Cloning of vertebrate Protogenin (Prtg) and comparative expression analysis during axis elongation.
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A murine cDNA encoding Protogenin, which belongs to the DCC/Neogenin family, was cloned in a screen performed to identify novel cDNAs regionally expressed in the neural plate. Isolation of the putative zebrafish orthologues allowed a comparative analysis of the expression patterns of Protogenin genes during embryogenesis in different vertebrate species. From mid-gastrulation to early somite stages, Protogenin expression is restricted to posterior neural plate and mesoderm, with an anterior limit at the level of the rhombencephalon in mouse, chicken, and zebrafish. During somitogenesis, the expression profiles in the three species share features in the neural tube but present also species-specific characteristics. The initiation of Protogenin expression just before somitogenesis and its maintenance in the neural tube and paraxial mesoderm during this process suggest a conserved role in axis elongation. (+info)
Analysis of axis induction mutant embryos reveals morphogenetic events associated with zebrafish yolk extension formation.
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We analyze patterning and morphogenetic events during somitogenesis in hecate mutant embryos, which exhibit early axis induction defects. The posterior region, in the absence of a dorsal axis, is capable of forming organized gene expression patterns. The aberrant morphogenesis of mutant embryos is associated with anteriorly directed cell movements, underlying the enveloping layer, from the posterior region. In both wild-type and mutant embryos, these changes result in an accumulation of cells, whose location correlates with a constriction in the posterior yolk cell, which in the wild-type corresponds to the yolk extension. The region encompassing the constriction corresponds to a region of expression of zangptl2 in the yolk syncytial layer, which expands anteriorly together with the anteriorly migrating tail bud-derived cell population. Our data indicate that yolk extension formation is associated with coordinated changes involving the anterior migration of cells from the posterior region, changes in surface cellular layers, and inductive gene expression events in the YSL. (+info)
Jun NH2-terminal kinase (JNK) prevents nuclear beta-catenin accumulation and regulates axis formation in Xenopus embryos.
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Jun NH(2)-terminal kinases (JNKs) regulate convergent extension movements in Xenopus embryos through the noncanonical Wnt/planar cell polarity pathway. In addition, there is a high level of maternal JNK activity spanning from oocyte maturation until the onset of gastrulation that has no defined functions. Here, we show that maternal JNK activation requires Dishevelled and JNK is enriched in the nucleus of Xenopus embryos. Although JNK activity is not required for the glycogen synthase kinase-3-mediated degradation of beta-catenin, inhibition of the maternal JNK signaling by morpholino-antisense oligos causes hyperdorsalization of Xenopus embryos and ectopic expression of the Wnt/beta-catenin target genes. These effects are associated with an increased level of nuclear and nonmembrane-bound beta-catenin. Moreover, ventral injection of the constitutive-active Jnk mRNA blocks beta-catenin-induced axis duplication, and dorsal injection of active Jnk mRNA into Xenopus embryos decreases the dorsal marker gene expression. In mammalian cells, activation of JNK signaling reduces Wnt3A-induced and beta-catenin-mediated gene expression. Furthermore, activation of JNK signaling rapidly induces the nuclear export of beta-catenin. Taken together, these results suggest that JNK antagonizes the canonical Wnt pathway by regulating the nucleocytoplasmic transport of beta-catenin rather than its cytoplasmic stability. Thus, the high level of sustained maternal JNK activity in early Xenopus embryos may provide a timing mechanism for controlling the dorsal axis formation. (+info)
Percutaneous vertebroplasty at C2: case report of a patient with multiple myeloma and a literature review.
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Percutaneous vertebroplasty (PVP) of the axis is a challenging procedure which may be performed by a percutaneous or a transoral approach. There are few reports of PVP at the C2 level. We report a case of unstable C2 fracture treated with the percutaneous approach. The fracture was the first manifestation of multiple myeloma in a previously healthy 47-year-old woman. After local radiotherapy and chemotherapy, the fracture was still unstable and the patient had been continuously wearing a stiff cervical collar for 9 months. Complication-free PVP resulted in pain relief and stabilization and use of the cervical collar could be discontinued. At 18 months follow-up the patient remained free from pain, the fracture was stable and she had returned to work. The purpose of this article is to present the technical facts and to highlight the benefits and potential complications of the procedure. The technical characteristics of the procedure, the indication and results of the present case are discussed together with previously reported cases of PVP treatment at C2. (+info)
Verticality perception during off-vertical axis rotation.
