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  1. Article: Description of the efficacy and safety of three new biologics in the treatment of rheumatoid arthritis.

    Storage, Steven S / Agrawal, Harsh / Furst, Daniel E

    The Korean journal of internal medicine

    2010  Volume 25, Issue 1, Page(s) 1–17

    Abstract: English articles on abatacept, golimumab, and tocilizumab in rheumatoid arthritis published between 2002 and 2009 were reviewed systematically. All randomized clinical trials, open-label extensions, meta-analyses, and reviews were examined. There were ... ...

    Abstract English articles on abatacept, golimumab, and tocilizumab in rheumatoid arthritis published between 2002 and 2009 were reviewed systematically. All randomized clinical trials, open-label extensions, meta-analyses, and reviews were examined. There were thirteen articles on abatacept, four on golimumab, and seven on tocilizumab. All three drugs were effective in methotrexate-naïve, methotrexate-incomplete responders, and tumor-necrosis-factor-failure rheumatoid arthritis patients. Of the three, only abatacept has been tested in a head-to-head trial with infliximab, in which it was found to be equivalent to infliximab. Golimumab resulted in a more modest improvement than the others in methotrexate-naïve patients, although no direct comparisons among the three drugs were possible or appropriate. Descriptive analysis of adverse events showed that patients receiving abatacept, golimumab, and tocilizumab were subject to more adverse events than controls overall, as expected. In the abatacept studies, a few cases of tuberculosis, more cardiovascular events and gastrointestinal bleedings and more basal cell carcinoma were seen. Golimumab was associated with more skin rashes and pneumonia, while tocilizumab was associated with increased lipids, more liver-function abnormalities, and neutropenia. These new medications are useful additions to the rheumatologic armamentarium and represent greater convenience (golimumab) or different mechanisms of action (abatacept and tocilizumab) than tumor-necrosis-factor inhibitors for treating rheumatoid arthritis. As expected, some adverse events occur when using these drugs and patients need to be watched carefully.
    MeSH term(s) Abatacept ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/adverse effects ; Antibodies, Monoclonal, Humanized ; Antirheumatic Agents/administration & dosage ; Antirheumatic Agents/adverse effects ; Arthritis, Rheumatoid/drug therapy ; Biological Therapy ; Humans ; Immunoconjugates/administration & dosage ; Immunoconjugates/adverse effects
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Monoclonal, Humanized ; Antirheumatic Agents ; Immunoconjugates ; Abatacept (7D0YB67S97) ; golimumab (91X1KLU43E) ; tocilizumab (I031V2H011)
    Language English
    Publishing date 2010-02-26
    Publishing country Korea (South)
    Document type Journal Article ; Review
    ZDB-ID 639023-7
    ISSN 1226-3303
    ISSN 1226-3303
    DOI 10.3904/kjim.2010.25.1.1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A positive relationship between harm avoidance and brain nicotinic acetylcholine receptor availability.

    Storage, Steven / Mandelkern, Mark A / Phuong, Jonathan / Kozman, Maggie / Neary, Meaghan K / Brody, Arthur L

    Psychiatry research

    2013  Volume 214, Issue 3, Page(s) 415–421

    Abstract: ... continuous infusion positron emission tomography (PET) scanning using the radiotracer 2-[18F]fluoro-3-(2(S ...

    Abstract Prior research indicates that disturbance of cholinergic neurotransmission reduces anxiety, leading to the hypothesis that people with heightened cholinergic function have a greater tendency toward anxiety-like and/or harm-avoidant behavior. We sought to determine if people with elevated levels of harm avoidance (HA), a dimension of temperament from the Temperament and Character Inventory (TCI), have high α4β2* nicotinic acetylcholine receptor (nAChR) availability. Healthy adults (n=105; 47 non-smokers and 58 smokers) underwent bolus-plus-continuous infusion positron emission tomography (PET) scanning using the radiotracer 2-[18F]fluoro-3-(2(S)azetidinylmethoxy) pyridine (abbreviated as 2-FA). During the uptake period of 2-FA, participants completed the TCI. The central study analysis revealed a significant association between total HA and mean nAChR availability, with higher total HA scores being linked with greater nAChR availability. In examining HA subscales, both 'Fear of Uncertainty' and 'Fatigability' were significant, based on higher levels of these characteristics being associated with greater nAChR availabilities. This study adds to a growing body of knowledge concerning the biological basis of personality and may prove useful in understanding the pathophysiology of psychiatric disorders (such as anxiety disorders) that have similar characteristics to HA. Study findings may indicate that heightened cholinergic neurotransmission is associated with increased anxiety-like traits.
    MeSH term(s) Adult ; Anxiety/physiopathology ; Anxiety/psychology ; Anxiety Disorders/physiopathology ; Anxiety Disorders/psychology ; Avoidance Learning/physiology ; Brain/metabolism ; Brain/physiopathology ; Character ; Cholinergic Neurons/metabolism ; Fear/physiology ; Fear/psychology ; Female ; Healthy Volunteers ; Humans ; Male ; Personality ; Positron-Emission Tomography ; Receptors, Nicotinic/metabolism ; Smoking ; Synaptic Transmission ; Temperament ; Uncertainty
    Chemical Substances Receptors, Nicotinic
    Language English
    Publishing date 2013-10-19
    Publishing country Ireland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 445361-x
    ISSN 1872-7123 ; 1872-7506 ; 0925-4927 ; 0165-1781
    ISSN (online) 1872-7123 ; 1872-7506
    ISSN 0925-4927 ; 0165-1781
    DOI 10.1016/j.pscychresns.2013.07.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Big genomes facilitate the comparative identification of regulatory elements.

