heart. Expression was inverted in inv/inv and randomized in homozygous iv mutant embryos. Left-sided heart-specific transcription of mouse Gal thus should be controlled by the left-right pathway. The asymmetric pattern was retained in cryptic mutant embryos, in which the Nodal signaling cascade is disrupted. Surprisingly, Pitx2c was found to be expressed in 50% of cryptic mutant hearts as well, suggesting that some aspects of asymmetric gene expression in the heart are independent of cryptic. Developmental Dynamics 237:3557,3564, 2008. © 2008 Wiley-Liss, Inc. [source] Pericardial effusion as primary manifestation of metastatic cutaneous adenoid cystic carcinoma: Diagnostic cytopathology from an exfoliative sampleDIAGNOSTIC CYTOPATHOLOGY, Issue 5 2008Maxime Benchetritt M.D. Abstract Adenoid cystic carcinoma (ACC) occurs not only as a tumor of salivary glands, but also in very unusual locations, such as in the skin. Only very few cases of primary cutaneous of ACC have metastasized to the lymph nodes and lungs. We present a 53-year-old man with metastasis of the pericardium from a primary cutaneous ACC (PCACC) of the scalp, which had been surgically treated 14 years ago. Exfoliative cytologic findings from pericardial effusion included small clusters of basaloid cells with occasional cystlike spaces containing mucoid material. To our knowledge, this is the first case of pericardial metastasis from a PCACC. Diagn. Cytopathol. 2008;36:351,354. © 2008 Wiley-Liss, Inc. [source] Prostaglandin E2 inhibits the proliferation of human gingival fibroblasts via the EP2 receptor and EpacJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2009Evgeny Weinberg Abstract Elevated levels of prostaglandins such as PGE2 in inflamed gingiva play a significant role in the tissue destruction caused by periodontitis, partly by targeting local fibroblasts. Only very few studies have shown that PGE2 inhibits the proliferation of a gingival fibroblast (GF) cell line, and we expanded this research by using primary human GFs (hGFs) and looking into the mechanisms of the PGE2 effect. GFs derived from healthy human gingiva were treated with PGE2 and proliferation was assessed by measuring cell number and DNA synthesis and potential signaling pathways were investigated using selective activators or inhibitors. PGE2 inhibited the proliferation of hGFs dose-dependently. The effect was mimicked by forskolin (adenylate cyclase stimulator) and augmented by IBMX (a cAMP-breakdown inhibitor), pointing to involvement of cAMP. Indeed, PGE2 and forskolin induced cAMP generation in these cells. Using selective EP receptor agonists we found that the anti-proliferative effect of PGE2 is mediated via the EP2 receptor (which is coupled to adenylate cyclase activation). We also found that the effect of PGE2 involved activation of Epac (exchange protein directly activated by cAMP), an intracellular cAMP sensor, and not PKA. While serum increased the amount of phospho-ERK in hGFs by ,300%, PGE2 decreased it by ,50%. Finally, the PGE2 effect does not require endogenous production of prostaglandins since it was not abrogated by two COX-inhibitors. In conclusion, in human gingival fibroblasts PGE2 activates the EP2,cAMP,Epac pathway, reducing ERK phosphorylation and inhibiting proliferation. This effect could hamper periodontal healing and provide further insights into the pathogenesis of inflammatory periodontal disease. J. Cell. Biochem. 108: 207,215, 2009. © 2009 Wiley-Liss, Inc. [source] Guest Lecture 9.00,9.45 Wednesday 17 September 2003CYTOPATHOLOGY, Issue 2003Peter A. Hall MD PhD FRCPath The past decades have seen an explosion in our knowledge of the molecular events underpinning the pathogenesis of many disease processes. Furthermore, there have been enormous technical advances with the ability to identify, clone and sequence genes and to characterize their protein products now being common place in research settings. However, despite many claims as to the utility of molecular and biochemical methods in pathology only very few laboratories employ such methods in a clinical setting. Indeed the impact of molecular medicine has been more talked about than real. Why is this? The goal of this presentation is to address this question and present some perspectives on the future of Molecular Pathology. I shall overview, for the BSCC, the current state of the technology available for gene analysis and to explore the developments needed before the mirage of molecular pathology becomes a clinical reality. [source] Sleep-related memory consolidation in depression: an emerging field of researchDEPRESSION AND ANXIETY, Issue 12 2008Orla Patricia Hornung Ph.D. Abstract Sleep-related memory consolidation has received increasing attention in recent years. Because previous research has focused on healthy young adults, only very few studies have been conducted in patients with psychiatric disorders so far. The investigation of sleep-related memory consolidation in depression offers a wide range of future research opportunities and can therefore be regarded as an emerging field of research. This article gives a short overview of current knowledge of sleep-related memory consolidation in healthy young adults and builds a bridge to psychiatry and depression, where further research is urgently needed. Depression and Anxiety, 2008. © 2007 Wiley-Liss, Inc. [source] Dendrogeomorphic reconstruction of past debris-flow activity