D.Litt. et Phil. / This study explored the impact of psoriasis on the self-concept (a multifaceted, hierarchical construct of self with both cognitive and emotional components) (Hattie & Marsh, 1996), of men and women who live with this cutaneous disease. Psoriasis is a common (frequently occurring), chronic inflammatory dermatological disease that can severely affect the sufferer's quality of life. While the underlying cause is unknown, the immediate cause of psoriasis is the rate of growth and differentiation of the outer layer of the skin. In a process known as hyper-proliferation (renewal of skin every four days as opposed to every 28 days), psoriasis is anatomically disfiguring. Symptoms include: the thickening of psoriatic plaques, the sloughing of silvery scales, severe itching of the affected areas and a thickening and yellowing of the fingernails. The severity of psoriasis varies from small scattered patches to total skin coverage (Young, 2005). Chronic skin diseases, such as psoriasis, can affect one's self-concept at the level of the physical, emotional, social and spiritual dimensions of self (Kew, Nevin & Cruickshank, 2002). According to Gupta and Gupta (1995), sufferers of psoriasis experience external shame (fear of negative evaluations and stigmatisation) as well as internal body shame (negative self-evaluations and self-focussed feelings). According to Stake, Huff and Zand (1995), a disturbance in one dimension of self (e.g. the physical self-concept), invariably effects other self-dimensions (e.g. the private, social self-dimensions). A study by Gupta and Gupta (1995) revealed that psoriasis was a major contributing factor to the onset of psychopathology such as depression, anxiety, unfocussed anger and obsessional behaviours. A study by Choi and Koo (as cited in Young, 2005), found that the impact of psoriasis on the psychological and emotional dimensions of self-concept to be comparable to that experienced by sufferers of more chronic diseases such as cancer, heart disease and clinical depression. General healthcare providers who treat the medical components of psoriasis may be surprised to learn that the emotional and social burdens of psoriasis are often greater than the physical toll of psoriasis on patients. Further, psoriasis is observed to be persistent, unpredictable and stressful over longer periods of time than more serious illnesses (Young, 2005). Although many people with disfiguring skin disorders cope remarkably well psychologically and socially, many do not and may require professional help in describing their bodily being in relation to the world and to come to terms with the positive and negative aspects of self (Van Deurzen-Smith, 1997). Significantly, studies in psychoneuroendocrineimmunology have shown the interconnectedness of emotions and mental attitude to physical health and which underscores the importance of treating the whole person and not just the symptoms (Linsteadt, 2002). Consistently, studies have shown the importance of self-concept to psychological health (Francis, 2002; Hattie & Marsh, 1996; Newell, 2000; Young, 2005) and body satisfaction as being pivotal in one's overall concept of self (Tiggemann & Williamson, 2000). Problematic however is that the literature indicates a dearth of dermatological studies detailing the meaning-making experiences of individuals who have undergone changes to their physical appearance as a result of this and the impact of cutaneous disease on the self-concept (Hill, 2004; Papadopoulos, Bor & Legg, 1999; Thompson & Kent, 2001). Our experiences and how we make sense of what we experience is primarily dependent upon the kinds of bodies we have and also on the ways we interact with the various environments we inhabit. It is through our embodied interactions that we inhabit a world, and it is through our bodies that we are able to understand and act within this world with varying degrees of success (Johnson, 1999). The importance of skin for an individual's psychosocial equilibrium can easily be appreciated. First, the skin represents the outward packaging of our being. Second, the cutaneous surface is what society initially perceives and with dermatological disease being the basis for social stigma. Arguably, having a healthy, unblemished skin can enhance one's self-esteem, self-identity and not infrequently, one's social standing (Koo & Yeung, 2002). Studies investigating the impact of disfiguring cutaneous disease on the self-concept appear to be lacking in the literature. In 2004, at a meeting of the Editorial Board for the Journal of Dermatology Nursing, the need for studies presenting the patient's experience of cutaneous disease was discussed. It was thought that qualitative exploration of the patient's experience of cutaneous disease would provide medical and mental healthcare professionals with valuable insights and important information to help improve dermatology patient care (Hill, 2004). Dermatology and self-concept phenomena tend to be investigated interdependently of each other. Furthermore, the majority of research in this area focuses on quantitative research design. Consequently, much of