Spatio-temporal manipulation of small GTPase activity at subcellular level and on timescale of seconds in living cells.

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DeRose, Robert; Pohlmeyer, Christopher; Umeda, Nobuhiro; Ueno, Tasuku; Nagano, Tetsuo; Kuo, Scot; Inoue, Takanari

2012-03-09

Dynamic regulation of the Rho family of small guanosine triphosphatases (GTPases) with great spatiotemporal precision is essential for various cellular functions and events(1, 2). Their spatiotemporally dynamic nature has been revealed by visualization of their activity and localization in real time(3). In order to gain deeper understanding of their roles in diverse cellular functions at the molecular level, the next step should be perturbation of protein activities at a precise subcellular location and timing. To achieve this goal, we have developed a method for light-induced, spatio-temporally controlled activation of small GTPases by combining two techniques: (1) rapamycin-induced FKBP-FRB heterodimerization and (2) a photo-caging method of rapamycin. With the use of rapamycin-mediated FKBP-FRB heterodimerization, we have developed a method for rapidly inducible activation or inactivation of small GTPases including Rac(4), Cdc42(4), RhoA(4) and Ras(5), in which rapamycin induces translocation of FKBP-fused GTPases, or their activators, to the plasma membrane where FRB is anchored. For coupling with this heterodimerization system, we have also developed a photo-caging system of rapamycin analogs. A photo-caged compound is a small molecule whose activity is suppressed with a photocleavable protecting group known as a caging group. To suppress heterodimerization activity completely, we designed a caged rapamycin that is tethered to a macromolecule such that the resulting large complex cannot cross the plasma membrane, leading to virtually no background activity as a chemical dimerizer inside cells(6). Figure 1 illustrates a scheme of our system. With the combination of these two systems, we locally recruited a Rac activator to the plasma membrane on a timescale of seconds and achieved light-induced Rac activation at the subcellular level(6).

Stage-specific functions of the small Rho GTPases Cdc42 and Rac1 for adult hippocampal neurogenesis

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Vadodaria, Krishna C; Brakebusch, Cord; Suter, Ueli

2013-01-01

The molecular mechanisms underlying the generation, maturation, and integration of new granule cells generated throughout life in the mammalian hippocampus remain poorly understood. Small Rho GTPases, such as Cdc42 and Rac1, have been implicated previously in neural stem/progenitor cell (NSPC......) proliferation and neuronal maturation during embryonic development. Here we used conditional genetic deletion and virus-based loss-of-function approaches to identify temporally distinct functions for Cdc42 and Rac1 in adult hippocampal neurogenesis. We found that Cdc42 is involved in mouse NSPC proliferation......, initial dendritic development, and dendritic spine maturation. In contrast, Rac1 is dispensable for early steps of neuronal development but is important for late steps of dendritic growth and spine maturation. These results establish cell-autonomous and stage-specific functions for the small Rho GTPases...

Epidermal activation of the small GTPase Rac1 in psoriasis pathogenesis.

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Winge, Mårten C G; Marinkovich, M Peter

2017-01-05

The small GTPase Ras-related C3 botulinum toxin substrate 1 (RAC1) plays a central role in skin homeostasis, including barrier function, wound healing and inflammatory responses. Psoriasis is a common skin disease characterized by deregulation of these functions, and affected skin exhibit keratinocyte hyperproliferation, inflammation and immune cell infiltration. Although psoriasis is often triggered by environmental stimulus, there is a strong genetic association with genes expressed in both immune cells and keratinocytes, of which several are linked to Rac1 signaling. Rac1 is highly active in human psoriatic lesional skin and keratinocytes, and keratinocyte-specific overexpression of an activated mutant of Rac1, Rac1 V12 , in a transgenic mouse model closely mimics the presentation of human psoriasis. Both Rac1 activation in keratinocytes and immune derived stimulus are required to drive psoriasiform signaling in transgenic mouse and human xenograft models of psoriasis. Therefore, understanding how increased Rac1 activation in psoriatic epidermis is regulated is central to understanding how the abnormal crosstalk between keratinocytes and immune cells is maintained.

Ablation of p120-Catenin Altering the Activity of Small GTPase in Human Lung Cancer Cells

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Nan LIU

2009-05-01

Full Text Available Background and objective p120-catenin (p120ctn, a member of the Armadillo gene family, has emerged as an important modulator of small GTPase activities. Therefore, it plays novel roles in tumor malignant phenotype, such as invasion and metastasis, whose mechanism are not well clarified yet. The aim of this study is to explore the roles of p120ctn on the regulation of small GTP family members in lung cancer and the effects to lung cancer invasions andmetastasis. Methods After p120ctn was knocked down by siRNA, in vivo and in vitro analysis was applied to investigate the role and possible mechanism of p120ctn in lung cancer, such as Western Blot, pull-down analysis, and nude mice models. Results p120ctn depletion inactivated RhoA, with the the activity of Cdc42 and Rac1 increased, the invasiveness of lung cancer cells was promoted both in vitro and in vivo . Conclusion p120ctn gene knockdown enhances the metastasis of lung cancer cells, probably by altering expression of small GTPase, such as inactivation of RhoA and activation of Cdc42/Rac1.

BAR domain proteins regulate Rho GTPase signaling.

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Aspenström, Pontus

2014-01-01

BAR proteins comprise a heterogeneous group of multi-domain proteins with diverse biological functions. The common denominator is the Bin-Amphiphysin-Rvs (BAR) domain that not only confers targeting to lipid bilayers, but also provides scaffolding to mold lipid membranes into concave or convex surfaces. This function of BAR proteins is an important determinant in the dynamic reconstruction of membrane vesicles, as well as of the plasma membrane. Several BAR proteins function as linkers between cytoskeletal regulation and membrane dynamics. These links are provided by direct interactions between BAR proteins and actin-nucleation-promoting factors of the Wiskott-Aldrich syndrome protein family and the Diaphanous-related formins. The Rho GTPases are key factors for orchestration of this intricate interplay. This review describes how BAR proteins regulate the activity of Rho GTPases, as well as how Rho GTPases regulate the function of BAR proteins. This mutual collaboration is a central factor in the regulation of vital cellular processes, such as cell migration, cytokinesis, intracellular transport, endocytosis, and exocytosis.

Essential role of the small GTPase Ran in postnatal pancreatic islet development.

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Fang Xia

Full Text Available The small GTPase Ran orchestrates pleiotropic cellular responses of nucleo-cytoplasmic shuttling, mitosis and subcellular trafficking, but whether deregulation of these pathways contributes to disease pathogenesis has remained elusive. Here, we generated transgenic mice expressing wild type (WT Ran, loss-of-function Ran T24N mutant or constitutively active Ran G19V mutant in pancreatic islet β cells under the control of the rat insulin promoter. Embryonic pancreas and islet development, including emergence of insulin(+ β cells, was indistinguishable in control or transgenic mice. However, by one month after birth, transgenic mice expressing any of the three Ran variants exhibited overt diabetes, with hyperglycemia, reduced insulin production, and nearly complete loss of islet number and islet mass, in vivo. Deregulated Ran signaling in transgenic mice, adenoviral over-expression of WT or mutant Ran in isolated islets, or short hairpin RNA (shRNA silencing of endogenous Ran in model insulinoma INS-1 cells, all resulted in decreased expression of the pancreatic and duodenal homeobox transcription factor, PDX-1, and reduced β cell proliferation, in vivo. These data demonstrate that a finely-tuned balance of Ran GTPase signaling is essential for postnatal pancreatic islet development and glucose homeostasis, in vivo.

Role of Rab family GTPases and their effectors in melanosomal logistics.

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Ohbayashi, Norihiko; Fukuda, Mitsunori

2012-04-01

Rab GTPases constitute a family of small GTPases that regulate a variety of membrane trafficking events in all eukaryotic cells by recruiting their specific effector molecules. Recent accumulating evidence indicates that members of the mammalian Rab small GTPase family are involved in certain physiological and pathological processes. In particular, functional impairments of specific Rab proteins, e.g. Rab38 and Rab27A, their regulators or their effectors cause pigmentation disorders in humans and coat colour variations in mice because such impairments cause defects in melanosomal logistics, i.e. defects in melanosome biogenesis and transport. Genetic and biochemical analyses of the gene products responsible for mammalian pigmentation disorders in the past decade have revealed that Rab-mediated endosomal transport systems and melanosome transport systems play crucial roles in the efficient darkening of mammalian hair and skin. In this article, we review current knowledge regarding melanosomal logistics, with particular focus on the roles of Rab small GTPases and their effectors.

Identification of potential small molecule binding pockets on Rho family GTPases.

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Juan Manuel Ortiz-Sanchez

Full Text Available Rho GTPases are conformational switches that control a wide variety of signaling pathways critical for eukaryotic cell development and proliferation. They represent attractive targets for drug design as their aberrant function and deregulated activity is associated with many human diseases including cancer. Extensive high-resolution structures (>100 and recent mutagenesis studies have laid the foundation for the design of new structure-based chemotherapeutic strategies. Although the inhibition of Rho signaling with drug-like compounds is an active area of current research, very little attention has been devoted to directly inhibiting Rho by targeting potential allosteric non-nucleotide binding sites. By avoiding the nucleotide binding site, compounds may minimize the potential for undesirable off-target interactions with other ubiquitous GTP and ATP binding proteins. Here we describe the application of molecular dynamics simulations, principal component analysis, sequence conservation analysis, and ensemble small-molecule fragment mapping to provide an extensive mapping of potential small-molecule binding pockets on Rho family members. Characterized sites include novel pockets in the vicinity of the conformationaly responsive switch regions as well as distal sites that appear to be related to the conformations of the nucleotide binding region. Furthermore the use of accelerated molecular dynamics simulation, an advanced sampling method that extends the accessible time-scale of conventional simulations, is found to enhance the characterization of novel binding sites when conformational changes are important for the protein mechanism.

Lynch syndrome-related small intestinal adenocarcinomas.

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Jun, Sun-Young; Lee, Eui-Jin; Kim, Mi-Ju; Chun, Sung Min; Bae, Young Kyung; Hong, Soon Uk; Choi, Jene; Kim, Joon Mee; Jang, Kee-Taek; Kim, Jung Yeon; Kim, Gwang Il; Jung, Soo Jin; Yoon, Ghilsuk; Hong, Seung-Mo

2017-03-28

Lynch syndrome is an autosomal-dominant disorder caused by defective DNA mismatch repair (MMR) genes and is associated with increased risk of malignancies in multiple organs. Small-intestinal adenocarcinomas are common initial manifestations of Lynch syndrome. To define the incidence and characteristics of Lynch syndrome-related small-intestinal adenocarcinomas, meticulous familial and clinical histories were obtained from 195 patients with small-intestinal adenocarcinoma, and MMR protein immunohistochemistry, microsatellite instability, MLH1 methylation, and germline mutational analyses were performed. Lynch syndrome was confirmed in eight patients (4%), all of whom had synchronous/metachronous malignancies without noticeable familial histories. Small-intestinal adenocarcinomas were the first clinical manifestation in 37% (3/8) of Lynch syndrome patients, and second malignancies developed within 5 years in 63% (5/8). The patients with accompanying Lynch syndrome were younger (≤50 years; P=0.04) and more likely to have mucinous adenocarcinomas (P=0.003), and tended to survive longer (P=0.11) than those with sporadic cases. A meticulous patient history taking, MMR protein immunolabeling, and germline MMR gene mutational analysis are important for the diagnosis of Lynch syndrome-related small-intestinal adenocarcinomas. Identifying Lynch syndrome in patients with small-intestinal adenocarcinoma can be beneficial for the early detection and treatment of additional Lynch syndrome-related cancers, especially in patients who are young or have mucinous adenocarcinomas.

NMR derived model of GTPase effector domain (GED self association: relevance to dynamin assembly.

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Swagata Chakraborty

Full Text Available Self-association of dynamin to form spiral structures around lipidic vesicles during endocytosis is largely mediated by its 'coiled coil' GTPase Effector Domain (GED, which, in vitro, self-associates into huge helical assemblies. Residue-level structural characterizations of these assemblies and understanding the process of association have remained a challenge. It is also impossible to get folded monomers in the solution phase. In this context, we have developed here a strategy to probe the self-association of GED by first dissociating the assembly using Dimethyl Sulfoxide (DMSO and then systematically monitoring the refolding into helix and concomitant re-association using NMR spectroscopy, as DMSO concentration is progressively reduced. The short segment, Arg109 - Met116, acts as the nucleation site for helix formation and self-association. Hydrophobic and complementary charge interactions on the surfaces drive self-association, as the helices elongate in both the directions resulting in an antiparallel stack. A small N-terminal segment remains floppy in the assembly. Following these and other published results on inter-domain interactions, we have proposed a plausible mode of dynamin self assembly.

GTPases and the origin of the ribosome

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Smith Temple F

2010-05-01

Full Text Available Abstract Background This paper is an attempt to trace the evolution of the ribosome through the evolution of the universal P-loop GTPases that are involved with the ribosome in translation and with the attachment of the ribosome to the membrane. The GTPases involved in translation in Bacteria/Archaea are the elongation factors EFTu/EF1, the initiation factors IF2/aeIF5b + aeIF2, and the elongation factors EFG/EF2. All of these GTPases also contain the OB fold also found in the non GTPase IF1 involved in initiation. The GTPase involved in the signal recognition particle in most Bacteria and Archaea is SRP54. Results 1 The Elongation Factors of the Archaea based on structural considerations of the domains have the following evolutionary path: EF1→ aeIF2 → EF2. The evolution of the aeIF5b was a later event; 2 the Elongation Factors of the Bacteria based on the topological considerations of the GTPase domain have a similar evolutionary path: EFTu→ IF→2→EFG. These evolutionary sequences reflect the evolution of the LSU followed by the SSU to form the ribosome; 3 the OB-fold IF1 is a mimic of an ancient tRNA minihelix. Conclusion The evolution of translational GTPases of both the Archaea and Bacteria point to the evolution of the ribosome. The elongation factors, EFTu/EF1, began as a Ras-like GTPase bringing the activated minihelix tRNA to the Large Subunit Unit. The initiation factors and elongation factor would then have evolved from the EFTu/EF1 as the small subunit was added to the evolving ribosome. The SRP has an SRP54 GTPase and a specific RNA fold in its RNA component similar to the PTC. We consider the SRP to be a remnant of an ancient form of an LSU bound to a membrane. Reviewers This article was reviewed by George Fox, Leonid Mirny and Chris Sander.

Role of the Small GTPase Rho3 in Golgi/Endosome trafficking through functional interaction with adaptin in Fission Yeast.

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Ayako Kita

Full Text Available BACKGROUND: We had previously identified the mutant allele of apm1(+ that encodes a homolog of the mammalian µ1A subunit of the clathrin-associated adaptor protein-1 (AP-1 complex, and we demonstrated the role of Apm1 in Golgi/endosome trafficking, secretion, and vacuole fusion in fission yeast. METHODOLOGY/PRINCIPAL FINDINGS: In the present study, we isolated rho3(+, which encodes a Rho-family small GTPase, an important regulator of exocystosis, as a multicopy-suppressor of the temperature-sensitive growth of the apm1-1 mutant cells. Overexpression of Rho3 suppressed the Cl(- sensitivity and immunosuppressant sensitivity of the apm1-1 mutant cells. Overexpression of Rho3 also suppressed the fragmentation of vacuoles, and the accumulation of v-SNARE Syb1 in Golgi/endosomes and partially suppressed the defective secretion associated with apm1-deletion cells. Notably, electron microscopic observation of the rho3-deletion cells revealed the accumulation of abnormal Golgi-like structures, vacuole fragmentation, and accumulation of secretory vesicles; these phenotypes were very similar to those of the apm1-deletion cells. Furthermore, the rho3-deletion cells and apm1-deletion cells showed very similar phenotypic characteristics, including the sensitivity to the immunosuppressant FK506, the cell wall-damaging agent micafungin, Cl(-, and valproic acid. Green fluorescent protein (GFP-Rho3 was localized at Golgi/endosomes as well as the plasma membrane and division site. Finally, Rho3 was shown to form a complex with Apm1 as well as with other subunits of the clathrin-associated AP-1 complex in a GTP- and effector domain-dependent manner. CONCLUSIONS/SIGNIFICANCE: Taken together, our findings reveal a novel role of Rho3 in the regulation of Golgi/endosome trafficking and suggest that clathrin-associated adaptor protein-1 and Rho3 co-ordinate in intracellular transport in fission yeast. To the best of our knowledge, this study provides the first evidence

Different roles of the small GTPases Rac1, Cdc42, and RhoG in CALEB/NGC-induced dendritic tree complexity.

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Schulz, Jana; Franke, Kristin; Frick, Manfred; Schumacher, Stefan

2016-10-01

Rho GTPases play prominent roles in the regulation of cytoskeletal reorganization. Many aspects have been elaborated concerning the individual functions of Rho GTPases in distinct signaling pathways leading to cytoskeletal rearrangements. However, major questions have yet to be answered regarding the integration and the signaling hierarchy of different Rho GTPases in regulating the cytoskeleton in fundamental physiological events like neuronal process differentiation. Here, we investigate the roles of the small GTPases Rac1, Cdc42, and RhoG in defining dendritic tree complexity stimulated by the transmembrane epidermal growth factor family member CALEB/NGC. Combining gain-of-function and loss-of-function analysis in primary hippocampal neurons, we find that Rac1 is essential for CALEB/NGC-mediated dendritic branching. Cdc42 reduces the complexity of dendritic trees. Interestingly, we identify the palmitoylated isoform of Cdc42 to adversely affect dendritic outgrowth and dendritic branching, whereas the prenylated Cdc42 isoform does not. In contrast to Rac1, CALEB/NGC and Cdc42 are not directly interconnected in regulating dendritic tree complexity. Unlike Rac1, the Rac1-related GTPase RhoG reduces the complexity of dendritic trees by acting upstream of CALEB/NGC. Mechanistically, CALEB/NGC activates Rac1, and RhoG reduces the amount of CALEB/NGC that is located at the right site for Rac1 activation at the cell membrane. Thus, Rac1, Cdc42, and RhoG perform very specific and non-redundant functions at different levels of hierarchy in regulating dendritic tree complexity induced by CALEB/NGC. Rho GTPases play a prominent role in dendritic branching. CALEB/NGC is a transmembrane member of the epidermal growth factor (EGF) family that mediates dendritic branching, dependent on Rac1. CALEB/NGC stimulates Rac1 activity. RhoG inhibits CALEB/NGC-mediated dendritic branching by decreasing the amount of CALEB/NGC at the plasma membrane. Palmitoylated, but not prenylated form

Catalysis of GTP Hydrolysis by Small GTPases at Atomic Detail by Integration of X-ray Crystallography, Experimental, and Theoretical IR Spectroscopy*

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Rudack, Till; Jenrich, Sarah; Brucker, Sven; Vetter, Ingrid R.; Gerwert, Klaus; Kötting, Carsten

2015-01-01

Small GTPases regulate key processes in cells. Malfunction of their GTPase reaction by mutations is involved in severe diseases. Here, we compare the GTPase reaction of the slower hydrolyzing GTPase Ran with Ras. By combination of time-resolved FTIR difference spectroscopy and QM/MM simulations we elucidate that the Mg2+ coordination by the phosphate groups, which varies largely among the x-ray structures, is the same for Ran and Ras. A new x-ray structure of a Ran·RanBD1 complex with improved resolution confirmed this finding and revealed a general problem with the refinement of Mg2+ in GTPases. The Mg2+ coordination is not responsible for the much slower GTPase reaction of Ran. Instead, the location of the Tyr-39 side chain of Ran between the γ-phosphate and Gln-69 prevents the optimal positioning of the attacking water molecule by the Gln-69 relative to the γ-phosphate. This is confirmed in the RanY39A·RanBD1 crystal structure. The QM/MM simulations provide IR spectra of the catalytic center, which agree very nicely with the experimental ones. The combination of both methods can correlate spectra with structure at atomic detail. For example the FTIR difference spectra of RasA18T and RanT25A mutants show that spectral differences are mainly due to the hydrogen bond of Thr-25 to the α-phosphate in Ran. By integration of x-ray structure analysis, experimental, and theoretical IR spectroscopy the catalytic center of the x-ray structural models are further refined to sub-Å resolution, allowing an improved understanding of catalysis. PMID:26272610

The small GTPase RhoH is an atypical regulator of haematopoietic cells

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Kubatzky Katharina F

2008-09-01

Full Text Available Abstract Rho GTPases are a distinct subfamily of the superfamily of Ras GTPases. The best-characterised members are RhoA, Rac and Cdc42 that regulate many diverse actions such as actin cytoskeleton reorganisation, adhesion, motility as well as cell proliferation, differentiation and gene transcription. Among the 20 members of that family, only Rac2 and RhoH show an expression restricted to the haematopoietic lineage. RhoH was first discovered in 1995 as a fusion transcript with the transcriptional repressor LAZ3/BCL6. It was therefore initially named translation three four (TTF but later on renamed RhoH due to its close relationship to the Ras/Rho family of GTPases. Since then, RhoH has been implicated in human cancer as the gene is subject to somatic hypermutation and by the detection of RHOH as a translocation partner for LAZ3/BCL6 or other genes in human lymphomas. Underexpression of RhoH is found in hairy cell leukaemia and acute myeloid leukaemia. Some of the amino acids that are crucial for GTPase activity are mutated in RhoH so that the protein is a GTPase-deficient, so-called atypical Rho GTPase. Therefore other mechanisms of regulating RhoH activity have been described. These include regulation at the mRNA level and tyrosine phosphorylation of the protein's unique ITAM-like motif. The C-terminal CaaX box of RhoH is mainly a target for farnesyl-transferase but can also be modified by geranylgeranyl-transferase. Isoprenylation of RhoH and changes in subcellular localisation may be an additional factor to fine-tune signalling. Little is currently known about its signalling, regulation or interaction partners. Recent studies have shown that RhoH negatively influences the proliferation and homing of murine haematopoietic progenitor cells, presumably by acting as an antagonist for Rac1. In leukocytes, RhoH is needed to keep the cells in a resting, non-adhesive state, but the exact mechanism has yet to be elucidated. RhoH has also been

Rac and Rho GTPases in cancer cell motility control

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Parri Matteo

2010-09-01

Full Text Available Abstract Rho GTPases represent a family of small GTP-binding proteins involved in cell cytoskeleton organization, migration, transcription, and proliferation. A common theme of these processes is a dynamic reorganization of actin cytoskeleton which has now emerged as a major switch control mainly carried out by Rho and Rac GTPase subfamilies, playing an acknowledged role in adaptation of cell motility to the microenvironment. Cells exhibit three distinct modes of migration when invading the 3 D environment. Collective motility leads to movement of cohorts of cells which maintain the adherens junctions and move by photolytic degradation of matrix barriers. Single cell mesenchymal-type movement is characterized by an elongated cellular shape and again requires extracellular proteolysis and integrin engagement. In addition it depends on Rac1-mediated cell polarization and lamellipodia formation. Conversely, in amoeboid movement cells have a rounded morphology, the movement is independent from proteases but requires high Rho GTPase to drive elevated levels of actomyosin contractility. These two modes of cell movement are interconvertible and several moving cells, including tumor cells, show an high degree of plasticity in motility styles shifting ad hoc between mesenchymal or amoeboid movements. This review will focus on the role of Rac and Rho small GTPases in cell motility and in the complex relationship driving the reciprocal control between Rac and Rho granting for the opportunistic motile behaviour of aggressive cancer cells. In addition we analyse the role of these GTPases in cancer progression and metastatic dissemination.

Catalysis of GTP hydrolysis by small GTPases at atomic detail by integration of X-ray crystallography, experimental, and theoretical IR spectroscopy.

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Rudack, Till; Jenrich, Sarah; Brucker, Sven; Vetter, Ingrid R; Gerwert, Klaus; Kötting, Carsten

2015-10-02

Small GTPases regulate key processes in cells. Malfunction of their GTPase reaction by mutations is involved in severe diseases. Here, we compare the GTPase reaction of the slower hydrolyzing GTPase Ran with Ras. By combination of time-resolved FTIR difference spectroscopy and QM/MM simulations we elucidate that the Mg(2+) coordination by the phosphate groups, which varies largely among the x-ray structures, is the same for Ran and Ras. A new x-ray structure of a Ran·RanBD1 complex with improved resolution confirmed this finding and revealed a general problem with the refinement of Mg(2+) in GTPases. The Mg(2+) coordination is not responsible for the much slower GTPase reaction of Ran. Instead, the location of the Tyr-39 side chain of Ran between the γ-phosphate and Gln-69 prevents the optimal positioning of the attacking water molecule by the Gln-69 relative to the γ-phosphate. This is confirmed in the RanY39A·RanBD1 crystal structure. The QM/MM simulations provide IR spectra of the catalytic center, which agree very nicely with the experimental ones. The combination of both methods can correlate spectra with structure at atomic detail. For example the FTIR difference spectra of RasA18T and RanT25A mutants show that spectral differences are mainly due to the hydrogen bond of Thr-25 to the α-phosphate in Ran. By integration of x-ray structure analysis, experimental, and theoretical IR spectroscopy the catalytic center of the x-ray structural models are further refined to sub-Å resolution, allowing an improved understanding of catalysis. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Merkel Cell Polyomavirus Small T Antigen Drives Cell Motility via Rho-GTPase-Induced Filopodium Formation.

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Stakaitytė, Gabrielė; Nwogu, Nnenna; Dobson, Samuel J; Knight, Laura M; Wasson, Christopher W; Salguero, Francisco J; Blackbourn, David J; Blair, G Eric; Mankouri, Jamel; Macdonald, Andrew; Whitehouse, Adrian

2018-01-15

Cell motility and migration is a complex, multistep, and multicomponent process intrinsic to progression and metastasis. Motility is dependent on the activities of integrin receptors and Rho family GTPases, resulting in the remodeling of the actin cytoskeleton and formation of various motile actin-based protrusions. Merkel cell carcinoma (MCC) is an aggressive skin cancer with a high likelihood of recurrence and metastasis. Merkel cell polyomavirus (MCPyV) is associated with the majority of MCC cases, and MCPyV-induced tumorigenesis largely depends on the expression of the small tumor antigen (ST). Since the discovery of MCPyV, a number of mechanisms have been suggested to account for replication and tumorigenesis, but to date, little is known about potential links between MCPyV T antigen expression and the metastatic nature of MCC. Previously, we described the action of MCPyV ST on the microtubule network and how it impacts cell motility and migration. Here, we demonstrate that MCPyV ST affects the actin cytoskeleton to promote the formation of filopodia through a mechanism involving the catalytic subunit of protein phosphatase 4 (PP4C). We also show that MCPyV ST-induced cell motility is dependent upon the activities of the Rho family GTPases Cdc42 and RhoA. In addition, our results indicate that the MCPyV ST-PP4C interaction results in the dephosphorylation of β 1 integrin, likely driving the cell motility pathway. These findings describe a novel mechanism by which a tumor virus induces cell motility, which may ultimately lead to cancer metastasis, and provides opportunities and strategies for targeted interventions for disseminated MCC. IMPORTANCE Merkel cell polyomavirus (MCPyV) is the most recently discovered human tumor virus. It causes the majority of cases of Merkel cell carcinoma (MCC), an aggressive skin cancer. However, the molecular mechanisms implicating MCPyV-encoded proteins in cancer development are yet to be fully elucidated. This study builds

Regulation of ER-Golgi Transport Dynamics by GTPases in Budding Yeast

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Yasuyuki Suda

2018-01-01

Full Text Available A large number of proteins are synthesized de novo in the endoplasmic reticulum (ER. They are transported through the Golgi apparatus and then delivered to their proper destinations. The ER and the Golgi play a central role in protein processing and sorting and show dynamic features in their forms. Ras super family small GTPases mediate the protein transport through and between these organelles. The ER-localized GTPase, Sar1, facilitates the formation of COPII transport carriers at the ER exit sites (ERES on the ER for the transport of cargo proteins from the ER to the Golgi. The Golgi-localized GTPase, Arf1, controls intra-Golgi, and Golgi-to-ER transport of cargo proteins by the formation of COPI carriers. Rab GTPases localized at the Golgi, which are responsible for fusion of membranes, are thought to establish the identities of compartments. Recent evidence suggests that these small GTPases regulate not only discrete sites for generation/fusion of transport carriers, but also membrane dynamics of the organelles where they locate to ensure the integrity of transport. Here we summarize the current understandings about the membrane traffic between these organelles and highlight the cutting-edge advances from super-resolution live imaging of budding yeast, Saccharomyces cerevisiae.

Rho GTPases in ameloblast differentiation

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Keishi Otsu

2016-05-01

Full Text Available During tooth development, ameloblasts differentiate from inner enamel epithelial cells to enamel-forming cells by modulating the signal pathways mediating epithelial–mesenchymal interaction and a cell-autonomous gene network. The differentiation process of epithelial cells is characterized by marked changes in their morphology and polarity, accompanied by dynamic cytoskeletal reorganization and changes in cell–cell and cell–matrix adhesion over time. Functional ameloblasts are tall, columnar, polarized cells that synthesize and secrete enamel-specific proteins. After deposition of the full thickness of enamel matrix, ameloblasts become smaller and regulate enamel maturation. Recent significant advances in the fields of molecular biology and genetics have improved our understanding of the regulatory mechanism of the ameloblast cell life cycle, mediated by the Rho family of small GTPases. They act as intracellular molecular switch that transduce signals from extracellular stimuli to the actin cytoskeleton and the nucleus. In our review, we summarize studies that provide current evidence for Rho GTPases and their involvement in ameloblast differentiation. In addition to the Rho GTPases themselves, their downstream effectors and upstream regulators have also been implicated in ameloblast differentiation.

The prevalence of Usher syndrome and other retinal dystrophy-hearing impairment associations.

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Rosenberg, T; Haim, M; Hauch, A M; Parving, A

1997-05-01

The study was undertaken to procure population-based prevalence data on the various types of Usher syndrome and other retinal dystrophy-hearing impairment associations. The medical files on 646 patients with a panretinal pigmentary dystrophy aged 20-49 years derived from the Danish Retinitis Pigmentosa (RP) register were scrutinised. The data were supplemented by a prior investigation on hearing ability in a part of the study population. After exclusion of patients with possibly extrinsic causes of hearing impairments, 118 patients, including 89 cases of Usher syndrome were allocated to one of five clinically defined groups. We calculated the following prevalence rates: Usher syndrome type I: 1.5/100,000, Usher syndrome type II: 2.2/100,000, and Usher syndrome type III: 0.1/100,000 corresponding to a 2:3 ratio between Usher syndrome type I and II. The overall prevalence rate of Usher syndrome was estimated to 5/100,000 in the Danish population, devoid of genetic isolates. The material comprised 11 cases with retinal dystrophy, hearing impairment, and additional syndromic features. Finally, 18 subjects with various retinal dystrophy-hearing impairment associations without syndromic features were identified, corresponding to a prevalence rate of 0.8/100,000. This group had a significant overrepresentation of X-linked RP, including two persons harboring a mutation in the retinitis pigmentosa GTP-ase regulator (RPGR) gene.

Rho GTPases, their post-translational modifications, disease-associated mutations and pharmacological inhibitors.

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Olson, Michael F

2018-05-04

The 20 members of the Rho GTPase family are key regulators of a wide-variety of biological activities. In response to activation, they signal via downstream effector proteins to induce dynamic alterations in the organization of the actomyosin cytoskeleton. In this review, post-translational modifications, mechanisms of dysregulation identified in human pathological conditions, and the ways that Rho GTPases might be targeted for chemotherapy will be discussed.

Crosstalk between Bcl-2 family and Ras family small GTPases: potential cell fate regulation?

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Kang, Jia; Pervaiz, Shazib

2013-01-01

Cell fate regulation is a function of diverse cell signaling pathways that promote cell survival and or inhibit cell death execution. In this regard, the role of the Bcl-2 family in maintaining a tight balance between cell death and cell proliferation has been extensively studied. The conventional dogma links cell fate regulation by the Bcl-2 family to its effect on mitochondrial permeabilization and apoptosis amplification. However, recent evidence provide a novel mechanism for death regulation by the Bcl-2 family via modulating cellular redox metabolism. For example overexpression of Bcl-2 has been shown to contribute to a pro-oxidant intracellular milieu and down-regulation of cellular superoxide levels enhanced death sensitivity of Bcl-2 overexpressing cells. Interestingly, gene knockdown of the small GTPase Rac1 or pharmacological inhibition of its activity also reverted death phenotype in Bcl-2 expressing cells. This appears to be a function of an interaction between Bcl-2 and Rac1. Similar functional associations have been described between the Bcl-2 family and other members of the Ras superfamily. These interactions at the mitochondria provide novel opportunities for strategic therapeutic targeting of drug-resistant cancers.

Rho GTPase function in tumorigenesis

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Karlsson, R; Pedersen, Esben Ditlev Kølle; Wang, Zhipeng

2009-01-01

, for that reason, Rho GTPases, their regulators, and their effectors have been suggested to control tumor formation and progression in humans. However, while the tumor-relevant functions of Rho GTPases are very well documented in vitro, we are only now beginning to assess their contribution to cancer in human...... patients and in animal models. This review will give a very brief overview of Rho GTPase function in general and then focus on in vivo evidence for a role of Rho GTPases in malignant tumors, both in human patients and in genetically modified mice....

Mechanisms of Membrane Binding of Small GTPase K-Ras4B Farnesylated Hypervariable Region*

Science.gov (United States)

Jang, Hyunbum; Abraham, Sherwin J.; Chavan, Tanmay S.; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth; Gaponenko, Vadim

2015-01-01

K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. PMID:25713064

Inhibition of endothelial cell proliferation by targeting Rac1 GTPase with small interference RNA in tumor cells

International Nuclear Information System (INIS)

Xue Yan; Bi Feng; Zhang Xueyong; Pan Yanglin; Liu Na; Zheng Yi; Fan Daiming

2004-01-01

Hypoxia-induced angiogenesis plays an important role in the malignancy of solid tumors. A number of recent studies including our own have suggested that Rho family small GTPases are involved in this process, and Rac1, a prominent member of the Rho family, may be critical in regulating hypoxia-induced gene activation of several angiogenesis factors and tumor suppressors. To further define Rac1 function in angiogenesis and to explore novel approaches to modulate angiogenesis, we employed the small interference RNA technique to knock down gene expression of Rac1 in gastric cancer cell line AGS that expresses a high level of Rac1. Both the mRNA and protein levels of Rac1 in the AGS cells were decreased dramatically after transfection with a Rac1-specific siRNA vector. When the conditioned medium derived from the Rac1 downregulated AGS cells was applied to the human endothelial cells, it could significantly inhibit the cell proliferation. Further study proved that, VEGF and HIF-1α, two angiogenesis promoting factors, were found to be downregulated whereas p53 and VHL, which are tumor suppressors and angiogenesis inhibitors, were upregulated in the Rac1 siRNA transfected cells. Our results suggest that Rac1 may be involved in angiogenesis by controlling the expression of angiogenesis-related factors and provide a possible strategy for the treatment of tumor angiogenesis by targeting the Rac1 GTPase

The Rho-GTPase binding protein IQGAP2 is required for the glomerular filtration barrier.

Science.gov (United States)

Sugano, Yuya; Lindenmeyer, Maja T; Auberger, Ines; Ziegler, Urs; Segerer, Stephan; Cohen, Clemens D; Neuhauss, Stephan C F; Loffing, Johannes

2015-11-01

Podocyte dysfunction impairs the size selectivity of the glomerular filter, leading to proteinuria, hypoalbuminuria, and edema, clinically defined as nephrotic syndrome. Hereditary forms of nephrotic syndrome are linked to mutations in podocyte-specific genes. To identify genes contributing to podocyte dysfunction in acquired nephrotic syndrome, we studied human glomerular gene expression data sets for glomerular-enriched gene transcripts differentially regulated between pretransplant biopsy samples and biopsies from patients with nephrotic syndrome. Candidate genes were screened by in situ hybridization for expression in the zebrafish pronephros, an easy-to-use in vivo assay system to assess podocyte function. One glomerulus-enriched product was the Rho-GTPase binding protein, IQGAP2. Immunohistochemistry found a strong presence of IQGAP2 in normal human and zebrafish podocytes. In zebrafish larvae, morpholino-based knockdown of iqgap2 caused a mild foot process effacement of zebrafish podocytes and a cystic dilation of the urinary space of Bowman's capsule upon onset of urinary filtration. Moreover, the glomerulus of zebrafish morphants showed a glomerular permeability for injected high-molecular-weight dextrans, indicating an impaired size selectivity of the glomerular filter. Thus, IQGAP2 is a Rho-GTPase binding protein, highly abundant in human and zebrafish podocytes, which controls normal podocyte structure and function as evidenced in the zebrafish pronephros.

Mechanisms of membrane binding of small GTPase K-Ras4B farnesylated hypervariable region.

Science.gov (United States)

Jang, Hyunbum; Abraham, Sherwin J; Chavan, Tanmay S; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I; Nussinov, Ruth; Gaponenko, Vadim

2015-04-10

K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Nucleophosmin1 is a negative regulator of the small GTPase Rac1

NARCIS (Netherlands)

Zoughlami, Younes; van Stalborgh, Anne M.; van Hennik, Paula B.; Hordijk, Peter L.

2013-01-01

The Rac1 GTPase is a critical regulator of cytoskeletal dynamics and controls many biological processes, such as cell migration, cell-cell contacts, cellular growth and cell division. These complex processes are controlled by Rac1 signaling through effector proteins. We have previously identified

Leucine-rich repeat kinase-1 regulates osteoclast function by modulating RAC1/Cdc42 Small GTPase phosphorylation and activation.

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Zeng, Canjun; Goodluck, Helen; Qin, Xuezhong; Liu, Bo; Mohan, Subburaman; Xing, Weirong

2016-10-01

Leucine-rich repeat kinase-1 (Lrrk1) consists of ankyrin repeats (ANK), leucine-rich repeats (LRR), a GTPase-like domain of Roc (ROC), a COR domain, a serine/threonine kinase domain (KD), and WD40 repeats (WD40). Previous studies have revealed that knockout (KO) of Lrrk1 in mice causes severe osteopetrosis, and a human mutation of Lrrk1 leads to osteosclerotic metaphysial dysplasia. The molecular mechanism by which Lrrk1 regulates osteoclast function is unknown. In this study, we generated a series of Lrrk1 mutants and evaluated their ability to rescue defective bone resorption in Lrrk1-deficient osteoclasts by use of pit formation assays. Overexpression of Lrrk1 or LRR-truncated Lrrk1, but not ANK-truncated Lrrk1, WD40-truncated Lrrk1, Lrrk1-KD, or K651A mutant Lrrk1, rescued bone resorption function of Lrrk1 KO osteoclasts. We next examined whether RAC1/Cdc42 small GTPases are direct substrates of Lrrk1 in osteoclasts. Western blot and pull-down assays revealed that Lrrk1 deficiency in osteoclasts resulted in reduced phosphorylation and activation of RAC1/Cdc42. In vitro kinase assays confirmed that recombinant Lrrk1 phosphorylated RAC1-GST protein, and immunoprecipitation showed that the interaction of Lrrk1 with RAC1 occurred within 10 min after RANKL treatment. Overexpression of constitutively active Q61L RAC1 partially rescued the resorptive function of Lrrk1-deficient osteoclasts. Furthermore, lack of Lrrk1 in osteoclasts led to reduced autophosphorylation of p21 protein-activated kinase-1 at Ser 144 , catalyzed by RAC1/Cdc42 binding and activation. Our data indicate that Lrrk1 regulates osteoclast function by directly modulating phosphorylation and activation of small GTPase RAC1/Cdc42 and that its function depends on ANK, ROC, WD40, and kinase domains. Copyright © 2016 the American Physiological Society.

[Congenital sensorineural deafness and associated syndromes].

Science.gov (United States)

Moatti, L; Garabedian, E N; Lacombe, H; Spir-Jacob, C

1990-01-01

The etiology of perceptive deafness, especially the congenital variety, requires investigation. The presence of a variety of signs associated with deafness constitutes an "associated syndrome" and helps to define a possible genetic origin. These syndromes only represent a small percentage of overall causes of deafness in children, since at most they account for only 10% of cases. Certain syndromes are encountered more often or are well known, others are extremely rare or have only been described recently. The authors report six of these very rare syndromes discovered among their patients: a KID syndrome, a Leopard syndrome, a Norrie syndrome, a Jervell and Lange Nielsen syndrome, a recently described entity called CEE with deafness and an External Neuro-Cochleo-Pancreatic syndrome which would not appear to have been previously described.

2D-DIGE and MALDI TOF/TOF MS analysis reveal that small GTPase signaling pathways may play an important role in cadmium-induced colon cell malignant transformation

International Nuclear Information System (INIS)

Lu, Jian; Zhou, Zhongping; Zheng, Jianzhou; Zhang, Zhuyi; Lu, Rongzhu; Liu, Hanqing; Shi, Haifeng; Tu, Zhigang

2015-01-01

Cadmium is a toxic heavy metal present in the environment and in industrial materials. Cadmium has demonstrated carcinogenic activity that induces cell transformation, but how this occurs is unclear. We used 2D-DIGE and MALDI TOF/TOF MS combined with bioinformatics and immunoblotting to investigate the molecular mechanism of cadmium transformation. We found that small GTPases were critical for transformation. Additionally, proteins involved in mitochondrial transcription, DNA repair, and translation also had altered expression patterns in cadmium treated cells. Collectively, our results suggest that activation of small GTPases contributes to cadmium-induced transformation of colon cells. - Highlights: • Colon epithelial cell line is firstly successfully transformed by cadmium. • 2D-DIGE is applied to visualize the differentially expressed proteins. • RhoA plays an important role in cadmium induced malignant transformation. • Bioinformatic and experimental methods are combined to explore new mechanisms.

2D-DIGE and MALDI TOF/TOF MS analysis reveal that small GTPase signaling pathways may play an important role in cadmium-induced colon cell malignant transformation

Energy Technology Data Exchange (ETDEWEB)

Lu, Jian, E-mail: lujian@ujs.edu.cn [School of Medicine, Jiangsu University, Zhenjiang 212013 (China); Institute of Life Sciences, Jiangsu University, Zhenjiang 212013 (China); Zhou, Zhongping [School of Medicine, Jiangsu University, Zhenjiang 212013 (China); Institute of Life Sciences, Jiangsu University, Zhenjiang 212013 (China); Zheng, Jianzhou [Department of Respiration Medicine, Changzhou No.2 People' s Hospital, Changzhou 213003 (China); Zhang, Zhuyi [School of Medicine, Jiangsu University, Zhenjiang 212013 (China); Institute of Life Sciences, Jiangsu University, Zhenjiang 212013 (China); Lu, Rongzhu [School of Medicine, Jiangsu University, Zhenjiang 212013 (China); Liu, Hanqing [School of Pharmacy, Jiangsu University, Zhenjiang 212013 (China); Shi, Haifeng [Institute of Life Sciences, Jiangsu University, Zhenjiang 212013 (China); Tu, Zhigang, E-mail: tuzg_ujs@ujs.edu.cn [Institute of Life Sciences, Jiangsu University, Zhenjiang 212013 (China)

2015-10-01

Cadmium is a toxic heavy metal present in the environment and in industrial materials. Cadmium has demonstrated carcinogenic activity that induces cell transformation, but how this occurs is unclear. We used 2D-DIGE and MALDI TOF/TOF MS combined with bioinformatics and immunoblotting to investigate the molecular mechanism of cadmium transformation. We found that small GTPases were critical for transformation. Additionally, proteins involved in mitochondrial transcription, DNA repair, and translation also had altered expression patterns in cadmium treated cells. Collectively, our results suggest that activation of small GTPases contributes to cadmium-induced transformation of colon cells. - Highlights: • Colon epithelial cell line is firstly successfully transformed by cadmium. • 2D-DIGE is applied to visualize the differentially expressed proteins. • RhoA plays an important role in cadmium induced malignant transformation. • Bioinformatic and experimental methods are combined to explore new mechanisms.

A novel small deletion in the NHS gene associated with Nance-Horan syndrome

OpenAIRE

Li, Huajin; Yang, Lizhu; Sun, Zixi; Yuan, Zhisheng; Wu, Shijing; Sui, Ruifang

2018-01-01

Nance-Horan syndrome is a rare X-linked recessive inherited disease with clinical features including severe bilateral congenital cataracts, characteristic facial and dental abnormalities. Data from Chinese Nance-Horan syndrome patients are limited. We assessed the clinical manifestations of a Chinese Nance-Horan syndrome pedigree and identified the genetic defect. Genetic analysis showed that 3 affected males carried a novel small deletion in NHS gene, c.263_266delCGTC (p.Ala89TrpfsTer106), a...

The Drosophila small GTPase Rac2 is required for normal feeding and mating behaviour.

Science.gov (United States)

Goergen, Philip; Kasagiannis, Anna; Schiöth, Helgi B; Williams, Michael J

2014-03-01

All multicellular organisms require the ability to regulate bodily processes in order to maintain a stable condition, which necessitates fluctuations in internal metabolics, as well as modifications of outward behaviour. Understanding the genetics behind this modulation is important as a general model for the metabolic modification of behaviour. This study demonstrates that the activity of the small GTPase Rac2 is required in Drosophila for the proper regulation of lipid storage and feeding behaviour, as well as aggression and mating behaviours. Rac2 mutant males and females are susceptible to starvation and contain considerably less lipids than controls. Furthermore, Rac2 mutants also have disrupted feeding behaviour, eating fewer but larger meals than controls. Intriguingly, Rac2 mutant males rarely initiate aggressive behaviour and display significantly increased levels of courtship behaviour towards other males and mated females. From these results we conclude that Rac2 has a central role in regulating the Drosophila homeostatic system.

Stage-specific control of neural crest stem cell proliferation by the small rho GTPases Cdc42 and Rac1

DEFF Research Database (Denmark)

Fuchs, Sebastian; Herzog, Dominik; Sumara, Grzegorz

2009-01-01

-renewal and proliferation of later stage, but not early migratory NCSCs. This stage-specific requirement for small Rho GTPases is due to changes in NCSCs that, during development, acquire responsiveness to mitogenic EGF acting upstream of both Cdc42 and Rac1. Thus, our data reveal distinct mechanisms for growth control......The neural crest (NC) generates a variety of neural and non-neural tissues during vertebrate development. Both migratory NC cells and their target structures contain cells with stem cell features. Here we show that these populations of neural crest-derived stem cells (NCSCs) are differentially...

Segmental small bowel necrosis associated with antiphospholipid syndrome: a case report.

Science.gov (United States)

Wang, Qun-Ying; Ye, Xiao-Hua; Ding, Jin; Wu, Xiao-Kang

2015-04-07

Antiphospholipid syndrome is a multi-system disease characterized by the formation of thromboembolic complications and/or pregnancy morbidity, and with persistently increased titers of antiphospholipid antibodies. We report the case of a 50-year-old, previously healthy man who presented with fever and new-onset, dull abdominal pain. A contrast-enhanced computed tomography scan showed segmental small bowel obstruction, for which an emergency laparotomy was performed. Histopathologic examination of resected tissues revealed multiple intestinal and mesenteric thromboses of small vessels. Laboratory tests for serum antiphospholipid (anticardiolipin IgM) and anti-β2-glycoprotein I antibodies were positive. Despite proactive implementation of anticoagulation, steroid, and antibiotic therapies, the patient's condition rapidly deteriorated, and he died 22 d after admission. This case highlights that antiphospholipid syndrome should be suspected in patients with unexplainable ischemic bowel and intestinal necrosis presenting with insidious clinical features that may be secondary to the disease, as early diagnosis is critical to implement timely treatments in order to ameliorate the disease course.

ATPase and GTPase Tangos Drive Intracellular Protein Transport.

Science.gov (United States)

Shan, Shu-Ou

2016-12-01

The GTPase superfamily of proteins provides molecular switches to regulate numerous cellular processes. The 'GTPase switch' paradigm, in which external regulatory factors control the switch of a GTPase between 'on' and 'off' states, has been used to interpret the regulatory mechanism of many GTPases. However, recent work unveiled a class of nucleotide hydrolases that do not adhere to this classical paradigm. Instead, they use nucleotide-dependent dimerization cycles to regulate key cellular processes. In this review article, recent studies of dimeric GTPases and ATPases involved in intracellular protein targeting are summarized. It is suggested that these proteins can use the conformational plasticity at their dimer interface to generate multiple points of regulation, thereby providing the driving force and spatiotemporal coordination of complex cellular pathways. Copyright © 2016 Elsevier Ltd. All rights reserved.

Small bowel endoscopy in familial adenomatous polyposis and Lynch syndrome

NARCIS (Netherlands)

Koornstra, Jan Jacob

Patients with familial adenomatous polyposis (FAP) and patients with Lynch syndrome have an increased risk of developing small intestinal neoplasia. In both conditions, the lifetime risk to develop small bowel cancer is estimated to be around 5%. In FAP, this risk is associated with the degree of

A novel small deletion in the NHS gene associated with Nance-Horan syndrome.

Science.gov (United States)

Li, Huajin; Yang, Lizhu; Sun, Zixi; Yuan, Zhisheng; Wu, Shijing; Sui, Ruifang

2018-02-05

Nance-Horan syndrome is a rare X-linked recessive inherited disease with clinical features including severe bilateral congenital cataracts, characteristic facial and dental abnormalities. Data from Chinese Nance-Horan syndrome patients are limited. We assessed the clinical manifestations of a Chinese Nance-Horan syndrome pedigree and identified the genetic defect. Genetic analysis showed that 3 affected males carried a novel small deletion in NHS gene, c.263_266delCGTC (p.Ala89TrpfsTer106), and 2 female carriers were heterozygous for the same variant. All 3 affected males presented with typical Nance-Horan syndrome features. One female carrier displayed lens opacities centered on the posterior Y-suture in both eyes, as well as mild dental abnormalities. We recorded the clinical features of a Chinese Nance-Horan syndrome family and broadened the spectrum of mutations in the NHS gene.

Gain-of-function mutant p53 activates small GTPase Rac1 through SUMOylation to promote tumor progression.

Science.gov (United States)

Yue, Xuetian; Zhang, Cen; Zhao, Yuhan; Liu, Juan; Lin, Alan W; Tan, Victor M; Drake, Justin M; Liu, Lianxin; Boateng, Michael N; Li, Jun; Feng, Zhaohui; Hu, Wenwei

2017-08-15

Tumor suppressor p53 is frequently mutated in human cancer. Mutant p53 often promotes tumor progression through gain-of-function (GOF) mechanisms. However, the mechanisms underlying mutant p53 GOF are not well understood. In this study, we found that mutant p53 activates small GTPase Rac1 as a critical mechanism for mutant p53 GOF to promote tumor progression. Mechanistically, mutant p53 interacts with Rac1 and inhibits its interaction with SUMO-specific protease 1 (SENP1), which in turn inhibits SENP1-mediated de-SUMOylation of Rac1 to activate Rac1. Targeting Rac1 signaling by RNAi, expression of the dominant-negative Rac1 (Rac1 DN), or the specific Rac1 inhibitor NSC23766 greatly inhibits mutant p53 GOF in promoting tumor growth and metastasis. Furthermore, mutant p53 expression is associated with enhanced Rac1 activity in clinical tumor samples. These results uncover a new mechanism for Rac1 activation in tumors and, most importantly, reveal that activation of Rac1 is an unidentified and critical mechanism for mutant p53 GOF in tumorigenesis, which could be targeted for therapy in tumors containing mutant p53. © 2017 Yue et al.; Published by Cold Spring Harbor Laboratory Press.

The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes

Science.gov (United States)

Khatter, Divya; Raina, Vivek B.; Dwivedi, Devashish; Sindhwani, Aastha; Bahl, Surbhi; Sharma, Mahak

2015-01-01

The homotypic fusion and protein sorting (HOPS) complex is a multi-subunit complex conserved from yeast to mammals that regulates late endosome and lysosome fusion. However, little is known about how the HOPS complex is recruited to lysosomes in mammalian cells. Here, we report that the small GTPase Arl8b, but not Rab7 (also known as RAB7A), is essential for membrane localization of the human (h)Vps41 subunit of the HOPS complex. Assembly of the core HOPS subunits to Arl8b- and hVps41-positive lysosomes is guided by their subunit–subunit interactions. RNA interference (RNAi)-mediated depletion of hVps41 resulted in the impaired degradation of EGFR that was rescued upon expression of wild-type but not an Arl8b-binding-defective mutant of hVps41, suggesting that Arl8b-dependent lysosomal localization of hVps41 is required for its endocytic function. Furthermore, we have also identified that the Arl8b effector SKIP (also known as PLEKHM2) interacts with and recruits HOPS subunits to Arl8b and kinesin-positive peripheral lysosomes. Accordingly, RNAi-mediated depletion of SKIP impaired lysosomal trafficking and degradation of EGFR. These findings reveal that Arl8b regulates the association of the human HOPS complex with lysosomal membranes, which is crucial for the function of this tethering complex in endocytic degradation. PMID:25908847

The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes.

Science.gov (United States)

Khatter, Divya; Raina, Vivek B; Dwivedi, Devashish; Sindhwani, Aastha; Bahl, Surbhi; Sharma, Mahak

2015-05-01

The homotypic fusion and protein sorting (HOPS) complex is a multi-subunit complex conserved from yeast to mammals that regulates late endosome and lysosome fusion. However, little is known about how the HOPS complex is recruited to lysosomes in mammalian cells. Here, we report that the small GTPase Arl8b, but not Rab7 (also known as RAB7A), is essential for membrane localization of the human (h)Vps41 subunit of the HOPS complex. Assembly of the core HOPS subunits to Arl8b- and hVps41-positive lysosomes is guided by their subunit-subunit interactions. RNA interference (RNAi)-mediated depletion of hVps41 resulted in the impaired degradation of EGFR that was rescued upon expression of wild-type but not an Arl8b-binding-defective mutant of hVps41, suggesting that Arl8b-dependent lysosomal localization of hVps41 is required for its endocytic function. Furthermore, we have also identified that the Arl8b effector SKIP (also known as PLEKHM2) interacts with and recruits HOPS subunits to Arl8b and kinesin-positive peripheral lysosomes. Accordingly, RNAi-mediated depletion of SKIP impaired lysosomal trafficking and degradation of EGFR. These findings reveal that Arl8b regulates the association of the human HOPS complex with lysosomal membranes, which is crucial for the function of this tethering complex in endocytic degradation. © 2015. Published by The Company of Biologists Ltd.

Enrichment of Phosphatidylethanolamine in Viral Replication Compartments via Co-opting the Endosomal Rab5 Small GTPase by a Positive-Strand RNA Virus.

Directory of Open Access Journals (Sweden)

Kai Xu

2016-10-01

Full Text Available Positive-strand RNA viruses build extensive membranous replication compartments to support replication and protect the virus from antiviral responses by the host. These viruses require host factors and various lipids to form viral replication complexes (VRCs. The VRCs built by Tomato bushy stunt virus (TBSV are enriched with phosphatidylethanolamine (PE through a previously unknown pathway. To unravel the mechanism of PE enrichment within the TBSV replication compartment, in this paper, the authors demonstrate that TBSV co-opts the guanosine triphosphate (GTP-bound active form of the endosomal Rab5 small GTPase via direct interaction with the viral replication protein. Deletion of Rab5 orthologs in a yeast model host or expression of dominant negative mutants of plant Rab5 greatly decreases TBSV replication and prevents the redistribution of PE to the sites of viral replication. We also show that enrichment of PE in the viral replication compartment is assisted by actin filaments. Interestingly, the closely related Carnation Italian ringspot virus, which replicates on the boundary membrane of mitochondria, uses a similar strategy to the peroxisomal TBSV to hijack the Rab5-positive endosomes into the viral replication compartments. Altogether, usurping the GTP-Rab5-positive endosomes allows TBSV to build a PE-enriched viral replication compartment, which is needed to support peak-level replication. Thus, the Rab family of small GTPases includes critical host factors assisting VRC assembly and genesis of the viral replication compartment.

Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation

Energy Technology Data Exchange (ETDEWEB)

Vallon, Mario, E-mail: m.vallon@arcor.de [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany); Rohde, Franziska; Janssen, Klaus-Peter [Chirurgische Klinik und Poliklinik, Technische Universitaet Muenchen, Munich (Germany); Essler, Markus [Nuklearmedizinische Klinik und Poliklinik, Technische Universitaet Muenchen, Ismaninger Strasse 22, 81675 Munich (Germany)

2010-02-01

Tumor endothelial marker (TEM) 5 is an adhesion G-protein-coupled receptor upregulated in endothelial cells during tumor and physiologic angiogenesis. So far, the mechanisms leading to upregulation of TEM5 and its function during angiogenesis have not been identified. Here, we report that TEM5 expression in endothelial cells is induced during capillary-like network formation on Matrigel, during capillary morphogenesis in a three-dimensional collagen I matrix, and upon confluence on a two-dimensional matrix. TEM5 expression was not induced by a variety of soluble angiogenic factors, including VEGF and bFGF, in subconfluent endothelial cells. TEM5 upregulation was blocked by toxin B from Clostridium difficile, an inhibitor of the small GTPases Rho, Rac, and Cdc42. The Rho inhibitor C3 transferase from Clostridium botulinum did not affect TEM5 expression, whereas the Rac inhibitor NSC23766 suppressed TEM5 upregulation. An excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5 antibody blocked contact inhibition of endothelial cell proliferation resulting in multilayered islands within the endothelial monolayer and increased vessel density during capillary formation. Based on our results we conclude that TEM5 expression during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of proliferation in endothelial cells.

Rab GTPases in Immunity and Inflammation.

Science.gov (United States)

Prashar, Akriti; Schnettger, Laura; Bernard, Elliott M; Gutierrez, Maximiliano G

2017-01-01

Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking. In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation.

Rab GTPases in Immunity and Inflammation

Directory of Open Access Journals (Sweden)

Akriti Prashar

2017-09-01

Full Text Available Strict spatiotemporal control of trafficking events between organelles is critical for maintaining homeostasis and directing cellular responses. This regulation is particularly important in immune cells for mounting specialized immune defenses. By controlling the formation, transport and fusion of intracellular organelles, Rab GTPases serve as master regulators of membrane trafficking. In this review, we discuss the cellular and molecular mechanisms by which Rab GTPases regulate immunity and inflammation.

Rho GTPase expression in human myeloid cells.

