Dermatology Commons^™

Quantitative Proteomic Analysis Of Stratum Corneum Dysfunction In Adult Chronic Atopic Dermatitis., Jason M Winget, Deborah Finlay, Kevin J Mills, Tom Huggins, Charles Bascom, Robert J Isfort, Robert L Moritz

Articles, Abstracts, and Reports

No abstract provided.

The Behavioral Addiction Indoor Tanning Screener (Baits): An Evaluation Of A Brief Measure Of Behavioral Addictive Symptoms, Jerod L. Stapleton, Joel J. Hillhouse, Rob Turrisi, Katie Baker, Sharon L. Manne, Elliot J. Coups

ETSU Faculty Works

No abstract provided.

Rebound Growth Of Infantile Hemangiomas After Propranolol Therapy., Sonal D. Shah, Eulalia Baselga, Catherine Mccuaig, Elena Pope, Julien Coulie, Laurence M. Boon, Maria C. Garzon, Anita N. Haggstrom, Denise Adams, Beth A. Drolet, Brandon D. Newell, Julie Powell, Maria Teresa García-Romero, Carol Chute, Esther Roe, Dawn H. Siegel, Barbara Grimes, Ilona J. Frieden

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND AND OBJECTIVES: Propranolol is first-line therapy for problematic infantile hemangiomas (IHs). Rebound growth after propranolol discontinuation is noted in 19% to 25% of patients. Predictive factors for rebound are not completely understood and may alter the management approach. The goal of the study was to describe a cohort of patients with IHs treated with propranolol and to identify predictors for rebound growth.

METHODS: A multicenter retrospective cohort study was conducted in patients with IHs treated with propranolol. Patient demographic characteristics, IH characteristics, and specifics of propranolol therapy were obtained. Episodes of rebound growth were recorded. Patients' responses to propranolol …

Increased Expression Of Napdh Oxidase 4 In Systemic Sclerosis Dermal Fibroblasts: Regulation By Transforming Growth Factor Β., Sonsoles Piera-Velazquez, Alma Makul, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Systemic sclerosis (SSc) is characterized by severe and often progressive fibrosis of the skin and multiple internal organs. The mechanisms responsible for these alterations remain obscure, although excessive reactive oxygen species (ROS)-mediated oxidative stress has been implicated. NOX-4 is 1 of 7 isoforms of NADPH oxidase responsible for the generation of ROS. The purpose of this study was to examine NOX-4 expression in skin and cultured dermal fibroblasts from SSc patients and to examine its regulation by transforming growth factor β1 (TGFβ1).

METHODS: NOX-4 was assessed in normal and SSc skin by immunohistologic analysis and in normal and SSc …

Rac1 P29s Regulates Pd-L1 Expression In Melanoma., Ha Linh Vu, Sheera Rosenbaum, Timothy J. Purwin, Michael A. Davies, Andrew E. Aplin

Department of Cancer Biology Faculty Papers

Whole exome sequencing of cutaneous melanoma has led to the detection of P29 mutations in RAC1 in 5-9% of samples, but the role of RAC1 P29 mutations in melanoma biology remains unclear. Using reverse phase protein array analysis to examine the changes in protein/phospho-protein expression, we identified cyclin B1, PD-L1, Ets-1, and Syk as being selectively upregulated with RAC1 P29S expression and downregulated with RAC1 P29S depletion. Using the melanoma patient samples in TCGA, we found PD-L1 expression to be significantly increased in RAC1 P29S patients compared to RAC1 WT as well as other RAC1 mutants. The finding that PD-L1 …

Genetic Heterogeneity Of Pseudoxanthoma Elasticum: The Chinese Signature Profile Of Abcc6 And Enpp1 Mutations., Liang Jin, Qiujie Jiang, Zhengsheng Wu, Changxia Shao, Yong Zhou, Luting Yang, Jouni Uitto, Gang Wang