the depth of information regarding the experiential world of sufferers of cutaneous disease is invariably lost (Hill, 2004; Thompson & Kent, 2001). In light of that stated above, this study explored the meaning-making experience of men and women who suffer from psoriasis and the impact of this on the various dimensions of the self-concept. Due to the sparsity of South African studies investigating qualitatively, the experiences of persons suffering from a common, chronic dermatological condition, this study followed an existential phenomenological approach in describing the impact of psoriasis on the self-concept as told from the perspective of the men and women who live with this. Existential phenomenology seeks to explicate the essence, structure and form of both human experiences and behaviour as revealed through essentially descriptive techniques that includes disciplined reflection (Sokolowski, 2000). Given the apparent lack of awareness and knowledge of psychological processes, meaning-making and coping strategies utilised by psoriasis sufferers in their experience of this, this methodology was thought most appropriate (Hill, 2004; Newell, 2000; Papadopoulos, et al., 1999; Thompson & Kent, 2001). In terms of the areas of participation, three male and four female sufferers of psoriasis participated in the study. For all participants, psoriasis was in the active phase and covered most parts of their body. Data was collected using a questionnaire set consisting of semi-structured questions and the research question, which was open-ended. The method of data analysis was based on an integration of the works by various phenomenologists and involved six phases, namely: bracketing, intuitive grasp, eidetic reduction, textural and structural descriptions, composite textural and structural descriptions, and the final synthesis. The participants confirmed that the statements generated were accurately reflected. The results evidenced several prominent themes shared by the group, namely: (a) that the severity of the physical manifestations and the painful symptoms of psoriasis can result in negative self-concept evaluations; (b) a lack of empathy and a failure to provide knowledge on psoriasis and a priori caution of the side-effects of psoriatic medications by the medical doctors consulted was experienced by the participants as disempowering and adversely affected their emotional well-being; (c) the doctor/patient relationship was observed as pivotal in influencing the participants general concept of self; (d) the participants acceded that medical aids need to place psoriasis on the list of chronic medical conditions; (e) social stigma adversely affects self-concept evaluations; (f) public education on psoriasis is required; (g) drawing on various methods of coping was deemed crucial to the enhancement of the self-concept in the participants journey towards psychological health; (h) positive meaning-making from the psoriatic/self-concept experience enhanced quality of life issues; and finally, (i) trait self-esteem and healthy self-concept development may be important determinant factors in the psychological recovery of patients suffering from psoriasis. More specifically, in terms of self-evaluation, the participants experienced psoriasis as an assault on the physical self that was painful, embarrassing and humiliating. In redefining psoriasis in this way, the participants redefined their body image (mental construct of the body), and with the pervasiveness of negative self-evaluations an offshoot of continuous negative cognitive and emotional schemas of the body. Regarding the doctor/patient relationship, the results of the study show a need for medical doctors to expand their focus of treating the symptoms of psoriasis to incorporate a more holistic treatment approach that places emphasis on psychological, social and nutritional processes. The willingness of medical professionals to network with psychologists and other healthcare professionals and also being prepared to integrate the concept of holism into their treatment programmes was thought one method of attaining a holistic approach to the treatment and management of dermatology patients. Significantly, the doctor/patient relationship was also experienced as being an important factor in the patients drive to want to heal (healing is not here equated with cure but rather being able to approach living with psoriasis more positively). The participants in this study experienced doctors to be largely unsympathetic and not well versed in the physiology of psoriasis. Additionally, the degree of psychological trauma experienced by the participants in their suffering with psoriasis seemed to go unnoticed by the treating doctors. To this end, helplessness and feelings of disempowerment were heightened. In terms of treatment implications, the participants claimed that their treating doctors failed to inform them of the severity of the side-effects, the dangers of various treatments, and the possible inefficacy of many treatments utilised. The participants experience of this resulted in the following: a) diminished trust in the doctor/patient