Browsing by Author "Katona, Terrence"
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Item Baseline Biomechanical Properties of Epithelia prior to Tissue Expansion in Dogs(Lippincott, Williams & Wilkins, 2018-05-14) Bowling, Jay; Davidson, Darrell D.; Tholpady, Sunil S.; Park, Kinam; Eckert, George J.; Katona, Terrence; Chu, Tien-Min G.; Barco, Clark T.; Periodontology, School of DentistryBackground: Soft-tissue deficiencies pose a challenge in a variety of disease processes when the end result is exposure of underlying tissue. Although multiple surgical techniques exist, the transposition of tissue from one location to another can cause donor-site morbidity, long incisions prone to dehiscence, and poor patient outcomes as a result. Use of tissue expansion prior to grafting procedures has been shown to have success in increasing available soft tissue to aid in repairing wounds. However, the current tissue expanders have biomechanical limits to the extent and rate of expansion that usually exceeds the tissue capacity, leading to incisional dehiscence or expander extrusion. Understanding the baseline biomechanical properties of the tissue to be expanded would provide useful information regarding surgical protocol employed for a given anatomical location. Therefore, the aim of this study was to test and compare the baseline (preexpansion) biomechanical properties of different common expansion sites in dogs. Methods: Four samples measuring approximately 20 × 15 × 1 mm were harvested from 8 dogs. The samples were collected from the hard palate, alveolar mucosa, scalp, and chest of the animal and analyzed for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength using a Texture Technologies TA.XT texture analyzer with corresponding biomechanical measurement software. Samples were compared as to their baseline biomechanical properties prior to any soft-tissue expansion. Histological sections of the samples were analyzed using hematoxylin eosin in an attempt to correlate the histological description to the biomechanical properties seen during testing. Summary statistics (mean, standard deviation, standard error, range) are reported for stress, strain, maximum tangential stiffness, maximum tangential modulus, and tensile strength and for the histological parameters by intraoral site. Analysis of variance was used to compare the biomechanical and histological parameters among the 4 locations while accounting for multiple measurements from each dog. Results: The scalp had significantly higher maximum stress (σmax) than chest, mucosa, and palate (P < 0.0001), with no differences among the other 3 locations (P > 0.63). Scalp site also had significantly higher maximum tangential modulus (ε) than chest, mucosa, and palate (P < 0.006), with no differences among the other 3 locations (P > 0.17). The locations did not have significantly different maximum tangential stiffness (k; P = 0.72). Histologically, 2 separate patterns of collagen disruption were evident. Conclusion: Although different results were obtained than theorized, this study showed that the scalp had the greatest resiliency to expand prior to tearing, and the highest tangential modulus, with all sites having statistically similar modulus of elasticity. Based on this study, the scalp could be expanded more aggressively compared with the other sites.Item Epidermal PPARγ Is a Key Homeostatic Regulator of Cutaneous Inflammation and Barrier Function in Mouse Skin(MDPI, 2021-08-11) Konger, Raymond L.; Derr-Yellin, Ethel; Zimmers, Teresa A.; Katona, Terrence; Xuei, Xiaoling; Liu, Yunlong; Zhou, Hong-Ming; Simpson, Ed Ronald, Jr.; Turner, Matthew J.; Pathology and Laboratory Medicine, School of MedicineBoth agonist studies and loss-of-function models indicate that PPARγ plays an important role in cutaneous biology. Since PPARγ has a high level of basal activity, we hypothesized that epidermal PPARγ would regulate normal homeostatic processes within the epidermis. In this current study, we performed mRNA sequencing and differential expression analysis of epidermal scrapings from knockout mice and wildtype littermates. Pparg-/-epi mice exhibited a 1.5-fold or greater change in the expression of 11.8% of 14,482 identified transcripts. Up-regulated transcripts included those for a large number of cytokines/chemokines and their receptors, as well as genes associated with inflammasome activation and keratinization. Several of the most dramatically up-regulated pro-inflammatory genes in Pparg-/-epi mouse skin included Igfl3, 2610528A11Rik, and Il1f6. RT-PCR was performed from RNA obtained from non-lesional full-thickness skin and verified a marked increase in these transcripts, as well as transcripts for Igflr1, which encodes the receptor for Igfl3, and the 2610528A11Rik receptor (Gpr15). Transcripts for Il4 were detected in Pparg-/-epi mouse skin, but transcripts for Il17 and Il22 were not detected. Down-regulated transcripts included sebaceous gland markers and a number of genes associated with lipid barrier formation. The change in these transcripts correlates with an asebia phenotype, increased transepidermal water loss, alopecia, dandruff, and the appearance of spontaneous inflammatory skin lesions. Histologically, non-lesional skin showed hyperkeratosis, while inflammatory lesions were characterized by dermal inflammation and epidermal acanthosis, spongiosis, and parakeratosis. In conclusion, loss of epidermal Pparg alters a substantial set of genes that are associated with cutaneous inflammation, keratinization, and sebaceous gland function. The data indicate that epidermal PPARγ plays an important role in homeostatic epidermal function, particularly epidermal differentiation, barrier function, sebaceous gland development and function, and inflammatory signaling.Item Immune Checkpoint Inhibitor-Induced Colitis Presenting As Lymphocytic Colitis(Cureus, 2021-09-18) Khan, Jaffar; Katona, Terrence; Pathology and Laboratory Medicine, School of MedicineCheckpoint inhibitors (CPIs) are a new class of drugs that have changed the treatment and prognosis of several malignancies, even in their advanced stages. These drugs have increased patient survival rates. CPIs stimulate the immune system and include cytotoxic T-lymphocyte antigen-4 inhibitors (ipilimumab), programmed cell death inhibitors such as pembrolizumab, nivolumab, and avelumab, and programmed cell death protein ligand-1 inhibitors such as atezolizumab. Herein, we present a case of CPI-induced colitis in a 45-year-old woman with a history of melanoma. The melanoma was BRAF-positive with a V600 mutation. She had metastasis to the brain and the right 10th rib, which underwent surgery and radiation treatment, respectively. She was treated with nivolumab and denosumab. The patient presented with chronic watery diarrhea. Biopsy revealed lymphocytic colitis-like changes in the colon and terminal ileum. Thus, given the history of CPIs, a diagnosis of CPIS-induced colitis was made.Item Trichodysplasia Spinulosa in Gorlin Syndrome Treated With Vismodegib—Reply(2015-04) Richey, Justin D.; Katona, Terrence; Travers, Jeffrey B.; Department of Pathology and Laboratory Medicine, IU School of Medicine