Publications by authors named "Annette George"

Article Synopsis
  • The study examined the long-term efficacy and safety of nusinersen in adults with 5q-associated spinal muscular atrophy (SMA) over a period of 38 months, utilizing a large cohort from Germany, Switzerland, and Austria.
  • Overall, significant improvements were noted in various motor performance measures (HFMSE, RULM, and 6MWT) at multiple time points compared to baseline, indicating ongoing benefits from the treatment.
  • No new safety concerns were found, reinforcing the idea that nusinersen remains a viable therapy for adults with SMA over extended periods.
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Frutexites-like microstructures are described from the exhumed Late Devonian reef complexes of the northern Canning Basin, Western Australia. Several high-resolution imaging techniques, including X-ray microcomputerised tomography, scanning electron microscopy and X-ray fluorescence microscopy, were used to investigate morphology and composition in two samples. Three types of Frutexites-like microstructures (Types I-III) have been identified.

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Fibrous-radiating carbonate spherulites spatially associated with poorly crystalline Mg-Si substances have formed within conical microbialites in modern hypersaline lakes on Rottnest Island, Western Australia. Two spherulitic fabrics can be distinguished based on compositional and textural differences. The oldest (lowermost) fabric comprises variably intergrown aragonitic spherulites 100-500 μm wide, containing micritic nuclei with coccoid cell molds in various stages of cell division.

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Background: The Pr55(gag) (Gag) polyprotein of HIV serves as a scaffold for virion assembly and is thus essential for progeny virion budding and maturation. Gag localizes to the plasma membrane (PM) and membranes of late endosomes, allowing for release of infectious virus directly from the cell membrane and/or upon exocytosis. The host factors involved in Gag trafficking to these sites are largely unknown.

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Excitability measurements on human motor and sensory nerves have provided new insights into axonal membrane changes in peripheral nerve disorders. The aim of this study was to establish an in vivo rat preparation suitable for threshold tracking of sensory nerve action potentials (SNAPs) to model clinical sensory nerve excitability studies. In Sprague-Dawley rats anesthetized with ketamine and xylazine, current stimuli were applied to the base of the tail and SNAPs recorded from distal needle electrodes.

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To improve knowledge about axonal membrane properties in nociceptive and non-nociceptive C fibres, we studied impulse-dependent velocity changes by in vivo microneurography in the rat sciatic nerve. Cutaneous C fibres were classified, based primarily on their activity-dependent slowing profile, as Type 1A (mechano-responsive nociceptors; CMR; n = 23), Type 1B (mechano-insensitive nociceptors; CMI; n = 24), Type 2 (cold units; n = 2), Type 3 units (unknown function; n = 4) or Type 4 (presumed sympathetics; n = 23) units. They were excited by single, double and triple electrical stimuli to the skin at mean rates of 0.

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C-fiber nociceptors can be divided into two groups based on growth factor dependency and isolectin B4 (IB4) binding. IB4-negative nociceptors have been proposed to contribute to inflammatory pain. Since the TRPV1 receptor is critical for inflammatory heat hyperalgesia, we hypothesized that inflammation would sensitize IB4 negative but not IB4-positive small-diameter neurons to TRPV1 stimuli.

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The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF) is involved in injury-induced peripheral nerve pathology and in the generation of neuropathic pain. Here, we investigated local protein levels of the two known TNF receptors, TNF receptor 1 and 2 (TNFR1, TNFR2), on days 0, 1, 3, 7, 14, and 28 after unilateral crush or chronic constriction injury (CCI) of mouse sciatic nerves using enzyme-linked immunoassay. Both receptors were detectable at a low level in nerve homogenates from naive mice.

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Background: Myotonic dystrophy type 2/proximal myotonic myopathy (DM2/PROMM) is an autosomal dominant multisystem disorder. Musculoskeletal pain is one of its frequent symptoms but also occurs in other chronic noninflammatory muscle disorders (OMD).

Objectives: To characterize the phenotype of DM2/PROMM-associated musculoskeletal pain and to test whether it shows features distinct from OMD.

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The pro-inflammatory cytokine tumor necrosis factor-alpha (TNF) contributes to injury-induced peripheral nerve pathology and to the development of neuropathic pain. Here, we investigated whether TNF protein is altered at the site of crush injury of rat sciatic nerve using enzyme-linked immunoassay (ELISA) and immunohistochemistry (IHC). TNF protein levels determined by ELISA were low in nerve homogenates from naive rats.

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We used enzyme-linked immunoassay (ELISA), immunohistochemistry (IHC), and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to determine whether interleukin (IL)-10 protein is changed after unilateral crush or chronic constriction injury (CCI) of mouse or rat sciatic nerve and whether IL-10 protein and mRNA are differentially regulated. In the mouse sciatic nerve, IL-10 protein declined rapidly to 10-20% of baseline early after crush or CCI, while the IL10 mRNA was up-regulated with a maximum on Days 1 and 3. In the rat sciatic nerve, IL-10 protein was significantly reduced on Day 3 after CCI, and IL-10 mRNA was up-regulated in both models.

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Thalidomide reduces thermal hyperalgesia and mechanical allodynia in chronic constrictive sciatic nerve injury (CCI). Since thalidomide mainly inhibits tumor necrosis factor alpha (TNF-alpha) synthesis with less well defined effects on other cytokines, we investigated the effect of the drug on the expression of the proinflammatory cytokines TNF-alpha, interleukin-1beta (IL-1beta) and interleukin 6 (IL-6), and of the anti-inflammatory cytokine interleukin-10 (IL-10) in the lesioned rat sciatic nerve. The increase of endoneurial TNF-alpha during the first week after CCI was reduced after thalidomide treatment, as shown with immunohistochemistry and enzyme-linked-immunosorbent assay.

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