relationship and the medical profession generally; b) heightened body shame and repulsion of self (as opposed to feeling repulsed by the psoriasis alone); c) intense anger and with some participants describing emotional anarchy; and finally, d) in feeling left out of the treatment decision-making process, participants felt as though they had lost control over their own body. In terms of medical aid support, the participants pointed out that psoriasis is not on the government approved list of chronic conditions and as such, given their experiences, acceded that this is something that needed to be challenged. Regarding social stigma, the participants’ experience of this appeared to result in re-enforcing a sense of their feeling socially shunned and physically alienated from their familiar body. Furthermore, it would appear that social stigma might play a participatory role in increasing the severity of the psoriatic condition due to the stress evoked in the experience of feeling socially stigmatised and also the heightening of psychological difficulties experienced as participants moved from pride to shame. All participants felt public education and awareness of the onset, cause and course of psoriasis was required. Methods of coping utilised by the participants included: the seeking out of empathetic medical practitioners, psychotherapy, hypnotherapy, assertiveness skills training, implementing spirituality in their lives, and drawing upon the support of family and friends. Finally, in the midst of much adversity, the participants found an inner strength from which to reclaim their sense of self and which they attribute to having had a positive demeanour prior to suffering from psoriasis. In the deconstruction (fracturing) of self, the participants seemed to have felt compelled into a process of change that could be characterised as a reconstruction of self - an evolving of the old and new dimensions of self that would evolve further into a stronger and more resilient sense of self that characterises the participants today. The participants to this study embarked upon a journey of self-empowerment and which was a defining factor in their making meaning from their suffering. Not alluded to in the literature is that, for the participants, psoriasis became a tool that they utilised to reclaim their lives and to re-build the self anew. The results of this study reveal many important areas for future research with persons suffering from psoriasis and dermatological conditions generally, such as: i) the focussing on levels of trait self-esteem in effecting how positive change in one's self-concept may or may not occur; ii) the exploration of disfiguring skin conditions as an impetus for self-concept enhancement and creating meaning in one’s life; iii) exploring the efficacy of combining psychotherapy with medical treatments in the management of dermatology patients; iv) exploring the role of the doctor/patient relationship in the patient’s drive towards psychological health and treatment compliance; and finally, v) exploring the impact of dermatological disease on the family of the sufferer, especially given the significance of the familial system in the sufferers coping. Importantly, the results of this study suggest that having a healthy self-concept prior to the development of illness or disease is pivotal in accounting for why some people recover remarkably well psychologically and others do not. The findings of this study are valuable and will have important implications for all within the healing profession in helping to effect positive change in their future endeavours with persons who suffer from dermatological disease.

Carrapatos são parasitas hematófagos que secretam, em sua saliva, componentes imunomoduladores capazes de promover sua alimentação e suprimir as respostas imunológicas do hospedeiro. Dentre as classes de imunomoduladores presentes na saliva, encontram-se as evasinas, proteínas com capacidade de ligarem-se a quimiocinas, inibindo sua atividade relacionada ao recrutamento de células imunes. Neste trabalho, nós descrevemos a produção recombinante e caracterização estrutural e funcional de uma nova evasina putativa, a proteína Bm-nr-264079, identificada no sialotranscriptoma do carrapato bovino R. microplus. Observamos que a proteína Bm-nr-264079 apresenta similaridade estrutural com outras evasinas de carrapatos Rhipicephalus sanguineus já caracterizadas. A proteína foi produzida na forma recombinante com sucesso a partir da expressão em Escherichia coli Rosetta e purificação em condição desnaturante por cromatografia de afinidade a metais. Esta proteína apresentou atividade inibitória sobre o desenvolvimento de psoríase em modelo animal, limitando o desenvolvimento de lesão local nos animais tratados após a indução da doença por aplicação de imiquimode. A proteína Bm-nr- 264079 não apresentou efeito inibidor do crescimento de Staphylococcus aureus e Streptococcus uberis, bactérias que comumente colonizam a pele de bovinos suscetíveis à infestação por R. microplus. Os resultados aqui apresentados demonstram que a proteína Bm-nr-264079, em sua forma recombinante, apresenta