Directory of Open Access Journals (Sweden)

Suzanne F G van Helden

Full Text Available Myeloid cells are critical for innate immunity and the initiation of adaptive immunity. Strict regulation of the adhesive and migratory behavior is essential for proper functioning of these cells. Rho GTPases are important regulators of adhesion and migration; however, it is unknown which Rho GTPases are expressed in different myeloid cells. Here, we use a qPCR-based approach to investigate Rho GTPase expression in myeloid cells.We found that the mRNAs encoding Cdc42, RhoQ, Rac1, Rac2, RhoA and RhoC are the most abundant. In addition, RhoG, RhoB, RhoF and RhoV are expressed at low levels or only in specific cell types. More differentiated cells along the monocyte-lineage display lower levels of Cdc42 and RhoV, while RhoC mRNA is more abundant. In addition, the Rho GTPase expression profile changes during dendritic cell maturation with Rac1 being upregulated and Rac2 downregulated. Finally, GM-CSF stimulation, during macrophage and osteoclast differentiation, leads to high expression of Rac2, while M-CSF induces high levels of RhoA, showing that these cytokines induce a distinct pattern. Our data uncover cell type specific modulation of the Rho GTPase expression profile in hematopoietic stem cells and in more differentiated cells of the myeloid lineage.

GTPase activity plays a key role in the pathobiology of LRRK2.

Directory of Open Access Journals (Sweden)

Yulan Xiong

2010-04-01

Full Text Available Mutations in the leucine-rich repeat kinase 2 (LRRK2 gene are associated with late-onset, autosomal-dominant, familial Parkinson's disease (PD and also contribute to sporadic disease. The LRRK2 gene encodes a large protein with multiple domains, including functional Roc GTPase and protein kinase domains. Mutations in LRRK2 most likely cause disease through a toxic gain-of-function mechanism. The expression of human LRRK2 variants in cultured primary neurons induces toxicity that is dependent on intact GTP binding or kinase activities. However, the mechanism(s underlying LRRK2-induced neuronal toxicity is poorly understood, and the contribution of GTPase and/or kinase activity to LRRK2 pathobiology is not well defined. To explore the pathobiology of LRRK2, we have developed a model of LRRK2 cytotoxicity in the baker's yeast Saccharomyces cerevisiae. Protein domain analysis in this model reveals that expression of GTPase domain-containing fragments of human LRRK2 are toxic. LRRK2 toxicity in yeast can be modulated by altering GTPase activity and is closely associated with defects in endocytic vesicular trafficking and autophagy. These truncated LRRK2 variants induce similar toxicity in both yeast and primary neuronal models and cause similar vesicular defects in yeast as full-length LRRK2 causes in primary neurons. The toxicity induced by truncated LRRK2 variants in yeast acts through a mechanism distinct from toxicity induced by human alpha-synuclein. A genome-wide genetic screen identified modifiers of LRRK2-induced toxicity in yeast including components of vesicular trafficking pathways, which can also modulate the trafficking defects caused by expression of truncated LRRK2 variants. Our results provide insight into the basic pathobiology of LRRK2 and suggest that the GTPase domain may contribute to the toxicity of LRRK2. These findings may guide future therapeutic strategies aimed at attenuating LRRK2-mediated neurodegeneration.

Reverse engineering GTPase programming languages with reconstituted signaling networks.

Science.gov (United States)

Coyle, Scott M

2016-07-02

The Ras superfamily GTPases represent one of the most prolific signaling currencies used in Eukaryotes. With these remarkable molecules, evolution has built GTPase networks that control diverse cellular processes such as growth, morphology, motility and trafficking. (1-4) Our knowledge of the individual players that underlie the function of these networks is deep; decades of biochemical and structural data has provided a mechanistic understanding of the molecules that turn GTPases ON and OFF, as well as how those GTPase states signal by controlling the assembly of downstream effectors. However, we know less about how these different activities work together as a system to specify complex dynamic signaling outcomes. Decoding this molecular "programming language" would help us understand how different species and cell types have used the same GTPase machinery in different ways to accomplish different tasks, and would also provide new insights as to how mutations to these networks can cause disease. We recently developed a bead-based microscopy assay to watch reconstituted H-Ras signaling systems at work under arbitrary configurations of regulators and effectors. (5) Here we highlight key observations and insights from this study and propose extensions to our method to further study this and other GTPase signaling systems.

Glutaminase 2 is a novel negative regulator of small GTPase Rac1 and mediates p53 function in suppressing metastasis

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Zhang, Cen; Liu, Juan; Zhao, Yuhan; Yue, Xuetian; Zhu, Yu; Wang, Xiaolong; Wu, Hao; Blanco, Felix; Li, Shaohua; Bhanot, Gyan; Haffty, Bruce G; Hu, Wenwei; Feng, Zhaohui

2016-01-01

Glutaminase (GLS) isoenzymes GLS1 and GLS2 are key enzymes for glutamine metabolism. Interestingly, GLS1 and GLS2 display contrasting functions in tumorigenesis with elusive mechanism; GLS1 promotes tumorigenesis, whereas GLS2 exhibits a tumor-suppressive function. In this study, we found that GLS2 but not GLS1 binds to small GTPase Rac1 and inhibits its interaction with Rac1 activators guanine-nucleotide exchange factors, which in turn inhibits Rac1 to suppress cancer metastasis. This function of GLS2 is independent of GLS2 glutaminase activity. Furthermore, decreased GLS2 expression is associated with enhanced metastasis in human cancer. As a p53 target, GLS2 mediates p53’s function in metastasis suppression through inhibiting Rac1. In summary, our results reveal that GLS2 is a novel negative regulator of Rac1, and uncover a novel function and mechanism whereby GLS2 suppresses metastasis. Our results also elucidate a novel mechanism that contributes to the contrasting functions of GLS1 and GLS2 in tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.10727.001 PMID:26751560

Identification of the GTPase superfamily in Mycoplasma synoviae and Mycoplasma hyopneumoniae

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Clayton Luiz Borges

2007-01-01

Full Text Available Mycoplasmas are the smallest known prokaryotes with self-replication ability. They are obligate parasites, taking up many molecules of their hosts and acting as pathogens in men, animals, birds and plants. Mycoplasma hyopneumoniae is the infective agent of swine mycoplasmosis and Mycoplasma synoviae is responsible for subclinical upper respiratory infections that may result in airsacculitis and synovitis in chickens and turkeys. These highly infectious organisms present a worldwide distribution and are responsible for major economic problems. Proteins of the GTPase superfamily occur in all domains of life, regulating functions such as protein synthesis, cell cycle and differentiation. Despite their functional diversity, all GTPases are believed to have evolved from a single common ancestor. In this work we have identified mycoplasma GTPases by searching the complete genome databases of Mycoplasma synoviae and Mycoplasma hyopneumoniae, J (non-pathogenic and 7448 (pathogenic strains. Fifteen ORFs encoding predicted GTPases were found in M. synoviae and in the two strains of M. hyopneumoniae. Searches for conserved G domains in GTPases were performed and the sequences were classified into families. The GTPase phylogenetic analysis showed that the subfamilies were well resolved into clades. The presence of GTPases in the three strains suggests the importance of GTPases in 'minimalist' genomes.

Retrotransposition and mutation events yield Rap1 GTPases with differential signalling capacity

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Penzkofer Tobias

2010-02-01

Full Text Available Abstract Background Retrotransposition of mRNA transcripts gives occasionally rise to functional retrogenes. Through acquiring tempero-spatial expression patterns distinct from their parental genes and/or functional mutations in their coding sequences, such retrogenes may in principle reshape signalling networks. Results Here we present evidence for such a scenario, involving retrogenes of Rap1 belonging to the Ras family of small GTPases. We identified two murine and one human-specific retrogene of Rap1A and Rap1B, which encode proteins that differ by only a few amino acids from their parental Rap1 proteins. Markedly, human hRap1B-retro and mouse mRap1A-retro1 acquired mutations in the 12th and 59th amino acids, respectively, corresponding to residues mutated in constitutively active oncogenic Ras proteins. Statistical and structural analyses support a functional evolution scenario, where Rap1 isoforms of retrogenic origin are functionally distinct from their parental proteins. Indeed, all retrogene-encoded GTPases have an increased GTP/GDP binding ratio in vivo, indicating that their conformations resemble that of active GTP-bound Rap1. We furthermore demonstrate that these three Rap1 isoforms exhibit distinct affinities for the Ras-binding domain of RalGDS. Finally, when tested for their capacity to induce key cellular processes like integrin-mediated cell adhesion or cell spreading, marked differences are seen. Conclusions Together, these data lend strong support for an evolution scenario, where retrotransposition and subsequent mutation events generated species-specific Rap1 isoforms with differential signaling potential. Expression of the constitutively active human Rap1B-retro in cells like those derived from Ramos Burkitt's lymphoma and bone marrow from a patient with myelodysplastic syndrome (MDS warrants further investigation into its role in disease development.

A Case of Churg-Strauss Syndrome Associated with Antiphospholipid Antibodies

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Ferenczi, Katalin; Chang, Timothy; Camouse, Melissa; Han, Rujing; Stern, Robert; Willis, Joseph; Cooper, Kevin D.; Gilliam, Anita C.

2008-01-01

BACKGROUND Churg-Strauss syndrome (CSS) is a systemic vasculitis affecting small and medium-sized blood vessels, almost invariably affecting the lung and frequently associated with cutaneous involvement. Microvascular vaso-occlusion leading to digital gangrene is not a feature of CSS. OBSERVATIONS We report an unusual case of a patient with Churg Strauss Syndrome with antiphospholipid antibodies who developed severe digital gangrene in addition to cutaneous vasculitis. CONCLUSION The presence of antiphospholipid antibodies is not a feature usually seen in association with Churg-Strauss syndrome. While the full clinical spectrum of Churg Strauss Syndrome is still being defined, identification of additional features associated with this syndrome might help to better understand the pathogenesis of the disease and to have an impact on management and prognosis. PMID:17175066

Sevoflurane Inhalation Accelerates the Long-Term Memory Consolidation via Small GTPase Overexpression in the Hippocampus of Mice in Adolescence.

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Nakamura, Emi; Kinoshita, Hiroyuki; Feng, Guo-Gang; Hayashi, Hisaki; Satomoto, Maiko; Sato, Motohiko; Fujiwara, Yoshihiro

2016-01-01

Sevoflurane exposure impairs the long-term memory in neonates. Whether the exposure to animals in adolescence affects the memory, however, has been unclear. A small hydrolase enzyme of guanosine triphosphate (GTPase) rac1 plays a role in the F-actin dynamics related to the synaptic plasticity, as well as superoxide production via reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation. The current study was designed to examine whether sevoflurane exposure to mice in early adolescence modifies the long-term learning ability concomitantly with the changes in F-actin constitution as well as superoxide production in the hippocampus according to the levels of rac1 protein expression. Four-week-old mice were subjected to the evaluation of long-term learning ability for three days. On day one, each mouse was allowed to enter a dark chamber for five min to acclimatization. On day two, the procedure was repeated with the addition of an electric shock as soon as a mouse entered the dark chamber. All mice subsequently inhaled 2 L/min air with (Sevoflurane group) and without (Control group) 2.5% sevoflurane for three hours. On day three, each mouse was placed on the platform and retention time, which is the latency to enter the dark chamber, was examined. The brain removed after the behavior test, was used for analyses of immunofluorescence, Western immunoblotting and intracellular levels of superoxide. Sevoflurane exposure significantly prolonged retention time, indicating the enhanced long-term memory. Sevoflurane inhalation augmented F-actin constitution coexisting with the rac1 protein overexpression in the hippocampus whereas it did not alter the levels of superoxide. Sevoflurane exposure to 4-week-old mice accelerates the long-term memory concomitantly with the enhanced F-actin constitution coexisting with the small GTPase rac1 overexpression in the hippocampus. These results suggest that sevoflurane inhalation may amplify long-term memory

Hallermann-Streiff syndrome associated with small cerebellum, endocrinopathy and increased chromosomal breakage.

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Hou, J W

2003-07-01

Hallermann-Streiff syndrome (HSS) is a rare clinic entity of unknown aetiology. Further clinical and metabolic-genetic evaluations are indicated. A 2-mo-old female baby presented with ocular abnormalities and severe failure to thrive since birth. The clinical features were compatible with the diagnosis of HSS. Further imaging, metabolic and cytogenetic examinations were performed. Features characteristic of HSS were dyscephaly with mandibular and nasal cartilage hypoplasia, microphthalmia, bilateral cataracts with congenital glaucoma, natal teeth and proportionate dwarfism. Rare anomalies such as choanal atresia and small cerebellum, very low insulin-like growth factor I level, hypothyroidism, generalized organic aciduria were also noticed. An increased chromosomal breakage rate is suggestive of the existence of some DNA repair defects in HSS patients. The associated anomalies in this patient may broaden the clinical spectrum of HSS. Underlying conditions of organic aciduria, growth factor deficiency and impaired DNA repair are likely to contribute to the progeria-like facies, congenital cataracts and growth failure.

Mesenteric vein thrombosis associated with Klinefelters syndrome--a case report.

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Murray, F E

1988-01-01

A case of mesenteric vein thrombosis presenting as gastrointestinal hemorrhage in a patient with Klinefelter's syndrome is reported, an association not previously described. The diagnosis was made preoperatively and was confirmed by angiography. The patient underwent a small bowel resection and made an uneventful recovery. A possible association between Klinefelter's syndrome and a hypercoagulable state, previously suggested elsewhere, is emphasized.

Rab27 GTPases Distribute Extracellular Nanomaps for Invasive Growth and Metastasis: Implications for Prognosis and Treatment

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Olivier De Wever

2013-05-01

Full Text Available The Rab27 family of small GTPases regulates exocytosis of distinct vesicle types including multivesicular endosomes, which results in the release of exosomes. Exosomes are nanometer-sized membrane vesicles that enclose soluble factors such as proteins and nucleic acids within a lipid bilayer and can travel toward distant tissues to influence multiple aspects of cell behavior. In our view that tumors are endocrine organs producing exosomes, Rab27 GTPases and their effector proteins are critical determinants for invasive growth and metastasis. Rab27 proteins and their effectors may serve as prognostic biomarkers or as targets for patient-tailored therapy.

PlexinA2 Forward Signaling through Rap1 GTPases Regulates Dentate Gyrus Development and Schizophrenia-like Behaviors

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Xiao-Feng Zhao

2018-01-01

Full Text Available Summary: Dentate gyrus (DG development requires specification of granule cell (GC progenitors in the hippocampal neuroepithelium, as well as their proliferation and migration into the primordial DG. We identify the Plexin family members Plxna2 and Plxna4 as important regulators of DG development. Distribution of immature GCs is regulated by Sema5A signaling through PlxnA2 and requires a functional PlxnA2 GTPase-activating protein (GAP domain and Rap1 small GTPases. In adult Plxna2−/− but not Plxna2-GAP-deficient mice, the dentate GC layer is severely malformed, neurogenesis is compromised, and mossy fibers form aberrant synaptic boutons within CA3. Behavioral studies with Plxna2−/− mice revealed deficits in associative learning, sociability, and sensorimotor gating—traits commonly observed in neuropsychiatric disorder. Remarkably, while morphological defects are minimal in Plxna2-GAP-deficient brains, defects in fear memory and sensorimotor gating persist. Since allelic variants of human PLXNA2 and RAP1 associate with schizophrenia, our studies identify a biochemical pathway important for brain development and mental health. : Zhao et al. find that Sema5A-PlexinA2 forward signaling through Rap1 GTPases is required for progenitor distribution in the developing mouse dentate gyrus. Adult Plxna2−/−, but not Plxna2-GAP-deficient, mice show defects in dentate morphology, neurogenesis, and mossy fiber connectivity. Plxna2−/− and Plxna2-GAP mice exhibit behavioral defects suggestive of neuropsychiatric illness. Keywords: PlexinA2, semaphoring, Rap1, GAP, dentate gyrus, adult neurogenesis, mossy fiber, fear memory, sensorimotor gating, schizophrenia

Churg-Strauss Syndrome associated with montelukast: Three Case Reports

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Fatih Yildiz

2014-04-01

Full Text Available Churg-Strauss syndrome (new name Eosinophilic granulomatosis and polyangiitis; asthma, fever, peripheral blood eosinophilia, eosinophilic tissue infiltration, small and medium sized arteries characterized by necrotizing granulomatous inflammation is a multisystemic disorder. Classified in ANCA associated vasculitis. The drugs such as leukotriene receptor antagonists (montelukast, zafirlukast, pranlukast, inhaled glucocorticoids, omalizumab, cocaine and clarithromycin is thought to be associated with Churg-Strauss Syndrome cases have been reported. Herein we presented a rare three CSS cases associated with montelukast. [Cukurova Med J 2014; 39(2.000: 347-352

Expression of GIMAP1, a GTPase of the immunity-associated protein family, is not up-regulated in malaria

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Carter Christine

2009-04-01

Full Text Available Abstract Background GIMAP (GTPase of the immunity-associated protein family proteins are a family of putative GTPases believed to be regulators of cell death in lymphomyeloid cells. GIMAP1 was the first reported member of this gene family, identified as a gene up-regulated at the RNA level in the spleens of mice infected with the malarial parasite, Plasmodium chabaudi. Methods A monoclonal antibody against mouse GIMAP1 was developed and was used to analyse the expression of the endogenous protein in tissues of normal mice and in defined sub-populations of cells prepared from lymphoid tissues using flow cytometry. It was also used to assess the expression of GIMAP1 protein after infection and/or immunization of mice with P. chabaudi. Real-time PCR analysis was employed to measure the expression of GIMAP1 for comparison with the protein level analysis. Results GIMAP1 protein expression was detected in all lineages of lymphocytes (T, B, NK, in F4/80+ splenic macrophages and in some lymphoid cell lines. Additional evidence is presented suggesting that the strong expression by mature B cells of GIMAP1 and other GIMAP genes and proteins seen in mice may be a species-dependent characteristic. Unexpectedly, no increase was found in the expression of GIMAP1 in P. chabaudi infected mice at either the mRNA or protein level, and this remained so despite applying a number of variations to the protocol. Conclusion The model of up-regulation of GIMAP1 in response to infection/immunization with P. chabaudi is not a robustly reproducible experimental system. The GIMAP1 protein is widely expressed in lymphoid cells, with an interesting increase in expression in the later stages of B cell development. Alternative approaches will be required to define the functional role of this GTPase in immune cells.

[Association Budd Chiari syndrome, antiphospholipid syndrome and Grave's disease].

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Mouelhi, Leila; Chaieb, Mouna; Debbeche, Radhouane; Salem, Mohamed; Sfar, Imene; Trabelsi, Sinda; Gorgi, Yosr; Najjar, Taoufik

2009-02-01

Antiphospholipid syndrome is revealed by Budd Chiari syndrome in 5% of the cases. Antiphospholipid syndrome is characterized by venous or arterial thrombosis, foetal loss and positivity of antiphospholipid antibodies, namely lupus anticoagulant, anticardiolipin antibodies and anti-beta2-glycoprotein I. Anticardiolipin antibodies was reported in auto-immune thyroid disorders, particularly in Grave's disease. Antiphospholipid syndrome associated to Grave's disease was reported in only three cases. To describe a case report of association of Grave's disease and antiphospholipid syndrome. We report the first case of Grave's disease associated with antiphospholipid syndrome, revealed by Budd Chiari syndrome. Our observation is particular by the fact that it is about a patient presenting a Grave's disease associated with antiphospholipid syndrome revealed by Budd Chiari syndrome. This triple association has never been reported in literature. Although association between antiphospholipid syndrome and Grave's disease was previously described, further studies evaluating the coexistence of these two affections in the same patient would be useful.

Sequential fluctuating paraneoplastic ocular flutter-opsoclonus-myoclonus syndrome and Lambert-Eaton myasthenic syndrome in small-cell lung cancer.

LENUS (Irish Health Repository)

Simister, Robert J

2011-03-01

Paraneoplastic cerebellar degeneration may occur in association with Lambert-Eaton myasthenic syndrome (LEMS), but to our knowledge, the co-occurrence of paraneoplastic opsoclonus-myoclonus syndrome and LEMS has not been previously reported. A 67-year-old woman presented with a complex partial seizure and evolving ocular flutter, opsoclonus, myoclonus and \\'cerebellar\\' signs, all of which improved spontaneously within 6 weeks. Approximately 8 weeks after symptom onset, the patient became encephalopathic, she had a further complex partial seizure, and she became areflexic with potentiation of deep tendon reflexes. Radiological, bronchoscopic and histological investigations revealed small-cell lung cancer, and neurophysiological investigations confirmed a diagnosis of LEMS. High-titre anti-P\\/Q-type voltage-gated calcium-channel antibodies were identified in the serum, which increased as the signs of opsoclonus and myoclonus resolved. The encephalopathy and clinical features of LEMS responded dramatically to chemotherapy and radiotherapy. Spontaneous improvement of paraneoplastic opsoclonus-myoclonus syndrome may occur, and this syndrome may occur in association with LEMS. Antivoltage-gated calcium-channel antibodies are not implicated in the pathogenesis of paraneoplastic opsoclonus-myoclonus syndrome.

Neurotrophin Promotes Neurite Outgrowth by Inhibiting Rif GTPase Activation Downstream of MAPKs and PI3K Signaling.

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Tian, Xiaoxia; Yan, Huijuan; Li, Jiayi; Wu, Shuang; Wang, Junyu; Fan, Lifei

2017-01-13

Members of the well-known semaphorin family of proteins can induce both repulsive and attractive signaling in neural network formation and their cytoskeletal effects are mediated in part by small guanosine 5'-triphosphatase (GTPases). The aim of this study was to investigate the cellular role of Rif GTPase in the neurotrophin-induced neurite outgrowth. By using PC12 cells which are known to cease dividing and begin to show neurite outgrowth responding to nerve growth factor (NGF), we found that semaphorin 6A was as effective as nerve growth factor at stimulating neurite outgrowth in PC12 cells, and that its neurotrophic effect was transmitted through signaling by mitogen-activated protein kinases (MAPKs) and phosphatidylinositol-3-kinase (PI3K). We further found that neurotrophin-induced neurite formation in PC12 cells could be partially mediated by inhibition of Rif GTPase activity downstream of MAPKs and PI3K signaling. In conclusion, we newly identified Rif as a regulator of the cytoskeletal rearrangement mediated by semaphorins.

Increased Contractile Response to Noradrenaline Induced By Factors Associated with the Metabolic Syndrome in Cultured Small Mesenteric Arteries

DEFF Research Database (Denmark)

Blædel, Martin; Sams, Anette; Boonen, Harrie C M

2016-01-01

UNLABELLED: This study investigated the effect of the metabolic syndrome associated risk factors hyperglycemia (glucose [Glc]), hyperinsulinemia (insulin [Ins]) and low-grade inflammation (tumor necrosis factor α [TNFα]) on the vasomotor responses of resistance arteries. Isolated small mesenteric...... arteries from 3-month-old Sprague-Dawley rats, were suspended for 21-23 h in tissue cultures containing either elevated Glc (30 mmol/l), Ins (100 nmol/l), TNFα (100 ng/ml) or combinations thereof. After incubation, the vascular response to noradrenaline (NA), phenylephrine, isoprenaline and NA...... in vascular tone....

Implications of Rho GTPase signaling in glioma cell invasion and tumor progression

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Shannon Patricia Fortin Ensign

2013-10-01

Full Text Available Glioblastoma (GB is the most malignant of primary adult brain tumors, characterized by a highly locally-invasive cell population, as well as abundant proliferative cells, neoangiogenesis, and necrosis. Clinical intervention with chemotherapy or radiation may either promote or establish an environment for manifestation of invasive behavior. Understanding the molecular drivers of invasion in the context of glioma progression may be insightful in directing new treatments for patients with GB. Here, we review current knowledge on Rho family GTPases, their aberrant regulation in GB, and their effect on GB cell invasion and tumor progression. Rho GTPases are modulators of cell migration through effects on actin cytoskeleton rearrangement; in non-neoplastic tissue, expression and activation of Rho GTPases are normally under tight regulation. In GB, Rho GTPases are deregulated, often via hyperactivity or overexpression of their activators, Rho GEFs. Downstream effectors of Rho GTPases have been shown to promote invasiveness and, importantly, glioma cell survival. The study of aberrant Rho GTPase signaling in GB is thus an important investigation of cell invasion as well as treatment resistance and disease progression.

The Tip of the Four N-Terminal α-Helices of Clostridium sordellii Lethal Toxin Contains the Interaction Site with Membrane Phosphatidylserine Facilitating Small GTPases Glucosylation

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Carolina Varela Chavez

2016-03-01

Full Text Available Clostridium sordellii lethal toxin (TcsL is a powerful virulence factor responsible for severe toxic shock in man and animals. TcsL belongs to the large clostridial glucosylating toxin (LCGT family which inactivates small GTPases by glucosylation with uridine-diphosphate (UDP-glucose as a cofactor. Notably, TcsL modifies Rac and Ras GTPases, leading to drastic alteration of the actin cytoskeleton and cell viability. TcsL enters cells via receptor-mediated endocytosis and delivers the N-terminal glucosylating domain (TcsL-cat into the cytosol. TcsL-cat was found to preferentially bind to phosphatidylserine (PS-containing membranes and to increase the glucosylation of Rac anchored to the lipid membrane. We have previously reported that the N-terminal four helical bundle structure (1–93 domain recognizes a broad range of lipids, but that TcsL-cat specifically binds to PS and phosphatidic acid. Here, we show using mutagenesis that the PS binding site is localized on the tip of the four-helix bundle which is rich in positively-charged amino acids. Residues Y14, V15, F17, and R18 on loop 1, between helices 1 and 2, in coordination with R68 from loop 3, between helices 3 and 4, form a pocket which accommodates L-serine. The functional PS-binding site is required for TcsL-cat binding to the plasma membrane and subsequent cytotoxicity. TcsL-cat binding to PS facilitates a high enzymatic activity towards membrane-anchored Ras by about three orders of magnitude as compared to Ras in solution. The PS-binding site is conserved in LCGTs, which likely retain a common mechanism of binding to the membrane for their full activity towards membrane-bound GTPases.

Guanine nucleotide exchange factor αPIX leads to activation of the Rac 1 GTPase/glycogen phosphorylase pathway in interleukin (IL)-2-stimulated T cells

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Llavero, Francisco; Urzelai, Bakarne; Osinalde, Nerea

2015-01-01

Recently, we have reported that the active form of Rac 1 GTPase binds to the glycogen phosphorylase muscle isoform (PYGM) and modulates its enzymatic activity leading to T cell proliferation. In the lymphoid system, Rac 1 and in general other small GTPases of the Rho family participate...... in the signaling cascades that are activated after engagement of the T cell antigen receptor. However, little is known about the IL-2-dependent Rac 1 activator molecules. For the first time, a signaling pathway leading to the activation of Rac 1/PYGM in response to IL-2-stimulated T cell proliferation is described....... More specifically, αPIX, a known guanine nucleotide exchange factor for the small GTPases of the Rho family, preferentially Rac 1, mediates PYGM activation in Kit 225 T cells stimulated with IL-2. Using directed mutagenesis, phosphorylation of αPIX Rho-GEF serines 225 and 488 is required for activation...

In situ detection of the activation of Rac1 and RalA small GTPases in mouse adipocytes by immunofluorescent microscopy following in vivo and ex vivo insulin stimulation.

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Takenaka, Nobuyuki; Nihata, Yuma; Ueda, Sho; Satoh, Takaya

2017-11-01

Rac1 has been implicated in insulin-dependent glucose uptake by mechanisms involving plasma membrane translocation of the glucose transporter GLUT4 in skeletal muscle. Although the uptake of glucose is also stimulated by insulin in adipose tissue, the role for Rac1 in adipocyte insulin signaling remains controversial. As a step to reveal the role for Rac1 in adipocytes, we aimed to establish immunofluorescent microscopy to detect the intracellular distribution of activated Rac1. The epitope-tagged Rac1-binding domain of a Rac1-specific target was utilized as a probe that specifically recognizes the activated form of Rac1. Rac1 activation in response to ex vivo and in vivo insulin stimulations in primary adipocyte culture and mouse white adipose tissue, respectively, was successfully observed by immunofluorescent microscopy. These Rac1 activations were mediated by phosphoinositide 3-kinase. Another small GTPase RalA has also been implicated in insulin-stimulated glucose uptake in skeletal muscle and adipose tissue. Similarly to Rac1, immunofluorescent microscopy using an activated RalA-specific polypeptide probe allowed us to detect intracellular distribution of insulin-activated RalA in adipocytes. These novel approaches to visualize the activation status of small GTPases in adipocytes will largely contribute to the understanding of signal transduction mechanisms particularly for insulin action. Copyright © 2017 Elsevier Inc. All rights reserved.

Haematuria in association with Lynch syndrome

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Marwan Ma'ayeh

2012-04-01

Full Text Available A 40-year-old Caucasian male presented to the Emergency Department complaining of intermittent painless frank haematuria. Past medical history was significant for Hereditary Non-Polyposis Colon Cancer (HNPCC and a prophylactic total colectomy. Computed tomography urogram showed thickening in the posterior wall of the bladder. Cystoscopy showed a small bladder mass. Histology showed a papillary urothelial neoplasm of low malignant potential. HNPCC, also known as Lynch Syndrome, is an autosomal dominant disorder responsible for 3-5% of colorectal cancers. There are certain cancers known to be associated with HNPCC; colorectal cancer, endometrial, ovarian, stomach, pancreas, biliary tract, small bowel, brain, renal pelvic and ureteric tumours, sebaceous gland adenomas and keratocanthomas. An association with bladder tumours is not well established.

The small Rho GTPase Rac1 controls normal human dermal fibroblasts proliferation with phosphorylation of the oncoprotein c-myc

International Nuclear Information System (INIS)

Nikolova, Ekaterina; Mitev, Vanio; Zhelev, Nikolai; Deroanne, Christophe F.; Poumay, Yves

2007-01-01

Proliferation of dermal fibroblasts is crucial for the maintenance of skin. The small Rho GTPase, Rac1, has been identified as a key transducer of proliferative signals in various cell types, but in normal human dermal fibroblasts its significance to cell growth control has not been studied. In this study, we applied the method of RNA interference to suppress endogenous Rac1 expression and examined the consequences on human skin fibroblasts. Rac1 knock-down resulted in inhibition of DNA synthesis. This effect was not mediated by inhibition of the central transducer of proliferative stimuli, ERK1/2 or by activation of the pro-apoptotic p38. Rather, as a consequence of the suppressed Rac1 expression we observed a significant decrease in phosphorylation of c-myc, revealing for the first time that in human fibroblasts Rac1 exerts control on proliferation through c-myc phosphorylation. Thus Rac1 activates proliferation of normal fibroblasts through stimulation of c-myc phosphorylation without affecting ERK1/2 activity

A heterozygous mutation in RPGR associated with X-linked retinitis pigmentosa in a patient with Turner syndrome mosaicism (45,X/46,XX).

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Zhou, Qi; Yao, Fengxia; Wang, Feng; Li, Hui; Chen, Rui; Sui, Ruifang

2018-01-01

Turner syndrome with retinitis pigmentosa (RP) is rare, with only three cases reported based on clinical examination alone. We summarized the 4-year follow-up and molecular findings in a 28-year-old patient with Turner syndrome and the typical features of short stature and neck webbing, who also had X-linked RP. Her main complaints were night blindness and progressive loss of vision since the age of 9 years. Ophthalmologic examination, optical coherent tomographic imaging, and visual electrophysiology tests showed classic manifestations of RP. The karyotype of peripheral blood showed mosaicism (45,X [72%]/46,XX[28%]). A novel heterozygous frameshift mutation (c.2403_2406delAGAG, p.T801fsX812) in the RP GTPase regulator (RPGR) gene was detected using next generation sequencing and validated by Sanger sequencing. We believe that this is the first report of X-linked RP in a patient with Turner syndrome associated with mosaicism, and an RPGR heterozygous mutation. We hypothesize that X-linked RP in this woman is not related to Turner syndrome, but may be a manifestation of the lack of a normal paternal X chromosome with intact but mutated RPGR. © 2017 Wiley Periodicals, Inc.

Characterization of a Rab11-like GTPase, EhRab11, of Entamoeba histolytica.

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McGugan, Glen C; Temesvari, Lesly A

2003-07-01

The Entamoeba histolytica Rab11 family of small molecular weight GTPases consists of three members, EhRab11, EhRab11B, and EhRab11C. The functions of these Rabs in Entamoeba have not been determined. Therefore, as an approach to elucidate the role of the Rab11 family of GTPases in Entamoeba, immunofluorescence microscopy was undertaken to define the subcellular localization of one member of this family, EhRab11. Under conditions of growth, EhRab11 displayed a punctate pattern in the cytoplasm of trophozoites. EhRab11 did not colocalize with markers for the Golgi apparatus, endoplasmic reticulum, pinosomes, phagosomes, or compartments formed by receptor-mediated endocytosis, suggesting that this Rab may not play a role in vesicle trafficking between these organelles. Under conditions of iron and serum starvation, EhRab11 was translocated to the periphery of the cell. The altered cellular localization was accompanied by multinucleation of the cells as well as the acquisition of detergent resistance by the cells, features that are characteristic of Entamoeba cysts. The translocation of EhRab11 to the periphery of the cell during iron and serum starvation was specific as the subcellular localizations of two other Rab GTPases, EhRab7 and EhRabA, were not altered under the same conditions. In addition, the formation of multinucleated cells by inhibition of cytokinesis was not sufficient to induce the translocation of EhRab11 to the cell periphery. Taken together, the data suggest that iron and serum starvation may induce encystation in E. histolytica and that EhRab11 may play a role in this process. Moreover, these studies are the first to describe a putative role for a Rab GTPase in encystation in Entamoeba sp.

Chlamydia abortus YhbZ, a truncated Obg family GTPase, associates with the Escherichia coli large ribosomal subunit.

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Polkinghorne, Adam; Vaughan, Lloyd

2011-01-01

The stringent stress response is vital for bacterial survival under adverse environmental conditions. Obligate intracellular Chlamydia lack key stringent response proteins, but nevertheless can interrupt the cell cycle and enter stasis or persistence upon amino acid starvation. A possible key protein retained is YhbZ, a homologue of the ObgE guanosine triphosphatase (GTPase) superfamily connecting the stringent stress response to ribosome maturation. Curiously, chlamydial YhbZ lacks the ObgE C-terminal domain thought to be essential for binding the large ribosomal subunit. We expressed recombinant Chlamydia abortus YhbZ and showed it to be a functional GTPase, with similar activity to other Obg GTPase family members. As Chlamydia are resistant to genetic manipulation, we performed heterologous expression and gradient centrifugation experiments in Escherichia coli and found that, despite the missing C-terminal domain, C. abortus YhbZ co-fractionates with the E. coli 50S large ribosomal subunit. In addition, overexpression of chlamydial YhbZ in E. coli leads to growth defects and elongation, as reported for other Obg members. YhbZ did not complement an E. coli obgE temperature-sensitive mutant, indicating the C-terminal acidic domain may have an additional role. This data supports a role for YhbZ linking the chlamydial stress response to ribosome function and cellular growth. Copyright © 2010 Elsevier Ltd. All rights reserved.

Regulation of cerebral cortex development by Rho GTPases: insights from in vivo studies

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Roberta eAzzarelli

2015-01-01

Full Text Available The cerebral cortex is the site of higher human cognitive and motor functions. Histologically, it is organized into six horizontal layers, each containing unique populations of molecularly and functionally distinct excitatory projection neurons and inhibitory interneurons. The stereotyped cellular distribution of cortical neurons is crucial for the formation of functional neural circuits and it is predominantly established during embryonic development. Cortical neuron development is a multiphasic process characterized by sequential steps of neural progenitor proliferation, cell cycle exit, neuroblast migration and neuronal differentiation. This series of events requires an extensive and dynamic remodeling of the cell cytoskeleton at each step of the process. As major regulators of the cytoskeleton, the family of small Rho GTPases has been shown to play essential functions in cerebral cortex development. Here we review in vivo findings that support the contribution of Rho GTPases to cortical projection neuron development and we address their involvement in the etiology of cerebral cortex malformations.

Rapunzel Syndrome: a rare cause of acute small bowel obstruction ...

African Journals Online (AJOL)

The Rapunzel syndrome is a very rare condition where trichobezoar has extended up to the small bowel. Here we are reporting a rare case of Rapunzel syndrome in an adolescent girl with history of trichophagia who presented with small bowel obstruction. Patient underwent exploratory laparotomy and bezoar was ...

Interaction between the p21ras GTPase activating protein and the insulin receptor

NARCIS (Netherlands)

Pronk, G.J.; Medema, R.H.; Burgering, B.M.T.; Clark, R.; McCormick, F.; Bos, J.L.

1992-01-01

We investigated the involvement of the p21ras-GTPase activating protein (GAP) in insulin-induced signal transduction. In cells overexpressing the insulin receptor, we did not observe association between GAP and the insulin receptor after insulin treatment nor the phosphorylation of GAP on tyrosine

Dual paraneoplastic syndromes: small cell lung carcinoma-related oncogenic osteomalacia, and syndrome of inappropriate antidiuretic hormone secretion: report of a case and review of the literature.

Science.gov (United States)

Tantisattamo, Ekamol; Ng, Roland C K

2011-07-01

Acquired isolated renal phosphate wasting associated with a tumor, known as oncogenic osteomalacia or tumor-induced osteomalacia, is a rare paraneoplastic syndrome caused by overproduction of fibroblast growth factor 23. Oncogenic osteomalacia is usually associated with benign mesenchymal tumors. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), on the other hand, is a common paraneoplastic syndrome caused by small cell carcinoma (SCC). Concomitant oncogenic osteomalacia and SIADH associated with SCC is very rare with only 4 other cases reported in the literature. The authors report a case of small cell lung cancer (SCLC)-related renal wasting hypophosphatemia and concurrent SIADH, and review the literature reporting 9 other cases of SCC associated with oncogenic osteomalacia. Almost half of reported cases of renal phosphate wasting associated with SCC concomitantly presented with SIADH. These cases had initial serum phosphorus level lower and survival periods shorter than those without SIADH. This rare combination of a dual paraneoplastic syndrome and low serum phosphorus may be a poor prognostic sign. In addition, both renal phosphate wasting and SIADH usually occur in a short period of time before identification of SCC. Therefore, renal wasting hypophosphatemia with concomitant SIADH/hyponatremia should prompt a search for SCC rather than a benign mesenchymal tumor.

The GTPase Rab37 Participates in the Control of Insulin Exocytosis.

Directory of Open Access Journals (Sweden)

Sanda Ljubicic

Full Text Available Rab37 belongs to a subclass of Rab GTPases regulating exocytosis, including also Rab3a and Rab27a. Proteomic studies indicate that Rab37 is associated with insulin-containing large dense core granules of pancreatic β-cells. In agreement with these observations, we detected Rab37 in extracts of β-cell lines and human pancreatic islets and confirmed by confocal microscopy the localization of the GTPase on insulin-containing secretory granules. We found that, as is the case for Rab3a and Rab27a, reduction of Rab37 levels by RNA interference leads to impairment in glucose-induced insulin secretion and to a decrease in the number of granules in close apposition to the plasma membrane. Pull-down experiments revealed that, despite similar functional effects, Rab37 does not interact with known Rab3a or Rab27a effectors and is likely to operate through a different mechanism. Exposure of insulin-secreting cells to proinflammatory cytokines, fatty acids or oxidized low-density lipoproteins, mimicking physiopathological conditions that favor the development of diabetes, resulted in a decrease in Rab37 expression. Our data identify Rab37 as an additional component of the machinery governing exocytosis of β-cells and suggest that impaired expression of this GTPase may contribute to defective insulin release in pre-diabetic and diabetic conditions.

Small bowel involvement documented by capsule endoscopy in Churg-Strauss syndrome.

Science.gov (United States)

Beye, Birane; Lesur, Gilles; Claude, Pierre; Martzolf, Lionel; Kieffer, Pierre; Sondag, Daniel

2015-01-01

Churg-Strauss syndrome is a small and medium vessel vasculitis and is also known as allergic granulomatous angiitis. Gastrointestinal involvement is common in patients with Churg-Strauss syndrome (20-50%). The most common symptoms are abdominal pain, diarrhoea and occasionally gastrointestinal bleeding and perforation. We present a case of Churg-Strauss syndrome with small bowel lesions documented by video capsule endoscopy.

Characterization of mitochondrion-targeted GTPases in Plasmodium falciparum.

Science.gov (United States)

Gupta, Kirti; Gupta, Ankit; Haider, Afreen; Habib, Saman

2018-04-12

Ribosome assembly is critical for translation and regulating the response to cellular events and requires a complex interplay of ribosomal RNA and proteins with assembly factors. We investigated putative participants in the biogenesis of the reduced organellar ribosomes of Plasmodium falciparum and identified homologues of two assembly GTPases - EngA and Obg that were found in mitochondria. Both are indispensable in bacteria and P. berghei EngA is among the 'essential' parasite blood stage proteins identified recently. PfEngA and PfObg1 interacted with parasite mitoribosomes in vivo. GTP stimulated PfEngA interaction with the 50S subunit of Escherichia coli surrogate ribosomes. Although PfObg1-ribosome interaction was independent of nucleotide binding, GTP hydrolysis by PfObg1 was enhanced upon ribosomal association. An additional function for PfObg1 in mitochondrial DNA transactions was suggested by its specific interaction with the parasite mitochondrial genome in vivo. Deletion analysis revealed that the positively-charged OBG (spoOB-associated GTP-binding protein) domain mediates DNA-binding. A role for PfEngA in mitochondrial genotoxic stress response was indicated by its over-expression upon methyl methanesulfonate-induced DNA damage. PfEngA had lower sensitivity to an E. coli EngA inhibitor suggesting differences with bacterial counterparts. Our results show the involvement of two important GTPases in P. falciparum mitochondrial function, with the first confirmed localization of an EngA homologue in eukaryotic mitochondria.

Gallic acid inhibits gastric cancer cells metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-κB activity

Energy Technology Data Exchange (ETDEWEB)

Ho, Hsieh-Hsun [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Chang, Chi-Sen [Department of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Division of Gastroenterology, Taichung Veterans General Hospital, Taichung 402, Taiwan (China); Ho, Wei-Chi [Division of Gastroenterology, Jen-Ai Hospital, Taichung 402, Taiwan (China); Liao, Sheng-You [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Lin, Wea-Lung [Department of Pathology, School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Pathology, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China); Wang, Chau-Jong, E-mail: wcj@csmu.edu.tw [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung 402, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China)

2013-01-01

Our previous study demonstrated the therapeutic potential of gallic acid (GA) for controlling tumor metastasis through its inhibitory effect on the motility of AGS cells. A noteworthy finding in our previous experiment was increased RhoB expression in GA-treated cells. The aim of this study was to evaluate the role of RhoB expression on the inhibitory effects of GA on AGS cells. By applying the transfection of RhoB siRNA into AGS cells and an animal model, we tested the effect of GA on inhibition of tumor growth and RhoB expression. The results confirmed that RhoB-siRNA transfection induced GA to inhibit AGS cells’ invasive growth involving blocking the AKT/small GTPase signals pathway and inhibition of NF-κB activity. Finally, we evaluated the effect of GA on AGS cell metastasis by colonization of tumor cells in nude mice. It showed GA inhibited tumor cells growth via the expression of RhoB. These data support the inhibitory effect of GA which was shown to inhibit gastric cancer cell metastasis and invasive growth via increased expression of RhoB, downregulation of AKT/small GTPase signals and inhibition of NF-κB activity. Thus, GA might be a potential agent in treating gastric cancer. Highlights: ► GA could downregulate AKT signal via increased expression of RhoB. ► GA inhibits metastasis in vitro in gastric carcinoma. ► GA inhibits tumor growth in nude mice model.

The interdependence of the Rho GTPases and apicobasal cell polarity.

Science.gov (United States)

Mack, Natalie Ann; Georgiou, Marios

2014-01-01

Signaling via the Rho GTPases provides crucial regulation of numerous cell polarization events, including apicobasal (AB) polarity, polarized cell migration, polarized cell division and neuronal polarity. Here we review the relationships between the Rho family GTPases and epithelial AB polarization events, focusing on the 3 best-characterized members: Rho, Rac and Cdc42. We discuss a multitude of processes that are important for AB polarization, including lumen formation, apical membrane specification, cell-cell junction assembly and maintenance, as well as tissue polarity. Our discussions aim to highlight the immensely complex regulatory mechanisms that encompass Rho GTPase signaling during AB polarization. More specifically, in this review we discuss several emerging common themes, that include: 1) the need for Rho GTPase activities to be carefully balanced in both a spatial and temporal manner through a multitude of mechanisms; 2) the existence of signaling feedback loops and crosstalk to create robust cellular responses; and 3) the frequent multifunctionality that exists among AB polarity regulators. Regarding this latter theme, we provide further discussion of the potential plasticity of the cell polarity machinery and as a result the possible implications for human disease.

Purification, crystallization and X-ray diffraction analysis of human dynamin-related protein 1 GTPase-GED fusion protein

International Nuclear Information System (INIS)

Klinglmayr, Eva; Wenger, Julia; Mayr, Sandra; Bossy-Wetzel, Ella; Puehringer, Sandra

2012-01-01

The crystallization and initial diffraction analysis of human Drp1 GTPase-GED fusion protein are reported. The mechano-enzyme dynamin-related protein 1 plays an important role in mitochondrial fission and is implicated in cell physiology. Dysregulation of Drp1 is associated with abnormal mitochondrial dynamics and neuronal damage. Drp1 shares structural and functional similarities with dynamin 1 with respect to domain organization, ability to self-assemble into spiral-like oligomers and GTP-cycle-dependent membrane scission. Structural studies of human dynamin-1 have greatly improved the understanding of this prototypical member of the dynamin superfamily. However, high-resolution structural information for full-length human Drp1 covering the GTPase domain, the middle domain and the GTPase effector domain (GED) is still lacking. In order to obtain mechanistic insights into the catalytic activity, a nucleotide-free GTPase-GED fusion protein of human Drp1 was expressed, purified and crystallized. Initial X-ray diffraction experiments yielded data to 2.67 Å resolution. The hexagonal-shaped crystals belonged to space group P2 1 2 1 2, with unit-cell parameters a = 53.59, b = 151.65, c = 43.53 Å, one molecule per asymmetric unit and a solvent content of 42%. Expression of selenomethionine-labelled protein is currently in progress. Here, the expression, purification, crystallization and X-ray diffraction analysis of the Drp1 GTPase-GED fusion protein are presented, which form a basis for more detailed structural and biophysical analysis

The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast

Energy Technology Data Exchange (ETDEWEB)

Tsukamoto, Yuta; Katayama, Chisako [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Shinohara, Miki; Shinohara, Akira [Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871 (Japan); Maekawa, Shohei [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Miyamoto, Masaaki, E-mail: miya@kobe-u.ac.jp [Graduate School of Science, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan); Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho Nada, Kobe 657-8501 (Japan)

2013-11-29

Highlights: •Multiple functions of Rab5 GTPase in fission yeast were found. •Roles of Rab5 in fission yeast were discussed. •Relation between Rab5 and actin cytoskeleton were discussed. -- Abstract: Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our data strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions.

The small GTPase Rab5 homologue Ypt5 regulates cell morphology, sexual development, ion-stress response and vacuolar formation in fission yeast

International Nuclear Information System (INIS)

Tsukamoto, Yuta; Katayama, Chisako; Shinohara, Miki; Shinohara, Akira; Maekawa, Shohei; Miyamoto, Masaaki

2013-01-01

Highlights: •Multiple functions of Rab5 GTPase in fission yeast were found. •Roles of Rab5 in fission yeast were discussed. •Relation between Rab5 and actin cytoskeleton were discussed. -- Abstract: Inner-membrane transport is critical to cell function. Rab family GTPases play an important role in vesicle transport. In mammalian cells, Rab5 is reported to be involved in the regulation of endosome formation, phagocytosis and chromosome alignment. Here, we examined the role of the fission yeast Rab5 homologue Ypt5 using a point mutant allele. Mutant cells displayed abnormal cell morphology, mating, sporulation, endocytosis, vacuole fusion and responses to ion stress. Our data strongly suggest that fission yeast Rab5 is involved in the regulation of various types of cellular functions

Small-bowel cancer in Lynch syndrome : is it time for surveillance?

NARCIS (Netherlands)

Koornstra, Jan J.; Kleibeuker, Jan H.; Vasen, Hans F. A.

Small-bowel cancer is part of the tumour spectrum of Lynch syndrome. Lynch syndrome, or hereditary non-polyposis colorectal cancer, is caused by germline mutations in one of the mismatch repair genes. Mutation carriers have an estimated lifetime risk for the development of small-bowel cancer of

Coupling mechanical tension and GTPase signaling to generate cell and tissue dynamics

Science.gov (United States)

Zmurchok, Cole; Bhaskar, Dhananjay; Edelstein-Keshet, Leah

2018-07-01

Regulators of the actin cytoskeleton such Rho GTPases can modulate forces developed in cells by promoting actomyosin contraction. At the same time, through mechanosensing, tension is known to affect the activity of Rho GTPases. What happens when these effects act in concert? Using a minimal model (1 GTPase coupled to a Kelvin–Voigt element), we show that two-way feedback between signaling (‘RhoA’) and mechanical tension (stretching) leads to a spectrum of cell behaviors, including contracted or relaxed cells, and cells that oscillate between these extremes. When such ‘model cells’ are connected to one another in a row or in a 2D sheet (‘epithelium’), we observe waves of contraction/relaxation and GTPase activity sweeping through the tissue. The minimal model lends itself to full bifurcation analysis, and suggests a mechanism that explains behavior observed in the context of development and collective cell behavior.

Plant Rho-type (Rop) GTPase-dependent activation of receptor-like cytoplasmic kinases in vitro.

Science.gov (United States)

Dorjgotov, Dulguun; Jurca, Manuela E; Fodor-Dunai, Csilla; Szucs, Attila; Otvös, Krisztina; Klement, Eva; Bíró, Judit; Fehér, Attila

2009-04-02

Plants have evolved distinct mechanisms to link Rho-type (Rop) GTPases to downstream signaling pathways as compared to other eukaryotes. Here, experimental data are provided that members of the Medicago, as well as Arabidopsis, receptor-like cytoplasmic kinase family (RLCK Class VI) were strongly and specifically activated by GTP-bound Rop GTPases in vitro. Deletion analysis indicated that the residues implicated in the interaction might be distributed on various parts of the kinases. Using a chimaeric Rop GTPase protein, the importance of the Rho-insert region in kinase activation could also be verified. These data strengthen the possibility that RLCKs may serve as Rop GTPase effectors in planta.

Two Components of Aversive Memory in Drosophila, Anesthesia-Sensitive and Anesthesia-Resistant Memory, Require Distinct Domains Within the Rgk1 Small GTPase.

Science.gov (United States)

Murakami, Satoshi; Minami-Ohtsubo, Maki; Nakato, Ryuichiro; Shirahige, Katsuhiko; Tabata, Tetsuya

2017-05-31

Multiple components have been identified that exhibit different stabilities for aversive olfactory memory in Drosophila These components have been defined by behavioral and genetic studies and genes specifically required for a specific component have also been identified. Intermediate-term memory generated after single cycle conditioning is divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We determined that the ASM and ARM pathways converged on the Rgk1 small GTPase and that the N-terminal domain-deleted Rgk1 was sufficient for ASM formation, whereas the full-length form was required for ARM formation. Rgk1 is specifically accumulated at the synaptic site of the Kenyon cells (KCs), the intrinsic neurons of the mushroom bodies, which play a pivotal role in olfactory memory formation. A higher than normal Rgk1 level enhanced memory retention, which is consistent with the result that Rgk1 suppressed Rac-dependent memory decay; these findings suggest that rgk1 bolsters ASM via the suppression of forgetting. We propose that Rgk1 plays a pivotal role in the regulation of memory stabilization by serving as a molecular node that resides at KC synapses, where the ASM and ARM pathway may interact. SIGNIFICANCE STATEMENT Memory consists of multiple components. Drosophila olfactory memory serves as a fundamental model with which to investigate the mechanisms that underlie memory formation and has provided genetic and molecular means to identify the components of memory, namely short-term, intermediate-term, and long-term memory, depending on how long the memory lasts. Intermediate memory is further divided into anesthesia-sensitive memory (ASM) and anesthesia-resistant memory (ARM), with the latter being more stable. We have identified a small GTPase in Drosophila , Rgk1, which plays a pivotal role in the regulation of olfactory memory stability. Rgk1 is required for both ASM and ARM. Moreover, N

Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

Energy Technology Data Exchange (ETDEWEB)

Wang, Xiang; Zhao, Fang [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Lv, Zhong-ming; Shi, Wei-qin [Jiangsu Provincial Center for Disease Control and Prevention, Nanjing (China); Zhang, Lu-yong, E-mail: lyzhang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing (China); State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Yan, Ming, E-mail: brookming@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)

2016-11-01

Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

International Nuclear Information System (INIS)

Wang, Xiang; Zhao, Fang; Lv, Zhong-ming; Shi, Wei-qin; Zhang, Lu-yong; Yan, Ming

2016-01-01

Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

Prevalence Of Burnout Syndrome And Factors Associated With University Teachers

Directory of Open Access Journals (Sweden)

Ericka Silva Holmes

2017-03-01

Full Text Available This is a systematic review that sought to identify the prevalence and factors associated with Burnout Syndrome in university teachers. The collection of the studies was done through descriptors in databases, which resulted in the selection of 8 articles. The prevalence for burnout had a small variation, but presented worrying values. The most frequent associated factors were: work overload, accumulation of activities beyond teaching, high employment ties, devaluation of the work performed and low remuneration. Burnout is still little recognized and studied in the category of university teachers, and it is difficult to identify an exact prevalence for this category. However, the associated factors are well defined and should be considered as a starting point for the prevention of the syndrome.

Activation of the Small GTPase Rap1 Inhibits Choroidal Neovascularization by Regulating Cell Junctions and ROS Generation in Rats.

Science.gov (United States)

Li, Jiajia; Zhang, Rong; Wang, Caixia; Wang, Xin; Xu, Man; Ma, Jingxue; Shang, Qingli

2018-03-30

Choroidal neovascularization (CNV) is a common vision-threatening complication associated with many  fundus diseases. The retinal pigment epithelial (RPE) cell junction barrier has critical functions in preventing CNV, and oxidative stress can cause compromise of barrier integrity and induce angiogenesis. Rap1, a small guanosine triphosphatase (GTPase), is involved in regulating endothelial and epithelial cell junctions. In this work, we explored the function and mechanism of Rap1 in CNV in vivo. A laser-induced rat CNV model was developed. Rap1 was activated through intravitreal injection of the Rap1 activator 8CPT-2'-O-Me-cAMP (8CPT). At 14 days after laser treatment, CNV size in RPE/choroid flat mounts was measured by fluorescein isothiocyanate-dextran staining. Expression of vascular endothelial growth factor (VEGF) and cell junction proteins in RPE/choroid tissues were analyzed by western blots and quantitative real-time PCR assays. Reactive oxygen species (ROS) in RPE cells were detectedbydichloro-dihydro-fluorescein diacetate assays. The antioxidant apocynin was intraperitoneally injected into rats. Activating Rap1 by 8CPT significantly reduced CNV size and VEGF expression in the rat CNV model. Rap1 activation enhanced protein and mRNA levels of ZO-1 and occludin, two tight junction proteins in the RPE barrier. In addition, reducing ROS generation by injection of apocynin, a NADPH oxidase inhibitor, inhibited CNV formation. Rap1 activation reduced ROS generation and expression of NADPH oxidase 4. Rap1 activation inhibits CNV through regulating barrier integrity and ROS generation of RPE in vivo, and selectively activating Rap1 may be a way to reduce vision loss from CNV.

Superior Vena Cava Syndrome in a Patient with Small-Cell Lung Cancer: A Case Report

OpenAIRE

Christina Brzezniak; Bryan Oronsky; Corey A. Carter; Bennett Thilagar; Scott Caroen; Karen Zeman

2017-01-01

Superior vena cava (SVC) syndrome, a potential oncologic emergency, is closely associated with malignancy and right-sided lung cancer in particular. A case of SVC syndrome presenting with facial swelling, neck distension, and enlarged veins of the upper chest, which developed over a period of 5 weeks in a 46-year-old patient on a clinical trial with small-cell lung cancer, is reported. Computed tomography scan of the chest revealed slight enlargement of a superior conglomerate mediastinal lym...

Human Mammary Epithelial Cell Transformation by Rho GTPase Through a Novel Mechanism

Science.gov (United States)

2009-08-01

87: 635-44. 18. Burbelo P, Wellstein A, Pestell RG. Altered Rho GTPase signaling pathways in breast cancer cells. Breast Cancer Res Treat 2004; 84...Burbelo P, Wellstein A, Pestell RG. Altered Rho GTPase signaling pathways in breast cancer cells. Breast Cancer Res Treat 2004;84:43–8. 19. Band V

Comprehensive behavioral analysis of mice deficient in Rapgef2 and Rapgef6, a subfamily of guanine nucleotide exchange factors for Rap small GTPases possessing the Ras/Rap-associating domain.

Science.gov (United States)

Maeta, Kazuhiro; Hattori, Satoko; Ikutomo, Junji; Edamatsu, Hironori; Bilasy, Shymaa E; Miyakawa, Tsuyoshi; Kataoka, Tohru

2018-05-10

Rapgef2 and Rapgef6 define a subfamily of guanine nucleotide exchange factors for Rap small GTPases, characterized by the possession of the Ras/Rap-associating domain. Previous genomic analyses suggested their possible involvement in the etiology of schizophrenia. We recently demonstrated the development of an ectopic cortical mass (ECM), which resembles the human subcortical band heterotopia, in the dorsal telencephalon-specific Rapgef2 conditional knockout (Rapgef2-cKO) brains. Additional knockout of Rapgef6 in Rapgef2-cKO mice resulted in gross enlargement of the ECM whereas knockout of Rapgef6 alone (Rapgef6-KO) had no discernible effect on the brain morphology. Here, we performed a battery of behavioral tests to examine the effects of Rapgef2 or Rapgef6 deficiency on higher brain functions. Rapgef2-cKO mice exhibited hyperlocomotion phenotypes. They showed decreased anxiety-like behavior in the elevated plus maze and the open-field tests as well as increased depression-like behavior in the Porsolt forced swim and tail suspension tests. They also exhibited increased sociability especially in novel environments. They showed defects in cognitive function as evidenced by reduced learning ability in the Barnes circular maze test and by impaired working memory in the T maze tests. In contrast, although Rapgef6 and Rapgef2 share similarities in biochemical roles, Rapgef6-KO mice exhibited mild behavioral abnormalities detected with a number of behavioral tests, such as hyperlocomotion phenotype in the open-field test and the social interaction test with a novel environment and working-memory defects in the T-maze test. In conclusion, although there were differences in their brain morphology and the magnitude of the behavioral abnormalities, Rapgef2-cKO mice and Rapgef6-KO mice exhibited hyperlocomotion phenotype and working-memory defect, both of which could be recognized as schizophrenia-like behavior.

Small GTPase R-Ras participates in neural tube formation in zebrafish embryonic spinal cord.

