FGF8 signaling is chemotactic for cardiac neural crest cells.

Cardiac neural crest cells migrate into the pharyngeal arches where they support development of the pharyngeal arch arteries. The pharyngeal endoderm and ectoderm both express high levels of FGF8. We hypothesized that FGF8 is chemotactic for cardiac crest cells. To begin testing this hypothesis, cardiac crest was explanted for migration assays under various conditions. Cardiac neural crest cells migrated more in response to FGF8. Single cell tracing indicated that this was not due to proliferation and subsequent transwell assays showed that the cells migrate toward an FGF8 source. The migratory response was mediated by FGF receptors (FGFR) 1 and 3 and MAPK/ERK intracellular signaling. To test whether FGF8 is chemokinetic and/or chemotactic in vivo, dominant negative FGFR1 was electroporated into the premigratory cardiac neural crest. Cells expressing the dominant negative receptor migrated slower than normal cardiac neural crest cells and were prone to remain in the vicinity of the neural tube and die. Treating with the FGFR1 inhibitor, SU5402 or an FGFR3 function-blocking antibody also slowed neural crest migration. FGF8 over-signaling enhanced neural crest migration. Neural crest cells migrated to an FGF8-soaked bead placed dorsal to the pharynx. Finally, an FGF8 producing plasmid was electroporated into an ectopic site in the ventral pharyngeal endoderm. The FGF8 producing cells attracted a thick layer of mesenchymal cells. DiI labeling of the neural crest as well as quail-to-chick neural crest chimeras showed that neural crest cells migrated to and around the ectopic site of FGF8 expression. These results showing that FGF8 is chemotactic and chemokinetic for cardiac neural crest adds another dimension to understanding the relationship of FGF8 and cardiac neural crest in cardiovascular defects.

The Synthetic Cannabinoid WIN 55,212-2 Elicits Death in Human Cancer Cell Lines.

BACKGROUND: Studies have revealed that cancer might be treated with cannabinoids since they can influence cancer cell survival. These findings suggest an alternative treatment option to chemo- and radiotherapy, that are associated with numerous adverse side-effects for the patients. MATERIALS AND METHODS: Viability staining was conducted on lung cancer, testicular cancer and neuroblastoma cells treated with different concentrations of the synthetic cannabinoid WIN 55,212-2 and the percentage of dead cells was compared. Activity of apoptosis-related enzymes was investigated by the presence of DNA ladder in gel electrophoresis. RESULTS: Treatment with different WIN 55,212-2 concentrations led to a significant dose-dependent reduction of cell viability. A DNA ladder was observed after WIN 55,212-2 treatment of testicular cancer and lung cancer cells. CONCLUSION: The application of WIN 55,212-2 was found to trigger cell death in the investigated cell lines. The decline in lung cancer and testicular cancer cell viability seems to have been caused by apoptosis. These findings may contribute to development of alternative cancer therapy strategies.

Cost effectiveness of magnetic resonance imaging in the workup of the dysosmia patient.

BACKGROUND: Intracranial causes of dysosmia are uncommon. Nonetheless, a missed intracranial disorder or neoplasm is worrisome. Magnetic resonance imaging (MRI) may be used in diagnosis; however, the cost effectiveness of this practice is unclear. We hypothesize that MRI scans for idiopathic dysosmia will demonstrate sufficient significant findings to be a cost-effective screening tool. METHODS: Tertiary-care otolaryngology clinic records were queried for smell and taste disturbance. The patients underwent anosmia-protocol MRI of the brain for idiopathic dysosmia in 122 cases. Each MRI report was reviewed for dysosmia findings, intracranial neoplasms, and incidental findings. RESULTS: MRI was normal in 44.3%, there were dysosmia-related findings in 25.4%, and incidental findings in 40.2%. The most common related diagnosis was occult frontoethmoid sinusitis (18.8%). The most common incidental diagnosis was small vessel disease (21.1%). Intracranial neoplasms were observed in 6 patients (4.9%). Nine patients had intracranial causes of dysosmia including olfactory meningiomas, infarct, trauma, and atrophy. MRI cost per dysosmia etiology diagnosis was $9445. Costs increased to $32,355 and $48,880 per intracranial cause or neoplasm, respectively. Cost to diagnose 1 causal intracranial neoplasm was $146,400. From 1997 to 2003, median medical malpractice settlements ranged from $625,616 for misdiagnosis to $682,500 for delay in treatment to $1,750,000 for brain injury. The median jury award was $975,000 for misdiagnosis, $1,550,000 for delayed treatment, and $6,000,000 for brain injury. CONCLUSION: MRI in idiopathic dysosmia yielded information regarding the diagnosis in one-quarter of cases. The implications of missing an intracranial neoplasm alone justify the cost of screening MRI for idiopathic dysosmia.

Use of makeup, hairstyles, glasses, and prosthetics as adjuncts to scar camouflage.

Scars after facial trauma or surgery can be a source of distress for patients, and facial plastic surgeons are frequently called upon to help manage them. Although no technique can remove a scar, numerous treatment modalities have been developed to improve facial scar appearance with varying levels of invasiveness. This article reviews techniques that camouflage scars without surgical intervention. Topical scar treatments, camouflage cosmetics, use of hairstyling and glasses, and facial prosthetics are discussed. In addition, professional counseling is provided on selection and application of topical cosmetics for use as part of an office practice.

Successful thoracoscopic resection of a large mediastinal liposarcoma.

We report a case of a rare, large mediastinal liposarcoma diagnosed in a 74-year-old woman after a syncopal episode. Chest roentgenogram and computed tomographic scan showed a large mass occupying most of the right chest and abutting the great vessels and pericardium. A thoracoscopic approach was used for exploration and surgical excision of this large mediastinal mass. Despite the large size of the mass, the thoracoscopic approach offered excellent visualization of all the mass attachments and required only a small extension of the access incision for tumor removal. The mass was a well-differentiated liposarcoma, which was completely resected with clear margins. The patient remains disease-free almost 3 years after the resection.

Increasing the range of unambiguity in step-height measurement with multiple-wavelength interferometry--application to absolute long gauge block measurement.

An instrument for step-height measurement by multiple-wavelength interferometry is described. The addition of a 1152-nm wavelength to a multiple-wavelength scheme applying wavelengths of 633, 612, and 543 nm relaxes the tolerance range of the required preliminary measurement to +/- 140 microm, if the total uncertainty in the fringe fraction measurement can be kept below 2%. For larger fringe fraction measurement uncertainty, numerical simulations show that the integer number of interference orders can still be determined unambiguously if the range in the preliminary knowledge of the length has been correspondingly reduced. The interferometer instrument is described, and experimental data are presented in the context of long gauge block calibration at the National Research Council of Canada.