Skin and Connective Tissue Diseases Commons^™

Skin Barrier Function: The Interplay Of Physical, Chemical, And Immunologic Properties, Paola Baker, Christina Huang, Rakan Radi, Samara B Moll, Emmanuela Jules, Jack L Arbiser

Student Papers, Posters & Projects

An intact barrier function of the skin is important in maintaining skin health. The regulation of the skin barrier depends on a multitude of molecular and immunological signaling pathways. By examining the regulation of a healthy skin barrier, including maintenance of the acid mantle and appropriate levels of ceramides, dermatologists can better formulate solutions to address issues that are related to a disrupted skin barrier. Conversely, by understanding specific skin barrier disruptions that are associated with specific conditions, such as atopic dermatitis or psoriasis, the development of new compounds could target signaling pathways to provide more effective relief for patients. …

Her3 Targeting Augments The Efficacy Of Panobinostat In Claudin-Low Triple-Negative Breast Cancer Cells, Hui Lyu, Defu Hou, Hao Liu, Sanbao Ruan, Congcong Tan, Jiande Wu, Chindo Hicks, Bolin Liu

School of Medicine Faculty Publications

Patients with triple-negative breast cancer (TNBC) have a poor prognosis and high relapse rate due to limited therapeutic options. This study was conducted to determine the mechanisms of action of panobinostat, a pan-inhibitor of histone deacetylase (HDAC) and FDA-approved medication for multiple myeloma, in TNBC and to provide a rationale for effective drug combinations against this aggressive disease. RNA sequencing analyses of the claudin-low (CL) TNBC (MDA-MB-231) cells untreated or treated with panobinostat were performed to identify the differentially expressed genes. Adaptive alterations in gene expression were analyzed and validated in additional CL TNBC cells. Tumor xenograft models were used …

Hereditary Angioedema: Diagnosis, Clinical Implications, And Pathophysiology, Evan S. Sinnathamby, Peter P. Issa, Logan Roberts, Haley Norwood, Kevin Malone, Harshitha Vemulapalli, Shahab Ahmadzadeh, Elyse M. Cornett, Sahar Shekoohi, Alan D. Kaye

School of Medicine Faculty Publications

Hereditary angioedema (HAE) is an autosomal dominant disorder caused by a mutation in the C1 esterase inhibitor gene. HAE affects 1/50,000 people worldwide. Three main types of HAE exist: type I, type II, and type III. Type I is characterized by a deficiency in C1-INH. C1-INH is important in the coagulation complement, contact systems, and fibrinolysis. Most HAE cases are type I. Type I and II HAE result from a mutation in the SERPING1 gene, which encodes C1-INH. Formally known as type III HAE is typically an estrogen-dependent or hereditary angioedema with normal C1-INH activity. Current guidelines now recommend subdividing …

Modification Of The Tumor Microenvironment Enhances Anti-Pd-1 Immunotherapy In Metastatic Melanoma, Guilan Shi, Megan Scott, Cathryn G. Mangiamele, Richard Heller

Bioelectrics Publications

Resistance to checkpoint-blockade treatments is a challenge in the clinic. Both primary and acquired resistance have become major obstacles, greatly limiting the long-lasting effects and wide application of blockade therapy. Many patients with metastatic melanoma eventually require further therapy. The absence of T-cell infiltration to the tumor site is a well-accepted contributor limiting immune checkpoint inhibitor efficacy. In this study, we combined intratumoral injection of plasmid IL-12 with electrotransfer and anti-PD-1 in metastatic B16F10 melanoma tumor model to increase tumor-infiltrating lymphocytes and improve therapeutic efficacy. We showed that effective anti-tumor responses required a subset of tumor-infiltrating CD8⁺ and CD4 …