    Peterson, Brant K / Hare, Emily E / Iyer, Venky N / Storage, Steven / Conner, Laura / Papaj, Daniel R / Kurashima, Rick / Jang, Eric / Eisen, Michael B

    PloS one

    2009  Volume 4, Issue 3, Page(s) e4688

    Abstract: The identification of regulatory sequences in animal genomes remains a significant challenge. Comparative genomic methods that use patterns of evolutionary conservation to identify non-coding sequences with regulatory function have yielded many new ... ...

    Abstract The identification of regulatory sequences in animal genomes remains a significant challenge. Comparative genomic methods that use patterns of evolutionary conservation to identify non-coding sequences with regulatory function have yielded many new vertebrate enhancers. However, these methods have not contributed significantly to the identification of regulatory sequences in sequenced invertebrate taxa. We demonstrate here that this differential success, which is often attributed to fundamental differences in the nature of vertebrate and invertebrate regulatory sequences, is instead primarily a product of the relatively small size of sequenced invertebrate genomes. We sequenced and compared loci involved in early embryonic patterning from four species of true fruit flies (family Tephritidae) that have genomes four to six times larger than those of Drosophila melanogaster. Unlike in Drosophila, where virtually all non-coding DNA is highly conserved, blocks of conserved non-coding sequence in tephritids are flanked by large stretches of poorly conserved sequence, similar to what is observed in vertebrate genomes. We tested the activities of nine conserved non-coding sequences flanking the even-skipped gene of the teprhitid Ceratis capitata in transgenic D. melanogaster embryos, six of which drove patterns that recapitulate those of known D. melanogaster enhancers. In contrast, none of the three non-conserved tephritid non-coding sequences that we tested drove expression in D. melanogaster embryos. Based on the landscape of non-coding conservation in tephritids, and our initial success in using conservation in tephritids to identify D. melanogaster regulatory sequences, we suggest that comparison of tephritid genomes may provide a systematic means to annotate the non-coding portion of the D. melanogaster genome. We also propose that large genomes be given more consideration in the selection of species for comparative genomics projects, to provide increased power to detect functional non-coding DNAs and to provide a less biased view of the evolution and function of animal genomes.
    MeSH term(s) Animals ; Databases, Genetic ; Genome ; Regulatory Sequences, Nucleic Acid ; Species Specificity
    Language English
    Publishing date 2009-03-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0004688
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Big Genomes Facilitate the Comparative Identification of Regulatory Elements

    Peterson, Brant K. / Hare, Emily E. / Iyer, Venky N. / Storage, Steven / Conner, Laura / Papaj, Daniel R. / Kurashima, Rick / Jang, Eric / Eisen, Michael B. / Hahn, Matthew W.

    PloS one

    Volume v. 4,, Issue no. 3

    Abstract: The identification of regulatory sequences in animal genomes remains a significant challenge. Comparative genomic methods that use patterns of evolutionary conservation to identify non-coding sequences with regulatory function have yielded many new ... ...

    Abstract The identification of regulatory sequences in animal genomes remains a significant challenge. Comparative genomic methods that use patterns of evolutionary conservation to identify non-coding sequences with regulatory function have yielded many new vertebrate enhancers. However, these methods have not contributed significantly to the identification of regulatory sequences in sequenced invertebrate taxa. We demonstrate here that this differential success, which is often attributed to fundamental differences in the nature of vertebrate and invertebrate regulatory sequences, is instead primarily a product of the relatively small size of sequenced invertebrate genomes. We sequenced and compared loci involved in early embryonic patterning from four species of true fruit flies (family Tephritidae) that have genomes four to six times larger than those of Drosophila melanogaster . Unlike in Drosophila , where virtually all non-coding DNA is highly conserved, blocks of conserved non-coding sequence in tephritids are flanked by large stretches of poorly conserved sequence, similar to what is observed in vertebrate genomes. We tested the activities of nine conserved non-coding sequences flanking the even-skipped gene of the teprhitid Ceratis capitata in transgenic D. melanogaster embryos, six of which drove patterns that recapitulate those of known D. melanogaster enhancers. In contrast, none of the three non-conserved tephritid non-coding sequences that we tested drove expression in D. melanogaster embryos. Based on the landscape of non-coding conservation in tephritids, and our initial success in using conservation in tephritids to identify D. melanogaster regulatory sequences, we suggest that comparison of tephritid genomes may provide a systematic means to annotate the non-coding portion of the D. melanogaster genome. We also propose that large genomes be given more consideration in the selection of species for comparative genomics projects, to provide increased power to detect functional non-coding DNAs and to provide a less biased view of the evolution and function of animal genomes.
    Keywords vertebrates ; genes ; loci ; regulatory sequences ; invertebrates ; evolution ; Tephritidae ; cod ; Drosophila melanogaster ; intergenic DNA ; genetically modified organisms ; genomics ; fruit flies
    Language English
    Document type Article
    ISSN 1932-6203
    Database AGRIS - International Information System for the Agricultural Sciences and Technology

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