Science.gov (United States)

Ohata, Shinya; Uga, Hideko; Okamoto, Hitoshi; Katada, Toshiaki

2018-06-27

Ras related (R-Ras), a small GTPase, is involved in the maintenance of apico-basal polarity in neuroepithelial cells of the zebrafish hindbrain, axonal collapse in cultured murine hippocampal neurons, and maturation of blood vessels in adult mice. However, the role of R-Ras in neural tube formation remains unknown. Using antisense morpholino oligonucleotides (AMOs), we found that in the spinal cord of zebrafish embryos, the lumen was formed bilaterally in rras morphants, whereas it was formed at the midline in control embryos. As AMO can cause off-target effects, we generated rras mutant zebrafish lines using CRISPR/Cas9 technology. Although these rras mutant embryos did not have a bilateral lumen in the spinal cord, the following findings suggest that the phenotype is unlikely due to an off-target effect of rras AMO: 1) The rras morphant phenotype was rescued by an injection of AMO-resistant rras mRNA, and 2) a bilaterally segregated spinal cord was not observed in rras mutant embryos injected with rras AMO. The results suggest that the function of other ras family genes may be redundant in rras mutants. Previous research reported a bilaterally formed lumen in the spinal cord of zebrafish embryos with a mutation in a planar cell polarity (PCP) gene, van gogh-like 2 (vangl2). In the present study, in cultured cells, R-Ras was co-immunoprecipitated with Vangl2 but not with another PCP regulator, Pricke1. Interestingly, the interaction between R-Ras and Vangl2 was stronger in guanine-nucleotide free point mutants of R-Ras than in wild-type or constitutively active (GTP-bound) forms of R-Ras. R-Ras may regulate neural tube formation in cooperation with Vangl2 in the developing zebrafish spinal cord. Copyright © 2018 Elsevier Inc. All rights reserved.

Lynch syndrome-associated neoplasms

DEFF Research Database (Denmark)

Shia, Jinru; Holck, Susanne; Depetris, Giovanni

2013-01-01

It was a century ago that Warthin, a pathologist, first described the clinical condition now known as Lynch syndrome. One hundred years later, our understanding of this syndrome has advanced significantly. Much of the progress took place over the last 25 years and was marked by a series...... of interacting developments from the disciplines of clinical oncology, pathology, and molecular genetics, with each development serving to guide or enhance the next. The advancement of our understanding about the pathology of Lynch syndrome associated tumors exemplifies such intimate interplay among disciplines....... Today, accumulative knowledge has enabled surgical pathologists to detect tumors that are likely to be associated with Lynch syndrome, and the pathologist is playing an increasingly more important role in the care of these patients. The pathologist's ability is afforded primarily by information gained...

Rho GTPase activity modulates paramyxovirus fusion protein-mediated cell-cell fusion

International Nuclear Information System (INIS)

Schowalter, Rachel M.; Wurth, Mark A.; Aguilar, Hector C.; Lee, Benhur; Moncman, Carole L.; McCann, Richard O.; Dutch, Rebecca Ellis

2006-01-01

The paramyxovirus fusion protein (F) promotes fusion of the viral envelope with the plasma membrane of target cells as well as cell-cell fusion. The plasma membrane is closely associated with the actin cytoskeleton, but the role of actin dynamics in paramyxovirus F-mediated membrane fusion is unclear. We examined cell-cell fusion promoted by two different paramyxovirus F proteins in three cell types in the presence of constitutively active Rho family GTPases, major cellular coordinators of actin dynamics. Reporter gene and syncytia assays demonstrated that expression of either Rac1 V12 or Cdc42 V12 could increase cell-cell fusion promoted by the Hendra or SV5 glycoproteins, though the effect was dependent on the cell type expressing the viral glycoproteins. In contrast, RhoA L63 decreased cell-cell fusion promoted by Hendra glycoproteins but had little affect on SV5 F-mediated fusion. Also, data suggested that GTPase activation in the viral glycoprotein-containing cell was primarily responsible for changes in fusion. Additionally, we found that activated Cdc42 promoted nuclear rearrangement in syncytia

The Rho-family GTPase Rac1 regulates integrin localization in Drosophila immunosurveillance cells.

Directory of Open Access Journals (Sweden)

Miguel J Xavier

Full Text Available BACKGROUND: When the parasitoid wasp Leptopilina boulardi lays an egg in a Drosophila larva, phagocytic cells called plasmatocytes and specialized cells known as lamellocytes encapsulate the egg. The Drosophila β-integrin Myospheroid (Mys is necessary for lamellocytes to adhere to the cellular capsule surrounding L. boulardi eggs. Integrins are heterodimeric adhesion receptors consisting of α and β subunits, and similar to other plasma membrane receptors undergo ligand-dependent endocytosis. In mammalian cells it is known that integrin binding to the extracellular matrix induces the activation of Rac GTPases, and we have previously shown that Rac1 and Rac2 are necessary for a proper encapsulation response in Drosophila larvae. We wanted to test the possibility that Myospheroid and Rac GTPases interact during the Drosophila anti-parasitoid immune response. RESULTS: In the current study we demonstrate that Rac1 is required for the proper localization of Myospheroid to the cell periphery of haemocytes after parasitization. Interestingly, the mislocalization of Myospheroid in Rac1 mutants is rescued by hyperthermia, involving the heat shock protein Hsp83. From these results we conclude that Rac1 and Hsp83 are required for the proper localization of Mys after parasitization. SIGNIFICANCE: We show for the first time that the small GTPase Rac1 is required for Mysopheroid localization. Interestingly, the necessity of Rac1 in Mys localization was negated by hyperthermia. This presents a problem, in Drosophila we quite often raise larvae at 29°C when using the GAL4/UAS misexpression system. If hyperthermia rescues receptor endosomal recycling defects, raising larvae in hyperthermic conditions may mask potentially interesting phenotypes.

RAC1 GTP-ase signals Wnt-beta-catenin pathway mediated integrin-directed metastasis-associated tumor cell phenotypes in triple negative breast cancers.

Science.gov (United States)

De, Pradip; Carlson, Jennifer H; Jepperson, Tyler; Willis, Scooter; Leyland-Jones, Brian; Dey, Nandini

2017-01-10

The acquisition of integrin-directed metastasis-associated (ID-MA) phenotypes by Triple-Negative Breast Cancer (TNBC) cells is caused by an upregulation of the Wnt-beta-catenin pathway (WP). We reported that WP is one of the salient genetic features of TNBC. RAC-GTPases, small G-proteins which transduce signals from cell surface proteins including integrins, have been implicated in tumorigenesis and metastasis by their role in essential cellular functions like motility. The collective percentage of alteration(s) in RAC1 in ER+ve BC was lower as compared to ER-ve BC (35% vs 57%) (brca/tcga/pub2015). High expression of RAC1 was associated with poor outcome for RFS with HR=1.48 [CI: 1.15-1.9] p=0.0019 in the Hungarian ER-veBC cohort. Here we examined how WP signals are transduced via RAC1 in the context of ID-MA phenotypes in TNBC. Using pharmacological agents (sulindac sulfide), genetic tools (beta-catenin siRNA), WP modulators (Wnt-C59, XAV939), RAC1 inhibitors (NSC23766, W56) and WP stimulations (LWnt3ACM, Wnt3A recombinant) in a panel of 6-7 TNBC cell lines, we studied fibronectin-directed (1) migration, (2) matrigel invasion, (3) RAC1 and Cdc42 activation, (4) actin dynamics (confocal microscopy) and (5) podia-parameters. An attenuation of WP, which (a) decreased cellular levels of beta-catenin, as well as its nuclear active-form, (b) decreased fibronectin-induced migration, (c) decreased invasion, (d) altered actin dynamics and (e) decreased podia-parameters was successful in blocking fibronectin-mediated RAC1/Cdc42 activity. Both Wnt-antagonists and RAC1 inhibitors blocked fibronectin-induced RAC1 activation and inhibited the fibronectin-induced ID-MA phenotypes following specific WP stimulation by LWnt3ACM as well as Wnt3A recombinant protein. To test a direct involvement of RAC1-activation in WP-mediated ID-MA phenotypes, we stimulated brain-metastasis specific MDA-MB231BR cells with LWnt3ACM. LWnt3ACM-stimulated fibronectin-directed migration was blocked by

Moyamoya disease associated with asymptomatic mosaic Turner syndrome: a rare cause of hemorrhagic stroke.

Science.gov (United States)

Manjila, Sunil; Miller, Benjamin R; Rao-Frisch, Anitha; Otvos, Balint; Mitchell, Anna; Bambakidis, Nicholas C; De Georgia, Michael A

2014-01-01

Moyamoya disease is a rare cerebrovascular anomaly involving the intracranial carotid arteries that can present clinically with either ischemic or hemorrhagic disease. Moyamoya syndrome, indistinguishable from moyamoya disease at presentation, is associated with multiple clinical conditions including neurofibromatosis type 1, autoimmune disease, prior radiation therapy, Down syndrome, and Turner syndrome. We present the first reported case of an adult patient with previously unrecognized mosaic Turner syndrome with acute subarachnoid and intracerebral hemorrhage as the initial manifestation of moyamoya syndrome. A 52-year-old woman was admitted with a subarachnoid hemorrhage with associated flame-shaped intracerebral hemorrhage in the left frontal lobe. Physical examination revealed short stature, pectus excavatum, small fingers, micrognathia, and mild facial dysmorphism. Cerebral angiography showed features consistent with bilateral moyamoya disease, aberrant intrathoracic vessels, and an unruptured 4-mm right superior hypophyseal aneurysm. Genetic analysis confirmed a diagnosis of mosaic Turner syndrome. Our case report is the first documented presentation of adult moyamoya syndrome with subarachnoid and intracerebral hemorrhage as the initial presentation of mosaic Turner syndrome. It illustrates the utility of genetic evaluation in patients with cerebrovascular disease and dysmorphism. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Bowel-associated dermatosis-arthritis syndrome in an adolescent with short bowel syndrome.

Science.gov (United States)

Pereira, Ester; Estanqueiro, Paula; Almeida, Susana; Ferreira, Ricardo; Tellechea, Oscar; Salgado, Manuel

2014-09-01

Bowel-associated dermatosis-arthritis syndrome (BADAS) is a neutrophilic dermatosis, characterized by the occurrence of arthritis and skin lesions related to bowel disease with or without bowel bypass. We report an unusual case of BADAS in a 15-year-old white male with congenital aganglionosis of the colon and hypoganglionosis of the small intestine and multiple bowel surgeries in childhood complicated by short bowel syndrome. He presented with recurrent peripheral polyarthritis, tenosynovitis, and painful erythematous subcutaneous nodules located on the dorsolateral regions of the legs and on the dorsa of the feet. Histological examination disclosed a neutrophilic dermatosis confirming the diagnosis of BADAS.Although an uncommon disease, especially at pediatric age, it is important to evoke the diagnosis of BADAS in children and adolescents with bowel disease, because treatment options and prognosis are distinct from other rheumatologic conditions.

Stagnant loop syndrome resulting from small-bowel irradiation injury and intestinal by-pass

International Nuclear Information System (INIS)

Swan, R.W.

1974-01-01

Stagnant or blind-loop syndrome includes vitamin B12 malabsorption, steatorrhea, and bacterial overgrowth of the small intestine. A case is presented to demonstrate this syndrome occurring after small-bowel irradiation injury with exaggeration postenterocolic by-pass. Alteration of normal small-bowel flora is basic to development of the stagnant-loop syndrome. Certain strains of bacteria as Bacteriodes and E. coli are capable of producing a malabsorption state. Definitive therapy for this syndrome developing after severe irradiation injury and intestinal by-pass includes antibiotics. Rapid symptomatic relief from diarrhea and improved malabsorption studies usually follow appropriate antibiotic therapy. Recolonization of the loop(s) with the offending bacterial species may produce exacerbation of symptoms. Since antibiotics are effective, recognition of this syndrome is important. Foul diarrheal stools should not be considered a necessary consequence of irradiation injury and intestinal by-pass

RhoGDI: multiple functions in the regulation of Rho family GTPase activities

DEFF Research Database (Denmark)

Dovas, Athanassios; Couchman, John R

2005-01-01

necessary for the correct targeting and regulation of Rho activities by conferring cues for spatial restriction, guidance and availability to effectors. These potential functions are discussed in the context of RhoGDI-associated multimolecular complexes, the newly emerged shuttling capability...... insight as to how RhoGDI exerts its effects on nucleotide binding, the membrane association-dissociation cycling of the GTPase and how these activities are controlled. Despite the initial negative roles attributed to RhoGDI, recent evidence has come to suggest that it may also act as a positive regulator...... of activities....

A Small Molecule that Targets r(CGG)exp and Improves Defects in Fragile X-Associated Tremor Ataxia Syndrome

Science.gov (United States)

Disney, Matthew D.; Liu, Biao; Yang, Wang-Yong; Sellier, Chantal; Tran, Tuan; Charlet-Berguerand, Nicolas; Childs-Disney, Jessica L.

2012-01-01

The development of small molecule chemical probes or therapeutics that target RNA remains a significant challenge despite the great interest in such compounds. The most significant barrier to compound development is a lack of knowledge of the chemical and RNA motif spaces that interact specifically. Herein, we describe a bioactive small molecule probe that targets expanded r(CGG) repeats, or r(CGG)exp , that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5’CGG/3’GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp -protein complex in vitro. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition to r(CGG)exp . Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)exp -protein aggregates. This approach may establish a general strategy to identify lead ligands that target RNA while also providing a chemical probe to dissect the varied mechanisms by which r(CGG)exp promotes toxicity. PMID:22948243

Aberrant cortical associative plasticity associated with severe adult Tourette syndrome.

Science.gov (United States)

Martín-Rodríguez, Juan Francisco; Ruiz-Rodríguez, María Adilia; Palomar, Francisco J; Cáceres-Redondo, María Teresa; Vargas, Laura; Porcacchia, Paolo; Gómez-Crespo, Mercedes; Huertas-Fernández, Ismael; Carrillo, Fátima; Madruga-Garrido, Marcos; Mir, Pablo

2015-03-01

Recent studies have shown altered cortical plasticity in adult patients with Tourette syndrome. However, the clinical significance of this finding remains elusive. Motor cortical plasticity was evaluated in 15 adult patients with severe Tourette syndrome and 16 healthy controls using the paired associative stimulation protocol by transcranial magnetic stimulation. Associations between paired associative stimulation-induced plasticity and relevant clinical variables, including cortical excitability, psychiatric comorbidities, drug treatment and tic severity, were assessed. Motor cortical plasticity was abnormally increased in patients with Tourette syndrome compared with healthy subjects. This abnormal plasticity was independently associated with tic severity. Patients with severe Tourette syndrome display abnormally increased cortical associative plasticity. This aberrant cortical plasticity was associated with tic severity, suggesting an underlying mechanism for tic pathophysiology. © 2015 International Parkinson and Movement Disorder Society.

Anti-Ma-associated encephalitis due to dysgerminoma in a woman with Swyer syndrome.

Science.gov (United States)

Al-Thubaiti, Ibtisam; Al-Hayek, Kefah; Binfalah, Mohammed

2013-04-09

Paraneoplastic limbic encephalitis (PLE)/diencephalitis associated with anti-Ma2 antibodies was linked to testicular cancer and non-small-cell lung cancer (non-SCLC).(1,2) We report a case of anti-Ma-associated PLE/diencephalitis due to dysgerminoma in a woman with gonadal dysgenesis, or Swyer syndrome.

Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma

OpenAIRE

Marko, Tracy A.; Shamsan, Ghaidan A.; Edwards, Elizabeth N.; Hazelton, Paige E.; Rathe, Susan K.; Cornax, Ingrid; Overn, Paula R.; Varshney, Jyotika; Diessner, Brandon J.; Moriarity, Branden S.; O?Sullivan, M. Gerard; Odde, David J.; Largaespada, David A.

2016-01-01

Osteosarcoma is the most common primary bone tumor, with metastatic disease responsible for most treatment failure and patient death. A forward genetic screen utilizing Sleeping Beauty mutagenesis in mice previously identified potential genetic drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2). This study evaluates the potential role of SRGAP2 in metastases-associated properties of osteosarcoma cell lines through Srgap2 knockout via the CRISPR/Cas9 n...

Association of Amelogenesis Imperfecta and Bartter's Syndrome.

Science.gov (United States)

Kumar, A C V; Alekya, V; Krishna, M S V V; Alekya, K; Aruna, M; Reddy, M H K; Sangeetha, B; Ram, R; Kumar, V S

2017-01-01

Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure. Bartter's syndrome is associated with hypercalciuria and nephrocalcinosis. Amelogenesis imperfecta (AI) is a group of hereditary disorders that affect dental enamel. AI could be part of several syndromes. The enamel renal syndrome is the association of AI and nephrocalcinosis. We report two patients of AI with Bartter's syndrome.

Mutation spectrum in the large GTPase dynamin 2, and genotype-phenotype correlation in autosomal dominant centronuclear myopathy

DEFF Research Database (Denmark)

Böhm, Johann; Biancalana, Valérie; Dechene, Elizabeth T

2012-01-01

Centronuclear myopathy (CNM) is a genetically heterogeneous disorder associated with general skeletal muscle weakness, type I fiber predominance and atrophy, and abnormally centralized nuclei. Autosomal dominant CNM is due to mutations in the large GTPase dynamin 2 (DNM2), a mechanochemical enzym...

Haploinsufficiency of a spliceosomal GTPase encoded by EFTUD2 causes mandibulofacial dysostosis with microcephaly.

Science.gov (United States)

Lines, Matthew A; Huang, Lijia; Schwartzentruber, Jeremy; Douglas, Stuart L; Lynch, Danielle C; Beaulieu, Chandree; Guion-Almeida, Maria Leine; Zechi-Ceide, Roseli Maria; Gener, Blanca; Gillessen-Kaesbach, Gabriele; Nava, Caroline; Baujat, Geneviève; Horn, Denise; Kini, Usha; Caliebe, Almuth; Alanay, Yasemin; Utine, Gulen Eda; Lev, Dorit; Kohlhase, Jürgen; Grix, Arthur W; Lohmann, Dietmar R; Hehr, Ute; Böhm, Detlef; Majewski, Jacek; Bulman, Dennis E; Wieczorek, Dagmar; Boycott, Kym M

2012-02-10

Mandibulofacial dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

A role for Sar1 and ARF1 GTPases during Golgi biogenesis in the protozoan parasite Trypanosoma brucei

Science.gov (United States)

Yavuz, Sevil; Warren, Graham

2017-01-01

A single Golgi stack is duplicated and partitioned into two daughter cells during the cell cycle of the protozoan parasite Trypanosoma brucei. The source of components required to generate the new Golgi and the mechanism by which it forms are poorly understood. Using photoactivatable GFP, we show that the existing Golgi supplies components directly to the newly forming Golgi in both intact and semipermeabilized cells. The movement of a putative glycosyltransferase, GntB, requires the Sar1 and ARF1 GTPases in intact cells. In addition, we show that transfer of GntB from the existing Golgi to the new Golgi can be recapitulated in semipermeabilized cells and is sensitive to the GTP analogue GTPγS. We suggest that the existing Golgi is a key source of components required to form the new Golgi and that this process is regulated by small GTPases. PMID:28495798

Association of amelogenesis imperfecta and Bartter's syndrome

Directory of Open Access Journals (Sweden)

A. C. V. Kumar

2017-01-01

Full Text Available Bartter's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemia, hypochloremia, metabolic alkalosis, and hyperreninemia with normal blood pressure. Bartter's syndrome is associated with hypercalciuria and nephrocalcinosis. Amelogenesis imperfecta (AI is a group of hereditary disorders that affect dental enamel. AI could be part of several syndromes. The enamel renal syndrome is the association of AI and nephrocalcinosis. We report two patients of AI with Bartter's syndrome.

Insight into temperature dependence of GTPase activity in human guanylate binding protein-1.

Directory of Open Access Journals (Sweden)

Anjana Rani

Full Text Available Interferon-γ induced human guanylate binding protein-1(hGBP1 belongs to a family of dynamin related large GTPases. Unlike all other GTPases, hGBP1 hydrolyzes GTP to a mixture of GDP and GMP with GMP being the major product at 37°C but GDP became significant when the hydrolysis reaction was carried out at 15°C. The hydrolysis reaction in hGBP1 is believed to involve with a number of catalytic steps. To investigate the effect of temperature in the product formation and on the different catalytic complexes of hGBP1, we carried out temperature dependent GTPase assays, mutational analysis, chemical and thermal denaturation studies. The Arrhenius plot for both GDP and GMP interestingly showed nonlinear behaviour, suggesting that the product formation from the GTP-bound enzyme complex is associated with at least more than one step. The negative activation energy for GDP formation and GTPase assay with external GDP together indicate that GDP formation occurs through the reversible dissociation of GDP-bound enzyme dimer to monomer, which further reversibly dissociates to give the product. Denaturation studies of different catalytic complexes show that unlike other complexes the free energy of GDP-bound hGBP1 decreases significantly at lower temperature. GDP formation is found to be dependent on the free energy of the GDP-bound enzyme complex. The decrease in the free energy of this complex at low temperature compared to at high is the reason for higher GDP formation at low temperature. Thermal denaturation studies also suggest that the difference in the free energy of the GTP-bound enzyme dimer compared to its monomer plays a crucial role in the product formation; higher stability favours GMP but lower favours GDP. Thus, this study provides the first thermodynamic insight into the effect of temperature in the product formation of hGBP1.

Colobomata associated with Noonan's syndrome.

OpenAIRE

Kleanthous, L.; Cruz, D.; D'Graham, E.; Efthimiou, J.

1987-01-01

A patient with Noonan's syndrome and fundal colobomata in both eyes is described. To our knowledge, this is the first report of the association of colobomata with Noonan's syndrome. Although the patient had poor sight since early childhood and dyspnea on exertion as a teenager, the diagnosis of Noonan's syndrome was not made until early adulthood. We hope this report will encourage recognition of this syndrome and its implications at an earlier stage.

Role of Arf GTPases in fungal morphogenesis and virulence.

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Hayet Labbaoui

2017-02-01

Full Text Available Virulence of the human fungal pathogen Candida albicans depends on the switch from budding to filamentous growth, which requires sustained membrane traffic and polarized growth. In many organisms, small GTPases of the Arf (ADP-ribosylation factor family regulate membrane/protein trafficking, yet little is known about their role in fungal filamentous growth. To investigate these GTPases in C. albicans, we generated loss of function mutants in all 3 Arf proteins, Arf1-Arf3, and 2 Arf-like proteins, Arl1 and Arl3. Our results indicate that of these proteins, Arf2 is required for viability and sensitivity to antifungal drugs. Repressible ARF2 expression results in defects in filamentous growth, cell wall integrity and virulence, likely due to alteration of the Golgi. Arl1 is also required for invasive filamentous growth and, although arl1/arl1 cells can initiate hyphal growth, hyphae are substantially shorter than that of the wild-type, due to the inability of this mutant to maintain hyphal growth at a single site. We show that this defect does not result from an alteration of phospholipid distribution and is unlikely to result from the sole Golgin Imh1 mislocalization, as Imh1 is not required for invasive filamentous growth. Rather, our results suggest that the arl1/arl1 hyphal growth defect results from increased secretion in this mutant. Strikingly, the arl1/arl1 mutant is drastically reduced in virulence during oropharyngeal candidiasis. Together, our results highlight the importance of Arl1 and Arf2 as key regulators of hyphal growth and virulence in C. albicans and identify a unique function of Arl1 in secretion.

The Arf GTPase-activating protein family is exploited by Salmonella enterica serovar Typhimurium to invade nonphagocytic host cells.

Science.gov (United States)

Davidson, Anthony C; Humphreys, Daniel; Brooks, Andrew B E; Hume, Peter J; Koronakis, Vassilis

2015-02-10

To establish intracellular infections, Salmonella bacteria trigger host cell membrane ruffling and invasion by subverting cellular Arf guanine nucleotide exchange factors (GEFs) that activate Arf1 and Arf6 GTPases by promoting GTP binding. A family of cellular Arf GTPase-activating proteins (GAPs) can downregulate Arf signaling by stimulating GTP hydrolysis, but whether they do this during infection is unknown. Here, we uncovered a remarkable role for distinct Arf GAP family members in Salmonella invasion. The Arf6 GAPs ACAP1 and ADAP1 and the Arf1 GAP ASAP1 localized at Salmonella-induced ruffles, which was not the case for the plasma membrane-localized Arf6 GAPs ARAP3 and GIT1 or the Golgi-associated Arf1 GAP1. Surprisingly, we found that loss of ACAP1, ADAP1, or ASAP1 impaired Salmonella invasion, revealing that GAPs cannot be considered mere terminators of cytoskeleton remodeling. Salmonella invasion was restored in Arf GAP-depleted cells by expressing fast-cycling Arf derivatives, demonstrating that Arf GTP/GDP cycles facilitate Salmonella invasion. Consistent with this view, both constitutively active and dominant-negative Arf derivatives that cannot undergo GTP/GDP cycles inhibited invasion. Furthermore, we demonstrated that Arf GEFs and GAPs colocalize at invading Salmonella and collaborate to drive Arf1-dependent pathogen invasion. This study revealed that Salmonella bacteria exploit a remarkable interplay between Arf GEFs and GAPs to direct cycles of Arf GTPase activation and inactivation. These cycles drive Salmonella cytoskeleton remodeling and enable intracellular infections. To initiate infections, the Salmonella bacterial pathogen remodels the mammalian actin cytoskeleton and invades host cells by subverting host Arf GEFs that activate Arf1 and Arf6 GTPases. Cellular Arf GAPs deactivate Arf GTPases and negatively regulate cell processes, but whether they target Arfs during infection is unknown. Here, we uncovered an important role for the Arf GAP

Congenital Heart Diseases associated with Identified Syndromes ...

African Journals Online (AJOL)

Recognised syndromes were seen in 69(68%) cases. Down syndrome with 54 children contributed 78.3% of those with known syndromes. Other identified syndromes and associations were Marfan's, Noonan's, Edwards, Prune Belly, Apert, Ellis-van creveld syndrome and congenital rubella syndrome. Congenital heart ...

Fournier gangrene associated with hyper IgE syndrome (Job syndrome).

Science.gov (United States)

Hori, Junichi; Yamaguchi, Satoshi; Watanabe, Masaki; Osanai, Hiroaki; Hori, Masako

2008-04-01

We report a case of a 32-year-old man with hyper IgE syndrome (Job syndrome) who developed Fournier gangrene due to infectious multiple atheromas of the scrotal skin that progressed to the right groin and thigh. The patient required surgical debridement and subsequent skin grafting. This is a rare case of Fournier gangrene associated with hyper IgE syndrome (Job syndrome). When a patient without diabetes mellitus has repeated infections and atopic-like dermatitis, Job syndrome should be considered.

An extracellular-matrix-specific GEF-GAP interaction regulates Rho GTPase crosstalk for 3D collagen migration.

Science.gov (United States)

Kutys, Matthew L; Yamada, Kenneth M

2014-09-01

Rho-family GTPases govern distinct types of cell migration on different extracellular matrix proteins in tissue culture or three-dimensional (3D) matrices. We searched for mechanisms selectively regulating 3D cell migration in different matrix environments and discovered a form of Cdc42-RhoA crosstalk governing cell migration through a specific pair of GTPase activator and inhibitor molecules. We first identified βPix, a guanine nucleotide exchange factor (GEF), as a specific regulator of migration in 3D collagen using an affinity-precipitation-based GEF screen. Knockdown of βPix specifically blocks cell migration in fibrillar collagen microenvironments, leading to hyperactive cellular protrusion accompanied by increased collagen matrix contraction. Live FRET imaging and RNAi knockdown linked this βPix knockdown phenotype to loss of polarized Cdc42 but not Rac1 activity, accompanied by enhanced, de-localized RhoA activity. Mechanistically, collagen phospho-regulates βPix, leading to its association with srGAP1, a GTPase-activating protein (GAP), needed to suppress RhoA activity. Our results reveal a matrix-specific pathway controlling migration involving a GEF-GAP interaction of βPix with srGAP1 that is critical for maintaining suppressive crosstalk between Cdc42 and RhoA during 3D collagen migration.

Psychiatric disorders associated with Cushing's syndrome.

Science.gov (United States)

Bratek, Agnieszka; Koźmin-Burzyńska, Agnieszka; Górniak, Eliza; Krysta, Krzysztof

2015-09-01

Cushing's syndrome is the term used to describe a set of symptoms associated with hypercortisolism, which in most cases is caused by hypophysial microadenoma over-secreting adrenocorticotropic hormone. This endocrine disorder is often associated with psychiatric comorbidities. The most important include mood disorders, psychotic disorders, cognitive dysfunctions and anxiety disorders. The aim of this article was to review the prevalence, symptoms and consequences of psychiatric disorders in the course of Cushing's syndrome. We therefore performed a literature search using the following keywords: Cushing's syndrome and psychosis, Cushing's syndrome and mental disorders, Cushing's syndrome and depression, Cushing's syndrome and anxiety. The most prevalent psychiatric comorbidity of Cushing's syndrome is depression. Psychiatric manifestations can precede the onset of full-blown Cushing's syndrome and therefore be misdiagnosed. Despite the fact that treatment of the underlying endocrine disease in most cases alleviates psychiatric symptoms, the loss of brain volume persists. It is important to be alert to the symptoms of hypercortisolism in psychiatric patients to avoid misdiagnosis and enable them receiving adequate treatment.

Metabolic complications in the small intestine syndrome

International Nuclear Information System (INIS)

Mora, Rafael; Orozco, Reynaldo

2000-01-01

Metabolic complications in the syndrome of small intestine is presented in a patient of masculine sex, 27 years old, who consulted for a square of inflammation gingival, migraine, fever, anorexia and adinamia for three days, followed by maculopapular-eritematose eruption for 8 days, coincident with the ampicillin ingestion, and later on severe abdominal pain and diarrhea

Obstructive Sleep Apnea Syndrome (OSAS, metabolic syndrome and mental health in small enterprise workers. feasibility of an Action for Health.

Directory of Open Access Journals (Sweden)

Sergio Garbarino

Full Text Available OBJECTIVE: To determine the frequency of obstructive sleep apnea syndrome (OSAS, metabolic syndrome and common mental disorders in the working population of 11 small enterprises and the feasibility of a program of action for health. METHOD: The clinical risk of OSAS, the prevalence of metabolic syndrome, and the level of psychological disorders were assessed during routine medical examination at the workplace in 2012. The response to medical advice was assessed in 2013. RESULTS: 12.3% of the workers were suspected of being affected by OSAS. One or more components of metabolic syndrome were present in 24.5% of cases. OSAS in "healthy" workers was significantly associated with the presence of one or more components of metabolic syndrome (OR = 3.83; 95%CI 1.45-10.13 and with a psychological disorders score in the highest quartile (OR = 4.67; 95%CI = 1.72-12.64. Workers with suspected OSAS were reluctant to follow advice about undergoing further tests under the NHS. However, in some cases, confirmation of the OSAS diagnosis and subsequent treatment led to an improvement in metabolic condition. CONCLUSION: Although participation in treatment was limited, anecdotal cases support the idea that prevention of obstructive sleep apnea in the workplace might be useful for workers' health.

Apical accumulation of the Sevenless receptor tyrosine kinase during Drosophila eye development is promoted by the small GTPase Rap1.

Science.gov (United States)

Baril, Caroline; Lefrançois, Martin; Sahmi, Malha; Knævelsrud, Helene; Therrien, Marc

2014-08-01

The Ras/MAPK-signaling pathway plays pivotal roles during development of metazoans by controlling cell proliferation and cell differentiation elicited, in several instances, by receptor tyrosine kinases (RTKs). While the internal mechanism of RTK-driven Ras/MAPK signaling is well understood, far less is known regarding its interplay with other co-required signaling events involved in developmental decisions. In a genetic screen designed to identify new regulators of RTK/Ras/MAPK signaling during Drosophila eye development, we identified the small GTPase Rap1, PDZ-GEF, and Canoe as components contributing to Ras/MAPK-mediated R7 cell differentiation. Rap1 signaling has recently been found to participate in assembling cadherin-based adherens junctions in various fly epithelial tissues. Here, we show that Rap1 activity is required for the integrity of the apical domains of developing photoreceptor cells and that reduced Rap1 signaling hampers the apical accumulation of the Sevenless RTK in presumptive R7 cells. It thus appears that, in addition to its role in cell-cell adhesion, Rap1 signaling controls the partitioning of the epithelial cell membrane, which in turn influences signaling events that rely on apico-basal cell polarity. Copyright © 2014 by the Genetics Society of America.

Mutations of the catalytic subunit of RAB3GAP cause Warburg Micro syndrome

DEFF Research Database (Denmark)

Aligianis, Irene A; Johnson, Colin A; Gissen, Paul

2005-01-01

Warburg Micro syndrome (WARBM1) is a severe autosomal recessive disorder characterized by developmental abnormalities of the eye and central nervous system and by microgenitalia. We identified homozygous inactivating mutations in RAB3GAP, encoding RAB3 GTPase activating protein, a key regulator...

Vesicular Trafficking Defects, Developmental Abnormalities, and Alterations in the Cellular Death Process Occur in Cell Lines that Over-Express Dictyostelium GTPase, Rab2, and Rab2 Mutants

Directory of Open Access Journals (Sweden)

Katherine Maringer

2014-08-01

Full Text Available Small molecular weight GTPase Rab2 has been shown to be a resident of pre-Golgi intermediates and required for protein transport from the ER to the Golgi complex, however, the function of Rab2 in Dictyostelium has yet to be fully characterized. Using cell lines that over-express DdRab2, as well as cell lines over-expressing constitutively active (CA, and dominant negative (DN forms of the GTPase, we report a functional role in vesicular transport specifically phagocytosis, and endocytosis. Furthermore, Rab2 like other GTPases cycles between an active GTP-bound and an inactive GDP-bound state. We found that this GTP/GDP cycle for DdRab2 is crucial for normal Dictyostelium development and cell–cell adhesion. Similar to Rab5 and Rab7 in C. elegans, we found that DdRab2 plays a role in programmed cell death, possibly in the phagocytic removal of apoptotic corpses.

Fragile X syndrome and fragile X-associated tremor ataxia syndrome.

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Hall, Deborah A; Berry-Kravis, Elizabeth

2018-01-01

Fragile X-associated disorders encompass several conditions, which are caused by expansion mutations in the fragile X mental retardation 1 (FMR1) gene. Fragile X syndrome is the most common inherited etiology of intellectual disability and results from a full mutation or >200 CGG repeats in FMR1. It is associated with developmental delay, autism spectrum disorder, and seizures. Fragile X-associated tremor/ataxia syndrome is a progressive neurodegenerative disease that occurs in premutation carriers of 55-200 CGG repeats in FMR1 and is characterized by kinetic tremor, gait ataxia, parkinsonism, executive dysfunction, and neuropathy. Fragile X-associated primary ovarian insufficiency also occurs in premutation carrier women and manifests with infertility and early menopause. The diseases constituting fragile X-associated disorders differ mechanistically, due to the distinct molecular properties of premutation versus full mutations. Fragile X syndrome occurs when there is a lack of fragile X mental retardation protein (FMRP) due to FMR1 methylation and silencing. In fragile X-associated tremor ataxia syndrome, a toxic gain of function is postulated with the production of excess CGG repeat-containing FMR1 mRNA, abnormal translation of the repeat sequence leading to production of polyglycine, polyalanine, and other polypeptides and to outright deficits in translation leading to reduced FMRP at larger premutation sizes. The changes in underlying brain chemistry due to FMR1 mutations have led to therapeutic studies in these disorders, with some progress being made in fragile X syndrome. This paper also summarizes indications for testing, genetic counseling issues, and what the future holds for these disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Adrenocortical carcinoma, an unusual extracolonic tumor associated with Lynch II syndrome.

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Medina-Arana, V; Delgado, L; González, L; Bravo, A; Díaz, H; Salido, E; Riverol, D; González-Aguilera, J J; Fernández-Peralta, A M

2011-06-01

Lynch syndrome (LS) is an autosomal dominant condition that predisposes to colorectal cancer and specific other tumors. Extracolonic tumors occur mainly in the endometrium, stomach, ovary, small intestine and urinary tract. The presence of rare tumors in patients belonging to families who have Lynch syndrome is always interesting, because the question arises whether these tumors should be considered as a coincidence or are related with the syndrome. In this last case, they are also the result of the defect in the mismatch repair system, opening the possibility of extending the tumor spectrum associated with the syndrome. Here we describe a patient from a Lynch syndrome family with a germline mutation c.2063T>G (p.M688R) in the MSH2 gene, who developed an adrenal cortical carcinoma, a tumor not usually associated with LS. We analyzed the adrenocortical tumour for microsatellite instability (MSI), LOH and the presence of the germline c.2063T>G (M688R) mutation. The adrenal cortical carcinoma showed the MSH2 mutation, loss of heterozygosity of the normal allele in the MSH2 gene and loss of immunohistochemical expression for MSH2 protein, but no microsatellite instability. Additionally, the adrenal cortical carcinoma did not harbour a TP53 mutation. The molecular study indicates that this adrenal cortical cancer is probably due to the mismatch repair defect.

Crohn's Disease Associated with Sweet's Syndrome and Sjögren's Syndrome Treated with Infliximab

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Erina N. Foster

2005-01-01

Full Text Available The association of Crohn's disease (CD and Sweet's syndrome is rare and the presence of Sjögren's syndrome in Crohn's disease is even rarer, with only three reports found in the literature. We describe two cases of Crohn's disease associated with Sweet's syndrome, one of which is the first case of CD and Sweet's concomitantly associated with Sjögren's syndrome. Both cases responded rapidly to Infliximab therapy with complete resolution of the skin lesions.

Proteus syndrome: association with gingival hyperplasia.

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Arendorf, T M; Hanslo, B

1995-09-01

A 9-year old Black boy with gigantism of the hands and feet, and recurrent gingival hyperplasia, diagnosed as Proteus syndrome is presented. The oral manifestations of this syndrome are described. To the best of our knowledge, this is the first reported case of gingival hyperplasia associated with Proteus syndrome.

Novel Activities of Select NSAID R-Enantiomers against Rac1 and Cdc42 GTPases.

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Tudor I Oprea

Full Text Available Rho family GTPases (including Rac, Rho and Cdc42 collectively control cell proliferation, adhesion and migration and are of interest as functional therapeutic targets in numerous epithelial cancers. Based on high throughput screening of the Prestwick Chemical Library® and cheminformatics we identified the R-enantiomers of two approved drugs (naproxen and ketorolac as inhibitors of Rac1 and Cdc42. The corresponding S-enantiomers are considered the active component in racemic drug formulations, acting as non-steroidal anti-inflammatory drugs (NSAIDs with selective activity against cyclooxygenases. Here, we show that the S-enantiomers of naproxen and ketorolac are inactive against the GTPases. Additionally, more than twenty other NSAIDs lacked inhibitory action against the GTPases, establishing the selectivity of the two identified NSAIDs. R-naproxen was first identified as a lead compound and tested in parallel with its S-enantiomer and the non-chiral 6-methoxy-naphthalene acetic acid (active metabolite of nabumetone, another NSAID as a structural series. Cheminformatics-based substructure analyses-using the rotationally constrained carboxylate in R-naproxen-led to identification of racemic [R/S] ketorolac as a suitable FDA-approved candidate. Cell based measurement of GTPase activity (in animal and human cell lines demonstrated that the R-enantiomers specifically inhibit epidermal growth factor stimulated Rac1 and Cdc42 activation. The GTPase inhibitory effects of the R-enantiomers in cells largely mimic those of established Rac1 (NSC23766 and Cdc42 (CID2950007/ML141 specific inhibitors. Docking predicts that rotational constraints position the carboxylate moieties of the R-enantiomers to preferentially coordinate the magnesium ion, thereby destabilizing nucleotide binding to Rac1 and Cdc42. The S-enantiomers can be docked but are less favorably positioned in proximity to the magnesium. R-naproxen and R-ketorolac have potential for rapid

Klinefelter syndrome and its association with male infertility

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V Ramakrishnan

2014-03-01

Full Text Available Klinefelter's syndrome is the most common genetic disorder in which there is at least one extra X chromosome. Males normally have an X chromosome and a Y chromosome (XY. But males who have Klinefelter syndrome have an extra X chromosome (XXY, giving them a total of 47 instead of the normal 46 chromosomes. Sex chromosome abnormalities are more frequently associated with male infertility. The prevalence of XXYs has risen from 1.09 to 1.72 per 1 000 male births. A patient attended to fertility and genetic clinic, during the clinical diagnosis we found the following complaints of loss of secondary sexual characteristics and infertility. Physical examination revealed breast development, thin built, small size testes, and absence of beard and pubic hairs. Karyotype and biochemical analysis were performed to detect chromosomal abnormality as well as hormonal level to confirm the diagnosis of Klinefelter's syndrome. Chromosomal analysis of the peripheral blood lymphocytes demonstrated the constitutional karyotype of 47, XXY. Using karyotype the presence of extra X chromosome was confirmed, supporting the cytogenetic finding. The 47, XXY syndrome is relatively uncommon and can be missed clinically because of its variable clinical presentations. Accurate diagnosis of this constitutional karyotype provides a valuable aid in the counselling and early management of the patients who undertake fertility evaluation.

Targeting GTPases in Parkinson’s disease: comparison to the historic path of kinase drug discovery and perspectives

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LIN eHONG

2014-06-01

Full Text Available Neurological diseases have placed heavy social and financial burdens on modern society. As the life expectancy of humans is extended, neurological diseases, such as Parkinson’s disease, have become increasingly common among senior populations. Although the enigmas of Parkinson’s diseases await resolution, more vivid pictures on the cause, progression and control of the illness are emerging after years of research. On the molecular level, GTPases are implicated in the etiology of Parkinson’s disease and are rational pharmaceutical targets for their control. However, targeting individual GTPases, which belong to a superfamily of proteins containing multiple members with a conserved guanine nucleotide binding domain, has proven to be challenging. In contrast, pharmaceutical pursuit of inhibition of kinases, which constitute another superfamily of proteins with more than 500 members, has been fairly successful. We reviewed the breakthroughs in the history of kinase drug discovery to provide guidance for the GTPase field. We summarize recent progress made in the regulation of GTPase activity. We also present an efficient and cost effective approach to drug screening, which uses multiplex flow cytometry and mixture-based positional scanning libraries. These methods allow simultaneous measurements of both the activity and the selectivity of the screened library. Several GTPase activator clusters were identified which showed selectivity against different GTPase subfamilies. While the clusters need to be further deconvoluted to identify individual active compounds, the method described here and the structure information gathered create a foundation for further developments to build upon.

Association of Down's syndrome and testicular cancer.

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Dieckmann, K P; Rübe, C; Henke, R P

1997-05-01

We present additional clinical evidence for the suspected association of Down's syndrome and testicular germ cell tumors. Four cases of Down's syndrome and testicular cancer are reported. The literature was reviewed for previous cases and analysis regarding common features. The 4 patients were 29 to 35 years old and had clinical stage I seminoma of the testis. Two patients received prophylactic abdominal radiotherapy, 1 is being followed and 1 received adjuvant carboplatin treatment. There was no relapse at followup of 1 to 8 years. One patient also had contralateral cryptorchidism. A total of 16 cases with the association of Down's syndrome and testicular germ cell cancer was documented previously. Evidence for the suspected association of Down's syndrome and testicular cancer is now accumulating. Etiologically it is suspected that, along with genetically determined malformations in many other organs in trisomy 21, the gonads also undergo maldevelopment, thus creating the conditions for step 1 of germ cell tumor oncogenesis in utero. Physicians caring for patients with Down's syndrome should be aware of the possible association with testicular neoplasms.

Association of fat mass and obesity-associated and retinitis pigmentosa guanosine triphosphatase (GTPase) regulator-interacting protein-1 like polymorphisms with body mass index in Chinese women.

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Chen, Boyu; Li, Zhiqiang; Chen, Jianhua; Ji, Jue; Shen, Jingyi; Xu, Yufeng; Zhao, Yingying; Liu, Danping; Shen, Yinhuan; Zhang, Weijie; Shen, Jiawei; Wang, Yonggang; Shi, Yongyong

2018-04-14

Body mass index (BMI) is the most commonly used quantitative measure of adiposity. It is a kind of complex genetic diseases which are caused by multiple susceptibility genes. The first intron of fat mass and obesity-associated (FTO) has been widely discovered to be associated with BMI. Retinitis pigmentosa GTPase regulator-interacting protein-1 like (RPGRIP1L) is located in the upstream region of FTO and has been proved to be linked with obesity through functional tests. We carried out a genetic association analysis to figure out the role of the FTO gene and the RPGRIP1L gene in BMI. A quantitative traits study with 6,102 Chinese female samples, adjusted for age, was performed during our project. Among the twelve SNPs, rs1421085, rs1558902, rs17817449, rs8050136, rs9939609, rs7202296, rs56137030, rs9930506 and rs12149832 in the FTO gene were significantly associated with BMI after Bonferroni correction. Meanwhile, rs9934800 in the RPGRIP1L gene showed significance with BMI before Bonferroni correction, but this association was eliminated after Bonferroni correction. Our results suggested that genetic variants in the FTO gene were strongly associated with BMI in Chinese women, which may serve as targets of pharmaceutical research and development concerning BMI. Meanwhile, we didn't found the significant association between RPGRIP1L and BMI in Chinese women.

IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.

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Zhao, Huan-Yu; Han, Yang; Wang, Jian; Yang, Lian-He; Zheng, Xiao-Ying; Du, Jiang; Wu, Guang-Ping; Wang, En-Hua

2017-06-01

IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.

Inter-cellular transport of ran GTPase.

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Deepak Khuperkar

Full Text Available Ran, a member of the Ras-GTPase superfamily, has a well-established role in regulating the transport of macromolecules across the nuclear envelope (NE. Ran has also been implicated in mitosis, cell cycle progression, and NE formation. Over-expression of Ran is associated with various cancers, although the molecular mechanism underlying this phenomenon is unclear. Serendipitously, we found that Ran possesses the ability to move from cell-to-cell when transiently expressed in mammalian cells. Moreover, we show that the inter-cellular transport of Ran is GTP-dependent. Importantly, Ran displays a similar distribution pattern in the recipient cells as that in the donor cell and co-localizes with the Ran binding protein Nup358 (also called RanBP2. Interestingly, leptomycin B, an inhibitor of CRM1-mediated export, or siRNA mediated depletion of CRM1, significantly impaired the inter-cellular transport of Ran, suggesting a function for CRM1 in this process. These novel findings indicate a possible role for Ran beyond nucleo-cytoplasmic transport, with potential implications in inter-cellular communication and cancers.

Extensive in silico analysis of Mimivirus coded Rab GTPase homolog suggests a possible role in virion membrane biogenesis

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Amrutraj eZade

2015-09-01

Full Text Available Rab GTPases are the key regulators of intracellular membrane trafficking in eukaryotes. Many viruses and intracellular bacterial pathogens have evolved to hijack the host Rab GTPase functions, mainly through activators and effector proteins, for their benefit. Acanthamoeba polyphaga mimivirus (APMV is one of the largest viruses and belongs to the monophyletic clade of nucleo-cytoplasmic large DNA viruses (NCLDV. The inner membrane lining is integral to the APMV virion structure. APMV assembly involves extensive host membrane modifications, like vesicle budding and fusion, leading to the formation of a membrane sheet that is incorporated into the virion. Intriguingly, APMV and all group I members of the Mimiviridae family code for a putative Rab GTPase protein. APMV is the first reported virus to code for a Rab GTPase (encoded by R214 gene. Our thorough in silico analysis of the subfamily specific (SF region of Mimiviridae Rab GTPase sequences suggests that they are related to Rab5, a member of the group II Rab GTPases, of lower eukaryotes. Because of their high divergence from the existing three isoforms, A, B and C of the Rab5-family, we suggest that Mimiviridae Rabs constitute a new isoform, Rab5D. Phylogenetic analysis indicated probable horizontal acquisition from a lower eukaryotic ancestor followed by selection and divergence. Furthermore, interaction network analysis suggests that vps34 (a Class III P13K homolog, coded by APMV L615, Atg-8 and dynamin (host proteins are recruited by APMV Rab GTPase during capsid assembly. Based on these observations, we hypothesize that APMV Rab plays a role in the acquisition of inner membrane during virion assembly.

The immunity-related GTPase Irga6 dimerizes in a parallel head-to-head fashion.

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Schulte, Kathrin; Pawlowski, Nikolaus; Faelber, Katja; Fröhlich, Chris; Howard, Jonathan; Daumke, Oliver

2016-03-02

The immunity-related GTPases (IRGs) constitute a powerful cell-autonomous resistance system against several intracellular pathogens. Irga6 is a dynamin-like protein that oligomerizes at the parasitophorous vacuolar membrane (PVM) of Toxoplasma gondii leading to its vesiculation. Based on a previous biochemical analysis, it has been proposed that the GTPase domains of Irga6 dimerize in an antiparallel fashion during oligomerization. We determined the crystal structure of an oligomerization-impaired Irga6 mutant bound to a non-hydrolyzable GTP analog. Contrary to the previous model, the structure shows that the GTPase domains dimerize in a parallel fashion. The nucleotides in the center of the interface participate in dimerization by forming symmetric contacts with each other and with the switch I region of the opposing Irga6 molecule. The latter contact appears to activate GTP hydrolysis by stabilizing the position of the catalytic glutamate 106 in switch I close to the active site. Further dimerization contacts involve switch II, the G4 helix and the trans stabilizing loop. The Irga6 structure features a parallel GTPase domain dimer, which appears to be a unifying feature of all dynamin and septin superfamily members. This study contributes important insights into the assembly and catalytic mechanisms of IRG proteins as prerequisite to understand their anti-microbial action.

WAVE regulatory complex activation by cooperating GTPases Arf and Rac1

DEFF Research Database (Denmark)

Koronakis, Vassilis; Hume, Peter J; Humphreys, Daniel

2011-01-01

The WAVE regulatory complex (WRC) is a critical element in the control of actin polymerization at the eukaryotic cell membrane, but how WRC is activated remains uncertain. While Rho GTPase Rac1 can bind and activate WRC in vitro, this interaction is of low affinity, suggesting other factors may...... be important. By reconstituting WAVE-dependent actin assembly on membrane-coated beads in mammalian cell extracts, we found that Rac1 was not sufficient to engender bead motility, and we uncovered a key requirement for Arf GTPases. In vitro, Rac1 and Arf1 were individually able to bind weakly to recombinant...... be central components in WAVE signalling, acting directly, alongside Rac1....

Mazabraud syndrome associated with McCune-Albright syndrome: a case report and review of the literature.

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Biazzo, Alessio; Di Bernardo, Andrea; Parafioriti, Antonina; Confalonieri, Norberto

2017-08-23

Mazabraud syndrome is a very rare benign disorder characterized by the association of monostotic or polyostotic fibrous dysplasia and one or multiple intramuscular myxomas. McCune -Albright syndrome is a rare benign disorder characterized by the association of polyostotic fibrous dysplasia, cafè-au-lait skin pigmentations and endocrine dysfunction, such as precocious puberty, diabetes mellitus, goiter and breast fibroadenomatosis. The association of Mazabraud syndrome and McCune-Albright in the same patient is an anecdotal event. We report the case of a 28-year-old girl with Mazabraud syndrome associated with McCune-Albright syndrome. Our literature review shows that in these patients there is a higher risk of malignant transformation of fibrous dysplasia into osteosarcoma, confirming previous reports. Conversely, no malignant transformation has been reported for myxomas in isolated Mazabraud syndrome or in the association with McCune-Albright syndrome. We conclude that these patients should be scheduled to a close and long-term follow-up.

The Rac1 hypervariable region in targeting and signaling

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Lam, B. Daniel; Hordijk, Peter L.

2013-01-01

Cellular signaling by small GTPases is critically dependent on proper spatio-temporal orchestration of activation and output. In addition to their core G (guanine nucleotide binding)-domain, small GTPases comprise a hypervariable region (HVR) and a lipid anchor that are generally accepted to control subcellullar localization. The HVR encodes in many small GTPases a polybasic region (PBR) that permits charge-mediated association to the inner leaflet of the plasma membrane or to intracellular organelles. Over the past 15–20 years, evidence has accumulated for specific protein–protein interactions, mediated by the HVR, that control both targeting and signaling specificity of small GTPases. Using the RhoGTPase Rac1 as a paradigm we here review a series of protein partners that require the Rac1 HVR for association and that control various aspects of localized Rac1 signaling. Some of these proteins represent Rac1 activators, whereas others mediate Rac1 inactivation and degradation and yet others potentiate Rac1 downstream signaling. Finally, evidence is discussed which shows that the HVR of Rac1 also contributes to effector interactions, co-operating with the N-terminal effector domain. The complexity of localized Rac1 signaling, reviewed here, is most likely exemplary for many other small GTPases as well, representing a challenge to identify and define similar mechanisms controlling the specific signaling induced by small GTPases. PMID:23354415

Churg-Strauss syndrome associated with montelukast therapy

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Tuggey, J; Hosker, H

2000-01-01

Churg-Strauss syndrome is a rare form of eosinophilic vasculitis associated with asthma. There have been several recent case reports of the condition in association with leukotriene antagonists and it has been speculated that the Churg-Strauss syndrome was unmasked when oral corticosteroids were withdrawn. We report a case of Churg-Strauss syndrome associated with montelukast therapy in an asthmatic patient in whom there had been no recent oral corticosteroid use. We believe that this is the first such reported case and would suggest that clinicians need to be vigilant in all patients who develop systemic symptoms when starting treatment with leukotriene antagonists.

 PMID:10950903

[A case of hemorrhagic cholecystitis associated with Churg-Strauss syndrome].

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Koizumi, Satomi; Kamisawa, Terumi; Kuruma, Sawako; Chiba, Kazuro; Tabata, Taku; Koizumi, Koichi; Kurata, Masanao; Horiguchi, Shinichiro; Hishima, Tsunekazu

2016-01-01

A woman in her 70s with Churg-Strauss syndrome presented with epigastric pain. She was being treated with steroids at the time of admission. Computed tomography showed swelling of the gallbladder, and percutaneous transhepatic cholangiography revealed bloody secretion. On duodenoscopy, bleeding was observed from the orifice of the major duodenal papilla. Emergency cholecystectomy was performed under a diagnosis of hemorrhagic cholecystitis;intraoperatively, extensive hematoma was detected in the thickened wall of the gallbladder. Subsequent histopathological examination revealed mucosal ulceration with infiltration of inflammatory cells, torn small vessels, and extensive transmural bleeding and abscess formation in the thickened wall of the gallbladder. We considered that the hemorrhagic cholecystitis was induced by either vasculitis or corticosteroid therapy. To the best of our knowledge, this is the first report of hemorrhagic cholecystitis associated with Churg-Strauss syndrome.

Interstitial Cystitis/Painful Bladder Syndrome and Associated Medical Conditions With an Emphasis on Irritable Bowel Syndrome, Fibromyalgia and Chronic Fatigue Syndrome

DEFF Research Database (Denmark)

Nickel, J.C.; Tripp, D.A.; Pontari, M.

2010-01-01

of associated conditions increased (ie localized, regional, systemic), pain, stress, depression and sleep disturbance increased while social support, sexual functioning and quality of life deteriorated. Anxiety and catastrophizing remained increased in all groups. Symptom duration was associated......Purpose: We characterized and compared the impact of clinical phenotypic associations between interstitial cystitis/painful bladder syndrome and controls in relation to potentially related conditions, particularly irritable bowel syndrome, fibromyalgia and chronic fatigue syndrome. Materials...... cystitis/painful bladder syndrome vs controls was irritable bowel syndrome 38.6% vs 5.2%, fibromyalgia 17.7% vs 2.6% and chronic fatigue syndrome 9.5% vs 1.7% (all p

[Origin and morphological features of small supernumerary marker chromosomes in Turner syndrome].

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Liu, Nan; Tong, Tong; Chen, Yue; Chen, Yanling; Cai, Chunquan

2018-02-10

OBJECTIVE To explore the origin and morphological features of small supernumerary marker chromosomes (sSMCs) in Turner syndrome. METHODS For 5 cases of Turner syndrome with a sSMC identified by conventional G-banding, dual-color fluorescence in situ hybridization (FISH) was applied to explore their origin and morphological features. RESULTS Among the 5 cases, 3 have derived from the X chromosome, which included 2 ring chromosomes and 1 centric minute. For the 2 sSMCs derived from the Y chromosome, 1 was ring or isodicentric chromosome, while the other was an isodicentric chromosome. CONCLUSION The sSMCs found in Turner syndrome have almost all derived from sex chromosomes. The majority of sSMCs derived from the X chromosome will form ring chromosomes, while a minority will form centric minute. While most sSMC derived from Y chromosome may exist as isodicentric chromosomes, and a small number may exist as rings. For Turner syndrome patients with sSMCs, dual-color FISH may be used to delineate their origins to facilitate genetic counseling and selection of clinical regime.

Plasma exchange in Goodpasture syndrome associated with ...

African Journals Online (AJOL)

Background: Good pasture syndrome (GPS) has been paid much attention recently for the dangerous illnessand high mortality. Objective: To investigate the efficiency of plasma exchange (PE) to treat Goodpasture syndrome (GPS) in children associated with Turner's syndrome. Method: We report a case of a 15 year old ...

Human Lsg1 defines a family of essential GTPases that correlates with the evolution of compartmentalization

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Scheffzek Klaus

2005-10-01

Full Text Available Abstract Background Compartmentalization is a key feature of eukaryotic cells, but its evolution remains poorly understood. GTPases are the oldest enzymes that use nucleotides as substrates and they participate in a wide range of cellular processes. Therefore, they are ideal tools for comparative genomic studies aimed at understanding how aspects of biological complexity such as cellular compartmentalization evolved. Results We describe the identification and characterization of a unique family of circularly permuted GTPases represented by the human orthologue of yeast Lsg1p. We placed the members of this family in the phylogenetic context of the YlqF Related GTPase (YRG family, which are present in Eukarya, Bacteria and Archea and include the stem cell regulator Nucleostemin. To extend the computational analysis, we showed that hLsg1 is an essential GTPase predominantly located in the endoplasmic reticulum and, in some cells, in Cajal bodies in the nucleus. Comparison of localization and siRNA datasets suggests that all members of the family are essential GTPases that have increased in number as the compartmentalization of the eukaryotic cell and the ribosome biogenesis pathway have evolved. Conclusion We propose a scenario, consistent with our data, for the evolution of this family: cytoplasmic components were first acquired, followed by nuclear components, and finally the mitochondrial and chloroplast elements were derived from different bacterial species, in parallel with the formation of the nucleolus and the specialization of nuclear components.

Usher syndrome associated with Fuchs' heterochromic uveitis.

