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Sample records for atypical ra domain

  1. Feasibility and Domain Validation of RA Flare Core Domain Set: A Report of the OMERACT 2014 RA Flare Group Plenary

    PubMed Central

    Bartlett, Susan J.; Bykerk, Vivian P.; Cooksey, Roxanne; Choy, Ernest H.; Alten, Rieke; Christensen, Robin; Furst, Daniel E.; Guillemin, Francis; Halls, Serena; Hewlett, Sarah; Leong, Amye L.; Lyddiatt, Anne; March, Lyn; Montie, Pamela; Orbai, Ana Maria; Pohl, Christoph; Voshaar, Marieke Scholte; Woodworth, Thasia G.; Bingham, Clifton O.

    2015-01-01

    Objective The OMERACT RA Flare Group was established to develop an approach to identify and measure rheumatoid arthritis (RA) flares. Here, we provide an overview of our OMERACT 2014 plenary. Methods Feasibility and validity of flare domains endorsed at OMERACT 11 (2012) were described based on initial data from three international studies collected using a common set of questions specific to RA flare. Mean flare frequency, severity, and duration data were presented, and domain scores were compared by flare status to examine known-groups validity. Breakout groups provided input for stiffness, self-management, contextual factors, and measurement considerations. Results Flare data from 501 patients in a observational study indicated 39% were in a flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were r’s from 0.46 to 0.93. A combined definition (patient-report of flare and DAS28 increase) was evaluated in two other trials with similar results. Breakout groups debated specific measurement issues. Conclusion These data contribute initial evidence of feasibility and content validation of the OMERACT RA Flare Core Domain Set. Our research agenda for OMERACT 2016 includes establishing duration/intensity criteria and developing criteria to identify RA flares using existing disease activity measures. Ongoing work will also address discordance between patients and physician ratings, facilitate applications to clinical care, elucidate the role of self-management and help finalize recommendations for RA flare measurement. PMID:25684764

  2. Symptom domains of schizophrenia: the role of atypical antipsychotic agents.

    PubMed

    Burton, Simon

    2006-11-01

    Given their more obvious presentation, the reduction of positive symptoms and their associated behavioural problems have been considered the most important treatment outcome parameter in patients with schizophrenia. However, the development of the atypical antipsychotic agents in the early 1990s resulted in the adoption of more wide-reaching measures of therapeutic outcome. The aim of this review was to evaluate the efficacy of currently available atypical agents across multiple symptom domains of schizophrenia with a specific focus on negative symptoms, neurocognition, social functioning, quality of life and insight. As such, studies published between January 1990 and December 2005 that evaluated the clinical efficacy and tolerability of atypical antipsychotics in different symptom domains of schizophrenia were reviewed as identified from literature researches using MEDLINE and Embase. Abstracts and posters presented at key psychiatry and schizophrenia congresses during this period were also reviewed where available in the public domain. Results from the studies identified have consistently demonstrated that atypical antipsychotics have substantial advantages over conventional antipsychotics with a broader spectrum of efficacy across symptomatic domains of schizophrenia as proven by greater improvements in negative symptoms and cognitive function and a beneficial effect on affective symptoms and quality of life. However, their clinical advantages have often been limited by patients' partial compliance with therapy. As such, the development of a long-acting atypical antipsychotic agent may provide a new and valuable treatment option for patients with schizophrenia.

  3. RA diagnostics applying optical tomography in frequency domain

    NASA Astrophysics Data System (ADS)

    Klose, Alexander D.; Prapavat, Viravuth; Minet, Olaf; Beuthan, Juergen; Mueller, Gerhard J.

    1998-01-01

    Our aim is to reconstruct the optical parameters in a slice of a finger joint phantom for further investigations about rheumatoid arthritis (RA). Therefore, we have developed a flexible NIR scanning system in order to collect amplitude and phase delay of photon density waves in frequency-domain. A cylindrical finger joint phantom was embedded in a container of Intralipid solution due to the application of an inverse method for infinite geometry. The joint phantom was investigated by a laser beam obtaining several projections. The average optical parameters of each projection was calculated. Using different reconstruction techniques, e.g. ART and SIRT with a special projection operator, we reconstructed the optical parameters in a slice. The projection operator can be heuristically described by a photon path density function of a homogeneous media with infinite geometry. Applied to an object with an unknown distribution of optical parameters it calculates the expectation value of the investigated object. The potentials and limits of these fast reconstruction methods will be presented.

  4. A-type granites from the Guéra Massif, Central Chad: Petrology, geochemistry, geochronology, and petrogenesis.

    NASA Astrophysics Data System (ADS)

    Pham, Ngoc Ha T.; Shellnutt, J. Gregory; Yeh, Meng-Wan; Lee, Tung-Yi

    2017-04-01

    The poorly studied Saharan Metacraton of North-Central Africa is located between the Arabian-Nubian Shield in the east, the Tuareg Shield in the west and the Central African Orogenic Belt in the south. The Saharan Metacraton is composed of Neoproterozoic juvenile crust and the relics of pre-Neoproterozoic components reactivated during the Pan-African Orogeny. The Republic of Chad, constrained within the Saharan Metacraton, comprises a Phanerozoic cover overlying Precambrian basement outcroppings in four distinct massifs: the Mayo Kebbi, Tibesti, Ouaddaï, and the Guéra. The Guéra massif is the least studied of the four massifs but it likely preserves structures that were formed during the collision between Congo Craton and Saharan Metacraton. The Guéra Massif is composed of mostly granitic rocks. The granitoids have petrologic features that are consistent with A-type granite, such as micrographic intergrowth of sodic and potassic feldspar, the presence of sodic- and iron-rich amphibole, and iron-rich biotite. Compositionally, the granitic rocks of the Guéra Massif have high silica (SiO2 ≥ 68.9 wt.%) content and are metaluminous to marginally peraluminous. The rocks are classified as ferroan calc-alkalic to alkali-calcic with moderately high to very high Fe* ratios. The first zircon U/Pb geochronology of the silicic rocks from the Guéra Massif yielded three main age groups: 590 Ma, 570 Ma, 560 Ma, while a single gabbro yielded an intermediate age ( 580 Ma). A weakly foliated biotite granite yielded two populations, in which the emplacement age is interpreted to be 590 ± 10 Ma, whereas the younger age (550 ± 11 Ma) is considered to be a deformation age. Furthermore, inherited Meso- to Paleoproterozoic zircons are found in this sample. The geochemical and geochronology data indicate that there is a temporal evolution in the composition of rocks with the old, high Mg# granitoids shifting to young, low Mg# granitoids. This reveals that the A-type granites in

  5. Feasibility and Domain Validation of Rheumatoid Arthritis (RA) Flare Core Domain Set: Report of the OMERACT 2014 RA Flare Group Plenary.

    PubMed

    Bartlett, Susan J; Bykerk, Vivian P; Cooksey, Roxanne; Choy, Ernest H; Alten, Rieke; Christensen, Robin; Furst, Daniel E; Guillemin, Francis; Halls, Serena; Hewlett, Sarah; Leong, Amye L; Lyddiatt, Anne; March, Lyn; Montie, Pamela; Orbai, Ana Maria; Pohl, Christoph; Voshaar, Marieke Scholte; Woodworth, Thasia G; Bingham, Clifton O

    2015-11-01

    The Outcome Measures in Rheumatology (OMERACT) Rheumatoid Arthritis (RA) Flare Group was established to develop an approach to identify and measure RA flares. An overview of our OMERACT 2014 plenary is provided. Feasibility and validity of flare domains endorsed at OMERACT 11 (2012) were described based on initial data from 3 international studies collected using a common set of questions specific to RA flare. Mean flare frequency, severity, and duration data were presented, and domain scores were compared by flare status to examine known-groups validity. Breakout groups provided input for stiffness, self-management, contextual factors, and measurement considerations. Flare data from 501 patients in an observational study indicated 39% were in flare, with mean (SD) severity of 6.0 (2.6) and 55% lasting > 14 days. Pain, physical function, fatigue, participation, and stiffness scores averaged ≥ 2 times higher (2 of 11 points) in flaring individuals. Correlations between flare domains and corresponding legacy instruments were obtained: r = 0.46 to 0.93. A combined definition (patient report of flare and 28-joint Disease Activity Score increase) was evaluated in 2 other trials, with similar results. Breakout groups debated specific measurement issues. These data contribute initial evidence of feasibility and content validation of the OMERACT RA Flare Core Domain Set. Our research agenda for OMERACT 2016 includes establishing duration/intensity criteria and developing criteria to identify RA flares using existing disease activity measures. Ongoing work will also address discordance between patient and physician ratings, facilitate application of flare criteria to clinical care, elucidate the role of self-management, and finalize recommendations for RA flare measurement.

  6. Harmonic Domains and Synchronization in Typically and Atypically Developing Hebrew-Speaking Children

    ERIC Educational Resources Information Center

    Bat-El, Outi

    2009-01-01

    This paper presents a comparative study of typical and atypical consonant harmony (onset-onset place harmony), with emphasis on (i) the size of the harmonic domain, (ii) the position of the harmonic domain within the prosodic word, and (iii) the maximal size of the prosodic word that exhibits consonant harmony. The data, drawn from typically and…

  7. Harmonic Domains and Synchronization in Typically and Atypically Developing Hebrew-Speaking Children

    ERIC Educational Resources Information Center

    Bat-El, Outi

    2009-01-01

    This paper presents a comparative study of typical and atypical consonant harmony (onset-onset place harmony), with emphasis on (i) the size of the harmonic domain, (ii) the position of the harmonic domain within the prosodic word, and (iii) the maximal size of the prosodic word that exhibits consonant harmony. The data, drawn from typically and…

  8. Stacking fault domains as sources of a-type threading dislocations in III-nitride heterostructures

    NASA Astrophysics Data System (ADS)

    Smalc-Koziorowska, J.; Bazioti, C.; Albrecht, M.; Dimitrakopulos, G. P.

    2016-02-01

    A mechanism for the nucleation of a-type threading dislocation half-loops from basal stacking faults in wurtzite III-nitride heterostructures is presented. Transmission electron microscopy observations, in conjunction with topological and strain analysis, show that there are two possible configurations of closed domains comprising basal stacking faults of I1 type. It is shown that the lattice dislocation may emanate when the sphalerite structural units of the stacking faults in the closed domain are oriented in a parallel manner. The closed domain configurations do not introduce any shift on the basal planes, resulting in zero defect content along the growth direction. The stacking fault domains are hexagonal, with sides along the ⟨ 10 1 ¯ 0 ⟩ directions, and the threading dislocation half loops nucleate at the line nodes. The mechanism was found to be operational in multiple III-nitride systems.

  9. Atypical features of nanophthalmic macula--a spectral domain OCT study.

    PubMed

    Rao, Aparna; Padhi, Tapas Ranjan; Jena, Sananu; Mandal, Souvik; Das, Taraprasad

    2012-06-06

    To report atypical features on Spectral domain optical coherence tomography (SD-OCT) in a case of non-familial pure adult nanophthalmos. A 39 year old male hyperope was found to have biometric and fundus findings typical of nanophthalmos. The additional atypical features included serous pigment epithelial detachment (PED) in right eye and a cuff of subretinal fluid with underlying yellow deposits along superotemporal arcade in the left eye. Fundus flourescein angiogram showed hyperfluorescence due to window defect, dye pooling due to serous PED in right eye and leak superior to disc in right eye and superotemporally in left eye. Cirrus-SD OCT horizontal line scan passing through the fovea showed extensive inner limiting membrane corrugations causing distorted foveal contour in both eyes. A large juxtafoveal serous PED and a small extrafoval PED were seen with folds in the retinal pigment epithelium (RPE)-choriocapillary layer in the right eye. Structural disruptions in the RPE-choriocapillary complex in the form of folds or juxtafoveal serous PED and RPE folds can be atypical features of nanophthalmic macula better discerned on high resolution OCT.

  10. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold

    SciTech Connect

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M.F.; Downes, C. Peter; Batty, Ian H.

    2012-10-16

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.

  11. IQGAP proteins reveal an atypical phosphoinositide (aPI) binding domain with a pseudo C2 domain fold.

    PubMed

    Dixon, Miles J; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R; van Aalten, Daan M F; Downes, C Peter; Batty, Ian H

    2012-06-29

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP(3)). The binding affinity for PtdInsP(3), together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP(3) effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.

  12. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold*

    PubMed Central

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M. F.; Downes, C. Peter; Batty, Ian H.

    2012-01-01

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105–107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules. PMID:22493426

  13. Identifying flares in rheumatoid arthritis: reliability and construct validation of the OMERACT RA Flare Core Domain Set

    PubMed Central

    Bykerk, Vivian P; Bingham, Clifton O; Choy, Ernest H; Lin, Daming; Alten, Rieke; Christensen, Robin; Furst, Daniel E; Hewlett, Sarah; Leong, Amye; March, Lyn; Woodworth, Thasia; Boire, Gilles; Haraoui, Boulos; Hitchon, Carol; Jamal, Shahin; Keystone, Edward C; Pope, Janet; Tin, Diane; Thorne, J Carter

    2016-01-01

    Objective To evaluate the reliability of concurrent flare identification using 3 methods (patient, rheumatologist and Disease Activity Score (DAS)28 criteria), and construct validity of candidate items representing the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Core Domain Set. Methods Candidate flare questions and legacy measures were administered at consecutive visits to Canadian Early Arthritis Cohort (CATCH) patients between November 2011 and November 2014. The American College of Rheumatology (ACR) core set indicators were recorded. Concordance to identify flares was assessed using the agreement coefficient. Construct validity of flare questions was examined: convergent (Spearman's r); discriminant (mean differences between flaring/non-flaring patients); and consequential (proportions with prior treatment reductions and intended therapeutic change postflare). Results The 849 patients were 75% female, 81% white, 42% were in remission/low disease activity (R/LDA), and 16–32% were flaring at the second visit. Agreement of flare status was low–strong (κ's 0.17–0.88) and inversely related to RA disease activity level. Flare domains correlated highly (r's≥0.70) with each other, patient global (r's≥0.66) and corresponding measures (r's 0.49–0.92); and moderately highly with MD and patient-reported joint counts (r's 0.29–0.62). When MD/patients agreed the patient was flaring, mean flare domain between-group differences were 2.1–3.0; 36% had treatment reductions prior to flare, with escalation planned in 61%. Conclusions Flares are common in rheumatoid arthritis (RA) and are often preceded by treatment reductions. Patient/MD/DAS agreement of flare status is highest in patients worsening from R/LDA. OMERACT RA flare questions can discriminate between patients with/without flare and have strong evidence of construct and consequential validity. Ongoing work will identify optimal scoring and cut points to identify RA flares. PMID

  14. Structural basis for controlling the dimerization and stability of the WW domains of an atypical subfamily.

    PubMed

    Ohnishi, Satoshi; Tochio, Naoya; Tomizawa, Tadashi; Akasaka, Ryogo; Harada, Takushi; Seki, Eiko; Sato, Manami; Watanabe, Satoru; Fujikura, Yukiko; Koshiba, Seizo; Terada, Takaho; Shirouzu, Mikako; Tanaka, Akiko; Kigawa, Takanori; Yokoyama, Shigeyuki

    2008-09-01

    The second WW domain in mammalian Salvador protein (SAV1 WW2) is quite atypical, as it forms a beta-clam-like homodimer. The second WW domain in human MAGI1 (membrane associated guanylate kinase, WW and PDZ domain containing 1) (MAGI1 WW2) shares high sequence similarity with SAV1 WW2, suggesting comparable dimerization. However, an analytical ultracentrifugation study revealed that MAGI1 WW2 (Leu355-Pro390) chiefly exists as a monomer at low protein concentrations, with an association constant of 1.3 x 10(2) M(-1). We determined its solution structure, and a structural comparison with the dimeric SAV1 WW2 suggested that an Asp residue is crucial for the inhibition of the dimerization. The substitution of this acidic residue with Ser resulted in the dimerization of MAGI1 WW2. The spin-relaxation data suggested that the MAGI1 WW2 undergoes a dynamic process of transient dimerization that is limited by the charge repulsion. Additionally, we characterized a longer construct of this WW domain with a C-terminal extension (Leu355-Glu401), as the formation of an extra alpha-helix was predicted. An NMR structural determination confirmed the formation of an alpha-helix in the extended C-terminal region, which appears to be independent from the dimerization regulation. A thermal denaturation study revealed that the dimerized MAGI1 WW2 with the Asp-to-Ser mutation gained apparent stability in a protein concentration-dependent manner. A structural comparison between the two constructs with different lengths suggested that the formation of the C-terminal alpha-helix stabilized the global fold by facilitating contacts between the N-terminal linker region and the main body of the WW domain.

  15. Applicability of the Common Safety Method for Risk Evaluation and Assessment (CSM-RA) to the Space Domain

    NASA Astrophysics Data System (ADS)

    Moreira, Francisco; Silva, Nuno

    2016-08-01

    Safety systems require accident avoidance. This is covered by application standards, processes, techniques and tools that support the identification, analysis, elimination or reduction to an acceptable level of system risks and hazards. Ideally, a safety system should be free of hazards. However, both industry and academia have been struggling to ensure appropriate risk and hazard analysis, especially in what concerns completeness of the hazards, formalization, and timely analysis in order to influence the specifications and the implementation. Such analysis is also important when considering a change to an existing system. The Common Safety Method for Risk Evaluation and Assessment (CSM- RA) is a mandatory procedure whenever any significant change is proposed to the railway system in a European Member State. This paper provides insights on the fundamentals of CSM-RA based and complemented with Hazard Analysis. When and how to apply them, and the relation and similarities of these processes with industry standards and the system life cycles is highlighted. Finally, the paper shows how CSM-RA can be the basis of a change management process, guiding the identification and management of the hazards helping ensuring the similar safety level as the initial system. This paper will show how the CSM-RA principles can be used in other domains particularly for space system evolution.

  16. The Extracellular Domain of Myelin Oligodendrocyte Glycoprotein Elicits Atypical Experimental Autoimmune Encephalomyelitis in Rat and Macaque Species

    PubMed Central

    Curtis, Alan D.; Taslim, Najla; Reece, Shaun P.; Grebenciucova, Elena; Ray, Richard H.; Rosenbaum, Matthew D.; Wardle, Robert L.; Van Scott, Michael R.; Mannie, Mark D.

    2014-01-01

    Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund’s adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund’s adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6–7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord

  17. The extracellular domain of myelin oligodendrocyte glycoprotein elicits atypical experimental autoimmune encephalomyelitis in rat and Macaque species.

    PubMed

    Curtis, Alan D; Taslim, Najla; Reece, Shaun P; Grebenciucova, Elena; Ray, Richard H; Rosenbaum, Matthew D; Wardle, Robert L; Van Scott, Michael R; Mannie, Mark D

    2014-01-01

    Atypical models of experimental autoimmune encephalomyelitis (EAE) are advantageous in that the heterogeneity of clinical signs appears more reflective of those in multiple sclerosis (MS). Conversely, models of classical EAE feature stereotypic progression of an ascending flaccid paralysis that is not a characteristic of MS. The study of atypical EAE however has been limited due to the relative lack of suitable models that feature reliable disease incidence and severity, excepting mice deficient in gamma-interferon signaling pathways. In this study, atypical EAE was induced in Lewis rats, and a related approach was effective for induction of an unusual neurologic syndrome in a cynomolgus macaque. Lewis rats were immunized with the rat immunoglobulin variable (IgV)-related extracellular domain of myelin oligodendrocyte glycoprotein (IgV-MOG) in complete Freund's adjuvant (CFA) followed by one or more injections of rat IgV-MOG in incomplete Freund's adjuvant (IFA). The resulting disease was marked by torticollis, unilateral rigid paralysis, forelimb weakness, and high titers of anti-MOG antibody against conformational epitopes of MOG, as well as other signs of atypical EAE. A similar strategy elicited a distinct atypical form of EAE in a cynomolgus macaque. By day 36 in the monkey, titers of IgG against conformational epitopes of extracellular MOG were evident, and on day 201, the macaque had an abrupt onset of an unusual form of EAE that included a pronounced arousal-dependent, transient myotonia. The disease persisted for 6-7 weeks and was marked by a gradual, consistent improvement and an eventual full recovery without recurrence. These data indicate that one or more boosters of IgV-MOG in IFA represent a key variable for induction of atypical or unusual forms of EAE in rat and Macaca species. These studies also reveal a close correlation between humoral immunity against conformational epitopes of MOG, extended confluent demyelinating plaques in spinal cord and

  18. ATRX ADD Domain Links an Atypical Histone Methylation Recognition Mechanism to Human Mental-Retardation Syndrome

    SciTech Connect

    S Iwase; B Xiang; S Ghosh; T Ren; P Lewis; J Cochrane; C Allis; D Picketts; D Patel; et al.

    2011-12-31

    ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.

  19. ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome

    SciTech Connect

    Iwase, Shigeki; Xiang, Bin; Ghosh, Sharmistha; Ren, Ting; Lewis, Peter W.; Cochrane, Jesse C.; Allis, C. David; Picketts, David J.; Patel, Dinshaw J.; Li, Haitao; Shi, Yang

    2011-07-19

    ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket, which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.

  20. A point mutation in domain 4-segment 6 of the skeletal muscle sodium channel produces an atypical inactivation state.

    PubMed Central

    O'Reilly, J P; Wang, S Y; Wang, G K

    2000-01-01

    We compared wild-type rat skeletal muscle NaChs (micro1) and a mutant NaCh (Y1586K) that has a single amino acid substitution, lysine (K) for tyrosine (Y), at position 1586 in the S6 transmembrane segment of domain 4. In Y1586K, macroscopic current decay is faster, the V(1/2) of the activation curve is shifted in the depolarized direction, and the fast-inactivation curve is less steep compared with mu1. After an 8-ms depolarization pulse, Y1586K recovers from inactivation much more slowly than mu1. The recovery is double exponential, suggesting recovery from two inactivation states. Varying the depolarization protocols isolates entry into an additional, "atypical" inactivation state in Y1586K that is distinct from typical fast or slow inactivation. Substitution of positively charged arginine (R) at Y1586 produces an inactivation phenotype similar to that of Y1586K. Substitution by negatively charged aspartic acid (D) or uncharged alanine (A) at Y1586 produces an inactivation phenotype similar to mu1. Our results suggest that the positive charge of lysine (K) produces the atypical inactivation state in Y1586K. We propose that a conformational change during depolarization alters the relative position of the 1586K residue in the D4-S6 segment and that atypical inactivation in Y1586K occurs via an electrostatic interaction in or near the inner pore region. PMID:10653790

  1. COORDINATED ACTIVATION OF THE RAC-GAP β2-CHIMAERIN BY AN ATYPICAL PROLINE-RICH DOMAIN AND DIACYLGLYCEROL

    PubMed Central

    Gutierrez-Uzquiza, Alvaro; Colon-Gonzalez, Francheska; Leonard, Thomas A.; Canagarajah, Bertram J.; Wang, HongBin; Mayer, Bruce J.; Hurley, James H.; Kazanietz, Marcelo G.

    2013-01-01

    Chimaerins, a family of GTPase activating proteins (GAPs) for the small G-protein Rac, have been implicated in development, neuritogenesis, and cancer. These Rac-GAPs are regulated by the lipid second messenger diacylglycerol (DAG) generated by tyrosine-kinases such as the epidermal growth factor receptor (EGFR). Here we identify an atypical Pro-rich motif in chimaerins that binds to the adaptor protein Nck1. Unlike most Nck1 partners, chimaerins bind to the third SH3 domain of Nck1. This association is mediated by electrostatic interactions of basic residues within the Pro-rich motif with acidic clusters in the SH3 domain. EGF promotes the binding of β2-chimaerin to Nck1 in the cell periphery in a DAG-dependent manner. Moreover, β2-chimaerin translocation to the plasma membrane and its peripheral association with Rac1 requires Nck1. Our studies underscore a coordinated mechanism for β2-chimaerin activation that involves lipid interactions via the C1 domain and protein-protein interactions via the N-terminal Pro-rich region. PMID:23673634

  2. NMR Study Reveals the Receiver Domain of Arabidopsis ETHYLENE RESPONSE1 Ethylene Receptor as an Atypical Type Response Regulator

    PubMed Central

    Lee, Yi-Zong; Wen, Chi-Kuang; Sue, Shih-Che

    2016-01-01

    The gaseous plant hormone ethylene, recognized by plant ethylene receptors, plays a pivotal role in various aspects of plant growth and development. ETHYLENE RESPONSE1 (ETR1) is an ethylene receptor isolated from Arabidopsis and has a structure characteristic of prokaryotic two-component histidine kinase (HK) and receiver domain (RD), where the RD structurally resembles bacteria response regulators (RRs). The ETR1 HK domain has autophosphorylation activity, and little is known if the HK can transfer the phosphoryl group to the RD for receptor signaling. Unveiling the correlation of the receptor structure and phosphorylation status would advance the studies towards the underlying mechanisms of ETR1 receptor signaling. In this study, using the nuclear magnetic resonance technique, our data suggested that the ETR1-RD is monomeric in solution and the rigid structure of the RD prevents the conserved aspartate residue phosphorylation. Comparing the backbone dynamics with other RRs, we propose that backbone flexibility is critical to the RR phosphorylation. Besides the limited flexibility, ETR1-RD has a unique γ loop conformation of opposite orientation, which makes ETR1-RD unfavorable for phosphorylation. These two features explain why ETR1-RD cannot be phosphorylated and is classified as an atypical type RR. As a control, phosphorylation of the ETR1-RD was also impaired when the sequence was swapped to the fragment of the bacterial typical type RR, CheY. Here, we suggest a molecule insight that the ETR1-RD already exists as an active formation and executes its function through binding with the downstream factors without phosphorylation. PMID:27486797

  3. Mapping of receptor binding sites on IL-1 beta by reconstruction of IL-1ra-like domains.

    PubMed

    Boraschi, D; Bossù, P; Ruggiero, P; Tagliabue, A; Bertini, R; Macchia, G; Gasbarro, C; Pellegrini, L; Melillo, G; Ulisse, E; Visconti, U; Bizzarri, C; Del Grosso, E; Mackay, A R; Frascotti, G; Frigerio, F; Grifantini, R; Grandi, G

    1995-11-15

    Upon structure comparison between IL-1 beta and its antagonist IL-1ra, single or multiple residues along the IL-1 beta sequence were replaced with the corresponding amino acids present in the IL-1ra protein, in the attempt to identify sites important for receptor binding and for biologic activity on the two molecules. Ten of fifteen mutant proteins had activity comparable to that of wild-type IL-1 beta in three different biologic assays and in receptor binding, indicating that the introduced changes did not influence the functional structure of the protein. Conversely, three mutants (SMIL-9: 127/263 R/T-->W/Y; SMIL-10: 125/127/263/265 T/R/T/Q-->R/W/Y/E; SMIL-15:222/227 I/E-->S/S) showed an increased binding capacity for IL-1RI, not paralleled by increased agonist activity, indicating that the introduced IL-1ra residues could be involved in the nonagonist IL-1RI binding site. On the other hand, two mutants showed diminished binding capacity with concomitant decrease in biologic activity. Both mutants (SMIL-1, five substitutions in the loop 202-214; and SMIL-3, total replacement of the loop 164-173 with the IL-1ra stretch 52-55) included substitutions of residues allegedly important for agonist binding to IL-1RI. Mutant SMIL-3 showed the most profound reduction in binding capacity for IL-1RI (CDw121a) and a more than 1,000-fold reduced biologic activity both in vitro and in vivo, but it retained full capacity of binding to IL-1RII (CDw121b) and acted as a selective antagonist of IL-1RII. From these results the following conclusions can be drawn. IL-1 beta binds to IL-1RI and to IL-1RII through different sites, and the loop 164-173 appears as one of the areas involved in the selective interaction with IL-1RI. Agonist (IL-1 beta) and nonagonist (IL-1ra) binding to IL-1RI occur through distinct sites, with loops 164-173 and 202-214 of IL-1 beta identified as two of the sites selectively involved in agonist binding to the activating receptor.

  4. An atypical segment swap in the DN and DC domains of the Acr_tran family resistance-nodulation-cell division pump.

    PubMed

    Acharya, Giriraj; Kaur, Gurmeet; Subramanian, Srikrishna

    2016-12-01

    Domain/segment swapping is an exchange of equivalent secondary structure element(s) among two or more protein domains resulting in the reconstitution of the original fold while simultaneously causing oligomerization. Here we report an example of the outer membrane factor docking region of the Acr_tran family (PF00873) resistance-nodulation-cell division pump, in which a swapped, misfolded state, of the ferredoxin-like fold of the DN and DC domains, effectuates oligomerization. The atypical segment swap and the associated displacement of a region of the ferredoxin-like fold leads to a topology that is distinct from the original fold. To our knowledge, such segment swaps and associated fold change are rare. This exemplifies the role of functional constraints including oligomerization that determine the interplay between sequence and the three-dimensional structure of proteins. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Synthesis of the Tetracyclic ABCD Ring Domain of Calyciphylline A-Type Alkaloids via Reductive Radical Cyclizations.

    PubMed

    Coussanes, Guilhem; Bonjoch, Josep

    2017-02-17

    A tetracyclic compound with the ABCD ring framework of calyciphylline A-type alkaloids was synthesized from a cis-3a-methyloctahydroindole triggered by a 5-endo radical cyclization. The synthesis required two additional ring-forming steps: the construction of a seven-membered ring by aldol cyclization and the azabicyclic fragment by a radical ring closure of a trichloroacetamide-tethered enol acetate followed by a diastereoselective α-methylation of the lactam group.

  6. Illusory memories of emotionally charged words in autism spectrum disorder: further evidence for atypical emotion processing outside the social domain.

    PubMed

    Gaigg, Sebastian B; Bowler, Dermot M

    2009-07-01

    Recent evidence suggests that individuals with ASD may not accumulate distinct representations of emotional information throughout development. On the basis of this observation we predicted that such individuals would not be any less likely to falsely remember emotionally significant as compared to neutral words when such illusory memories are induced by asking participants to study lists of words that are orthographically associated to these words. Our findings showed that typical participants are far less likely to experience illusory memories of emotionally charged as compared to neutral words. Individuals with ASD, on the other hand, did not exhibit this emotional modulation of false memories. We discuss this finding in relation to the role of emotional processing atypicalities in ASD.

  7. Solution structure of the region 51–160 of human KIN17 reveals an atypical winged helix domain

    PubMed Central

    Carlier, Ludovic; Couprie, Joël; le Maire, Albane; Guilhaudis, Laure; Milazzo-Segalas, Isabelle; Courçon, Marie; Moutiez, Mireille; Gondry, Muriel; Davoust, Daniel; Gilquin, Bernard; Zinn-Justin, Sophie

    2007-01-01

    Human KIN17 is a 45-kDa eukaryotic DNA- and RNA-binding protein that plays an important role in nuclear metabolism and in particular in the general response to genotoxics. Its amino acids sequence contains a zinc finger motif (residues 28–50) within a 30-kDa N-terminal region conserved from yeast to human, and a 15-kDa C-terminal tandem of SH3-like subdomains (residues 268–393) only found in higher eukaryotes. Here we report the solution structure of the region 51–160 of human KIN17. We show that this fragment folds into a three-α-helix bundle packed against a three-stranded β-sheet. It belongs to the winged helix (WH) family. Structural comparison with analogous WH domains reveals that KIN17 WH module presents an additional and highly conserved 310-helix. Moreover, KIN17 WH helix H3 is not positively charged as in classical DNA-binding WH domains. Thus, human KIN17 region 51–160 might rather be involved in protein–protein interaction through its conserved surface centered on the 310-helix. PMID:18029424

  8. Pleckstrin Homology (PH) Domain Leucine-rich Repeat Protein Phosphatase Controls Cell Polarity by Negatively Regulating the Activity of Atypical Protein Kinase C.

    PubMed

    Xiong, Xiaopeng; Li, Xin; Wen, Yang-An; Gao, Tianyan

    2016-11-25

    The proper establishment of epithelial polarity allows cells to sense and respond to signals that arise from the microenvironment in a spatiotemporally controlled manner. Atypical PKCs (aPKCs) are implicated as key regulators of epithelial polarity. However, the molecular mechanism underlying the negative regulation of aPKCs remains largely unknown. In this study, we demonstrated that PH domain leucine-rich repeat protein phosphatase (PHLPP), a novel family of Ser/Thr protein phosphatases, plays an important role in regulating epithelial polarity by controlling the phosphorylation of both aPKC isoforms. Altered expression of PHLPP1 or PHLPP2 disrupted polarization of Caco2 cells grown in 3D cell cultures as indicated by the formation of aberrant multi-lumen structures. Overexpression of PHLPP resulted in a decrease in aPKC phosphorylation at both the activation loop and the turn motif sites; conversely, knockdown of PHLPP increased aPKC phosphorylation. Moreover, in vitro dephosphorylation experiments revealed that both aPKC isoforms were substrates of PHLPP. Interestingly, knockdown of PKCζ, but not PKCι, led to similar disruption of the polarized lumen structure, suggesting that PKCζ likely controls the polarization process of Caco2 cells. Furthermore, knockdown of PHLPP altered the apical membrane localization of aPKCs and reduced the formation of aPKC-Par3 complex. Taken together, our results identify a novel role of PHLPP in regulating aPKC and cell polarity. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Atypical Antigen Recognition Mode of a Shark Immunoglobulin New Antigen Receptor (IgNAR) Variable Domain Characterized by Humanization and Structural Analysis

    PubMed Central

    Kovalenko, Oleg V.; Olland, Andrea; Piché-Nicholas, Nicole; Godbole, Adarsh; King, Daniel; Svenson, Kristine; Calabro, Valerie; Müller, Mischa R.; Barelle, Caroline J.; Somers, William; Gill, Davinder S.; Mosyak, Lidia; Tchistiakova, Lioudmila

    2013-01-01

    The immunoglobulin new antigen receptors (IgNARs) are a class of Ig-like molecules of the shark immune system that exist as heavy chain-only homodimers and bind antigens by their single domain variable regions (V-NARs). Following shark immunization and/or in vitro selection, V-NARs can be generated as soluble, stable, and specific high affinity monomeric binding proteins of ∼12 kDa. We have previously isolated a V-NAR from an immunized spiny dogfish shark, named E06, that binds specifically and with high affinity to human, mouse, and rat serum albumins. Humanization of E06 was carried out by converting over 60% of non-complementarity-determining region residues to those of a human germ line Vκ1 sequence, DPK9. The resulting huE06 molecules have largely retained the specificity and affinity of antigen binding of the parental V-NAR. Crystal structures of the shark E06 and its humanized variant (huE06 v1.1) in complex with human serum albumin (HSA) were determined at 3- and 2.3-Å resolution, respectively. The huE06 v1.1 molecule retained all but one amino acid residues involved in the binding site for HSA. Structural analysis of these V-NARs has revealed an unusual variable domain-antigen interaction. E06 interacts with HSA in an atypical mode that utilizes extensive framework contacts in addition to complementarity-determining regions that has not been seen previously in V-NARs. On the basis of the structure, the roles of various elements of the molecule are described with respect to antigen binding and V-NAR stability. This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs. PMID:23632026

  10. Atypical antigen recognition mode of a shark immunoglobulin new antigen receptor (IgNAR) variable domain characterized by humanization and structural analysis.

    PubMed

    Kovalenko, Oleg V; Olland, Andrea; Piché-Nicholas, Nicole; Godbole, Adarsh; King, Daniel; Svenson, Kristine; Calabro, Valerie; Müller, Mischa R; Barelle, Caroline J; Somers, William; Gill, Davinder S; Mosyak, Lidia; Tchistiakova, Lioudmila

    2013-06-14

    The immunoglobulin new antigen receptors (IgNARs) are a class of Ig-like molecules of the shark immune system that exist as heavy chain-only homodimers and bind antigens by their single domain variable regions (V-NARs). Following shark immunization and/or in vitro selection, V-NARs can be generated as soluble, stable, and specific high affinity monomeric binding proteins of ∼12 kDa. We have previously isolated a V-NAR from an immunized spiny dogfish shark, named E06, that binds specifically and with high affinity to human, mouse, and rat serum albumins. Humanization of E06 was carried out by converting over 60% of non-complementarity-determining region residues to those of a human germ line Vκ1 sequence, DPK9. The resulting huE06 molecules have largely retained the specificity and affinity of antigen binding of the parental V-NAR. Crystal structures of the shark E06 and its humanized variant (huE06 v1.1) in complex with human serum albumin (HSA) were determined at 3- and 2.3-Å resolution, respectively. The huE06 v1.1 molecule retained all but one amino acid residues involved in the binding site for HSA. Structural analysis of these V-NARs has revealed an unusual variable domain-antigen interaction. E06 interacts with HSA in an atypical mode that utilizes extensive framework contacts in addition to complementarity-determining regions that has not been seen previously in V-NARs. On the basis of the structure, the roles of various elements of the molecule are described with respect to antigen binding and V-NAR stability. This information broadens the general understanding of antigen recognition and provides a framework for further design and humanization of shark IgNARs.

  11. Analysis of chitin-binding proteins from Manduca sexta provides new insights into evolution of peritrophin A-type chitin-binding domains in insects.

    PubMed

    Tetreau, Guillaume; Dittmer, Neal T; Cao, Xiaolong; Agrawal, Sinu; Chen, Yun-Ru; Muthukrishnan, Subbaratnam; Haobo, Jiang; Blissard, Gary W; Kanost, Michael R; Wang, Ping

    2015-07-01

    In insects, chitin is a major structural component of the cuticle and the peritrophic membrane (PM). In nature, chitin is always associated with proteins among which chitin-binding proteins (CBPs) are the most important for forming, maintaining and regulating the functions of these extracellular structures. In this study, a genome-wide search for genes encoding proteins with ChtBD2-type (peritrophin A-type) chitin-binding domains (CBDs) was conducted. A total of 53 genes encoding 56 CBPs were identified, including 15 CPAP1s (cuticular proteins analogous to peritrophins with 1 CBD), 11 CPAP3s (CPAPs with 3 CBDs) and 17 PMPs (PM proteins) with a variable number of CBDs, which are structural components of cuticle or of the PM. CBDs were also identified in enzymes of chitin metabolism including 6 chitinases and 7 chitin deacetylases encoded by 6 and 5 genes, respectively. RNA-seq analysis confirmed that PMP and CPAP genes have differential spatial expression patterns. The expression of PMP genes is midgut-specific, while CPAP genes are widely expressed in different cuticle forming tissues. Phylogenetic analysis of CBDs of proteins in insects belonging to different orders revealed that CPAP1s from different species constitute a separate family with 16 different groups, including 6 new groups identified in this study. The CPAP3s are clustered into a separate family of 7 groups present in all insect orders. Altogether, they reveal that duplication events of CBDs in CPAP1s and CPAP3s occurred prior to the evolutionary radiation of insect species. In contrast to the CPAPs, all CBDs from individual PMPs are generally clustered and distinct from other PMPs in the same species in phylogenetic analyses, indicating that the duplication of CBDs in each of these PMPs occurred after divergence of insect species. Phylogenetic analysis of these three CBP families showed that the CBDs in CPAP1s form a clearly separate family, while those found in PMPs and CPAP3s were clustered

  12. Atypical Fibroxanthoma.

    PubMed

    López, Liurka; Vélez, Román

    2016-04-01

    Atypical fibroxanthoma is a malignant skin tumor with histologic features similar to those of undifferentiated pleomorphic sarcoma, but lacking its more aggressive behavior. The tumor is composed of pleomorphic cells with hyperchromatic nuclei and abundant cytoplasm, commonly arranged in a spindle cell pattern. Recent genetic studies have identified similarities between atypical fibroxanthoma and undifferentiated pleomorphic sarcoma, such as the presence of 9p and 13q deletions in both tumors, favoring a common histogenesis. However, the lack of K-ras and H-ras mutations in atypical fibroxanthoma compared with undifferentiated pleomorphic sarcoma could explain the difference in aggressiveness and continued separation of these entities. Exclusion of other neoplasms by histology and immunohistochemistry followed by complete surgical removal remains the standard of care.

  13. Atypical Cities

    ERIC Educational Resources Information Center

    DiJulio, Betsy

    2011-01-01

    In this creative challenge, Surrealism and one-point perspective combine to produce images that not only go "beyond the real" but also beyond the ubiquitous "imaginary city" assignment often used to teach one-point perspective. Perhaps the difference is that in the "atypical cities challenge," an understanding of one-point perspective is a means…

  14. Atypical Cities

    ERIC Educational Resources Information Center

    DiJulio, Betsy

    2011-01-01

    In this creative challenge, Surrealism and one-point perspective combine to produce images that not only go "beyond the real" but also beyond the ubiquitous "imaginary city" assignment often used to teach one-point perspective. Perhaps the difference is that in the "atypical cities challenge," an understanding of one-point perspective is a means…

  15. Atypical presentations of atypical antipsychotics.

    PubMed

    Lind, Cpt Christopher K; Carchedi, Cpt Lisa R; Staudenmeier, Ltc James J; Diebold, Ltc P Carroll J

    2005-06-01

    The atypical antipsychotics have been touted by many as having minimal extrapyramidal symptoms. This case series from the Tripler Army Medical Center Psychiatry Graduate Medical Education Program presents the extrapyramidal symptoms observed with four different atypical antipsychotic medications. Also reviewed are the mechanisms of action that atypical antipsychotics and first-generation antipsychotics use to treat the symptoms of schizophrenia. Cases reviewed include a schizophrenic male patient whose dose of risperidone was doubled from 6mg to 12mg overnight and developed an acute dystonic reaction; a young male patient with a substance-induced psychosis who unintentionally doubled his ziprasidone dose in 24 hours, resulting in an acute dystonic reaction; a young female patient on paroxetine who also recently started olanzapine and had complaints consistent with akathisia that resolved with treatment; and an adolescent female patient on escitalopram for obsessive-compulsive disorder who after starting aripiprazole developed Parkinsonism. All four cases illustrate that even though atypical antipsychotics are less likely to cause extrapyramidal symptoms than their first generation cousins, the physician should be aware that these symptoms may still occur and need to be treated.

  16. Atypical Presentations of Atypical Antipsychotics

    PubMed Central

    Carchedi, CPT. Lisa R.; Staudenmeier, LTC. James J.; Diebold, LTC(P). Carroll J.

    2005-01-01

    The atypical antipsychotics have been touted by many as having minimal extrapyramidal symptoms. This case series from the Tripler Army Medical Center Psychiatry Graduate Medical Education Program presents the extrapyramidal symptoms observed with four different atypical antipsychotic medications. Also reviewed are the mechanisms of action that atypical antipsychotics and first-generation antipsychotics use to treat the symptoms of schizophrenia. Cases reviewed include a schizophrenic male patient whose dose of risperidone was doubled from 6mg to 12mg overnight and developed an acute dystonic reaction; a young male patient with a substance-induced psychosis who unintentionally doubled his ziprasidone dose in 24 hours, resulting in an acute dystonic reaction; a young female patient on paroxetine who also recently started olanzapine and had complaints consistent with akathisia that resolved with treatment; and an adolescent female patient on escitalopram for obsessive-compulsive disorder who after starting aripiprazole developed Parkinsonism. All four cases illustrate that even though atypical antipsychotics are less likely to cause extrapyramidal symptoms than their first generation cousins, the physician should be aware that these symptoms may still occur and need to be treated. PMID:21152153

  17. Atypical GTPases as drug targets.

    PubMed

    Soundararajan, Meera; Eswaran, Jeyanthy

    2012-01-01

    The Ras GTPases are the founding members of large Ras superfamily, which constitutes more than 150 of these important class of enzymes. These GTPases function as GDP-GTP-regulated binary switches that control many fundamental cellular processes. There are a number of GTPases that have been identified recently, which do not confine to this prototype termed as "atypical GTPases" but have proved to play a remarkable role in vital cellular functions. In this review, we provide an overview of the crucial physiological functions mediated by RGK and Centaurin class of multi domain atypical GTPases. Moreover, the recently available atypical GTPase structures of the two families, regulation, physiological functions and their critical roles in various diseases will be discussed. In summary, this review will highlight the emerging atypical GTPase family which allows us to understand novel regulatory mechanisms and thus providing new avenues for drug discovery programs.

  18. Atypical fibroxanthoma†

    PubMed Central

    Zogbi, Luciano; Juliano, Camila; Neutzling, Aluísio

    2015-01-01

    Atypical fibroxanthoma (AFX) is a rare skin neoplasm of low-grade malignancy and fibroblastic origin. AFX is a curable cutaneous disease and the diagnosis depends on knowledge of its clinical and histological features and combined immunohistochemistry markers. This study presents a case of a male patient, aged 90 years, presented with painless skin lesion in his ear. The lesion had been growing progressively for 2 months, measured ∼1.5 cm, ulcerated, fixed and firm. After a biopsy, the patient underwent a complete resection with adequate surgical margins and showed favorable evolution without complications or recurrence. The histopathological evaluation showed a poorly circumscribed ulcerated dermal nodule, mesenchymal proliferation, with pleomorphic spindle cells. There was infiltration of the deep dermis and subcutis, showing malignant features, but there was no invasion of cartilage. The immunohistochemical analysis confirmed the diagnosis of AFX. PMID:25742967

  19. Zinc- and iron-dependent cytosolic metallo-β-lactamase domain proteins exhibit similar zinc-binding affinities, independent of an atypical glutamate at the metal-binding site

    PubMed Central

    2004-01-01

    ZiPD (zinc phosphodiesterase; synonyms are ElaC, ecoZ, RNaseZ and 3′ tRNase) and the iron-dependent redox enzyme FlRd (flavorubredoxin) from Escherichia coli represent prototypical cases of proteins sharing the metallo-β-lactamase fold that require strict metal selectivity for catalytic activity, yet their metal selectivity has only been partially understood. In contrast with hydrolytic metallo-β-lactamase proteins, iron-dependent FlRd-like enzymes have an atypical glutamate ligand, which replaces one otherwise conserved histidine ligand. X-ray absorption spectroscopy revealed that the FlRd metallo-β-lactamase domain is capable of incorporating two zinc ions into the binuclear metal-binding site. Zinc dissociation constants, determined by isothermal titration calorimetry are similar for zinc binding to E. coli ZiPD (Kd1=2.2±0.2 μM and Kd2=23.0±0.6 μM) and to the E. coli FlRd metallo-β-lactamase domain (Kd1=0.7±0.1 μM and Kd2=26.0±0.1 μM). In good correspondence, apo-ZiPD requires incubation with 10 μM zinc for full reconstitution of the phosphodiesterase activity. Accordingly, metal selectivity of ZiPD and FlRd only partially relies on first shell metal ligands. Back mutation of the atypical glutamate in FlRd to a histidine unexpectedly resulted in an increased first zinc dissociation constant (Kd1=30±4 μM and Kd2=23±2 μM). In combination with a recent mutational study on ZiPD [Vogel, Schilling and Meyer-Klaucke (2004) Biochemistry 43, 10379–10386], we conclude that the atypical glutamate does not guide metal selectivity of the FlRd metallo-β-lactamase domain but suppresses possible hydrolytic cross-activity. PMID:15324305

  20. "Redefining RA": The RA Tool Kit

    ERIC Educational Resources Information Center

    Wyatt, Neal

    2008-01-01

    No one likes being two steps behind, and the fastest way to fall off the pace is by not keeping up with major titles and hot authors. Fortunately, there are numerous resources, both prepublication and postpublication, that can help. It is best when readers' advisory (RA) librarians know what is coming out months ahead of time--in order to think…

  1. Martin RA-30 Baltimore

    NASA Technical Reports Server (NTRS)

    1943-01-01

    Martin RA-30 Baltimore: The Martin RA-30 Baltimore was a light bomber ordered by the Royal Air Force. Some examples were retained in the United States as part of a 'Reverse Lend-Lease.' This example was flown by the NACA from June 1943 until March 1944.

  2. Genes encoding proteins with peritrophin A-type chitin-binding domains in Tribolium castaneum are grouped into three distinct families based on phylogeny, expression and function

    USDA-ARS?s Scientific Manuscript database

    This study is focused on the characterization and expression of genes in the red flour beetle, Tribolium castaneum, encoding proteins that possess six-cysteine-containing chitin-binding domains (CBDs) related to the peritrophin A domain (ChtBD2). An exhaustive bioinformatics search of the genome of...

  3. ATRX binds to atypical chromatin domains at the 3′ exons of zinc finger genes to preserve H3K9me3 enrichment

    PubMed Central

    Chowdhury, Asif H.; Hasson, Dan; Dyer, Michael A.

    2016-01-01

    ABSTRACT ATRX is a SWI/SNF chromatin remodeler proposed to govern genomic stability through the regulation of repetitive sequences, such as rDNA, retrotransposons, and pericentromeric and telomeric repeats. However, few direct ATRX target genes have been identified and high-throughput genomic approaches are currently lacking for ATRX. Here we present a comprehensive ChIP-sequencing study of ATRX in multiple human cell lines, in which we identify the 3′ exons of zinc finger genes (ZNFs) as a new class of ATRX targets. These 3′ exonic regions encode the zinc finger motifs, which can range from 1–40 copies per ZNF gene and share large stretches of sequence similarity. These regions often contain an atypical chromatin signature: they are transcriptionally active, contain high levels of H3K36me3, and are paradoxically enriched in H3K9me3. We find that these ZNF 3′ exons are co-occupied by SETDB1, TRIM28, and ZNF274, which form a complex with ATRX. CRISPR/Cas9-mediated loss-of-function studies demonstrate (i) a reduction of H3K9me3 at the ZNF 3′ exons in the absence of ATRX and ZNF274 and, (ii) H3K9me3 levels at atypical chromatin regions are particularly sensitive to ATRX loss compared to other H3K9me3-occupied regions. As a consequence of ATRX or ZNF274 depletion, cells with reduced levels of H3K9me3 show increased levels of DNA damage, suggesting that ATRX binds to the 3′ exons of ZNFs to maintain their genomic stability through preservation of H3K9me3. PMID:27029610

  4. Discovery of novel interacting partners of PSMD9, a proteasomal chaperone: Role of an Atypical and versatile PDZ-domain motif interaction and identification of putative functional modules

    PubMed Central

    Sangith, Nikhil; Srinivasaraghavan, Kannan; Sahu, Indrajit; Desai, Ankita; Medipally, Spandana; Somavarappu, Arun Kumar; Verma, Chandra; Venkatraman, Prasanna

    2014-01-01

    PSMD9 (Proteasome Macropain non-ATPase subunit 9), a proteasomal assembly chaperone, harbors an uncharacterized PDZ-like domain. Here we report the identification of five novel interacting partners of PSMD9 and provide the first glimpse at the structure of the PDZ-domain, including the molecular details of the interaction. We based our strategy on two propositions: (a) proteins with conserved C-termini may share common functions and (b) PDZ domains interact with C-terminal residues of proteins. Screening of C-terminal peptides followed by interactions using full-length recombinant proteins, we discovered hnRNPA1 (an RNA binding protein), S14 (a ribosomal protein), CSH1 (a growth hormone), E12 (a transcription factor) and IL6 receptor as novel PSMD9-interacting partners. Through multiple techniques and structural insights, we clearly demonstrate for the first time that human PDZ domain interacts with the predicted Short Linear Sequence Motif (SLIM) at the C-termini of the client proteins. These interactions are also recapitulated in mammalian cells. Together, these results are suggestive of the role of PSMD9 in transcriptional regulation, mRNA processing and editing, hormone and receptor activity and protein translation. Our proof-of-principle experiments endorse a novel and quick method for the identification of putative interacting partners of similar PDZ-domain proteins from the proteome and for discovering novel functions. PMID:25009770

  5. Downregulation of 5-HT7 Serotonin Receptors by the Atypical Antipsychotics Clozapine and Olanzapine. Role of Motifs in the C-Terminal Domain and Interaction with GASP-1.

    PubMed

    Manfra, Ornella; Van Craenenbroeck, Kathleen; Skieterska, Kamila; Frimurer, Thomas; Schwartz, Thue W; Levy, Finn Olav; Andressen, Kjetil Wessel

    2015-07-15

    The human 5-HT7 serotonin receptor, a G-protein-coupled receptor (GPCR), activates adenylyl cyclase constitutively and upon agonist activation. Biased ligands differentially activate 5-HT7 serotonin receptor desensitization, internalization and degradation in addition to G protein activation. We have previously found that the atypical antipsychotics clozapine and olanzapine inhibited G protein activation and, surprisingly, induced both internalization and lysosomal degradation of 5-HT7 receptors. Here, we aimed to determine the mechanism of clozapine- and olanzapine-mediated degradation of 5-HT7 receptors. In the C-terminus of the 5-HT7 receptor, we identified two YXXΦ motifs, LR residues, and a palmitoylated cysteine anchor as potential sites involved in receptor trafficking to lysosomes followed by receptor degradation. Mutating either of these sites inhibited clozapine- and olanzapine-mediated degradation of 5-HT7 receptors and also interfered with G protein activation. In addition, we tested whether receptor degradation was mediated by the GPCR-associated sorting protein-1 (GASP-1). We show that GASP-1 binds the 5-HT7 receptor and regulates the clozapine-mediated degradation. Mutations of the identified motifs and residues, located in or close to Helix-VIII of the 5-HT7 receptor, modified antipsychotic-stimulated binding of proteins (such as GASP-1), possibly by altering the flexibility of Helix-VIII, and also interfered with G protein activation. Taken together, our data demonstrate that binding of clozapine or olanzapine to the 5-HT7 receptor leads to antagonist-mediated lysosomal degradation by exposing key residues in the C-terminal tail that interact with GASP-1.

  6. Measuring the radium quartet (228Ra, 226Ra, 224Ra, 223Ra) in seawater samples using gamma spectrometry.

    PubMed

    van Beek, P; Souhaut, M; Reyss, J-L

    2010-07-01

    Radium isotopes are widely used in marine studies (eg. to trace water masses, to quantify mixing processes or to study submarine groundwater discharge). While 228Ra and 226Ra are usually measured using gamma spectrometry, short-lived Ra isotopes (224Ra and 223Ra) are usually measured using a Radium Delayed Coincidence Counter (RaDeCC). Here we show that the four radium isotopes can be analyzed using gamma spectrometry. We report 226Ra, 228Ra, 224Ra, 223Ra activities measured using low-background gamma spectrometry in standard samples, in water samples collected in the vicinity of our laboratory (La Palme and Vaccarès lagoons, France) but also in seawater samples collected in the plume of the Amazon river, off French Guyana (AMANDES project). The 223Ra and 224Ra activities determined in these samples using gamma spectrometry were compared to the activities determined using RaDeCC. Activities determined using the two techniques are in good agreement. Uncertainties associated with the 224Ra activities are similar for the two techniques. RaDeCC is more sensitive for the detection of low 223Ra activities. Gamma spectrometry thus constitutes an alternate method for the determination of short-lived Ra isotopes. 2009 Elsevier Ltd. All rights reserved.

  7. A Novel Heterozygous Mutation in the STAT1 SH2 Domain Causes Chronic Mucocutaneous Candidiasis, Atypically Diverse Infections, Autoimmunity, and Impaired Cytokine Regulation

    PubMed Central

    Meesilpavikkai, Kornvalee; Dik, Willem A.; Schrijver, Benjamin; Nagtzaam, Nicole M. A.; van Rijswijk, Angelique; Driessen, Gertjan J.; van der Spek, Peter J.; van Hagen, P. Martin; Dalm, Virgil A. S. H.

    2017-01-01

    Chronic mucocutaneous candidiasis (CMC) is a primary immunodeficiency characterized by persistent or recurrent skin and mucosal surface infections with Candida species. Different gene mutations leading to CMC have been identified. These include various heterozygous gain-of-function (GOF) mutations in signal transducer and activator of transcription 1 (STAT1) that are not only associated with infections but also with autoimmune manifestations. Recently, two STAT1 GOF mutations involving the Src homology 2 (SH2) domain have been reported, while so far, over 50 mutations have been described mainly in the coiled coil and the DNA-binding domains. Here, we present two members of a Dutch family with a novel STAT1 mutation located in the SH2 domain. T lymphocytes of these patients revealed STAT1 hyperphosphorylation and higher expression of STAT1 target genes. The clinical picture of CMC in our patients could be explained by diminished production of interleukin (IL)-17 and IL-22, cytokines important in the protection against fungal infections. PMID:28348565

  8. Genes encoding proteins with peritrophin A-type chitin-binding domains in Tribolium castaneum are grouped into three distinct families based on phylogeny, expression and function.

    PubMed

    Jasrapuria, Sinu; Arakane, Yasuyuki; Osman, Gamal; Kramer, Karl J; Beeman, Richard W; Muthukrishnan, Subbaratnam

    2010-03-01

    This study is focused on the characterization and expression of genes in the red flour beetle, Tribolium castaneum, encoding proteins that possess one or more six-cysteine-containing chitin-binding domains related to the peritrophin A domain (ChtBD2). An exhaustive bioinformatics search of the genome of T. castaneum queried with ChtBD2 sequences yielded 13 previously characterized chitin metabolic enzymes and 29 additional proteins with signal peptides as well as one to 14 ChtBD2s. Using phylogenetic analyses, these additional 29 proteins were classified into three large families. The first family includes 11 proteins closely related to the peritrophins, each containing one to 14 ChtBD2s. These are midgut-specific and are expressed only during feeding stages. We propose the name "Peritrophic Matrix Proteins" (PMP) for this family. The second family contains eight proteins encoded by seven genes (one gene codes for 2 splice variants), which are closely related to gasp/obstructor-like proteins that contain 3 ChtBD2s each. The third family has ten proteins that are of diverse sizes and sequences with only one ChtBD2 each. The genes of the second and third families are expressed in non-midgut tissues throughout all stages of development. We propose the names "Cuticular Proteins Analogous to Peritophins 3" (CPAP3) for the second family that has three ChtBD2s and "Cuticular Proteins Analogous to Peritophins 1 (CPAP1) for the third family that has 1 ChtBD2. Even though proteins of both CPAP1 and CPAP3 families have the "peritrophin A" domain, they are expressed only in cuticle-forming tissues. We determined the exon-intron organization of the genes, encoding these 29 proteins as well as the domain organization of the encoded proteins with ChtBD2s. All 29 proteins have predicted cleavable signal peptides and ChtBD2s, suggesting that they interact with chitin in extracellular locations. Comparison of ChtBD2s-containing proteins in different insect species belonging to

  9. The RA Role Revisited: Differences in Perspectives of RA Responsibilities.

    ERIC Educational Resources Information Center

    Schuh, John H.; And Others

    1982-01-01

    Determined resident assistants' (RA) role perceptions of students, parents, faculty, and administrators, full-time professional residence life staff, and resident assistants. Compared various constituent groups' perceptions of the RA role. (RC)

  10. Take the RA Talk Online

    ERIC Educational Resources Information Center

    Wyatt, Neal

    2008-01-01

    As a group, readers' advisory (RA) librarians are a chatty bunch when it comes to what they are reading. They share book ideas with their friends and families. The adoption of online RA conversation forms is helping to extend these opportunities even further and offers a fascinating testing ground for RA work. Librarians have found that offering…

  11. [Atypical depression: Clinical perspectives].

    PubMed

    Lutz, M; Morali, A; Lang, J-P

    2013-09-01

    This paper examines whether atypical depression is still a valid entity as a diagnosis subtype in the light of publications with most recent antidepressants. First, we present the origins of the diagnosis sub-specification of atypical depression, which is based on a different drug response to tricyclic antidepressants and mono amino oxydase inhibitors. Secondly, we discuss the different definitions that can be found for the terms of atypical depression. We present more specifically the definition of atypical depression as it is described in the DSM-IV, with its most important criterion: mood reactivity. Then we present a review of scientific publications questioning atypical depression validity as a clinical syndrome (based on medline researches). We will see whether this diagnosis is still relevant with the latest drugs used to treat mood disorders. A special focus is made on the link between atypical depression and bipolar disorder, based on Benazzi's work. Most of publications confirm that atypical depression is a valid syndrome regarding first antidepressants clinical trials. Nevertheless, more studies with the latest antidepressants and atypical antipsychotics are needed to confirm this hypothesis. The link between atypical depression and bipolar disorders seems to be quite strong although it requires further investigations. There are very few double-blind drug trials focusing on atypical depressions and results need to be confirmed by trials with new drugs. Moreover, we regret that there are no studies including cerebral imagery. More studies are also needed on neurobiology and psychotherapy specificity. Atypical depression is still a useful concept, because of its specific clinical presentation, evolution and treatments, even if more studies should be done. Atypical depression could also be useful to diagnose more easily some bipolar disorders and should help clinicians to focus more on suicidal risks and addiction evaluation for these patients, considering

  12. Atypical autoerotic deaths

    SciTech Connect

    Gowitt, G.T.; Hanzlick, R.L. )

    1992-06-01

    So-called typical' autoerotic fatalities are the result of asphyxia due to mechanical compression of the neck, chest, or abdomen, whereas atypical' autoeroticism involves sexual self-stimulation by other means. The authors present five atypical autoerotic fatalities that involved the use of dichlorodifluoromethane, nitrous oxide, isobutyl nitrite, cocaine, or compounds containing 1-1-1-trichloroethane. Mechanisms of death are discussed in each case and the pertinent literature is reviewed.

  13. Occurrence of 224Ra, 226Ra, 228Ra, gross alpha, and uranium in California groundwater.

    PubMed

    Ruberu, Shiyamalie R; Liu, Yun-Gang; Perera, S Kusum

    2005-12-01

    One hundred and twelve groundwater wells sampled from all the major aquifers in California were analyzed for 224Ra, 226Ra, 228Ra, gross alpha, and uranium. The results showed that radium is found in relatively low concentration, 1.56 x 10(-2)-1.23 Bq L(-1) (0.42-33 pCi L(-1)) for 224Ra, 2.2 x 10(-3)-0.81 Bq L(-1) (0.06-22 pCi L(-1)) for 226Ra, and 8.5 x 10(-3)-1.31 Bq L(-1) (0.23-35 pCi L(-1)) for 228Ra in California groundwater. Uranium was found at the highest concentration on both mass and activity basis and was correlated with the gross alpha measurement. Short-lived radioisotopes showed no significant contribution to gross alpha measurements. There was a strong correlation between 224Ra and 228Ra activities, suggesting the latter to be an indicator for the occurrence of the former. Comparison of 226Ra to 238U, 224Ra to 226Ra, and 226Ra to 228Ra showed scattered data indicating no correlation between each of these isotope pairs. Approximately 4% of the wells were found to exceed the U.S. Environmental Protection Agency (EPA) established maximum contaminant level for total radium of 0.185 Bq L(-1) (5 pCi L(-1)). Analysis of 228Ra by gamma-ray spectroscopy was in good agreement with the U.S. EPA-approved procedure.

  14. 226Ra and 228Ra in Iowa drinking water.

    PubMed

    Kriege, L B; Hahne, R M

    1982-10-01

    The University Hygienic Laboratory has been performing radiochemical analyses on drinking water in the state of Iowa for over 20 yr. Approximately one half of the 1250 community water supplies that exist in Iowa have been sampled roughly once every 3 yr for the past decade. Originally, raw and finished waters that showed a gross alpha activity of greater than or equal to 3.0 pCi/L were analyzed for 226Ra, but starting in July 1976, finished waters were analyzed for both 226Ra and 228Ra if the gross alpha activity was greater than or equal to 2.0 pCi/L. As of 10 June 1981, 604 community water supplies had submitted composited samples that have been analyzed for gross alpha, 226Ra, and 228Ra concentrations in compliance with the federal Safe Drinking Water Act (Public Law 93-523). Approximately 10% of these supplies were found to exceed the EPA-established maximum contaminant level (MCL) for 226Ra plus 228Ra of 5 pCi/L. The results revealed, consistent with several other investigators (Mc81; Mi80; Mic80), that some supplies had higher concentrations of 228Ra than of 226Ra. It was also concluded, in agreement with McCurdy and Mellor (Mc81), that some ground water samples cannot be accurately measured for gross alpha activity due to their high dissolved solids content.

  15. Atypical combinations and scientific impact.

    PubMed

    Uzzi, Brian; Mukherjee, Satyam; Stringer, Michael; Jones, Ben

    2013-10-25

    Novelty is an essential feature of creative ideas, yet the building blocks of new ideas are often embodied in existing knowledge. From this perspective, balancing atypical knowledge with conventional knowledge may be critical to the link between innovativeness and impact. Our analysis of 17.9 million papers spanning all scientific fields suggests that science follows a nearly universal pattern: The highest-impact science is primarily grounded in exceptionally conventional combinations of prior work yet simultaneously features an intrusion of unusual combinations. Papers of this type were twice as likely to be highly cited works. Novel combinations of prior work are rare, yet teams are 37.7% more likely than solo authors to insert novel combinations into familiar knowledge domains.

  16. [Atypical panic attacks].

    PubMed

    Boulenger, Jean-Philippe

    2009-04-20

    Panic attacks are acute episodes of severe anxiety characterized by a brutal onset and a progressive ending. When atypical, this symptomatic picture is often the cause of diagnostic errors sometimes costly in terms of clinical work-up and repeated specialized advices. Each of the classical components of panic attacks (psychological, physical, behavioural) being able to give rise to an atypical presentation, these components must be systematically evaluated. The semiological analysis of these attacks, their clinical background and their occurrence in young adults, mostly women, will contribute to the right diagnosis of these emotional reactions so frequent in general practice.

  17. Atypical Hemolytic Uremic Syndrome

    PubMed Central

    Kavanagh, David; Goodship, Tim H.; Richards, Anna

    2013-01-01

    Summary Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The atypical form of HUS is a disease characterized by complement overactivation. Inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Incomplete penetrance of mutations in all predisposing genes is reported, suggesting that a precipitating event or trigger is required to unmask the complement regulatory deficiency. The underlying genetic defect predicts the prognosis both in native kidneys and after renal transplantation. The successful trials of the complement inhibitor eculizumab in the treatment of atypical HUS will revolutionize disease management. PMID:24161037

  18. Radium isotope ((223)Ra, (224)Ra, (226)Ra and (228)Ra) distribution near Brazil's largest port, Paranaguá Bay, Brazil.

    PubMed

    Dias, Thais H; de Oliveira, Joselene; Sanders, Christian J; Carvalho, Franciane; Sanders, Luciana M; Machado, Eunice C; Sá, Fabian

    2016-10-15

    This work investigates the (223)Ra, (224)Ra, (226)Ra and (228)Ra isotope distribution in river, estuarine waters and sediments of the Paranaguá Estuarine Complex (PEC). The stratification of the Ra isotopes along water columns indicate differing natural sources. In sediments, the radium isotope activities was inversely proportional to the particle size. The highest concentrations of (223)Ra, (224)Ra, (226)Ra and (228)Ra in the water column were found in the bottom more saline waters and towards the inner of the estuary. These relatively high concentrations towards the bottom of the estuary may be attributed to the influence of tidally driven groundwater source and desorption from particles at the maximum turbidity zone. The apparent river water ages from the radium isotope ratios, (223)Ra/(224)Ra and (223)Ra/(228)Ra, indicate that the principal rivers that flow into the estuary have residence times from between 6 and 11days. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Atypical adenomatous hyperplasia —

    Cancer.gov

    Focal and diffuse lesions involving alveoli and terminal bronchioles and consisting of relatively uniform atypical cuboidal to columnar cells with dense chromatin. Degrees of cellular hypertrophy and hyperchromasia are variable. Cellular and nuclear atypia are the distinctive features as compared with hyperplasia. Their relevance to human AAH and mouse adenomas remains to be determined.

  20. Melorheostosis: Two atypical cases

    PubMed Central

    Sureka, Binit; Mittal, Mahesh Kumar; Udhaya, KK; Sinha, Mukul; Mittal, Aliza; Thukral, Brij Bhushan

    2014-01-01

    Melorheostosis is an uncommon mesenchymal dysplasia that rarely affects the axial skeleton. We describe two atypical cases of melorheostosis with classical imaging findings – the first one involving the cervico-dorsal spine with encroachment of left vertebral artery canal causing attenuation of the left vertebral artery and the second one of mixed sclerosing bony dysplasia (monomelic involvement coexisting with osteopoikilosis). PMID:25024532

  1. Melorheostosis: Two atypical cases.

    PubMed

    Sureka, Binit; Mittal, Mahesh Kumar; Udhaya, Kk; Sinha, Mukul; Mittal, Aliza; Thukral, Brij Bhushan

    2014-04-01

    Melorheostosis is an uncommon mesenchymal dysplasia that rarely affects the axial skeleton. We describe two atypical cases of melorheostosis with classical imaging findings - the first one involving the cervico-dorsal spine with encroachment of left vertebral artery canal causing attenuation of the left vertebral artery and the second one of mixed sclerosing bony dysplasia (monomelic involvement coexisting with osteopoikilosis).

  2. Understanding Rheumatoid Arthritis (RA): Research

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Research Past Issues / Summer 2014 Table of ... a project plan to address relevant challenges for rheumatoid arthritis. Read Part 1 on Lupus in MedlinePlus magazine, ...

  3. Atypical Cogan's Syndrome

    PubMed Central

    Queirós, João; Maia, Sofia; Seca, Mariana; Friande, António; Araújo, Maria; Meireles, Angelina

    2013-01-01

    Background. Cogan's syndrome is a rare clinical entity whose etiopathology is still unknown, and the treatment strategies are not clearly defined. Case. A 23-year-old male presented with symptoms of headache, peripheral facial palsy, persistent right hearing loss and bilateral papillitis. Workup excluded all infectious, granulomatous, neoplastic, and immune causes. The diagnosis of atypical Cogan's syndrome was established, and the patient was treated with systemic corticosteroids and later on with cyclophosphamide and methotrexate. There were improvement of visual symptoms and stabilisation of left hearing. Conclusion. Cogan's syndrome is a very rare disease with no specific biological tests for the diagnosis. The diagnostic exams are mostly important to exclude other etiologies. The atypical ocular and audiovestibular manifestations make the diagnosis difficult, delaying the institution of appropriate therapy which may result in profound bilateral deafness. PMID:23691387

  4. [Atypical ubiquitination of proteins].

    PubMed

    Buneeva, O A; Medvedev, A E

    2016-07-01

    Ubiquitination is a type of posttranslational modification of intracellular proteins characterized by covalent attachment of one (monoubiquitination) or several (polyubiquitination) of ubiquitin molecules to target proteins. In the case of polyubiquitination, linear or branched polyubiquitin chains are formed. Their formation involves various lysine residues of monomeric ubiquitin. The best studied is Lys48-polyubiquitination, which targets proteins for proteasomal degradation. In this review we have considered examples of so-called atypical polyubiquitination, which mainly involves other lysine residues (Lys6, Lys11, Lys27, Lys29, Lys33, Lys63) and also N-terminal methionine. The considered examples convincingly demonstrate that polyubiquitination of proteins not necessarily targets proteins for their proteolytic degradation in proteasomes. Atypically polyubiquitinated proteins are involved in regulation of various processes and altered polyubiquitination of certain proteins is crucial for development of serious diseases.

  5. [Atypical presentation of preeclampsia].

    PubMed

    Ditisheim, A; Boulvain, M; Irion, O; Pechère-Bertschi, A

    2015-09-09

    Preeclampsia is a pregnancy-related syndrome, which still represents one of the major causes of maternal-fetal mortality and morbidity. Diagnosis can be made difficult due to the complexity of the disorder and its wide spectrum of clinical manifestations. In order to provide an efficient diagnostic tool to the clinician, medical societies regularly rethink the definition criteria. However, there are still clinical presentations of preeclampsia that escape the frame of the definition. The present review will address atypical forms of preeclampsia, such as preeclampsia without proteinuria, normotensive preeclampsia, preeclampsia before 20 weeks of gestation and post-partum preeclampsia.

  6. Atypical neuroleptics: compulsive disorders.

    PubMed

    2014-02-01

    Compulsive disorders are known adverse effects of dopamine agonists. Atypical neuroleptics (amisulpride, aripiprazole, olanzapine, paliperidone, quetiapine and risperidone) have also been implicated in cases of pathological gambling, hypersexuality, and compulsive eating and shopping, with sometimes serious social and familial consequences. The compulsive disorders improved or ceased when the neuroleptic was withdrawn or replaced. Patients must be informed of these possible adverse effects and monitored for behavioural changes. If such disorders occur, they can be managed by withdrawing the drug, reducing the dosage, or switching to another neuroleptic.