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE), an autosomal recessive disorder characterized by ectopic mineralization, is caused by mutations in the ABCC6 gene. We examined clinically 29 Chinese PXE patients from unrelated families, so far the largest cohort of Asian PXE patients. In a subset of 22 patients, we sequenced ABCC6 and another candidate gene, ENPP1, and conducted pathogenicity analyses for each variant. We identified a total of 17 distinct mutations in ABCC6, 15 of them being, to our knowledge, previously unreported, including 5 frameshift and 10 missense variants. In addition, a missense mutation in combination with a recurrent nonsense mutation in ENPP1 was …

Jewish Dermatologists In Nazi Germany., Walter H.C. Burgdorf, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

With the development of medical specialties beginning in the 1860’s, physicians could devote their time to the study of specific organ systems or surgical approaches. Although Jews had been given full rights in the new Germany by 1871, prejudice and other restrictions often precluded hospital and university appointments. Major specialities like internal medicine and surgery were almost closed to Jews, as were obstetrics and gynecology. Dermatology with its heavy emphasis on sexually transmitted diseases evolved into a suitable domain for Jewish physicians almost by default. Even those Jews who converted to Christianity were not spared from discrimination. Paul Gerson Unna …

Steatocystoma Multiplex: Those Little Tumours., Ellen H. De Moll, W. Clark Lambert, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Language Barriers To Informed Consent For Dermatologic Interventions., Jordan Wang, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

CASE SCENARIO

A 39-year-old Spanish-speaking woman with limited English-language proficiency presents with her 13-year-old son to your private dermatology practice. Through her son, you learn the patient is worried about a mole that has significantly grown in size over the past 3 months. After examination, you recommend the nevus be biopsied to better evaluate it. However, you are barely able to communicate with the patient, and you suspect that her son is not interpreting everything you say based on his especially brief communications with her. To proceed with the biopsy, you must first obtain informed consent.

As the dermatologist, you …

Images In Clinical Medicine. Rumpel-Leede Sign., Krystle Wang, Jason Lee

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Inverse Lichen Planus, Michael D Lee, Laurel R Schwartz

Department of Dermatology and Cutaneous Biology Faculty Papers

A Case of Inverse Lichen Planus

Lichen planus (LP) is a pruritic, papular eruption characterized by its violaceous color and polygonal shape. It is most commonly found on the flexor surfaces of the upper extremities, on the genitalia, and on the mucous membranes. We herein report a classic case of LP in an inverse distribution.

Outdated Dermatologic Drug Samples And Obligations To The Patient., Jordan Wang, Matthew Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

CASE SCENARIO

A 37-year-old man with a slightly raised, red, scaly patch on his left arm is seen in the clinic of an academic teaching hospital by a young dermatologist. Following examination and biopsy, he is found to have squamous cell carcinoma in situ. The patient was recently laid off from work and had lost access to his health insurance. He is struggling to make ends meet for his family, so it would be difficult for him to cover any extraneous health-related expenses. Upon relaying this information to the dermatologist, the patient is provided with a full course of 5-fluorouracil …

Strategies For Anti-Fibrotic Therapies., Joel Rosenbloom, Fabian A. Mendoza, Md, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

The fibrotic diseases encompass a wide spectrum of entities including such multisystemic diseases as systemic sclerosis, nephrogenic systemic fibrosis and sclerodermatous graft versus host disease, as well as organ-specific disorders such as pulmonary, liver, and kidney fibrosis. Collectively, given the wide variety of affected organs, the chronic nature of the fibrotic processes, and the large number of individuals suffering their devastating effects, these diseases pose one of the most serious health problems in current medicine and a serious economic burden to society. Despite these considerations there is currently no accepted effective treatment. However, remarkable progress has been achieved in the …

Altered Drainage Patterns In Patients With Melanoma And Previous Axillary Dissection., Caitlyn M. Johnson, Charles Intenzo, Michael Mastrangelo, Kendra Feeney, Adam C. Berger

Department of Surgery Faculty Papers

The incidence of melanoma is increasing rapidly in the United States. Sentinel lymph node biopsy is an important diagnostic tool in the treatment and staging of melanoma. However, many patients with melanoma will have had lymph node surgery for previous melanoma or breast cancer. We set out to examine alterations in drainage patterns in patients with previous axillary dissection for breast cancer. We reviewed four patients with truncal and/or extremity melanomas and examined their lymphoscintigraphy and drainage patterns. Three patients with truncal melanoma mapped to cervical lymph nodes and a fourth patient with an arm melanoma mapped to her previously …