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Lichtinger, Alejandro; Chowers, Itay; Amer, Radgonde

2010-10-01

The purpose of this study is to report two new cases of Usher syndrome associated with Fuchs' heterochromic uveitis (FHU), to confirm our previous observation of the association between FHU and retinitis pigmentosa (RP), and to evaluate if FHU is particularly associated with Usher syndrome. Retrospective medical record review of all new RP cases at Hadassah Medical Center between the years 2000 and 2007, review of our previously published data, and a meta-analysis of published relevant articles in peer reviewed journals. During the time frame of the study we diagnosed 58 new cases of RP, of whom one male and one female had the typical findings of FHU, and both had Usher syndrome type II. The difference in the occurrence of FHU between the 616 controls and the patients with RP was significant (p = 0.0073, Fisher's exact test). In our combined data, FHU occurred only in two types of RP; RP simplex with an incidence of 0.57%, and Usher syndrome with an incidence of 13.5%. This difference between the incidence of FHU in patients with Usher syndrome and other types of RP was significant (p Usher syndrome type II. Although infectious agents seem to play a role, the cause for this significant correlation is still unclear.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (I

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Chih-Ping Chen

2008-03-01

Full Text Available Fetuses with neural tube defects (NTDs maybe associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization (Ds-like human malformations, isolated hemihyper-plasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Syndromes, disorders and maternal risk factors associated with neural tube defects (I).

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Chen, Chih-Ping

2008-03-01

Fetuses with neural tube defects (NTDs) may be associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as acrocallosal syndrome, autosomal dominant brachydactyly-clinodactyly syndrome, Manouvrier syndrome, short rib-polydactyly syndrome, Disorganization ( Ds )-like human malformations, isolated hemihyperplasia, X-linked NTDs, meroanencephaly, schisis association, diprosopus, fetal valproate syndrome, DiGeorge syndrome/velocardiofacial syndrome, Waardenburg syndrome, folic acid antagonists, diabetes mellitus, and obesity. NTDs associated with syndromes, disorders, and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Prune belly syndrome associated with incomplete VACTERL

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Ghritlaharey R

2007-01-01

Full Text Available A Prune Belly syndrome with VATER/VACTERL association is an extremely rare. They are either stillborn or die within few days of life, only few such cases have been reported in literature. We are presenting here a male neonate of Prune Belly syndrome associated with incomplete VACTERL with brief review of literature.

Candidate gene association studies in syndromic and non-syndromic cleft lip and palate

Energy Technology Data Exchange (ETDEWEB)

Daack-Hirsch, S.; Basart, A.; Frischmeyer, P. [Univ. of Iowa, IA (United States)] [and others

1994-09-01

Using ongoing case ascertainment through a birth defects registry, we have collected 219 nuclear families with non-syndromic cleft lip and/or palate and 111 families with a collection of syndromic forms. Syndromic cases include 24 with recognized forms and 72 with unrecognized syndromes. Candidate gene studies as well as genome-wide searches for evidence of microdeletions and isodisomy are currently being carried out. Candidate gene association studies, to date, have made use of PCR-based polymorphisms for TGFA, MSX1, CLPG13 (a CA repeat associated with a human homologue of a locus that results in craniofacial dysmorphogenesis in the mouse) and an STRP found in a Van der Woude syndrome microdeletion. Control tetranucleotide repeats, which insure that population-based differences are not responsible for any observed associations, are also tested. Studies of the syndromic cases have included the same list of candidate genes searching for evidence of microdeletions and a genome-wide search using tri- and tetranucleotide polymorphic markers to search for isodisomy or structural rearrangements. Significant associations have previously been identified for TGFA, and, in this report, identified for MSX1 and nonsyndromic cleft palate only (p = 0.04, uncorrected). Preliminary results of the genome-wide scan for isodisomy has returned no true positives and there has been no evidence for microdeletion cases.

Duane retraction syndrome type 1 with Usher syndrome type 2: an unreported association.

Science.gov (United States)

Khurana, Bhawna Piplani; Khurana, Aruj Kumar; Grover, Sumit

2015-05-07

Duane retraction syndrome is characterized by globe retraction and palpebral fissure narrowing on adduction, with restriction of abduction, adduction, or both. Usher syndrome type 2 consists of congenital bilateral sensorineural hearing loss and retinitis pigmentosa. The authors present a case with a yet unreported association between Duane retraction syndrome type 1 and Usher syndrome type 2. Copyright 2015, SLACK Incorporated.

Uncoupling of dynamin polymerization and GTPase activity revealed by the conformation-specific nanobody dynab.

Science.gov (United States)

Galli, Valentina; Sebastian, Rafael; Moutel, Sandrine; Ecard, Jason; Perez, Franck; Roux, Aurélien

2017-10-12

Dynamin is a large GTPase that forms a helical collar at the neck of endocytic pits, and catalyzes membrane fission (Schmid and Frolov, 2011; Ferguson and De Camilli, 2012). Dynamin fission reaction is strictly dependent on GTP hydrolysis, but how fission is mediated is still debated (Antonny et al., 2016): GTP energy could be spent in membrane constriction required for fission, or in disassembly of the dynamin polymer to trigger fission. To follow dynamin GTP hydrolysis at endocytic pits, we generated a conformation-specific nanobody called dynab, that binds preferentially to the GTP hydrolytic state of dynamin-1. Dynab allowed us to follow the GTPase activity of dynamin-1 in real-time. We show that in fibroblasts, dynamin GTP hydrolysis occurs as stochastic bursts, which are randomly distributed relatively to the peak of dynamin assembly. Thus, dynamin disassembly is not coupled to GTPase activity, supporting that the GTP energy is primarily spent in constriction.

A morphometric CT study of Down's syndrome showing small posterior fossa and calcification of basal ganglia

International Nuclear Information System (INIS)

Ieshima, A.; Yoshino, K.; Takashima, S.; Takeshita, K.; Kisa, T.

1984-01-01

We report characteristic and morphometric changes of cranial computed tomography (CT) with increasing age in 56 patients with Down's syndrome aged from 0 month to 37 years. Patients were compared with 142 normal controls aged 0 to 59 years. Width of ventricles, Sylvian fissures, posterior fossa, pons and cisterna magna were measured on CT. The incidences of the cavum septi pellucidi, cavum vergae and cavum veli interpositi and high density in the basal ganglia were examined. There was high incidence (10.7%) of bilateral calcification of basal ganglia in Down's syndrome, although that of pineal body and choroid plexus calcification was similar in Down's syndrome and controls. Basal ganglia calcification is more frequently seen in young Down's syndrome and may be related to the premature aging characteristic of Down's syndrome. The CT in Down's syndrome showed relatively small posterior fossa, small cerebellum, small brain stem and relatively large Sylvian fissures in those under one year of age. There was a high frequency of midline cava and large cisterna magna. There were no significant atrophic changes on CT except after the fifth decade comparing with controls. (orig.)

Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VII

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2008-09-01

Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders and maternal risk factors. This article provides a comprehensive review of the syndromes, disorders and maternal risk factors associated with NTDs, including DK phocomelia syndrome (von Voss-Cherstvoy syndrome, Siegel-Bartlet syndrome, fetal warfarin syndrome, craniotelencephalic dysplasia, Czeizel-Losonci syndrome, maternal cocaine abuse, Weissenbacher-Zweymüller syndrome, parietal foramina (cranium bifidum, Apert syndrome, craniomicromelic syndrome, XX-agonadism with multiple dysraphic lesions including omphalocele and NTDs, Fryns microphthalmia syndrome, Gershoni-Baruch syndrome, PHAVER syndrome, periconceptional vitamin B6 deficiency, and autosomal dominant Dandy-Walker malformation with occipital cephalocele. NTDs associated with these syndromes, disorders and maternal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders and maternal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

Ras GTPases Modulate Morphogenesis, Sporulation and Cellulase Gene Expression in the Cellulolytic Fungus Trichoderma reesei

Science.gov (United States)

Zhang, Jiwei; Zhang, Yanmei; Zhong, Yaohua; Qu, Yinbo; Wang, Tianhong

2012-01-01

Background The model cellulolytic fungus Trichoderma reesei (teleomorph Hypocrea jecorina) is capable of responding to environmental cues to compete for nutrients in its natural saprophytic habitat despite its genome encodes fewer degradative enzymes. Efficient signalling pathways in perception and interpretation of environmental signals are indispensable in this process. Ras GTPases represent a kind of critical signal proteins involved in signal transduction and regulation of gene expression. In T. reesei the genome contains two Ras subfamily small GTPases TrRas1 and TrRas2 homologous to Ras1 and Ras2 from S. cerevisiae, but their functions remain unknown. Methodology/Principal Findings Here, we have investigated the roles of GTPases TrRas1 and TrRas2 during fungal morphogenesis and cellulase gene expression. We show that both TrRas1 and TrRas2 play important roles in some cellular processes such as polarized apical growth, hyphal branch formation, sporulation and cAMP level adjustment, while TrRas1 is more dominant in these processes. Strikingly, we find that TrRas2 is involved in modulation of cellulase gene expression. Deletion of TrRas2 results in considerably decreased transcription of cellulolytic genes upon growth on cellulose. Although the strain carrying a constitutively activated TrRas2G16V allele exhibits increased cellulase gene transcription, the cbh1 and cbh2 expression in this mutant still strictly depends on cellulose, indicating TrRas2 does not directly mediate the transmission of the cellulose signal. In addition, our data suggest that the effect of TrRas2 on cellulase gene is exerted through regulation of transcript abundance of cellulase transcription factors such as Xyr1, but the influence is independent of cAMP signalling pathway. Conclusions/Significance Together, these findings elucidate the functions for Ras signalling of T. reesei in cellular morphogenesis, especially in cellulase gene expression, which contribute to deciphering the

NADPH oxidase complex-derived reactive oxygen species, the actin cytoskeleton, and rho GTPases in cell migration

DEFF Research Database (Denmark)

Stanley, Alanna; Thompson, Kerry; Hynes, Ailish

2014-01-01

Abstract Significance: Rho GTPases are historically known to be central regulators of actin cytoskeleton reorganization. This affects many processes including cell migration. In addition, members of the Rac subfamily are known to be involved in reactive oxygen species (ROS) production through...... mediating cytoskeletal reorganization. Critical Issues: The role of the actin cytoskeleton in providing a scaffold for components of the Nox complex needs to be examined in the light of these new advances. During cell migration, Rho GTPases, ROS, and cytoskeletal organization appear to function as a complex...... compartments. This in conjunction with the analysis of tissues lacking specific Rho GTPases, and Nox components will facilitate a detailed examination of the interactions of these structures with the actin cytoskeleton. In combination with the analysis of ROS production, including its subcellular location...

Vocal cord paralysis associated with Ramsay Hunt syndrome

DEFF Research Database (Denmark)

Rasmussen, Eva Rye; Mey, Kristianna

2014-01-01

Ramsay Hunt syndrome is defined by herpes zoster oticus and peripheral facial nerve palsy which is often associated with otalgia. The syndrome is, in rare cases, associated with other cranial nerve paralyses including the vagal nerve causing unilateral vocal cord paralysis. Vocal cord paralysis...

A Novel Plasma Membrane-Anchored Protein Regulates Xylem Cell-Wall Deposition through Microtubule-Dependent Lateral Inhibition of Rho GTPase Domains.

Science.gov (United States)

Sugiyama, Yuki; Wakazaki, Mayumi; Toyooka, Kiminori; Fukuda, Hiroo; Oda, Yoshihisa

2017-08-21

Spatial control of cell-wall deposition is essential for determining plant cell shape [1]. Rho-type GTPases, together with the cortical cytoskeleton, play central roles in regulating cell-wall patterning [2]. In metaxylem vessel cells, which are the major components of xylem tissues, active ROP11 Rho GTPases form oval plasma membrane domains that locally disrupt cortical microtubules, thereby directing the formation of oval pits in secondary cell walls [3-5]. However, the regulatory mechanism that determines the planar shape of active Rho of Plants (ROP) domains is still unknown. Here we show that IQD13 associates with cortical microtubules and the plasma membrane to laterally restrict the localization of ROP GTPase domains, thereby directing the formation of oval secondary cell-wall pits. Loss and overexpression of IQD13 led to the formation of abnormally round and narrow secondary cell-wall pits, respectively. Ectopically expressed IQD13 increased the presence of parallel cortical microtubules by promoting microtubule rescue. A reconstructive approach revealed that IQD13 confines the area of active ROP domains within the lattice of the cortical microtubules, causing narrow ROP domains to form. This activity required the interaction of IQD13 with the plasma membrane. These findings suggest that IQD13 positively regulates microtubule dynamics as well as their linkage to the plasma membrane, which synergistically confines the area of active ROP domains, leading to the formation of oval secondary cell-wall pits. This finding sheds light on the role of microtubule-plasma membrane linkage as a lateral fence that determines the planar shape of Rho GTPase domains. Copyright © 2017 Elsevier Ltd. All rights reserved.

[Association between Williams syndrome and adrenal insufficiency].

Science.gov (United States)

Rchachi, Meryem; Larwanou, Maazou Mahamane; El Ouahabi, Hanan; Ajdi, Farida

2017-01-01

Williams syndrome is a developmental disorder including dysmorphia, cardiovascular malformations and a specific neuropsychological profile together with other associated disorders. We report the case of a 17-year old girl, born of a non-inbred marriage, with Williams syndrome discovered during an assessment of degree of failure to thrive. Its association with primary adrenal insufficiency makes it unique. Diagnosis is confirmed by cytogenetic and molecular analysis. Its management consists of the implementation of treatment for adrenal insufficiency associated with a clinico-biological monitoring.

Rab4GTPase modulates CFTR function by impairing channel expression at plasma membrane

International Nuclear Information System (INIS)

Saxena, Sunil K.; Kaur, Simarna; George, Constantine

2006-01-01

Cystic fibrosis (CF), an autosomal recessive disorder, is caused by the disruption of biosynthesis or the function of a membrane cAMP-activated chloride channel, CFTR. CFTR regulatory mechanisms include recruitment of channel proteins to the cell surface from intracellular pools and by protein-protein interactions. Rab proteins are small GTPases involved in regulated trafficking controlling vesicle docking and fusion. Rab4 controls recycling events from endosome to the plasma membrane, fusion, and degradation. The colorectal cell line HT-29 natively expresses CFTR and responds to cAMP stimulation with an increase in CFTR-mediated currents. Rab4 over-expression in HT-29 cells inhibits both basal and cAMP-stimulated CFTR-mediated currents. GTPase-deficient Rab4Q67L and GDP locked Rab4S22N both inhibit channel activity, which appears characteristically different. Active status of Rab4 was confirmed by GTP overlay assay, while its expression was verified by Western blotting. The pull-down and immunoprecipitation experiments suggest that Rab4 physically interacts with CFTR through protein-protein interaction. Biotinylation with cell impermeant NHS-Sulfo-SS-Biotin implies that Rab4 impairs CFTR expression at cell surface. The enhanced cytosolic CFTR indicates that Rab4 expression restrains CFTR appearance at the cell membrane. The study suggests that Rab4 regulates the channel through multiple mechanisms that include protein-protein interaction, GTP/GDP exchange, and channel protein trafficking. We propose that Rab4 is a dynamic molecule with a significant role in CFTR function

Mutation-Specific Mechanisms of Hyperactivation of Noonan Syndrome SOS Molecules Detected with Single-molecule Imaging in Living Cells.

Science.gov (United States)

Nakamura, Yuki; Umeki, Nobuhisa; Abe, Mitsuhiro; Sako, Yasushi

2017-10-26

Noonan syndrome (NS) is a congenital hereditary disorder associated with developmental and cardiac defects. Some patients with NS carry mutations in SOS, a guanine nucleotide exchange factor (GEF) for the small GTPase RAS. NS mutations have been identified not only in the GEF domain, but also in various domains of SOS, suggesting that multiple mechanisms disrupt SOS function. In this study, we examined three NS mutations in different domains of SOS to clarify the abnormality in its translocation to the plasma membrane, where SOS activates RAS. The association and dissociation kinetics between SOS tagged with a fluorescent protein and the living cell surface were observed in single molecules. All three mutants showed increased affinity for the plasma membrane, inducing excessive RAS signalling. However, the mechanisms by which their affinity was increased were specific to each mutant. Conformational disorder in the resting state, increased probability of a conformational change on the plasma membrane, and an increased association rate constant with the membrane receptor are the suggested mechanisms. These different properties cause the specific phenotypes of the mutants, which should be rescuable with different therapeutic strategies. Therefore, single-molecule kinetic analyses of living cells are useful for the pathological analysis of genetic diseases.

The association between the metabolic syndrome and metabolic syndrome score and pulmonary function in non-smoking adults.

Science.gov (United States)

Yoon, Hyun; Gi, Mi Young; Cha, Ju Ae; Yoo, Chan Uk; Park, Sang Muk

2018-03-01

This study assessed the association of metabolic syndrome and metabolic syndrome score with the predicted forced vital capacity and predicted forced expiratory volume in 1 s (predicted forced expiratory volume in 1 s) values in Korean non-smoking adults. We analysed data obtained from 6684 adults during the 2013-2015 Korean National Health and Nutrition Examination Survey. After adjustment for related variables, metabolic syndrome ( p metabolic syndrome score ( p metabolic syndrome score with metabolic syndrome score 0 as a reference group showed no significance for metabolic syndrome score 1 [1.061 (95% confidence interval, 0.755-1.490)] and metabolic syndrome score 2 [1.247 (95% confidence interval, 0.890-1.747)], but showed significant for metabolic syndrome score 3 [1.433 (95% confidence interval, 1.010-2.033)] and metabolic syndrome score ⩾ 4 [1.760 (95% confidence interval, 1.216-2.550)]. In addition, the odds ratio of restrictive pulmonary disease of the metabolic syndrome [1.360 (95% confidence interval, 1.118-1.655)] was significantly higher than those of non-metabolic syndrome. Metabolic syndrome and metabolic syndrome score were inversely associated with the predicted forced vital capacity and forced expiratory volume in 1 s values in Korean non-smoking adults. In addition, metabolic syndrome and metabolic syndrome score were positively associated with the restrictive pulmonary disease.

Moyamoya disease associated with antiphospholipid syndrome

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Mahmut Abuhandan

2011-12-01

Full Text Available Moyamoya (MMD is a disease that often involves the vascular structures of anterior cerebral circulation, particularly the proximal segments of anterior and middle cerebral arteries. The etiology of the disease is unknown. MMD often presents with cerebral ischemia and rarely with cerebral hemorrhage. The pathology is termed Moyamoya syndrome (MMS when the pathological cerebral angiography findings are accompanied by meningitis, neurofibromatosis, neoplasm, Down syndrome or polycystic kidney disease. Autoimmune diseases including Graves’ disease, Behcet’s disease and antiphospholipid syndrome might also lead to the development of MMS. In this manuscript, we presented an interesting case of MMD associated with antiphospholipid syndrome, which is quite a rare cause of acute cerebral infarction in childhood

Bartter syndrome associated with nephropathic cystinosis.

Science.gov (United States)

Osman, Nader M; Sanosi, Ali Al

2016-01-01

Bartter syndrome is a rare inherited defect in the thick ascending limb of the loop of Henle. It is characterized by low potassium levels (hypokalaemia), increased blood pH (alkalosis) and normal to low blood pressure. There are three types of Bartter syndrome: neonatal, the classic type and Gitelman syndrome. Nephropathic cystinosis is an autosomal recessive disorder characterized by accumulation of free cystine in lysosomes due to disorder of lysosomal transport that can lead to end stage renal failure within 10 years and multiorgan impairment. We report a 5 year 9 month old child with Bartter syndrome associated with nephropathic cystinosis, hypothyroidism and rickets. Hitherto, only a handful of similar cases have been reported in the literature.

Association of Bone Mineral Density with the Metabolic Syndrome

International Nuclear Information System (INIS)

Kang, Yeong Han; Kam, Shin

2008-01-01

The purpose of this study was to examine the relationship between bone mineral density (BMD) and the metabolic syndrome. We conducted a cross-sectional study of 1204 adults(males: 364 females: 840) in a general hospital health promotion center. They were grouped into the normal and lower BMD group according to bone loss(osteopenia, osteoporosis), as determined by duel energy X-ray absorptiometery (DEXA). We analyzed the association between BMD and metabolic syndrome by multiple logistic regression analysis. After adjustment for age, weight, alcohol intake, smoking, regular exercise, regular intake of meals, and menopausal status, odds ratios for the prevalence of the metabolic syndrome by gender were calculated for lower BMD. After adjustment for the effect of potential covariates, the prevalence of metabolic syndrome was associated with bone loss in men (p<0.001). If the odds ratio of normal group is 1.00, then that of the lower BMD group is 3.07 (95% CI=1.83-5.16). The prevalence of metabolic alterations fitting the criteria of metabolic syndrome was significantly decreased in High BMI, Low HDL in men and in High BMI in women (p<0.05). This study shows that BMD was associated with metabolic syndrome. Further studies needed to obtain evidence concerning the association between BMD and metabolic syndrome.

Association of Bone Mineral Density with the Metabolic Syndrome

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Kang, Yeong Han [Dept. of Diagnostic Radiology, Daegu Catholic University Hospital, Daegu (Korea, Republic of); Kam, Shin [Dept. of Preventtive MedicinE, College of Medicine, Kyungpook National University, Daegu (Korea, Republic of)

2008-09-15

The purpose of this study was to examine the relationship between bone mineral density (BMD) and the metabolic syndrome. We conducted a cross-sectional study of 1204 adults(males: 364 females: 840) in a general hospital health promotion center. They were grouped into the normal and lower BMD group according to bone loss(osteopenia, osteoporosis), as determined by duel energy X-ray absorptiometery (DEXA). We analyzed the association between BMD and metabolic syndrome by multiple logistic regression analysis. After adjustment for age, weight, alcohol intake, smoking, regular exercise, regular intake of meals, and menopausal status, odds ratios for the prevalence of the metabolic syndrome by gender were calculated for lower BMD. After adjustment for the effect of potential covariates, the prevalence of metabolic syndrome was associated with bone loss in men (p<0.001). If the odds ratio of normal group is 1.00, then that of the lower BMD group is 3.07 (95% CI=1.83-5.16). The prevalence of metabolic alterations fitting the criteria of metabolic syndrome was significantly decreased in High BMI, Low HDL in men and in High BMI in women (p<0.05). This study shows that BMD was associated with metabolic syndrome. Further studies needed to obtain evidence concerning the association between BMD and metabolic syndrome.

Yersinia outer protein YopE affects the actin cytoskeleton in Dictyostelium discoideum through targeting of multiple Rho family GTPases

LENUS (Irish Health Repository)

Vlahou, Georgia

2009-07-14

Abstract Background All human pathogenic Yersinia species share a virulence-associated type III secretion system that translocates Yersinia effector proteins into host cells to counteract infection-induced signaling responses and prevent phagocytosis. Dictyostelium discoideum has been recently used to study the effects of bacterial virulence factors produced by internalized pathogens. In this study we explored the potential of Dictyostelium as model organism for analyzing the effects of ectopically expressed Yersinia outer proteins (Yops). Results The Yersinia pseudotuberculosis virulence factors YopE, YopH, YopM and YopJ were expressed de novo within Dictyostelium and their effects on growth in axenic medium and on bacterial lawns were analyzed. No severe effect was observed for YopH, YopJ and YopM, but expression of YopE, which is a GTPase activating protein for Rho GTPases, was found to be highly detrimental. GFP-tagged YopE expressing cells had less conspicuous cortical actin accumulation and decreased amounts of F-actin. The actin polymerization response upon cAMP stimulation was impaired, although chemotaxis was unaffected. YopE also caused reduced uptake of yeast particles. These alterations are probably due to impaired Rac1 activation. We also found that YopE predominantly associates with intracellular membranes including the Golgi apparatus and inhibits the function of moderately overexpressed RacH. Conclusion The phenotype elicited by YopE in Dictyostelium can be explained, at least in part, by inactivation of one or more Rho family GTPases. It further demonstrates that the social amoeba Dictyostelium discoideum can be used as an efficient and easy-to-handle model organism in order to analyze the function of a translocated GAP protein of a human pathogen.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (II

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2008-03-01

Full Text Available Fetuses with neural tube defects (NTDs maybe associated with syndromes, disorders, and maternal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal risk factors associated with NTDs, such as Currarino syndrome, sacral defect with anterior meningocele, Jarcho-Levin syndrome (spondylo-costal dysostosis, lateral meningocele syndrome, neurofibromatosis type I, Marfan syndrome, and hyperthermia. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders, and maternal risk factors may be different from those of non-syndromic multifactorial NTDs. Perinatal identification of NTDs should alert one to the syndromes, disorders, and maternal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling.

Rare variants in SOS2 and LZTR1 are associated with Noonan syndrome.

Science.gov (United States)

Yamamoto, Guilherme Lopes; Aguena, Meire; Gos, Monika; Hung, Christina; Pilch, Jacek; Fahiminiya, Somayyeh; Abramowicz, Anna; Cristian, Ingrid; Buscarilli, Michelle; Naslavsky, Michel Satya; Malaquias, Alexsandra C; Zatz, Mayana; Bodamer, Olaf; Majewski, Jacek; Jorge, Alexander A L; Pereira, Alexandre C; Kim, Chong Ae; Passos-Bueno, Maria Rita; Bertola, Débora Romeo

2015-06-01

Noonan syndrome is an autosomal dominant, multisystemic disorder caused by dysregulation of the RAS/mitogen activated protein kinase (MAPK) pathway. Heterozygous, pathogenic variants in 11 known genes account for approximately 80% of cases. The identification of novel genes associated with Noonan syndrome has become increasingly challenging, since they might be responsible for very small fractions of the cases. A cohort of 50 Brazilian probands negative for pathogenic variants in the known genes associated with Noonan syndrome was tested through whole-exome sequencing along with the relatives in the familial cases. Families from the USA and Poland with mutations in the newly identified genes were included subsequently. We identified rare, segregating or de novo missense variants in SOS2 and LZTR1 in 4% and 8%, respectively, of the 50 Brazilian probands. SOS2 and LZTR1 variants were also found to segregate in one American and one Polish family. Notably, SOS2 variants were identified in patients with marked ectodermal involvement, similar to patients with SOS1 mutations. We identified two novel genes, SOS2 and LZTR1, associated with Noonan syndrome, thereby expanding the molecular spectrum of RASopathies. Mutations in these genes are responsible for approximately 3% of all patients with Noonan syndrome. While SOS2 is a natural candidate, because of its homology with SOS1, the functional role of LZTR1 in the RAS/MAPK pathway is not known, and it could not have been identified without the large pedigrees. Additional functional studies are needed to elucidate the role of LZTR1 in RAS/MAPK signalling and in the pathogenesis of Noonan syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The association between self-reported sleep quality and metabolic syndrome.

Directory of Open Access Journals (Sweden)

Hao-Chang Hung

Full Text Available OBJECTIVES: Short and long sleep duration are associated with metabolic syndrome. However, there is limited research on the association between sleep quality and metabolic syndrome, and thus the aim of this study is to investigate this relationship. MATERIALS AND METHODS: The cross-sectional baseline data were collected from the decoded database of the Prevention Health Center of National Cheng Kung University Hospital from 2002 to 2006. The diagnosis of metabolic syndrome was according to the statement of the American Heart Association/National Heart, Lung, and Blood Institute. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI. A higher global PSQI score indicates poorer sleep quality, and a global PSQI score greater than five differentiates poor from good sleepers. RESULTS: Of the 3,435 subjects recruited, 899 (26.2% had metabolic syndrome. Subjects with metabolic syndrome had higher PSQI and prevalence of poor sleepers than those without metabolic syndrome. The multivariate lineal regression analysis showed that female gender, metabolic syndrome, sleep duration, snoring, alcohol drinking, and habitual exercise were independent predictors of PSQI. When substituting metabolic syndrome with the five components, hyperglycemia and low high-density lipoprotein cholesterol (HDL-C were positively associated with PSQI. The multivariate logistic regression analyses showed that female gender, metabolic syndrome, sleep duration, and snoring were independently associated with being poor sleepers. Of the five components, only low HDL-C was an independent predictor of being poor sleepers. CONCLUSIONS: Subjects with metabolic syndrome have higher global PSQI scores and a higher risk of being poor sleepers. Of the five components of metabolic syndrome, hyperglycemia and low HDL-C are independently associated with the global PSQI scores, while low HDL-C is an independent predictor of being poor sleepers.

[Anticonvulsant hypersensitivity syndrome and lamotrigine-associated anticonvulsant hypersensitivity syndrome].

Science.gov (United States)

Taillia, H; Alla, P; Fournier, B; Bounolleau, P; Ouologem, M; Ricard, D; Sallansonnet-Froment, M; de Greslan, T; Renard, J-L

2009-10-01

Anticonvulsant hypersensitivity syndrome (AHS) is defined by the association of high fever, cutaneous rash and multiorgan-system abnormalities (incidence, one in 1000 to one in 10,000 exposures). Fatal complications are described in 10%. This reaction usually develops 1 to 12 weeks after initiation of an aromatic anticonvulsant. Drug rash with eosinophilia and systemic symptoms (DRESS) can be discussed as differential diagnosis. Several hypotheses have been put forward to explain the pathogenesis of AHS. These include accumulation of toxic metabolites, antibody production and viral infection. The one based on toxic metabolites has found the greatest acceptance due to the fact that it can be proven by an in vitro test, the lymphocyte toxicity assay. In vivo, skin biopsies show characteristic findings of erythema multiform or typical leucocytoclastic angitis. The patch-test is positive in 80% of the cases. Lamotrigine-associated anticonvulsant hypersensitivity syndrome (LASH) is rare and was described in 1998. We report two new cases demonstrating the two particular configurations of apparition of LASH found in the 14 cases from the review of literature (Pubmed: anticonvulsant hypersensitivity syndrome - lamotrigine): high doses of lamotrigine (or lamotrigine in very young or old patients), and lamotrigine associated with another anti-epileptic (phenobarbital or sodium valproate). We discuss the links between DRESS after lamotrigine and LASH as illustrated in a new case.

Cardiac involvement in antiphospholipid syndrome associated with Sneddon syndrome: a challenging diagnosis.

Science.gov (United States)

Faustino, Ana; Paiva, Luís; Morgadinho, Ana; Trigo, Emília; Botelho, Ana; Costa, Marco; Leitão-Marques, António

2014-02-01

Sneddon syndrome is a rare clinical entity characterized by the association of ischemic cerebrovascular disease and livedo reticularis. The authors report a case of stroke and myocardial infarction in a 39-year-old man with Sneddon syndrome and antiphospholipid syndrome who subsequently met some criteria for systemic lupus erythematosus, highlighting the complexity of cardiovascular involvement in systemic diseases. Copyright © 2013 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Association between Metabolic Syndrome and Job Rank.

Science.gov (United States)

Mehrdad, Ramin; Pouryaghoub, Gholamreza; Moradi, Mahboubeh

2018-01-01

The occupation of the people can influence the development of metabolic syndrome. To determine the association between metabolic syndrome and its determinants with the job rank in workers of a large car factory in Iran. 3989 male workers at a large car manufacturing company were invited to participate in this cross-sectional study. Demographic and anthropometric data of the participants, including age, height, weight, and abdominal circumference were measured. Blood samples were taken to measure lipid profile and blood glucose level. Metabolic syndrome was diagnosed in each participant based on ATPIII 2001 criteria. The workers were categorized based on their job rank into 3 groups of (1) office workers, (2) workers with physical exertion, and (3) workers with chemical exposure. The study characteristics, particularly the frequency of metabolic syndrome and its determinants were compared among the study groups. The prevalence of metabolic syndrome in our study was 7.7% (95% CI 6.9 to 8.5). HDL levels were significantly lower in those who had chemical exposure (p=0.045). Diastolic blood pressure was significantly higher in those who had mechanical exertion (p=0.026). The frequency of metabolic syndrome in the office workers, workers with physical exertion, and workers with chemical exposure was 7.3%, 7.9%, and 7.8%, respectively (p=0.836). Seemingly, there is no association between metabolic syndrome and job rank.

Structure of the ribosomal interacting GTPase YjeQ from the enterobacterial species Salmonella typhimurium

International Nuclear Information System (INIS)

Nichols, C. E.; Johnson, C.; Lamb, H. K.; Lockyer, M.; Charles, I. G.; Hawkins, A. R.; Stammers, D. K.

2007-01-01

The X-ray crystal structure of the GTPase YjeQ from S. typhimurium is presented and compared with those of orthologues from T. maritima and B. subtilis. The YjeQ class of P-loop GTPases assist in ribosome biogenesis and also bind to the 30S subunit of mature ribosomes. YjeQ ribosomal binding is GTP-dependent and thought to specifically direct protein synthesis, although the nature of the upstream signal causing this event in vivo is as yet unknown. The attenuating effect of YjeQ mutants on bacterial growth in Escherichia coli makes it a potential target for novel antimicrobial agents. In order to further explore the structure and function of YjeQ, the isolation, crystallization and structure determination of YjeQ from the enterobacterial species Salmonella typhimurium (StYjeQ) is reported. Whilst the overall StYjeQ fold is similar to those of the previously reported Thematoga maritima and Bacillus subtilis orthologues, particularly the GTPase domain, there are larger differences in the three OB folds. Although the zinc-finger secondary structure is conserved, significant sequence differences alter the nature of the external surface in each case and may reflect varying signalling pathways. Therefore, it may be easier to develop YjeQ-specific inhibitors that target the N- and C-terminal regions, disrupting the metabolic connectivity rather than the GTPase activity. The availability of coordinates for StYjeQ will provide a significantly improved basis for threading Gram-negative orthologue sequences and in silico compound-screening studies, with the potential for the development of species-selective drugs

Structure of the ribosomal interacting GTPase YjeQ from the enterobacterial species Salmonella typhimurium

Energy Technology Data Exchange (ETDEWEB)

Nichols, C. E. [Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Johnson, C.; Lamb, H. K. [Institute of Cell and Molecular Biosciences, Catherine Cookson Building, Medical School, Framlington Place, Newcastle University, Newcastle-upon-Tyne NE2 4HH (United Kingdom); Lockyer, M. [Arrow Therapeutics Ltd, Britannia House, Trinity Street, Borough, London SE1 1DA (United Kingdom); Charles, I. G. [The Wolfson Institute for Biomedical Research, The Cruciform Building, University College London, Gower Street, London WC1E 6BT (United Kingdom); Hawkins, A. R. [Institute of Cell and Molecular Biosciences, Catherine Cookson Building, Medical School, Framlington Place, Newcastle University, Newcastle-upon-Tyne NE2 4HH (United Kingdom); Stammers, D. K., E-mail: daves@strubi.ox.ac.uk [Division of Structural Biology, The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

2007-11-01

The X-ray crystal structure of the GTPase YjeQ from S. typhimurium is presented and compared with those of orthologues from T. maritima and B. subtilis. The YjeQ class of P-loop GTPases assist in ribosome biogenesis and also bind to the 30S subunit of mature ribosomes. YjeQ ribosomal binding is GTP-dependent and thought to specifically direct protein synthesis, although the nature of the upstream signal causing this event in vivo is as yet unknown. The attenuating effect of YjeQ mutants on bacterial growth in Escherichia coli makes it a potential target for novel antimicrobial agents. In order to further explore the structure and function of YjeQ, the isolation, crystallization and structure determination of YjeQ from the enterobacterial species Salmonella typhimurium (StYjeQ) is reported. Whilst the overall StYjeQ fold is similar to those of the previously reported Thematoga maritima and Bacillus subtilis orthologues, particularly the GTPase domain, there are larger differences in the three OB folds. Although the zinc-finger secondary structure is conserved, significant sequence differences alter the nature of the external surface in each case and may reflect varying signalling pathways. Therefore, it may be easier to develop YjeQ-specific inhibitors that target the N- and C-terminal regions, disrupting the metabolic connectivity rather than the GTPase activity. The availability of coordinates for StYjeQ will provide a significantly improved basis for threading Gram-negative orthologue sequences and in silico compound-screening studies, with the potential for the development of species-selective drugs.

Korsakoff's syndrome is preventable

NARCIS (Netherlands)

Oudman, Erik; Wijnia, Jan W.

2014-01-01

Wernicke-Korsakoff syndrome (WKS) is a life-threatening neuropsychiatric disorder caused by thiamine (vitamin B1) deficiency. Wernicke-Korsakoff syndrome is associated with mammillary body edema and small vessel ischemia. Many patients who develop WKS have a history of serious alcoholism and

Fragile X-associated tremor/ataxia syndrome.

Science.gov (United States)

Hoem, Gry; Koht, Jeanette

2017-10-31

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a hereditary neurodegenerative disorder caused by a mutation on the X chromosome. The major signs and symptoms are tremor, ataxia and parkinsonism. Up to one in 2 000 persons over 50 years of age will develop the syndrome. There is reason to believe that too few individuals in Norway undergo testing for this condition.

De novo mutations in ARID1B associated with both syndromic and non-syndromic short stature.

Science.gov (United States)

Yu, Yongguo; Yao, RuEn; Wang, Lili; Fan, Yanjie; Huang, Xiaodong; Hirschhorn, Joel; Dauber, Andrew; Shen, Yiping

2015-09-16

Human height is a complex trait with a strong genetic basis. Recently, a significant association between rare copy number variations (CNVs) and short stature has been identified, and candidate genes in these rare CNVs are being explored. This study aims to evaluate the association between mutations in ARID1B gene and short stature, both the syndromic and non-syndromic form. Based on a case-control study of whole genome chromosome microarray analysis (CMA), three overlapping CNVs were identified in patients with developmental disorders who exhibited short stature. ARID1B, a causal gene for Coffin Siris syndrome, is the only gene encompassed by all three CNVs. A following retrospective genotype-phenotype analysis based on a literature review confirmed that short stature is a frequent feature in those Coffin-Siris syndrome patients with ARID1B mutations. Mutation screening of ARID1B coding regions was further conducted in a cohort of 48 non-syndromic short stature patients,andfour novel missense variants including two de novo mutations were found. These results suggest that haploinsufficient mutations of ARID1B are associated with syndromic short stature including Coffin-Siris syndrome and intellectual disability, while rare missense variants in ARID1B are associated with non-syndromic short stature. This study supports the notion that mutations in genes related to syndromic short stature may exert milder effect and contribute to short stature in the general population.

Association of Metabolic Syndrome and Its Components with Knee Osteoarthritis

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Shahpoor Maddah

2015-12-01

Full Text Available The association of obesity and other metabolic conditions with osteoarthritis is under debate; however, a strong link between metabolic disturbances is suggested to contribute to increased incidences and progression of osteoarthritis. We examined the association of metabolic syndrome and its components with the incidence of knee osteoarthritis in Iranian population. A community-based study was conducted on a total of 625 Iranian volunteers with the complaint of knee pain. Weight-bearing and anteroposterior plain radiographs of both knees were taken on the day of admission. Metabolic syndrome was diagnosed using the modified Adult Treatment Panel III of the National Cholesterol Education Program criteria. Prevalence rates of metabolic syndrome were 22.5% in males and 11.6% in females (P=0.002. The prevalence rate of knee osteoarthritis was 20.0% in males and 43.8% of females (P<0.001. In both genders, osteoarthritis group had higher serum levels of triglyceride and systolic blood pressure in comparison with non-osteoarthritis group. Women with osteoarthritis had higher Body Mass Index (BMI, however, this association was not observed in men. In females, the presence of osteoarthritis was significantly associated with the presence of metabolic syndrome, with the risk of metabolic syndrome in the osteoarthritis group at 2.187 fold the risk in the non-osteoarthritis group. But, the presence of osteoarthritis was not associated with metabolic syndrome in males. Metabolic syndrome mainly through high BMI is associated with knee osteoarthritis in the Iranian women, but neither metabolic syndrome nor any related components are associated with knee osteoarthritis in men.

Genetics Home Reference: fragile X-associated tremor/ataxia syndrome

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... Share: Email Facebook Twitter Home Health Conditions FXTAS Fragile X-associated tremor/ataxia syndrome Printable PDF Open All ... Javascript to view the expand/collapse boxes. Description Fragile X-associated tremor/ataxia syndrome ( FXTAS ) is characterized by ...

Palmitoylation of the immunity related GTPase, Irgm1: impact on membrane localization and ability to promote mitochondrial fission.

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Stanley C Henry

Full Text Available The Immunity-Related GTPases (IRG are a family of large GTPases that mediate innate immune responses. Irgm1 is particularly critical for immunity to bacteria and protozoa, and for inflammatory homeostasis in the intestine. Although precise functions for Irgm1 have not been identified, prior studies have suggested roles in autophagy/mitophagy, phagosome remodeling, cell motility, and regulating the activity of other IRG proteins. These functions ostensibly hinge on the ability of Irgm1 to localize to intracellular membranes, such as those of the Golgi apparatus and mitochondria. Previously, it has been shown that an amphipathic helix, the αK helix, in the C-terminal portion of the protein partially mediates membrane binding. However, in absence of αK, there is still substantial binding of Irgm1 to cellular membranes, suggesting the presence of other membrane binding motifs. In the current work, an additional membrane localization motif was found in the form of palmitoylation at a cluster of cysteines near the αK. An Irgm1 mutant possessing alanine to cysteine substitutions at these amino acids demonstrated little residual palmitoylation, yet it displayed only a small decrease in localization to the Golgi and mitochondria. In contrast, a mutant containing the palmitoylation mutations in combination with mutations disrupting the amphipathic character of the αK displayed a complete loss of apparent localization to the Golgi and mitochondria, as well as an overall loss of association with cellular membranes in general. Additionally, Irgm1 was found to promote mitochondrial fission, and this function was undermined in Irgm1 mutants lacking the palmitoylation domain, and to a greater extent in those lacking the αK, or the αK and palmitoylation domains combined. Our data suggest that palmitoylation together with the αK helix firmly anchor Irgm1 in the Golgi and mitochondria, thus facilitating function of the protein.

Structural Pituitary Abnormalities Associated With CHARGE Syndrome

Science.gov (United States)

Gregory, Louise C.; Gevers, Evelien F.; Baker, Joanne; Kasia, Tessa; Chong, Kling; Josifova, Dragana J.; Caimari, Maria; Bilan, Frederic; McCabe, Mark J.

2013-01-01

Introduction: CHARGE syndrome is a multisystem disorder that, in addition to Kallmann syndrome/isolated hypogonadotrophic hypogonadism, has been associated with anterior pituitary hypoplasia (APH). However, structural abnormalities such as an ectopic posterior pituitary (EPP) have not yet been described in such patients. Objective: The aims of the study were: 1) to describe the association between CHARGE syndrome and a structurally abnormal pituitary gland; and 2) to investigate whether CHD7 variants, which are identified in 65% of CHARGE patients, are common in septo-optic dysplasia /hypopituitarism. Methods: We describe 2 patients with features of CHARGE and EPP. CHD7 was sequenced in these and other patients with septo-optic dysplasia/hypopituitarism. Results: EPP, APH, and GH, TSH, and probable LH/FSH deficiency were present in 1 patient, and EPP and APH with GH, TSH, LH/FSH, and ACTH deficiency were present in another patient, both of whom had features of CHARGE syndrome. Both had variations in CHD7 that were novel and undetected in control cohorts or in the international database of CHARGE patients, but were also present in their unaffected mothers. No CHD7 variants were detected in the patients with septo-optic dysplasia/hypopituitarism without additional CHARGE features. Conclusion: We report a novel association between CHARGE syndrome and structural abnormalities of the pituitary gland in 2 patients with variations in CHD7 that are of unknown significance. However, CHD7 mutations are an uncommon cause of septo-optic dysplasia or hypopituitarism. Our data suggest the need for evaluation of pituitary function/anatomy in patients with CHARGE syndrome. PMID:23526466

Rho GTPase protein Cdc42 is critical for postnatal cartilage development

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Nagahama, Ryo [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Department of Orthodontics, School of Dentistry, Showa University, Tokyo (Japan); Yamada, Atsushi, E-mail: yamadaa@dent.showa-u.ac.jp [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Tanaka, Junichi [Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo (Japan); Aizawa, Ryo [Department of Periodontology, School of Dentistry, Showa University, Tokyo (Japan); Suzuki, Dai [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan); Kassai, Hidetoshi [Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Yamamoto, Matsuo [Department of Periodontology, School of Dentistry, Showa University, Tokyo (Japan); Mishima, Kenji [Department of Oral Diagnostic Sciences, School of Dentistry, Showa University, Tokyo (Japan); Aiba, Atsu [Laboratory of Animal Resources, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Tokyo (Japan); Maki, Koutaro [Department of Orthodontics, School of Dentistry, Showa University, Tokyo (Japan); Kamijo, Ryutaro [Department of Biochemistry, School of Dentistry, Showa University, Tokyo (Japan)

2016-02-19

Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 {sup fl/fl}; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 {sup fl/fl}) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.

Unusual paraneoplastic syndromes of breast carcinoma: a combination of cerebellar degeneration and Lambert-Eaton Myasthenic Syndrome.

LENUS (Irish Health Repository)

Romics, L

2011-06-01

Paraneoplastic neurological disorders are rare complications of breast carcinoma. Lambert-Eaton Myasthenic Syndrome (LEMS) is most commonly associated with small cell lung cancer. However, a combination of LEMS and subacute cerebellar degeneration as paraneoplastic syndromes is extremely rare, and has never been described in association with breast cancer.

Reduced Flexibility Associated with Metabolic Syndrome in Community-Dwelling Elders

Science.gov (United States)

Chang, Ke-Vin; Hung, Chen-Yu; Li, Chia-Ming; Lin, Yu-Hung; Wang, Tyng-Guey; Tsai, Keh-Sung; Han, Der-Sheng

2015-01-01

Background The ageing process may lead to reductions in physical fitness, a known risk factor in the development of metabolic syndrome. The purpose of the current study was to evaluate cross-sectional and combined associations of metabolic syndrome with body composition and physical fitness in a community based geriatric population. Methods A total of 628 community-dwelling elders attending a geriatric health examination were enrolled in the study. The diagnosis of metabolic syndrome was based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criterion with Asian cutoff of waist girth was adopted in this study. Body composition was obtained using bioimpedance analysis, and physical fitness was evaluated through the measurement of muscle strength (handgrip force), lower extremity muscle endurance (sit-to-stand test), flexibility (sit-and-reach test), and cardiorespiratory endurance (2-minute step test). Multivariable logistic regression and correlation analysis were performed to determine the association of metabolic syndrome with body composition and functionality variables. Results Metabolic syndrome was associated with increased skeletal muscle index (SMI) (odds ratio (OR), 1.61, 95% confidence interval (CI), 1.25–2.07) and decreased flexibility (OR, 0.97, 95% CI, 0.95–0.99) compared with those without metabolic syndrome. When body mass index was accounted for in the analysis, the association of SMI with metabolic syndrome was reduced. Waist circumference was positively correlated with SMI but negatively correlated with flexibility, whereas high density lipoprotein was positively correlated with flexibility but negatively correlated with SMI. Conclusion Reduced flexibility was positively associated with metabolic syndrome independent of age, gender, body composition, and functionality measurements in a community based geriatric population. Significant associations between metabolic syndrome with muscle strength

Reduced flexibility associated with metabolic syndrome in community-dwelling elders.

Directory of Open Access Journals (Sweden)

Ke-Vin Chang

Full Text Available The ageing process may lead to reductions in physical fitness, a known risk factor in the development of metabolic syndrome. The purpose of the current study was to evaluate cross-sectional and combined associations of metabolic syndrome with body composition and physical fitness in a community based geriatric population.A total of 628 community-dwelling elders attending a geriatric health examination were enrolled in the study. The diagnosis of metabolic syndrome was based on the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III criterion with Asian cutoff of waist girth was adopted in this study. Body composition was obtained using bioimpedance analysis, and physical fitness was evaluated through the measurement of muscle strength (handgrip force, lower extremity muscle endurance (sit-to-stand test, flexibility (sit-and-reach test, and cardiorespiratory endurance (2-minute step test. Multivariable logistic regression and correlation analysis were performed to determine the association of metabolic syndrome with body composition and functionality variables.Metabolic syndrome was associated with increased skeletal muscle index (SMI (odds ratio (OR, 1.61, 95% confidence interval (CI, 1.25-2.07 and decreased flexibility (OR, 0.97, 95% CI, 0.95-0.99 compared with those without metabolic syndrome. When body mass index was accounted for in the analysis, the association of SMI with metabolic syndrome was reduced. Waist circumference was positively correlated with SMI but negatively correlated with flexibility, whereas high density lipoprotein was positively correlated with flexibility but negatively correlated with SMI.Reduced flexibility was positively associated with metabolic syndrome independent of age, gender, body composition, and functionality measurements in a community based geriatric population. Significant associations between metabolic syndrome with muscle strength and cardiorespiratory fitness in the

MULTIMODAL IMAGING OF ANGIOID STREAKS ASSOCIATED WITH TURNER SYNDROME.

Science.gov (United States)

Chiu, Bing Q; Tsui, Edmund; Hussnain, Syed Amal; Barbazetto, Irene A; Smith, R Theodore

2018-02-13

To report multimodal imaging in a novel case of angioid streaks in a patient with Turner syndrome with 10-year follow-up. Case report of a patient with Turner syndrome and angioid streaks followed at Bellevue Hospital Eye Clinic from 2007 to 2017. Fundus photography, fluorescein angiography, and optical coherence tomography angiography were obtained. Angioid streaks with choroidal neovascularization were noted in this patient with Turner syndrome without other systemic conditions previously correlated with angioid streaks. We report a case of angioid streaks with choroidal neovascularization in a patient with Turner syndrome. We demonstrate that angioid streaks, previously associated with pseudoxanthoma elasticum, Ehlers-Danlos syndrome, Paget disease of bone, and hemoglobinopathies, may also be associated with Turner syndrome, and may continue to develop choroidal neovascularization, suggesting the need for careful ophthalmic examination in these patients.

Rheumatic fever associated with antiphospholipid syndrome: systematic review.

Science.gov (United States)

da Silva, Felipe; de Carvalho, Jozélio

2014-01-01

To evaluate the clinical associations between rheumatic fever and antiphospholipid syndrome and the impact of coexistence of these two diseases in an individual. Systematic review in electronics databases, regarding the period from 1983 to 2012. The keywords: "Rheumatic Fever," "Antiphospholipid Syndrome," and "Antiphospholipid Antibody Syndrome" are used. were identified 11 cases described in the literature about the association of rheumatic fever and antiphospholipid syndrome. Clinical presentation of rheumatic fever was characterized by the predominance of carditis (11/11) and chorea (7/11). Regarding the manifestations of APS, the stroke was observed in 7/11 (63.6%), with one of them having probable embolic origin. The present study brings the information that the association between APS and RF is quite rare, however, is of great clinical importance. Doctors who deal with the RF should include in their differential diagnosis the APS, especially in the presence of stroke in patients with RF and whose echocardiogram does not show intracavitary thrombi.

Is Duane retraction syndrome part of the VACTERL association?

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Akar S

2013-03-01

Full Text Available Serpil Akar,1 Birsen Gokyigit,1 Isilay Kavadarli,2 Ahmet Demirok11Pediatric Ophthalmology and Strabismus Department, Prof Dr N Resat Belger Beyoglu Education and Research Eye Hospital, Istanbul, 2Department of Ophthalmology, Gaziantep, Kilis State Hospital, Kilis, TurkeyAbstract: We report here a patient with type 1 Duane’s retraction syndrome and multiple congenital abnormalities as a result of the VACTERL association. The presented combination of Duane’s retraction syndrome and the VACTERL association has not been reported in the literature. The present case was instructive for reviewing the continuous spectrum of ocular anomalies that accompany the VACTERL association.Keywords: Duane’s retraction syndrome, VACTERL association, combination

A Case of Swyer Syndrome Associated with Advanced Gonadal Dysgerminoma Involving Long Survival

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Salete Da Silva Rios

2015-03-01

Full Text Available Swyer syndrome is caused by abnormal sex differentiation during the embryonic period, resulting in incomplete intrauterine masculinization and undifferentiated gonads. The current case report describes a patient with Swyer syndrome associated with stage 3 gonadal dysgerminoma who has survived for 23 years. At age 18, this patient sought assistance for primary amenorrhea from the Gynecological Services Department of the University of Brasília Hospital. A physical examination revealed that the patient was at Tanner stage 4 with respect to axillary hair, breasts, and pubic hair; she presented with a eutrophic vagina and a small cervix. She was treated with a combination of estrogens and progestogens to induce cycling. Approximately 4 years later, a complex tumor was found and resected; a histopathological analysis revealed that this tumor was a right adnexal dysgerminoma with peritoneal affection. The patient was also subjected to chemotherapy. Her follow-up has continued to the present time, with no signs of tumor recurrence. In conclusion, this report describes an extremely rare case in which Swyer syndrome was associated with ovarian dysgerminoma; relative to similar patients, the described patient has survived for an unusually prolonged time.

Primary Sjogren's syndrome associated with inappropriate ...

African Journals Online (AJOL)

A patient in whom primary Sjogren's syndrome and inappropriate antiduretic hormone secretion were associated is reported. This is the first report of such an association. The possible pathophysiological mechanisms are discussed and vasculitis proposed as the underlying pathogenetic mechanism.

The monomeric GTPase RabA2 is required for progression and maintenance of membrane integrity of infection threads during root nodule symbiosis.

Science.gov (United States)

Dalla Via, Virginia; Traubenik, Soledad; Rivero, Claudio; Aguilar, O Mario; Zanetti, María Eugenia; Blanco, Flavio Antonio

2017-04-01

Progression of the infection canal that conducts rhizobia to the nodule primordium requires a functional Rab GTPase located in Golgi/trans-Golgi that also participate in root hair polar growth. Common bean (Phaseolus vulgaris) symbiotically associates with its partner Rhizobium etli, resulting in the formation of root nitrogen-fixing nodules. Compatible bacteria can reach cortical cells in a tightly regulated infection process, in which the specific recognition of signal molecules is a key step to select the symbiotic partner. In this work, we show that RabA2, a monomeric GTPase from common bean, is required for the progression of the infection canal, referred to as the infection thread (IT), toward the cortical cells. Expression of miss-regulated mutant variants of RabA2 resulted in an increased number of abortive infection events, including bursting of ITs and a reduction in the number of nodules. Nodules formed in these plants were small and contained infected cells with disrupted symbiosome membranes, indicating either early senescence of these cells or defects in the formation of the symbiosome membrane during bacterial release. RabA2 localized to mobile vesicles around the IT, but mutations that affect GTP hydrolysis or GTP/GDP exchange modified this localization. Colocalization of RabA2 with ArfA1 and a Golgi marker indicates that RabA2 localizes in Golgi stacks and the trans-Golgi network. Our results suggest that RabA2 is part of the vesicle transport events required to maintain the integrity of the membrane during IT progression.

Idiopathic hypertrophic cranial pachymeningitis associated with Sweet's Syndrome

International Nuclear Information System (INIS)

Cano, Antonio; Ribes, Ramon; Riva, Andres de la; Rubio, Fernando Lopez; Sanchez, Carmen; Sancho, Jose L.

2002-01-01

A case of hypertrophic cranial pachymeningitis associated with Sweet's Syndrome is presented. Both entities have been described in association with several other chronic systemic inflammatory diseases and autoimmune conditions. To our knowledge the coexistence between Sweet's Syndrome and hypertrophic cranial pachymeningitis has not been reported up to date. We suggest a possible autoimmune or dysimmune mechanism in the pathogenesis of these two entities

Chiari I malformation associated with turner syndrome

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Kamble Jayaprakash Harsha

2017-01-01

Full Text Available Turner syndrome (TS is a rare genetic disease due to the absence of one X chromosome. Patients with TS have more subtle neurological/neuropsychiatric problems, while headache is an uncommon clinical presentation which needs attention. We report a 12-year-old child presenting with typical cough headache. Her magnetic resonance imaging revealed Chiari I malformation associated with TS. To the best of our knowledge, Chiari I malformation associated with TS is not described in literature. We report the first case of TS associated with Chiari I malformation. Interestingly, Chiari I malformation is also associated with Noonan's syndrome, which is a close morphological mimicker of TS, raising the possibility of sharing similar pathogenesis in both conditions.

A class of dynamin-like GTPases involved in the generation of the tubular ER network

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Hu, Junjie; Shibata, Yoko; Zhu, Peng-Peng; Voss, Christiane; Rismanchi, Neggy; Prinz, William A.; Rapoport, Tom A.; Blackstone, Craig

2009-01-01

The endoplasmic reticulum (ER) consists of tubules that are shaped by the reticulons and DP1/Yop1p, but how the tubules form an interconnected network is unknown. Here, we show that mammalian atlastins, which are dynamin-like, integral membrane GTPases, interact with the tubule-shaping proteins. The atlastins localize to the tubular ER and are required for proper network formation in vivo and in vitro. Depletion of the atlastins or overexpression of dominant-negative forms inhibits tubule interconnections. The Sey1p GTPase in S. cerevisiae is likely a functional ortholog of the atlastins; it shares the same signature motifs and membrane topology and interacts genetically and physically with the tubule-shaping proteins. Cells simultaneously lacking Sey1p and a tubule-shaping protein have ER morphology defects. These results indicate that formation of the tubular ER network depends on conserved dynamin-like GTPases. Since atlastin-1 mutations cause a common form of hereditary spastic paraplegia, we suggest ER shaping defects as a novel neuropathogenic mechanism. PMID:19665976

Influence of bacterial toxins on the GTPase activity of transducin from bovine retinal rod outer segments

International Nuclear Information System (INIS)

Rybin, V.O.; Gureeva, A.A.

1986-01-01

The action of cholera toxin, capable of ADP-ribosylation of the activator N/sub s/ protein, and pertussis toxin, capable of ADP-ribosylation of the inhibitor N/sub i/ protein of the adenylate cyclase complex, on transducin, the GTP-binding protein of the rod outer segments of the retina, was investigated. It was shown that under the action of pertussis and cholera toxins, the GTPase activity of transducin is inhibited. Pertussin toxin inhibits the GTPase of native retinal rod outer segments by 30-40%, while GTPase of homogeneous transducin produces a 70-80% inhibition. The action of toxins on transducin depends on the presence and nature of the guanylic nucleotide with which incubation is performed. On the basis of the data obtained it is suggested that pertussis toxin interacts with pretransducin and with the transducin-GDP complex, while cholera toxin ADP-ribosylates the transducin-GTP complex and does not act on transducin lacking GTP

Maffucci's syndrome associated with chondrosarcoma and aneurysm: case report

International Nuclear Information System (INIS)

Lim, Hyoung Gun; Yoo, Won Jong; Lim, Yeon Soo; Sung, Mi Sook; Chung, Myung Hee; Lee, Hae Giu; Jung, So Lyung; Kim, Jae Na

2002-01-01

Maffucci syndrome is rare congenital non-inherited condition characterized by multiple enchondromas and cutaneous hemangiomas. It is associated with increased risk of malignancy, including chondrosarcomas, and because of generalized mesodermal dysplasia, aneurysms can develop. We present a case of maffucci syndrome associated with intracranial chondrosarcoma and aneurysm

Genetics Home Reference: Lenz microphthalmia syndrome

Science.gov (United States)

... eyeballs that are abnormally small ( microphthalmia ) or absent (anophthalmia), leading to vision loss or blindness. Other eye ... Lenz dysplasia Lenz syndrome MAA MCOPS1 microphthalmia or anophthalmos with associated anomalies microphthalmia, syndromic 1 Related Information ...