atividade inibidora da inflamação, com potencial atividade de evasina. Novos estudos são necessários para uma caracterização mais específica das possíveis atividades farmacológicas desta proteína / Ticks are hematophagous parasites that secrete, in their saliva, immunomodulatory components capable of promoting their feeding and suppressing the immune responses of the host. Among the classes of immunomodulators present in saliva, we have the evasins, proteins capable of binding to chemokines, inhibiting the recruitment of immune cells. In this work, we describe the recombinant production and structural and functional characterization of a novel putative evasin, the protein Bm-nr-264079, identified in the sialotranscriptome of the R. microplus cattle tick. We have found that the protein Bm-nr-264079 shows structural similarity to other already characterized Rhipicephalus sanguineus tick evasins. The protein was successfully produced with expression in Escherichia coli Rosetta and purification in denaturing condition by metal affinity chromatography. This protein showed inhibitory activity on the development of psoriasis in the animal model, limiting the development of local lesion in the treated animals after the induction of the disease by the application of imiquimod. The protein Bm-nr-264079 showed no inhibitory effect on the growth of Staphylococcus aureus and Streptococcus uberis, bacteria that commonly colonize the skin of cattle susceptible to R. microplus infestations. The results presented herein demonstrate that Bm-nr-264079, in its recombinant form, exhibits antiinflammatory activity with potential evasin activity. Further studies are needed to characterize more specifically the pharmacological activities of this protein

Epigenetic regulation is now known to play an important role in determining stem cell fate during normal tissue development and disease pathogenesis. In this study, we report loss of 5-hydroxymethylcytosine (5-hmC) mediated by ten-eleven translocation (TET) methylcytosine dioxygenases in keratinocyte stem cells (KSCs) and in their progenitor transit-amplifying (TA) cells of psoriatic lesions. We establish the DNA hydroxymethylation profile in both human psoriasis as well as in the imiquimod (IMQ)-induced mouse psoriasis model. Genome-wide mapping of 5-hmC in IMQ-treated mice epithelium revealed a loci-specific reduction of 5-hmC in genes associated with maintaining stem cell homeostasis including those involved in the RAR and Wnt/β-catenin signaling pathways. Restoration of TET expression in human KSC cultures via vitamin C treatment increased 5-hmC levels and induced more normal KSC differentiation. We found that by modulating 5-hmC levels in vitro, we could alter downstream expression of genes important in regulating stem cell homeostasis like nestin as well as IL-17R known to promote the psoriatic phenotype. Our findings demonstrate that loss of 5-hmC is a critical epigenomic phenomenon in KSCs and TA cells during psoriasis pathogenesis. / 2019-12-17T00:00:00Z

Background: Psoriatic arthritis (PsA) is a chronic heterogenous inflammatory arthritis with five phenotypes. The two least studied phenotypes are investigated in this thesis, including: psoriatic spondyloarthropathy (PsSpA) and psoriatic arthritis mutilans (PAM). The aims of this thesis were to determine the prevalence, clinical characteristics and radiographic characteristics of PsSpA and PAM in a cohort of PsA patients, and serum-soluble bone- turnover biomarkers of these phenotypes. Aims: Comparisons were made with PsA patients without axial disease (pPsA), and ankylosing spondylitis (AS) patients. Methods: A prospective single-centre cross-sectional study was conducted of PsA and AS patients. Serum on psoriasis-only patients (PsC) and healthy controls (HC) were also obtained. Multivariate clinical, radiographic, genetic and serum biomarker comparisons were made between these five groups of subjects. Results: The study enrolled 201 PsA and 201 AS patients, who were then reclassified as 118 PsSpA, 127 pPsA and 157 AS cases, alongside 200 PsC and 50 HC subjects. Several clinical biomarkers, imaging biomarkers, serum-soluble biomarkers and genetic biomarkers were identified that differentiate PsSpA from pPsA and AS. PsSpA affected a significant proportion of PsA patients, and was not a milder version of AS. PsSpA involvement was as disabling and clinically impactful as AS. PAM was found to be associated with PsSpA, and clinical biomarkers of PAM occurrence and radiographic progression were identified. Conclusions: In conclusion, this thesis indicates that PsSpA is on a spectrum of musculoskeletal disease, in between pPsA and AS; with PsSpA comprising a continuum itself, and with a phenotype expression related to disease duration. These findings may prompt the inception of an international-consensus classification system for PsSpA, for which there is a great clinical need. Given that PsSpA has its own discrete clinical and biomarker signature, its clinical management and research should be tailored from that of pPsA and AS. Ultimately this may further the effort for stratified and personalised medicine.

