Papers by Karen Chandross
Springer eBooks, 1996
Myelinating Schwann cells in adult peripheral nerve express the gap junction protein connexin32 (... more Myelinating Schwann cells in adult peripheral nerve express the gap junction protein connexin32 (Cx32), which is localized to paranodal loops and Schmidt-Lantermann incisures.1 Cx32 is thought to form reflexive contacts within individual Schwann cells providing direct pathways for intracellular ionic and metabolic exchange from the cell body to the innermost periaxonal cytoplasmic regions. However, nerve injury induces coordinated phenotypic and functional changes in the distal Schwann cells no longer in contact with the viable nerve, including the downregulation of Cx32 mRNA and protein2,3 and the upregulation of connexin46 (Cx46).2 The cascade of Schwann cell responses seen after the injury-induced decrease in Cx32, and the observation that cultured Schwann cells express Cx46 and are coupled by a connexin(s) distinct from Cx32,4–6 raise the intriguing possibility that there are coordinated changes in Schwann cell proliferation and junctional coupling and that Cx46 may be involved in Schwann cell injury responses. Consistent with this hypothesis, dividing Schwann cells are preferentially dye coupled compared to nondividing cells,6 directly demonstrating an association between proliferation and coupling. Moreover, the strength of junctional coupling among cultured Schwann cells is modulated by a number of inflammatory cytokines to which Schwann cells are exposed to in vivo and Cx46 mRNA and protein expression correlate with the degree of junctional coupling.5,6
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Microscopy Research and Technique, 2001
Over the past decade, advances in strategies to tag cells have opened new avenues for examining t... more Over the past decade, advances in strategies to tag cells have opened new avenues for examining the development of myelin‐forming glial cells and for monitoring transplanted cells in animal models of myelin insufficiency. The strategies for labelling glial cells have encompassed a range of genetic modifications as well as methods for directly attaching labels to cells. Genetically modified oligodendrocytes have been engineered to express enzymatic (e.g., β‐galactosidase, alkaline phosphatase), naturally fluorescent (e.g., green fluorescent protein), and antibiotic resistance (e.g., neomycin, zeomycin) reporters. Genes have been introduced in vivo and in vitro with viral or plasmid vectors to somatically label glial cells. To generate germ‐line transmission of tagged oligodendrocytes, transgenic mice have been created both by direct injection into mouse fertilized eggs and by “knock‐in” of reporters targetted to myelin gene loci in embryonic stem cells. Each experimental approach has advantages and limitations that need to be considered for individual applications. The availability of tagged glial cells has expanded our basic understanding of how oligodendrocytes are specified from stem cells and should continue to fill in the gaps in our understanding of how oligodendrocytes differentiate, myelinate, and maintain their myelin sheaths. Moreover, the ability to select oligodendrocytes by virtue of their acquired antibiotic resistance has provided an important new tool for isolating and purifying oligodendrocytes. Tagged glial cells have also been invaluable in evaluating cell transplant therapies in the nervous system. The tracking technologies that have driven these advances in glial cell biology are continuing to evolve and present new opportunities for examining oligodendrocytes in living systems. Microsc. Res. Tech. 52:766–777, 2001. Published 2001 Wiley‐Liss, Inc.
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Epidemiology, May 26, 2023
It has been well established that randomized clinical trials have poor external validity, resulti... more It has been well established that randomized clinical trials have poor external validity, resulting in findings that may not apply to relevant—or target—populations. When the trial is sampled from the target population, generalizability methods have been proposed to address the applicability of trial findings to target populations. When the trial sample and target populations are distinct, transportability methods may be applied for this purpose. However, generalizability and transportability studies present challenges, particularly around the strength of their conclusions. We review and summarize state-of-the-art methods for translating trial findings to target populations. We additionally provide a novel step-by-step guide to address these challenges, illustrating principles through a published case study. When conducted with rigor, generalizability and transportability studies can play an integral role in regulatory decisions by providing key real-world evidence.
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arXiv (Cornell University), Feb 1, 2022
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Journal of Neuroscience Research, 2000
ABSTRACT The effect of fibroblast growth factor (FGF)-9 on the expression of FGF receptors (FGFR)... more ABSTRACT The effect of fibroblast growth factor (FGF)-9 on the expression of FGF receptors (FGFR) and the major myelin proteins was examined in cultures of developing rat brain oligodendrocytes (OLs), using immunological techniques. FGFR-1, -3, and -4 were expressed at all developmental stages but were not present in isolated myelin fractions. By contrast, FGFR-2 protein was predominantly localized to differentiating cells and myelin. FGF-9 altered FGFR and myelin protein levels during OL differentiation; there was increased expression of FGFR-1 and decreased levels of both FGFR-2 and myelin proteins. Further, FGF-9 stimulated mitogen-associated protein kinase (MAPK) phosphorylation. The effect of FGF-9 on MAPK, however, was transient and less robust in progenitor cells than in differentiated oligodendrocytes. The effects of FGF-9 and FGF-2 on FGFR and myelin protein levels were comparable; both up-regulated FGFR-1, and down-regulated FGFR-2, CNP, PLP and MBP. These findings suggest that FGF-9 may be important for glial cell development.