using injured broad-leaved treesEARTH SURFACE PROCESSES AND LANDFORMS, Issue 4 2010Estelle Arbellay Abstract Tree-ring records from conifers have been regularly used over the last few decades to date debris-flow events. The reconstruction of past debris-flow activity was, in contrast, only very rarely based on growth anomalies in broad-leaved trees. Consequently, this study aimed at dating the occurrence of former debris flows from growth series of broad-leaved trees and at determining their suitability for dendrogeomorphic research. Results were obtained from gray alder (Alnus incana (L.) Moench), silver birch and pubescent birch (Betula pendula Roth and Betula pubescens Ehrh.), aspen (Populus tremula L.), white poplar, black poplar and gray poplar (Populus alba L., Populus nigra L. and Populus x canescens (Ait.) Sm.), goat willow (Salix caprea L.) and black elder (Sambucus nigra L.) injured by debris-flow activity at Illgraben (Valais, Swiss Alps). Tree-ring analysis of 104 increment cores, 118 wedges and 93 cross-sections from 154 injured broad-leaved trees allowed the reconstruction of 14 debris-flow events between AD 1965 and 2007. These events were compared with archival records on debris-flow activity at Illgraben. It appears that debris flows are very common at Illgraben, but only very rarely left the channel over the period AD 1965,2007. Furthermore, analysis of the spatial distribution of disturbed trees contributed to the identification of six patterns of debris-flow routing and led to the determination of preferential breakout locations of events. The results of this study demonstrate the high potential of broad-leaved trees for dendrogeomorphic research and for the assessment of the travel distance and lateral spread of debris-flow surges. Copyright © 2010 John Wiley & Sons, Ltd. [source] Application of Bacterial Biocathodes in Microbial Fuel CellsELECTROANALYSIS, Issue 19-20 2006Zhen He Abstract This review addresses the development and experimental progress of biocathodes in microbial fuel cells (MFCs). Conventional MFCs consist of biological anodes and abiotic cathodes. The abiotic cathode usually requires a catalyst or an electron mediator to achieve high electron transfer, increasing the cost and lowering the operational sustainability. Such disadvantages can be overcome by biocathodes, which use microorganisms to assist cathodic reactions. Biocathodes are feasible in potentiostat-poised half cells, but only very few studies have investigated them in complete MFCs. The classification of biocathodes is based on which terminal electron acceptor is available. For aerobic biocathodes with oxygen as the terminal electron acceptor, electron mediators, such as iron and manganese, are first reduced by the cathode (abiotically) and then reoxidized by bacteria. Anaerobic biocathodes directly reduce terminal electron acceptors, such as nitrate and sulfate, by accepting electrons from a cathode electrode through microbial metabolism. Biocathodes are promising in MFCs, and we anticipate a successful application after several breakthroughs are made. [source] Empirical Bayes estimators and non-parametric mixture models for space and time,space disease mapping and surveillanceENVIRONMETRICS, Issue 5 2003Dankmar Böhning Abstract The analysis of the geographic variation of disease and its representation on a map is an important topic in epidemiological research and in public health in general. Identification of spatial heterogeneity of relative risk using morbidity and mortality data is required. Frequently, interest is also in the analysis of space data with respect to time, where typically data are used which are aggregated in certain time windows like 5 or 10 years. The occurrence measure of interest is usually the standardized mortality (morbidity) ratio (SMR). It is well known that disease maps in space or in space and time should not solely be based upon the crude SMR but rather some smoothed version of it. This fact has led to a tremendous amount of theoretical developments in spatial methodology, in particular in the area of hierarchical modeling in connection with fully Bayesian estimation techniques like Markov chain Monte Carlo. It seems, however, that at the same time, where these theoretical developments took place, on the practical side only very few of these developments have found their way into daily practice of epidemiological work and surveillance routines. In this article we focus on developments that avoid the pitfalls of the crude SMR and simultaneously retain a simplicity and, at least approximately, the validity of more complex models. After an illustration of the typical pitfalls of the crude SMR the article is centered around three issues: (a) the separation of spatial random variation from spatial structural variation; (b) a simple mixture model for capturing spatial heterogeneity; (c) an extension of this model for capturing temporal information. The techniques are illustrated by numerous examples. Public domain software like Dismap is mentioned that enables easy mixture modeling in the context of disease mapping. Copyright © 2003 John Wiley & Sons, Ltd. [source] Non-Covalent Interactions of Organic Halogen Compounds with Aromatic Systems , Analyses of Crystal Structure DataEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 6 2005Dariusz Swierczynski Abstract The Cambridge Structural Database showed in mid 2002 about 