subject:(systemic sclerosis)

University of Manchester

1. Harrison, Elizabeth. A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis.

Degree: PhD, 2016, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800

► Background: Malnutrition and gastrointestinal (GI) involvement are common in patients with systemic sclerosis (SSc). Despite malnutrition being common, little is known about its associations and… (more)

▼ Background: Malnutrition and gastrointestinal (GI) involvement are common in patients with systemic sclerosis (SSc). Despite malnutrition being common, little is known about its associations and predictors. Although patients are frequently screened and assessed for malnutrition, different clinically applicable assessment modalities in SSc have not been compared. An understanding of the relationship between dietary intake and energy expenditure is important for nutritional assessment and management. However, studies have not compared these. For many years, home parenteral nutrition (HPN) has been used in patients with intestinal failure, but little outcome data exists to support its role in SSc. GI involvement results in dysmotility, the underlying mechanism for the development of which is unknown. However, autonomic dysfunction has been proposed. Aims: To explore aspects of the nutritional assessment and management of patients with SSc. To seek associations and predictors of nutritional decline. To investigate for a link between GI dysmotility and autonomic dysfunction. Methods: Study 1: A retrospective review of the survival and outcome data of patients commenced on HPN over 22 years. Study 2: An assessment of 168 patients recruited over 12 months and restudied after approximately 1 year. Assessment included demographics, clinical data, GI and functional questionnaires, nutrition screening tool, oral aperture, mid-upper arm and 4-site anthropometry, bioelectrical impedance and biochemical testing. Re-study included weight change. Study 3: A 3 day assessment of dietary intake and energy expenditure using food record charts and SenseWear® Armband involving 36 patients recruited to Study 2. Study 4: Patients and matched controls completed GI and autonomic questionnaires, an autonomic battery, a gastric emptying study and postprandial cardiovascular measures and GI sensations and symptoms scores. Results: Study 1: The cumulative probabilities of surviving on HPN at 2, 5 and 10 years were 75%, 37% and 23%. HPN-associated complication rates were low. Study 2: Nutritional screening failed to identify all patients who lost weight. Mid-arm circumference correlated with body mass index (BMI) and weight change. Four-site anthropometry correlated with BMI more strongly (r=0.65 vs. r=0.49) than bioelectrical impedance analysis. Small intestinal, but not oesophageal, involvement correlated with baseline nutritional status. No clear predictors of nutritional decline were identified. Study 3: Predicted energy intakes correlated with measured expenditures, but absolute values differed. Energy intakes did not correlate with expenditures. Study 4: Autonomic measures did not correlate with gastric emptying. However, autonomic results were hindered by patient-related and technical limitations. Conclusion: Nutritional screening tools cannot be relied upon to detect all at risk patients. MAC and 4-site anthropometry may have a role in nutritional assessment. When an accurate appreciation of energy requirements is needed, kinematic…

Subjects/Keywords: 616.7; systemic sclerosis; gastrointestinal; nutrition

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Harrison, E. (2016). A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800

Chicago Manual of Style (16^th Edition):

Harrison, Elizabeth. “A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis.” 2016. Doctoral Dissertation, University of Manchester. Accessed December 09, 2019. https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800.

MLA Handbook (7^th Edition):

Harrison, Elizabeth. “A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis.” 2016. Web. 09 Dec 2019.

Vancouver:

Harrison E. A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2019 Dec 09]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800.

Council of Science Editors:

Harrison E. A prospective assessment of gastrointestinal disease and nutritional status in patients with systemic sclerosis. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/a-prospective-assessment-of-gastrointestinal-disease-and-nutritional-status-in-patients-with-systemic-sclerosis(683a2e56-8b59-4202-882f-5f22a98f46e0).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.686800

University of Manchester

2. Harrison, Elizabeth. A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS.

Degree: 2016, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347

► Background: Malnutrition and gastrointestinal (GI) involvement are common in patients with systemic sclerosis (SSc). Despite malnutrition being common, little is known about its associations and… (more)

▼ Background: Malnutrition and gastrointestinal (GI) involvement are common in patients with systemic sclerosis (SSc). Despite malnutrition being common, little is known about its associations and predictors. Although patients are frequently screened and assessed for malnutrition, different clinically applicable assessment modalities in SSc have not been compared. An understanding of the relationship between dietary intake and energy expenditure is important for nutritional assessment and management. However, studies have not compared these. For many years, home parenteral nutrition (HPN) has been used in patients with intestinal failure, but little outcome data exists to support its role in SSc. GI involvement results in dysmotility, the underlying mechanism for the development of which is unknown. However, autonomic dysfunction has been proposed.Aims: To explore aspects of the nutritional assessment and management of patients with SSc. To seek associations and predictors of nutritional decline. To investigate for a link between GI dysmotility and autonomic dysfunction.Methods: Study 1: A retrospective review of the survival and outcome data of patients commenced on HPN over 22 years. Study 2: An assessment of 168 patients recruited over 12 months and restudied after approximately 1 year. Assessment included demographics, clinical data, GI and functional questionnaires, nutrition screening tool, oral aperture, mid-upper arm and 4-site anthropometry, bioelectrical impedance and biochemical testing. Re-study included weight change. Study 3: A 3 day assessment of dietary intake and energy expenditure using food record charts and SenseWear® Armband involving 36 patients recruited to Study 2. Study 4: Patients and matched controls completed GI and autonomic questionnaires, an autonomic battery, a gastric emptying study and postprandial cardiovascular measures and GI sensations and symptoms scores.Results: Study 1: The cumulative probabilities of surviving on HPN at 2, 5 and 10 years were 75%, 37% and 23%. HPN-associated complication rates were low. Study 2: Nutritional screening failed to identify all patients who lost weight. Mid-arm circumference correlated with body mass index (BMI) and weight change. Four-site anthropometry correlated with BMI more strongly (r=0.65 vs. r=0.49) than bioelectrical impedance analysis. Small intestinal, but not oesophageal, involvement correlated with baseline nutritional status. No clear predictors of nutritional decline were identified. Study 3: Predicted energy intakes correlated with measured expenditures, but absolute values differed. Energy intakes did not correlate with expenditures. Study 4: Autonomic measures did not correlate with gastric emptying. However, autonomic results were hindered by patient-related and technical limitations.Conclusion: Nutritional screening tools cannot be relied upon to detect all at risk patients. MAC and 4-site anthropometry may have a role in nutritional assessment. When an accurate appreciation of energy requirements is needed, kinematic monitors… Advisors/Committee Members: HERRICK, ARIANE AL, LAL, SIMON S, Herrick, Ariane, Mclaughlin, John, Lal, Simon.

Subjects/Keywords: systemic sclerosis; gastrointestinal; nutrition

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Harrison, E. (2016). A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347

Chicago Manual of Style (16^th Edition):

Harrison, Elizabeth. “A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS.” 2016. Doctoral Dissertation, University of Manchester. Accessed December 09, 2019. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347.

MLA Handbook (7^th Edition):

Harrison, Elizabeth. “A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS.” 2016. Web. 09 Dec 2019.

Vancouver:

Harrison E. A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2019 Dec 09]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347.

Council of Science Editors:

Harrison E. A PROSPECTIVE ASSESSMENT OF GASTROINTESTINAL DISEASE AND NUTRITIONAL STATUS IN PATIENTS WITH SYSTEMIC SCLEROSIS. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:300347

Boston University

3. Creed, Mitchell Peterson. Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation.

Degree: MA, Biochemistry, 2013, Boston University

URL: http://hdl.handle.net/2144/21141

► Systemic sclerosis (SSc) is a clinically heterogenous chronic fibrotic disease which affects skin and internal organs. While the pathogenesis of SSc remains unknown, the hallmark… (more)

▼ Systemic sclerosis (SSc) is a clinically heterogenous chronic fibrotic disease which affects skin and internal organs. While the pathogenesis of SSc remains unknown, the hallmark of both localized and diffuse SSc in the skin is the replacement of normal dermal architecture with excessive deposition of collagen and other connective tissue macromolecules. Progressive replacement of tissue architecture by collagen-rich extracellular matrix (ECM) results in functional impairment of affected organs. Fibrotic damage to these affected organs accounts for much of the morbidity and mortality concomitant with SSc, particularly in the lungs. Myofibroblasts are the primary ECM-secreting cells during wound healing and fibrosis. Myocardin-related transcription factor A (MRTF-A), is an important regulator of myofibroblast differentiation, depending on serum response factor (SRF) for smooth muscle actin (SMA) and Sp1 in the regulation of collagen gene expression. MRTF-A continually shuttles between the nucleus and cytoplasm in unstimulated cells. Signals of stress, mechanical force, and migration control MRTF-A movement by a mechanism in which Rho-activated cytoskeletal actin polymerization induces its relocation from the cytoplasm to the nucleus. The major hypothesis in this thesis is that MRTF-A is dysregulated (impairment of a physiological regulatory mechanisms) and/or activated in SSc patients in part through transforming growth factor beta (TGF-β). To test this hypothesis, immunohistochemistry using MRTF-A antibodies was performed on SSc patient skin lesions and healthy control skin. Staining was observed in the epidermis, epidermal structures, vasculature and dermis of SSc and healthy control skin. In the epidermal layer of patients with SSc, there was significantly more nuclear localization of MRTF-A then in normal controls. Prominent staining is also present in endothelial, perivascular and some perivascular inflammatory cells of SSc patients. Perivascular staining was not seen in healthy controls. Interestingly, there was some accumulation of nuclear MRTF-A in areas typical of myofibroblasts in SSc skin, but this staining is not as striking as vascular staining. TGF-β activates MRTF-A in a cell-specific manner. As SSc typically begins within the skin, human dermal fibroblasts (HDF) were grown in culture. HDFs synthesize and secrete collagen to a greater extent when compared to human lung fibroblasts (IMR90 cells). Treatment with TGF-β enhances cytoplasmic localization of MRTF-A at 4-8 hours in HDFs and prolongs nuclear localization. Transgenic mouse lung cells were isolated from an MRTF-A loss-of-function mouse carrying the 3.6 kb proximal promoter of the rat COL1A1 gene driving topaz green fluorescent protein (GFP) (pOB3.6COLGFPtpz). Since angiotensin II (ANG II) may enhance TGF-β response or collagen transcription directly, wild type (WT) and MRTF-A knockout (KO) cells were treated with ANG II and TGF-β. Quantification of collagen transcription by GFP fluorescence and protein synthesis by Western and secretion…

Subjects/Keywords: Medicine; Biochemistry; Systemic sclerosis

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Creed, M. P. (2013). Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/21141

Chicago Manual of Style (16^th Edition):

Creed, Mitchell Peterson. “Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation.” 2013. Masters Thesis, Boston University. Accessed December 09, 2019. http://hdl.handle.net/2144/21141.

