Skin and Connective Tissue Diseases Commons^™

The Effect Of Function-Blocking Rhamm Peptides In A Mouse Model Of Bleomycin-Induced Systemic Sclerosis, Kitty Y. Wu

Electronic Thesis and Dissertation Repository

Systemic sclerosis is a chronic, fibrotic disorder associated with high disease-specific mortality and morbidity. Cutaneous manifestations include dermal thickening and obliteration of dermal adipose tissue. The efficacy of function-blocking Rhamm peptides, NPI-110 and NPI-106, were tested in reducing skin fibrosis and promoting adipogenesis in a bleomycin-induced mouse model of systemic sclerosis. NPI-110 reduced both visible measures of fibrosis (dermal thickness, collagen density, and fibril bundling) and mRNA expression of pro-fibrotic genes (Tgfb1, c-Myc, Col1a1, Col3a1). While there was no measurable change in dermal adipose thickness, NPI-110 treatment upregulated Perilipin mRNA and Adiponectin protein expression and is therefore hypothesized to create ...

Widespread Presentation And Spontaneous Regression Of Porokeratotic Eccrine Ostial And Dermal Duct Nevus, Stephanie Petkiewicz, Julia Baltz, Kristine M. Cornejo, April C. Deng, Karen Wiss

Open Access Articles

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is an uncommon hamartomatous growth with disordered keratinization. The lesions typically appear on the limbs, often at birth or in early childhood, as linearly distributed papules and plaques. We report 4 cases of PEODDN, 2 of which showed significant spontaneous regression.

In Vitro And Ex-Vivo Evaluation Of Topical Formulations Designed To Minimize Transdermal Absorption Of Vitamin K1, Ramina Nabiee, Barent Dubois, Laura Green, Ajay Sharma, Siu Fun Wong, Hamidreza Montazeri Aliabadi

Pharmacy Faculty Articles and Research

Topical application of Vitamin K1 has been demonstrated to effectively treat papulopustular skin rash, a serious and frequently encountered side effect of Epidermal Growth Factor Inhibitors (EGFRIs). Systemic absorption of vitamin K1 from skin and the resultant consequence of antagonizing EGFRIs anticancer effects jeopardizes the clinical acceptability of this rather effective treatment. The purpose of the present study was to rationally formulate and evaluate the release rate and transdermal absorption of a wide range of Vitamin K1 dermal preparations with a variety of physiochemical properties. A library of 33 formulations with were compounded and tested for Vitamin K1 permeation using ...

The Importance Of Early Arthritis In Patients With Rheumatoid Arthritis, Georgiana Iftimie, Ana Maria Alexandra Stanescu, Mihaela A. Iancu, Anca Pantea Stoian, Razvan Hainarosie, Bogdan Socea, Gheorghita Isvoranu, Dragos Marcu, Tiberiu P. Neagu, Camelia C. Diaconu

Journal of Mind and Medical Sciences

Rheumatoid arthritis (RA) is a systemic inflammatory disorder that manifests predominantly in the synovial joint, where it causes a chronic inflammatory process, leading to early osteoarticular destructions. These destructions are progressive and irreversible, generating a significant functional deficiency. During the last years, the diagnostic approach of RA has focused on early arthritis. Early arthritis can develop into established RA or another established arthropathy, like systemic lupus erythematosus or psoriatic arthritis. It can have a spontaneous resolution or may remain undifferentiated for indefinite periods of time.

The management of early arthritis has changed considerably in the past few years, under the ...

Hand Issues On Scleroderma Patients, Ana Font Hernandez

Publications and Research

Based on the design of a 3D-printed spoon prototype, we surveyed scleroderma patients about the device's value. 75% of patients mentioned having problems on their hands due to scleroderma. 85% of patients said their hand form changed because of the disease. Answers to the frequency or speed of the changes provide inconclusive results. The 3D printing technology has the potential to solve specific issues scleroderma patients face in their daily lives. Nevertheless, further research is needed to fully understand how hands shape change over time.