  7. Testing atypical depression definitions.

    PubMed

    Benazzi, Franco

    2005-01-01

    The evidence supporting the DSM-IV definition of atypical depression (AD) is weak. This study aimed to test different definitions of AD. Major depressive disorder (MDD) patients (N = 254) and bipolar-II (BP-II) outpatients (N = 348) were interviewed consecutively, during major depressive episodes, with the Structured Clinical Interview for DSM-IV. DSM-IV criteria for AD were followed. AD validators were female gender, young onset, BP-II, axis I comorbidity, bipolar family history. Frequency of DSM-IV AD was 43.0%. AD, versus non-AD, was significantly associated with all AD validators, apart from comorbidity when controlling for age and sex. Factor analysis of atypical symptoms found factor 1 including oversleeping, overeating and weight gain (leaden paralysis at trend correlation), and factor 2 including interpersonal sensitivity, mood reactivity, and leaden paralysis. Multiple logistic regression of factor 1 versus AD validators found significant associations with several validators (including bipolar family history), whereas factor 2 had no significant associations. Findings may support a new definition of AD based on the state-dependent features oversleeping and overeating (plus perhaps leaden paralysis) versus the current AD definition based on a combination of state and trait features. Pharmacological studies are required to support any new definition of AD, as the current concept of AD is based on different response to TCA antidepressants versus non-AD.

  8. Opposing RA and FGF signals control proximodistal vertebrate limb development through regulation of Meis genes.

    PubMed

    Mercader, N; Leonardo, E; Piedra, M E; Martínez-A, C; Ros, M A; Torres, M

    2000-09-01

    Vertebrate limbs develop in a temporal proximodistal sequence, with proximal regions specified and generated earlier than distal ones. Whereas considerable information is available on the mechanisms promoting limb growth, those involved in determining the proximodistal identity of limb parts remain largely unknown. We show here that retinoic acid (RA) is an upstream activator of the proximal determinant genes Meis1 and Meis2. RA promotes proximalization of limb cells and endogenous RA signaling is required to maintain the proximal Meis domain in the limb. RA synthesis and signaling range, which initially span the entire lateral plate mesoderm, become restricted to proximal limb domains by the apical ectodermal ridge (AER) activity following limb initiation. We identify fibroblast growth factor (FGF) as the main molecule responsible for this AER activity and propose a model integrating the role of FGF in limb cell proliferation, with a specific function in promoting distalization through inhibition of RA production and signaling.

  9. Atypical causes of cholestasis

    PubMed Central

    Nguyen, Ken D; Sundaram, Vinay; Ayoub, Walid S

    2014-01-01

    Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population, while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population. In infants, the causes are usually congenital or inherited. Even though jaundice is a hallmark of cholestasis, it is not always seen in adult patients with chronic liver disease. Patients can have “silent” progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus. In this review, we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis, progressive familial intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury. PMID:25071336

  10. ATYPICAL KAWASAKI DISEASE.

    PubMed

    Ristovski, Ljiljana; Milankov, Olgica; Vislavski, Melanija; Savić, Radojica; Bjelica, Milena

    2016-01-01

    Kawasaki disease is an acute vasculitis which occurs primarily in children under the age of 5. The etiology of the disease is still unknown. Diagnostic criteria for Kawasaki disease are fever and at least four of the five additional clinical signs. Incomplete Kawasaki disease should be taken into consideration in case of all children with unexplained fever for more than 5 days, associated with 2 or 3 of the main clinical findings of Kawasaki disease. The diagnosis of incomplete Kawasaki disease is based on echocardiographic findings indicating the involvement of the coronary arteries. Cardiac complications, mostly coronary artery aneurysm, can occur in 20% to 25% of untreated patients and in 4% of treated patients. CASE REPORT. In this report we present a case of atypical Kawasaki disease in a 3.5-month-old infant. As soon as the diagnosis was made, the patient received high doses of intravenous immunoglobulin, with the initial introduction of ibuprofen, then aspirin with a good clinical response. Due to the presence of aneurysm of coronary arteries, further therapy involved aspirin and clopidogrel over the following 3 months, and then only aspirin for 2 years. There was a gradual regression of the changes in the coronary blood vessels to the normalization of the echocardiographic findings after 2 years. Kawasaki disease is the second most common vasculitis of childhood, so it should be included in the differential diagnosis for any child with a prolonged unexplained fever. Atypical Kawasaki disease should be taken into consideration in cases when not all clinical criteria are present but coronary abnormalities are documented.

  11. Atypical manifestations of tinea corporis.

    PubMed

    Ziemer, Mirjana; Seyfarth, Florian; Elsner, Peter; Hipler, Uta-Christina

    2007-01-01

    Tinea corporis classically presents as an erythematous annular plaque with a scaly, centrifugally advancing border. However, sometimes vesicles and pustules are observed. Occasionally, even frank bullae appear secondary to severe inflammation. Diagnostic difficulties arise when atypical manifestations mimic other inflammatory skin diseases, including atopic or seborrheic dermatitis, subacute cutaneous lupus erythematosus, or vesicular diseases. We report five cases of atypical tinea corporis, where the initial clinical diagnosis was different from dermatophytosis. The differential diagnoses and the diagnostic difficulties related to atypical manifestations of fungal infections are discussed. Moreover, our cases emphasise the importance of conventional histological examination, which enables a fast, correct diagnosis.

  12. [Atypical hemolytic uremic syndrome].

    PubMed

    Blasco Pelicano, Miquel; Rodríguez de Córdoba, Santiago; Campistol Plana, Josep M

    2015-11-20

    The hemolytic uremic syndrome (HUS) is a clinical entity characterized by thrombocytopenia, non-immune hemolytic anemia and renal impairment. Kidney pathology shows thrombotic microangiopathy (TMA) with endothelial cell injury leading to thrombotic occlusion of arterioles and capillaries. Traditionally, HUS was classified in 2 forms: Typical HUS, most frequently occurring in children and caused by Shiga-toxin-producing bacteria, and atypical HUS (aHUS). aHUS is associated with mutations in complement genes in 50-60% of patients and has worse prognosis, with the majority of patients developing end stage renal disease. After kidney transplantation HUS may develop as a recurrence of aHUS or as de novo disease. Over the last years, many studies have demonstrated that complement dysregulation underlies the endothelial damage that triggers the development of TMA in most of these patients. Advances in our understanding of the pathogenic mechanisms of aHUS, together with the availability of novel therapeutic options, will enable better strategies for the early diagnosis and etiological treatment, which are changing the natural history of aHUS. This review summarizes the aHUS clinical entity and describes the role of complement dysregulation in the pathogenesis of aHUS. Finally, we review the differential diagnosis and the therapeutic options available to patients with aHUS. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

  13. Atypical manifestations of leptospirosis.

    PubMed

    Rajapakse, Senaka; Rodrigo, Chaturaka; Balaji, Krishan; Fernando, Sumadhya Deepika

    2015-05-01

    Leptospirosis is an illness with a wide spectrum of clinical manifestations and severe illness affects nearly all organ systems. Serious and potentially life-threatening clinical manifestations of acute leptospirosis are caused by both direct tissue invasion by spirochaetes and by the host immune responses. In its severe form, leptospirosis can cause multi-organ dysfunction and death in a matter of days. Therefore it is critical to suspect and recognize the disease early, in order to initiate timely treatment. While the classical presentation of the disease is easily recognized by experienced clinicians practising in endemic regions, rarer manifestations can be easily missed. In this systematic review, we summarize the atypical manifestations reported in literature in patients with confirmed leptospirosis. Awareness of these unusual manifestations would hopefully guide clinicians towards early diagnosis. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  14. Compilation of Spectroscopic Data of Radium (Ra I and Ra II)

    NASA Astrophysics Data System (ADS)

    Dammalapati, U.; Jungmann, K.; Willmann, L.

    2016-03-01

    Energy levels, wavelengths, lifetimes, and hyperfine structure constants for the isotopes of the first and second spectra of radium, Ra I and Ra II, have been compiled. Wavelengths and wavenumbers are tabulated for 226Ra and for other Ra isotopes. Isotope shifts and hyperfine structure constants of even and odd-A isotopes of neutral radium atom and singly ionized radium are included. Experimental lifetimes of the states for both neutral and ionic Ra are also added, where available. The information is beneficial for present and future experiments aimed at different physics motivations using neutral Ra and singly ionized Ra.

  15. IL2RA — EDRN Public Portal

    Cancer.gov

    The interleukin 2 receptor exists in three forms which differ in their ability to bind interleukin 2. The low affinity form of the receptor is a monomer of IL2RA, the alpha subunit. The alpha/beta subunit heterodimer, formed by IL2RA and IL2RB, is an intermediate affinity form. The alpha/beta/gamma heterotrimer formed by IL2RA, IL2RB, and IL2RG is the high affinity form. IL2RA is normally an integral membrane protein, although soluble IL2RA has been isolated. There are known alternately-spliced versions of IL2RA mRNAs, but their functions are unknown. Mutations in the IL2RA gene are associated with diabetes mellitus insulin-dependent type 10 (IDDM10). Complications of IDDM10 can adversely affect the eyes, kidneys, nerves, and blood vessels.

  16. Atypical hemolytic uremic syndrome

    PubMed Central

    2011-01-01

    Hemolytic uremic syndrome (HUS) is defined by the triad of mechanical hemolytic anemia, thrombocytopenia and renal impairment. Atypical HUS (aHUS) defines non Shiga-toxin-HUS and even if some authors include secondary aHUS due to Streptococcus pneumoniae or other causes, aHUS designates a primary disease due to a disorder in complement alternative pathway regulation. Atypical HUS represents 5 -10% of HUS in children, but the majority of HUS in adults. The incidence of complement-aHUS is not known precisely. However, more than 1000 aHUS patients investigated for complement abnormalities have been reported. Onset is from the neonatal period to the adult age. Most patients present with hemolytic anemia, thrombocytopenia and renal failure and 20% have extra renal manifestations. Two to 10% die and one third progress to end-stage renal failure at first episode. Half of patients have relapses. Mutations in the genes encoding complement regulatory proteins factor H, membrane cofactor protein (MCP), factor I or thrombomodulin have been demonstrated in 20-30%, 5-15%, 4-10% and 3-5% of patients respectively, and mutations in the genes of C3 convertase proteins, C3 and factor B, in 2-10% and 1-4%. In addition, 6-10% of patients have anti-factor H antibodies. Diagnosis of aHUS relies on 1) No associated disease 2) No criteria for Shigatoxin-HUS (stool culture and PCR for Shiga-toxins; serology for anti-lipopolysaccharides antibodies) 3) No criteria for thrombotic thrombocytopenic purpura (serum ADAMTS 13 activity > 10%). Investigation of the complement system is required (C3, C4, factor H and factor I plasma concentration, MCP expression on leukocytes and anti-factor H antibodies; genetic screening to identify risk factors). The disease is familial in approximately 20% of pedigrees, with an autosomal recessive or dominant mode of transmission. As penetrance of the disease is 50%, genetic counseling is difficult. Plasmatherapy has been first line treatment until presently

  17. The Rab GTPase-activating protein TBC1D4/AS160 contains an atypical phosphotyrosine-binding domain that interacts with plasma membrane phospholipids to facilitate GLUT4 trafficking in adipocytes.

    PubMed

    Tan, Shi-Xiong; Ng, Yvonne; Burchfield, James G; Ramm, Georg; Lambright, David G; Stöckli, Jacqueline; James, David E

    2012-12-01

    The Rab GTPase-activating protein TBC1D4/AS160 regulates GLUT4 trafficking in adipocytes. Nonphosphorylated AS160 binds to GLUT4 vesicles and inhibits GLUT4 translocation, and AS160 phosphorylation overcomes this inhibitory effect. In the present study we detected several new functional features of AS160. The second phosphotyrosine-binding domain in AS160 encodes a phospholipid-binding domain that facilitates plasma membrane (PM) targeting of AS160, and this function is conserved in other related RabGAP/Tre-2/Bub2/Cdc16 (TBC) proteins and an AS160 ortholog in Drosophila. This region also contains a nonoverlapping intracellular GLUT4-containing storage vesicle (GSV) cargo-binding site. The interaction of AS160 with GSVs and not with the PM confers the inhibitory effect of AS160 on insulin-dependent GLUT4 translocation. Constitutive targeting of AS160 to the PM increased the surface GLUT4 levels, and this was attributed to both enhanced AS160 phosphorylation and 14-3-3 binding and inhibition of AS160 GAP activity. We propose a model wherein AS160 acts as a regulatory switch in the docking and/or fusion of GSVs with the PM.

  18. Atypical depression: a valid subtype?

    PubMed

    Parker, Gordon B

    2007-01-01

    The concept of atypical depression has evolved over the past several decades, yet remains inadequately defined. As currently defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR), the main criterion of atypical depression is the presence of mood reactivity in combination with at least 2 of 4 secondary criteria (hypersomnia, hyperphagia and weight gain, leaden paralysis, and oversensitivity to criticism and rejection). The focus on mood reactivity as the primary distinguishing criterion remains questionable among researchers who have been unable to verify the primacy of this symptom in relation to the other diagnostic criteria for atypical depression. A model challenging the DSM-IV-TR definition of atypical depression has been developed, redefining the disorder as a dimensional nonmelancholic syndrome in which individuals with a personality subtype of "interpersonal rejection sensitivity" have a tendency toward the onset of anxiety disorders and depression, thereby exhibiting a variety of dysregulated emotional and self-consolatory responses. This reformulated definition of atypical depression (in arguing for the primacy of a personality style or rejection sensitivity as against mood reactivity) may lead to a better understanding and recognition of the disorder and its symptoms as well as other "spectrum" disorders within the scope of major depression.

  19. Atypical Cutaneous Manifestations in Syphilis.

    PubMed

    Ivars Lleó, M; Clavo Escribano, P; Menéndez Prieto, B

    2016-05-01

    Although the diversity of the clinical manifestations of syphilis is well-known, atypical presentations can also occur. Such atypical presentations are associated with a high risk of transmission as a result of diagnostic confusion and treatment delays owing to the disease's ability to mimic other common skin diseases, deviate from classic clinical presentations, and adopt unique forms. Cases of atypical syphilis have been described most frequently in patients with concomitant human immunodeficiency virus (HIV) infection. Because the incidence of syphilis has been growing over recent years -particularly in patients with HIV co-infection- dermatologists need to be familiar with the less well-known clinical presentations of this venereal disease. Copyright © 2015 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

  20. Identification of atypical flight patterns

    NASA Technical Reports Server (NTRS)

    Statler, Irving C. (Inventor); Ferryman, Thomas A. (Inventor); Amidan, Brett G. (Inventor); Whitney, Paul D. (Inventor); White, Amanda M. (Inventor); Willse, Alan R. (Inventor); Cooley, Scott K. (Inventor); Jay, Joseph Griffith (Inventor); Lawrence, Robert E. (Inventor); Mosbrucker, Chris (Inventor)

    2005-01-01

    Method and system for analyzing aircraft data, including multiple selected flight parameters for a selected phase of a selected flight, and for determining when the selected phase of the selected flight is atypical, when compared with corresponding data for the same phase for other similar flights. A flight signature is computed using continuous-valued and discrete-valued flight parameters for the selected flight parameters and is optionally compared with a statistical distribution of other observed flight signatures, yielding atypicality scores for the same phase for other similar flights. A cluster analysis is optionally applied to the flight signatures to define an optimal collection of clusters. A level of atypicality for a selected flight is estimated, based upon an index associated with the cluster analysis.

  1. Dual Regulation of RA-RhoGAP Activity by Phosphatidic Acid and Rap1 during Neurite Outgrowth*

    PubMed Central

    Kurooka, Takao; Yamamoto, Yasunori; Takai, Yoshimi; Sakisaka, Toshiaki

    2011-01-01

    During neurite outgrowth, Rho small G protein activity is spatiotemporally regulated to organize the neurite sprouting, extension, and branching. We have previously identified a potent Rho GTPase-activating protein (GAP), RA-RhoGAP, as a direct downstream target of Rap1 small G protein in the neurite outgrowth. In addition to the Ras-associating (RA) domain for Rap1 binding, RA-RhoGAP has the pleckstrin homology (PH) domain for lipid binding. Here, we showed that phosphatidic acid (PA) bound to the PH domain and enhanced GAP activity for Rho. RA-RhoGAP induced extension of neurite in a diacylglycerol kinase-mediated synthesis of the PA-dependent manner. Knockdown of RA-RhoGAP reduced the diacylglycerol kinase-induced neurite extension. In contrast to the effect of the RA domain, the PH domain was specifically involved in the neurite extension, not in the sprouting and branching. These results indicate that PA and Rap1 cooperatively regulate RA-RhoGAP activity for promoting neurite outgrowth. PMID:21169361

  2. TLRs, future potential therapeutic targets for RA.

    PubMed

    Elshabrawy, Hatem A; Essani, Abdul E; Szekanecz, Zoltán; Fox, David A; Shahrara, Shiva

    2017-02-01

    Toll like receptors (TLR)s have a central role in regulating innate immunity and in the last decade studies have begun to reveal their significance in potentiating autoimmune diseases such as rheumatoid arthritis (RA). Earlier investigations have highlighted the importance of TLR2 and TLR4 function in RA pathogenesis. In this review, we discuss the newer data that indicate roles for TLR5 and TLR7 in RA and its preclinical models. We evaluate the pathogenicity of TLRs in RA myeloid cells, synovial tissue fibroblasts, T cells, osteoclast progenitor cells and endothelial cells. These observations establish that ligation of TLRs can transform RA myeloid cells into M1 macrophages and that the inflammatory factors secreted from M1 and RA synovial tissue fibroblasts participate in TH-17 cell development. From the investigations conducted in RA preclinical models, we conclude that TLR-mediated inflammation can result in osteoclastic bone erosion by interconnecting the myeloid and TH-17 cell response to joint vascularization. In light of emerging unique aspects of TLR function, we summarize the novel approaches that are being tested to impair TLR activation in RA patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines.

    PubMed

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the "kinome". Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression.

  4. Phosphoproteome and Transcriptome of RA-Responsive and RA-Resistant Breast Cancer Cell Lines

    PubMed Central

    Carrier, Marilyn; Joint, Mathilde; Lutzing, Régis; Page, Adeline; Rochette-Egly, Cécile

    2016-01-01

    Retinoic acid (RA), the main active vitamin A metabolite, controls multiple biological processes such as cell proliferation and differentiation through genomic programs and kinase cascades activation. Due to these properties, RA has proven anti-cancer capacity. Several breast cancer cells respond to the antiproliferative effects of RA, while others are RA-resistant. However, the overall signaling and transcriptional pathways that are altered in such cells have not been elucidated. Here, in a large-scale analysis of the phosphoproteins and in a genome-wide analysis of the RA-regulated genes, we compared two human breast cancer cell lines, a RA-responsive one, the MCF7 cell line, and a RA-resistant one, the BT474 cell line, which depicts several alterations of the “kinome”. Using high-resolution nano-LC-LTQ-Orbitrap mass spectrometry associated to phosphopeptide enrichment, we found that several proteins involved in signaling and in transcription, are differentially phosphorylated before and after RA addition. The paradigm of these proteins is the RA receptor α (RARα), which was phosphorylated in MCF7 cells but not in BT474 cells after RA addition. The panel of the RA-regulated genes was also different. Overall our results indicate that RA resistance might correlate with the deregulation of the phosphoproteome with consequences on gene expression. PMID:27362937

  5. Biotinidase deficiency: an atypical presentation.

    PubMed

    Jagadeesh, Sujatha; Suresh, Beena; Seshadri, Suresh; Suzuki, Yoichi

    2013-01-01

    Biotinidase deficiency is a rare metabolic disorder which can cause dermatological manifestations and lead to severe neurological sequelae if untreated. Holocarboxylase synthetase deficiency also has similar manifestations and needs to be differentiated. We present a neonate who had atypical early onset symptoms and was diagnosed to have biotinidase deficiency. Copyright 2012, NMJI.

  6. Atypical presentations of orbital cysticercosis.

    PubMed

    Pushker, Neelam; Chaturvedi, Amrita; Balasubramanya, Ramamurthy; Bajaj, Mandeep S; Kumar, Neena; Sony, Parul

    2005-01-01

    We describe three patients with orbital cysticercosis who presented with atypical clinical or radiologic features previously unreported. All three patients had a cyst with a scolex on imaging studies. After 6 weeks of treatment, all three had almost complete resolution of their features.

  7. Occurrence of 222Rn, 226Ra, 228Ra and U in groundwater in Fujian Province, China.

    PubMed

    Zhuo, W; Iida, T; Yang, X

    2001-01-01

    222Rn, 226Ra, 228Ra and U were determined in a total of 552 groundwater samples collected throughout Fujian Province of China. The geometric mean concentrations of 222Rn, 226Ra, 228Ra and total U in the groundwater were 147.8 kBq m-3, 12.7 Bq m-3, 30.2 Bq m-3 and 0.54 microgram kg-1, respectively. High groundwater 222Rn was explained by the predominantly granitic rock aquifers in Fujian. A lifetime risk of 1.7 x 10(-3) was estimated for the ingestion of groundwater 222Rn. High ratios of 228Ra to 226Ra contents (geometric mean of 2.4) and their disproportion suggest that 228Ra should also be measured in the assessment of population doses from drinking water in the regions of high rock or soil 232Th. No significant correlation between the 222Rn concentrations in groundwater and air was found.

  8. Cardiovascular risk factor management in patients with RA compared to matched non-RA patients.

    PubMed

    Alemao, Evo; Cawston, Helene; Bourhis, Francois; Al, Maiwenn; Rutten-van Mölken, Maureen P M H; Liao, Katherine P; Solomon, Daniel H

    2016-05-01

    RA is associated with a 50-60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology.

  9. Mortality in Rheumatoid Arthritis (RA): factors associated with recording RA on death certificates.

    PubMed

    Molina, Emily; del Rincon, Inmaculada; Restrepo, Jose Felix; Battafarano, Daniel F; Escalante, Agustin

    2015-10-05

    Death certificates can be used to assess disease prevalence and incidence; however, rheumatoid arthritis (RA) often remains unreported in death certificates. We sought to determine to what extent RA is underreported and what demographic and clinical characteristics could predict mention of RA in the death certificate. We recruited 1328 patients with RA from private, public and military rheumatology practices and followed them prospectively for yearly evaluations. A rheumatologist assessed clinical characteristics of RA and comorbidities at each evaluation. Deaths were identified through family members, other physicians, obituaries and public death databases. All were confirmed with state-issued death certificates. Patients with and without RA in death certificate were compared using bivariate and multivariate analyses. By December 2013, 326 deaths had occurred. We received and reviewed death certificates for all confirmed deaths, of which 58 (17.7 %) mentioned RA on the death certificate. Bivariate analysis revealed that younger age, a greater number of deformities, higher Sharp score and lower socioeconomic status were each associated with recording RA. Multivariable analyses revealed that comorbidity [OR (95 % CI) = 0.84 (0.73, 0.97); P = 0.022] was inversely associated with listing RA on the death certificate, while the number of deformities [OR (95 % CI) = 1.04 (1.00, 1.07); P = 0.033] and a certified physician's signature on the death certificate [OR (95 % CI) = 4.79 (1.35, 16.9); P = 0.015] increased likelihood of reporting RA. In this cohort, RA was not listed in over 80 % of death certificates. Younger patients with fewer comorbidities and more joint deformities were more likely to have RA reported. RA is often not included in death certificates. The findings of this study suggest that older patients may have a greater number of comorbidities, thus decreasing the likelihood that RA be included when completing the death certificate.

  10. Cardiovascular risk factor management in patients with RA compared to matched non-RA patients

    PubMed Central

    Cawston, Helene; Bourhis, Francois; Al, Maiwenn; Rutten-van Mölken, Maureen P. M. H.; Liao, Katherine P.; Solomon, Daniel H.

    2016-01-01

    Objective. RA is associated with a 50–60% increase in risk of cardiovascular (CV) death. This study aimed to compare management of CV risk factors in RA and matched non-RA patients. Methods. A retrospective cohort study was conducted using UK clinical practice data. Patients presenting with an incident RA diagnosis were matched 1:4 to non-RA patients based on a propensity score for RA, entry year, CV risk category and treatment received at index date (date of RA diagnosis). Patients tested and treated for CV risk factors as well as those attaining CV risk factor management goals were evaluated in both groups. Results. Between 1987 and 2010, 24 859 RA patients were identified and matched to 87 304 non-RA patients. At index date, groups had similar baseline characteristics. Annual blood pressure, lipids and diabetes-related testing were similar in both groups, although CRP and ESR were higher in RA patients at diagnosis and decreased over time. RA patients prescribed antihypertensives increased from 38.2% at diagnosis to 45.7% at 5 years, from 14.0 to 20.6% for lipid-lowering treatments and from 5.1 to 6.4% for antidiabetics. Similar treatment percentages were observed in non-RA patients, although slightly lower for antihypertensives. Modest (2%) but significantly lower attainment of lipid and diabetes goals at 1 year was observed in RA patients. Conclusion. There were no differences between groups in the frequency of testing and treatment of CV risk factors. Higher CV risk in RA patients seems unlikely to be driven by differences in traditional CV risk factor management. PMID:26705329

  11. Nuclear Structure of {sup 231}Ra

    SciTech Connect

    Boutami, R.; Fraile, L.M.; Borge, M.J.G.; Aas, A.J.; Fogelberg, B.; Garcia-Raffi, L.M.; Grant, I.S.; Gulda, K.; Hagebo, E.; Kurcewicz, W.; Lopez-Jimenez, M.J.; Lovhoiden, G.; Mach, H.; Martinez, T.; Rubio, B.; Tain, J.L.; Teijeiro, A.G.; Tengblad, O.; Thorsteinsen, T.F.

    1999-12-31

    The study of the upper border of the octupole deformation region near A=225, where the octupole deformation vanishes in the presence of a well developed quadrupole field, is of great relevance in order to understand the interplay of octupole and quadrupole collectivities. Within the IS322 collaboration at CERN we carry out a systematic investigation of the heavy Fr - Th nuclei that presently includes {sup 227}Fr, {sup 227,228,229}Ra, {sup 229}Ac and {sup 229,231}Th. The heaviest Ra isotope we have studied so far and in which the fast timing {beta}{gamma}{gamma}(t) method has been applied is {sup 231}Ra.

  12. Nuclear structure of {sup 231}Ra

    SciTech Connect

    Boutami, R.; Fraile, L. M.; Borge, M. J. G.; Lopez-Jimenez, M. J.; Teijeiro, A. G.; Aas, A. J.; Hageboe, E.; Fogelberg, B.; Mach, H.; Garcia-Raffi, L. M.; Martinez, T.; Rubio, B.; Tain, J. L.; Grant, I. S.; Gulda, K.; Kurcewicz, W.; Loevhoeiden, G.; Tengblad, O.; Thorsteinsen, T. F.

    1999-11-16

    The study of the upper border of the octupole deformation region near A=225, where the octupole deformation vanishes in the presence of a well developed quadrupole field, is of great relevance in order to understand the interplay of octupole and quadrupole collectivities. Within the IS322 collaboration at CERN we carry out a systematic investigation of the heavy Fr-Th nuclei that presently includes {sup 227}Fr, {sup 227,228,229}Ra, {sup 229}Ac and {sup 229,231}Th. The heaviest Ra isotope we have studied so far and in which the fast timing {beta}{gamma}{gamma}(t) method has been applied is {sup 231}Ra.

  13. A case of atypical progressive supranuclear palsy

    PubMed Central

    Spaccavento, Simona; Del Prete, Marina; Craca, Angela; Loverre, Anna

    2014-01-01

    Background Progressive supranuclear palsy (PSP) is a neurodegenerative extrapyramidal syndrome. Studies have demonstrated that PSP can present clinically as an atypical dementing syndrome dominated by a progressive apraxia of speech (AOS) and aphasia. Aim We aimed to investigate the clinical presentation of PSP, using a comprehensive multidimensional evaluation, and the disease response to various pharmacological treatments. Methods A 72-year-old right-handed male, with 17 years education, who first presented with aphasia, AOS, depression, apathy, and postural instability at 69 years; a complete neuropsychological evaluation, tapping the different cognitive domains, was performed. Results Testing revealed a moderate global cognitive deficit (Mini-Mental State Examination test score =20), low memory test scores (story recall, Rey’s 15-word Immediate and Delayed Recall), and poor phonemic and semantic fluency. The patient’s language was characterized by AOS, with slow speech rate, prolonged intervals between syllables and words, decreased articulatory accuracy, sound distortions, and anomia. Behavioral changes, such as depression, anxiety, apathy, and irritability, were reported. The neurological examination revealed supranuclear vertical gaze palsy, poor face miming, and a mild balance deficit. Magnetic resonance imaging showed only widespread cortical atrophy. Single photon emission computed tomography demonstrated left > right frontotemporal cortical abnormalities. After 6 months, a further neuropsychological assessment showed a progression in cognitive deficits, with additional attention deficits. The patient reported frequent falls, but the neurological deficits remained unchanged. Neuroimaging tests showed the same brain involvement. Conclusion Our case highlights the heterogeneity of the clinical features in this syndrome, demonstrating that atypical PSP can present as AOS and aphasia, without the classical features or involvement of the subcortical gray

  14. Sleep Disorders in Atypical Parkinsonism

    PubMed Central

    Abbott, Sabra M.; Videnovic, Aleksandar

    2014-01-01

    Sleep disorders are commonly seen in atypical parkinsonism, with particular disorders occurring more frequently in specific parkinsonian disorders. Multiple systems atrophy (MSA) is a synucleinopathy often associated with nocturnal stridor which is a serious, but treatable condition highly specific to MSA. In addition, this disorder is strongly associated with rapid eye movement (REM) sleep behavior disorder (RBD), which is also seen in dementia with Lewy bodies (DLB). RBD is far less prevalent in progressive supranuclear palsy (PSP), which is a tauopathy. Insomnia and impaired sleep architecture are the most common sleep abnormalities seen in PSP. Corticobasilar degeneration (CBD) is also a tauopathy, but has far fewer sleep complaints associated with it than PSP. In this manuscript we review the spectrum of sleep dysfunction across the atypical parkinsonian disorders, emphasize the importance of evaluating for sleep disorders in patients with parkinsonian symptoms, and point to sleep characteristics that can provide diagnostic clues to the underlying parkinsonian disorder. PMID:24955381

  15. Atypical Steatocystoma Multiplex with Calcification

    PubMed Central

    Rahman, Muhammad Hasibur; Islam, Muhammad Saiful; Ansari, Nazma Parvin

    2011-01-01

    A 60-year-old male reported to us with an atypical case of giant steatocystoma multiplex in the scrotum with calcification. There was no family history of similar lesions. Yellowish, creamy material was expressed from a nodule during punch biopsy. The diagnosis was based on clinical as well as histological findings. Successful surgical excision was done to cure the case without any complications. PMID:22363850

  16. Atypical centrioles during sexual reproduction.

    PubMed

    Avidor-Reiss, Tomer; Khire, Atul; Fishman, Emily L; Jo, Kyoung H

    2015-01-01

    Centrioles are conserved, self-replicating, microtubule-based, 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, called the proximal centriole-like structure (PCL). We also discuss another type of atypical centriole, the "zombie" centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology.

  17. Atypical centrioles during sexual reproduction

    PubMed Central

    Avidor-Reiss, Tomer; Khire, Atul; Fishman, Emily L.; Jo, Kyoung H.

    2015-01-01

    Centrioles are conserved, self-replicating, microtubule-based, 9-fold symmetric subcellular organelles that are essential for proper cell division and function. Most cells have two centrioles and maintaining this number of centrioles is important for animal development and physiology. However, how animals gain their first two centrioles during reproduction is only partially understood. It is well established that in most animals, the centrioles are contributed to the zygote by the sperm. However, in humans and many animals, the sperm centrioles are modified in their structure and protein composition, or they appear to be missing altogether. In these animals, the origin of the first centrioles is not clear. Here, we review various hypotheses on how centrioles are gained during reproduction and describe specialized functions of the zygotic centrioles. In particular, we discuss a new and atypical centriole found in sperm and zygote, called the proximal centriole-like structure (PCL). We also discuss another type of atypical centriole, the “zombie” centriole, which is degenerated but functional. Together, the presence of centrioles, PCL, and zombie centrioles suggests a universal mechanism of centriole inheritance among animals and new causes of infertility. Since the atypical centrioles of sperm and zygote share similar functions with typical centrioles in somatic cells, they can provide unmatched insight into centriole biology. PMID:25883936

  18. [Atypical wounds: definition and classification].

    PubMed

    Situm, Mirna; Kolić, Maja

    2012-10-01

    Wound represents disruption of the anatomic and physiologic continuity of the skin. Regarding the healing process, wounds can be classified as acute or chronic wounds. A wound is considered chronic if healing does not occur within the expected period according to its etiology and localization. Chronic wounds can be classified as typical and atypical. Typical wounds include ischemic, neurotrophic and hypostatic ulcers and two separate entities: diabetic foot and decubitus ulcers. Eighty percent of chronic wounds localized on the lower leg are the result of chronic venous insufficiency, in 5-10 percent the cause is of arterial etiology, whereas the remainder is mostly neuropathic ulcer. Ninety-five percent of chronic wounds manifest as one of the above mentioned entities. Other forms of chronic wounds represent atypical chronic wounds, which can be caused by autoimmune disorders, infectious diseases, vascular diseases and vasculopathies, metabolic and genetic diseases, neoplasm, external factors, psychiatric disorders, drug related reactions, etc. Numerous systemic diseases can present with atypical wounds. The primary cause of the wound can be either systemic disease itself (Crohn's disease) or aberrant immune response due to systemic disease (pyoderma gangrenosum, paraneoplastic syndrome).

  19. Understanding Rheumatoid Arthritis (RA): Treatment and Causes

    MedlinePlus

    ... this page please turn JavaScript on. Feature: Understanding Rheumatoid Arthritis (RA) Treatment and Causes Past Issues / Summer 2014 Table of Contents How Is Rheumatoid Arthritis Treated? Doctors have many ways to treat this ...

  20. RA Construction KC, LLC Information Sheet

    EPA Pesticide Factsheets

    RA Construction KC, LLC (the Company) is located in Gladstone, Missouri. The settlement involves renovation activities conducted at a property constructed prior to 1978, located in Kansas City, Missouri.

  1. SoRa first flight. Summer 2009

    NASA Astrophysics Data System (ADS)

    Pirrotta, S.; Flamini, E.

    The SoRa (Sounding Radar) experiment was successfully launched from Longyearbyen (Svalbard, Norway) during the summer 2009 campaign managed by the Italian/Norwegian "Nobile Amundsen / Stratospheric Balloon Centre" (NA/SBC). SoRa is part of the Italian Space Agency (ASI) programs for Long Duration Balloon Flights. Carried by the biggest balloon (800.000 m3) ever launched in polar regions, SoRa main experiment and its three piggyback payloads (DUSTER, ISA and SIDERALE) performed a nominal flight of almost 4 days over the North Sea and Greenland, until the separation, landing and recovery in Baffin Island (Canada). Despite the final destructive event that compromise the scientific main goal of SoRa, the 2009 ASI balloon campaign can be considered an important milestone, because of the obtained scientific and technical results but also for the lesson learned by the science, engineering and managerial teams looking at the future ASI scientific balloon-born activities.

  2. Preparation of (228)Ra standard solution.

    PubMed

    Havelka, Miroslav

    2016-03-01

    For the preparation of a standard solution of (228)Ra, (228)Ra was isolated from (232)Th salt. Two simple methods were developed for Th-Ra separation. Both are based on a very good solubility of thorium nitrate in organic solvents. The first one used Ra co-precipitation with Pb in the form of Pb(NO3)2 from acetic acid solution. The second method was based on solvent extraction, remaining Th in the organic phase, while Ra was concentrated in the aqueous phase. The activity of (228)Ra (up to 20kBq) in the standard solution was related to the (232)Th standard by means of gamma ray spectrometry measurement. The obtained uncertainty was less than 0.7% (k=1). The standard solution was free of (232)Th and contained the carrier in the usual concentration (1gL(-1) BaCl2, 10gL(-1) HCl). Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Distribution and flux of /sup 226/Ra and /sup 228/Ra in the Amazon River estuary

    SciTech Connect

    Key, R.M.; Sarmiento, J.L.; Stallard, R.F.; Moore, W.S.

    1985-07-20

    Measurements of /sup 226/Ra and /sup 228/Ra in the Amazon River estuary show that desorption from riverborne suspended particulate matter in the estuary increases the riverine flux of both isotopes to the ocean by a factor of approximately 5 over the flux attributable to radium dissolved in the river water alone. The total Amazon flux supplies approximately 0.20% of the /sup 226/Ra and approximately 2.6% of the /sup 228/Ra standing crops in the near-surface Atlantic (0-200 m). Diffusive flux from estuarine and shelf sediments and desorption from resuspended sediments in the region of the estuary approximately double the estuarine /sup 226/Ra concentration and quadruple the estuarine /sup 228/Ra concentration above that caused by the dissolved and desorbed river components alone.

  4. Removal of 226Ra and 228Ra from TENORM sludge waste using surfactants solutions.

    PubMed

    Attallah, M F; Hamed, Mostafa M; El Afifi, E M; Aly, H F

    2015-01-01

    The feasibility of using surfactants as extracting agent for the removal of radium species from TENORM sludge produced from petroleum industry is evaluated. In this investigation cationic and nonionic surfactants were used as extracting agents for the removal of radium radionuclides from the sludge waste. Two surfactants namely cetyltrimethylammonium bromide (CTAB) and Triton X-100 (TX100) were investigated as the extracting agents. Different parameters affecting the removal of both (226)Ra and (228)Ra by the two surfactants as well as their admixture were studied by the batch technique. These parameters include effect of shaking time, surfactants concentration and temperature as well as the effect of surfactants admixture. It was found that, higher solution temperature improves the removal efficiency of radium species. Combined extraction of nonionic and cationic surfactants produces synergistic effect in removal both (226)Ra and (228)Ra, where the removals reached 84% and 80% for (226)Ra and (228)Ra, respectively, were obtained using surfactants admixture.

  5. Estuarine geochemistry of /sup 224/Ra, /sup 226/Ra, and /sup 222/Rn

    SciTech Connect

    Elsinger, R.J.

    1982-01-01

    Desorption from river borne sediments is the most likely source of the excess /sup 226/Ra. Laboratory mixing experiments on Pee Dee River sediments show an increase in /sup 226/Ra desorption with increasing salinities with maximum desorption occurring at or above 20/sup 0//oo salinity. Desorption and diffusion are the sources for /sup 226/Ra in the estuarine systems. In Winyah Bay the /sup 228/Ra//sup 226/Ra activity ratio does not change significantly with salinity, averaging around 1.4, indicating desorption as the major source of /sup 228/Ra. In the Yangtze River the /sup 228/Ra//sup 226/Ra activity ratio is constant (approx.1.90) until increasing linearly above 16/sup 0//oo. A diffusive flux from regeneration by /sup 232/Th decay in shelf sediments is the source of the increase. In Delaware Bay /sup 228/Ra increases faster than /sup 226/Ra in the less than or equal to22/sup 0//oo water, indicating a source in addition to desorption. The increase can be balanced by a 0.33 dpm/cm/sup 2/-year flux over the upper part of the Bay where fine grained sediments predominate. /sup 224/Ra behavior is controlled by its 3.64 day half-life. In Winyah Bay a flux of around 0.4 dpm/cm/sup 2/-day is necessary to support the standing crop of non-desorbed /sup 224/Ra in the water column. In Delaware Bay the nearly constant /sup 224/Ra in concentration over the 2.5/sup 0//oo to 12/sup 0//oo salinity range are maintained by regeneration from /sup 228/Th in the turbidity maximum zones and diffusion from bottom sediments. Water leaving on ebb tide from a salt marsh on Delaware Bay had increases in all three radium isotopes (/sup 224/Ra > /sup 228/Ra > /sup 226/Ra) compared to water coming in on the flood tide. Excess /sup 222/Rn concentrations in a fresh water section of the Pee Dee River show a decreasing downstream gradient. Using these gradients to determine evasion rates, stagnant film thicknesses range from 21..mu.. to 62..mu...

  6. Information Display System for Atypical Flight Phase

    NASA Technical Reports Server (NTRS)

    Statler, Irving C. (Inventor); Ferryman, Thomas A. (Inventor); Amidan, Brett G. (Inventor); Whitney, Paul D. (Inventor); White, Amanda M. (Inventor); Willse, Alan R. (Inventor); Cooley, Scott K. (Inventor); Jay, Joseph Griffith (Inventor); Lawrence, Robert E. (Inventor); Mosbrucker, Chris J. (Inventor); Rosenthal, Loren J. (Inventor); Lynch, Robert E. (Inventor); Chidester, Thomas R. (Inventor); Prothero, Gary L. (Inventor); Andrei, Adi (Inventor); Romanowski, Timothy P. (Inventor); Robin, Daniel E. (Inventor); Prothero, Jason W. (Inventor)

    2007-01-01

    Method and system for displaying information on one or more aircraft flights, where at least one flight is determined to have at least one atypical flight phase according to specified criteria. A flight parameter trace for an atypical phase is displayed and compared graphically with a group of traces, for the corresponding flight phase and corresponding flight parameter, for flights that do not manifest atypicality in that phase.

  7. Ra-226 and Pb-210/Ra-226 Activity Ratio in the Northern South China Sea

    NASA Astrophysics Data System (ADS)

    Chi-Ju, L.; Yu-Chia, C.; Tsung-En, W.

    2004-05-01

    The surface water distributions and vertical profiles of Ra-226 in the northern South China Sea (SCS) have been measured. Surface water Ra-226 varies between 10 and 16 dpm/100 kg with higher values at stations adjacent to the landmass. Each Ra-226 profile shows an increase from the surface toward the bottom. Above 1000m depth Ra-226 is systematically about 5 dpm/100kg higher in the northern South China Sea than in the western North Pacific. This difference may be attributed to a strong Ra-226 source from the shelf and slope area of the SCS. Below this depth Ra-226 displays large variation within some of the profiles with lower limits being comparable to the activities of the western North Pacific but higher limits being systematically about 5 dpm/100kg higher. These high Ra-226 activities may reflect effects of the longer isolation time for the deep water in the SCS basin and strong Ra input from the underlying sediments. The Pb-210/Ra-226 activity ratio ranges between 1.4 and 2.7 in the surface water with higher activity ratio at the station closer to the Luzon Strait. The Pb-210 in excess over Ra-226 in the surface water due to atmospheric input may penetrate to a depth of about 200 to 500m. Below this depth, Pb-210/Ra-226 activity ratio ranges between 0.5 and 0.7 because Pb-210 is scavenged by settling particulates. Box model calculations within a mixed layer of 50m in the area yield a mean residence time of about 1 yr for Pb-210 if an atmospheric Pb-210 flux of 1 dpm/cm2/y is adopted. The activity ratio of about 0.5 to 0.7 in the deep water corresponds to a Pb-210 mean residence time of about 30 to 70 yrs with respect to particulate scavenging.

  8. Myometrial dysplasia (atypical myometrial hyperplasia).

    PubMed

    Cramer, Stewart F; Newcomb, Patricia M; Bonfiglio, Thomas A

    2007-04-01

    Although precursor lesions are well known for cervical and endometrial neoplasms, precursor lesions are not currently recognized for the most common tumor of the uterus-leiomyomas. Myometrial hyperplasia has been recently described and evaluated by morphometry, but its relationship to uterine leiomyomas has not been systematically explored. Myometrial dysplasia (atypical myometrial hyperplasia) has not been previously recognized. We herein report a case of myometrial dysplasia with immunostains for proliferation marker MIB-1 (Ki-67) and for p53. The paradoxical rarity of myometrial dysplasia is considered in comparison to the striking frequency of uterine leiomyomas.

  9. Atypical presentation of infective endocarditis.

    PubMed

    Arunachalam, Karuppiah

    2016-07-01

    The HACEK group of organisms are one of the infrequent causes of infective endocarditis. Infective endocarditis should be recognized and treated promptly to prevent excessive morbidity and mortality associated with the disease. Sometimes the diagnosis is delayed due to vague and subtle presentation. Through this case report, risk factors of Cardiobacterium hominis endocarditis and its atypical presentation is illustrated to increase the recognition of infective endocarditis as one of the differential diagnosis. [Full article available at http://rimed.org/rimedicaljournal-2016-07.asp, free with no login].

  10. Simultaneous measurement of (226)Ra and (228)Ra in natural water by liquid scintillation counting.

    PubMed

    Lasheen, Yasser F; Seliman, Ayman F; Abdel-Rassoul, A A

    2007-01-01

    Several types of bottled drinking water originating from three different areas in Egypt are studied through measurement of radium activity, assessment of related annual dose for adults and finally to define the role of water quality on radium levels. The mean levels of (226)Ra activity range from 0.44 to 0.92 Bq/L and the mean levels of (228)Ra from 0.30 to 0.78 Bq/L, with related (226)Ra/(228)Ra ratios ranging from 2.61 to 0.56. Water types originating from the Eastern Nile Delta area are characterized by low (226)Ra levels and relatively high (228)Ra activity, presumably due to the muddy agricultural nature of this area, which is subject to water from several surface resources for irrigation. In general, the mean activity levels for both (226)Ra and (228)Ra are within those in drinking water in several other countries and the annual ingested dose is comparable with the typical range reported by UNSCEAR. Also, the effect of TDS, pH, calcium, bicarbonate, sulphate and chloride ion concentrations on radium levels is studied and discussed.

  11. Techniques for precise mapping of 226Ra and 228Ra in the ocean

    NASA Astrophysics Data System (ADS)

    Moore, Willard S.; Key, Robert M.; Sarmiento, Jorge L.

    1985-01-01

    Improvements in the analyses of 226Ra and 228Ra in seawater made possible by better extraction and processing techniques reduce significantly the errors associated with these measurements. These improvements and the extensive sampling for Ra isotopes conducted on the TTO North Atlantic Study should enable us to use the distribution of 228Ra to study mixing processes on a 3-15 year time scale in both the upper and deep North Atlantic. The 228Ra profiles already analyzed show a closer resemblance to GEOSECS tritium data than to TTO tritium data in the upper ocean. This is because the transient tracer tritium was responding on a 10-year time scale during GEOSECS and a 20-year time scale during TTO. The steady state tracer 228Ra should always respond on a time scale of 8 years. Thus the 228Ra data obtained on TTO should provide a means to extend the features of the GEOSECS tritium field to the regions of the TTO study. The 226Ra data are of high enough quality to identify features associated with different water masses. Changes in the positions of the deep-water masses since the GEOSECS cruise are revealed by the 226Radata.

  12. The Sophomore RA Experience: An Examination of Job Satisfaction, Turnover Intentions, and RA Self-Efficacy

    ERIC Educational Resources Information Center

    Brandt Brecheisen, Shannon M.

    2014-01-01

    The purpose of this national, quantitative study was to (1) provide psychometrics for the ACUHO-I/EBI RA Survey, a joint project between between Educational Benchmarking, Inc (EBI) and The Association of College and University Housing Officers--International (ACUHO-I), and (2) explore the sophomore resident assistant (RA) experience. This study…

  13. [Atypical Cogan's syndrome. Based on a case].

    PubMed

    Nandu, A; Salu, P; Caspers, L; Gordts, F; Sennesael, J

    2004-01-01

    Cogan's syndrome is a systemic inflammatory disease that associates typical (interstitial keratitis) and atypical (such as anterior uveitis) ocular manifestations to vestibulo-auditory dysfunction. It has also a systemic vascular association of vasculitis type. We report a case of a 64 years old woman who presented an atypical form with anterior uveitis.

  14. An alternative method for Ra determinations in water.

    PubMed

    Loyd, D H; Drake, E N

    1989-07-01

    Concentrations of 226Ra and 224Ra in 13 wells distributed throughout McCulloch and Mason counties in the Hickory Aquifer of the Llano Uplift Region of West-Central Texas are reported. Measurable alpha-particle activity is present in all wells, with seven wells having 226Ra radioactivity concentrations greater than 185 Bq m-3 (5 pCi L-1). An alternative methodology for measuring 226Ra, 224Ra and 228Ra is described. The EPA-approved methodology for estimating total Ra is shown to be invalid for aquifers containing significant levels of 224Ra. Alpha-particle activity measurements made in the interval of 12 to 300 h after Ra isolation lead to self-consistent solutions for radioactivity concentrations of 226Ra and 224Ra, with negligible contributions from 228Ra. Radioactivity concentrations of 228Ra can be calculated from grow-in terms for this isotope used with alpha-particle activity measurements at post-isolation times significantly longer than 800 h. Comparison of the 226Ra radioactivity concentration with that reported previously by the Texas Department of Health for a single well indicates acceptable agreement. However, the radioactivity concentration attributable to 228Ra for the same well was found to be in significant disagreement with the Texas Department of Health value.

  15. An alternative method for Ra determinations in water

    SciTech Connect

    Loyd, D.H.; Drake, E.N. 2d.

    1989-07-01

    Concentrations of /sup 226/Ra and /sup 224/Ra in 13 wells distributed throughout McCulloch and Mason counties in the Hickory Aquifer of the Llano Uplift Region of West-Central Texas are reported. Measurable alpha-particle activity is present in all wells, with seven wells having /sup 226/Ra radioactivity concentrations greater than 185 Bq m-3 (5 pCi L-1). An alternative methodology for measuring /sup 226/Ra, /sup 224/Ra and /sup 228/Ra is described. The EPA-approved methodology for estimating total Ra is shown to be invalid for aquifers containing significant levels of /sup 224/Ra. Alpha-particle activity measurements made in the interval of 12 to 300 h after Ra isolation lead to self-consistent solutions for radioactivity concentrations of /sup 226/Ra and /sup 224/Ra, with negligible contributions from /sup 228/Ra. Radioactivity concentrations of /sup 228/Ra can be calculated from grow-in terms for this isotope used with alpha-particle activity measurements at post-isolation times significantly longer than 800 h. Comparison of the /sup 226/Ra radioactivity concentration with that reported previously by the Texas Department of Health for a single well indicates acceptable agreement. However, the radioactivity concentration attributable to /sup 228/Ra for the same well was found to be in significant disagreement with the Texas Department of Health value.

  16. Discovery of radioactive decay of /sup 222/Ra and /sup 224/Ra by /sup 14/C emission

    SciTech Connect

    Price, P.B.; Stevenson, J.D.; Barwick, S.W.; Ravn, H.L.

    1985-01-28

    Using the ISOLDE on-line isotope separator at CERN to produce sources of /sup 221/Fr, /sup 221/Ra, /sup 222/Ra, /sup 223/Ra, and /sup 224/Ra, and using polycarbonate track-recording films sensitive to energetic carbon nuclei but not to alpha particles, we have discovered two new cases of the rare /sup 14/C decay mode: in /sup 222/Ra and /sup 224/Ra. Our results for branching ratios, B, relative to alpha decay are for /sup 221/Fr and /sup 221/Ra, B<4.4 x 10/sup -12/; for /sup 222/Ra, B = (3.7 +- 0.6) x 10/sup -10/; for /sup 223/Ra, B = (6.1 +- 1.0) x 10/sup -10/; for /sup 224/Ra, B = (4.3 +- 1.2) x 10/sup -11/. .AE

  17. Rapid Method for Ra-226 and Ra-228 in Water Samples

    SciTech Connect

    Maxwell, Sherrod, L. III

    2006-02-10

    The measurement of radium isotopes in natural waters is important for oceanographic studies and for public health reasons. Ra-226 (1620 year half-life) is one of the most toxic of the long-lived alpha emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The analysis of radium-226 and radium-228 in natural waters can be tedious and time-consuming. Different sample preparation methods are often required to prepare Ra-226 and Ra-228 for separate analyses. A rapid method has been developed at the Savannah River Environmental Laboratory that effectively separates both Ra-226 and Ra-228 (via Ac-228) for assay. This method uses MnO{sub 2} Resin from Eichrom Technologies (Darien, IL, USA) to preconcentrate Ra-226 and Ra-228 rapidly from water samples, along with Ba-133 tracer. DGA Resin{reg_sign} (Eichrom) and Ln-Resin{reg_sign} (Eichrom) are employed in tandem to prepare Ra-226 for assay by alpha spectrometry and to determine Ra-228 via the measurement of Ac-228 by gas proportional counting. After preconcentration, the manganese dioxide is dissolved from the resin and passed through stacked Ln-Resin-DGA Resin cartridges that remove uranium and thorium interferences and retain Ac-228 on DGA Resin. The eluate that passed through this column is evaporated, redissolved in a lower acidity and passed through Ln-Resin again to further remove interferences before performing a barium sulfate microprecipitation. The Ac-228 is stripped from the resin, collected using cerium fluoride microprecipitation and counted by gas proportional counting. By using vacuum box cartridge technology with rapid flow rates, sample preparation time is minimized.

  18. Atypical immunoglobulin light chain amyloidosis

    PubMed Central

    Wu, Xia; Feng, Jun; Cao, Xinxin; Zhang, Lu; Zhou, Daobin; Li, Jian

    2016-01-01

    Abstract Background: Primary immunoglobulin light chain amyloidosis (AL amyloidosis) is a plasma cell disorder which mainly affects heart, kidneys, liver, and peripheral nervous system. Cases of atypical AL amyloidosis presented as spontaneous vertebral compression fractures have been rarely reported, and data about the management and clinical outcomes of the patients are scarce. Methods: Herein, we present 3 new cases of AL amyloidosis with spontaneous vertebral compression fracture and review 13 cases retrieved from the literature. Results: Moreover, we observed overrepresentations of liver involvement and bone marrow involvement in AL amyloidosis with spontaneous vertebral compression fracture. Conclusion: We believe that better awareness of the rare clinical presentation as spontaneous vertebral compression fracture of AL amyloidosis can facilitate earlier diagnosis and earlier treatment. PMID:27603350

  19. Typical and atypical AIS. Pathogenesis.

    PubMed

    Dudin, M; Pinchuk, D

    2012-01-01

    AIS hypothesis has the right to recognition, if it explains the transition of "healthy" vertebra column into status of "scoliotic" one. AIS is the most investigated disease in the history of orthopedics, but up the present time there is no clear explanation of some its phenomena: vertebra column mono-form deformation along with its poly etiology character, interrelation of its origin and development and child's growth process etc. The key for authors' view at AIS was scoliosis with non-standard (concave side) rotation. On the bases of its' multifunctional instrumental investigation results (Rtg, EMG, EEG, optical topography, hormonal and neuropeptides trials, thermo-vision methods and other) in comparison with typical AIS was worked out the new hypothesis, part of it is suggested for discussion. In the work under observation is the sequence of appearance of typical and atypical scoliosis symptomatology beginning from the preclinical stage.

  20. Atypical parasitic ischiopagus conjoined twins.

    PubMed

    Corona-Rivera, J Román; Corona-Rivera, Enrique; Franco-Topete, Ramón; Acosta-León, Jorge; Aguila-Dueñas, Virginia; Corona-Rivera, Alfredo

    2003-02-01

    Occurrence of asymmetrical or parasitic conjoined twins (CT) is rare, and currently they are classified analogically to the common unions of symmetrical CT. The authors report on an infant with a parasitic third limb attached to the left lateral aspect of the autosite trunk, in whom male gonadal tissue was found histologically. Parasite parts included complete left lower limb, hemipelvis, lumbosacral vertebral column, spinal cord, and one kidney with ureter and adrenal gland. Autosite anomalies comprised a small left diaphragmatic defect, omphalocele, exstrophy of cloaca, and lumbar meningomyelocele. The authors considered this case to be a rare atypical parasitic ischiopagus CT. The differential diagnosis of the type of twining and other entities with caudal duplications is analyzed briefly.

  1. Does a family history of RA influence the clinical presentation and treatment response in RA?

    PubMed

    Frisell, Thomas; Saevarsdottir, Saedis; Askling, Johan

    2016-06-01

    To assess whether family history of rheumatoid arthritis (RA), among the strongest risk factors for developing RA, also carries information on the clinical presentation and treatment response. The prospective Swedish Rheumatology register was linked to family history of RA, defined as diagnosed RA in any first-degree relative, ascertained through the Swedish Multi-Generation and Patient registers. Clinical presentation was examined among patients with early RA 2000-2011 (symptom onset <12 months before inclusion, N=6869), and response to methotrexate (MTX) monotherapy in the subset starting this treatment (N=4630). Response to tumour necrosis factor inhibitors (TNFi) was examined among all patients with RA starting a TNFi as the first biological disease-modifying antirheumatic drug 2000-2011 (N=9249). Association of family history with clinical characteristics, drug survival, European League Against Rheumatism (EULAR) response and change in disease activity at 3 and 6 months was estimated using linear and generalised logistic regression models. Correlation in relatives' response measures was also assessed. Patients with early RA with family history of RA were more often rheumatoid factor positive, but with no other clinically meaningful differences in their clinical presentation. Family history of RA did not predict response to MTX or TNFi, with the possible exception of no versus good EULAR response to TNFi at 6 months (OR=1.4, 95% CI 1.1 to 1.7). Having a relative who discontinued TNFi within a year increased the odds of doing the same (OR=3.7, 95% CI 1.8 to 7.5), although we found no significant familial correlations in change in disease activity measures. Family history of RA did not modify the clinical presentation of RA or predict response to standard treatment with MTX or TNFi. Treatment response, particularly drug survival, may itself be familial. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a

  2. An improved method for the simultaneous determination of /sup 224/Ra, /sup 226/Ra and /sup 228/Ra in water, soils and sediments

    SciTech Connect

    Lucas, H.F.

    1987-01-01

    The naturally occurring concentrations of radium (/sup 226/Ra and /sup 228/Ra) in public and private water supplies have been studied for many years. Both general surveys ad local studies have established the geographical regions where well waters exceed 3 pCi/L (1-17). In general, the /sup 226/Ra was determined by the emanation method, while the /sup 228/Ra was determined from the beta activity of the /sup 228/Ac daughter. In a recent review (18) of the methods used ''a number of approved analytic methods can bear improvement, especially the method for 228Ra.'' The purpose of the work described here was to develop an improved method for the simultaneous determination of /sup 226/Ra and /sup 228/Ra. 22 refs., 3 tabs.

  3. (228)Ra and (226)Ra measurement on a BaSO4 co-precipitation source.

    PubMed

    Medley, Peter; Martin, Paul; Bollhöfer, Andreas; Parry, David

    2014-10-14

    One of the most commonly-used methods for determination of (226)Ra, particularly in water samples, utilises co-precipitation of Ra with BaSO4, followed by microfiltration to produce a source for alpha counting. This paper describes two extensions to BaSO4 co-precipitation methods which enable determination of (228)Ra using the same source. The adaptations presented here do not introduce any contaminants that will affect the separation of radium or alpha counting for (226)Ra, and can be used for re-analysis of already existing sources prepared by BaSO4 co-precipitation. The first adaptation uses detection of (228)Ac on the source by gamma spectrometry. The detection efficiency is high, allowing analysis of water samples at sufficiently low activity to be suitable in testing for compliance with drinking water quality standards. As (228)Ac grows in quickly, taking less than 2 days to reach equilibrium with the (228)Ra parent, this can also be useful in radiological emergency response situations. The second adaptation incorporates a method for the digestion of BaSO4 sources, allowing separation of thorium and subsequent determination of (228)Th activity. Although ingrowth periods for (228)Th can be lengthy, very low detection limits for (228)Ra can be achieved with this technique. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

  4. SB-RA-2001 Inhibits Bacterial Proliferation by Targeting FtsZ Assembly

    PubMed Central

    2015-01-01

    FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium smegmatis cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in B. subtilis 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in B. subtilis 168 cells. The agent also did not appear to perturb the membrane potential of B. subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials. PMID:24749867

  5. SB-RA-2001 inhibits bacterial proliferation by targeting FtsZ assembly.

    PubMed

    Singh, Dipty; Bhattacharya, Anusri; Rai, Ankit; Dhaked, Hemendra Pal Singh; Awasthi, Divya; Ojima, Iwao; Panda, Dulal

    2014-05-13

    FtsZ has been recognized as a promising antimicrobial drug target because of its vital role in bacterial cell division. In this work, we found that a taxane SB-RA-2001 inhibited the proliferation of Bacillus subtilis 168 and Mycobacterium smegmatis cells with minimal inhibitory concentrations of 38 and 60 μM, respectively. Cell lengths of these microorganisms increased remarkably in the presence of SB-RA-2001, indicating that it inhibits bacterial cytokinesis. SB-RA-2001 perturbed the formation of the FtsZ ring in B. subtilis 168 cells and also affected the localization of the late cell division protein, DivIVA, at the midcell position. Flow cytometric analysis of the SB-RA-2001-treated cells indicated that the compound did not affect the duplication of DNA in B. subtilis 168 cells. Further, SB-RA-2001 treatment did not affect the localization of the chromosomal partitioning protein, Spo0J, along the two ends of the nucleoids and also had no discernible effect on the nucleoid segregation in B. subtilis 168 cells. The agent also did not appear to perturb the membrane potential of B. subtilis 168 cells. In vitro, SB-RA-2001 bound to FtsZ with modest affinity, promoted the assembly and bundling of FtsZ protofilaments, and reduced the GTPase activity of FtsZ. GTP did not inhibit the binding of SB-RA-2001 to FtsZ, suggesting that it does not bind to the GTP binding site on FtsZ. A computational analysis indicated that SB-RA-2001 binds to FtsZ in the cleft region between the C-terminal domain and helix H7, and the binding site of SB-RA-2001 on FtsZ resembled that of PC190723, a well-characterized inhibitor of FtsZ. The findings collectively suggested that SB-RA-2001 inhibits bacterial proliferation by targeting the assembly dynamics of FtsZ, and this can be exploited further to develop potent FtsZ-targeted antimicrobials.

  6. Development and validation of a Patient Reported Experience Measure (PREM) for patients with rheumatoid arthritis (RA) and other rheumatic conditions.

    PubMed

    Bosworth, Ailsa; Cox, Maureen; O'Brien, Anne; Jones, Peter; Sargeant, Ify; Elliott, Alison; Bukhari, Marwan

    2015-05-21

    Patient experience is not routinely measured in rheumatoid arthritis (RA) and no accepted standardised Patient Reported Experience Measures (PREM) tools currently exist. Commissioning for Quality in Rheumatoid Arthritis (CQRA) has developed, piloted and validated PREMs for RA and other rheumatic conditions. Focus groups were held with RA patients to identify key elements of the patient experience. These were mapped against the UK Department of Health Patient Experience Framework and a PREM questionnaire developed with questions specifically relating to RA and rheumatology services. The RA PREM was piloted and Cronbach's alpha used to assess internal consistency. The PREM was modified to capture experience of patients with other rheumatic conditions and further validated. Ten UK sites and 524 patients were included in the RA PREM pilot and validation analysis. The RA PREM reliably captured RA patient experience and had good construct validity. Cronbach's alpha within the multiquestion domains ranged from 0.61 to 0.90 and the percentage agreement ranged from 22.5% to 70.4% with overall care. The modified PREM was evaluated in 11 UK sites and 110 patients with a range of rheumatic conditions. Cronbach's alpha ranged from 0.76 to 0.91 and the percentage agreement similarly ranged from 70% to 90% with the question on overall care. The RA PREM and the modified PREM provide new valuable validated tools for capturing the patient experience in a range of rheumatic conditions. The RA PREM is currently being used in a UK National Clinical Audit of Rheumatoid and Early Inflammatory Arthritis.

  7. Genetics of RA susceptibility, what comes next?

    PubMed Central

    Ding, James; Eyre, Stephen; Worthington, Jane

    2015-01-01

    Summary Genome-wide association studies (GWASs) have been used to great effect to identify genetic susceptibility loci for complex disease. A series of GWAS and meta-analyses have informed the discovery of over 100 loci for rheumatoid arthritis (RA). In common with findings in other autoimmune diseases the lead signals for the majority of these loci do not map to known gene sequences. In order to realise the benefit of investment in GWAS studies it is vital we determine how disease associated alleles function to influence disease processes. This is leading to rapid development in our knowledge as to the function of non-coding regions of the genome. Here we consider possible functional mechanisms for intergenic RA-associated variants which lie within lncRNA sequences. PMID:26509058

  8. Sulfur flows of Ra Patera, Io

    NASA Technical Reports Server (NTRS)

    Pieri, D. C.; Nelson, R. M.; Baloga, S. M.; Sagan, C.

    1984-01-01

    Voyager 1 imaging data have been used to investigate the color and morphology of several radial flow-like features at Ra Patera, a broad volcanic structure at approximately 8 deg latitude and 325 deg longitude on the Galilean satellite Io. It was found that downstream progressions of flow color and morphology are consistent with lava of a predominately sulfur composition cooling radiatively and erupting in the range of 470 to 520 K at effusion rates at 10 to the 10th to 10 to the 11th cubic cm/sec. This implies global resurfacing rates by volcanic flows on Io of the order of 1 cm/year. Calculated energy content and effusion rates for flows at Ra Patera, using the physical parameters of sulfur, are of the order of the largest known terrestrial basaltic eruptions and are consistent with calculations of globally available energy.

  9. QUANTIFYING ATYPICALITY IN AFFECTIVE FACIAL EXPRESSIONS OF CHILDREN WITH AUTISM SPECTRUM DISORDERS.

    PubMed

    Metallinou, Angeliki; Grossman, Ruth B; Narayanan, Shrikanth

    2013-01-01

    We focus on the analysis, quantification and visualization of atypicality in affective facial expressions of children with High Functioning Autism (HFA). We examine facial Motion Capture data from typically developing (TD) children and children with HFA, using various statistical methods, including Functional Data Analysis, in order to quantify atypical expression characteristics and uncover patterns of expression evolution in the two populations. Our results show that children with HFA display higher asynchrony of motion between facial regions, more rough facial and head motion, and a larger range of facial region motion. Overall, subjects with HFA consistently display a wider variability in the expressive facial gestures that they employ. Our analysis demonstrates the utility of computational approaches for understanding behavioral data and brings new insights into the autism domain regarding the atypicality that is often associated with facial expressions of subjects with HFA.

  10. Atypical CF and CF related diseases.

    PubMed

    Kerem, Eitan

    2006-01-01

    The clinical characteristics of atypical CF are: symptoms that may start in infancy but the disease become clinically significant only after 10 years of age, survival into adulthood, chronic sinopulmonary disease, pancreatic sufficiency, and sweat chloride <60 meq/L. Other patients may present with single organ involvement such as CBAVD, biliary cirrhosis and portal hypertension, chronic or recurrent pancreatitis, giant nasal polyposis or hypochloremic alkalosis. It is recommended to refer such patients for CFTR genotyping, however, absence of known common mutation does not rule out CFTR associated disease, since mutations causing atypical CF are rare and whole genome scan is required for their identification. Nasal PD measurements may be helpful to establish the diagnosis of these patients; however, measurements might be also atypical. Several explanations have been suggested to explain the atypical CF disease.

  11. Atypical Fractures Following Bisphosphonate Therapy.

    PubMed

    Patel, Rati N; Ashraf, Anwar; Sundaram, Murali

    2016-09-01

    Bisphosphonates have been widely used in the treatment of osteoporosis with well-documented long-term efficacy and safety, particularly in postmenopausal patients. But over the past decade, low-energy atypical subtrochanteric and proximal diaphyseal femoral fractures have emerged as an unexpected complication of prolonged bisphosphonate use. To the radiologist unfamiliar with this entity, the findings may be subtle and often missed, potentially evolving from an early incomplete fracture to a displaced complete fracture with a delay in diagnosis.In such instances where the radiographic findings are negative or equivocal and patients present with prodromal symptoms of aching or dull groin or thigh pain, additional work-up with advanced imaging techniques, such as magnetic resonance imaging, computed tomography, or bone scintigraphy, may prove diagnostic owing to their multiplanar capabilities and earlier detection of subtle periosteal changes. It is imperative that radiologists develop a search pattern to help identify such fractures and consider imaging evaluation of the contralateral extremity in suspected cases with prodromal symptoms to assess for an incomplete asymptomatic or minimally symptomatic fracture. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  12. [Atypical onset cryoglobulinemia: case report].

    PubMed

    Consolo, M; Amoroso, A; D'Amico, G; La Rosa, L; Vinci, M

    2012-01-01

    Cryoglobulinemia is a disease mediated by antibodies with the property to precipitate at temperatures below 37°C. It can be distinguished into a primitive form (also referred to as 'essential mixed cryoglobulinemia'), and a secondary form. In the essential mixed variant a key role is played by HCV infection. The pathogenesis of mixed cryoglobulinemia is mediated by immune complexes that are the most important cause of the vasculitic phenomena, typical of the disease. However, the severity of the clinical manifestations is not always related to the serum levels of cryoglobulins and immune complexes. In our case report, a 46-year old man came to our observation with asymmetric diffuse and invalidating arthralgies, with both substitutive and additive behaviour, located at pelvic girdle, inferior limbs and elbows, associated to skin lesion vascultis-like. The remote pathological anamnesis was characterized by a previous surgically treated non-Hodgkin lymphoma, and HCV infection. Despite several attempts were done, it was not possible to reveal cryoglobulins, nor reumatoid factor in the serum. Cryoglobulins resulted positive only after the third day of hospitalization, along with a new fever attack and a worsening of the vasculitic manifestations. In conclusion, this case demonstrated that cryoglobulinemia can occur with a totally atypical sequence of clinical manifestations which can be present before and in absence of the typical laboratory proofs.

  13. Atypical cases of Angelman syndrome.

    PubMed

    Lawson-Yuen, Amy; Wu, Bai-Lin; Lip, Va; Sahoo, Trilochan; Kimonis, Virginia

    2006-11-01

    Angelman syndrome (AS) is a profound disorder notable for mental retardation and severe language deficits that results from lack of function of the maternally inherited copy of the UBE3A gene. Chromosome deletions of 15q11q13, paternal uniparental disomy (UPD), UBE3A gene mutations, and imprinting center defects are all commonly recognized mechanisms that disrupt the function of the maternal copy of the UBE3A gene. We report here two patients with different atypical etiologies of AS. The first patient is a 3-year-old boy with global developmental delay, severe speech deficits, seizures, and very happy disposition. Southern blot analysis for the maternal and paternal chromosome 15 methylation products showed a mosaic methylation pattern, suggesting an imprinting center defect. The second patient is a 4(1/2)-year-old boy with global developmental delay, no expressive language, microcephaly, seizures, and ataxic gait. Array-based comparative genomic hybridization (CGH) demonstrated a loss in copy number for two overlapping clones encompassing the UBE3A gene, indicating a partial deletion within UBE3A. His mother, who was adopted, had an identical pattern, suggesting that her deletion was probably on her paternally imprinted allele. These patients illustrate the expanding spectrum of molecular findings in AS, reinforce the need to maintain suspicion when clinical features suggest AS but initial testing is normal, and show the power of CGH as a tool to uncover partial UBE3A deletions.

  14. Quetiapine: a new atypical antipsychotic.

    PubMed

    Misra, L K; Erpenbach, J E; Hamlyn, H; Fuller, W C

    1998-06-01

    Quetiapine has recently been approved for treatment of psychotic disorders. In short term (6 weeks) trials this atypical antipsychotic was shown to be as efficacious as the standard antipsychotics for the treatment of the positive symptoms of schizophrenia without causing any extrapyramidal symptoms or increase in the prolactin levels. Its efficacy for treating the negative symptoms was variable. Preliminary observations suggest its potential to improve the cognitive deficits of schizophrenia. It is metabolized by the p450 CYP 3A4 system with an estimated elimination half life of 6 hours. The optimal treatment is 300 mg to 400 mg/day in two to three divided oral doses. The most common side effects include dizziness, hypotension, somnolence and weight gain. Changes in the ECG, the thyroid hormone and hepatic enzymes levels appear to be clinically insignificant. Quetiapine interacts with phenytoin, carbamazepine, barbiturates, rifampin and glucocorticoids; and coadministration with these drugs may require dosage adjustment. Doses need not be adjusted when fluoxetine, imipramine, haloperidol and resperidone are coadministered. Quetiapine may enhance the effects of antihypertensive agents and may antagonize those of levodopa and dopamine. Long term efficacy of quetiapine has not been determined. Also undetermined are its effectiveness for treating the first episode and treatment-refractory schizophrenia. Data suggest that quetiapine may be used for the management of psychotic disorders in patients who may not tolerate the side effects of the typical antipsychotics and clozapine. It may also be helpful in patients whose psychotic manifestations did not adequately respond to risperidone and olanzapine.

