32 research outputs found
HSCT corrects primary immunodeficiency and immune dysregulation in patients with POMP-related auto-inflammatory disease
No full textInborn errors of immunity that present with concomitant immunodeficiency and auto-inflammation are therapeutically challenging; furthermore, complexity is added when they are caused by mutations in genes that encode for proteins expressed beyond immune cells. The ubiquitin-proteasome system is the main intracellular proteolytic machinery and participates in most cellular processes by degrading ubiquitinated proteins. Mutations in proteasome subunits resulting in proteasome deficiency cause a severe auto-inflammatory disease characterized by chronic auto-inflammation neutrophilic dermatosis and fever, collectively referred to as Proteasome Associated Auto-inflammatory Syndromes (PRAAS). POMP is a chaperone for proteasome assembly and AD mutations in POMP cause a form of PRAAS with prominent immunodeficiency referred to as POMP-related auto-inflammation and immune dysregulation (PRAID) manifesting with recurrent, severe and opportunistic infections in addition to inflammatory features that are characteristic for all PRAAS disorders, most importantly early-onset neutrophilic dermatosis. JAK inhibitors partially control the disease in individuals with PRAAS, however life-threatening, recurrent and opportunistic infections in patients with POMP mutations limit immunosuppressive therapies and prompted consideration of hematopoietic stem cell transplant (HSCT). We describe successful HSCT in two patients with POMP deficiency. Despite POMP being ubiquitously expressed, the immunologic and auto-inflammatory phenotype were both ameliorated through HSCT which suggests that the clinical and immunological features of PRAID are predominantly derived from a proteasome defect in hematopoietic cells. To our knowledge, these are the first patients with a form of PRAAS cured by HSCT, opening new therapeutic possibilities for these diseases
Ausente pero siempre presente: reflexiones sobre el secreto en la tradición šī‛i y en el misticismo sunní
No full textThe article analyzes a tradition (ḥadīṯh) that is found in Sunnī and in Shī‛ī sources alike and which portrays the ideal believer as a hidden man who chooses to practice his religion away from the eyes of others. According to the author’s analysis, this tradition has its origins in the religious-political conflicts (fitness) of the 2nd/8th century. These conflicts gave rise to a pietistic attitude of noninvolvement and withdrawal from society in times of civil strife. In Shī‛ī versions of the tradition, the element of secrecy and taqiyya is added to the description of the ideal believer. These various motifs were to play an important role in Islamic mysticism, particularly in the teachings of movements such as the malāmatiyya. The author argues that while both Shī‛ī esotericism and Sunnī mysticism incorporated similar, early ḥadīṯhs in their discussions of the figure of the hidden saint, the Shī‛ī tradition contributed much to the development of this theme in its ethical-psychological and esoteric aspects.Este artículo analiza el ḥadīṯ que se encuentra tanto en las fuentes šī‛íes como sunníes que retrata al creyente ideal como un hombre escondido que elige practicar su religión apartado de los ojos de los otros. Según el autor, esta tradición tiene su origen en las luchas político-religiosas (fintas) del siglo II/VIII, que propiciaron una actitud piadosa de retiro de la sociedad y no participación en tiempos de lucha civil. En las versiones šī‛íes del ḥadīṯ el elemento de secreto, taqiyya, se anade a la descripción del creyente ideal. Estos motivos habrán de desempenar un papel importante en movimientos místicos como el de malāmatiyya. Aunque el esoterismo šī‛í y el misticismo sunní incorporaron hadices similares a su elaboración del santo escondido, la tradición šī‛í contribuyó particularmente al desarrollo de este tema tanto en términos ético-psicológicos como esotéricos
Protein kinase R is an innate immune sensor of proteotoxic stress via accumulation of cytoplasmic IL-24
No full textProteasome dysfunction can lead to autoinflammatory disease associated with elevated type I interferon (IFN-αβ) and NF-κB signaling; however, the innate immune pathway driving this is currently unknown. Here, we identified protein kinase R (PKR) as an innate immune sensor for proteotoxic stress. PKR activation was observed in cellular models of decreased proteasome function and in multiple cell types from patients with proteasome-associated autoinflammatory disease (PRAAS). Furthermore, genetic deletion or small-molecule inhibition of PKR in vitro ameliorated inflammation driven by proteasome deficiency. In vivo, proteasome inhibitor-induced inflammatory gene transcription was blunted in PKR-deficient mice compared with littermate controls. PKR also acted as a rheostat for proteotoxic stress by triggering phosphorylation of eIF2α, which can prevent the translation of new proteins to restore homeostasis. Although traditionally known as a sensor of RNA, under conditions of proteasome dysfunction, PKR sensed the cytoplasmic accumulation of a known interactor, interleukin-24 (IL-24). When misfolded IL-24 egress into the cytosol was blocked by inhibition of the endoplasmic reticulum-associated degradation pathway, PKR activation and subsequent inflammatory signaling were blunted. Cytokines such as IL-24 are normally secreted from cells; therefore, cytoplasmic accumulation of IL-24 represents an internal danger-associated molecular pattern. Thus, we have identified a mechanism by which proteotoxic stress is detected, causing inflammation observed in the disease PRAAS.Sophia Davidson, Chien-Hsiung Yu, Annemarie Steiner, Frederic Ebstein, Paul J. Baker, Valentina Jarur-Chamy, Katja Hrovat Schaale, Pawat Laohamonthonkul, Klara Long, Dale J. Calleja, Cassandra R. Harapas, Katherine R. Balka, Jacob Mitchell, Jacob T. Jackson, Niall D. Geohegan, Fiona Moghaddas, Kelly L. Rogers, Katrin D. Mayer-Barber, Adriana A. De Jesus, Dominic De Nardo, Benjamin T. Kile, Anthony J. Sadler, M. Cecilia Poli, Elke Kruger, Raphaela Goldbach Mansky and Seth L. Master