Medical Norm Of Psychiatric Misdiagnoses In Rare Disease Patients, Rachel Han

Publications and Research

Spring 2022 ENG 120 Student Final Research Paper on the medical norm of psychiatric misdiagnosis throughout the diagnostic journeys of rare disease patients. The idea of a norm was taken from Chimamanda Ngozi Adichie's Tedx Talk "The Danger of a Single Story". Paper discusses prevalence, harmful effects, and origin of this medical norm. Includes discussion of statistical data quoted relating to prevalence of rare diseases as well as anecdotal evidence of the severe ramifications of this norm. Discussion of how medically unexplained symptoms such as mysterious chronic pain often lead to the phenomenon of the psychogenic inference. Origins of this …

Actinic Granuloma Responding To Doxycycline, George M. Jeha, Kathryn Olivier Luckett, Lauren Kole

School of Medicine Faculty Publications

No abstract provided.

Post-Surgical Pyoderma Gangrenosum After Breast Surgery: A Case Series, Jahan Tajran, Daniella Anderson, Arif Chaudhry, Dennis Hammond

Medical Student Research Symposium

Background:

Pyoderma gangrenosum (PG) is a rare inflammatory cutaneous disorder that is thought to be due to innate immune system dysfunction, specifically of neutrophils. PG has been well documented in patients with autoimmune disorders like Ulcerative Colitis and Rheumatoid Arthritis. PG can also present in surgical patients, imitating a potential wound infection and necrotizing fasciitis. Although PG is a diagnosis of exclusion, prompt recognition is essential to attaining desired aesthetic outcomes, especially with breast involvement. We present a case series of four patients who developed PG following breast surgery. We analyze each patient’s medical history, symptoms, wound progression and management …

Biological Pathway Involvement In Melanoma Heterogeneity And Drug-Induced Resistance, Sarah V. Pack

STAR Program Research Presentations

Tumors develop resistance to numerous drug therapies, and this remains a major obstacle in treating many types of non-surgical cancers. Melanoma provides a good model system for studying drug resistance in cancer due to its high propensity to incur resistance after a significant initial response to a drug. Genes that are highly expressed in melanoma cancer cells have been studied, but in order to further understand the collective function of these highly expressed genes we must analyze gene sets, or pathways. A single gene’s function is rarely independent of other genes, and pathway analysis takes this into account.

Our objective …

Towards Stable Electrochemical Sensing For Wearable Wound Monitoring, Sohini Roychoudhury

FIU Electronic Theses and Dissertations

Wearable biosensing has the tremendous advantage of providing point-of-care diagnosis and convenient therapy. In this research, methods to stabilize the electrochemical sensing response from detection of target biomolecules, Uric Acid (UA) and Xanthine, closely linked to wound healing, have been investigated. Different kinds of materials have been explored to address such detection from a wearable, healing platform. Electrochemical sensing modalities have been implemented in the detection of purine metabolites, UA and Xanthine, in the physiologically relevant ranges of the respective biomarkers. A correlation can be drawn between the concentrations of these bio-analytes and wound severity, thus offering probable quantitative insights …

Plasmonic Gold Nanoparticle For Detection Of Fungi And Human Cutaneous Fungal Infections, Tobiloba Sojinrin, Kangze Liu, Joao Conde, Hugh Byrne, James Curtin, Daxiang Cui, Furong Tian

Articles

Fungi, which are common in the environment, can cause a multitude of diseases. Warm, humid conditions allow fungi to grow and infect humans via the respiratory, digestive and reproductive tracts, genital area and other bodily interfaces. Fungi can be detected directly by microscopy, using the potassium hydroxide (KOH) test, which is the gold standard and most popular method for fungal screening. However, this test requires trained personnel operating specialist equipment, including a fluorescent microscope and culture facilities. As most acutely infected patients seek medical attention within the first few days of symptoms, the optimal diagnostic test would be rapid and …

In Vivo Bioluminescence Imaging To Evaluate Systemic And Topical Antibiotics Against Community-Acquired Methicillin-Resistant Staphylococcus Aureus-Infected Skin Wounds In Mice, Yi Guo, Romela Irene Ramos, John S. Cho, Niles P. Donegan, Ambrose L. Cheung, Lloyd S. Miller