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During prolonged rotation about a tilted yaw axis, often referred to as off-vertical axis rotation (OVAR), a percept of being translated along a conical path slowly emerges as the sense of rotation subsides. Recently, we found that these perceptual changes are consistent with a canal-otolith interaction model that attributes the illusory translation percept to improper interpretation of the ambiguous otolith signals. The model further predicts that the illusory translation percept must be accompanied by slowly worsening tilt underestimates. Here, we tested this prediction in six subjects by measuring the time course of the subjective visual vertical (SVV) during OVAR stimulation at three different tilt-rotation speed combinations, in complete darkness. Throughout the 2-min run, at each left-ear-down and right-ear-down position, the subject indicated whether a briefly flashed line deviated clockwise or counterclockwise from vertical to determine the SVV with an adaptive staircase procedure. Typically, SVV errors indicating tilt underestimation were already present at rotation onset and then increased exponentially to an asymptotic value, reached at about 60 s after rotation onset. The initial error in the SVV was highly correlated to the response error in a static tilt control experiment. The subsequent increase in error depended on both rotation speed and OVAR tilt angle, in a manner predicted by the canal-otolith interaction model. We conclude that verticality misjudgments during OVAR reflect a dynamic component linked to canal-otolith interaction, superimposed on a tilt-related component that is also expressed under stationary conditions. (+info)
Intra-operative Iso-C3D navigation for pedicle screw instrumentation of hangman's fracture: a case report.
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Pedicle screw instrumentation of the upper cervical spine is rarely performed in trauma surgery because of the risk of damaging neurovascular structures. We report successful treatment of an unstable hangman's fracture with posterior pedicle screw fixation using Iso-C3D fluoroscopy-based computer navigation guidance. Postoperative computed tomographic images confirmed accurate placement of the pedicle screws. The navigation system is useful, especially in an unstable upper cervical spine injury where the likelihood of change in the inter-segmental relationship is maximal before and after positioning for surgery. The navigation system has the advantage of data acquisition after patient positioning, thus making safe pedicle fixation of the C1 and C2 vertebrae possible despite fractured posterior elements. (+info)
Performance of referral recommendations in patients with chronic back pain and suspected axial spondyloarthritis.
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BACKGROUND: Ankylosing spondylitis (AS) and its early form account for up to 5% of all patients with chronic back pain. Interest has recently focused on shortening the delay of 5-10 years between the appearance of first symptoms and the diagnosis of AS, particularly because effective treatments have now become available. Referral parameters that are easy for doctors in primary care to apply to patients presenting with possible AS could contribute to earlier diagnosis. METHODS: Orthopaedists and primary-care doctors were requested to refer patients with (1) chronic low back pain (duration >3 months) and (2) onset of back pain before <45 years of age to a specialist rheumatology outpatient clinic for further diagnostic investigation if at least one of the following screening parameters was present: (1) inflammatory back pain, (2) positive human leucocyte antigen B27, and (3) sacroiliitis detected by imaging. The final diagnosis was made according to expert opinion. RESULTS: In total, 350 referred cases were analysed. A diagnosis of definite axial spondyloarthritis (axial SpA), comprising established AS and pre-radiographic axial SpA, could be made in 45.4% of all referred patients (of which 50.3% were classified as AS and 49.7% as preradiographic axial SpA), whereas 45.4% were classified as non-SpA and 9.1% as possible SpA. A diagnosis of definite axial SpA could be made in 34.2% if only one referral parameter was positive, and in 62.6% if there was >1 positive referral parameter. CONCLUSIONS: The proposed referral parameters have proven useful when applied in primary care in identifying patients with AS/pre-radiographic axial SpA among young to middle-aged patients with chronic low back pain. (+info)
Using peripheral stimulation to reduce the pain of C2-mediated occipital headaches: a preliminary report.
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BACKGROUND: Peripheral nerve stimulation (PNS) is an accepted treatment for neuropathic pain. Recent studies have focused on its potential for relieving headache pain. OBJECTIVES: To investigate the effectiveness of PNS in reducing occipital headache pain. DESIGN: A prospective, 12-week pilot study involving 11 patients evaluated before and after implantation of PNS systems to treat C2-mediated occipital headaches. METHODS: Prior to and at 4 and 12 weeks after implantation, patients completed the Short-Form McGill Pain Questionnaire (SF-MPQ), Visual Analog Scale (VAS), and Present Pain Index (PPI). Patients also answered questionnaires and kept diaries to record stimulator use, medication consumption, and numbers of headaches. RESULTS: A comparison of pre- and post-implantation evaluations showed statistically significant declines in scores on the SF-MPQ (64%; p = 0.0013), VAS (67%; p < 0.0001), and PPI (68%; p = 0.0009). Most patients (91% and 64% respectively) reported reductions in medication use and numbers of headaches. Patients also reported a reduction in headache symptoms and the impact of headaches on activities. Two adverse events were encountered, one due to a loose connection and, the other caused by lead migration. CONCLUSIONS: PNS reduced headache pain, headache frequency and medication use. (+info)