MLA Handbook (7^th Edition):

Creed, Mitchell Peterson. “Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation.” 2013. Web. 09 Dec 2019.

Vancouver:

Creed MP. Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation. [Internet] [Masters thesis]. Boston University; 2013. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/2144/21141.

Council of Science Editors:

Creed MP. Characterization of myocardin related transcription factor A expression and function in systemic scleroderma and collagen gene regulation. [Masters Thesis]. Boston University; 2013. Available from: http://hdl.handle.net/2144/21141

University of Dundee

4. McSwiggan, Stephen John. Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).

Degree: PhD, 2014, University of Dundee

URL: http://hdl.handle.net/10588/163dc6e5-b5dd-4945-9756-8dae629cff48

► Background: Systemic sclerosis (SSc) is an autoimmune disease associated with significant mortality and morbidity. Cardiovascular causes are the single largest contributor to premature death. To… (more)

▼ Background: Systemic sclerosis (SSc) is an autoimmune disease associated with significant mortality and morbidity. Cardiovascular causes are the single largest contributor to premature death. To date, much of the focus on managing the care of SSc patients has concentrated on traditional risk factors related to fibrotic and microvascular dysfunction. There is, however, evidence of a strong cardiovascular component to the disease and points to macrovascular dysfunction as being a key contributor to the premature mortality associated with SSc. This thesis reports on the conduct of a multi-centre, randomised, placebo-controlled clinical trial (the SSTEP Study). The aim of the study was to assess whether oral Iloprost was more effective than placebo in reducing cardiovascular events and disease progression in SSc. Methods: Two hundred and sixteen patients with systemic sclerosis were recruited, between February 2002 and February 2005, at nine centres in the UK and Ireland. After one month placebo run-in, participants were randomised to either oral Iloprost (50-200mcg daily) or matched placebo. Baseline demographics, disease characteristics and organ screening data were collected, and participants were reviewed annually for endpoint measurements; CV events, SSc disease progression and mortality, with regular safety reviews between these annual visits. Participants were followed up for a period of 4 to 7 years. Results: Data analysis of the combination of the two measures (survival free from death or a cardiovascular event) demonstrated a trend towards favouring Iloprost over placebo but the difference was not statistically significant (Logrank test: Chi square=0.75, p=0.39). When time to a confirmed cardiovascular endpoint alone was examined there was a suggestion of a benefit from Iloprost, but the difference was again not statistically significant (Logrank test, Chi square =0.82, p=0.37). There was no statistically significant change in the rate at which organ screening endpoints occurred throughout follow-up, and for each endpoint there was no statistically significant difference between results in patients randomised to Iloprost compared to those randomised to placebo. Withdrawal from the treatment to which the patient was randomised was frequent with 97 (45%) of the total participants discontinuing study medication. ‘On treatment’ analysis, undertaken using the endpoint of death or confirmed cardiovascular endpoint, just failed to show statistical significance at the 5% level (p=0.054). Conclusion: The results of the SSTEP study showed that there was a trend towards favouring oral Iloprost over placebo in systemic sclerosis, though there was no statistically significant evidence to recommend its use to prevent disease progression. The high rate of withdrawal from both Iloprost and placebo hindered the possibility of demonstrating that Iloprost was effective in this study. It cannot be concluded that it is a useful therapy that may prevent premature mortality or progression to cardiovascular disease in this patient…

Subjects/Keywords: 610; Systemic sclerosis; Iloprost; Cardiovascular disease

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

McSwiggan, S. J. (2014). Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). (Doctoral Dissertation). University of Dundee. Retrieved from http://hdl.handle.net/10588/163dc6e5-b5dd-4945-9756-8dae629cff48

Chicago Manual of Style (16^th Edition):

McSwiggan, Stephen John. “Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).” 2014. Doctoral Dissertation, University of Dundee. Accessed December 09, 2019. http://hdl.handle.net/10588/163dc6e5-b5dd-4945-9756-8dae629cff48.

MLA Handbook (7^th Edition):

McSwiggan, Stephen John. “Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).” 2014. Web. 09 Dec 2019.

Vancouver:

McSwiggan SJ. Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). [Internet] [Doctoral dissertation]. University of Dundee; 2014. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/10588/163dc6e5-b5dd-4945-9756-8dae629cff48.

Council of Science Editors:

McSwiggan SJ. Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). [Doctoral Dissertation]. University of Dundee; 2014. Available from: http://hdl.handle.net/10588/163dc6e5-b5dd-4945-9756-8dae629cff48

Temple University

5. Zacharakis, Nikolaos. Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells.

Degree: PhD, 2014, Temple University

URL: http://digital.library.temple.edu/u?/p245801coll10,249827

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Microbiology and Immunology

Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissue. Immune system dysregulation, excessive deposition of collagen and microvascular damage… (more)

▼

Microbiology and Immunology

Systemic sclerosis (SSc) is a chronic autoimmune disease of the connective tissue. Immune system dysregulation, excessive deposition of collagen and microvascular damage in the skin and multiple internal organs are the main pathologic characteristics of the disease. Little is known about the mechanisms that are responsible for the pathogenesis of SSc. However, evidence has been accumulated demonstrating that T cells play a key role in the initiation and propagation of the disease. Previous studies in our laboratory have identified the presence of high proportions of identical β–chains TCR transcripts, demonstrating the presence of clonal expansion of T cells in skin biopsies from patients with SSc of recent onset. These T cells have undergone proliferation and clonal expansion in response to as yet unidentified antigen(s). The hypothesis that has been tested in this study is whether clonally expanded T cells in skin biopsies of patients with SSc of recent onset recognize self or non–self (possibly viral) putative SSc antigens, including DNA topoisomerase I, cytomegalovirus (CMV) and parvovirus. With the objective to identify the antigens recognized by clonally expanded T cells in skin biopsies of patients with SSc, we examined the presence of α– and β–chain TCR transcripts. Amplification of α–chain TCR transcripts by the non–palindromic adaptor PCR (NPA–PCR)/Vα specific PCR followed by cloning and sequencing revealed the presence of several clonally expanded α–chain TCR transcripts in skin biopsies from four patients with SSc and peripheral blood from one of these patients. Additionally, several clonally expanded β–chain TCR transcripts were identified in skin biopsies from all three of these patients with SSc examined, after NPA–PCR/Vβ specific amplification followed by cloning and sequencing. To identify the antigens recognized by these in vivo clonally expanded α– and β–chain TCR clones, full length α– and β– chain TCR transcripts containing the identified CDR3 regions from the clonally expanded TCR clones from the patients SSc–21 and SSc–22 were constructed. Pairs of clonally expanded, full length α– and β–chain TCR transcripts and appropriate controls were expressed in mutant TCR negative cells of the Jurkat T cell line (J.RT3–T3.5) by using a retroviral gene transfer and expression system. Each clonally expanded α–chain TCR transcript was combined with each clonally expanded β–chain TCR transcript from the same patient, generating T cells lines containing all pairing combinations of the clonally expanded TCR transcripts for each SSc patient. A total of 52 T cell lines were generated, including 10 control T cell lines. The surface expression of the TCR complex on these T cell lines was verified by flow cytometric analysis using antibodies against the α/β TCR…

Advisors/Committee Members: Platsoucas, Chris D., Tsygankov, Alexander;, Oleszak, Emilia, Soprano, Kenneth J., Skorski, Tomasz, Henderson, Earl E., Monos, Dimitrios;.

Subjects/Keywords: Immunology;

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zacharakis, N. (2014). Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,249827

Chicago Manual of Style (16^th Edition):

Zacharakis, Nikolaos. “Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells.” 2014. Doctoral Dissertation, Temple University. Accessed December 09, 2019. http://digital.library.temple.edu/u?/p245801coll10,249827.

MLA Handbook (7^th Edition):

Zacharakis, Nikolaos. “Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells.” 2014. Web. 09 Dec 2019.

Vancouver:

Zacharakis N. Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2019 Dec 09]. Available from: http://digital.library.temple.edu/u?/p245801coll10,249827.