Il-16/Mir-125a Axis Controls Neutrophil Recruitment In Pristane-Induced Lung Inflammation, Siobhan Smith, Hardy Kornfeld, Caroline A. Jefferies

Open Access Articles

Severe lung inflammation and alveolar hemorrhage can be life-threatening in systemic lupus erythematosus (SLE) patients if not treated early and aggressively. Neutrophil influx is the driver key of this pathology, but little is known regarding the molecular events regulating this recruitment. Here, we uncover a role for IL-16/mir-125a in this pathology and show not only that IL-16 is a target for miR-125a but that reduced miR-125a expression in SLE patients associates with lung involvement. Furthermore, in the pristane model of acute "SLE-like" lung inflammation and alveolar hemorrhage, we observed reduced pulmonary miR-125a and enhanced IL-16 expression. Neutrophil infiltration was ...

Methods For High-Dimensonal Analysis Of Cells Dissociated From Cyropreserved Synovial Tissue, Laura T. Donlin, Ellen M. Gravallese, Jennifer H. Anolik

Open Access Articles

BACKGROUND: Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples.

METHODS: Multiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface ...

Therapeutic Benefit Of Apremilast On Enthesitis And Dactylitis In Patients With Psoriatic Arthritis: A Pooled Analysis Of The Palace 1-3 Studies, Dafna D. Gladman, Arthur Kavanaugh, Juan J. Gomez-Reino, Jurgen Wollenhaupt, Maurizio Cutolo, Georg Schett, Eric Lespessailles, Benoit Guerette, Nikolay Delev, Lichen Teng, Christopher J. Edwards, Charles Birbara, Philip J. Mease

Open Access Articles

Objective: The Psoriatic Arthritis Long-term Assessment of Clinical Efficacy (PALACE) clinical trial programme findings demonstrated that apremilast, an oral phosphodiesterase 4 inhibitor, is effective for treating psoriatic arthritis (PsA). Enthesitis and dactylitis are difficult-to-treat features of PsA leading to disability and affecting quality of life. PALACE 1, 2 and 3 data were pooled to assess the efficacy of apremilast on enthesitis and dactylitis outcomes in patients with these conditions at baseline.

Methods: Patients with enthesitis (n=945) or dactylitis (n=633) at baseline were analysed after receiving double-blind treatment with placebo, apremilast 30 mg two times per day or apremilast ...

Fas Ligand Promotes An Inducible Tlr-Dependent Model Of Cutaneous Lupus-Like Inflammation, Purvi Mande, Bahar Zirak, Wei-Che Ko, Keyon Taravati, Karen L. Bride, Tia Bumpus Brodeur, April C. Deng, Karen A. Dresser, Zhaozhao Jiang, Rachel Ettinger, Katherine A. Fitzgerald, Michael D. Rosenblum, John E. Harris, Ann Marshak-Rothstein

University of Massachusetts Medical School Faculty Publications

Toll-like receptors TLR7 and TLR9 are both implicated in the activation of autoreactive B cells and other cell types associated with systemic lupus erythematosus (SLE) pathogenesis. However, Tlr9-/- autoimmune-prone strains paradoxically develop more severe disease. We have now leveraged the negative regulatory role of TLR9 to develop an inducible rapid-onset murine model of systemic autoimmunity that depends on T cell detection of a membrane-bound OVA fusion protein expressed by MHC class II+ cells, expression of TLR7, expression of the type I IFN receptor, and loss of expression of TLR9. These mice are distinguished by a high frequency of OVA-specific Tbet ...

Doacs Least Harmful For Patients With Calciphylaxis On Hemodialysis Needing Anticoagulation, Mona Fayad

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of King BJ, El-Azhary RA, Mcevoy MT, et al. Direct oral anticoagulant medications in calciphylaxis. International Journal of Dermatology. 30 August 2017;56(1):1065-1070. doi: 10.1111/ijd.13685

Inflammation And Immune Evasion Coexist In Treponema Pallidum-Infected Skin, Rodolfo Trujillo, Jorge Cervantes, Kelly L. Hawley, Adriana R. Cruz, Sankhiros Babapoor, Michael Murphy, Soheil S. Dadras, Juan C. Salazar

Biology Faculty Publications

Syphilis is a systemic, multistage, sexually transmitted infection caused by the highly invasive spirochetal bacterium, Treponema pallidum, subspecies pallidum. In the United States, the annual rate of primary and secondary syphilis (SS) between 2002 and 2016 has increased from 2.1 to 8.7 cases per 100,000.¹ Gestational and congenital syphilis cases have also increased in the last few years. There is no evidence of a change in T pallidum susceptibility to penicillin as an explanation for the significant increase in the number of syphilis cases in the United States. It is more likely that changes in risk-taking ...