The relationships among coping, occupational stress, and emotional intelligence in newly hired nurses in an oncology setting
No full textOncology work environments are stressful due to increasing workloads, decreasing staffing levels, and rising patient acuity, which may contribute to the physical stress and emotional exhaustion experienced by oncology nurses. Empirical evidence supports that individual Emotional Intelligence levels may be predictive of whether nurses can successfully cope with the occupational stress emanating from the work environment. Theorists contend that individual Emotional Intelligence may moderate the selection of coping strategies when managing occupational stress in the nursing environment. This study explored the relationships among coping strategies, occupational stress, and Emotional Intelligence in newly hired oncology nurses, as well as the degree to which Emotional Intelligence moderated the use of coping strategies in the presence of occupational stress. The EQ-i 2.0 TM, the Ways of Coping Questionnaire and the Nursing Stress Scale were used to measure the study variables. Newly hired nurses, with no prior oncology experience in a National Cancer Institute-designated comprehensive cancer center, were invited to participate in the study though email/web link to online surveys. Data were collected from October 2013 through January 2015, after 98 completed surveys were obtained. Data were analyzed to determine correlations between coping strategies (Emotion-Focused and Problem-Focused Coping), occupational stress and Emotional Intelligence. A moderation model was built to determine whether Emotional Intelligence moderated the effect of Problem-Focused and Emotion-Focused Coping during occupational stress. Results of this study found significant relationships between variables, however Emotional Intelligence did not moderate an effect on the choice of coping strategies. Findings concluded that newly hired nurses in this research had average to high Emotional Intelligence and used Problem-Focused Coping to deal with their occupational stress. The stress experienced by the newly hired nurses in this study was higher compared to experienced nurses in other studies. These findings concluded that the newly hired oncology nurses in this research experienced occupational stress within the first three months post hire, and contributed to the empirical nursing literature that explains coping, occupational stress and Emotional Intelligence in this sample of oncology nurses during their initial employment period.Ph.D.Includes bibliographical referencesby Ann Marie Mazzella Ebstei
A new carboxamide compound exerts immuno-suppressive activity by inhibiting dendritic cell maturation
No full textAuthor Correction: Risk variants and polygenic architecture of disruptive behavior disorders in the context of attention-deficit/hyperactivity disorder
No full textThe original version of this Article contained an error in the spelling of the author Marta Ribasés, which was incorrectly given as Marta Ribasas. This has now been corrected in both the PDF and HTML versions of the Article
Inducible expression of RANKL in transgenic pigs under the control of the Tet-On system
No full textBecause of the tremendous need for transgenic large animal models for human diseases, the process of SCNT is a crucial step in transgenic pig production. In our study, we evaluated the particular steps during the production for their impact on the efficiency of cloning transgenic pigs. For this purpose, statistical analysis was performed for all SCNT data from the years 2006 until June 2010. The RANKL transgenic osteoporosis model was chosen for an example for the production steps needed to finally achieve a disease model, to elucidate pitfalls and chances of SCNT procedure. In total 151 in vivo SCNT experiments using different transgenic cell lines were carried out, resulting in 243 piglets and fetuses. Statistical analysis revealed that donor cells treated exclusively in our laboratory had a significant better birth rate than donor cell originated of other laboratories. Furthermore, there was a significant relation between number of transferred NT embryos and later pregnancy checks, birth rate and abortion rate. The more NT embryos were transferred, the more pregnancies finished to terms. It was also elucidated that in our studies a different in vitro culture time of 24 or 48 hours had no significant impact on the outcome like pregnancy or birth rate. Seasonal changes during the years had no significant influence on pregnancy rate, birth or abortion. But there was a strong tendency that autumn showed best performance of all seasons, and most pregnancies were lost after embryo transfers during the summer. All these findings will be integrated in future in vivo SCNT experiments and embryo transfers. For the production of a transgenic osteoporosis model 17 in vivo experiments took place so far, with an outcome of 4 fetuses and 25 piglets. For gaining a controllable expression of RANKL, it was necessary to establish double transgenic pigs to sidestep harmful effects of RANKL overexpression during the fetal development. First attempts to integrate both genes, tetracycline controlled transactivator (Tet-On) and RANKL, in a single step of cell transfection and SCNT, had no satisfying result. We obtained 4 fetuses and stillborn recloned piglets carrying both genes, but they showed only expression of Tet-On and it was impossible to induce RANKL overexpression. Therefore the strategy was changed in favor to two rounds of transfection and nuclear transfer. First Tet-On transgenic piglets were established and screened for integration