Perlecan Domain V Induces Vegf Secretion In Brain Endothelial Cells Through Integrin Α5Β1 And Erk-Dependent Signaling Pathways., Douglas N Clarke, Abraham Al Ahmad, Boyeon Lee, Christi Parham, Lisa Auckland, Andrezj Fertala, Michael Kahle, Courtney S Shaw, Jill Roberts, Gregory J Bix

Department of Dermatology and Cutaneous Biology Faculty Papers

Perlecan Domain V (DV) promotes brain angiogenesis by inducing VEGF release from brain endothelial cells (BECs) following stroke. In this study, we define the specific mechanism of DV interaction with the α(5)β(1) integrin, identify the downstream signal transduction pathway, and further investigate the functional significance of resultant VEGF release. Interestingly, we found that the LG3 portion of DV, which has been suggested to possess most of DV's angio-modulatory activity outside of the brain, binds poorly to α(5)β(1) and induces less BEC proliferation compared to full length DV. Additionally, we implicate DV's DGR sequence as an important element for the interaction …

Dermatofibroma: A Curious Tumor., Lawrence Parish, Shideh Yazdanian, W Clark Lambert, Peter C Lambert

Department of Dermatology and Cutaneous Biology Faculty Papers

A tumor, such as a dermatofibroma, causes consternation among many patients, but it rarely creates problems on its own. Also called a histiocytoma, it remains one of the most common mesenchymal growths. Its etiology is unknown with the previous theory that it is a dermal response to injury, such as an insect bite, being challenged. As much as patients like to blame spiders or other arthropods for traumatizing an arm or leg, no definitive explanation is available for its etiology.

Effect Of Oxidative Stress On Protein Tyrosine Phosphatase 1b In Scleroderma Dermal Fibroblasts., Pei-Suen Tsou, Nadine N. Talia, Adam J. Pinney, Ann Kendzicky, Sonsoles Piera-Velazquez, Sergio A. Jimenez, James R. Seibold, Kristine Phillips, Alisa E Koch

Department of Dermatology and Cutaneous Biology Faculty Papers

OBJECTIVE: Platelet-derived growth factor (PDGF) and its receptor, PDGFR, promote fibrosis in systemic sclerosis (SSc; scleroderma) dermal fibroblasts, and such cells in scleroderma skin lesions produce excessive reactive oxygen species (ROS). PDGFR is phosphorylated upon PDGF stimulation, and is dephosphorylated by protein tyrosine phosphatases (PTPs), including PTP1B. This study was undertaken to determine whether the thiol-sensitive PTP1B is affected by ROS in SSc dermal fibroblasts, thereby enhancing the phosphorylation of PDGFR and synthesis of type I collagen. This study also sought to investigate the effect of a thiol antioxidant, N-acetylcysteine (NAC), in SSc.

METHODS: Fibroblasts were isolated from the skin …

A Prospective Observational Study Of Mycophenolate Mofetil Treatment In Progressive Diffuse Cutaneous Systemic Sclerosis Of Recent Onset., Fabian A. Mendoza, Md, Sarah J. Nagle, Jason B. Lee, Md, Sergio A. Jimenez

Jefferson Institute of Molecular Medicine Papers and Presentations

OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset.

METHODS: Twenty-five previously untreated consecutive patients with recent-onset (< 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients.

RESULTS: At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR …

Lymph Node Ratio Is An Important And Independent Prognostic Factor For Patients With Stage Iii Melanoma, Adam C. Berger, Michael Fierro, John C. Kairys, David Berd, Takami Sato, Jocelyn Andrel, Terry Hyslop, Michael J. Mastrangelo

Kimmel Cancer Center Faculty Papers

INTRODUCTION:

The incidence of melanoma is dramatically increasing worldwide. We hypothesized that the ratio of metastatic to examined lymph node ratio (LNR) would be the most important prognostic factor for stage III patients.