Rare association of prune belly syndrome with pouch colon

Directory of Open Access Journals (Sweden)

M Ragavan

2011-01-01

Full Text Available M Ragavan1, U Haripriya1, PV Pradeep1, J Sarvavinothini21Department of Endocrine Surgery, 2Department of Anaesthesia, Narayana Medical College and Superspeciality Hospital, Nellore, Andhra Pradesh, IndiaAbstract: Prune belly syndrome is a triad characterized by abdominal wall musculature deficiency, cryptorchidism and urinary tract abnormalities, and is often associated with other anomalies. Although associated anorectal anomalies have been reported with this syndrome, only two cases of pouch colon, a rare type of anorectal malformation, have been reported. We report a case of prune belly syndrome with pouch colon presenting with retention of urine.Keywords: prune belly, triad syndrome, pouch colon, anorectal malformation

Shift Work Is Associated with Metabolic Syndrome in Young Female Korean Workers.

Science.gov (United States)

Yu, Kyoung Hwa; Yi, Yu Hyeon; Kim, Yun Jin; Cho, Byung Mann; Lee, Sang Yeoup; Lee, Jeong Gyu; Jeong, Dong Wook; Ji, So Yeon

2017-03-01

Shift work is associated with health problems, including metabolic syndrome. This study investigated the association between shift work and metabolic syndrome in young workers. A total of 3,317 subjects aged 20-40 years enrolled in the 2011-2012 Korean National Health and Nutrition Examination Survey were divided into shift and day workers. We conducted a cross-sectional study and calculated odds ratios using multivariate logistic regression analysis in order to examine the association between shift work and metabolic syndrome. The prevalence of metabolic syndrome was 14.3% and 7.1% among male and female shift workers, respectively. After adjusting for confounding factors, shift work was associated with metabolic syndrome in female workers (odds ratio, 2.53; 95% confidence interval, 1.12 to 5.70). Shift work was associated with metabolic syndrome in young women. Timely efforts are necessary to manage metabolic syndrome in the workplace.

Sedentary activity associated with metabolic syndrome independent of physical activity

DEFF Research Database (Denmark)

Bankoski, Andrea; Harris, Tamara B; McClain, James J

2011-01-01

This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults.......This study examined the association between objectively measured sedentary activity and metabolic syndrome among older adults....

Maffucci's syndrome associated with chondrosarcoma and aneurysm: case report

International Nuclear Information System (INIS)

Lim, Hyoung Gun; Yoo, Won Jong; Lim, Yeon Soo; Sung, Mi Sook; Chung Myung Hee; Lee, Hae Giu; Jung, So Lyung; Kim, Jea NA

2002-01-01

Maffucci syndrome is a rare congenital non-inherited condition characterized by multiple enchondromas and cutaneous hemangiomas. It is associated with increased risk of malignancy, including chondrosarcomas, and because of generalized mesodermal dysplasia, aneurysms can develop. We present a case of Maffucci syndrome associated with intracranial chondrosarcoma and aneurysm

[Association between metabolic syndrome and its components with presbycusis].

Science.gov (United States)

Zhao, Jingbo; Zhang, Mengsi; Li, Yuanyuan; Zhang, Jiarui; Wang, Ningning; Yang, Xiaoshan

2015-07-01

To investigate the effect of metabolic syndrome and its components on presbycusis. Total of 165 cases and 202 controls were continuously collected in Harbin Ninth Hospital from June 2013 to August 2014, these subjects were investigated and received anthropometry and received biochemical test in hospital laboratory. Statistics analysis was adopted by χ2 test, t test and logistic regression model. Only triglyceride abnormal proportion of case group was higher than that of control group among components of metabolic syndrome, and it were associated with age-related hearing loss whether before adjustment or not after adjustment, OR (95% CI) were 1.69 (1.09-2.63) and 1.96 (1.08-3.54) respectively, and others were not associated with presbycusis. In addition, among all of the various combinations of the components of the metabolic syndrome, combination of triglycerides and high-density lipoprotein, combination of triglycerides and blood glucose, combination of triglycerides and blood pressure were associated with age-related hearing loss before adjustment and after adjustment, OR were 5.31 (95% CI 1.63-17.27), 2.66 (95% CI 1.04-6.85) and 2.09 (95% CI 1.04-4.18) respectively. Further more, the metabolic syndrome was not statistically associated with presbycusis, OR were 1.27 (95% CI 0.83-1.94) and 0.92 (95% CI 0.54-1.57) respectively before adjustment and after adjustment. In addition, stratified by age, the metabolic syndrome was still not statistically associated with presbycusis in each stratification, OR were 0.89 (95% CI 0.44-1.82) and 1.49 (95% CI 0.67-3.30) respectively. The triglyceride was associated with presbycusis. Among all of combinations of the components of the metabolic syndrome, combination of triglycerides and high-density lipoprotein, combination of triglycerides and blood glucose, combination of triglycerides and blood pressure were associated with age-related hearing loss.

Megacystis-microcolon-intestinal hypoperistalsis syndrome associated with prune belly syndrome: a case report.

Science.gov (United States)

Akhtar, Tanveer; Alladi, Anand; Siddappa, O S

2012-01-01

Megacystis Microcolon Intestinal Hypoperistalsis Syndrome is a quite rare congenital anomaly that presents with a functional obstruction of the gastrointestinal tract which is usually fatal. It is three to four times more prevalent in females. We present a case of a rare association of a male neonate with Megacystis Microcolon Intestinal Hypoperistalsis Syndrome who in addition had the classical triad of Prune Belly Syndrome and thus suggest a possibility of different spectrums with a common pathogenesis.

Structural Dynamics Control Allosteric Activation of Cytohesin Family Arf GTPase Exchange Factors

Energy Technology Data Exchange (ETDEWEB)

Malaby, Andrew W.; Das, Sanchaita; Chakravarthy, Srinivas; Irving, Thomas C.; Bilsel, Osman; Lambright, David G.

2018-01-01

Membrane dynamic processes including vesicle biogenesis depend on Arf guanosine triphosphatase (GTPase) activation by guanine nucleotide exchange factors (GEFs) containing a catalytic Sec7 domain and a membrane-targeting module such as a pleckstrin homology (PH) domain. The catalytic output of cytohesin family Arf GEFs is controlled by autoinhibitory interactions that impede accessibility of the exchange site in the Sec7 domain. These restraints can be relieved through activator Arf-GTP binding to an allosteric site comprising the PH domain and proximal autoinhibitory elements (Sec7-PH linker and C-terminal helix). Small-angle X-ray scattering and negative-stain electron microscopy were used to investigate the structural organization and conformational dynamics of cytohesin-3 (Grp1) in autoinhibited and active states. The results support a model in which hinge dynamics in the autoinhibited state expose the activator site for Arf-GTP binding, while subsequent C-terminal helix unlatching and repositioning unleash conformational entropy in the Sec7-PH linker to drive exposure of the exchange site.

Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

DEFF Research Database (Denmark)

Benyamin, B; Sørensen, T I A; Schousboe, K

2007-01-01

and environmental factors influencing this cluster in a general population of twin pairs. MATERIALS AND METHODS: A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry. RESULTS: All......AIMS/HYPOTHESIS: The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic...... endophenotypes showed moderate to high heritability (0.31-0.69) and small cial environmental background...

Association of Vogt Koyanagi Harada Syndrome and Seronegative ...

African Journals Online (AJOL)

Association of Vogt Koyanagi Harada Syndrome and Seronegative Rheumatoid Arthritis. Teoman Aydin, Ozgur Taspinar, Meryem Guneser, Yasar Keskin. Abstract. Background: Vogt Koyanagi Harada (VKH) Syndrome is a rarely-seen multi-systemic, autoimmune and inflammatory disease. It observed frequently with ...

Recurrent thrombo-embolic episodes: the association of cholangiocarcinoma with antiphospholipid syndrome

Science.gov (United States)

Samadian, S; Estcourt, L

1999-01-01

Antiphospholipid syndrome is a disorder of recurrent vascular thrombosis, pregnancy loss and thrombocytopenia associated with persistently elevated levels of antiphospholipid antibodies. It was first described in a group of patients with systemic lupus erythematosus but has since been associated with a wide range of conditions, including other autoimmune disorders and malignancy. It can also occur in isolation, the so-called primary antiphospholipid syndrome. We describe an elderly woman with the antiphospholipid syndrome thought to be associated with a cholangiocarcinoma.


Keywords: antiphospholipid syndrome; cholangiocarcinoma; deep vein thrombosis PMID:10396590

Polycystic ovary syndrome and prolactinoma association.

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Yavasoglu, Irfan; Kucuk, Mert; Coskun, Adil; Guney, Engin; Kadikoylu, Gurhan; Bolaman, Zahit

2009-01-01

Hyperprolactinemia is the most common pituitary hormone hypersecretion syndrome in both men and women. Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies affecting 5%-10% of reproductive age women. Here, we present a patient with irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia who was diagnosed as PCOS and prolactinoma and admitted to our clinic. Prolactinoma and PCOS association is a rare condition. This 33-year-old woman was admitted to the internal medicine outpatient clinic for irregular menses, obesity, hirsutism and infertility, and hyperprolactinemia. Her laboratory results were as follows: prolactin was 74 ng/mL (normal range:1.8-20.3 ng/mL). Pelvic ultrasonography was correlated with polycystic ovary syndrome. Pituitary MRI showed 6x8 mm microadenoma at left half. Bromocriptine was started with 1.25 mg/day and increased to 5 mg/day. After six months of bromocriptine treatment her prolactin level was normal and no adenoma was detected in pituitary MRI. PCOS and prolactinoma association should be taken into account in PCOS cases with mild hyperprolactinoma.

Pure Red Cell Aplasia Associated with Good Syndrome

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Masayuki Okui

2017-04-01

Full Text Available Pure red cell aplasia (PRCA and hypogammaglobulinemia are paraneoplastic syndromes that are rarer than myasthenia gravis in patients with thymoma. Good syndrome coexisting with PRCA is an extremely rare pathology. We report the case of a 50-year-old man with thymoma and PRCA associated with Good syndrome who achieved complete PRCA remission after thymectomy and postoperative immunosuppressive therapy, and provide a review of the pertinent literature.

Rho GTPase protein Cdc42 is critical for postnatal cartilage development

International Nuclear Information System (INIS)

Nagahama, Ryo; Yamada, Atsushi; Tanaka, Junichi; Aizawa, Ryo; Suzuki, Dai; Kassai, Hidetoshi; Yamamoto, Matsuo; Mishima, Kenji; Aiba, Atsu; Maki, Koutaro; Kamijo, Ryutaro

2016-01-01

Cdc42, a small Rho GTPase family member, has been shown to regulate multiple cellular functions in vitro, including actin cytoskeletal reorganization, cell migration, proliferation, and gene expression. However, its tissue-specific roles in vivo remain largely unknown, especially in postnatal cartilage development, as cartilage-specific Cdc42 inactivated mice die within a few days after birth. In this study, we investigated the physiological functions of Cdc42 during cartilage development after birth using tamoxifen-induced cartilage-specific inactivated Cdc42 conditional knockout (Cdc42 "f"l"/"f"l; Col2-CreERT) mice, which were generated by crossing Cdc42 flox mice (Cdc42 "f"l"/"f"l) with tamoxifen-induced type II collagen (Col2) Cre transgenic mice using a Cre/loxP system. The gross morphology of the Cdc42 cKO mice was shorter limbs and body, as well as reduced body weight as compared with the controls. In addition, severe defects were found in growth plate chondrocytes of the long bones, characterized by a shorter proliferating zone (PZ), wider hypertrophic zone (HZ), and loss of columnar organization of proliferating chondrocytes, resulting in delayed endochondral bone formation associated with abnormal bone growth. Our findings demonstrate the importance of Cdc42 for cartilage development during both embryonic and postnatal stages. - Highlights: • Tamoxifen-induced cartilage specific inactivated Cdc42 mutant mice were generated. • Cdc42 mutant mice were shorter limbs and body. • Severe defects were found in growth plate chondrocytes.

Rab GTPases Regulate Endothelial Cell Protein C Receptor-Mediated Endocytosis and Trafficking of Factor VIIa

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Nayak, Ramesh C.; Keshava, Shiva; Esmon, Charles T.; Pendurthi, Usha R.; Rao, L. Vijaya Mohan

2013-01-01

Recent studies have established that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR). FVIIa binding to EPCR may promote the endocytosis of this receptor/ligand complex. Rab GTPases are known to play a crucial role in the endocytic and exocytic pathways of receptors or receptor/ligand complexes. The present study was undertaken to investigate the role of Rab GTPases in the intracellular trafficking of EPCR and FVIIa. CHO-EPCR cells and human umbilical vein endothelial cells (HUVEC) were transduced with recombinant adenoviral vectors to express wild-type, constitutively active, or dominant negative mutant of various Rab GTPases. Cells were exposed to FVIIa conjugated with AF488 fluorescent probe (AF488-FVIIa), and intracellular trafficking of FVIIa, EPCR, and Rab proteins was evaluated by immunofluorescence confocal microscopy. In cells expressing wild-type or constitutively active Rab4A, internalized AF488-FVIIa accumulated in early/sorting endosomes and its entry into the recycling endosomal compartment (REC) was inhibited. Expression of constitutively active Rab5A induced large endosomal structures beneath the plasma membrane where EPCR and FVIIa accumulated. Dominant negative Rab5A inhibited the endocytosis of EPCR-FVIIa. Expression of constitutively active Rab11 resulted in retention of accumulated AF488-FVIIa in the REC, whereas expression of a dominant negative form of Rab11 led to accumulation of internalized FVIIa in the cytoplasm and prevented entry of internalized FVIIa into the REC. Expression of dominant negative Rab11 also inhibited the transport of FVIIa across the endothelium. Overall our data show that Rab GTPases regulate the internalization and intracellular trafficking of EPCR-FVIIa. PMID:23555015

RhoA GTPase regulates radiation-induced alterations in endothelial cell adhesion and migration

International Nuclear Information System (INIS)

Rousseau, Matthieu; Gaugler, Marie-Hélène; Rodallec, Audrey; Bonnaud, Stéphanie; Paris, François; Corre, Isabelle

2011-01-01

Highlights: ► We explore the role of RhoA in endothelial cell response to ionizing radiation. ► RhoA is rapidly activated by single high-dose of radiation. ► Radiation leads to RhoA/ROCK-dependent actin cytoskeleton remodeling. ► Radiation-induced apoptosis does not require the RhoA/ROCK pathway. ► Radiation-induced alteration of endothelial adhesion and migration requires RhoA/ROCK. -- Abstract: Endothelial cells of the microvasculature are major target of ionizing radiation, responsible of the radiation-induced vascular early dysfunctions. Molecular signaling pathways involved in endothelial responses to ionizing radiation, despite being increasingly investigated, still need precise characterization. Small GTPase RhoA and its effector ROCK are crucial signaling molecules involved in many endothelial cellular functions. Recent studies identified implication of RhoA/ROCK in radiation-induced increase in endothelial permeability but other endothelial functions altered by radiation might also require RhoA proteins. Human microvascular endothelial cells HMEC-1, either treated with Y-27632 (inhibitor of ROCK) or invalidated for RhoA by RNA interference were exposed to 15 Gy. We showed a rapid radiation-induced activation of RhoA, leading to a deep reorganisation of actin cytoskeleton with rapid formation of stress fibers. Endothelial early apoptosis induced by ionizing radiation was not affected by Y-27632 pre-treatment or RhoA depletion. Endothelial adhesion to fibronectin and formation of focal adhesions increased in response to radiation in a RhoA/ROCK-dependent manner. Consistent with its pro-adhesive role, ionizing radiation also decreased endothelial cells migration and RhoA was required for this inhibition. These results highlight the role of RhoA GTPase in ionizing radiation-induced deregulation of essential endothelial functions linked to actin cytoskeleton.

Differential regulation of the Rac1 GTPase-activating protein (GAP) BCR during oxygen/glucose deprivation in hippocampal and cortical neurons.

Science.gov (United States)

Smith, Katharine R; Rajgor, Dipen; Hanley, Jonathan G

2017-12-08

Brain ischemia causes oxygen and glucose deprivation (OGD) in neurons, triggering a cascade of events leading to synaptic accumulation of glutamate. Excessive activation of glutamate receptors causes excitotoxicity and delayed cell death in vulnerable neurons. Following global cerebral ischemia, hippocampal CA1 pyramidal neurons are more vulnerable to injury than their cortical counterparts, but the mechanisms that underlie this difference are unclear. Signaling via Rho-family small GTPases, their upstream guanine nucleotide exchange factors, and GTPase-activating proteins (GAPs) is differentially dysregulated in response to OGD/ischemia in hippocampal and cortical neurons. Increased Rac1 activity caused by OGD/ischemia contributes to neuronal death in hippocampal neurons via diverse effects on NADPH oxidase activity and dendritic spine morphology. The Rac1 guanine nucleotide exchange factor Tiam1 mediates an OGD-induced increase in Rac1 activity in hippocampal neurons; however, the identity of an antagonistic GAP remains elusive. Here we show that the Rac1 GAP breakpoint cluster region (BCR) associates with NMDA receptors (NMDARs) along with Tiam1 and that this protein complex is more abundant in hippocampal compared with cortical neurons. Although total BCR is similar in the two neuronal types, BCR is more active in hippocampal compared with cortical neurons. OGD causes an NMDAR- and Ca 2+ -permeable AMPAR-dependent deactivation of BCR in hippocampal but not cortical neurons. BCR knockdown occludes OGD-induced Rac1 activation in hippocampal neurons. Furthermore, disrupting the Tiam1-NMDAR interaction with a fragment of Tiam1 blocks OGD-induced Tiam1 activation but has no effect on the deactivation of BCR. This work identifies BCR as a critical player in Rac1 regulation during OGD in hippocampal neurons. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

[Anti-VGKC antibody-associated limbic encephalitis/Morvan syndrome].

Science.gov (United States)

Misawa, Tamako; Mizusawa, Hidehiro

2010-04-01

Anti-voltage-gated potassium channel antibodies (anti-VGKC-Ab) cause hyperexcitability of the peripheral nerve and central nervous system. Peripheral nerve hyperexcitability is the chief manifestation of Issacs syndrome and cramp-fasciculation syndrome. Morvan syndrome is characterized by neuromyotonia with autonomic and CNS involvement. Manifestations involving the CNS without peripheral involvement are characteristic of limbic encephalitis and epilepsy. The clinical features of anti-VGKC-Ab-associated limbic encephalitis are subacute onset of episodic memory impairment, disorientation and agitation. Hyponatremia is also noted in most patients. Cortico-steroid therapy, plasma exchange and intravenous immunoglobulin are effective in treating to not only the clinical symptoms but also hyponatremia. Unlike other anti-VGKC-Ab-associated neurological disorders, paraneoplastic cases are rare. Thus, anti-VGKC-Ab-associated limbic encephalopathy is considered to be an autoimmune, non-paraneoplastic, potentially treatable encephalitis. Morvan syndrome is characterized by widespread neurological symptoms involving the peripheral nervous system (neuromyotonia), autonomic system (hyperhidrosis, severe constipation, urinary incontinence, and cardiac arrhythmia) and the CNS (severe insomnia, hallucinations, impairment of short-term memory and epilepsy). Many patients have an underlying tumor, for example thymoma, lung cancer, testicular cancer and lymphoma; this indicates the paraneoplastic nature of the disease. Needle electro-myography reveals myokimic discharge. In nerve conduction study, stimulus-induced repetitive descharges are frequently demonstrated in involved muscles. Plasma exchange is an effective treatment approach, and tumor resection also improves symptoms. Both VGKC-Ab-associated limbic encephalitis and Morvan syndrome can be successfully treated. Therefore, when these diseases are suspected, it's important to measure the anti-VGKC-Ab level.

Syndromes, Disorders and Maternal Risk Factors Associated with Neural Tube Defects (III

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Chih-Ping Chen

2008-06-01

Full Text Available Fetuses with neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of syndromes, disorders, and maternal and fetal risk factors associated with NTDs, such as omphalocele, OEIS (omphalocele-exstrophy-imperforate anus-spinal defects complex, pentalogy of Cantrell, amniotic band sequence, limb-body wall complex, Meckel syndrome, Joubert syndrome, skeletal dysplasia, diabetic embryopathy, and single nucleotide polymorphisms in genes of glucose metabolism. NTDs associated with syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multi facto rial NTDs. Perinatal identification of NTDs should alert the clinician to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt a thorough etiologic investigation and genetic counseling. [Taiwan J Obstet Cynecol 2008;47(2:131-140

Renal involvement in primary antiphospholipid syndrome.

Science.gov (United States)

Marcantoni, Carmelita; Emmanuele, Carmela; Scolari, Francesco

2016-08-01

Antiphospholipid syndrome is an autoimmune disorder characterized by recurrent venous or arterial thrombosis and/or pregnancy-related problems associated with persistently elevated levels of antiphospholipid antibodies. The kidney is a major target organ in both primary and secondary antiphospholipid syndrome. This review describes several aspects of the renal involvement in the primary form of the syndrome, in particular the histological pattern of the so-called antiphospholipid syndrome nephropathy (APSN). APSN is a vascular nephropathy characterized by small vessel vaso-occlusive lesions associated with fibrous intimal hyperplasia of interlobular arteries, recanalizing thrombi in arteries and arterioles, and focal atrophy, a constellation of morphological lesions suggestive of primary antiphospholipid syndrome.

Rab GTPases and the Autophagy Pathway: Bacterial Targets for a Suitable Biogenesis and Trafficking of Their Own Vacuoles

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María Milagros López de Armentia

2016-03-01

Full Text Available Autophagy is an intracellular process that comprises degradation of damaged organelles, protein aggregates and intracellular pathogens, having an important role in controlling the fate of invading microorganisms. Intracellular pathogens are internalized by professional and non-professional phagocytes, localizing in compartments called phagosomes. To degrade the internalized microorganism, the microbial phagosome matures by fusion events with early and late endosomal compartments and lysosomes, a process that is regulated by Rab GTPases. Interestingly, in order to survive and replicate in the phagosome, some pathogens employ different strategies to manipulate vesicular traffic, inhibiting phagolysosomal biogenesis (e.g., Staphylococcus aureus and Mycobacterium tuberculosis or surviving in acidic compartments and forming replicative vacuoles (e.g., Coxiella burnetti and Legionella pneumophila. The bacteria described in this review often use secretion systems to control the host’s response and thus disseminate. To date, eight types of secretion systems (Type I to Type VIII are known. Some of these systems are used by bacteria to translocate pathogenic proteins into the host cell and regulate replicative vacuole formation, apoptosis, cytokine responses, and autophagy. Herein, we have focused on how bacteria manipulate small Rab GTPases to control many of these processes. The growing knowledge in this field may facilitate the development of new treatments or contribute to the prevention of these types of bacterial infections.

Syndromes and constitutional chromosomal abnormalities associated with Wilms tumour

Science.gov (United States)

Scott, R H; Stiller, C A; Walker, L; Rahman, N

2006-01-01

Wilms tumour has been reported in association with over 50 different clinical conditions and several abnormal constitutional karyotypes. Conclusive evidence of an increased risk of Wilms tumour exists for only a minority of these conditions, including WT1 associated syndromes, familial Wilms tumour, and certain overgrowth conditions such as Beckwith‐Wiedemann syndrome. In many reported conditions the rare co‐occurrence of Wilms tumour is probably due to chance. However, for several conditions the available evidence cannot either confirm or exclude an increased risk, usually because of the rarity of the syndrome. In addition, emerging evidence suggests that an increased risk of Wilms tumour occurs only in a subset of individuals for some syndromes. The complex clinical and molecular heterogeneity of disorders associated with Wilms tumour, together with the apparent absence of functional links between most of the known predisposition genes, suggests that abrogation of a variety of pathways can promote Wilms tumorigenesis. PMID:16690728

Bullous eosinophilic cellulitis (Wells' syndrome) associated with Churg-Strauss syndrome

NARCIS (Netherlands)

Schuttelaar, M L A; Jonkman, M F

We report a patient with Churg-Strauss syndrome (CSS) with asthma, eosinophilia, nasal polyposis and ANCA-associated multisystem vasculitis, who's skin eruption started with erythematous urticarial-plaques followed by haemorrhagic bullae. Histology of the plaques revealed 'flame figures' in the

Syndromes, Disorders and Maternal Risk Factors Associated With Neural Tube Defects (VI

Directory of Open Access Journals (Sweden)

Chih-Ping Chen

2008-09-01

Full Text Available Neural tube defects (NTDs may be associated with syndromes, disorders, and maternal and fetal risk factors. This article provides a comprehensive review of the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, including maternal fumonisin consumption, periconceptional zinc deficiency, parental occupational exposure and residential proximity to pesticides, lower socioeconomic status, fetal alcohol syndrome, mutations in the VANGL1 gene, human athymic Nude/SCID fetus, and single nucleotide polymorphism in the NOS3 gene. NTDs associated with these syndromes, disorders, and maternal and fetal risk factors are a rare but important cause of NTDs. The recurrence risk and the preventive effect of maternal folic acid intake in NTDs associated with syndromes, disorders and maternal risk factors may be different from those of nonsyndromic multifactorial NTDs. Perinatal diagnosis of NTDs should alert doctors to the syndromes, disorders, and maternal and fetal risk factors associated with NTDs, and prompt thorough etiologic investigation and genetic counseling.

Rare Association of Anti-Hu Antibody Positive Paraneoplastic Neurological Syndrome and Transitional Cell Bladder Carcinoma

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S. Lukacs

2012-01-01

Full Text Available Introduction. Paraneoplastic encephalomyelitis (PEM and subacute sensory neuronopathy (SSN are remote effects of cancer, usually associated with small-cell lung carcinoma and positive anti-Hu antibody. We describe the rare association of bladder transitional cell carcinoma (TCC with anti-Hu antibody positivity resulting in this paraneoplastic neurological syndrome. Patient. A 76-year-old female presented with bilateral muscle weakness and paraesthesia of the upper and lower limbs in a length-dependent “glove and stocking” distribution. Central nervous system symptoms included cognitive problems, personality change, and truncal ataxia. Case notes and the literature were reviewed. Result. Autoantibody screening was positive for anti-Hu antibody (recently renamed antineuronal nuclear antibody 1, ANNA-1. The diagnosis of PEM and SSN was supported by MRI and lumbar puncture results. A superficial bladder TCC was demonstrated on CT and subsequently confirmed on histology. No other primary neoplasm was found on full-body imaging. The neurological symptoms were considered to be an antibody-mediated paraneoplastic neurological syndrome and improved after resection of the tumour. Discussion. The association of anti-Hu positive paraneoplastic neurological syndrome and TCC has not been described in the literature previously. We emphasize the need for detailed clinical examination and the importance of a multidisciplinary thought process and encourage further awareness of this rare association.

Cdc42 is a key regulator of B cell differentiation and is required for antiviral humoral immunity

DEFF Research Database (Denmark)

Burbage, Marianne; Keppler, Selina J; Gasparrini, Francesca

2015-01-01

The small Rho GTPase Cdc42, known to interact with Wiskott-Aldrich syndrome (WAS) protein, is an important regulator of actin remodeling. Here, we show that genetic ablation of Cdc42 exclusively in the B cell lineage is sufficient to render mice unable to mount antibody responses. Indeed Cdc42-de...

Small carpal bone surface area, a characteristic of Turner's syndrome

International Nuclear Information System (INIS)

Cleveland, R.H.; Done, S.; Correia, J.A.; Crawford, J.D.; Kushner, D.C.; Herman, T.E.

1985-01-01

An abnormality which has received little attention but may be easily recognized on radiographs of the hand of patients with Turner's syndrome is described. Eleven of thirty-one patients (35.5%) with Turner's syndrome were shown on radiographs of the hand to have a visually detectable smallness of the bone surface area of the carpus when compared to the area of the second through fifth metacarpals. Values for the ''C/M'' ratio (the area of the carpals divided by the area of the second through fifth metacarpals) were calculated for films of 31 individuals with gonadal dysgenesis and compared with those from bone age-matched films of seventy-six individuals with normal development of the hand and wrist. A consistent difference with minimal overlap was documented. (orig./WL)

Guillain-Barre syndrome associated with hemorrhagic fever with renal syndrome in China: a case report.

Science.gov (United States)

Jiao, Jie; Wu, Lei; Yin, Jianyuan; Quan, Xiaojiao; Chen, Wei; Hu, Jie

2018-03-27

We describe a case of Guillain-Barre syndrome (GBS) associated with hemorrhagic fever with renal syndrome. To our knowledge, only five cases of GBS associated with Hantavirus infection have been reported so far. A 62-year-old man presented intermittent fever, chill and oliguria. According to remarkable leukocytosis, atypical lymphocytes, thrombocytopenia and former dwelling in hemorrhagic fever-endemic area, he was suspected as hemorrhagic fever with renal syndromeand certified with positive Hantavirus IgG. Later, the patient had symmetrical flaccid paralysis of all extremities. Electromyography showed peripheral nerve injury (mainly in axon). The patient was diagnosed as having acute motor sensory axonal neuropathy (AMSAN). After immunoglobulin infusion, patient showed progressive recovery and was transferred 3 weeks after his first admission to a rehabilitation center. Our case was the 6th reported case of GBS associated with hemorrhagic fever with renal syndrome. Moreover, we for the first time classified the subtype of GBS (AMSAN) based on the electrophysiology characteristics. GBS should be suspected in patients who are already diagnosed as hemorrhagic fever with renal syndrome when delayed symmetrical limb paralysis occurs. Until recent now, GBS was only reported in hemorrhagic fever patients in Europe and Asia, which termed as hemorrhagic fever with renal syndrome.

Nanofibrillar scaffolds induce preferential activation of Rho GTPases in cerebral cortical astrocytes

Science.gov (United States)

Tiryaki, Volkan Mujdat; Ayres, Virginia M; Khan, Adeel A; Ahmed, Ijaz; Shreiber, David I; Meiners, Sally

2012-01-01

Cerebral cortical astrocyte responses to polyamide nanofibrillar scaffolds versus poly-L-lysine (PLL)-functionalized planar glass, unfunctionalized planar Aclar coverslips, and PLL-functionalized planar Aclar surfaces were investigated by atomic force microscopy and immunocytochemistry. The physical properties of the cell culture environments were evaluated using contact angle and surface roughness measurements and compared. Astrocyte morphological responses, including filopodia, lamellipodia, and stress fiber formation, and stellation were imaged using atomic force microscopy and phalloidin staining for F-actin. Activation of the corresponding Rho GTPase regulators was investigated using immunolabeling with Cdc42, Rac1, and RhoA. Astrocytes cultured on the nanofibrillar scaffolds showed a unique response that included stellation, cell–cell interactions by stellate processes, and evidence of depression of RhoA. The results support the hypothesis that the extracellular environment can trigger preferential activation of members of the Rho GTPase family, with demonstrable morphological consequences for cerebral cortical astrocytes. PMID:22915841

Mismatch repair deficiency commonly precedes adenoma formation in Lynch Syndrome-Associated colorectal tumorigenesis.

Science.gov (United States)

Sekine, Shigeki; Mori, Taisuke; Ogawa, Reiko; Tanaka, Masahiro; Yoshida, Hiroshi; Taniguchi, Hirokazu; Nakajima, Takeshi; Sugano, Kokichi; Yoshida, Teruhiko; Kato, Mamoru; Furukawa, Eisaku; Ochiai, Atsushi; Hiraoka, Nobuyoshi

2017-08-01

Lynch syndrome is a cancer predisposition syndrome caused by germline mutations in mismatch repair (MMR) genes. MMR deficiency is a ubiquitous feature of Lynch syndrome-associated colorectal adenocarcinomas; however, it remains unclear when the MMR-deficient phenotype is acquired during tumorigenesis. To probe this issue, the present study examined genetic alterations and MMR statuses in Lynch syndrome-associated colorectal adenomas and adenocarcinomas, in comparison with sporadic adenomas. Among the Lynch syndrome-associated colorectal tumors, 68 of 86 adenomas (79%) and all adenocarcinomas were MMR-deficient, whereas all the sporadic adenomas were MMR-proficient, as determined by microsatellite instability testing and immunohistochemistry for MMR proteins. Sequencing analyses identified APC or CTNNB1 mutations in the majority of sporadic adenomas (58/84, 69%) and MMR-proficient Lynch syndrome-associated adenomas (13/18, 72%). However, MMR-deficient Lynch syndrome-associated adenomas had less APC or CTNNB1 mutations (25/68, 37%) and frequent frameshift RNF43 mutations involving mononucleotide repeats (45/68, 66%). Furthermore, frameshift mutations affecting repeat sequences constituted 14 of 26 APC mutations (54%) in MMR-deficient adenomas whereas these frameshift mutations were rare in MMR-proficient adenomas in patients with Lynch syndrome (1/12, 8%) and in sporadic adenomas (3/52, 6%). Lynch syndrome-associated adenocarcinomas exhibited mutation profiles similar to those of MMR-deficient adenomas. Considering that WNT pathway activation sufficiently drives colorectal adenoma formation, the distinct mutation profiles of WNT pathway genes in Lynch syndrome-associated adenomas suggest that MMR deficiency commonly precedes adenoma formation.

Cryopyrin-Associated Autoinflammatory Syndromes (CAPS) - Juvenile

Science.gov (United States)

... all ethnic groups can be affected. What are CAPS? Cryopyrin-associated autoinflammatory syndromes (CAPS) consist of three ... ears by magnetic resonance imaging (MRI). How is CAPS treated? Medications that target interleukin-1 are very ...

Rac1 GTPase Promotes Interaction of Hematopoietic Stem/Progenitor Cell with Niche and Participates in Leukemia Initiation and Maintenance in Mouse.

Science.gov (United States)

Chen, Shuying; Li, Huan; Li, Shouyun; Yu, Jing; Wang, Min; Xing, Haiyan; Tang, Kejing; Tian, Zheng; Rao, Qing; Wang, Jianxiang

2016-07-01

Interaction between hematopoietic stem/progenitor cells (HSPCs) with their niche is critical for HSPC function. The interaction also plays an important role in the multistep process of leukemogenesis. Rac1 GTPase has been found to be highly expressed and activated in leukemia patients. Here, by forced expression of constitutively active form of Rac1 (Rac1-V12) in HSPCs, we demonstrate that active Rac1 promotes interaction of HSPC with niche. We then established an active Rac1 associated acute myeloid leukemia (AML) model by expression of Rac1-V12 cooperated with AML1-ETO9a (AE9a) in mouse HSPCs. Compared with AE9a alone, Rac1-V12 cooperated with AE9a (AER) drives an AML with a short latency, demonstrating that activation of Rac1 GTPase in mice promotes AML development. The mechanism of this AML promotion is by a better homing and lodging of leukemia cells in niche, which further enhancing their colony formation, quiescence and preventing leukemia cells from apoptosis. Further study showed that an inhibitor targeting activated Rac1 can increase the efficacy of chemotherapeutic agents to leukemia cells. This study provides evidence that activation of Rac1 promotes leukemia development through enhancing leukemia cells' homing and retention in niche, and suggests that inhibition of Rac1 GTPase could be an effective way of eliminating AML cells. Stem Cells 2016;34:1730-1741. © 2016 AlphaMed Press.

An Animal Model for Human EBV-Associated Hemophagocytic Syndrome

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Hayashi, Kazuhiko; Ohara, Nobuya; Teramoto, Norihiro; Onoda, Sachiyo; Chen, Hong-Li; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Yates, John; Akagi, Tadaatsu

2001-01-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis. However, the animal model for EBV-AHS has not been developed. We reported the first animal model for EBV-AHS using rabbits infected with EBV-related herpesvirus of baboon (HVP). Eleven of 13 (85%) rabbits inoculated intravenously with HVP-producing cells developed fatal lymphoproliferative disorders (LPD) between 22 and 105 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in nine of these 11 rabbits. The peroral spray of cell-free HVP induced the virus infection with increased anti-EBV-viral capsid antigen-IgG titers in three of five rabbits, and two of these three infected rabbits died of LPD with HPS. Autopsy revealed hepatosplenomegaly and swollen lymph nodes. Atypical lymphoid T cells expressing EBV-encoded small RNA-1 infiltrated diffusely in many organs, frequently involving the lymph nodes, spleen, and liver. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by polymerase chain reaction or Southern blot analysis. Reverse transcriptase-polymerase chain reaction revealed both HVP-EBNA1 and HVP-EBNA2 transcripts, suggesting latency type III infection. These data indicate that the high rate of rabbit LPD with HPS induction is caused by HVP. This system is useful for studying the pathogenesis, prevention, and treatment of human EBV-AHS. PMID:11290571

Kaufman oculo-cerebro-facial syndrome in a child with small and absent terminal phalanges and absent nails.

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Kariminejad, Ariana; Ajeawung, Norbert Fonya; Bozorgmehr, Bita; Dionne-Laporte, Alexandre; Molidperee, Sirinart; Najafi, Kimia; Gibbs, Richard A; Lee, Brendan H; Hennekam, Raoul C; Campeau, Philippe M

2017-04-01

Kaufman oculo-cerebro-facial syndrome (KOS) is caused by recessive UBE3B mutations and presents with microcephaly, ocular abnormalities, distinctive facial morphology, low cholesterol levels and intellectual disability. We describe a child with microcephaly, brachycephaly, hearing loss, ptosis, blepharophimosis, hypertelorism, cleft palate, multiple renal cysts, absent nails, small or absent terminal phalanges, absent speech and intellectual disability. Syndromes that were initially considered include DOORS syndrome, Coffin-Siris syndrome and Dubowitz syndrome. Clinical investigations coupled with karyotype analysis, array-comparative genomic hybridization, exome and Sanger sequencing were performed to characterize the condition in this child. Sanger sequencing was negative for the DOORS syndrome gene TBC1D24 but exome sequencing identified a homozygous deletion in UBE3B (NM_183415:c.3139_3141del, p.1047_1047del) located within the terminal portion of the HECT domain. This finding coupled with the presence of characteristic features such as brachycephaly, ptosis, blepharophimosis, hypertelorism, short palpebral fissures, cleft palate and developmental delay allowed us to make a diagnosis of KOS. In conclusion, our findings highlight the importance of considering KOS as a differential diagnosis for patients under evaluation for DOORS syndrome and expand the phenotype of KOS to include small or absent terminal phalanges, nails, and the presence of hallux varus and multicystic dysplastic kidneys.

PREVALENCE OF SMALL INTESTINAL BACTERIAL OVERGROWTH IN IRRITABLE BOWEL SYNDROME

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Premaletha Narayanan

2017-12-01

Full Text Available BACKGROUND Irritable Bowel Syndrome (IBS is a common functional disorder and the pathophysiology of IBS is poorly understood. The aim of the study is to assess the prevalence of SIBO in patients with IBS using Lactulose Hydrogen Breath Test (LHBT. Diagnosis of IBS was made according to the Rome III Criteria and Lactulose Hydrogen Breath Test (LHBT was done. MATERIALS AND METHODS The current hypothesis suggests that altered gastrointestinal motility, disturbance of visceral hypersensitivity and infection may contribute to the symptoms. Gut microbiota and intestinal pathogens are likely to influence the pathogenesis of IBS. Small Intestinal Bacterial Overgrowth (SIBO is defined as an abnormally high bacterial count (≥105 colony-forming units/mL in the proximal small intestine. RESULTS Out of the 120 patients, 9 were LHBT positive (7.5% compared to none in controls (p <0.01. IBS patients with LHBT positivity was correlated well with the increased frequency of stools. There was no correlation noted with LHBT positivity and abdominal pain or flatulence or bloating compared to IBS patients who were LHBT negative. CONCLUSION These findings may suggest that patients with chronic diarrhoea including IBS should be tested for SIBO. Our study also showed that LHBT positivity is associated with increased frequency of stools and diarrhoea. If SIBO is found in patients with chronic diarrhoea, specific treatment with antibiotics may benefit them.

The small GTPase Rac1 is required for smooth muscle contraction

DEFF Research Database (Denmark)

Rahman, Awahan; Davis, Benjamin; Lövdahl, Cecilia

2014-01-01

The role of the small GTP-binding protein Rac1 in smooth muscle contraction was examined using small molecule inhibitors (EHT1864, NSC23766) and a novel smooth muscle-specific, conditional, Rac1 knockout mouse strain. EHT1864, which affects nucleotide binding and inhibits Rac1 activity, concentra...

Atrioventricular canal defect and associated genetic disorders: new insights into polydactyly syndromes

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M. Cristina Digilio

2011-07-01

Full Text Available Atrioventricular canal defect (AVCD is a common congenital heart defect (CHD, representing 7.4% of all cardiac malformations, considered secondary to an extracellular matrix anomaly. The AVCD is associated with extracardiac defects in about 75% of the cases. In this review we analyzed different syndromic AVCDs, in particular those associated with polydactyly disorders, which show remarkable genotype-phenotype correlations. Chromo - some imbalances more frequently associated with AVCD include Down syndrome, deletion 8p23 and deletion 3p25, while mendelian disorders include Noonan syndrome and related RASopathies, several polydactyly syndromes, CHARGE and 3C (cranio-cerebello-cardiac syndrome. The complete form of AVCD is prevalent in patients with chromosomal imbalances. Additional cardiac defects are found in patients affected by chromosomal imbalances different from Down syndrome. Left-sided obstructive lesions are prevalently found in patients with RASopathies. Patients with deletion 8p23 often display AVCD with tetralogy of Fallot or with pulmonary valve stenosis. Tetralogy of Fallot is the only additional cardiac defect found in patients with Down syndrome and AVCD. On the other hand, the association of AVCD and tetralogy of Fallot is also quite characteristic of CHARGE and 3C syndromes. Heterotaxia defects, including common atrium and anomalous pulmonary venous return, occur in patients with AVCD associated with polydactyly syndromes (Ellis-van Creveld, short rib polydactyly, oral-facial-digital, Bardet-Biedl, and Smith-Lemli-Opitz syndromes. The initial clinical evidence of anatomic similarities between AVCD and heterotaxia in polydactyly syndromes was corroborated and explained by experimental studies in transgenic mice. These investigations have suggested the involvement of the Sonic Hedgehog pathway in syndromes with postaxial polydactyly and heterotaxia, and ciliary dysfunction was detected as pathomechanism for these disorders

SNEDDON’S SYNDROME

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Valentin Valtchev

2008-10-01

Full Text Available Sneddon’s syndrome is usually characterized by the association of an ischemic cerebrovascular disease and a widespread livedo reticularis. The incidence of Sneddon syndrome is 4/1000 000. We present 42-year-old woman with livedo reticularis, recurrence ischaemic cerebrovascular accidents, two repetitive miscarriages and positive anti-2GPi antibodies. Skin biopsy specimens reveal inflammatory changes of small- to medium-sized arteries and subendothelial proliferation and fibrosis. The diagnosis Sneddon syndrome is confirmed by skin biopsy, and MR evidence. We suggest that anti-2GPi antibodies may be pathophysiologically related to the clinical manifestation observed in some patients with Sneddon syndrome.

Associations Between Adiposity and Metabolic Syndrome Over Time: The Healthy Twin Study.

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Song, Yun-Mi; Sung, Joohon; Lee, Kayoung

2017-04-01

We evaluated the association between changes in adiposity traits including anthropometric and fat mass indicators and changes in metabolic syndrome traits including metabolic syndrome clustering and individual components over time. We also assessed the shared genetic and environmental correlations between the two traits. Participants were 284 South Korean twin individuals and 279 nontwin family members had complete data for changes in adiposity traits and metabolic syndrome traits of the Healthy Twin study. Mixed linear model and bivariate variance-component analysis were applied. Over a period of 3.1 ± 0.6 years of study, changes in adiposity traits [body mass index (BMI), waist circumference, total fat mass, and fat mass to lean mass ratio] had significant associations with changes in metabolic syndrome clustering [high blood pressure, high serum glucose, high triglycerides (TG), and low high-density lipoprotein cholesterol] after adjusting for intra-familial and sibling correlations, age, sex, baseline metabolic syndrome clustering, and socioeconomic factors and health behaviors at follow-up. Change in BMI associated significantly with changes in individual metabolic syndrome components compared to other adiposity traits. Change in metabolic syndrome component TG was a better predictor of changes in adiposity traits compared to changes in other metabolic components. These associations were explained by significant environmental correlations but not by genetic correlations. Changes in anthropometric and fat mass indicators were positively associated with changes in metabolic syndrome clustering and those associations appeared to be regulated by environmental influences.

GTPase ROP2 binds and promotes activation of target of rapamycin, TOR, in response to auxin.

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Schepetilnikov, Mikhail; Makarian, Joelle; Srour, Ola; Geldreich, Angèle; Yang, Zhenbiao; Chicher, Johana; Hammann, Philippe; Ryabova, Lyubov A

2017-04-03

Target of rapamycin (TOR) promotes reinitiation at upstream ORFs (uORFs) in genes that play important roles in stem cell regulation and organogenesis in plants. Here, we report that the small GTPase ROP2, if activated by the phytohormone auxin, promotes activation of TOR, and thus translation reinitiation of uORF-containing mRNAs. Plants with high levels of active ROP2, including those expressing constitutively active ROP2 (CA-ROP2), contain high levels of active TOR ROP2 physically interacts with and, when GTP-bound, activates TOR in vitro TOR activation in response to auxin is abolished in ROP-deficient rop2 rop6 ROP4 RNAi plants. GFP-TOR can associate with endosome-like structures in ROP2-overexpressing plants, indicating that endosomes mediate ROP2 effects on TOR activation. CA-ROP2 is efficient in loading uORF-containing mRNAs onto polysomes and stimulates translation in protoplasts, and both processes are sensitive to TOR inhibitor AZD-8055. TOR inactivation abolishes ROP2 regulation of translation reinitiation, but not its effects on cytoskeleton or intracellular trafficking. These findings imply a mode of translation control whereby, as an upstream effector of TOR, ROP2 coordinates TOR function in translation reinitiation pathways in response to auxin. © 2017 The Authors.

Small fiber neuropathy is a common feature of Ehlers-Danlos syndromes

Science.gov (United States)

Cazzato, Daniele; Castori, Marco; Lombardi, Raffaella; Caravello, Francesca; Bella, Eleonora Dalla; Petrucci, Antonio; Grammatico, Paola; Dordoni, Chiara; Colombi, Marina

2016-01-01

Objective: To investigate the involvement of small nerve fibers in Ehlers-Danlos syndrome (EDS). Methods: Patients diagnosed with EDS underwent clinical, neurophysiologic, and skin biopsy assessment. We recorded sensory symptoms and signs and evaluated presence and severity of neuropathic pain according to the Douleur Neuropathique 4 (DN4) and ID Pain questionnaires and the Numeric Rating Scale (NRS). Sensory action potential amplitude and conduction velocity of sural nerve was recorded. Skin biopsy was performed at distal leg and intraepidermal nerve fiber density (IENFD) obtained and referred to published sex- and age-adjusted normative reference values. Results: Our cohort included 20 adults with joint hypermobility syndrome/hypermobility EDS, 3 patients with vascular EDS, and 1 patient with classic EDS. All except one patient had neuropathic pain according to DN4 and ID Pain questionnaires and reported 7 or more symptoms at the Small Fiber Neuropathy Symptoms Inventory Questionnaire. Pain intensity was moderate (NRS ≥4 and <7) in 8 patients and severe (NRS ≥7) in 11 patients. Sural nerve conduction study was normal in all patients. All patients showed a decrease of IENFD consistent with the diagnosis of small fiber neuropathy (SFN), regardless of the EDS type. Conclusions: SFN is a common feature in adults with EDS. Skin biopsy could be considered an additional diagnostic tool to investigate pain manifestations in EDS. PMID:27306637

Loose anagen hair syndrome associated with colobomas and dysmorphic features

DEFF Research Database (Denmark)

Hansen, Lars Kjaersgård; Brandrup, Flemming; Clemmensen, Ole

2004-01-01

Loose anagen hair syndrome is an uncommon congenital disorder. It may occur in association with other syndromes and dysmorphic features. We report a girl who fulfilled the diagnostic criteria for this syndrome as proposed by Tosti (Arch Dermatol 2002, 138: 521-522). She also had several other...

Goldenhar Syndrome in Association with Duane Syndrome

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U D Shrestha

2012-03-01

Full Text Available Goldenhar syndrome (GHS is also known as Oculo-Auriculo-Vertebral (OAV syndrome or Branchial arch syndrome. Duane retraction syndrome (DRS is a congenital disorder of ocular motility characterized by limited abduction, adduction or both. It is unilateral in 80% of cases. The important and interesting part of this eight months old child is presence of GHS with DRS. She has bilateral invol-vement, which is seen in only 5-8% of GHS, as compared to high incidence of unilateral involve-ment. This child also had refractive error of + 6.00/ - 1.5 * 180. At four year of age her vision with glass was 6/9. Children with GHS and DRS should have early eye examination done to treat the problem of refractive error. Keywords: Duane retraction syndrome; goldenhar syndrome, refractive error.

Anti Ma2-associated myeloradiculopathy: expanding the phenotype of anti-Ma2 associated paraneoplastic syndromes

OpenAIRE

Murphy, Sinead M; Khan, Usman; Alifrangis, Constantine; Hazell, Steven; Hrouda, David; Blake, Julian; Ball, Joanna; Gabriel, Carolyn; Markarian, Pierre; Rees, Jeremy; Karim, Abid; Seckl, Michael J; Lunn, Michael P; Reilly, Mary M

2011-01-01

Anti-Ma2 associated paraneoplastic syndrome usually presents as limbic encephalitis in association with testicular tumours.1, 2 Only four patients have been reported with involvement outside the CNS, two of whom also had limbic or brainstem encephalitis.2, 3 We report a man with anti- Ma2 associated myeloradiculopathy and previous testicular cancer whose neurological syndrome stabilised and anti-Ma2 titres fell following orchidectomy of a microscopically normal testis.

Intrinsic factors associated with medial tibial stress syndrome in ...

African Journals Online (AJOL)

Intrinsic factors associated with medial tibial stress syndrome in athletes: A large case-control study. ... Medial tibial stress syndrome (MTSS) is the most common lower-leg injury in athletes, and is thought to be caused by ... from 32 Countries:.

Laron syndrome abnormalities: spinal stenosis, os odontoideum, degenerative changes of the atlanto-odontoid joint, and small oropharynx.

Science.gov (United States)

Kornreich, Liora; Horev, Gadi; Schwarz, Michael; Karmazyn, Boaz; Laron, Zvi

2002-04-01

Patients with Laron syndrome have an inborn growth hormone resistance. We investigated abnormalities in the upper airways and cervical spine in patients with Laron syndrome. We prospectively examined 11 patients (one child aged 9 years and 10 adults aged 36-68 years), 10 of whom underwent MR imaging of the spine or head; nine, radiography of the cervical spine; and four, CT of C1-C2. The width of the spinal canal was evaluated visually and quantitatively and compared with reference values. The smallest diameter of the oropharynx and the thickness of the palate were measured and compared with reference values. Nine age-matched female patients referred for MR imaging for unrelated reasons served as control subjects. Cervical spinal stenosis was present in seven of the adult patients, within a confidence interval of 95%. Anomaly of the dens compatible with os odontoideum was present in three patients, causing focal myelomalacia in two. The atlanto-odontoid joint showed osteoarthritic changes in six of the adult patients. The mediolateral diameter of the oropharynx was significantly smaller in the patients with Laron syndrome than in the control subjects (P Laron syndrome develop significant narrowing of the cervical spinal canal and early degenerative changes of the atlanto-odontoid joint. Laron syndrome is associated with os odontoideum causing myelomalacia. The dimensions of the oropharynx are small. Patients may be prone to neurologic morbidity and sleep disturbances. Routine MR imaging of the cervical spine is recommended in these patients.

Waardenburg syndrome presenting with constipation since birth.

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Gupta, R; Sharma, S B; Mathur, P; Agrawal, L D

2014-12-01

Shah-Waardenburg syndrome is Waardenburg syndrome associated with Hirschsprung's disease. A 10-day-old full-term male neonate of Waardenburg syndrome presented with constipation since birth along with features of small bowel obstruction. Exploratory laparotomy revealed distended proximal jejunal and ileal loops along with microcolon; an ileostomy was performed. Postoperatively patient developed sepsis and died. Histopathology confirmed total colonic aganglionosis. Suspect familial Shah-Waardenburg syndrome in a neonate of Waardenburg syndrome presenting with constipation since birth or intestinal obstruction.

Hypertrophic remodeling of subcutaneous small resistance arteries in patients with Cushing's syndrome.

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Rizzoni, Damiano; Porteri, Enzo; De Ciuceis, Carolina; Rodella, Luigi F; Paiardi, Silvia; Rizzardi, Nicola; Platto, Caterina; Boari, Gianluca E M; Pilu, Annamaria; Tiberio, Guido A M; Giulini, Stefano M; Favero, Gaia; Rezzani, Rita; Rosei, Claudia Agabiti; Bulgari, Giuseppe; Avanzi, Daniele; Rosei, Enrico Agabiti

2009-12-01

Structural alterations of small resistance arteries in essential hypertensive patients (EH) are mostly characterized by inward eutrophic remodeling. However, we observed hypertrophic remodeling in patients with renovascular hypertension, in those with acromegaly, as well as in patients with non-insulin-dependent diabetes mellitus, suggesting a relevant effect of humoral growth factors on vascular structure, even independent from the hemodynamic load. Cortisol may stimulate the renin-angiotensin system and may induce cardiac hypertrophy. However, presently no data are available about small artery structure in patients with Cushing's syndrome. We have investigated the structure of sc small resistance arteries in 12 normotensive subjects (NT), in 12 EH subjects, and in eight patients with Cushing's syndrome (CS). Small arteries from sc fat were dissected and mounted on a micromyograph. The normalized internal diameter, media thickness, media to lumen ratio, and the media cross-sectional area were measured, as well as indices of oxidative stress. Demographic variables were similar in the three groups, except for clinic blood pressure. The media to lumen ratio was significantly greater in EH and CS, compared with NT; no difference was observed between EH and CS. The media cross-sectional area was significantly greater in CS compared with EH and with NT. An increased vascular oxidative stress was present in CS, as demonstrated by increased levels of superoxide anions, cyclooxygenase-1 and endothelial nitric oxide synthase in the microvessels. Our results suggest the presence of hypertrophic remodeling in sc small resistance arteries of CS, probably as a consequence of growth-promoting properties of circulating cortisol and/or increased vascular oxidative stress.

Drug-induced hypersensitivity syndrome associated with Epstein-Barr virus infection.

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Descamps, V; Mahe, E; Houhou, N; Abramowitz, L; Rozenberg, F; Ranger-Rogez, S; Crickx, B

2003-05-01

Association of drug-induced hypersensitivity syndrome with viral infection is debated. Human herpesvirus 6 (HHV-6) reactivation has been the most frequently reported infection associated with this syndrome. However, a case of cytomegalovirus (CMV) infection was recently described associated with anticonvulsant-induced hypersensitivity syndrome. We report a case of severe allopurinol-induced hypersensitivity syndrome with pancreatitis associated with Epstein-Barr virus (EBV) infection. Active EBV infection was demonstrated in two consecutive serum samples by the presence of anti-EBV early antigen (EA) IgM antibodies and an increase in anti-EBV EA IgG antibodies, whereas no anti-EBV nuclear antigen IgG antibodies were detected. EBV DNA was detected by polymerase chain reaction (PCR) in peripheral blood mononuclear cells. Reactivation of HHV-6 was suggested only by the presence of anti-HHV-6 IgM antibodies, but HHV-6 DNA was not detected by PCR in the serum. Other viral investigations showed previous infection (CMV, rubella, measles, parvovirus B19), immunization after vaccination (hepatitis B virus), or absence of previous infection (hepatitis C virus, human immunodeficiency virus). We suggest that EBV infection may participate in some cases, as do the other herpesviruses HHV-6 or CMV, in the development of drug-induced hypersensitivity syndrome.

Genome-wide association studies of obesity and metabolic syndrome.

Science.gov (United States)

Fall, Tove; Ingelsson, Erik

2014-01-25

Until just a few years ago, the genetic determinants of obesity and metabolic syndrome were largely unknown, with the exception of a few forms of monogenic extreme obesity. Since genome-wide association studies (GWAS) became available, large advances have been made. The first single nucleotide polymorphism robustly associated with increased body mass index (BMI) was in 2007 mapped to a gene with for the time unknown function. This gene, now known as fat mass and obesity associated (FTO) has been repeatedly replicated in several ethnicities and is affecting obesity by regulating appetite. Since the first report from a GWAS of obesity, an increasing number of markers have been shown to be associated with BMI, other measures of obesity or fat distribution and metabolic syndrome. This systematic review of obesity GWAS will summarize genome-wide significant findings for obesity and metabolic syndrome and briefly give a few suggestions of what is to be expected in the next few years. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[A patient with Noonan syndrome].

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Bins, A; Gortzak, R A Th

2013-12-01

Noonan syndrome is a relatively common autosomal dominant genetic disorder which is characterised by typical facial features, congenital heart diseases and small stature. In 50% of the cases the syndrome is caused by a mutation on the PTPN11-gen. The expression of symptoms associated with Noonan syndrome can be very mild in nature and facial features usually become less pronounced with age, which can sometimes make a correct diagnosis more difficult. Despite a wide range of associated symptoms most adults with Noonan syndrome can be self-sustaining, with a good quality of life. It is important that the dentist is well-informed about this syndrome due to the heart diseases and bleeding disorders which can be present with these patients and may influence a dentist's choice of therapy when invasive treatment is indicated.

Activation of Rho GTPases by Cytotoxic Necrotizing Factor 1 Induces Macropinocytosis and Scavenging Activity in Epithelial Cells

Science.gov (United States)

Fiorentini, Carla; Falzano, Loredana; Fabbri, Alessia; Stringaro, Annarita; Logozzi, Mariaantonia; Travaglione, Sara; Contamin, Stéphanette; Arancia, Giuseppe; Malorni, Walter; Fais, Stefano

2001-01-01

Macropinocytosis, a ruffling-driven process that allows the capture of large material, is an essential aspect of normal cell function. It can be either constitutive, as in professional phagocytes where it ends with the digestion of captured material, or induced, as in epithelial cells stimulated by growth factors. In this case, the internalized material recycles back to the cell surface. We herein show that activation of Rho GTPases by a bacterial protein toxin, the Escherichia coli cytotoxic necrotizing factor 1 (CNF1), allowed epithelial cells to engulf and digest apoptotic cells in a manner similar to that of professional phagocytes. In particular, we have demonstrated that 1) the activation of all Rho, Rac, and Cdc42 by CNF1 was essential for the capture and internalization of apoptotic cells; and 2) such activation allowed the discharge of macropinosomal content into Rab7 and lysosomal associated membrane protein-1 acidic lysosomal vesicles where the ingested particles underwent degradation. Taken together, these findings indicate that CNF1-induced “switching on” of Rho GTPases may induce in epithelial cells a scavenging activity, comparable to that exerted by professional phagocytes. The activation of such activity in epithelial cells may be relevant, in mucosal tissues, in supporting or integrating the scavenging activity of resident macrophages. PMID:11452003

Syndromic Hirschsprung's disease and associated congenital heart disease: a systematic review.