20.000 structures containing halogen atoms and aryl rests with distances d between the aryl center and the halogen atom, which would allow both hydrogen bonds with the aromatic hydrogens and/or van der Waalsinteractions with the ,-cloud. The latter are characterized by short distances d and by small angles , between the vector along the aryl centroid,halogen line and the perpendicular vector originating in the aryl center (the plane normal). The cases with d < 3.0 Å for F; and d < 3.5 Å for Cl, Br or I (outliers neglected), and , , 10 ± 5°, indicating predominating van der Waals forces, amount to several hundreds. The majority of fragments exhibit larger d and , values, in line with avoidance of electrostatic repulsion between the negative partial charges of the halogens and the ,-cloud center, and with an increasing electrostatic attraction with the aromatic hydrogen atoms. The corresponding hydrogen bonds are characterized by longer distances d and by angle values of , > 60° (about 40 % of the fragments), with only very few cases close to linear hydrogen bonds (then with , = 90°). Compounds containing metal,halogen bonds were omitted in view of possible strong orientational interferences. The structures were screened with four different halogen binding modes, all of them containing the halogen attached to a carbon atom, but with different hybrizations at the connecting carbon centers. The results show only small differences in the distance distributions, with a slight preference for smaller , values for sp2 frameworks. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] Prevalence of HBV genotypes in Central and Eastern EuropeJOURNAL OF MEDICAL VIROLOGY, Issue 10 2008Katja Deterding Abstract The importance of hepatitis B virus (HBV) genotypes for disease progression and response to interferon-alpha-based treatment is well established. While almost all patients in the Mediterranean area are infected with HBV genotype D, HBV genotype A is dominant in Northern Europe. However, the distribution of HBV genotypes is unknown for several Central and Eastern European countries. Data are described of 1313 HBsAg-positive patients recruited at 14 referral centers in eight countries. There were only very few cases of HBV genotype B, C, E, F, and H infection while HBV genotypes A and D were found in 42% and 48% of patients, respectively. Eight percent of patients had positive bands for more than one genotype using the hybridization assay. The frequency of genotype A was higher in Poland (77%) and the Czech Republic (67%) as compared to Hungary (47%), Lithuania (41%), Croatia (8%), and Germany (32%). In contrast, HBV genotype D was most frequent in Croatian, Romanian, and Russian patients with 80%, 67%, and 93% of cases, respectively. In conclusion, HBV genotype A versus D showed significantly different distribution patterns in Central and Eastern Europe which deserves consideration for national guidelines and treatment decisions. J. Med. Virol. 80:1707,1711, 2008. © 2008 Wiley-Liss, Inc. [source] Identity and function of ,-secretaseJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2003W. Taylor Kimberly Abstract ,-Secretase catalyzes intramembrane proteolysis of various type I membrane proteins, including the amyloid-, precursor protein and the Notch receptor. Despite its importance in the pathogenesis of Alzheimer's disease and to normal development, this protease has eluded identification until only very recently. Four membrane proteins are now known to be members of the protease complex: presenilin, nicastrin, aph-1, and pen-2. Recent findings suggest that these four proteins are sufficient to reconstitute the active ,-secretase complex and that together they mediate the cell surface signaling of a variety of receptors via intramembrane proteolysis. © 2003 Wiley-Liss, Inc. [source] Identity of TUNEL-positive cells in the oral buccal epithelium of normal mucosa and lichen lesionsJOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 5 2004Andreas Karatsaidis Background:,In situ detection of DNA fragmentation by TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick end labeling (TUNEL) is a widely used technique to identify apoptotic cells in the terminal phases of cell death. Several studies have shown that there are statistically increased numbers of TUNEL+ cells within the epithelium of oral lichen (OL). It was suggested that this indicates an increased rate of apoptosis among basal and suprabasal keratinocytes in OL epithelium. The aim of this study was to identify the TUNEL+ cells in the epithelium of erythematous (ERY) OL and normal oral mucosa (NOM). Methods:, Sections of biopsies from NOM and ERY OL were processed for TUNEL combined with immunostaining for pan-cytokeratin or for cell markers specifically expressed by different leukocytes. Results:, In NOM, TUNEL+ keratinocytes were almost exclusively seen in the outermost epithelial layers. This labeling was absent in ERY OL. In the basal and lower spinous layers, more TUNEL+ cell nuclei were seen in ERY OL as compared with NOM, in accordance with previous studies. The present observations show, however, that only very few of these cells were keratinocytes, but rather were CD4+ lymphocytes and CD68+ macrophages. There was no difference between the numbers of TUNEL+ keratinocytes in basal and lower spinous layers in ERY OL and NOM epithelium. No intraepithelial CD8+ lymphocytes, Langerhans