Assistive Utensil: A Spork For Hand Tremors And Spatial Awareness, Ana Font Hernandez, Jacob Kabariti, Troy Taylor

Publications and Research

In this poster, we present a 3D printed solution for hand tremors and special awareness. Our spork is an assistive device designed and 3D printed for patients suffering from scleroderma, systemic sclerosis, Parkinson's, multiple sclerosis, drug withdrawal, etc. The scale-based handle will act as a counterweight to offset the contents on the other end and reduce shakiness. The larger grip allows an easy and comfortable hold. The product will be 3D printed for a customizable fit and at an affordable price. Lastly, the product will include a haptic feedback sensor to assist the visually impaired in locating food contents ...

Periostin Antisense Oligonucleotide Suppresses Bleomycin-Induced Formation Of A Lung Premetastatic Niche For Melanoma, Takashi Semba, Eiji Sugihara, Nagisa Kamoshita, Sayaka Ueno, Keitaro Fukuda, Masafumi Yoshino, Kazumasa Takao, Kazunori Yoshikawa, Kenji Izuhara, Yoshimi Arima, Makoto Suzuki, Hideyuki Saya

Open Access Articles

Metastasis is the leading cause of cancer death. A tumor-supportive microenvironment, or premetastatic niche, at potential secondary tumor sites plays an important role in metastasis, especially in tumor cell colonization. Although a fibrotic milieu is known to promote tumorigenesis and metastasis, the underlying molecular contributors to this effect have remained unclear. Here we show that periostin, a component of the extracellular matrix that functions in tissue remodeling, has a key role in formation of a fibrotic environment that promotes tumor metastatic colonization. We found that periostin was widely expressed in fibrotic lesions of mice with bleomycin-induced lung fibrosis, and that ...

Infections Not Fought: Antibiotic Resistance In Underserved Communities, Derek Lillestolen

Senior Honors Theses

In 1928, the profound effects of penicillin were discovered and antibiotic treatments became extremely popular. Broad-spectrum antibiotics, like tetracyclines, have been since branded as cure-all prescriptions and used profusely in the Western World and abroad. Due to ignorance of specific biochemical mechanisms and the misuse of antibiotics these drugs inadvertently allowed the rise in prevalence of antibiotic resistant strains of certain bacteria as the century progressed. Now, the specific genetic causes and mechanisms of antibiotic resistance are being understood, but the fight against antimicrobial resistance is far from over. In the United States, thousands of fatalities are caused annually by ...

Differential Diagnosis Of Pan-Uveitis: Behçet’S Disease, Peter Blosser, Remil Simon, Courtney Ridner

Appalachian Student Research Forum

This report describes the case of a 56-year-old man who presented with blurry vision, increased intraocular pressure, and conjunctival injection after posterior chamber intraocular lens implantation. Initially post-operative endophalmitis and foreign body inflammation were considered as differential diagnoses, but after further examination pan-uveitis was diagnosed. Uveitis is an ocular finding that may indicate several diseases, one of which is Behçet’s Disease. During the interview, the patient mentioned a history of apthous ulcers and genital ulcers which then lead to the clinical diagnosis of Behçet’s Disease. This report emphasizes that Behçet’s Disease is rare in Caucasians. Therefore, is ...