Science.gov (United States)

Duess, Johannes W; Puri, Prem

2015-08-01

Hirschsprung's disease (HD) occurs as an isolated phenotype in 70% of infants and is associated with additional congenital anomalies or syndromes in approximately 30% of patients. The cardiac development depends on neural crest cell proliferation and is closely related to the formation of the enteric nervous system. HD associated with congenital heart disease (CHD) has been reported in 5-8% of cases, with septation defects being the most frequently recorded abnormalities. However, the prevalence of HD associated with CHD in infants with syndromic disorders is not well documented. This systematic review was designed to determine the prevalence of CHD in syndromic HD. A systematic review of the literature using the keywords "Hirschsprung's disease", "aganglionosis", "congenital megacolon", "congenital heart disease" and "congenital heart defect" was performed. Resulting publications were reviewed for epidemiology and morbidity. Reference lists were screened for additional relevant studies. A total of fifty-two publications from 1963 to 2014 reported data on infants with HD associated with CHD. The overall reported prevalence of HD associated with CHD in infants without chromosomal disorders was 3%. In infants with syndromic disorders, the overall prevalence of HD associated with CHD ranged from 20 to 80 % (overall prevalence 51%). Septation defects were recorded in 57% (atrial septal defects in 29%, ventricular septal defects in 32%), a patent ductus arteriosus in 39%, vascular abnormalities in 16%, valvular heart defects in 4% and Tetralogy of Fallot in 7%. The prevalence of HD associated with CHD is much higher in infants with chromosomal disorders compared to infants without associated syndromes. A routine echocardiogram should be performed in all infants with syndromic HD to exclude cardiac abnormalities.

Parry-Romberg syndrome (progressive hemifacial atrophy) with spasmodic dysphonia--a rare association.

Science.gov (United States)

Mugundhan, K; Selvakumar, C J; Gunasekaran, K; Thiruvarutchelvan, K; Sivakumar, S; Anguraj, M; Arun, S

2014-04-01

Parry-Romberg syndrome is a rare clinical entity characterised by progressive hemifacial atrophy with appearance of 'saber'. Various neurological and otorhinolaryngological disorders are associated with this syndrome. The association of Parry -Romberg syndrome with Spasmodic dysphonia has rarely been reported. A 37 year old female presented with progressive atrophy of tissues of left side of face for 10 years and change in voice for 1 year. On examination, wasting and atrophy of tissues including tongue was noted on left side of the face. ENT examination revealed adductor spasmodic dysphonia. We report the rare association of Parry -Romberg syndrome with spasmodic dysphonia.

Gain-of-function mutations in RIT1 cause Noonan syndrome, a RAS/MAPK pathway syndrome.

Science.gov (United States)

Aoki, Yoko; Niihori, Tetsuya; Banjo, Toshihiro; Okamoto, Nobuhiko; Mizuno, Seiji; Kurosawa, Kenji; Ogata, Tsutomu; Takada, Fumio; Yano, Michihiro; Ando, Toru; Hoshika, Tadataka; Barnett, Christopher; Ohashi, Hirofumi; Kawame, Hiroshi; Hasegawa, Tomonobu; Okutani, Takahiro; Nagashima, Tatsuo; Hasegawa, Satoshi; Funayama, Ryo; Nagashima, Takeshi; Nakayama, Keiko; Inoue, Shin-Ichi; Watanabe, Yusuke; Ogura, Toshihiko; Matsubara, Yoichi

2013-07-11

RAS GTPases mediate a wide variety of cellular functions, including cell proliferation, survival, and differentiation. Recent studies have revealed that germline mutations and mosaicism for classical RAS mutations, including those in HRAS, KRAS, and NRAS, cause a wide spectrum of genetic disorders. These include Noonan syndrome and related disorders (RAS/mitogen-activated protein kinase [RAS/MAPK] pathway syndromes, or RASopathies), nevus sebaceous, and Schimmelpenning syndrome. In the present study, we identified a total of nine missense, nonsynonymous mutations in RIT1, encoding a member of the RAS subfamily, in 17 of 180 individuals (9%) with Noonan syndrome or a related condition but with no detectable mutations in known Noonan-related genes. Clinical manifestations in the RIT1-mutation-positive individuals are consistent with those of Noonan syndrome, which is characterized by distinctive facial features, short stature, and congenital heart defects. Seventy percent of mutation-positive individuals presented with hypertrophic cardiomyopathy; this frequency is high relative to the overall 20% incidence in individuals with Noonan syndrome. Luciferase assays in NIH 3T3 cells showed that five RIT1 alterations identified in children with Noonan syndrome enhanced ELK1 transactivation. The introduction of mRNAs of mutant RIT1 into 1-cell-stage zebrafish embryos was found to result in a significant increase of embryos with craniofacial abnormalities, incomplete looping, a hypoplastic chamber in the heart, and an elongated yolk sac. These results demonstrate that gain-of-function mutations in RIT1 cause Noonan syndrome and show a similar biological effect to mutations in other RASopathy-related genes. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy

NARCIS (Netherlands)

Haanstra, Jasmijn F.; Al-Toma, Abdul; Dekker, Evelien; Vanhoutvin, Steven A. L. W.; Nagengast, Fokko M.; Mathus-Vliegen, Elisabeth M.; van Leerdam, Monique E.; Cappel, Wouter H. de Vos tot Nederveen; Sanduleanu, Silvia; Veenendaal, Roeland A.; Cats, Annemieke; Vasen, Hans F. A.; Kleibeuker, Jan H.; Koornstra, Jan J.

2015-01-01

Objective The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). Design After obtaining informed consent, asymptomatic proven gene mutation carriers aged 3570 years were included in this prospective

Nutcracker syndrome associated with celiacomesentric trunk anomaly: case report

Directory of Open Access Journals (Sweden)

Al-Zoubi NA

2017-12-01

Full Text Available Nabil A Al-Zoubi,1 Ibrahim F Al-Ghalayini,1,2 Radwan Al-Okour1,2 1Department of Surgery, 2Division of Urology, Jordan University of Science and Technology, Irbid, Jordan Introduction: Nutcracker syndrome is a rare disease entity that is caused by entrapment of the left renal vein between the aorta and superior mesenteric artery, usually due to abnormal branching of the superior mesenteric artery from the aorta causing renal venous hypertension. The symptoms vary from asymptomatic hematuria to severe pelvic congestion. Celiacomesenteric trunk anomaly is a rare variation of splanchnic artery anomaly that occurs when the celiac trunk and superior mesenteric arteries have a common origin from the aorta. A disease involving the rarely encountered celiacomesenteric trunk anomaly is extremely uncommon. To our knowledge, association between nutcracker syndrome and celiacomesentric trunk anomaly has not been reported in the literature.Case presentation: A 14-year-old boy with no significant past medical history presented with a 3-year painless hematuria. CT-angiogram revealed anterior nutcracker syndrome with celiacomesenteric trunk anomaly. The patient was managed conservatively with close follow-up.Conclusion: Nutcracker syndrome associated with celiacomesenteric trunk anomaly is extremely uncommon and is a rare cause of hematuria in children. Whether this abnormal anatomy is the cause of nutcracker syndrome or just an association should be investigated. Moreover, awareness of this anatomical variation may help in planning therapeutic options and reducing the chance of surgical iatrogenic injuries. Keywords: nutcracker syndrome, celiacomesenteric trunk, hematuria in children

Tandem duplications of a degenerated GTP-binding domain at the origin of GTPase receptors Toc159 and thylakoidal SRP

International Nuclear Information System (INIS)

Hernandez Torres, Jorge; Maldonado, Monica Alexandra Arias; Chomilier, Jacques

2007-01-01

The evolutionary origin of some nuclear encoded proteins that translocate proteins across the chloroplast envelope remains unknown. Therefore, sequences of GTPase proteins constituting the Arabidopsis thaliana translocon at the outer membrane of chloroplast (atToc) complexes were analyzed by means of HCA. In particular, atToc159 and related proteins (atToc132, atToc120, and atToc90) do not have proven homologues of prokaryotic or eukaryotic ancestry. We established that the three domains commonly referred to as A, G, and M originate from the GTPase G domain, tandemly repeated, and probably evolving toward an unstructured conformation in the case of the A domain. It resulted from this study a putative common ancestor for these proteins and a new domain definition, in particular the splitting of A into three domains (A1, A2, and A3), has been proposed. The family of Toc159, previously containing A. thaliana and Pisum sativum, has been extended to Medicago truncatula and Populus trichocarpa and it has been revised for Oryza sativa. They have also been compared to GTPase subunits involved in the cpSRP system. A distant homology has been revealed among Toc and cpSRP GTP-hydrolyzing proteins of A. thaliana, and repetitions of a GTPase domain were also found in cpSRP protein receptors, by means of HCA analysis

Rheumatic Fever Associated with Antiphospholipid Syndrome: Systematic Review

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Felipe da Silva

2014-01-01

Full Text Available Objective. To evaluate the clinical associations between rheumatic fever and antiphospholipid syndrome and the impact of coexistence of these two diseases in an individual. Methods. Systematic review in electronics databases, regarding the period from 1983 to 2012. The keywords: “Rheumatic Fever,” “Antiphospholipid Syndrome,” and “Antiphospholipid Antibody Syndrome” are used. Results. were identified 11 cases described in the literature about the association of rheumatic fever and antiphospholipid syndrome. Clinical presentation of rheumatic fever was characterized by the predominance of carditis (11/11 and chorea (7/11. Regarding the manifestations of APS, the stroke was observed in 7/11 (63.6%, with one of them having probable embolic origin. Conclusion. The present study brings the information that the association between APS and RF is quite rare, however, is of great clinical importance. Doctors who deal with the RF should include in their differential diagnosis the APS, especially in the presence of stroke in patients with RF and whose echocardiogram does not show intracavitary thrombi.

Association of metabolic syndrome in patients with osteoarthritis

International Nuclear Information System (INIS)

Malik, S.; Salim, B.; Khalil, Z.; Nasim, A.

2015-01-01

Objective: To determine association of osteoarthritis (OA) with metabolic syndrome in a tertiary care hospital of Pakistan. Methodology: A cross-sectional study was conducted at Fauji Foundation Hospital, Rawalpindi, Pakistan. Patients were randomly interviewed in the Female Rheumatology department and a total of 240 patients with single rheumatologic disease and age >35 years were selected. Informed consent was taken and patients were interviewed using a self-made questionnaire to evaluate their medical history, physical and laboratory examination. SPSS version 17 was used to analyze the data. Results: Out of 240 subjects, 81 patients had OA and another 81 patients were randomly selected from the age and gender matched control (non-OA) group. The mean age of patients in OA and non-OA group was 56.68 ± 09.76 and 53.57 ± 11.01 years, respectively. In OA group, 48.1% and in non-OA group 22.2% of patients were falling in category of being obese/morbidly obese. According to AHA criteria for Metabolic Syndrome, percentage of OA patients labeled to have metabolic syndrome was 58.8% as compared to 19.5% in non-OA group. Conclusion: There was a strong association of metabolic syndrome with OA and would surely make a foreground for future studies to be conducted on developing preventive strategies and ultimately reducing the morbidities and mortalities associated with Metabolic Osteoarthritis. (author)

Secretion of soluble vascular endothelial growth factor receptor 1 (sVEGFR1/sFlt1 requires Arf1, Arf6, and Rab11 GTPases.

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Jae-Joon Jung

Full Text Available The soluble form of vascular endothelial growth factor receptor 1 (sVEGFR-1/sFlt1 is generated by alternative splicing of the FLT1 gene. Secretion of sFlt1 from endothelial cells plays an important role in blood vessel sprouting and morphogenesis. However, excess sFlt1 secretion is associated with diseases such as preeclampsia and chronic kidney disease. To date, the secretory transport process involved in the secretion of sFlt1 is poorly understood. In the present study, we investigated the itinerary of sFlt1 trafficking along the secretory pathway. To understand the timecourse of sFlt1 secretion, endothelial cells stably expressing sFlt1 were metabolically radiolabeled with [(35S]-methionine and cysteine. Our results indicate that after initial synthesis the levels of secreted [(35S]-sFlt1 in the extracellular medium peaks at 8 hours. Treatment with brefeldin A (BFA, a drug which blocks trafficking between the endoplasmic reticulum (ER and the Golgi complex, inhibited extracellular release of sFlt1 suggesting that ER to Golgi and intra-Golgi trafficking of sFlt1 are essential for its secretion. Furthermore, we show that ectopic expression of dominant-negative mutant forms of Arf1, Arf6, and Rab11 as well as siRNA-mediated knockdown of these GTPases block secretion of sFlt1 during normoxic and hypoxic conditions suggesting role for these small GTPases. This work is the first to report role of regulatory proteins involved in sFlt1 trafficking along the secretory pathway and may provide insights and new molecular targets for the modulation of sFlt-1 release during physiological and pathological conditions.

Dengue infection associated hemophagocytic syndrome: Therapeutic interventions and outcome.

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Wan Jamaludin, Wan Fariza; Periyasamy, Petrick; Wan Mat, Wan Rahiza; Abdul Wahid, S Fadilah

2015-08-01

Infection associated hemophagocytic syndrome is increasingly recognized as a potentially fatal complication of dengue fever. It should be suspected with prolonged fever beyond seven days associated with hepatosplenomegaly, hyperferritinemia, worsening cytopenias and development of multiorgan dysfunction. Surge of similar pro-inflammatory cytokines observed in dengue associated hemophagocytic syndrome and multiorgan dysfunction may indicate they are part of related inflammatory spectrum. A proportion of patients recovered with supportive therapy, however most required interventions with corticosteroids, intravenous immunoglobulin or chemotherapy. We report three cases of dengue associated IAHS with good outcome following early recognition and treatment with dexamethasone and intravenous immunoglobulin. Copyright © 2015 Elsevier B.V. All rights reserved.

Association between habitual coffee consumption and metabolic syndrome in type 1 diabetes.

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Stutz, B; Ahola, A J; Harjutsalo, V; Forsblom, C; Groop, P-H

2018-05-01

In the general population, habitual coffee consumption is inversely associated with the metabolic syndrome, a syndrome that is rather common also in patients with type 1 diabetes. However, whether coffee intake is beneficially related to the metabolic syndrome also in type 1 diabetes, is not known. We, therefore, studied the potential association between coffee consumption and the metabolic syndrome in a large population of individuals with type 1 diabetes. Furthermore, we investigated whether coffee consumption is associated with insulin resistance (estimated glucose disposal rate, eGDR), kidney function (estimated glomerular filtration rate, eGFR), and low-grade chronic inflammation (high-sensitivity C-reactive protein, hsCRP). Data from 1040 participants in the Finnish Diabetic Nephropathy Study were included in these cross-sectional analyses. Metabolic syndrome was assumed if at least 3 of the following cardiovascular risk factors were present: central obesity, high blood pressure, low HDL-cholesterol concentration, high triglyceride concentration, and hyperglycaemia. Subjects were categorized based on self-reported daily coffee intake: non-consumers (metabolic syndrome. Moreover, any level of coffee consumption was associated with increased risk of the blood pressure-component. An increasing trend was observed in the eGFR with increasing coffee consumption. In type 1 diabetes, high coffee intake is associated with the metabolic syndrome, and especially its blood pressure-component. Copyright © 2018. Published by Elsevier B.V.

Wernicke-Korsakoff Syndrome following Small Bowel Obstruction

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Shoumitro Deb

2002-01-01

Full Text Available We report a case of a 64-year-old lady who developed clinical features of Wernicke-Korsakoff syndrome following a laparotomy for small bowel obstruction. Following the operation she developed paralytic ileus and required total parenteral nutrition for one month. A suspected history of average 40 units of weekly alcohol consumption prior to the operation could not be confirmed and the patient did not show any sign of alcohol dependence. Within a few months of treatment with a daily oral dose of thiamine 200 mgs supplemented by multivitamins the patient showed subjective evidence of improvement in confusion, confabulation, and anterograde amnesia, although objective tests showed residual deficits in many areas of cognitive functioning, including immediate and delayed recall of verbal and non-verbal materials, planning and switching of attention.

Wernicke-Korsakoff Syndrome following Small Bowel Obstruction

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Deb, Shoumitro; Law-Min, Richard; Fearnley, David

2002-01-01

We report a case of a 64-year-old lady who developed clinical features of Wernicke-Korsakoff syndrome following a laparotomy for small bowel obstruction. Following the operation she developed paralytic ileus and required total parenteral nutrition for one month. A suspected history of average 40 units of weekly alcohol consumption prior to the operation could not be confirmed and the patient did not show any sign of alcohol dependence. Within a few months of treatment with a daily oral dose of thiamine 200 mgs supplemented by multivitamins the patient showed subjective evidence of improvement in confusion, confabulation, and anterograde amnesia, although objective tests showed residual deficits in many areas of cognitive functioning, including immediate and delayed recall of verbal and non-verbal materials, planning and switching of attention. PMID:12446948

Comprehensive functional analysis of Rab GTPases in Drosophila nephrocytes.

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Fu, Yulong; Zhu, Jun-Yi; Zhang, Fujian; Richman, Adam; Zhao, Zhanzheng; Han, Zhe

2017-06-01

The Drosophila nephrocyte is a critical component of the fly renal system and bears structural and functional homology to podocytes and proximal tubule cells of the mammalian kidney. Investigations of nephrocyte cell biological processes are fundamental to understanding the insect renal system. Nephrocytes are highly active in endocytosis and vesicle trafficking. Rab GTPases regulate endocytosis and trafficking but specific functions of nephrocyte Rabs remain undefined. We analyzed Rab GTPase expression and function in Drosophila nephrocytes and found that 11 out of 27 Drosophila Rabs were required for normal activity. Rabs 1, 5, 7, 11 and 35 were most important. Gene silencing of the nephrocyte-specific Rab5 eliminated all intracellular vesicles and the specialized plasma membrane structures essential for nephrocyte function. Rab7 silencing dramatically increased clear vacuoles and reduced lysosomes. Rab11 silencing increased lysosomes and reduced clear vacuoles. Our results suggest that Rab5 mediates endocytosis that is essential for the maintenance of functionally critical nephrocyte plasma membrane structures and that Rabs 7 and 11 mediate alternative downstream vesicle trafficking pathways leading to protein degradation and membrane recycling, respectively. Elucidating molecular pathways underlying nephrocyte function has the potential to yield important insights into human kidney cell physiology and mechanisms of cell injury that lead to disease. The Drosophila nephrocyte is emerging as a useful in vivo model system for molecular target identification and initial testing of therapeutic approaches in humans.

Intracerebral hemorrhage associated with Sneddon's syndrome: is ischemia-related angiogenesis the cause? Case report and review of the literature

International Nuclear Information System (INIS)

Aquino Gondim, F. de A.; Leacock, R.O.; Subrammanian, T.A.; Cruz-Flores, S.

2003-01-01

Sneddon's syndrome is characterized by livedo reticularis and multiple ischemic infarcts often associated with antiphospholipid antibodies. Intracerebral hemorrhage (ICH) is unusual in Sneddon's syndrome and has not been reported as the presenting complaint. We report a 38-year-old woman with a history of two miscarriages, Raynaud's phenomenon and livedo reticularis who presented acutely with ICH. Angiography showed prominent leptomeningeal and transdural anastomoses (pseudoangiomatosis). Anticardiolipin antibodies were positive. A right frontal brain biopsy failed to reveal vasculitis and a skin biopsy was nonspecific. MRI showed residual intracerebral hemorrhage (ICH), diffuse atrophy, multiple small white matter infarcts and leptomeningeal enhancement. This is the first report of Sneddon's syndrome presenting with an ICH. It shares features with the Divry-van Bogaert syndrome. We discuss the cause of the pseudoangiomatosis pattern and its role in the genesis of the hemorrhage and suggest that cerebral angiography should be done in every patient with Sneddon's syndrome, as it could impact therapy. (orig.)

Vasoactive intestinal peptide-induced neurite remodeling in human neuroblastoma SH-SY5Y cells implicates the Cdc42 GTPase and is independent of Ras-ERK pathway

International Nuclear Information System (INIS)

Alleaume, Celine; Eychene, Alain; Harnois, Thomas; Bourmeyster, Nicolas; Constantin, Bruno; Caigneaux, Evelyne; Muller, Jean-Marc; Philippe, Michel

2004-01-01

Vasoactive intestinal peptide (VIP) is known to regulate proliferation or differentiation in normal and tumoral cells. SH-SY5Y is a differentiated cell subclone derived from the SK-N-SH human neuroblastoma cell line and possess all the components for an autocrine action of VIP. In the present study, we investigated the morphological changes and intracellular signaling pathways occurring upon VIP treatment of SH-SY5Y cells. VIP induced an early remodeling of cell projections: a branched neurite network spread out and prominent varicosities developed along neurites. Although activated by VIP, the Ras/ERK pathway was not required for the remodeling process. In contrast, pull-down experiments revealed a strong Cdc42 activation by VIP while expression of a dominant-negative Cdc42 prevented the VIP-induced neurite changes, suggesting an important role for this small GTPase in the process. These data provide the first evidence for a regulation of the activity of Rho family GTPases by VIP and bring new insights in the signaling pathways implicated in neurite remodeling process induced by VIP in neuroblastoma cells

Prevalence of small-bowel neoplasia in Lynch syndrome assessed by video capsule endoscopy

NARCIS (Netherlands)

Haanstra, Jasmijn F.; Al-Toma, Abdul; Dekker, Evelien; Vanhoutvin, Steven A. L. W.; Nagengast, Fokko M.; Mathus-Vliegen, Elisabeth M.; van Leerdam, Monique E.; de Vos tot Nederveen Cappel, Wouter H.; Sanduleanu, Silvia; Veenendaal, Roeland A.; Cats, Annemieke; Vasen, Hans F. A.; Kleibeuker, Jan H.; Koornstra, Jan J.

2015-01-01

The aim was to determine the prevalence of small-bowel neoplasia in asymptomatic patients with Lynch syndrome (LS) by video capsule endoscopy (VCE). After obtaining informed consent, asymptomatic proven gene mutation carriers aged 35-70 years were included in this prospective multicentre study in

Chronic intestinal pseudoobstruction syndrome

Energy Technology Data Exchange (ETDEWEB)

Yeon, Kyung Mo; Seo, Jeong Kee; Lee, Yong Seok [Seoul National University Children' s Hospital, Seoul (Korea, Republic of)

1992-03-15

Chronic intestinal pseudoobstruction syndrome is a rare clinical condition in which impaired intestinal peristalsis causes recurrent symptoms of bowel obstruction in the absence of a mechanical occlusion. This syndrome may involve variable segments of small or large bowel, and may be associated with urinary bladder retention. This study included 6 children(3 boys and 3 girls) of chronic intestinal obstruction. Four were symptomatic at birth and two were of the ages of one month and one year. All had abdominal distension and deflection difficulty. Five had urinary bladder distension. Despite parenteral nutrition and surgical intervention(ileostomy or colostomy), bowel obstruction persisted and four patients expired from sepses within one year. All had gaseous distension of small and large bowel on abdominal films. In small bowel series, consistent findings were variable degree of dilatation, decreased peristalsis(prolonged transit time) and microcolon or microrectum. This disease entity must be differentiated from congenital megacolon, ileal atresia and megacystis syndrome.

The 'invisible hand': regulation of RHO GTPases by RHOGDIs.

Science.gov (United States)

Garcia-Mata, Rafael; Boulter, Etienne; Burridge, Keith

2011-07-22

The 'invisible hand' is a term originally coined by Adam Smith in The Theory of Moral Sentiments to describe the forces of self-interest, competition and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, using similar forces to regulate the RHO GTPase cycle.

The invisible hand: regulation of RHO GTPases by RHOGDIs

Science.gov (United States)

Garcia-Mata, Rafael; Boulter, Etienne; Burridge, Keith

2011-01-01

Preface The 'invisible hand' is a term originally coined by Adam Smith in the Theory of Moral Sentiments to describe the forces of self-interest, competition, and supply and demand that regulate the resources in society. This metaphor continues to be used by economists to describe the self-regulating nature of a market economy. The same metaphor can be used to describe the RHO-specific guanine nucleotide dissociation inhibitor (RHOGDI) family, which operates in the background, as an invisible hand, using similar forces to regulate the RHO GTPase cycle. PMID:21779026

The GTPase Rab43 Controls the Anterograde ER-Golgi Trafficking and Sorting of GPCRs

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Chunman Li

2017-10-01

Full Text Available G-protein-coupled receptors (GPCRs constitute the largest superfamily of cell-surface signaling proteins. However, mechanisms underlying their surface targeting and sorting are poorly understood. Here, we screen the Rab family of small GTPases in the surface transport of multiple GPCRs. We find that manipulation of Rab43 function significantly alters the surface presentation and signaling of all GPCRs studied without affecting non-GPCR membrane proteins. Rab43 specifically regulates the transport of nascent GPCRs from the endoplasmic reticulum (ER to the Golgi. More interestingly, Rab43 directly interacts with GPCRs in an activation-dependent fashion. The Rab43-binding domain identified in the receptors effectively converts non-GPCR membrane protein transport into a Rab43-dependent pathway. These data reveal a crucial role for Rab43 in anterograde ER-Golgi transport of nascent GPCRs, as well as the ER sorting of GPCR members by virtue of its ability to interact directly.

Early diagnosis of Bardet-Biedl syndrome associated with obesity

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2008-03-01

Full Text Available One of the urgent problems of modern health care is the increase in the prevalence of obesity among children and adolescents. Late diagnosis and delayed initiation of treatment lead to serious complications such as hypertension, type 2 diabetes mellitus. At present there are quite rare syndromes associated with obesity: Prader-Willi syndrome, Bardet-Biedl, Alström. Bardet-Biedl syndrome, - a disease characterized by obesity central origin, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal dysfunction.

Clinical Syndromes Associated with Cardiovascular Diseases: A Review

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Xing Sheng Yang, MD, PhD, FACC, FAHA

2017-02-01

Full Text Available In clinical practice, a variety of syndromes are associated with cardiovascular disease and have characteristic findings. Most of them are an autosomal dominant genetic disorder and have different types of cardiovascular abnormalities, including electrocardiographic conduction defects, arrhythmias, cardiomyopathy, vascular and valvular diseases, cardiac septal defects, and pulmonary problems. There is a growing need for physicians to pay more attention to these syndromes.

Hopkins syndrome and phantom hernia: a rare association.

Science.gov (United States)

Elizabeth, K E; Guruprasad, C S; Sindhu, T G

2011-06-01

Acute flaccid paralysis (AFP), other than paralytic poliomyelitis, are usually due to demyelination like Guillian Barre syndrome (GBS), transverse myelitis and traumatic neuritis. Poliomyelitis like illness, Hopkins syndrome or Post Asthmatic Amotrophy, associated with bronchial asthma and hyperIgEemia has been reported in literature. We present a two and a half year old child who developed AFP with phantom hernia following an episode of bronchial asthma.

Neuropsychological findings associated with Panayiotopoulos syndrome in three children.

Science.gov (United States)

Hodges, Samantha L; Gabriel, Marsha T; Perry, M Scott

2016-01-01

Panayiotopoulos syndrome is a common idiopathic benign epilepsy that has a peak age of onset in early childhood. The syndrome is multifocal and shows significant electroencephalogram (EEG) variability, with occipital predominance. Although a benign syndrome often refers to the absence of neurological and neuropsychological deficits, the syndrome has recently been associated with cognitive impairments. Also, despite frequent occipital EEG abnormalities, research regarding the visual functioning of patients is less reported and often contradictory. The purpose of this study was to gain additional knowledge regarding the neurocognitive functioning of patients with Panayiotopoulos syndrome and specifically to address any visual processing deficits associated with the syndrome. Following diagnosis of the syndrome based on typical clinical and electrophysiological criteria, three patients, aged 5, 8, and 10years were referred by epileptologists for neuropsychological evaluation. Neuropsychological findings suggest that the patients had notable impairments on visual memory tasks, especially in comparison with verbal memory. Further, they demonstrated increased difficulty on picture memory suggesting difficulty retaining information from a crowded visual field. Two of the three patients showed weakness in visual processing speed, which may account for weaker retention of complex visual stimuli. Abilities involving attention were normal for all patients, suggesting that inattention is not responsible for these visual deficits. Academically, the patients were weak in numerical operations and spelling, which both rely partially on visual memory and may affect achievement in these areas. Overall, the results suggest that patients with Panayiotopoulos syndrome may have visual processing and visual memory problems that could potentially affect their academic capabilities. Identifying such difficulties may be helpful in creating educational and remedial assistance programs for

Possible association between phantom vibration syndrome and occupational burnout

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Chen CP

2014-12-01

Full Text Available Chao-Pen Chen,1 Chi-Cheng Wu,2 Li-Ren Chang,3 Yu-Hsuan Lin4 1Department of Education, National Taiwan University Hospital, 2Department of Family Medicine, Min-Sheng General Hospital, Taoyuan City, 3Department of Psychiatry, National Taiwan University, College of Medicine, 4Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan Background: Phantom vibration syndrome (PVS and phantom ringing syndrome (PRS occur in many cell phone users. Previous studies have indicated an association between PVS/PRS and job stress. The aim of this study was to determine if PVS/PRS were also associated with occupational burnout.Methods: This was a cross-sectional study of 384 employees of a high-tech company in northern Taiwan. They all completed a phantom vibration and ringing questionnaire, the Hospital Anxiety and Depression Scale, and the Chinese version of the Occupational Burnout Inventory.Results: Significantly more women and people with at least a college education were in the population with PRS and PVS, respectively. Anxiety and depression had no associations with PVS/PRS. Higher scores for personal fatigue, job fatigue, and service target fatigue had an independent impact on the presence of PVS, but only a higher score for service target fatigue had an independent impact on the presence of PRS.Conclusion: The independent association between work-related burnout and PVS/PRS suggests that PVS/PRS may be a harbinger of mental stress or a component of the clinical burnout syndrome, and may even be a more convenient and accurate predictor of occupational burnout. Keywords: phantom vibration syndrome, phantom ringing syndrome, occupational burnout

Parry-Romberg Syndrome Associated with Localized Scleroderma

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Jelena Maletic

2010-06-01

Full Text Available Parry-Romberg syndrome is a rare neurocutaneous disorder of unknown origin. It is characterized by progressive facial hemiatrophy and frequently overlaps with a condition known as linear scleroderma ‘en coup de sabre’. Neurological involvement is frequently described in these patients, including migraine, facial pain and epilepsy, which represent the commonest neurological conditions, sometimes associated with brain abnormalities ipsilaterally to the skin lesions. We present a case of Parry-Romberg syndrome with neurological involvement in a patient with diagnosed localized scleroderma (morphea.

Parry-Romberg Syndrome Associated with Localized Scleroderma

Science.gov (United States)

Maletic, Jelena; Tsirka, Vassiliki; Ioannides, Panos; Karacostas, Dimitrios; Taskos, Nikolaos

2010-01-01

Parry-Romberg syndrome is a rare neurocutaneous disorder of unknown origin. It is characterized by progressive facial hemiatrophy and frequently overlaps with a condition known as linear scleroderma ‘en coup de sabre’. Neurological involvement is frequently described in these patients, including migraine, facial pain and epilepsy, which represent the commonest neurological conditions, sometimes associated with brain abnormalities ipsilaterally to the skin lesions. We present a case of Parry-Romberg syndrome with neurological involvement in a patient with diagnosed localized scleroderma (morphea). PMID:20671858

A new case of keratoconus associated with Williams-Beuren syndrome.

Science.gov (United States)

Viana, Melissa Machado; Frasson, Maria; Leão, Letícia Lima; Stofanko, Martin; Gonçalves-Dornelas, Higgor; Cunha, Pricila da Silva; de Aguiar, Marcos José Burle

2013-09-01

Williams-Beuren syndrome is a multisystemic genetic disorder caused by a contiguous gene deletion at 7q11.23. Keratoconus is a complex disease and it is suspected to have a genetic origin, although the specific gene responsible for keratoconus has not been identified. Although there are several ocular features in Williams-Beuren syndrome, keratoconus is not regularly described as part of this syndrome. To report a new patient with keratoconus and Williams-Beuren syndrome. This is the third case of an association between Williams-Beuren syndrome and keratoconus. The authors believe that the Williams-Beuren syndrome chromosome region can be a possible target for further investigation as the genetic basis of keratoconus.

An association between diet, metabolic syndrome and lower urinary ...

African Journals Online (AJOL)

Diet is a key factor in the aetiology of many diseases, including metabolic syndrome and lower urinary tract disorders. Metabolic syndrome is a growing and increasingly expensive health problem in both the developed and the developing world, with an associated rise in morbidity and mortality. On the other hand, lower ...

Idiopathic hypertrophic cranial pachymeningitis associated with Sweet's Syndrome

Energy Technology Data Exchange (ETDEWEB)

Cano, Antonio E-mail: acano@hrs.sas.junta-andalucia.es; Ribes, Ramon; Riva, Andres de la; Rubio, Fernando Lopez; Sanchez, Carmen; Sancho, Jose L

2002-11-01

A case of hypertrophic cranial pachymeningitis associated with Sweet's Syndrome is presented. Both entities have been described in association with several other chronic systemic inflammatory diseases and autoimmune conditions. To our knowledge the coexistence between Sweet's Syndrome and hypertrophic cranial pachymeningitis has not been reported up to date. We suggest a possible autoimmune or dysimmune mechanism in the pathogenesis of these two entities.

Macrophage activation syndrome associated with griscelli syndrome type 2: case report and review of literature

Science.gov (United States)

Sefsafi, Zakia; Hasbaoui, Brahim El; Kili, Amina; Agadr, Aomar; Khattab, Mohammed

2018-01-01

Abstract Macrophage activation syndrome (MAS) is a severe and potentially fatal life-threatening condition associated with excessive activation and expansion of T cells with macrophages and a high expression of cytokines, resulting in an uncontrolled inflammatory response, with high levels of macrophage colony-stimulating factor and causing multiorgan damage. This syndrome is classified into primary (genetic/familial) or secondary forms to several etiologies, such as infections, neoplasias mainly hemopathies or autoimmune diseases. It is characterised clinically by unremitting high fever, pancytopaenia, hepatosplenomegaly, hepatic dysfunction, encephalopathy, coagulation abnormalities and sharply increased levels of ferritin. The pathognomonic feature of the syndrome is seen on bone marrow examination, which frequently, though not always, reveals numerous morphologically benign macrophages exhibiting haemophagocytic activity. Because MAS can follow a rapidly fatal course, prompt recognition of its clinical and laboratory features and immediate therapeutic intervention are essential. However, it is difficult to distinguish underlying disease flare, infectious complications or medication side effects from MAS. Although, the pathogenesis of MAS is unclear, the hallmark of the syndrome is an uncontrolled activation and proliferation of T lymphocytes and macrophages, leading to massive hypersecretion of pro-inflammatory cytokines. Mutations in cytolytic pathway genes are increasingly being recognised in children who develop MAS in his secondary form. We present here a case of Macrophage activation syndrome associated with Griscelli syndrome type 2 in a 3-years-old boy who had been referred due to severe sepsis with non-remitting high fever, generalized lymphoadenopathy and hepato-splenomegaly. Laboratory data revealed pancytopenia with high concentrations of triglycerides, ferritin and lactic dehydrogenase while the bone marrow revealed numerous morphologically benign

Toxic metabolic syndrome associated with HAART

DEFF Research Database (Denmark)

Haugaard, Steen B

2006-01-01

(HAART) may encounter the HIV-associated lipodystrophy syndrome (HALS), which attenuates patient compliance to this treatment. HALS is characterised by impaired glucose and lipid metabolism and other risk factors for cardiovascular disease. This review depicts the metabolic abnormalities associated...... with HAART by describing the key cell and organ systems that are involved, emphasising the role of insulin resistance. An opinion on the remedies available to treat the metabolic abnormalities and phenotype of HALS is provided....

Modifiable Lifestyle Behaviors Are Associated With Metabolic Syndrome in a Taiwanese Population.

Science.gov (United States)

Lin, Kuei-Man; Chiou, Jeng-Yuan; Ko, Shu-Hua; Tan, Jung-Ying; Huang, Chien-Ning; Liao, Wen-Chun

2015-11-01

To explore associations between metabolic syndrome and modifiable lifestyle behaviors among the adult population in Taiwan. This cross-sectional study analyzed data from a nationally representative sample that participated in the 2005-2008 Nutrition and Health Survey in Taiwan. The sample (2,337 participants older than 19 years) provided data on demographic characteristics, modifiable lifestyle behaviors, anthropometric measurements, and blood chemistry panel. These data were analyzed by descriptive statistics, univariate logistic regression, and multivariate logistic regression to determine factors associated with metabolic syndrome. Metabolic syndrome had a prevalence of 25.2%, and this prevalence increased with age. In univariate regression analysis, metabolic syndrome was associated with age, living with family members, educational level, and modifiable lifestyle behaviors (smoking, drinking, betel quid chewing, and physical activity). Individuals with a smoking history and currently chewing betel quid had the highest risk for metabolic syndrome. The risk for metabolic syndrome might be reduced by public health campaigns to encourage people to quit smoking cigarettes and chewing betel quid. Implementing more modifiable lifestyle behaviors in daily life will decrease metabolic syndrome in Taiwan. Considering that betel quid chewing and tobacco smoking interact to adversely affect metabolic syndrome risk, public health campaigns against both behaviors seem to be a cost-effective and efficient health promotion strategy to reduce the prevalence rate of metabolic syndrome. © 2015 Sigma Theta Tau International.

Are there common genetic and environmental factors behind the endophenotypes associated with the metabolic syndrome?

DEFF Research Database (Denmark)

Benyamin, B.; Sørensen, T.I.A.; Schousboe, K.

2007-01-01

and environmental factors influencing this cluster in a general population of twin pairs. MATERIALS AND METHODS: A multivariate genetic analysis was performed on nine endophenotypes associated with the metabolic syndrome from 625 adult twin pairs of the GEMINAKAR study of the Danish Twin Registry. RESULTS: All......AIMS/HYPOTHESIS: The cluster of obesity, insulin resistance, dyslipidaemia and hypertension, called the metabolic syndrome, has been suggested as a risk factor for cardiovascular disease and type 2 diabetes. The aim of the present study was to evaluate whether there are common genetic...... endophenotypes showed moderate to high heritability (0.31-0.69) and small common environmental variance (0.05-0.21). In general, genetic and phenotypic correlations between the endophenotypes were strong only within sets of physiologically similar endophenotypes, but weak to moderate for other pairs...

Association between habitual daytime napping and metabolic syndrome: a population-based study.

Science.gov (United States)

Lin, Diaozhu; Sun, Kan; Li, Feng; Qi, Yiqin; Ren, Meng; Huang, Chulin; Tang, Juying; Xue, Shengneng; Li, Yan; Yan, Li

2014-12-01

Our objective was to evaluate the association between habitual daytime napping and the prevalence of metabolic syndrome. We conducted a population-based study of 8,547 subjects aged 40 years or older. Metabolic syndrome was defined according to a harmonized definition from a joint statement and the recommended thresholds for the Chinese population. Information about sleep duration was self-reported. The prevalence of metabolic syndrome in the no daytime napping group, the 0 to 1 hour daytime napping group and the more than 1 hour daytime napping group were 35.0%, 36.0% and 44.5% among the females (Pnapping hours were positively associated with parameters of metabolic syndrome in the female subjects, including waist circumference, systolic blood pressure, triglycerides and fasting plasma glucose (Pnapping females, napping for more than 1 hour was independently associated with an increased prevalence of metabolic syndrome (odds ratio 1.39, 95% confidence interval, 1.13-1.72). Compared to the female subjects in the no daytime napping group, those habitually napped for more than 1 hour exhibited 46% and 26% increases in the prevalence of central obesity and hypertriglyceridemia (all Pnapping hours and metabolic syndrome among the male subjects. Daytime napping is associated with an increased prevalence of metabolic syndrome in middle-aged non-obese Chinese women. Copyright © 2014. Published by Elsevier Inc.

Subpleural lung cysts in Down syndrome: prevalence and association with coexisting diagnoses

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Biko, David M. [Pennsylvania Hospital, Department of Radiology, Philadelphia, PA (United States); Schwartz, Michael; Anupindi, Sudha A. [Children' s Hospital of Philadelphia, Philadelphia, PA (United States); Altes, Talissa A. [Children' s Hospital of Philadelphia, Philadelphia, PA (United States); University of Virginia, Charlottesville, VA (United States)

2008-03-15

Although subpleural cysts are known to be associated with Down syndrome, their etiology and prevalence remains unknown. To determine the prevalence of subpleural cysts in children with Down syndrome and the association with prematurity, congenital heart disease (CHD), extracorporeal membrane oxygenation (ECMO), and chronic ventilator support. A review of the CT examinations of 25 children with Down syndrome was performed to determine the presence, location, and distribution of cysts along with associated abnormalities. Charts were reviewed and coexistent diagnoses and past treatments were recorded. The prevalence of subpleural cysts was 36% with no significant association with CHD, ECMO, or chronic ventilator support. An association was found in the two children with a history of prematurity. The cysts were most commonly found in the anteromedial portion of the lung. Subpleural cysts are common in Down syndrome and should not be confused with another pathological process. An association with prematurity was found, but the low number of children in this study makes the connection uncertain. The etiology remains unclear, but it has been hypothesized that the cysts are associated with lung hypoplasia. (orig.)

Subpleural lung cysts in Down syndrome: prevalence and association with coexisting diagnoses

International Nuclear Information System (INIS)

Biko, David M.; Schwartz, Michael; Anupindi, Sudha A.; Altes, Talissa A.

2008-01-01

Although subpleural cysts are known to be associated with Down syndrome, their etiology and prevalence remains unknown. To determine the prevalence of subpleural cysts in children with Down syndrome and the association with prematurity, congenital heart disease (CHD), extracorporeal membrane oxygenation (ECMO), and chronic ventilator support. A review of the CT examinations of 25 children with Down syndrome was performed to determine the presence, location, and distribution of cysts along with associated abnormalities. Charts were reviewed and coexistent diagnoses and past treatments were recorded. The prevalence of subpleural cysts was 36% with no significant association with CHD, ECMO, or chronic ventilator support. An association was found in the two children with a history of prematurity. The cysts were most commonly found in the anteromedial portion of the lung. Subpleural cysts are common in Down syndrome and should not be confused with another pathological process. An association with prematurity was found, but the low number of children in this study makes the connection uncertain. The etiology remains unclear, but it has been hypothesized that the cysts are associated with lung hypoplasia. (orig.)

An intriguing association of Turner syndrome with severe nephrotic syndrome: searching for a diagnosis.

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Minzala, G; Ismail, G

2016-10-01

Systemic lupus erythematosus (SLE) is a chronic disease caused by an aberrant autoimmune response, with a large spectrum of clinical manifestations. It strikingly affects women. Recent papers reveal that the men with Klinefelter syndrome (47, XXY) have a higher incidence of lupus than the men in the general population, similar with that of genotypic females. On the other hand, there is a great lack of information regarding the association of SLE with Turner syndrome, but it seems to be a lower risk for females with Turner to develop SLE. We present a rare association of a Turner syndrome with SLE, with negative immunology for SLE and with diagnosis made on renal biopsy. These data suggest that the presence of two X chromosomes may predispose to SLE, the ligand (CD40 ligand) for one of the genes that contributes to the pathogenesis of SLE being located on the X chromosome. © The Author(s) 2016.

Cefepime Associated With Phenytoin Induced Stevens-Johnson Syndrome.

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Marco-Del Río, José; Domingo-Chiva, Esther; Cuesta-Montero, Pablo; Valladolid-Walsh, Ana; García-Martínez, Eva María

We describe a recent case of Stevens-Johnson Syndrome. A 49-year-old man was admitted to the Intensive Care Unit of an Anaesthesia and Resuscitation Department because of a Fournier gangrene that derived in a sepsis, ventilator-associated pneumonia, and renal failure. He was under treatment with cefepime and suffered a generalized status epilepticus, so started treatment with phenytoin. The next day he developed a "maculous cutaneous eruption in trunk and lower limbs" compatible with a Stevens-Johnson Syndrome. Stevens-Johnson Syndrome is a very severe and potentially fatal multiorganic disease, especially when present in critically ill patients, with a strong drug-related etiology, especially with antiepileptic drugs.

Novel COL4A1 mutations associated with HANAC syndrome: a role for the triple helical CB3[IV] domain.

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Plaisier, Emmanuelle; Chen, Zhiyong; Gekeler, Florian; Benhassine, Safa; Dahan, Karine; Marro, Béatrice; Alamowitch, Sonia; Paques, Michel; Ronco, Pierre

2010-10-01

The COL4A1 gene encodes the α1-chain of type IV collagen, which is ubiquitously expressed in basement membranes. Mutations in COL4A1 have been reported in autosomal-dominant porencephaly and in patients with symptomatic small vessel brain disease, inconstantly associated with eye defects. We have previously reported three COL4A1 mutations associated with a systemic phenotype that we called HANAC (Hereditary Angiopathy, Nephropathy, Aneurysms, and Cramps). We carried out a clinical and genetic study of three families presenting with characteristic features of HANAC syndrome. Common systemic signs included arterial retinal tortuosity and muscle cramps, with a variable combination of small vessel brain disease, Raynaud phenomena, and kidney defects. Three novel COL4A1 missense substitutions are described, which affect highly conserved glycine residues within the collagenous domain of the protein. All six known mutations associated with the HANAC phenotype are localized within the CB3[IV] fragment of COL4A1, which encompasses major integrin-binding sites. Our results confirm that HANAC syndrome is a distinct clinical entity within the COL4A1-related disorders, which is characterized by systemic involvement and usually asymptomatic brain disease. The restricted distribution of COL4A1 mutations within the CB3[IV] region is a characteristic of the reports of patients with HANAC, which suggests that abnormal cell-type IV collagen interactions may underlie the systemic defects observed in this syndrome. Copyright © 2010 Wiley-Liss, Inc.

Association of Wolfram syndrome with Fallot tetralogy in a girl.

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Korkmaz, Hüseyin A; Demir, Korcan; Hazan, Filiz; Yıldız, Melek; Elmas, Özlem N; Özkan, Behzat

2016-06-01

Wolfram syndrome (DIDMOAD: diabetes insipidus, diabetes mellitus, optic atrophy and deafness) is a rare neurodegenerative disorder. Mutations of the WFS1 (wolframin) on chromosome 4 are responsible for the clinical manifestations in majority of patients with Wolfram syndrome. Wolfram syndrome is also accompanied by neurologic and psychiatric disorders, urodynamic abnormalities, restricted joint motility, cardiovascular and gastrointestinal autonomic neuropathy, hypergonadotrophic hypogonadism in males and diabetic microvascular disorders. There are very limited data in the literature regarding cardiac malformations associated in children with Wolfram syndrome. A 5-year-old girl with Wolfram syndrome and tetralogy of Fallot is presented herein. Sociedad Argentina de Pediatría.

A Case of Microangiopathic Antiphospholipid-Associated Syndromes during Pregnancy: Review of the Literature

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Nobuhiro Suzumori

2012-01-01

Full Text Available Microangiopathic antiphospholipid-associated syndromes (MAPSs are reported as encompassing several conditions mainly affecting the microvasculature of selected organs: the liver in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet; kidney, brain, and skin in TTP (thrombotic thrombocytopenic purpura. It is predominant in patients with catastrophic antiphospholipid syndrome (APS. A recent report suggests that APS is not only a thrombotic disease but also associated with microangiopathic features, and it can explain the greater prevalence of HELLP syndrome in these patients. We here report a case of MAPS during pregnancy associated with systemic lupus erythematosus (SLE in early second trimester.

Association Between Vitamin D Insufficiency and Metabolic Syndrome in Patients With Psychotic Disorders.

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Yoo, Taeyoung; Choi, Wonsuk; Hong, Jin-Hee; Lee, Ju-Yeon; Kim, Jae-Min; Shin, Il-Seon; Yang, Soo Jin; Amminger, Paul; Berk, Michael; Yoon, Jin-Sang; Kim, Sung-Wan

2018-04-01

This study examined the association between vitamin D and metabolic syndrome in patients with psychotic disorders. The study enrolled 302 community-dwelling patients with psychotic disorders. Sociodemographic and clinical characteristics, including blood pressure, physical activity, and dietary habit were gathered. Laboratory examinations included vitamin D, lipid profile, fasting plasma glucose, HbA1c, liver function, and renal function. Vitamin D insufficiency was defined as vitamin D insufficiency were identified. Among the 302 participants, 236 patients (78.1%) had a vitamin D insufficiency and 97 (32.1%) had metabolic syndrome. Vitamin D insufficiency was significantly associated with the presence of metabolic syndrome (p=0.006) and hypertension (p=0.017). Significant increases in triglycerides and alanine transaminase were observed in the group with a vitamin D insufficiency (p=0.002 and 0.011, respectively). After adjusting for physical activity and dietary habit scores, vitamin D insufficiency remained significantly associated with metabolic syndrome and hypertension. Vitamin D insufficiency was associated with metabolic syndrome and was particularly associated with high blood pressure, although the nature, direction and implications of this association are unclear.

Association of ghrelin polymorphisms with metabolic syndrome in Han Nationality Chinese.

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Xu, Ling-Ling; Xiang, Hong-Ding; Qiu, Chang-Chun; Xu, Qun

2008-06-01

To investigate the association of ghrelin gene polymorphisms with metabolic syndrome in Han Nationality Chinese. A total of 240 patients with metabolic syndrome and 427 adults aged above forty years were recruited. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The allelic frequency of the Leu72Met polymorphism was 17.3% in the patient group and 11.9% in the control group (chi2 = 7.36, P = 0.007). Metabolic syndrome was more prevalent among carriers of the Met72 variant (43.8 vs 33.1%, age- and sex-adjusted odds ratio = 1.57, P = 0.01). No Arg51Gln variants were found in our study subjects. Rather than being associated with its individual components, Leu72Met polymorphism is associated with metabolic syndrome in the Han Nationality Chinese. Arg51Gln polymorphism is rare in the Han Nationality Chinese.

The Association of Metabolic Syndrome and Urolithiasis

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Yee V. Wong

2015-01-01

Full Text Available There has been an increasing prevalence of kidney stones over the last 2 decades worldwide. Many studies have indicated a possible association between metabolic syndrome and kidney stone disease, particularly in overweight and obese patients. Many different definitions of metabolic syndrome have been suggested by various organizations, although the definition by the International Diabetes Federation (IDF is universally considered as the most acceptable definition. The IDF definition revolves around 4 core components: obesity, dyslipidemia, hypertension, and diabetes mellitus. Several hypotheses have been proposed to explain the pathophysiology of urolithiasis resulting from metabolic syndrome, amongst which are the insulin resistance and Randall’s plaque hypothesis. Similarly the pathophysiology of calcium and uric acid stone formation has been investigated to determine a connection between the two conditions. Studies have found many factors contributing to urolithiasis in patients suffering from metabolic syndrome, out of which obesity, overweight, and sedentary lifestyles have been identified as major etiological factors. Primary and secondary prevention methods therefore tend to revolve mainly around lifestyle improvements, including dietary and other preventive measures.

Williams Syndrome and 15q Duplication: Coincidence versus Association.

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Khokhar, Aditi; Agarwal, Swashti; Perez-Colon, Sheila

2017-01-01

Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN -specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.

Eaton-Lambert syndrome with small cell carcinoma of the lung. A case with a favorable clinical course through chemotherapy and radiation

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Matsushita, Shigeki; Hanyu, Norinao; Ichiyoshi, Takeo; Yanagisawa, Nobuo

1987-04-01

A case of Eaton-Lambert syndrome with small cell carcinoma of the lung responding favorably to chemotherapy and radiation was described. The patient, 56-year-old man, began to feel weakness of the upper limbs in 1982 (age 52). His condition deteriorated gradually, followed by weakness of the lower limbs, dysphagia and bilateral ptosis. He was admitted to our hospital in Janualy 1984. We started radiation therapy for the lung mass and his neurological findings improved slightly. In June 1984, he complained of pain in the left elbow accompanied by increased ptosis and weakness in the limbs. The biopsy of left elbow lymphnode revealed the metastasis of intermediate cell type small cell carcinoma of the lung, and the diagnosis of Eaton-Lambert syndrome was confirmed. Metastases were also found at the right parietal bone and cervical lymphnode. We started a combination chemotherapy consisting of ACNU, vincristine, methotrexate and cyclophosphamide, adding prophylactic irradiation to the cranium and metastatic regions. After treatment, the metastases disappeared completely and no abnormal findings were found except for decreased tendon reflexes of the upper limbs. Post-treatment electromyography showed marked reduction of waxing and post-tetanic facilitation. We have intermittently continued a combination chemotherapy for consolidation. The patient is living well 21 months after the distant metastases became apparent, and is showing marked improvement of Eaton-Lambert syndrome through chemotherapy and radiation. We propose that anti-neoplastic treatment is the first choice for the treatment of Eaton-Lambert syndorame associated with small cell carcinoma of long. (J.P.N.).

Paraneoplastic syndromes and autoimmune encephalitis

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Rosenfeld, Myrna R.; Titulaer, Maarten J.

2012-01-01

Summary We review novel findings in paraneoplastic syndromes including the Lambert-Eaton myasthenic syndrome, and then focus on the novel disorders associated with antibodies against cell surface antigens, discussing the importance and caveats of antibody testing, and providing an algorithm for interpretation of results. In anti-NMDAR encephalitis 2 novel findings include the recognition of a characteristic EEG pattern (“extreme delta brush”) in 30% of patients and the demonstration of a fronto-temporo-occipital gradient of glucose metabolism that correlates with disease activity. In limbic encephalitis, antibodies to GABA(B) receptor are the most frequently detected in patients with small-cell lung cancer who are anti-Hu negative, and antibodies to mGluR5 distinctively associate with Hodgkin lymphoma (Ophelia syndrome). We also address the syndromes associated with “VGKC-complex antibodies,” a problematic term that groups well-characterized immune-mediated disorders (LGI1, Caspr2) with others that lack syndrome specificity, are less responsive to treatment, and for which the target antigens are unknown. PMID:23634368

Congenital high airway obstruction syndrome (CHAOS) associated with cervical myelomeningocele.

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Adin, Mehmet Emin

2017-10-01

Congenital high airway obstruction syndrome (CHAOS) is a rare and potentially fatal entity resulting from complete or near complete developmental airway obstruction. Although most reported cases of CHAOS are sporadic, the condition may also be associated with certain syndromes and a variety of cervical masses. Meningocele and myelomeningocele have not yet been reported in association with CHAOS. We describe the typical constellation of sonographic findings in a case of early diagnosis of CHAOS associated with cervical myelomeningocele. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:507-510, 2017. © 2016 Wiley Periodicals, Inc.

Possible association between phantom vibration syndrome and occupational burnout.

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Chen, Chao-Pen; Wu, Chi-Cheng; Chang, Li-Ren; Lin, Yu-Hsuan

2014-01-01

Phantom vibration syndrome (PVS) and phantom ringing syndrome (PRS) occur in many cell phone users. Previous studies have indicated an association between PVS/PRS and job stress. The aim of this study was to determine if PVS/PRS were also associated with occupational burnout. This was a cross-sectional study of 384 employees of a high-tech company in northern Taiwan. They all completed a phantom vibration and ringing questionnaire, the Hospital Anxiety and Depression Scale, and the Chinese version of the Occupational Burnout Inventory. Significantly more women and people with at least a college education were in the population with PRS and PVS, respectively. Anxiety and depression had no associations with PVS/PRS. Higher scores for personal fatigue, job fatigue, and service target fatigue had an independent impact on the presence of PVS, but only a higher score for service target fatigue had an independent impact on the presence of PRS. The independent association between work-related burnout and PVS/PRS suggests that PVS/PRS may be a harbinger of mental stress or a component of the clinical burnout syndrome, and may even be a more convenient and accurate predictor of occupational burnout.

Epigenome-wide association study of metabolic syndrome in African-American adults.

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Akinyemiju, Tomi; Do, Anh N; Patki, Amit; Aslibekyan, Stella; Zhi, Degui; Hidalgo, Bertha; Tiwari, Hemant K; Absher, Devin; Geng, Xin; Arnett, Donna K; Irvin, Marguerite R

2018-01-01

The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies. Data on metabolic syndrome and DNA methylation was assessed on 614 African-Americans from the Hypertension Genetic Epidemiology Network (HyperGEN) study. Metabolic syndrome was defined using the joint harmonized criteria, and DNA methylation was assessed using the Illumina HumanMethylation450K Bead Chip assay on DNA extracted from buffy coat. Linear mixed effects regression models were used to examine the association between CpG methylation at > 450,000 CpG sites and metabolic syndrome adjusted for study covariates. Replication using DNA from a separate sample of 69 African-Americans, as well as meta-analysis combining both cohorts, was conducted. Two differentially methylated CpG sites in the IGF2BP1 gene on chromosome 17 (cg06638433; p value = 3.10 × 10 - 7 ) and the ABCG1 gene on chromosome 21 (cg06500161; p value = 2.60 × 10 - 8 ) were identified. Results for the ABCG1 gene remained statistically significant in the replication dataset and meta-analysis. Metabolic syndrome was consistently associated with increased methylation in the ABCG1 gene in the discovery and replication datasets, a gene that encodes a protein in the ATP-binding cassette transporter family and is involved in intra- and extra-cellular signaling and lipid transport.

Association and pattern of diastolic dysfunction in patients of metabolic syndrome

International Nuclear Information System (INIS)

Khan, A.R.; Khan, M.Q.

2008-01-01

Diastolic dysfunction is important predictor of morbidity and mortality in patients with metabolic syndrome. This prospective study is to evaluate an association and pattern of diastolic dysfunction in patients of metabolic syndrome in our population. This cross-sectional study was performed at Armed Forces Institute of Cardiology Rawalpindi for a period of 6 months from 20th November 2007 to 20th April 2008. One hundred eligible and consenting patients having metabolic syndrome reporting in the OPD were registered. Inclusion criteria included patients of metabolic syndrome with negative ETT and normal systolic function. Exclusion criteria were patients with age above 60 years and valvular heart disease. Data was collected by a structured clinical interview with a physician, ECG and a transthoracic M-mode, 2D and TDI echocardiogram. The metabolic syndrome was defined according to International Diabetes Federation. There was a positive association between the degree of the metabolic syndrome-assessed as number of concurrently present components-and parameters of cardiac structure and function, with a consistent and statistically significant trend for all cardiac variables considered(p=0.000). There was also a positive association between each parameter and the cardiac diastolic dysfunction grading, e.g., systolic blood pressure (p=0.000), diastolic blood pressure (p=0.005), waist circumference (p=0.004), fasting blood sugar (p=0.008), triglycerides (p=0.006), HDL cholesterol (p=0.001). Several cardiac functional abnormalities regardless of symptoms increased progressively with increasing degree of metabolic syndrome. (author)

Rho GTPases: Novel Players in the Regulation of the DNA Damage Response?

