Dermatology Commons^™

Review Article: Pathogenesis And Clinical Manifestations Of Gastrointestinal Involvement In Systemic Sclerosis., Sumit Kumar, Jagmohan Singh, Satish Rattan, Anthony J. Dimarino, Sidney Cohen, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Gastrointestinal tract (GIT) involvement is a common cause of debilitating symptoms in patients with systemic sclerosis (SSc). There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis.

AIMS: To investigate novel aspects of the pathogenesis of gastrointestinal involvement in SSc. To summarise existing knowledge regarding the cardinal clinical gastrointestinal manifestations of SSc and its pathogenesis, emphasising recent investigations that may be valuable in identifying potentially novel therapeutic targets.

METHODS: Electronic (PubMed/Medline) and manual Google search.

RESULTS: The GIT is the most common internal …

Challenges To Smartphone Applications For Melanoma Detection, Jordan V. Wang, Lance W. Chapman, Matthew S. Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

This commentary addresses the emerging market for health-related smartphone applications. Specific to dermatology, there has been a significant increase not only in applications that promote skin cancer awareness and education but also in those meant for detection. With evidence showing that 365 dermatology-related applications were available in 2014--up from 230 in 2012--and that 1 in 5 patients under the age of 50 have used a smartphone to help diagnose a skin problem, there is clearly a large subset of patients participating in this growing trend. Therefore, we are obligated to take a closer look into this phenomenon. Studies have shown …

Ladarixin, A Dual Cxcr1/2 Inhibitor, Attenuates Experimental Melanomas Harboring Different Molecular Defects By Affecting Malignant Cells And Tumor Microenvironment., Daria Marley Kemp, Alyson Pidich, Mary Larijani, Rebecca Jonas, Elizabeth Lash, Takami Sato, Mizue Terai, Maria De Pizzol, Marcello Allegretti, Olga Igoucheva, Vitali Alexeev

Department of Dermatology and Cutaneous Biology Faculty Papers

CXCR1 and CXCR2 chemokine receptors and their ligands (CXCL1/2/3/7/8) play an important role in tumor progression. Tested to date CXCR1/2 antagonists and chemokine-targeted antibodies were reported to affect malignant cells in vitro and in animal models. Yet, redundancy of chemotactic signals and toxicity hinder further clinical development of these approaches. In this pre-clinical study we investigated the capacity of a novel small molecule dual CXCR1/2 inhibitor, Ladarixin (LDX), to attenuate progression of experimental human melanomas. Our data showed that LDX-mediated inhibition of CXCR1/2 abrogated motility and induced apoptosis in cultured cutaneous and uveal melanoma cells and xenografts independently of the …

Hyaline Fibromatosis Syndrome: A Novel Mutation And Recurrent Founder Mutation In The Cmg2/Antxr2 Gene., Leila Youssefian, Hassan Vahidnezhad, Yahya Aghighi, Vahid Ziaee, Sirous Zeinali, Maryam Abiri, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Joseph Albin Witkowski, Md (1925–2015), A Dermatologist For All Seasons, Lawrence Charles Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Distinct Cell Stress Responses Induced By Atp Restriction In Quiescent Human Fibroblasts., Nirupama Yalamanchili, Andres Kriete, David Alfego, Kelli M Danowski, Csaba Kari, Ulrich Rodeck

Department of Dermatology and Cutaneous Biology Faculty Papers

Quiescence is the prevailing state of many cell types under homeostatic conditions. Yet, surprisingly little is known about how quiescent cells respond to energetic and metabolic challenges. To better understand compensatory responses of quiescent cells to metabolic stress, we established, in human primary dermal fibroblasts, an experimental 'energy restriction' model. Quiescence was achieved by short-term culture in serum-deprived media and ATP supply restricted using a combination of glucose transport inhibitors and mitochondrial uncouplers. In aggregate, these measures led to markedly reduced intracellular ATP levels while not compromising cell viability over the observation period of 48 h. Analysis of the transcription …

Bibliography Of Secondary Sources On The History Of Dermatology Ii. Obituaries And Biographies In English Supplemented Through 2015, Sarah Brenner, Md (Editor), Lawrence Parish, Md, Michael J. Lavery, Mb Bch Bao; Mrcp, Andrzej Grzybowski, Md, Phd, Jennifer L. Parish, Md, Daniel H. Parish, Md, Jd

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

A bibliographic record on the history of dermatology has been a project that started over 4 decades ago. It is a collection of all forms of history, ranging from dermatologic conditions, to famous dermatologists and physicians who have advanced the field of both dermatology and medicine, to the different countries that promoted the development of scientists, researchers and physicians alike.

