Browsing by Author "Miller, Christopher J."

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    Differential Iron Requirements for Osteoblast and Adipocyte Differentiation
    (Wiley, 2021-07-26) Edwards, Daniel F., III.; Miller, Christopher J.; Quintana-Martinez, Arelis; Wright, Christian S.; Prideaux, Matthew; Atkins, Gerald J.; Thompson, William R.; Clinkenbeard, Erica L.; Medical and Molecular Genetics, School of Medicine
    Bone marrow mesenchymal progenitor cells are precursors for various cell types including osteoblasts, adipocytes, and chondrocytes. The external environment and signals act to direct the pathway of differentiation. Importantly, situations such as aging and chronic kidney disease display alterations in the balance of osteoblast and adipocyte differentiation, adversely affecting bone integrity. Iron deficiency, which can often occur during aging and chronic kidney disease, is associated with reduced bone density. The purpose of this study was to assess the effects of iron deficiency on the capacity of progenitor cell differentiation pathways. Mouse and human progenitor cells, differentiated under standard osteoblast and adipocyte protocols in the presence of the iron chelator deferoxamine (DFO), were used. Under osteogenic conditions, 5μM DFO significantly impaired expression of critical osteoblast genes, including osteocalcin, type 1 collagen, and dentin matrix protein 1. This led to a reduction in alkaline phosphatase activity and impaired mineralization. Despite prolonged exposure to chronic iron deficiency, cells retained viability as well as normal hypoxic responses with significant increases in transferrin receptor and protein accumulation of hypoxia inducible factor 1α. Similar concentrations of DFO were used when cells were maintained in adipogenic conditions. In contrast to osteoblast differentiation, DFO modestly suppressed adipocyte gene expression of peroxisome-proliferating activated receptor gamma, lipoprotein lipase, and adiponectin at earlier time points with normalization at later stages. Lipid accumulation was also similar in all conditions. These data suggest the critical importance of iron in osteoblast differentiation, and as long as the external stimuli are present, iron deficiency does not impede adipogenesis.
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    Systematic Review and Meta-Analysis of Local Recurrence Rates of Head and Neck Cutaneous Melanomas after Wide Local Excision, Mohs Micrographic Surgery, or Staged Excision
    (Science Direct, 2021-09-01) Bittar, Peter G.; Bittar, Julie M.; Etzkorn, Jeremy R.; Brewer, Jerry D.; Aizman, Leora; Shin, Thuzar M.; Sobanko, Joseph F.; Higgins, Harold W.; Giordano, Cerrene N.; Cohen, Justine V.; Pride, Renee; Wan, Marilyn T.; Leitenberger, Justin J.; Bar, Anna A.; Aasi, Sumaira; Bordeaux, Jeremy S.; Miller, Christopher J.; Dermatology, School of Medicine
    Background Prospective trials have not compared local recurrence rates for different excision techniques for cutaneous melanomas on the head and neck. Objective To determine local recurrence rates of cutaneous head and neck melanoma after wide local excision (WLE), Mohs micrographic surgery (MMS), or staged excision. Methods A systematic review of PubMed, EMBASE, and Web of Science identified all English case series, cohort studies and randomized controlled trials that reported local recurrence rates after surgery of cutaneous head and neck melanoma. A meta-analysis utilizing a random effects model calculated weighted local recurrence rates and confidence intervals (CI) for each surgical technique and for subgroups of MMS and staged excision. Results Among one-hundred manuscripts with 13,998 head and neck cutaneous melanomas, 51.0% (7138) of melanomas were treated by WLE; 34.5% (4,826) by MMS; and 14.5% (2,034) by staged excision. Local recurrence rates were lowest for MMS (0.61%; 95%CI, 0.1%-1.4%); followed by staged excision (1.8%; 95%CI, 0.1%-2.9%) and WLE (7.8%; 95%CI, 6.4%-9.3%). Limitations Definitions of local recurrence varied. Surgical techniques included varying proportions of invasive melanomas. Studies had heterogeneity. Conclusion Systematic review and meta-analysis show lower local recurrence rates for cutaneous head and neck melanoma after treatment with MMS or staged excision compared to WLE.