cells, or mast cells were found to be TUNEL+. Conclusion:, The findings indicate that the pathologic changes in ERY OL epithelium cannot be explained by increased prevalence of terminal keratinocyte cell death identified by TUNEL. [source] Heart Rate Variability and Sympathetic Skin Response in Male Patients Suffering From Acute Alcohol Withdrawal SyndromeALCOHOLISM, Issue 9 2006Karl-Jürgen Bär Background: Many symptoms of alcohol withdrawal (AW) such as tachycardia or elevated blood pressure might be explained by increased peripheral and central adrenergic activity. In contrast to many neurochemical studies of sympathetic activation during AW, only very few studies investigated autonomic balance using neurophysiological methods. Methods: We investigated heart rate variability (HRV) and sympathetic skin response (SSR) in male patients suffering from mild AW syndrome (n=20, no treatment required) and in patients with moderate to severe AW syndrome (n=20, clomethiazole treatment) in the acute stage. Sympathovagal influence was quantified using measures of time and frequency domain of HRV as well as modern nonlinear parameters (compression entropy). Furthermore, we obtained latencies and amplitudes of SSR to quantify isolated sympathetic influence. Measures were obtained during the climax of withdrawal symptomatology before treatment, 1 day after climax, and shortly before discharge from hospital. Alcohol withdrawal scores were obtained and correlated to autonomic measures. Results: Ambulatory blood pressure and AW scores revealed characteristic withdrawal symptoms in both patient groups. Apart from the nonlinear parameter compression entropy, Hc, measures of HRV revealed no sign of autonomic dysfunction in contrast to the significantly increased heart rates at the time of admission. Latencies and amplitudes of SSR did not indicate any increase of sympathetic activity. A negative correlation was found between Hc and mental withdrawal symptoms. Conclusions: We show here that classical measures for autonomic nervous system activity such as HRV and SSR are not suitable for describing the autonomic changes seen in acute AW, although a major role for the sympathetic nervous system has been proposed. This might be due to multiple dysregulation of metabolites in AWS or to subtle alcohol-induced damage to neuronal structures, issues that should be addressed in future studies. [source] Speciation of oxidation states of elements by capillary electrophoresisJOURNAL OF SEPARATION SCIENCE, JSS, Issue 11 2003Marek Trojanowicz Abstract Progress made in the last five years in the application of capillary electrophoresis methods to chemical speciation of elements is reported on the basis of over 100 literature references. The main trends observed include development of new on- and off-capillary derivatization methods, application of new detection methods, and especially coupling of CE separation systems to powerful atomic spectroscopy and mass spectrometry instruments with various ionization techniques, providing either a sensitive element-specific detection method or a third dimension for high performance separation. Besides numerous CZE and MEKC capillary electrophoresis methods only very few examples of CE speciation with capillary electrochromatography can be found. Concerning the chemical forms of elements determined, the new procedures developed are mostly focused on redox speciation of various oxidation states of elements, metal-bound high molecular compounds, and organometallic species. [source] Modelling price paths in on-line auctions: smoothing sparse and unevenly sampled curves by using semiparametric mixed modelsJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES C (APPLIED STATISTICS), Issue 2 2008Florian Reithinger Summary., On-line auctions pose many challenges for the empirical researcher, one of which is the effective and reliable modelling of price paths. We propose a novel way of modelling price paths in eBay's on-line auctions by using functional data analysis. One of the practical challenges is that the functional objects are sampled only very sparsely and unevenly. Most approaches rely on smoothing to recover the underlying functional object from the data, which can be difficult if the data are irregularly distributed. We present a new approach that can overcome this challenge. The approach is based on the ideas of mixed models. Specifically, we propose a semiparametric mixed model with boosting to recover the functional object. As well as being able to handle sparse and unevenly distributed data, the model also results in conceptually more meaningful functional objects. In particular, we motivate our method within the framework of eBay's on-line auctions. On-line auctions produce monotonic increasing price curves that are often correlated across auctions. The semiparametric mixed model accounts for this correlation in a parsimonious way. It also manages to capture the underlying monotonic trend in the data without imposing model constraints. Our application shows that the resulting functional objects are conceptually more appealing. Moreover, when used to forecast the outcome of an on-line auction, our approach also results in more accurate price predictions compared with standard approaches. We illustrate our model on a set of 183 closed auctions for Palm M515 personal digital assistants. [source] Identification of operationally tolerant liver