and expression. Piglet 9894 showed the best expression and severed as donor for next cell transfection step. These Tet-On + TARE RANKL cells were in vitro tested for their inducibility. Thereafter SCNT and embryo transfer of the best candidate were performed and they resulted in 4 pregnancies which all finished to term. One double transgenic piglet could be raised and will be kept until adulthood to establish a line of Tet-On +TARE RANKL transgenic pigs. Importantly, this founder animal showed inducible RANKL overexpression. Other constructs might be based on the existing Tet-On cell line in the future, offering an inducible system for a broad variety of different transgenes. Thus a functional Tet-On system in the pig is reported for the first time.Da es einen enormen Bedarf an transgenen Großtieren als Modelltiere für humane Erkrankungen gibt, wie zum Beispiel für Osteoporose, wurde die Generierung von transgenen Schweinen mittels somatischen Kerntransfers genauer untersucht. Dabei war das Ziel herauszufinden, welchen Einfluss die einzelnen Arbeitsschritte auf die Produktionseffizienz haben. Aus diesem Grund wurde eine statistische Analyse aller in vivo Kerntransfers von Anfang 2006 bis zum Juni 2010 durchgeführt. An dem Beispiel eines RANKL transgenen Osteoporose-Models wurden alle nötigen Produktionsschritte dargestellt und die Schwierigkeiten und Vorteile des somatischen Kerntransfers beschrieben. Die insgesamt 151 in vivo Experimente, wobei unterschiedliche transgene Zelllinien genutzt wurden, resultierten in 243 Ferkeln und Feten. Statistische Analysen zeigten, dass Spenderzellen, die ausschließlich in unserem Labor behandelt wurden, nach Kerntransfer zu einer signifikant höheren Geburtsrate der trächtigen Empfänger führten als Spenderzellen aus anderen Laboren. Weiterhin ergab sich ein Zusammenhang zwischen der Anzahl übertragener Kerntransfer-Embryonen und der späteren Trächtigkeitsrate, Geburtsrate und der Abortrate. Je mehr Embryonen übertragen wurden, desto mehr Trächtigkeiten wurden erfolgreich beendet. Es wurde auch sichtbar, dass in unseren Versuchen eine unterschiedliche in vitro-Kulturdauer der Kerntransfer-Embryonen von 24 bzw. 48 Stunden keinen signifikanten Unterschied in der Trächtigkeits- oder Geburtsrate verursachte. Auch für die verschiedenen Jahreszeiten konnte kein signifikanter Einfluss auf Trächtigkeit oder Geburt nachgewiesen werden. Es zeigte sich aber die Tendenz, dass im Herbst die besten Bedingungen für einen positiven Verlauf der Trächtigkeit herrschen und nach Embryotransfers im Sommer die höchste Abortrate auftritt. All diese Untersuchungsergebnisse werden zukünftig in unseren Arbeitsalltag integriert und der Kerntransfer und Embryotransferablauf optimiert. Zur Erstellung eines transgenen Osteoporosemodells wurden 17 Embryotransfers durchgeführt, die in 4 gewonnenen Feten und 25 geborenen Ferkeln resultierten. Um eine regulierbare RANKL Expression zu erhalten war es notwendig, doppelt transgene Schweine zu erstellen, so dass negative Nebeneffekte der RANKL Überexpression während der Fetalentwicklung vermieden wurden. Die ersten Versuche, Tetrazyklin Transaktivator (Tet-On) und RANKL in einem einzigen Schritt der Zelltransfektion und des in vivo Kerntransfers zu integrieren, führte zu wenig befriedigenden Ergebnissen. Es wurden 4 doppelt transgene Feten und 2 totgeborene Ferkel gewonnen, doch es konnte nur die Expression von Tet-On nachgewiesen werden, da die RANKL Expression nicht induzierbar war. Deswegen wurde die Strategie zu Gunsten von zwei Einzelschritten der Zelltransfektion und in vivo Kerntransfers gewechselt. Zuerst wurden Tet-On transgene Ferkel erstellt und auf Integration und Expression hin untersucht. Das Ferkel 8994 zeigte die beste Expression und seine Zellen wurden für den nächsten Zelltransfektionsschritt verwendet. Die daraus resultierenden Tet-On + TARE RANKL-Zellen wurden in vitro auf ihre Induzierbarkeit getestet. Als Spenderzellen für weitere in vivo Kerntransfers diente der beste Kandidat aus diesen Tests. Alle 4 Embryotransfers resultierten in Trächtigkeiten, die alle auch ausgetragen wurden. Ein doppelt transgenes Ferkel konnte aufgezogen werden, das zum einen nach Erreichen der Geschlechtsreife als Gründer einer transgenen Schweinelinie dienen wird, und im in vivo-Test eine induzierbare Expression von RANKL zeigte. Die regulierbaren Tet-On Zelllinien können auch für weitere zukünftige Konstrukte Verwendung finden, was die Möglichkeit mannigfaltiger genetischer Manipulation durch ein induzierbares System eröffnet. Hiermit wird das erste Mal von einem funktionalen und kontrollierbaren Tet-On System im Schwein berichtet
Genetics of schizophrenia and affective psychoses
No full textPART 1 - THE GENETICS OF SCHIZOPHRENIA AND AFFECTIVE PSYCHOSES (pages 4-
69)This comprises an overview and critique of the work that led to the publications
that form the thesis.PART 2 - THE REFERENCE LISTS OF THE PUBLICATIONS DISCUSSED, (pages 70-124)1987Kutcher, S.P., Blackwood, D.H.R., St. Clair, D.M., Gaskell, D.F., and Muir, W.J.
(1987) Major author
"Auditory P300 in borderline personality disorder and schizophrenia"
Archives of General Psychiatry, 44: 645-6501988Blackwood, D.H.R., St. Clair, D.M., Muir, W.J., Oliver, C.J., and Dickens, P.
(1988) Minor author
"The development of Alzheimer's diseases in Down's syndrome assessed by
auditory event-related potentials"
Journal of Mental Deficiency Research, 32: 439-453
Muir, W.J., Squire, I., Blackwood, D.H.R., Speight, M.D., St. Clair, D.M., Oliver,
C., and Dickens, P. (1988)
"Auditory P300 response in the assessment of Alzheimer's disease in Down's
syndrome: a two year follow-up study" Major author
Journal of Mental Deficiency Research, 32: 455-4631989Blackwood, D.H.R., Muir, W.J., St. Clair, D.M., and Evans, H.J. (1989) Major
author
"Schizophrenia and chromosomes" (Letter)
Lancet, ii: 1459
Kutcher, S.P., Blackwood, D.H.R., Gaskell, D.F., Muir, W.J., and St. Clair, D.M.
