Abnormal Uterine Bleeding during Pubertal Induction with Transdermal Estrogen in Individuals with Turner Syndrome.

STUDY OBJECTIVE: Incidence of abnormal uterine bleeding (AUB) during pubertal induction among individuals with Turner syndrome (TS) has not been described previously. We estimated the incidence and characterized factors associated with AUB among individuals with TS. A secondary objective was to evaluate the management of AUB among this patient population. DESIGN, SETTING, PARTICIPANTS, AND INTERVENTION: We conducted a retrospective chart review to evaluate individuals with TS undergoing hormone replacement therapy (HRT) for pubertal induction with transdermal estrogen. A total of 45 participants were identified between January 2007 and June 2019. RESULTS: Of the 45 individuals with TS included, 16 (35%) experienced AUB. Individuals with AUB most commonly experienced prolonged (44%), prolonged and heavy (25%), and intermenstrual (19%) bleeding. Individuals who experienced AUB were more likely to experience spontaneous bleeding (69% vs 28%) and a duration of unopposed estrogen greater than 18 months (63% vs 41%), undergo progestin cycling less often than monthly (69% vs 0%), use a micronized progestin dose of less than 200 mg (25% vs 14%), and be noncompliant with HRT (19% vs 0%) compared with those who did not experience AUB. CONCLUSION: There is a relatively high incidence of AUB among individuals with TS undergoing pubertal induction with transdermal estrogen. Care providers should consider the clinical factors examined to guide monitoring and management of individuals with TS on HRT.

Characterization of an Electronic Corneal Prosthesis System.

PURPOSE: Corneal opacity is a leading cause of reversible blindness worldwide. An electronic corneal prosthesis, or intraocular projector, could potentially restore high-quality vision without need for corneal clarity. MATERIALS AND METHODS: Four intraocular projection systems were constructed from commercially available electronic components and encased in biocompatible plastic housing. They were tested for optical properties, biocompatibility, heat dissipation, waterproofing, and accelerated wear. A surgical implantation technique was developed. RESULTS: Intraocular projectors were produced of a size that can fit within the eye. Their optics produce better than 20/200 equivalent visual acuity. MTT assay demonstrated no cytotoxicity of devices in vitro. Temperature testing demonstrated less than 2°C increase in temperature after 1 h. Three devices lasted over 12 weeks under accelerated wear conditions. Implantation surgery was demonstrated via corneal trephination insertion in a cadaver eye. CONCLUSION: This is the first study to demonstrate and characterize fully functional intraocular projection systems. This technology has the potential to be an important new tool in the treatment of intractable corneal blindness.

Feasibility of Intraocular Projection for Treatment of Intractable Corneal Opacity.

Despite many decades of research and development, corneal opacity remains a leading cause of reversible blindness worldwide. Corneal transplantation and keratoprosthesis can restore corneal clarity, but both have well-known limitations. High-resolution electronic microdisplays may offer an alternative to traditional methods of treating corneal disease using an intraocular implant to project imagery onto the retina, obviating the need for a clear cornea. In this study, we review previous work and recent technologic developments relevant to the development of such an intraocular projection system.

Regulation of cell proliferation and migration by keratin19-induced nuclear import of early growth response-1 in breast cancer cells.

PURPOSE: Keratin19 (KRT19) is the smallest known type I intermediate filament and is used as a marker for reverse transcriptase PCR-mediated detection of disseminated tumors. In this study, we investigated the functional analysis of KRT19 in human breast cancer. EXPERIMENTAL DESIGN: Using a short hairpin RNA system, we silenced KRT19 in breast cancer cells. KRT19 silencing was verified by Western blot analysis and immunocytochemistry. We further examined the effect of KRT19 silencing on breast cancer cells by cell proliferation, migration, invasion, colony formation assay, cell-cycle analysis, immunocytochemistry, immunohistochemistry, and mouse xenograft assay. RESULTS: Silencing of KRT19 resulted in increased cell proliferation, migration, invasion, and survival. These effects were mediated by upregulation of Akt signaling as a result of reduced PTEN mRNA expression. Silencing of KRT19 decreased the nuclear import of early growth response-1 (Egr1), a transcriptional factor for PTEN transcription, through reduced association between Egr1 and importin-7. We also confirmed that silencing of KRT19 increased tumor formation in a xenograft model. CONCLUSIONS: KRT19 is a potential tumor suppressor that negatively regulates Akt signaling through modulation of Egr1 nuclear localization.

Hematopoetic prostaglandin D synthase: an ESR1-dependent oviductal epithelial cell synthase.

