Showing papers by "The Cyprus Institute published in 2006"
TL;DR: The hypothesis that antibodies to mature surface membrane-expressed Shaker-type K+ channels cause acquired neuromyotonia, MoS and LE is supported, and it is suggested that future assays based on immunofluorescence of cells expressing individual Kv1 subunits will prove more sensitive than the immunoprecipitation assay.
Abstract: Autoantibodies to Shaker -type (Kv1) K+ channels are now known to be associated with three syndromes. Peripheral nerve hyperexcitability is the chief manifestation of acquired neuromyotonia; the combination of neuromyotonia with autonomic and CNS involvement is called Morvan's syndrome (MoS); and CNS manifestations without peripheral involvement is called limbic encephalitis (LE). To determine the cellular basis of these clinical manifestations, we immunostained mouse neural tissues with sera from patients with neuromyotonia ( n = 10), MoS ( n = 2) or LE ( n = 5), comparing with specific antibodies to relevant K+ channel subunits. Fourteen of 17 patients' sera were positive for Kv1.1, Kv1.2 or Kv1.6 antibodies by immunoprecipitation of 125I-α-dendrotoxin-labelled rabbit brain K+ channels. Most sera (11 out of 17) labelled juxtaparanodes of peripheral myelinated axons, co-localizing with Kv1.1 and Kv1.2. In the CNS, all sera tested ( n = 12) co-localized with one or more areas of high Kv1.1, Kv1.2 or Kv1.6 channel expression: 10 out of 12 sera co-localized with Kv1.1 and Kv1.2 at spinal cord juxtaparanodes or cerebellar layers, while 3 out of 12 sera co-localized additionally ( n = 2) or exclusively ( n = 1) with Kv1.6 subunits in Purkinje cells, motor and hippocampal neurons. However, only sera from LE patients labelled the hippocampal areas that are enriched in excitatory, Kv1.1-positive axon terminals. All sera (17 out of 17) labelled one or more of these Kv1 subunits when expressed at the cell membrane of transfected HeLa cells, but not when they were retained in the endoplasmic reticulum. Again, LE sera labelled Kv1.1 subunits more prominently than did MoS or neuromyotonia sera, suggesting an association between higher Kv1.1 specificity and limbic manifestations. In contrast, neuromyotonia sera bound more strongly to Kv1.2 subunits than to Kv1.1 or Kv1.6. These studies support the hypothesis that antibodies to mature surface membrane-expressed Shaker -type K+ channels cause acquired neuromyotonia, MoS and LE, and suggest that future assays based on immunofluorescence of cells expressing individual Kv1 subunits will prove more sensitive than the immunoprecipitation assay. Although more than one type of antibody is often detectable in individual sera, higher affinity for certain subunits or subunit combinations may determine the range of clinical manifestations.
148 citations
TL;DR: These novel connexin32 (Cx32) mutations cause a spectrum of clinical manifestations characteristic of Charcot–Marie–Tooth disease (CMT1X), including demyelinating or intermediate polyneuropathy, which is often asymmetric, and CNS involvement in one family.
Abstract: Objective: To determine the phenotypic and cellular expression of two novel connexin32 (Cx32) mutations causing X-linked Charcot–Marie–Tooth disease (CMT1X). Methods: The authors evaluated several members of two families with CMT1X clinically, electrophysiologically, pathologically, and by genetic testing. The Cx32 mutations were expressed in vitro and studied by immunocytochemistry. Results: In both families, men were more severely affected than women with onset in the second decade of life. In the first family, the phenotype was that of demyelinating polyneuropathy with variable involvement of peripheral nerves. There was clinical evidence of CNS involvement in at least three of the patients, with extensor plantar responses and brisk reflexes. In the second family, the affected man presented with symmetric polyneuropathy and intermediate slowing of conduction velocities, whereas affected women had prominent asymmetric atrophy of the leg muscles. The authors identified two novel missense mutations resulting in L143P amino acid substitution in the first family and in V140E substitution in the second family, both located in the third transmembrane domain of Cx32. Expression of these Cx32 mutations in communication-incompetent HeLa cells and immunocytochemical analysis revealed that both mutants were retained intracellularly and were localized in the Golgi apparatus. In contrast to wild-type protein, they did not form gap junctions. Conclusion: These novel connexin32 (Cx32) mutations cause a spectrum of clinical manifestations characteristic of Charcot–Marie–Tooth disease (CMT1X), including demyelinating or intermediate polyneuropathy, which is often asymmetric, and CNS involvement in one family. The position and cellular expression of Cx32 mutations alone cannot fully predict these phenotypic variations in CMT1X.
51 citations
01 Oct 2006
TL;DR: A collection of algorithms that are used to provide motion trajectory estimates from atherosclerotic plaque ultrasound videos are described, based on the use of four different optical flow methods to estimate motion vectors.
Abstract: In this paper, we describe a collection of algorithms that are used to provide motion trajectory estimates from atherosclerotic plaque ultrasound videos Our approach is based on the use of four different optical flow methods to estimate motion vectors (Horn and Schunk, Lucas, Nagel and Uras) To estimate the optimal motion estimation parameters, we perform hundreds of experiments on a Linux cluster, and further validate the results using synthetic simulations Following motion estimation, we compute pixel motion trajectories over the plaque regions and vessel walls Pixel trajectories are then used to assess plaque deformation
11 citations