(1989) Major author
"Auditory P300 does not differentiate borderline personality disorder from
schizotypal personality disorder"
Biological Psychiatry, 26: 766-774
St. Clair, D.M., Blackwood, D.H.R., and Muir, W.J. (1989a) Major author
"P300 abnormality in schizophrenic subtypes"
Journal of Psychiatric Research, 23: 49-551990Blackburn, I.M., Roxborough, H.M., Muir, W.J., Glabus, M., and Blackwood,
D.H.R. (1990) Minor author
"Perceptual and physiological dysfunction in depression"
Psychological. Medicine, 20: 95-103
St. Clair, D., Blackwood, D., Muir, W., Carothers, A., Walker, M., Spowart, G.,
Gosden, C., and Evans, H.J. (1990) Major author
"Association within a family of a balanced autosomal translocation with major
mental illness"
Lancet, 336: 13-161991Blackwood, D., St. Clair, D., and Muir, W. (1991a) Major author
"DNA markers and biological vulnerability markers in families multiply affected
with schizophrenia"
European Archives of Psychiatry and Clinical Neuroscience, 240: 191-196
Blackwood, D.H.R., St. Clair, D.M., Muir, W.J., and Duffy, J. (1991b) Major
author
"Auditory P300 and eye tracking dysfunction in schizophrenic pedigrees"
Archives of General Psychiatry, 48: 899-909
Blackwood, D.H.R., Young, A.H., McQueen, J.K., Martin, M.J., Roxborough,
H.M., Muir, W.J., St Clair, D.M., and Kean, D.M. (1991) Major author
"Magnetic resonance imaging in schizophrenia: altered brain morphology
associated with P300 abnormalities and eye tracking dysfunction"
Biological Psychiatry, 30: 753-769
Morris, S.W., Muir, W., and St. Clair, D. (1991) Major author
"Dinucleotide repeat polymorphism at the human tyrosinase gene"
Nucleic Acids Research, 19: 69681993Evans, K.L., Fantes, J., Simpson, C., Arvelier, B., Muir, W., Fletcher, J., Van
Heyningen, V., Steel, K.P., Brown, K.A., Brown, S.D.M., St. Clair, D., and
Porteous, D. (1993) Minor author
"Fluman olfactory marker protein maps close to tyrosinase and is a candidate
gene for Usher syndrome type I"
Human Molecular Genetics, 2: 115-118
Fletcher, J.M., Evans, K., Baillie, D., Byrd, P., Hanratty, D., Leach, S., Julier, C.,
Gosden, J.R., Muir, W., Porteous, D.J., St. Clair, D., and Van Heyningen, V.
(1993) Minor author
"Schizophrenia-associated chromosome 11 q21 translocation: identification of
flanking markers and development of chromosome 11 q fragment hybrids as
cloning and mapping resources"
American Journal of Human Genetics, 52: 478-490
Roxborough, H.M., Muir, W.J., Blackwood, D.H.R., Walker, M.T. and Blackburn,
I.M. (1993) Major author
"Neuropsychological and P300 abnormalities in schizophrenics and their
relatives"
Psychological Medicine, 23: 305-3141994Blackwood, D.H.R., Ebmeier, K.P., Muir, W.J., Sharp, C.W., Glabus, M., Walker,
M., Souza, V., Dunan, J.R., Murray, C., Dougall, N., and Goodwin, G.M. (1994)
Major author
"Correlation of regional cerebral blood flow measured by single photon emission
tomography with P300 latency and eye movement abnormalities in
schizophrenia"
Acta Psychiatrica Scandinavica, 90: 157-166
Blackwood D.H.R., Muir, W.J., Roxborough, H.M., Walker, M.T., Townshend, R.,
Glabus, M., and Wolff, S. (1994) Major author
"Schizoid personality in childhood: auditory P300 and eye tracking responses at
follow up in adult life"
Journal of Autism and Developmental Disorders, 24: 487-500
Dr Walter J Muir, Doctor of Science Thesis, the University of Edinburgh 75
Glabus, M.F., Blackwood, D.H.R., Ebmeier, K.P., Walker, M.T., Souza, V.,
Dunan, J.R., Sharp, C.W. and Muir, W.J. (1994) Major author
"Methodological considerations in measurement of the P300 component of the
auditory ERP in schizophrenia"
Electroencephalography Clinical Neurophysiology, 90: 123-134
Morris, S., Leung, J., Sharp, C., Blackwood, D., Muir, W., and St. Clair, D. (1994)
Major author
"Screening schizophrenic patients for mutations in the amyloid precursor protein
gene"
Psychiatric Genetics, 4: 23-27
Sham, P.C., Morton, N.E., Muir, W.J., Walker, M., Collins, A., Shields, D.C., St.
Clair, D.M., and Blackwood, D.H.R. (1994) Major author
"Segregation analysis of complex phenotypes: an application to schizophrenia
and auditory P300 latency"
Psychiatric Genetics, 4: 29-38
Sharp, C.W., Muir, W.J., Blackwood, D.H.R., Walker, M., Gosden, C., St. Clair,
D.M. (1994) Major author
"Schizophrenia and mental retardation associated in a pedigree with retinitis
pigmentosa and sensorineural deafness"
American Journal of Medical Genetics, (Neuropsychiatric Genetics), 54: 354-3601995Brookes, A.J., Slorach, E.M., Evans, K.L., Thomson, M.L., Gosden, C.M., Muir,
W.J., and Porteous DJ. (1995) Major author
"Identifying genes within microdissected genomic DNA: Isolation of brain
expressed genes from a translocation region associated with inherited mental
illness"
Mammalian Genome, 6: 257-262
de Souza, V.B.N., Muir, W.J., Walker, M.T., Glabus, M., Roxborough, H.M.,
Sharp, C.W., Dunan, J.R., and Blackwood, D.H.R. (1995) Major author
"Auditory P300 event-related potentials and neuropsychological performance in
schizophrenia and bipolar affective disorder"
Biological Psychiatry, 37: 300-310