Council of Science Editors:

Zacharakis N. Identification of putative antigens in Systemic Sclerosis utilizing in vivo clonally expanded T cells. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,249827

University of Dundee

6. McSwiggan, Stephen John. Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).

Degree: PhD, 2014, University of Dundee

URL: https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768

► Background: Systemic sclerosis (SSc) is an autoimmune disease associated with significant mortality and morbidity. Cardiovascular causes are the single largest contributor to premature death. To… (more)

▼ Background: Systemic sclerosis (SSc) is an autoimmune disease associated with significant mortality and morbidity. Cardiovascular causes are the single largest contributor to premature death. To date, much of the focus on managing the care of SSc patients has concentrated on traditional risk factors related to fibrotic and microvascular dysfunction. There is, however, evidence of a strong cardiovascular component to the disease and points to macrovascular dysfunction as being a key contributor to the premature mortality associated with SSc. This thesis reports on the conduct of a multi-centre, randomised, placebo-controlled clinical trial (the SSTEP Study). The aim of the study was to assess whether oral Iloprost was more effective than placebo in reducing cardiovascular events and disease progression in SSc. Methods: Two hundred and sixteen patients with systemic sclerosis were recruited, between February 2002 and February 2005, at nine centres in the UK and Ireland. After one month placebo run-in, participants were randomised to either oral Iloprost (50-200mcg daily) or matched placebo. Baseline demographics, disease characteristics and organ screening data were collected, and participants were reviewed annually for endpoint measurements; CV events, SSc disease progression and mortality, with regular safety reviews between these annual visits. Participants were followed up for a period of 4 to 7 years. Results: Data analysis of the combination of the two measures (survival free from death or a cardiovascular event) demonstrated a trend towards favouring Iloprost over placebo but the difference was not statistically significant (Logrank test: Chi square=0.75, p=0.39). When time to a confirmed cardiovascular endpoint alone was examined there was a suggestion of a benefit from Iloprost, but the difference was again not statistically significant (Logrank test, Chi square =0.82, p=0.37). There was no statistically significant change in the rate at which organ screening endpoints occurred throughout follow-up, and for each endpoint there was no statistically significant difference between results in patients randomised to Iloprost compared to those randomised to placebo. Withdrawal from the treatment to which the patient was randomised was frequent with 97 (45%) of the total participants discontinuing study medication. ‘On treatment’ analysis, undertaken using the endpoint of death or confirmed cardiovascular endpoint, just failed to show statistical significance at the 5% level (p=0.054). Conclusion: The results of the SSTEP study showed that there was a trend towards favouring oral Iloprost over placebo in systemic sclerosis, though there was no statistically significant evidence to recommend its use to prevent disease progression. The high rate of withdrawal from both Iloprost and placebo hindered the possibility of demonstrating that Iloprost was effective in this study. It cannot be concluded that it is a useful therapy that may prevent premature mortality or progression to cardiovascular disease in this patient…

Subjects/Keywords: 610; Systemic sclerosis; Iloprost; Cardiovascular disease

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

McSwiggan, S. J. (2014). Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). (Doctoral Dissertation). University of Dundee. Retrieved from https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768

Chicago Manual of Style (16^th Edition):

McSwiggan, Stephen John. “Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).” 2014. Doctoral Dissertation, University of Dundee. Accessed December 09, 2019. https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768.

MLA Handbook (7^th Edition):

McSwiggan, Stephen John. “Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression).” 2014. Web. 09 Dec 2019.

Vancouver:

McSwiggan SJ. Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). [Internet] [Doctoral dissertation]. University of Dundee; 2014. [cited 2019 Dec 09]. Available from: https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768.

Council of Science Editors:

McSwiggan SJ. Cardiovascular events and mortality in systemic sclerosis : a study of the effect of Iloprost on these and on disease progression : the SSTEP Study (Systemic Sclerosis Trial of Events and Progression). [Doctoral Dissertation]. University of Dundee; 2014. Available from: https://discovery.dundee.ac.uk/en/studentTheses/163dc6e5-b5dd-4945-9756-8dae629cff48 ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620768

7. Marut, Wioleta. ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique.

Degree: Docteur es, Immunologie, 2012, Université Paris Descartes – Paris V

URL: http://www.theses.fr/2012PA05T079

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Plusieurs rapports ont suggéré que les formes réactives de l'oxygène (FRO) et d'azote sont impliquées dans la pathogénèse de la ScS. Les fibroblastes ScS de… (more)

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Plusieurs rapports ont suggéré que les formes réactives de l'oxygène (FRO) et d'azote sont impliquées dans la pathogénèse de la ScS. Les fibroblastes ScS de la peau et des organes internes surproduisent des FRO qui déclenchent la prolifération des fibroblastes et la synthèse de collagène de type I, conduisant à l'initiation et à la progression de la ScS. Le laboratoire a mis au point un modèle de souris ScS, induite par injections itératives de HOCl. Comme dans la ScS humaine, les fibroblastes de la peau de souris ScS produisent de manière constitutive de grandes quantités de FRO. Nous avons utilisé cette propriété pour induire sélectivement l'apoptose de fibroblastes de souris ScS. Le catalyseur organotelluride-(PHTE) 2NQ et le composé naturel Dipropyltertrasulfide (DPTTS) sont capables d'augmenter specifiquement la production de FRO par les fibroblastes et d’induire un stress oxydatif létal dans les fibroblastes sclérodermiques. Ce phénomène n'a aucun impact sur les fibroblastes normaux qui présentent des taux de FRO basaux faible et un statut oxydant / antioxydant normal. De nombreuses études ont également prouvé l’importance des espèces azotées dans la l’induction de la ScS. Chez les patients atteints de SSc, le taux sérique de l'oxyde nitrique est considérablement accru. De plus, le NO peut se combiner avec d'autres radicaux libres comme l'anion superoxyde (O•-2) pour former le peroxynitrite (ONOO-) qui est hautement cytotoxique et contribue à l'inflammation, la fibrose et l'apoptose des cellules endothéliales. La production de NO par les cellules endothéliales ou les fibroblastes peut être stimulée par l'angiotensine II, principal peptide de la voie rénine-angiotensine (RAS). Comme chez les patients atteints de sclérodermie, les souris HOCl/ScS présentent des taux sériques d'angiotensine II élevés, ce qui est favorable à la prolifération des fibroblastes, à la fibrose, et à l'inflammation. Ces observations nous ont conduites à tester les effets de l'Irbésartan, un antagoniste des récepteurs de l’angiotensine II de type I (AT1 RA) dans le ScS modèle murin. Un nouveau modèle animal basé sur l'exposition chronique à des ROS et présentant de nombreuses similitudes avec la maladie humaine, m'a permis d'étudier de nouveaux traitements de la ScS. Ces nouvelles approches sont basées sur l'action cytotoxique de composés pro-oxydants - (PHTE) 2NQ et DPTTS - et sur les effets anti-nitrosatifs de molécules comme l'Irbésartan. Ces stratégies thérapeutiques originales ouvrent des perspectives intéressantes dans le traitement de la ScS, où l'arsenal thérapeutique est actuellement encore limité.

Several reports have suggested that reactive oxygen and nitrogen species are involved in SSc pathogenesis. SSc fibroblast from skin and internal organs overproduce ROS that trigger the proliferation of fibroblasts and the synthesis of type I collagen leading to the initiation and progresion of SSc. As in human SSc, skin fibroblasts from SSc mice constitutively produce large amounts of ROS. We have used this property to selectively…

Advisors/Committee Members: Batteux, Frédéric (thesis director).

Subjects/Keywords: Traitement de la sclérodermie systémique; Systemic sclerosis treatment; 610

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Marut, W. (2012). ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique. (Doctoral Dissertation). Université Paris Descartes – Paris V. Retrieved from http://www.theses.fr/2012PA05T079

Chicago Manual of Style (16^th Edition):

Marut, Wioleta. “ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique.” 2012. Doctoral Dissertation, Université Paris Descartes – Paris V. Accessed December 09, 2019. http://www.theses.fr/2012PA05T079.

MLA Handbook (7^th Edition):

Marut, Wioleta. “ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique.” 2012. Web. 09 Dec 2019.

Vancouver:

Marut W. ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique. [Internet] [Doctoral dissertation]. Université Paris Descartes – Paris V; 2012. [cited 2019 Dec 09]. Available from: http://www.theses.fr/2012PA05T079.