METHODS:

We retrospectively reviewed our institutional database of melanoma patients and identified 168 patients who underwent lymph node dissection (LND) for stage III disease between 1993 and 2007. Patients were divided into three groups based on LNR (≤10%, n = 93; 10-≤25%, n = 45; and >25%, n = 30). Univariate and multivariate analysis was performed using Cox proportional hazards model.

RESULTS:

The median survival time of …

Abca12-Mediated Lipid Transport And Snap29-Dependent Trafficking Of Lamellar Granules Are Crucial For Epidermal Morphogenesis In A Zebrafish Model Of Ichthyosis., Qiaoli Li, Michael Frank, Masashi Akiyama, Shiu-Ying Ho, Hiroshi Shimizu, Christine Thisse, Bernard Thisse, Eli Sprecher, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Zebrafish (Danio rerio) can serve as a model system to study heritable skin diseases. The skin is rapidly developed during the first 5-6 days of embryonic growth, accompanied by expression of skin-specific genes. Transmission electron microscopy (TEM) of wild-type zebrafish at day 5 reveals a two-cell-layer epidermis separated from the underlying collagenous stroma by a basement membrane with fully developed hemidesmosomes. Scanning electron microscopy (SEM) reveals an ordered surface contour of keratinocytes with discrete microridges. To gain insight into epidermal morphogenesis, we have employed morpholino-mediated knockdown of the abca12 and snap29 genes, which are crucial for secretion of lipids and …

Mechanisms Of Resistance To Raf Inhibitors In Melanoma., A E Aplin, Fred M Kaplan, Yongping Shao

Department of Cancer Biology Faculty Papers

The recent RAF inhibitor trial with PLX4032/RG7204 in late-stage mutant B-RAF melanoma patients has been lauded as a success story for personalized cancer therapy since short-term clinical responses were observed in the majority of patients. However, initial responses were followed by subsequent tumor re-growth, and a subset of patients showed intrinsic resistance. Bi-directional translational efforts are now essential to determine the mechanisms underlying acquired/secondary and intrinsic resistance to RAF inhibitors.

Differential Regulation Of P53 Function By The N-Terminal Δnp53 And Δ113p53 Isoforms In Zebrafish Embryos., William R Davidson, Csaba Kari, Qing Ren, Borbala Daroczi, Adam P Dicker, Ulrich Rodeck

Department of Radiation Oncology Faculty Papers

BACKGROUND: The p53 protein family coordinates stress responses of cells and organisms. Alternative promoter usage and/or splicing of p53 mRNA gives rise to at least nine mammalian p53 proteins with distinct N- and C-termini which are differentially expressed in normal and malignant cells. The human N-terminal p53 variants contain either the full-length (FL), or a truncated (ΔN/Δ40) or no transactivation domain (Δ133) altogether. The functional consequences of coexpression of the different p53 isoforms are poorly defined. Here we investigated functional aspects of the zebrafish ΔNp53 ortholog in the context of FLp53 and the zebrafish Δ133p53 ortholog (Δ113p53) coexpressed in the …

Granuloma Annulare: Not As Simple As It Seems., Lawrence Charles Parish, Joseph A. Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Updating The Dermatologic Nomenclature: Names That Are Good Or Bad., Lawrence Charles Parish, Joseph A. Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

Dermatology probably has the largest vocabulary of any of the medical specialties,¹ a statement to which we can attest when we reviewed aspects of the Dermatology Lexicon project. Some terms are derived from the Latin or Greek and present spelling problems to all but a select few. Examples include acrokeratosis verruciformis and pterigium. Other diseases carry names that are such a mouthful that few can call them out without the interruption of breathing. These might include erosio interdigitalis blastomycetica and dermatitis exudative discoid and lichenoid of Sulzberger and Garbe. No wonder the former is now referred to simply as …

Human Papillomavirus And Survival Of Patients With Oropharyngeal Cancer., K Kian Ang, Jonathan Harris, Richard Wheeler, Randal Weber, David I Rosenthal, Phuc Felix Nguyen-Tân, William H Westra, Christine H Chung, Richard C Jordan, Charles Lu, Harold Kim, Rita S. Axelrod, Md, C Craig Silverman, Kevin P Redmond, Maura L Gillison

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: Oropharyngeal squamous-cell carcinomas caused by human papillomavirus (HPV) are associated with favorable survival, but the independent prognostic significance of tumor HPV status remains unknown.