Oviductal disease is a primary cause of infertility, a problem that largely stems from excessive inflammation of this key reproductive organ. Our poor understanding of the mechanisms regulating oviductal inflammation restricts our ability to diagnose, treat, and/or prevent oviductal disease. Using mice, our objective was to determine the spatial localization, regulatory mechanism, and functional attributes of a hypothesized regulator of oviductal inflammation, the hematopoietic form of prostaglandin D synthase (HPGDS). Immunohistochemistry revealed specific localization of HPGDS to the oviduct's epithelium. In the isthmus, expression of HPGDS was consistent. In the ampulla, expression of HPGDS appeared dependent upon stage of the estrous cycle. HPGDS was expressed in the epithelium of immature and cycling mice but not in the oviducts of estrogen receptor α knockouts. Two receptor subtypes bind PGD2: PGD2 receptor and G protein-coupled receptor 44. Expression of mRNA for Ptgdr was higher in the epithelial cells (EPI) than in the stroma (P < 0.05), whereas mRNA for Gpr44 was higher in the stroma than epithelium (P < 0.05). Treatment of human oviductal EPI with HQL-79, an inhibitor of HPGDS, decreased cell viability (P < 0.05). Treatment of mice with HQL-79 increased mRNA for chemokine (C-C motif) ligands 3, 4, and 19; chemokine (C-X-C motif) ligands 11 and 12; IL-13 and IL-17B; and TNF receptor superfamily, member 1b (P < 0.02 for each mRNA). Overall, these results suggest that HPGDS may play a role in the regulation of inflammation and EPI health within the oviduct.

Crowded bis ligand complexes of Ttz(Ph,Me) with first row transition metals rearrange due to ligand field effects: structural and electronic characterization (Ttz(Ph,Me) = tris(3-phenyl-5-methyl-1,2,4-triazolyl)borate).

The tris(3-phenyl-5-methyl-1,2,4-triazolyl)borate (Ttz(Ph,Me)) ligand provides intermediate steric bulk and forms predominantly bis(ligand) complexes of the form M(Ttz(Ph,Me))(2) with first row divalent transition metals (1(M), M = Zn, Cu, Ni, Co, Fe, Mn). Due to ligand field effects that are greatest with Ni and Cu, ligand rearrangement is favored with these metals and Cu(Ttz(Ph,Me)*)(2) (1(Cu)*) and (Ttz(Ph,Me)*)Ni(Ttz(Ph,Me)) (1(Ni)*) were isolated by selective recrystallization and fully characterized (* indicates a rearranged Ttz ligand with Ph and Me in swapped positions in one triazole ring). For comparison with Co(Ttz(Ph,Me))(2), the less bulky analogs (Ttz(H,H))(2)Co (4) and (Ttz(Me,Me))(2)Co (5) were studied by NMR and EPR spectroscopy, and 5 was crystallographically characterized. These complexes allow for a study of how slight changes in structure and electron donor properties (for Ni and Cu), as well as dramatic changes in steric bulk (for Co), influence the physical properties; specifically there are significant changes in the UV-Vis, EPR and NMR spectra. Bis(ligand) complexes predominate with all metals, but (Ttz(Ph,Me))Ni(OH(2))Cl (2) and (Ttz(Ph,Me))ZnBr (3) were also isolated and these show that Ttz(Ph,Me) is coordinatively flexible.

Expression of coxsackievirus and adenovirus receptor isoforms in developing mouse bladder uroepithelium.

OBJECTIVES: Tight junctions are important for uroepithelial paracellular permeability barriers. In the present study, we examined the developmental changes in the expression of coxsackievirus and adenovirus receptor (CAR) isoforms in mouse bladder uroepithelium. METHODS: Multiplex reverse transcriptase polymerase chain reaction using CAR isoform-specific primer sets and Western blotting were conducted on gestational day 19 and postnatal days 1, 7, and 55. Subcellular localization of CAR was examined, together with occludin and zonula occludens-1, in neonatal and adult bladder using light microscopy and immunofluorescence microscopy. RESULTS: The total CAR and short CAR isoform mRNA were significantly increased from gestational day 19 to birth. Long CAR isoform mRNA was transiently decreased on postnatal day 7 and had recovered during adulthood. On Western blotting, molecular weight 46-kDa CAR was abundant in the mucosa and increased postnatally. In the neonatal, as well as the adult, bladder uroepithelium, CAR immunoreactivity was observed, together with occludin and zonula occludens-1 at the apical tight junctions and basolateral contacts between the adjacent uroepithelial cells. In adult bladder uroepithelium, CAR was increased at the interface between the basal cells and basal lamina. CONCLUSIONS: The expression patterns of CAR isoforms changed during the late fetal to adult development of the mouse bladder. CAR at the apical tight junctions and cellular adhesions between the uroepithelial cells and the interfaces between the basal cells and basal lamina might support the paracellular permeability barrier and structural integrity of the uroepithelium in the mouse bladder. The expression of CAR in the uroepithelial cells can be integrated as a part of the strategy for virus-mediated gene therapy in the bladder uroepithelium.