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Full-Text Articles in Skin and Connective Tissue Diseases

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing May 2023

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations & Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …


Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong May 2022

Targeting Neuronal Nitric Oxide Synthase (Nnos) For Melanoma Treatment, Shirley Tong

Pharmaceutical Sciences (PhD) Dissertations

Human cutaneous melanoma is the most aggressive form of skin cancer and the incidence rates have continued to increase over the years. Neuronal nitric oxide synthase (nNOS) produces nitric oxide (NO) has been found to be overexpressed in human melanoma and the expression of nNOS is induced by interferon-gamma (IFN-γ). In our studies, nNOS has been implicated in IFN-γ-stimulated melanoma progression and the inhibition of nNOS using novel inhibitors effectively inhibited IFN-γ-stimulated tumor growth in a xenograft mouse model. Programmed death-ligand 1 (PD-L1) is overexpressed in melanoma and plays an important role in suppressing the immune system 12-14. Our …


An Investigation Of Chronic Pain As A Much-Neglected Symptom Of Hypermobile Ehlers-Danlos Syndrome, Sydney Collins Dec 2021

An Investigation Of Chronic Pain As A Much-Neglected Symptom Of Hypermobile Ehlers-Danlos Syndrome, Sydney Collins

Honors Theses

Ehlers Danlos Syndrome is a group of heritable loose connective tissue disorders with 13 distinguished subtypes. The hypermobile type of Ehlers Danlos Syndrome (hEDS) is the most common subtype and is caused by a genetic mutation that leads to defective collagen fibrils. This leads to joint instability and hypermobility, skin elasticity, widespread pain, fatigue, and generalized tissue fragility. Chronic pain is reported to be a symptom in as high as 92% of the hEDS population (Voermans et al., 2010); despite this prevalence, there is a significant lack of research, awareness, and treatment standardization regarding pain in hEDS. This literature review …


Kindlin-1 Is Involved In Spreading, Migration, And Protein Regulation In Epidermal Scc-13 Cells, Naomi Mishan Dec 2021

Kindlin-1 Is Involved In Spreading, Migration, And Protein Regulation In Epidermal Scc-13 Cells, Naomi Mishan

Electronic Thesis and Dissertation Repository

Kindlin-1 is a scaffold protein linking the cytoskeleton to the extracellular matrix. Loss of function mutations in the FERMT1 gene (encoding Kindlin-1) cause gastrointestinal and skin defects associated with increased susceptibility to aggressive epidermal squamous cell carcinoma (SCC). This study investigated the consequences of targeted FERMT1 inactivation in the SCC-13 cell line of epidermal SCC. My studies demonstrate Kindlin-1 is not essential for SCC-13 proliferation or clonogenic potential in culture. Kindlin-1 was required for cell spreading on collagen I, but not on laminin-332, and its absence enhanced SCC-13 directional migration. Finally, I identified several proteins involved in tumor formation and …


Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker Aug 2021

Gene Expression Profiling Of Mapk Pathway Inhibitor Resistance In Cutaneous Melanoma: Can Bioinformatics Be Used To Select Better Melanoma Cell Lines?, Stephen Luebker

Theses & Dissertations

Melanoma is the deadliest form of skin cancer, and incidence has continued to increase. Half of all melanomas have a BRAF V600E mutation and respond to MAPK pathway inhibitors, including BRAF inhibitor therapy or BRAF/MEK inhibitor combination therapy, but nearly all patients develop treatment resistance. Melanoma cell lines produce variable results as models of MAPK pathway inhibitor resistance. To better understand how the genomic similarity of a melanoma cell line to patient-derived tumors affects resistance mechanisms, differences in DNA mutations and copy-number alterations were compared between melanoma cell lines profiled by the Cancer Cell Line Encyclopedia and cutaneous melanoma tumors …


The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo Aug 2021

The Regulation Of Pannexin1 And Pannexin2 In The Skin In Health And Disease, Rafael E. Sanchez Pupo

Electronic Thesis and Dissertation Repository

Pannexins (PANX1, 2, 3) are a family of channel-forming glycoproteins that mediate intracellular and paracrine signaling. In contrast to PANX2, PANX1 has been extensively investigated in the skin, modulating cell differentiation, wound healing, and melanoma development. PANX1 and PANX2 can co-exist in the same cell and form mixed channels where their glycosylation seems to regulate their intermixing. N-glycosylation and caspase cleavage have been proposed as modulators of the function of PANX1, but their effects on PANX2 are unknown. We explored the PANX2 expression in mouse skin and showed that a Panx2 splice variant (PANX2-202) is continuously expressed throughout aging skin. …


Epidemiology And Pathophysiology Of Common Skin Diseases In West Africa: An Immunodermatological Framework, Osazomon Imarenezor Nov 2020

Epidemiology And Pathophysiology Of Common Skin Diseases In West Africa: An Immunodermatological Framework, Osazomon Imarenezor

All HCAS Student Capstones, Theses, and Dissertations

This capstone reviews the common skin diseases on a global scale. With these dermatoses being further funneled into Africa and then magnified into common West African dermatoses, the meta-analyses of literature available paints a clear picture of the epidemiological & pathological factors and their contribution to the skin disease. Each article analysed in this analysis was taken from a 20-year span of January 2000 to December 2019. The selection of articles was fine-tuned by identifying the distribution of skin disease, revealing the populations affected (age, gender, ethnicity, etc), the main causes, country of origin, the prognosis of disease, and the …


Functional Analysis Of A Critical Glycine (Glycine 12) In Beta-Type Connexins Of Human Skin, Rasheed Bailey May 2020