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Gerhard Fritz

2015-09-01

Full Text Available The Ras-related C3 botulinum toxin substrate 1 (Rac1 belongs to the family of Ras-homologous small GTPases. It is well characterized as a membrane-bound signal transducing molecule that is involved in the regulation of cell motility and adhesion as well as cell cycle progression, mitosis, cell death and gene expression. Rac1 also adjusts cellular responses to genotoxic stress by regulating the activity of stress kinases, including c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK and p38 kinases as well as related transcription factors. Apart from being found on the inner side of the outer cell membrane and in the cytosol, Rac1 has also been detected inside the nucleus. Different lines of evidence indicate that genotoxin-induced DNA damage is able to activate nuclear Rac1. The exact mechanisms involved and the biological consequences, however, are unclear. The data available so far indicate that Rac1 might integrate DNA damage independent and DNA damage dependent cellular stress responses following genotoxin treatment, thereby coordinating mechanisms of the DNA damage response (DDR that are related to DNA repair, survival and cell death.

Diagnostic criteria for cryopyrin-associated periodic syndrome (CAPS)

NARCIS (Netherlands)

Kuemmerle-Deschner, Jasmin B.; Ozen, Seza; Tyrrell, Pascal N.; Kone-Paut, Isabelle; Goldbach-Mansky, Raphaela; Lachmann, Helen; Blank, Norbert; Hoffman, Hal M.; Weissbarth-Riedel, Elisabeth; Hugle, Boris; Kallinich, Tilmann; Gattorno, Marco; Gul, Ahmet; Ter Haar, Nienke; Oswald, Marlen; Dedeoglu, Fatma; Cantarini, Luca; Benseler, Susanne M.

2017-01-01

Cryopyrin-associated periodic syndrome (CAPS) is a rare, heterogeneous disease entity associated with NLRP3 gene mutations and increased interleukin-1 (IL-1) secretion. Early diagnosis and rapid initiation of IL-1 inhibition prevent organ damage. The aim of the study was to develop and validate

Association of Objectively Measured Physical Activity and Metabolic Syndrome Among US Adults With Osteoarthritis.

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Liu, Shao-Hsien; Waring, Molly E; Eaton, Charles B; Lapane, Kate L

2015-10-01

To investigate the association between objectively measured physical activity and metabolic syndrome among adults with osteoarthritis (OA). Using cross-sectional data from the 2003-2006 National Health and Nutrition Examination Survey, we identified 566 adults with OA with available accelerometer data assessed using Actigraph AM-7164 and measurements necessary to determine metabolic syndrome by the Adult Treatment Panel III. Analysis of variance was conducted to examine the association between continuous variables in each activity level and metabolic syndrome components. Logistic models estimated the relationship of quartile of daily minutes of different physical activity levels to odds of metabolic syndrome adjusted for socioeconomic and health factors. Among persons with OA, most were women average age of 62.1 years and average disease duration of 12.9 years. Half of adults with OA had metabolic syndrome (51.0%; 95% confidence interval [95% CI] 44.2%-57.8%), and only 9.6% engaged in the recommended 150 minutes per week of moderate/vigorous physical activity. Total sedentary time was associated with higher rates of metabolic syndrome and its components, while light and objectively measured moderate/vigorous physical activity was inversely associated with metabolic syndrome and its components. Higher levels of light activity were associated with lower prevalence of metabolic syndrome (quartile 4 versus quartile 1: adjusted odds ratio 0.45, 95% CI 0.24-0.84, P for linear trend physical activity, especially in light intensity, is more likely to be associated with decreasing prevalence of metabolic syndrome among persons with OA. © 2015, American College of Rheumatology.

Primary biliary cirrhosis--autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

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Pamfil, Cristina; Candrea, Elisabeta; Berki, Emese; Popov, Horațiu I; Radu, Pompilia I; Rednic, Simona

2015-03-01

Autoimmune liver diseases may be associated with extrahepatic autoimmune pathology. We report the case of a 52-year old woman who initially presented to the gastroenterology department for extreme fatigue, pale stools, dark urine and pruritus. Laboratory tests showed significant cholestasis and elevation of aminotransferase levels. Immunological tests revealed positive antinuclear (ANA=1:320) and antimitochondrial antibodies (AMA=1:40) with negative anti-smooth muscle and liver kidney microsomal type 1 antibodies. The biopsy was compatible with overlap syndrome type 1. The patient was commenced on immunosuppressive therapy according to standard of care (azathioprine 50mg, ursodeoxycholic acid and prednisone 0.5mg/kg), with moderate biochemical improvement. She subsequently developed proximal symmetrical weakness and cutaneous involvement and was diagnosed with biopsy-proven dermatomyositis. The immunosuppressive regimen was intensified to 150 mg azathioprine. At the three-month follow-up, her symptoms subsided and aminotransferases and muscle enzymes normalized. Upon further investigation the patient was diagnosed with autoimmune thyroiditis and antiphospholipid syndrome. To our knowledge, this is the first case of primary biliary cirrhosis - autoimmune hepatitis overlap syndrome associated with dermatomyositis, autoimmune thyroiditis and antiphospholipid syndrome.

Association of Marijuana Use and Cyclic Vomiting Syndrome

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Mithun B. Pattathan

2012-06-01

Full Text Available Cannabis use has become one of the most commonly abused drugs in the world. It is estimated that each year 2.6 million individuals in the USA become new users and most are younger than 19 years of age. Reports describe marijuana use as high as 40–50% in male Cyclic Vomiting Syndrome patients. It is this interest in cannabis in the World, coupled with recognition of a cyclic vomiting illness associated with its chronic use that beckons a review of the most current articles, as well as a contribution from our own experiences in this area. The similarities we have demonstrated for both cannibinoid hyperemesis syndrome and cyclic vomiting make the case that cannibinoid hyperemesis syndrome is a subset of patients who have the diagnoses of cyclic vomiting syndrome and the role of marijuana should always be considered in the diagnosis of CVS, particularly in males.

Association of Sicca Syndrome with Proviral Load and Proinflammatory Cytokines in HTLV-1 Infection

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Clara Mônica Lima

2016-01-01

Full Text Available The Sjögren syndrome has been diagnosed in patients with HTLV-1 associated myelopathy and dry mouth and dry eyes are documented in HTLV-1 carriers. However the diagnosis of Sjögren syndrome in these subjects has been contested. In this cross-sectional study, we evaluated the role of immunological factors and proviral load, in sicca syndrome associated with HTLV-1 in patients without myelopathy. Subjects were recruited in the HTLV-1 Clinic, from 2009 to 2011. The proviral load and cytokine levels (IFN-γ, TNF-α, IL-5, and IL-10 were obtained from a database containing the values presented by the subjects at admission in the clinic. Of the 272 participants, 59 (21.7% had sicca syndrome and in all of them anti-Sjögren syndrome related antigen A (SSA and antigen B (SSB were negatives. The production of TNF-α and IFN-γ was higher in the group with sicca syndrome (P<0.05 than in HTLV-1 infected subjects without sicca syndrome. Our data indicates that patients with sicca syndrome associated with HTLV-1 do not have Sjögren syndrome. However the increased production of TNF-α and IFN-γ in this group of patients may contribute to the pathogenesis of sicca syndrome associated with HTLV-1.

Severe Psychomotor Delay in a Severe Presentation of Cat-Eye Syndrome

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Guillaume Jedraszak

2015-01-01

Full Text Available Cat-eye syndrome is a rare genetic syndrome of chromosomal origin. Individuals with cat-eye syndrome are characterized by the presence of preauricular pits and/or tags, anal atresia, and iris coloboma. Many reported cases also presented with variable congenital anomalies and intellectual disability. Most patients diagnosed with CES carry a small supernumerary bisatellited marker chromosome, resulting in partial tetrasomy of 22p-22q11.21. There are two types of small supernumerary marker chromosome, depending on the breakpoint site. In a very small proportion of cases, other cytogenetic anomalies are reportedly associated with the cat-eye syndrome phenotype. Here, we report a patient with cat-eye syndrome caused by a type 1 small supernumerary marker chromosome. The phenotype was atypical and included a severe developmental delay. The use of array comparative genomic hybridization ruled out the involvement of another chromosomal imbalance in the neurological phenotype. In the literature, only a few patients with cat-eye syndrome present with a severe developmental delay, and all of the latter carried an atypical partial trisomy 22 or an uncharacterized small supernumerary marker chromosome. Hence, this is the first report of a severe neurological phenotype in cat-eye syndrome with a typical type 1 small supernumerary marker chromosome. Our observation clearly complicates prognostic assessment, particularly when cat-eye syndrome is diagnosed prenatally.

Rab5 GTPase controls chromosome alignment through Lamin disassembly and relocation of the NuMA-like protein Mud to the poles during mitosis

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Capalbo, Luisa; D'Avino, Pier Paolo; Archambault, Vincent; Glover, David M.

2011-01-01

The small GTPase Rab5 is a conserved regulator of membrane trafficking; it regulates the formation of early endosomes, their transport along microtubules, and the fusion to the target organelles. Although several members of the endocytic pathway were recently implicated in spindle organization, it is unclear whether Rab5 has any role during mitosis. Here, we describe that Rab5 is required for proper chromosome alignment during Drosophila mitoses. We also found that Rab5 associated in vivo with nuclear Lamin and mushroom body defect (Mud), the Drosophila counterpart of nuclear mitotic apparatus protein (NuMA). Consistent with this finding, Rab5 was required for the disassembly of the nuclear envelope at mitotic entry and the accumulation of Mud at the spindle poles. Furthermore, Mud depletion caused chromosome misalignment defects that resembled the defects of Rab5 RNAi cells, and double-knockdown experiments indicated that the two proteins function in a linear pathway. Our results indicate a role for Rab5 in mitosis and reinforce the emerging view of the contributions made by cell membrane dynamics to spindle function. PMID:21987826

Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

International Nuclear Information System (INIS)

Tsukamoto, Yuta; Kagiwada, Satoshi; Shimazu, Sayuri; Takegawa, Kaoru; Noguchi, Tetsuko; Miyamoto, Masaaki

2015-01-01

The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed

Coordinated regulation by two VPS9 domain-containing guanine nucleotide exchange factors in small GTPase Rab5 signaling pathways in fission yeast

Energy Technology Data Exchange (ETDEWEB)

Tsukamoto, Yuta [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Kagiwada, Satoshi [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Shimazu, Sayuri [Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Takegawa, Kaoru [Department of Bioscience and Biotechnology, Graduate School of Bioresource and Bioenvironmental Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan); Noguchi, Tetsuko [Department of Biological Sciences, Faculty of Science, Nara Women' s University, Kitauoyanishi-machi, Nara 630-8506 (Japan); Miyamoto, Masaaki, E-mail: miya@kobe-u.ac.jp [Department of Biology, Graduate School of Science, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan); Center for Supports to Research and Education Activities, Kobe University, 1-1 Rokkodai-cho, Nada, Kobe 657-8501 (Japan)

2015-03-20

The small GTPase Rab5 is reported to regulate various cellular functions, such as vesicular transport and endocytosis. VPS9 domain-containing proteins are thought to activate Rab5(s) by their guanine-nucleotide exchange activities. Numerous VPS9 proteins have been identified and are structurally conserved from yeast to mammalian cells. However, the functional relationships among VPS9 proteins in cells remain unclear. Only one Rab5 and two VPS9 proteins were identified in the Schizosaccharomyces pombe genome. Here, we examined the cellular function of two VPS9 proteins and the relationship between these proteins in cellular functions. Vps901-GFP and Vps902-GFP exhibited dotted signals in vegetative and differentiated cells. vps901 deletion mutant (Δvps901) cells exhibited a phenotype deficient in the mating process and responses to high concentrations of ions, such as calcium and metals, and Δvps901Δvps902 double mutant cells exhibited round cell shapes similar to ypt5-909 (Rab5 mutant allele) cells. Deletion of both vps901 and vps902 genes completely abolished the mating process and responses to various stresses. A lack of vacuole formation and aberrant inner cell membrane structures were also observed in Δvps901Δvps902 cells by electron microscopy. These data strongly suggest that Vps901 and Vps902 are cooperatively involved in the regulation of cellular functions, such as cell morphology, sexual development, response to ion stresses, and vacuole formation, via Rab5 signaling pathways in fission yeast cells. - Highlights: • Roles of Rab5 activator VPS9 proteins in cellular functions. • Cooperation between VPS9 proteins in Rab5 signaling pathway. • Roles of each VPS9 protein in Rab5 signaling pathway are discussed.

Usher syndrome associated with a variant of Dandy-Walker malformation.

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Simsek, Tulay; Ozdamar, Yasemin; Simsek, Enver; Men, Gamze

2010-05-21

Three cases of Usher syndrome associated with a variant of Dandy-Walker malformation in three siblings from consanguineous Turkish parents are described. The siblings had retinitis pigmentosa and hearing loss. Two of the siblings also had mental retardation, which is not a constant finding in Usher syndrome. Dandy-Walker malformation might have contributed to the mental retardation in two of these patients and might be a coincidental finding with Usher syndrome. Copyright 2010, SLACK Incorporated.

Association of cortisol and the metabolic syndrome in Korean men and women.

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Park, Sat Byul; Blumenthal, James A; Lee, Soon Young; Georgiades, Anastasia

2011-07-01

Obesity and the metabolic syndrome are closely related and have become increasingly prevalent in Korea. The cardiovascular disease (CVD) risk factors comprising the metabolic syndrome have previously been associated with increased hypothalamic-pituitary-adrenal axis (HPAA) activity, but the associations have not been extensively examined in non-Caucasian populations. The aim of the present study was to investigate the relationships between cortisol, adiposity and the metabolic syndrome in a Korean population. A total of 1,881 adults participated in the study between January 2001 and February 2008. Sociodemographic data were assessed by questionnaires. Body composition, clinic blood pressures as well as metabolic variables including glucose, insulin, and lipid profile were assessed and analyzed in relation to cortisol levels. Mean age of the participants was 58.7 ± 10.8 yr. Higher levels of cortisol was associated with elevated blood pressure, fasting glucose and total cholesterol in men, and between cortisol and systolic blood pressure, fasting glucose and total cholesterol in women. There was an increased risk for the metabolic syndrome associated with higher cortisol levels in both men (P cortisol levels are associated with several CVD risk factors and the metabolic syndrome, independent of overall of adiposity level, in Korean men and women.

Imaging Findings of Central Nervous System Vasculitis Associated with Goodpasture's Syndrome: a Case Report

International Nuclear Information System (INIS)

Kim, Jee Young; Ahn, Kook Jin; Jung, Jung Im; Jung, So Lyung; Kim, Bum Soo; Hahn, Seong Tae

2007-01-01

We report a rare case of CNS vasculitis associated with Goodpasture's syndrome in a 34-year-old man, who presented with a seizure and sudden onset of right sided weakness. He also had recurrent hemoptysis of one month's duration. Goodpasture's syndrome is histologically diagnosed by intense linear deposits of IgG along the glomerular basement membrane in both renal and lung tissues. oodpasture's syndrome is a rare disease, characterized by rapidly progressive glomerulonephritis, diffuse pulmonary hemorrhage and circulating antiglomerular basement membrane antibody (anti-GBM antibody). Central nervous system (CNS) manifestations in Goodpasture's syndrome are extremely rare, with only a few cases having been reported in the literature (8 10). Therefore, we present our imaging findings of CNS vasculitis associated with Goodpasture's syndrome, together with a review of the relevant literature. In summary, CNS vasculitis associated with Goodpasture's syndrome is extremely rare. Awareness of the imaging findings, as well as the clinical significance of CNS vasculitis associated with Goodpasture's syndrome, can be helpful in making the correct diagnosis and subsequent management of this rare condition

Association of hereditary elliptocytosis and Gilbert’s syndrome as the cause of biliary calculosis: Case report

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Radlović Nedeljko

2011-01-01

Full Text Available Introduction. Biliary calculosis is rare in children. It occurs associated with different haemolytic and non-haemolytic disorders, which are sometimes also combined. Case Outline. A 15-year-old male was hospitalized due to biliary calculosis and non-conjugated hyper-bilirubinemia. A mild non-conjugated hyperbilirubinemia, without anaemia and other symptoms of liver dysfunction, was registered at age 8 years, and 7 years later cholelithiasis with transitory choledocholithiasis. The finding of ellyptocytes in blood smear, which was also verified in mother, normal haemoglobin count and the absence of diseases followed by secondary dysmorphic erythrocytes of this type, indicated a clinically milder (compensated hereditary ellyptocytosis, while more than a double increase of non-conjugated serum bilirubin fracture after a three-day hypocaloric diet (400 kcal per day showed the concurrent presence of Gilbert’s syndrome. In the laparascopically removed gallbladder a larger number of small pigmented calculi were disclosed. Conclusion. Gilbert’s syndrome is an essential precipitating factor of biliary calculosis in patients with chronic haemolytic condition. Thus, in all cases of biliary calculosis and non-conjugated hyperbilirubinemia with absent clinical and laboratory parameters of liver disorders and anaemia, except in compensated haemolytic disease and Gilbert’s syndrome as isolated disorders, a possibility of their association should be taken into consideration.

Management of extracolonic tumours in patients with Lynch syndrome

NARCIS (Netherlands)

Koornstra, Jan J; Mourits, Marian Je; Sijmons, Rolf H; Leliveld-Kors, Anna; Hollema, Harry; Kleibeuker, Jan H

Hereditary nonpolyposis colorectal cancer, or Lynch syndrome, is responsible for 2-3% of all colorectal cancers. Lynch syndrome is also associated with a high risk of extracolonic cancers, including endometrial, stomach, small bowel, pancreas, biliary tract, ovary, urinary tract, brain, and skin

Association of Serum Ferritin Levels with Metabolic Syndrome and Insulin Resistance.

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Padwal, Meghana K; Murshid, Mohsin; Nirmale, Prachee; Melinkeri, R R

2015-09-01

The impact of CVDs and Type II DM is increasing over the last decade. It has been estimated that by 2025 their incidence will double. Ferritin is one of the key proteins regulating iron homeostasis and is a widely available clinical biomarker of iron status. Some studies suggest that prevalence of atherosclerosis and insulin resistance increases significantly with increasing serum ferritin. Metabolic syndrome is known to be associated with increased risk of atherosclerosis as well as insulin resistance. The present study was designed to explore the association of serum ferritin levels with metabolic syndrome and insulin resistance. The present study was prospective, cross sectional. The study protocol was approved by IEC. The study group consisted of 90 participants (50 cases of metabolic syndrome and 40 age and sex matched controls). Diagnosis of metabolic syndrome was done as per NCEP ATP III criteria. Estimation of serum Ferritin and Insulin was done by Chemiluminescence Immunoassay (CLIA) while Glucose by Glucose Oxidase and Peroxidase (GOD-POD) method. Insulin Resistance was calculated by HOMA IR score. Data obtained was statistically analysed by using student t-test. We found statistically significant rise in the levels of serum ferritin (p=syndrome as compared with controls. High serum ferritin levels though within normal range are significantly associated with both metabolic syndrome and insulin resistance.

Genome-wide association study of Tourette's syndrome

NARCIS (Netherlands)

Scharf, J. M.; Yu, D.; Mathews, C. A.; Neale, B. M.; Stewart, S. E.; Fagerness, J. A.; Evans, P.; Gamazon, E.; Edlund, C. K.; Service, S. K.; Tikhomirov, A.; Osiecki, L.; Illmann, C.; Pluzhnikov, A.; Konkashbaev, A.; Davis, L. K.; Han, B.; Crane, J.; Moorjani, P.; Crenshaw, A. T.; Parkin, M. A.; Reus, V. I.; Lowe, T. L.; Rangel-Lugo, M.; Chouinard, S.; Dion, Y.; Girard, S.; Cath, D. C.; Smit, J. H.; King, R. A.; Fernandez, T. V.; Leckman, J. F.; Kidd, K. K.; Kidd, J. R.; Pakstis, A. J.; State, M. W.; Herrera, L. D.; Romero, R.; Fournier, E.; Sandor, P.; Barr, C. L.; Phan, N.; Gross-Tsur, V.; Benarroch, F.; Pollak, Y.; Budman, C. L.; Bruun, R. D.; Erenberg, G.; Naarden, A. L.; Hoekstra, P. J.

2013-01-01

Tourette's syndrome (TS) is a developmental disorder that has one of the highest familial recurrence rates among neuropsychiatric diseases with complex inheritance. However, the identification of definitive TS susceptibility genes remains elusive. Here, we report the first genome-wide association

Association syndrome de Gougerot Sjogren et maladie coeliaque ...

African Journals Online (AJOL)

association avec un syndrome de Gougerot Sjogren (SGS) a rarement été rapportée, mais une association due au simple hasard ne peut être exclue. Dans ce cas, le risque d'oncogenèse est double et une surveillance régulière s'impose.

Prevalence of metabolic syndrome and its association with depression in patients with schizophrenia

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Suttajit S

2013-07-01

Full Text Available Sirijit Suttajit, Sutrak PilakantaDepartment of Psychiatry, Faculty of Medicine, Chiang Mai University, Chiang Mai, ThailandPurpose: To identify the point prevalence of metabolic syndrome in patients with schizophrenia and to evaluate the association between depressive symptoms and metabolic syndrome in patients with schizophrenia.Patients and methods: Metabolic syndrome was assessed based on an updated definition derived from the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III and the International Diabetes Federation criteria. The 17-item Hamilton Depression Rating Scale (HDRS-17 was used to measure depressive symptoms in 80 patients with schizophrenia. Odds ratios and 95% confidence intervals were calculated using logistic regression for the association between each depressive symptom and metabolic syndrome.Results: The point prevalence rates of metabolic syndrome according to the modified NCEP-ATP III and International Diabetes Federation criteria were 37% and 35%, respectively. The risk of having metabolic syndrome significantly increased in those who were widowed or separated, or had longer duration of illness. Central obesity was the metabolic feature with the highest odds ratios for metabolic syndrome at 19.3. Three out of 17 items of HDRS subscales were found to be significantly associated with metabolic syndrome, including depressed mood, middle insomnia, and retardation with the odds ratios of 3.0, 3.4, and 3.6, respectively.Conclusion: This study showed that the prevalence of metabolic syndrome in patients with schizophrenia was higher than the overall rate but was slightly lower than in the general population in the USA. Central obesity, measured by waist circumference, was found to be highly correlated with metabolic syndrome. Depressed mood, middle insomnia, and retardation were significantly associated with metabolic syndrome in patients with schizophrenia. Waist circumference and screening

Frank-ter Haar syndrome associated with sagittal craniosynostosis and raised intracranial pressure.

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Bendon, Charlotte L; Fenwick, Aimée L; Hurst, Jane A; Nürnberg, Gudrun; Nürnberg, Peter; Wall, Steven A; Wilkie, Andrew O M; Johnson, David

2012-11-09

Frank-ter Haar syndrome is a rare disorder associated with skeletal, cardiac, ocular and craniofacial features including hypertelorism and brachycephaly. The most common underlying genetic defect in Frank-ter Haar syndrome appears to be a mutation in the SH3PXD2B gene on chromosome 5q35.1. Craniosynostosis, or premature fusion of the calvarial sutures, has not previously been described in Frank-ter Haar syndrome. We present a family of three affected siblings born to consanguineous parents with clinical features in keeping with a diagnosis of Frank-ter Haar syndrome. All three siblings have a novel mutation caused by the deletion of exon 13 of the SH3PXD2B gene. Two of the three siblings also have non-scaphocephalic sagittal synostosis associated with raised intracranial pressure. The clinical features of craniosynostosis and raised intracranial pressure in this family with a confirmed diagnosis of Frank-ter Haar syndrome expand the clinical spectrum of the disease. The abnormal cranial proportions in a mouse model of the disease suggests that the association is not coincidental. The possibility of craniosynostosis should be considered in individuals with a suspected diagnosis of Frank-ter Haar syndrome.

Multiple jaw cysts not associated with basal cell nevus syndrome

International Nuclear Information System (INIS)

Yoon, Suk Ja; Kang, Byung Cheol

2003-01-01

We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

Multiple jaw cysts not associated with basal cell nevus syndrome

Energy Technology Data Exchange (ETDEWEB)

Yoon, Suk Ja; Kang, Byung Cheol [Chonnam National University College of Medicine, Kwangju (Korea, Republic of)

2003-09-15

We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

Oral manifestations associated with systemic complications of prune belly syndrome.

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Pessoa, Larissa; Galvão, Virgilio

2013-01-01

Prune belly syndrome (PBS) is a rare congenital malformation of unknown etiology characterized by congenital abnormalities including abdominal wall flaccidity, urinary tract alterations, and bilateral cryptorchidism. The incidence of the syndrome is between 1/35000 and 1/50000 live births and there is little information about the oral findings. The present case describes the oral manifestations of a 15-year-old boy diagnosed with PBS. The findings include enamel hypoplasia associated with generalized hypocalcemic dental lines. In the radiographic exam, pronounced demineralization of the trabecular bone of the jaws, loss of lamina dura in all the teeth, and discontinuity of the mandibular cortical bone were observed. Prune belly syndrome is a rare disease, whose clinical dental aspects are not pathognomonic of the syndrome. The comprehension of the systemic mechanism of PBS and its comorbidities enable an understanding of the systemic etiologic factors associated with oral manifestations. Copyright © 2013 Elsevier Inc. All rights reserved.

It's not All Doom and Gloom: Prune Belly Syndrome Associated with VACTERL.

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Awad, Karim; Lall, Anupam

2016-01-01

Prune belly syndrome is a rare abnormality; its association with VACTERL is even rarer. This association has been reported in literature a few times since first reported in 1993 and so far the majority have either been stillbirths or died shortly after birth. We present a case of Prune belly syndrome associated with VACTERL who is now one year old.

Genetic Syndromes, Maternal Diseases and Antenatal Factors Associated with Autism Spectrum Disorders (ASD).

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Ornoy, Asher; Weinstein-Fudim, Liza; Ergaz, Zivanit

2016-01-01

Autism spectrum disorder (ASD) affecting about 1% of all children is associated, in addition to complex genetic factors, with a variety of prenatal, perinatal, and postnatal etiologies. In addition, ASD is often an important clinical presentation of some well-known genetic syndromes in human. We discuss these syndromes as well as the role of the more important prenatal factors affecting the fetus throughout pregnancy which may also be associated with ASD. Among the genetic disorders we find Fragile X, Rett syndrome, tuberous sclerosis, Timothy syndrome, Phelan-McDermid syndrome, Hamartoma tumor syndrome, Prader-Willi and Angelman syndromes, and a few others. Among the maternal diseases in pregnancy associated with ASD are diabetes mellitus (PGDM and/or GDM), some maternal autoimmune diseases like antiphospholipid syndrome (APLS) with anti-β2GP1 IgG antibodies and thyroid disease with anti-thyroid peroxidase (TPO) antibodies, preeclampsia and some other autoimmune diseases with IgG antibodies that might affect fetal brain development. Other related factors are maternal infections (rubella and CMV with fetal brain injuries, and possibly Influenza with fever), prolonged fever and maternal inflammation, especially with changes in a variety of inflammatory cytokines and antibodies that cross the placenta and affect the fetal brain. Among the drugs are valproic acid, thalidomide, misoprostol, and possibly SSRIs. β2-adrenergic receptor agonists and paracetamol have also lately been associated with increased rate of ASD but the data is too preliminary and inconclusive. Associations were also described with ethanol, cocaine, and possibly heavy metals, heavy smoking, and folic acid deficiency. Recent studies show that heavy exposure to pesticides and air pollution, especially particulate matter ASD. Finally, we have to remember that many of the associations mentioned in this review are only partially proven, and not all are "clean" of different confounding factors. The

Intracerebral hemorrhage associated with Sneddon's syndrome: is ischemia-related angiogenesis the cause? Case report and review of the literature

Energy Technology Data Exchange (ETDEWEB)

Aquino Gondim, F. de A.; Leacock, R.O.; Subrammanian, T.A. [Department of Neurology, Saint Louis University Hospital, 3635 Vista Avenue at Grand Blvd, MO 63110, Saint Louis, MO (United States); Cruz-Flores, S. [Department of Neurology, Saint Louis University Hospital, 3635 Vista Avenue at Grand Blvd, MO 63110, Saint Louis, MO (United States); Neurology Service, John Cochran Veterans Administration Hospital, St. Louis, MO (United States)

2003-06-01

Sneddon's syndrome is characterized by livedo reticularis and multiple ischemic infarcts often associated with antiphospholipid antibodies. Intracerebral hemorrhage (ICH) is unusual in Sneddon's syndrome and has not been reported as the presenting complaint. We report a 38-year-old woman with a history of two miscarriages, Raynaud's phenomenon and livedo reticularis who presented acutely with ICH. Angiography showed prominent leptomeningeal and transdural anastomoses (pseudoangiomatosis). Anticardiolipin antibodies were positive. A right frontal brain biopsy failed to reveal vasculitis and a skin biopsy was nonspecific. MRI showed residual intracerebral hemorrhage (ICH), diffuse atrophy, multiple small white matter infarcts and leptomeningeal enhancement. This is the first report of Sneddon's syndrome presenting with an ICH. It shares features with the Divry-van Bogaert syndrome. We discuss the cause of the pseudoangiomatosis pattern and its role in the genesis of the hemorrhage and suggest that cerebral angiography should be done in every patient with Sneddon's syndrome, as it could impact therapy. (orig.)

Acute myeloblastic leukemia-associated Marfan syndrome and Davidoff-Dyke-Masson syndrome: a case report

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Ahmet Faik Öner

2008-12-01

Full Text Available We present herein a 23-year-old man with acute myeloblastic leukemia (AML associated with Davidoff-Dyke-Masson syndrome (DDMS and Marfan syndrome (MS. The diagnosis of DDMS was based on findings including left facial asymmetry, left hemiparesis, mental retardation, right cerebral hemiatrophy, dilatation of the ipsilateral lateral ventricle and calvarial thickening. The diagnosis of MS was based on clinical findings including tall stature, myopia, retinitis pigmentosa, blue scleras, scoliosis, pectus excavatum, arachnodactyly and low ratio of upper/lower body segment. The patient developed hepatosplenomegaly, gingival hypertrophy and pancytopenia. Peripheral blood film and bone marrow examination showed that most of nucleated cells were blasts; immunophenotype of those cells showed CD11+, CD13+, CD14+, CD33+ and HLA-DR+. These findings confirmed the diagnosis of AML (FAB-M5. After induction chemotherapy, remission was obtained. To the best of our knowledge, our case is the third report of AML in MS syndrome, while AML associated with DDMS and MS has not been previously reported in the literature.

Uveitis-glaucoma-hyphema syndrome associated with recurrent vitreous hemorrhage.

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Alfaro-Juárez, A; Vital-Berral, C; Sánchez-Vicente, J L; Alfaro-Juárez, A; Muñoz-Morales, A

2015-08-01

A 61-year-old pseudophakic male with recurrent blurred vision episodes associated with uveitis, hyphema, glaucoma and vitreous hemorrhage. Iris transillumination defects and apposition of the optic and iris were found. The patient was diagnosed with Uveitis-Glaucoma-Hyphema (UGH) Syndrome. Mechanical irritation of the iris is a consequence of intraocular lens malposition and causes UGH Syndrome. Occasionally it is associated with vitreous hemorrhage. Lens malposition is detected by optical coherence tomography and/or ultrasound biomicroscopy. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

Depression is associated with the metabolic syndrome among patients with type 1 diabetes.

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Ahola, Aila J; Thorn, Lena M; Saraheimo, Markku; Forsblom, Carol; Groop, Per-Henrik

2010-10-01

Both depression and the metabolic syndrome are frequently found among patients with type 1 diabetes, but their potential association has not yet been investigated. In this paper the relationship between depression and the metabolic syndrome among patients with type 1 diabetes was evaluated. A total of 1226 patients participating in the Finnish Diabetic Nephropathy Study between 2003 and 2009 were included. Depression was defined as use of antidepressive medication or Beck Depression Inventory (BDI) score ≥16. The metabolic syndrome was defined using the criteria established by the International Diabetes Federation Task Force on Epidemiology and Prevention (IDF); National Heart, Lung, and Blood Institute (NHLBI); American Heart Association (AHA); World Heart Federation (WHF); International Atherosclerosis Society (IAS); and International Association for the Study of Obesity (IASO). The metabolic syndrome was more frequently observed among depressed patients (57% versus 46%, P = 0.008). Of the individual components of the metabolic syndrome, waist, triglyceride, and HDL components were more frequently fulfilled among patients with depression. The BDI score increased with the number of components of the metabolic syndrome present. The BDI score was independently associated with the waist component (odds ratio 1.03, 95% confidence interval 1.01-1.05) when adjusted for gender, age, socio-economic status, smoking, nephropathy, and HbA(1c). The metabolic syndrome is frequently found among depressed patients with type 1 diabetes. Whether this association influences the development of diabetic complications is not known.

Association of sedentary behaviour with metabolic syndrome: a meta-analysis.

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Charlotte L Edwardson

Full Text Available In recent years there has been a growing interest in the relationship between sedentary behaviour (sitting and health outcomes. Only recently have there been studies assessing the association between time spent in sedentary behaviour and the metabolic syndrome. The aim of this study is to quantify the association between sedentary behaviour and the metabolic syndrome in adults using meta-analysis.Medline, Embase and the Cochrane Library were searched using medical subject headings and key words related to sedentary behaviours and the metabolic syndrome. Reference lists of relevant articles and personal databases were hand searched. Inclusion criteria were: (1 cross sectional or prospective design; (2 include adults ≥ 18 years of age; (3 self-reported or objectively measured sedentary time; and (4 an outcome measure of metabolic syndrome. Odds Ratio (OR and 95% confidence intervals for metabolic syndrome comparing the highest level of sedentary behaviour to the lowest were extracted for each study. Data were pooled using random effects models to take into account heterogeneity between studies. Ten cross-sectional studies (n = 21393 participants, one high, four moderate and five poor quality, were identified. Greater time spent sedentary increased the odds of metabolic syndrome by 73% (OR 1.73, 95% CI 1.55-1.94, p<0.0001. There were no differences for subgroups of sex, sedentary behaviour measure, metabolic syndrome definition, study quality or country income. There was no evidence of statistical heterogeneity (I(2 = 0.0%, p = 0.61 or publication bias (Eggers test t = 1.05, p = 0.32.People who spend higher amounts of time in sedentary behaviours have greater odds of having metabolic syndrome. Reducing sedentary behaviours is potentially important for the prevention of metabolic syndrome.

Loss of Ranbp2 in motoneurons causes disruption of nucleocytoplasmic and chemokine signaling, proteostasis of hnRNPH3 and Mmp28, and development of amyotrophic lateral sclerosis-like syndromes

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Kyoung-in Cho

2017-05-01

Full Text Available The pathogenic drivers of sporadic and familial motor neuron disease (MND, such amyotrophic lateral sclerosis (ALS, are unknown. MND impairs the Ran GTPase cycle, which controls nucleocytoplasmic transport, ribostasis and proteostasis; however, cause-effect mechanisms of Ran GTPase modulators in motoneuron pathobiology have remained elusive. The cytosolic and peripheral nucleoporin Ranbp2 is a crucial regulator of the Ran GTPase cycle and of the proteostasis of neurological disease-prone substrates, but the roles of Ranbp2 in motoneuron biology and disease remain unknown. This study shows that conditional ablation of Ranbp2 in mouse Thy1 motoneurons causes ALS syndromes with hypoactivity followed by hindlimb paralysis, respiratory distress and, ultimately, death. These phenotypes are accompanied by: a decline in the nerve conduction velocity, free fatty acids and phophatidylcholine of the sciatic nerve; a reduction in the g-ratios of sciatic and phrenic nerves; and hypertrophy of motoneurons. Furthermore, Ranbp2 loss disrupts the nucleocytoplasmic partitioning of the import and export nuclear receptors importin β and exportin 1, respectively, Ran GTPase and histone deacetylase 4. Whole-transcriptome, proteomic and cellular analyses uncovered that the chemokine receptor Cxcr4, its antagonizing ligands Cxcl12 and Cxcl14, and effector, latent and activated Stat3 all undergo early autocrine and proteostatic deregulation, and intracellular sequestration and aggregation as a result of Ranbp2 loss in motoneurons. These effects were accompanied by paracrine and autocrine neuroglial deregulation of hnRNPH3 proteostasis in sciatic nerve and motoneurons, respectively, and post-transcriptional downregulation of metalloproteinase 28 in the sciatic nerve. Mechanistically, our results demonstrate that Ranbp2 controls nucleocytoplasmic, chemokine and metalloproteinase 28 signaling, and proteostasis of substrates that are crucial to motoneuronal homeostasis and

Small intestinal bacterial overgrowth prevalence in celiac disease patients is similar in healthy subjects and lower in irritable bowel syndrome patients.

Science.gov (United States)

Lasa, J S; Zubiaurre, I; Fanjul, I; Olivera, P; Soifer, L

2015-01-01

Untreated celiac disease has traditionally been linked to a greater risk for small intestinal bacterial overgrowth, but the existing evidence is inconclusive. To compare the prevalence of small intestinal bacterial overgrowth in subjects with celiac disease compared with control subjects and patients with irritable bowel syndrome. The study included 15 untreated celiac disease patients, 15 subjects with irritable bowel syndrome, and 15 healthy controls. All enrolled patients underwent a lactulose breath test measuring hydrogen and methane. Small intestinal bacterial overgrowth was defined according to previously published criteria. No differences were found in relation to age or sex. The prevalence of small intestinal bacterial overgrowth was similar between the celiac disease patients and the controls (20 vs. 13.33%, P=NS), whereas it was higher in patients with irritable bowel syndrome (66.66%, Pintestinal bacterial overgrowth between the untreated celiac disease patients and healthy controls. Copyright © 2015 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Association between Lifestyle Factors and Metabolic Syndrome among African Americans in the United States

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Chintan J. Bhanushali

2013-01-01

Full Text Available Background. Although there is a reported association between lifestyle factors and metabolic syndrome, very few studies have used national level data restricted to the African Americans (AAs in the United States (US. Methods. A cross-sectional evaluation was conducted using the National Health and Nutrition Examination Survey from 1999 to 2006 including men and nonpregnant women of 20 years or older. Multiple logistic regression models were constructed to evaluate the association between lifestyle factors and metabolic syndrome. Results. AA women had a higher prevalence of metabolic syndrome (39.43% than AA men (26.77%. After adjusting for sociodemographic factors, no significant association was found between metabolic syndrome and lifestyle factors including alcohol drinking, cigarette smoking, and physical activity. Age and marital status were significant predictors for metabolic syndrome. With increase in age, both AA men and AA women were more likely to have metabolic syndrome (AA men: ORadj=1.05, 95% CI 1.04–1.06, AA women: ORadj=1.06, 95% CI 1.04–1.07. Single AA women were less likely to have metabolic syndrome than married women (ORadj=0.66, 95% CI 0.43–0.99. Conclusion. Lifestyle factors had no significant association with metabolic syndrome but age and marital status were strong predictors for metabolic syndrome in AAs in the US.

Factors associated with metabolic syndrome and related medical costs by the scale of enterprise in Korea.

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Kong, Hyung-Sik; Lee, Kang-Sook; Yim, Eun-Shil; Lee, Seon-Young; Cho, Hyun-Young; Lee, Bin Na; Park, Jee Young

2013-10-21

The purpose of this study was to identify the risk factors of metabolic syndrome (MS) and to analyze the relationship between the risk factors of MS and medical cost of major diseases related to MS in Korean workers, according to the scale of the enterprise. Data was obtained from annual physical examinations, health insurance qualification and premiums, and health insurance benefits of 4,094,217 male and female workers who underwent medical examinations provided by the National Health Insurance Corporation in 2009. Logistic regression analyses were used to the identify risk factors of MS and multiple regression was used to find factors associated with medical expenditures due to major diseases related to MS. The study found that low-income workers were more likely to work in small-scale enterprises. The prevalence rate of MS in males and females, respectively, was 17.2% and 9.4% in small-scale enterprises, 15.9% and 8.9% in medium-scale enterprises, and 15.9% and 5.5% in large-scale enterprises. The risks of MS increased with age, lower income status, and smoking in small-scale enterprise workers. The medical costs increased in workers with old age and past smoking history. There was also a gender difference in the pattern of medical expenditures related to MS. Health promotion programs to manage metabolic syndrome should be developed to focus on workers who smoke, drink, and do little exercise in small scale enterprises.

Cardiomyopathies in Noonan syndrome and the other RASopathies

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Gelb, Bruce D.; Roberts, Amy E.; Tartaglia, Marco

2015-01-01

Noonan syndrome and related disorders (Noonan syndrome with multiple lentigines, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with loose anagen hair, and other related traits) are autosomal dominant traits. Mutations causing these disorders alter proteins relevant for signaling through RAS. Thus, these traits are now collectively called the RASopathies. While the RASopathies have pleiomorphic features, this review will focus on the hypertrophic cardiomyopathy observed in varying percentages of all of these traits. In addition, inherited abnormalities in one pathway gene, RAF1, cause pediatric-onset dilated cardiomyopathy. The pathogeneses for the RASopathy-associated cardiomyopathies are being elucidated, principally using animal models, leading to genotype-specific insights into how signal transduction is perturbed. Based on those findings, small molecule therapies seem possible for RASopathy-associated cardiomyopathies. PMID:26380542

Possible association between phantom vibration syndrome and occupational burnout

Science.gov (United States)

Chen, Chao-Pen; Wu, Chi-Cheng; Chang, Li-Ren; Lin, Yu-Hsuan

2014-01-01

Background Phantom vibration syndrome (PVS) and phantom ringing syndrome (PRS) occur in many cell phone users. Previous studies have indicated an association between PVS/PRS and job stress. The aim of this study was to determine if PVS/PRS were also associated with occupational burnout. Methods This was a cross-sectional study of 384 employees of a high-tech company in northern Taiwan. They all completed a phantom vibration and ringing questionnaire, the Hospital Anxiety and Depression Scale, and the Chinese version of the Occupational Burnout Inventory. Results Significantly more women and people with at least a college education were in the population with PRS and PVS, respectively. Anxiety and depression had no associations with PVS/PRS. Higher scores for personal fatigue, job fatigue, and service target fatigue had an independent impact on the presence of PVS, but only a higher score for service target fatigue had an independent impact on the presence of PRS. Conclusion The independent association between work-related burnout and PVS/PRS suggests that PVS/PRS may be a harbinger of mental stress or a component of the clinical burnout syndrome, and may even be a more convenient and accurate predictor of occupational burnout. PMID:25750984

Upper Extremity Steal Syndrome Is Associated with Atherosclerotic Burden and Access Configuration.

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Kudlaty, Elizabeth A; Kendrick, Daniel E; Allemang, Matthew T; Kashyap, Vikram S; Wong, Virginia L

2016-08-01

Clinically significant steal syndrome occurs in a subset of dialysis patients with arteriovenous (AV) access. Factors associated with steal are poorly understood. Severe symptoms require access revision or sacrifice, potentially jeopardizing access options. Our objective was to review our dialysis access experience to identify factors associated with significant steal syndrome. We reviewed all adult patients undergoing their first permanent upper extremity access, AV fistula (AVF) or AV graft (AVG), between January 2008 and July 2011 at a single center. Medical, demographic, and access characteristics were collected from our electronic medical record and a local dialysis center's database. Patients who required correction of steal syndrome were compared with the larger access cohort. Statistical analysis included Fisher's exact test and χ(2) for noncontinuous variables and unpaired t-test for continuous variables. Of the 303 patients, 15 required correction for steal syndrome (8 of 232 AVF and 7 of 71 AVG). Eight were ligated; 2 were initially banded, then ligated; and 5 underwent distal revascularization with interval ligation. Coronary artery disease was more prevalent in steal syndrome patients (66.7% vs. 25%, P = 0.001); the same was found with peripheral arterial disease (40% vs. 13.8%, P = 0.02). Furthermore, more patients with steal syndrome were on clopidogrel for cardiovascular reasons (40% vs. 9%, P = 0.002). Steal syndrome only developed with AVF and AVG using brachial artery inflow. No cases of steal syndrome arose from radial/ulnar inflow (P = 0.03). All AVG with steal syndrome had a straight configuration; no looped AVG developed steal (P = 0.02). Other patient characteristics such as age, sex, race, hypertension, diabetes mellitus, congestive heart failure, cerebrovascular accident, cause of end-stage renal disease, and other medication history were not different between groups. Clinically significant steal syndrome is associated with

Turner syndrome and meningioma: support for a possible increased risk of neoplasia in Turner syndrome.

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Pier, Danielle B; Nunes, Fabio P; Plotkin, Scott R; Stemmer-Rachamimov, Anat O; Kim, James C; Shih, Helen A; Brastianos, Priscilla; Lin, Angela E

2014-01-01

Neoplasia is uncommon in Turner syndrome, although there is some evidence that brain tumors are more common in Turner syndrome patients than in the general population. We describe a woman with Turner syndrome (45,X) with a meningioma, in whom a second neoplasia, basal cell carcinomas of the scalp and nose, developed five years later in the absence of therapeutic radiation. Together with 7 cases of Turner syndrome with meningioma from a population-based survey in the United Kingdom, and 3 other isolated cases in the literature, we review this small number of patients for evidence of risk factors related to Turner syndrome, such as associated structural anomalies or prior treatment. We performed histological and fluorescent in situ hybridization (FISH) of 22q (NF2 locus) analyses of the meningeal tumor to search for possible molecular determinants. We are not able to prove causation between these two entities, but suggest that neoplasia may be a rare associated medical problem in Turner syndrome. Additional case reports and extension of population-based studies are needed. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Association between Michelin tire baby syndrome and congenital panhyopituitarism in an Iranian girl.

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Haghshenas, Zahra; Tajziehchi, Leila; Ghavami, Fakhredin

2014-08-01

Michelin tire baby syndrome is a rare syndrome, diagnosed clinically by multiple circumferential skin folds. Multiple noncutaneous anomalies have been described with this syndrome. We report a case of Michelin tire baby syndrome with congenital panhypopituitarism. To date, there is no report of association between these two disorders.

The association between neuroblastoma and opsoclonus-myoclonus syndrome: a historical review

International Nuclear Information System (INIS)

Rothenberg, Alexis B.; Berdon, Walter E.; D'Angio, Giulio J.; Yamashiro, Darrell J.; Cowles, Robert A.

2009-01-01

An association between neuroblastoma and opsoclonus-myoclonus syndrome (OMS) was described as early as 1927 within the first report on the transformation of malignant neuroblastoma to a benign ganglioneuroma. It was not recognized at that time nor was it appreciated in the subsequent follow-up report on the same patient in 1959. Myoclonic encephalopathy of infancy, an alternative name for OMS, was described by a pediatric neurologist in 1962; however, its connection to neuroblastoma was not known. It was only in 1968 that the association between these two conditions was first reported. The neuroblastoma tumors associated with OMS are almost all small, stage I-II with no associated MYCN amplification or metastases. OMS occurs in 2-3% of patients with neuroblastoma, but neuroblastoma is found in as many as 50% of children who present with OMS. Nearly 100% of the children with neuroblastoma associated with OMS survive, and this has led to speculation that the OMS is a result of an autoimmune process, not metastases. Affected children are treated with steroids, ACTH, or intravenous immunoglobulin, but many have persistent neurologic and developmental deficits. Using the original case reported in 1927, we summarize a century of literature in this review on OMS and its association with neuroblastoma. (orig.)

A small molecule mitigates hearing loss in a mouse model of Usher syndrome III.

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Alagramam, Kumar N; Gopal, Suhasini R; Geng, Ruishuang; Chen, Daniel H-C; Nemet, Ina; Lee, Richard; Tian, Guilian; Miyagi, Masaru; Malagu, Karine F; Lock, Christopher J; Esmieu, William R K; Owens, Andrew P; Lindsay, Nicola A; Ouwehand, Krista; Albertus, Faywell; Fischer, David F; Bürli, Roland W; MacLeod, Angus M; Harte, William E; Palczewski, Krzysztof; Imanishi, Yoshikazu

2016-06-01

Usher syndrome type III (USH3), characterized by progressive deafness, variable balance disorder and blindness, is caused by destabilizing mutations in the gene encoding the clarin-1 (CLRN1) protein. Here we report a new strategy to mitigate hearing loss associated with a common USH3 mutation CLRN1(N48K) that involves cell-based high-throughput screening of small molecules capable of stabilizing CLRN1(N48K), followed by a secondary screening to eliminate general proteasome inhibitors, and finally an iterative process to optimize structure-activity relationships. This resulted in the identification of BioFocus 844 (BF844). To test the efficacy of BF844, we developed a mouse model that mimicked the progressive hearing loss associated with USH3. BF844 effectively attenuated progressive hearing loss and prevented deafness in this model. Because the CLRN1(N48K) mutation causes both hearing and vision loss, BF844 could in principle prevent both sensory deficiencies in patients with USH3. Moreover, the strategy described here could help identify drugs for other protein-destabilizing monogenic disorders.

Association between serum CA 19-9 and metabolic syndrome: A cross-sectional study.

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Du, Rui; Cheng, Di; Lin, Lin; Sun, Jichao; Peng, Kui; Xu, Yu; Xu, Min; Chen, Yuhong; Bi, Yufang; Wang, Weiqing; Lu, Jieli; Ning, Guang

2017-11-01

Increasing evidence suggests that serum CA 19-9 is associated with abnormal glucose metabolism. However, data on the association between CA 19-9 and metabolic syndrome is limited. The aim of the present study was to investigate the association between serum CA 19-9 and metabolic syndrome. A cross-sectional study was conducted on 3641 participants aged ≥40 years from the Songnan Community, Baoshan District in Shanghai, China. Logistic regression analysis was used to evaluate the association between serum CA 19-9 and metabolic syndrome. Multivariate logistic regression analysis showed that compared with participants in the first tertile of serum CA 19-9, those in the second and third tertiles had increased odds ratios (OR) for prevalent metabolic syndrome (multivariate adjusted OR 1.46 [95% confidence interval {CI} 1.11-1.92] and 1.51 [95% CI 1.14-1.98]; P trend  = 0.005). In addition, participants with elevated serum CA 19-9 (≥37 U/mL) had an increased risk of prevalent metabolic syndrome compared with those with serum CA 19-9 metabolic syndrome. In order to confirm this association and identify potential mechanisms, prospective cohort and mechanic studies should be performed. © 2017 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.

Case report: Guillain-Barre syndrome with pneumococcus - A new association in pediatrics.

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Khatib, Hassan El; Naous, Amal; Ghanem, Soha; Dbaibo, Ghassan; Rajab, Mariam

2018-01-01

Guillain-Barre Syndrome, an acute flaccid paralysis known to be caused by recent Gastro-intestinal infections mainly campylobacter, and Respiratory infections mainly mycoplasma pneumoniae and influenza. One reported case of severe invasive pneumococcal disease in a 68 year old female, that presented with Austrian's triad of meningitis, pneumonia and endocarditis, and progressed to develop Guillain Barre syndrome, an association never been documented before. We present a case of 13 year old male, presented with hypoactivity and inability to bare his own weight, developed septic shock due to pneumococcus with Acute Respiratory Distress Syndrome, and was found to have neurological findings of Guillain-Barre Syndrome. A new association in pediatric age group, never been reported before.

Segmental reversal of distal small intestine in short bowel syndrome

DEFF Research Database (Denmark)

Grave, Pernille Kock; Thomsen, Sabrina Valentin; Clark, Pia Susanne

2018-01-01

were the influence on cell proliferation and mucosal architecture shown by histological analysis. Methods: Sixteen piglets underwent a 60% resection of the distal small intestine and were randomized into two groups. Group 1 short bowel syndrome alone (SBS) (n = 8) and group 2 with reversal of a distal...... small intestinal segment (SBS-RS) (n = 8). Body weight was measured daily and the pigs were euthanized after 1 month. Crypt depths, villus heights and muscle layers thicknesses were measured. For the evaluation of microvilli of the brush border of the epithelium and cell proliferation...... was found in the SBS group and increase in the thickness of the circular and longitudinal muscle layers in the SBS-RS group. In the distal ileal segment the longitudinal muscle layer thicknesses were increased in the SBS group. Otherwise, no significant changes were found. Conclusion: Reversal of a 20-cm...

Bladder pain syndrome/interstitial cystitis is associated with hyperthyroidism.

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Chung, Shiu-Dong; Liu, Shih-Ping; Lin, Ching-Chun; Li, Hsien-Chang; Lin, Herng-Ching

2013-01-01

Although the etiology of bladder pain syndrome/interstitial cystitis (BPS/IC) is still unclear, a common theme with BPS/IC patients is comorbid disorders which are related to the autonomic nervous system that connects the nervous system to end-organs. Nevertheless, no study to date has reported the association between hyperthyroidism and BPS/IC. In this study, we examined the association of IC/BPS with having previously been diagnosed with hyperthyroidism in Taiwan. Data in this study were retrieved from the Longitudinal Health Insurance Database. Our study consisted of 736 female cases with BPS/IC and 2208 randomly selected female controls. We performed a conditional logistic regression to calculate the odds ratio (OR) for having previously been diagnosed with hyperthyroidism between cases and controls. Of the 2944 sampled subjects, there was a significant difference in the prevalence of prior hyperthyroidism between cases and controls (3.3% vs. 1.5%, phyperthyroidism among cases was 2.16 (95% confidence interval (CI): 1.27∼3.66). Furthermore, the OR for prior hyperthyroidism among cases was 2.01 (95% CI: 1.15∼3.53) compared to controls after adjusting for diabetes, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma. Our study results indicated an association between hyperthyroidism and BPS/IC. We suggest that clinicians treating female subjects with hyperthyroidism be alert to urinary complaints in this population.

MDA-9/Syntenin (SDCBP) modulates small GTPases RhoA and Cdc42 via transforming growth factor β1 to enhance epithelial-mesenchymal transition in breast cancer.

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Menezes, Mitchell E; Shen, Xue-Ning; Das, Swadesh K; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B

2016-12-06

Epithelial-mesenchymal transition (EMT) is one of the decisive steps regulating cancer invasion and metastasis. However, the molecular mechanisms underlying this transition require further clarification. MDA-9/syntenin (SDCBP) expression is elevated in breast cancer patient samples as well as cultured breast cancer cells. Silencing expression of MDA-9 in mesenchymal metastatic breast cancer cells triggered a change in cell morphology in both 2D- and 3D-cultures to a more epithelial-like phenotype, along with changes in EMT markers, cytoskeletal rearrangement and decreased invasion. Conversely, over expressing MDA-9 in epithelial non-metastatic breast cancer cells instigated a change in morphology to a more mesenchymal phenotype with corresponding changes in EMT markers, cytoskeletal rearrangement and an increase in invasion. We also found that MDA-9 upregulated active levels of known modulators of EMT, the small GTPases RhoA and Cdc42, via TGFβ1. Reintroducing TGFβ1 in MDA-9 silenced cells restored active RhoA and cdc42 levels, modulated cytoskeletal rearrangement and increased invasion. We further determined that MDA-9 interacts with TGFβ1 via its PDZ1 domain. Finally, in vivo studies demonstrated that silencing the expression of MDA-9 resulted in decreased lung metastasis and TGFβ1 re-expression partially restored lung metastases. Our findings provide evidence for the relevance of MDA-9 in mediating EMT in breast cancer and support the potential of MDA-9 as a therapeutic target against metastatic disease.

Rabbit Model for Human EBV-Associated Hemophagocytic Syndrome (HPS)

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Hayashi, Kazuhiko; Jin, Zaishun; Onoda, Sachiyo; Joko, Hiromasa; Teramoto, Norihiro; Ohara, Nobuya; Oda, Wakako; Tanaka, Takehiro; Liu, Yi-Xuan; Koirala, Tirtha Raj; Oka, Takashi; Kondo, Eisaku; Yoshino, Tadashi; Takahashi, Kiyoshi; Akagi, Tadaatsu

2003-01-01

Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS) is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD). To elucidate the true nature of fatal LPD observed in Herpesvirus papio (HVP)-induced rabbit hemophagocytosis, reactive or neoplastic, we analyzed sequential development of HVP-induced rabbit LPD and their cell lines. All of the seven Japanese White rabbits inoculated intravenously with HVP died of fatal LPD 18 to 27 days after inoculation. LPD was also accompanied by hemophagocytic syndrome (HPS) in five of these seven rabbits. Sequential autopsy revealed splenomegaly and swollen lymph nodes, often accompanied by bleeding, which developed in the last week. Atypical lymphoid cells infiltrated many organs with a “starry sky” pattern, frequently involving the spleen, lymph nodes, and liver. HVP-small RNA-1 expression in these lymphoid cells was clearly demonstrated by a newly developed in situ hybridization (ISH) system. HVP-ISH of immunomagnetically purified lymphoid cells from spleen or lymph nodes revealed HVP-EBER1+ cells in each CD4+, CD8+, or CD79a+ fraction. Hemophagocytic histiocytosis was observed in the lymph nodes, spleen, bone marrow, and thymus. HVP-DNA was detected in the tissues and peripheral blood from the infected rabbits by PCR or Southern blot analysis. Clonality analysis of HVP-induced LPD by Southern blotting with TCR gene probe revealed polyclonal bands, suggesting polyclonal proliferation. Six IL-2-dependent rabbit T-cell lines were established from transplanted scid mouse tumors from LPD. These showed latency type I/II HVP infection and had normal karyotypes except for one line, and three of them showed tumorigenicity in nude mice. These data suggest that HVP-induced fatal LPD in rabbits is reactive polyclonally in nature. PMID:12707056

Tourette's syndrome and associated disorders: a systematic review

Directory of Open Access Journals (Sweden)

Bárbara R. Ferreira

2014-09-01

Full Text Available Objective: To compile data on Tourette's syndrome (TS, tics and associated disorders.Methods: A systematic review of the literature was conducted using the 5S levels of organization of healthcare research evidence (systems, summaries, synopses, syntheses, studies, based on the model described by Haynes. The search keywords were Tourette, tics and comorbidity, which were cross-referenced. Studies provided by publishers and articles being processed on July 31, 2013, were also included.Results: Of all studies retrieved during the search, 64 were selected because they analyzed the epidemiology, clinical features and etiopathogenesis of TS and its comorbidities. TS is classified as a hyperkinetic movement disorder, and at least 90% of the patients have neuropsychiatric comorbidities, of which attention deficit hyperactivity and obsessive-compulsive disorders are the most common. The syndrome is clinically heterogeneous and has been associated with a dysfunction of cortico-striatal-thalamic-cortical circuits involving various neurotransmitters. Although its genetic etiology has been widely studied, other factors may be important to understand this syndrome and its associated disorders.Conclusions: TS is a neurodevelopmental disorder that results from the impact of stress factors on a vulnerable biological substrate during the critical periods of neurodevelopment. The study of TS and its comorbidities may contribute, at different levels, to the understanding of several neuropsychiatric disorders of clinical and therapeutic relevance.