  15. Atypical manifestations of pulmonary atelectasis.

    PubMed

    Gurney, J W

    1996-01-01

    Recognizing atelectasis has always been a challenge. Atypical patterns further our knowledge of this subject. The lung has two mechanisms to help keep the lobes inflated: collateral ventilation and trapped nitrogen both tend to inflate the lungs when the airways are obstructed. Peripheral upper-lobe atelectasis resembles apical pleural fluid. Instead of collapsing superomedially, the upper lobe collapses posterolaterally, marginated by either the middle lobe or the superior segment of the lower lobe. This pattern may also be produced by segmental atelectasis of the apical-posterior segments of the upper lobe. Combined right-upper- and middle-lobe atelectasis usually stems from malignancy and violates Felson's double lesion sign. Upper-lobe atelectasis may produce a localized pneumothorax (pneumothorax ex vacuo), analogous to the vacuum joint phenomenon. Conversely, a large pneumothorax may cause torsion of an upper-lobe bronchus, leading to atelectasis. It is important to distinguish between these two conditions in order to choose the appropriate treatment-bronchoscopy in the former and chest tube drainage in the latter. Round atelectasis is a form of peripheral atelectasis that is variable in size and is thought to occur either when the lung collapses around a cleft in the presence of a pleural effusion or when shrinkage of a pleural scar pinches the adjacent lung. Round atelectasis has many features of plate atelectasis and may represent a special form of this condition.

  16. Error-control and processes optimization of (223/224)Ra measurement using Delayed Coincidence Counter (RaDeCC).

    PubMed

    Xiaoqing, Cheng; Lixin, Yi; Lingling, Liu; Guoqiang, Tang; Zhidong, Wang

    2015-11-01

    RaDeCC has proved to be a precise and standard way to measure (224)Ra and (223)Ra in water samples and successfully made radium a tracer of several environmental processes. In this paper, the relative errors of (224)Ra and (223)Ra measurement in water samples via a Radium Delayed Coincidence Count system are analyzed through performing coincidence correction calculations and error propagation. The calculated relative errors range of 2.6% ∼ 10.6% for (224)Ra and 9.6% ∼ 14.2% for (223)Ra. For different radium activities, effects of decay days and counting time on final radium relative errors are evaluated and the results show that these relative errors can decrease by adjusting the two measurement factors. Finally, to minimize propagated errors in Radium activity, a set of optimized RaDeCC measurement parameters are proposed. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. Analysis of the Origin of Atypical Scanning Laser Polarimetry Patterns by Polarization-Sensitive Optical Coherence Tomography

    PubMed Central

    Götzinger, Erich; Pircher, Michael; Baumann, Bernhard; Hirn, Cornelia; Vass, Clemens; Hitzenberger, Christoph K.

    2010-01-01

    Purpose To analyze the physical origin of atypical scanning laser polarimetry (SLP) patterns. To compare polarization-sensitive optical coherence tomography (PS-OCT) scans to SLP images. To present a method to obtain pseudo-SLP images by PS-OCT that are free of atypical artifacts. Methods Forty-one eyes of healthy subjects, subjects with suspected glaucoma, and patients with glaucoma were imaged by SLP (GDx VCC) and a prototype spectral domain PS-OCT system. The PS-OCT system acquires three-dimensional (3D) datasets of intensity, retardation, and optic axis orientation simultaneously within 3 seconds. B-scans of intensity and retardation and en face maps of retinal nerve fiber layer (RNFL) retardation were derived from the 3D PS-OCT datasets. Results were compared with those obtained by SLP. Results Twenty-two eyes showed atypical retardation patterns, and 19 eyes showed normal patterns. From the 22 atypical eyes, 15 showed atypical patterns in both imaging modalities, five were atypical only in SLP images, and two were atypical only in PS-OCT images. In most (15 of 22) atypical cases, an increased penetration of the probing beam into the birefringent sclera was identified as the source of atypical patterns. In such cases, the artifacts could be eliminated in PS-OCT images by depth segmentation and exclusion of scleral signals. Conclusions PS-OCT provides deeper insight into the contribution of different fundus layers to SLP images. Increased light penetration into the sclera can distort SLP retardation patterns of the RNFL. PMID:19036999

  18. A rapid and inexpensive method for 226Ra and 228Ra measurements of high TDS groundwaters.

    PubMed

    El-Shrakawy, A; Ebaid, Y Y; Burnett, W C; Aldaihan, Soaad K

    2013-07-01

    A series of laboratory-scale studies was conducted by preconcentrating (226)Ra from spiked water test samples using Purolite ion-exchange resin to evaluate the adsorption efficiency of the resin under varying conditions. After removing the resin from the columns, it was sealed in gas-tight containers and measured via gamma spectrometry. The Purolite resin showed high radium uptake and retention from natural waters in the presence of high iron and total dissolved solids (TDS). This procedure allowed us to process a large number of high TDS samples at a typical rate of 15 samples/day using three germanium detectors. Quality assurance and method validation have been achieved by analyzing selected groundwater samples, with different (226)Ra activities and high TDS values, and comparing the results to those using alpha spectrometry with a (133)Ba yield tracer. There was very good agreement between the obtained (226)Ra activities by both methods.

  19. Domain walls in antiferromagnetically coupled multilayer films.

    PubMed

    Hellwig, Olav; Berger, Andreas; Fullerton, Eric E

    2003-11-07

    We report experimentally observed magnetic domain-wall structures in antiferromagnetically coupled multilayer films with perpendicular anisotropy. Our studies reveal a first-order phase transition from domain walls with no net moment to domain walls with ferromagnetic cores. The transition originates from the competition between dipolar and exchange energies, which we tune by means of layer thickness. Although observed in a synthetic antiferromagnetic system, such domain-wall structures may be expected to occur in A-type antiferromagnets with anisotropic exchange coupling.

  20. High-Speed RaPToRS

    NASA Astrophysics Data System (ADS)

    Henchen, Robert; Esham, Benjamin; Becker, William; Pogozelski, Edward; Padalino, Stephen; Sangster, Thomas; Glebov, Vladimir

    2008-11-01

    The High-Speed Rapid Pneumatic Transport of Radioactive Samples (HS-RaPToRS) system, designed to quickly and safely move radioactive materials, was assembled and tested at the Mercury facility of the Naval Research Laboratory (NRL) in Washington D.C. A sample, which is placed inside a four-inch-diameter carrier, is activated before being transported through a PVC tube via airflow. The carrier travels from the reaction chamber to the end station where it pneumatically brakes prior to the gate. A magnetic latch releases the gate when the carrier arrives and comes to rest. The airflow, optical carrier-monitoring devices, and end gate are controlled manually or automatically with LabView software. The installation and testing of the RaPToRS system at NRL was successfully completed with transport times of less than 3 seconds. The speed of the carrier averaged 16 m/s. Prospective facilities for similar systems include the Laboratory for Laser Energetics and the National Ignition Facility.

  1. Ra-226 bioaccumulation and growth indices in fish.

    PubMed

    Shi, Xiaopei; Smith, Richard; Seymour, Colin; Mothersill, Carmel

    2017-06-01

    To determine the accumulated activity of Ra-226 in fathead minnows fed with environmentally relevant levels of Ra-226 for 5 months in water at 20 °C, and to evaluate the influence of this level of Ra-226 on the growth of fathead minnows. Fathead minnows were fed with fish food containing 10-10,000 mBq/g Ra-226 for 5 months. At the end of the experiment, the fish were sacrificed, flash frozen in liquid nitrogen and kept at -20 °C. Longitudinal sections of 40 μm thickness were cut at the middle of the fish body using a cryostat. The activity of Ra-226 in each section was determined using autoradiography with a nuclear track detector CR-39. According to the weight and the width of the fish, the activity of Ra-226 in the whole fish body could be estimated. In addition, the length and the weight of the fish were measured and the condition factor was calculated to evaluate the growth and fitness of the fish. There is a positive but non-linear relationship between the accumulated activity of Ra-226 in fish body and the concentration of Ra-226 in fish food. The highest activity of Ra-226 accumulated in fish body was found from fish fed with 10,000 mBq/g Ra-226 food. This was calculated as 256.4 ± 49.1 mBq/g, p < 0.05, and the calculated dose rate was 6.2 ± 1.2 mGy/y. For fish fed with food containing lower concentration of Ra-226 (up to 1000 mBq/g), the bioaccumulation of Ra-226 in the body saturated. The Ra-226 concentration factor (CF) for fish was inversely proportional to the Ra-226 activity in food, and the highest CF value was 2.489, obtained from the lowest dietary Ra-226 activity (10 mBq/g). In addition, condition factors (K) of fish in all Ra-226-treated groups were significantly lower than those of the controls. The results show that the bioaccumulation of Ra-226 in fish is not simply related to the dietary Ra-226 activity, and has a saturation value when the dietary activity is low. In addition, the environmental level of Ra-226 in the fish

  2. Atypical antipsychotics for psychosis in adolescents.

    PubMed

    Kumar, Ajit; Datta, Soumitra S; Wright, Stephen D; Furtado, Vivek A; Russell, Paul S

    2013-10-15

    Schizophrenia often presents in adolescence, but current treatment guidelines are based largely on studies of adults with psychosis. Over the past decade, the number of studies on treatment of adolescent-onset psychosis has increased. The current systematic review collates and critiques evidence obtained on the use of various atypical antipsychotic medications for adolescents with psychosis. To investigate the effects of atypical antipsychotic medications in adolescents with psychosis. We reviewed in separate analyses various comparisons of atypical antipsychotic medications with placebo or a typical antipsychotic medication or another atypical antipsychotic medication or the same atypical antipsychotic medication but at a lower dose. We searched the Cochrane Schizophrenia Group Register (October 2011), which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. We inspected references of all identified studies and contacted study authors and relevant pharmaceutical companies to ask for more information. We included all relevant randomised controlled trials (RCTs) that compared atypical antipsychotic medication with placebo or another pharmacological intervention or with psychosocial interventions, standard psychiatric treatment or no intervention in children and young people aged 13 to 18 years with a diagnosis of schizophrenia, schizoaffective disorder, acute and transient psychoses or unspecified psychosis. We included studies published in English and in other languages that were available in standardised databases. Review authors AK and SSD selected the studies, rated the quality of the studies and performed data extraction. For dichotomous data, we estimated risk ratios (RRs) with 95% confidence intervals (CIs) using a fixed-effect model. When possible, for binary data presented in the 'Summary of findings' table, we calculated illustrative comparative risks. We summated continuous data using the mean difference (MD). Risk of

  3. Atypical E2Fs inhibit tumor angiogenesis.

    PubMed

    Weijts, B G M W; Westendorp, B; Hien, B T; Martínez-López, L M; Zijp, M; Thurlings, I; Thomas, R E; Schulte-Merker, S; Bakker, W J; de Bruin, A

    2017-09-18

    Atypical E2F transcription factors (E2F7 and E2F8) function as key regulators of cell cycle progression and their inactivation leads to spontaneous cancer formation in mice. However, the mechanism of the tumor suppressor functions of E2F7/8 remain obscure. In this study we discovered that atypical E2Fs control tumor angiogenesis, one of the hallmarks of cancer. We genetically inactivated atypical E2Fs in epithelial and mesenchymal neoplasm and analyzed blood vessel formation in three different animal models of cancer. Tumor formation was either induced by application of 7,12-Dimethylbenz(a)anthracene/12-O-Tetradecanoylphorbol-13-acetate or by Myc/Ras overexpression. To our surprise, atypical E2Fs suppressed tumor angiogenesis in all three cancer models, which is in a sharp contrast to previous findings showing that atypical E2Fs promote angiogenesis during fetal development in mice and zebrafish. Real-time imaging in zebrafish displayed that fluorescent-labeled blood vessels showed enhanced intratumoral branching in xenografted E2f7/8-deficient neoplasms compared with E2f7/8-proficient neoplasms. DLL4 expression, a key negative inhibitor of vascular branching, was decreased in E2f7/8-deficient neoplastic cells, indicating that E2F7/8 might inhibit intratumoral vessel branching via induction of DLL4.Oncogene advance online publication, 18 September 2017; doi:10.1038/onc.2017.336.

  4. The photoreceptors in atypical achromatopsia.

    PubMed Central

    Hess, R F; Mullen, K T; Sharpe, L T; Zrenner, E

    1989-01-01

    1. The receptoral mechanisms underlying the vision of two atypical achromats of the complete variety were studied with standard psychophysical procedures. 2. Under scotopic conditions the spectral sensitivity of each achromat was well described by the CIE (Commission Internationale de l'Eclairage) scotopic sensitivity function and the recovery of sensitivity after a retinal bleach showed characteristic duplex behaviour with the time constant of recovery of the slower phase matching that of normal rod vision for both foveal and peripheral stimulation. 3. Their spectral sensitivity was measured under conditions of chromatic adaptation in order to reveal any residual middle or long wavelength cone activity. Only one photopic spectral responses was found and this was adequately described by the spectral sensitivity function of Stiles pi 3 mechanism of normal vision. 4. Increment threshold measurements as a function of background intensity revealed a double-branched function in the fovea. The lower branch was found to have the spectral sensitivity of the rods; the upper branch that of Stiles' pi 3 mechanism. Stiles-Crawford measurements of directional sensitivity confirmed that the branch with the rhodopsin action spectrum had the directional sensitivity of rods and that the branch with the action spectrum of pi 3 had the directional sensitivity of cones. 5. These was no evidence for hue discrimination under photopic conditions. Regions of apparently normal performance on hue discrimination tests on more careful examination could be explained by luminosity judgements mediated by short wavelength-absorbing receptors. 6. We reject the notion of there being rhodopsin-filled cones in the fovea of these subjects. The foveal and peripheral vision of each of these achromats can be adequately described in terms of the participation of only two types of receptor, namely normally functional rods under scotopic conditions and normally functioning short wavelength-absorbing cones

  5. Behavior of atypical amphiphilic molecules

    NASA Astrophysics Data System (ADS)

    Ko, John

    1997-08-01

    The physical behavior of several atypical amphiphilic molecules was studied in various environments including micelles, model bilayer membranes, and emulsions. The molecules under investigation were nor-chenodeoxycholic acid (nor-CDCA), ursodeoxycholic acid (UDCA), sphingosine (Sp), sphingosine hydrochloride (SpċHCl), and tetrahydrolipstatin (THL). The bile acids, nor-CDCA and UDCA, were studied using 13C-Nuclear Magnetic Resonance ([13C) -NMR) in micelles of taurocholate and in bilayers of phosphatidylcholine. The pK a values of the bile acids in each environment were determined by [13C) -NMR and are as follows: 6.08 ±.03 for nor-CDCA and 6.27 ±.01 for UDCA in micelles, and 7.04 ± 12 for nor-CDCA and 6.89 ±.05 for UDCA in vesicles. Using line shape analysis, the transbilayer movement rate at 36oC for nor-CDCA and UDCA was calculated to be 580 sec--1 and 409 sec-1, respectively. [13C) -NMR titration of Sp gave pK a values of 9.09 ±.02 in micelles and 9.69 ±.21 in bilayers. Differential scanning calorimetry (DSC) and X-ray diffraction were used to establish the Spċwater and SpċHClċwater phase diagrams. Anhydrous and hydrated samples ranging from 5- 90% water were analyzed. The DSC thermograms traced out the transition temperatures of each molecule while the X- ray diffraction patterns revealed their chain and crystalline lattice packing structures. In general, sphingosine exists as a hydrated crystal with β packing phase below 43oC and melts into an Lα phase. Sphingosine hydrochloride, however, exists as a gel phase (L_beta or /beta/sp') below 42oC that swells to 61% hydration. At low water concentrations (0-64%), a lamellar liquid crystal phase (L_alpha) is formed above the chain melting transition of 42oC. At medium concentration (65%), a Hexagonal I phase is present, and at high water concentrations (66-90%), a micellar phase is present. THL, a specific inhibitor of lipases, was analyzed with [ 13C) -NMR to study its behavior in various environments

  6. Natural radioactivity of 226Ra and 228Ra in thermal and mineral waters in Croatia.

    PubMed

    Bituh, Tomislav; Marovic, Gordana; Petrinec, Branko; Sencar, Jasminka; Franulovic, Iva

    2009-01-01

    Thermal waters are known as valuable natural resources of a country. They contain certain degree of natural radioactivity attributable to the elements of the uranium and thorium natural decay series. Among these elements, the most radiotoxic and the most important is radium that exists in several isotopic forms (226Ra and 228Ra). The focus of attention was the content of radium in samples of thermal and mineral spring water from several spas in Croatia. These waters are mainly used for medical, bathing and recreational purposes, and some of them are used for drinking. Measured activity concentrations of 226Ra ranged from 87 to 6200 mBq l(-1) which, in some springs, exceed the maximal permissible level of 1 Bq l(-1) for drinking water. Measured activity concentrations of 228Ra ranged from 23 to 3480 mBq l(-1). The study showed that radium content for the investigated thermal and mineral waters is below the levels at which negative consequences would arise due to ingestion.

  7. Ra-224 and Ra-226: A New Method for Measuring Groundwater Seepage in Lake Michigan

    NASA Astrophysics Data System (ADS)

    Stevens, K. R.; Buyan, A. C.; Waples, J. T.

    2008-12-01

    Radium isotopes have been used to estimate groundwater discharge (GWD) in coastal marine waters for decades, but this technique has never before been used in the Laurentian Great Lakes. In this study, we used a RAD7 radon-in-air monitor to measure naturally-occurring radium isotopes Ra-224 (half-life= 3.64 d) and Ra-226 (half-life = 1600 a) in groundwater and three shallow water sites along Lake Michigan's Wisconsin coastline. Radium-224 activities in groundwater ranged from 1153 dpm m-3 in a deep aquifer (New Berlin well no.7) to 31 dpm m-3 in a shallow aquifer (Pryor well). Nearshore Lake Michigan measurements of Ra-224 were lowest at Red Arrow Beach (0.2 dpm m-3), higher in the Milwaukee harbor (GLWI slip, 1.1 dpm m-3) and highest at Harrington Beach (4.1 dpm m-3) and correspond well with groundwater seepage estimates made by Cherkauer et al. (1990) using alternate methods (i.e., where higher radium activity is indicative of higher GWD). These Ra-224 measurements are the first ever made in Lake Michigan (and presumably any of the Great Lakes) and we conclude that, by sampling offshore radium activity gradients, this RAD7 technique is a viable method for directly measuring GWD in Lake Michigan and other freshwater systems.

  8. Atypical Pityriasis Rosea with Unilateral Presentation

    PubMed Central

    Fadaei, Fahameh; Badakhsh, Mahin; Balouchi, Abbas

    2016-01-01

    Pityriasis Rosea (PR) is a common skin disease and characterized by generalized scaly eruptions typically on the trunk and proximal extremities. Atypical presentations of PR are common and can be a diagnostic challenge for clinicians. Here we present a case of a 26-year-old female who presented with a sudden onset of several asymptomatic, erythematous and scaly plaques on her trunk. Plaques sized 0.5-1cm in diameter that were distributed unilaterally (right side) on her chest, back and axilla. Atypical cases of PR are fairly common and less readily recognized. Careful history, clinical evaluation and follow-up are important to avoid misdiagnosis of PR and physicians should be aware of PR variants so that appropriate management and reassurance can be offered. For atypical eruptions without a definite diagnosis, it is safer to consider lesional skin biopsy. PMID:28208986

  9. [Atypical antipsychotic-induced weight gain].

    PubMed

    Godlewska, Beata R; Olajossy-Hilkesberger, Luiza; Marmurowska-Michałowska, Halina; Olajossy, Marcin; Landowski, Jerzy

    2006-01-01

    Introduction of a new group of antipsychotic drugs, called atypical because of the proprieties differing them from classical neuroleptics, gave hope for the beginning of a new era in treatment of psychoses, including schizophrenia. Different mechanisms of action not only resulted in a broader spectrum of action and high efficacy but also in a relative lack of extrapiramidal symptoms. However, atypical neuroleptics are not totally free from adverse effects. Symptoms such as sedation, metabolic changes and weight gain, often very quick and severe - present also in the case of classical drugs, but put to the background by extrapiramidal symptoms--have become prominent. Weight gain is important both from the clinical and subjective point of view--as associated with serious somatic consequences and as a source of enormous mental distress. These problems are addressed in this review, with the focus on weight gain associated with the use of specific atypical neuroleptics.

  10. Modifiable risk factors for RA: prevention, better than cure?

    PubMed Central

    Lahiri, Manjari; Morgan, Catharine; Symmons, Deborah P. M.

    2012-01-01

    Objective. To perform a meta-synthesis of the evidence for modifiable lifestyle risk factors for inflammatory polyarthritis (IP) and RA. Methods. We performed a MEDLINE literature search. Case–control and cohort studies and systematic reviews published from 1948 through February 2011 and studying modifiable risk factors for RA were retrieved. The main outcome measure was diagnosis of RA according to the standard criteria. Results. Smoking contributes up to 25% of the population burden of RA. The risk is dose related, stronger in males and especially strong for anti-citrullinated peptide antibody positive (ACPA+) RA through an interaction with the shared epitope. After smoking cessation, there is, however, a latency of up to 20 years to return to baseline risk. Other associations are less definitive; however, prospective studies suggest that dietary antioxidants and breastfeeding may be protective and that high coffee consumption may increase RA risk. An inverse association with alcohol intake (especially in smokers) and with education/social class (especially seropositive RA) and an increased risk with obesity (seronegative RA) is also noted. Conclusion. There is a need for further large-scale prospective studies with a consistent definition of RA phenotype (undifferentiated IP through to ACPA+/RF+ disease). This will ultimately afford the opportunity to evaluate preventative population strategies for RA akin to the well-established programmes for cardiovascular disease and cancer, targeting common risk factors. PMID:22120459

  11. Do A-type stars flare?

    NASA Astrophysics Data System (ADS)

    Pedersen, M. G.; Antoci, V.; Korhonen, H.; White, T. R.; Jessen-Hansen, J.; Lehtinen, J.; Nikbakhsh, S.; Viuho, J.

    2017-04-01

    For flares to be generated, stars have to have a sufficiently deep outer convection zone (F5 and later), strong large-scale magnetic fields (Ap/Bp-type stars) or strong, radiatively driven winds (B5 and earlier). Normal A-type stars possess none of these and therefore should not flare. Nevertheless, flares have previously been detected in the Kepler light curves of 33 A-type stars and interpreted to be intrinsic to the stars. Here, we present new and detailed analyses of these 33 stars, imposing very strict criteria for the flare detection. We confirm the presence of flare-like features in 27 of the 33 A-type stars. A study of the pixel data and the surrounding field of view reveals that 14 of these 27 flaring objects have overlapping neighbouring stars and five stars show clear contamination in the pixel data. We have obtained high-resolution spectra for 2/3 of the entire sample and confirm that our targets are indeed A-type stars. Detailed analyses revealed that 11 out of 19 stars with multiple epochs of observations are spectroscopic binaries. Furthermore, and contrary to previous studies, we find that the flares can originate from a cooler, unresolved companion. We note the presence of Hα emission in eight stars. Whether this emission is circumstellar or magnetic in origin is unknown. In summary, we find possible alternative explanations for the observed flares for at least 19 of the 33 A-type stars, but find no truly convincing target to support the hypothesis of flaring A-type stars.

  12. Atypical RNAs in the coelacanth transcriptome.

    PubMed

    Nitsche, Anne; Doose, Gero; Tafer, Hakim; Robinson, Mark; Saha, Nil Ratan; Gerdol, Marco; Canapa, Adriana; Hoffmann, Steve; Amemiya, Chris T; Stadler, Peter F

    2014-09-01

    Circular and apparently trans-spliced RNAs have recently been reported as abundant types of transcripts in mammalian transcriptome data. Both types of non-colinear RNAs are also abundant in RNA-seq of different tissue from both the African and the Indonesian coelacanth. We observe more than 8,000 lincRNAs with normal gene structure and several thousands of circularized and trans-spliced products, showing that such atypical RNAs form a substantial contribution to the transcriptome. Surprisingly, the majority of the circularizing and trans-connecting splice junctions are unique to atypical forms, that is, are not used in normal isoforms.

  13. An atypical monomelic presentation of Mazabraud syndrome

    PubMed Central

    Wan, Jun; He, Hong-Bo; Liao, Qian-De; Zhang, Can

    2014-01-01

    Mazabraud syndrome is a rare condition characterized by a combination of fibrous dysplasia and intramuscular myxomas. In Mazabraud syndrome, the distribution of fibrous dysplasia is mostly polyomelic and frequently located in the femur, with myxomas adjacent to the fibrous dysplasia lesion of bone (mostly in the quadriceps muscle). However, when presented as atypical clinical features, patients of Mazabraud syndrome is either misdiagnosed or difficult to diagnose. We report an atypical monomelic case of Mazabraud syndrome in the right upper arm and discuss the difficulties in making an accurate diagnosis. PMID:25143651

  14. RaPToRS Sample Delivery System

    NASA Astrophysics Data System (ADS)

    Henchen, Robert; Shibata, Kye; Krieger, Michael; Pogozelski, Edward; Padalino, Stephen; Glebov, Vladimir; Sangster, Craig

    2010-11-01

    At various labs (NIF, LLE, NRL), activated material samples are used to measure reaction properties. The Rapid Pneumatic Transport of Radioactive Samples (RaPToRS) system quickly and safely moves these radioactive samples through a closed PVC tube via airflow. The carrier travels from the reaction chamber to the control and analysis station, pneumatically braking at the outlet. A reversible multiplexer routes samples from various locations near the shot chamber to the analysis station. Also, the multiplexer allows users to remotely load unactivated samples without manually approaching the reaction chamber. All elements of the system (pneumatic drivers, flow control valves, optical position sensors, multiplexers, Geiger counters, and release gates at the analysis station) can be controlled manually or automatically using a custom LabVIEW interface. A prototype is currently operating at NRL in Washington DC. Prospective facilities for Raptors systems include LLE and NIF.

  15. The role of rheumatoid arthritis (RA) flare and cumulative burden of RA severity in the risk of cardiovascular disease.

    PubMed

    Myasoedova, Elena; Chandran, Arun; Ilhan, Birkan; Major, Brittny T; Michet, C John; Matteson, Eric L; Crowson, Cynthia S

    2016-03-01

    To examine the role of rheumatoid arthritis (RA) flare, remission and RA severity burden in cardiovascular disease (CVD). In a population-based cohort of patients with RA without CVD (age ≥30 years; 1987 American College of Rheumatology criteria met in 1988-2007), we performed medical record review at each clinical visit to estimate flare/remission status. The previously validated RA medical Records-Based Index of Severity (RARBIS) and Claims-Based Index of RA Severity (CIRAS) were applied. Age- and sex-matched non-RA subjects without CVD comprised the comparison cohort. Cox models were used to assess the association of RA activity/severity with CVD, adjusting for age, sex, calendar year of RA, CVD risk factors and antirheumatic medications. Study included 525 patients with RA and 524 non-RA subjects. There was a significant increase in CVD risk in RA per time spent in each acute flare versus remission (HR 1.07 per 6-week flare, 95% CI 1.01 to 1.15). The CVD risk for patients with RA in remission was similar to the non-RA subjects (HR 0.90, 95% CI 0.51 to 1.59). Increased cumulative moving average of daily RARBIS (HR 1.16, 95% CI 1.03 to 1.30) and CIRAS (HR 1.38, 95% CI 1.12 to 1.70) was associated with CVD. CVD risk was higher in patients with RA who spent more time in medium (HR 1.08, 95% CI 0.98 to 1.20) and high CIRAS tertiles (HR 1.18, 95% CI 1.06 to 1.31) versus lower tertile. Our findings show substantial detrimental role of exposure to RA flare and cumulative burden of RA disease severity in CVD risk in RA, suggesting important cardiovascular benefits associated with tight inflammation control and improved flare management in patients with RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  16. Developing a construct to evaluate flares in rheumatoid arthritis: a conceptual report of the OMERACT RA Flare Definition Working Group.

    PubMed

    Alten, Rieke; Pohl, Christof; Choy, Ernest H; Christensen, Robin; Furst, Daniel E; Hewlett, Sarah E; Leong, Amye; May, James E; Sanderson, Tessa C; Strand, Vibeke; Woodworth, Thasia G; Bingham, Clifton O

    2011-08-01

    Rheumatoid arthritis (RA) patients and healthcare professionals (HCP) recognize that episodic worsening disease activity, often described as a "flare," is a common feature of RA that can contribute to impaired function and disability. However, there is no standard definition to enable measurement of its intensity and impact. The conceptual framework of the Outcome Measures in Rheumatology Clinical Trials (OMERACT) RA Flare Definition Working Group includes an anchoring statement, developed at OMERACT 9 in 2008: "flare in RA" is defined as worsening of signs and symptoms of sufficient intensity and duration to lead to change in therapy. Subsequently, domains characterizing flare have been identified by comprehensive literature review, patient focus groups, and patient/HCP Delphi exercises. This led to a consensus regarding preliminary domains and a research agenda at OMERACT 10 in May 2010. The conceptual framework of flare takes into account validated approaches to measurement in RA: (1) various disease activity indices (e.g., Disease Activity Score, Clinical Disease Activity Index, Simplified Disease Activity Index); (2) use of patient-reported outcomes (PRO); and (3) characterization of minimally clinically detectable and important differences (MCDD, MCID). The measurement of RA flare is composed of data collection assessing a range of unique domains describing key features of RA worsening at the time of patient self-report of flare, and then periodically for the duration of the flare. The components envisioned are: (1) Patient self-report using a "patient global question" with well characterized and validated anchors; (2) Patient assessment using a flare questionnaire and PRO available at the time of each self-report; (3) Physician/HCP assessment of disease activity status; and (4) Physician's determination whether to change treatment. In randomized controlled trials and observational studies, such a conceptual approach is intended to lead to a valid measure of

  17. Gene expression analysis in RA: towards personalized medicine

    PubMed Central

    Burska, A N; Roget, K; Blits, M; Soto Gomez, L; van de Loo, F; Hazelwood, L D; Verweij, C L; Rowe, A; Goulielmos, G N; van Baarsen, L G M; Ponchel, F

    2014-01-01

    Gene expression has recently been at the forefront of advance in personalized medicine, notably in the field of cancer and transplantation, providing a rational for a similar approach in rheumatoid arthritis (RA). RA is a prototypic inflammatory autoimmune disease with a poorly understood etiopathogenesis. Inflammation is the main feature of RA; however, many biological processes are involved at different stages of the disease. Gene expression signatures offer management tools to meet the current needs for personalization of RA patient's care. This review analyses currently available information with respect to RA diagnostic, prognostic and prediction of response to therapy with a view to highlight the abundance of data, whose comparison is often inconclusive due to the mixed use of material source, experimental methodologies and analysis tools, reinforcing the need for harmonization if gene expression signatures are to become a useful clinical tool in personalized medicine for RA patients. PMID:24589910

  18. Preparing concentrated carrier-free /sup 228/Ra

    SciTech Connect

    Volynskii, L.D.; Garbuzov, V.M.; Tsirlin, V.A.

    1988-05-01

    A scheme has been devised for processing large amounts of old thorium salts to obtain concentrated carrier-free /sup 228/Ra preparations. The process includes simple regeneration of the original thorium salt. The main stages in concentrating the /sup 228/Ra are precipitation and separation of thorium peroxide, isolating the radium with a carrier, ion-exchange separation of the radium from the carrier, and final purification by electrolysis. The /sup 228/Ra recovery is 70%.

  19. Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA)

    DTIC Science & Technology

    2017-03-24

    Rheumatoid Arthritis (RA) presented at/published to American Pharmacists Association (Journal/Abstract) & American Pharmacists Association Annual...Adherence in Patients with Rheumatoid Arthritis (RA) 6. TITLE OF MATERIAL TO BE PUBLISHED OR PRESENTED: A ssessing Medication A dherence in...Patients with Rheumato id Arthritis (RA) 7. FUNDING RECEIVED FOR THIS STUDY? 0 YES cgj NO FUNDING SOURCE: 8. DO YOU NEED FUNDING SUPPORT FOR PUBLICATION

  20. Drugs or disease: evaluating salivary function in RA patients.

    PubMed

    Torres, Sandra Regina; Pedrazas, Carlos Henrique Silva; Correia, Marcos Paulo Veloso; Azevedo, Mario Newton Leitão de; Zamprogno, Thaís; Silva, Arley; Gonçalves, Lucio Souza; Papi, José Angelo de Souza

    2016-10-10

    Oral complications of RA may include temporomandibular joint disorders, mucosa alterations and symptoms of dry mouth. The aim of this study was to evaluate the salivary gland function of subjects with rheumatoid arthritis (RA) comparing it to healthy controls. Subjects with other systemic conditions known to affect salivary functions were excluded. A questionnaire was applied for the evaluation of xerostomia. Resting and chewing-stimulated salivary flow rates (SFR) were obtained under standard conditions. There were 145 subjects included of the study (104 RA and 38 controls). About 66.7% of the RA subjects and 2.4% in control group presented xerostomia. The median resting SFR were 0.24 ml/min for RA subjects and 0.40 mL/min for controls (p = 0.04). The median stimulated SFR were 1.31 mL/min for RA subjects and 1.52 ml/min for controls (p = 0.33). No significant differences were found between resting and stimulated SFR of RA subjects not using xerogenic medications and controls. There was significantly higher number of subjects presenting hyposalivation in the RA group than among controls, even when subjects using xerogenic medications were eliminated from the analysis. In conclusion, hyposalivation and xerostomia were more frequent among RA subjects not using xerogenic medication than among controls, although there were no significant differences in the median SFR between groups.

  1. Heavy cigarette smoking is strongly associated with rheumatoid arthritis (RA), particularly in patients without a family history of RA

    PubMed Central

    Hutchinson, D; Shepstone, L; Moots, R; Lear, J; Lynch, M

    2001-01-01

    OBJECTIVES—To investigate the potential relation between cumulative exposure to cigarette smoking in patients with or without rheumatoid arthritis (RA) and a positive family history of the disease.
METHODS—239 outpatient based patients with RA were compared with 239 controls matched for age, sex, and social class. A detailed smoking history was recorded and expressed as pack years smoked. Conditional logistic regression was used to calculate the association between RA and pack years smoked. The patients with RA were also interviewed about a family history of disease and recorded as positive if a first or second degree relative had RA. The smoking history at the time of the study of the patients with RA with or without a family history of the disease was compared directly with that of their respective controls. Patients with RA with or without a family history of the disease were also compared retrospectively for current smoking at the time of disease onset.
RESULTS—An increasing association between increased pack years smoked and RA was found. There was a striking association between heavy cigarette smoking and RA. A history for 41-50 pack years smoked was associated with RA (odds ratio (OR) 13.54, 95% confidence interval (95% CI) 2.89 to 63.38; p<0.001). The association between ever having smoked and RA was modest (OR 1.81, CI 1.22 to 2.19; p=0.002). Furthermore, cigarette smoking in the patients with RA without a positive family history of RA was more prevalent than in the patients with a positive family history of RA for ever having smoked (72% v 54%; p=0.006), the number of pack years smoked (median 25.0 v 4.0; p<0.001), and for smoking at the time of disease onset (58% v 39%; p=0.003).
CONCLUSIONS—Heavy cigarette smoking, but not smoking itself, is strongly associated with RA requiring hospital follow up and is markedly more prevalent in patients with RA without a family history of RA.

 PMID:11171682

  2. Atypical Visuomotor Performance in Children with PDD

    ERIC Educational Resources Information Center

    Schlooz, Wim A. J. M.; Hulstijn, Wouter

    2012-01-01

    Children with autism spectrum disorders (ASD) frequently encounter difficulties in visuomotor tasks, which are possibly caused by atypical visuoperceptual processing. This was tested in children (aged 9-12 years) with pervasive developmental disorder (PDD; including PDD-NOS and Asperger syndrome), and two same-age control groups (Tourette syndrome…

  3. Atypical Pyoderma Gangrenosum Mimicking an Infectious Process

    PubMed Central

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics. PMID:25024856

  4. Atypical pyoderma gangrenosum mimicking an infectious process.

    PubMed

    To, Derek; Wong, Aaron; Montessori, Valentina

    2014-01-01

    We present a patient with atypical pyoderma gangrenosum (APG), which involved the patient's arm and hand. Hemorrhagic bullae and progressive ulcerations were initially thought to be secondary to an infectious process, but a biopsy revealed PG. Awareness of APG by infectious disease services may prevent unnecessary use of broad-spectrum antibiotics.

  5. Atypical anti-glomerular basement membrane disease

    PubMed Central

    Troxell, Megan L.; Houghton, Donald C.

    2016-01-01

    Background Anti-glomerular basement membrane (anti-GBM) disease classically presents with aggressive necrotizing and crescentic glomerulonephritis, often with pulmonary hemorrhage. The pathologic hallmark is linear staining of GBMs for deposited immunoglobulin G (IgG), usually accompanied by serum autoantibodies to the collagen IV alpha-3 constituents of GBMs. Methods Renal pathology files were searched for cases with linear anti-GBM to identify cases with atypical or indolent course. Histopathology, laboratory studies, treatment and outcome of those cases was reviewed in detail. Results Five anti-GBM cases with atypical clinicopathologic features were identified (accounting for ∼8% of anti-GBM cases in our laboratory). Kidney biopsies showed minimal glomerular changes by light microscopy; one patient had monoclonal IgG deposits in an allograft (likely recurrent). Three patients did not have detectable serum anti-GBM by conventional assays. Three patients had indolent clinical courses after immunosuppressive treatment. One patient, untreated after presenting with brief mild hematuria, re-presented after a short interval with necrotizing and crescentic glomerulonephritis. Conclusions Thorough clinicopathologic characterization and close follow-up of patients with findings of atypical anti-GBM on renal biopsy are needed. Review of the literature reveals only rare well-documented atypical anti-GBM cases to date, only one of which progressed to end-stage kidney disease. PMID:26985371

  6. [Antibiotherapy in children with atypical bacterial infections].

    PubMed

    Haas, H

    2005-04-01

    Atypical bacteria responsible for infections in children are mainly Mycoplasma pneumoniae, Chlamydia pneumoniae and Legionella pneumophila. Atypical pneumonia is a frequent disease in children. Until recently, the outcome was thought to be rather benign and antibiotherapy to have only a minor impact on the prognosis. Recent studies have demonstrated that M. pneumoniae and C. pneumoniae were involved in a variety of infections, including acute upper airway disease, otitis and pharyngitis under five. Antibiotherapy was proven able to decrease the rate of complications and recurrence, notably episodes of wheezing and exacerbations of asthma. Atypical bacteria infections may be severe in immunocompromised children and children with underlying disease such as sickle cell anaemia. Whenever bacteriological documentation is lacking, one of the critical issues in choosing an antibiotic is to consider its activity against Streptococcus pneumoniae, especially in lower respiratory tract infections. The main available molecules are reviewed and discussed, with a special emphasis on ketolides, a newer family of molecules active on both atypical bacteria and S. pneumoniae.

  7. An Atypical Case of Foreign Accent Syndrome

    ERIC Educational Resources Information Center

    Ryalls, Jack; Whiteside, Janet

    2006-01-01

    A new case of Foreign Accent Syndrome is described. This American woman presented with a British- or Australian- sounding accent after stroke, which resulted in a lacunar infarct in the left internal capsule. The atypical etiology and apparent changes in lexical use are described. It is hypothesized that an abnormally tense vocal tract posture may…

  8. Atypical pathogens and respiratory tract infections.

    PubMed

    Blasi, F

    2004-07-01

    The atypical respiratory pathogens Chlamydia pneumoniae, Mycoplasma pneumoniae and Legionella pneumophila are now recognised as a significant cause of acute respiratory-tract infections, implicated in community-acquired pneumonia, acute exacerbations of chronic bronchitis, asthma, and less frequently, upper respiratory-tract infections. Chronic infection with C. pneumoniae is common among patients with chronic obstructive pulmonary disease and may also play a role in the natural history of asthma, including exacerbations. The lack of a gold standard for diagnosis of these pathogens still handicaps the current understanding of their true prevalence and role in the pathogenesis of acute and chronic respiratory infections. While molecular diagnostic techniques, such as polymerase chain reaction, offer improvements in sensitivity, specificity and rapidity over culture and serology, the need remains for a consistent and reproducible diagnostic technique, available to all microbiology laboratories. Current treatment guidelines for community-acquired pneumonia recognise the importance of atypical respiratory pathogens in its aetiology, for which macrolides are considered suitable first-line agents. The value of atypical coverage in antibiotic therapy for acute exacerbations of chronic bronchitis and exacerbations of asthma is less clear, while there is no evidence to suggest that atypical pathogens should be covered in antibiotic treatment of upper respiratory-tract infections.

  9. Atypical Gifted Learners and Their Characteristics.

    ERIC Educational Resources Information Center

    Diket, Read M., Ed.; Abel, Trudy, Ed.

    This collection of 12 handouts focuses on different categories of atypical gifted learners and their characteristics. The handouts are generally two pages long and present a summary of the literature on the topic, some practical teaching suggestions, and references. The handouts include: (1) "Socioeconomically Disadvantaged Gifted Students" (Pam…

  10. Atypical and Typical Antipsychotics in the Schools

    ERIC Educational Resources Information Center

    Noggle, Chad A.; Dean, Raymond S.

    2009-01-01

    The use of antipsychotic medications within the school-age population is rapidly increasing. Although typical antipsychotics may be used in rare cases, this influx is largely secondary to the availability of the atypical antipsychotics. Reduction of possible adverse effects and increased efficacy represent the primary basis for the atypical…

  11. Atypical Neural Self-Representation in Autism

    ERIC Educational Resources Information Center

    Lombardo, Michael V.; Chakrabarti, Bhismadev; Bullmore, Edward T.; Sadek, Susan A.; Pasco, Greg; Wheelwright, Sally J.; Suckling, John; Baron-Cohen, Simon

    2010-01-01

    The "self" is a complex multidimensional construct deeply embedded and in many ways defined by our relations with the social world. Individuals with autism are impaired in both self-referential and other-referential social cognitive processing. Atypical neural representation of the self may be a key to understanding the nature of such impairments.…

  12. On Atypical Dynamics of Reticulated Systems

    NASA Astrophysics Data System (ADS)

    Boutin, C.; Chesnais, C.; Hans, S.

    2010-09-01

    This paper deals with the dynamics of reticulated beams. Through the homogenization method of periodic discrete media and a systematic use of scaling, the existence of atypical behaviours is established. These latter appear when the elastic moment is balanced by the rotation inertia, and/or when macro dynamics occurs conjointly with inner local dynamics.

  13. Atypical Neural Self-Representation in Autism

    ERIC Educational Resources Information Center

    Lombardo, Michael V.; Chakrabarti, Bhismadev; Bullmore, Edward T.; Sadek, Susan A.; Pasco, Greg; Wheelwright, Sally J.; Suckling, John; Baron-Cohen, Simon

    2010-01-01

    The "self" is a complex multidimensional construct deeply embedded and in many ways defined by our relations with the social world. Individuals with autism are impaired in both self-referential and other-referential social cognitive processing. Atypical neural representation of the self may be a key to understanding the nature of such impairments.…

  14. Infant Perception of Atypical Speech Signals

    ERIC Educational Resources Information Center

    Vouloumanos, Athena; Gelfand, Hanna M.

    2013-01-01

    The ability to decode atypical and degraded speech signals as intelligible is a hallmark of speech perception. Human adults can perceive sounds as speech even when they are generated by a variety of nonhuman sources including computers and parrots. We examined how infants perceive the speech-like vocalizations of a parrot. Further, we examined how…

  15. Infant Perception of Atypical Speech Signals

    ERIC Educational Resources Information Center

    Vouloumanos, Athena; Gelfand, Hanna M.

    2013-01-01

    The ability to decode atypical and degraded speech signals as intelligible is a hallmark of speech perception. Human adults can perceive sounds as speech even when they are generated by a variety of nonhuman sources including computers and parrots. We examined how infants perceive the speech-like vocalizations of a parrot. Further, we examined how…

  16. Atypical Alpha Asymmetry in Adults with ADHD

    ERIC Educational Resources Information Center

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.

    2009-01-01

    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  17. Atypical Ligon Lintless-2 Phenotype in Cotton

    USDA-ARS?s Scientific Manuscript database

    The mutant Li2 is reported to be a dominant single gene mutation in cotton, Gossypium hirsutum L. It has normal vegetative phenotypic morphology and the phenotype of the seed cotton is reported to be fuzzy seed with short fibers. The objective of this research was to report on atypical phenotypes ob...

  18. [Atypical depression in Japan--39 case series].

    PubMed

    Tada, Koji; Yamayoshi, Kayoko; Matsuzaki, Yamato; Kojima, Takuya

    2005-01-01

    In Japan, relatively little attention has been paid to atypical depression, which is defined as the presence of mood reactivity and two of four associated features: hyperphagia, hypersomnia, leaden paralysis, rejection sensitivity. The present study was undertaken to obtain detailed clinical information from patients with a diagnosis of atypical depression. We assessed clinical characteristics of each atypical feature, comorbidity of other psychiatric disorders, presence of a stressful life event, and underlying psychological stress in 39 psychiatric outpatients. We also examined the relationship of interpersonal sensitivity to each atypical feature. Mean age of onset was 22 +/- 6, 74% were female, 20 patients (51%) had comorbid social phobia. Thirty (77%) had hyperphagia and 25 of these were women. Twenty (74%) had hypersomnia. Only seven patients reported daytime sleepiness and others (13) reported difficulty in staying awake due to lack of energy. Nineteen (49%) had leaden paralysis. Thirty-two patients (82%) had rejection sensitivity and this symptom correlated with scores of FNE (fears of negative evaluation), LSAS (Liebowits social anxiety scale) and Brief social phobia scale (BSPA). Seven patients reported disappointment in love as a stressful life event preceding the depressive episode. In patients with comorbid social phobia, loss of confidence due to hypersensitivity to rejection or criticism seemed to be the most important factor as a chronic psychologica stress. Seven patients met criteria for bipolar disorder and five out of seven had comorbid generalized social phobia. The clinical and theoretical implications of these findings were discussed.

  19. Atypical and Typical Antipsychotics in the Schools

    ERIC Educational Resources Information Center

    Noggle, Chad A.; Dean, Raymond S.

    2009-01-01

    The use of antipsychotic medications within the school-age population is rapidly increasing. Although typical antipsychotics may be used in rare cases, this influx is largely secondary to the availability of the atypical antipsychotics. Reduction of possible adverse effects and increased efficacy represent the primary basis for the atypical…

  20. Atypical Alpha Asymmetry in Adults with ADHD

    ERIC Educational Resources Information Center

    Hale, T. Sigi; Smalley, Susan L.; Hanada, Grant; Macion, James; McCracken, James T.; McGough, James J.; Loo, Sandra K.

    2009-01-01

    Introduction: A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha…

  1. Atypical Visuomotor Performance in Children with PDD

    ERIC Educational Resources Information Center

    Schlooz, Wim A. J. M.; Hulstijn, Wouter

    2012-01-01

    Children with autism spectrum disorders (ASD) frequently encounter difficulties in visuomotor tasks, which are possibly caused by atypical visuoperceptual processing. This was tested in children (aged 9-12 years) with pervasive developmental disorder (PDD; including PDD-NOS and Asperger syndrome), and two same-age control groups (Tourette syndrome…

  2. Doses from 222Rn, 226Ra, and 228Ra in groundwater from Guarani aquifer, South America.

    PubMed

    Bonotto, D M

    2004-01-01

    Groundwater samples were analysed for 222Rn, 226Ra, and 228Ra in Guarani aquifer spreading around 1 million km2 within four countries in South America, and it was found that their activity concentrations are lognormally distributed. Population-weighted average activity concentration for these radionuclides allowed to estimate a value either slightly higher (0.13 mSv/year) than 0.1 mSv for the total effective dose or two times higher (0.21 mSv/year) than this limit, depending on the choice of the dose conversion factor. Such calculation adds useful information for the appropriate management of this transboundary aquifer that is socially and economically very important to about 15 million inhabitants living in Brazil, Argentina, Uruguay and Paraguay.

  3. A Comparative Study of Drosophila and Human A-Type Lamins

    PubMed Central

    Schulze, Sandra R.; Curio-Penny, Beatrice; Speese, Sean; Dialynas, George; Cryderman, Diane E.; McDonough, Caitrin W.; Nalbant, Demet; Petersen, Melissa; Budnik, Vivian; Geyer, Pamela K.; Wallrath, Lori L.

    2009-01-01

    Nuclear intermediate filament proteins, called lamins, form a meshwork that lines the inner surface of the nuclear envelope. Lamins contain three domains: an N-terminal head, a central rod and a C-terminal tail domain possessing an Ig-fold structural motif. Lamins are classified as either A- or B-type based on structure and expression pattern. The Drosophila genome possesses two genes encoding lamins, Lamin C and lamin Dm0, which have been designated A- and B-type, respectively, based on their expression profile and structural features. In humans, mutations in the gene encoding A-type lamins are associated with a spectrum of predominantly tissue-specific diseases known as laminopathies. Linking the disease phenotypes to cellular functions of lamins has been a major challenge. Drosophila is being used as a model system to identify the roles of lamins in development. Towards this end, we performed a comparative study of Drosophila and human A-type lamins. Analysis of transgenic flies showed that human lamins localize predictably within the Drosophila nucleus. Consistent with this finding, yeast two-hybrid data demonstrated conservation of partner-protein interactions. Drosophila lacking A-type lamin show nuclear envelope defects similar to those observed with human laminopathies. Expression of mutant forms of the A-type Drosophila lamin modeled after human disease-causing amino acid substitutions revealed an essential role for the N-terminal head and the Ig-fold in larval muscle tissue. This tissue-restricted sensitivity suggests a conserved role for lamins in muscle biology. In conclusion, we show that (1) localization of A-type lamins and protein-partner interactions are conserved between Drosophila and humans, (2) loss of the Drosophila A-type lamin causes nuclear defects and (3) muscle tissue is sensitive to the expression of mutant forms of A-type lamin modeled after those causing disease in humans. These studies provide new insights on the role of lamins in

  4. Atypical leiomyoma: An unusual variant of cutaneous pilar leiomyoma.

    PubMed

    Nocito, Mabel Jimena; Lustia, María Marcela; Luna, Paula Carolina; Cañadas, Nadia Guadalupe; Castellanos Posse, María Laura; Marchesi, Carolina; Carabajal, Graciela; Mazzini, Miguel Angel

    2009-03-15

    Cutaneous atypical leiomyoma is an unusual benign tumor arising from arrector pili muscle that shares histological features with uterine atypical or symplastic leiomyoma: atypical cellularity with pleomorphic nuclei but minimal or no mitosis. Six other cases have been reported so far and, in spite of its name and of being a smooth muscle proliferation, no recurrences nor metastasis have been reported.

  5. Atypical Patterns of Early Attachment: Theory, Research, and Current Directions.

    ERIC Educational Resources Information Center

    Barnett, Douglas; Vondra, Joan I.

    1999-01-01

    Reviews conceptual background on atypical patterns of early attachments, including basic theoretical terms and constructs of attachment theory; the nature and function of the original classification system; notions of "exceptional cases" or "atypical patterns"; and implications of atypicality for both a classification system of attachment behavior…

  6. Diagnostic Approach to Atypical Parkinsonian Syndromes

    PubMed Central

    McFarland, Nikolaus R.

    2016-01-01

    ABSTRACT Purpose of Review: Although increasingly recognized, atypical parkinsonian syndromes remain challenging to diagnose and are underrecognized due to overlap with other parkinsonisms. This article provides a diagnostic approach to atypical parkinsonian syndromes, including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy bodies. The goal of this review is to aid the clinician in recognizing key clinical and pathologic features and to raise awareness of recent advances in diagnostics and treatment. Recent Findings: Diagnostic criteria for atypical parkinsonian syndromes are evolving to encompass increasingly recognized heterogeneity in the presentation of these disorders and information gleamed from clinicopathologic correlations. PSP and CBD in particular now share similar pathologic clinical features and include a number of phenotypic variants. Pathologic diagnoses are increasingly used in clinical practice, and there is frequent reference now by clinicians to tauopathies, including PSP and CBD, and the synucleinopathies, which include MSA and dementia with Lewy bodies (as well as Parkinson disease). Research into biomarkers, including both tissue and imaging modalities and genetics, has the potential to increase disease recognition and make earlier diagnosis and treatment possible. Although novel therapeutics are being studied for atypical parkinsonian syndromes such as PSP, no new breakthrough interventions have emerged for the treatment of PSP, CBD, and MSA. Current therapeutic management for these disorders frequently uses a multidisciplinary team approach. Summary: The approach to atypical parkinsonian syndromes requires recognition of a constellation of overlapping but distinct clinical features that help with identifying and distinguishing them from Parkinson disease and other similar disorders. PMID:27495201

  7. Immune memory in CD4+ CD45RA+ T cells.

    PubMed Central

    Richards, D; Chapman, M D; Sasama, J; Lee, T H; Kemeny, D M

    1997-01-01

    This study addresses the question of whether human peripheral CD4+ CD45RA+ T cells possess antigen-specific immune memory. CD4+ CD45RA+ T cells were isolated by a combination of positive and negative selection. Putative CD4+ CD45RA+ cells expressed CD45RA (98.9%) and contained < 0.1% CD4+ CD45RO+ and < 0.5% CD4+ CD45RA+ CD45RO+ cells. Putative CD45RO+ cells expressed CD45RO (90%) and contained 9% CD45RA+ CD45RO+ and < 0.1% CD4+ CD45RA+ cells. The responder frequency of Dermatophagoides pteronyssinus-stimulated CD4+ CD45RA+ and CD4+ CD45RO+ T cells was determined in two atopic donors and found to be 1:11,314 and 1:8031 for CD4+ CD45RA+ and 1:1463 and 1:1408 for CD4+ CD45RO+ T cells. The responder frequencies of CD4+ CD45RA+ and CD4+ CD45RO+ T cells from two non-atopic, but exposed, donors were 1:78031 and 1:176,903 for CD4+ CD45RA+ and 1:9136 and 1:13,136 for CD4+ CD45RO+ T cells. T cells specific for D. pteronyssinus were cloned at limiting dilution following 10 days of bulk culture with D. pteronyssinus antigen. Sixty-eight clones were obtained from CD4+ CD45RO+ and 24 from CD4+ CD45RA+ T cells. All clones were CD3+ CD4+ CD45RO+ and proliferated in response to D. pteronyssinus antigens. Of 40 clones tested, none responded to Tubercule bacillus purified protein derivative (PPD). No difference was seen in the pattern of interleukin-4 (IL-4) or interferon-gamma (IFN-gamma) producing clones derived from CD4+ CD45RA+ and CD4+ CD45RO+ precursors, although freshly isolated and polyclonally activated CD4+ CD45RA+ T cells produced 20-30-fold lower levels of IL-4 and IFN-gamma than their CD4+ CD45RO+ counterparts. Sixty per cent of the clones used the same pool of V beta genes. These data support the hypothesis that immune memory resides in CD4+ CD45RA+ as well as CD4+ CD45RO+ T cells during the chronic immune response to inhaled antigen. PMID:9301520

  8. Determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in drinking water using a single sample preparation procedure.

    PubMed

    Parsa, Bahman; Obed, Reynaldo N; Nemeth, William K; Suozzo, Gail P

    2005-12-01

    The current federal and New Jersey State regulations have greatly increased the number of gross alpha and radium tests for public and private drinking water supplies. The determination of radium isotopes in water generally involves lengthy and complicated processes. In this study, a new approach is presented for the determination of gross alpha, 224Ra, 226Ra, and 228Ra activities in water samples. The method includes a single sample preparation procedure followed by alpha counting and gamma-ray spectroscopy. The sample preparation technique incorporates an EPA-approved co-precipitation methodology for gross alpha determination with a few alterations and improvements. Using 3-L aliquots of sample, spiked with 133Ba tracer, the alpha-emitting radionuclides are isolated by a BaSO4 and Fe(OH)3 co-precipitation scheme. First the gross alpha-particle activity of the sample is measured with a low-background gas-flow proportional counter, followed by radium isotopes assay by gamma-ray spectroscopy, using the same prepared sample. Gamma-ray determination of 133Ba tracer is used to assess the radium chemical recovery. The 224Ra, 226Ra, and 228Ra activities in the sample are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb/214Bi, and 228Ac, respectively. In cases where 224Ra determination is required, the gamma-ray counting should be performed within 2-4 d from sample collection. To measure 226Ra activity in the sample, the gamma-ray spectroscopy can be repeated 21 d after sample preparation to ensure that 226Ra and its progeny have reached the equilibrium state. At this point, the 228Ac equilibration with parent 228Ra is already established. Analysis of aliquots of de-ionized water spiked with NIST-traceable 230Th, 224Ra, 226Ra, and 228Ra standards demonstrated the accuracy and precision of this method. Various performance evaluation samples were also assayed for gross alpha as well as radium isotope activity determination using this procedure and the

  9. Rainfall Manipulation Plot Study (RaMPS)

    DOE Data Explorer

    Blair, John [Kansas State University; Fay, Phillip [USDA-ARS; Knapp, Alan [Colorado State University; Collins, Scott [University of New Mexico; Smith, Melinda [Yale University

    Rainfall Manipulation Plots facility (RaMPs) is a unique experimental infrastructure that allows us to manipulate precipitation events and temperature, and assess population community, and ecosystem responses in native grassland. This facility allows us to manipulate the amount and timing of individual precipitation events in replicated field plots at the Konza Prairie Long-Term Ecological Research (LTER) site. Questions we are addressing include: • What is the relative importance of more extreme precipitation patterns (increased climatic variability) vs. increased temperatures (increased climatic mean) with regard to their impact on grassland ecosystem structure and function? Both projected climate change factors are predicted to decrease soil water availability, but the mechanisms by which this resource depletion occurs differ. • Will altered precipitation patterns, increased temperatures and their interaction increase opportunities for invasion by exotic species? • Will long-term (6-10 yr) trajectories of community and ecosystem change in response to more extreme precipitation patterns continue at the same rate as initial responses from years 1-6? Or will non-linear change occur as potential ecological thresholds are crossed? And will increased temperatures accelerate these responses? Data sets are available as ASCII files, in Excel spreadsheets, and in SAS format. (Taken from http://www.konza.ksu.edu/ramps/backgrnd.html

  10. Autistics’ Atypical Joint Attention: Policy Implications and Empirical Nuance

    PubMed Central

    Gernsbacher, Morton Ann; Stevenson, Jennifer L.; Khandakar, Suraiya; Goldsmith, H. Hill

    2014-01-01

    Burack and Russo (2008) applaud our approach to understanding autistics’ atypical joint attention (Gernsbacher, Stevenson, Khandakar, & Goldsmith, 2008) but express some concerns about the evidence we drew upon to support our thesis. In response, we underscore the empirical nuance of our thesis—that autistics’ atypical manifestations of joint attention arise from their atypical resistance to distraction, atypical parallel perception, and atypical execution of volitional actions. We recap how our hypothesis derives from fresh interpretations, well-replicated findings, and underlying mechanisms. PMID:25404951

  11. Improved limit on the Ra225 electric dipole moment

    DOE PAGES

    Bishof, Michael; Parker, Richard H.; Bailey, Kevin G.; ...

    2016-08-03

    In this study, octupole-deformed nuclei, such as that of 225Ra, are expected to amplify observable atomic electric dipole moments (EDMs) that arise from time-reversal and parity-violating interactions in the nuclear medium. In 2015 we reported the first “proof-of-principle” measurement of the 225Ra atomic EDM.

  12. 226Ra determination in phosphogypsum by alpha-particle spectrometry

    NASA Astrophysics Data System (ADS)

    Aguado, J. L.; Bolívar, J. P.; García-Tenorio, R.

    1999-01-01

    A radiochemical method for226Ra determination by alpha-particle spectrometry in environmental samples has been developed in our laboratory. The method has been validated by measurements in samples with known concentrations of this radionuclide and it has been applied in studies related to226Ra behaviour in phosphogypsum (the main by-product of producing phosphoric acid from phosphate rocks).

  13. Paraprofessional Staff in Transition: The Sophomore RA Experience

    ERIC Educational Resources Information Center

    Brandt Brecheisen, Shannon M.

    2015-01-01

    The sophomore resident assistant (RA) experience exists at the point where the sophomore experience and the RA position intersect. Sophomore students contend with specific transition struggles and challenges unique to their class standing as they make decisions about their sense of purpose and future career, and those who choose to become RAs face…

  14. Relationship between atypical depression and social anxiety disorder.

    PubMed

    Koyuncu, Ahmet; Ertekin, Erhan; Ertekin, Banu Aslantaş; Binbay, Zerrin; Yüksel, Cağrı; Deveci, Erdem; Tükel, Raşit

    2015-01-30

    In this study, we aimed to investigate the effects of atypical and non-atypical depression comorbidity on the clinical characteristics and course of social anxiety disorder (SAD). A total of 247 patients with SAD were enrolled: 145 patients with a current depressive episode (unipolar or bipolar) with atypical features, 43 patients with a current depressive episode with non-atypical features and 25 patients without a lifetime history of depressive episodes were compared regarding sociodemographic and clinical features, comorbidity rates, and severity of SAD, depression and functional impairment. Thirty four patients with a past but not current history of major depressive episodes were excluded from the comparisons. 77.1% of current depressive episodes were associated with atypical features. Age at onset of SAD and age at initial major depressive episode were lower in the group with atypical depression than in the group with non-atypical depression. History of suicide attempts and bipolar disorder comorbidity was more common in the atypical depression group as well. Atypical depression group has higher SAD and depression severity and lower functionality than group with non-atypical depression. Our results indicate that the presence of atypical depression is associated with more severe symptoms and more impairment in functioning in patients with SAD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  15. Radium Ra 223 dichloride in castration-resistant prostate cancer.

    PubMed

    Joung, J Y; Ha, Y S; Kim, I Y

    2013-08-01

    Radium Ra 223 dichloride (Xofigo®, formerly Alpharadin) is one of the representative α-particle-emitting isotopes that delivers radiation with a higher biological effect to a more localized area. Preclinical studies in mouse, rat and canine models have demonstrated that radium Ra 223 dichloride has a definite skeletal affinity and antitumor effect with a relatively low toxicity on bone marrow. More recently, in a large randomized phase III trial (ALSYMPCA), patients with bone metastasis and castration-resistant prostate cancer (CRPC) received six cycles of 50 kBq/kg of radium Ra 223 dichloride in 4-week intervals. In these men, radium Ra 223 dichloride improved the median overall survival by 3.6 months when compared to the placebo group. Collectively, these results suggest that radium Ra 223 dichloride is a promising candidate for managing bone metastases in patients with CRPC.

  16. Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency

    PubMed Central

    Lévy, Romain; Okada, Satoshi; Béziat, Vivien; Moriya, Kunihiko; Liu, Caini; Chai, Louis Yi Ann; Migaud, Mélanie; Hauck, Fabian; Al Ali, Amein; Cyrus, Cyril; Vatte, Chittibabu; Patiroglu, Turkan; Unal, Ekrem; Ferneiny, Marie; Hyakuna, Nobuyuki; Nepesov, Serdar; Oleastro, Matias; Ikinciogullari, Aydan; Dogu, Figen; Asano, Takaki; Ohara, Osamu; Yun, Ling; Della Mina, Erika; Bronnimann, Didier; Itan, Yuval; Gothe, Florian; Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Tahuil, Natalia; Aytekin, Caner; Salhi, Aicha; Al Muhsen, Saleh; Kobayashi, Masao; Toubiana, Julie; Abel, Laurent; Li, Xiaoxia; Camcioglu, Yildiz; Celmeli, Fatih; Klein, Christoph; AlKhater, Suzan A.; Casanova, Jean-Laurent; Puel, Anne

    2016-01-01

    Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC—autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency—was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface. PMID:27930337

  17. Genetic, immunological, and clinical features of patients with bacterial and fungal infections due to inherited IL-17RA deficiency.

    PubMed

    Lévy, Romain; Okada, Satoshi; Béziat, Vivien; Moriya, Kunihiko; Liu, Caini; Chai, Louis Yi Ann; Migaud, Mélanie; Hauck, Fabian; Al Ali, Amein; Cyrus, Cyril; Vatte, Chittibabu; Patiroglu, Turkan; Unal, Ekrem; Ferneiny, Marie; Hyakuna, Nobuyuki; Nepesov, Serdar; Oleastro, Matias; Ikinciogullari, Aydan; Dogu, Figen; Asano, Takaki; Ohara, Osamu; Yun, Ling; Della Mina, Erika; Bronnimann, Didier; Itan, Yuval; Gothe, Florian; Bustamante, Jacinta; Boisson-Dupuis, Stéphanie; Tahuil, Natalia; Aytekin, Caner; Salhi, Aicha; Al Muhsen, Saleh; Kobayashi, Masao; Toubiana, Julie; Abel, Laurent; Li, Xiaoxia; Camcioglu, Yildiz; Celmeli, Fatih; Klein, Christoph; AlKhater, Suzan A; Casanova, Jean-Laurent; Puel, Anne

    2016-12-20

    Chronic mucocutaneous candidiasis (CMC) is defined as recurrent or persistent infection of the skin, nails, and/or mucosae with commensal Candida species. The first genetic etiology of isolated CMC-autosomal recessive (AR) IL-17 receptor A (IL-17RA) deficiency-was reported in 2011, in a single patient. We report here 21 patients with complete AR IL-17RA deficiency, including this first patient. Each patient is homozygous for 1 of 12 different IL-17RA alleles, 8 of which create a premature stop codon upstream from the transmembrane domain and have been predicted and/or shown to prevent expression of the receptor on the surface of circulating leukocytes and dermal fibroblasts. Three other mutant alleles create a premature stop codon downstream from the transmembrane domain, one of which encodes a surface-expressed receptor. Finally, the only known missense allele (p.D387N) also encodes a surface-expressed receptor. All of the alleles tested abolish cellular responses to IL-17A and -17F homodimers and heterodimers in fibroblasts and to IL-17E/IL-25 in leukocytes. The patients are currently aged from 2 to 35 y and originate from 12 unrelated kindreds. All had their first CMC episode by 6 mo of age. Fourteen patients presented various forms of staphylococcal skin disease. Eight were also prone to various bacterial infections of the respiratory tract. Human IL-17RA is, thus, essential for mucocutaneous immunity to Candida and Staphylococcus, but otherwise largely redundant. A diagnosis of AR IL-17RA deficiency should be considered in children or adults with CMC, cutaneous staphylococcal disease, or both, even if IL-17RA is detected on the cell surface.

  18. Retinoic acid signaling and mouse embryonic stem cell differentiation: Cross talk between genomic and non-genomic effects of RA.

    PubMed

    Rochette-Egly, Cécile

    2015-01-01

    Retinoic acid (RA), the active derivative of vitamin A, a fat-soluble vitamin, plays key roles in cell growth and differentiation by activating nuclear receptors, RARs (α, β and γ), which are ligand dependent regulators of transcription. The past years highlighted several novelties in the field that increased the complexity of RA effects. Indeed, in addition to its classical genomic effects, RA also has extranuclear and non-transcriptional effects. RA induces the rapid and transient activation of kinase cascades, which are integrated in the nucleus via the phosphorylation of RARs at a conserved serine residue located in the N-terminal domain and their coregulators. In order to investigate the relevance of RARs' phosphorylation in cell differentiation, mouse embryonic stem (mES) cells were used as a model. When treated with RA, these pluripotent cells give rise to neuronal cells. Cells invalidated for each RAR were generated as well as stable rescue lines expressing RARs mutated in phosphor acceptor sites. Such a strategy revealed that RA-induced neuronal differentiation involves the RARγ2 subtype and requires RARγ2 phosphorylation. Moreover, in gene expression profiling experiments, the phosphorylated form of RARγ2 was found to regulate a small subset of genes through binding a novel RA response element consisting of two direct repeats with a 7 base pair spacer. These new findings suggest an important role for RAR phosphorylation during cell differentiation, and pave the way for further investigations with other cell types and during embryonic development. This article is part of a Special Issue entitled Linking transcription to physiology in lipodomics. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. RA and FGF Signalling Are Required in the Zebrafish Otic Vesicle to Pattern and Maintain Ventral Otic Identities

    PubMed Central

    Maier, Esther C.; Whitfield, Tanya T.

    2014-01-01

    During development of the zebrafish inner ear, regional patterning in the ventral half of the otic vesicle establishes zones of gene expression that correspond to neurogenic, sensory and non-neural cell fates. FGF and Retinoic acid (RA) signalling from surrounding tissues are known to have an early role in otic placode induction and otic axial patterning, but how external signalling cues are translated into intrinsic patterning during otic vesicle (OV) stages is not yet understood. FGF and RA signalling pathway members are expressed in and around the OV, suggesting important roles in later patterning or maintenance events. We have analysed the temporal requirement of FGF and RA signalling for otic development at stages after initial anteroposterior patterning has occurred. We show that high level FGF signalling acts to restrict sensory fates, whereas low levels favour sensory hair cell development; in addition, FGF is both required and sufficient to promote the expression of the non-neural marker otx1b in the OV. RA signalling has opposite roles: it promotes sensory fates, and restricts otx1b expression and the development of non-neural fates. This is surprisingly different from the earlier requirement for RA signalling in specification of non-neural fates via tbx1 expression, and highlights the shift in regulation that takes place between otic placode and vesicle stages in zebrafish. Both FGF and RA signalling are required for the development of the otic neurogenic domain and the generation of otic neuroblasts. In addition, our results indicate that FGF and RA signalling act in a feedback loop in the anterior OV, crucial for pattern refinement. PMID:25473832

  20. Increased Sensory Processing Atypicalities in Parents of Multiplex ASD Families Versus Typically Developing and Simplex ASD Families.

    PubMed

    Donaldson, Chelsea K; Stauder, Johannes E A; Donkers, Franc C L

    2017-03-01

    Recent studies have suggested that sensory processing atypicalities may share genetic influences with autism spectrum disorder (ASD). To further investigate this, the adolescent/adult sensory profile (AASP) questionnaire was distributed to 85 parents of typically developing children (P-TD), 121 parents from simplex ASD families (SPX), and 54 parents from multiplex ASD families (MPX). After controlling for gender and presence of mental disorders, results showed that MPX parents significantly differed from P-TD parents in all four subscales of the AASP. Differences between SPX and MPX parents reached significance in the Sensory Sensitivity subscale and also in subsequent modality-specific analyses in the auditory and visual domains. Our finding that parents with high genetic liability for ASD (i.e., MPX) had more sensory processing atypicalities than parents with low (i.e., SPX) or no (i.e., P-TD) ASD genetic liability suggests that sensory processing atypicalities may contribute to the genetic susceptibility for ASD.

  1. Prognosis of pneumocystis pneumonia complicated in patients with rheumatoid arthritis (RA) and non-RA rheumatic diseases.

    PubMed

    Yoshida, Yuji; Takahashi, Yuko; Minemura, Nobuyoshi; Ueda, Yo; Yamashita, Hiroyuki; Kaneko, Hiroshi; Mimori, Akio

    2012-08-01

    Clinical presentation of pneumocystis pneumonia (PCP) during immunosuppressive therapy for rheumatic diseases was compared between patients with rheumatoid arthritis (RA; n = 7) and those without RA (non-RA; n = 12) based on a chart review. Both RA and non-RA patients with PCP were treated with methotrexate (n = 7) combined with steroids (n = 6) and/or biologics (n = 4). RA-PCP patients were found to have a higher mortality rate than non-RA-PCP patients (3/7 vs. 0/12, respectively; p = 0.036) due to a later exacerbation of interstitial pneumonia and a higher presentation rate of diffuse pulmonary lesions (4/7 vs. 1/12, respectively; p = 0.036) despite lower mean levels of serum beta-D: -glucan (314 ± 214 vs. 1139 ± 1114 pg/ml, respectively; p = 0.02) that suggested a lower burden of Pneumocystis jirovecii. In conclusion, PCP in RA patients with existing pulmonary lesions may trigger subsequent progression to lethal interstitial pneumonia.