Evans, K.L., Brown, J., Shibasaki, Y., Devon, R.S., Arvelier, B., Christie, S.,
Maule, J.C., Baillie, D., Slorach, E.M., Anderson, S.M., Gosden, J.R., He, L.,
Petit, J., Weith, A., Gosden, C.M., Blackwood, D.H.R., St. Clair, D.M., Muir, W.J.,
Brookes, A.J., and Porteous, D.J. (1995) Minor author
"A three megabase contiguous clone map on the long arm of chromosome 11
across a balanced translocation associated with schizophrenia"
Genomics, 28: 420-428
He, L., Mansfield, D.C., Brown, A.F., Green, D.K., St. Clair, D.M., Muir, W.J.,
Morris, S.W., Wright, A.F., and Blackwood, D.H.R. (1995) Minor author
"Automated linkage analysis in psychiatric disorders"
American Journal of Medical Genetics, (Neuropsychiatric Genetics) 60: 192-198
Petit, J., Bosseau, P., Evans, K., Gosden, C., Muir, W., St. Clair, D., Porteous,
D., and Arvelier, B. (1995) Minor author
Seeding of YAC's over regions 1 q41 -42,3 and 11 q14.3-q23 with microdissection
clones"
European Journal of Human Genetics, 3: 351-3561996Battersby, S., Ogilvie, A.D., Smith, C.A.D., Blackwood, D.H.R., Muir, W.J.,
Quinn, J., Fink, G., Goodwin, G.M., and Harmar, A.J. (1996) Minor author
"Structure of a variable number tandem repeat of the serotonin transporter gene
and association with affective disorder"
Psychiatric Genetics, 6: 177-181
Blackwood, D.H.R. Muir, W.J., Stevenson, A., Wentzel, J., Ad'hiah, A., Walker,
M.T., Papiha, S.S., St. Clair, D.M., and Roberts, D.F., (1996) Major author
"Reduced expression of HLA B35 in schizophrenia"
Psychiatric Genetics, 6: 51-59
Harmar A.J., Ogilvie, A.D., Battersby S., Smith, C.A.D., Blackwood, D.H.R, Muir,
W.J., Fink, G., and Goodwin, F.M. (1996) Minor author
"The serotonin transporter gene and affective disorder"
Cold Spring Harbor Symposia on Quantitative Biology, LXI: 791-795
He, L., Carothers, A., Blackwood, D.H.R., Teague, P., Maclean, A.W., Brown, J.,
Wright, A.W., Muir, W.J., Porteous, D.J., and St. Clair, D.M. (1996) Minor author
"Recombination patterns around the breakpoint of a balanced 1:11 autosomal
translocation associated with major mental illness"
Psychiatric Genetics, 6: 201-208
He, L., Morris, S., Lennon, A., St. Clair, D.M., Porteous, D.J., Wright, A.F., Muir,
W.J., and Blackwood, D.H.R. (1996) Major author
"A genome-wide search for linkage in a large bipolar family: comparison of
genotyping accuracy using di- and tetra-nucleotide repeat microsatellite markers"
Psychiatric Genetics, 6: 123-129
Schizophrenia Linkage Collaborative Group For Chromosomes 3, 6, and 8:
Levinson, D.F., Wildenauer, D.B., Schwab, S.G., Albus, M., Hallmayer, J., Lerer,
B., Maier, W., Blackwood, D., Muir, W., StClair, D., Morris, S., Moises, H.W.,
Yang, L., Kristbjarnarson, H., Helgason, T., Wiese, C., Collier, D.A., Holmans, P.,
Daniels, J., Rees, M., Asherson, P., Roberts, Q., Cardno, A., Arranz, M.J.,
Vallada, H., McGuffin, D., Owen, M.J., Pulver, A.E., Antonarakis, S.E., Babb, R.,
Blouin, J.L., Demarchi, N., Dombroski, B., Housman, D., Karayiorgou, M., Ott, J.,
Kasch, L., Kazazian, H., Lasseter, V.K., Loetscher, E., Luebbert, H., Nestadt, G.,
Ton, C., Wolyniec, P.S., Laurent, C., Dechaldee, M., Thibaut, F., Jay, M.,
Samolyk, D., Petit, M., Campion, D., Mallet, J., Straub, R.E., Maclean, C.J.,
Easter, S.M., Oneill, F.A., Walsh, D., Kendler, K.S., Gejman, P.V., Cao, Q.H.,
Gershon, E., Badner, J., Beshah, E., Zhang, J., Riley, B.P., Rajagopalan, S.,
Mogudicarter, M., Jenkins, T., Williamson, R., DeLisi, L.E., Garner, C., Kelly, M.,
Leduc, C., Cardon, L., Lichter, J., Harris, T., Loftus, J., Shields, G., Comasi, M.,
Vita, A., Smith, A., Dann, J., Joslyn, G., Gurling, H., Kalsi, G., Brynjolfsson, J.,
Curtis, D., Sigmundsson, T., Butler, R., Read, T., Murphy, P., Chen, A.C.H.,
Petursson, H., Byerley, B., Hoff, M., Holik, J., Coon, H., Nancarrow, D.J., Crowe,
R.R., Andreasen, N., Silverman, J.M., Mohs, R.C., Siever, L.J., Endicott, J.,
Sharpe, L., Walters, M.K., Lennon, D.P., Hayward, N.K., Sandkuijl, L.A., Mowry,
B.J., Aschauer, H.N., Meszaros, K., Lenzinger, E., Fuchs, K., Heiden, A.M.,
Kruglyak, L., Daly, M.J., and Matise, T.C. (1996) Minor author
"Additional support for schizophrenia linkage on chromosomes 6 and 8: a
multicenter study"
American Journal of Medical Genetics 67: 580-594
Schizophrenia Collaborative Linkage Group for Chromosome 22 (1996) - Gill, M.,
Vallada, H., Collier, D., Sham, P., Holmans, P., Murray, R., McGuffin, P., Nanko,
S., Owen, M., Lasseter, V.K., Pulver, A.E., Meyers, D., Nestadt, G., Antonarkis,
S., Housman, D, Childs, B., Straub, R., Su, Y., MacLean, C., Murphy, B., Wang,
S., Walsh, D., Kendler, K., Polymeropoulos, M., Coon, H., Byerley, W., Gershon,
E., Golden, L., Crow, T., DeLisi, L., Freedman, R., Reimherr, F., Wnder, P.,
Larent, C., Dumas, J-B., D'Amato, T., Jay, M., Martinez, M., Campion, D., Mallet,
J., Wildenauer, D., Flallmayer, J., Lerer, B., Maier, W., Schwab, S., Ebstein, R.,
Gurling, H, Curtis, D., Blackwood, D., Muir, W., St. Clair, D., Fie, L., Maguire, S.,
Moises, Ft., Yang, L., Wiese, C., Kristbjarnson, Ft., Levinson, D., and Mowry, B.