METHODS: We performed a retrospective analysis of the association between tumor HPV status and survival among patients with stage III or IV oropharyngeal squamous-cell carcinoma who were enrolled in a randomized trial comparing accelerated-fractionation radiotherapy (with acceleration by means of concomitant boost radiotherapy) with standard-fractionation radiotherapy, each combined with cisplatin therapy, in patients with squamous-cell carcinoma of the head and neck. Proportional-hazards models were used to compare the risk of death among patients with HPV-positive …

Biomarkers In Systemic Sclerosis., Susan V. Castro, Sergio A. Jimenez

Scleroderma Center Faculty Papers

Systemic sclerosis is an autoimmune inflammatory disorder of unknown etiologycharacterized b y pronounced fibroproliferative alterations in the microvasculature, and frequent cellular and humoral immunity abnormalities, culminating in a severe and often progressive fibrotic process. Numerous biomarkers reflecting the three main pathogenetic mechanisms in systemic sclerosis have been described; however, aside from several disease-specific autoantibodies, other biomarkers have not been thoroughly validated and require further study. Thus, there is an unmet need for validated biomarkers for diagnosis, disease classification, and evaluation of organ involvement and therapeutic response in systemic sclerosis.

The Most Important Medical Source: Aunt Mabel Knows Best., Lawrence Parish, Joseph A Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

Not so long ago, one of us was consulted by a middle-aged woman with rosacea. For many years, she had had periodic flares of red papules and pustules on her nose and the adjoining areas. The confluent telangiectasia on her cheeks gave a permanent appearance of well-applied rouge. She had seen several dermatologists and had received a wide variety of medications, all of which seemed appropriate except to her as would be subsequently revealed. She wanted a new approach, but there were limitations placed upon her request: no pills or capsules; nothing odiferous; no agent that might bleach clothing; and …

R992c (P.R1192c) Substitution In Collagen Ii Alters The Structure Of Mutant Molecules And Induces The Unfolded Protein Response., Hye Jin Chung, Deborah A. Jensen, Katarzyna Gawron, Andrzej Steplewski, Andrzej Fertala

Department of Dermatology and Cutaneous Biology Faculty Papers

We investigated the molecular bases of spondyloepiphyseal dysplasia (SED) associated with the R992C (p.R1192C) substitution in collagen II. At the protein level, we analyzed the structure and integrity of mutant molecules, and at the cellular level, we specifically studied the effects of the presence of the R992C collagen II on the biological processes taking place in host cells. Our studies demonstrated that mutant collagen II molecules were characterized by altered electrophoretic mobility, relatively low thermostability, the presence of atypical disulfide bonds, and slow rates of secretion into the extracellular space. Analyses of cellular responses to the presence of the mutant …

Freedom For The Bulgarian Nurses And A Palestinian Doctor., Lawrence Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

On July 24, 2007, the five Bulgarian nurses and the Palestinian, unjustly accused of infecting Libyan children with the AIDS virus, were freed by the Libyan government. They had spent a tumultuous seven years in prison, much of the time on death row, having been accused of injecting the children with tainted blood they had brought with them. This was not only preposterous but also an impossibility as the particular strain of the AIDS virus had been found in Libya, two years prior. [1]

Dermatology 75 Years Ago., Lawrence Parish, Joseph A Witkowski

Department of Dermatology and Cutaneous Biology Faculty Papers

It seems that the practicing dermatologist in 2007 is being attacked on all fronts. The Food and Drug Administration has mandated a cumbersome program for monitoring isotrentinoin usage, its analogue barely comes under scrutiny. iPledge is just a plain nightmare. The acumen of the board certified dermatologist is being challenged by Maintenance of Certification proposals because other specialties are doing it; yet, the neighborhood pharmacist is unhampered in dispensing all sorts of advice about treatment. The insurance clerk thrives on denying medication, prescribed by the physician, using flawed reasoning or else suggesting that a ten days’ supply of medicine should …