Androgenic Alopecia; The Risk–Benefit Ratio Of Finasteride, David L. Rowland, Ion G. Motofei, Ioana Păunică, Petrișor Banu, Mihaela F. Nistor, Stana Păunică, Vlad D. Constantin

Journal of Mind and Medical Sciences

Finasteride is currently approved and largely used as a therapeutic option for androgenetic alopecia. Apparently a safe drug and effective at the onset of its application, several concerns have since appeared over the years regarding the frequency and magnitude of finasteride adverse effects, which in some cases appear irreversible even after drug termination.

This paper discusses the use of finasteride for androgenic alopecia from two distinct perspectives. On the one hand, androgenic alopecia is a condition that especially affects a person’s self-image and esteem, aspects that are subjectively-constructed and thus relative and changeable. On the other hand, this condition ...

Studies Of Amino Acid Mutations In Drug Resistance Of The Smo Protein, Eunice Wintona

Student Research and Creative Activity Fair

Smoothened receptor (SMO) is a protein that in humans, is encoded by the SMO gene. A systemic mutation in its binding pocket helps predict the sensitivity of mutant proteins to different drugs. Known as a GPCR-like receptor, it is a component of the hedgehog signaling pathway; a pathway involved in body patterning and the regulation of adult stem cells. An uncontrolled or inappropriate activation of the Hedgehog pathway drives tumor progression in cancers and a number of birth defects. To achieve these goals, the molecular modeling software MOE was used to build small molecules and drug molecules like Vismodegib and ...

Cluster-Randomized Trial Of A Behavioral Intervention To Incorporate A Treat-To-Target Approach To Care Of Us Patients With Rheumatoid Arthritis, Leslie R. Harrold, George W. Reed, Ani John, Christine J. Barr, Kevin Soe, Robert P. Magner, Katherine C. Saunders, Eric M. Ruderman, Tmirah Haselkorn, Jeffrey D. Greenberg, Allan Gibofsky, J. Timothy Harrington, Joel M. Kremer

Open Access Articles

OBJECTIVE: To assess the feasibility and efficacy of implementing a treat-to-target approach versus usual care in a US-based cohort of rheumatoid arthritis patients.

METHODS: In this behavioral intervention trial, rheumatology practices were cluster-randomized to provide treat-to-target care or usual care. Eligible patients with moderate/high disease activity (Clinical Disease Activity Index [CDAI] score > 10) were followed for 12 months. Both treat-to-target and usual care patients were seen every 3 months. Treat-to-target providers were to have monthly visits with treatment acceleration at a minimum of every 3 months in patients with CDAI score > 10; additional visits and treatment acceleration were at ...

The Conundrum Of Indeterminate Quantiferon-Tb Gold Results Before Anti-Tumor Necrosis Factor Initiation, Shahrad Hakimian, Yevgeniy Popov, Abbas Rupawala, Karen I. Salomon-Escoto, Steven Hatch, Randall Pellish

Open Access Articles

Background: Tumor necrosis factor alpha (TNFalpha) is a key cytokine in both the pathogenesis of inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) and the host defense against tuberculosis (TB). Consequently, anti-TNFalpha medications result in an increased risk of latent TB infection (LTBI) reactivation. Here, we sought to evaluate the factors affecting the results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay as a screening tool for LTBI.

Methods: We conducted an observational, retrospective study in patients with IBD and RA who underwent LTBI screening using QFT-GIT at UMass Memorial Medical Center between 2008 and 2016 prior to initiation of anti-TNF medications ...

Metastatic Extramammary Paget's Disease: Pathogenesis And Novel Therapeutic Approach, Keitaro Fukuda, Takeru Funakoshi

Open Access Articles

Extramammary Paget's disease (EMPD) is a rare, slow-growing, cutaneous adenocarcinoma that usually originates in the anogenital area and axillae outside the mammary glands. EMPD mostly progresses slowly and is often diagnosed as carcinoma in situ; however, upon becoming invasive, it promptly and frequently metastasizes to regional lymph nodes, leading to subsequent distant metastasis. To date, several chemotherapy regimens have been used to treat metastatic EMPD; however, they present limited effect and patients with distant metastasis exhibit a poor prognosis. Recently, basic and translational investigative research has elucidated factors and molecular mechanisms underlying the promotion of metastasis, which can lead ...