  2. Measurement of 224Ra and 226Ra activities in natural waters using a radon-in-air monitor

    USGS Publications Warehouse

    Kim, G.; Burnett, W.C.; Dulaiova, H.; Swarzenski, P.W.; Moore, W.S.

    2001-01-01

    We report a simple new technique for measuring low-level radium isotopes (224Ra and 226Ra) in natural waters. The radium present in natural waters is first preconcentrated onto MnO2-coated acrylic fiber (Mn fiber) in a column mode. The radon produced from the adsorbed radium is then circulated through a closed air-loop connected to a commercial radon-in-air monitor. The monitor counts alpha decays of radon daughters (polonium isotopes) which are electrostatically collected onto a silicon semiconductor detector. Count data are collected in energy-specific windows, which eliminate interference and maintain very low backgrounds. Radium-224 is measured immediately after sampling via 220Rn (216Po), and 226Ra is measured via 222Rn (218Po) after a few days of ingrowth of 222Rn. This technique is rapid, simple, and accurate for measurements of low-level 224Ra and 226Ra activities without requiring any wet chemistry. Rapid measurements of short-lived 222Rn and 224Ra, along with long-lived 226Ra, may thus be made in natural waters using a single portable system for environmental monitoring of radioactivity as well as tracing of various geochemical and geophysical processes. The technique could be especially useful for the on-site rapid determination of 224Ra which has recently been found to occur at elevated activities in some groundwater wells.

  3. Measurement of 224Ra and 225Ra activities in natural waters using a radon-in-air monitor.

    PubMed

    Kim, G; Burnett, W C; Dulaiova, H; Swarzenski, P W; Moore, W S

    2001-12-01

    We report a simple new technique for measuring low-level radium isotopes (224Ra and 226Ra) in natural waters. The radium present in natural waters is first preconcentrated onto MnO2-coated acrylic fiber (Mn fiber) in a column mode. The radon produced from the adsorbed radium is then circulated through a closed air-loop connected to a commercial radon-in-air monitor. The monitor counts alpha decays of radon daughters (polonium isotopes) which are electrostatically collected onto a silicon semiconductor detector. Count data are collected in energy-specific windows, which eliminate interference and maintain very low backgrounds. Radium-224 is measured immediately after sampling via 220Rn (216Po), and 226Ra is measured via 222Rn 218Po) after a few days of ingrowth of 222Rn. This technique is rapid, simple, and accurate for measurements of low-level 224Ra and 226Ra activities without requiring any wet chemistry. Rapid measurements of short-lived 222Rn and 224Ra, along with long-lived 226Ra, may thus be made in natural waters using a single portable system for environmental monitoring of radioactivity as well as tracing of various geochemical and geophysical processes. The technique could be especially useful for the on-site rapid determination of 224Ra which has recently been found to occur at elevated activities in some groundwater wells.

  4. Herpes zoster - typical and atypical presentations.

    PubMed

    Dayan, Roy Rafael; Peleg, Roni

    2017-08-01

    Varicella- zoster virus infection is an intriguing medical entity that involves many medical specialties including infectious diseases, immunology, dermatology, and neurology. It can affect patients from early childhood to old age. Its treatment requires expertise in pain management and psychological support. While varicella is caused by acute viremia, herpes zoster occurs after the dormant viral infection, involving the cranial nerve or sensory root ganglia, is re-activated and spreads orthodromically from the ganglion, via the sensory nerve root, to the innervated target tissue (skin, cornea, auditory canal, etc.). Typically, a single dermatome is involved, although two or three adjacent dermatomes may be affected. The lesions usually do not cross the midline. Herpes zoster can also present with unique or atypical clinical manifestations, such as glioma, zoster sine herpete and bilateral herpes zoster, which can be a challenging diagnosis even for experienced physicians. We discuss the epidemiology, pathophysiology, diagnosis and management of Herpes Zoster, typical and atypical presentations.

  5. Recurrent conjunctival atypical fibroxanthoma in Pigmentosum Xeroderma.

    PubMed

    Cerdà-Ibáñez, M; Barreiro-González, A; Barranco González, H; Aviñó Martínez, J; Évole-Buselli, M; Harto-Castaño, M Á

    2017-08-23

    A 7 year-old boy with Xeroderma Pigmentosum (XP) and who presents a recurrent conjunctival atypical fibroxanthoma after two surgeries. This is the third procedure and the patient is treated with a surgical excision of the tumour and cryotherapy at the surgical bed. Due to the risk of recurrence, topical Mitomycin C 0,02% was added at post-operative care achieving a good clinical outcome. Surgical exeresis with cryotherapy and topical Mitomycin C is an effective treatment for a case of an atypical fibroxanthoma with a high potential for recurrence and invasion. An ophthalmologic follow-up is required for these patients, as well as general paediatric care and support aids. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  6. [Psychotic forms of atypical autism in children].

    PubMed

    Simashkova, N V

    2006-01-01

    The aim of the study was to determine clinical borders of psychotic forms of atypical autism in children, its psychopathological and age-specific manifestations as well as nosological peculiarities and to specify its pathogenetic features. Eighty patients with childhood endogenous autism, Rett syndrome, fragile X syndrome, Down syndrome have been studied during 14 years. The study showed that psychoses similar by symptoms and course, which are characterized by attacks and regressive-catatonic disorders, may develop in the course of atypical autism. These psychoses develop on the background of dysontogenesis with consequent replacement of the following stages: autistic, regressive, catatonic, with returning to the autistic stage between attacks. Psychopathological similarity of these psychoses in different disorders correlated with EEG changes of the same type (appearance of the marked I-rhythm at the regressive stage of psychosis).

  7. Large-eddy simulation and deduced scaling analysis of Rayleigh Bénard convection up to Ra = 109**

    NASA Astrophysics Data System (ADS)

    Peng, S.-H.; Hanjalic, K.; Davidson, L.

    Large-eddy simulation of turbulent Rayleigh Bénard (RB) convection has been performed for a 6:1:6 open-ended domain for Rayleigh numbers ranging from 6.3 × 105 to 109 at Prandtl number of Pr = 0.71. The scaling analysis based on the LES data shows that the heat transfer follows a single relation of Nu = 0.162 Ra0.286, which is consistent with the scaling law for the hard turbulence regime reported in several earlier experimental and DNS studies. The present LES also supports some earlier experimental and DNS findings that most of characteristic parameters can be scaled reasonably well with Ra number in the considered Ra number range using a single relation. Nonetheless, it is found that the scaling of several quantities shows a sensible offset from a single relation, and could be fitted better with the separate scaling relations for the soft and hard convective turbulence transitioned at about Ra = 4 × 107. It has been argued that the transition, reflected in the scaling relation, may be attributed to the increasing ‘containing effect’ of the plume leaving the horizontal wall on the plume approaching the wall at large Ra numbers in the near-wall region. **This paper is a modified version from the paper presented at the Forth International Symposium of Turbulence and Shear Flow Phenomena (Williamsburg, Virginia, 27 29 June 2005).

  8. The Atypical Calpains: Evolutionary Analyses and Roles in Caenorhabditis elegans Cellular Degeneration

    PubMed Central

    Joyce, Peter I.; Satija, Rahul; Chen, Maozi; Kuwabara, Patricia E.

    2012-01-01

    The calpains are physiologically important Ca2+-activated regulatory proteases, which are divided into typical or atypical sub-families based on constituent domains. Both sub-families are present in mammals, but our understanding of calpain function is based primarily on typical sub-family members. Here, we take advantage of the model organism Caenorhabditis elegans, which expresses only atypical calpains, to extend our knowledge of the phylogenetic evolution and function of calpains. We provide evidence that a typical human calpain protein with a penta EF hand, detected using custom profile hidden Markov models, is conserved in ancient metazoans and a divergent clade. These analyses also provide evidence for the lineage-specific loss of typical calpain genes in C. elegans and Ciona, and they reveal that many calpain-like genes lack an intact catalytic triad. Given the association between the dysregulation of typical calpains and human degenerative pathologies, we explored the phenotypes, expression profiles, and consequences of inappropriate reduction or activation of C. elegans atypical calpains. These studies show that the atypical calpain gene, clp-1, contributes to muscle degeneration and reveal that clp-1 activity is sensitive to genetic manipulation of [Ca2+]i. We show that CLP-1 localizes to sarcomeric sub-structures, but is excluded from dense bodies (Z-disks). We find that the muscle degeneration observed in a C. elegans model of dystrophin-based muscular dystrophy can be suppressed by clp-1 inactivation and that nemadipine-A inhibition of the EGL-19 calcium channel reveals that Ca2+ dysfunction underlies the C. elegans MyoD model of myopathy. Taken together, our analyses highlight the roles of calcium dysregulation and CLP-1 in muscle myopathies and suggest that the atypical calpains could retain conserved roles in myofilament turnover. PMID:22479198

  9. Atypical presentations of malignant otitis externa.

    PubMed

    Vourexakis, Z; Kos, M-I; Guyot, J-P

    2010-11-01

    Malignant otitis externa is a life-threatening infection of the skull base. Its presentation is not always typical. We report three cases of malignant otitis externa which illustrate the diversity of its clinical manifestations and the difficulties in its diagnosis. The perception of malignant otitis externa as an infection caused by Pseudomonas aeruginosa in diabetic patients is not always correct. The adoption of diagnostic criteria could be helpful in identifying atypical cases.

  10. Atypical antipsychotics for insomnia: a systematic review.

    PubMed

    Thompson, Wade; Quay, Teo A W; Rojas-Fernandez, Carlos; Farrell, Barbara; Bjerre, Lise M

    2016-06-01

    Observational evidence suggests that atypical antipsychotics such as quetiapine are increasingly being used to manage insomnia. This is concerning given the uncertain efficacy and potential adverse effects associated with these medications. The objectives of this study are to evaluate the benefits and adverse effects of atypical antipsychotics used specifically for insomnia. The methods used in this study are systematic review and narrative synthesis. The data were collected from PubMed; EMBASE; Cochrane Library; PsycINFO; grey literature; and the manufacturers of risperidone, quetiapine and olanzapine. Adult patients ≥18 years of age using atypical antipsychotics specifically for primary or co-morbid insomnia for ≥ 1 week were compared to those receiving active intervention or placebo. Two independent reviewers screened titles, abstracts and full-text articles; extracted data; and conducted risk-of-bias analysis. Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment was completed. One double-blind randomized controlled trial (n = 13) met the eligibility criteria. Statistically significant differences were not observed from baseline between quetiapine and placebo after 2 weeks for primary insomnia in terms of total sleep time (mean difference (MD) 52.68 min, 95% CI -27.27 to 132.6), reduction in sleep latency (MD 72.44 min, 95% CI -2.65 to 147.5) or improved sleep satisfaction measured with a visual analogue scale out of 100 (MD 6.16, 95% CI -12.32 to 24.64), despite a trend towards improved sleep parameters. The study was rated as very low quality. Very low quality evidence suggests that quetiapine does not significantly improve sleep parameters compared with placebo in primary insomnia, despite a trend towards clinical improvements. Atypical antipsychotics should be avoided in the first-line treatment of primary insomnia until further evidence is available. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Body piercing complicated by atypical mycobacterial infections.

    PubMed

    Ferringer, Tammie; Pride, Howard; Tyler, William

    2008-01-01

    Body piercing is a growing trend, especially in young people, but the literature on complications of piercing consists mostly of case reports involving ear piercing. Previous reported complications of piercing include contact dermatitis, keloids, traumatic tearing, viral transmission, and bacterial infections. We report two patients who presented with atypical mycobacterial infections of body piercing sites. It is important to recognize the association of piercing and mycobacterial infections so that tissue can be obtained for histopathologic examination and appropriate culture.

  12. Atypical Histiocytosis in Red Squirrels (Sciurus vulgaris).

    PubMed

    Smith, S H; Stevenson, K; Del-Pozo, J; Moss, S; Meredith, A

    2017-03-17

    Four red squirrels (Sciurus vulgaris) were subjected to necropsy examination over a 3-year period as part of a broader surveillance study. The squirrels presented with cutaneous, subcutaneous and/or internal swellings and nodules that consisted microscopically of sheets of atypical round cells and multinucleated giant cells. There was moderate anisokaryosis with rare mitoses. Nuclei ranged from oval to indented or C-shaped and some were bizarre, twisted or multilobulated. Many giant cells also had a bizarre morphology, with anisokaryosis within individual cells. Giant cell nuclei were often multilobulated, ring-shaped or segmented. Affected internal organs varied depending on the squirrel, but included lymph node, kidney, intestinal tract and lungs. Representative lesions from each of the four squirrels were negative for acid-fast organisms. Formalin-fixed tissues from all four squirrels and ethanol-fixed tissue from one animal were negative for Mycobacterium by polymerase chain reaction. Immunohistochemically, the majority of mononuclear and multinucleated giant cells in all four squirrels strongly expressed vimentin and class II molecules of the major histocompatibility complex. Otherwise, the atypical mononuclear and multinucleated cells were negative for CD3, Pax-5, Mac387, CD18 and E-cadherin. Based on the combination of cellular morphology, arrangement and immunophenotype, a novel form of atypical histiocytosis is considered most likely in these squirrels, although the exact origin and triggering factors remain uncertain.

  13. Aggressive papillary adenocarcinoma on atypical localization

    PubMed Central

    Balci, Mecdi Gurhan; Tayfur, Mahir; Deger, Ayse Nur; Cimen, Orhan; Eken, Huseyin

    2016-01-01

    Abstract Introduction: Aggressive digital papillary adenocarcinoma (ADPA) is a rare sweat gland tumor that is found on the fingers, toes, and the digits. To date, <100 cases have been reported in the literature. Apart from 1 case reported in the thigh, all of them were on digital or nondigital acral skin. Case presentation: A 67-year-old Caucasian woman was admitted to the hospital due to a mass on the scalp. This lesion was present for almost a year. It was a semimobile cyctic mass that elevated the scalp. There was no change in the skin color. Its dimensions were 1.5 × 1 × 0.6 cm. The laboratory, clinic, and radiologic findings (head x-ray) of the patient were normal. It was evaluated as a benign lesion such as lipoma or epidermal cyst by a surgeon due to a small semimobile mass and no erosion of the skull. It was excised by a local surgery excision. The result of the pathologic examination was aggressive papillary adenocarcinoma. This diagnosis is synonymous with ADPA. Conclusion: In our case, localization was scalp. This localization is the first for this tumor in the literature. In addition, another atypical localization of this tumor (ADPA) is thigh in the literature. This case was presented due to both the rare and atypical localizations. That is why, in our opinion, revision of “digital” term in ADPA is necessary due to seem in atypical localizations like thigh and scalp. PMID:27428196

  14. Altered gut microbiota in RA: implications for treatment.

    PubMed

    Kang, Y; Cai, Y; Zhang, X; Kong, X; Su, J

    2017-06-01

    Rheumatoid arthritis (RA) is an autoimmune disease with progressive joint disorder. The complex interplay of genetic and environmental influences is important for the development of the disease. A growing body of evidence has shed light on the association of dysbiosis of gut microbiota with RA. Certain gut microbial strains have been shown to inhibit or attenuate immune responses in RA experimental models, suggesting that specific species among intestinal commensal bacteria may play either a pathogenic or a protective role in the development of RA. Oral intake of probiotics/prebiotics can therefore represent a therapeutic approach for RA treatment. However, the relevant scientific work has only just begun, and the available data in this field remain limited. Fortunately, utilization of new sequencing technologies allows expanded research on the association of intestinal bacterial flora and human diseases to be attempted. In this review, we summarize the role of gut microbiota in RA progression and address how specific bacterial strains regulate the immune response in disease process. Probiotics/prebiotics in the treatment of RA is also discussed.

  15. Transpupillary thermotherapy for atypical central serous chorioretinopathy

    PubMed Central

    Kawamura, Ryosuke; Ideta, Hidenao; Hori, Hideyuki; Yuki, Kenya; Uno, Tsuyoshi; Tanabe, Tatsurou; Tsubota, Kazuo; Kawasaki, Tsutomu

    2012-01-01

    Background Central serous chorioretinopathy (CSC) has been traditionally treated with laser photocoagulation. We thought that transpupillary thermotherapy (TTT) utilizing a lower temperature than that of conventional laser photocoagulation might minimize permanent retinal and choroidal damage. Studies suggest that undesirable effects on vision due to TTT are minimal even if it is applied to foveal and/or parafoveal lesions when TTT requires a larger irradiation spot. The aim of this study was to evaluate the efficacy of TTT in the management of atypical CSC. Methods We defined atypical CSC as bullous retinal detachment with diffuse or several leakages, severe leakage with fibrin formation under serous retinal detachment, or leakage within a pigment epithelium detachment. Eight consecutive patients with atypical CSC underwent visual acuity testing, ophthalmic examination, color photography, fluorescein angiography, and optical coherence tomography to evaluate the results of transpupillary thermotherapy. Retreatment of atypical CSC was based on ophthalmic examination, optical coherence tomography, and fluorescein angiography. TTT was performed on the leaking spots shown in fluorescein angiography, with a power of 50–250 mW, spot size of 500–1200 μm, and exposure time of 13–60 seconds to minimize retinal damage. Results In five of eight affected eyes, serous detachments completely resolved within 1 month after the initial TTT. One eye had persistent subretinal fluid and required a second TTT treatment. Two eyes showed no resolution of CSC and were treated by conventional photocoagulation. Initial best-corrected visual acuity (BCVA) ranged from 20/600 to 20/20 (mean, 20/40; median, 20/30). Final BCVA ranged from 20/200 to 20/20 (mean, 20/25; median, 20/20). BCVA improved in all cases. Only two eyes with persistent subretinal fibrin and existing retinal pigment epithelial alternations in macular area showed limited improvement of BCVA despite the absence of

  16. Concurrent determination of 224Ra, 226Ra, 228Ra, and unsupported 212Pb in a single analysis for drinking water and wastewater: dissolved and suspended fractions.

    PubMed

    Parsa, Bahman; Obed, Reynaldo N; Nemeth, William K; Suozzo, Gail

    2004-02-01

    A technique has been developed for the measurement of 224Ra, 226Ra, 228Ra, and unsupported 2t2Pb concurrently in a single analysis. The procedure can be applied to both drinking water and wastewater, including the dissolved and suspended fractions of a sample. For drinking water samples, using 3-L aliquots, the radium isotopes are isolated by a fast PbSO4 co-precipitation and then quantified by gamma-ray spectroscopy. The radium isotopes 224Ra, 226Ra, and 228Ra are measured through their gamma-ray-emitting decay products, 212Pb, 214Pb (and/or 214Bi), and 228Ac, respectively. Because of the short half-life of 224Ra (T1/2 = 3.66 d), the precipitate should be counted within 4 d of the sample collection date. In case the measurement of unsupported 212Pb (T1/2 = 10.64 h) is required, the gamma-ray analysis should be initiated as soon as possible, preferably on the same day of collection. The counting is repeated after about 21 d to ensure the 226Ra progeny are in equilibrium with their parent. At this point, the 228Ac equilibration with its 228Ra parent is already established. In the case of samples containing suspended materials, an aliquot of sample is filtered and then the filtrate is treated as described above for drinking water samples. The suspended fraction of sample, collected on the filter, is directly analyzed by gamma-ray spectroscopy with no further chemical separation. Aliquots of de-ionized water spiked with various radium standards were analyzed to check the accuracy and precision of the method. In addition, analysis results of actual samples using this method were compared with the ones performed using U.S. Environmental Protection Agency-approved procedures, and the measured values were in close agreement. This method simplifies the analytical procedures and reduces the labor while achieving the precision, accuracy, and minimum detection concentration requirements of EPA's Regulations.

  17. Chimeric antigen receptor-redirected CD45RA-negative T cells have potent antileukemia and pathogen memory response without graft-versus-host activity.

    PubMed

    Chan, W K; Suwannasaen, D; Throm, R E; Li, Y; Eldridge, P W; Houston, J; Gray, J T; Pui, C-H; Leung, W

    2015-02-01

    Chimeric antigen receptor (CAR)-redirected cellular therapy is an attractive modality for cancer treatment. We hypothesized that allogeneic CAR-engineered CD45RA-negative T cells can control cancer and infection without the risk of graft-versus-host disease (GVHD). We used CD19(+) MLL-rearranged leukemia as prototype because it is an aggressive and generally drug-resistant malignancy. CD45RA(-) cells that were transduced with anti-CD19 CAR containing 4-1BB and CD3ζ signaling domains effectively lysed MLL-rearranged leukemia cell lines and primary blasts in vitro. In a disseminated leukemia mouse model, CAR(+)CD45RA(-) cells significantly reduced leukemia burdens and prolonged overall survival without GVHD. CAR(+) cells were sustainable in blood, and all the treated mice remained leukemia-free even after they were re-challenged with leukemia cells. Despite the transduction process, CD45RA(-) cells retained recall activity both in vitro and in vivo against human pathogens commonly found in cancer patients. In comparison with CD45RA(+) cells, CD45RA(-) cells showed less allogeneic activity in mixed leukocyte reactions and in mouse models. Thus, the use of CAR(+)CD45RA(-) cells can separate GVHD from graft-versus-malignancy effect and infection control. These cells should also be useful in nontransplant settings and may be administered as off-the-shelf third-party cells.

  18. Ra: The Sun for Science and Humanity

    NASA Technical Reports Server (NTRS)

    1996-01-01

    To guide the development of the Ra Strategic Framework, we defined scientific and applications objectives. For our primary areas of scientific interest, we choose the corona, the solar wind, the Sun's effect on the Earth, and solar theory and model development. For secondary areas of scientific interest, we selected sunspots, the solar constant, the Sun's gravitational field, helioseismology and the galactic cosmic rays. We stress the importance of stereoscopic imaging, observations at high spatial, spectral, and temporal resolutions, as well as of long duration measurements. Further exploration of the Sun's polar regions is also important, as shown already by the Ulysses mission. From an applications perspective, we adopted three broad objectives that would derive complementary inputs for the Strategic Framework. These were to identify and investigate: possible application spin-offs from science missions, possible solar-terrestrial missions dedicated to a particular application, and possible future applications that require technology development. The Sun can be viewed as both a source of resources and of threats. Our principal applications focus was that of threat mitigation, by examining ways to improve solar threat monitoring and early warning systems. We compared these objectives to the mission objectives of past, current, and planned international solar missions. Past missions (1962-1980) seem to have been focused on improvement of scientific knowledge, using multiple instrument spacecraft. A ten year gap followed this period, during which the results from previous missions were analyzed and solar study programmes were prepared in international organizations. Current missions (1990-1996) focus on particular topics such as the corona, solar flares, and coronal mass ejections. In planned missions, Sun/Earth interactions and environmental effects of solar activity are becoming more important. The corona is the centre of interest of almost all planned missions

  19. Leaching of 226Ra from components of uranium mill tailings

    USGS Publications Warehouse

    Landa, E.R.

    1991-01-01

    A sequential extraction procedure was used to characterize the geochemical forms of 226Ra retained by mixtures of quartz sand and a variety of fine-grained rock and mineral species. These mixtures had previously been exposed to the sulfuric acid milling liquor of a simulated acid-leach uranium milling circuit. For most test cases, the major fraction of the 226Ra was extracted with 1 mol/1 NH4Cl and was deemed to be exchangeable. However, 226Ra retained by the barite-containing mixture was resistant to both 1 mol/1 NH4Cl and 1 mol/HCHCl extraction. ?? 1991.

  20. Progress toward an EDM measurement in {sup225}Ra.

    SciTech Connect

    Holt, R. J.; Ahmad, I.; Bailey, K.; Graner, B.; Greene, J. P.; Korsch, W.; Lu, Z.-T.; Mueller, P.; O'Connor, T. P.; Sulai, I. A.; Trimble, W. L.

    2010-11-01

    Permanent electric dipole moments (EDMs) in atoms or molecules are a signature of time-reversal and parity violation and represent an important window onto physics beyond the Standard Model. We are developing a next generation EDM search based on laser-cooled and trapped {sup 225}Ra atoms. Due to octupole deformation of the nucleus, {sup 225}Ra is predicted to be two to three orders of magnitude more sensitive to T-violating interactions than {sup 199}Hg, which currently sets the most stringent limits in the nuclear sector. We will discuss progress toward realizing a first EDM measurement for {sup 225}Ra.

  1. The Role of Retinoic Acid (RA) in Spermatogonial Differentiation.

    PubMed

    Busada, Jonathan T; Geyer, Christopher B

    2016-01-01

    Retinoic acid (RA) directs the sequential, but distinct, programs of spermatogonial differentiation and meiotic differentiation that are both essential for the generation of functional spermatozoa. These processes are functionally and temporally decoupled, as they occur in distinct cell types that arise over a week apart, both in the neonatal and adult testis. However, our understanding is limited in terms of what cellular and molecular changes occur downstream of RA exposure that prepare differentiating spermatogonia for meiotic initiation. In this review, we describe the process of spermatogonial differentiation and summarize the current state of knowledge regarding RA signaling in spermatogonia.

  2. Pulmonary cryptococcosis in rheumatoid arthritis (RA) patients: comparison of imaging characteristics among RA, acquired immunodeficiency syndrome, and immunocompetent patients.

    PubMed

    Yanagawa, Noriyo; Sakai, Fumikazu; Takemura, Tamiko; Ishikawa, Satoru; Takaki, Yasunobu; Hishima, Tsunekazu; Kamata, Noriko

    2013-11-01

    The imaging characteristics of cryptococcosis in rheumatoid arthritis (RA) patients were analyzed by comparing them with those of acquired immunodeficiency syndrome (AIDS) and immunocompetent patients, and the imaging findings were correlated with pathological findings. Two radiologists retrospectively compared the computed tomographic (CT) findings of 35 episodes of pulmonary cryptococcosis in 31 patients with 3 kinds of underlying states (10 RA, 12 AIDS, 13 immunocompetent), focusing on the nature, number, and distribution of lesions. The pathological findings of 18 patients (8 RA, 2 AIDS, 8 immunocompetent) were analyzed by two pathologists, and then correlated with imaging findings. The frequencies of consolidation and ground glass attenuation (GGA) were significantly higher, and the frequency of peripheral distribution was significantly lower in the RA group than in the immunocompetent group. Peripheral distribution was less common and generalized distribution was more frequent in the RA group than in the AIDS group. The pathological findings of the AIDS and immunocompetent groups reflected their immune status: There was lack of a granuloma reaction in the AIDS group, and a complete granuloma reaction in the immunocompetent group, while the findings of the RA group varied, including a complete granuloma reaction, a loose granuloma reaction and a hyper-immune reaction. Cases with the last two pathologic findings were symptomatic and showed generalized or central distribution on CT. Cryptococcosis in the RA group showed characteristic radiological and pathological findings compared with the other 2 groups. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  3. Microbial release of 226Ra2+ from (Ba,Ra)SO4 sludges from uranium mine wastes.

    PubMed Central

    Fedorak, P M; Westlake, D W; Anders, C; Kratochvil, B; Motkosky, N; Anderson, W B; Huck, P M

    1986-01-01

    226Ra2+ is removed from uranium mine effluents by coprecipitation with BaSO4. (Ba,Ra)SO4 sludge samples from two Canadian mine sites were found to contain active heterotrophic populations of aerobic, anaerobic, denitrifying, and sulfate-reducing bacteria. Under laboratory conditions, sulfate reduction occurred in batch cultures when carbon sources such as acetate, glucose, glycollate, lactate, or pyruvate were added to samples of (Ba,Ra)SO4 sludge. No external sources of nitrogen or phosphate were required for this activity. Further studies with lactate supplementation showed that once the soluble SO4(2-) in the overlying water was depleted, Ba2+ and 226Ra2+ were dissolved from the (Ba,Ra)SO4 sludge, with the concurrent production of S2-. Levels of dissolved 226Ra2+ reached approximately 400 Bq/liter after 10 weeks of incubation. Results suggest that the ultimate disposal of these sludges must maintain conditions to minimize the activity of the indigenous sulfate-reducing bacteria to ensure that unacceptably high levels of 226Ra2+ are not released to the environment. PMID:3752993

  4. Coelimination and Survival in Gene Network Evolution: Dismantling the RA-Signaling in a Chordate.

    PubMed

    Martí-Solans, Josep; Belyaeva, Olga V; Torres-Aguila, Nuria P; Kedishvili, Natalia Y; Albalat, Ricard; Cañestro, Cristian

    2016-09-01

    The bloom of genomics is revealing gene loss as a pervasive evolutionary force generating genetic diversity that shapes the evolution of species. Outside bacteria and yeast, however, the understanding of the process of gene loss remains elusive, especially in the evolution of animal species. Here, using the dismantling of the retinoic acid metabolic gene network (RA-MGN) in the chordate Oikopleura dioica as a case study, we combine approaches of comparative genomics, phylogenetics, biochemistry, and developmental biology to investigate the mutational robustness associated to biased patterns of gene loss. We demonstrate the absence of alternative pathways for RA-synthesis in O. dioica, which suggests that gene losses of RA-MGN were not compensated by mutational robustness, but occurred in a scenario of regressive evolution. In addition, the lack of drastic phenotypic changes associated to the loss of RA-signaling provides an example of the inverse paradox of Evo-Devo. This work illustrates how the identification of patterns of gene coelimination-in our case five losses (Rdh10, Rdh16, Bco1, Aldh1a, and Cyp26)-is a useful strategy to recognize gene network modules associated to distinct functions. Our work also illustrates how the identification of survival genes helps to recognize neofunctionalization events and ancestral functions. Thus, the survival and extensive duplication of Cco and RdhE2 in O. dioica correlated with the acquisition of complex compartmentalization of expression domains in the digestive system and a process of enzymatic neofunctionalization of the Cco, while the surviving Aldh8 could be related to its ancestral housekeeping role against toxic aldehydes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  5. Characterization of the atypical lymphocytes in African swine fever

    PubMed Central

    Karalyan, Z. A.; Ter-Pogossyan, Z. R.; Abroyan, L. O.; Hakobyan, L. H.; Avetisyan, A. S.; Karalyan, N. Yu; Karalova, E. M.

    2016-01-01

    Aim: Atypical lymphocytes usually described as lymphocytes with altered shape, increased DNA amount, and larger size. For analysis of cause of genesis and source of atypical lymphocytes during African swine fever virus (ASFV) infection, bone marrow, peripheral blood, and in vitro model were investigated. Materials and Methods: Atypical lymphocytes under the influence of ASFV were studied for morphologic, cytophotometric, and membrane surface marker characteristics and were used in vivo and in vitro models. Results: This study indicated the increased size, high metabolic activity, and the presence of additional DNA amount in atypical lymphocytes caused by ASFV infection. Furthermore, in atypical lymphocytes, nuclear-cytoplasmic ratio usually decreased, compared to normal lymphocytes. In morphology, they looking like lymphocytes transformed into blasts by exposure to mitogens or antigens in vitro. They vary in morphologic detail, but most of them are CD2 positive. Conclusions: Our data suggest that atypical lymphocytes may represent an unusual and specific cellular response to ASFV infection. PMID:27536044

  6. Atypical neoglottis after supracricoid laryngectomy: a morphological and functional analysis.

    PubMed

    Alicandri-Ciufelli, Matteo; Piccinini, Alessia; Bergamini, Giuseppe; Ruberto, Marco; Ghidini, Angelo; Marchioni, Daniele; Presutti, Livio

    2011-07-01

    The objective of this study was to analyze atypical neoglottis after supracricoid subtotal laryngectomy (SSL) from a morphological and functional point-of-view using retrospective case series reviewin a Tertiary university referral center setting. From May 2003 until January 2010, 106 patients underwent SSL (CHEP, CHP, THEP, THP) for laryngeal cancer, in the Otolaryngology Department of the University Hospital of Modena. We performed a retrospective analysis of recorded videos in our database of patients who underwent SSL. Patients with atypical neoglottis were included in the study. Six patients with atypical neoglottis were identified and morphologically evaluated. The functional outcomes were collected and analyzed. Atypical neoglottis may form after SSL, in particular in the case of CHEP. In most cases, these atypical conformations are due to anomalous positioning of the epiglottis, or involvement of the lateral pharyngeal wall in the sphincteric and vibratory function of the neoglottis. Atypical neoglottis formation seems to guarantee adequate functional outcomes in terms of vocal and swallowing performance.

  7. Seasonal changes in submarine groundwater discharge to coastal salt ponds estimated using 226Ra and 228Ra as tracers

    USGS Publications Warehouse

    Hougham, A.L.; Moran, S.B.; Masterson, J.P.; Kelly, R.P.

    2008-01-01

    Submarine groundwater discharge (SGD) to coastal southern Rhode Island was estimated from measurements of the naturally-occurring radioisotopes 226Ra (t1/2 = 1600??y) and 228Ra (t1/2 = 5.75??y). Surface water and porewater samples were collected quarterly in Winnapaug, Quonochontaug, Ninigret, Green Hill, and Pt. Judith-Potter Ponds, as well as nearly monthly in the surface water of Rhode Island Sound, from January 2002 to August 2003; additional porewater samples were collected in August 2005. Surface water activities ranged from 12-83??dpm 100??L- 1 (60??dpm = 1??Bq) and 21-256??dpm 100??L- 1 for 226Ra and 228Ra, respectively. Porewater 226Ra activities ranged from 16-736??dpm 100??L- 1 (2002-2003) and 95-815??dpm 100??L- 1 (2005), while porewater 228Ra activities ranged from 23-1265??dpm 100??L- 1. Combining these data with a simple box model provided average 226Ra-based submarine groundwater fluxes ranging from 11-159??L m- 2 d- 1 and average 228Ra-derived fluxes of 15-259??L m- 2 d- 1. Seasonal changes in Ra-derived SGD were apparent in all ponds as well as between ponds, with SGD values of 30-472??L m- 2 d- 1 (Winnapaug Pond), 6-20??L m- 2 d- 1 (Quonochontaug Pond), 36-273??L m- 2 d- 1 (Ninigret Pond), 29-76??L m- 2 d- 1 (Green Hill Pond), and 19-83??L m- 2 d- 1 (Pt. Judith-Potter Pond). These Ra-derived fluxes are up to two orders of magnitude higher than results predicted by a numerical model of groundwater flow, estimates of aquifer recharge for the study period, and values published in previous Ra-based SGD studies in Rhode Island. This disparity may result from differences in the type of flow (recirculated seawater versus fresh groundwater) determined using each technique, as well as variability in porewater Ra activity. ?? 2007 Elsevier B.V. All rights reserved.

  8. Validation of FLARE-RA, a Self-Administered Tool to Detect Recent or Current Rheumatoid Arthritis Flare.

    PubMed

    Fautrel, Bruno; Morel, Jacques; Berthelot, Jean-Marie; Constantin, Arnaud; De Bandt, Michel; Gaudin, Philippe; Maillefert, Jean-Francis; Meyer, Olivier; Pham, Thao; Saraux, Alain; Solau-Gervais, Elisabeth; Vittecoq, Olivier; Wendling, Daniel; Erpelding, Marie-Line; Guillemin, Francis

    2017-02-01

    To validate the measurement properties and the detection performance of the FLARE-RA questionnaire in a longitudinal prospective study. To validate the FLARE-RA self-administered questionnaire, we conducted a prospective trial in rheumatoid arthritis (RA) patients to document: 1) content and construct validity by factor analysis, convergent validity by Pearson's correlation with routine assessment of patient index data (Routine Assessment of Patient Index Data 3 [RAPID-3] questionnaire), RA Impact of Disease (RAID) score, Disease Activity Score in 28 joints (DAS28), and Health Assessment Questionnaire (HAQ), 2) reliability (intraclass correlation coefficient [ICC] and Bland-Altman plot), and 3) feasibility of use. Patients were examined and questionnaires were collected at baseline and 3 months, and every week in between for RAPID-3. We recruited 138 patients from 13 centers: 81.9% women, mean age 57.4 years, mean DAS28 2.9, mean C-reactive protein level 6.2 mg/liter, 84.4% rheumatoid factor positive, 78.0% anti-citrullinated protein antibody positive, and 78.8% with erosive disease. At baseline, the mean ± SD FLARE-RA score was 2.3 ± 2.3. The content and construct validity of FLARE-RA was good. A substantial floor effect, but no ceiling effect, was observed. Principal components analysis revealed 1 domain disentangled in 2 subdomains: physical and emotional. The FLARE-RA total score was correlated with the DAS28 (r = 0.63, P < 0.001), RAID (r = 0.80, P < 0.001), RAPID-3 (r = 0.77, P < 0.001), and HAQ (r = 0.53, P < 0.001). The ICC for reliability was 0.94 (95% confidence interval 0.92-0.96). The FLARE-RA self-administered questionnaire represents a valid and valuable instrument to detect RA flare between visits to the physician. © 2016, American College of Rheumatology.

  9. Rapid determination of 226Ra in emergency urine samples

    DOE PAGES

    Maxwell, Sherrod L.; Culligan, Brian K.; Hutchison, Jay B.; ...

    2014-02-27

    A new method has been developed at the Savannah River National Laboratory (SRNL) that can be used for the rapid determination of 226Ra in emergency urine samples following a radiological incident. If a radiological dispersive device event or a nuclear accident occurs, there will be an urgent need for rapid analyses of radionuclides in urine samples to ensure the safety of the public. Large numbers of urine samples will have to be analyzed very quickly. This new SRNL method was applied to 100 mL urine aliquots, however this method can be applied to smaller or larger sample aliquots as needed.more » The method was optimized for rapid turnaround times; urine samples may be prepared for counting in <3 h. A rapid calcium phosphate precipitation method was used to pre-concentrate 226Ra from the urine sample matrix, followed by removal of calcium by cation exchange separation. A stacked elution method using DGA Resin was used to purify the 226Ra during the cation exchange elution step. This approach combines the cation resin elution step with the simultaneous purification of 226Ra with DGA Resin, saving time. 133Ba was used instead of 225Ra as tracer to allow immediate counting; however, 225Ra can still be used as an option. The rapid purification of 226Ra to remove interferences using DGA Resin was compared with a slightly longer Ln Resin approach. A final barium sulfate micro-precipitation step was used with isopropanol present to reduce solubility; producing alpha spectrometry sources with peaks typically <40 keV FWHM (full width half max). This new rapid method is fast, has very high tracer yield (>90 %), and removes interferences effectively. The sample preparation method can also be adapted to ICP-MS measurement of 226Ra, with rapid removal of isobaric interferences.« less

  10. Concentration of {sup 226}Ra in human teeth

    SciTech Connect

    Yamamoto, Masayoishi; Ueno, Kaoru; Hinoide, Moriyo; Ohkubo, Yoshiteru

    1994-11-01

    {sup 226}Ra concentrations in human teeth from several cities, mainly Tokyo, Japan, were determined with emphasis on the measurement of low-level {sup 226}Ra by alpha-ray spectrometry following chemical separation. No appreciable differences in {sup 226}Ra concentration were found among various permanent teeth samples of different age groups in Tokyo. The mean {sup 226}Ra concentration for Tokyo was 0.51 {+-} 0.06 mBq (g CA){sup -1}. {sup 226}Ra concentration [mean: 0.67 {+-} 0.11 mBq (g Ca){sup -1}] in teeth in western regions of the country was statistically higher than that [mean: 0.48 {+-} 0.09 mBq (g Ca){sup -1}] in eastern ones. The mean {sup 226}Ra concentration [0.51 mBq (g CA){sup -1}] in teeth from Tokyo was less than the concentration [1.11 mBq (g CA){sup -1}] reported for vertebral bone samples of this city. 27 refs., 1 fig., 5 tabs.

  11. [Expression of telomerase genes in mamary atypical ductal hyperplasia].

    PubMed

    Song, Min; Mi, Xiaoyi; Li, Bailin; Zhu, Jijiang; Gao, Yingxian; Cui, Shuang; Song, Jiye

    2002-02-01

    To investigate the relationship of telomerase genes and the malignant transformation of atypical mammary ductal hyperplasia. Telomerase genes hTR and hTRT in 50 cases of mammary hyperplasia (the cases included 6 benign hyperplasia, 9 mild atypical hyperplasia, 12 medium atypical hyperplasia, 23 severe atypical hyperplasia) and 26 cases of breast carcinoma were detected by in situ hybridization. The expression of hTR and hTRT mRNA were weak or negative in benign hyperplasia (1/6, 0), weaker in mild-moderate atypical hyperplasia (2/9, 1/9, 4/12, and 3/12), strong in severe atypical hyperplasia (14/23, 60.9% and 12/23, 52.1%), while very strong expression (23/26, 88.5% and 21/25, 80.8%) in carcinoma of the breast. The difference between mild-moderate atypical hyperplasia, invasive ductal carcinoma and severe atypical hyperplasia was significant (P < 0.05) and the difference between severe atypital hyperplasia and intraductal carcinoma was not significant (P > 0.05). Telmerase genes (hTR, hTRT) expression is closely related to the malignant transformation of atypical hyperplasia. The reactivated telomerase may play a crucial role in the development of breast cancer.

  12. Atypical causes of nontraumatic intracranial subarachnoid hemorrhage.

    PubMed

    Carvi y Nievas, Mario Nazareno; Archavlis, Eleftherios

    2009-05-01

    To analyze the management and outcome of patients presenting with atypical causes of intracranial subarachnoid hemorrhage (SAH). We performed a review of our last 820 nontraumatic-SAH patients and analyzed the management and outcome of patients where the SAH origin was not a ruptured aneurysm. The Glasgow Outcome Scale (GOS) was used to assess outcome 3 months after event. Thirty-two patients had atypical causes of SAH. In 15 patients with Hunt and Hess (H&H) scores from 1 to 3 without focal neurological deficit (FND), 8 perimesencephalic non-aneurysmal SAH, 4 blood coagulation disorders, 1 sinus thrombosis, 1 vasculitis, and 1 unknown-origin-SAH (UOS) were diagnosed. Fourteen (93%) of these 15 patients were conservatively treated. In 17 patients with H&H scores from 3 to 5 and FND, 8 tumors, 1 cavernoma, 1 sinus thrombosis, 1 arteriovenous malformation, 1 blood coagulation disorders, 2 UOS, and 3 dural fistulas were diagnosed. Fifteen (88%) of these 17 patients were interventionally treated. The neurological condition 3 months later was good (GOS 4 and 5) in 12 of the 15 cases (80%) admitted with low-H&H scores, as well as in 13 of the 17 cases (76%) admitted with high-H&H scores. Three patients died and four developed a severe disability. Patients presenting with atypical causes of SAH and high-H&H scores at admission are likely to harbor an intracranial organic process producing the bleeding. Despite this poor initial condition, their 3-month outcome can be similar to those of patients with low-H&H scores if the origin of the bleeding is properly treated.

  13. Trisomy 18 with unilateral atypical ectrodactyly

    SciTech Connect

    Rogers, R.C.

    1994-01-01

    Becerra et al. recently reported on an infant with multiple congenital anomalies who had trisomy 18. This preterm infant presented with bilateral ectrodactyly of feet, small cleft palate, esophageal atresia with associated tracheoesophageal fistula, congenital heart disease and other anomalies. The authors referenced article by Castle and Bernstein, in which they reported a male with trisomy 18 and cleft foot as well as a review of the literature which showed 2 other infants with trisomy 18 and ectrodactyly of the feet. An additional case of trisomy 18 associated with multiple congenital anomalies, including unilaterial, atypical ectrodactyly of the left foot.

  14. Atypical neuroimaging in Wilson’s disease

    PubMed Central

    Patell, Rushad; Dosi, Rupal; Joshi, Harshal K; Storz, Dennis

    2014-01-01

    Wilson's disease is a rare metabolic disease involving copper metabolism. Neuroimaging plays an important part in evaluation of patients with a neuropsychiatric presentation. We present a case of a 14-year-old girl with atypical confluent white matter disease and cystic degeneration on MRI, with a rapidly progressive course, who succumbed to complications despite treatment with trientine. Wilson's disease should be considered as a differential for leucoencephalopathy in young patients with progressive neurological disease for its early recognition and optimum outcome. PMID:24907221

  15. Atypical outcome in attention deficit hyperactivity disorder.

    PubMed

    Schmidt, K; Freidson, S

    1990-07-01

    This report describes the course of psychiatric illness in two boys. Both presented with attention deficit hyperactivity disorder (ADHD) in midchildhood; after puberty, one boy developed a schizophrenic illness while the other boy developed a major affective illness. Although the major ADHD outcome studies have found no link between the childhood occurrence of ADHD and psychosis in adulthood, occasionally such a link may exist. The theoretical and practical implications of this finding are discussed. It should be noted, however, that such outcome is highly atypical and very rare.

  16. Massive Hemoptysis Caused by Atypical Behcet's Disease

    PubMed Central

    Lee, Won-Young; Hoon, Choi Se

    2014-01-01

    Pulmonary and/or bronchial aneurysm with systemic thrombophlebitis can be seen in the case of both Behcet's disease and Hughes-Stovin syndrome. These two diseases may be indistinguishable since the clinical, radiological, and histopathological findings are similar in both cases. In particular, from the perspective of pulmonary involvement, hemoptysis is the leading cause of death in both conditions and is followed by aneurysmal rupture. Here, we report a case in which surgical resection was performed for a patient presenting recurrent hemoptysis as an atypical presentation of Behcet's disease. PMID:24782975

  17. [Treatment of atypical and neurotic depression].

    PubMed

    Leitner, P; Umann, E; Kulawik, H

    1986-10-01

    Hitherto it has not been usual to talk in the German language about the therapy-oriented concept of two forms of the progress of atypical depression (Type A and Type V). The characteristic symptom of Type A is angst, together with phobias, physical complaints, etc. In Type V there are vegetative symptoms, often towards evening (Hypersomnia, difficulty in getting to sleep, increased appetite, increased weight, increased libido), accompanied by hysterical extrovert personality traits, and of intermittent occurrence. These clinical pictures are amenable to psychopharmalogical therapy. In conformity with the assumption of "somatic accommodation" treatment with antidepressives is recommended in the case neurotic depression, too, at least in the initial stages of treatment.

  18. Amyloid imaging in dementias with atypical presentation.

    PubMed

    Wolk, David A; Price, Julie C; Madeira, Charles; Saxton, Judy A; Snitz, Beth E; Lopez, Oscar L; Mathis, Chester A; Klunk, William E; DeKosky, Steven T

    2012-09-01

    With the potential emergence of disease specific therapies, an accurate biomarker of Alzheimer's Disease pathology is needed in cases in which the underlying etiology is uncertain. We explored the potential value of amyloid imaging in patients with atypical presentations of dementia. Twenty-eight patients with atypical dementia underwent positron emission tomography imaging with the amyloid imaging tracer Pittsburgh compound B (PiB). Twenty-six had [18F]fluoro-2-deoxy-D-glucose positron emission tomography scans. After extensive clinical evaluation, this group of patients generated considerable diagnostic uncertainty and received working diagnoses that included possible Alzheimer's disease (AD), focal dementias (e.g., posterior cortical atrophy [PCA]), or cases in which no clear diagnostic category could be determined (dementia of uncertain etiology). Patients were classified as PiB-positive, PiB-negative, or PiB-intermediate, based on objective criteria. Anterior-posterior and left-right indices of PiB and [18F]fluoro-2-deoxy-D-glucose uptake were calculated to examine differences in distribution of amyloid pathology and metabolic changes associated with clinical phenotype. Eleven patients (39%) were PiB positive, 16 were PiB negative (57%), and one (4%) was PiB intermediate. By diagnostic category, three of 10 patients (30%) with dementia of uncertain etiology, one of five (20%) with primary progressive aphasia, three of five (60%) with PCA, and four of seven (57%) with possible AD were PiB positive. Brain metabolism of both PiB-positive and PiB-negative patients was generally similar by phenotype, but appeared to differ from typical AD. PCA patients also appeared to differ in their relative distribution of PiB compared with typical AD, consistent with their atypical phenotype. AD pathology is frequently present in atypical presentations of dementia and can be identified by amyloid imaging. Clinical phenotype is more related to the pattern of cerebral

  19. Atypical intrauterine parvo b19 infection.

    PubMed

    Drašković, Biljana; Uram-Benka, Anna; Fabri, Izabela; Velisavljev Filipović, Gordana

    2012-08-01

    Human parvovirus B19 is a single-stranded DNA virus. During pregnancy, parvovirus B19 infection can be asymptomatic or cause a variety of signs of fetal damage, fetal anemia, nonimmune hydrops fetalis, spontaneous abortion and can result in fetal death. Recent improvements in diagnosing parvovirus infections and the availability of intrauterine transfusion have reduced the overall rate of fetal loss after maternal exposure. There is an approximately 30% risk of vertical transmission and 1% of hydrops. We report of the first case of vertical parvovirus B19 infection with atypical manifestations in our clinic. The neonate had pleural effusion associated with anaemia.

  20. 76 FR 63701 - Culturally Significant Objects Imported for Exhibition Determinations: “Johan Zoffany RA: Society...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-13

    ... for Exhibition Determinations: ``Johan Zoffany RA: Society Observed'' SUMMARY: Notice is hereby given... objects to be included in the exhibition ``Johan Zoffany RA: Society Observed,'' imported from abroad...

  1. Extending the application of DSAM to atypical stopping media

    NASA Astrophysics Data System (ADS)

    Das, S.; Samanta, S.; Bhattacharjee, R.; Raut, R.; Ghugre, S. S.; Sinha, A. K.; Garg, U.; Chakrabarti, R.; Mukhopadhyay, S.; Dhal, A.; Raju, M. Kumar; Madhavan, N.; Muralithar, S.; Singh, R. P.; Suryanarayana, K.; Rao, P. V. Madhusudhana; Palit, R.; Saha, S.; Sethi, J.

    2017-01-01

    A methodology that manifolds the possibilities of level lifetime measurements using the Doppler Shift Attenuation Method (DSAM), and extends its application beyond the conventional thin-target-on-thick-elemental-backing setups, is presented. This has been achieved primarily through application of the TRIM code to simulate the stopping of the recoils in the target and the backing media. Using the TRIM code, primarily adopted in the domain of materials research, in the context of lifetime analysis require rendition of the simulation results into a representation that appropriately incorporates the nuances of nuclear reaction along with the associated kinematics, besides the transformation from an energy-coordinate representation to a velocity-direction profile as required for lifetime analysis. The present development makes it possible to practice DSAM in atypical experimental scenarios such as those using molecular or multi-layered target and/or backing as the stopping medium. These aberrant cases, that were beyond representation in the customary Doppler shape analysis can, in the light of the present work, be conveniently used in the DSAM based investigations. The new approach has been validated through re-examination of known lifetimes measured both in the conventional as well as in the deviant setups.

  2. Atypical developmental of dorsal and ventral attention networks in autism.

    PubMed

    Farrant, Kristafor; Uddin, Lucina Q

    2016-07-01

    Individuals with autism spectrum disorders (ASD) exhibit early and lifelong impairments in attention across multiple domains. While the disorder is known to affect attention processes, very little is currently known about the brain networks underlying attention in ASD, and even less is known about whether these atypicalities persist across the lifespan. We used functional connectivity analysis applied to resting state functional magnetic resonance imaging (fMRI) data to explore the dorsal (DAN) and ventral (VAN) attention networks in two separate age cohorts of children and adults with and without ASD. We find significant developmental differences in functional connectivity of brain regions that are critical for attention in children and adults with ASD. Specifically, children with ASD show hyper-connectivity of regions-of-interest (ROIs) in both attention networks compared with both typically developing (TD) children and adults with ASD. In contrast, adults with ASD show hypo-connectivity of these networks compared with neurotypical adults. These findings are consistent with the notion that consideration of developmental stage is critical in studies of functional connectivity in ASD. This study further illustrates diverging developmental patterns for top-down and bottom-up attention systems in autism. © 2015 John Wiley & Sons Ltd.

  3. Determining groundwater Ra end-member values for the estimation of the magnitude of submarine groundwater discharge using Ra isotope tracers

    NASA Astrophysics Data System (ADS)

    Cho, Hyung-Mi; Kim, Guebuem

    2016-04-01

    Radium isotopes (228Ra and 226Ra) are excellent tracers of submarine groundwater discharge (SGD). To estimate SGD magnitudes, information on the end-member values of Ra concentrations in groundwater is critical; however, the distribution characteristics of Ra in coastal aquifers are poorly understood. In this study, we show that Ra concentrations in coastal groundwater are primarily dependent on salinity based on the data (n > 500) obtained from global coastal aquifers, although previous end-member calculations averaged all Ra concentrations without considering salinity. If we assume that SGD is composed mainly of seawater infiltrating the aquifer, previous estimates of SGD for the Atlantic Ocean and the global ocean were overestimated twofold to threefold. This may be similar for other applications using different Ra isotopes. Our study highlights that the end-members of Ra isotopes in groundwater should be carefully considered when estimating SGD using Ra isotope mass balances in the ocean.

  4. Pontine Infarct Presenting with Atypical Dental Pain: A Case Report.

    PubMed

    Goel, Rajat; Kumar, Sanjeev; Panwar, Ajay; Singh, Abhishek B

    2015-01-01

    Orofacial pain' most commonly occurs due to dental causes like caries, gingivitis or periodontitis. Other common causes of 'orofacial pain' are sinusitis, temporomandibular joint(TMJ) dysfunction, otitis externa, tension headache and migraine. In some patients, the etiology of 'orofacial pain' remains undetected despite optimal evaluation. A few patients in the practice of clinical dentistry presents with dental pain without any identifiable dental etiology. Such patients are classified under the category of 'atypical odontalgia'. 'Atypical odontalgia' is reported to be prevalent in 2.1% of the individuals. 'Atypical orofacial pain' and 'atypical odontalgia' can result from the neurological diseases like multiple sclerosis, trigeminal neuralgia and herpes infection. Trigeminal neuralgia has been frequently documented as a cause of 'atypical orofacial pain' and 'atypical odontalgia'. There are a few isolated case reports of acute pontine stroke resulting in 'atypical orofacial pain' and 'atypical odontalgia'. However, pontine stroke as a cause of atypical odontalgia is limited to only a few cases, hence prevalence is not established. This case is one, where a patient presented with acute onset atypical dental pain with no identifiable dental etiology, further diagnosed as an acute pontine infarct on neuroimaging. A 40 years old male presented with acute onset, diffuse teeth pain on right side. Dental examination was normal. Magnetic resonance imaging(MRI) of the brain had an acute infarct in right pons near the trigeminal root entry zone(REZ). Pontine infarct presenting with dental pain as a manifestation of trigeminal neuropathy, has rarely been reported previously. This stresses on the importance of neuroradiology in evaluation of atypical cases of dental pain.

  5. The subtlety of sex-atypicality.

    PubMed

    Dunne, M P; Bailey, J M; Kirk, K M; Martin, N G

    2000-12-01

    Memories of sex-atypical behavior and interests in childhood usually differ between homosexual and heterosexual people. However, variation within these broad groups has not previously been explored in detail, especially among women. We utilized data from a postal survey of a nationwide sample of Australian adult twins (n = 4,901, age range: 19-52 years). Among men, 15.2% reported homosexual behavior (ever), 11.5% said they had been sexually attracted to the same sex, and 6.4% said they were not heterosexual; the corresponding figures for women were 7.9, 10.6, and 3.5%. A continuous measure of childhood gender nonconformity (CGN) was sensitive to slight variations in homosexual attraction and behavior. In particular, among both men and women who identified as heterosexual, there were significant differences between "complete" heterosexuals and those who admitted to only one or a few same-sex behaviors but no homosexual attraction. Among men, CGN scores distinguished between heterosexuals who admitted to same-sex behavior only and those who admitted to some homosexual attraction. The sexual subgroups also differed on a measure of gender atypicality in adulthood. Implications for developmental theories of sexuality are discussed.

  6. Wernicke encephalopathy with atypical magnetic resonance imaging.

    PubMed

    Liou, Kuang-Chung; Kuo, Shu-Fan; Chen, Lu-An

    2012-11-01

    Wernicke encephalopathy (WE) is a medical emergency caused by thiamine (vitamin B1) deficiency. Typical clinical manifestations are mental change, ataxia, and ocular abnormalities. Wernicke encephalopathy is an important differential diagnosis in all patients with acute mental change. However, the disorder is greatly underdiagnosed. Clinical suspicion, detailed history taking, and neurologic evaluations are important for early diagnosis. Magnetic resonance imaging (MRI) is currently considered the diagnostic method of choice. Typical MRI findings of WE are symmetrical involvement of medial thalamus, mammillary body, and periaqueductal gray matter. Prompt thiamine supplement is important in avoiding unfavorable outcomes. Here, we report a case of alcoholic WE with typical clinical presentation but with atypical MRI. Axial fluid-attenuated inversion recovery images showing symmetrical hyperintensity lesions in dentate nuclei of cerebellum, olivary bodies, and dorsal pons. Although atypical MRI findings are more common in nonalcoholic WE, it can also occur in alcoholic WE. This article is aimed to highlight the potential pitfalls in diagnosing acute mental change, the importance of clinical suspicion, and early treatment in WE.

  7. Atypical inheritance: new horizons for neurology.

    PubMed

    Wilson, G N

    1994-11-01

    Rediscovery of Mendel's laws produced an enthusiastic new discipline at the turn of this century. The eugenics movement had many disciples in the United States, and it should be noted that the term "final solution" was first used by the National Association of Charities and Corrections in the 1920s. American advocates of eugenics accomplished mass sterilization of retarded individuals and the prohibition of Jewish immigration from Germany during World War II. It is interesting that the close of this century has produced a similar revolution in genetics. These newer genetic mechanisms expose the major fallacy of eugenics: traits may be genetic without showing obvious familial transmission. Sanctions against reproduction or immigration thus will have little effect on the gene pool. The clinical implications of atypical inheritance are enormous. Almost every medical disorder must be reinvestigated for evidence of subtle chromosome changes, for worsening in progressive generations, and for influence of parental origin. The classical Mendelian model taught that extreme and rare phenotypes shed light on more frequent ones, hence the definition of genes responsible for hypercholesterolemia, for Alzheimer disease, and for amyotrophic lateral sclerosis. Atypical inheritance mechanisms further enhance this approach, bringing all of neurology under the light of genetic technology. The lure for the practitioner, then, is not the hyperbole of molecular biology; it is the need for a seasoned hand so emphasized by Huntington's disease and the duty to protect the next century from disasters of the current one.

  8. Inverse agonist properties of atypical antipsychotic drugs.

    PubMed

    Akam, Elizabeth; Strange, Philip G

    2004-06-01

    Mechanisms of action of several atypical antipsychotic drugs have been examined at the D(2) dopamine receptor expressed in CHO cells. The drugs tested were found to exhibit inverse agonist activity at the D(2) dopamine receptor based on their effects to potentiate forskolin-stimulated cyclic AMP (cAMP) accumulation. Each of the antipsychotic drugs tested (clozapine, olanzapine, quetiapine and risperidone) increased cAMP accumulation to the same extent. The increase in cAMP was also similar to that seen with typical antipsychotic drugs. Inverse agonism at the D(2) dopamine receptor seems, therefore, to be a property common to all classes of antipsychotic drugs. The effect of sodium ions on the binding of the drugs to the receptor was also assessed. Each of the atypical antipsychotic drugs tested here bound with higher affinity in the absence of sodium ions. Previous studies have shown that some antipsychotic drugs are insensitive to sodium ions and some bind with higher affinity in the presence of sodium ions. Given that all of these antipsychotic drugs are inverse agonists, it may be concluded that this sodium ion sensitivity is unrelated to mechanisms of inverse agonism.

  9. Radium isotopes ((226)Ra and (228)Ra) in Na-Cl type groundwaters from Tohoku District (Aomori, Akita and Yamagata Prefectures) in Japan.

    PubMed

    Tomita, Jumpei; Zhang, Jing; Yamamoto, Masayoshi

    2014-11-01

    A total of 28 Na-Cl type groundwater samples were collected from Aomori, Akita and Yamagata Prefectures, in the Tohoku District of Japan, and their radium isotope ((226)Ra and (228)Ra) concentrations were measured along with their chemical components and stable isotope ratios (δ(2)H and δ(18)Os). The (226)Ra concentrations in groundwater samples varied widely, ranging from 8.8 to 1587 mBq kg(-1). These concentrations showed an increasing tendency with the increase of the total dissolved solid (TDS) contents. The (228)Ra/(226)Ra activity ratios were in the range from 0.3 to 4.2, with most data being around 0.5-2. These ratios were within those of (232)Th/(238)U found in granitic and related rocks and so on in Japan, indicating that Ra isotopes mainly ejected into the groundwater by the alpha-recoil process. The relationship between (226)Ra and other parameters suggested that Ra isotopes in groundwater samples in this study were mainly constrained by adsorption-desorption reactions depending on salinity with wide variation. Clear correlation between (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS observed in sulfate-free groundwater samples indicated that Ra isotopes of them were constrained by adsorption-desorption reactions depending on salinity under reducing condition. In contrast, relationship of (226)Ra-Ca, (226)Ra-Sr, (226)Ra-Ba and (226)Ra-TDS in sulfate-containing groundwater samples varied widely, and then, removal or enhanced mobility of Ra isotopes of them were observed.

  10. Typical and Atypical Dementia Family Caregivers: Systematic and Objective Comparisons

    ERIC Educational Resources Information Center

    Nichols, Linda O.; Martindale-Adams, Jennifer; Burns, Robert; Graney, Marshall J.; Zuber, Jeffrey

    2011-01-01

    This systematic, objective comparison of typical (spouse, children) and atypical (in-law, sibling, nephew/niece, grandchild) dementia family caregivers examined demographic, caregiving and clinical variables. Analysis was of 1,476 caregivers, of whom 125 were atypical, from the Resources for Enhancing Alzheimer's Caregivers Health (REACH I and II)…

  11. Atypical appendicitis: the impact of CT and its management.

    PubMed

    See, T C; Watson, C J E; Arends, M J; Ng, C S

    2008-04-01

    Acute appendicitis is a diagnosis that can be made on clinical symptoms and signs but can often be extremely challenging. Difficulties arise particularly when the presentation is atypical, and this can lead to untoward sequelae. In this review, we present the range of presentations of atypical appendicitis, the variety of management options and the potential value of CT.

  12. Atypical Patterns of Early Attachment: Discussion and Future Directions.

    ERIC Educational Resources Information Center

    Barnett, Douglas; Butler, Christine M.; Vondra, Joan I.

    1999-01-01

    Discusses the role of a study of atypical patterns of attachment behavior for the understanding of attachment theory, parenting, and child socioemotional development. Notes that research on atypical attachments suggest that the developmental integration of biological, psychological, and behavioral responses is more profoundly dependent on social-…

  13. Typical and Atypical Dementia Family Caregivers: Systematic and Objective Comparisons

    ERIC Educational Resources Information Center

    Nichols, Linda O.; Martindale-Adams, Jennifer; Burns, Robert; Graney, Marshall J.; Zuber, Jeffrey

    2011-01-01

    This systematic, objective comparison of typical (spouse, children) and atypical (in-law, sibling, nephew/niece, grandchild) dementia family caregivers examined demographic, caregiving and clinical variables. Analysis was of 1,476 caregivers, of whom 125 were atypical, from the Resources for Enhancing Alzheimer's Caregivers Health (REACH I and II)…

  14. Association of a bovine prion gene haplotype with atypical BSE

    USDA-ARS?s Scientific Manuscript database

    Transmissible spongiform encephalopathies (TSEs), also known as prion diseases, are a class of fatal neurodegenerative disorders that occur in humans, ruminants, cats, and mink. Three distinct TSEs afflict cattle: classical bovine spongiform encephalopathy (BSE), atypical H-type BSE, and atypical ...

  15. Mutation in the transcriptional regulator PhoP contributes to avirulence of Mycobacterium tuberculosis H37Ra strain.

    PubMed

    Lee, Jong Seok; Krause, Roland; Schreiber, Jörg; Mollenkopf, Hans-Joachim; Kowall, Jane; Stein, Robert; Jeon, Bo-Young; Kwak, Jeong-Yeon; Song, Min-Kyong; Patron, Juan Pablo; Jorg, Sabine; Roh, Kyoungmin; Cho, Sang-Nae; Kaufmann, Stefan H E

    2008-02-14

    Attenuated strains of mycobacteria can be exploited to determine genes essential for their pathogenesis and persistence. To this goal, we sequenced the genome of H37Ra, an attenuated variant of Mycobacterium tuberculosis H37Rv strain. Comparison with H37Rv revealed three unique coding region polymorphisms. One polymorphism was located in the DNA-binding domain of the transcriptional regulator PhoP, causing the protein's diminished DNA-binding capacity. Temporal gene expression profiles showed that several genes with reduced expression in H37Ra were also repressed in an H37Rv phoP knockout strain. At later time points, genes of the dormancy regulon, typically expressed in a state of nonreplicating persistence, were upregulated in H37Ra. Complementation of H37Ra with H37Rv phoP partially restored its persistence in a murine macrophage infection model. Our approach demonstrates the feasibility of identifying minute but distinct differences between isogenic strains and illustrates the consequences of single point mutations on the survival stratagem of M. tuberculosis.

  16. The genome of Chelonid herpesvirus 5 harbors atypical genes

    USGS Publications Warehouse

    Ackermann, Mathias; Koriabine, Maxim; Hartmann-Fritsch, Fabienne; de Jong, Pieter J.; Lewis, Teresa D.; Schetle, Nelli; Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Leong, Jo-Ann C.

    2012-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV; ChHV5) is believed to be the causative agent of fibropapillomatosis (FP), a neoplastic disease of marine turtles. While clinical signs and pathology of FP are well known, research on ChHV5 has been impeded because no cell culture system for its propagation exists. We have cloned a BAC containing ChHV5 in pTARBAC2.1 and determined its nucleotide sequence. Accordingly, ChHV5 has a type D genome and its predominant gene order is typical for the varicellovirus genus within thealphaherpesvirinae. However, at least four genes that are atypical for an alphaherpesvirus genome were also detected, i.e. two members of the C-type lectin-like domain superfamily (F-lec1, F-lec2), an orthologue to the mouse cytomegalovirus M04 (F-M04) and a viral sialyltransferase (F-sial). Four lines of evidence suggest that these atypical genes are truly part of the ChHV5 genome: (1) the pTARBAC insertion interrupted the UL52 ORF, leaving parts of the gene to either side of the insertion and suggesting that an intact molecule had been cloned. (2) Using FP-associated UL52 (F-UL52) as an anchor and the BAC-derived sequences as a means to generate primers, overlapping PCR was performed with tumor-derived DNA as template, which confirmed the presence of the same stretch of “atypical” DNA in independent FP cases. (3) Pyrosequencing of DNA from independent tumors did not reveal previously undetected viral sequences, suggesting that no apparent loss of viral sequence had happened due to the cloning strategy. (4) The simultaneous presence of previously known ChHV5 sequences and F-sial as well as F-M04 sequences was also confirmed in geographically distinct Australian cases of FP. Finally, transcripts of F-sial and F-M04 but not transcripts of lytic viral genes were detected in tumors from Hawaiian FP-cases. Therefore, we suggest that F-sial and F-M04 may play a role in FP pathogenesis

  17. The Genome of Chelonid Herpesvirus 5 Harbors Atypical Genes

    PubMed Central

    Ackermann, Mathias; Koriabine, Maxim; Hartmann-Fritsch, Fabienne; de Jong, Pieter J.; Lewis, Teresa D.; Schetle, Nelli; Work, Thierry M.; Dagenais, Julie; Balazs, George H.; Leong, Jo-Ann C.

    2012-01-01

    The Chelonid fibropapilloma-associated herpesvirus (CFPHV; ChHV5) is believed to be the causative agent of fibropapillomatosis (FP), a neoplastic disease of marine turtles. While clinical signs and pathology of FP are well known, research on ChHV5 has been impeded because no cell culture system for its propagation exists. We have cloned a BAC containing ChHV5 in pTARBAC2.1 and determined its nucleotide sequence. Accordingly, ChHV5 has a type D genome and its predominant gene order is typical for the varicellovirus genus within the alphaherpesvirinae. However, at least four genes that are atypical for an alphaherpesvirus genome were also detected, i.e. two members of the C-type lectin-like domain superfamily (F-lec1, F-lec2), an orthologue to the mouse cytomegalovirus M04 (F-M04) and a viral sialyltransferase (F-sial). Four lines of evidence suggest that these atypical genes are truly part of the ChHV5 genome: (1) the pTARBAC insertion interrupted the UL52 ORF, leaving parts of the gene to either side of the insertion and suggesting that an intact molecule had been cloned. (2) Using FP-associated UL52 (F-UL52) as an anchor and the BAC-derived sequences as a means to generate primers, overlapping PCR was performed with tumor-derived DNA as template, which confirmed the presence of the same stretch of “atypical” DNA in independent FP cases. (3) Pyrosequencing of DNA from independent tumors did not reveal previously undetected viral sequences, suggesting that no apparent loss of viral sequence had happened due to the cloning strategy. (4) The simultaneous presence of previously known ChHV5 sequences and F-sial as well as F-M04 sequences was also confirmed in geographically distinct Australian cases of FP. Finally, transcripts of F-sial and F-M04 but not transcripts of lytic viral genes were detected in tumors from Hawaiian FP-cases. Therefore, we suggest that F-sial and F-M04 may play a role in FP pathogenesis. PMID:23056373

  18. Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for 223Ra and 225Ra for targeted alpha therapy

    DOE PAGES

    Rojas, J. V.; Woodward, J. D.; Chen, N.; ...

    2015-03-19

    Targeted alpha therapy (TAT) has the potential for killing specific tumor cells with minimum collateral damage to surrounding healthy tissue. Radionuclides such as 223Ra, 225Ra, and 225Ac are of special interest for radiotherapeutic applications as they emit multiple -particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. Methods. In this work, core and core+2 shells (NPs with 2 additional layers of cold LaPO4 deposited on the core surfaces) LaPO4 nanoparticles (NPs)more » were synthesized containing either 223Ra or 225Ra/225Ac and the retention of the parents and daughters within the NPs in vitro was investigated. Results. The NPs crystallized in rhabdophane phase with mean diameters of 3.4 and 6.3 nm for core and core+2 shells, respectively. The core LaPO 4 NPs retained up to 88% of 223Ra over 35 days. However, in the core+2 shell NPs, the retention of 223Ra and its daughter, 211Pb, was improved to > 99.9% over 27 days. Additionally, the retention of 225Ra/225Ac parents was > 99.98% and ~80% for the 221Fr and 213Bi daughters over 35 days for the core+2 shell NPs. Conclusions. These results suggest that LaPO4 NPs are potentially effective carriers of radium isotopes.« less

  19. A putative RA-like region in the brain of the scale-backed antbird, Willisornis poecilinotus (Furnariides, Suboscines, Passeriformes, Thamnophilidae)

    PubMed Central

    de Lima, Jamily L.R.; Soares, Fabricio A.; Remedios, Ana C.S.; Thom, Gregory; Wirthlin, Morgan; Aleixo, Alexandre; Schneider, Maria Paula C.; Mello, Claudio V.; Schneider, Patricia N.

    2015-01-01

    The memorization and production of song in songbirds share important parallels with the process of speech acquisition in humans. In songbirds, these processes are dependent on a group of specialized telencephalic nuclei known as the song system: HVC (used as a proper name), RA (robust nucleus of arcopallium), LMAN (lateral magnocellular nucleus of the nidopallium) and striatal Area X. A recent study suggested that the arcopallium of the Sayornis phoebe, a non vocal learner suboscine species, contains a nucleus with some properties similar to those of songbird RA, suggesting that the song system may have been present in the last common ancestor of these groups. Here we report morphological and gene expression evidence that a region with some properties similar to RA is present in another suboscine, the Amazonian endemic Willisornis poecilinotus. Specifically, a discrete domain with a distinct Nissl staining pattern and that expresses the RA marker RGS4 was found in the arcopallium where the oscine RA is localized. Our findings, combined with the previous report on the S. phoebe, suggest that an arcopallial region with some RA-like properties was present in the ancestor of both Suboscines infraorders Tyranni and Furnarii, and is possibly an ancestral feature of Passeriformes. PMID:26500428

  20. The "RA" Expeditions: The Archaeological and Anthropological Background. The "RA" Expeditions: The Coriolis Effect. The "RA" Expeditions: The Papyrus Reed. Learning Experiences for Coastal and Oceanic Awareness Studies, Nos. 211, 212, 213. [Project COAST].