transplant recipients,LIVER TRANSPLANTATION, Issue S2 2010Alberto Sánchez-Fueyo KEY POINTS: (1) Liver allografts exhibit intrinsic tolerogenic properties that result in their spontaneous acceptance in many experimental animal models. (2) In clinical transplantation, liver allografts require milder immunosuppression (IS) regimens than other organs, are remarkably resistant to antibody-mediated rejection, and only very rarely are lost because of immunological insults. (3) A fraction of stable liver transplant recipients can withdraw from all IS therapy and then maintain normal graft function and not experience rejection. This phenomenon is known as spontaneous operational tolerance. (4) The intentional discontinuation of IS in stable liver transplant recipients has led to successful weaning in almost 20% of recipients, but the true prevalence of spontaneous operational tolerance in unselected recipients is still unknown. (5) The prevalence could be higher in pediatric recipients undergoing transplantation before 1 year of age and in adult recipients with more than 10 years of posttransplant follow-up. (6) Rejection occurring during medically supervised IS weaning trials tends to be mild and, in the overwhelming majority of cases, can be easily resolved without the administration of high-dose IS. (7) Tolerant liver recipients exhibit specific transcriptional patterns in peripheral blood and in liver tissue that may constitute future diagnostic markers of tolerance. (8) There is still no formal proof that the discontinuation of low-dose IS in long-term surviving liver recipients improves the morbidity and mortality rates associated with IS therapy. Liver Transpl 16:S82-S86, 2010. © 2010 AASLD. [source] Chronic patients in undergraduate education: didactic value as perceived by studentsMEDICAL EDUCATION, Issue 8 2006Joseph P M Diederiks Objectives, Medical education should prepare students for future clinical practice. However, this preparation is inadequate for the most prevalent problem in health care: chronic disease. This applies to the continuous aspect of chronic disease. Within the context of a newly developed programme, we investigated what makes a chronic patient interesting in the eyes of medical students, what they learned from a specific programme in which each student had contact with a chronic patient 4 times in 8 months, and what they learned from their patients. Methods, A total of 240 Year 3 students were enrolled in the programme, 89 of whom filled in questionnaires at both the start and end of the programme. Topics included the characteristics of the ideal and the actual patient, the Ideal Physician Questionnaire, and several questions on the expected and actual amount of knowledge gained from the patient. Results, Students preferred patients who demonstrated clear symptoms and had frequent contacts with health care professionals during the programme to ,well adapted' patients. The perceived knowledge obtained from the patient was less than they had expected at the start of the programme. A didactic gain perceived as low was mainly due to low expectations of gaining knowledge at the start of the programme, a doctor-centred attitude and a high level of discrepancy between the student's ideal patient and the actual patient. Conclusions, Programmes that aim to present chronic patients to medical students focus on patient selection so that patients who differ only very slightly from healthy persons are eliminated. In addition, realistic information on the types of patients with whom students can expect to have contact may help students appreciate the knowledge to be gained from these patients. [source] Small effective population sizes in a widespread selfing species, Lymnaea truncatula (Gastropoda: Pulmonata)MOLECULAR ECOLOGY, Issue 9 2004C. MEUNIER Abstract We present here a spatial and temporal population genetic survey of a common freshwater snail, also a predominantly selfing species, Lymnaea truncatula. The rate of genetic diversity loss was quantified by estimating the effective size (Ne) of the snail populations, using two different methods. A temporal survey allowed estimation of a variance effective size of the populations, and a spatial survey allowed the estimation of an inbreeding effective size, from two-locus identity disequilibria estimates. Both methods were consistent and provided low Ne values. Drift due to (i) high amounts of selfing and (ii) fluctuations in population sizes because of temporary habitats, and also selection coupled to genome-wide linkage disequilibria, could explain such reductions in Ne. The loss of genetic diversity appears to be counterbalanced only very partially by low apparent rates of gene flow. [source] Extra pair paternity in birds: a review of interspecific variation and adaptive functionMOLECULAR ECOLOGY, Issue 11 2002Simon C. Griffith Abstract The application of molecular genetic techniques has revolutionized our view of avian mating systems. Contrary to prior expectations, birds are only very rarely sexually monogamous, with ,extra-pair offspring' found in approximately 90% of species. Even among socially monogamous species, over 11% of offspring are, on average, the result of extra-pair paternity (EPP). Based on over 150 molecular genetic studies of EPP in birds, we review two topical areas: (i) ecological explanations for interspecific variation in the rate of EPP; and (ii) evidence bearing on