It was decided that the bibliographic record would encompass journals, books and a compilation of obituaries. A pertinent question is whether a manually created bibliographic project is still warranted in the 21^st century. In short, yes. While Index …

Bibliography Of Secondary Sources On The History Of Dermatology, Sarah Brenner, Md (Editor), Lawrence Parish, Md, Michael J. Lavery, Mb Bch Bao; Mrcp, Andrzej Grzybowski, Md, Phd, Jennifer L. Parish, Md, Daniel H. Parish, Md, Jd

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

A bibliographic record on the history of dermatology has been a project that started over 4 decades ago. It is a collection of all forms of history, ranging from dermatologic conditions, to famous dermatologists and physicians who have advanced the field of both dermatology and medicine, to the different countries that promoted the development of scientists, researchers and physicians alike.

It was decided that the bibliographic record would encompass journals, books and a compilation of obituaries. A pertinent question is whether a manually created bibliographic project is still warranted in the 21^st century. In short, yes. While Index …

Bibliography Of Secondary Sources On The History Of Dermatology Iii. Books, Monographs, And Chapters In English Supplemented Through 2015, Sarah Brenner, Md (Editor), Lawrence Parish, Md, Michael J. Lavery, Mb Bch Bao; Mrcp (Uk, Andrzej Grzybowski, Md, Phd, Jennifer L. Parish, Md, Daniel H. Parish, Md, Jd

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

A bibliographic record on the history of dermatology has been a project that started over 4 decades ago. It is a collection of all forms of history, ranging from dermatologic conditions, to famous dermatologists and physicians who have advanced the field of both dermatology and medicine, to the different countries that promoted the development of scientists, researchers and physicians alike.

It was decided that the bibliographic record would encompass journals, books and a compilation of obituaries. A pertinent question is whether a manually created bibliographic project is still warranted in the 21^st century. In short, yes. While Index …

Bullous Leukemia Cutis In A Patient With T-Cell Prolymphocytic Leukemia, Sarah Y. Siu, Qiujie Jiang, Ashley Gochoco, Jason B. Lee, Md, Joya Sahu, Onder Alpdogan, Jerald Z. Gong, Md

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Amlodipine-Induced Hypersensitivity Reaction Mimicking Cd30(+) Mycosis Fungoides., Ashley Gochoco, Elizabeth Jones, Christine Soutendijk, Onder Alpdogan, Wenyin Shi, Joya Sahu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

An Atrophic Plaque On The Breast Six Years After Breast Reconstruction Surgery, Michelle Khurana, Richard Torbeck, Young C. Kauh

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Lasers In Tattoo And Pigmentation Control: Role Of The Picosure(®) Laser System., Richard Torbeck, Richard Bankowski, Sarah Henize, Nazanin Saedi

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND AND OBJECTIVES: The use of picosecond lasers to remove tattoos has greatly improved due to the long-standing outcomes of nanosecond lasers, both clinically and histologically. The first aesthetic picosecond laser available for this use was the PicoSure(®) laser system (755/532 nm). Now that a vast amount of research on its use has been conducted, we performed a comprehensive review of the literature to validate the continued application of the PicoSure(®) laser system for tattoo removal.

STUDY DESIGN AND METHODS: A PubMed search was conducted using the term "picosecond" combined with "laser", "dermatology", and "laser tattoo removal".

RESULTS: A total …

Endothelial To Mesenchymal Transition (Endomt) In The Pathogenesis Of Systemic Sclerosis-Associated Pulmonary Fibrosis And Pulmonary Arterial Hypertension. Myth Or Reality?, Sergio A. Jimenez, Sonsoles Piera-Velazquez

Department of Dermatology and Cutaneous Biology Faculty Papers

Systemic Sclerosis (SSc) is a systemic autoimmune disease characterized by progressive fibrosis of skin and multiple internal organs and severe functional and structural microvascular alterations. SSc is considered to be the prototypic systemic fibrotic disorder. Despite currently available therapeutic approaches SSc has a high mortality rate owing to the development of SSc-associated interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), complications that have emerged as the most frequent causes of disability and mortality in SSc. The pathogenesis of the fibrotic process in SSc is complex and despite extensive investigation the exact mechanisms have remained elusive. Myofibroblasts are the cells …

Ectopic Mineralization Of Cartilage And Collagen-Rich Tendons And Ligaments In Enpp1asj-2j Mice., Jieyu Zhang, Nathaniel A Dyment, David W Rowe, Sarah Y Siu, John P Sundberg, Jouni Uitto, Qiaoli Li

