Browsing by Author "Balkin, Daniel M."

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    Association of Demographic Factors and Infantile Hemangioma Characteristics With Risk of PHACE Syndrome
    (American Medical Association, 2021) Cotton, Colleen H.; Ahluwalia, Jusleen; Balkin, Daniel M.; Frieden, Ilona J.; Haggstrom, Anita N.; Castelo-Soccio, Leslie A.; Liy-Wong, Carmen; Pope, Elena; Steiner, Jack E.; Siegel, Dawn H.; Fernandez-Faith, Esteban; Morel, Kimberly D.; Lauren, Christine T.; Garzon, Maria C.; Mancini, Anthony J.; Chamlin, Sarah L.; Tollefson, Megha M.; Liang, Marilyn G.; Delano, Sophia; Glick, Sharon A.; Hogeling, Marcia; Barrio, Victoria R.; PHACE Retrospective Study Group; Dermatology, School of Medicine
    Importance: A 2010 prospective study of 108 infants estimated the incidence of PHACE (posterior fossa malformations, hemangioma, arterial anomalies, cardiac defects, eye anomalies) syndrome to be 31% in children with facial infantile hemangiomas (IHs) of at least 22 cm2. There is little evidence regarding the associations among IH characteristics, demographic characteristics, and risk of PHACE syndrome. Objectives: To evaluate demographic characteristics and comorbidities in a large cohort of patients at risk for PHACE syndrome and assess the clinical features of large head and neck IH that may be associated with a greater risk of a diagnosis of PHACE syndrome. Design, setting, and participants: This multicenter, retrospective cohort study assessed all patients with a facial, head, and/or neck IH who were evaluated for PHACE syndrome from August 1, 2009, to December 31, 2014, at 13 pediatric dermatology referral centers across North America. Data analysis was performed from June 15, 2017, to February 29, 2020. Main outcomes and measures: The main outcome was presence or absence of PHACE syndrome. Data included age at diagnosis, sex, patterns of IH presentation (including size, segment location, and depth), diagnostic procedures and results, and type and number of associated anomalies. Results: A total of 238 patients (mean [SD] age, 2.96 [4.71] months; 184 [77.3%] female) were included in the analysis; 106 (44.5%) met the criteria for definite (n = 98) or possible (n = 8) PHACE syndrome. A stepwise linear regression model found that a surface area of 25 cm2 or greater (odds ratio [OR] 2.99; 95% CI, 1.49-6.02) and involvement of 3 or more locations (OR, 17.96; 95% CI, 6.10-52.85) to be statistically significant risk factors for PHACE syndrome. Involvement of the parotid gland (OR, 0.39; 95% CI, 0.18-0.85) and segment S2 (OR, 0.38; 95% CI, 0.16-0.91) was associated with a lower risk. Race and ethnicity may also be associated with PHACE syndrome risk, although more studies are needed. Conclusions and relevance: This cohort study further described factors associated with both a higher and lower risk of PHACE syndrome. The presence of multiple anatomical sites and large surface area were associated with greater risk, whereas S2 or parotid IHs were associated with lower, but still potential, risk. These findings can help in counseling families and decision-making regarding evaluation of infants with large head and neck IHs.
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    Smad3 Mediates Activin-Induced Transcription of Follicle-Stimulating Hormone β-Subunit Gene
    (Oxford University Press, 2005-07-01) Suszko, Magdalena I.; Balkin, Daniel M.; Chen, Yan; Woodruff, Teresa K.; Medical and Molecular Genetics, School of Medicine
    Synthesis of FSH by the anterior pituitary is regulated by activin, a member of the TGFβ superfamily of ligands. Activin signals through a pathway that involves the activation of the transcriptional coregulators Smad2 and Smad3. Previous work from our laboratory demonstrated that Smad3, and not Smad2, is sufficient for stimulation of the rat FSHβ promoter in a pituitary-derived cell line LβT2. Here, we used RNA interference technology to independently decrease the expression of Smad proteins in LβT2 cells to further investigate Smad2 and Smad3 roles in activin-dependent regulation of the FSHβ promoter. Down-regulation of Smad2 protein by small interfering RNA duplexes affects only basal transcription of FSHβ, whereas decreased expression of Smad3 abrogates activin-mediated stimulation of FSHβ transcription. Although highly related, Smad2 and Smad3 differ in their Mad homolog (MH) 1 domains, where the Smad2 protein contains two additional stretches of amino acids that prevent this factor from binding to DNA. We investigated whether these structural features contribute to differential FSHβ transactivation by Smad2 and Smad3. A variety of Smad chimera constructs were generated and used in transient transfection studies to address this question. Only cotransfection of chimera constructs that contain the MH1 domain of Smad3 results in activin-mediated stimulation of the rat FSHβ promoter. Furthermore, the insertion of Smad2 loops into Smad3 protein renders it inactive, suggesting that DNA binding is necessary for Smad3-mediated stimulation of the rat FSHβ promoter. Taken together, these results indicate that the functional differences between Smad2 and Smad3 in their ability to transactivate the rat FSHβ promoter lie primarily within the MH1 domain and involve structural motifs that affect DNA binding.