Council of Science Editors:

Marut W. ROS/RNS modulation in Systemic sclerosis treatment : Modulation ROS/RNS dans le traitement de la sclérose systémique. [Doctoral Dissertation]. Université Paris Descartes – Paris V; 2012. Available from: http://www.theses.fr/2012PA05T079

8. Huang, Hongtai. On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer.

Degree: 2015, Johns Hopkins University

URL: http://jhir.library.jhu.edu/handle/1774.2/37905

► This work seeks to develop reliable biomarkers of disease activity, progression and outcomes through the identification of significant associations between high-throughput flow cytometry data and… (more)

▼ This work seeks to develop reliable biomarkers of disease activity, progression and outcomes through the identification of significant associations between high-throughput flow cytometry data and a scleroderma clinical phenotype – initially, interstitial lung disease (ILD) - which is the leading cause of morbidity and mortality in Systemic Sclerosis (SSc). A specific aim of the work involves developing a clinically useful screening tool (hereafter a filter). Such a filter could yield accurate assessments of disease state such as the risk or presence of SSc-ILD, the activity of lung involvement and the possibility to respond to therapeutic intervention. Ultimately this instrument should facilitate a refined stratification of SSc patients into clinically relevant subsets at the time of diagnosis and subsequently during the course of the disease, preventing bad outcomes from disease progression or unnecessary treatment side effects. This role could involve a scenario in which an SSc patient passes the presumptive (FVCstpp) test for ILD, but the filter indicates that their flow cytometry (FC) profile is consistent with ILD. In such a case, a physician might: 1) increase frequency of testing to detect early development of ILD; 2) implement more sophisticated diagnostic procedures (e.g., high resolution chest CT scan - HRCT) to confirm the presence of ILD; and 3) consider prophylactic disease modifying treatments. Note that the intention of this research is not to develop screening tools that merely aim at predictive accuracy, but to produce methods that also contribute to the understanding of disease mechanisms. Having used ILD as phenotype, subsequent analyses in this thesis used different phenotypes: antiTopoisomerase (ATA), antiCentromere Anti Nuclear Antibodies (these antibodies are most strongly associated with diffuse and limited systemic sclerosis respectively) and cancer. This research was based on clinical and peripheral blood flow cytometry data (Immune Response In Scleroderma, IRIS) from consented patients followed at the Johns Hopkins Scleroderma Center. Methods. The methods utilized in the work involve: (1) data mining (Conditional Random Forests - CRF) to identify subsets of FC variables that are highly effective in classifying ILD patients; (2) Gene Set Enrichment Analysis (GSEA) to further refine FC subsets; (3) stochastic simulation and Classification and Regression Trees (CART) to design, test and validate ILD filters; and (4) Stepwise Generalized Linear Model (GLM) regression and Drop-in-Deviance testing to identify minimal size, best performing models for predicting ILD status from both FC and selected clinical variables. Results. IRIS flow cytometry data provides useful information in assessing the ILD status of SSc patients. Our hybrid analysis approach proved successful in predicting SSc patient ILD status with a high degree of success (out-of-sample > 82%; training data set 79 patients, validation data set 40 patients). Pre-partitioning patients into groups using CART significantly increased… Advisors/Committee Members: Burke, Thomas A (advisor).

Subjects/Keywords: Data Analysis; Flow Cytometry; Systemic Sclerosis; Autoimmune disorders

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Huang, H. (2015). On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer. (Thesis). Johns Hopkins University. Retrieved from http://jhir.library.jhu.edu/handle/1774.2/37905

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Huang, Hongtai. “On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer.” 2015. Thesis, Johns Hopkins University. Accessed December 09, 2019. http://jhir.library.jhu.edu/handle/1774.2/37905.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Huang, Hongtai. “On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer.” 2015. Web. 09 Dec 2019.

Vancouver:

Huang H. On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer. [Internet] [Thesis]. Johns Hopkins University; 2015. [cited 2019 Dec 09]. Available from: http://jhir.library.jhu.edu/handle/1774.2/37905.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Huang H. On the Identification of Associations between Flow Cytometry Data, Systemic Sclerosis and Cancer. [Thesis]. Johns Hopkins University; 2015. Available from: http://jhir.library.jhu.edu/handle/1774.2/37905

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidade do Rio Grande do Sul

9. Pavan, Thais Rohde. Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica.

Degree: 2015, Universidade do Rio Grande do Sul

URL: http://hdl.handle.net/10183/150716

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Introdução: A capilaroscopia periungueal (CPU) tem sido relacionada ao dano a órgãos-alvo na esclerose sistêmica (ES). No entanto, estudos relativos à gravidade das alterações da… (more)

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Introdução: A capilaroscopia periungueal (CPU) tem sido relacionada ao dano a órgãos-alvo na esclerose sistêmica (ES). No entanto, estudos relativos à gravidade das alterações da CPU com a mortalidade evidenciam resultados discrepantes. Este estudo tem como objetivo verificar associação da gravidade da microangiopatia periférica na CPU com o risco de morte na ES. Pacientes e métodos: Cento e setenta pacientes com ES foram prospectivamente avaliados e acompanhados em média de 9,3 anos. Além da avaliação clínica, os pacientes foram submetidos à sorologia, testes de função pulmonar, ecocardiograma e tomografia computadorizada pulmonar de alta resolução (TCAR). A perda capilar na CPU foi avaliada pelo escore avascular (EA), que varia de 0 a 3. O número médio de ectasias, megacapillaries e hemorragias por dedo também foi registrado. O modelo de Cox proporcional Uni e Multivariado foi utilizado para analisar a associação do escore avascular com o risco de morte através da associação Hazard ratio (HR). Resultados: Por análise de Cox univariada, o escore avascular associado à mortalidade foi estatisticamente significativo (HR = IC 1.54, 95%: 1.13-2.09, p = 0.006), mas outras variáveis capilaroscópicas (número de ectasias, megacapillaries e hemorragias por dedo) não foram (p> 0,40 para todos os testes). Após o ajuste para escore de pele, idade, sexo, origem étnica, e sinais de isquemia digital, a associação entre o escore avascular perdeu significância estatística (HR = 1.23, IC: 0.84-1.81, p = 0.276). Também não houve associação significativa do escore avascular quando ajustado para uma combinação de resultados de exames complementares. Conclusões: A gravidade da desvascularização na CPU está relacionada a um maior risco de mortalidade na ES; No entanto, a associação não é estatisticamente significativa após ajuste para outras variáveis clínicas e laboratoriais. Apesar do fato de não mostrar uma associação independente do EA com a mortalidade, consideramos que é útil na avaliação de pacientes com diagnóstico de esclerose sistêmica, uma vez que pode dar uma visão geral e confiável da gravidade da doença.

Introduction: The nailfold capillaroscopy (NCF) has been related to end-organ damage in Systemic sclerosis (SSc). However, studies relating the severity of NCF alterations with mortality have rendered mixed results. This study aims to verify the association of the severity of peripheral microangiopathy in the NFC with the risk of death in SSc. Patients and methods: One hundred and seventy SSc patients were prospectively evaluated and followed a mean of 9.3 years. Besides clinical evaluation, patients underwent serology, pulmonary function tests, Doppler echocardiography, and pulmonary high resolution computed tomography (HRCT). Capillary loss on NCF was evaluated using the avascular score (AS), ranging from 0 to 3. The mean number of ectasias, megacapillaries and hemorrhages per finger was also recorded; univariate and multivariate Cox proportional models were used to analyze the association of the AS with the risk of…

Advisors/Committee Members: Xavier, Ricardo Machado, Chakr, Rafael Mendonça da Silva.

Subjects/Keywords: Systemic sclerosis; Escleroderma sistêmico; Mortalidade; Capillaroscopy; Angioscopia microscópica; Mortality; Cohort studies

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Pavan, T. R. (2015). Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica. (Thesis). Universidade do Rio Grande do Sul. Retrieved from http://hdl.handle.net/10183/150716

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Pavan, Thais Rohde. “Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica.” 2015. Thesis, Universidade do Rio Grande do Sul. Accessed December 09, 2019. http://hdl.handle.net/10183/150716.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Pavan, Thais Rohde. “Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica.” 2015. Web. 09 Dec 2019.

Vancouver:

Pavan TR. Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica. [Internet] [Thesis]. Universidade do Rio Grande do Sul; 2015. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/10183/150716.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Pavan TR. Capilaroscopia periungueal como preditor de mortalidade em uma coorte de pacientes com esclerose sistêmica. [Thesis]. Universidade do Rio Grande do Sul; 2015. Available from: http://hdl.handle.net/10183/150716

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester

10. Arthur, Donna Louise. Doppler optical coherence tomography for microcirculation studies.

Degree: PhD, 2014, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145

► This thesis forms part of an ongoing long-term project to investigate the suitability of Doppler optical coherence tomography (OCT) as a measurement tool to investigate… (more)

Subjects/Keywords: 616.07; OCT; Optical Coherence Tomography; Imaging; Doppler; Systemic sclerosis; Microcirculation

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Arthur, D. L. (2014). Doppler optical coherence tomography for microcirculation studies. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145

Chicago Manual of Style (16^th Edition):

Arthur, Donna Louise. “Doppler optical coherence tomography for microcirculation studies.” 2014. Doctoral Dissertation, University of Manchester. Accessed December 09, 2019. https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145.

MLA Handbook (7^th Edition):

Arthur, Donna Louise. “Doppler optical coherence tomography for microcirculation studies.” 2014. Web. 09 Dec 2019.

Vancouver:

Arthur DL. Doppler optical coherence tomography for microcirculation studies. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2019 Dec 09]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145.

