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  1. Article: Current concepts in targeted therapies for the pathophysiology of diabetic microvascular complications.

    Cumbie, Brian C / Hermayer, Kathie L

    Vascular health and risk management

    2008  Volume 3, Issue 6, Page(s) 823–832

    Abstract: ... protein kinase c, vascular epithelium growth factor, and the superoxide pathway. The review further focuses ...

    Abstract Microvascular complications characterized by retinopathy, nephropathy, and neuropathy are highly prevalent among diabetics. Glycemic control has long been the mainstay for preventing progression of these complications; however, such control is not easily achieved. Currently, alternative adjunctive approaches to treating and preventing microvascular damage are being undertaken by targeting the molecular pathogenesis of diabetic complications. This review summarizes the specific pathogenic mechanisms of microvascular complications for which clinical therapies have been developed, including the polyol pathway, advanced glycation end products, protein kinase c, vascular epithelium growth factor, and the superoxide pathway. The review further focuses on therapies for these targets that are currently available or are undergoing late-stage clinical trials.
    MeSH term(s) Aldehyde Reductase/antagonists & inhibitors ; Antioxidants/pharmacology ; Antioxidants/therapeutic use ; Diabetes Complications/physiopathology ; Diabetes Complications/prevention & control ; Enzyme Inhibitors/pharmacology ; Enzyme Inhibitors/therapeutic use ; Glycation End Products, Advanced/antagonists & inhibitors ; Humans ; Protein Kinase C/antagonists & inhibitors ; Reactive Oxygen Species ; Vascular Endothelial Growth Factors/antagonists & inhibitors
    Chemical Substances Antioxidants ; Enzyme Inhibitors ; Glycation End Products, Advanced ; Reactive Oxygen Species ; Vascular Endothelial Growth Factors ; Aldehyde Reductase (EC 1.1.1.21) ; Protein Kinase C (EC 2.7.11.13)
    Language English
    Publishing date 2008-01-17
    Publishing country New Zealand
    Document type Journal Article ; Review
    ZDB-ID 2186568-1
    ISSN 1178-2048 ; 1176-6344
    ISSN (online) 1178-2048
    ISSN 1176-6344
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: The genome of tolypocladium inflatum: evolution, organization, and expression of the cyclosporin biosynthetic gene cluster.

    Bushley, Kathryn E / Raja, Rajani / Jaiswal, Pankaj / Cumbie, Jason S / Nonogaki, Mariko / Boyd, Alexander E / Owensby, C Alisha / Knaus, Brian J / Elser, Justin / Miller, Daniel / Di, Yanming / McPhail, Kerry L / Spatafora, Joseph W

    PLoS genetics

    2013  Volume 9, Issue 6, Page(s) e1003496

    Abstract: The ascomycete fungus Tolypocladium inflatum, a pathogen of beetle larvae, is best known as the producer of the immunosuppressant drug cyclosporin. The draft genome of T. inflatum strain NRRL 8044 (ATCC 34921), the isolate from which cyclosporin was ... ...

    Abstract The ascomycete fungus Tolypocladium inflatum, a pathogen of beetle larvae, is best known as the producer of the immunosuppressant drug cyclosporin. The draft genome of T. inflatum strain NRRL 8044 (ATCC 34921), the isolate from which cyclosporin was first isolated, is presented along with comparative analyses of the biosynthesis of cyclosporin and other secondary metabolites in T. inflatum and related taxa. Phylogenomic analyses reveal previously undetected and complex patterns of homology between the nonribosomal peptide synthetase (NRPS) that encodes for cyclosporin synthetase (simA) and those of other secondary metabolites with activities against insects (e.g., beauvericin, destruxins, etc.), and demonstrate the roles of module duplication and gene fusion in diversification of NRPSs. The secondary metabolite gene cluster responsible for cyclosporin biosynthesis is described. In addition to genes necessary for cyclosporin biosynthesis, it harbors a gene for a cyclophilin, which is a member of a family of immunophilins known to bind cyclosporin. Comparative analyses support a lineage specific origin of the cyclosporin gene cluster rather than horizontal gene transfer from bacteria or other fungi. RNA-Seq transcriptome analyses in a cyclosporin-inducing medium delineate the boundaries of the cyclosporin cluster and reveal high levels of expression of the gene cluster cyclophilin. In medium containing insect hemolymph, weaker but significant upregulation of several genes within the cyclosporin cluster, including the highly expressed cyclophilin gene, was observed. T. inflatum also represents the first reference draft genome of Ophiocordycipitaceae, a third family of insect pathogenic fungi within the fungal order Hypocreales, and supports parallel and qualitatively distinct radiations of insect pathogens. The T. inflatum genome provides additional insight into the evolution and biosynthesis of cyclosporin and lays a foundation for further investigations of the role of secondary metabolite gene clusters and their metabolites in fungal biology.
    MeSH term(s) Animals ; Coleoptera/microbiology ; Cyclosporine/metabolism ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genome ; Hypocreales/enzymology ; Hypocreales/genetics ; Multienzyme Complexes/genetics ; Multienzyme Complexes/metabolism ; Multigene Family ; Peptide Synthases/genetics ; Peptide Synthases/metabolism ; Phylogeny ; Sequence Analysis, RNA
    Chemical Substances Multienzyme Complexes ; cyclosporin A synthetase ; Cyclosporine (83HN0GTJ6D) ; Peptide Synthases (EC 6.3.2.-)
    Language English
    Publishing date 2013-06-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1003496
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Critical evaluation of chest computed tomography scans for blunt descending thoracic aortic injury.