Psoriasis kan ha en stark påverkan på den hälsorelaterade livskvaliteten. Sjukdomen kan medföra hinder i psykiska och fysiska funktioner, hinder som är jämförbara med dem som ses vid cancer, ledinflammation, hypertoni, hjärtsjukdom, diabetes och depression. Det finns idag ingen behandling som helt botar psoriasis eller följdsjukdomen psoriasisartrit, i stället verkar den behandling som erbjuds främst symtomlindrande. Syftet med studien är att undersöka hur det är att leva med psoriasis och på vilket sätt sjukdomen kan medföra lidande. Metoden som används är litteraturstudier för att skapa en litteraturöversikt där likheter och skillnader mellan de ingående studiernas resultatdel undersöks. Resultatet visar att psoriasis har en kraftig påverkan på livskvaliteten och därmed medför olika former av lidande för de drabbade. Missnöjet kring behandlingarna är stort. Ett problem är att det finns lite tidigare forskning gjord kring psoriasis och livskvalitet med den kvalitativa ansatsen. Människor med psoriasis blir på grund av andra människors okunskap drabbade av missförstånd och inte minst nedvärderas allvaret i lidandet vid sjukdomen. Diskussionen visar att visst lidande, inte minst vårdlidandet, går att minska genom en ökad förståelse för hur det är att leva med psoriasis. Även attityden hos vårdpersonal behöver förändras. En ökad medvetenhet hos vårdare kan minska lidandet och öka den hälsorelaterade livskvaliteten. / <p>Program: Sjuksköterskeutbildning</p><p>Uppsatsnivå: C</p>

No description available.

According to the National Psoriasis Foundation (1976), psoriasis is a little known and poorly understood skin disease afflicting an estimated eight million victims in the United States. About fifteen thousand new cases of psoriasis are diagnosed each year. It affects men and women in equal numbers at any age, most often between the ages of fifteen and thirty-five.

The leucine-rich repeats and immunoglobulin-like domains (LRIG) family consists of three integral membrane proteins that are important in human cancer. LRIG1 is a negative regulator of growth factor signaling. Its expression is associated with longer survival in several cancer types, and the gene has been shown to function as a tumor suppressor. The roles of LRIG2 and LRIG3 are less well known. The aim of this thesis was to improve our understanding of the expression and function of the LRIG protein family in psoriasis and cancer. To investigate their expression in psoriasis, the mRNA levels and subcellular localization of the LRIG proteins were analyzed and compared between normal and psoriatic human skin. There were no differences in the LRIG mRNA levels between psoriatic and normal skin samples. However, the subcellular localization of all three LRIG proteins differed between psoriatic and normal skin. To study the physiological and molecular functions of Lrig2, we generated Lrig2E12-/- mice. These mice were viable and born at a Mendelian rate, but Lrig2E12-/- mice had an increased rate of spontaneous mortality and a transient reduction in growth rate compared to Lrig2 wild-type (wt) mice. In an orthotopic platelet-derived growth factor (PDGF)B-driven brain tumor mouse model, we studied the effect of Lrig2 on gliomagenesis. All Lrig2 wt mice developed tumors; 82% developed grade II/III tumors, and 18% developed grade IV tumors. Only 77% of the Lrig2E12-/- mice developed tumors, and they were all grade II/III tumors. Thus, Lrig2 increased the incidence and malignancy rates of PDGFB-driven gliomas. We then analyzed the effect of Lrig2 on Pdgf receptor (Pdgfr) signaling. Lrig2 had no effect on Pdgfr steady-state levels, the starvation-induced up-regulation of Pdgfrs, the phosphorylation of Pdgfrs, primary cilium formation or the PDGFBB-induced phosphorylation of Akt or Erk1/2. However, the kinetics of induction of the immediate-early genes Fos and Egr2 were altered, resulting in a more rapid induction in Lrig2E12-/- cells. We then analyzed the clinical and biological importance of LRIG1 in lung cancer. In a human lung cancer tissue micro-array (TMA), LRIG1 expression was found to be an independent positive prognostic factor for adenocarcinoma. To study the importance of Lrig1 regarding lung cancer development in vivo, we used an