Council of Science Editors:

Arthur DL. Doppler optical coherence tomography for microcirculation studies. [Doctoral Dissertation]. University of Manchester; 2014. Available from: https://www.research.manchester.ac.uk/portal/en/theses/doppler-optical-coherence-tomography-for-microcirculation-studies(a18d59c3-6cfb-4266-98b1-188040bc120f).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.603145

University of Southern California

11. Chen, Chider. From mesenchymal stem cell therapy to discovery of drug therapy for systemic sclerosis.

Degree: PhD, Cranio-Facial Biology, 2014, University of Southern California

URL: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2914

► Bone marrow mesenchymal stem cells (BMMSCs) are non‐hematopoietic multipotent stem cells capable of differentiating into both mesenchymal and non‐mesenchymal cell types. In addition to generate… (more)

▼ Bone marrow mesenchymal stem cells (BMMSCs) are non‐hematopoietic multipotent stem cells capable of differentiating into both mesenchymal and non‐mesenchymal cell types. In addition to generate bone structure to replace damaged and diseased tissues, preclinical and clinical studies have shown that BMMSCs display profound immunomodulatory functions via inhibiting the proliferation and function of several major immune cells such as T lymphocytes, B lymphocytes, natural killer (NK), and dendritic cells. Thus, systemic infusion of BMMSCs has been used to treat a variety of diseases, including acute graft-versus-host-disease (GVHD), ameliorating HSC engraftment, systemic lupus erythematosus (SLE), intestinal and bowel disease (IBD), and sepsis. However, the detailed mechanism in which BMMSCs regulate immune function is not fully understood. ❧ In the first part of Chapter 2 of this study, we show that systemic infusion of BMMSCs induces a transient T cell apoptosis via the Fas Ligand (FasL)‐mediated Fas pathway and ameliorates diseased phenotypes in fibrillin-1 (FBN1) mutated systemic sclerosis (SSc) and dextran sulfate sodium‐induced experimental colitis mice. The therapeutic mechanism of BMMSC infusion is associated with phagocytosis of apoptotic T cell debris, leading to a high level of macrophage‐mediated transforming growth factor beta (TGFβ) production and a subsequent immune tolerance. Importantly, we provided clinical evidence to show that MSC infusion in SSc patients resulted in a T cell apoptosis and up‐regulation of Tregs. Additionally, we revealed that Fas null BMMSCs, with normal FasL function, failed to induce T cell apoptosis and offer therapeutic effect for SS and colitis mice. Mechanistic study showed that Fas governed monocyte chemotactic protein 1 (MCP-1) secretion in BMMSCs, which plays a crucial role in the recruitment of T cells to BMMSCs for FasL‐mediated apoptosis. In summary, BMMSCs use Fas to control MCP-1 secretion for the recruitment of T cells and subsequently use FasL to induce activated T cell apoptosis. Macrophages take debris of apoptotic T cells to release a high level of TGFβ, leading to up‐regulation of regulatory T cells (Tregs) and, ultimately, immune tolerance for immunotherapies. ❧ This study uncovers the role of Fas and FasL in BMMSC‐based immune therapies, which may serve as a basis to develop novel strategies for improving cell‐based therapies. The significance of this study is to identify a novel mechanism of BMMSC‐associated immunomodulation and immune therapy. Also, Fas and FasL collaboratively induce immune tolerance suggests a potential new mechanism that receptor/ligand coupled to execute therapeutic effect in cell‐based treatment. This study covered experimental evidences for stem cell biology, molecular mechanism of BMMSC associated immunomodulation, and stem cell-based immunotherapies. ❧ In second part of Chapter 2 of this study, we showed for the first time that telomerase activity is required for maintaining the immunomodulatory properties of MSCs. Telomerase deficient… Advisors/Committee Members: Shi, Songtao (Committee Chair), Chai, Yang (Committee Member), Chuong, Cheng-Ming (Committee Member), Ying, Qi-Long (Committee Member), Paine, Michael L. (Committee Member), Le, Anh (Committee Member).

Subjects/Keywords: immunomodulation; mesenchymal stem cell; osteopenia; rapamycin; systemic sclerosis; telomerase

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chen, C. (2014). From mesenchymal stem cell therapy to discovery of drug therapy for systemic sclerosis. (Doctoral Dissertation). University of Southern California. Retrieved from http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2914

Chicago Manual of Style (16^th Edition):

Chen, Chider. “From mesenchymal stem cell therapy to discovery of drug therapy for systemic sclerosis.” 2014. Doctoral Dissertation, University of Southern California. Accessed December 09, 2019. http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2914.

MLA Handbook (7^th Edition):

Chen, Chider. “From mesenchymal stem cell therapy to discovery of drug therapy for systemic sclerosis.” 2014. Web. 09 Dec 2019.

Vancouver:

Chen C. From mesenchymal stem cell therapy to discovery of drug therapy for systemic sclerosis. [Internet] [Doctoral dissertation]. University of Southern California; 2014. [cited 2019 Dec 09]. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2914.

Council of Science Editors:

Chen C. From mesenchymal stem cell therapy to discovery of drug therapy for systemic sclerosis. [Doctoral Dissertation]. University of Southern California; 2014. Available from: http://digitallibrary.usc.edu/cdm/compoundobject/collection/p15799coll3/id/370638/rec/2914

12. P.A. Lonati. LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.

Degree: 2013, Università degli Studi di Milano

URL: http://hdl.handle.net/2434/215886

► IL-17 cytokine family has recently emerged as critical players in immunity and inflammatory diseases, both involved in initiating or maintaining the fibrosis process. Indeed, an… (more)

▼ IL-17 cytokine family has recently emerged as critical players in immunity and inflammatory diseases, both involved in initiating or maintaining the fibrosis process. Indeed, an inflammatory infiltrate is characteristic of the early phases of fibrosis development and inflammatory cells may profoundly affect the ECM production by releasing soluble products or by direct cell-to-cell interactions that modify fibroblast metabolism. Fibrosis is characteristic of many diseases, as systemic sclerosis (SSc), morphea, acrodermatitis chronica atrophicans, Shulman fasciitis and the cutaneous form of graft versus host disease (GVHD). In particular has been shown that IL-17A is present not only in the biological fluids but also in the skin of individuals affected by SSc. The aims of this study are to understand if the IL-17 isoforms are expressed in the skin of individuals affected by these diseases and which are the cells responsible for the production of IL-17A. Moreover we are interested in understanding if the treatment with Iloprost or NAC can modify the expression of the IL-17 isoforms in the skin of SSc patients and if also the cells responsible for the production of IL-17A are modified by these drugs. Bioptic material was obtained from the involved individuals affected by different fibrotic diseases and from healthy donors (HD) undergoing plastic surgery. We adopted an immunohistochemistry and immunofluorescence approach to identify and quantify in vivo the presence of cells positive for the IL-17 isoforms, the IL-17 receptors, IL-4, IL-22, INF-γ, CD3 and Tryptase. All the IL-17 isoforms are expressed in all the bioptic samples analyzed, without significant differences between the HD and the pathologic groups. IL-17A is produced by both CD3 and mast cells, and are significantly more numerous in the HD than in the SSc skin (p=0,0485). The expression of the IL-17 isoforms in the skin of SSc patients treated with Iloprost changes unevenly in all the patients. The same happens for the expression of IL-17C in the skin of SSc individuals treated with NAC, while these patients show a marked (but not significant) increase number of IL-17A and IL-17F positive cells and a decreased number of IL-17E positive cells. The treatment with Iloprost induces also the decrease in the number of both CD3 and mast cells producing IL-17A, while NAC induces the increase in the number of CD3 IL-17A producing cells. The number of mast cells producing IL-17A in patients treated with NAC changes unevenly. The number of CD3 and mast cells that produce IL-17A does not reflect the total number of IL-17A positive cells localized in the analyzed samples. This could mean that other cell types are responsible for IL-17A production. Given the role of the IL-17 isoforms in the immunity and inflammatory pathway, the presence of these cytokines in the skin of patients affected by fibrotic diseases can mean that they can be involved in the fibrotic process. This is confirmed by the modification of the expression of the IL-17 isoforms in the skin of… Advisors/Committee Members: tutor: C. Chizzolini, P. Meroni, M.O. Borghi, coordinatore: A. Gianni, MERONI, PIERLUIGI, GIANNI, ALESSANDRO.

Subjects/Keywords: interleukin 17; fibrosis; systemic sclerosis; Iloprost; Settore MED/16 - Reumatologia

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❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lonati, P. (2013). LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. (Thesis). Università degli Studi di Milano. Retrieved from http://hdl.handle.net/2434/215886

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Lonati, P.A.. “LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.” 2013. Thesis, Università degli Studi di Milano. Accessed December 09, 2019. http://hdl.handle.net/2434/215886.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Lonati, P.A.. “LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE.” 2013. Web. 09 Dec 2019.

Vancouver:

Lonati P. LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. [Internet] [Thesis]. Università degli Studi di Milano; 2013. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/2434/215886.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Lonati P. LOCALIZZAZIONE E QUANTIFICAZIONE DELLE ISOFORME DELL'INTERLEUCHINA 17 NEL DERMA DI PAZIENTI AFFETTI DA PATOLOGIE FIBROSANTI CUTENAEE. [Thesis]. Università degli Studi di Milano; 2013. Available from: http://hdl.handle.net/2434/215886

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

13. Sobanski, Vincent. Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity.

Degree: Docteur es, Sciences de la vie et de la santé, 2017, Université Lille II – Droit et Santé

URL: http://www.theses.fr/2017LIL2S027

► La sclérodermie systémique (ScS) est une connectivite associant atteinte vasculaire, auto-immunité et fibrose. Cette pathologie est associée à une morbi-mortalité importante, et les ressources thérapeutiques… (more)