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Glia, Sep 1, 1998
In the peripheral nervous system (PNS), myelinating Schwann cells express the gap junction protei... more In the peripheral nervous system (PNS), myelinating Schwann cells express the gap junction protein connexin32 (Cx32) and lower levels of connexin43 (Cx43). Although the function of Cx43 in Schwann cells is not yet known, in adult mammals Cx32 is thought to form reflexive contacts within individual myelinating glial cells and provide direct pathways for intracellular ionic and metabolic exchange from the cell body to the innermost periaxonal cytoplasmic regions. In response to nerve injury, Schwann cells in the degenerating region down-regulate expression of Cx32 and there is increased expression of connexin46 (Cx46) mRNA and protein. The cascade of Schwann cell responses seen after the injury-induced decrease in Cx32, and the observation that dividing Schwann cells express Cx46, and possibly other connexins, and are coupled through gap junction channels, raise the intriguing possibility that there are coordinated changes in Schwann cell proliferation and connexin expression. Moreover, intercellular junctional coupling among cells in general may be important during injury responses. Consistent with this hypothesis, dividing Schwann cells are preferentially coupled through junctional channels as compared to non-dividing cells, which are generally uncoupled. Moreover, the strength of junctional coupling among cultured Schwann cells is modulated by a number of cytokines to which Schwann cells are exposed to in vivo after nerve injury, and Cx46 mRNA and protein levels correlate with the degree of coupling. Other injury-induced cellular changes in connexin expression that may be functionally important during injury responses include a transient increase in Cx43 in endoneurial fibroblasts. This paper reviews what is known about connexin expression and function in the adult mammalian PNS, and focuses on some of the changes that occur following nerve injury. Moreover, evidence that inflammatory cytokines released after injury modulate connexin expression and junctional coupling strength is presented.
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Progress in Cell Research, 1995
The Schwann cell is the principal glial component of peripheral nerve. Schwann cells regulate dev... more The Schwann cell is the principal glial component of peripheral nerve. Schwann cells regulate development of peripheral nerves, myelinate and help to maintain physiological homeostasis in intact nerves, and participate in repair processes after nerve injury. The association of point mutations in the gap junction protein connexin32 with the X-linked form of Charcot-Marie Tooth syndrome [44] has implicated junctional channels in intra cellular ion exchange and normal nerve function. This review addresses mechanisms regulating gap junction expression and function in Schwann cells, and the role of intr cellular junctional communication in coordinating Schwann cell responses to injury.
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PLOS ONE, Dec 15, 2022
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IEEE transactions on neural networks and learning systems, Apr 1, 2023
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Brain Research, Jul 1, 1995
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The Journal of Neuroscience, 1995
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The Journal of General Physiology, Nov 1, 1993
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Asn Neuro, 2018
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Current Medical Research and Opinion, Jun 28, 2022
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BMC Neurology, 2021
Background Characterization of prediagnostic Parkinson’s Disease (PD) and early prediction of sub... more Background Characterization of prediagnostic Parkinson’s Disease (PD) and early prediction of subsequent development are critical for preventive interventions, risk stratification and understanding of disease pathology. This study aims to characterize the role of the prediagnostic period in PD and, using selected features from this period as novel interception points, construct a prediction model to accelerate the diagnosis in a real-world setting. Methods We constructed two sets of machine learning models: a retrospective approach highlighting exposures up to 5 years prior to PD diagnosis, and an alternative model that prospectively predicted future PD diagnosis from all individuals at their first diagnosis of a gait or tremor disorder, these being features that appeared to represent the initiation of a differential diagnostic window. Results We found many novel features captured by the retrospective models; however, the high accuracy was primarily driven from surrogate diagnoses f...
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The Journal of Neuroscience, Jan 15, 1999
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Advances in Cell Aging and Gerontology, 2002
... Ed. by Mark P. Mattson and Gary Van Zant. 73 -- 95 2002 Elsevier Science BV All rights reserv... more ... Ed. by Mark P. Mattson and Gary Van Zant. 73 -- 95 2002 Elsevier Science BV All rights reserved. KAREN J. CHANDROSS and I~VA MEZEY 73 74 74 78 78 78 79 80 80 80 85 86 86 89 89 90 91 91 Introduction . . . . . ...
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Regulatory Peptides, 1993
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Annals of Neurology, 2006
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Papers by Karen Chandross