Osteomyelitis of the central skull base poses significant challenges for timely and accurate diagnosis. Aggressive management with antimicrobials, coupled with surgical debridement in select cases, may avoid serious neurologic morbidity and mortality.

Abstract-In moderate sodium-replete states, dopamine 1-like receptors (D 1 R/D 5 R) are responsible for regulating Ͼ50% of renal sodium excretion. This is partly mediated by internalization and inactivation of NaKATPase, when associated with adapter protein 2. We used dopaminergic stimulation via fenoldopam (D 1 -like receptor agonist) to study the interaction among D 1 -like receptors, caveolin-1 (CAV1), and the G protein-coupled receptor kinase type 4 in cultured human renal proximal tubule cells (RPTCs). We compared 2 groups of RPTCs, 1 of cell lines that were isolated from normal subjects (nRPTCs) and a second group of cell lines that have D 1 -like receptors that are uncoupled (uncoupled RPTCs) from adenylyl cyclase second messengers. In nRPTCs, fenoldopam increased the plasma membrane expression of D 1 R (10.0-fold) and CAV1 (1.3-fold) and markedly decreased G protein-coupled receptor kinase type 4 by 94Ϯ8%; no effects were seen in uncoupled RPTCs. Fenoldopam also increased the association of adapter protein 2 and NaKATPase by 53Ϯ9% in nRPTCs but not in uncoupled RPTCs. When CAV1 expression was reduced by 86.0Ϯ8.5% using small interfering RNA, restimulation of the D 1 -like receptors with fenoldopam in nRPTCs resulted in only a 7Ϯ9% increase in association between adapter protein 2 and NaKATPase. Basal CAV1 expression and association with G protein-coupled receptor kinase type 4 was decreased in uncoupled RPTCs (58Ϯ5% decrease in association) relative to nRPTCs. We conclude that the scaffolding protein CAV1 is necessary for the association of D 1 -like receptors with G protein-coupled receptor kinase type 4 and the adapter protein 2-associated reduction in plasma membrane NaKATPase.

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4 Laryngoscope, 128:2170-2177, 2018.

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Stent assisted aneurysm treatment was a safe and effective option in this series of ACoA aneurysms with maximum diameter less than 15 mm. ACoA aneurysms may be more likely to recur regardless of treatment option, but stent assisted embolization may be durable after stable initial radiographic follow-up.

CD11d encodes the latest ␣-subunit of the leukocyte integrin family to be discovered, and it is expressed predominantly in myelomonocytic cells. We have isolated a genomic clone that contains CD11d and showed this gene to be 11,461 bp downstream and oriented in the same direction as the related CD11c gene. CD11d transcription begins 69 -79 nucleotides upstream of the ATG codon. Transfection analysis of CD11d-luc reporter constructs revealed that the ؊173 to ؉74 region is sufficient to confer leukocyte-specific expression of luciferase in myelomonocytic cells (THP1 and HL60), B-cells (IM9), and T-cells (Jurkat). Transfection analysis showed that down-regulation of CD11d expression by phorbol ester was myelomonocyte-specific and is mediated by one or more cis-elements within the ؊173 to ؉74 region. In vitro DNase I footprint analysis and electrophoretic mobility shift analysis showed that Sp1 and Sp3 bind at ؊63 to ؊40. Deletion of the Sp-binding site significantly reduced CD11d promoter activity. Overexpression of either Sp1 or Sp3 in THP1 cells led to activation of the CD11d promoter even in the presence of phorbol ester, whereas down-regulation of either factor by antisense oligonucleotides decreased CD11d promoter activity. In contrast, overexpression of Sp3 in IM9 and Jurkat cells down-regulated CD11d promoter expression. In vivo genomic footprinting revealed that the ؊63 to ؊40 region is bound by a Sp protein in unstimulated HL60 cells but not in phorbol ester-stimulated HL60 cells. In contrast, this site is bound in both unstimulated and phorbol ester-stimulated IM9 and Jurkat cells. Together, these results show that myelomonocyte-specific phorbol ester down-regulation of CD11d is mediated through both Sp1 and Sp3.

CD11d encodes the ␣ D subunit for a leukocyte integrin that is expressed on myeloid cells. In this study we show that the ؊100 to ؊20 region of the CD11d promoter confers myeloid-specific activation of the CD11d promoter. Transforming growth factor ␤-inducible early gene-1 (TIEG1) was isolated in a yeast one-hybrid screen using the ؊100 to ؊20 region of the CD11d promoter as bait. Purified GST⅐TIEG1 protein was able to bind within the ؊61 to ؊45 region that overlaps a shorter binding site for Sp1. Transient overexpression of TIEG1 activated the CD11d promoter specifically in myeloid cells, whereas, down-regulation of TIEG1 with small interfering TIEG1 RNA also down-regulated expression of CD11d. In vivo, TIEG1 does not physically interact with Sp1. Cotransfection and electrophoretic mobility shift analyses of TIEG1, Sp1, and Sp3 revealed that TIEG1 competes with these Sp proteins for binding to overlapping sites in the CD11d promoter. Although TIEG1 and Sp1 are ubiquitously expressed in myeloid and non-myeloid cells, chromatin immunoprecipitation assays revealed differential occupancy of the CD11d promoter by these factors. In undifferentiated myeloid and non-myeloid cells, occupancy of the CD11d promoter by TIEG1 is similar. Upon differentiation of myeloid cells and subsequent up-regulation of CD11d expression, TIEG1 occupancy increases. In contrast, occupancy by TIEG1 remains low in non-myeloid cells exposed to phorbol ester. We propose that up-regulation of CD11d expression following differentiation of myeloid cells is mediated through increased binding of TIEG1 binding to the CD11d promoter.