▼ La sclérodermie systémique (ScS) est une connectivite associant atteinte vasculaire, auto-immunité et fibrose. Cette pathologie est associée à une morbi-mortalité importante, et les ressources thérapeutiques sont limitées. La physiopathologie de la ScS n’est que partiellement connue, mais il apparait que les liens entre le système immunitaire et la fibrose sont étroits. Ainsi, la ScS peut être considérée comme un modèle prototypique d’étude des liens immunité-fibrose. Il s’agit d’une maladie hétérogène, c’est-à-dire que les phénotypes cliniques présentés par les patients sont variables, rendant complexe l’établissement d’une classification des patients en groupes homogènes. Mieux comprendre cette hétérogénéité est un préalable indispensable à la constitution d’endotypes, permettant l’étude des mécanismes physiopathologiques propres à chacun d’entre eux.L’objectif de cette Thèse a été de mieux appréhender cette hétérogénéité clinique et d’étudier la place des marqueurs immunologiques, en particulier les auto-anticorps, en tant que biomarqueurs de cette hétérogénéité.Le premier travail a été une classification sans a priori des patients de la cohorte européenne EUSTAR (European Scleroderma Trials and Research Group) par une analyse en cluster sur 24 variables sélectionnées (atteintes cliniques, auto-anticorps). Deux puis 6 groupes de patients homogènes ont été obtenus, dont la survie était significativement différente. Ce travail a suggéré qu’il existait des groupes homogènes de patients au-delà de la dichotomie historique forme cutanée diffuse vs. limitée. La présence d’atteintes viscérales et le statut des auto-anticorps apparaissent comme des éléments importants dans la constitution des groupes.Le deuxième travail s’est intéressé au dosage des chaines légères libres sériques (serum free light chain : SFLC) dans la ScS. Le taux de SFLC est plus élevé chez les patients ScS que chez les contrôles et est associé à des paramètres de gravité de la maladie tels que le score de Rodnan, les scores d’activité, les pressions pulmonaires et la DLCO. Cette étude apporte des arguments supplémentaires pour évoquer la participation active des lymphocytes B à la physiopathologie de la ScS.Nous avons ensuite réalisé une estimation de la prévalence des anticorps anti-ARN polymérase de type III dans notre cohorte de patients avec ScS avant d’inclure ces données dans une revue systématique avec méta-analyse. Ce travail a montré que la prévalence de ces anticorps était hétérogène entre les centres. Les facteurs potentiels pouvant expliquer une partie de cette hétérogénéité sont des facteurs géographiques, suggérant l’implication de facteurs génétiques et/ou environnementaux.Le dernier travail a été dédié à l’hypertension artérielle pulmonaire (HTAP) des connectivites, en particulier de la ScS. A partir d’une cohorte de patients provenant du centre de référence de l’HTAP du Royaume-Uni, les anticorps anti-U1RNP ont été analysés en tant que marqueur pronostique. Ces anticorps sont associés de façon significative à une meilleure survie des… Advisors/Committee Members: Dubucquoi, Sylvain (thesis director).

Subjects/Keywords: Hétérogénéité; Endotypes; Sclérodermie systémique; Auto-anticorps; Auto-antibodies; Systemic sclerosis; Heterogeneity

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sobanski, V. (2017). Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity. (Doctoral Dissertation). Université Lille II – Droit et Santé. Retrieved from http://www.theses.fr/2017LIL2S027

Chicago Manual of Style (16^th Edition):

Sobanski, Vincent. “Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity.” 2017. Doctoral Dissertation, Université Lille II – Droit et Santé. Accessed December 09, 2019. http://www.theses.fr/2017LIL2S027.

MLA Handbook (7^th Edition):

Sobanski, Vincent. “Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity.” 2017. Web. 09 Dec 2019.

Vancouver:

Sobanski V. Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity. [Internet] [Doctoral dissertation]. Université Lille II – Droit et Santé 2017. [cited 2019 Dec 09]. Available from: http://www.theses.fr/2017LIL2S027.

Council of Science Editors:

Sobanski V. Les auto-anticorps, marqueurs immunologiques de l’hétérogénéité de la sclérodermie systémique : Auto-antibodies in systemic sclerosis, immunological markers of heterogeneity. [Doctoral Dissertation]. Université Lille II – Droit et Santé 2017. Available from: http://www.theses.fr/2017LIL2S027

University of Manchester

14. Arthur, Donna Louise. Doppler Optical Coherence Tomography for Microcirculation Studies.

Degree: 2014, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264

► This thesis forms part of an ongoing long-term project to investigate the suitability of Doppler optical coherence tomography (OCT) as a measurement tool to investigate… (more)

Subjects/Keywords: OCT; Optical Coherence Tomography; Imaging; Doppler; Systemic sclerosis; Microcirculation

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APA (6^th Edition):

Arthur, D. L. (2014). Doppler Optical Coherence Tomography for Microcirculation Studies. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264

Chicago Manual of Style (16^th Edition):

Arthur, Donna Louise. “Doppler Optical Coherence Tomography for Microcirculation Studies.” 2014. Doctoral Dissertation, University of Manchester. Accessed December 09, 2019. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264.

MLA Handbook (7^th Edition):

Arthur, Donna Louise. “Doppler Optical Coherence Tomography for Microcirculation Studies.” 2014. Web. 09 Dec 2019.

Vancouver:

Arthur DL. Doppler Optical Coherence Tomography for Microcirculation Studies. [Internet] [Doctoral dissertation]. University of Manchester; 2014. [cited 2019 Dec 09]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264.

Council of Science Editors:

Arthur DL. Doppler Optical Coherence Tomography for Microcirculation Studies. [Doctoral Dissertation]. University of Manchester; 2014. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:216264

McMaster University

15. Parthasarathy, Pavithra. Identification of Markers of Profibrotic Macrophages Shared Between Human and Murine Systems, and Their Relevance to Systemic Sclerosis.

Degree: MSc, 2017, McMaster University

URL: http://hdl.handle.net/11375/23455

►

Systemic sclerosis (SSc), or scleroderma, is a complex, rare disease of unknown etiology. Macrophages constitute a large portion of the immune cell infiltrate in the… (more)

▼

Systemic sclerosis (SSc), or scleroderma, is a complex, rare disease of unknown etiology. Macrophages constitute a large portion of the immune cell infiltrate in the skin of patients with SSc, and are an important target of study. Particularly, the M2 macrophage has been implicated scleroderma and other fibrotic diseases as a key contributor to fibrotic processes. However, the definition of an M2 macrophage appears to change with context, and is poorly elucidated in different species. With varying characterizations between species and disease models, there is a need to establish some consensus on how to identify this macrophage in an uniform manner across species. We used a bioinformatic approach to identify a unique gene signature for the M2 macrophage phenotype, which is shared between human and mouse systems. We were able to confirm a 7-gene subset of this theorized signature using human and mouse in vitro systems. In addition, we selected one of the identified genes, Clec7a, and characterized its expression at the protein level on different macrophage phenotypes, across several human and mouse models. Our data show that Clec7a is a more selective marker of murine M2 macrophages than current reference markers, and is useful in human models as well. Using our M2-specific gene signature, we also identified a potential inhibitor of the signature and showed its effects on M2 marker expression. Finally, we showed some preliminary work into Clec7a expression in skin tissue from patients with scleroderma. Overall, our data suggest that Clec7a may be a valuable addition to the panel of markers used to characterize M2 macrophages and distinguish between macrophage phenotypes, and perhaps provide clarity into the development and function of the M2 macrophage. Better understanding of the M2 macrophage would ultimately be useful to the study of fibrotic diseases such as scleroderma, wherein this macrophage phenotype may be a viable target for antifibrotic therapy.

Thesis

Master of Science (MSc)

Advisors/Committee Members: Ask, Kjetil, Medical Sciences.

Subjects/Keywords: Macrophages; Scleroderma; Fibrosis; Systemic Sclerosis; Clec7a; Bioinformatics; M2 macrophages

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Parthasarathy, P. (2017). Identification of Markers of Profibrotic Macrophages Shared Between Human and Murine Systems, and Their Relevance to Systemic Sclerosis. (Masters Thesis). McMaster University. Retrieved from http://hdl.handle.net/11375/23455

Chicago Manual of Style (16^th Edition):

Parthasarathy, Pavithra. “Identification of Markers of Profibrotic Macrophages Shared Between Human and Murine Systems, and Their Relevance to Systemic Sclerosis.” 2017. Masters Thesis, McMaster University. Accessed December 09, 2019. http://hdl.handle.net/11375/23455.

MLA Handbook (7^th Edition):

Parthasarathy, Pavithra. “Identification of Markers of Profibrotic Macrophages Shared Between Human and Murine Systems, and Their Relevance to Systemic Sclerosis.” 2017. Web. 09 Dec 2019.

Vancouver:

Parthasarathy P. Identification of Markers of Profibrotic Macrophages Shared Between Human and Murine Systems, and Their Relevance to Systemic Sclerosis. [Internet] [Masters thesis]. McMaster University; 2017. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/11375/23455.

Council of Science Editors:

Parthasarathy P. Identification of Markers of Profibrotic Macrophages Shared Between Human and Murine Systems, and Their Relevance to Systemic Sclerosis. [Masters Thesis]. McMaster University; 2017. Available from: http://hdl.handle.net/11375/23455

University of Manchester

16. Hughes, Michael. Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.

Degree: PhD, 2016, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427

► Introduction: Digital ulcers (DUs) are responsible for much of the pain and disability associated with systemic sclerosis (SSc), and are a biomarker of internal organ… (more)