    ERIC Educational Resources Information Center

    Delaware Univ., Newark. Coll. of Education.

    Included are three units related to coastal and oceanic awareness. These are: (1) The "RA" Expeditions: The Archaeological and Anthropological Background; (2) The "RA" Expeditions: The Coriolis Effect; and (3) The "RA" Expeditions: The Papyrus Reed. Each of the three units are designed for students in grades 6-12.…

  1. The "RA" Expeditions: The Archaeological and Anthropological Background. The "RA" Expeditions: The Coriolis Effect. The "RA" Expeditions: The Papyrus Reed. Learning Experiences for Coastal and Oceanic Awareness Studies, Nos. 211, 212, 213. [Project COAST].

    ERIC Educational Resources Information Center

    Delaware Univ., Newark. Coll. of Education.

    Included are three units related to coastal and oceanic awareness. These are: (1) The "RA" Expeditions: The Archaeological and Anthropological Background; (2) The "RA" Expeditions: The Coriolis Effect; and (3) The "RA" Expeditions: The Papyrus Reed. Each of the three units are designed for students in grades 6-12.…

  2. [Atypical cerebellar neurocytoma resembling a hemangioblastoma. A case report].

    PubMed

    Lista Martínez, Olalla; Rivas López, Luis Alfredo; Pombo Otero, Jorge Francisco; Amaro Cendón, Santiago; Bravo García, Christian; Villa Fernández, Juan Manuel

    2014-01-01

    Through August 2013, 105 cases of intracranial extraventricular neurocytoma (EVN) had been described; 6% were located in cerebellum and 22% were atypical EVN. A rare morphologic form of neurocytoma, atypical EVN has had only 24 cases reported to date. Its prognosis is poorer than the typical central neurocytoma. This case report describes an atypical cerebellar EVN, a form that has not been reported yet, hence the interest of this article. We emphasise its cystic nature and mural nodule, in an infrequent presentation. EVN are low-incidence tumours that we need to take into consideration when making the differential diagnosis of cystic cerebellar lesions with mural nodule. Given that the prognosis of atypical EVNs depends on the atypical nature and on the grade of resection, medical follow up has to be more constant, due to the greater degree of recurrence. Copyright © 2013 Sociedad Española de Neurocirugía. Published by Elsevier España. All rights reserved.

  3. An efficient and simple method for measuring (226)Ra using the scintillation cell in a delayed coincidence counting system (RaDeCC).

    PubMed

    Waska, Hannelore; Kim, Seolwon; Kim, Guebuem; Peterson, Richard N; Burnett, William C

    2008-12-01

    A delayed coincidence counter (RaDeCC), developed to determine ultra-low levels of (223)Ra (half life = 11.1 days) and (224)Ra (half life = 3.6 days) in seawater, was adapted to measure (226)Ra (half life = 1622 years). After pre-concentration of Ra from seawater onto MnO(2)-coated fiber we show in this study that the (226)Ra activity can be determined using the RaDeCC's ability to record alpha decay of its daughters as total counts. For sufficient ingrowth of (222)Rn, the Mn-fiber is hermetically sealed in a column for a few days. Then, the ingrown (222)Rn is circulated through the RaDeCC air-loop system followed by shutting down of the pump and closure of the scintillation cell for equilibration. Counting may be completed within a few hours for seawater samples. Sample measurements with this method agreed well with data obtained using gamma-ray spectrometry. This proves that a set of Ra isotopes ((223)Ra, (224)Ra, and (226)Ra), commonly used for geophysical studies such as mixing rates of different water masses and submarine groundwater discharge, can be efficiently and rapidly measured using the RaDeCC.

  4. Imaging the neurobiological substrate of atypical depression by SPECT.

    PubMed

    Pagani, Marco; Salmaso, Dario; Nardo, Davide; Jonsson, Cathrine; Jacobsson, Hans; Larsson, Stig A; Gardner, Ann

    2007-01-01

    Neurobiological abnormalities underlying atypical depression have previously been suggested. The purpose of this study was to explore differences at functional brain imaging between depressed patients with and without atypical features and healthy controls. Twenty-three out-patients with chronic depressive disorder recruited from a service for patients with audiological symptoms were investigated. Eleven fulfilled the DSM-IV criteria for atypical depression (mood reactivity and at least two of the following: weight gain, hypersomnia, leaden paralysis and interpersonal rejection sensitivity). Twenty-three healthy subjects served as controls. Voxel-based analysis was applied to explore differences in (99m)Tc-HMPAO uptake between groups. Patients in the atypical group had a higher prevalence of bilateral hearing impairment and higher depression and somatic distress ratings at the time of SPECT. Significantly higher tracer uptake was found bilaterally in the atypical group as compared with the non-atypicals in the sensorimotor (Brodmann areas, BA1-3) and premotor cortex in the superior frontal gyri (BA6), in the middle frontal cortex (BA8), in the parietal associative cortex (BA5, BA7) and in the inferior parietal lobule (BA40). Significantly lower tracer distribution was found in the right hemisphere in the non-atypicals compared with the controls in BA6, BA8, BA44, BA45 and BA46 in the frontal cortex, in the orbito-frontal cortex (BA11, BA47), in the postcentral parietal cortex (BA2) and in the multimodal association parietal cortex (BA40). The differences found between atypical and non-atypical depressed patients suggest different neurobiological substrates in these patient groups. The putative links with the clinical features of atypical depression are discussed. These findings encourage the use of functional neuroimaging in psychiatric disorders.

  5. Quantum-state-selective decay spectroscopy of 213Ra

    NASA Astrophysics Data System (ADS)

    Lorenz, Ch.; Sarmiento, L. G.; Rudolph, D.; Ward, D. E.; Block, M.; Heßberger, F. P.; Ackermann, D.; Andersson, L.-L.; Cortés, M. L.; Droese, C.; Dworschak, M.; Eibach, M.; Forsberg, U.; Golubev, P.; Hoischen, R.; Kojouharov, I.; Khuyagbaatar, J.; Nesterenko, D.; Ragnarsson, I.; Schaffner, H.; Schweikhard, L.; Stolze, S.; Wenzl, J.

    2017-09-01

    An experimental scheme combining the mass resolving power of a Penning trap with contemporary decay spectroscopy has been established at GSI Darmstadt. The Universal Linear Accelerator (UNILAC) at GSI Darmstadt provided a 48Ca beam impinging on a thin 170Er target foil. Subsequent to velocity filtering of reaction products in the Separator for Heavy Ion reaction Products (SHIP), the nuclear ground state of the 5 n evaporation channel 213Ra was mass-selected in SHIPTRAP, and the 213Ra ions were finally transferred into an array of silicon strip detectors surrounded by large composite germanium detectors. Based on comprehensive geant4 simulations and supported by theoretical calculations, the spectroscopic results call for a revision of the decay path of 213Ra, thereby exemplifying the potential of a combination of a mass-selective Penning trap device with a dedicated nuclear decay station and contemporary geant4 simulations.

  6. Synthesis and characterization of lanthanum phosphate nanoparticles as carriers for (223)Ra and (225)Ra for targeted alpha therapy.

    PubMed

    Rojas, J V; Woodward, J D; Chen, N; Rondinone, A J; Castano, C H; Mirzadeh, S

    2015-07-01

    Targeted alpha therapy (TAT) has the potential for killing micro-metastases with minimum collateral damage to surrounding healthy tissue. In-vivo generator radionuclides, such as(223)Ra, (225)Ra, and (225)Ac, are of special interest for radiotherapeutic applications as they emit multiple α-particles during their decay. Utilizing appropriate carriers capable of retaining both the parent radioisotope as well as daughter products is important for the effective delivery of the radioisotope to the tumor site while mitigating global in vivo radiotoxicity. In this work, LaPO4 core and core+2 shells nanoparticles (NPs) (NPs with 2 layers of cold LaPO4 deposited on the core surfaces) were synthesized containing either (223)Ra or(225)Ra/(225)Ac, and the retention of the parents and daughters within the NPs in vitro was investigated. Core LaPO4 NPs were synthesized in aqueous solution by reacting 1 equivalent of La(NO3)3, along with few microcuries of either (223)Ra or (225)Ra/(225)Ac, with 1 equivalent of sodium tripolyphosphate (TPP) under moderate heating and purified by membrane dialysis. Core-shell NPs were also synthesized with one (core+1 shell) and two (core+2 shells) cold LaPO4 layers deposited onto the radioactive cores. The NPs were then characterized by transmission electron microscopy (TEM) and powder x-ray diffraction (XRD). Identification and quantification of radioactive parents and daughters released from the NPs in vitro were investigated using gamma-ray spectroscopy. XRD and TEM analysis revealed that the NPs crystallized in the rhabdophane phase with mean diameters of 3.4 and 6.3nm for core and core+2 shells, respectively. The core LaPO4 NPs retained up to 88% of (223)Ra over 35days. However, in the core+2 shells NPs, the retention of (223)Ra and its daughter, (211)Pb, was improved to >99.9% over 27days. Additionally, the retention of (225)Ra/(225)Ac parents was >99.98% and ~80% for the (221)Fr and (213)Bi daughters over 35days for the core+2 shells NPs

  7. Case Report: Atypical Cornelia de Lange Syndrome

    PubMed Central

    Leanza, Vito; Rubbino, Gabriella; Leanza, Gianluca

    2015-01-01

    Cornelia de Lange Syndrome (CdLS) (also called Bushy Syndrome or Amsterdam dwarfism), is a genetic disorder that can lead to several alterations. This disease affects both physical and neuropsychiatric development. The various abnormalities include facial dysmorphia (arched eyebrows, synophrys, depressed nasal bridge, long philtrum, down-turned angles of the mouth), upper-extremity malformations, hirsutism, cardiac defects, and gastrointestinal alterations. The prevalence of this syndrome is approximately one per 15,000. Ultrasound is not the perfect means to diagnose CdLS, however, many abnormalities can be detected prenatally by scrupulous image observation. We report an atypical CdLS case characterized by increased nuchal translucency in the first trimester, normal karyotype, saddle nose, micrognathia with receding jaw, low set ears, facies senilis, arthrogryposis of the hands, absence of the Aranzio ductus venous, dilatation of gallbladder and bowel, a unique umbilical artery, increased volume of amniotic fluid, and intrauterine growth retardation ending with the interruption of pregnancy. PMID:26834972

  8. Clinical grand rounds: atypical hemolytic uremic syndrome.

    PubMed

    Hodgkins, Kavita S; Bobrowski, Amy E; Lane, Jerome C; Langman, Craig B

    2012-01-01

    Atypical hemolytic uremic syndrome (aHUS) is a rare, lifethreatening, chronic, genetic disease of uncontrolled alternative pathway complement activation. The understanding of the pathophysiology and genetics of this disease has expanded over recent decades and promising new developments in the management of aHUS have emerged. Regardless of the cause of aHUS, with or without a demonstrated mutation or autoantibody, blockade of terminal complement activation through C5 is of high interest as a mechanism to ameliorate the disease. Eculizumab, an existing monoclonal antibody directed against C5 with high affinity, prevents the perpetuation of the downstream activation of the complement cascade and the damage caused by generation of the anaphylotoxin C5a and the membrane attack complex C5b-9, by blocking C5 cleavage. We report the successful use of eculizumab in a patient after kidney transplantation and discuss the disease aHUS.

  9. Linguistic recycling in typical and atypical interaction.

    PubMed

    Perkins, Michael R

    2014-01-01

    I present evidence that linguistic "recycling" - i.e., the redeployment of linguistic material from prior utterances during conversation - is a striking and prevalent feature not only of interaction between typical speakers, but also, and notably, of interaction involving the communication impaired. In the latter case, recycling may sometimes be used as a compensatory communicative resource when linguistic ability is compromised. Despite its prevalence, however, recycling has largely been ignored by clinical linguists. In addition to providing illustrations of linguistic recycling across a range of communication disorders, I also examine how it is subserved by phenomena such as priming, short-term memory and alignment. I subsequently argue for a shift in perspective that puts recycling at the heart of our perception of how typical and atypical interaction works, and suggest a number of potential benefits for clinical linguistics, ranging from the way we understand and analyse communication disorders to how we assess and treat them.

  10. Treatment of Morbidity with Atypical Chest Pain

    PubMed Central

    Cott, Arthur

    1987-01-01

    The appropriate management of atypical chest pain requires an integration of medical and behavioural treatments. Unnecessary medicalization can increase morbidity. A sensitivity to the behavioural factors contributing to symptoms and disability may reduce both. The purpose of this paper is to provide physicians with a cognitive-behavioural perspective of the nature of morbidity and disability associated with chronic chest discomfort; some strategies for detecting heretofore unsuspected disability associated with chronic chest pain and related discomfort in patients with organic findings (both cardiac and non-cardiac), as well those with no identifiable disease process or organic cause; and some simple behavioural and cognitive-behavioural therapeutic techniques for treating and preventing such problems. PMID:21263912

  11. Atypical chemokine receptors: from silence to sound.

    PubMed

    Cancellieri, Cinzia; Vacchini, Alessandro; Locati, Massimo; Bonecchi, Raffaella; Borroni, Elena M

    2013-02-01

    ACRs (atypical chemokine receptors) were initially referred to as 'silent' receptors on the basis of a lack of signalling and functional activities that are typically observed with conventional chemokine receptors. Although ACRs do not directly induce cell migration, they indirectly control leucocyte recruitment by shaping chemokine gradients in tissues through degradation, transcytosis or local concentration of their cognate ligands. Recent evidence also suggests that these biological activities are supported by G-protein-independent, β-arrestin-dependent signalling events. In the present article, we review current knowledge on structural and signalling properties of ACRs that are changing our view on this entire class of receptors from silent to endogenous β-arrestin-biased signalling receptors.

  12. Indications of atypical antipsychotics in the elderly.

    PubMed

    McKean, Andrew; Monasterio, Erik

    2015-01-01

    Atypical antipsychotics (AAP) have become some of the most commonly prescribed medications in primary and specialist care settings. Off-label prescribing accounts for much of the expanded use of AAPs. This has become common in the elderly. Marketing by pharmaceutical companies appears to have contributed to the off-label use of AAPs, in situations where their safety and efficacy is far from established. Although evidence provides varying degrees of support for their use for behavioural and psychological symptoms of dementia, augmentation of antidepressants in depression, anxiety, insomnia and in the management of psychosis in Parkinson's Disease, there are a number of potential problems with their expanded use in the elderly. These include weight gain, type two diabetes mellitus, sudden cardiac death and increased mortality rates in the elderly with dementia. It is recommended that whenever AAPs are used off-label, a review date is identified, informed consent is obtained and treatment and side-effects are closely monitored.

  13. An overview of atypical enteropathogenic Escherichia coli.

    PubMed

    Hernandes, Rodrigo T; Elias, Waldir P; Vieira, Mônica A M; Gomes, Tânia A T

    2009-08-01

    The enteropathogenic Escherichia coli (EPEC) pathotype is currently divided into two groups, typical EPEC (tEPEC) and atypical EPEC (aEPEC). The property that distinguishes these two groups is the presence of the EPEC adherence factor plasmid, which is only found in tEPEC. aEPEC strains are emerging enteropathogens that have been detected worldwide. Herein, we review the serotypes, virulence properties, genetic relationships, epidemiology, reservoir and diagnosis of aEPEC, including those strains not belonging to the classical EPEC serogroups (nonclassical EPEC serogroups). The large variety of serotypes and genetic virulence properties of aEPEC strains from nonclassical EPEC serogroups makes it difficult to determine which strains are truly pathogenic.

  14. Statistical Detection of Atypical Aircraft Flights

    NASA Technical Reports Server (NTRS)

    Statler, Irving; Chidester, Thomas; Shafto, Michael; Ferryman, Thomas; Amidan, Brett; Whitney, Paul; White, Amanda; Willse, Alan; Cooley, Scott; Jay, Joseph; Rosenthal, Loren; Swickard, Andrea; Bates, Derrick; Scherrer, Chad; Webb, Bobbie-Jo; Lawrence, Robert; Mosbrucker, Chris; Prothero, Gary; Andrei, Adi; Romanowski, Tim; Robin, Daniel; Prothero, Jason; Lynch, Robert; Lowe, Michael

    2006-01-01

    A computational method and software to implement the method have been developed to sift through vast quantities of digital flight data to alert human analysts to aircraft flights that are statistically atypical in ways that signify that safety may be adversely affected. On a typical day, there are tens of thousands of flights in the United States and several times that number throughout the world. Depending on the specific aircraft design, the volume of data collected by sensors and flight recorders can range from a few dozen to several thousand parameters per second during a flight. Whereas these data have long been utilized in investigating crashes, the present method is oriented toward helping to prevent crashes by enabling routine monitoring of flight operations to identify portions of flights that may be of interest with respect to safety issues.

  15. Therapeutic drug monitoring of atypical antipsychotic drugs.

    PubMed

    Grundmann, Milan; Kacirova, Ivana; Urinovska, Romana

    2014-12-01

    Schizophrenia is a severe psychiatric disorder often associated with cognitive impairment and affective, mainly depressive, symptoms. Antipsychotic medication is the primary intervention for stabilization of acute psychotic episodes and prevention of recurrences and relapses in patients with schizophrenia. Typical antipsychotics, the older class of antipsychotic agents, are currently used much less frequently than newer atypical antipsychotics. Therapeutic drug monitoring (TDM) of antipsychotic drugs is the specific method of clinical pharmacology, which involves measurement of drug serum concentrations followed by interpretation and good cooperation with the clinician. TDM is a powerful tool that allows tailor-made treatment for the specific needs of individual patients. It can help in monitoring adherence, dose adjustment, minimizing the risk of toxicity and in cost-effectiveness in the treatment of psychiatric disorders. The review provides complex knowledge indispensable to clinical pharmacologists, pharmacists and clinicians for interpretation of TDM results.

  16. Clinical management of an atypical dental invagination

    PubMed Central

    Badran, Zahi; Lopez-Cazaux, Serena; Crauste, Eléonore; Bray, Estelle; Soueidan, Assem; Armengol, Valérie

    2016-01-01

    Dental invagination (DI) is a tooth malformation that usually affects permanent teeth. Its precise etiology is still controversial and represents a clinical challenge as it can favor the development of carious lesion or periodontal inflammation. This paper presents a case of a 23-year-old Caucasian male, where an atypical buccal DI could not be completely diagnosed in the dens invaginatus category. Furthermore, other differential diagnoses could not be confirmed. The dental malformation was seen on a permanent maxillary first incisor and was associated with periodontal inflammation and attachment loss. Successful clinical management of this case consisted of surgical restorative treatment and regular follow-up, accompanied by thorough oral hygiene procedures. PMID:28042279

  17. Achilles tendon rupture in atypical patient populations.

    PubMed

    Kingsley, Peter

    2016-03-01

    Rupture of the Achilles tendon is a significant injury, and the likelihood of a good recovery is directly associated with early diagnosis and appropriate referral. Such injuries are commonly assessed and identified by practitioners working in 'minors' areas of emergency departments or urgent care settings. The literature frequently describes rupture of the Achilles tendon as 'typically sport-related' affecting 'middle-aged weekend warriors', but this aetiology accounts for only about 70% of such injuries. Factors such as the natural ageing process, obesity and use of some commonly prescribed medications, can increase the risk of developing a tendinopathy and subsequent rupture, often from a seemingly insignificant incident. However, research suggests that injuries in this patient population are more likely be missed on first examination. This article describes risk factors that should alert clinicians to the possibility of Achilles tendon rupture in 'atypical' patient populations.

  18. [Atypical course of cholera in poultry].

    PubMed

    Tsonev, Ts S; Karaivanov, L; Shishkov, N; Milanov, M L; Chilev, D

    1979-01-01

    Atypically developing chicken septicemia was studied at 3 farms in Bulgaria. In one of the observed centers of chicken septicemia infection no pathologic anatomical changes were evident while in the other two centers of infection serofibrinose and serofibrinose vitelline peritonitis, as well as pleurisy were present. In the bacteriological investigation carried out on 2969 samples 233 strains of chicken septicemia were isolated. Identification of 84 of them by the aid of the specific bacteriophage P. multocida 115 and of sugar and alcohol fermantation revealed that they can be classified as P. multocida. They are lyzated by a phage but do not reproduce it. Chicken septicemia cultures are virulent for white mice. In intramuscular injections of pullets these cultures prove not virulent, but their intravenous application kills the pullets in 5--10 days and the initial strain is isolated from all inner organs. The biological test on pullets is suitable for determining chicken septicemia culture virulence.

  19. Atypical parakeratosis: a marker of dysplasia?

    PubMed

    Voytek, T M; Kannan, V; Kline, T S

    1996-11-01

    The Bethesda System categorizes atypical parakeratosis (APK) as "ASCUS or SIL depending on the degree of cellular abnormalities." APK, however, is not well-defined. We retrospectively reviewed 68 cervicovaginal specimens with follow-up material to identify specific criteria and clinical significance of APK. APK cells were small cells, 2-3 times the diameter of neutrophil, with dense, orangeophilic cytoplasm, high nuclear cytoplasmic ratio, dense, often uneven chromatin, and irregular nuclear contour. Of 62 cases with APK, 37 had accompanying dysplastic cells. Of 25 cases with APK alone, follow-up revealed 12 with squamous intraepithelial lesion (5 HSIL and 7 LSIL) and 13 with benign changes. A major diagnostic pitfall of APK was inflammation with degeneration. Abundant APK cells, minimal inflammation and degeneration, and previous history of dysplasia frequently were associated with follow-up SIL. The findings of this study identify APK as an important marker for dysplasia that warrants careful evaluation and follow-up.

  20. Refractory Rheumatic Disorder: Atypical Postpregnancy Osteoporosis

    PubMed Central

    Mourgues, Cindy; Malochet-Guinamand, Sandrine; Soubrier, Martin

    2015-01-01

    This is a case report on a young patient with severe osteoporosis that was initially revealed when she presented with polyarthralgia during her second pregnancy. Postpartum, the pain increased and her X-ray did not show any abnormalities. A bone scintigraphy was performed. It indicated an inflammatory rheumatic disorder. Six months after partum, an investigation of right coxalgia revealed a spontaneous basicervical fracture. Given the persistent polyarthralgia, the patient underwent a new scintigraphy, which revealed areas of what looked to be old rib and L1 fractures. A subsequent full body magnetic resonance imaging (MRI) scan revealed signal abnormalities that could indicate multiple lower limb bone fractures. Despite exhaustive biological, radiological, and histological testing, no secondary cause for the osteoporosis was found. The patient was started on teriparatide. We finally concluded that, despite the atypical presentation, the patient was suffering from postpregnancy osteoporosis. It is possible that the frequency of occurrence of this still poorly understood disease is underestimated. PMID:25785219

  1. Vestibular Schwannoma Atypically Invading Temporal Bone

    PubMed Central

    Park, Soo Jeong; Yang, Na-Rae

    2015-01-01

    Vestibular schwannoma (VS) usually present the widening of internal auditory canal (IAC), and these bony changes are typically limited to IAC, not extend to temporal bone. Temporal bone invasion by VS is extremely rare. We report 51-year-old man who revealed temporal bone destruction beyond IAC by unilateral VS. The bony destruction extended anteriorly to the carotid canal and inferiorly to the jugular foramen. On histopathologic examination, the tumor showed typical benign schwannoma and did not show any unusual vascularity or malignant feature. Facial nerve was severely compressed and distorted by tumor, which unevenly eroded temporal bone in surgical field. Vestibular schwannoma with atypical invasion of temporal bone can be successfully treated with combined translabyrinthine and lateral suboccipiral approach without facial nerve dysfunction. Early detection and careful dissection of facial nerve with intraoperative monitoring should be considered during operation due to severe adhesion and distortion of facial nerve by tumor and eroded temporal bone. PMID:25932298

  2. Rapid determination of 226Ra in environmental samples

    SciTech Connect

    Maxwell, Sherrod L.; Culligan, Brian K.

    2012-02-04

    A new rapid method for the determination of {sup 228}Ra in natural water samples has been developed at the SRNL/EBL (Savannah River National Lab/ Environmental Bioassay Laboratory) that can be used for emergency response or routine samples. While gamma spectrometry can be employed with sufficient detection limits to determine {sup 228}Ra in solid samples (via {sup 228}Ac) , radiochemical methods that employ gas flow proportional counting techniques typically provide lower MDA (Minimal Detectable Activity) levels for the determination of {sup 228}Ra in water samples. Most radiochemical methods for {sup 228}Ra collect and purify {sup 228}Ra and allow for {sup 228}Ac daughter ingrowth for ~36 hours. In this new SRNL/EBL approach, {sup 228}Ac is collected and purified from the water sample without waiting to eliminate this delay. The sample preparation requires only about 4 hours so that {sup 228}Ra assay results on water samples can be achieved in < 6 hours. The method uses a rapid calcium carbonate precipitation enhanced with a small amount of phosphate added to enhance chemical yields (typically >90%), followed by rapid cation exchange removal of calcium. Lead, bismuth, uranium, thorium and protactinium isotopes are also removed by the cation exchange separation. {sup 228}Ac is eluted from the cation resin directly onto a DGA Resin cartridge attached to the bottom of the cation column to purify {sup 228}Ac. DGA Resin also removes lead and bismuth isotopes, along with Sr isotopes and {sup 90}Y. La is used to determine {sup 228}Ac chemical yield via ICP-MS, but {sup 133}Ba can also be used instead if ICP-MS assay is not available. Unlike some older methods, no lead or strontium holdback carriers or continual readjustment of sample pH is required.

  3. IL7RA polymorphisms are not associated with AIDS progression.

    PubMed

    Medrano, Luz María; Jiménez, José Luis; Jiménez-Sousa, María A; Fernández-Rodíguez, Amanda; Gutiérrez-Rivas, Mónica; Bellón, José María; Blanco, José Ramón; Inciarte, Alexy; Muñoz-Fernández, Mª Ángeles; Resino, Salvador

    2017-08-10

    Our aim was to determine whether α-chain of the IL-7 receptor (IL7RA) polymorphisms (rs10491434, rs6897932 and rs987106) are associated with the clinical pattern of AIDS progression in ART-naïve HIV-infected patients. We carried out a cross-sectional study in 673 HIV-infected patients who were classified into three groups according to the clinical pattern of AIDS progression (188 long-term nonprogressors (LTNPs), 334 moderate progressors (MPs) and 151 rapid progressors (RPs)). Additionally, 134 healthy blood donors participated as a Control-group. We selected three IL7RA polymorphisms located at three regulatory regions [rs6897932 (exon 6), rs987106 (intronic region) and rs10491434 (3'UTR)]. DNA genotyping was performed using Sequenom's MassARRAY platform. The Control-group and all HIV-infected patients had similar age and percentage of males. LTNP-group was older at HIV diagnosis and at the inclusion in the study and had higher percentage of intravenous drug users (IDU) (P < 0·001). Besides, LTNP-group had lower proportion of male patients and homosexual HIV transmission than MP and RP groups (P < 0·001). Moreover, similar values of allelic, genotypic and haplotype frequencies for IL7RA polymorphisms were found between healthy controls and HIV-infected patients (P > 0·05), and among different subgroups of HIV patients according to AIDS progression (LTNPs, MPs and RPs) (P > 0·05). The adjusted logistic regression did not show any significant association between IL7RA polymorphisms and AIDS progression. IL7RA polymorphisms (rs6897932, rs987106 and rs10491434) were not associated with AIDS progression in Spanish population. Therefore, IL7RA polymorphisms do not seem to help us to understand HIV pathogenesis in untreated HIV-infected patients with different clinical evolution. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  4. Amisulpride the 'atypical' atypical antipsychotic--comparison to haloperidol, risperidone and clozapine.

    PubMed

    Natesan, Sridhar; Reckless, Greg E; Barlow, Karren B L; Nobrega, José N; Kapur, Shitij

    2008-10-01

    Amisulpride's high and selective affinity for dopamine D2/3 (Ki 1.3/2.4 nM) receptors, lack of affinity for serotonin receptors, and its unusually high therapeutic doses (400-800 mg/day) makes it unique among atypical antipsychotics and prompted us to compare its actions with other antipsychotics in animal models. Amisulpride's effects on amphetamine and phencyclidine induced locomotor activity (AIL/PIL), conditioned avoidance response, catalepsy (CAT), subcortical Fos expression, and plasma prolactin was correlated to its time-course striatal D2/3 and prefrontal 5-HT2 receptor occupancy (D(2/3)/5-HT2RO); in comparison to haloperidol, clozapine, and risperidone. Unlike the atypicals clozapine and risperidone, amisulpride lacked 5-HT2RO and showed a 'delayed' pattern of D2/3RO: 43, 60 and 88% after 1, 2 and 6 h (100 mg/kg), respectively, despite a quick onset (1 h) and decline (6 h) of prolactin elevation. While haloperidol and risperidone were effective at D2RO>60%, clozapine at D2/3RO<50%, amisulpride was effective only when its D2RO exceeded 60% with a delayed latency and lasted longer than other antipsychotics. CAT was observed for haloperidol and risperidone when D2RO exceeded 80%, while in the case of amisulpride, CAT was not observed even when doses exceeded 90% D2/3RO. Amisulpride also displayed functional limbic selectivity in Fos expression like the other atypicals. Amisulpride's "delayed" functional profile on acute administration and the need for high doses is most likely due to its poor blood-brain-barrier penetration; however, it is distinct from other atypicals in showing low motor side-effects, activity against phencyclidine, and a mesolimbic preference, despite no action on serotonin receptors.

  5. Atypical Neurotransmitters and the Neurobiology of Depression.

    PubMed

    Joca, Samia Regiane; Moreira, Fabricio Araujo; Wegener, Gregers

    2015-01-01

    Since the first report that the mechanism of action of antidepressants involves the facilitation of monoaminergic neurotransmission in the brain in the 1960s, the leading hypothesis about the neurobiology of depression has been the so called "monoaminergic hypothesis". However, a growing body of evidence from the last two decades also supports important involvement of non-monoaminergic mechanisms in the neurobiology of depression and antidepressant action. The discovery of nitric oxide (NO) and endocannabinoid signaling in the brain during the 1990s challenged the wellestablished criteria of classical neurotransmission. These transmitters are synthesized and released on demand by the postsynaptic neurons, and may act as a retrograde messenger on the presynaptic terminal, modulating neurotransmitter release. These unconventional signaling mechanisms and the important role as neural messengers have classified NO and endocannabinoids as atypical neurotransmitters. They are able to modulate neural signaling mediated by the main conventional neurotransmitters systems in the brain, including the monoaminergic, glutamatergic and GABAergic signaling systems. This review aims at discussing the fundamental aspects of NO- and endocannabinoid-mediated signaling in the brain, and how they can be related to the neurobiology of depression. Both preclinical and clinical evidence supporting the involvement of these atypical neurotransmitters in the neurobiology of depression, and in the antidepressant effects are presented here. The evidence is discussed on basis of their ability to modulate different neurotransmitter systems in the brain, including monoaminergic and glutamatergic ones. A better comprehension of NO and endocannabinoid signaling mechanisms in the neurobiology depression could provide new avenues for the development of novel non-monoamine based antidepressants.

  6. Spitz nevus and atypical spitzoid neoplasm.

    PubMed

    Miteva, Maria; Lazova, Rossitza

    2010-09-01

    Spitz nevus (SN) and Spitzoid malignant melanoma (SMM) represent benign and malignant counterparts at both ends of the spectrum of Spitzoid lesions. Atypical Spitzoid neoplasm (ASN) is a poorly defined and characterized category of melanocytic tumors with histologic features of both benign Spitz nevi and malignant melanomas. The group of ASN represents a mixture of Spitz nevi with atypical features and Spitzoid melanomas. However, at the current moment in time, histopathologists are not capable of differentiating between the 2 in some cases and are forced to place them in this ambiguous category, where the behavior of these lesions cannot be predicted with certainty. Because this group encompasses both benign and malignant lesions, and perhaps also a separate category of melanocytic tumors that behave better than conventional melanomas, some of these neoplasms can metastasize and kill patients, whereas others have no metastatic potential, and yet others might only metastasize to regional lymph nodes. Although diagnostic accuracy has improved over the years, many of these lesions remain controversial, and there is still poor interobserver agreement in classifying problematic Spitzoid lesions among experienced dermatopathologists. The objective of this review article is to summarize the most relevant information about SN and ASNs. At this time histologic examination remains the golden standard for diagnosing these melanocytic neoplasms. We therefore concentrate on the histopathologic, clinical, and dermoscopic aspects of these lesions. We also review the most recent advances in immunohistochemical and molecular diagnostics as well as discuss the controversies and dilemma regarding whether to consider sentinel lymph node biopsy for diagnostically ambiguous melanocytic neoplasms. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. RAPID DETERMINATION OF RA-226 IN ENVIRONMENTAL SAMPLES

    SciTech Connect

    Maxwell, S.

    2012-01-03

    A new rapid method for the determination of {sup 226}Ra in environmental samples has been developed at the Savannah River Site Environmental Lab (Aiken, SC, USA) that can be used for emergency response or routine sample analyses. The need for rapid analyses in the event of a Radiological Dispersive Device or Improvised Nuclear Device event is well-known. In addition, the recent accident at Fukushima Nuclear Power Plant in March, 2011 reinforces the need to have rapid analyses for radionuclides in environmental samples in the event of a nuclear accident. {sup 226}Ra (T1/2 = 1,620 years) is one of the most toxic of the long-lived alpha-emitters present in the environment due to its long life and its tendency to concentrate in bones, which increases the internal radiation dose of individuals. The new method to determine {sup 226}Ra in environmental samples utilizes a rapid sodium hydroxide fusion method for solid samples, calcium carbonate precipitation to preconcentrate Ra, and rapid column separation steps to remove interferences. The column separation process uses cation exchange resin to remove large amounts of calcium, Sr Resin to remove barium and Ln Resin as a final purification step to remove {sup 225}Ac and potential interferences. The purified {sup 226}Ra sample test sources are prepared using barium sulfate microprecipitation in the presence of isopropanol for counting by alpha spectrometry. The method showed good chemical recoveries and effective removal of interferences. The determination of {sup 226}Ra in environmental samples can be performed in less than 16 h for vegetation, concrete, brick, soil, and air filter samples with excellent quality for emergency or routine analyses. The sample preparation work takes less than 6 h. {sup 225}Ra (T1/2 = 14.9 day) tracer is used and the {sup 225}Ra progeny {sup 217}At is used to determine chemical yield via alpha spectrometry. The rapid fusion technique is a rugged sample digestion method that ensures that any

  8. Process waste assessment: Color print processing (RA-4)

    SciTech Connect

    Catlett, P.

    1994-05-01

    The Kodak RA-4 process is used to develop prints and overhead transparencies from photographic negatives. The assessment was based on usage, effluent discharge, and final disposition of waste generated by the process. Two options explored were bleach-fix regeneration and the conversion to a digital image processing system. The RA-4 process is process is environmentally sound and generates a relatively small amount of waste. The bleach-fix option would provide only a small effluent reduction. The digital imaging conversion option, if fully implemented, could greatly reduce waste generated in the photo lab.

  9. Atypical Neonatal Marfan Syndrome with p.Glu1073Lys Mutation of FBN1: the First Case in Korea

    PubMed Central

    2017-01-01

    Neonatal Marfan syndrome (nMFS) is considered to be on the most severe end of the spectrum of type I fibrillinopathies. The common features of nMFS include ascending aortic dilatation, severe mitral and/or tricuspid valve insufficiency, ectopia lentis, arachnodactyly, joint contractures, crumpled ear, loose skin, and pulmonary emphysema.We describe a newborn male diagnosed with nMFS. He presented several atypical features, such as diaphragmatic eventration, severe hydronephrosis with hydroureter, and dilated cisterna magna. Molecular analysis revealed a missense mutation at nucleotide 3217 (c.3217G>A) in exon 26 of the fibrillin-1 (FBN1) gene, resulting in the substitution of a glutamate for a lysine at codon 1073 (E1073K) in the 12th calcium binding epidermal growth factor-like domain of the FBN1 protein. Here we report a rare case of Nmfs with several combined atypical features, such as diaphragmatic eventration, severe hydronephrosis with hydroureter, and dilated cisterna magna. Our report is the first atypical nMFS case with p.Glu1073Lys mutation of FBN1 in Korea and may help clinicians with the diagnosis and follow-up of atypical nMFS. PMID:27914124

  10. Atypical Neonatal Marfan Syndrome with p.Glu1073Lys Mutation of FBN1: the First Case in Korea.

    PubMed

    Heo, Ju Sun; Song, Joo Young; Choi, Eun Young; Kim, Eun Hee; Kim, Ji Hee; Park, So Eun; Jeon, Ji Hyun

    2017-01-01

    Neonatal Marfan syndrome (nMFS) is considered to be on the most severe end of the spectrum of type I fibrillinopathies. The common features of nMFS include ascending aortic dilatation, severe mitral and/or tricuspid valve insufficiency, ectopia lentis, arachnodactyly, joint contractures, crumpled ear, loose skin, and pulmonary emphysema.We describe a newborn male diagnosed with nMFS. He presented several atypical features, such as diaphragmatic eventration, severe hydronephrosis with hydroureter, and dilated cisterna magna. Molecular analysis revealed a missense mutation at nucleotide 3217 (c.3217G>A) in exon 26 of the fibrillin-1 (FBN1) gene, resulting in the substitution of a glutamate for a lysine at codon 1073 (E1073K) in the 12th calcium binding epidermal growth factor-like domain of the FBN1 protein. Here we report a rare case of Nmfs with several combined atypical features, such as diaphragmatic eventration, severe hydronephrosis with hydroureter, and dilated cisterna magna. Our report is the first atypical nMFS case with p.Glu1073Lys mutation of FBN1 in Korea and may help clinicians with the diagnosis and follow-up of atypical nMFS.

  11. Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2

    PubMed Central

    Perander, Maria; Al-Mahdi, Rania; Jensen, Thomas C.; Nunn, Jennifer A. L.; Kildalsen, Hanne; Johansen, Bjarne; Gabrielsen, Mads; Keyse, Stephen M.; Seternes, Ole-Morten

    2017-01-01

    The atypical MAP kinases ERK3 and ERK4 are activated by phosphorylation of a serine residue lying within the activation loop signature sequence S-E-G. However, the regulation of ERK3 and ERK4 phosphorylation and activity is poorly understood. Here we report that the inducible nuclear dual-specificity MAP kinase phosphatase (MKP) DUSP2, a known regulator of the ERK and p38 MAPKs, is unique amongst the MKP family in being able to bind to both ERK3 and ERK4. This interaction is mediated by a conserved common docking (CD) domain within the carboxyl-terminal domains of ERK3 and ERK4 and the conserved kinase interaction motif (KIM) located within the non-catalytic amino terminus of DUSP2. This interaction is direct and results in the dephosphorylation of ERK3 and ERK4 and the stabilization of DUSP2. In the case of ERK4 its ability to stabilize DUSP2 requires its kinase activity. Finally, we demonstrate that expression of DUSP2 inhibits ERK3 and ERK4-mediated activation of its downstream substrate MK5. We conclude that the activity of DUSP2 is not restricted to the classical MAPK pathways and that DUSP2 can also regulate the atypical ERK3/4-MK5 signalling pathway in mammalian cells. PMID:28252035

  12. Preparation and characterization of human ADCK3, a putative atypical kinase.

    PubMed

    Wheeler, Brody; Jia, Zongchao

    2015-04-01

    AarF domain containing kinase 3 (ADCK3) is a mitochondrial protein known to have a role in the electron transport chain. Despite being required for the biosynthesis of coenzyme Q10, a lipid-soluble electron transporter found to be essential for aerobic cellular respiration, the precise biological function of ADCK3 remains unknown. Patients with mutations in ADCK3 experience an onset of neurological disorders from childhood, including cerebellar ataxia and exercise intolerance. After extensive screening for soluble recombinant protein expression, an N-terminal fusion of maltose-binding protein was found to facilitate the overexpression of the human ADCK3 kinase domain in Escherichia coli as a soluble and biologically active entity. For the first time our work reveals Mg(2+)-dependent ATPase activity of ADCK3, providing strong support for the theoretical prediction of this protein being a functional atypical kinase.

  13. Integrated genomic analyses of de novo pathways underlying atypical meningiomas

    PubMed Central

    Harmancı, Akdes Serin; Youngblood, Mark W.; Clark, Victoria E.; Coşkun, Süleyman; Henegariu, Octavian; Duran, Daniel; Erson-Omay, E. Zeynep; Kaulen, Leon D.; Lee, Tong Ihn; Abraham, Brian J.; Simon, Matthias; Krischek, Boris; Timmer, Marco; Goldbrunner, Roland; Omay, S. Bülent; Baranoski, Jacob; Baran, Burçin; Carrión-Grant, Geneive; Bai, Hanwen; Mishra-Gorur, Ketu; Schramm, Johannes; Moliterno, Jennifer; Vortmeyer, Alexander O.; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A.; Günel, Murat

    2017-01-01

    Meningiomas are mostly benign brain tumours, with a potential for becoming atypical or malignant. On the basis of comprehensive genomic, transcriptomic and epigenomic analyses, we compared benign meningiomas to atypical ones. Here, we show that the majority of primary (de novo) atypical meningiomas display loss of NF2, which co-occurs either with genomic instability or recurrent SMARCB1 mutations. These tumours harbour increased H3K27me3 signal and a hypermethylated phenotype, mainly occupying the polycomb repressive complex 2 (PRC2) binding sites in human embryonic stem cells, thereby phenocopying a more primitive cellular state. Consistent with this observation, atypical meningiomas exhibit upregulation of EZH2, the catalytic subunit of the PRC2 complex, as well as the E2F2 and FOXM1 transcriptional networks. Importantly, these primary atypical meningiomas do not harbour TERT promoter mutations, which have been reported in atypical tumours that progressed from benign ones. Our results establish the genomic landscape of primary atypical meningiomas and potential therapeutic targets. PMID:28195122

  14. Atypical antipsychotics to treat the neuropsychiatric symptoms of dementia

    PubMed Central

    Lee, Philip E; Gill, Sudeep S; Rochon, Paula

    2006-01-01

    Neuropsychiatric symptoms are common in older adults with dementia and can be associated with a rapid decline in cognitive and functional status. This article reviews the current literature supporting the use of atypical antipsychotic medications in this population. Among the currently available atypical antipsychotics, risperidone and olanzapine have been the most widely studied in double-blind, randomized, placebo-controlled clinical trials. Despite the common use of other atypical antipsychotic medications, their efficacy and safety in older adults with dementia has not been as extensively studied. Some controversy surrounds the use of atypical antipsychotic agents in older adults with the suggestion that they may increase the incidence of stroke or even death. Despite the potential for increased risk of harm from the use of these medications, atypical antipsychotics are often effective in treating troublesome neuropsychiatric symptoms refractory to other treatments. Whenever possible, these atypical antipsychotic drug treatments should be combined with non-pharmacological treatments to limit the need and dose of antipsychotic drugs and constant monitoring for potential harms should be maintained. The choice of which atypical antipsychotic agent can be guided by the nature and severity of the target symptom and the medication least likely to cause harm to the patient. PMID:19412500

  15. Raman-assisted vector Brillouin optical time domain analysis

    NASA Astrophysics Data System (ADS)

    Angulo-Vinuesa, X.; Bacquet, D.; Martin-Lopez, S.; Corredera, P.; Szriftgiser, P.; Gonzalez-Herraez, M.

    2013-05-01

    Raman-assistance (RA) has become a promising technique to enhance the sensing range of standard Brillouin Optical Time Domain Analysis (BOTDA) fiber sensors due to its ability to amplify in a distributed way all the interacting signals within the fiber. Unfortunately, Raman amplification introduces a great amount of Relative Intensity Noise (RIN) to the detected low-frequency probe wave. This RIN transfer problem has been widely identified as a major limitation in RABOTDA. In Vector Brillouin Optical Time Domain Analysis (VBOTDA) the detected signal is transferred to a highfrequency carrier where the Raman RIN transfer turns out to be much less harmful. In this work we demonstrate, for the first time to our knowledge, Raman-assistance in a VBOTDA. Our results show significant reduction of the RIN transfer effect in RA-VBOTDA compared to standard RA-BOTDA, making this type of scheme particularly interesting for long range distributed sensing.

  16. CD45RA+ T cells: not simple virgins.

    PubMed

    Lightstone, L; Marvel, J

    1993-11-01

    1. The T cells which mediate immunological memory remain elusive. Identification of such cells would open the door to increasingly specific immunotherapy in areas such as transplantation and autoimmunity. 2. Over the last few years attempts have been made to identify phenotypic markers which can distinguish naive or virgin T cells from primed or memory ones. In humans, great hopes were raised when it was shown that the level of expression of the higher-molecular-mass isoforms (CD45RA) of the tyrosine phosphatase, CD45, correlated with previous exposure to antigen. 4. However, our studies in the mouse and more recent studies in rat and human suggest that expression of CD45RA more closely correlates with the state of responsiveness of the T cell. 5. Thus, with time, activated/memory T cells return to a state of quiescence or hypo-responsiveness and express high levels of CD45RA. Hence, not all CD45RA+ T cells are virgins.

  17. Observation of the negative ions: Ra[sup [minus

    SciTech Connect

    Zhao, X.; Nadeau, M.; Garwan, M.A.; Kilius, L.R.; Litherland, A.E. )

    1993-11-01

    The negative ions of the isotopes [sup 226]Ra, [sup 231]Pa, and [sup 244]Pu have been observed by means of accelerator mass spectrometry and their properties compared with the negative ions of Th and U. The electron affinities of all these elements have been estimated to be similar and greater than 50 meV.

  18. "LJ" Series "Redefining RA": Keeping up with Genres

    ERIC Educational Resources Information Center

    Wyatt, Neal

    2008-01-01

    Genre is a hot issue in readers' advisory (RA) circles right now. Many people are looking at how genre functions and morphs. Studying a genre is not a new idea. Over two decades ago, and even longer in less formal ways, librarians began gathering to study genres--asking such questions as in what genre does this book fit and why, what are its…

  19. "LJ" Series "Redefining RA": Keeping up with Genres

    ERIC Educational Resources Information Center

    Wyatt, Neal

    2008-01-01

    Genre is a hot issue in readers' advisory (RA) circles right now. Many people are looking at how genre functions and morphs. Studying a genre is not a new idea. Over two decades ago, and even longer in less formal ways, librarians began gathering to study genres--asking such questions as in what genre does this book fit and why, what are its…

  20. Mitochondrial function is altered in horse atypical myopathy.

    PubMed

    Lemieux, Hélène; Boemer, François; van Galen, Gaby; Serteyn, Didier; Amory, Hélène; Baise, Etienne; Cassart, Dominique; van Loon, Gunther; Marcillaud-Pitel, Christel; Votion, Dominique-M

    2016-09-01

    Equine atypical myopathy in Europe is a fatal rhabdomyolysis syndrome that results from the ingestion of hypoglycin A contained in seeds and seedlings of Acer pseudoplatanus (sycamore maple). Acylcarnitine concentrations in serum and muscle OXPHOS capacity were determined in 15 atypical myopathy cases. All but one acylcarnitine were out of reference range and mitochondrial respiratory capacity was severely decreased up to 49% as compared to 10 healthy controls. The hallmark of atypical myopathy thus consists of a severe alteration in the energy metabolism including a severe impairment in muscle mitochondrial respiration that could contribute to its high death rate.

  1. Intracranial Tuberculoma Presenting as Atypical Eclampsia: A Case Report.

    PubMed

    Arumugam, Sendhil Coumary; Murugesan, Sharmila; Pradeep, Sunitha; John, Lopamudra; Kolluru, Vasavi

    2016-06-01

    Occurrence of eclampsia before 20 weeks of pregnancy and after 48 hours of delivery in the absence of typical signs of hypertension and or proteinuria is termed as atypical eclampsia. Atypical or non-classic eclampsia will have some symptoms of eclampsia but without the usual proteinuria or hypertension. All patients with atypical onset should undergo neurological evaluation to rule out neurologic causes of seizures. Cerebral tuberculosis is a rare and serious form of disease secondary to haematogenous spread of Mycobacterium tuberculosis. Here we present a case of cerebral tuberculoma with seizures in late pregnancy mimicking eclampsia.

  2. Diapycnal nutrient fluxes across the benthic boundary layers at the continental slopes off Peru and Mauritania based on 224Ra/223Ra-ratios

    NASA Astrophysics Data System (ADS)

    Reichert, P.; Scholten, J. C.; Eisenhauer, A.; Miquel, J. C.; Gasser, B.; Liebetrau, V.; Sommer, S.; Dengler, M.; Bryant, L. D.

    2014-12-01

    Marine sediments may act as sources and/or sinks of nutrients in oxygen minimum zones (OMZs) where solute fluxes between sediments and the above water column are believed to be an important component for the bioproductivity in the mixed layer. However, solute fluxes between sediments and the water column above are difficult to obtain. We determined the diapycnal nutrient fluxes across the benthic boundary layer at the OMZs off Peru and Mauritania using nutrient concentration profiles and vertical diffusion coefficients derived from 224Ra/223Ra isotope ratios. The radium isotopes 223Ra (half-life: 11.4 days) and 224Ra (half-life: 3.66 days) are produced in sediments by radioactive decay of 227Th and 228Th ,respectively: Diffusion of radium out of the sediments results in gradients of 224Ra/223Ra above the sediments; and these gradients may be used to estimate vertical diffusion coefficients. We determined 224Ra/223Ra along two transects at the continental slopes off Peru (12° S) and off Mauritania (18° N) in water depths between 65m - 1000mand 53m - 1100m, respectively. For the 223Ra/224Ra sampling we used acrylic fibers/cartridges coated with MnO2. The Mn-fibers were attached to benthic landers (moored for ~ 24 hours at the sea floor) and the Mn-cartridges were placed in series on several in-situ filtration pumps (Challenger Oceanic and McLane pumps). 223Ra and 224Ra were measured on-board using a delayed coincidence counting system (RaDeCC). In our presentation we will present the 224Ra/223Ra distribution along these transects investigated and we will compare the diapycnal radium-derived nutrient fluxes with those determined using benthic chambers and microstructure measurements.

  3. [The modern concept of atypical depression: four definitions].

    PubMed

    Ohmae, Susumu

    2010-01-01

    This report describes and compares four current concepts and definitions of atypical depression. Since its emergence, atypical depression has been considered a depressive state that can be relieved by MAO inhibitors. Davidson classified the symptomatic features of atypical depression into type A, which is predominated by anxiety symptoms, and type V, which is represented by atypical vegetative symptoms, such as hyperphagia, weight gain, oversleeping, and increased sexual drive. Features that are shared by both subtypes include: early onset, female predominance, outpatient predominance, mildness, few suicide attempts, nonbipolarity, nonendogeneity, and few psychomotor changes. Based on these features, bipolar depression can also be defined as atypical depression type V. Herein, we examine and classify four concepts of atypical depression according to the endogenous-nonendogenous (melancholic-nonmelancholic) and unipolar-bipolar dichotomies. The Columbia University group (see Quitkin, Stewart, McGrath, Klein et al.) and the New South Wales University group (see Parker) consider atypical depression to be chronic, mild, nonendogenous (nonmelancholic), unipolar depression. The former group postulates that mood reactivity is necessary, while the latter asserts the structural priority of anxiety symptoms over mood symptoms and the significance of interpersonal rejection sensitivity. For the Columbia group, the significance of mood reactivity reflects the theory that mood nonreactivity is the essential symptom of "endogenomorphic depression", which was proposed by Klein as typical depression. Thus, mood reactivity is not related to overreactivity or hyperactivity, which are often observed in atypical depressives. However, Parker postulates that psychomotor symptoms are the essential features of melancholia, which he recognizes as typical depression; therefore, the New South Wales group does not recognize the significance of mood reactivity. The New South Wales group

  4. Direct observation of inclined a-type threading dislocation with a-type screw dislocation in GaN

    NASA Astrophysics Data System (ADS)

    Matsubara, Tohoru; Sugimoto, Kohei; Goubara, Shin; Inomoto, Ryo; Okada, Narihito; Tadatomo, Kazuyuki

    2017-05-01

    We investigated both the atomic arrangements in the core structure of threading dislocations (TDs) and their behaviors in unintentionally doped c-plane-GaN layers grown by metalorganic vapor phase epitaxy and hydride vapor phase epitaxy using high angle annular dark-field scanning transmission electron microscopy (HAADF-STEM). The extra image contrast near the core was attributed to an extra displacement in a-type TDs in addition to the core structures revealed in previous reports; we used the notation "with displacement" to describe the new core structure. We found that TDs incline towards both the m- and a-directions from the c-direction. The transition of a-type TDs from the conventional core structure to the structure with displacement was deduced from its relationship to the TD inclination. We also found similarities between a-type screw dislocations and a-type TDs with displacement in the atomic-scale HAADF-STEM images. We concluded that a-type TDs could incline towards the a-direction via a-type screw dislocations, and that these inclined a-type TDs are observed as the core structure with displacement.

  5. Rainbow Trout Sleeping Disease Virus Is an Atypical Alphavirus

    PubMed Central

    Villoing, Stéphane; Béarzotti, Monique; Chilmonczyk, Stefan; Castric, Jeannette; Brémont, Michel

    2000-01-01

    Sleeping disease (SD) is currently a matter of concern for salmonid fish farmers in most parts of the world. A viral etiology of SD has recently been suspected, since virus-like particles have been observed in infected rainbow trout cells. In salmonid-derived cell lines, the maximal rate of virus production was observed at 10°C, while little virus was produced at 14°C. Through biochemical, physicochemical, and morphological studies, SD virus (SDV) was shown to be an enveloped virus of roughly 60 nm in diameter. The genome consists of 12 kb of RNA, with the appearance of a 26S subgenomic RNA during the time course of SDV replication. The screening of a random-primed cDNA library constructed from the genomic RNA of semipurified virions facilitated the identification of a specific SDV cDNA clone having an open reading frame related to the alphavirus E2 glycoproteins. To extend the comparison between SDV structural proteins and the alphavirus protein counterparts, the nucleotide sequence of the total 4.1-kb subgenomic RNA has been determined. The 26S RNA encodes a 1,324-amino-acid polyprotein exhibiting typical alphavirus structural protein organization. SDV structural proteins showed several remarkable features compared to other alphaviruses: (i) unusually large individual proteins, (ii) very low homology (ranging from 30 to 34%) (iii) an unglycosylated E3 protein, and (iv) and E1 fusion domain sharing mutations implicated in the pH threshold. Although phylogenetically related to the Semliki Forest virus group of alphaviruses, SDV should be considered an atypical member, able to naturally replicate in lower vertebrates. PMID:10590104

  6. Ponticulin is an atypical membrane protein

    PubMed Central

    1994-01-01

    We have cloned and sequenced ponticulin, a 17,000-dalton integral membrane glycoprotein that binds F-actin and nucleates actin assembly. A single copy gene encodes a developmentally regulated message that is high during growth and early development, but drops precipitously during cell streaming at approximately 8 h of development. The deduced amino acid sequence predicts a protein with a cleaved NH2-terminal signal sequence and a COOH-terminal glycosyl anchor. These predictions are supported by amino acid sequencing of mature ponticulin and metabolic labeling with glycosyl anchor components. Although no alpha- helical membrane-spanning domains are apparent, several hydrophobic and/or sided beta-strands, each long enough to traverse the membrane, are predicted. Although its location on the primary sequence is unclear, an intracellular domain is indicated by the existence of a discontinuous epitope that is accessible to antibody in plasma membranes and permeabilized cells, but not in intact cells. Such a cytoplasmically oriented domain also is required for the demonstrated role of ponticulin in binding actin to the plasma membrane in vivo and in vitro (Hitt, A. L., J. H. Hartwig, and E. J. Luna. 1994. Ponticulin is the major high affinity link between the plasma membrane and the cortical actin network in Dictyostelium. J. Cell Biol. 126:1433-1444). Thus, ponticulin apparently represents a new category of integral membrane proteins that consists of proteins with both a glycosyl anchor and membrane-spanning peptide domain(s). PMID:8089175

  7. The Use of Electroconvulsive Therapy in Atypical Psychotic Presentations

    PubMed Central

    Vasu, Devi

    2007-01-01

    Convulsive therapy and its progeny, electroconvulsive therapy (ECT), were originally used for the treatment of catatonic schizophrenia, and there is little doubt that ECT remains an effective intervention for the treatment of schizophrenia. However, current practice tends to favor the use of ECT in severe or treatment refractory affective disorders, and its use in schizophrenia and other nonaffective (atypical) psychotic disorders has become controversial. Case reports have suggested a role for ECT in two specific atypical psychotic disorders: Cotard's syndrome and cycloid psychosis. In this article, we review the atypical psychotic disorders and report a series of five case examples that signify the role of ECT in atypical psychotic presentations, particularly when the symptoms resemble those found in Cotard's syndrome and cycloid psychosis. PMID:20428309

  8. Depression With Atypical Features: Diagnostic Validity, Prevalence, and Treatment.

    PubMed

    Quitkin, Frederic M.

    2002-06-01

    Depression with atypical features is a treatable and relatively common disorder among depressed outpatients. A growing body of evidence suggests this is a biologically distinct subtype of depression. This assertion is supported by genetic epidemiologic studies and by a preferential response of the subtype to monoamine oxidase inhibitors compared with tricyclic antidepressants. The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) includes atypical features as a parenthetical modifier for depressive illness. According to DSM-IV diagnostic criteria ("atypical features" specifier), the disorder is primarily characterized by 2 or more of the following symptoms as predominant features in patients with major depression or dysthymic disorder: overeating, oversleeping, "leaden paralysis," and interpersonal rejection sensitivity. Patients also show mood reactivity in response to actual or potential positive events. Despite aspects of the disorder resembling a maladaptive, persistent mode of behavior, patients diagnosed with depression with atypical features demonstrate a good response to antidepressant treatment.

  9. Treating DSM-IV depression with atypical features.

    PubMed

    Stewart, Jonathan W; Thase, Michael E

    2007-04-01

    Depression with atypical features is characterized by mood reactivity and 2 or more symptoms of vegetative reversal (including overeating, oversleeping, severe fatigue or leaden paralysis, and a history of rejection sensitivity). Another important feature of atypical depression is its preferential response to monoamine oxidase inhibitor (MAOI) treatment, especially phenelzine, relative to tricyclic antidepressants (TCAs). The efficacy of newer agents relative to MAOIs and TCAs is unclear. This presentation reviews currently available treatments for DSM-IV depression with atypical features, focusing specifically on placebo-controlled trials. Although phenelzine shows the most efficacy in this population, treatment with TCAs, selective serotonin reuptake inhibitors, cognitive-behavioral therapy, MAOIs other than phenelzine, and other agents are discussed. Following this presentation is a discussion on the treatment of depression with atypical features by experts in this subject area.

  10. Invasive atypical thymic carcinoid: three case reports and literature review

    PubMed Central

    Zhu, Shan; Wang, Zhong-Tang; Liu, Wen-Zhi; Zong, Shi-Xiang; Li, Bao-Sheng

    2016-01-01

    Atypical thymic carcinoid is an extremely rare thymic neuroendocrine tumor derived from the neuroendocrine system. The aims of this paper were to investigate the clinical features of atypical thymic carcinoid and collate information and experience to improve the diagnosis and treatment of this disease. We describe three cases of atypical carcinoid of the thymus; clinical features, pathological data, treatment modalities, and short-term patient outcomes were summarized and analyzed. The initial clinical symptoms and signs of all three patients were nonspecific and an anterior mediastinal mass was found in each patient on chest computed tomography scan. All three patients underwent surgical resection (total thymectomy and complete excision of the tumor), followed by postoperative radiotherapy, with or without chemotherapy. The diagnoses of three patients were confirmed by pathological and immunohistochemical evaluation. We also present a review of the literature to collate as much information as possible and provide a reference for proper diagnosis and treatment of atypical thyroid carcinoid. PMID:27785065

  11. Atrial Flutter, Typical and Atypical: A Review

    PubMed Central

    2017-01-01

    Clinical electrophysiology has made the traditional classification of rapid atrial rhythms into flutter and tachycardia of little clinical use. Electrophysiological studies have defined multiple mechanisms of tachycardia, both re-entrant and focal, with varying ECG morphologies and rates, authenticated by the results of catheter ablation of the focal triggers or critical isthmuses of re-entry circuits. In patients without a history of heart disease, cardiac surgery or catheter ablation, typical flutter ECG remains predictive of a right atrial re-entry circuit dependent on the inferior vena cava-tricuspid isthmus that can be very effectively treated by ablation, although late incidence of atrial fibrillation remains a problem. Secondary prevention, based on the treatment of associated atrial fibrillation risk factors, is emerging as a therapeutic option. In patients subjected to cardiac surgery or catheter ablation for the treatment of atrial fibrillation or showing atypical ECG patterns, macro-re-entrant and focal tachycardia mechanisms can be very complex and electrophysiological studies are necessary to guide ablation treatment in poorly tolerated cases. PMID:28835836

  12. Atrial Flutter, Typical and Atypical: A Review.

    PubMed

    Cosío, Francisco G

    2017-06-01

    Clinical electrophysiology has made the traditional classification of rapid atrial rhythms into flutter and tachycardia of little clinical use. Electrophysiological studies have defined multiple mechanisms of tachycardia, both re-entrant and focal, with varying ECG morphologies and rates, authenticated by the results of catheter ablation of the focal triggers or critical isthmuses of re-entry circuits. In patients without a history of heart disease, cardiac surgery or catheter ablation, typical flutter ECG remains predictive of a right atrial re-entry circuit dependent on the inferior vena cava-tricuspid isthmus that can be very effectively treated by ablation, although late incidence of atrial fibrillation remains a problem. Secondary prevention, based on the treatment of associated atrial fibrillation risk factors, is emerging as a therapeutic option. In patients subjected to cardiac surgery or catheter ablation for the treatment of atrial fibrillation or showing atypical ECG patterns, macro-re-entrant and focal tachycardia mechanisms can be very complex and electrophysiological studies are necessary to guide ablation treatment in poorly tolerated cases.

  13. Atypical Miyoshi distal myopathy: A case report

    PubMed Central

    Wang, Meiling; Guo, Yujie; Fu, Yong; Jia, Rui; Chen, Gang

    2016-01-01

    Five distinct predominant distal myopathies have been identified with discrete clinical and genetic patterns. Miyoshi myopathy (MM; early adult-onset, type 2) is a subtype of dysferlinopathy. Furthermore, MM is the most common form of autosomal recessive distal myopathy. MM is typically characterized by muscular weakness, initially affecting the gastrocnemius or soleus muscle from the late teens or early adulthood. The present study reports a case of MM that was confirmed by pathological and immunohistochemical methods, in addition to a review of the relevant literature. A 37-year-old male patient presented with muscular weakness in the left foot. This clinical manifestation was not typical of MM, and the patient was initially diagnosed with inflammatory myopathy. He was treated with dexamethasone at a dose of 10 mg for 5 days followed by gradual tapering, following which the symptoms were alleviated; however, the pathology, immunohistochemistry and electromyography eventually confirmed the diagnosis of MM. The treatment was then terminated and the patient was discharged. The present study further supports the underlying heterogeneity in atypical MM-like phenotypes. Dysferlin protein deficiency can be identified by pathological examination. The pathology of dysferlinopathy is characterized by changes of muscular dystrophy. Inflammatory cellular infiltration is a relatively common finding in the muscle biopsies from numerous patients with dysferlinopathy. Therefore, the detection of dysferlin deficiency or marked reduction on the sarcolemma using immunohistochemical staining is important for the diagnosis of dysferlinopathy. PMID:27882118

  14. Atypical alpha asymmetry in adults with ADHD.

    PubMed

    Hale, T Sigi; Smalley, Susan L; Hanada, Grant; Macion, James; McCracken, James T; McGough, James J; Loo, Sandra K

    2009-08-01

    A growing body of literature suggests atypical cerebral asymmetry and interhemispheric interaction in ADHD. A common means of assessing lateralized brain function in clinical populations has been to examine the relative proportion of EEG alpha activity (8-12 Hz) in each hemisphere (i.e., alpha asymmetry). Increased rightward alpha asymmetry has been associated with ADHD-like traits such as reduced reward responsiveness, a lack of inhibition toward aversive experience, and increased approach behaviors, and previous work has indicated increased rightward alpha asymmetry in children with ADHD. The current study explores whether increased rightward alpha asymmetry is also evident in adults with ADHD. We assessed low (8-10 Hz) and high (10-12 Hz) alpha asymmetry in adults with ADHD (n=29) versus controls (n=62) during baseline and cognitive activation conditions for nine homologous electrode pairs along the anterior-posterior axis. Seven results emerged (p<.05) showing increased rightward alpha asymmetry in adults with ADHD. This occurred in three specific electrode pairs across two testing conditions, and five of six results occurred in the lower alpha band. Finally, post hoc analysis indicated that increased rightward alpha asymmetry was generally associated with greater numbers of ADHD symptoms--with a possible parietal association for inattentive and a fronto-temporal association for hyperactivity symptoms. Increased rightward alpha asymmetry previously observed in children with ADHD appears to be a developmentally persistent feature of ADHD.

  15. Atypical Bilateral Fuchs Uveitis: Diagnostic Challenges

    PubMed Central

    Couto, Cristóbal; Hurtado, Erika; Faingold, Dana; Demetrio, Carmen; Schlaen, Ariel; Zas, Marcelo; Zarate, Jorge; Rosetti, Silvia; de Lima, Andrea Paes; Croxatto, Juan Oscar; Chiaradía, Pablo; Burnier, Miguel N.

    2015-01-01

    Bilateral Fuchs uveitis associated with vitreous infiltration and posterior segment involvement requires a thorough diagnostic evaluation. The lack of well-defined diagnostic criteria makes identification of this entity difficult. The aim of this case report was to present the characteristics of a patient with atypical Fuchs uveitis and the procedures needed to rule out the differential diagnosis with specific attention to the utility of in vivo confocal microscopy (IVCM). Case Report One case of chronic bilateral uveitis with severe vitreous opacities is presented. After extensive systemic workup, including vitrectomy, the case had no identifiable systemic etiology. IVCM of the cornea revealed the presence of dendritiform keratic precipitates. Conclusion The diagnosis of Fuchs uveitis is based on clinical findings as no confirmatory laboratory tests are available. A high index of suspicion is key to an early diagnosis, especially in the cases with vitreous opacities and posterior segment manifestations. Auxiliary tests such as IVCM may aid the clinician in the diagnosis of Fuchs uveitis. PMID:26483668

  16. Atypical mitochondrial inheritance patterns in eukaryotes.

    PubMed

    Breton, Sophie; Stewart, Donald T

    2015-10-01

    Mitochondrial DNA (mtDNA) is predominantly maternally inherited in eukaryotes. Diverse molecular mechanisms underlying the phenomenon of strict maternal inheritance (SMI) of mtDNA have been described, but the evolutionary forces responsible for its predominance in eukaryotes remain to be elucidated. Exceptions to SMI have been reported in diverse eukaryotic taxa, leading to the prediction that several distinct molecular mechanisms controlling mtDNA transmission are present among the eukaryotes. We propose that these mechanisms will be better understood by studying the deviations from the predominating pattern of SMI. This minireview summarizes studies on eukaryote species with unusual or rare mitochondrial inheritance patterns, i.e., other than the predominant SMI pattern, such as maternal inheritance of stable heteroplasmy, paternal leakage of mtDNA, biparental and strictly paternal inheritance, and doubly uniparental inheritance of mtDNA. The potential genes and mechanisms involved in controlling mitochondrial inheritance in these organisms are discussed. The linkage between mitochondrial inheritance and sex determination is also discussed, given that the atypical systems of mtDNA inheritance examined in this minireview are frequently found in organisms with uncommon sexual systems such as gynodioecy, monoecy, or andromonoecy. The potential of deviations from SMI for facilitating a better understanding of a number of fundamental questions in biology, such as the evolution of mtDNA inheritance, the coevolution of nuclear and mitochondrial genomes, and, perhaps, the role of mitochondria in sex determination, is considerable.

  17. Atypical Presentation of a Pediatric Cerebellar Ganglioglioma.

    PubMed

    Bram, Richard; Seidman, Roberta J; Chesler, David

    2017-09-20

    Gangliogliomas (GGs) are rare central nervous system tumors occurring primarily in the supratentorial compartment with infratentorial instances most often involving the brain stem. Infratentorial GGs typically present with signs and symptoms of increased intracranial pressure (ICP), cranial nerve deficits, or focal cerebellar findings; rarely, these tumors have been associated with focal seizures. In this report, we describe an atypical presentation of a cerebellar GG in a 20-month-old male who initially presented with syncope and emesis in the absence of electrographic evidence of seizures, radiographic evidence of hydrocephalus, or elevated ICP. The epidemiology, radiographic, and pathological findings as well as the treatment of these tumors are also discussed. After gross total resection, the patient experienced full resolution of all his preoperative symptoms without the development of new neurological deficits. Unlike their supratentorial counterparts, infratentorial GGs do not commonly present with seizures although rare reports exist in the literature of seizures attributed to cerebellar GG. Moreover, cerebellar GGs may produce nonspecific symptoms in the absence of concrete diagnostic findings. Such a presentation should prompt further neurological evaluation. Most cases of isolated cerebellar GG can be successfully treated with surgical resection and carry a favorable prognosis. © 2017 S. Karger AG, Basel.

  18. Atypical clinical response patterns to ipilimumab.

    PubMed

    Ledezma, Blanca; Binder, Sandra; Hamid, Omid

    2011-08-01

    Patients with advanced melanoma have few treatment options, and survival is poor. However, improved understanding of how the immune system interacts with cancer has led to the development of novel therapies. Ipilimumab is a monoclonal antibody that inhibits cytotoxic T-lymphocyte antigen-4 (CTLA-4), a key negative regulator of host T-cell responses. This article presents cases of patients receiving ipilimumab in clinical trials along with a discussion of their significance and relevance to nursing practice. The patients showed different response patterns to ipilimumab and also had various typical immune-related adverse events (irAEs), which were managed successfully. The atypical response patterns produced by ipilimumab likely reflect its mechanism of action, which requires time for the immune system to mount an effective antitumor response. Meanwhile, lesions may appear to enlarge as a consequence of enhanced T-cell infiltration, although this may not necessarily be true disease progression. Patients receiving ipilimumab may respond very differently compared to how they might react to chemotherapy. Responses can take weeks or months to develop; therefore, clinicians should not terminate treatment prematurely, providing the patient's condition allows for continuation. Early recognition of irAEs combined with prompt management will ensure that events are more likely to resolve without serious consequences.

  19. Observing Behavior and Atypically Restricted Stimulus Control

    PubMed Central

    Dube, William V; Dickson, Chata A; Balsamo, Lyn M; O'Donnell, Kristin Lombard; Tomanari, Gerson Y; Farren, Kevin M; Wheeler, Emily E; McIlvane, William J

    2010-01-01

    Restricted stimulus control refers to discrimination learning with atypical limitations in the range of controlling stimuli or stimulus features. In the study reported here, 4 normally capable individuals and 10 individuals with intellectual disabilities (ID) performed two-sample delayed matching to sample. Sample-stimulus observing was recorded with an eye-tracking apparatus. High accuracy scores indicated stimulus control by both sample stimuli for the 4 nondisabled participants and 4 participants with ID, and eye tracking data showed reliable observing of all stimuli. Intermediate accuracy scores indicated restricted stimulus control for the remaining 6 participants. Their eye-tracking data showed that errors were related to failures to observe sample stimuli and relatively brief observing durations. Five of these participants were then given interventions designed to improve observing behavior. For 4 participants, the interventions resulted initially in elimination of observing failures, increased observing durations, and increased accuracy. For 2 of these participants, contingencies sufficient to maintain adequate observing were not always sufficient to maintain high accuracy; subsequent procedure modifications restored it, however. For the 5th participant, initial improvements in observing were not accompanied by improved accuracy, an apparent instance of observing without attending; accuracy improved only after an additional intervention that imposed contingencies on observing behavior. Thus, interventions that control observing behavior seem necessary but may not always be sufficient for the remediation of restricted stimulus control. PMID:21541173

  20. Atypical presentation of mucopolysaccharidosis type IVA.

    PubMed

    Rush, Eric T

    2016-09-01

    A 14 year old patient with short stature, type I diabetes, and cataracts was referred for evaluation of avascular necrosis of the femoral head. Radiography was suggestive of spondyloepiphyseal dysplasia with decreased bone mineral density for age. Targeted molecular and biochemical testing were normal in this patient. Whole exome sequencing was performed and showed compound heterozygosity for previously reported pathogenic GALNS variants which were diagnostic of mucopolysaccharidosis, type IVA (Morquio A). While this case describes neither a novel condition nor a new mutation, it does illustrate three important points in the diagnosis of patients with atypical forms of MPS IVA. First, that in many instances urine glycosaminoglycan analysis is not sufficient to rule out MPS IVA as a potential diagnosis. Patients in whom biochemical screening is advised should have measurement of leukocyte enzymatic activity. Second, that in patients with radiographic evidence of spondyloepiphyseal dysplasia with additional features or with normal targeted testing, MPS IVA should remain in the differential diagnosis. Third, that whole exome sequencing represents a viable diagnostic platform for evaluation of patients with unknown skeletal or metabolic disease.