inducible EGFRL858R-driven mouse lung cancer model. The mice developed diffuse lung adenocarcinoma, and the tumor burden was greater in Lrig1-/- mice than in Lrig1+/+ mice (p = 0.025) at 60 days. The human lung cancer cell line H1975, with either normal or Tet-induced expression of LRIG1, was injected into the flanks of Balb/cA nude mice. Tumors formed by LRIG1-overexpressing cells were smaller than those formed by parental cells, further indicating that LRIG1 is important during lung tumor formation or growth. In vitro, LRIG1 suppressed the proliferation of H1975 cells and down-regulated the phosphorylation of MET and RET. To investigate the molecular functions of LRIG proteins further, we performed a yeast two-hybrid (YTH) screen using a peptide from the cytosolic tail of LRIG3 as bait. This screen identified LMO7 and LIMCH1 as prominent interaction partners for LRIG3. Proximity ligation assays showed that LMO7 interacted with all of the LRIG proteins at endogenous expression levels. LMO7 and LIMCH1 were expressed in all human tissues analyzed. Their expression was dramatically decreased in lung cancer compared to normal lung tissue. The expression of LMO7 was analyzed in a human lung cancer TMA. LMO7 was expressed in respiratory epithelial cells in normal lungs. However, LMO7 was only expressed in a quarter of the lung tumors. LMO7 expression was found to be an independent negative prognostic factor for lung cancer. In summary, we found that the LRIG proteins were redistributed in psoriatic skin. In a mouse glioma model, Lrig2 promoted oligodendroglioma genesis. LRIG1 was an independent positive prognostic factor in human lung cancer. Lrig1 ablation increased the tumor size in an EGFRL858R-driven lung cancer mouse model. LRIG1 expression decreased the tumor growth of human lung cancer cells in a xenograft mouse model. LMO7 interacted with all three LRIG proteins and was an independent negative prognostic factor in human lung cancer. These data demonstrate the importance of LRIG proteins in human disease.

Thesis (Ph. D.)--Case Western Reserve University, 2004. / [School of Medicine] Department of Neurosciences. Includes bibliographical references. Available online via OhioLINK's ETD Center.

Aim: Most of the patients with Psoriatic Arthritis (PsA) develop arthritis following the onset of psoriasis. The aim of the project is to identify genetic and environmental risk factors for PsA among psoriasis patients. Methods: PsA and psoriasis patients from two prospective cohorts were analyzed. The incidence of PsA among a prospective cohort of psoriasis patients was assessed. The distribution of Human Leukocyte Antigen (HLA) alleles and Killer Cell Immunoglobulin like Receptors (KIRs) and their combinations was compared between PsA, psoriasis and healthy controls. In addition, the association between a wide range of environmental exposures and PsA was evaluated by comparing the frequencies of exposed individuals among patients with recent onset PsA and psoriasis. The association between smoking and PsA was further investigated. The prevalence of smoking was in PsA, psoriasis and the general population. The interaction between HLA-C*06 and smoking was also tested. Results: The genetic analysis revealed several HLA-B alleles and HLA haplotypes that are associated with PsA compared to psoriasis and can potentially serve as independent markers for PsA. Furthermore, several combinations of KIR genes and their respective HLA ligands were also found to be associated with PsA compared to psoriasis. The incidence of PsA among psoriasis patients was found to be higher than previously reported and its rate was constant over time. HLA-C*06 was associated with increased interval between psoriasis onset and PsA. Several environmental factors including occupational exposures, infections, injuries and smoking were associated with development of PsA. The prevalence of smoking was decreased among PsA patients compared to psoriasis. The interaction between HLA-C*06 and smoking was found to be significant. Conclusions: Genetic and environmental factors are associated with the development of PsA in patients with psoriasis. These factors may serve as specific markers to identify psoriasis patients at increased risk for PsA.