▼ Introduction: Digital ulcers (DUs) are responsible for much of the pain and disability associated with systemic sclerosis (SSc), and are a biomarker of internal organ involvement and poor prognosis. DUs are often used as the primary end-point in SSc clinical trials, although the reliability of rheumatologists in grading DUs is poor to moderate at best. Fingertip DUs are believed to be ischaemic in aetiology, whereas, extensor DUs are thought to occur due to mechanical factors and recurrent microtrauma. Treatments for DUs are often poorly tolerated due to systemic vasodilation. The overarching aim was to investigate the definition and objective measurement of SSc-related DUs, their pathophysiology, and a new light treatment. Method: Five studies were undertaken. (1) A web-based study in which photographs of digital lesions were graded, all either with or without clinical context. (2) A pilot study to assess the feasibility and tolerability of high-frequency ultrasound (HFUS) imaging to measure DUs. (3) A retrospective study examining whether thermographic abnormalities are associated with DUs. (4) A double-blind, randomised, crossover, controlled study of glyceryl trinitrate (GTN) to explore the pathophysiology of DUs in SSc. (5). A feasibility study of a novel light (red, infrared and blue) device to treat SSc-related DUs. Results: (1) 51 rheumatologists graded ≥ 4500 images. The clinical context (without vs with, weighted kappa statistic) did not significantly improve the intra- (0.32,0.36) or inter-rater (0.64,0.71) reliability. (2) HFUS was performed on 15 DUs and was well tolerated and feasible in the majority. DU measurement was possible in most (n=13) DUs, the mean DU depth and width were 0.99mm and 5.74mm, respectively. (3) Patients (n=138) with abnormal (compared to normal) thermography were more likely (adjusted odds ratio = 2.84) to develop future DUs, including multiple episodes. (4) 16 DUs were studied; the microvessels of the DU centre were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. There was less of a clear signal in the DU periphery. (5) Light treatment was safe, feasible and well tolerated (46 light treatments administered in 8 patients, one studied on three separate occasions). There was a significant improvement (change in visual analogue score per visit) in DUs as assessed by both patient (-7.1, P = < 0.001) and clinician opinion (-5.2, P = < 0.001). DU perfusion (measured by LDI) significantly increased post-treatment. Conclusion: The reliability of DU grading did not improve with clinical context. HFUS was feasible and well tolerated, and measurement was possible in most DUs. Our data suggests that many DUs might have an ischaemic drive, including extensor DUs. A novel light treatment was safe, feasible and well tolerated, with a tentative suggestion of treatment efficacy.

Subjects/Keywords: Outcome measures; Systemic sclerosis; Scleroderma; Digital ulcers; Pathophysiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hughes, M. (2016). Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427

Chicago Manual of Style (16^th Edition):

Hughes, Michael. “Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.” 2016. Doctoral Dissertation, University of Manchester. Accessed December 09, 2019. https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427.

MLA Handbook (7^th Edition):

Hughes, Michael. “Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.” 2016. Web. 09 Dec 2019.

Vancouver:

Hughes M. Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2019 Dec 09]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427.

Council of Science Editors:

Hughes M. Digital ulcers in systemic sclerosis : investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. [Doctoral Dissertation]. University of Manchester; 2016. Available from: https://www.research.manchester.ac.uk/portal/en/theses/digital-ulcers-in-systemic-sclerosis-investigating-the-outcome-measures-of-treatment-efficacy-pathophysiology-and-the-development-of-local-treatments(a2d6fb1e-f347-4abf-9d8f-5319d2d0aeed).html ; https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.764427

University of Manchester

17. Hughes, Michael. Digital ulcers in systemic sclerosis: investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.

Degree: 2016, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671

►

Introduction: Digital ulcers (DUs) are responsible for much of the pain and disability associated with systemic sclerosis (SSc), and are a biomarker of internal organ… (more)

▼

Introduction: Digital ulcers (DUs) are responsible for much of the pain and disability associated with systemic sclerosis (SSc), and are a biomarker of internal organ involvement and poor prognosis. DUs are often used as the primary end-point in SSc clinical trials, although the reliability of rheumatologists in grading DUs is poor to moderate at best. Fingertip DUs are believed to be ischaemic in aetiology, whereas, extensor DUs are thought to occur due to mechanical factors and recurrent microtrauma. Treatments for DUs are often poorly tolerated due to systemic vasodilation. The overarching aim was to investigate the definition and objective measurement of SSc-related DUs, their pathophysiology, and a new light treatment.Method: Five studies were undertaken. (1) A web-based study in which photographs of digital lesions were graded, all either with or without clinical context. (2) A pilot study to assess the feasibility and tolerability of high-frequency ultrasound (HFUS) imaging to measure DUs. (3) A retrospective study examining whether thermographic abnormalities are associated with DUs. (4) A double-blind, randomised, crossover, controlled study of glyceryl trinitrate (GTN) to explore the pathophysiology of DUs in SSc. (5). A feasibility study of a novel light (red, infrared and blue) device to treat SSc-related DUs.Results: (1) 51 rheumatologists graded ≥4500 images. The clinical context (without vs with, weighted kappa statistic) did not significantly improve the intra- (0.32,0.36) or inter-rater (0.64,0.71) reliability. (2) HFUS was performed on 15 DUs and was well tolerated and feasible in the majority. DU measurement was possible in most (n=13) DUs, the mean DU depth and width were 0.99mm and 5.74mm, respectively. (3) Patients (n=138) with abnormal (compared to normal) thermography were more likely (adjusted odds ratio = 2.84) to develop future DUs, including multiple episodes. (4) 16 DUs were studied; the microvessels of the DU centre were responsive to GTN, with an increase in perfusion, with a similar effect in both fingertip and extensor DUs. There was less of a clear signal in the DU periphery. (5) Light treatment was safe, feasible and well tolerated (46 light treatments administered in 8 patients, one studied on three separate occasions). There was a significant improvement (change in visual analogue score per visit) in DUs as assessed by both patient (-7.1, P=<0.001) and clinician opinion (-5.2, P=<0.001). DU perfusion (measured by LDI) significantly increased post-treatment.Conclusion: The reliability of DU grading did not improve with clinical context. HFUS was feasible and well tolerated, and measurement was possible in most DUs. Our data suggests that many DUs might have an ischaemic drive, including extensor DUs. A novel light treatment was safe, feasible and well tolerated, with a tentative suggestion of treatment efficacy.

None

Advisors/Committee Members: ROBERTS, CHRISTOPHER CT, MURRAY, ANDREA AK, Roberts, Christopher, Herrick, Ariane, Murray, Andrea.

Subjects/Keywords: Systemic sclerosis; Scleroderma; Digital ulcers; Outcome measures; Pathophysiology

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Hughes, M. (2016). Digital ulcers in systemic sclerosis: investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671

Chicago Manual of Style (16^th Edition):

Hughes, Michael. “Digital ulcers in systemic sclerosis: investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.” 2016. Doctoral Dissertation, University of Manchester. Accessed December 09, 2019. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671.

MLA Handbook (7^th Edition):

Hughes, Michael. “Digital ulcers in systemic sclerosis: investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments.” 2016. Web. 09 Dec 2019.

Vancouver:

Hughes M. Digital ulcers in systemic sclerosis: investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. [Internet] [Doctoral dissertation]. University of Manchester; 2016. [cited 2019 Dec 09]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671.

Council of Science Editors:

Hughes M. Digital ulcers in systemic sclerosis: investigating the outcome measures of treatment efficacy, pathophysiology, and the development of local treatments. [Doctoral Dissertation]. University of Manchester; 2016. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:305671

Vrije Universiteit Amsterdam

18. Overbeek, M.J. Pulmonary arterial hypertension in systemic sclerosis .

Degree: 2010, Vrije Universiteit Amsterdam

URL: http://hdl.handle.net/1871/16052

Subjects/Keywords: systemic sclerosis; pulmonary arterial hypertension

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Overbeek, M. J. (2010). Pulmonary arterial hypertension in systemic sclerosis . (Doctoral Dissertation). Vrije Universiteit Amsterdam. Retrieved from http://hdl.handle.net/1871/16052

Chicago Manual of Style (16^th Edition):

Overbeek, M J. “Pulmonary arterial hypertension in systemic sclerosis .” 2010. Doctoral Dissertation, Vrije Universiteit Amsterdam. Accessed December 09, 2019. http://hdl.handle.net/1871/16052.

MLA Handbook (7^th Edition):

Overbeek, M J. “Pulmonary arterial hypertension in systemic sclerosis .” 2010. Web. 09 Dec 2019.

Vancouver:

Overbeek MJ. Pulmonary arterial hypertension in systemic sclerosis . [Internet] [Doctoral dissertation]. Vrije Universiteit Amsterdam; 2010. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/1871/16052.

Council of Science Editors:

Overbeek MJ. Pulmonary arterial hypertension in systemic sclerosis . [Doctoral Dissertation]. Vrije Universiteit Amsterdam; 2010. Available from: http://hdl.handle.net/1871/16052

Boston University

19. Rice, Lisa. Biomarkers in systemic scelrosis.

Degree: PhD, Molecular and Translational Medicine, 2016, Boston University

URL: http://hdl.handle.net/2144/16736

► Systemic sclerosis (SSc; scleroderma) is a chronic multisystem autoimmune disease that includes prominent skin involvement in all patients and is characterized by fibrosis, inflammation, and… (more)

▼ Systemic sclerosis (SSc; scleroderma) is a chronic multisystem autoimmune disease that includes prominent skin involvement in all patients and is characterized by fibrosis, inflammation, and microvascular injury of the skin and internal organs. Clinical trial design for patients with systemic sclerosis (SSc) has been confounded by the heterogeneity of disease progression and lack of objective outcome measures. This has hampered identification of therapies for patients who have frequently fatal fibrotic complications. Direct pulmonary complications are the leading cause of death in SSc. For clinical trials in patients with diffuse cutaneous SSc, identification of a pharmacodynamic biomarker associated with clinical improvement would allow for alternative approaches to trial design. Furthermore, identification of a diagnostic biomarker for SSc complicated by pulmonary arterial hypertension (SSc-PAH) would provide a reliable non-invasive method for diagnosis of pulmonary arterial hypertension. Through the combination of high throughput technologies and clinical information we have identified three preliminary biomarkers for SSc: i) Two pharmacodynamic biomarkers for diffuse skin disease (dcSSc), one in using mRNA from skin biopsies and one using proteomic profiles from sera; ii) a serum based proteomic classifier for the screening and diagnostic evaluation of pulmonary arterial hypertension in systemic sclerosis. We show these biomarkers can be applied to assess changes in skin disease in dSSc patients over time and with further development could be used to supplement or replace the physical examination assessment (Modified Rodnan Skin Score, MRSS) as an outcome measure in clinical trials for dcSSc patients. Routine use of these biomarkers in SSc clinical trial design could expand treatment options for a patient population that currently has few if any treatment options that slow progression of disease. Furthermore we identified a serum biomarker for the major SSc pulmonary complication, SSc-PAH. This diagnostic SSc-PAH biomarker has the potential to be used as a screening tool in order to reduce the need for unnecessary invasive diagnostic procedures. This non-invasive screening method could lead to early diagnosis thus improving patient survival and aid in clinical management of a complication for which there are several treatments but which is still frequently fatal.

