Multidisciplinary clinic for care of children with complex obstructive sleep apnea.

Objective: While adenotonsillectomy (AT) remains first line therapy for pediatric obstructive sleep apnea (OSA), management of children who are not candidates for AT or who have residual OSA post AT varies and spans across multiple specialties. We aim to report our experience in managing this population through a multidisciplinary sleep clinic composed of specialists in pediatric dentistry, otolaryngology, plastic surgery, and pulmonary/sleep medicine.

Study Design: Retrospective chart review.

Small molecule inhibitors of the host cell COX/AREG/EGFR/ERK pathway attenuate cytomegalovirus-induced pathogenesis.

As with other herpesviruses, human cytomegalovirus (hCMV) has the ability to establish lifelong persistence and latent infection following primary exposure, salivary glands (SMGs) being the primary site of both. In the immunocompromised patient, hCMV is a common cause of opportunistic infections, and subsequent morbidity and mortality. Elucidating the molecular pathogenesis of CMV-induced disease is critical to the development of more effective and safer drug therapies.

CRTC1 expression during normal and abnormal salivary gland development supports a precursor cell origin for mucoepidermoid cancer.

Dysregulation of the transcription factor CRTC1 by a t(11;19) chromosomal rearrangement mediates the formation of mucoepidermoid salivary gland carcinoma (MEC). Although the CRTC1 promoter is consistently active in fusion-positive MEC and low levels of CRTC1 transcripts have been reported in normal adult salivary glands, the distribution of CRTC1 protein in the normal salivary gland is not known. The aim of this study was to determine if CRTC1, like many known oncogenes, is expressed during early submandibular salivary gland (SMG) development and re-expressed in an experimental tumor model.

Cytomegalovirus induces stage-dependent enamel defects and misexpression of amelogenin, enamelin and dentin sialophosphoprotein in developing mouse molars.

Of the approximately 8,400 children born each year in the US with cytomegalovirus (CMV)-induced birth defects, more than one third exhibit hypoplasia and hypocalcification of tooth enamel. Our prior studies indicated that CMV severely delayed, but did not completely interrupt, early mouse mandibular first molar morphogenesis in vitro. The aim of the present study was to examine the effects of CMV infection on progressive tooth differentiation and amelogenesis.

Cytomegalovirus induces abnormal chondrogenesis and osteogenesis during embryonic mandibular development.

Background: Human clinical studies and mouse models clearly demonstrate that cytomegalovirus (CMV) disrupts normal organ and tissue development. Although CMV is one of the most common causes of major birth defects in humans, little is presently known about the mechanism(s) underlying CMV-induced congenital malformations. Our prior studies have demonstrated that CMV infection of first branchial arch derivatives (salivary glands and teeth) induced severely abnormal phenotypes and that CMV has a particular tropism for neural crest-derived mesenchyme (NCM).

Cytomegalovirus inhibition of embryonic mouse tooth development: a model of the human amelogenesis imperfecta phenocopy.

Objective: Cytomegalovirus (CMV) is one of the most common causes of major birth defects in humans. Of the approximately 8400 children born each year in the U.S.

Cytomegalovirus-induced embryopathology: mouse submandibular salivary gland epithelial-mesenchymal ontogeny as a model.

Background: Human studies suggest, and mouse models clearly demonstrate, that cytomegalovirus (CMV) is dysmorphic to early organ and tissue development. CMV has a particular tropism for embryonic salivary gland and other head mesenchyme. CMV has evolved to co-opt cell signaling networks so to optimize replication and survival, to the detriment of infected tissues.

Embryonic salivary gland dysmorphogenesis in Twisted gastrulation deficient mice.

Objective: Mouse Twisted gastrulation gene (Twsg1) expression is found throughout embryonic development, including substantial levels in the first branchial arch that gives rise to the submandibular salivary gland (SMG). We addressed the proposition that normal Twsg1 expression is critical to normal SMG ontogenesis.

Design: Utilizing C57BL/6 embryos that were Twsg1-/- homozygotes, as well as wild type and heterozygote littermates, we investigated SMG development from gestational day 13 to newborn.

FGF10/FGFR2b signaling plays essential roles during in vivo embryonic submandibular salivary gland morphogenesis.

Background: Analyses of Fgf10 and Fgfr2b mutant mice, as well as human studies, suggest that FGF10/FGFR2b signaling may play an essential, nonredundant role during embryonic SMG development. To address this question, we have analyzed the SMG phenotype in Fgf10 and Fgfr2b heterozygous and null mutant mice. In addition, although previous studies suggest that the FGF10/FGFR2b and FGF8/FGFR2c signaling pathways are functionally interrelated, little is known about the functional relationship between these two pathways during SMG development.