the adaptive function of EPP. We highlight the remaining challenges of understanding the relative roles of genes and ecology in determining variation between taxa in the rate of extra paternity, and testing for differences between extra-pair offspring and those sired within-pair. [source] Molecular Connectivity: Polarity Correction to Improve Correlation with HydrophobicityMOLECULAR INFORMATICS, Issue 2-3 2004Abstract Contrary to belief in some quarters, molecular connectivites correlate only very poorly with hydrophobicity. We have devised a simple polarity correction to the calculation of first-order molecular connectivity (1,), which involves subtracting, instead of adding, the bond contributions (, values) for bonds between atoms i and j where j is a heteroatom other than halogen, to give a 1,p value. For a set of 23 diverse substituents, the correlation between 1, and , (the hydrophobic substituent constant) yielded r2=0.123, whilst that between 1,p and , yielded r2=0.771. When the method was applied to the correlation of the protein-binding constants for a set of 42 diverse compounds with 1,, r2 improved from 0.078 to 0.443., [source] Prenatal diagnosis of a de novo supernumerary marker derived from chromosome 16PRENATAL DIAGNOSIS, Issue 6 2001Markus Hengstschläger Abstract Marker chromosomes are supernumerary chromosomes of unknown origin and are seldom found in prenatal diagnosis. Application of fluorescent in situ hybridization (FISH) allows the identification of the chromosomal origin of markers. Estimation of the risk of an abnormal phenotype outcome can be enabled by collecting data on phenotypes associated with markers of the same chromosomal origin. So far only very few cases of prenatal diagnosis of de novo supernumerary markers derived from chromosome 16 have been reported. Here the prenatal diagnosis of a de novo supernumerary marker chromosome 16 is described and the relevant literature discussed. Copyright © 2001 John Wiley & Sons, Ltd. [source] Subungual melanoma: Histological examination of 50 cases from early stage to bone invasionTHE JOURNAL OF DERMATOLOGY, Issue 11 2008Miki IZUMI ABSTRACT Subungual melanoma is a rare form of malignant melanoma. It is extremely difficult to differentiate it histologically from benign melanonychia striata or melanocytic nevus, especially in the early stage. We divided 50 cases of subungual melanoma into four groups according to clinical progress, and examined their histological findings in each respective stage. In the early stage (19 cases), atypical melanocytes were polygonal showing slight nuclear atypia with no mitoses at all. In six out of 19 cases (31.6%), the atypical melanocytes proliferated more in the hyponychium than in the nail matrix, and only very few in the nail bed. Periungual pigmentation (Hutchinson's sign) appeared from the early stage in almost all cases. With stage progression (middle stage, 13 cases; progressive stage, 13 cases; and bone invasive stage, five cases) the number of atypical melanocytes and their degree of nuclear atypia increased, and the ascent of atypical melanocytes and pagetoid spread became conspicuous. Mitoses became apparent only from the progressive stage. From these observations, we would like to propose three new pathological clues of early stage subungual melanoma: (i) "skip lesion", proliferation of the tumor cells are more prominent in the hyponychium than in the nail bed or nail matrix; (ii) histological confirmation of Hutchinson's sign; and (iii) epithelial thickening and/or compact arrangement of the elongated basal cells. [source] 1141636674 Differential serine and tyrosine phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) in Jeg-3 choriocarcinoma cell linesAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2006J Roediger Background:, Signal Transducer and Activator of Transcription 3 (STAT3) is an intracellular signalling molecule, which is used by several cytokines, including leukemia inhibitory factor (LIF), epithelial growth factor (EGF), and interleukin-6 (IL-6). It induces a variety of gene transcripts and cell functions. In trophoblast cells and in tumor cells, its tyrosine phosphorylation is directly linked to their invasiveness. The regulation and function of STAT3 serine phosphorylation is still widely unclear. Material and Methods:, Jeg-3 choriocarcinoma cells were stimulated with different concentrations of EGF, IL-6 and LIF. STAT3 serine (727) and tyrosine (705) phosphorylation were analyzed 5,60 min after stimulation by SDS-PAGE electrophoresis followed by Western blotting. Results:, Jeg-3 cells display spontaneous STAT3 serine phosphorylation. 