Department of Dermatology and Cutaneous Biology Faculty Papers

Generalized arterial calcification of infancy (GACI), an autosomal recessive disorder caused by mutations in the ENPP1 gene, manifests with extensive mineralization of the cardiovascular system. A spontaneous asj-2J mutant mouse has been characterized as a model for GACI. Previous studies focused on phenotypic characterization of skin and vascular tissues. This study further examined the ectopic mineralization phenotype of cartilage, collagen-rich tendons and ligaments in this mouse model. The mice were placed on either control diet or the "acceleration diet" for up to 12 weeks of age. Soft connective tissues, such as ear (elastic cartilage) and trachea (hyaline cartilage), were processed …

Pressure To Publish For Residency Applicants In Dermatology, Jordan V. Wang, Matthew S. Keller

Department of Dermatology and Cutaneous Biology Faculty Papers

As it grows increasingly difficult to match into a dermatology residency program each year, there is a widening gap in research accomplishments between those who have and have not matched successfully. Applicants should be aware of the current trends in order to maximize their chances of matching. Such research inequality may subsequently lead to increases in the pressure to publish and the incidence of academic misrepresentation. Academic dermatology programs should be aware of these issues in order to help their students successfully match and exercise caution when reviewing the curricula vitae of applicants. We believe that student mentors in dermatology …

C-Src/Cav1-Dependent Activation Of The Egfr By Dsg2., Andrew M. Overmiller, Kathleen P. Mcguinn, Brett J. Roberts, Felicia Cooper, Donna M. Brennan-Crispi, Takahiro Deguchi, Sirkku Peltonen, James K. Wahl, Mỹ G. Mahoney

Department of Dermatology and Cutaneous Biology Faculty Papers

The desmosomal cadherin, desmoglein 2 (Dsg2), is deregulated in a variety of human cancers including those of the skin. When ectopically expressed in the epidermis of transgenic mice, Dsg2 activates multiple mitogenic signaling pathways and increases susceptibility to tumorigenesis. However, the molecular mechanism responsible for Dsg2-mediated cellular signaling is poorly understood. Here we show overexpression as well as co-localization of Dsg2 and EGFR in cutaneous SCCs in vivo. Using HaCaT keratinocytes, knockdown of Dsg2 decreases EGFR expression and abrogates the activation of EGFR, c-Src and Stat3, but not Erk1/2 or Akt, in response to EGF ligand stimulation. To determine whether …

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 …

Lysyl Hydroxylase 3 Localizes To Epidermal Basement Membrane And Is Reduced In Patients With Recessive Dystrophic Epidermolysis Bullosa., Stephen A Watt, Jasbani H S Dayal, Sheila Wright, Megan Riddle, Celine Pourreyron, James R Mcmillan, Roy M Kimble, Marco Prisco, Ulrike Gartner, Emma Warbrick, W H Irwin Mclean, Irene M Leigh, John A Mcgrath, Julio C Salas-Alanis, Jakub Tolar, Andrew P South

Department of Dermatology and Cutaneous Biology Faculty Papers

Recessive dystrophic epidermolysis bullosa (RDEB) is caused by mutations in COL7A1 resulting in reduced or absent type VII collagen, aberrant anchoring fibril formation and subsequent dermal-epidermal fragility. Here, we identify a significant decrease in PLOD3 expression and its encoded protein, the collagen modifying enzyme lysyl hydroxylase 3 (LH3), in RDEB. We show abundant LH3 localising to the basement membrane in normal skin which is severely depleted in RDEB patient skin. We demonstrate expression is in-part regulated by endogenous type VII collagen and that, in agreement with previous studies, even small reductions in LH3 expression lead to significantly less secreted LH3 …

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 …

Spontaneous Asj-2j Mutant Mouse As A Model For Generalized Arterial Calcification Of Infancy: A Large Deletion/Insertion Mutation In The Enpp1 Gene., Qiaoli Li, C Herbert Pratt, Louise A Dionne, Heather Fairfield, Son Yong Karst, John P Sundberg, Jouni Uitto, Yin Tintut

Department of Dermatology and Cutaneous Biology Faculty Papers

Generalized arterial calcification of infancy (GACI), an autosomal recessive disorder caused by mutations in the ENPP1 gene, manifests with extensive mineralization of the cardiovascular system. The affected individuals in most cases die within the first year of life, and there is currently no effective treatment for this disorder. In this study, we characterized a spontaneous mutant mouse, asj-2J, as a model for GACI. These mice were identified as part of a phenotypic deviant search in a large-scale production colony of BALB/cJ mice at The Jackson Laboratory. They demonstrated a characteristic gait due to stiffening of the joints, with phenotypic similarity …

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.