(1996) Minor author
"A combined analysis of D22S278 marker alleles in affected sib-pairs: support for
a susceptibility locus for schizophrenia at 22q12"
American Journal of Medical Genetics (Neuropsychiatric Genetics) 67: 40-451997Lindholm, E., Cavelier, L., Ffowell, M., Eriksson, I., Jalonen, P., Adolfsson, R.,
Blackwood, D.FI.R., Muir, W.J., Brookes, A.J., Gyllensten, U., and Jazin, E.E.
(1997) Minor author
"Mitochondrial sequence variants in patients with schizophrenia"
European Journal of Fluman Genetics, 5: 406-412
Mors, O., Ewald, FL, Blackwood, D., and Muir, W. (1997) Major author
"Cytogenetic abnormalities on chromosome 18 associated with bipolar affective
disorder or schizophrenia"
British Journal of Psychiatry, 170: 278-280
Wilson-Annan, J.C., Blackwood, D.FI.R., Muir, W., Millar, J.K., and Porteous, D.J.
(1997) Major author
"An allelic association study of two polymorphic markers in close proximity to a
balanced translocation breakpoint t(1 ;11) which co-segregates with mental
illness"
Psychiatric Genetics 7: 171-1741998Asherson, P., Mant, R., Williams, N., Cardno, A., Jones, L., Murphy, K., Collier,
D.A., Nanko, S., Craddock, N., Morris, S., Muir, W., Blackwood, D., McGuffin, P.,
and Owen, M.J. (1998) Minor author
"A study of chromosome 4p markers and dopamine D5 receptor gene in
schizophrenia and bipolar disorder"
Molecular Psychiatry, 3: 310-320
Doris, A.B., Wahle, K., MacDonald, A., Morris, S., Coffey, I., Muir, W., and
Blackwood, D. (1998) Major author
"Red cell membrane fatty acids, cytosolic phospholipase-A2 and schizophrenia"
Schizophrenia Research, 31: 185-196
Millar, J.K., Brown, J., Maule, J.C., Shibasaki, Y., Christie, S., Lawson, D.,
Anderson, S., Wilson-Annan, J.C., Devon, R.S., St. Clair, D.M., Blackwood,
D.H.R., Muir, W.J., and Porteous, D.J. (1998) Major author
"A long-range restriction map across 3 Mb of the chromosome 11 breakpoint of a
translocation linked to schizophrenia: Localisation of the breakpoint and the
search for neighbouring genes."
Psychiatric Genetics, 8: 175-182
Souery, D., Lipp, O., Serretti, A., Mahieu, B., Rivelli, S.K., Cavallini, C.,
Ackenheil, M., Adolfsson, R., Aschauer, H., Blackwood, D., Dam, H., Delcoigne,
B., Demartelaer, V., Dikeos, D., Fuchshuber, S., Heiden, M., Jablensky, A.,
Jakovljevic, M., Kessing, L., Lerer B., Macedo, A., Mellerup, T., Milanova, V.,
Muir, W., Nylander, P.O., Oruc, L., Papadimitriou, G.N., Pekkarinen, P.,
Peltonen, L., Pinto De Azevedo, M.H., Pull, C., Shapira, R., Smeraldi, E., Staner,
L., Stefanis, C., and Verga, M. (1998) Minor author
"European collaborative project on affective disorders: interactions between
genetic and psychosocial vulnerability factors" Minor author
Psychiatric Genetics, 8: 197-205
Williams, J., Spurlock, G., Holmans, P., Mant, R., Murphy, K., Jones, L., Cardno,
A., Asherson, P., Blackwood, D., Muir, W., Meszaros, K., Aschauer, H., Mallet,
J., Laurent, C., Pekkarinen, P., Seppala, J., Stefanis, C.N., Papadimitriou, G.N.,
Macciardi, F., Verga, M., Pato, C., Azevedo, H., Crocq, M-A., Gurling, H., Kalsi,
G., Curtis, D., McGuffin, P., and Owen, M.J. (1998) Minor author
"A meta-analysis and transmission disequilibrium study of association between
the dopamine D3 receptor gene and schizophrenia"
Molecular Psychiatry, 3: 141-149
Vallada, H., Curtis, D., Sham, P., Kunugi, H., Zhao, J.H., Murray, R., McGuffin,
P., Nanko, S., Owen, M., Gill, M., Collier, D.A., Antonarakis, S., Housman, D.,
Kazazian, H., Nestadt, G., Pulver, A.E., Straub, R.E., MacLean, C.J., Walsh, D.,
Kendler, K.S., DeLisi, L., Polymeropoulos, M., Coon, H., Byerley, W., Lofthouse,
R., Gershon, E., Goldin, L., Freedman, R., Laurent, C., Bodeau-Pean, S.,
d'Amato, T., Jay, M., Campion, D., Mallet, J., Wildenauer, D.B., Lerer, B., Albus,
M., Ackenheil, M., Ebstein, R.P., Hallmayer, J., Maier, W., Gurling, H., Curtis, D.,
Kalsi, G., Brynjolfsson, J., Sigmundson, T., Petursson, H., Blackwood D., Muir,
W., St Clair, D., He, L., Maguire, S., Moises, H.W., Hwu, H.G., Yang, L., Wiese,
C., Kristbjarnarson, H., Levinson, D.F., Mowry, B.J., Donis-Keller, H., Hayward,
N.K., Crowe, R.R., Silverman, J.M., Nancarrow, D.J., Read, C.M. (1998) Minor
author
"A transmission disequilibrium and linkage analysis of D22S278 marker alleles in
574 families: further support for a susceptibility locus for schizophrenia at 22q12"
Schizophrenia Research 32: 115-1211999Battersby, S., Ogilvie, A.D., Blackwood, D.H., Shen, S., Muqit, M.M., Muir, W.J.,
Teague P., Goodwin, G.M., and Harmar, A.J. (1999) Minor author
"Presence of multiple functional polyadenylation signals and a single nucleotide
polymorphism in the 3' untranslated region of the human serotonin transporter
gene"
Journal of Neurochemistry, 72: 1384-1388
Blackwood, D.H.R., Glabus, M.F., Dunan, J., O'Carroll, R.E., Muir, W.J., and