Usher syndrome associated with Fuchs’ heterochromic uveitis: a case report

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Turan-Vural E

2011-04-01

Full Text Available Ece Turan-Vural, Banu Torun-Acar, Nejla Tükenmez, M Şahin Sevim, Bulent Buttanri, Suphi AcarOphthalmology Clinic, Haydarpasa Numune Education and Research Hospital, Istanbul, TurkeyAbstract: We report a case of Usher syndrome in association with unilateral Fuchs' heterochromic uveitis.Keywords: Fuchs’ heterochromic uveitis, Usher syndrome, deafness, blindness

[Large vessel vasculitis with myelodysplastic syndrome: A rare association].

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Galland, J; Kawski, H; Guichard, J-F; Maurier, F

2017-07-01

The vasculitis can be the consequence of malignancy: most often hematologic rather than solid tumors. The association between large vessels vasculitis and myelodysplastic syndrome is rare. A 55-year-old man experienced asthenia, fever, polyarthritis and inflammatory syndrome. Haematological investigations found a type 2 refractory anemia with excess blasts (RAEB-2) with discovery of severe anemia (Hb: 7,8g/dl) and thrombopenia (platelets: 40,000/mm 3 ). Radiological examinations found thoracic aortitis and carotid vasculitis. Treatment in the form of steroids and azacitidine was instituted. The lack of control of both RAEB-2 and vasculitis was responsible for the death of the patient. Myelodysplastic syndrome and large vessels vasculitis is a rare but serious association disease. The lack of efficiency of corticosteroids seems to be common. Prognosis depends on the haematological treatment effectiveness. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.

Association between Elder Abuse and Metabolic Syndromes: Findings from the Chicago Health and Aging Project.

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Dong, XinQi; Simon, Melissa

2015-01-01

Elder abuse and metabolic syndromes are both important public health issues and are associated with increased morbidity and mortality. This study aimed to examine the associations between elder abuse and risk for metabolic syndromes. The Chicago Health and Aging Project (CHAP) cohort is a population-based study (n = 4,586). We identified 676 participants with some form of elder abuse reported to a social services agency. The primary independent variable was elder abuse reported to a social services agency. Outcomes were metabolic syndrome as categorized by World Health Organization (WHO), American Heart Association (AHA) and International Diabetes Federation (IDF) criteria. Bivariate and logistic regression analyses were used to assess the association between elder abuse and different definitions of metabolic syndromes. In the bivariate analyses, elder abuse victims were more likely than those without elder abuse to have metabolic syndromes [22.4 vs. 10.7% (WHO), 50.7 vs. 40.0% (AHA) and 47.7 vs. 33.5% (IDF)]. After adjusting for potential confounding factors, elder abuse was associated with an increased risk for metabolic syndromes according to WHO [OR, 3.95 (2.86-5.47)], AHA [OR, 2.03 (1.56-2.64)] and IDF [OR, 2.55 (1.97-3.29)] criteria. Interaction term analyses indicate that the association between elder abuse and metabolic syndromes may be moderated by sociodemographic characteristics but not by health-related or psychosocial factors. Elder abuse is associated with an increased risk for metabolic syndromes. Research is needed to examine the association between elder abuse and cardiovascular disease.

Upper tract urothelial carcinomas: frequency of association with mismatch repair protein loss and lynch syndrome.

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Harper, Holly L; McKenney, Jesse K; Heald, Brandie; Stephenson, Andrew; Campbell, Steven C; Plesec, Thomas; Magi-Galluzzi, Cristina

2017-01-01

Increased risk for upper tract urothelial carcinoma is described in patients with Lynch syndrome, caused by germline mutations in mismatch repair genes. We aimed to identify the frequency of mismatch repair protein loss in upper tract urothelial carcinoma and its potential for identifying an association with Lynch syndrome. We queried our database to identify upper tract urothelial carcinomas. Patients were cross-referenced for history of colorectal carcinoma or other common Lynch syndrome-associated neoplasms to enrich for potential Lynch syndrome cases. Tumor histopathologic characteristics were reviewed and each case was analyzed for loss of mismatch repair proteins, MLH1, MSH2, MSH6, and PMS2, by immunohistochemistry. Of 444 patients with upper tract urothelial carcinoma, a subset of 215 (encompassing 30 with upper tract urothelial carcinoma and another common Lynch syndrome-associated neoplasm) was analyzed for loss of mismatch repair protein expression. Of 30 patients with Lynch syndrome-associated neoplasms, six had documented Lynch syndrome, including two with Muir-Torre syndrome. Mismatch repair protein loss was identified in 7% of total upper tract urothelial carcinomas and 30% of patients with Lynch syndrome-associated neoplasms (including all patients with Lynch syndrome/Muir-Torre syndrome). Of patients without history of Lynch syndrome-associated neoplasms, 5 of 184 (2.7%) had loss of mismatch repair protein expression. Twelve cases with mismatch repair protein loss demonstrated loss of MSH2 and MSH6, and 2 had isolated loss of MSH6. MLH1 and PMS2 expression were consistently retained. Although increased intratumoral lymphocytes, inverted growth, pushing tumor-stromal interface, and lack of nuclear pleomorphism were more commonly seen in cases with mismatch repair protein loss, only intratumoral lymphocytes and presence of pushing borders were statistically significant. MLH1 and PMS2 testing appear to have little utility in upper tract urothelial

The interaction properties of the human Rab GTPase family--comparative analysis reveals determinants of molecular binding selectivity.

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Matthias Stein

Full Text Available Rab GTPases constitute the largest subfamily of the Ras protein superfamily. Rab proteins regulate organelle biogenesis and transport, and display distinct binding preferences for effector and activator proteins, many of which have not been elucidated yet. The underlying molecular recognition motifs, binding partner preferences and selectivities are not well understood.Comparative analysis of the amino acid sequences and the three-dimensional electrostatic and hydrophobic molecular interaction fields of 62 human Rab proteins revealed a wide range of binding properties with large differences between some Rab proteins. This analysis assists the functional annotation of Rab proteins 12, 14, 26, 37 and 41 and provided an explanation for the shared function of Rab3 and 27. Rab7a and 7b have very different electrostatic potentials, indicating that they may bind to different effector proteins and thus, exert different functions. The subfamily V Rab GTPases which are associated with endosome differ subtly in the interaction properties of their switch regions, and this may explain exchange factor specificity and exchange kinetics.We have analysed conservation of sequence and of molecular interaction fields to cluster and annotate the human Rab proteins. The analysis of three dimensional molecular interaction fields provides detailed insight that is not available from a sequence-based approach alone. Based on our results, we predict novel functions for some Rab proteins and provide insights into their divergent functions and the determinants of their binding partner selectivity.

A Small Ras-like protein Ray/Rab1c modulates the p53-regulating activity of PRPK

International Nuclear Information System (INIS)

Abe, Yasuhito; Takeuchi, Takashi; Imai, Yoshinori; Murase, Ryuichi; Kamei, Yoshiaki; Fujibuchi, Taketsugu; Matsumoto, Suguru; Ueda, Norifumi; Ogasawara, Masahito; Shigemoto, Kazuhiro; Kito, Katsumi

2006-01-01

PRPK phosphorylates serine-15 residue of p53 and enhances transcriptional activity. PRPK possesses a bipartite nuclear localization signal and localizes in nucleus when over-expressed in cells. However, intrinsic PRPK localizes mainly in the cytosol in situ. While studying the mechanisms in the distribution of intrinsic PRPK, we identified a PRPK binding protein, an ubiquitously expressed Small Ras-like GTPase, Rab1c, also named Ray or Rab35. The over-expressed Ray was distributed in the nucleus, cytosol, and cell membrane. Both Ray wild type and GTP-restrictively binding mutant Ray-Q67L, but not guanine nucleotide unstable binding mutant Ray-N120I, partially distributed the over-expressed PRPK to the cytosol and also suppressed the PRPK-induced p53-transcriptional activity profoundly. A Small Ras-like GTPase protein Ray was thus indicated to modulate p53 transcriptional activity of PRPK

Refeeding syndrome in a small-for-dates micro-preemie receiving early parenteral nutrition.

Science.gov (United States)

Mizumoto, Hiroshi; Mikami, Masamitsu; Oda, Hirotsugu; Hata, Daisuke

2012-10-01

This report describes a small-for-date extremely low birth weight infant who manifested bradycardic events, respiratory failure, and hemolytic jaundice during her first week of life. These complications were attributed to severe hypophosphatemia and hypokalemia. Inadequate supply and refeeding syndrome triggered by early aggressive parenteral nutrition were responsible for electrolyte abnormalities. © 2012 The Authors. Pediatrics International © 2012 Japan Pediatric Society.

Police trauma and cardiovascular disease: association between PTSD symptoms and metabolic syndrome.

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Violanti, John M; Fekedulegn, Desta; Hartley, Tara A; Andrew, Michael E; Charles, Luenda E; Mnatsakanova, Anna; Burchfiel, Cecil M

2006-01-01

Although prior evidence exists concerning the association between posttraumatic stress disorder (PTSD) and cardiovascular disease, few studies have examined associations of PTSD symptomatology and the metabolic syndrome in the high stress occupation of police work. The metabolic syndrome is a clustering of cardiovascular disease risk factors that have also been independently associated with psychological conditions. The aim of this study was to examine associations between the PTSD symptoms and metabolic syndrome in police officers. A stratified sample of 115 police officers was randomly selected from the Buffalo, NY Police Department. PTSD symptoms were measured with the Impact of Event scale (IES), divided into categories of subclinical, mild, moderate and severe symptom levels. The metabolic syndrome was considered present if three or more of its component parameters (obesity, elevated blood pressure, reduced high density lipoprotein (HDL) cholesterol, elevated triglycerides, and abnormal glucose levels) were present in each officer. Results indicated a significantly increased prevalence of the metabolic syndrome among those officers in the severe PTSD symptom category compared with the lowest PTSD severity category (prevalence ratio (PR) = 3.31, 95% C.I. = 1.19 - 9.22). Adjustment for age did not alter the association appreciably (PR = 3.12, 95% C.I. = 1.15 - 8.50). Adjustment for several demographic and lifestyle factors (age, education, smoking, alcohol intake) reduced the magnitude of the prevalence ratio slightly for the severe versus subclinical PTSD category (PR = 2.69, 95% C.I. = 0. 79 - 9.13), with adjustment for age and education accounting for most of the attenuation (PR = 2.71, 95% C.I. = 0.99 - 7.37). Thus, officers with severe PTSD symptoms were approximately three times more likely to have the metabolic syndrome and education may account for some of this association.

The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABAA Receptor Endocytosis in the vmPFC.

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Wang, Weisheng; Ju, Yun-Yue; Zhou, Qi-Xin; Tang, Jian-Xin; Li, Meng; Zhang, Lei; Kang, Shuo; Chen, Zhong-Guo; Wang, Yu-Jun; Ji, Hui; Ding, Yu-Qiang; Xu, Lin; Liu, Jing-Gen

2017-07-26

Extinction of aversive memories has been a major concern in neuropsychiatric disorders, such as anxiety disorders and drug addiction. However, the mechanisms underlying extinction of aversive memories are not fully understood. Here, we report that extinction of conditioned place aversion (CPA) to naloxone-precipitated opiate withdrawal in male rats activates Rho GTPase Rac1 in the ventromedial prefrontal cortex (vmPFC) in a BDNF-dependent manner, which determines GABA A receptor (GABA A R) endocytosis via triggering synaptic translocation of activity-regulated cytoskeleton-associated protein (Arc) through facilitating actin polymerization. Active Rac1 is essential and sufficient for GABA A R endocytosis and CPA extinction. Knockdown of Rac1 expression within the vmPFC of rats using Rac1-shRNA suppressed GABA A R endocytosis and CPA extinction, whereas expression of a constitutively active form of Rac1 accelerated GABA A R endocytosis and CPA extinction. The crucial role of GABA A R endocytosis in the LTP induction and CPA extinction is evinced by the findings that blockade of GABA A R endocytosis by a dynamin function-blocking peptide (Myr-P4) abolishes LTP induction and CPA extinction. Thus, the present study provides first evidence that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories and reveals the sequence of molecular events that contribute to learning experience modulation of synaptic GABA A R endocytosis. SIGNIFICANCE STATEMENT This study reveals that Rac1-dependent GABA A R endocytosis plays a crucial role in extinction of aversive memories associated with drug withdrawal and identifies Arc as a downstream effector of Rac1 regulations of synaptic plasticity as well as learning and memory, thereby suggesting therapeutic targets to promote extinction of the unwanted memories. Copyright © 2017 the authors 0270-6474/17/377096-15$15.00/0.

[Sotos syndrome associated with focal dystonia].

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Bravo, M; Chacón, J; Bautista, E; Pérez-Camacho, I; Trujillo, A; Grande, M A

Sotos syndrome is a form of infantile gigantism characterized by excessive body size from the time of birth, particular facies, acromegalic changes and signs of non-progressive cerebral involvement. The etiology is unknown. Diagnosis is based on somatometric data and the particular phenotype traits. Biochemical and endocrine studies are normal. Torticollis is a focal dystonia and therefore more common in adults. A 20 year old woman with macrosomic features since birth presented with: weight 104 kg, height 182 cm; prognathism, hypertelorism, a broad over hanging forehead with a high hair line; large ears, hands and feet; torticollis towards the right with elevation and anteroversion of the right shoulder which caused symptomatic scoliosis. She was bradypsychic and rather slow in speech. The complementary tests done (cerebral and cervical CT and MR, bone gammography, evoked potentials, EMG-ENG, sural nerve biopsy, biopsy of skin and muscle, EEG and hormone and biochemistry studies) were normal. The torticollis was treated with botulinus toxin and improved considerably, as did the scoliosis. To date, dystonia has not been described in association with Sotos syndrome. This may be a causal association, or even perhaps hereditary, since the patient's mother had dystonia (in the form of blepharospasm).

Multivalent adhesion molecule 7 clusters act as signaling platform for host cellular GTPase activation and facilitate epithelial barrier dysfunction.

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Jenson Lim

2014-09-01

Full Text Available Vibrio parahaemolyticus is an emerging bacterial pathogen which colonizes the gastrointestinal tract and can cause severe enteritis and bacteraemia. During infection, V. parahaemolyticus primarily attaches to the small intestine, where it causes extensive tissue damage and compromises epithelial barrier integrity. We have previously described that Multivalent Adhesion Molecule (MAM 7 contributes to initial attachment of V. parahaemolyticus to epithelial cells. Here we show that the bacterial adhesin, through multivalent interactions between surface-induced adhesin clusters and phosphatidic acid lipids in the host cell membrane, induces activation of the small GTPase RhoA and actin rearrangements in host cells. In infection studies with V. parahaemolyticus we further demonstrate that adhesin-triggered activation of the ROCK/LIMK signaling axis is sufficient to redistribute tight junction proteins, leading to a loss of epithelial barrier function. Taken together, these findings show an unprecedented mechanism by which an adhesin acts as assembly platform for a host cellular signaling pathway, which ultimately facilitates breaching of the epithelial barrier by a bacterial pathogen.

Mutations in RIT1 cause Noonan syndrome - additional functional evidence and expanding the clinical phenotype.

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Koenighofer, M; Hung, C Y; McCauley, J L; Dallman, J; Back, E J; Mihalek, I; Gripp, K W; Sol-Church, K; Rusconi, P; Zhang, Z; Shi, G-X; Andres, D A; Bodamer, O A

2016-03-01

RASopathies are a clinically heterogeneous group of conditions caused by mutations in 1 of 16 proteins in the RAS-mitogen activated protein kinase (RAS-MAPK) pathway. Recently, mutations in RIT1 were identified as a novel cause for Noonan syndrome. Here we provide additional functional evidence for a causal role of RIT1 mutations and expand the associated phenotypic spectrum. We identified two de novo missense variants p.Met90Ile and p.Ala57Gly. Both variants resulted in increased MEK-ERK signaling compared to wild-type, underscoring gain-of-function as the primary functional mechanism. Introduction of p.Met90Ile and p.Ala57Gly into zebrafish embryos reproduced not only aspects of the human phenotype but also revealed abnormalities of eye development, emphasizing the importance of RIT1 for spatial and temporal organization of the growing organism. In addition, we observed severe lymphedema of the lower extremity and genitalia in one patient. We provide additional evidence for a causal relationship between pathogenic mutations in RIT1, increased RAS-MAPK/MEK-ERK signaling and the clinical phenotype. The mutant RIT1 protein may possess reduced GTPase activity or a diminished ability to interact with cellular GTPase activating proteins; however the precise mechanism remains unknown. The phenotypic spectrum is likely to expand and includes lymphedema of the lower extremities in addition to nuchal hygroma. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Dietary patterns are associated with metabolic syndrome in adult Samoans.

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DiBello, Julia R; McGarvey, Stephen T; Kraft, Peter; Goldberg, Robert; Campos, Hannia; Quested, Christine; Laumoli, Tuiasina Salamo; Baylin, Ana

2009-10-01

The prevalence of metabolic syndrome has reached epidemic levels in the Samoan Islands. In this cross-sectional study conducted in 2002-2003, dietary patterns were described among American Samoan (n = 723) and Samoan (n = 785) adults (> or =18 y) to identify neo-traditional and modern eating patterns and to relate these patterns to the presence of metabolic syndrome using Adult Treatment Panel III criteria. The neo-traditional dietary pattern, similar across both polities, was characterized by high intake of local foods, including crab/lobster, coconut products, and taro, and low intake of processed foods, including potato chips and soda. The modern pattern, also similar across both polities, was characterized by high intake of processed foods such as rice, potato chips, cake, and pancakes and low intake of local foods. The neo-traditional dietary pattern was associated with significantly higher serum HDL-cholesterol in American Samoa (P-trend = 0.05) and a decrease in abdominal circumference in American Samoa and Samoa (P-trend = 0.004 and 0.01, respectively). An inverse association was found with metabolic syndrome, although it did not reach significance (P = 0.23 in American Samoa; P = 0.13 in Samoa). The modern pattern was significantly positively associated with metabolic syndrome in Samoa (prevalence ratio = 1.21 for the fifth compared with first quintile; 95% CI: 0.93.1.57; P-trend = 0.05) and with increased serum triglyceride levels in both polities (P fiber, seafood, and coconut products may help to prevent growth in the prevalence of metabolic syndrome in the Samoan islands.

Association of reversible splenial lesion syndrome (RESLES) with Anti-VGKC autoantibody syndrome: a case report.

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Gilder, Thomas R; Hawley, Jason S; Theeler, Brett J

2016-05-01

A 50-year-old male presented with complaints of fatigue, confusion, and memory problems. Neurological evaluation revealed altered cognition, unsteady gait, ataxia, dysmetria, and weakness. MRI of the brain was initially unremarkable. Over several days, the patient experienced improvement of symptoms and a follow-up MRI revealed a small lesion in the splenium of the corpus callosum seen on diffusion weighted and T2 sequences. The patient was discovered to have elevated anti-voltage gated potassium channel serum autoantibodies. Follow-up MRI revealed resolution of the splenial lesion. The patient was treated with intravenous immune globulin, and improved back to his pre-treatment baseline. We believe this to be the first case of a reversible splenial lesion syndrome as a manifestation of the anti-voltage gated potassium channel autoantibody syndrome, and propose a pathophysiologic mechanism.

Hajdu-Cheney syndrome associated with serpentine fibulae and polycystic kidney disease

International Nuclear Information System (INIS)

Currarino, Guido

2009-01-01

Six patients who presented with craniofacial anomalies, musculoskeletal anomalies including elongated and bowed (serpentine) fibulae, and polycystic kidneys are reported. This association of anomalies is referred to as serpentine fibula polycystic kidney syndrome (SFPKS) and is currently interpreted as a manifestation of Hajdu-Cheney syndrome (HCS). We report a new instance of this association of anomalies and review the clinical and radiographic features of HCS and of the reported cases of SFPKS. (orig.)

Reiter's Syndrome associated with the Acquired Immunodeficiency Syndrome: a case report

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J.B.N.S. Malta

Full Text Available The association of Reiter's Syndrome (RS with the Acquired Immunodeficiency Syndrome (AIDS is seldom mentioned in the medical literature. This report illustrates this relationship in a 46 years old male patient suffering from AIDS (CD4+ = 240 cells/mm³, CD8+ = 1,301 cells/mm³ and viral load = 330,000 copies/ml, pulmonary tuberculosis (positive catarrhal bacilluscopy, and RS. The diagnosis of RS was based on the combination of dermatological and articular alterations. The patient's cutaneous lesions were characterized by exfoliation and the formation of crusts located on the face, scalp, genitals, hands, and feet; onychodystrophy with opacity; yellowish coloring; and hyperkeratosis of the nails. Articular lesions led to progressive deformity of phalangeal joints of the hands, and intensive arthralgia, mainly of the larger joints (shoulders, elbows, hips and knees. AIDS treatment was administered with anti-retroviral drugs (zidovudine and didanosine; for tuberculosis (isoniazid, rifampicine, and pyrazinamide; and (prednisone and inometacine for the RS. The patient recovered with the improvement of articular symptoms; however, on the eighth day of treatment, the patient showed significant hemoptysis and hypovolemic shock, and died. The association of RS and HIV infection is reviewed.

Transmission of severe acute respiratory syndrome in dynamical small-world networks

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Masuda, Naoki; Konno, Norio; Aihara, Kazuyuki

2004-03-01

The outbreak of severe acute respiratory syndrome (SARS) is still threatening the world because of a possible resurgence. In the current situation that effective medical treatments such as antiviral drugs are not discovered yet, dynamical features of the epidemics should be clarified for establishing strategies for tracing, quarantine, isolation, and regulating social behavior of the public at appropriate costs. Here we propose a network model for SARS epidemics and discuss why superspreaders emerged and why SARS spread especially in hospitals, which were key factors of the recent outbreak. We suggest that superspreaders are biologically contagious patients, and they may amplify the spreads by going to potentially contagious places such as hospitals. To avoid mass transmission in hospitals, it may be a good measure to treat suspected cases without hospitalizing them. Finally, we indicate that SARS probably propagates in small-world networks associated with human contacts and that the biological nature of individuals and social group properties are factors more important than the heterogeneous rates of social contacts among individuals. This is in marked contrast with epidemics of sexually transmitted diseases or computer viruses to which scale-free network models often apply.

Involvement of astrocyte metabolic coupling in Tourette syndrome pathogenesis

OpenAIRE

Mathews, CA; de Leeuw, C; Goudriaan, A; Smit, AB; Yu, D; Scharf, J; Verheijen, MHG; Posthuma, D

2015-01-01

textabstractTourette syndrome is a heritable neurodevelopmental disorder whose pathophysiology remains unknown. Recent genome-wide association studies suggest that it is a polygenic disorder influenced by many genes of small effect. We tested whether these genes cluster in cellular function by applying gene-set analysis using expert curated sets of brain-expressed genes in the current largest available Tourette syndrome genome-wide association data set, involving 1285 cases and 4964 controls....

Eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome as a differential diagnosis of hypereosinophilic syndromes

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Yuri Albuquerque Pessoa Santos

2017-01-01

Full Text Available Eosinophilic granulomatosis with polyangiitis (EGPA, formerly known as Churg-Strauss syndrome, is a rare systemic disease situated between primary small vessel vasculitides associated with antineutrophil cytoplasmic antibodies (ANCAs and hypereosinophilic syndromes (HES. Here, we present a case of EGPA in a 38-year-old male, with a previous diagnosis of asthma, who presented with fever, migratory lung infiltrates and systemic eosinophilia that was refractory to previous courses of antibiotics. This case highlights the importance of the primary care physician understanding the differential diagnosis of pulmonary eosinophilic syndromes.

Dominantly inherited isolated hyperparathyroidism: a syndromic association?

International Nuclear Information System (INIS)

Kozlowski, K.; Czerminska-Kowalska, A.; Kulczycka, H.; Rowinska, E.; Pronicka, E.

1999-01-01

Dominantly inherited isolated hyperparathyroidism (DIIH) is rare in childhood. It may be the first biochemical abnormality in the multiple endocrine neoplasia type I (MEN I) and type II (MEN II) syndromes. Its clinical course is usually asymptomatic or of low morbidity. Radiographic examination is most often normal. We describe six members of a family with distinctive phenotype and DIIH. Limited systemic symptoms and severe radiographic osteitis fibrosa cystica were further unusual features in this family. The diagnosis of DIIH was made only after a 9-year-old girl developed hypercalcaemic crisis after a pathological femoral fracture. Distinctive phenotype, unusual clinical course and unparalleled radiographic changes suggest a not yet described syndromic association. (orig.)

Bladder Pain Syndrome/Interstitial Cystitis Is Associated with Hyperthyroidism

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Liu, Shih-Ping; Lin, Ching-Chun; Lin, Herng-Ching

2013-01-01

Background Although the etiology of bladder pain syndrome/interstitial cystitis (BPS/IC) is still unclear, a common theme with BPS/IC patients is comorbid disorders which are related to the autonomic nervous system that connects the nervous system to end-organs. Nevertheless, no study to date has reported the association between hyperthyroidism and BPS/IC. In this study, we examined the association of IC/BPS with having previously been diagnosed with hyperthyroidism in Taiwan. Design Data in this study were retrieved from the Longitudinal Health Insurance Database. Our study consisted of 736 female cases with BPS/IC and 2208 randomly selected female controls. We performed a conditional logistic regression to calculate the odds ratio (OR) for having previously been diagnosed with hyperthyroidism between cases and controls. Results Of the 2944 sampled subjects, there was a significant difference in the prevalence of prior hyperthyroidism between cases and controls (3.3% vs. 1.5%, phyperthyroidism among cases was 2.16 (95% confidence interval (CI): 1.27∼3.66). Furthermore, the OR for prior hyperthyroidism among cases was 2.01 (95% CI: 1.15∼3.53) compared to controls after adjusting for diabetes, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma. Conclusions Our study results indicated an association between hyperthyroidism and BPS/IC. We suggest that clinicians treating female subjects with hyperthyroidism be alert to urinary complaints in this population. PMID:23991081

Luteinizing hormone/chorionic gonadotrophin receptor overexpressed in granulosa cells from polycystic ovary syndrome ovaries is functionally active.

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Kanamarlapudi, Venkateswarlu; Gordon, Uma D; López Bernal, Andrés

2016-06-01

Polycystic ovarian syndrome (PCOS) is associated with anovulatory infertility. Luteinizing hormone/chorionic gonadotrophin receptor (LHCGR), which is critical for ovulation, has been suggested to be expressed prematurely in the ovarian follicles of women with PCOS. This study aimed to analyse the expression and activity of LHCGR in ovarian granulosa cells from PCOS patients and the involvement of ARF6 small GTPase in LHCGR internalization. Granulosa cells (GC) isolated from follicular fluid collected during oocyte retrieval from normal women (n = 19) and women with PCOS (n = 17) were used to study differences in LHCGR protein expression and activity between normal and PCOS patients. LHCGR expression is up-regulated in GC from PCOS women. LHCGR in PCOS GC is functionally active, as shown by increased cAMP production upon human gonadotrophin (HCG)-stimulation. Moreover, ARF6 is highly expressed in GC from PCOS patients and HCG-stimulation increases the concentrations of active ARF6. The inhibition of ARF6 activation attenuates HCG-induced LHCGR internalization in both normal and PCOS GC, indicating that there are no alterations in LHCGR internalisation in GC from PCOS. In conclusion, the expression and activation of LHCGR and ARF6 are up-regulated in GC from PCOS women but the mechanism of agonist-induced LHCGR internalization is unaltered. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Maternal Burnout Syndrome: Contextual and Psychological Associated Factors

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Astrid Lebert-Charron

2018-06-01

Full Text Available Background: Becoming a parent is one of the most significant experiences in a woman’s life. Including substantial and long-lasting mental, social, and physical charge, the parenting experience may also be a potentially stressful and overwhelming task. Since the eighties, the notion of parental burnout syndrome has gained increasing attention, but its contextual and psychological factors need to be better identified.Aims: To investigate a large array of contextual and psychological factors associated with maternal burnout syndrome in a French community-based population in order to contribute to better operationalize the notion of parental burnout and to explore its determinants.Method: A total of 304 French-speaking mothers (mean age = 34.8 years, SD = 6.72 completed a set of questionnaires including a sociodemographic form (in order to gather general information about the mothers, their spouses, and children living at home. The Perceived Stress Scale, the Maslach Burnout Inventory adapted to parents (MBI-parental, the Hospital Anxiety and Depression Scale, the Parental Stress Index-Short Form and the Ways of Coping Checklist were used in this study.Results: Multivariate linear regression analyses revealed that scores on the MBI-parental version were strongly and positively associated with depressive and anxiety symptoms, as well as with perceived stress related to parenthood and parenting stress levels. Moreover, using the task-oriented coping style in parenthood was strongly and positively associated with personal accomplishment. Conversely, some sociodemographic characteristics were found to be negatively associated with maternal burnout: being employed, working full time and being a mother living without a coparent.Conclusion: The construct of maternal burnout syndrome seems to be linked to a conjunction of psychological and contextual factors associated with maternal exhaustion. The implication of the results for prevention and

Maternal Burnout Syndrome: Contextual and Psychological Associated Factors

Science.gov (United States)

Lebert-Charron, Astrid; Dorard, Géraldine; Boujut, Emilie; Wendland, Jaqueline

2018-01-01

Background: Becoming a parent is one of the most significant experiences in a woman’s life. Including substantial and long-lasting mental, social, and physical charge, the parenting experience may also be a potentially stressful and overwhelming task. Since the eighties, the notion of parental burnout syndrome has gained increasing attention, but its contextual and psychological factors need to be better identified. Aims: To investigate a large array of contextual and psychological factors associated with maternal burnout syndrome in a French community-based population in order to contribute to better operationalize the notion of parental burnout and to explore its determinants. Method: A total of 304 French-speaking mothers (mean age = 34.8 years, SD = 6.72) completed a set of questionnaires including a sociodemographic form (in order to gather general information about the mothers, their spouses, and children living at home). The Perceived Stress Scale, the Maslach Burnout Inventory adapted to parents (MBI-parental), the Hospital Anxiety and Depression Scale, the Parental Stress Index-Short Form and the Ways of Coping Checklist were used in this study. Results: Multivariate linear regression analyses revealed that scores on the MBI-parental version were strongly and positively associated with depressive and anxiety symptoms, as well as with perceived stress related to parenthood and parenting stress levels. Moreover, using the task-oriented coping style in parenthood was strongly and positively associated with personal accomplishment. Conversely, some sociodemographic characteristics were found to be negatively associated with maternal burnout: being employed, working full time and being a mother living without a coparent. Conclusion: The construct of maternal burnout syndrome seems to be linked to a conjunction of psychological and contextual factors associated with maternal exhaustion. The implication of the results for prevention and intervention strategies

Congenital megalourethra in 2 weeks old boy associated with Prune-Belly syndrome

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Lawal Barau Abdullahi

2015-02-01

Full Text Available The megalourethra is a rare congenital anomaly of the penile urethra. It is characterized by the congenital absence of the corpus spongiosum and/or corpus cavernosum. It is especially common associated with Prune-Belly syndrome, and with upper tract abnormalities. We present a 2 weeks old boy with congenital megalourethra because of its association with the Prune-Belly syndrome.

Association of Shah-Waardenburgh syndrome: a review of 6 cases.

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Jan, Iftikhar A; Stroedter, Lutz; Haq, Anwaar-ul; Din, Zaheer-ud

2008-04-01

Shah-Waardenburg syndrome (SWS) is a neurocristopathy and is characterized by Hirschsprung's disease (HD), deafness, and depigmentation of hairs, skin, and iris. The aim of the article is to study the relative frequency of associations in 6 consecutive cases of SWS. A review of 6 consecutive patients with SWS was performed to study the frequency of various components of the syndrome. Six patients had features of SWS. All patients had HD; of these, 3 had rectosigmoid HD, whereas 3 had extended HD. All patients had white forelock of hairs with skin depigmentation. One patient had sensorineural deafness, whereas other babies were less than 1 year, and thus, full evaluation of hearing deficiency was not assessed. Three patients had blue eyes, whereas other babies had normal iris pigmentation. Skin depigmentation was noted in 5 of the 6 patients. Three babies were seriously malnourished and showed higher association of enterocolitis. Shah-Waardenburg syndrome is an uncommon association of HD. Depigmentation with a white forelock and skin manifestations are common, whereas blue iris, long segment disease, and enterocolitis are present in nearly half of the patients.

[Prevalence of metabolic syndrome and associated factors in children and adolescents with obesity].

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Romero-Velarde, Enrique; Aguirre-Salas, Liuba Marina; Álvarez-Román, Yussani Arelhi; Vásquez-Garibay, Edgar Manuel; Casillas-Toral, Erika; Fonseca-Reyes, Salvador

2016-01-01

The prevalence of overweight and obesity in children in Mexico are high, as well as the complications associated with their presence. The objective of this work was to estimate the prevalence of metabolic syndrome in obese children and adolescents attending a Hospital Clinic and identify the associated factors. Cross sectional design with 120 children and adolescents; of either sex, with exogenous obesity and BMI > 2.0 standard deviations. Personal and family history was collected, blood pressure was measured and determination of serum glucose, insulin, lipoprotein HDL cholesterol and triglycerides were performed. The presence of metabolic syndrome with the ATPIII, WHO and International Diabetes Federation criteria was identified. The association of metabolic syndrome with different variables was identified with chi square test and calculation of odds ratio. Mean age was 10.6 ± 2.7 years. The prevalence of metabolic syndrome was 37.5% to 54.5% depending on the criteria used. The presence of metabolic syndrome was associated with a history of large birth weight (OR= 2.21 [1.01-4.82]), and insulin resistance (OR= 6.53 [2.40-18.2]). The prevalence of metabolic syndrome is high in this group of children and adolescents with obesity. The history of large birth weight and the presence of insulin resistance should alert us to the presence of the disease.

Goldenhar syndrome and medulloblastoma: a coincidental association? The first case report.

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Aizenbud, Dror; Shoham, Natasha V; Constantini, Shlomi; Nevo, Neta; Ben Arush, Myriam; Raz, Michal; Rachmiel, Adi; Goldsher, Dorit

2014-07-01

Features of Goldenhar syndrome include several craniofacial anomalies of structures derived from the first and second pharyngeal arches, as well as vertebral, cardiac and renal systems abnormalities. In addition, Goldenhar patients were reported to manifest a variety of central nervous system anomalies and several types of neoplasias. The first case of medulloblastoma in a patient with Goldenhar syndrome is presented here. There is no clear association between these two pathologies. We speculate that aberrant events during the migration of neural crest cells in early stages of development could be the basis of an association between medulloblastoma and Goldenhar syndrome. The case history suggests other possible etiological contributing factors to the development of medulloblastoma, such as patient's history of trauma and/or early childhood exposure to ionizing radiation. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

Association of metabolic syndrome and 25-hydroxyvitamin D with cognitive impairment among elderly Koreans.

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Lee, Eun Young; Lee, Su Jin; Kim, Kyoung Min; Yun, Young Mi; Song, Bo Mi; Kim, Jong Eun; Kim, Hyeon Chang; Rhee, Yumie; Youm, Yoosik; Kim, Chang Oh

2017-07-01

Metabolic syndrome and vitamin D deficiency are prevalent in older adults, and are considered risk factors for cognitive impairment. We investigated the combined effects of MetS and serum 25-hydroxyvitamin D (25[OH]D) levels on cognitive function in older adults. We studied 2940 participants aged ≥65 years from the Korean Urban Rural Elderly cohort study. Metabolic syndrome was defined according to the updated Adult Treatment Panel III criteria. Serum 25(OH)D levels were categorized into four groups: metabolic syndrome prevalence and lower serum 25(OH)D levels than those without cognitive impairment. In univariate analysis, both metabolic syndrome and low 25(OH)D levels were associated with cognitive impairment. These associations remained unchanged after adjusting for potential confounders including age, sex, season and education. In addition, participants with metabolic syndrome and low 25(OH)D had significantly increased odds for cognitive impairment (odds ratio 3.06, 95% CI 1.61-5.80) when compared with those with no metabolic syndrome and high 25(OH)D. Metabolic syndrome was associated with cognitive impairment, and this risk was synergistically increased when metabolic syndrome was combined with low 25(OH)D. A focus on individuals with metabolic syndrome and low 25(OH)D might be helpful to identify older adults who are at risk of cognitive impairment. Geriatr Gerontol Int 2017; 17: 1069-1075. © 2016 Japan Geriatrics Society.

OPA1-associated disorders: phenotypes and pathophysiology

DEFF Research Database (Denmark)

Amati-Bonneau, Patrizia; Milea, Dan; Bonneau, Dominique

2009-01-01

in patients with hereditary optic neuropathies indicates that the clinical spectrum of ADOA is larger than previously thought. Specific OPA1 mutations are responsible for several distinct clinical presentations, such as ADOA with deafness (ADOAD), and severe multi-systemic syndromes, the so-called "ADOA plus......The OPA1 gene, encoding a dynamin-like mitochondrial GTPase, is involved in autosomal dominant optic atrophy (ADOA, OMIM #165500). ADOA, also known as Kjer's optic atrophy, affects retinal ganglion cells and the axons forming the optic nerve, leading to progressive visual loss. OPA1 gene sequencing...

Ras-dva1 small GTPase regulates telencephalon development in Xenopus laevis embryos by controlling Fgf8 and Agr signaling at the anterior border of the neural plate

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Maria B. Tereshina

2014-07-01

Full Text Available We previously found that the small GTPase Ras-dva1 is essential for the telencephalic development in Xenopus laevis because Ras-dva1 controls the Fgf8-mediated induction of FoxG1 expression, a key telencephalic regulator. In this report, we show, however, that Ras-dva1 and FoxG1 are expressed in different groups of cells; whereas Ras-dva1 is expressed in the outer layer of the anterior neural fold, FoxG1 and Fgf8 are activated in the inner layer from which the telencephalon is derived. We resolve this paradox by demonstrating that Ras-dva1 is involved in the transduction of Fgf8 signal received by cells in the outer layer, which in turn send a feedback signal that stimulates FoxG1 expression in the inner layer. We show that this feedback signal is transmitted by secreted Agr proteins, the expression of which is activated in the outer layer by mediation of Ras-dva1 and the homeodomain transcription factor Otx2. In turn, Agrs are essential for maintaining Fgf8 and FoxG1 expression in cells at the anterior neural plate border. Our finding reveals a novel feedback loop mechanism based on the exchange of Fgf8 and Agr signaling between neural and non-neural compartments at the anterior margin of the neural plate and demonstrates a key role of Ras-dva1 in this mechanism.

Association of Serum Adiponectin Levels with Metabolic Syndrome Risk Factors in Malay Adults

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Nur Firdaus Isa

2017-09-01

Full Text Available Introduction: This study aimed to investigate the relationship between serum adiponectin and metabolic syndrome in adults living in rural Malaysia. Methods: A total of 299 Malay adults (men=124; women = 175 with a mean age 48.8 (11.7 years were recruited. Measurements for waist circumference and blood pressure were taken before drawing an overnight fasting blood samples. Biochemical tests for triglycerides, HDL cholesterol, glucose and serum adiponectin concentration were measured. Results: Our results show that the adiponectin level in the subjects with metabolic syndrome was significantly lower than those without metabolic syndrome (p < 0.05. Among the metabolic syndrome risk factors, adiponectin level was significantly associated with hypertriglyceridemia and reduced HDL cholesterol (p < 0.001. Conclusion: The outcome from this study which highlights the association of hypoadiponectinemia with risk factors of metabolic syndrome in Malay adults, suggests that the reduced level of adiponectin may play a pivotal role in the development of metabolic syndrome in this ethnic group.

Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

International Nuclear Information System (INIS)

Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

2015-01-01

Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management

Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report

Energy Technology Data Exchange (ETDEWEB)

Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali [Dept. of Conservative Dentistry and Endodontics, Manubhai Patel Dental College, Maharaja Krishnakumarsinhji Bhavnagar University, Vadodara (India)

2015-09-15

Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

Enamel renal syndrome with associated amelogenesis imperfecta, nephrolithiasis, and hypocitraturia: A case report.

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Bhesania, Dhvani; Arora, Ankit; Kapoor, Sonali

2015-09-01

Numerous cases of enamel renal syndrome have been previously reported. Various terms, such as enamel renal syndrome, amelogenesis imperfecta and gingival fibromatosis syndrome, and enamel-renal-gingival syndrome, have been used for patients presenting with the dental phenotype characteristic of this condition, nephrocalcinosis or nephrolithiasis, and gingival findings. This report describes a case of amelogenesis imperfecta of the enamel agenesis variety with nephrolithiasis in a 21-year-old male patient who complained of small teeth. The imaging modalities employed were conventional radiography, cone-beam computed tomography, and renal sonography. Such cases are first encountered by dentists, as other organ or metabolic diseases are generally hidden. Hence, cases of amelogenesis imperfecta should be subjected to advanced diagnostic modalities, incorporating both dental and medical criteria, in order to facilitate comprehensive long-term management.

SNP association study in PMS2-associated Lynch syndrome.

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Ten Broeke, Sanne W; Elsayed, Fadwa A; Pagan, Lisa; Olderode-Berends, Maran J W; Garcia, Encarna Gomez; Gille, Hans J P; van Hest, Liselot P; Letteboer, Tom G W; van der Kolk, Lizet E; Mensenkamp, Arjen R; van Os, Theo A; Spruijt, Liesbeth; Redeker, Bert J W; Suerink, Manon; Vos, Yvonne J; Wagner, Anja; Wijnen, Juul T; Steyerberg, E W; Tops, Carli M J; van Wezel, Tom; Nielsen, Maartje

2017-11-17

Lynch syndrome (LS) patients are at high risk of developing colorectal cancer (CRC). Phenotypic variability might in part be explained by common susceptibility loci identified in Genome Wide Association Studies (GWAS). Previous studies focused mostly on MLH1, MSH2 and MSH6 carriers, with conflicting results. We aimed to determine the role of GWAS SNPs in PMS2 mutation carriers. A cohort study was performed in 507 PMS2 carriers (124 CRC cases), genotyped for 24 GWAS SNPs, including SNPs at 11q23.1 and 8q23.3. Hazard ratios (HRs) were calculated using a weighted Cox regression analysis to correct for ascertainment bias. Discrimination was assessed with a concordance statistic in a bootstrap cross-validation procedure. Individual SNPs only had non-significant associations with CRC occurrence with HRs lower than 2, although male carriers of allele A at rs1321311 (6p21.31) may have increased risk of CRC (HR = 2.1, 95% CI 1.2-3.0). A polygenic risk score (PRS) based on 24 HRs had an HR of 2.6 (95% CI 1.5-4.6) for the highest compared to the lowest quartile, but had no discriminative ability (c statistic 0.52). Previously suggested SNPs do not modify CRC risk in PMS2 carriers. Future large studies are needed for improved risk stratification among Lynch syndrome patients.

Medications Associated with Geriatric Syndromes (MAGS) and their Prevalence in Older Hospitalized Adults Discharged to Skilled Nursing Facilities

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Saraf, Avantika A.; Peterson, Alec W.; Simmons, Sandra F.; Schnelle, John F.; Bell, Susan P.; Kripalani, Sunil; Myers, Amy P.; Mixon, Amanda S.; Long, Emily A.; Jacobsen, J. Mary Lou; Vasilevskis, Eduard E.

2016-01-01

Background More than half of the hospitalized older adults discharged to skilled nursing facilities (SNFs) have more than three geriatric syndromes. Pharmacotherapy may be contributing to geriatric syndromes in this population. Objectives Develop a list of medications associated with geriatric syndromes and describe their prevalence in patients discharged from acute care to skilled nursing facilities (SNFs) Design Literature review and multidisciplinary expert panel discussion, followed by cross-sectional analysis. Setting Academic Medical Center in the United States Participants 154 hospitalized Medicare beneficiaries discharged to SNFs Measurements Development of a list of medications that are associated with six geriatric syndromes. Prevalence of the medications associated with geriatric syndromes was examined in the hospital discharge sample. Results A list of 513 medications was developed as potentially contributing to 6 geriatric syndromes: cognitive impairment, delirium, falls, reduced appetite or weight loss, urinary incontinence, and depression. Medications included 18 categories. Antiepileptics were associated with all syndromes while antipsychotics, antidepressants, antiparkinsonism and opioid agonists were associated with 5 geriatric syndromes. In the prevalence sample, patients were discharged to SNFs with an overall average of 14.0 (±4.7) medications, including an average of 5.9 (±2.2) medications that could contribute to geriatric syndromes, with falls having the most associated medications at discharge, 5.5 (±2.2). Conclusions Many commonly prescribed medications are associated with geriatric syndromes. Over 40% of all medications ordered upon discharge to SNFs were associated with geriatric syndromes and could be contributing to the high prevalence of geriatric syndromes experienced by this population. PMID:27255830

Association of glucocorticoid receptor polymorphisms with clinical and metabolic profiles in polycystic ovary syndrome

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Gustavo A.Rosa Maciel

2014-03-01

Full Text Available OBJECTIVES: We aimed to investigate whether glucocorticoid receptor gene polymorphisms are associated with clinical and metabolic profiles in patients with polycystic ovary syndrome. Polycystic ovary syndrome is a complex endocrine disease that affects 5-8% of women and may be associated with metabolic syndrome, which is a risk factor for cardiovascular disease. Cortisol action and dysregulation account for metabolic syndrome development in the general population. As glucocorticoid receptor gene (NR3C1 polymorphisms regulate cortisol sensitivity, we hypothesized that variants of this gene may be involved in the adverse metabolic profiles of patients with polycystic ovary syndrome. METHOD: Clinical, metabolic and hormonal profiles were evaluated in 97 patients with polycystic ovary syndrome who were diagnosed according to the Rotterdam criteria. The alleles of the glucocorticoid gene were genotyped. Association analyses were performed using the appropriate statistical tests. RESULTS: Obesity and metabolic syndrome were observed in 42.3% and 26.8% of patients, respectively. Body mass index was positively correlated with blood pressure, triglyceride, LDL-c, total cholesterol, glucose and insulin levels as well as HOMA-IR values and inversely correlated with HDL-c and SHBG levels. The BclI and A3669G variants were found in 24.7% and 13.4% of alleles, respectively. BclI carriers presented a lower frequency of insulin resistance compared with wild-type subjects. CONCLUSION: The BclI variant is associated with a lower frequency of insulin resistance in women with polycystic ovary syndrome. Glucocorticoid gene polymorphism screening during treatment of the syndrome may be useful for identifying subgroups of at-risk patients who would benefit the most from personalized treatment.

GDNF gene is associated with tourette syndrome in a family study.

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Huertas-Fernández, Ismael; Gómez-Garre, Pilar; Madruga-Garrido, Marcos; Bernal-Bernal, Inmaculada; Bonilla-Toribio, Marta; Martín-Rodríguez, Juan Francisco; Cáceres-Redondo, María Teresa; Vargas-González, Laura; Carrillo, Fátima; Pascual, Alberto; Tischfield, Jay A; King, Robert A; Heiman, Gary A; Mir, Pablo

2015-07-01

Tourette syndrome is a disorder characterized by persistent motor and vocal tics, and frequently accompanied by the comorbidities attention deficit hyperactivity disorder and obsessive-compulsive disorder. Impaired synaptic neurotransmission has been implicated in its pathogenesis. Our aim was to investigate the association of 28 candidate genes, including genes related to synaptic neurotransmission and neurotrophic factors, with Tourette syndrome. We genotyped 506 polymorphisms in a discovery cohort from the United States composed of 112 families and 47 unrelated singletons with Tourette syndrome (201 cases and 253 controls). Genes containing significant polymorphisms were imputed to fine-map the signal(s) to potential causal variants. Allelic analyses in Tourette syndrome cases were performed to check the role in attention deficit hyperactivity disorder and obsessive-compulsive disorder comorbidities. Target polymorphisms were further studied in a replication cohort from southern Spain composed of 37 families and three unrelated singletons (44 cases and 73 controls). The polymorphism rs3096140 in glial cell line-derived neurotrophic factor gene (GDNF) was significant in the discovery cohort after correction (P = 1.5 × 10(-4) ). No linkage disequilibrium was found between rs3096140 and other functional variants in the gene. We selected rs3096140 as target polymorphism, and the association was confirmed in the replication cohort (P = 0.01). No association with any comorbidity was found. As a conclusion, a common genetic variant in GDNF is associated with Tourette syndrome. A defect in the production of GDNF could compromise the survival of parvalbumin interneurons, thus altering the excitatory/inhibitory balance in the corticostriatal circuitry. Validation of this variant in other family cohorts is necessary. © 2015 International Parkinson and Movement Disorder Society.

GDNF Gene Is Associated With Tourette Syndrome in a Family Study

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Huertas-Fernández, Ismael; Gómez-Garre, Pilar; Madruga-Garrido, Marcos; Bernal-Bernal, Inmaculada; Bonilla-Toribio, Marta; Martín-Rodríguez, Juan Francisco; Cáceres-Redondo, María Teresa; Vargas-González, Laura; Carrillo, Fátima; Pascual, Alberto; Tischfield, Jay A.; King, Robert A.; Heiman, Gary A.; Mir, Pablo

2016-01-01

Background Tourette syndrome is a disorder characterized by persistent motor and vocal tics, and frequently accompanied by the comorbidities attention deficit hyperactivity disorder and obsessive-compulsive disorder. Impaired synaptic neurotransmission has been implicated in its pathogenesis. Our aim was to investigate the association of 28 candidate genes, including genes related to synaptic neurotransmission and neurotrophic factors, with Tourette syndrome. Methods We genotyped 506 polymorphisms in a discovery cohort from the United States composed of 112 families and 47 unrelated singletons with Tourette syndrome (201 cases and 253 controls). Genes containing significant polymorphisms were imputed to fine-map the signal(s) to potential causal variants. Allelic analyses in Tourette syndrome cases were performed to check the role in attention deficit hyperactivity disorder and obsessive-compulsive disorder comorbidities. Target polymorphisms were further studied in a replication cohort from southern Spain composed of 37 families and three unrelated singletons (44 cases and 73 controls). Results The polymorphism rs3096140 in glial cell line–derived neurotrophic factor gene (GDNF) was significant in the discovery cohort after correction (P = 1.5 × 10−4). No linkage disequilibrium was found between rs3096140 and other functional variants in the gene. We selected rs3096140 as target polymorphism, and the association was confirmed in the replication cohort (P = 0.01). No association with any comorbidity was found. Conclusions As a conclusion, a common genetic variant in GDNF is associated with Tourette syndrome. A defect in the production of GDNF could compromise the survival of parvalbumin interneurons, thus altering the excitatory/inhibitory balance in the corticostriatal circuitry. Validation of this variant in other family cohorts is necessary. PMID:26096985

Physical Activity and Sedentary Behavior Associated with Components of Metabolic Syndrome among People in Rural China.

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Xiao, Jing; Shen, Chong; Chu, Min J; Gao, Yue X; Xu, Guang F; Huang, Jian P; Xu, Qiong Q; Cai, Hui

2016-01-01

Metabolic syndrome is prevalent worldwide and its prevalence is related to physical activity, race, and lifestyle. Little data is available for people living in rural areas of China. In this study we examined associations of physical activity and sedentary behaviors with metabolic syndrome components among people in rural China. The Nantong Metabolic Syndrome Study recruited 13,505 female and 6,997 male participants between 2007 and 2008. Data of socio-demographic characteristics and lifestyle were collected. The associations of physical activity and sedentary behaviors with metabolic syndrome components were analyzed. Prevalence of metabolic syndrome was 21.6%. It was significantly lower in men than in women. Low risks of metabolic syndrome were observed in those who did less sitting and engaged in more vigorous physical activity. The highest tertile of vigorous physical activity was associated with 15-40% decreased odds of metabolic syndrome and all of its components, except for low high-density lipoprotein cholesterol in men. Women with the highest tertile of moderate physical activity had 15-30% lower odds of central obesity, high glucose, and high triglycerides compared with those in the lowest tertile. Sitting time >42 hours per week had a 4%-12% attributable risk of metabolic syndrome, central obesity, and high triglycerides in both genders, and abnormal glucose and diastolic blood pressure in women. Sleeping for more than 8 hours per day was associated with risk of high serum glucose and lipids. Our data suggested that physical activity has a preventive effect against metabolic syndrome and all its abnormal components, and that longer sitting time and sleep duration are associated with an increased risk of metabolic syndrome components, including central obesity and high triglycerides, glucose, and diastolic blood pressure. This study could provide information for future investigation into these associations. Also, recommendations are developed to reduce

Usher syndrome associated with Fuchs’ heterochromic uveitis: a case report

OpenAIRE

Turan-Vural, Ece; Turan-Vural,Ece; TORUN ACAR,Banu; Tükenmez,Nejla

2011-01-01

Ece Turan-Vural, Banu Torun-Acar, Nejla Tükenmez, M Şahin Sevim, Bulent Buttanri, Suphi AcarOphthalmology Clinic, Haydarpasa Numune Education and Research Hospital, Istanbul, TurkeyAbstract: We report a case of Usher syndrome in association with unilateral Fuchs' heterochromic uveitis.Keywords: Fuchs’ heterochromic uveitis, Usher syndrome, deafness, blindness

Association between pancreatic fat and incidence of metabolic syndrome: a 5-year Japanese cohort study.

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Yamazaki, Hajime; Tauchi, Shinichi; Kimachi, Miho; Dohke, Mitsuru; Hanawa, Nagisa; Kodama, Yoshihisa; Katanuma, Akio; Yamamoto, Yosuke; Fukuma, Shingo; Fukuhara, Shunichi

2018-04-26

Previous cross-sectional studies showed that pancreatic fat was associated with metabolic syndrome. However, no longitudinal study has evaluated whether people with high pancreatic fat are likely to develop future metabolic syndrome. This study investigated the association between baseline pancreatic fat and metabolic syndrome incidence. In 2008-2009, 320 participants without metabolic syndrome underwent health checks, which included unenhanced computed tomography, and were followed up annually for 4-5 years. Baseline pancreatic fat amounts were evaluated using a histologically validated method that measured differences between pancreas and spleen attenuations on computed tomography. The participants were divided into low (reference), intermediate, and high pancreatic fat groups based on pancreas and spleen attenuation tertiles. Metabolic syndrome incidence was evaluated annually over a median follow-up period of 4.99 (interquartile range, 4.88-5.05) years, in accordance with the 2009 harmonized criteria. Risk ratios (RRs) for the association between baseline pancreatic fat amounts and metabolic syndrome incidence were estimated using Poisson regression models adjusted for age, sex, body mass index, liver fat, pre-metabolic syndrome, cigarette use, alcohol use, and physical activity. Metabolic syndrome incidence was 30.6% (98/320). Pancreatic fat was associated with an increased incidence of metabolic syndrome, based on a univariate analysis (RRs [95% confidence interval], 3.14 [1.74-5.67] and 3.96 [2.23-7.03] in the intermediate and high pancreatic fat groups, respectively). The association remained statistically significant in the multivariate analysis (RR [95% confidence interval], 2.04 [1.14-3.64] and 2.30 [1.28-4.14] for the same groups, respectively). Pancreatic fat predicts the future risk of metabolic syndrome. © 2018 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Update on antiphospholipid antibody syndrome.

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Lopes, Michelle Remião Ugolini; Danowski, Adriana; Funke, Andreas; Rêgo, Jozelia; Levy, Roger; Andrade, Danieli Castro Oliveira de

2017-11-01

Antiphospholipid syndrome (APS) is an autoimmune disease characterized by antiphospholipid antibodies (aPL) associated with thrombosis and/or pregnancy morbidity. Most APS events are directly related to thrombotic events, which may affect small, medium or large vessels. Other clinical features like thrombocytopenia, nephropathy, cardiac valve disease, cognitive dysfunction and skin ulcers (called non-criteria manifestations) add significant morbidity to this syndrome and represent clinical situations that are challenging. APS was initially described in patients with systemic lupus erythematosus (SLE) but it can occur in patients without any other autoimmune disease. Despite the autoimmune nature of this syndrome, APS treatment is still based on anticoagulation and antiplatelet therapy.

Bladder pain syndrome/interstitial cystitis is associated with hyperthyroidism.

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Shiu-Dong Chung

Full Text Available BACKGROUND: Although the etiology of bladder pain syndrome/interstitial cystitis (BPS/IC is still unclear, a common theme with BPS/IC patients is comorbid disorders which are related to the autonomic nervous system that connects the nervous system to end-organs. Nevertheless, no study to date has reported the association between hyperthyroidism and BPS/IC. In this study, we examined the association of IC/BPS with having previously been diagnosed with hyperthyroidism in Taiwan. DESIGN: Data in this study were retrieved from the Longitudinal Health Insurance Database. Our study consisted of 736 female cases with BPS/IC and 2208 randomly selected female controls. We performed a conditional logistic regression to calculate the odds ratio (OR for having previously been diagnosed with hyperthyroidism between cases and controls. RESULTS: Of the 2944 sampled subjects, there was a significant difference in the prevalence of prior hyperthyroidism between cases and controls (3.3% vs. 1.5%, p<0.001. The conditional logistic regression analysis revealed that compared to controls, the OR for prior hyperthyroidism among cases was 2.16 (95% confidence interval (CI: 1.27∼3.66. Furthermore, the OR for prior hyperthyroidism among cases was 2.01 (95% CI: 1.15∼3.53 compared to controls after adjusting for diabetes, coronary heart disease, obesity, hyperlipidemia, chronic pelvic pain, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, depression, panic disorder, migraines, sicca syndrome, allergies, endometriosis, and asthma. CONCLUSIONS: Our study results indicated an association between hyperthyroidism and BPS/IC. We suggest that clinicians treating female subjects with hyperthyroidism be alert to urinary complaints in this population.

[Turner syndrome and genetic polymorphism: a systematic review].

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Trovó de Marqui, Alessandra Bernadete

2015-01-01

To present the main results of the literature on genetic polymorphisms in Turner Syndrome and their association with the clinical signs and the etiology of this chromosomal disorder. The review was conducted in the PubMed database without any time limit, using the terms Turner syndrome and genetic polymorphism. A total of 116 articles were found, and based on the established inclusion and exclusion criteria 17 were selected for the review. The polymorphisms investigated in patients with Turner Syndrome were associated with growth deficit, causing short stature, low bone mineral density, autoimmunity and cardiac abnormalities, which are frequently found in patients with Turner Syndrome. The role of single nucleotide polymorphisms (SNPs) in the etiology of Turner syndrome, i.e., in chromosomal nondisjunction, was also confirmed. Genetic polymorphisms appear to be associated with Turner Syndrome. However, in view of the small number of published studies and their contradictory findings, further studies in different populations are needed in order to clarify the role of genetic variants in the clinical signs and etiology of the Turner Syndrome. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.