100 ng/mL EGF induces a time-dependent reduction starting 15 min after stimulation. Tyrosine phosphorylation does not occur spontaneously, but is strongly induced by EGF at all analyzed time points. LIF induces tyrosine phosphorylation, but affects serine phosphorylation only very slightly. IL-6 did not influence neither serine phosphorylation nor tyrosine phosphorylation. Discussion:, The EGF induced STAT3 tyrosine phosphorylation may be responsible for its invasion triggering capacities. The parallel reduction of serine phosphorylation may enhance this effect. LIF was formerly shown to enhance trophoblast invasion via STAT3 tyrosine phosphorylation. IL-6 displays very little effects on STAT3 and seems to use other pathways for signalling. [source] Finite Mixture Models for Mapping Spatially Dependent Disease CountsBIOMETRICAL JOURNAL, Issue 1 2009Marco Alfó Abstract A vast literature has recently been concerned with the analysis of variation in disease counts recorded across geographical areas with the aim of detecting clusters of regions with homogeneous behavior. Most of the proposed modeling approaches have been discussed for the univariate case and only very recently spatial models have been extended to predict more than one outcome simultaneously. In this paper we extend the standard finite mixture models to the analysis of multiple, spatially correlated, counts. Dependence among outcomes is modeled using a set of correlated random effects and estimation is carried out by numerical integration through an EM algorithm without assuming any specific parametric distribution for the random effects. The spatial structure is captured by the use of a Gibbs representation for the prior probabilities of component membership through a Strauss-like model. The proposed model is illustrated using real data (© 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] Demonstration of "Möbius" Aromaticity in Planar MetallacyclesCHEMISTRY - A EUROPEAN JOURNAL, Issue 26 2010Michael Mauksch Dr. Abstract Möbius aromaticity, predicted by Edgar Heilbronner in 1964, is a stabilizing effect exhibited by 4,n electron fully conjugated cyclic molecules (or transition states) with an odd number of orbital phase inversions. Although it has previously been suggested that this effect might also apply to planar metallacycles in which a transition metal employs a d orbital in ,-type binding mode, only very few examples of stable twisted molecules composed of main group elements are known. We report herein, the first computationally confirmed 4,n,, aromatic planar metallacyclic examples and their building principles. Aromatic stabilization energy (ASE) of a 8,, metalla-cycloheptatriene [Fe(CH)6H2], with four doubly occupied , orbitals and a HOMA value of +0.80 (cf. benzene=+1.0), an NICS(0) value of ,8.5 (benzene=,9.8, NICS=nucleus independent chemical shift), and with one phase inversion, is +27.5,kcal,mol,1 (about two-thirds of the value for benzene). In contrast, an unknown non-Möbius 1,4-dimetallabenzene [Fe2(CH)4H4], also with 8,, electrons, and without phase inversions, has an ASE of ,4.1,kcal,mol,1 and a NICS(0)=+15.6, indicative of antiaromaticity. Aromaticity of the proposed Möbius aromatic metallacycles is confirmed by using magnetic (NICS(0), NICS(1)zz, ,1H) and geometric (HOMA) aromaticity criteria, planarity, and near equalized CC bond lengths, bonding analysis (Wiberg bond indices, NBO, and NLMO analysis). The role of wave function boundary conditions (periodic vs. antiperiodic) in chemistry is further stressed, being equivalent to Zimmerman's concept of nodal parity for Möbius/Hückel systems. [source] ADME Investigations of Unnatural Peptides: Distribution of a 14C-Labeled ,,3 -Octaarginine in RatsCHEMISTRY & BIODIVERSITY, Issue 7 2007Markus Weiss Abstract The highly positively charged, cell-penetrating ,,3 -octaarginine has been prepared with a radioactive label by acetylation at the N-terminus with a doubly 14C-labeled acetyl group (14CH314CO). With the radioactive compound, an ADME study (Absorption, Distribution, Metabolism, Excretion) was performed in male rats following an intravenous or oral dose of 1,mg/kg. Sampling was carried out after periods ranging from 5,min to 4,d or 7,d for blood/excretia and quantitative whole-body autoradioluminography (QWBA), respectively. After p.o. dosing, no systemic exposure to peptide-related radioactivity was observed, and the dose was completely excreted in the feces within 24,h suggesting the absence of relevant absorption; less than 3% of the i.v. dose was excreted from the animals within 4,d. Blood levels, after i.v. dosing, dropped within 4,d to less than 2% of Cmax and decreased afterwards only very slowly. No metabolites were observed in the systemic circulation. QWBA Data indicated that the distribution of the acetyl- , -octaarginine-related radioactivity in the organs and tissues shifted over time. Notably, after 7,d, the highest concentration was measured in the lymph nodes, and the largest amount was found in the liver. A comparison with the results of two previous ADME investigations of , -peptides (cf. Table,1) reveals that the distribution of the compounds within the animals is structure-dependent, and that there is a full range from oral availability with rather rapid excretion (of a tetrapeptide) to essentially complete lack of both oral absorption and excretion after i.v. administration (of a highly charged octapeptide). A discussion is presented about the in vivo stability and ,drug-ability' of peptides. In general, , -peptides bearing proteinogenic side chains are compared with peptides consisting entirely of D - , -amino acid residues (the enantiomers of the ,natural' building blocks), and suggestions are made regarding a possible focus of future biomedical investigations with , -peptides. [source] Examining Genetic and Environmental Effects on Social Aggression: A Study of 6-Year-Old TwinsCHILD DEVELOPMENT, Issue 4 2005Mara Brendgen Using a genetic design of 234 six-year-old twins, this study examined (a) the contribution of genes and environment to social versus physical aggression, and (b) whether the correlation between social and physical aggression can be explained by similar