Endoscopic transpterygoidal repair of a large cranial defect with cerebrospinal fluid leak in a patient with extensive osteoradionecrosis of the skull base: case report and technical note.

BACKGROUND: Endoscopic endonasal techniques have recently become the method of choice in dealing with cerebrospinal fluid leak involving the anterior cranial fossa. However, most surgeons prefer an intracranial approach when leaks involve the middle cranial fossa. This case report illustrates the possibilities of using endoscopic techniques for cerebrospinal fluid leaks involving the middle fossa. CASE REPORT: A 37-year-old male patient presented with multiple areas of cranial defect with cerebrospinal fluid leak due to osteoradionecrosis following radiation for nasopharyngeal carcinoma 4 years earlier. Clinical examination showed involvement of all cranial nerves except the IInd and XIth nerves on the left side. A prior attempt to repair the cerebrospinal fluid leak with craniotomy was not successful. CONCLUSION: This case demonstrates the successful endoscopic repair of a large cranial defect with cerebrospinal fluid leak.

Matrix metalloproteinases 2 and 9 in the cochlea: expression and activity after aminoglycoside exposition.

The matrix metalloproteinases (MMPs) are a family of proteins involved in the remodelling and homeostasis of the extracellular matrix. These proteases have been well studied in the retina and the brain, marking their importance in neuronal cell survival and death [Chintala (2006) Exp Eye Res 82:5-12; Candelario-Jalil et al. (2009) Neuroscience 158:983-994]. The neuroepithelia of the eye and the inner ear share common characteristics. Therefore, we hypothesized that MMPs could play a similar role in the cochlea as described in the retina. We focused on the localization and function of MMP-2 and MMP-9 in the cochlea, by determining their expression and activity under normal conditions and after cochlear damage via aminoglycoside exposition. We examined their expression in 5-day-old Wistar rat cochleas by RT-PCR, real-time PCR, and Western blot. We used immunohistochemistry to investigate their location in the cochleas of adult C57BL/6 mice. We also determined whether or not the exposure of the organs of Corti to aminoglycosides would change MMP-2 and MMP-9 expression patterns. Western blotting identified MMP-2 and MMP-9 in neonatal spiral ganglion, stria vascularis, and to a lesser extent the organ of Corti. Neonatal mRNA expression of MMP-2 was approximately equivalent in all three tissues, while MMP-9 mRNA was highest in spiral ganglion. Immunohistochemistry showed MMP-2 primarily in adult spiral ganglion neurons and inner hair cells, while MMP-9 was found mainly in spiral ganglion neurons, inner hair cells and supporting cells. Organs of Corti treated with gentamicin for 24 h showed an upregulation of MMP-2 and MMP-9 proteins, but did not show a significant upregulation of mRNA expression 3, 6, 12, 24, and 36 h after gentamicin exposure. Inhibition of MMP activity in organs of Corti incubated with an MMP inhibitor in organotypic cultures resulted in hair cell death-suggesting that a basal level of MMP activity is required for hair cell survival.

Gene structure, promoter characterization, and basis for alternative mRNA splicing of the human CD58 gene.

The 60-kDa lymphocyte function-associated Ag-3 (LFA-3/CD58), a highly glycosylated adhesion molecule that serves as ligand for the T cell-restricted glycoprotein CD2, is encoded by a gene at the human chromosome locus 1p13. We have elucidated the exon-intron organization of the entire human CD58 gene, including approximately 2.5 kilobases (kb) of 5'-flanking DNA. Four overlapping genomic clones, spanning approximately 65 kb, contained the entire approximately 1-kb coding sequence of CD58 and consisted of six separate exons, which varied from 72 to 294 bp in size. At least two different CD58 mRNA precursors can be generated from the human gene as a result of alternative choice of one of the two acceptor splice sites located within exon 5. DNA sequence analysis of about 2.5 kb of 5'-flanking sequence of the CD58 gene indicated the absence of a CAAT box. However, potential binding sites for the transcriptional activators AP-2, GATA, PU.1, and Sp-1 are present. Two consensus TATAA elements, located approximately 2.4 kb upstream of the transcriptional start site, have been identified. The 2.5-kb CD58 promoter sequence displayed functional activity in transient transfection assays in the hepatocellular carcinoma cell line HepG2. Comparing the response of CD58 promoter-driven luciferase plasmids to several cytokines and other agents suggests that the CD58 promoter is regulated by up-regulatory, enhancer-like and down-regulatory, silencer-like elements. Further analysis of this region should allow researchers to gain insight into the molecular mechanisms by which this gene is regulated, e.g., during inflammatory responses.