Ebmeier, K.P. (1999)
"Altered cerebral perfusion measured by SPET in relatives of schizophrenic
patients: correlations with memory and P300" Major author
British Journal of Psychiatry, 175: 357-366
Craddock, N., Lendon, C., Cichon, S., Culverhouse, R., Detera-Wadleigh, S.,
Devon, R., Faraone, S., Foroud, T., Gejman, P., Leonard, S., Mclnnis, M., Owen,
M.J., Riley, B., Armstrong, C., Barden, N., van Broeckhoven, C., Ewald, H.,
Folstein, S., Gerhard, D., Goldman, D., Gurling, H., Kelsoe, J., Levinson, D.,
Muir, W., Philippe, A., Pulver, A., Wildenauer, D. (1999) Minor author
"Chromosome Workshop: Chromosomes 11, 14, and 15"
American Journal of Medical Genetics; Neuropsychiatric Genetics 88:244-254
Furlong, R.A., Rubinsztein, J.S., Ho L, Walsh, C., Coleman, T.A., Muir, W.J.,
Paykel, E.S., Blackwood, D.H.R., and Rubinsztein, D.C. (1999) Minor author
"Analysis and meta-analysis of two polymorphisms within the tyrosine
hydroxylase gene in bipolar and unipolar affective disorders"
American Journal of Medical Genetics: Neuropsychiatric Genetics 88: 88-94
Hampson, R.M., Malloy, M.P., Mors, O., Ewald, H., Flannery, A.V., Morten, J.,
Porteous, D.J., Muir, W.J., and Blackwood, D.H.R. (1999) Major author
"Mapping studies on a pericentric inversion (18) (p11.31 q21.1) in a family with
both schizophrenia and learning disability"
Psychiatric Genetics, 9: 161-163
Souery, D., Lipp, O, Mahieu, B., Rivelli, S.K., Massat, I., Seretti, A., Cavallini, C.,
Ackenheil, M., Adolfsson, R., Aschauer, H., Blackwood, D., Dam, H., Dikeos, D.,
Fuchshuber, S., Heiden, M., Jakovljevic, M., Kaneva, R., Kessing, L., Lerer, B.,
Lonnqvist, J., Mellerup, T., Milanova, V., Muir, W., Nylander, P.O., Oruc, L.,
Papadimitriou, G.N., Pekkarinen, P., Peltonen, L., Pull, C., Raeymaekers, P.,
Shapira, B., Smeraldi, E., Staner, L., Stefanis, C., Verga, M., Verheyen, G.,
Macciardi, F., Van Broeckhoven, C., and Mendelwicz, J. (1999) Minor author
"Tyrosine hydroxylase polymorphism and phenotypic heterogeneity in bipolar
affective disorder: a multicenter association study"
American Journal of Medical Genetics (Neuropsychiatric Genetics), 88: 527-532
Visscher, P.M., Haley, C.S., Heath, S.C., Muir, W.J., and Blackwood, D.FI.R.
(1999) Major author
"Detecting QTLs for uni and bipolar disorder using a variance component
method"
Psychiatric Genetics, 9: 75-84.2000Serretti, A., Macciardi, F., Cusin, C., Lattuada, E., Souery, D., Lipp, O., Mahieu,
B., Van Broeckhoven, C., Blackwood, D., Muir, W„, Aschauer, H.N., Heiden,
A.M., Ackenheil, M., Fuchshuber, S., Raeymaekers, P., Verheyen, G., Kaneva,
R., Jablensky, A., Papadimitriou, G.N., Dikeos, D.G., Stefanis, C.N., Smeraldi, E.,
and Mendlewicz, J. (2000) Minor author
"Linkage of mood disorders with D2, D3 and TH genes: a multicenter study"
Journal of Affective Disorders 58: 51-612001Borglum, A.D., Hampson, M., Kjeldsen, T.E., Muir, W., Murray, V., Ewald, H.,
Mors, O., Blackwood, D., and Kruse, T.A. (2001) Minor author
"Dopa decarboxylase genotypes may influence age at onset in schizophrenia"
Molecular Psychiatry, 6: 712-717
Devon, R.S., Anderson, S., Teague, P.W., Muir, W.J., Murray, V., Pelosi A.J.,
Blackwood, D.H.R and Porteous, D.J. (2001a) Minor author
"The genomic organisation of the metabotropic glutamate receptor subtype 5
gene and its association with schizophrenia"
Molecular Psychiatry 6: 311-314
Devon, R.S., Anderson, S., Teague, P.W., Burgess, P., Kipari, T.M.J., Semple,
C.A.M., Millar, J.K., Muir, W.J., Murray, V., Pelosi, A.J., Blackwood, D.H.R., and
Porteous, D.J. (2001b) Minor author
"Identification of polymorphisms within disrupted in schizophrenia 1 and disrupted
in schizophrenia 2, and an investigation of their association with schizophrenia
and bipolar disorder"
Psychiatric Genetics, 11: 71-78
Evans, K.L., Le Hellard, S., Morris, S.W., Lawson, D., Whitton, C., Semple,
C.A.M., Fantes, J.A., Malloy, M.P., Maule, J.C., Humphray, S.J., Ross, M.T.,
Bentley, D.R., Muir, W.J., Blackwood, D.H.R., and Porteous, D.J. (2001) Major
author
"A 6Mb high-resolution BAC/PAC contig of human 4p15.3-16.1, a candidate
region for bipolar affective disorder"
Genomics 71: 315-323
Millar, J.K., Christie, S., Anderson, S., Lawson, D., Loh, D. H-W., Devon, R.S.,
Arveiler, B., Muir, W.J., Blackwood, D.H.R., and Porteous, D.J. (2001) Minor
author
"Genomic structure and localisation within a linkage hotspot of Disrupted in
Schizophrenia 1, a gene disrupted by a translocation segregating with
schizophrenia"
Molecular Psychiatry 6: 173-178
Muir, W.J., Thomson, M.L., McKeon P, Mynett-Johnson L, Evans, K.L., Porteous
DJ and Blackwood, D.H.R. (2001) Major author
"Markers close to the dopamine D5 receptor gene (DRD5) show significant
association with schizophrenia but not bipolar disorder."