genetic or environmental factors or by a directional link between the phenotypes. For social aggression, substantial (shared and unique) environmental effects but only weak genetic effects were found. For physical aggression, significant effects of genes and unique environment were found. Bivariate modeling suggests that social and physical aggression share most of their underlying genes but only very few overlapping environmental factors. The correlation between the two phenotypes can also be explained by a directional effect from physical to social aggression. [source] Immunohistochemical localization of somatostatin receptor subtypes in benign and malignant adrenal tumoursCLINICAL ENDOCRINOLOGY, Issue 6 2008Nicole Unger Summary Background, Somatostatin mediates its action through five receptor subtypes (sst1,5) that are widely distributed in various endocrine tissues and tumours. Because of the inhibitory effects of somatostatin, long-acting analogues have been synthesized. In contrast to their well-established use in neuroendocrine and pituitary tumours, little is known about their potential use in adrenal tumours. Objective, We examined somatostatin receptor protein expression in adrenal tumours of various aetiologies. Immunostaining was performed with specific polyclonal antibodies for sst1,5. Design, Seven benign and eight malignant pheochromocytomas (PHEOs), eight aldosterone-secreting adenomas (APAs), nine cortisol-secreting adenomas (CPAs), seven nonfunctioning adrenal tumours (NFAs) and 25 adrenal carcinomas (CAs) as well as eight normal adrenal glands were investigated. Measurements, Staining pattern, distribution and subcellular localization of the somatostatin receptor subtypes were evaluated. Results, In the majority of normal cortices the expression of sst1,5 was limited to the reticular zone. The medulla was predominantly positive for sst3. Most cortical adenomas were positive for all five subtypes. However, in the majority of these tumours, less than 30% of cells were positively stained. A high expression of sst4 was found in CPAs but only very few cortical carcinomas exhibited sst immunostaining. All benign PHEOs were positive for sst3. The majority presented with more than 60% of tumour cells stained. By contrast, only six out of eight malignant PHEOs were positive for sst3. Conclusions, Somatostatin receptor subtypes are expressed in PHEOs as well as in tumours of the adrenal cortex with tumour-specific distribution patterns. This may offer new diagnostic and therapeutic possibilities. [source] Therapy goals in inpatient psychotherapy: differences between diagnostic groups and psychotherapeutic orientationsCLINICAL PSYCHOLOGY AND PSYCHOTHERAPY (AN INTERNATIONAL JOURNAL OF THEORY & PRACTICE), Issue 1 2006Jörg Dirmaier Many studies have suggested the importance of therapy goals for the treatment process, especially in a multi-professional treatment context such as inpatient psychotherapy. However, only very few studies have examined differences between various groups of patients with regard to their respective treatment goals. Using a previously developed system for the categorization of therapy goals based on computer-assisted, qualitative data analysis, we have extracted 7157 therapy goals from a sample of 1192 discharge reports of treatment periods from inpatient psychotherapy in Germany. To test the inter-rater reliability of the system, a sample of 400 randomly chosen goals was classified by two independent raters. Logistic regression analysis was used to test whether different goal areas prove to be of different predictive value with regard to the respective dependent variables (diagnostic groups, psychotherapeutic orientations). Inter-rater reliability ranged between 0.73 and 0.82. Results of using the logistic regression model indicate that the selection of certain goal categories predicts affiliation to specific diagnostic groups and psychotherapeutic orientations. The resulting odds ratios vary between 1.2 and 16. These findings can be used for a more individualized treatment planning and outcome measurement in inpatient psychotherapeutic treatment. However, there are also goal categories that do not differentiate and therefore need to be further investigated.,Copyright © 2006 John Wiley & Sons, Ltd. [source] The development of roof color in ancient China,COLOR RESEARCH & APPLICATION, Issue 4 2010Aiping Gou Abstract The roof in ancient Chinese building is sloped roof which plays an important role in chromatic townscape. In earlier time, the colors in roofs were gray. With the development of technique in tiles making, tiles color was becoming colorful. However, the color usage in ancient architecture is regulated by hierarchy and the theory of five colors and five essences. Even there were a lot of colored glaze pieces in construction, only very few colors were used in royal and temple buildings' roof. Those regulations and laws made the characters of roof colors in different zones outstanding and legible. With specific color samples of different dynasties tested on site, and related laws and documentations analysis, as well as the theory of five colors and five essences, this article reports research on the characters of the roof colors in different periods, to draw out the turning points and reasons of roof color changes in crucial periods. © 2010 Wiley Periodicals, Inc. Col Res Appl, 2010 [source] | ||||||||||||||||||||||