Tumour-Stroma Crosstalk In The Development Of Squamous Cell Carcinoma., Yok Zuan Lim, Andrew P South

Department of Dermatology and Cutaneous Biology Faculty Papers

Squamous cell carcinoma (SCC) represents one of the most frequently diagnosed tumours and contributes significant mortality worldwide. Recent deep sequencing of cancer genomes has identified common mutations in SCC arising across different tissues highlighting perturbation of squamous differentiation as a key event. At the same time significant data have been accumulating to show that common tumour-stroma interactions capable of driving disease progression are also evident when comparing SCC arising in different tissues. We and others have shown altered matrix composition surrounding SCC can promote tumour development. This review focuses on some of the emerging data with particular emphasis on SCC …

Mouse Models For Pseudoxanthoma Elasticum: Genetic And Dietary Modulation Of The Ectopic Mineralization Phenotypes., Qiaoli Li, Haitao Guo, David W Chou, Annerose Berndt, John P Sundberg, Jouni Uitto

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE), a heritable ectopic mineralization disorder, is caused by mutations in the ABCC6 gene. Null mice (Abcc6(-/-) ) recapitulate the genetic, histopathologic and ultrastructural features of PXE, and they demonstrate early and progressive mineralization of vibrissae dermal sheath, which serves as a biomarker of the overall mineralization process. Recently, as part of a mouse aging study at The Jackson Laboratory, 31 inbred mouse strains were necropsied, and two of them, KK/HlJ and 129S1/SvImJ, were noted to have vibrissae dermal mineralization similar to Abcc6(-/-) mice. These two strains were shown to harbor a single nucleotide polymorphism (rs32756904) in the …

Human Adipose-Derived Stem Cell Transplantation As A Potential Therapy For Collagen Vi-Related Congenital Muscular Dystrophy., Vitali Alexeev, Machiko Arita, Adele Donahue, Paolo Bonaldo, Daniel A. Monti, Olga Igoucheva

Department of Dermatology and Cutaneous Biology Faculty Papers

INTRODUCTION: Congenital muscular dystrophies (CMD) are a clinically and genetically heterogeneous group of neuromuscular disorders characterized by muscle weakness within the first two years of life. Collagen VI-related muscle disorders have recently emerged as one of the most common types of CMD. COL6 CMD is caused by deficiency and/or dysfunction of extracellular matrix (ECM) protein collagen VI. Currently, there is no specific treatment for this disabling and life-threatening disease. The primary cellular targets for collagen VI CMD therapy are fibroblasts in muscle, tendon and skin, as opposed to muscle cells for other types of muscular dystrophies. However, recent advances in …

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.

Clinical Phenotypes And Abcc6 Gene Mutations In Brazilian Families With Pseudoxanthoma Elasticum., Caroline Silvério Faria, Qiaoli Li, Haitao Guo, Jouni Uitto, Sylvia Satomi Takeno, Marilia De Arruda Cardoso Smith, Dertia Villalba Freire-Maia

Department of Dermatology and Cutaneous Biology Faculty Papers

Pseudoxanthoma elasticum (PXE; OMIM 264800) manifests with characteristic skin lesions of yellowish papules which coalesce into plaques of inelastic and leathery skin on the predilection sites (1). The ocular findings consist of angioid streaks, choroidal neovascularization and subretinal hemorrhages resulting in loss of visual acuity and occasional blindness. Cardiovascular problems include hypertension, intermittent claudication, and occasional myocardial infarcts and stroke. The prevalence of PXE is estimated to be in the range of 1:50,000-70,000 and to be more frequent in females than in males. The diagnosis can be challenging to clinicians due to late-onset of clinical manifestations and considerable heterogeneity. PXE …

Controversies In Dermatology: Part V., Ronni Wolf, Lawrence Parish

Department of Dermatology and Cutaneous Biology Faculty Papers

“It were not best that we should all think alike; it is difference of opinion that makes horse-races” Mark Twain (Samuel L. Clemens) in The Tragedy of Pudd’nead Wilson, Ch. 19, “Pudd’nead Wilson’s Calendar”.

Part V of Controversies in Dermatology continues the precedent of earlier issues by providing a platform for discussion of a broad range of contemporary and controversial issues. In this issue of Clinics in Dermatology, we will forego the temptation to expose hidden agendas and witches brews, rather, we shall focus on accepted beliefs, principles, doctrines, and paradigms, which you may find even more astonishing.