Functional Analysis Of A Critical Glycine (Glycine 12) In Beta-Type Connexins Of Human Skin, Rasheed Bailey

Biology Theses

At least five beta-type connexins are expressed in various layers of the skin (Cx26, Cx30, Cx30.3, Cx31, and Cx32) and all include a glycine residue at position 12. Glycine12 (G12) is located about halfway through the cytoplasmic amino terminus and has been the focus of several studies related to connexin diseases and gap junction channel structure. The importance of this residue is evident in the severity and diversity of diseases associated with amino acid substitutions at G12 including hereditary forms of skin disease, deafness and neuropathy. This study uses bioinformatic analysis in combination with mutational analysis and electrophysiology to better …


Hybridized Polymeric Nano-Assemblies: Key Insights Into Addressing Mdr Infections, Ryan Landis Mar 2019

Hybridized Polymeric Nano-Assemblies: Key Insights Into Addressing Mdr Infections, Ryan Landis

Doctoral Dissertations

Multidrug-resistant (MDR) bacteria contribute to more than 700,000 annual deaths world-wide. Millions more suffer from limb amputations or face high healthcare treatment costs where prolonged and costly therapeutic regimens are used to counter MDR infections. While there is an international push to develop novel and more powerful antimicrobials to address the impending threat, one particularly interesting approach that has re-emerged are essential oils, phytochemical extracts derived from plant sources. While their antimicrobial activity demonstrates a promising avenue, their stability in aqueous media, limits their practical use in or on mammals. Inspired by the versatility of polymer nanotechnology and the sustainability …


Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes Jul 2018

Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes

LSU Doctoral Dissertations

Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses …


Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh Dec 2017

Integrative Cancer Immunogenomic Analysis Of Serial Melanoma Biopsies Reveals Correlates Of Response And Resistance To Sequential Ctla-4 And Pd-1 Blockade Treatment, Whijae Roh

Dissertations & Theses (Open Access)

Melanoma is the most malignant form of skin cancer. The five-year survival rate for metastatic melanoma is 19.9%. Although targeted therapy of BRAF and MEK inhibitors were developed for melanoma, resistance to therapy is inevitable. Immune checkpoint blockade, which reverses the suppression of the immune system, on the other hand, has shown a durable response in 20-30% of patients with metastatic melanoma. However, more predictive and robust biomarkers of response to this therapy are still needed, and resistance mechanisms remain incompletely understood. To address this, we examined a cohort of metastatic melanoma patients treated with sequential checkpoint blockade against cytotoxic …


Medical Interns', Residents' And Attending Physicians' Attitudes Towards Integrative Medicine And Recommended Treatments For Patients With Psoriasis, Jennifer L. Pacyon Jan 2016

Medical Interns', Residents' And Attending Physicians' Attitudes Towards Integrative Medicine And Recommended Treatments For Patients With Psoriasis, Jennifer L. Pacyon

PCOM Psychology Dissertations

Background: Psoriasis is a multifactorial disease that effect approximately 7.5 million Americans. There are a variety of traditional treatments for psoriasis (e.g. topical medications, biologics) that for many, are effective in combating the disease. However, traditional treatments often have aversive side effects and may not be appropriate for every patient (e.g. pregnant women). Additionally, the efficacy of these medications are variable leaving some looking for adjunctive treatment options. There is increasing evidence to support the use of adjunctive treatments for psoriatic patients (e.g. psychotherapy, mindfulness). However, research is variable in regards to medical professionals’ attitudes towards integrative medicine (IM) as …


Functional Analysis Of The Molluscum Contagiosum Virus Mc160 Death Effector Domain-Containing Protein Rxdl Motif, Sarah Weber May 2015

Functional Analysis Of The Molluscum Contagiosum Virus Mc160 Death Effector Domain-Containing Protein Rxdl Motif, Sarah Weber

Seton Hall University Dissertations and Theses (ETDs)

The Molluscum contagiosum virus (MCV) is a member of the Poxviridae family that causes benign skin lesions. MCV lesions persist on average for 8-12 months in otherwise healthy individuals. MCV lesions are characterized by reduced inflammation. The persistence and reduction of inflammation at the site of MCV lesions have been attributed to MCV immune evasion genes. MCV encodes two death effector domain (DED) containing proteins, MC159 and MC160. DEDs are found in cellular proteins such as FADD and procaspase-8. These cellular proteins are involved in several innate immune responses such as apoptosis and activation of interferon (IFN). Presumably, MC159 and …


Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu May 2013

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations & Theses (Open Access)

CD8+ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8+ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8+ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8+ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8+CD57+ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …


Plasmacytoid Dendritic Cells Sense Skin Injury And Promote Wound Healing Through Type I Interferons, Josh D. Gregorio Dec 2010

Plasmacytoid Dendritic Cells Sense Skin Injury And Promote Wound Healing Through Type I Interferons, Josh D. Gregorio

Dissertations & Theses (Open Access)

Plasmacytoid dendritic cells (pDCs) are a rare population of circulating cells, which selectively express intracellular Toll-like receptors (TLR)-7 and TLR-9 and have the capacity to produce large amounts of type I IFNs (IFN-a/b) in response to viruses or host derived nucleic acid containing complexes. pDCs are normally absent in skin but accumulate in the skin of psoriasis patients where their chronic activation to produce IFN-a/b drives the disease formation. Whether pDCs and their activation to produce IFN-a/b play a functional role in healthy skin is unknown. Here we show that pDCs are rapidly and transiently recruited into healthy human and …