  1. Nocturnal manifestations of atypical parkinsonian disorders.

    PubMed

    Bhidayasiri, Roongroj; Jitkritsadakul, Onanong; Colosimo, Carlo

    2014-01-01

    Although nocturnal disturbances are increasingly recognized as an integral part of the continuum of daytime manifestations of Parkinson's disease (PD), there is still little evidence in the medical literature to support the occurrence of these complex phenomena in patients with atypical parkinsonian disorders (APDs). Based on the anatomical substrates in APDs, which are considered to be more extensive outside the basal ganglia than in PD, we might expect that patients with APDs encounter the whole range of nocturnal disturbances, including motor, sleep disorders, autonomic dysfunctions, and neuropsychiatric manifestations at a similar, or even greater, frequency than in PD. This article is a review of the current literature on the problems at nighttime of patients with progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and dementia with Lewy bodies. MEDLINE, life science journals and online books were searched by querying appropriate key words. Reports were included if the studies were related to nocturnal manifestations in APDs. Forty articles fulfilled the selection criteria. Differences between these symptoms in APDs and PD are highlighted, given the evidence available about each manifestation. This analysis of nocturnal manifestations of APDs suggests the need for future studies to address these issues to improve the quality of life not only of patients with APDs but the caregivers who encounter the challenges of supporting these patients on a daily basis.

  2. Atypical Takotsubo syndrome during anagrelide therapy.

    PubMed

    Proietti, Riccardo; Rognoni, Andrea; Ardizzone, Fabio; Maccio, Sergio; Santagostino, Alberto; Rognoni, Giorgio

    2009-07-01

    Anagrelide is a phosphodiesterase III inhibitor utilized in the treatment of essential thrombocythemia. Anagrelide can be responsible for positive inotropic and chonotropic activity of the cardiovascular system. Moreover, it can induce vasospam directly on the epicardial coronary arteries. In the literature, it is well reported that this inhibitor can determine serious cardiovascular side effects, including congestive heart failure, arrhythmia and acute coronary syndrome. We describe the case of a 75-year-old woman who developed a mid-ventricular Takotsubo syndrome while on anagrelide therapy. Takotsubo cardiomyopathy, also known as left ventricular ballooning syndrome, is characterized by a reversible ventricular contractile dysfunction with akinesis and expansion of apical segments and hyperkinesis of the basal segments. Recently, atypical cases with akinesia and dilation of mid-ventricular segment and hypercontraction of the apical segments, also called mid-ventricular and inverted Takotsubo syndrome, have been described. Even though the pathogenesis of Takotsubo syndrome is poorly understood, several mechanisms have been proposed, including catecholamine-induced myocardial stunning, and ischemia-mediated stunning due to multivessel epicardial or microvascular spasm. We think that in our case, the adverse response of anagrelide therapy was determined, by accumulated dosage of the drug, through an intensive inotropic stimulation and a sympathetic hyperactivation in a vulnerable myocardium. To our knowledge, this is one of the first reports of an association between anagrelide therapy and Takotsubo cardiomyopathy.

  3. [Sturge-Weber syndrome with atypical calcifications].

    PubMed

    Prieto, M L; de Juan, J; Antón, M; Roiz, C; Crespo, M

    1997-09-01

    The syndrome, or disease, or Sturge Weber (SSW) is a neuro-ectodermic disorder of unknown incidence, sporadic presentation and specific sex incidence. It is characterized by the presence of a flat, facial angioma which affects at least the first branch of the trigeminal nerve, association with ipsilateral leptomeningeal vascular anomalies, one or more symptoms (epilepsy, hemiparesia, hemiplegia or mental retardation) and ipsilateral vascular lesions of the choroid which lead to glaucoma. As a consequence of lepto-meningeal involvement, homolateral cerebral hemi-atrophy develops together with cortico-subcortical calcifications with a characteristic "railway line" appearance. We present the case of a six month old girl with a flat port wine angioma on the left half of her face, including three branches of the trigeminal nerve and the left half of her body. She had partial motor crises of the right leg. On the cranial CT there were left periventricular calcifications and calcifications of the choroid plexus. Gadolinium-MR showed signs of left cerebral hemi-atrophy, which was confirmed on the cerebral SPECT (left temporal hypoperfusion). This case is interesting on account of the presence of atypical calcifications, both with regard to the sites and age of presentation. We emphasize the need for cranial CT to rule out the presence of calcifications, (as in this case) not seen on Xray of the skull or on MR. We favour the use of cerebral SPECT as a complementary diagnostic technique.

  4. Echovirus 22 is an atypical enterovirus.

    PubMed Central

    Coller, B A; Chapman, N M; Beck, M A; Pallansch, M A; Gauntt, C J; Tracy, S M

    1990-01-01

    Although echovirus 22 (EV22) is classified as an enterovirus in the family Picornaviridae, it is atypical of the enterovirus paradigm, typified by the polioviruses and the coxsackie B viruses. cDNA reverse transcribed from coxsackievirus B3 (CVB3) RNA does not hybridize to genomic RNA of EV22, and conversely, cDNA made to EV22 does not hybridize to CVB3 genomic RNA or to molecular clones of CVB3 or poliovirus type 1. EV22 cDNA does not hybridize to viral RNA of encephalomyocarditis virus or to a molecular clone of Theiler's murine encephalomyelitis virus, members of the cardiovirus genus. The genomic RNA of EV22 cannot be detected by the polymerase chain reaction using generic enteroviral primers. EV22 does not shut off host cell protein synthesis, and the RNA of EV22 is efficiently translated in vitro in rabbit reticulocyte lysates. Murine enterovirus-immune T cells recognize and proliferate against EV22 as an antigen in vitro, demonstrating that EV22 shares an epitope(s) common to enteroviruses but not found among other picornaviruses. Images PMID:2159539

  5. Clinical pharmacology of atypical antipsychotics: an update

    PubMed Central

    Mauri, M.C.; Paletta, S.; Maffini, M.; Colasanti, A.; Dragogna, F.; Di Pace, C.; Altamura, A.C.

    2014-01-01

    This review will concentrate on the clinical pharmacology, in particular pharmacodynamic data, related to atypical antipsychotics, clozapine, risperidone, paliperidone, olanzapine, que¬tiapine, amisulpride, ziprasidone, aripiprazole, asenapine, iloperidone, lurasidone and cariprazine. A summary of their acute pharmacokinetics properties are also reported. Four new second-generation antipsychotics are available: iloperidone, asenapine, lurasidone and in the next future cariprazine. Similar to ziprasidone and aripiprazole, these new agents are advisable for the lower propensity to give weight gain and metabolic abnormalities in comparison with older second-generation antipsychotics such as olanzapine or clozapine. Actually lurasidone seems to be best in terms of minimizing unwanted alterations in body weight and metabolic variables. Therapeutic drug monitoring is not strictly necessary for all of the new antipsychotic drugs because there are no unequivocal data supporting a relationship between plasma drug levels and clinical outcomes or side effects. The exception can be represented by clozapine for which plasma levels of 350-420 ng/ml are reported to be associated with an increased probability of a good clinical response. Also for olanzapine an established therapeutic range (20-50 ng/ml) is proposed to yield an optimal response and minimize side effects. PMID:26417330

  6. Transformation of a meningioma with atypical imaging

    PubMed Central

    Kumar, Ashish; Deopujari, Chandrashekhar; Karmarkar, Vikram

    2016-01-01

    Meningiomas are benign tumors of the central nervous system. They have long term curability if they are excised completely. If not, they can recur after a prolonged period and can lead to increased morbidity during re-surgery. Recurrence is rarely associated with invasiveness. Usually de-differentiation in case of meningiomas is uncommon without any predisposing factors including different genetic mutations or radiation to the involved region. We report a case of a 38-year-old female who was operated for a benign para-sagittal meningioma 8 years back and subsequently developed an invasive recurrence off late. Also this time, the imaging morphology was slightly different for a meningioma and gross as well as microscopic findings were very atypical. Awareness for such cases must be there while dealing with recurrent meningiomas as invasiveness may not always be associated with adverse predisposing factors like radiation. As invasiveness is always a histopathological diagnosis, picking up such features on imaging is a daunting task and if done, can help neurosurgeons prognosticate such invasive recurrences in a better fashion. PMID:27366271

  7. Fluphenazine (oral) versus atypical antipsychotics for schizophrenia.

    PubMed

    Sampford, James R; Sampson, Stephanie; Li, Bao Guo; Zhao, Sai; Xia, Jun; Furtado, Vivek A

    2016-07-02

    Fluphenazine is a typical antipsychotic drug from the phenothiazine group of antipsychotics. It has been commonly used in the treatment of schizophrenia, however, with the advent of atypical antipsychotic medications, use has declined over the years. To measure the outcomes (both beneficial and harmful) of the clinical effectiveness, safety and cost-effectiveness of oral fluphenazine versus atypical antipsychotics for schizophrenia. We searched the Cochrane Central Register of Studies (25 April 2013). For the economic search, we searched the Cochrane Schizophrenia Group Health Economic Database (CSzGHED) on 31 January 2014 SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing fluphenazine (oral) with any other oral atypical antipsychotics. Review authors worked independently to inspect citations and assess the quality of the studies and to extract data. For homogeneous dichotomous data we calculated the risk ratio (RR) and 95% confidence interval (CI), and calculated the mean differences (MDs) for continuous data. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to rate the quality of the evidence. Four studies randomising a total of 202 people with schizophrenia are included. Oral fluphenazine was compared with oral amisulpride, risperidone, quetiapine and olanzapine.Comparing oral fluphenazine with amisulpride, there was no difference between groups for mental state using the Brief Psychiatric Rating Scale (BPRS) (1 RCT, n = 57, MD 5.10 95% CI -2.35 to 12.55, very low-quality evidence), nor was there any difference in numbers leaving the study early for any reason (2 RCTs, n = 98, RR 1.19 95% CI 0.63 to 2.28, very low-quality evidence). More people required concomitant anticholinergic medication in the fluphenazine group compared to amisulpride (1 RCT, n = 36, RR 7.82 95% CI 1.07 to 57.26, very low-quality evidence). No data were reported for important outcomes

  8. Evaluating North Sea carbon sources using radiogenic (224Ra and 228Ra) and stable carbon isotope (DI13C) tracers

    NASA Astrophysics Data System (ADS)

    Burt, William; Thomas, Helmuth; Hagens, Mathilde; Brenner, Heiko; Paetsch, Johannes; Clargo, Nikki

    2015-04-01

    In the North Sea, much uncertainty still exists regarding the role of boundary fluxes (e.g. benthic input from sediments or lateral inputs from the coastline) in the overall biogeochemical cycling of the system. The stable carbon isotope signature of dissolved inorganic carbon (δ13C-DIC) is a common tool for following transformations of carbon in the water column and identifying carbon sources and sinks. Here, analyses of the first basin-wide observations of δ13C-DIC reveal that a balance between biological production and respiration, as well as a freshwater input near the European continental coast, predominantly control surface distributions in the North Sea. A strong relationship between the biological component of DIC (DICbio) and δ13C-DIC is then used to quantify the metabolic DIC flux associated with changes in the carbon isotopic signature. Correlations are also found between δ13C-DIC and naturally-occurring Radium isotopes (224Ra and 228Ra), which have well-identified sources from the seafloor and coastal boundaries. The relationship between δ13C-DIC and the longer-lived 228Ra isotope (half-life = 5.8 years) is used to derive a metabolic DIC flux from the European continental coastline. 228Ra is also shown to be a highly effective tracer of North Sea total alkalinity (TA) compared to the more conventional use of salinity as a tracer. Coastal alkalinity inputs are calculated using relationships with 228Ra, and ratios of DIC and TA suggest denitrification as the main metabolic pathway for the formation of these coastal inputs. Finally, coastal TA inputs are translated into inputs of protons to quantify their impact on the buffering capacity of the Southern North Sea.

  9. Atypical presentation of pheochromocytoma: Central nervous system pseudovasculitis

    PubMed Central

    Rupala, Ketankumar; Mittal, Varun; Gupta, Rajiv; Yadav, Rajiv

    2017-01-01

    Pheochromocytoma has atypical presentation in 9%–10% of patients. Atypical presentations include myocardial infarction, renal failure, and rarely cerebrovascular events. Various etiologies for central nervous system (CNS) involvement in pheochromocytoma have been described in the literature. A rare association of CNS vasculitis-like features has been described with pheochromocytoma. We report a rare case of pheochromocytoma detected on evaluation for CNS vasculitis-like symptoms. PMID:28197038

  10. Catheter Ablation of Atypical Atrioventricular Nodal Reentrant Tachycardia.

    PubMed

    Katritsis, Demosthenes G; Marine, Joseph E; Contreras, Fernando M; Fujii, Akira; Latchamsetty, Rakesh; Siontis, Konstantinos C; Katritsis, George D; Zografos, Theodoros; John, Roy M; Epstein, Lawrence M; Michaud, Gregory F; Anter, Elad; Sepahpour, Ali; Rowland, Edward; Buxton, Alfred E; Calkins, Hugh; Morady, Fred; Stevenson, William G; Josephson, Mark E

    2016-11-22

    Because of its low prevalence, data on atypical atrioventricular nodal reentrant tachycardia (AVNRT) are scarce, and the optimal ablation method has not been established. Our study aimed at assessing the efficacy and safety of conventional slow pathway ablation, as applied for typical cases, in atypical AVNRT. We studied 2079 patients with AVNRT subjected to slow pathway ablation. In 113 patients, mean age 48.5±18.1 years, 68 female, atypical AVNRT or coexistent atypical and typical AVNRT without other concomitant arrhythmia was diagnosed. Ablation data and outcomes were compared with a group of age- and sex-matched control patients with typical AVNRT. Fluoroscopy and radiofrequency current delivery times were not different in the atypical and typical groups, 20.3±12.2 versus 20.8±12.9 minutes (P=0.730) and 5.9±5.0 versus 5.5±4.5 minutes (P=0.650), respectively. Slow pathway ablation was accomplished from the right septum in 110 patients, and from the left septum in 3 patients, in the atypical group. There was no need for additional ablation lesions at other anatomic sites, and no cases of atrioventricular block were encountered. Recurrence rates of the arrhythmia were 5.6% in the atypical (6/108 patients) and 1.8% in the typical (2/111 patients) groups in the next 3 months following ablation (P=0.167). Conventional ablation at the anatomic area of the slow pathway is the therapy of choice for symptomatic AVNRT, regardless of whether the typical or atypical form is present. © 2016 American Heart Association, Inc.

  11. Atypical mycobacterial tenosynovitis and bursitis of the wrist.

    PubMed

    Sanal, Hatice Tuba; Zor, Fatih; Kocaoğlu, Murat; Bulakbaşi, Nail

    2009-12-01

    Atypical mycobacterial tenosynovitis of the wrist can easily be misdiagnosed as synovial chondromatosis. Both sonography and magnetic resonance imaging plays an important role in depicting "rice bodies" within the distended tendon sheaths and bursae of atypical mycobacterial infection. An endemic place for Mycobacterium species and the occupation of the patient should raise the suspicion for the disease. Polymerase chain reaction of the distended tendon fluid is a sensitive, specific and rapid method in identification of the mycobacteria.

  12. Atypical presentation of macrophagic myofasciitis 10 years post vaccination.

    PubMed

    Ryan, Aisling M; Bermingham, Niamh; Harrington, Hugh J; Keohane, Catherine

    2006-12-01

    Macrophagic myofasciitis (MMF) is an uncommon inflammatory disorder of muscle believed to be due to persistence of vaccine-derived aluminium hydroxide at the site of injection. The condition is characterised by diffuse myalgias, arthralgia and fatigue. We describe a patient with histologically confirmed MMF whose presentation was atypical with left chest and upper limb pain beginning more than 10 years post vaccination. Treatment with steroids led to symptomatic improvement. Although rare, clinicians should consider MMF in cases of atypical myalgia.

  13. Generic penetration in the retail atypical antipsychotic market.

    PubMed

    Lenderts, Susan; Kalali, Amir H; Buckley, Peter

    2010-03-01

    In this article, we explore the penetration of generic atypical antipsychotics in the United States market before and after the availability of generic risperidone in July 2008. Analysis suggests that, overall, generic penetration into the atypical antipsychotic market has grown from approximately three percent in January 2008 to more than 25 percent in December 2009. Similar trends are uncovered when branded and generic prescriptions are analyzed by specialty.

  14. Factor structure of the Edinburgh Handedness Inventory versus the Fazio Laterality Inventory in a population with established atypical handedness.

    PubMed

    Fazio, Rachel L; Cantor, James M

    2015-01-01

    The Edinburgh Handedness Inventory (EHI) has consistently remained the most used handedness inventory despite its limitations. The psychometric properties of handedness inventories, however, are increasingly important due to their use in matching groups for neuroimaging research. This study compared the performance of the EHI and the Fazio Laterality Inventory (FLI) in a population with atypical handedness. Whereas the EHI demonstrated a single-factor loading in this population, the FLI's previously demonstrated single factor dissociated into two factors: fine motor/ballistic movements and expressive/instrumental movements. This dissociation is similar to that seen when tests of cognitive constructs--which tend to load on a single factor in intact populations--dissociate when administered to populations with difficulties in the assessed domain. This pattern of performance lends further support for the use of the FLI to more accurately assess handedness. Future research in other populations with atypical laterality may illuminate additional factors of the FLI.

  15. IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction via PLCβ3 during Airway Inflammation.

    PubMed

    Jeong, Jee-Yeong; Kim, Jiwook; Kim, Bokyoum; Kim, Joowon; Shin, Yusom; Kim, Judeok; Ryu, Siejeong; Yang, Yu-Mi; Song, Kyoung Seob

    2016-01-01

    Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y2 complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates MUC5AC gene expression via the inhibition of Gαq-induced Ca(2+) signaling. IL-1ra inhibited IL-1α protein expression and secretion, and vice versa. Interestingly, ATP/P2Y2-induced IL-1ra and IL-1α secretion were both mediated by PLCβ3. A dominant-negative mutation in the PDZ-binding domain of PLCβ3 inhibited ATP/P2Y2-induced IL-1ra and IL-1α secretion. IL-1α in the presence of the ATP/P2Y2 complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y2 complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y2-induced MUC5AC gene expression, through inhibition of IL-1α secretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases.

  16. IL-1ra Secreted by ATP-Induced P2Y2 Negatively Regulates MUC5AC Overproduction via PLCβ3 during Airway Inflammation

    PubMed Central

    Kim, Jiwook; Kim, Bokyoum; Kim, Joowon; Shin, Yusom; Kim, Judeok; Ryu, Siejeong; Yang, Yu-Mi

    2016-01-01

    Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that the ATP/P2Y2 complex secretes many cytokines and chemokines to regulate airway inflammation, among which IL-1 receptor antagonist (IL-1ra) downregulates MUC5AC gene expression via the inhibition of Gαq-induced Ca2+ signaling. IL-1ra inhibited IL-1α protein expression and secretion, and vice versa. Interestingly, ATP/P2Y2-induced IL-1ra and IL-1α secretion were both mediated by PLCβ3. A dominant-negative mutation in the PDZ-binding domain of PLCβ3 inhibited ATP/P2Y2-induced IL-1ra and IL-1α secretion. IL-1α in the presence of the ATP/P2Y2 complex activated the ERK1/2 pathway in a greater degree and for a longer duration than the ATP/P2Y2 complex itself, which was dramatically inhibited by IL-1ra. These findings suggest that secreted IL-1ra exhibits a regulatory effect on ATP/P2Y2-induced MUC5AC gene expression, through inhibition of IL-1α secretion, to maintain the mucus homeostasis in the airway. Therefore, IL-1ra could be an excellent modality for regulating inflamed airway microenvironments in respiratory diseases. PMID:27034593

  17. The biological effects of {sup 224}Ra injected into dogs

    SciTech Connect

    Muggenburg, B.A.; Lloyd, R.D.; Hahn, F.F.; Griffith, W.C.; Boecker, B.B.

    1994-11-01

    The purpose of this study was to investigate the toxicity of injected {sup 224}Ra in the dog. Radium-224 is a short-lived isotope of radium with a half-life of 3.62 d. When administered parenterally, it deposits on bone surfaces; because of its short half-life, most of its energy is deposited on bone surfaces, in a manner similar to plutonium. The experimental design included a comparison to the exposed human population. Instead of using a single injection of {sup 224}Ra, groups were included in which dogs were injected once, 10 times, or 50 times. This design provided groups that could be compared to the multiple injections often used in people for the treatment of ankylosing spondylitis.

  18. Fast electric dipole transitions in Ra-Ac nuclei

    SciTech Connect

    Ahmad, I.

    1985-01-01

    Lifetime of levels in /sup 225/Ra, /sup 225/Ac, and /sup 227/Ac have been measured by delayed coincidence techniques and these have been used to determine the E1 gamma-ray transition probabilities. The reduced E1 transition probabilities. The reduced E1 transition probabilities in /sup 225/Ra and /sup 225/Ac are about two orders of magnitude larger than the values in mid-actinide nuclei. On the other hand, the E1 rate in /sup 227/Ac is similar to those measured in heavier actinides. Previous studies suggest the presence of octupole deformation in all the three nuclei. The present investigation indicates that fast E1 transitions occur for nuclei with octupole deformation. However, the studies also show that there is no one-to-one correspondence between E1 rate and octupole deformation. 13 refs., 4 figs.

  19. Enrichment of Vitamin D response elements in RA associated loci supports a role for vitamin D in the pathogenesis of RA

    PubMed Central

    Yarwood, Annie; Martin, Paul; Bowes, John; Lunt, Mark; Worthington, Jane; Barton, Anne; Eyre, Steve

    2013-01-01

    The aim of this study was to explore the role of vitamin-D in rheumatoid arthritis (RA) pathogenesis by investigating enrichment of vitamin-D response elements (VDREs) in confirmed RA susceptibility loci and testing variants associated with vitamin-D levels for association with RA. Bioinformatically, VDRE genomic positions were overlaid with non HLA confirmed RA susceptibility regions. The number of VDREs at RA loci was compared to a randomly selected set of genomic loci to calculate an average relative risk (RR). SNPs in the DHCR7/NADSYN1 and CYP2R1 loci, previously associated with circulating vitamin-D levels, were tested in UK RA cases (n = 3870) and controls (n = 8430). Significant enrichment of VDREs was seen at RA loci (p=9.23×10−8) when regions were defined either by gene (RR 5.50) or position (RR 5.86). SNPs in the DHCR7/NADSYN1 locus showed evidence of positive association with RA, rs4944076 (p=0.008, OR 1.14 95% CI 1.03-1.24). The significant enrichment of VDREs at RA associated loci and the modest association of variants in loci controlling levels of circulating vitamin-D, supports the hypothesis that vitamin-D plays a role in the development of RA. PMID:23636220

  20. Glucagon-like peptide-1 receptors agonists (GLP1 RA).

    PubMed

    Kalra, Sanjay

    2013-10-01

    The glucagon-like peptide-1 receptors agonists (GLP1RA) are a relatively new class of drugs, used for management of type 2 diabetes. This review studies the characteristics of these drugs, focusing upon their mechanism of action, intra-class differences, and utility in clinical practice. It compares them with other incretin based therapies, the dipeptidyl peptidase-IV inhibitors, and predicts future developments in the use of these molecules, while highlighting the robust indications for the use of these drugs.

  1. Characterization of the CpxRA regulon in Haemophilus ducreyi.

    PubMed

    Labandeira-Rey, Maria; Brautigam, Chad A; Hansen, Eric J

    2010-11-01

    The Haemophilus ducreyi 35000HP genome encodes a homolog of the CpxRA two-component cell envelope stress response system originally characterized in Escherichia coli. CpxR, the cytoplasmic response regulator, was shown previously to be involved in repression of the expression of the lspB-lspA2 operon (M. Labandeira-Rey, J. R. Mock, and E. J. Hansen, Infect. Immun. 77:3402-3411, 2009). In the present study, the H. ducreyi CpxR and CpxA proteins were shown to closely resemble those of other well-studied bacterial species. A cpxA deletion mutant and a CpxR-overexpressing strain were used to explore the extent of the CpxRA regulon. DNA microarray and real-time reverse transcriptase (RT) PCR analyses indicated several potential regulatory targets for the H. ducreyi CpxRA two-component regulatory system. Electrophoretic mobility shift assays (EMSAs) were used to prove that H. ducreyi CpxR interacted with the promoter regions of genes encoding both known and putative virulence factors of H. ducreyi, including the lspB-lspA2 operon, the flp operon, and dsrA. Interestingly, the use of EMSAs also indicated that H. ducreyi CpxR did not bind to the promoter regions of several genes predicted to encode factors involved in the cell envelope stress response. Taken together, these data suggest that the CpxRA system in H. ducreyi, in contrast to that in E. coli, may be involved primarily in controlling expression of genes not involved in the cell envelope stress response.

  2. Amisulpride versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; da Mota Neto, Joaquim I Silveira; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (atypical) antipsychotics have become first line drug treatments for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examine how the efficacy and tolerability of amisulpride differs from that of other second generation antipsychotics. Objectives To evaluate the effects of amisulpride compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE and PsycINFO. We updated this search in July 2012 and added 47 new trials to the awaiting classification section. Selection criteria We included randomised, at least single-blind, trials comparing oral amisulpride with oral forms of aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychoses. Data collection and analysis We extracted data independently. For continuous data we calculated weighted mean differences (MD), for dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. Main results The review currently includes ten short to medium term trials with 1549 participants on three comparisons: amisulpride versus olanzapine, risperidone and ziprasidone. The overall attrition rate was considerable (34.7%) with no significant difference between groups. Amisulpride was similarly effective as olanzapine and risperidone and more effective than ziprasidone (leaving the study early due to inefficacy: n=123, 1 RCT, RR 0.21 CI 0.05 to 0.94, NNT 8 CI 5 to 50

  3. An improved limit on the EDM of 225 Ra

    NASA Astrophysics Data System (ADS)

    Bishof, Michael; Bailey, Kevin; Dietrich, Matthew R.; Greene, John P.; Holt, Roy J.; Kalita, Mukut R.; Korsch, Wolfgang; Lemke, Nathan D.; Lu, Zheng-Tian; Mueller, Peter; O'Connor, Thomas P.; Parker, Richard H.; Rabga, Tenzin; Singh, Jaideep T.

    2016-05-01

    Searches for permanent electric dipole moments (EDMs) are sensitive probes of symmetry violation that could explain the dominance of matter over anti-matter. The 225 Ra (t1/2 = 15 days, I = 1/2) atom is a particularly attractive system to use for an EDM measurement because its octupole-deformed nucleus, closely spaced ground-state parity doublet, and large nuclear charge make 225 Ra uniquely sensitive to symmetry-violating interactions in the nuclear medium. In 2015, we reported the first ``proof of principle'' measurement of the 225 Ra EDM, giving a 95% confidence upper limit of 5* 10-22 e-cm; representing the first EDM measurement using laser-trapped atoms as well as the first EDM measurement of an atom with an octupole-deformed nucleus. After implementing upgrades to our apparatus, we now observe nuclear spin coherence after 20 s of free evolution - a factor of ten improvement. A new EDM measurement based on the upgraded system improved the 95% confidence upper limit by a factor of 36. We also report on the progress of current experimental upgrades that have the potential to further improve our EDM sensitivity by many orders of magnitude, allowing us to test symmetry violation at an unprecedented level. This work is supported by U.S. DOE, Office of Science, Office of Nuclear Physics, under Contract DE-AC02-06CH11357.

  4. [An atypical form of Kimura's disease].

    PubMed

    Chopinaud, M; Morice, C; Comoz, F; Petit, A; Battistella, M; Stefan, A; Verneuil, L

    2013-11-01

    Kimura's disease is a rare benign chronic inflammatory disease of unknown aetiology. An 18-year-old atopic Brazilian patient consulted for recurrent facial eczema that improved slightly under topical corticosteroids. He presented a large infiltrated and eczematous subcutaneous plaque on the right supraorbital area, together with eyelid oedema. This was associated with complete right eyebrow alopecia, oedema of the upper lip and infiltrated facial papules. The tests showed hypereosinophilia (4000/mm(3)), a high IgE level (3786 kIU/L) and proteinuria (0.3g/24h). Histological examination revealed a lymphocytic eosinophil-rich inflammatory infiltrate in the superficial and deep dermis, with some lymphoid follicles in depth and proliferation of post-capillary venules. All of these elements led to the diagnosis of Kimura's disease. We report an unusual clinical form of Kimura's disease in a Brazilian patient. This disease has been classically described in young Asian men. In our case, a particularly large infiltrated and oedematous subcutaneous plaque was noted. In fact, the more common forms appear as subcutaneous nodules on the head and neck, which may be associated with locoregional adenopathy, involvement of the salivary glands, hypereosinophilia and raised serum IgE. In our case, the skin lesions, characterized by a large infiltrated and oedematous subcutaneous plaque, were unusual and could evoke IgG4-related disease. We report a case of Kimura's disease with an atypical presentation. The diagnosis was established by comparing certain histopathological features, and the possibility of IgG4-related disease was discussed. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. Clozapine versus other atypical antipsychotics for schizophrenia.

    PubMed

    Asenjo Lobos, Claudia; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Leucht, Stefan

    2010-11-10

    Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation of results problematic. Clozapine had a higher attrition rate due to adverse effects than

  6. Chlorpromazine versus atypical antipsychotic drugs for schizophrenia.

    PubMed

    Saha, Kumar B; Bo, Li; Zhao, Sai; Xia, Jun; Sampson, Stephanie; Zaman, Rashid U

    2016-04-05

    Chlorpromazine is an aliphatic phenothiazine, which is one of the widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the most tested first generation antipsychotic drugs. It has been used as a 'gold standard' to compare the efficacy of older and newer antipsychotic drugs. Expensive new generation drugs are heavily marketed worldwide as a better treatment for schizophrenia, but this may not be the case and an unnecessary drain on very limited resources. To compare the effects of chlorpromazine with atypical or second generation antipsychotic drugs, for the treatment of people with schizophrenia. We searched the Cochrane Schizophrenia Group's Trials Register up to 23 September 2013. We included randomised controlled trials (RCTs) that compared chlorpromazine with any other atypical antipsychotic drugs for treating people with schizophrenia. Adults (as defined in each trial) diagnosed with schizophrenia, including schizophreniform, schizoaffective and delusional disorders were included in this review. At least two review authors independently screened the articles identified in the literature search against the inclusion criteria and extracted data from included trials. For homogeneous dichotomous data, we calculated the risk ratio (RR) and the 95% confidence intervals (CIs). For continuous data, we determined the mean difference (MD) values and 95% CIs. We assessed the risk of bias in included studies and rated the quality of the evidence using the GRADE approach. This review includes 71 studies comparing chlorpromazine to olanzapine, risperidone or quetiapine. None of the included trials reported any data on economic costs. 1. Chlorpromazine versus olanzapineIn the short term, there appeared to be a significantly greater clinical response (as defined in each study) in people receiving olanzapine (3 RCTs, N = 204; RR 2.34, 95% CI 1.37 to 3.99, low quality evidence). There was no difference between drugs for relapse (1 RCT

  7. Clozapine versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Asenjo Lobos, Claudia; Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Leucht, Stefan

    2014-01-01

    Background Clozapine is an atypical antipsychotic demonstrated to be superior in the treatment of refractory schizophrenia which causes fewer movement disorders. Clozapine, however, entails a significant risk of serious blood disorders such as agranulocytosis which could be potentially fatal. Currently there are a number of newer antipsychotics which have been developed with the purpose to find both a better tolerability profile and a superior effectiveness. Objectives To compare the clinical effects of clozapine with other atypical antipsychotics (such as amisulpride, aripiprazole, olanzapine, quetiapine, risperidone, sertindole, ziprasidone and zotepine) in the treatment of schizophrenia and schizophrenia-like psychoses. Search methods We searched the Cochrane Schizophrenia Groups Register (June 2007) and reference lists of all included randomised controlled trials. We also manually searched appropriate journals and conference proceedings relating to clozapine combination strategies and contacted relevant pharmaceutical companies. Selection criteria All relevant randomised, at least single-blind trials, comparing clozapine with other atypical antipsychotics, any dose and oral formulations, for people with schizophrenia or related disorders. Data collection and analysis We selected trials and extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD) again based on a random-effects model. Main results The review currently includes 27 blinded randomised controlled trials, which involved 3099 participants. Twelve randomised control trials compared clozapine with olanzapine, five with quetiapine, nine with risperidone, one with ziprasidone and two with zotepine. Attrition from these studies was high (overall 30.1%), leaving the interpretation

  8. Quality of life and its association with insight, adverse effects of medication and use of atypical antipsychotics in patients with bipolar disorder and schizophrenia in remission.

    PubMed

    Yen, Cheng-Fang; Cheng, Chung-Ping; Huang, Chi-Fen; Yen, Ju-Yu; Ko, Chih-Hung; Chen, Cheng-Sheng

    2008-07-01

    The present study aimed: (i) to compare the level of quality of life (QOL) among subjects with bipolar disorder (BD) and schizophrenia who were in remission and healthy control subjects and (ii) to examine the association of QOL with insight, adverse effects of medication and use of atypical antipsychotics among subjects with BD and schizophrenia who were in remission by controlling other confounding factors. The QOL on the four domains of the World Health Organization Questionnaire on Quality of Life: Short Form - Taiwan version (WHOQOL-BREF) were compared between 96 subjects with BD in remission, 96 subjects with schizophrenia in remission and 106 healthy control subjects. The association between the four QOL domains and subjects' insight, adverse effects of medication and use of atypical antipsychotics were examined using multiple regression analyses in the subjects with BD and schizophrenia in remission. The results demonstrated that the subjects with BD in remission had similarly poor levels of QOL in all four domains as those subjects with schizophrenia in remission, and both subjects with BD and schizophrenia had poorer QOL than those in the control group. For both subjects with BD and schizophrenia in remission, insight was negatively associated with QOL on the physical domain, and adverse effects of medication were negatively associated with QOL on the physical and environment domains. Use of atypical antipsychotics was not associated with QOL, but subjects with BD receiving olanzapine perceived better psychological QOL than those receiving risperidone and better psychological and social relationship QOL than those receiving no atypical antipsychotic. The results of the present study indicate that subjects with BD are dissatisfied with their QOL, even when they are in a remitted state. Clinicians must consider the negative influences of insight and adverse effects of medication on QOL of patients with BD and schizophrenia in remission.

  9. The Atypical Response Regulator Protein ChxR Has Structural Characteristics and Dimer Interface Interactions That Are Unique within the OmpR/PhoB Subfamily

    SciTech Connect

    Hickey, John M.; Lovell, Scott; Battaile, Kevin P.; Hu, Lei; Middaugh, C. Russell; Hefty, P. Scott

    2013-05-29

    Typically as a result of phosphorylation, OmpR/PhoB response regulators form homodimers through a receiver domain as an integral step in transcriptional activation. Phosphorylation stabilizes the ionic and hydrophobic interactions between monomers. Recent studies have shown that some response regulators retain functional activity in the absence of phosphorylation and are termed atypical response regulators. The two currently available receiver domain structures of atypical response regulators are very similar to their phospho-accepting homologs, and their propensity to form homodimers is generally retained. An atypical response regulator, ChxR, from Chlamydia trachomatis, was previously reported to form homodimers; however, the residues critical to this interaction have not been elucidated. We hypothesize that the intra- and intermolecular interactions involved in forming a transcriptionally competent ChxR are distinct from the canonical phosphorylation (activation) paradigm in the OmpR/PhoB response regulator subfamily. To test this hypothesis, structural and functional studies were performed on the receiver domain of ChxR. Two crystal structures of the receiver domain were solved with the recently developed method using triiodo compound I3C. These structures revealed many characteristics unique to OmpR/PhoB subfamily members: typical or atypical. Included was the absence of two {alpha}-helices present in all other OmpR/PhoB response regulators. Functional studies on various dimer interface residues demonstrated that ChxR forms relatively stable homodimers through hydrophobic interactions, and disruption of these can be accomplished with the introduction of a charged residue within the dimer interface. A gel shift study with monomeric ChxR supports that dimerization through the receiver domain is critical for interaction with DNA.

  10. Decay and In-Beam Studies of Neutron-Deficient Po and Ra Isotopes at JYFL

    NASA Astrophysics Data System (ADS)

    Leino, M.; Allatt, R. G.; Andreyev, A. N.; Cocks, J. F. C.; Dorvaux, O.; Enqvist, T.; Eskola, K.; Helariutta, K.; Huyse, M.; Jones, P. M.; Julin, R.; Juutinen, S.; Kankaanpaeae, H.; Keenan, A.; Kettunen, H.; Kuusiniemi, P.; Muikku, M.; Rahkila, P.; Savelius, A.; Trzaska, W. H.; Uusitalo, J.; van Duppen, P.

    1999-05-01

    An extensive program to study the production, decay properties, and nuclear structure of very neutron-deficient polonium and radium nuclei is underway at the Department of Physics, University of Jyvaeskylae, Finland (JYFL). The main tools used in these studies are the gas-filled recoil separator RITU and various germanium gamma-ray arrays. In the course of these studies, among others the following new isotopes have been produced: 204Ra, 203Ra, and 202Ra. Isomeric alpha decaying states have been discovered in 203Ra and 191Po. Fine structure in the decay of 192Po to the oblate and prolate band heads in 188Pb has been observed. In-beam gamma-ray spectra have been, for the first time, measured for 192Po, 206Ra, 208Ra, and 210Ra. Development of collectivity in nuclei in the Po-Ra region and the systematics of reduced alpha widths will be discussed.

  11. Atypical features in depression: Association with obesity and bipolar disorder.

    PubMed

    Łojko, Dorota; Buzuk, Grzegorz; Owecki, Maciej; Ruchała, Marek; Rybakowski, Janusz K

    2015-10-01

    Depression with atypical features amounts to a significant proportion of depressed patients. Studies have shown its association with bipolarity and, recently, with obesity. In this study, we investigated atypical features of depression in relation to overweight/obesity in three diagnostic categories: unipolar depression, bipolar depression and dysthymia. Out of 512 depressed patients screened, we recruited 182 research subjects, consisting of 91 pairs, matched by age, gender and diagnosis, in which one member of the pair was within the normal weight range (BMI≤25) and the other was either overweight or obese (BMI>25). There were 35 pairs with unipolar depression, 27 with bipolar depression and 29 with dysthymia. Symptoms of atypical depression, such as increased appetite, hypersomnia, leaden paralysis, longstanding pattern of interpersonal rejection sensitivity, and, a significant weight gain in the past 3 months, were assessed. All the symptoms of atypical depression were significantly more pronounced in those depressed patients with a BMI>25, compared with depressed subjects with a normal weight. Except for hypersomnia, these symptoms scored significantly higher in women compared to men. Among the diagnostic categories, symptoms of atypical depression were significantly higher in patients with bipolar disorder compared with both major depressive disorder and dysthymia. The preponderance of women, the assessment of atypical depression by adaptation of the DSM criteria, entirely Polish population, specificity of selection criteria. The results demonstrated a higher intensity of atypical depression's symptoms in overweight/obese depressed patients. They also confirm the association between obesity and bipolarity. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. An evaluation of ²²⁶Ra and ²²⁸Ra in drinking water in several counties in Texas, USA.

    PubMed

    Landsberger, S G; George, G

    2013-11-01

    Naturally Occurring Radioactive Material (NORM) or Technology Enhanced Naturally Occurring Radioactive Material (TENORM) can be a potential health risk. It is now well known that the underlying geology in many parts of Texas has given rise to levels of (226)Ra and (228)Ra that often exceed the limits set by the US Environmental Protection Agency. A detailed literature search was undertaken to assess the levels of (226)Ra and (228)Ra in all of the Texas counties. Several statistical evaluations of the data were performed. The Hickory aquifer in the Llano Uplift region of Texas has consistently had the highest number of (226)Ra and (228)Ra concentrations above the legal limit. As well many of the affected rural communities may not have the financial resources to rectify the problem.

  13. Protein splicing of inteins with atypical glutamine and aspartate C-terminal residues.

    PubMed

    Amitai, Gil; Dassa, Bareket; Pietrokovski, Shmuel

    2004-01-30

    Inteins are protein-splicing domains present in many proteins. They self-catalyze their excision from the host protein, ligating their former flanks by a peptide bond. The C-terminal residue of inteins is typically an asparagine (Asn). Cyclization of this residue to succinimide causes the final detachment of inteins from their hosts. We studied protein-splicing activity of two inteins with atypical C-terminal residues. One having a C-terminal glutamine (Gln), isolated from Chilo iridescent virus (CIV), and another unique intein, first reported here, with a C-terminal aspartate, isolated from Carboxydothermus hydrogenoformans (Chy). Protein-splicing activity was examined in the wild-type inteins and in several mutants with N- and C-terminal amino acid substitutions. We demonstrate that both wild-type inteins can protein splice, probably by new variations of the typical protein-splicing mechanism. Substituting the atypical C-terminal residue to the typical Asn retained protein-splicing only in the CIV intein. All diverse C-terminal substitutions in the Chy intein (Asp(345) to Asn, Gln, Glu, and Ala) abolished protein-splicing and generated N- and C-terminal cleavage. The observed C-terminal cleavage in the Chy intein ending with Ala cannot be explained by cyclization of this residue. We present and discuss several new models for reactions in the protein-splicing pathway.

  14. Non-motor symptoms in atypical and secondary parkinsonism: the PRIAMO study.

    PubMed

    Colosimo, Carlo; Morgante, Letterio; Antonini, Angelo; Barone, Paolo; Avarello, Tania P; Bottacchi, Edo; Cannas, Antonino; Ceravolo, Maria Gabriella; Ceravolo, Roberto; Cicarelli, Giulio; Gaglio, Rosa M; Giglia, Luisa; Iemolo, Francesco; Manfredi, Michela; Meco, Giuseppe; Nicoletti, Alessandra; Pederzoli, Massimo; Petrone, Alfredo; Pisani, Antonio; Pontieri, Francesco E; Quatrale, Rocco; Ramat, Silvia; Scala, Rossana; Volpe, Giampiero; Zappulla, Salvatore; Bentivoglio, Anna Rita; Stocchi, Fabrizio; Trianni, Giorgio; Del Dotto, Paolo; Simoni, Lucia; Marconi, Roberto

    2010-01-01

    The PRIAMO study is a cross-sectional longitudinal observational study aimed at describing epidemiology and evolution of non-motor symptoms (NMS) in patients with different forms of parkinsonism recruited in 55 Italian centres and evaluated over 24 months. In this paper, we are reporting prevalence and clinical characteristics of NMS in patients with atypical and secondary parkinsonism. Out of 1307 consecutive patients with a diagnosis of parkinsonism, 83 patients had vascular parkinsonism (VP), 34 had multiple system atrophy (MSA), 30 had progressive supranuclear palsy (PSP), 14 had dementia with Lewy bodies (DLB) and 11 had corticobasal degeneration (CBD). MSA and DLB had the highest number of NMS domains and symptoms, respectively. Gastrointestinal symptoms, pain, urinary problems and postural instability due to orthostatic hypotension were most frequent in MSA. Sleep disturbances were also common with a prevalence of approximately 70% in all diagnostic groups but CBD (36%). Psychiatric symptoms and attention and memory impairment were frequently observed in all diagnoses but were most prevalent among DLB patients, whereas the prevalence of skin and respiratory disorders was rather low in all forms, ranging between 10 and 30%. Atypical parkinsonism patients also reported a low QoL, with no significant differences among the different forms, whereas PD and VP patients had a better QoL.

  15. Atypical interactions of integrin αVβ8 with pro-TGF-β1.

    PubMed

    Wang, Jianchuan; Dong, Xianchi; Zhao, Bo; Li, Jing; Lu, Chafen; Springer, Timothy A

    2017-05-23

    Integrins αVβ6 and αVβ8 are specialized for recognizing pro-TGF-β and activating its growth factor by releasing it from the latency imposed by its surrounding prodomain. The integrin αVβ8 is atypical among integrins in lacking sites in its cytoplasmic domain for binding to actin cytoskeleton adaptors. Here, we examine αVβ8 for atypical binding to pro-TGF-β1. In contrast to αVβ6, αVβ8 has a constitutive extended-closed conformation, and binding to pro-TGF-β1 does not stabilize the open conformation of its headpiece. Although Mn(2+) potently activates other integrins and increases affinity of αVβ6 for pro-TGF-β1 25- to 55-fold, it increases αVβ8 affinity only 2- to 3-fold. This minimal effect correlates with the inability of Mn(2+) and pro-TGF-β1 to stabilize the open conformation of the αVβ8 headpiece. Moreover, αVβ8 was inhibited by high concentrations of Mn(2+) and was stimulated and inhibited at markedly different Ca(2+) concentrations than αVβ6 These unusual characteristics are likely to be important in the still incompletely understood physiologic mechanisms that regulate αVβ8 binding to and activation of pro-TGF-β.

  16. Immunodiagnostic Significance of Anti-RA33 Autoantibodies in Saudi Patients with Rheumatoid Arthritis

    PubMed Central

    Al-Mughales, Jamil A.

    2015-01-01

    The primary objective of this study was to evaluate and compare the immunodiagnostic significance and utility of anti-RA33 with anti-CCP, RF, and CRP in Saudi patients with rheumatoid arthritis. Methods. This was a prospective controlled clinical study conducted at King Abdul Aziz University Tertiary Medical Centre. The sera of 41 RA patients, 31 non-RA patients, and 29 healthy controls were collected. Anti-RA33 and anti-CCP were measured using commercially available ELISA principle kits. RF and CRP were measured using nephelometry. Results. Anti-RA33 antibodies had the lowest positive and negative predictive values and showed a sensitivity of 7.32% with 95.12% specificity. Of the other three markers (including anti-CCP antibodies, CRP, and RF), only anti-CCP showed specificity of 90.46% with sensitivity of 63.41% compared to non-RA patients + healthy control. There was a significant correlation with rheumatoid factor positivity with anti-CCP. With respect to CRP, a notable correlation was seen only with anti-RA33. Conclusion. Compared to rheumatoid factor, anti-CCP antibodies, and C-reactive proteins, the anti-RA33 autoantibodies seem to be not representing as an important additional immunodiagnostic marker in Saudi patients with established RA. RA33 may have more interest in early RA or less severe RA and other systemic connective tissue disorders. PMID:25883991

  17. 7 CFR 1940.577 - Rental Assistance (RA) for existing projects.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 13 2014-01-01 2013-01-01 true Rental Assistance (RA) for existing projects. 1940.577... Allocation of Loan and Grant Program Funds § 1940.577 Rental Assistance (RA) for existing projects. (a) Amount available for allocations. See § 1940.552(a) of this subpart. RA appropriated for existing...

  18. 7 CFR 1940.577 - Rental Assistance (RA) for existing projects.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 13 2011-01-01 2009-01-01 true Rental Assistance (RA) for existing projects. 1940.577... Allocation of Loan and Grant Program Funds § 1940.577 Rental Assistance (RA) for existing projects. (a) Amount available for allocations. See § 1940.552(a) of this subpart. RA appropriated for existing...

  19. 7 CFR 1940.577 - Rental Assistance (RA) for existing projects.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 13 2012-01-01 2012-01-01 false Rental Assistance (RA) for existing projects. 1940... Allocation of Loan and Grant Program Funds § 1940.577 Rental Assistance (RA) for existing projects. (a) Amount available for allocations. See § 1940.552(a) of this subpart. RA appropriated for existing...

  20. 7 CFR 1940.577 - Rental Assistance (RA) for existing projects.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 13 2013-01-01 2013-01-01 false Rental Assistance (RA) for existing projects. 1940... Allocation of Loan and Grant Program Funds § 1940.577 Rental Assistance (RA) for existing projects. (a) Amount available for allocations. See § 1940.552(a) of this subpart. RA appropriated for existing...

  1. Symptomatic atypical femoral fractures are related to underlying hip geometry.

    PubMed

    Taormina, David P; Marcano, Alejandro I; Karia, Raj; Egol, Kenneth A; Tejwani, Nirmal C

    2014-06-01

    The benefits of bisphosphonates are well documented, but prolonged use has been associated with atypical femur fractures. Radiographic markers for fracture predisposition could potentially aid in safer medication use. In this case-control designed study, we compared hip radiographic parameters and the demographic characteristics of chronic bisphosphonate users who sustained an atypical femoral fracture with a group of chronic bisphosphonate users who did not sustain an atypical femur fracture and also a group who sustained an intertrochanteric hip fracture. Radiographic parameters included were neck-shaft angle (NSA), hip-axis length (HAL) and center-edge angle (CE). Multivariate regression was used to evaluate the relationship between radiographic measures and femur fracture. Receiver-operating characteristic analysis determined cut-off points for neck-shaft angle and risk of atypical femur fracture. Ultimately, pre-fracture radiographs of 53 bisphosphonate users who developed atypical fracture were compared with 43 asymptomatic chronic bisphosphonate users and 64 intertrochanteric fracture patients. Duration of bisphosphonate use did not statistically differ between users sustaining atypical fracture and those without fracture (7.9 [±3.5] vs. 7.7 [±3.3] years, p=0.7). Bisphosphonate users who fractured had acute/varus pre-fracture neck-shaft angles (p<0.001), shorter hip-axis length (p<0.01), and narrower center-edge angles (p<0.01). Regression analysis revealed associations between neck-shaft angle (OR=0.89 [95% CI=0.81-0.97; p=0.01), center edge angle (OR=0.89 [95% CI=0.80-0.99]; p=0.03), and BMI (OR=1.15 [95% CI=1.02-1.31; p=0.03) with fracture development. ROC curve analysis (AUC=0.67 [95% CI=0.56-0.79]) determined that a cut-off point for neck-shaft angle <128.3° yielded 69% sensitivity and 63% specificity for development of atypical femoral fracture. Ultimately, an acute/varus angle of the femoral neck, high BMI, and narrow center-edge angle were

  2. Opening of the closed water area and consequent changes of ²²⁸Ra/²²⁶Ra activity ratios in coastal lagoon Nakaumi, southwest Japan.

    PubMed

    Nomura, Ritsuo; Nakamura, Kosaku; Seto, Koji; Inoue, Mutsuo; Kofuji, Hisaki

    2013-11-01

    In Lake Nakaumi, the second largest coastal lagoon in Japan, artificially closed (Honjyo) area, which was left untouched for 28 years, was partly opened in May, 2009. (228)Ra/(226)Ra ratio of waters in Honjyo area and Lake Nakaumi showed a well-tuned seasonal variation exhibiting high value in summer. After the opening event, however, the (228)Ra/(226)Ra ratios in the Honjyo water showed an unclear seasonal variation in both surface and deep water. This opening event caused the change of active movement of lake and marine water.

  3. Atypical pityriasis rosea: clinical evaluation of 27 patients.

    PubMed

    Kilinc, Fadime; Akbas, Ayse; Sener, Sertac; Aktaş, Akın

    2017-06-01

    Pityriasis rosea (PR) is a common, acute, self-limiting inflammatory skin disease. It can easily be recognized with its typical clinical presentation. However, unusual clinic presentations can cause difficulty in diagnosis. Up to now, not many atypical forms are reported. To determine the clinical characteristics of patients with atypical pityriasis rosea. A total of 27 cases, diagnosed as atypical PR by clinical and/or histopathological examination and applied to the outpatient clinic of dermatology department between the years 2007 and 2015 were analyzed retrospectively. The ages of patients ranged from 2 to 59 years. Of these patients, 15 (55.6%) were male and 12 (44.4%) were female. The male-to-female ratio was 5-4. Five patients had papular, four patients had purpuric, three patients had vesicular, two patients had follicular, one patient had erythema multiforme-like and one patient had eczematous drug-induced atypical form of pityriasis rosea. There were 12 cases of localized, two cases of segmental pityriasis rosea. Four of the localized forms also had atypical morphology. Histopathological evaluation was required for diagnosis in 12 (44.4%) patients. PR can appear in many different uncommon forms. Localization and skin rush can be misleading and diagnosis can be compelling.

  4. Acanthomatous ameloblastoma with atypical foci in five dogs.

    PubMed

    Malmberg, Jennifer L; Howerth, Elizabeth W; Powers, Barb E; Schaffer, Paula A

    2017-03-01

    Acanthomatous ameloblastoma is a common, locally invasive, nonmetastasizing tumor of the canine oral cavity. The long-term prognosis for canine acanthomatous ameloblastoma is good if complete excision can be achieved, usually by maxillectomy or mandibulectomy. A variant of acanthomatous ameloblastoma with atypical foci was noted in 5 dogs. There was no age, breed, or sex predisposition. Atypical cells were pleomorphic with a high mitotic rate. They were immunohistochemically negative for cytokeratin, vimentin, melan A, PNL2, CD3, Pax5, CD18, chromogranin A, and synaptophysin. Ultrastructurally, the atypical cells had modest amounts of electron-lucent cytoplasm, abundant rough endoplasmic reticulum, zonula adherens junctions, cleaved or irregular nuclei, and occasional cytoplasmic structures consistent with secretory granules or lysosomes. Complete excision was achieved by maxillectomy or mandibulectomy in 3 dogs; the lesion was incompletely excised in 2 dogs. No ancillary therapy was elected in any patient. No local recurrence or distant metastasis was reported in any case. One patient died of heart failure 20 mo following complete excision; all other patients were alive at last follow-up (average follow-up: 18.8 mo, range: 6-30 mo). The histogenesis of the atypical foci is unclear, but atypical foci within acanthomatous ameloblastoma do not appear to be associated with metastasis or with a poor prognosis relative to acanthomatous ameloblastoma with typical histologic morphology.

  5. Atypical periprosthetic acetabular fracture in long-term alendronate therapy

    PubMed Central

    Marongiu, Giuseppe; Capone, Antonio

    2016-01-01

    Summary Bisphosphonates have been commonly used in the treatment of osteoporosis, demonstrating its efficacy in fracture risk reduction. However, even if are generally safe and well tolerated, concerns have emerged about atypical fractures related to its prolonged use. Although atypical femoral fracture are more common, case reports demonstrated that even other skeletal areas can be involved by unusual pattern of fracture. We report a atypical acetabular periprosthetic fracture in a 83-year-old female patient after prolonged alendronate treatment for osteoporosis and isolated acetabular revision surgery. The patient underwent to clinical, bioumoral and radiological evaluation and all the history cases were fully reported. We believe this periprosthetic fracture, according to the available data, may have similar underlying pathology to atypical femoral fractures. Awareness of symptoms, in addition to a regular radiographic survey may facilitate early diagnosis and possible prevention of spontaneous periprosthetic fractures, in patients receiving bisphosphonate therapy beyond 5 years. The treatment of this atypical periprosthetic fracture should include both surgical than pharmacological therapy to obtained bone healing. PMID:28228784

  6. Atypical periprosthetic acetabular fracture in long-term alendronate therapy.

    PubMed

    Marongiu, Giuseppe; Capone, Antonio

    2016-01-01

    Bisphosphonates have been commonly used in the treatment of osteoporosis, demonstrating its efficacy in fracture risk reduction. However, even if are generally safe and well tolerated, concerns have emerged about atypical fractures related to its prolonged use. Although atypical femoral fracture are more common, case reports demonstrated that even other skeletal areas can be involved by unusual pattern of fracture. We report a atypical acetabular periprosthetic fracture in a 83-year-old female patient after prolonged alendronate treatment for osteoporosis and isolated acetabular revision surgery. The patient underwent to clinical, bioumoral and radiological evaluation and all the history cases were fully reported. We believe this periprosthetic fracture, according to the available data, may have similar underlying pathology to atypical femoral fractures. Awareness of symptoms, in addition to a regular radiographic survey may facilitate early diagnosis and possible prevention of spontaneous periprosthetic fractures, in patients receiving bisphosphonate therapy beyond 5 years. The treatment of this atypical periprosthetic fracture should include both surgical than pharmacological therapy to obtained bone healing.

  7. Clinically significant drug interactions with atypical antipsychotics.

    PubMed

    Kennedy, William Klugh; Jann, Michael W; Kutscher, Eric C

    2013-12-01

    Atypical antipsychotics [also known as second-generation antipsychotics (SGAs)] have become a mainstay therapeutic treatment intervention for patients with schizophrenia, bipolar disorders and other psychotic conditions. These agents are commonly used with other medications--most notably, antidepressants and antiepileptic drugs. Drug interactions can take place by various pharmacokinetic, pharmacodynamic and pharmaceutical mechanisms. The pharmacokinetic profile of each SGA, especially with phase I and phase II metabolism, can allow for potentially significant drug interactions. Pharmacodynamic interactions arise when agents have comparable receptor site activity, which can lead to additive or competitive effects without alterations in measured plasma drug concentrations. Additionally, the role of drug transporters in drug interactions continues to evolve and may effect both pharmacokinetic and pharmacodynamic interactions. Pharmaceutical interactions occur when physical incompatibilities take place between agents prior to drug absorption. Approximate therapeutic plasma concentration ranges have been suggested for a number of SGAs. Drug interactions that markedly increase or decrease the concentrations of these agents beyond their ranges can lead to adverse events or diminished clinical efficacy. Most clinically significant drug interactions with SGAs occur via the cytochrome P450 (CYP) system. Many but not all drug interactions with SGAs are identified during drug discovery and pre-clinical development by employing a series of standardized in vitro and in vivo studies with known CYP inducers and inhibitors. Later therapeutic drug monitoring programmes, clinical studies and case reports offer methods to identify additional clinically significant drug interactions. Some commonly co-administered drugs with a significant potential for drug-drug interactions with selected SGAs include some SSRIs. Antiepileptic mood stabilizers such as carbamazepine and valproate, as

  8. Management of atypical lobular hyperplasia, atypical ductal hyperplasia, and lobular carcinoma in situ.

    PubMed

    Clauser, Paola; Marino, Maria A; Baltzer, Pascal A T; Bazzocchi, Massimo; Zuiani, Chiara

    2016-01-01

    Atypical hyperplasia and lobular carcinoma in situ are rare proliferative breast lesions, growing inside ducts and terminal ducto-lobular units. They represent a marker of increased risk for breast cancer and a non-obligate precursor of malignancy. Evidence available on diagnosis and management is scarce. They are frequently found incidentally associated with other lesions, but can be visible through mammography, ultrasound or magnetic resonance. Due to the risk of underestimation, surgical excision is often performed. The analysis of imaging and histopathological characteristics could help identifying low-risk cases, for which surgery is not necessary. Chemopreventive agents can be used for risk reduction. Careful imaging follow up is mandatory; the role of breast MRI as screening modality is under discussion.

  9. 226Ra or 226Ra/Ba dating of Holocene volcanic rocks: application to Mt. Etna and Merapi volcanoes

    NASA Astrophysics Data System (ADS)

    Condomines, M.; Gauthier, P. J.; Tanguy, J. C.; Gertisser, R.; Thouret, J. C.; Berthommier, P.; Camus, G.

    2005-02-01

    This paper shows how 226Ra- 230Th disequilibria can be used to date Holocene volcanic rocks from some well selected volcanoes. A systematic study of these disequilibria on historical or well-dated volcanic samples is indeed first required to test the applicability of this method. Two examples are described here to illustrate its potential. In the case of Mt. Etna, the good correlation observed between ( 226Ra) 0 activities at the time of eruption and Th contents in lava flows from the last two millennia [M. Condomines, J.C. Tanguy, V. Michaud, Magma dynamics at Mt. Etna: constraints from U-Th-Ra-Pb radioactive disequilibria and Sr isotopes in historical lavas, Earth Planet. Sci. Lett. 132 (1995) 25-41] is used to infer the ages of several newly analysed lava flows. The calculated ages are in good agreement with those deduced from the archaeomagnetic curve describing the variation of the geomagnetic field direction in southern Italy [J.C. Tanguy, I. Bucur, J.F.C. Thompson, Geomagnetic secular variation in Sicily and revised ages of historic lavas from Mt. Etna, Nature 318 (1985) 453-455, J.C. Tanguy, M. Le Goff, V. Chillemi, A. Paiotti, C. Principe, S. La Delfa, G. Patane, Variation séculaire de la direction du champ géomagnétique enregistrée par les laves de l'Etna et du Vésuve pendant les deux derniers millénaires, C. R. Acad. Sci. Paris 329 (1999) 557-564, J.C. Tanguy, M. Le Goff, C. Principe, S. Arrighi, V. Chillemi, A. Paiotti, S. La Delfa, G. Patane, Archaeomagnetic dating of Mediterranean volcanics of the last 2100 years: validity and limits. Earth Planet. Sci. Lett. 211 (2003) 111-124]. We also present a whole set of new U-series data on historical, recent, and older samples from Merapi (Indonesia), and show that the ( 226Ra)/Ba ratio has probably maintained a quasi-steady state value during at least the past four millennia, and can be used to infer the ( 226Ra) 0/Ba ratio of old volcanics at the time of eruption, and thus their ages. Comparison with

  10. A survey for pulsations in A-type stars using SuperWASP

    NASA Astrophysics Data System (ADS)

    Holdsworth, Daniel L.

    2015-12-01

    "It is sound judgement to hope that in the not too distant future we shall be competent to understand so simple a thing as a star." - Sir Arthur Stanley Eddington, The Internal Constitution of Stars, 1926 A survey of A-type stars is conducted with the SuperWASP archive in the search for pulsationally variable stars. Over 1.5 million stars are selected based on their (J-H) colour. Periodograms are calculated for light curves which have been extracted from the archive and cleaned of spurious points. Peaks which have amplitudes greater than 0.5 millimagnitude are identified in the periodograms. In total, 202 656 stars are identified to show variability in the range 5-300 c/d. Spectroscopic follow-up was obtained for 38 stars which showed high-frequency pulsations between 60 and 235 c/d, and a further object with variability at 636 c/d. In this sample, 13 were identified to be normal A-type δ Sct stars, 14 to be pulsating metallic-lined Am stars, 11 to be rapidly oscillating Ap (roAp) stars, and one to be a subdwarf B variable star. The spectra were used not only to classify the stars, but to determine an effective temperature through Balmer line fitting. Hybrid stars have been identified in this study, which show pulsations in both the high- and low-overtone domains; an observation not predicted by theory. These stars are prime targets to perform follow-up observations, as a confirmed detection of this phenomenon will have significant impact on the theory of pulsations in A-type stars. The detected number of roAp stars has expanded the known number of this pulsator class by 22 per cent. Within these results both the hottest and coolest roAp star have been identified. Further to this, one object, KIC 7582608, was observed by the Kepler telescope for 4 yr, enabling a detailed frequency analysis. This analysis has identified significant frequency variations in this star, leading to the hypothesis that this is the first close binary star of its type. The observational

  11. Pak6 protein kinase is a novel effector of an atypical Rho family GTPase Chp/RhoV.

    PubMed

    Shepelev, M V; Korobko, I V

    2012-01-01

    Chp/RhoV is an atypical Rho GTPase whose functions are far from being fully understood. To date several effector proteins of Chp have been identified, including p21-activated kinases Pak1, Pak2, and Pak4. Using a yeast two-hybrid system and co-immunoprecipitation, here we show that another p21-activated kinase, Pak6, is a novel Chp-binding protein. Interaction between Chp and Pak6 depends on the activation state of the GTPase, suggesting that Pak6 is an effector protein for Chp. Point mutations in the effector domain of Chp or in the CRIB motif of Pak6 significantly impair the interaction between Chp and Pak6 upon co-immunoprecipitation, suggesting that the binding interface involves the effector domain of Chp and the CRIB motif in Pak6. We found that Chp does not affect the phosphorylation status of the S560 residue in the catalytic domain of Pak6 when Chp and Pak6 are co-expressed in HEK293 cells. Therefore, similarly to Cdc42, Chp is not likely to activate Pak6. In NCI-H1299 cells, Chp co-localizes with Pak6 on vesicular structures in activation state-dependent manner. Taking the data together, we report here the identification of p21-activated kinase Pak6 as a novel effector of the atypical Rho GTPase Chp. Our data suggest further directions in elucidating biological functions of these proteins.

  12. Crystallization of the head and galectin-like domains of porcine adenovirus isolate NADC-1 fibre

    PubMed Central

    Guardado-Calvo, Pablo; Llamas-Saiz, Antonio L.; Fox, Gavin C.; Glasgow, Joel N.; van Raaij, Mark J.

    2009-01-01

    The porcine adenovirus NADC-1 isolate, a strain of porcine adenovirus type 4, has a fibre with an atypical architecture. In addition to a classical virus-attachment region, shaft and head domains, it contains an additional galectin-like domain C-­terminal to the head domain and connected to the head domain by a long RGD-containing loop. The galectin-like domain contains two putative carbohydrate-recognition domains. The head and galectin-like domains have been independently crystallized. Diffraction data have been obtained to 3.2 Å resolution from crystals of the head domain and to 1.9 Å resolution from galectin-like domain crystals. PMID:19923738

  13. Olanzapine versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Hunger, Heike; Schmid, Franziska; Schwarz, Sandra; Duggan, Lorna; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second generation (“atypical”) antipsychotics have become the first line drug treatment for people with schizophrenia. The question as to whether, and if so how much, the effects of the various second generation antipsychotics differ is a matter of debate. In this review we examined how the efficacy and tolerability of olanzapine differs from that of other second generation antipsychotics. Objectives To evaluate the effects of olanzapine compared to other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the reference of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised trials that used at least single-blind (rater-blind) design, comparing oral olanzapine with oral forms of amisulpride, aripiprazole, clozapine, quetiapine, risperidone, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated weighted mean differences (WMD) again based on a random effects model. Main results The review currently includes 50 studies and 9476 participants which provided data for six comparisons (olanzapine compared to amisulpride, aripiprazole

  14. Risperidone versus other atypical antipsychotics for schizophrenia

    PubMed Central

    Komossa, Katja; Rummel-Kluge, Christine; Schwarz, Sandra; Schmid, Franziska; Hunger, Heike; Kissling, Werner; Leucht, Stefan

    2014-01-01

    Background In many countries of the industrialised world second-generation (“atypical”) antipsychotics (SGAs) have become the first line drug treatment for people with schizophrenia. The question as to whether and if so how much the effects of the various SGAs differ is a matter of debate. In this review we examined how the efficacy and tolerability of risperidone differs from that of other SGAs. Objectives To evaluate the effects of risperidone compared with other atypical antipsychotics for people with schizophrenia and schizophrenia-like psychosis. Search methods 1. Electronic searching We searched the Cochrane Schizophrenia Group Trials Register (April 2007) which is based on regular searches of BIOSIS, CENTRAL, CINAHL, EMBASE, MEDLINE and PsycINFO. 2. Reference searching We inspected the references of all identified studies for more trials. 3. Personal contact We contacted the first author of each included study for missing information. 4. Drug companies We contacted the manufacturers of all atypical antipsychotics included for additional data. Selection criteria We included all randomised, blinded trials comparing oral risperidone with oral forms of amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, sertindole, ziprasidone or zotepine in people with schizophrenia or schizophrenia-like psychosis. Data collection and analysis We extracted data independently. For dichotomous data we calculated risk ratio (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. We calculated numbers needed to treat/harm (NNT/NNH) where appropriate. For continuous data, we calculated mean differences (MD), again based on a random-effects model. Main results The review currently includes 45 blinded RCTs with 7760 participants. The number of RCTs available for each comparison varied: four studies compared risperidone with amisulpride, two with aripiprazole, 11 with clozapine, 23 with olanzapine, eleven with

  15. The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage.

    PubMed

    Del Prete, Annalisa; Martínez-Muñoz, Laura; Mazzon, Cristina; Toffali, Lara; Sozio, Francesca; Za, Lorena; Bosisio, Daniela; Gazzurelli, Luisa; Salvi, Valentina; Tiberio, Laura; Liberati, Chiara; Scanziani, Eugenio; Vecchi, Annunciata; Laudanna, Carlo; Mellado, Mario; Mantovani, Alberto; Sozzani, Silvano

    2017-09-07

    CCRL2 is a 7-transmembrane domain receptor that shares structural and functional similarities with the family of atypical chemokine receptors (ACKRs). CCRL2 is upregulated by inflammatory signals and, unlike other ACKRs, it is not a chemoattractant-scavenging receptor, does not activate β-arrestins, and is widely expressed by many leukocyte subsets. Therefore, the biological role of CCRL2 in immunity is still unclear. We report that CCRL2-deficient mice have a defect in neutrophil recruitment and are protected in 2 models of inflammatory arthritis. In vitro, CCRL2 was found to constitutively form homodimers and heterodimers with CXCR2, a main neutrophil chemotactic receptor. By heterodimerization, CCRL2 could regulate membrane expression and promote CXCR2 functions, including the activation of β2-integrins. Therefore, upregulation of CCRL2 observed under inflammatory conditions is functional to finely tune CXCR2-mediated neutrophil recruitment at sites of inflammation. © 2017 by The American Society of Hematology.

  16. Rare Posterior Pharyngeal Mass: Atypical Marginal Zone Hyperplasia.

    PubMed

    Eliçora, Sultan Şevik; Güven, Mehmet; Varli, Ali F; Yilmaz, Mahmut S; Alponat, Selin

    2016-03-01

    Cases of posterior pharyngeal masses are quite rare, and are typically derived from schwannoma or encephalocele, or are of vascular or infectious origin. They are clinically significant due to their tendency to cause airway obstruction. The aim of this study was to present a rare atypical marginal hyperplasia case of a posterior pharyngeal wall mass. A 10-year-old male was admitted to our clinic with dyspnea. A plane-surfaced 4 × 3 × 3 cm mass was observed on the posterior pharyngeal wall upon physical examination. The patient underwent magnetic resonance imaging and surgical treatment. Following excision of material from the patient's mass, a pathologic diagnosis of atypical marginal zone hyperplasia was made. Atypical marginal zone hyperplasia of the posterior pharyngeal wall has not yet been reported in the literature. Marginal zone hyperplasia associated with a lymphoproliferative disease should be considered when making differential diagnoses of posterior pharyngeal wall masses.

  17. Use of atypical antipsychotics in the elderly: a clinical review

    PubMed Central

    Gareri, Pietro; Segura-García, Cristina; Manfredi, Valeria Graziella Laura; Bruni, Antonella; Ciambrone, Paola; Cerminara, Gregorio; De Sarro, Giovambattista; De Fazio, Pasquale

    2014-01-01

    The use of atypical antipsychotic drugs in the elderly has become wider and wider in recent years; in fact, these agents have novel receptor binding profiles, good efficacy with regard to negative symptoms, and reduced extrapyramidal symptoms. However, in recent years, the use of both conventional and atypical antipsychotics has been widely debated for concerns about their safety in elderly patients affected with dementia and the possible risks for stroke and sudden death. A MEDLINE search was made using the words elderly, atypical antipsychotics, use, schizophrenia, psychosis, mood disorders, dementia, behavioral disorders, and adverse events. Some personal studies were also considered. This paper reports the receptor binding profiles and the main mechanism of action of these drugs, together with their main use in psychiatry and the possible adverse events in elderly people. PMID:25170260

  18. Genetics Underlying Atypical Parkinsonism and Related Neurodegenerative Disorders.

    PubMed

    Scholz, Sonja W; Bras, Jose

    2015-10-16

    Atypical parkinsonism syndromes, such as dementia with Lewy bodies, multiple system atrophy, progressive supranuclear palsy and corticobasal degeneration, are neurodegenerative diseases with complex clinical and pathological features. Heterogeneity in clinical presentations, possible secondary determinants as well as mimic syndromes pose a major challenge to accurately diagnose patients suffering from these devastating conditions. Over the last two decades, significant advancements in genomic technologies have provided us with increasing insights into the molecular pathogenesis of atypical parkinsonism and their intriguing relationships to related neurodegenerative diseases, fueling new hopes to incorporate molecular knowledge into our diagnostic, prognostic and therapeutic approaches towards managing these conditions. In this review article, we summarize the current understanding of genetic mechanisms implicated in atypical parkinsonism syndromes. We further highlight mimic syndromes relevant to differential considerations and possible future directions.