    Bruckner, Brian A / DiBardino, Daniel J / Cumbie, Todd C / Trinh, Charles / Blackmon, Shanda H / Fisher, Richard G / Mattox, Kenneth L / Wall, Mathew J

    The Annals of thoracic surgery

    2006  Volume 81, Issue 4, Page(s) 1339–1346

    Abstract: Background: Although aortography has been the long-held "gold standard" for diagnosis of traumatic blunt aortic injury, advances in imaging technology offer less-invasive, more-rapid, and potentially more cost-effective evaluation. The purpose of this ... ...

    Abstract Background: Although aortography has been the long-held "gold standard" for diagnosis of traumatic blunt aortic injury, advances in imaging technology offer less-invasive, more-rapid, and potentially more cost-effective evaluation. The purpose of this study was to review this hospital's experience with the screening and diagnosis of blunt aortic injury with emphasis on the critical evaluation of computed tomography (CT) scans for defining descending thoracic aortic injury.
    Methods: A retrospective single-center analysis of all patients undergoing aortography to evaluate for blunt aortic injury between January 1, 1997, and August 31, 2004, was performed. A policy of relying on CT scans to definitively diagnose blunt aortic injury was not in force, and all patients with positive, equivocal, and negative screening CT scans with significant injury mechanism underwent subsequent aortography; this contributed to an unbiased analysis. A subgroup of patients imaged with the latest generation multislice CT scanners (July 1, 2003, to August 31, 2004) was separately analyzed with rapid three-dimensional reconstruction.
    Results: Of 856 aortograms, 206 (24.1%) were preceded by chest CT scan. Of 31 patients with confirmed aortic injury, 20 had undergone CT scan with 16 positive for definite injury, 3 positive for possible injury, and 1 false-negative study. Of the 206 patients scanned, 114 (55.3%) showed possible injury, 76 (36.9%) were negative, and 16 (7.8%) were positive. Only 3 of the 114 with possible injury (2.6%) were true positives whereas 1 of the 76 negative scans (1.3%) was a false negative and all 16 positive scans were true positives. These data for CT scan imaging result in a sensitivity of 95%, a specificity of 40%, a positive predictive value of 15%, and a negative predictive value of 99%.
    Conclusions: Chest CT is an acceptable screening tool based on prerequisite high sensitivity and ease of performance in the trauma patient suspected of having a descending thoracic aortic injury. Although the excellent negative predictive value resulted in an algorithm change at this institution, there were a significant number of equivocal scans that required subsequent aortography. Three-dimensional software reconstruction of the aorta can aid in diagnosing blunt aortic injury when findings are equivocal, but there will continue to be artifacts and limitations that require aortography for clarification.
    MeSH term(s) Adolescent ; Adult ; Aged ; Algorithms ; Aorta, Thoracic/diagnostic imaging ; Aorta, Thoracic/injuries ; Aortography ; Child ; Child, Preschool ; Female ; Humans ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Retrospective Studies ; Tomography, X-Ray Computed ; Wounds, Nonpenetrating/diagnostic imaging
    Language English
    Publishing date 2006-04
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 211007-6
    ISSN 1552-6259 ; 0003-4975
    ISSN (online) 1552-6259
    ISSN 0003-4975
    DOI 10.1016/j.athoracsur.2005.11.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 252: Show issues Location:
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