American Journal of Medical Genetics 105:152-158
Lerer, B., Macciardi, F., Segman, R.H., Adolfsson, R., Blackwood, D., Blairy, S.,
Del Favero, J., Dikeos, D.G., Kaneva, R., Lilli, R., Massat, I., Milanova, V., Muir,
W., Noethen, M., Oruc, L., Petrova, T., Papadimitriou, G.N., Rietschel, M.,
Serretti, A., Souery, D., Van Gestel, S., Van Broeckhoven, C., and Menlewicz, J.
(2001) Minor author
"Variability of 5-FIT2C receptor cys23ser polymorphism among European
populations and vulnerability to affective disorder"
Molecular Psychiatry, 6: 579-585
Souery, D., Van Gestel, S., Massa
SAT0416 ULTRASOUND EVALUATION IN FOLLOW-UP OF URATE-LOWERING THERAPY IN GOUT PHASE 2 (USEFUL-2): DURATION OF FLARE PROPHYLAXIS
No full textO ambiente enriquecido influencia as propriedades reforçadoras do etanol em ratos
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Biológicas, Programa de Pós-Graduação em Farmacologia, Florianópolis, 2010O transtorno de déficit de atenção e hiperatividade (TDAH) ocorre freqüentemente em comorbidade com outros transtornos psiquiátricos como a ansiedade e a dependência às drogas. Os ratos espontaneamente hipertensos (SHR) apresentam características neuroquímicas e comportamentais que o tornam um modelo adequado para o estudo do TDAH. Esta linhagem de ratos também apresenta um elevado comportamento de busca por novidade e alta sensibilidade para distintas classes de abuso de drogas, o que faz dela um interessante modelo para o estudo da associação entre o TDAH e o uso abusivo de drogas. O propósito deste estudo é investigar a influência do ambiente de criação durante os estágios iniciais da vida sobre as propriedades motivacionais do etanol e sobre o comportamento relacionado à ansiedade dos ratos SHR. Os animais criados em ambiente padrão (AP) ou enriquecido (AE), desde o desmame até a idade adulta, foram submetidas a testes que avaliam a locomoção induzida por novidade, o consumo oral de substâncias reforçadoras (sacarina e etanol), a sensibilidade aos efeitos do etanol no campo aberto, na preferência condicionada do lugar (PCL) induzida por etanol e na tolerância aguda ao etanol no plano inclinado. SHR criados em um AE mostraram uma redução da locomoção induzida por novidade, beberam menos sacarina e etanol e não preferiram o etanol à água, em comparação aos ratos do AP. Além disso, os animais criados em AE não desenvolveram PCL, enquanto os animais do AP desenvolveram preferência ao lugar associado ao etanol (dose de 1,2 g/kg). Os dois grupos mostraram diferentes sensibilidades aos efeitos ansiolítico/estimulante do etanol, porém os ratos mantidos tanto em AP quanto AE desenvolveram tolerância aguda ao etanol. Estes resultados mostram que a exposição a estímulos que mimetizam experiências positivas (enriquecimento ambiental) induzem alterações persistentes no sistema de recompensa/motivacional dos ratos SHR, sugerindo um importante papel do ambiente de criação durante os primeiros estágios do neurodesenvolvimento, sobre a comorbidade entre o TDAH e abuso de drogas.Attention-deficit hyperactivity disorder (ADHD) often occurs in comorbidity with other psychiatric disorders, such as anxiety and drug addiction. The spontaneously hypertensive rats (SHR) show neurochemical and behavioral characteristics which make their suitable model of ADHD. This rat strain displays increased novelty seeking behavior and high sensitivity to distinct classes of abused drugs, which makes it an interesting model for the study of the association between ADHD and drug abuse. The purpose of this study is to investigate the influence of rearing environment during early stages of life on motivational properties of ethanol, novelty-induced locomotion and anxiety-like behavior of SHR rats. The animals reared from weaning to adulthood in standard (SE) or enriched (EE) environment were evaluated on novelty-induced locomotion, oral consumption of rewarding substances (saccharin and ethanol), sensitivity to the effects of ethanol in open field (OF), ethanol-induced conditioned place preference (CPP) and acute tolerance to ethanol on the tilting plane. SHR reared in an EE showed reduced novelty-induced locomotion, drank less saccharin and ethanol and showed less ethanol preference compared to SE rats. Moreover, EE rats did not develop CPP, whereas SE rats developed preference for ethanol-associated compartment (1.2 g/kg). They also showed different sensitivity to the anxiolytic/stimulant effects of ethanol and both groups developed acute tolerance to ethanol. These results show that exposure to stimuli mimicking positive life experiences (EE) induces persistent changes in the reward/motivational system of SHR rats, suggesting an important role of the familiar environment during early stages of the neurodevelopment on the co-morbidity of ADHD and drug abuse