  19. Perceived Changes in Communicative Interaction in Atypical Parkinsonism

    PubMed Central

    Hartelius, Lena; Lindberg, Johan; Petersson, Lena; Saldert, Charlotta

    2011-01-01

    The aim of this study was to examine if atypical parkinsonism affects the communicative ability in conversational interaction. Fifteen persons close to individuals with atypical parkinsonism answered a questionnaire, “Assessment of Change in Communicative Interaction” (ACCI), estimating perceived change in interactive skills compared to before the onset of the disease. The study also examined if perceived change correlated with disease duration. The results showed that at group level, the participants experienced change in many aspects of conversational interaction, particularly regarding the affected person's speech, body communication, response latency, phrase length, word finding, and ability to make themselves understood. There was no correlation between perceived change and disease duration. In conclusion, results indicated that the communicative interaction of individuals with atypical parkinsonism is significantly affected and that information elicited from significant others can help define specific problem areas or foci of concern that need to be targeted in communicative intervention or at least considered in interaction with these persons. PMID:22389810

  20. Atypical and malignant lipomatous lesions of the head and neck.

    PubMed

    Stewart, M G; Schwartz, M R; Alford, B R

    1994-10-01

    Although liposarcoma is the second most common soft-tissue sarcoma in adults, the incidence of liposarcoma of the head and neck is low. There are only 83 reported cases of head and neck liposarcoma. We report four cases of atypical and malignant lipomatous lesions of the head and neck and discuss their histologic classification and treatment implications. The histologic nature of liposarcoma is correlated clinically with treatment outcome. Recently, many authors have adopted the term atypical lipoma to describe well-differentiated lipomatous lesions in superficial extremity locations because of their tendency toward local recurrence only, without metastases or patient mortality. Although we accept the classification atypical lipoma for superficial, well-differentiated lesions, we believe that histologically similar lesions in nonsuperficial locations in the head and neck are best designated "well-differentiated liposarcoma."

  1. Atypical cellular blue nevus or malignant blue nevus?*

    PubMed Central

    Daltro, Luise Ribeiro; Yaegashi, Lygia Bertalha; Freitas, Rodrigo Abdalah; Fantini, Bruno de Carvalho; Souza, Cacilda da Silva

    2017-01-01

    Blue nevus is a benign melanocytic lesion whose most frequent variants are dendritic (common) blue nevus and cellular blue nevus. Atypical cellular blue nevus presents an intermediate histopathology between the typical and a rare variant of malignant blue nevus/melanoma arising in a cellular blue nevus. An 8-year-old child presented a pigmented lesion in the buttock since birth, but with progressive growth in the last two years. After surgical excision, histopathological examination revealed atypical cellular blue nevus. Presence of mitoses, ulceration, infiltration, cytological atypia or necrosis may occur in atypical cellular blue nevus, making it difficult to differentiate it from melanoma. The growth of blue nevus is unusual and considered of high-risk for malignancy, being an indicator for complete resection and periodic follow-up of these patients. PMID:28225968

  2. Atypical language representation in children with intractable temporal lobe epilepsy.

    PubMed

    Maulisova, Alice; Korman, Brandon; Rey, Gustavo; Bernal, Byron; Duchowny, Michael; Niederlova, Marketa; Krsek, Pavel; Novak, Vilem

    2016-05-01

    This study evaluated language organization in children with intractable epilepsy caused by temporal lobe focal cortical dysplasia (FCD) alone or dual pathology (temporal lobe FCD and hippocampal sclerosis, HS). We analyzed clinical, neurological, fMRI, neuropsychological, and histopathologic data in 46 pediatric patients with temporal lobe lesions who underwent excisional epilepsy surgery. The frequency of atypical language representation was similar in both groups, but children with dual pathology were more likely to be left-handed. Atypical receptive language cortex correlated with lower intellectual capacity, verbal abstract conceptualization, receptive language abilities, verbal working memory, and a history of status epilepticus but did not correlate with higher seizure frequency or early seizure onset. Histopathologic substrate had only a minor influence on neuropsychological status. Greater verbal comprehension deficits were noted in children with atypical receptive language representation, a risk factor for cognitive morbidity. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Cutaneous location of atypical teratoid/rhabdoid tumour.

    PubMed

    Bellon, Nathalia; Fraitag, Sylvie; Miquel, Catherine; Salomon, Laurent J; Bourdeaut, Franck; Bodemer, Christine; Roujeau, Thomas; Zerah, Michel; Hadj-Rabia, Smail

    2014-07-01

    Atypical teratoid/rhabdoid tumour is a rare and highly malignant tumour of the posterior fossae nervous system that occurs in children especially in the first few years of life. Cutaneous location is not previously reported. A newborn boy was referred for both aqueductal stenosis detected antenatally and skin tags mimicking hamartoma. The cerebral tumour increased in size during a few months leading to both skin and cerebral biopsies. Integrase Interactor-1 (INI-1) immunostaining and tumoural and leukocytes INI-1 gene sequencing confirmed the atypical teratoid/rhabdoid tumour nature of the cerebral tumour. INI-1 immunostaining in skin biopsy confirmed the dermal location of rhabdoid tumour. Thus, unusual cutaneous lesions may be part of atypical teratoid/rhabdoid tumour. The loss of Integrase INI-1 on immunohistochemical staining is characteristic.

  4. Familial Mediterranean fever variant with repeated atypical skin eruptions.

    PubMed

    Takahashi, Tomoko; Fujisawa, Tomomi; Kimura, Masaki; Ohnishi, Hidenori; Seishima, Mariko

    2015-09-01

    Familial Mediterranean fever (FMF) is characterized by self-limited bouts of fever and polyserositis. Skin involvement is not common in FMF, and erysipelas-like erythema is found to be the most frequent skin eruption which is often accompanied by arthritis and fever, and disappears within 12-72 h. We report a 40-year-old Japanese woman who presented with a 2-year history of recurrent fever with general fatigue, polyarthralgia and transient maculopapular eruptions on her lower extremities and trunk. The histological findings of the maculopapular eruption showed lymphocyte infiltration around the capillaries in the entire dermis. Mutation analysis showed a heterozygous E148Q-P369S mutation of MEFV. These findings suggested a diagnosis of late-onset FMF variant with atypical skin eruptions. The patient was successfully treated with colchicine. Thus, we should pay attention to repeated atypical skin eruptions for the early detection of atypical FMF. © 2015 Japanese Dermatological Association.

  5. Io, the Ra Patera, Mazda Catena, and Gibil Patera Area

    NASA Image and Video Library

    1998-06-04

    Io's volcanic plains are shown in this Voyager 1 image mosaic. Also visible are numerous volcanic calderas and lava flows. Ra Patera with its multihued lava flows is below and right of the mosaic's center. This scene is about 1300 miles (2100 km) long. The composition of Io's volcanic plains and lava flows has not been determined, but they could consist dominantly of sulfur or of silicates (such as basalt) coated with sulfur condensates. The bright whitish patches probably consist of freshly deposited SO2 frost. http://photojournal.jpl.nasa.gov/catalog/PIA00321

  6. Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA)

    DTIC Science & Technology

    2017-04-26

    REV1E\\\\’ER 50. "E PFlEV101JS EOmC»lS ARE C . E1E ?~e 3 01 3 FlIll!!S D ~.!!fitt Assessing Medication Adherence in Patients with Rheumatoid Arthritis (RA...Background • Rheumatoid arthritis - Affecting 1-3 million Americans - Seventy percent are women - Associated with higher risk of heart disease and stroke...and Objectives Purpose: Assess medication adherence in patients with rheumatoid arthritis Objectives: 1. Primary: Assess whether there is a correlation

  7. The isotype repertoire of antibodies against novel UH-RA peptides in rheumatoid arthritis.

    PubMed

    De Winter, Liesbeth M; Geusens, Piet; Lenaerts, Jan; Vanhoof, Johan; Stinissen, Piet; Somers, Veerle

    2016-06-07

    Recently, autoantibodies against novel UH-RA peptides (UH-RA.1 and UH-RA.21) were identified as candidate biomarkers for patients with rheumatoid arthritis (RA) who are seronegative for the current diagnostic markers rheumatoid factor and anticitrullinated protein antibodies. Previously, screening for anti-UH-RA autoantibodies was based on measuring the immunoglobulin (Ig) G response. We aimed to investigate whether measurement of other isotypes could improve the performance of diagnostic testing. In addition, assigning the isotype profile might provide valuable information on effector functions of the antibodies. The isotype profile of antibodies against UH-RA.1 and UH-RA.21 was studied. The IgG, IgM, and IgA classes, together with the 4 different IgG subclasses, were determined in 285 patients with RA, 88 rheumatic control subjects, and 90 healthy control subjects. Anti-UH-RA.1 antibodies were primarily of the IgM isotype and twice as prevalent as IgG (IgG3-dominated) and IgA. RA sensitivity when testing for anti-UH-RA.1 IgM was shown to be higher than when testing for the IgG isotype: 18 % versus 9 % sensitivity when RA specificity was set to 90 %. Within antibodies against UH-RA.21, IgG and IgA were more common than IgM. Different anti-UH-RA.21 IgG subclasses were found, with the highest prevalence found for IgG2. Combined testing for IgG and IgA slightly increased RA sensitivity of UH-RA.21-specific antibody testing to 27 % compared with solely testing for IgG (23 %). Notably, a higher number of anti-UH-RA.21 antibody isotypes was related to increased levels of erythrocyte sedimentation rate. Finally, for both antibody responses, the full antibody isotype use was demonstrated in early and seronegative disease. The isotype distribution of anti-UH-RA.1 and anti-UH-RA.21 antibodies was successfully outlined, and, for antibodies against UH-RA.1, we found that isotype-specific testing might have implications for diagnostic testing. The exact mechanisms by

  8. Novel antipsychotics: issues and controversies. Typicality of atypical antipsychotics.

    PubMed Central

    Stip, E

    2000-01-01

    The typicality of atypical antipsychotic drugs remains debatable. Preclinical studies and findings from randomized, controlled and open trials of clozapine, olanzapine, risperidone, quetiapine, sertindole, ziprasidone and a substituted benzamide were examined. A MEDLINE search was conducted using key words, including "extrapyramidal side effects," "cognition," "schizophrenia" and the generic drug names. Over 140 articles from peer-reviewed journals were reviewed, some of which were based on a meta-analysis. New-generation neuroleptic agents were found to have greater efficacy on the negative symptoms of schizophrenia and to cause fewer unwanted extrapyramidal side effects (EPS) than the traditional antipsychotic drugs. On one hand, atypical neuroleptic agents could be strictly defined as any neuroleptic agent with antipsychotic effects at a dosage that does not cause extrapyramidal side effects. Thus, clozapine is regarded as the "standard" atypical antipsychotic drug. On the other hand, typicality is about dimension rather than category, and we suggest the use of the term "spectrum of atypicality." For example, an emphasis is placed on quetiapine to illustrate where a new compound fits in this spectrum. Although dose-related, atypicality may be more a question of prescription attitude than of a specific characteristic of a compound. The degree to which a new compound is clinically superior to another atypical antipsychotic drug, in terms of improving positive, negative or affective symptoms, cognitive function and long-term outcome, will require further a priori hypotheses based on conceptual frameworks that are clinically meaningful. In addition, the results from industry-sponsored trials should be more comparable to those obtained from investigator-leading trials. Finally, the patient characteristics that define a patient's response to a specific antipsychotic drug are unknown. PMID:10740987

  9. Patterns of atypical antipsychotic subtherapeutic dosing among Oregon Medicaid patients.

    PubMed

    Hartung, Daniel M; Wisdom, Jennifer P; Pollack, David A; Hamer, Ann M; Haxby, Dean G; Middleton, Luke; McFarland, Bentson H

    2008-10-01

    To examine a cohort of Medicaid patients with new prescriptions for atypical antipsychotic medication to determine the prevalence of subtherapeutic atypical antipsychotic medication use and to identify patient and prescribing provider characteristics associated with occurrence of subtherapeutic use. This observational cohort study examined Medicaid administrative claims data for patients aged 20 to 64 years with a new prescription for an atypical antipsychotic medication (clozapine, olanzapine, quetiapine, risperidone, ziprasidone) between January 1, 2004, and December 31, 2004. Patient diagnostic information was identified using the International Classification of Diseases, Ninth Revision, Clinical Modification codes on submitted medical claims. Patient characteristics, prescribing provider characteristics, length of therapy, and dosing were examined. A logistic regression assessed the probability of subtherapeutic dosing. Among 830 individuals in our sample who began treatment with an atypical antipsychotic, only 15% had a documented diagnosis of schizophrenia, subtherapeutic dosing was common (up to 86% of patients taking quetiapine), and 40% continued less than 30 days with the index prescription. A logistic model indicated that a general practitioner as prescribing provider, length of therapy equal to or less than 30 days, and prescription of quetiapine were significantly associated with a subtherapeutic dose (p < .001, p = .028, and p < .001, respectively). These results suggest that there is extensive use of expensive atypical antipsychotic medications for off-label purposes such as sedation or for other practice patterns that should be explored further. Approaches that minimize off-label atypical antipsychotic use could be of considerable value to Medicaid programs. In addition, these findings support the need for the introduction or increased use of utilization monitoring and the implementation of medication practice guidelines as appropriate decision

  10. [Comprehensive assessment of atypical-extraction orthodontic treatment].

    PubMed

    Yijia, Xie; Zhou, Hu; Qing, Zhao; Fuwei, Lin; Yang, Zeng; Xiaomei, Xu; Lin, Zeng; Pu, Yang

    2017-04-01

    To discuss through retrospective study associated factors influencing orthodontists to develop orthodontic treatment plans and to calculate constituent ratio of a typical extraction in orthodontic treatment. Systematic sampling was performed among 7 344 orthodontic patients, who received orthodontic treatment from April 2012 to March 2014 in the Department of Orthodontics, West China Hospital of Stomatology, Sichuan University. The study included statistical data on factors that may influence development of treatment plans. Samples were used to calculate extraction-ratio and atypical-extraction-ratio. Research focused on associated factors influencing development of treatment plans while evaluating correlation significances of each factor. Finally, treatment outcomes of atypical-extraction were compared with those of typical-extraction. Among studied patients, 55.31% (406/734) received orthodontic extraction treatment. In orthodontic-extraction-treated patients, typical-extraction accounted for 59.11% (240/406), orthodontists-selected atypical-extraction accounted for 23.15% (94/406), and passive atypical-extraction accounted for 17.73% (72/406). With statistical analysis, we inferred associated factors influencing development of treatment plans as follows: sex and age of patients, sex of orthodontists, accurate condition of specific teeth, Angle's classification, and degree of midline deviation. Tooth loss before treatment also directly influences passive atypical-extraction. Statistically significant factors were not obtained. Significant difference of treatment outcome was not observed between atypical-extraction and typical-extraction-orthodontic treatment (P>0.05). Above mentioned factors may influence orthodontists to develop treatment plans. However, orthodontists should also consider expected results of treatment strategies to prepare individual treatment plans on the basis of comprehensive analysis. 
.

  11. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome.

    PubMed

    Palma, Lilian M Pereira; Langman, Craig B

    2016-01-01

    The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach.

  12. Atypical forms of lupus vulgaris - a case series.

    PubMed

    Saritha, Mohanan; Parveen, Basheer Ahamed; Anandan, Venkatesan; Priyavathani, Malathy R; Tharini, Karuvelan G

    2009-02-01

    Atypical presentations of cutaneous tuberculosis are not so uncommon and are frequently overlooked in clinical practice, leading to late diagnosis and increased morbidity. We report three cases of lupus vulgaris with atypical presentations. The cases mimicked other chronic skin lesions like actinomycosis, mycetoma, and so on. Strong clinical suspicion, histopathology, and response to antituberculous treatment led to the diagnosis and all three had excellent response to treatment. Today, when tuberculosis threatens to burst into pandemics again, early diagnosis and treatment are more important than ever for control and prevention of morbidity.

  13. Medicolegal aspects of atypical firearm injuries: a case report.

    PubMed

    Gürses, Murat Serdar; Akan, Okan; Eren, Bülent; Durak, Dilek; Türkmen, Nursel; Cetin, Selçuk

    2014-01-01

    Our case was a twenty year-old man, who was injured during the military duty with G3 infantry rifle in the training area. An atypical firearm entry wound on the left side of sternum which was 4.5 cm in diameter, and was surrounded by six irregular skin burn wounds by a flash-suppressor and a 0.7 cm diameter firearm exit wound at space on the left midscapular line. Our case emphasizes that the interpretation of properties of these atypical firearm entry wounds need to be carefully assessed by physicians.

  14. Anterior Plagiocephaly in an Atypical Case of Apert Syndrome

    PubMed Central

    Gupta, Madhumita; Pai, Ashwin Alke; Bhattacharya, Abhimanyu; Ramachandra, Ravi; Sawarappa, Raghavendra; Mohapatra, Subhakanta; Kanoi, Aditya

    2013-01-01

    Apert syndrome is a congenital craniosynostosis syndrome comprising of bilateral coronal synostosis , symmetric syndactyly of hands and feet and midface hypoplasia. We present an atypical phenotype of this syndrome with right sided unilateral coronal synostosis. However, type I apert hand and other clinical and radiological features suggestthe diagnosis. Genetic analysis revealed an absence of the specific missense mutations in the FGFR 2 gene that is found in patients with this syndrome. We conclude that this patient represented a rare atypical variant of Apert syndrome. Further analysis is required to map the associated genotype. PMID:25489515

  15. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine.

    PubMed

    Leonardo, Quevedo-Florez; Juliana, Granada-Romero; Fernando, Camargo-Arenas Juan

    2017-01-01

    The Neuroleptic Malignant Syndrome (NMS) is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease.

  16. Uremic parkinsonism with atypical phenotypes and radiologic features.

    PubMed

    Yoon, Jee-Eun; Kim, Ji Sun; Park, Jeong-Ho; Lee, Kyung-Bok; Roh, Hakjae; Park, Sung Tae; Cho, Jin Whan; Ahn, Moo-young

    2016-04-01

    Uremic encephalopathy with bilateral basal ganglia lesions has been reported as an acute neurometabolic disease which shows reversible clinical course and brain imaging features. The exact nature and pathophysiology have not been well established. We encountered two patients who showed a relapsing and aggravating course and an atypical phenotype including parkinsonism with paroxysmal dystonic head tremor and acute onset monoparesis of the lower extremity. They also showed unusual radiological findings which revealed combined lesions in the basal ganglia and cortex, persistent hemorrhagic transformation, and focal ischemic lesion in the internal capsule. Herein, we present the unusual phenomenology with atypical radiologic findings and suggest the possible multifactorial pathogenesis of uremic encephalopathy.

  17. Atypical Neuroleptic Malignant Syndrome Associated with Use of Clozapine

    PubMed Central

    Juliana, Granada-Romero; Fernando, Camargo-Arenas Juan

    2017-01-01

    The Neuroleptic Malignant Syndrome (NMS) is a medical emergency of infrequent presentation in the emergency department, which is associated with the use of psychiatric drugs, such as typical and atypical antipsychotics. Our case addresses a 55-year-old patient diagnosed with undifferentiated schizophrenia for 10 years, who had been receiving clozapine and clonazepam as part of their treatment. This patient presents the symptoms of Neuroleptic Malignant Syndrome without fever, which improves with treatment especially with the withdrawal of clozapine. In the absence of fever and clinical improvement, the patient is considered to have an atypical presentation of this disease. PMID:28303200

  18. Phosphorylation-Independent Activity of Atypical Response Regulators of Helicobacter pylori

    PubMed Central

    Schär, Jennifer; Sickmann, Albert; Beier, Dagmar

    2005-01-01

    The genome of the gastric pathogen Helicobacter pylori harbors a remarkably low number of regulatory genes, including three and five open reading frames encoding two-component histidine kinases and response regulators, respectively, which are putatively involved in transcriptional regulation. Two of the response regulator genes, hp1043 and hp166, proved to be essential for cell growth, and inactivation of the response regulator gene hp1021 resulted in a severe growth defect, as indicated by a small-colony phenotype. The sequences of the receiver domains of response regulators HP1043 and HP1021 differ from the consensus sequence of the acidic pocket of the receiver domain which is involved in the phosphotransfer reaction from the histidine kinase to the response regulator. Using a genetic complementation system, we demonstrated that the function of response regulator HP166, which is essential for cell growth, can be provided by a mutated derivative carrying a D52N substitution at the site of phosphorylation. We found that the atypical receiver sequences of HP1043 and HP1021 are not crucial for the function of these response regulators. Phosphorylation of the receiver domains of HP1043 and HP1021 is not needed for response regulator function and may not occur at all. Thus, the phosphorylation-independent action of these regulators differs from the well-established two-component paradigm. PMID:15838037

  19. Phosphorylation-independent activity of atypical response regulators of Helicobacter pylori.

    PubMed

    Schär, Jennifer; Sickmann, Albert; Beier, Dagmar

    2005-05-01

    The genome of the gastric pathogen Helicobacter pylori harbors a remarkably low number of regulatory genes, including three and five open reading frames encoding two-component histidine kinases and response regulators, respectively, which are putatively involved in transcriptional regulation. Two of the response regulator genes, hp1043 and hp166, proved to be essential for cell growth, and inactivation of the response regulator gene hp1021 resulted in a severe growth defect, as indicated by a small-colony phenotype. The sequences of the receiver domains of response regulators HP1043 and HP1021 differ from the consensus sequence of the acidic pocket of the receiver domain which is involved in the phosphotransfer reaction from the histidine kinase to the response regulator. Using a genetic complementation system, we demonstrated that the function of response regulator HP166, which is essential for cell growth, can be provided by a mutated derivative carrying a D52N substitution at the site of phosphorylation. We found that the atypical receiver sequences of HP1043 and HP1021 are not crucial for the function of these response regulators. Phosphorylation of the receiver domains of HP1043 and HP1021 is not needed for response regulator function and may not occur at all. Thus, the phosphorylation-independent action of these regulators differs from the well-established two-component paradigm.

  20. Atypical protein kinase Clambda binds and regulates p70 S6 kinase.

    PubMed Central

    Akimoto, K; Nakaya, M; Yamanaka, T; Tanaka, J; Matsuda, S; Weng, Q P; Avruch, J; Ohno, S

    1998-01-01

    p70 S6 kinase (p70 S6K) has been implicated in the regulation of cell cycle progression. However, the mechanism of its activation is not fully understood. In the present work, evidence is provided that an atypical protein kinase C (PKC) isotype, PKClambda, is indispensable, but not sufficient, for the activation of p70 S6K. Both the regulatory and kinase domains of PKClambda associate directly with p70 S6K. Overexpression of the kinase domain without kinase activity or the regulatory domain of PKClambda results in the suppression of the serum-induced activation of p70 S6K. In addition, two types of dominant-negative mutants of PKClambda, as well as a kinase-deficient mutant of p70 S6K, suppress serum-induced DNA synthesis and E2F activation. The overexpresion of the active form of PKClambda, however, fails to activate p70 S6K. These results suggest that PKClambda is a mediator in the regulation of p70 S6K activity and plays an important role in cell cycle progression. PMID:9761742

  1. Ra5G, a homologue of Ra5 in giant ragweed pollen: isolation, HLA-DR-associated activity and amino acid sequence.

    PubMed

    Goodfriend, L; Choudhury, A M; Klapper, D G; Coulter, K M; Dorval, G; Del Carpio, J; Osterland, C K

    1985-08-01

    Recent studies [Marsh et al. (1982) J. exp. Med. 155, 1439-1451; Coulter (1983) M.Sc. thesis, McGill University, Montreal, Canada; Coulter et al. (1983) in Genetic and Environmental Factors in Clinical Allergy (Edited by Marsh D.G., Blumenthal M.N. and Santilli J., Jr), University of Minnesota Press, Minneapolis, MN] have shown a highly significant association between HLA-Dw2/DR2 and host sensitivity to the 5000-D, 4-disulfide bonded protein Ra5S of short ragweed pollen. To extend these findings, we isolated Ra5G, an Ra5S-like protein, from giant ragweed pollen by gel and ion-exchange chromatography. The protein was homogeneous by polyacrylamide gel electrophoresis (pH 4.3), reverse-phase high-performance liquid chromatography, and antigenic assays. Its mol. wt and amino acid composition (including 8 half-cystine residues) were closely similar to Ra5S, but the two proteins had little or no antigenic or allergenic cross-reactivity. In a study of 200 ragweed-sensitive individuals, host sensitivity simultaneously to Ra5G and Ra5S was significantly associated with the DR2 allele. The amino acid sequence of Ra5G was determined and showed close homology with Ra5S. The potential function of a highly homologous decapeptidyl sequence stretch is discussed in relation to Ir gene control of immune response to the 2 proteins.

  2. (226) RA AND (228) RA ACTIVITIES ASSOCIATED WITH AGRICULTURAL DRAINAGE PONDS AND WETLAND PONDS IN THE KANKAKEE WATERSHED, IL-IN, USA

    EPA Science Inventory

    Background radioactivity is elevated in many agricultural drainage ponds and also constructed wetland ponds in the Kankakee watershed. During 1995-1999, gross-a and -B activities were measured up to 455 and 1650 mBq L-1, respectively. 226Ra and 228Ra averaged 139 and 192 mBq L-01...

  3. (226) RA AND (228) RA ACTIVITIES ASSOCIATED WITH AGRICULTURAL DRAINAGE PONDS AND WETLAND PONDS IN THE KANKAKEE WATERSHED, IL-IN, USA

    EPA Science Inventory

    Background radioactivity is elevated in many agricultural drainage ponds and also constructed wetland ponds in the Kankakee watershed. During 1995-1999, gross-a and -B activities were measured up to 455 and 1650 mBq L-1, respectively. 226Ra and 228Ra averaged 139 and 192 mBq L-01...

  4. Characterization of the RaD-X Mission Instruments

    NASA Technical Reports Server (NTRS)

    Gronoff, Guillaume; Mertens, Christopher J.; Norman, Ryan B.; Straume, Tore; Lusby, Terry C.

    2016-01-01

    The NASA Radiation Dosimetry Experiment (RaD-X) stratospheric balloon flight mission, launched on 25 September 2015, provided dosimetric measurements above the Pfotzer maximum. The goal of taking these measurements is to improve aviation radiation models by providing a characterization of cosmic ray primaries, which are the source of radiation exposure at aviation altitudes. The RaD-X science payload consists of four instruments. The main science instrument is a tissue-equivalent proportional counter (TEPC). The other instruments consisted of three solid state silicon dosimeters: Liulin, Teledyne total ionizing dose (TID) and RaySure detectors. To properly interpret the measurements, it is necessary to evaluate how the payload affects the radiation environment of the detectors. In addition, it is necessary to evaluate how the detectors react to the different particles impacting them. We present the results of the Geant-4 simulations of the interaction of the different radiations with the payload and the instruments. We show how it affect the measurements, and which instruments are better suited for future missions

  5. Creative trial design in RA: optimizing patient outcomes.

    PubMed

    Buch, Maya H; Pavitt, Sue; Parmar, Mahesh; Emery, Paul

    2013-03-01

    The rheumatology community has witnessed remarkable advances in the management of rheumatoid arthritis (RA) made possible by the development of highly effective biologic DMARDs. Robust randomized controlled trials of clinical efficacy, equipped with validated outcome measures, ensured these therapies could enter the clinical arena and thus substantially improve patient outcomes. Current management principles, which follow a 'treat-to-target' paradigm, advocate tight control of disease activity with the aim of achieving clinical remission. However, efficacy trials are not yet aligned with this approach, hampering patient recruitment. This impediment and the usual approach of inclusion of previously failed treatment arms (to protect methodological concerns) is prompting reappraisal of RA trial design and the consideration of more pragmatic studies that reflect real-life practice. In addition, the aspirations of the rheumatology community to strive for personalized medicine means innovative approaches to trial design are needed to complement the efficacy trial. This Review appraises the current trial landscape and provides insights and key concepts from other fields such as oncology as to the potential utility (as well as the limitations) of pragmatic trial designs such as adaptive trials and biomarker-driven trials.

  6. [ICO-166 monoclonal antibodies against the CD45RA antigen].

    PubMed

    Frolova, E A; Baryshnikov, A Iu; Novikov, V V; Syrkin, A B

    1993-07-01

    Monoclonal antibodies (MCA) ICO-166 against CD45RA antigen were generated and characterized. In the indirect IFA, MCA ICO-166 reacted with 54.1 +/- 1.9% lymphocytes of human peripheral blood and 15.2 +/- 2.3% monocytes but not with granulocytes or thrombocytes. The method of double labelling of cells demonstrated that MCA ICO-166 detected all B-lymphocytes, all NK-cells and 31% of mature T-lymphocytes but only 55% of CD8 suppressor cells and only 21% of CDA helper cells carried this antigen on the surface. Experiments were carried out to block binding of FITC-labeled MCA ALB11 against CD45RA antigen with human lymphocytes by pretreatment of cells with different concentrations of MCA ICO-166. Treatment of cells with MCA ALB11 blocked binding of MCA ALB11-FITC by 85% on the average. MCA ICO-166 blocked binding of MCA ALB11-FITC by 66% on the average. When different dilutions of MCA ICO-166 were used, the dose-dependent effect of blocking of MCA ALB11-FITC binding was observed. MCA ICO-166 immunoprecipitated a protein band of molecular weight 220 kDa from lysates of mononuclear cells of the human peripheral blood.

  7. The Bayo Canyon/radioactive lanthanum (RaLa) program

    SciTech Connect

    Dummer, J.E.; Taschner, J.C.; Courtright, C.C.

    1996-04-01

    LANL conducted 254 radioactive lanthanum (RaLa) implosion experiments Sept. 1944-March 1962, in order to test implosion designs for nuclear weapons. High explosives surrounding common metals (surrogates for Pu) and a radioactive source containing up to several thousand curies of La, were involved in each experiment. The resulting cloud was deposited as fallout, often to distances of several miles. This report was prepared to summarize existing records as an aid in evaluating the off-site impact, if any, of this 18-year program. The report provides a historical setting for the program, which was conducted in Technical Area 10, Bayo Canyon about 3 miles east of Los Alamos. A description of the site is followed by a discussion of collateral experiments conducted in 1950 by US Air Force for developing an airborne detector for tracking atmospheric nuclear weapons tests. All known off-site data from the RaLa program are tabulated and discussed. Besides the radiolanthanum, other potential trace radioactive material that may have been present in the fallout is discussed and amounts estimated. Off-site safety considerations are discussed; a preliminary off-site dose assessment is made. Bibliographical data on 33 persons important to the program are presented as footnotes.

  8. Characterization of the RaD-X Mission Instruments

    NASA Astrophysics Data System (ADS)

    Gronoff, G.; Mertens, C. J.; Norman, R. B.; Straume, T.

    2016-12-01

    The NASA Radiation Dosimetry Experiment (RaD-X) stratospheric balloon flight mission, launched on 25 September 2015, provided dosimetric measurements above the Pfotzer maximum. The goal of taking these measurements is to improve aviation radiation models by providing a characterization of cosmic ray primaries, which are the source of radiation exposure at aviation altitudes. The RaD-X science payload consists of four instruments. The main science instrument is a tissue-equivalent proportional counter (TEPC). The other instruments consisted of three solid state silicon dosimeters: Liulin, Teledyne total ionizing dose (TID) and RaySure detectors.To properly interpretate the measurements, it is necessary to evaluate how the payload affects the radiation environment of the detectors. In addition, it is necessary to evaluate how the detectors react to the different particle impacting them.We present the results of the Geant-4 simulations of the interaction of the different radiations with the payload and the instruments, and conclude on how it affect the results of the mission, and which are the instruments better suited for future missions.

  9. Evidence for Reduced Domain-Specificity in Auditory Processing in Autism

    ERIC Educational Resources Information Center

    Jarvinen-Pasley, Anna; Heaton, Pamela

    2007-01-01

    Neurological and behavioral findings indicate that atypical auditory processing characterizes autism. The present study tested the hypothesis that auditory processing is less domain-specific in autism than in typical development. Participants with autism and controls completed a pitch sequence discrimination task in which same/different judgments…

  10. Evidence for Reduced Domain-Specificity in Auditory Processing in Autism

    ERIC Educational Resources Information Center

    Jarvinen-Pasley, Anna; Heaton, Pamela

    2007-01-01

    Neurological and behavioral findings indicate that atypical auditory processing characterizes autism. The present study tested the hypothesis that auditory processing is less domain-specific in autism than in typical development. Participants with autism and controls completed a pitch sequence discrimination task in which same/different judgments…

  11. Decreased Cardiovascular Mortality in Patients with Incident Rheumatoid Arthritis (RA) in Recent Years: Dawn of a New Era in Cardiovascular Disease in RA?

    PubMed

    Myasoedova, Elena; Gabriel, Sherine E; Matteson, Eric L; Davis, John M; Therneau, Terry M; Crowson, Cynthia S

    2017-06-01

    To assess trends in cardiovascular (CV) mortality in patients with incident rheumatoid arthritis (RA) in 2000-07 versus the previous decades, compared with non-RA subjects. The study population consisted of Olmsted County, Minnesota, USA residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria was met in 1980-2007) and non-RA subjects from the same underlying population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2014. Followup was truncated for comparability. Aalen-Johansen methods were used to estimate CV mortality rates, adjusting for competing risk of other causes. Cox proportional hazards models were used to compare CV mortality by decade. The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 yrs; 68% women for both groups). Patients with incident RA in 2000-07 had markedly lower 10-year overall CV mortality (2.7%, 95% CI 0.6-4.9%) and coronary heart disease (CHD) mortality (1.1%, 95% CI 0.0-2.7%) than patients diagnosed in 1990-99 (7.1%, 95% CI 3.9-10.1% and 4.5%, 95% CI 1.9-7.1%, respectively; HR for overall CV death: 0.43, 95% CI 0.19-0.94; CHD death: HR 0.21, 95% CI 0.05-0.95). This improvement in CV mortality persisted after accounting for CV risk factors. Ten-year overall CV mortality and CHD mortality in 2000-07 RA incidence cohort was similar to non-RA subjects (p = 0.95 and p = 0.79, respectively). Our findings suggest significantly improved overall CV mortality, particularly CHD mortality, in patients with RA in recent years. Further studies are needed to examine the reasons for this improvement.

  12. Endothelial protein C receptor is overexpressed in rheumatoid arthritic (RA) synovium and mediates the anti‐inflammatory effects of activated protein C in RA monocytes

    PubMed Central

    Xue, Meilang; March, Lyn; Sambrook, Philip N; Fukudome, Kenji; Jackson, Christopher J

    2007-01-01

    Objectives (1) To investigate whether inflammatory synovial tissues from patients with rheumatoid arthritis (RA) express endothelial protein C receptor (EPCR) and (2) to determine the major cell type(s) that EPCR is associated with and whether EPCR functions to mediate the effects of activated protein C (APC) on these cells. Methods EPCR, CD68 and PC/APC in synovial tissues were detected by immunostaining and in situ PCR. Monocytes were isolated from peripheral blood of patients with RA and treated with APC, lipopolysaccharide (LPS), and/or EPCR blocking antibody RCR252. Cells and supernatants were collected for RT‐PCR, western blotting, enzyme‐linked immuosorbent assay and chemotaxis assay. Results: EPCR was expressed by both OA and RA synovial tissues but was markedly increased in RA synovium. EPCR was colocalised with PC/APC mostly on CD68 positive cells in synovium. In RA monocytes, APC upregulated EPCR expression and reduced monocyte chemoattractant protein‐1‐induced chemotaxis of monocytes by approximately 50%. APC also completely suppressed LPS‐stimulated NF‐κB activation and attenuated TNF‐α protein by more than 40% in RA monocytes. The inhibitory effects of APC were reversed by RCR252, indicating that EPCR is required. Conclusions Our results demonstrate for the first time that EPCR is expressed by synovial tissues, particularly in RA, where it co‐localises with PC/APC on monocytes/macrophages. In addition, APC inhibits the migration and activation of RA monocytes via EPCR. These inhibitory effects on RA monocytes suggest that PC pathway may have a beneficial therapeutic effect in RA. PMID:17491095

  13. A naturally occurring cowpox virus with an ectromelia virus A-type inclusion protein gene displays atypical A-type inclusions.

    PubMed

    Okeke, Malachy Ifeanyi; Hansen, Hilde; Traavik, Terje

    2012-01-01

    Human orthopoxvirus (OPV) infections in Europe are usually caused by cowpox virus (CPXV). The genetic heterogeneity of CPXVs may in part be due to recombination with other OPV species. We describe the characterization of an atypical CPXV (CPXV-No-H2) isolated from a human patient in Norway. CPXV-No-H2 was characterized on the basis of A-type inclusion (ATI) phenotype as well as the DNA region containing the p4c and atip open reading frames. CPXV-No-H2 produced atypical V(+/) ATI, in which virions are on the surface of ATI but not within the ATI matrix. Phylogenetic analysis showed that the atip gene of CPXV-No-H2 clustered closely with that of ectromelia virus (ECTV) with a bootstrap support of 100% whereas its p4c gene is diverged compared to homologues in other OPV species. By recombination analysis we identified a putative crossover event at nucleotide 147, downstream the start of the atip gene. Our results suggest that CPXV-No-H2 originated from a recombination between CPXV and ECTV. Our findings are relevant to the evolution of OPVs.

  14. Laser-trapping of {sup 225}Ra and {sup 226}Ra with repumping by room-temperature blackbody radiation.

    SciTech Connect

    Guest, J. R.; Scielzo, N. D.; Ahmad, I.; Bailey, K.; Greene, J. P.; Holt, R. J.; Lu, Z.-T.; O'Connor, T. P.; Potterveld, D. H.; Physics; Enrico Fermi Inst.; Univ. of Chicago

    2007-02-27

    We have demonstrated Zeeman slowing and capture of neutral {sup 225}Ra and {sup 226}Ra atoms in a magneto-optical trap. The intercombination transition {sup 1}S{sub 0} {yields} {sup 3}P{sub 1} is the only quasicycling transition in radium and was used for laser-cooling and trapping. Repumping along the {sup 3}D{sub 1} {yields} {sup 1}P{sub 1} transition extended the lifetime of the trap from milliseconds to seconds. Room-temperature blackbody radiation was demonstrated to provide repumping from the metastable {sup 3}P{sub 0} level. We measured the isotope shift and hyperfine splittings on the {sup 3}D{sub 1} {yields} {sup 1}P{sub 1} transition with the laser-cooled atoms, and set a limit on the lifetime of the {sup 3}D{sub 1} level based on the measured blackbody repumping rate. Laser-cooled and trapped radium is an attractive system for studying fundamental symmetries.

  15. Laser Trapping of {sup 225}Ra and {sup 226}Ra with Repumping by Room-Temperature Blackbody Radiation

    SciTech Connect

    Guest, J. R.; Scielzo, N. D.; Ahmad, I.; Bailey, K.; Greene, J. P.; Holt, R. J.; O'Connor, T. P.; Potterveld, D. H.; Lu, Z.-T.

    2007-03-02

    We have demonstrated Zeeman slowing and capture of neutral {sup 225}Ra and {sup 226}Ra atoms in a magneto-optical trap. The intercombination transition {sup 1}S{sub 0}{yields}{sup 3}P{sub 1} is the only quasicycling transition in radium and was used for laser-cooling and trapping. Repumping along the {sup 3}D{sub 1}{yields}{sup 1}P{sub 1} transition extended the lifetime of the trap from milliseconds to seconds. Room-temperature blackbody radiation was demonstrated to provide repumping from the metastable {sup 3}P{sub 0} level. We measured the isotope shift and hyperfine splittings on the {sup 3}D{sub 1}{yields}{sup 1}P{sub 1} transition with the laser-cooled atoms, and set a limit on the lifetime of the {sup 3}D{sub 1} level based on the measured blackbody repumping rate. Laser-cooled and trapped radium is an attractive system for studying fundamental symmetries.

  16. Middle aortic syndrome: an atypical case--a case report.

    PubMed

    Adovasio, R; Canci, U

    2000-06-01

    This case concerns a 61-year-old woman presenting with middle aortic syndrome treated by an aortoaortic thoracoabdominal polytetrafluoroethylene bypass and a right renal Dacron bypass. The case was atypical because of the patient's advanced age at the time of clinical presentation.

  17. Atypical extraventricular neurocytoma:A report of two cases.

    PubMed

    Kamboj, Meenakshi; Gandhi, Jatin S; Mehta, Anurag; Sharma, Anila

    2015-01-01

    Central neurocytomas are tumors with neuronal differentiation, generally arising in the lateral ventricles in the region of foramen of Monro. Whenever these tumors arise in the brain parenchyma they are called "extraventricular neurocytomas". We present two unusual cases of extraventricular atypical neurocytomas at uncommon locations with a very high Ki-67 index. The WHO grading of this tumor is yet to be answered.

  18. Late atypical atrial flutter after ablation of atrial fibrillation.

    PubMed

    Ferreira, Raquel; Primo, João; Adão, Luís; Gonzaga, Anabela; Gonçalves, Helena; Santos, Rui; Fonseca, Paulo; Santos, José; Gama, Vasco

    2016-10-01

    Cardiac surgery for structural heart disease (often involving the left atrium) and radiofrequency catheter ablation of atrial fibrillation have led to an increased incidence of regular atrial tachycardias, often presenting as atypical flutters. This type of flutter is particularly common after pulmonary vein isolation, especially after extensive atrial ablation including linear lesions and/or defragmentation. The authors describe the case of a 51-year-old man, with no relevant medical history, referred for a cardiology consultation in 2009 for paroxysmal atrial fibrillation. After failure of antiarrhythmic therapy, he underwent catheter ablation, with criteria of acute success. Three years later he again suffered palpitations and atypical atrial flutter was documented. The electrophysiology study confirmed the diagnosis of atypical left flutter and reappearance of electrical activity in the right inferior pulmonary vein. This vein was again ablated successfully and there has been no arrhythmia recurrence to date. In an era of frequent catheter ablation it is essential to understand the mechanism of this arrhythmia and to recognize such atypical flutters. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. Atypical pneumonia associated with a Mycoplasma isolate in a kitten.

    PubMed

    Bongrand, Yannick; Blais, Marie-Claude; Alexander, Kate

    2012-10-01

    An atypical case of Mycoplasma pneumonia with an unusual radiographic and computed tomographic pattern was diagnosed in a Siamese kitten. The cat showed no response to broad-spectrum antibiotic therapy including enrofloxacin. The administration of doxycycline led to a dramatic clinical and radiographic improvement.

  20. Subitizing and Counting in Typical and Atypical Development

    ERIC Educational Resources Information Center

    Schleifer, Patrick; Landerl, Karin

    2011-01-01

    Enumeration performance in standard dot counting paradigms was investigated for different age groups with typical and atypically poor development of arithmetic skills. Experiment 1 showed a high correspondence between response times and saccadic frequencies for four age groups with typical development. Age differences were more marked for the…

  1. Transposition with atypical coronary pattern: the Aubert technique.

    PubMed

    Pita-Fernández, Ana; González-López, María T; Gil-Jaurena, Juan M

    2017-03-06

    The arterial switch operation is currently the gold standard technique for repair of transposition of the great arteries. Some atypical coronary patterns such as intramural, interarterial, and a unique posterior button are associated with more complexity and surgical risk. We report a successful Aubert operation for transposition of the great arteries associated with a single and interarterial coronary artery arising from a posterior sinus.

  2. Atypical diaper dermatitis: contact allergy to mercapto compounds.

    PubMed

    Onken, Anna Theresa; Baumstark, Julia; Belloni, Benedetta; Ring, Johannes; Schnopp, Christina

    2011-01-01

    We present a case of allergic contact dermatitis in an 18-month-old boy caused by type-IV allergy to mercapto mix and mercaptobenzothiazole as components of the elastic border of diapers. Allergic contact dermatitis should be included in the differential diagnosis of diaper dermatitis, especially in difficult-to-treat cases or atypical clinical presentation.

  3. Atypical presentations of melioidosis as emerging threat: a case report.

    PubMed

    Mukhopadhyay, Chiranjoy; Dey, Arindam; Bairy, Indira

    2007-10-01

    We report two atypical presentations of melioidosis as mediastinal lymphadenitis and prostatic abscess with Burkholderia pseudomallei, the emerging category 2 organism which led to diagnostic and therapeutic dilemma and thereby, delay in appropriate management. Any similar presentation should always be supported by microbiological opinion without any delay, which can help in instituting proper antibiotics with successful outcome.

  4. Folie a Trois: Atypical Presentation as Shared Transient Psychotic Episode

    PubMed Central

    Aravind, V. K.; Krishnaram, V. D.; Vimala, Rupavathy A.

    2014-01-01

    Shared psychotic disorder or induced delusional disorder can occur in different clinical settings and profile and is not uncommon. A case of Folie a trois with atypical clinical presentation as shared acute transient episode in a bereavement setting is reported. Suggestibility, close association and intimacy of the affected persons and major stress as psychological trigger act as psychopathological factors. PMID:24860230

  5. Nonconvulsive Status Epilepticus Resembling Clinical Absence with Atypical EEG Pattern

    PubMed Central

    Mysore, Channaiah Srikanth; Zabad, Rana; Bertoni, John

    2017-01-01

    Objective. We are reporting two cases: a patient with steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) and another patient with secondary progressive multiple sclerosis (SPMS), both presenting with altered mental status (AMS) and later diagnosed with nonconvulsive atypical absence status epilepticus (AS), with atypical EEG changes. Methods. A report of two cases. Results. A patient with history of SREAT and the other with SPMS had multiple admissions due to AMS. For both, EEG revealed the presence of a high voltage generalized sharply contoured theta activity. A diagnosis of NCSE with clinical features of AS was made based on both clinical and EEG features. There was significant clinical and electrographic improvement with administration of levetiracetam for both patients in addition to sodium valproate and Solumedrol for the SREAT patient. Both patients continued to be seizure free on follow-up few months later. Conclusions. This is a report of two cases of atypical AS, with atypical EEG, in patients with different neurological conditions. Prompt clinical and EEG recovery occurred following appropriate medical treatment. We think that this condition might be underreported and could significantly benefit from prompt treatment when appropriately diagnosed. PMID:28203468

  6. Fractal Analysis May Improve the Preoperative Identification of Atypical Meningiomas.

    PubMed

    Czyz, Marcin; Radwan, Hesham; Li, Jian Y; Filippi, Christopher G; Tykocki, Tomasz; Schulder, Michael

    2017-02-01

    There is no objective and readily accessible method for the preoperative determination of atypical characteristics of a meningioma grade. To evaluate the feasibility of using fractal analysis as an adjunctive tool to conventional radiological techniques in visualizing histopathological features of meningiomas. A group of 27 patients diagnosed with atypical (WHO grade II) meningioma and a second group of 27 patients with benign (WHO grade I) meningioma were enrolled in the study. Preoperative brain magnetic resonance (MR) studies (T1-wieghted, post-gadolinium) were processed and analyzed to determine the average fractal dimension (FDa) and maximum fractal dimension (FDm) of the contrast-enhancing region of the tumor using box-count method. FDa and FDm as well as particular radiological features were included in the logistic regression model as possible predictors of malignancy. The cohort consisted of 34 women and 20 men, mean age of 62 ± 15 yr. Fractal analysis showed good interobserver reproducibility (Kappa >0.70). Both FDa and FDm were significantly higher in the atypical compared to the benign meningioma group (P < .0001). Multivariate logistic regression model reached statistical significance with P = .0001 and AUC = 0.87. The FDm, which was greater than 1.31 (odds ratio [OR], 12.30; P = .039), and nonskull base localization (OR, .052; P = .015) were confirmed to be statistically significant predictors of the atypical phenotype. Fractal analysis of preoperative MR images appears to be a feasible adjunctive diagnostic tool in identifying meningiomas with potentially aggressive clinical behavior.

  7. Atypical Autism and Tuberous Sclerosis in a Sibling Pair.

    ERIC Educational Resources Information Center

    Williamson, David A.; Bolton, Patrick

    1995-01-01

    This report describes a sibling pair (ages 21 and 18), both with tuberous sclerosis. One sibling has atypical autism (but no mental retardation or seizure disorder) and the other has a seizure disorder but no autism or mental retardation. Both siblings had multiple bilateral brain lesions. Clinical findings are discussed in relationship to the…

  8. [Cutaneous atypical mycobacteriosis due to Mycobacterium massiliense in a cat].

    PubMed

    Albini, S; Mueller, S; Bornand, V; Gutzwiller, M E Ricklin; Burnand, C; Hüssy, D; Abril, C; Reitt, K; Korczak, B M; Miserez, R

    2007-12-01

    Fast growing mycobacteria are saprophytic bacteria that prevail in water and soil. They are opportunistic pathogens and may cause various infections if gaining entry into the body through a trauma. We herein describe the clinical presentation, pathology and diagnosis of the first case of cutaneous atypical mycobacteriosis due to Mycobacterium massiliense in a cat.

  9. Exploring Atypical Verb+Noun Combinations in Learner Technical Writing

    ERIC Educational Resources Information Center

    Luzon Marco, Maria Jose

    2011-01-01

    Professional and academic discourse is characterised by a specific phraseology, which usually poses problems for students. This paper investigates atypical verb+noun collocations in a corpus of English technical writing of Spanish students. I focus on the type of verbs that most frequently occurred in these awkward or questionable combinations and…

  10. Use of atypical antipsychotics in nursing homes and pharmaceutical marketing.

    PubMed

    Pimentel, Camilla B; Donovan, Jennifer L; Field, Terry S; Gurwitz, Jerry H; Harrold, Leslie R; Kanaan, Abir O; Lemay, Celeste A; Mazor, Kathleen M; Tjia, Jennifer; Briesacher, Becky A

    2015-02-01

    To describe the current extent and type of pharmaceutical marketing in nursing homes (NHs) in one state and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. Forty-one NHs in Connecticut. NH administrators, directors of nursing, and medical directors (n = 93, response rate 75.6%). Quantitative data, including prescription drug dispensing data (September 2009-August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing, and NH quality. Qualitative data, including semistructured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. Leadership at 46.3% of NHs (n = 19) reported pharmaceutical marketing encounters, consisting of educational training, written and Internet-based materials, and sponsored training. No association was detected between level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  11. Smoking and Subclinical ILD in RA versus the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Johnson, Cheilonda; Giles, Jon T.; Bathon, Joan; Lederer, David; Hoffman, Eric A.; Barr, R. Graham; Danoff, Sonye K.

    2016-01-01

    A population-based cohort showed an association between cigarette smoking and subclinical parenchymal lung disease defined as regions of increased computed tomography (CT) lung densitometry. This technique has not been applied to the rheumatoid arthritis (RA) population where associated ILD is highly prevalent. The association between cumulative cigarette smoking and volume of areas of high attenuation (HAA: >-600 and <-250 Hounsfield Units) on full inspiratory CT was compared in 172 RA participants and 3,969 controls in a general population sample. Multivariable regression models were used to adjust for demography, anthropometrics, percent emphysema, and CT parameters. The mean cumulative cigarette smoking exposure was 25 (IQR 10–42) and 15(IQR 5–31) pack-years for the RA and non-RA cohorts, respectively. Mean HAA was 153(±57) cm3 and 129(±50) cm3 in the RA and non-RA cohorts, respectively. Each 10 cigarette pack-year increment was associated with a higher HAA by 0.03% (95% CI, 0.007–0.05%) in RA patients and by 0.008% (95% CI, 0.003–0.01%) in those without RA (interaction p = 0.001). Cigarette smoking was associated with higher lung attenuation; with a magnitude of association more pronounced in those with RA than in the general population. These data suggest that cigarette smoking may be a more potent ILD risk factor for RA patients than in the general population. PMID:27050433

  12. Smoking and Subclinical ILD in RA versus the Multi-Ethnic Study of Atherosclerosis.

    PubMed

    Johnson, Cheilonda; Giles, Jon T; Bathon, Joan; Lederer, David; Hoffman, Eric A; Barr, R Graham; Danoff, Sonye K

    2016-01-01

    A population-based cohort showed an association between cigarette smoking and subclinical parenchymal lung disease defined as regions of increased computed tomography (CT) lung densitometry. This technique has not been applied to the rheumatoid arthritis (RA) population where associated ILD is highly prevalent. The association between cumulative cigarette smoking and volume of areas of high attenuation (HAA: >-600 and <-250 Hounsfield Units) on full inspiratory CT was compared in 172 RA participants and 3,969 controls in a general population sample. Multivariable regression models were used to adjust for demography, anthropometrics, percent emphysema, and CT parameters. The mean cumulative cigarette smoking exposure was 25 (IQR 10-42) and 15(IQR 5-31) pack-years for the RA and non-RA cohorts, respectively. Mean HAA was 153(±57) cm3 and 129(±50) cm3 in the RA and non-RA cohorts, respectively. Each 10 cigarette pack-year increment was associated with a higher HAA by 0.03% (95% CI, 0.007-0.05%) in RA patients and by 0.008% (95% CI, 0.003-0.01%) in those without RA (interaction p = 0.001). Cigarette smoking was associated with higher lung attenuation; with a magnitude of association more pronounced in those with RA than in the general population. These data suggest that cigarette smoking may be a more potent ILD risk factor for RA patients than in the general population.

  13. Review of Management Options for Patients With Atypical Peyronie's Disease.

    PubMed

    Yafi, Faysal A; Hatzichristodoulou, Georgios; DeLay, Kenneth J; Hellstrom, Wayne J G

    2017-04-01

    Peyronie's disease (PD) is a wound-healing disorder of the tunica albuginea often associated with penile deformity. Less commonly, patients with PD might display atypical presentations such as ventral curvature, hourglass deformity, significantly shortened penis, and/or multiplanar curvature. To review the available literature on the prevalence of and management options for atypical PD. A literature review was performed through PubMed from 1982 through 2016 regarding atypical PD. Keywords used for the search were Peyronie's disease, atypical Peyronie's disease, ventral Peyronie's disease, ventral plaque, hourglass deformity, penile indentation, penile notching, short penis, shortened penis, shrunken penis, biplanar curvature, and multiplanar curvature. To assess the various surgical and non-surgical techniques used for the management of atypical PD. Collagenase Clostridium histolyticum is contraindicated for patients with ventral plaques and/or hourglass deformities. Patients with maintained erectile function and ventral PD plaques are best treated with intralesional injections of interferon alpha-2b or tunica plication. Patients with maintained erectile function with PD associated with hourglass deformity and/or multiplanar curvature are best treated with plaque incision or partial excision and grafting. Patients with a shortened penis could attempt conservative measures such as penile traction therapy and medical management. When erectile function is compromised, insertion of an inflatable penile prosthesis with or without ancillary straightening procedures should be recommended. Lengthening procedures can be attempted in very special circumstances by expert surgeons. There is a paucity of data regarding atypical PD. Ventral plaques can be treated with intralesional injections or surgery, hourglass deformity and multiplanar curvatures are best managed surgically, and a shortened penis should be treated with non-invasive approaches. When concomitant erectile

  14. Clinical Profile of Atypical Manifestations of Dengue Fever.

    PubMed

    Pothapregada, Sriram; Kamalakannan, Banupriya; Thulasingam, Mahalakshmy

    2016-06-01

    To study the clinical profile and outcome of the atypical manifestations of dengue fever in children. All children (0-12 y of age) diagnosed and confirmed as dengue fever at a tertiary care hospital at Puducherry, between the 1st of August 2012 and January 31st 2015 were reviewed retrospectively from hospital case records as per the revised World Health Organization (WHO) guidelines 2011 for dengue fever. The diagnosis was confirmed by NS1 antigen-based ELISA test or dengue serology for IgM and IgG antibodies and the data was analyzed using SPSS 16.0 statistical software. Out of 254 children admitted with dengue fever, non-severe dengue and severe dengue were seen in 62.6 % and 37.4 % respectively. Atypical manifestations were seen in 106 cases (41.7 %). Mean age of presentation was 6.9(3.3) y. M: F ratio was 1.2:1. The common manifestations of severe dengue infection were shock (37.4 %), bleeding (20.1 %) and multi-organ dysfunction (2.4 %). The most common atypical manifestations of dengue fever were lymphadenopathy (41.7 %), splenomegaly (21.2 %), biphasic fever (18.1 %), hepatitis (11.4 %), febrile diarrhea (6.3 %), refractory shock (2.4 %) and impaired consciousness (1.9 %). The other atypical manifestations present were portal hypertension, acalculous cholecystitis, appendicitis, acute respiratory distress syndrome (ARDS), myocarditis, pericardial effusion, paroxysmal supraventricular tachycardia (PSVT), myositis, acute kidney injury (AKI), hemophagocytic syndrome and disseminated intravascular coagulopathy (DIC). Platelet count did not always correlate well with the severity of bleeding. There were six deaths (2.4 %) and out of them four presented with impaired consciousness (66.6 %). The common causes for poor outcome were multiorgan failure, encephalopathy and refractory shock. The atypical manifestations of dengue fever are no more a rare entity. Clinicians should have a high index of suspicion and vigilance for atypical manifestations of

  15. RA induces differentiation of multipotent P19 cells towards male germ cell.

    PubMed

    Zhang, Lei; Tang, Jiangjing; Haines, Christopher J; Feng, Huai; Teng, Xiaoming; Han, Yibing

    2015-01-01

    Generating male germ cells in vitro from multipotent stem cells is still a challenge for stem cell biologists. The difficulty is caused by the lack of knowledge about spermatogenesis molecular-controlling mechanisms. In vivo, PGCs differentiate into male germ cells in a very complicated environment through many middle steps. In this study, we use the pluripotent p19 cells to test their responses to different retinoic acid (RA) concentrations by evaluating markers for stem cells (bmp4, egr3), primordial germ cells (ddx4), spermatogonia (c-kit), premeiotic cells (stra8), and male germ cells (dazl and plzf). We have found that cyp26b1, which will catalyze RA, increases dramatically in p19 cells 1 d after RA treatment. Bmp3, egr3, and stra8 are stimulated after 1 d of RA treatment and then recover to normal after 3 d of RA treatment. C-kit keeps being expressed when treated with 10 nM-4 μM RA. Dazl and plzf are gained after 3 d of stimulation. The morphology of RA (100 nM-4 μM)-treated cells changes distinctively, and cell colonies are formed. Typical neural cell-like and germ cell-like morphologies appear in the 100 nM and 4 μM RA groups, respectively. We conclude that 100-500 nM RA can cause responses in p19 cells, but a high concentration of RA (1-4 μM) can drive these pluripotent cells' differentiation towards male germ cells. However, high concentrations of RA are also toxic. Some colonies that survived from 4 μM RA begin to express ddx4 and c-kit. Selection of the c-kit(+), dazl(+), and ddx4(+) cells after RA stimulation and creating a special culture medium for their propagation might benefit successful spermatogenesis induction in vitro.

  16. Cutaneous and Subcutaneous Metastases From Atypical Laryngeal Carcinoids

    PubMed Central

    Wang, Kui-Rong; Jia, Yuan-Jing; Zhou, Shui-Hong; Wang, Qin-Ying; Bao, Yang-Yang; Feng, Zhi-Ying; Yao, Hong-Tian; Fan, Jun

    2016-01-01

    Abstract The incidence of cutaneous and subcutaneous metastases from atypical laryngeal carcinoids is approximately 20%. However, the pathogenesis and natural history of, and prognostic factors for, the condition remain poorly understood. We reported a 54-year-old female presented with cutaneous and subcutaneous metastases from atypical laryngeal carcinoid. Laryngoscopy revealed a 0.5 × 1.5-cm reddish mass on the laryngeal surface of the epiglottis. Under general anesthesia, a biopsy sample was obtained via suspension laryngoscopy. Routine pathology revealed atypical laryngeal carcinoid. Immunohistochemical staining of the sections of primary tumor was positive for cytokeratin, chromogranin A, synaptophysin, hypoxia-inducible factor-1α, P53, and CD56. GLUT-1, p-Akt, and PI3K were negative. The Ki-67 index was 15%. Supraglottic laryngectomy and selective right-neck dissection were performed. After 6 months, the patient complained of pain in the right wall of the chest; multiple cutaneous and subcutaneous nodules were evident at that site and in the abdomen. An abdominal nodule was biopsied and pathology revealed that the atypical metastatic carcinoid had metastasized to both cutaneous and subcutaneous areas of the abdomen. Chemotherapy was then prescribed. Currently, the intrathecal drug delivery system remains in place. No local recurrence has been detected. Furthermore, we systematically reviewed clinical manifestations of the disease, pathogenesis, prognostic factors, and treatment. The metastasis rate (cutaneous and subcutaneous) was approximately 12.2%. Thirty patients (62.5%) with cutaneous and subcutaneous metastases exhibited contemporaneous lymph node invasion. The 3-, 5-, and 10-year survival rates were 44.0%, 22.0%, and 13.0%, respectively. The prognosis of patients with atypical laryngeal carcinoids was poor. Relevant prognostic factors included the level of p53, human papilloma virus status, certain hypoxic markers, and distant metastasis. No

  17. Use of Atypical Antipsychotics in Nursing Homes and Pharmaceutical Marketing

    PubMed Central

    Pimentel, Camilla B.; Donovan, Jennifer L.; Field, Terry S.; Gurwitz, Jerry H.; Harrold, Leslie R.; Kanaan, Abir O.; Lemay, Celeste A.; Mazor, Kathleen M.; Tjia, Jennifer; Briesacher, Becky A.

    2014-01-01

    BACKGROUND Many nursing home (NH) residents are prescribed atypical antipsychotics despite US Food and Drug Administration warnings of increased risk of death in older adults with dementia. Aggressive pharmaceutical marketing has been cited as a potential cause, although data are scarce. The objectives of this study were to describe the current extent and type of pharmaceutical marketing in NHs in one state, and to provide preliminary evidence for the potential influence of pharmaceutical marketing on the use of atypical antipsychotics in NHs. DESIGN Nested mixed-methods, cross-sectional study of NHs in a cluster randomized trial. SETTING 41 NHs in Connecticut. PARTICIPANTS NH administrators, directors of nursing and medical directors (n = 93, response rate 75.6%). MEASUREMENTS Quantitative data, including prescription drug dispensing data (September 2009–August 2010) linked with Nursing Home Compare data (April 2011), were used to determine facility-level prevalence of atypical antipsychotic use, facility-level characteristics, NH staffing and NH quality. Qualitative data, including semi-structured interviews and surveys of NH leaders conducted in the first quarter of 2011, were used to determine encounters with pharmaceutical marketing. RESULTS Leadership at 46.3% of NHs (19/41) reported pharmaceutical marketing encounters, consisting of educational training, written/Internet-based materials and/or sponsored training. No association was detected between the level of atypical antipsychotic prescribing and reports of any pharmaceutical marketing by at least one NH leader. CONCLUSION NH leaders frequently encounter pharmaceutical marketing through a variety of ways, although the impact on atypical antipsychotic prescribing is unclear. PMID:25688605

  18. Upgrade Rate and Imaging Features of Atypical Apocrine Lesions.

    PubMed

    Chang Sen, Lauren Q; Berg, Wendie A; Carter, Gloria J

    2017-09-01

    The purpose of our work was to identify imaging features of atypical apocrine lesions and determine the rate of upgrade to ductal carcinoma in situ (DCIS) or invasive carcinoma at excision after such a diagnosis on percutaneous breast biopsy. From January 1, 2006, through October 8, 2013, a total of 33,157 breast core biopsies were performed at University of Pittsburgh Medical Center. Of those, 58 (0.2%) showed atypical apocrine lesions. For 24, atypical apocrine adenosis (AAA) or atypical apocrine metaplasia (AAM) was the only risk lesion, with no known ipsilateral malignancy, and the results of excision were available. The median patient age was 58 years (range 43-88). Among 24 atypical apocrine lesions (20 AAA and 4 AAM), four (16.7%; 95% confidence interval: 4.7, 37.4) were upgraded at excision: one invasive ductal carcinoma (grade 2, 0.2 cm, estrogen receptor positive, progesterone receptor positive, HER2/Neu negative) and three DCIS (two grade 3, one grade 2). All four upgraded lesions were AAA (20%; 4/20). Twelve AAA were seen as an irregular (n = 9) or circumscribed (n = 3) mass on ultrasound; three masses had calcifications. Six of 20 (30%) AAA were seen on biopsy of calcifications only and calcifications were within two AAA lesions at histopathology. One AAA (1/20, 5%) was asymmetry only, and one (1/20, 5%) a persistently enhancing MR focus. All four malignancies were masses on ultrasound (three irregular, one circumscribed), and three malignancies had calcifications (two coarse heterogeneous, one amorphous). While concordant with an irregular or circumscribed mass on imaging, with or without amorphous or coarse heterogeneous calcifications, AAA merits excision with a 20% upgrade rate to malignancy. Further study of AAM is warranted. © 2017 Wiley Periodicals, Inc.

  19. Risk of atypical femoral fracture during and after bisphosphonate use

    PubMed Central

    Schilcher, Jörg; Koeppen, Veronika; Aspenberg, Per; Michaëlsson, Karl

    2015-01-01

    Background and purpose Use of bisphosphonates in women is associated with higher risk of atypical femoral fractures. The risk in terms of timing of use and type of bisphosphonate, and in men, remains unclear. Patients and methods We reviewed radiographs of 5,342 Swedish women and men aged 55 years or more who had had a fracture of the femoral shaft in the 3-year period 2008–2010 (97% of those eligible), and found 172 patients with atypical fractures (93% of them women). We obtained data on medication and comorbidity. The risk of atypical fracture associated with bisphosphonate use was estimated in a nationwide cohort analysis. In addition, we performed a case-control analysis with comparison to 952 patients with ordinary shaft fractures. A short report of the findings has recently been presented (Schilcher et al. 2014a). Here we provide full details. Results The age-adjusted relative risk (RR) of atypical fracture associated with bisphosphonate use was 55 (95% CI: 39–79) in women and 54 (CI: 15–192) in men. In bisphosphonate users, women had a 3-fold higher risk than men (RR = 3.1, CI: 1.1–8.4). Alendronate users had higher risk than risedronate users (RR = 1.9, CI: 1.1–3.3). The RR after 4 years or more of use reached 126 (CI: 55–288), with a corresponding absolute risk of 11 (CI: 7–14) fractures per 10,000 person-years of use. The risk decreased by 70% per year since last use. Interpretation Women have a higher risk of atypical femoral fracture than men. The type of bisphosphonate used may affect risk estimates and the risk decreases rapidly after cessation. PMID:25582459

  20. Predictors of aggressive clinical phenotype among immunohistochemically confirmed atypical adenomas.

    PubMed

    Zaidi, Hasan A; Cote, David J; Dunn, Ian F; Laws, Edward R

    2016-12-01

    Despite formal pathological criteria, not all atypical pituitary adenomas display clinically aggressive behavior. We set out to determine which factors predict a clinically aggressive phenotype among a cohort of atypical pituitary adenomas. Medical records were retrospectively reviewed from April 2008 to July 2015. Of 569 pituitary adenomas, 47 (8.3%) patients were surgically treated for atypical adenomas as defined by the WHO criteria. Clinically aggressive adenomas were defined as occurring in those patients who necessitated additional therapeutic intervention after the index (first) surgery, including additional surgery, medical therapy, or radiosurgery. Forty-seven patients with histopathological and immunohistochemical confirmation of atypical adenomas were identified and of these, 23 were noted to have a clinically aggressive course. Among the remaining 24 patients, the disease remained quiescent after the index surgery. On univariate analysis, clinically aggressive lesions were more likely to have a larger axial diameter on MRI (2.9±1.9cm vs. 1.9±0.7cm, p=0.02), greater incidence of cavernous sinus invasion (65.2% vs. 20.8%, p<0.01), and greater incidence of clival extension (60.9% vs. 0, p<0.01) on preoperative imaging. The two groups were equivalent with regard to immunohistochemical staining for ACTH, HGH, LH, FSH, PRL, and TSH. Clinically aggressive lesions, however, trended towards a greater average MIB-1 proliferative index (7.5%±4.9 vs. 6.0%±3.6, p=0.03). On multivariate analysis, the MIB-1 proliferative index trended towards statistical significance (p=0.06) as an independent predictor of clinical aggressiveness. Atypical pituitary adenomas are defined by a rigid set of immunohistochemical markers, but not all necessarily demonstrate an aggressive clinical phenotype.

  1. Genome-wide association study of atypical psychosis.

    PubMed

    Kanazawa, Tetsufumi; Ikeda, Masashi; Glatt, Stephen J; Tsutsumi, Atsushi; Kikuyama, Hiroki; Kawamura, Yoshiya; Nishida, Nao; Miyagawa, Taku; Hashimoto, Ryota; Takeda, Masatoshi; Sasaki, Tsukasa; Tokunaga, Katsushi; Koh, Jun; Iwata, Nakao; Yoneda, Hiroshi

    2013-10-01

    Atypical psychosis with a periodic course of exacerbation and features of major psychiatric disorders [schizophrenia (SZ) and bipolar disorder (BD)] has a long history in clinical psychiatry in Japan. Based upon the new criteria of atypical psychosis, a Genome-Wide Association Study (GWAS) was conducted to identify the risk gene or variants. The relationships between atypical psychosis, SZ and BD were then assessed using independent GWAS data. Forty-seven patients with solid criteria of atypical psychosis and 882 normal controls (NCs) were scanned using an Affymetrics 6.0 chip. GWAS SZ data (560 SZ cases and 548 NCs) and GWAS BD (107 cases with BD type 1 and 107 NCs) were compared using gene-based analysis. The most significant SNPs were detected around the CHN2/CPVL genes (rs245914, P = 1.6 × 10(-7)) , COL21A1 gene (rs12196860, P = 2.45 × 10(-7) ), and PYGL/TRIM9 genes (rs1959536, P = 7.73 × 10(-7) ), although none of the single-nucleotide polymorphisms exhibited genome-wide significance (P = 5 × 10(-8) ). One of the highest peaks was detected on the major histocompatibility complex region, where large SZ GWASs have previously disclosed an association. The gene-based analysis suggested significant enrichment between SZ and atypical psychosis (P = 0.01), but not BD. This study provides clues about the types of patient whose diagnosis lies between SZ and BD. Studies with larger samples are required to determine the causal variant.

  2. 3C 57 as an atypical radio-loud quasar: implications for the radio-loud/radio-quiet dichotomy

    NASA Astrophysics Data System (ADS)

    Sulentic, J. W.; Martínez-Carballo, M. A.; Marziani, P.; del Olmo, A.; Stirpe, G. M.; Zamfir, S.; Plauchu-Frayn, I.

    2015-06-01

    Lobe-dominated radio-loud (LD RL) quasars occupy a restricted domain in the 4D Eigenvector 1 (4DE1) parameter space which implies restricted geometry/physics/kinematics for this subclass compared to the radio-quiet (RQ) majority of quasars. We discuss how this restricted domain for the LD RL parent population supports the notion for a RQ-RL dichotomy among type 1 sources. 3C 57 is an atypical RL quasar that shows both uncertain radio morphology and falls in a region of 4DE1 space where RL quasars are rare. We present new radio flux and optical spectroscopic measures designed to verify its atypical optical/UV spectroscopic behaviour and clarify its radio structure. The former data confirms that 3C 57 falls off the 4DE1 quasar `main sequence' with both extreme optical Fe II emission (R_{Fe II} ˜ 1) and a large C IV λ1549 profile blueshift (˜-1500 km s-1). These parameter values are typical of extreme Population A sources which are almost always RQ. New radio measures show no evidence for flux change over a 50+ year time-scale consistent with compact steep-spectrum (or young LD) over core-dominated morphology. In the 4DE1 context where LD RL are usually low L/LEdd quasars, we suggest that 3C 57 is an evolved RL quasar (i.e. large blackhole mass) undergoing a major accretion event leading to a rejuvenation reflected by strong Fe II emission, perhaps indicating significant heavy metal enrichment, high bolometric luminosity for a low-redshift source and resultant unusually high Eddington ratio giving rise to the atypical C IV λ1549.