Dartmouth Scholarship

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) frequently causes skin and soft tissue infections, including impetigo, cellulitis, folliculitis, and infected wounds and ulcers. Uncomplicated CA-MRSA skin infections are typically managed in an outpatient setting with oral and topical antibiotics and/or incision and drainage, whereas complicated skin infections often require hospitalization, intravenous antibiotics, and sometimes surgery. The aim of this study was to devel

Raman Spectroscopic Analysis Of Human Skin Tissue Sections Ex-Vivo: Evaluation Of The Effects Of Tissue Processing And Dewaxing, Syed Mehmood Ali, Franck Bonnier, Ali Tfayli, Helen Lambkin, Kathleen Flynn, Vincent Mcdonagh, Claragh Healy, Thomas Lee, Fiona Lyng, Hugh Byrne

Articles

Raman spectroscopy coupled with K-means clustering analysis (KMCA) is employed to elucidate the biochemical structure of human skin tissue sections, and the effects of tissue processing. Both hand and thigh sections of human cadavers were analysed in their unprocessed and formalin fixed paraffin processed (FFPP) and subsequently dewaxed forms. In unprocessed sections, KMCA reveals clear differentiation of the stratum corneum, intermediate underlying epithelium and dermal layers for sections from both anatomical sites. The stratum corneum is seen to be relatively rich in lipidic content; the spectrum of the subjacent layers is strongly influenced by the presence of melanin, while that …

Merkel Cell Carcinoma, Cynthia L. Bartus Md, Steven Oberlender Md, Phd, Christian W. Oram Do

Department of Medicine

No abstract provided.

The Mechanical Behavior Of Mutant K14-R125p Keratin Bundles And Networks In Neb-1 Keratinocytes, Daniel R. Beriault, Oualid Haddad, John V. Mccuaig, Zachary J. Robinson, David Russell, E. Birgitte Lane, Douglas S. Fudge

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Epidermolysis bullosa simplex (EBS) is an inherited skin-blistering disease that is caused by dominant mutations in the genes for keratin K5 or K14 proteins. While the link between keratin mutations and keratinocyte fragility in EBS patients is clear, the exact biophysical mechanisms underlying cell fragility are not known. In this study, we tested the hypotheses that mutant K14-R125P filaments and/or networks in human keratinocytes are mechanically defective in their response to large-scale deformations. We found that mutant filaments and networks exhibit no obvious defects when subjected to large uniaxial strains and have no negative effects on the ability of human …

Solar Radiation Damage To Human Skin Mitochondria, Luciene Zanchetta

Doctoral

The central objective of this study was to assess solar radiation-induced changes in cellular function, mitochondrial function and mitochondrial DNA to further investigate the role of these energy-dedicated and metabolically essential organelles in the response to the main environmental stressor associated with skin cancer initiation. An in vitro approach was chosen employing the human malignant melanoma (A375) and human amelanotic melanoma (C32) cells and the human spontaneously immortalized keratinocytes (HaCaT). A Q-Sun Solar Simulator was used to expose cells to low-level simulated solar radiation (SSR) as it provides a mimic of solar radiation that is environmentally relevant in the UV …

Expression And Function Of Hypoxia Inducible Factor-1 Alpha In Human Melanoma Under Non-Hypoxic Conditions, Caroline N. Mills, Sandeep S. Joshi, Richard M. Niles

Biochemistry and Microbiology

Background

Hypoxia inducible factor-1 alpha (HIF-1α) protein is rapidly degraded under normoxic conditions. When oxygen tensions fall HIF-1α protein stabilizes and transactivates genes involved in adaptation to hypoxic conditions. We have examined the normoxic expression of HIF-1α RNA and protein in normal human melanocytes and a series of human melanoma cell lines isolated from radial growth phase (RGP), vertical growth phase (VGP) and metastatic (MET) melanomas.

Results

HIF-1α mRNA and protein was increased in RGP vs melanocytes, VGP vs RGP and MET vs VGP melanoma cell lines. We also detected expression of a HIF-1α mRNA splice variant that lacks part …