  3. Clinical decision support for atypical orders: detection and warning of atypical medication orders submitted to a computerized provider order entry system.

    PubMed

    Woods, Allie D; Mulherin, David P; Flynn, Allen J; Stevenson, James G; Zimmerman, Christopher R; Chaffee, Bruce W

    2014-01-01

    The specificity of medication-related alerts must be improved to overcome the pernicious effects of alert fatigue. A systematic comparison of new drug orders to historical orders could improve alert specificity and relevance. Using historical order data from a computerized provider order entry system, we alerted physicians to atypical orders during the prescribing of five medications: calcium, clopidogrel, heparin, magnesium, and potassium. The percentage of atypical orders placed for these five medications decreased during the 92 days the alerts were active when compared to the same period in the previous year (from 0.81% to 0.53%; p=0.015). Some atypical orders were appropriate. Fifty of the 68 atypical order alerts were over-ridden (74%). However, the over-ride rate is misleading because 28 of the atypical medication orders (41%) were changed. Atypical order alerts were relatively few, identified problems with frequencies as well as doses, and had a higher specificity than dose check alerts.

  4. 230Th, 226Ra and 222Rn in abyssal sediments

    NASA Astrophysics Data System (ADS)

    Kadko, David

    1980-09-01

    A model that predicts the flux of 222Rn out of deep-sea sediment is presented. The radon is ultimately generated by 230Th which is stripped from the overlying water into the sediment. Data from many authors are compared with the model predictions. It is shown that the continental contribution of ionium is not significant, and that at low sedimentation rates, biological mixing and erosional processes strongly affect the surface concentration of the ionium. Two cores from areas of slow sediment accumulation, one from a manganese nodule region of the central Pacific and one from the Rio Grande Rise in the Atlantic were analyzed at closely spaced intervals for 230Th, 226Ra, and 210Pb. The Pacific core displayed evidence of biological mixing down to 12 cm and had a sedimentation rate of only 0.04 cm/kyr. The Atlantic core seemed to be mixed to 8 cm and had a sedimentation rate of 0.07 cm/kyr. Both cores had less total excess 230Th than predicted. Radium sediment profiles are generated from the 230Th model. Adsorbed, dissolved, and solid-phase radium is considered. According to the model, diffusional losses of radium are especially important at low sedimentation rates. Any particulate, or excess radium input is ignored in this model. The model fits the two analyzed cores if the fraction of total radium available for adsorption-desorption is about 0.5-0.7, and if K, the distribution coefficient, is about 1000. Finally, the flux of radon out of the sediments is derived from the model-generated radium profiles. It is shown that the resulting standing crop of 222Rn in the overlying water may be considered as an added constraint in budgeting 230Th and 226Ra in deep-sea sediments.

  5. Redox-Activating Dip-Pen Nanolithography (RA-DPN)

    PubMed Central

    Braunschweig, Adam B.; Senesi, Andrew J.; Mirkin, Chad A.

    2009-01-01

    Dip pen nanolithography (DPN) involves the direct transfer of an ink from a coated atomic force microscope (AFM) tip to a substrate of interest and uses as many as 55,000 pens to form arbitrary patterns of alkanethiols, oligonucleotides, proteins and viruses. Two limitations of DPN are the difficulty in transporting high molecular weight inks and the need to optimize individually the transport rates and tip inking methods of each molecule. As an alternative strategy that circumvents these two challenges, a method termed redox activating DPN (RA-DPN), is reported. In this strategy, an electrochemically active quinone functionalized surface is toggled from the reduced hydroquinone form to the oxidized benzoquinone form by the delivery of an oxidant by DPN. While the benzoquinone form is susceptible to nucleophilic attack in Michael-type additions, hydroquinone is not and acts as a passivating agent. Because both forms of the quinone are kinetically stable, the patterned surface can be immersed in a solution of a target containing any strong nucleophile, which will react only where the benzoquinone form persists on the surface. For proof-of-concept demonstrations, quinone surfaces were patterned by the delivery of the oxidant cerric ammonium nitrate and were immersed in solutions of AF549 labeled cholera toxin β subunit or oligonucleotides modified at the 5’ end with an amine and the 3’ end with a fluorophore. Fluorescent patterns of both the proteins and oligonucleotides were observed by epifluorescence microscopy. Additionally, RA-DPN maintains the advantageous ability of DPN to control feature size by varying the dwell time of the tip on the surface, and variation of this parameter has resulted in feature sizes as small as 165 nm. With this resolution, patterns of 50,000 spots could be made in a 100 × 100 µm grid. PMID:19128060

  6. IL13RA2 targeted alpha particle therapy against glioblastomas

    PubMed Central

    Pandya, Darpan N.; Almaguel, Frankis G.; Wadas, Thaddeus J.; Herpai, Denise M.; Debinski, Waldemar; Mintz, Akiva

    2017-01-01

    Glioblastoma (GBM) is the most aggressive primary malignant brain cancer that invariably results in a dismal prognosis. Chemotherapy and radiotherapy have not been completely effective as standard treatment options for patients due to recurrent disease. We and others have therefore developed molecular strategies to specifically target interleukin 13 receptor alpha 2 (IL13RA2), a GBM restricted receptor expressed abundantly on over 75% of GBM patients. In this work, we evaluated the potential of Pep-1L, a novel IL13RA2 targeted peptide, as a platform to deliver targeted lethal therapies to GBM. To demonstrate GBM-specificity, we radiolabeled Pep-1L with Copper-64 and performed in vitro cell binding studies, which demonstrated specific binding that was blocked by unlabeled Pep-1L. Furthermore, we demonstrated real-time GBM localization of [64Cu]Pep-1L to orthotopic GBMs using small animal PET imaging. Based on these targeting data, we performed an initial in vivo safety and therapeutic study using Pep-1L conjugated to Actinium-225, an alpha particle emitter that has been shown to potently and irreversibly kill targeted cells. We infused [225Ac]Pep-1L into orthotopic GBMs using convection-enhanced delivery and found no significant adverse events at injected doses. Furthermore, our initial data also demonstrated significantly greater overall, median and mean survival in treated mice when compared to those in control groups (p < 0.05). GBM tissue extracted from mice treated with [225Ac]Pep-1L showed double stranded DNA breaks, lower Ki67 expression and greater propidium iodide internalization, indicating anti-GBM therapeutic effects of [225Ac]Pep-1L. Based on our results, Pep-1L warrants further investigation as a potential targeted platform to deliver anti-cancer agents. PMID:28562337

  7. Annual intakes of (226)Ra, (228)Ra and (40)K in staple foodstuffs from a high background radiation area in the southwest region of Cameroon.

    PubMed

    Ele Abiama, P; Ben-Bolie, G H; Amechmachi, N; Najib, F; El Khoukhi, T; Owono Ateba, P

    2012-08-01

    Concentrations of naturally occurring radionuclides (226)Ra, (228)Ra and (40)K were determined in five most consumed vegetables in a high-level background radiation area (HLBRA) in the southwest region of Cameroon. A total of 25 foodstuff samples collected from Akongo, Ngombas, Awanda, Bikoué and Lolodorf rural districts were analyzed by gamma spectrometry. The average activity concentration values of (226)Ra, (228)Ra and (40)K were respectively 2.30, 1.50 and 140.40 Bq kg(-1) fresh-weights. The effective dose for individual consumption of the investigated foodstuff types was calculated on an estimated annual intake of such diets in the study area. The estimated total daily effective doses from the ingestion of the investigated foodstuffs for each studied long-life natural radionuclide were respectively 0.41 μSv for (226)Ra, 0.84 μSv for (228)Ra and 0.71 μSv for (40)K. The total annual effective dose was estimated at 0.70 mSv y(-1). (228)Ra (44%) and (40)K (36%) were found to be the main sources for internal irradiation which is very likely due to the specific uptake of these radionuclides by the studied plants. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. RA-dimer B, a New Dimeric RA-series Cyclopeptide Incorporating Two Different Types of Cycloisodityrosine Units, from Rubia cordifolia L.

    PubMed

    Hitotsuyanagi, Yukio; Tsuchiya, Takayuki; Ohata, Masako; Yoshida, Ayaka; Fukaya, Haruhiko; Park, Hyun Sun; Takeya, Koichi; Kawahara, Nobuo

    2016-12-06

    RA-dimer B, a new cytotoxic RA-series peptide, was isolated from the roots of Rubia cordifolia L. Its structure was elucidated on the basis of spectroscopic analysis to be a dimeric cyclopeptide composed of deoxybouvardin and allo-RA-V. Those two cyclopeptide units are connected by an ether linkage between the phenolic oxygen atom of deoxybouvardin and the ϵa carbon atom of Tyr-6 of allo-RA-V. RA-dimer B was synthesized by the coupling reaction of deoxybouvardin with the boronic acid derivative of allo-RA-V, and subsequent deprotection, confirming the relative stereochemistry and establishing the absolute configuration of this peptide. RA-dimer B showed cytotoxic activity against human promyelocytic leukaemia HL-60, human colonic carcinoma HCT-116, and human renal cell carcinoma ACHN cells with IC50 values of 0.59, 0.54, and 0.74 μm, respectively. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Spatial working memory and problem solving in schizophrenia: the effect of symptom stabilization with atypical antipsychotic medication.

    PubMed

    Snyder, Peter J; Jackson, Colleen E; Piskulic, Danijela; Olver, James; Norman, Trevor; Maruff, Paul

    2008-09-30

    Reasoning and problem solving in the spatial domain are important aspects of executive function that are reliably impaired in schizophrenia, and the Groton Maze Learning Test(c) (GMLT) provides a valid measure of spatial working memory. In the current study, 34 patients with first-episode schizophrenia and 20 matched controls were assessed for baseline spatial working memory abilities using this hidden maze learning test. Approximately one month after baseline assessment, allowing for symptoms to stabilize in response to treatment with therapeutic doses of atypical antipsychotic medications for individuals with schizophrenia, all participants were again assessed with the GMLT. Prior to pharmacologic intervention, patients with schizophrenia showed significant impairments in performance of all aspects of the GMLT, including measures of learning efficiency and error monitoring. One month of treatment was associated with a reliable improvement in these domains, although impairments in accuracy and error monitoring on this spatial working memory test persisted despite symptomatic improvement. These results indicate that impairments in spatial working memory are present at the earliest stages of the illness, and that such deficits in performance remain present, albeit ameliorated, after treatment with atypical antipsychotic medication.

  10. Functionalized NaA nanozeolites labeled with 224,225Ra for targeted alpha therapy

    NASA Astrophysics Data System (ADS)

    Piotrowska, Agata; Leszczuk, Edyta; Bruchertseifer, Frank; Morgenstern, Alfred; Bilewicz, Aleksander

    2013-11-01

    The 223Ra, 224Ra, and 225Ra radioisotopes exhibit very attractive nuclear properties for application in radionuclide therapy. Unfortunately the lack of appropriate bifunctional ligand for radium is the reason why these radionuclides have not found application in receptor-targeted therapy. In the present work, the potential usefulness of the NaA nanozeolite as a carrier for radium radionuclides has been studied. 224Ra and 225Ra, α-particle emitting radionuclides, have been absorbed in the nanometer-sized NaA zeolite (30-70 nm) through simple ion exchange. 224,225Ra-nanozeolites exhibited very high stability in solutions containing physiological salt, EDTA, amino acids, and human serum. To make NaA nanozeolite particles dispersed in water their surface was modified with a silane coupling agent containing poly(ethylene glycol) molecules. This functionalization approach let us covalently attach a biomolecule to the NaA nanozeolite surface.

  11. Functionalized NaA nanozeolites labeled with (224,225)Ra for targeted alpha therapy.

    PubMed

    Piotrowska, Agata; Leszczuk, Edyta; Bruchertseifer, Frank; Morgenstern, Alfred; Bilewicz, Aleksander

    2013-01-01

    The (223)Ra, (224)Ra, and (225)Ra radioisotopes exhibit very attractive nuclear properties for application in radionuclide therapy. Unfortunately the lack of appropriate bifunctional ligand for radium is the reason why these radionuclides have not found application in receptor-targeted therapy. In the present work, the potential usefulness of the NaA nanozeolite as a carrier for radium radionuclides has been studied. (224)Ra and (225)Ra, α-particle emitting radionuclides, have been absorbed in the nanometer-sized NaA zeolite (30-70 nm) through simple ion exchange. (224,225)Ra-nanozeolites exhibited very high stability in solutions containing physiological salt, EDTA, amino acids, and human serum. To make NaA nanozeolite particles dispersed in water their surface was modified with a silane coupling agent containing poly(ethylene glycol) molecules. This functionalization approach let us covalently attach a biomolecule to the NaA nanozeolite surface.

  12. 13cRA regulates the differentiation of antler chondrocytes through targeting Runx3.

    PubMed

    Zhang, Hong-Liang; Cao, Hang; Yang, Zhan-Qing; Geng, Shuang; Wang, Kai; Yu, Hai-Fan; Guo, Bin; Yue, Zhan-Peng

    2017-03-01

    Although 13cRA is involved in the regulation of cellular proliferation and differentiation, its physiological roles in chondrocyte proliferation and differentiation still remain unknown. Here, we showed that 13cRA could induce the proliferation of sika deer antler chondrocytes and expression of Ccnd3 and Cdk6. Administration of 13cRA to antler chondrocytes resulted in an obvious increase in the expression of chondrocyte marker Col II and hypertrophic chondrocyte marker Col X. Silencing of Crabp2 expression by specific siRNA could prevent the 13cRA-induced up-regulation of Col X, whereas overexpression of Crabp2 showed the opposite effects. Further study found that Crabp2 mediated the regulation of 13cRA on the expression of Runx3 which was highly expressed in the antler cartilage and inhibited the differentiation of antler chondrocytes. Moreover, attenuation of Runx3 expression greatly raised 13cRA-induced chondrocyte differentiation. Simultaneously, 13cRA could stimulate the expression of Cyp26a1 and Cyp26b1 in the antler chondrocytes. Inhibition of Cyp26a1 and/or Cyp26b1 reinforced the effects of 13cRA on the expression of Col X and Runx3, while overexpression of Cyp26b1 rendered the antler chondrocytes hyposensitive to 13cRA. Collectively, 13cRA may play an important role in the differentiation of antler chondrocytes through targeting Runx3. Crabp2 enhances the effects of 13cRA on chondrocyte differentiation, while Cyp26a1 and Cyp26b1 weaken the sensitivity of antler chondrocytes to 13cRA.

  13. Production of Ra225 precursor for Ac225/Bi213 generators. Final CRADA Report.

    SciTech Connect

    Ehst, D. A.; Nuclear Engineering Division

    2009-10-02

    Russian subcontractors shipped two small deliveries of Ra225 to PNNL for evaluation. The activity was close to the requisite amount in the subcontract. The first labeled properly; the second did not. This showed that the Russians could supply Ra225 to the US; however they proved unable to meet future demands for larger amounts of activity. The US DOE attempts to get Ra225 from Russian should be terminated; the Russians, under Rosatom, are not interested in this business.

  14. Hadfield holds bubble detectors for the RaDI-N Experiment in the Columbus Module

    NASA Image and Video Library

    2013-01-25

    ISS034-E-034506 (25 Jan. 2013) --- Canadian Space Agency astronaut Chris Hadfield, Expedition 34 flight engineer, holds bubble detectors for the RaDI-N experiment in the International Space Station?s Kibo laboratory. RaDI-N measures neutron radiation levels onboard the space station. RaDI-N uses bubble detectors as neutron monitors which have been designed to only detect neutrons and ignore all other radiation.

  15. Albuminuria in Rheumatoid Arthritis: Associations with RA Characteristics and Subclinical Atherosclerosis.

    PubMed

    Sammut, Amanda; Shea, Steven; Blumenthal, Roger S; Szklo, Moyses; Bathon, Joan M; Polak, Joseph F; Tracy, Russell; Giles, Jon T

    2017-03-03

    Background Albuminuria is a marker for subclinical cardiovascular disease (CVD) in the general population. It is uncertain whether this association is present in patients with rheumatoid arthritis (RA), a population with increased atherosclerosis and CVD events. Methods Urine albumin from a spot morning collection was measured and the ratio of urine albumin:creatinine (uACR) calculated for RA and a population-based sample of demographically matched non-RA controls. Associations of elevated uACR (≥25mg/g for women and ≥17mg/g for men) with CVD risk factors and measures of atherosclerosis [coronary artery calcification (CAC) and ultrasound-determined maximal intima-media thickness (IMT) of the common (CCA) and internal (ICA) carotid arteries, and presence of focal plaque in the ICA] were compared cross-sectionally according to RA status. Results 196 RA patients were compared with 271 non-RA controls. Elevated uACR was found in 18% of the RA patients vs. 17% of the controls (p=0.89). After adjustment, RA was associated with 67% lower odds of elevated uACR (p=0.016). Higher serum creatinine levels and hypertension were both strongly and significantly associated with elevated uACR in the control group, but not in the RA group (p-value for interaction<0.05 for both). Among RA characteristics, the adjusted prevalence of elevated uACR among TNF inhibitor users was less than half that of non-users (9% vs. 20%, respectively; p=0.047). Conclusion There was no association in the RA group of elevated uACR with measures of atherosclerosis, nor with several key cardiometabolic risk factors, suggesting a lower utility for elevated uACR as an indicator of subclinical CVD in RA. This article is protected by copyright. All rights reserved. © 2017, American College of Rheumatology.

  16. Tracking suspended particle transport via radium isotopes ((226)Ra and (228)Ra) through the Apalachicola-Chattahoochee-Flint River system.

    PubMed

    Peterson, Richard N; Burnett, William C; Opsahl, Stephen P; Santos, Isaac R; Misra, Sambuddha; Froelich, Philip N

    2013-02-01

    Suspended particles in rivers can carry metals, nutrients, and pollutants downstream which can become bioactive in estuaries and coastal marine waters. In river systems with multiple sources of both suspended particles and contamination sources, it is important to assess the hydrologic conditions under which contaminated particles can be delivered to downstream ecosystems. The Apalachicola-Chattahoochee-Flint (ACF) River system in the southeastern United States represents an ideal system to study these hydrologic impacts on particle transport through a heavily-impacted river (the Chattahoochee River) and one much less impacted by anthropogenic activities (the Flint River). We demonstrate here the utility of natural radioisotopes as tracers of suspended particles through the ACF system, where particles contaminated with arsenic (As) and antimony (Sb) have been shown to be contributed from coal-fired power plants along the Chattahoochee River, and have elevated concentrations in the surficial sediments of the Apalachicola Bay Delta. Radium isotopes ((228)Ra and (226)Ra) on suspended particles should vary throughout the different geologic provinces of this river system, allowing differentiation of the relative contributions of the Chattahoochee and Flint Rivers to the suspended load delivered to Lake Seminole, the Apalachicola River, and ultimately to Apalachicola Bay. We also use various geochemical proxies ((40)K, organic carbon, and calcium) to assess the relative composition of suspended particles (lithogenic, organic, and carbonate fractions, respectively) under a range of hydrologic conditions. During low (base) flow conditions, the Flint River contributed 70% of the suspended particle load to both the Apalachicola River and the bay, whereas the Chattahoochee River became the dominant source during higher discharge, contributing 80% of the suspended load to the Apalachicola River and 62% of the particles entering the estuary. Neither of these hydrologic

  17. Rapid method for the determination of 226Ra in hydraulic fracturing wastewater samples

    DOE PAGES

    Maxwell, Sherrod L.; Culligan, Brian K.; Warren, Richard A.; ...

    2016-03-24

    A new method that rapidly preconcentrates and measures 226Ra from hydraulic fracturing wastewater samples was developed in the Savannah River Environmental Laboratory. The method improves the quality of 226Ra measurements using gamma spectrometry by providing up to 100x preconcentration of 226Ra from this difficult sample matrix, which contains very high levels of calcium, barium, strontium, magnesium and sodium. The high chemical yield, typically 80-90%, facilitates a low detection limit, important for lower level samples, and indicates method ruggedness. Ba-133 tracer is used to determine chemical yield and correct for geometry-related counting issues. The 226Ra sample preparation takes < 2 hours.

  18. First Measurement of the Atomic Electric Dipole Moment of (225)Ra.

    PubMed

    Parker, R H; Dietrich, M R; Kalita, M R; Lemke, N D; Bailey, K G; Bishof, M; Greene, J P; Holt, R J; Korsch, W; Lu, Z-T; Mueller, P; O'Connor, T P; Singh, J T

    2015-06-12

    The radioactive radium-225 ((225)Ra) atom is a favorable case to search for a permanent electric dipole moment. Because of its strong nuclear octupole deformation and large atomic mass, (225)Ra is particularly sensitive to interactions in the nuclear medium that violate both time-reversal symmetry and parity. We have developed a cold-atom technique to study the spin precession of (225)Ra atoms held in an optical dipole trap, and demonstrated the principle of this method by completing the first measurement of its atomic electric dipole moment, reaching an upper limit of |d((225)Ra)|<5.0×10(-22)  e cm (95% confidence).

  19. Adult-onset Still's disease with atypical cutaneous manifestations

    PubMed Central

    Narváez Garcia, Francisco Javier; Pascual, María; López de Recalde, Mercè; Juarez, Pablo; Morales-Ivorra, Isabel; Notario, Jaime; Jucglà, Anna; Nolla, Joan M.

    2017-01-01

    Abstract The diagnosis of adult-onset Still's disease (AOSD) can be very difficult. There are no specific tests available, and diagnosis is usually based on a symptom complex and the well-described typical evanescent rash seen in the majority of patients. However, in recent years, other atypical cutaneous manifestations of AOSD have been reported. These atypical skin eruptions often present in addition to the typical evanescent rash but may also be the only skin manifestation, resulting in delayed diagnosis because of under-recognition. In this study, we present 3 new cases of AOSD with atypical cutaneous manifestations diagnosed during a 30-year period in our department and review 78 additional cases previously reported (PubMed 1990–2016). These 81 patients form the basis of the present analysis. The overall prevalence of atypical cutaneous manifestations in our AOSD population was 14%. These manifestations may appear at any time over the course of the disease, and usually occur in patients who have persistent and severe disease, with a considerable frequency of clinical complications (23%), including serositis, myopericarditis, lung involvement, abdominal pain, neurologic involvement, and reactive hemophagocytic syndrome. The most representative and frequent lesion among the nonclassical skin rashes is the development of persistent pruritic papules and/or plaques. Interestingly, these lesions show a distinctive histological pattern. Other, less frequently observed lesions include urticaria and urticaria-like eruptions, generalized or widespread non-pruritic persistent erythema, vesiculopustular eruptions, a widespread peau d’orange appearance of the skin, and edema of the eyelids mimicking dermatomyositis without any accompanying skin lesion. The great majority of these patients required medium or high doses of glucocorticoids (including intravenous methylprednisolone pulse therapy in some cases) and, in nearly 40%, a more potent or maintenance immunotherapy

  20. Impaired IL-7 signaling may explain a case of atypical JAK3-SCID.

    PubMed

    Li, Jun; Nara, Hidetoshi; Rahman, Mizanur; Juliana, Farha Matin; Araki, Akemi; Asao, Hironobu

    2010-02-01

    Janus kinase 3-severe combined immunodeficiency (JAK3-SCID) is an autosomal recessive immunodeficiency disease caused by various mutations in the JAK3 gene. Typical JAK3-SCID is characterized by a phenotype in which B cells are present but T and NK cells are not, the T(-)B(+)NK(-) phenotype, and by impaired signaling through cytokine receptors that use the common gamma chain (gammac) subunit. An atypical JAK3-SCID case carrying a single glutamate to glycine substitution mutation (E481G) in the JH3 domain of one JAK3 allele, and a deletion mutation (del482-596) in the JH3 and JH2 domains of the other allele was reported previously. Although this patient had CD4(+) T cells and NK cells unlike typical cases, the CD4(+) T cells were functionally impaired. We report here that the JAK3-E481G mutant transduced IL-2-, IL-4-, IL-15-, and IL-21-induced signals as efficiently as wild-type JAK3. However, this mutant failed to respond to IL-7 by phosphorylating JAK1, JAK3, or STAT5. The other mutant JAK3, JAK3-del482-596, was non-functional. Thus, an impaired IL-7 signal may cause SCID and compromise T-cell differentiation, even if the IL-15 signal is preserved and supports NK-cell development, as in this patient.

  1. Genomic and functional characterization of the modular broad-host-range RA3 plasmid, the archetype of the IncU group.

    PubMed

    Kulinska, Anna; Czeredys, Magdalena; Hayes, Finbarr; Jagura-Burdzy, Grazyna

    2008-07-01

    IncU plasmids are a distinctive group of mobile elements with highly conserved backbone functions and variable antibiotic resistance gene cassettes. The IncU archetype is conjugative plasmid RA3, whose sequence (45,909 bp) shows it to be a mosaic, modular replicon with a class I integron different from that of other IncU replicons. Functional analysis demonstrated that RA3 possesses a broad host range and can efficiently self-transfer, replicate, and be maintained stably in alpha-, beta-, and gammaproteobacteria. RA3 contains 50 open reading frames clustered in distinct functional modules. The replication module encompasses the repA and repB genes embedded in long repetitive sequences. RepA, which is homologous to antitoxin proteins from alpha- and gammaproteobacteria, contains a Cro/cI-type DNA-binding domain present in the XRE family of transcriptional regulators. The repA promoter is repressed by RepA and RepB. The minireplicon encompasses repB and the downstream repetitive sequence r1/r2. RepB shows up to 80% similarity to putative replication initiation proteins from environmental plasmids of beta- and gammaproteobacteria, as well as similarity to replication proteins from alphaproteobacteria and Firmicutes. Stable maintenance functions of RA3 are most like those of IncP-1 broad-host-range plasmids and comprise the active partitioning apparatus formed by IncC (ParA) and KorB (ParB), the antirestriction protein KlcA, and accessory stability components KfrA and KfrC. The RA3 origin of transfer was localized experimentally between the maintenance and conjugative-transfer operons. The putative conjugative-transfer module is highly similar in organization and in its products to transfer regions of certain broad-host-range environmental plasmids.

  2. Interactions between Melanin Enzymes and Their Atypical Recruitment to the Secretory Pathway by Palmitoylation.

    PubMed

    Upadhyay, Srijana; Xu, Xinping; Lin, Xiaorong

    2016-11-22

    Melanins are biopolymers that confer coloration and protection to the host organism against biotic or abiotic insults. The level of protection offered by melanin depends on its biosynthesis and its subcellular localization. Previously, we discovered that Aspergillus fumigatus compartmentalizes melanization in endosomes by recruiting all melanin enzymes to the secretory pathway. Surprisingly, although two laccases involved in the late steps of melanization are conventional secretory proteins, the four enzymes involved in the early steps of melanization lack a signal peptide or a transmembrane domain and are thus considered "atypical" secretory proteins. In this work, we found interactions among melanin enzymes and all melanin enzymes formed protein complexes. Surprisingly, the formation of protein complexes by melanin enzymes was not critical for their trafficking to the endosomal system. By palmitoylation profiling and biochemical analyses, we discovered that all four early melanin enzymes were strongly palmitoylated during conidiation. However, only the polyketide synthase (PKS) Alb1 was strongly palmitoylated during both vegetative hyphal growth and conidiation when constitutively expressed alone. This posttranslational lipid modification correlates the endosomal localization of all early melanin enzymes. Intriguingly, bioinformatic analyses predict that palmitoylation is a common mechanism for potential membrane association of polyketide synthases (PKSs) and nonribosomal peptide synthetases (NRPSs) in A. fumigatus Our findings indicate that protein-protein interactions facilitate melanization by metabolic channeling, while posttranslational lipid modifications help recruit the atypical enzymes to the secretory pathway, which is critical for compartmentalization of secondary metabolism. Subcellular compartmentalization is increasingly recognized as an important aspect of fungal secondary metabolism. It facilitates sequential enzymatic reactions, provides

  3. Phelan-McDermid syndrome in two adult brothers: atypical bipolar disorder as its psychopathological phenotype?

    PubMed Central

    Verhoeven, Willem MA; Egger, Jos IM; Willemsen, Marjolein H; de Leijer, Gert JM; Kleefstra, Tjitske

    2012-01-01

    The 22q13.3 deletion, or Phelan-McDermid syndrome, is characterized by global intellectual disability, generalized hypotonia, severely delayed or absent speech associated with features of autism spectrum disorder, and minor dysmorphisms. Its behavioral phenotype comprises sleep disturbances, communication deficits, and motor perseverations. Data on psychological dysfunctions are so far not available. Previous studies have suggested that the loss of one copy of the gene SH3 and multiple ankyrin repeat domains 3 (SHANK3) is related to the neurobehavioral phenotype. Additional genes proximal to SHANK3 are also likely to play a role in the phenotype of patients with larger deletions. The present paper describes two adult brothers with an identical 2.15 Mb 22qter (22q13.32q13.33) deletion, of whom the youngest was referred for evaluation of recurrent mood changes. In both patients, magnetic resonance imaging of the brain showed hypoplasia of the vermis cerebelli. Extensive clinical examinations led to a final diagnosis of atypical bipolar disorder, of which symptoms fully remitted during treatment with a mood stabilizer. In the older brother, a similar psychopathological picture appeared to be present, although less severe and with a later onset. It is concluded that the behavioral phenotype of the 22q13.3 deletion syndrome comprises absent or delayed speech and perseverations with associated autistic-like features, whereas its psychopathological phenotype comprises an atypical bipolar disorder. The latter may have implications for the treatment regime of the syndrome-related behavioral disturbances. PMID:22570549

  4. A-type Lamins Form Distinct Filamentous Networks with Differential Nuclear Pore Complex Associations.

    PubMed

    Xie, Wei; Chojnowski, Alexandre; Boudier, Thomas; Lim, John S Y; Ahmed, Sohail; Ser, Zheng; Stewart, Colin; Burke, Brian

    2016-10-10

    The nuclear lamina is a universal feature of metazoan nuclear envelopes (NEs) [1]. In mammalian cells, it appears as a 10-30 nm filamentous layer at the nuclear face of the inner nuclear membrane (INM) and is composed primarily of A- and B-type lamins, members of the intermediate filament family [2]. While providing structural integrity to the NE, the lamina also represents an important signaling and regulatory platform [3]. Two A-type lamin isoforms, lamins A and C (LaA and LaC), are expressed in most adult human cells. Encoded by a single gene, these proteins are largely identical, diverging only in their C-terminal tail domains. By contrast with that of LaC, the unique LaA tail undergoes extensive processing, including farnesylation and endo-proteolysis [4, 5]. However, functional differences between LaA and LaC are still unclear. Compounding this uncertainty, the structure of the lamina remains ill defined. In this study, we used BioID, an in vivo proximity-labeling method to identify differential interactors of A-type lamins [6]. One of these, Tpr, a nuclear pore complex (NPC) protein, is highlighted by its selective association with LaC. By employing superresolution microscopy, we demonstrate that this Tpr association is mirrored in enhanced interaction of LaC with NPCs. Further superresolution studies visualizing both endogenous A- and B-type lamins have allowed us to construct a nanometer-scale model of the mammalian nuclear lamina. Our data indicate that different A- and B-type lamin species assemble into separate filament networks that together form an extended composite structure at the nuclear periphery providing attachment sites for NPCs, thereby regulating their distribution.

  5. Mutation of the PAX6 gene in a sporadic patient with atypical aniridia

    SciTech Connect

    Zhu, D.; Li, Y.; Traboulsi, E.I.

    1994-09-01

    A 28 year-old man presented with poor vision since childhood and gradual further decline of several years duration. His visual acuity measures 20/200 OD with -11.50 + 0.50 x 150 and 20/100 OS with -12.25 + 0.25 x 35. He had a fine nystagmus. His visual fields were full. There was a circumferential pannus with areas of corneal stromal opacification. The iris was hypoplastic with atypical colobomatous defects. The lenses had scattered cortical opacities. The intraocular pressures were normal. The optic nerves had cup disk ratios of 0.6 OU. The family history was negative for similar defects. A diagnosis of aniridia was made and blood was drawn for analysis of the PAX6 gene. PCR amplification of exon 5 showed heterozygous fragments with one allele being larger than normal. Direct DNA sequencing of the individual heterozygous allele showed a 41 base pair insertion at nucleotide 483 in exon 5 of the paired domain. This frameshift mutation changed codon 71 to a stop codon. The diagnosis of aniridia was confirmed in this atypical patient, who will need to be monitored for his high risk of glaucoma. The risk of developing Wilms` tumor in patients with mutations within the aniridia gene is presumably negligible since the neighboring Wilms` tumor gene is unaffected. The identification of intragenic mutations of the PAX6 gene in patients with sporadic aniridia modifies the management of such patients because of recognition of the increased risk of glaucoma and by reducing the necessity for frequent monitoring for the presence of Wilms` tumor.

  6. Migration of the FDNPP-derived (134)Cs and (137)Cs along with (226)Ra and (228)Ra concentrations across the northwestern North Pacific Ocean.

    PubMed

    Inoue, M; Shirotani, Y; Nagao, S; Kofuji, H; Volkov, Y N; Nishioka, J

    2016-10-01

    We examined lateral distributions of (134)Cs, (137)Cs, (226)Ra, and (228)Ra in the surface seawaters around the Kuril Islands and the Kamchatka Peninsula in the northwestern North Pacific Ocean during June 2014. The sampling area included three water current areas, the Oyashio Current, the current from the Okhotsk Sea, and the coastal current along the east Kamchatka Peninsula. (226)Ra and (228)Ra distributions differed along the three currents. Low levels of (134)Cs were detected in the surface waters of the Oyashio Current (0.09-0.35 mBq/L), but it was <∼0.1 mBq/L at the surface along the other two currents. This indicates that the distribution of Fukushima Dai-ichi Nuclear Power Plant (FDNPP)-derived radiocesium in surface waters off the Kamchatka and along the Kuril Islands is predominantly governed by the Oyashio current system.

  7. Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions.

    PubMed

    Stewart, Jonathan W; Quitkin, Frederic M; McGrath, Patrick J; Klein, Donald F

    2005-06-01

    Treatment outcome and brain laterality differ between early onset (<20 years) chronically (no well-being >2 months) depressed patients with atypical features (early/chronic atypical) and those with either later onset or less chronic illness (late/nonchronic atypical). Because hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been hypothesized to distinguish atypical depression from melancholia, we examined whether HPA measures would also differentiate these two groups of depressed patients with atypical features. Three-hour afternoon cortisol levels, stimulation of cortisol by afternoon dextroamphetamine, and suppression of cortisol by dexamethasone were investigated in 85 depressed patients with atypical features. The latter group was divided into early/chronic atypical and late/nonchronic atypical based on chart review of course of illness. Patients with early/chronic atypical had significantly lower mean 3 h afternoon cortisol levels (N=21) and 4:00 p.m. post-dexamethasone cortisol levels (N=20) than did those with late/nonchronic atypical (N=43 with afternoon cortisol; N=26 with post-dexamethasone cortisol). Post-dextroamphetamine cortisol levels were numerically higher in the early/chronic atypical group (N=15 vs. 19), but this failed to reach conventional significance (0.05atypical features and course of illness limit the generalizability of these findings. These HPA data are consistent with earlier treatment and brain laterality findings that course of illness distinguishes biologically distinct groups within depressed patients with atypical features. The DSM should consider adding course of illness requirements to its criteria for atypical features.

  8. Association between anti-Porphyromonas gingivalis or anti-α-enolase antibody and severity of periodontitis or rheumatoid arthritis (RA) disease activity in RA.

    PubMed

    Lee, Joo Youn; Choi, In Ah; Kim, Jin-Hee; Kim, Kyoung-Hwa; Lee, Eun Young; Lee, Eun Bong; Lee, Yong-Moo; Song, Yeong Wook

    2015-08-12

    Periodontitis (PD) has been reported to be associated with rheumatoid arthritis (RA). Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium that is recognized as one of the major pathogenic organisms in PD and is the only bacterium known to express peptidylarginine deiminase (PAD). Antibody against human α-enolase (ENO1) is one of the autoantibodies in RA. ENO1 is a highly conserved protein, and could be a candidate molecule for molecular mimicry between bacterial and human proteins. In the present study, we measured serum antibody against P. gingivalis and human ENO1 in patients with RA and investigated their association with the severity of PD or disease activity of RA. Two hundred, forty-eight patients with RA and 85 age- and sex-matched healthy controls were evaluated by rheumatologic and periodontal examinations. The serum levels of anti-P. gingivalis and anti-ENO1 antibodies were measured by an enzyme-linked immunosorbent assay (ELISA). Patients with RA had significantly higher levels of anti-P. gingivalis and anti-ENO1 antibody titers than the controls (p = 0.002 and 0.0001, respectively). Anti-P. gingivalis antibody titers significantly correlated with anti-ENO1 antibody titers in RA patients (r = 0.30, p < 0.0001). There were significant correlations between anti-P. gingivalis antibody titers and the gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP) and clinical attachment level (CAL) (p = 0.038, 0.004, 0.004 and 0.002, respectively) in RA. Anti-P. gingivalis antibody titers were not correlated with disease activity score 28 (DAS28) or anti-CCP titer. However, anti-ENO1 antibody titers were significantly correlated not only with the periodontal indices, such as PPD, BOP, and CAL (p = 0.013, 0.023 and 0.017, respectively), but also RA clinical characteristics, such as DAS28, anti-CCP titer, and ESR (p = 0.009, 0.015 and 0.001, respectively). Anti-P. gingivalis and anti-ENO1 antibody

  9. Distribution of (223)Ra and (224)Ra in the Bo Sea embayment in Tianjin and its implication of submarine groundwater discharge.

    PubMed

    Liu, Lingling; Yi, Lixin; Cheng, Xiaoqing; Tang, Guoqiang

    2015-12-01

    Submarine groundwater discharge (SGD) is now recognized as an important pathway between land and sea. In this study, in order to analyze the distribution of naturally occurring short-lived radium isotopes and the relative SGD effect in Bo Sea embayment, (223)Ra and (224)Ra were measured in three parts of the embayment with the radium-delayed coincidence counting (RaDeCC) system. Subsequently, the mixing process was studied by the calculation of diffusion coefficients (Kx and Kz) and advection velocities (Vx and Vz) based on the 2D advection-diffusion model. Additionally, the apparent residence ages and SGD flux were quantified based on the (224)Ra and (223)Ra activities. The results showed that the Ra activities exponentially decreased with the distance offshore, and both the Kx and Vx took the order of northern part > southern part > middle part. In vertical direction, there was the maximum value of Vz and minimum Kz in middle part and the maximum Kz and minimum Vz in southern part. The average ages for the northern, middle and southern parts were 4.28, 7.38 and 3.73 days, respectively. The final SGD flux yielded by (224)Ra was 0.09, 0.01 and 0.03 m d(-1) in the northern, middle and southern parts, respectively. The SGD flux yielded by (223)Ra was 0.08, 0.01 and 0.03 m d(-1) in northern, middle and southern parts, respectively. The result indicates that there is the fastest exchange rate and the biggest SGD flux in the southern part in Bo Sea embayment.

  10. A Prospective Approach to Investigating the Natural History of Pre-Clinical Rheumatoid Arthritis (RA) Using First-Degree Relatives of Probands with RA

    PubMed Central

    Kolfenbach, Jason R.; Deane, Kevin D.; Derber, Lezlie A.; O’Donnell, Colin; Weisman, Michael H.; Buckner, Jane H.; Gersuk, Vivian H.; Wei, Shan; Mikuls, Ted R.; O’Dell, James; Gregersen, Peter K.; Keating, Richard M.; Norris, Jill M.; Holers, V. Michael

    2009-01-01

    Objective To describe a large, multi-center prospective cohort study of first-degree relatives (FDRs) of probands with rheumatoid arthritis (RA), and outline the utility of such a study in investigating the natural history of RA development. Methods 1058 FDRs, none of whom met the American College of Rheumatology (ACR) criteria for RA, have been enrolled into a prospective study investigating genetic and environmental influences on the development of RA-related autoimmunity. Demographic, epidemiologic, genetic, autoantibody, and physical examination data from the initial study enrollment visit is described for these FDRs, and the relationship is examined between genetic factors, autoantibodies, inflammation, and joint disease. Results Fifty-five percent of FDRs have ≥1 copy of the shared epitope (SE); 20% have ≥1 copy of PTPN22 polymorphism; ~16% are positive for rheumatoid factor (RF, including isotypes), and/or anti-cyclic citrullinated peptide (anti-CCP) antibody. RF-IgM positivity is associated with ≥1 tender joint/s on examination (OR 2.50, 95% CI 1.27 to 4.89, p<0.01), and elevated levels of CRP (OR 5.31, 95% CI 1.45 to 19.52, p = 0.01). Conclusion FDRs without RA demonstrate high prevalence of genetic risk factors and RA-related autoantibodies. Additionally, RF association with tender joints and elevated CRP suggests autoantibodies are a valid intermediate marker of RA-related autoimmunity in this cohort. This prospective FDR cohort will be a valuable resource for evaluating the relationship between genetic, epidemiologic factors and the development of RA-related autoimmunity. PMID:19950324

  11. Atypical epithelial hyperplasia of the breast: state of the art.

    PubMed

    Dion, Ludivine; Racin, Adelaïde; Brousse, Susie; Beltjens, Françoise; Cauchois, Aurélie; Levêque, Jean; Coutant, Charles; Lavoué, Vincent

    2016-09-01

    Atypical epithelial hyperplasia (AEH) of the breast is considered benign histological lesions with breast cancer risk. This review focuses on clinical signification and management of AEH that remains controversial. A review of published studies was performed using medline database. In this review, we fully describe the current evidence available. In particular, we describe 1) data from immunohistochemistry and molecular studies that suggest AEH is a precursor of breast cancer; 2) epidemiological studies demonstrate low rate of breast cancer in women with AEH; 3) surgical excision is necessary after diagnosis of AEH, such as lobular carcinoma in situ or atypical ductal hyperplasia, on core needle biopsy; 4) although current recommendations are evolving to fewer (if not no) excisions for flat epithelial with atypia and classic lobular neoplasia found on percutaneous biopsy (without radiologic indications for excision). Expert commentary: HEA management steel need prospective evidences, but recent retrospective data give some clue for less invasive management for some of HEA.

  12. Atypical presentations of acute disseminated encephalomyelitis (ADEM) in HIV infection.

    PubMed

    Naidoo, Ansuya; Paruk, Hoosain; Bhagwan, Bhupendra; Moodley, Anand

    2017-02-01

    Acute disseminated encephalomyelitis is a monophasic demyelinating disorder of the central nervous system associated with various viral infections including HIV infection. We present the findings of seven HIV-infected patients with mild to moderate immunosuppression presenting with atypical features. Four patients had a multiphasic course; three patients had tumefactive lesions, and two patients had corpus callosum lesions. Two patients with the multiphasic course also had tumefactive lesions. Their clinical and radiological findings are presented. Despite the few cases, we propose that the dysimmune process lying between marked immunosuppression (CD4 < 200 cells/μL) and normal CD4 counts (CD4 > 500 cells/μL) might be responsible for these atypical presentations.

  13. Healing of subtrochanteric atypical fractures after strontium ranelate treatment

    PubMed Central

    Negri, Armando Luis; Spivacow, Francisco Rodolfo

    2012-01-01

    Summary Oral bisphosphonates comprise the most widely prescribed class of antiosteoporotic drugs. Recent reports, however, suggest a link between prolonged bisphosphonate use and atypical low-energy, subtrochanteric fractures. We describe the clinical course of two patient treated for a long term with different bisphosphonates who developed subtrochanteric atypical fractures. They were treated initially with intramedullary rodding without pain disappearance or healing of the fracture. Strontium ranelate, a new orally administered agent for the treatment of osteoporosis, was given to these patients with complete closure of the fracture and pain disappearance after a few months. We conclude that based on the chronology of fracture healing and pain disappearance of our patients and published evidence that strontium ranelate can accelerate fracture healing in a rat model, that strontium ranelate had a positive anabolic effect that contributed to fracture healing that produced the secondary disappearance of pain. PMID:23289032

  14. Identification of the first case of atypical scrapie in Japan

    PubMed Central

    IMAMURA, Morikazu; MIYAZAWA, Kohtaro; IWAMARU, Yoshifumi; MATSUURA, Yuichi; YOKOYAMA, Takashi; OKADA, Hiroyuki

    2016-01-01

    A Corriedale ewe was confirmed as the first atypical scrapie case during an active surveillance program for transmissible spongiform encephalopathies in small ruminants in Japan. The animal was homozygous for the AF141RQ haplotype of PRNP. The animal showed clinical neurological signs possibly due to listeriosis before culling. Western blot analysis showed an unusual multiple banded pattern with a low-molecular fragment at ~7 kDa. Histopathology revealed suppurative meningoencephalitis caused by listeriosis in the brainstem. Fine granular to globular immunostaining of disease-associated prion proteins was mainly detected in the neuropil of the spinal tract of the trigeminal nerve and in the white matter of the spinocerebellar tract. Based on these results, this case was conclusively diagnosed as atypical scrapie with encephalitic listeriosis. PMID:27616556

  15. Real-world Data on Atypical Antipsychotic Medication Side Effects.

    PubMed

    Cascade, Elisa; Kalali, Amir H; Mehra, Sagar; Meyer, Jonathan M

    2010-07-01

    In this article, we provide information on patient-reported side effects from a cross-section of real-world patients. Specifically, data on side effects were tabulated for patients taking at least one of the following atypical antipsychotic medications: aripiprazole, olanzapine, paliperidone, quetiapine, risperidone, or ziprasidone. Approximately 54 percent of the 353 respondents reported having experienced a side effect as a result of taking an atypical antipsychotic medication. Most common side effects mentioned included the following: weight gain/hunger, tiredness/lethargy, and lack of coordination/muscle problems, such as tenderness, twitches, and tremors. Of those experiencing a side effect, less than 25 percent reported this side effect to their physician.

  16. Expected incidence of tardive dyskinesia associated with atypical antipsychotics.

    PubMed

    Glazer, W M

    2000-01-01

    Given the problematic nature of tardive dyskinesia in persons taking conventional antipsychotics, evaluation of newer atypical antipsychotic agents should include a systematic assessment of tardive dyskinesia liability. Results of a prospective double-blind, randomized study of schizophrenic patients who participated in 3 preclinical olanzapine studies and were treated with 5 to 20 mg/day of olanzapine (N = 1192) or haloperidol (N = 522) recently indicated a significantly lower risk of development of tardive dyskinesia with olanzapine treatment than haloperidol treatment. This article discusses the known effects of atypical antipsychotic medications on tardive dyskinesia movements (both withdrawal and persistent) and the incidence rate of tardive dyskinesia among schizophrenic patients undergoing long-term treatment with olanzapine or haloperidol.

  17. Monoclonal gammopathy of renal significance triggering atypical haemolytic uraemic syndrome.

    PubMed

    Mahmood, Usman; Isbel, Nicole; Mollee, Peter; Mallett, Andrew; Govindarajulu, Sridevi; Francis, Ross

    2017-02-01

    Haemolytic uraemic syndrome is a rare condition with an overall incidence of one to two cases in a population of 100 000 and approximately 10% of these cases are classified as atypical. Atypical haemolytic uraemic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by microangiopathic haemolytic anaemia (MAHA), thrombocytopenia and acute kidney injury. aHUS can be genetic, acquired or idiopathic (negative genetic screening and no environmental triggers). We describe a case of aHUS triggered by monoclonal gammopathy of renal significance (MGRS) successfully treated with plasmapheresis and a bortezomib-based chemotherapy regimen, resulting in marked improvement in renal function and other markers of haemolysis. This patient has been in remission for more than 2 years currently.

  18. Atypical form of cat scratch disease in immunocompetent patient.

    PubMed

    Kojić, Miroslav; Mikić, Dragan; Nozić, Darko; Zolotarevski, Lidija

    2013-01-01

    Cat scratch disease (CSD) is an acute infectious disease with benign course caused by the bacteria Bartonella henselae. Clinically, it is usually manifested as regional lymphadenopathy and mild infective syndrome. Rare forms of the disease which usually occur in immunocompromised presons are: encephalitis, transverse myelitis, neuroretinitis, granulomatosus conjunctivitis, arthritis, hepatitis etc. We presented an atypical form of cat scratch disease in a young immunocompetent female person. The disease was manifested with prolonged fever, rash, purulent lymphadenitis and hepatitis. The diagnosis was based on characteristic patohystological finding and exclusion of the other causes of lymphadenopathy. The patient was treated by antibiotics for a few weeks, with surgical incision and drainage of the purulent lymphadenitis. Atypical forms of CSD could be an important differential-diagnostic problem, especially if there is no opportunity for serological confirmation of the disease.

  19. Sensitivity of atypical lateral fire spread to wind and slope

    NASA Astrophysics Data System (ADS)

    Simpson, Colin. C.; Sharples, Jason J.; Evans, Jason P.

    2016-02-01

    This study presents new knowledge of the environmental sensitivity of a dynamic mode of atypical wildland fire spread on steep lee-facing slopes. This is achieved through a series of idealized numerical simulations performed with the Weather Research and Forecasting (WRF) and WRF-Fire coupled atmosphere-fire models. The sensitivity of the atypical lateral fire spread across lee slopes is tested for a varying background wind speed, wind direction relative to the terrain aspect, and lee slope steepness. The results indicate that the lateral spread characteristics are highly sensitive to each of these environmental conditions, and there is a broad agreement with the empirical thresholds calculated for lateral spread events observed in the 2003 Canberra bushfires. A theory to explain these environmental thresholds and their apparent interdependency is presented. The results are expected to have important implications for the management of wildland fires in rugged terrain.

  20. Atypical Behavior Identification in Large Scale Network Traffic

    SciTech Connect

    Best, Daniel M.; Hafen, Ryan P.; Olsen, Bryan K.; Pike, William A.

    2011-10-23

    Cyber analysts are faced with the daunting challenge of identifying exploits and threats within potentially billions of daily records of network traffic. Enterprise-wide cyber traffic involves hundreds of millions of distinct IP addresses and results in data sets ranging from terabytes to petabytes of raw data. Creating behavioral models and identifying trends based on those models requires data intensive architectures and techniques that can scale as data volume increases. Analysts need scalable visualization methods that foster interactive exploration of data and enable identification of behavioral anomalies. Developers must carefully consider application design, storage, processing, and display to provide usability and interactivity with large-scale data. We present an application that highlights atypical behavior in enterprise network flow records. This is accomplished by utilizing data intensive architectures to store the data, aggregation techniques to optimize data access, statistical techniques to characterize behavior, and a visual analytic environment to render the behavioral trends, highlight atypical activity, and allow for exploration.

  1. Combined Papillated Bowen Disease and Clear Cell Atypical Fibroxanthoma

    PubMed Central

    Suárez-Vilela, Dimas; Izquierdo-García, Francisco; Domínguez-Iglesias, Francisco; Méndez-Álvarez, Jose Ramón

    2010-01-01

    We describe a case of papillated Bowen disease (PBD), associated with a clear cell atypical fibroxanthoma (CCAFXA). The epidermal lesion showed a bowenoid papillomatous growth pattern with histologic features suggestive of infection by human papilloma virus (HPV). In the dermis a neoplasm made up by spindled or polygonal cells with wide clear cytoplasm and moderate nuclear pleomorphism was found. Immunohistochemical characteristics of these two lesions were clearly different. The atypical cells of the intraepidermal proliferation were positive for AE1-AE3 anticytokeratin antibody, EMA, p16, p53 and p63. The dermal tumor was positive for vimentin, CD10, CD68, CD99, alpha-1-antitrypsin and c-kit. Histological features and immunohistochemical profile of the dermal tumor corresponded to a CCAFXA, a very uncommon neoplasm of which only 10 cases have been reported. In situ hybridization for numerous types of HPVs was negative in both lesions. PMID:21103191

  2. Nightmare-induced atypical midventricular tako-tsubo cardiomyopathy.

    PubMed

    Fibbi, Veronica; Ballo, Piercarlo; Nannini, Marco; Consoli, Lorenzo; Chechi, Tania; Bribani, Andrea; Fiorentino, Francesca; Chiodi, Leandro; Zuppiroli, Alfredo

    2015-01-01

    Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy characterized by acute left ventricular segmental dysfunction, whose clinical presentation resembles that of acute myocardial infarction. The syndrome often follows a psychophysical stressful event and is characterized by echocardiographic evidence of akinesia of the left ventricular mid-apical segments. Atypical echocardiographic patterns of TTC have recently been described, often triggered by emotional stressors, rather than physical. In this report, we describe a case of atypical TTC triggered by an unusual stressor (recurrent nightmare) in a 45-year-old woman, with peculiar clinical presentation and evolution characterized by persistent loss of consciousness, neurological deterioration, absence of typical symptoms of TTC, and features suggestive of a hysterical crisis.

  3. Nightmare-Induced Atypical Midventricular Tako-Tsubo Cardiomyopathy

    PubMed Central

    Fibbi, Veronica; Ballo, Piercarlo; Nannini, Marco; Consoli, Lorenzo; Chechi, Tania; Bribani, Andrea; Fiorentino, Francesca; Chiodi, Leandro; Zuppiroli, Alfredo

    2015-01-01

    Tako-Tsubo cardiomyopathy (TTC) is a reversible cardiomyopathy characterized by acute left ventricular segmental dysfunction, whose clinical presentation resembles that of acute myocardial infarction. The syndrome often follows a psychophysical stressful event and is characterized by echocardiographic evidence of akinesia of the left ventricular mid-apical segments. Atypical echocardiographic patterns of TTC have recently been described, often triggered by emotional stressors, rather than physical. In this report, we describe a case of atypical TTC triggered by an unusual stressor (recurrent nightmare) in a 45-year-old woman, with peculiar clinical presentation and evolution characterized by persistent loss of consciousness, neurological deterioration, absence of typical symptoms of TTC, and features suggestive of a hysterical crisis. PMID:25788945

  4. Critical appraisal of eculizumab for atypical hemolytic uremic syndrome

    PubMed Central

    Palma, Lilian M Pereira; Langman, Craig B

    2016-01-01

    The biology of atypical hemolytic uremic syndrome has been shown to involve inability to limit activation of the alternative complement pathway, with subsequent damage to systemic endothelial beds and the vasculature, resulting in the prototypic findings of a thrombotic microangiopathy. Central to this process is the formation of the terminal membrane attack complex C5b-9. Recently, application of a monoclonal antibody that specifically binds to C5, eculizumab, became available to treat patients with atypical hemolytic uremic syndrome, replacing plasma exchange or infusion as primary therapy. This review focuses on the evidence, based on published clinical trials, case series, and case reports, on the efficacy and safety of this approach. PMID:27110144

  5. Diagnosis and management of typical and atypical lung carcinoids.

    PubMed

    Pusceddu, Sara; Lo Russo, Giuseppe; Macerelli, Marianna; Proto, Claudia; Vitali, Milena; Signorelli, Diego; Ganzinelli, Monica; Scanagatta, Paolo; Duranti, Leonardo; Trama, Annalisa; Buzzoni, Roberto; Pelosi, Giuseppe; Pastorino, Ugo; de Braud, Filippo; Garassino, Marina Chiara

    2016-04-01

    An estimated 20% to 30% of all neuroendocrine tumours originate in the bronchial tree and lungs. According to the 2015 World Health Organization categorization, these tumours are separated into four subtypes characterized by increasing biological aggressiveness: typical carcinoid, atypical carcinoid, large-cell neuroendocrine carcinoma and small-cell carcinoma. Although typical and atypical lung carcinoids account for less than 1-5% of all pulmonary malignancies, the incidence of these neoplasms has risen significantly in recent decades. Surgery is the treatment of choice for loco-regional disease but for advanced lung carcinoids there is no recognized standard of care and successful management requires a multidisciplinary approach. The aim of this review is to provide a useful guide for the clinical management of lung carcinoids.

  6. Transmission of atypical scrapie to homozygous ARQ sheep.

    PubMed

    Okada, Hiroyuki; Miyazawa, Kohtaro; Imamura, Morikazu; Iwamaru, Yoshifumi; Masujin, Kentaro; Matsuura, Yuichi; Yokoyama, Takashi

    2016-11-01

    Two Cheviot ewes homozygous for the A136L141R154Q171 (AL141RQ) prion protein (PrP) genotype were exposed intracerebrally to brain pools prepared using four field cases of atypical scrapie from the United Kingdom. Animals were clinically normal until the end of the experiment, when they were culled 7 years post-inoculation. Limited accumulation of disease-associated PrP (PrP(Sc)) was observed in the cerebellar molecular layer by immunohistochemistry, but not by western blot or enzyme-linked immunosorbent assay. In addition, PrP(Sc) was partially localized in astrocytes and microglia, suggesting that these cells have a role in PrP(Sc) processing, degradation or both. Our results indicate that atypical scrapie is transmissible to AL141RQ sheep, but these animals act as clinically silent carriers with long incubation times.

  7. Hyperglycemia secondary to consumption of cocaine and atypical antipsychotic drugs.

    PubMed

    Argente Villaplana, Carlos R; Civera Andrés, Miguel; Real Collado, José T; Martínez-Hervás, Sergio; Ascaso Gimilio, Juan F; Carmena Rodríguez, Rafael

    2008-10-01

    Drugs such as cocaine and atypical antipsychotic agents, such as olanzapine, are sometimes related to hyperglycemia. Whereas cocaine raises plasma glucose through catecholamine release, atypical antipsychotic agents mainly increase appetite and induce weight gain and the development of metabolic syndrome. Moreover, the latter group of drugs also act independently from weight gain or adiposity, due to inhibition of beta pancreatic cells and reduction of peripheral insulin action. We present the case of a 29-year-old non-diabetic woman with severe acute hyperglycemia in the context of a suicide attempt through intake of olanzapine and cocaine. After discontinuation of olanzapine and cocaine consumption, glycemia was immediately normalized without subsequent diagnosis of diabetes.

  8. Not only limbs in atypical restless legs syndrome.

    PubMed

    Turrini, Alessandra; Raggi, Alberto; Calandra-Buonaura, Giovanna; Martinelli, Paolo; Ferri, Raffaele; Provini, Federica

    2017-04-04

    Restless legs syndrome (RLS) typically affects the limbs, but the involvement of other body parts has also been reported. In this essay, we critically review all literature reports of atypical RLS cases with unusual localizations. Applying the updated diagnostic criteria of the International restless legs syndrome study group (IRLSSG), which also consider symptoms localized outside of the lower limbs, a few of these atypical cases reported in the previous literature resulted in a definitive diagnosis of RLS. We also discuss the relationship between RLS and burning mouth syndrome (BMS) or restless genital syndrome (RGS). We conclude clinical sleep specialists should be aware of unusual RLS localizations because they respond to the usual treatment for RLS. All the IRLSSG diagnostic criteria should be applied in every suspected case, in order to establish a correct diagnosis of this disabling but treatable condition. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Transmission of atypical scrapie to homozygous ARQ sheep

    PubMed Central

    OKADA, Hiroyuki; MIYAZAWA, Kohtaro; IMAMURA, Morikazu; IWAMARU, Yoshifumi; MASUJIN, Kentaro; MATSUURA, Yuichi; YOKOYAMA, Takashi

    2016-01-01

    Two Cheviot ewes homozygous for the A136L141R154Q171 (AL141RQ) prion protein (PrP) genotype were exposed intracerebrally to brain pools prepared using four field cases of atypical scrapie from the United Kingdom. Animals were clinically normal until the end of the experiment, when they were culled 7 years post-inoculation. Limited accumulation of disease-associated PrP (PrPSc) was observed in the cerebellar molecular layer by immunohistochemistry, but not by western blot or enzyme-linked immunosorbent assay. In addition, PrPSc was partially localized in astrocytes and microglia, suggesting that these cells have a role in PrPSc processing, degradation or both. Our results indicate that atypical scrapie is transmissible to AL141RQ sheep, but these animals act as clinically silent carriers with long incubation times. PMID:27320968

  10. Learning, plasticity, and atypical generalization in children with autism.

    PubMed

    Church, Barbara A; Rice, Courtney L; Dovgopoly, Alexander; Lopata, Christopher J; Thomeer, Marcus L; Nelson, Andrew; Mercado, Eduardo

    2015-10-01

    Individuals with autism spectrum disorder (ASD) show accelerated learning in some tasks, degraded learning in others, and distinct deficits when generalizing to novel situations. Recent simulations with connectionist models suggest that deficits in cortical plasticity mechanisms can account for atypical patterns of generalization shown by some children with ASD. We tested the surprising theoretical prediction, from past simulations, that the children with ASD who show atypical generalization in perceptual categorization tasks will benefit more from training with a single prototypical member of the category than from training with multiple examples, but children with ASD who generalize normally will be comparatively harmed. The experimental results confirmed this prediction, suggesting that plasticity deficits may well underlie the difficulties that some children with ASD have generalizing skills, and these deficits are not specific to the acquisition of social skills, but rather reflect a more general perceptual learning deficit that may impact many abilities.

  11. ACPA-Negative RA Consists of Two Genetically Distinct Subsets Based on RF Positivity in Japanese

    PubMed Central

    Terao, Chikashi; Ohmura, Koichiro; Ikari, Katsunori; Kochi, Yuta; Maruya, Etsuko; Katayama, Masaki; Yurugi, Kimiko; Shimada, Kota; Murasawa, Akira; Honjo, Shigeru; Takasugi, Kiyoshi; Matsuo, Keitaro; Tajima, Kazuo; Suzuki, Akari; Yamamoto, Kazuhiko; Momohara, Shigeki; Yamanaka, Hisashi; Yamada, Ryo; Saji, Hiroo; Matsuda, Fumihiko; Mimori, Tsuneyo

    2012-01-01

    HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10−6 and 0.0011, OR: 1.57 (1.28–1.91) and 1.37 (1.13–1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21–1.89) and 3.08 (1.68–5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote. PMID:22792215

  12. Analysis of the distribution characteristics of 226Ra and 228Ra and their sources in the western part of Qinghai Lake

    NASA Astrophysics Data System (ADS)

    Kong, Fancui; Sha, Zhanjiang; Du, Jinzhou; Su, Weigang; Yu, Chenguang; Zhao, Shunli; Hu, Jufang; Ye, Mei

    2015-11-01

    The 226Ra and 228Ra activities of Qinghai Lake surface water, groundwater, river water, suspended particles, and bottom sediments were measured in a gamma-ray spectrometer. The sources of 226Ra and 228Ra were discussed according to their distribution characteristics. 226Ra and 228Ra activities (dpm/(100 L)) ranged from 14.13±0.22 to 19.22±0.42 and 17.72±0.66 to 30.96±1.47 in the surface water of the North Bay, respectively, and from 7.88±0.24 to 33.80±0.47 and 15.73±0.74 to 57.31±1.44, respectively, in the South Bay. The surface water near the estuary had a lower salinity and had a higher concentration of radium isotopes than the samples collected further away. The farther offshore the sample, the higher the salinity was, and the lower the radium isotope activity. The distribution of radium activities in the western part of Qinghai Lake is controlled by several factors, including Buha River runoff, desorption from suspended particles derived from the river, groundwater discharge, and a small amount of diffusion from the sediment.

  13. Measurement of (238)U, (228)Ra, (226)Ra, (40)K and (137)Cs in foodstuffs samples collected from coastal areas of China.

    PubMed

    Tuo, Fei; Zhang, Qing; Zhou, Qiang; Xu, Cuihua; Zhang, Jing; Li, Wenhong; Zhang, Jianfeng; Su, Xu

    2016-05-01

    This study represents a total of 245 samples collected. The activities of (238)U, (228)Ra, (226)Ra, (40)K and (137)Cs were determined in samples of vegetables, tea, cereal (rice, wheat and corn), meat, poultry, freshwater product, seafood and seaweed that collected from the 30km safety zone of the Nuclear Power Plants (NPPs) area. All the samples radionuclide activities were quantified by using High Purity Germanium (HPGe) gamma spectrometry. The geometric mean concentrations (Bqkg(-1) wet weight) for (238)U, (228)Ra, (226)Ra, (40)K, and (137)Cs in all investigated foodstuffs samples, are 0.13, 0.16, 0.11, 68 and 0.02, respectively. The arithmetic mean concentrations (Bqkg(-1) wet weight) for (238)U, (228)Ra, (226)Ra, (40)K, and (137)Cs in all investigated foodstuffs samples, are 0.34, 0.65, 0.32, 111 and 0.09, respectively. Results of this study were compared with others, the measured values are the same with those of a previous investigation. Radiation doses due to the consumption of these foodstuffs to humans are estimated to comprise around 37-46% of the annual dose limit for public. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Buspirone hydrochloride in the treatment of an atypical paraphilia.

    PubMed

    Fedoroff, J P

    1992-08-01

    A case report involving buspirone hydrochloride in the successful treatment of a patient with an atypical paraphilia and transvestic fetishism is presented. Treatment outcome was assessed by the patient's self-report as well as by retrospective examination of detailed notes about paraphilia fantasies which unknown to the therapists, had been kept by the patient. Preliminary evidence indicates that buspirone appears to effectively treat some paraphilias.

  15. Gamma Knife Radiosurgery for Atypical and Anaplastic Meningiomas.

    PubMed

    Wang, Wei-Hsin; Lee, Cheng-Chia; Yang, Huai-Che; Liu, Kang-Du; Wu, Hsiu-Mei; Shiau, Cheng-Ying; Guo, Wan-You; Pan, David Hung-Chi; Chung, Wen-Yuh; Chen, Ming-Teh

    2016-03-01

    Atypical and anaplastic meningiomas have much higher recurrence rates after surgical resection compared with benign meningiomas, but the role of adjuvant radiosurgery remains unclear. This study was undertaken to evaluate the outcomes of gamma knife radiosurgery for patients with atypical and anaplastic meningiomas. In this retrospective analysis of a prospectively maintained database, 46 patients with histologically proven atypical or anaplastic meningiomas by current World Health Organization (WHO) criteria underwent postoperative Gamma Knife radiosurgery between 1993 and 2013. The median follow-up period was 32.6 months. The median tumor volume and margin dose were 11.7 mL (range, 2-53 mL) and 13.1 Gy (range, 12.0-16.5 Gy), respectively. Local control at 3 and 5 years was 50.6% and 32.1%, respectively. Gender (P = 0.013) and marginal dose less than or equal to 13 Gy (P = 0.049) were associated with the local control. The 3- and 5-year overall survival for patients with WHO grade II was 97.1% and 88.3%, respectively, compared with 66.7% and 66.7% for patients with WHO grade III meningiomas. Radiation therapy before Gamma Knife radiosurgery (GKRS; P = 0.018) and tumor grade (P = 0.019) were the factors associated with a worse overall survival rate. Fourteen patients (30.4%) developed adverse radiation effects after GKRS treatment, and all were Radiation Therapy Oncology Group grade I. Postoperative GKRS treatment for patients with atypical and anaplastic meningioma is challenging. More aggressive treatment, including of safely maximizing the extent of surgical resection and using a higher margin dose (>13Gy), should be applied to achieve better local control. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Atypical presentation of antiphospholipid syndrome: a case report.

    PubMed

    Mariotti, Cesare; Giovannini, Alfonso; Reibaldi, Michele; Saitta, Andrea; Viti, Francesca; Nicolai, Michele

    2014-09-01

    We report an atypical presentation of Antiphospholipid syndrome (APS) with concomitant subhyaloid hemorrhage, engorged and tortuous retinal veins, intraretinal hemorrhages, and cotton wool spots in a 38-year-old female. Medical treatment was preferred to any invasive treatment. The subhyaloid hemorrhage resolved spontaneously and the patient recovered a visual acuity of 20/20 in her right eye 3 months after the initial episode. A prompt diagnosis of this condition is fundamental to consider a systemic treatment to avoid any further thrombosis.

  17. Pharmacological management of atypical antipsychotic-induced weight gain.

    PubMed

    Baptista, Trino; ElFakih, Yamily; Uzcátegui, Euderruh; Sandia, Ignacio; Tálamo, Eduardo; Araujo de Baptista, Enma; Beaulieu, Serge

    2008-01-01

    Excessive bodyweight gain was reported during the 1950s as an adverse effect of typical antipsychotic drug treatment, but the magnitude of bodyweight gain was found to be higher with the atypical antipsychotic drugs that were introduced after 1990. Clozapine and olanzapine produce the greatest bodyweight gain, ziprasidone and aripiprazole have a neutral influence, and quetiapine and risperidone cause an intermediate effect. In the CATIE study, the percentage of patients with bodyweight gain of >7% compared with baseline differed significantly between the antipsychotic drugs, i.e. 30%, 16%, 14%, 12% and 7% for olanzapine, quetiapine, risperidone, perphenazine (a typical antipsychotic) and ziprasidone, respectively (p<0.001). Appetite stimulation is probably a key cause of bodyweight gain, but genetic polymorphisms modify the bodyweight response during treatment with atypical antipsychotics. In addition to nutritional advice, programmed physical activity, cognitive-behavioural training and atypical antipsychotic switching, pharmacological adjunctive treatments have been assessed to counteract excessive bodyweight gain. In some clinical trials, nizatidine, amantadine, reboxetine, topiramate, sibutramine and metformin proved effective in preventing or reversing atypical antipsychotic-induced bodyweight gain; however, the results are inconclusive since few randomized, placebo-controlled clinical trials have been conducted. Indeed, most studies were short-term trials without adequate statistical power and, in the case of metformin, nizatidine and sibutramine, the results are contradictory. The tolerability profile of these agents is adequate. More studies are needed before formal recommendations on the use of these drugs can be made. Meanwhile, clinicians are advised to use any of these adjunctive treatments according to their individual pharmacological and tolerability profiles, and the patient's personal and family history of bodyweight gain and metabolic dysfunction.

  18. An atypical presentation of the Fitz-Hugh-Curtis syndrome.

    PubMed

    McCormick, M; DelCastillo, J; Berk, R S

    1990-01-01

    We present an unusual case of the Fitz-Hugh-Curtis syndrome as manifested in a young woman with right upper quadrant pain. The presentation was atypical and misleading because of the presence of a colonic ileus and the lack of salpingitis by pelvic exam. Diagnosis was made by exclusion of other abdominal disease processes, the detection of Chlamydia trachomatis antibody from a cervical specimen, and a dramatic response to appropriate antibiotic therapy.

  19. Atypical spatiotemporal signatures of working memory brain processes in autism

    PubMed Central

    Urbain, C M; Pang, E W; Taylor, M J

    2015-01-01

    Working memory (WM) impairments may contribute to the profound behavioural manifestations in children with autism spectrum disorder (ASD). However, previous behavioural results are discrepant as are the few functional magnetic resonance imaging (fMRI) results collected in adults and adolescents with ASD. Here we investigate the precise temporal dynamics of WM-related brain activity using magnetoencephalography (MEG) in 20 children with ASD and matched controls during an n-back WM task across different load levels (1-back vs 2-back). Although behavioural results were similar between ASD and typically developing (TD) children, the between-group comparison performed on functional brain activity showed atypical WM-related brain processes in children with ASD compared with TD children. These atypical responses were observed in the ASD group from 200 to 600 ms post stimulus in both the low- (1-back) and high- (2-back) memory load conditions. During the 1-back condition, children with ASD showed reduced WM-related activations in the right hippocampus and the cingulate gyrus compared with TD children who showed more activation in the left dorso-lateral prefrontal cortex and the insulae. In the 2-back condition, children with ASD showed less activity in the left insula and midcingulate gyrus and more activity in the left precuneus than TD children. In addition, reduced activity in the anterior cingulate cortex was correlated with symptom severity in children with ASD. Thus, this MEG study identified the precise timing and sources of atypical WM-related activity in frontal, temporal and parietal regions in children with ASD. The potential impacts of such atypicalities on social deficits of autism are discussed. PMID:26261885

  20. Psychological and Behavioral Dynamics in Chronic Atypical Facial Pain

    PubMed Central

    Baile, Walter F.; Myers, Daniel

    1986-01-01

    The authors discuss the relationship between atypical facial pain and psychiatric disturbance. They present contemporary viewpoints and describe four cases that illustrate underlying psychodynamic mechanisms associated with pain in patients who had undergone various dental procedures and other treatments without success. They identify factors which might lead to the early detection of underlying psychological problems and discuss the role of learning, the family system and other factors in producing a chronic pain syndrome. PMID:3465263