Subjects/Keywords: Medicine; Biomarkers; mRNA; Proteins; Systemic sclerosis; Pulmonary arterial hypertension

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rice, L. (2016). Biomarkers in systemic scelrosis. (Doctoral Dissertation). Boston University. Retrieved from http://hdl.handle.net/2144/16736

Chicago Manual of Style (16^th Edition):

Rice, Lisa. “Biomarkers in systemic scelrosis.” 2016. Doctoral Dissertation, Boston University. Accessed December 09, 2019. http://hdl.handle.net/2144/16736.

MLA Handbook (7^th Edition):

Rice, Lisa. “Biomarkers in systemic scelrosis.” 2016. Web. 09 Dec 2019.

Vancouver:

Rice L. Biomarkers in systemic scelrosis. [Internet] [Doctoral dissertation]. Boston University; 2016. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/2144/16736.

Council of Science Editors:

Rice L. Biomarkers in systemic scelrosis. [Doctoral Dissertation]. Boston University; 2016. Available from: http://hdl.handle.net/2144/16736

Univerzitet u Beogradu

20. Zlatanović, Maja B., 1976-. Uticaj sistemske skleroze na građu i funkciju srca i perifernu mikrocirkulaciju.

Degree: Medicinski fakultet, 2018, Univerzitet u Beogradu

URL: https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get

►

Medicina - Interna medicina - reumatologija / Medicine - Internal medicine – rheumatology

Sistemska skleroza je kompleksno autoimuno oboljenje koje karakteriše sistemska fibroza i vaskularno… (more)

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Medicina - Interna medicina - reumatologija / Medicine - Internal medicine – rheumatology

Sistemska skleroza je kompleksno autoimuno oboljenje koje karakteriše sistemska fibroza i vaskularno oštećenje. Kardiološke i pulmološke manifestacije bolesti su glavni uzroci morbiditeta i mortaliteta. Fibroza dovodi do strukturnog, funkcionalnog i mehaniĉkog remodelovanja leve i desne komore, što dalje moţe izazvati poremećaje sprovoĊenja i aritmije. Nove ehokardiografske tehnike pruţaju uvid u srĉanu funkciju i mehaniku uporedivu sa onim kod magnetne rezonance srca, "zlatnog standarda" meĊu metodama vizuelizacije srca. Varijabilnost srĉane frekvencije je vrlo pouzdana neinvazivna tehnika koja ispituje autonomni nervni sistem, simpatiĉku i parasimpatiĉku aktivnost, dobijenu iz 24-ĉasovnog EKG zapisa. MeĊutim, još uvek je nedovoljno ispitan odnos izmeĊu parametara mehanike srca i neravnoteţe autonomne funkcije kod bolesnika sa sistemskom sklerozom, a koji moţe imati znaĉajne kliniĉke implikacije u predviĊanju nepovoljnog ishoda kod ovih bolesnika. Cilj: Ovo istraţivanje je imalo za cilj da ispita strukturu, funkciju i mehaniku srca, i proceni autonomnu funkciju kod bolesnika sa sistemskom sklerozom. TakoĊe, imalo je za cilj da ispita meĊusobni odnos izmeĊu novih ehokardiografski parametara i parametara autonomne funkcije srca, kao i njihov odnos sa pokazateljima periferne mikroangiopatije kod ovih bolesnika. Metodologija: Istraţivanje je obuhvatilo 45 bolesnika sa sistemskom sklerozom, bez kardiovaskularnih simptoma, koji se leĉe u Institutu za reumatologiju u Beogradu i 30 zdravih dobrovoljaca uparenih prema uzrastu i polu. Kod svih bolesnika ukljuĉenih u istraţivanje obavljen je kliniĉki pregled, modifikovani Rodnanov skin skor, serološki testovi, testovi plućne funkcije, kapilaroskopija, indeks aktivnosti bolesti, 24-ĉasovni Holter EKG putem koga je analizirana varijabilnost srĉane frekvencije u vremenskom i frekventnom domenu, i kompletna dvodimenzionalna ehokardiografija, ukljuĉujući analizu straina putem speckle tracking metode. Rezultati: Parametri strukture leve komore (debljina meĊukomorskog septuma, relativna debljina zida leve komore, indeks mase leve komore, indeks volumena leve pretkomore, p<0.01) i desne ventrikularne strukture (debljina zida desne komore, p<0.01) znaĉajno su bili veći kod bolesnika sa sistemskom sklerozom...

Advisors/Committee Members: Damjanov, Nemanja, 1955-.

Subjects/Keywords: systemic sclerosis; heart; echocardiography; mechanics; heart rate variability; microangiopathy; capillaroscopy

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APA (6^th Edition):

Zlatanović, Maja B., 1. (2018). Uticaj sistemske skleroze na građu i funkciju srca i perifernu mikrocirkulaciju. (Thesis). Univerzitet u Beogradu. Retrieved from https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zlatanović, Maja B., 1976-. “Uticaj sistemske skleroze na građu i funkciju srca i perifernu mikrocirkulaciju.” 2018. Thesis, Univerzitet u Beogradu. Accessed December 09, 2019. https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zlatanović, Maja B., 1976-. “Uticaj sistemske skleroze na građu i funkciju srca i perifernu mikrocirkulaciju.” 2018. Web. 09 Dec 2019.

Vancouver:

Zlatanović, Maja B. 1. Uticaj sistemske skleroze na građu i funkciju srca i perifernu mikrocirkulaciju. [Internet] [Thesis]. Univerzitet u Beogradu; 2018. [cited 2019 Dec 09]. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zlatanović, Maja B. 1. Uticaj sistemske skleroze na građu i funkciju srca i perifernu mikrocirkulaciju. [Thesis]. Univerzitet u Beogradu; 2018. Available from: https://fedorabg.bg.ac.rs/fedora/get/o:18999/bdef:Content/get

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Lund

21. Andréasson, Kristofer. Systemic sclerosis. Novel molecular and epidemiological features of disease.

Degree: 2013, University of Lund

URL: http://lup.lub.lu.se/record/4175733 ; http://portal.research.lu.se/ws/files/3716319/4175734.pdf

► Systemic sclerosis (SSc) is a systemic rheumatic disease with significant mortality and morbidity. Different estimations of disease prevalence and incidence have been presented from various… (more)

▼ Systemic sclerosis (SSc) is a systemic rheumatic disease with significant mortality and morbidity. Different estimations of disease prevalence and incidence have been presented from various parts of the world. While lung involvement is a common cause of SSc-related death, a majority of SSc patients suffer from symptoms originating in the gastrointestinal (GI) tract. By combining data from a population based register with individual case ascertainment, we investigated the epidemiology of SSc in a defined region in southern Sweden comprising one million adult inhabitants. The investigation was performed by using classification criteria presented in 1980 and in 2013 respectively. SSc prevalence was estimated to 305 per million and the annual incidence 19 per million and year by application of the 2013 classification criteria. We show that the novel criteria identify SSc subjects who were overlooked by the previous criteria. Usage of either criteria set resulted in prevalence estimates that are higher than previous reports from northern Europe, but similar to reports from southern Europe. Cartilage oligomeric matrix protein (COMP) is a promising biomarker of skin fibrosis in SSc. We have investigated the potential for S-COMP to serve as a biomarker for SSc associated lung fibrosis and as a predictor of SSc survival. S-COMP showed only minimal associations with the development or presence of pulmonary fibrosis. SSc patients with pathological S-COMP in early SSc were at an increased risk of death. To further explore the mechanisms behind COMP and fibrosis, we investigated skin fibrosis in mice deficient in COMP. These mice were not resistant to skin fibrosis. GI disease is a common visceral manifestation of SSc. The inflammatory protein complex S100A8/A9, also known as calprotectin, has been associated with several rheumatic diseases. Faecal calprotectin (FC) is a validated biomarker in inflammatory bowel disease. We have explored the biomarker potential of FC in SSc. FC correlated with SSc manifestations in the GI tract. FCs showed little variation upon repeated testing. FC was higher in SSc compared to other rheumatic diseases. The development of inflammation and fibrosis was investigated in reference to S100A8/A9 in an experimental mouse model. S100A8 and S100A9 were found to localise to inflamed and fibrotic skin tissue. Using the same model, we could not identify any significant reduction of inflammation or fibrosis in S100A9 deficient mice. I suggest that FC, a feasible biomarker already available in routine clinical care, could be a valid biomarker of GI disease in SSc. Further studies are warranted to elucidate the mechanisms behind pathological FC testing in SSc.

Subjects/Keywords: Reumatologi och inflammation; Systemic sclerosis; fibrosis; COMP; calprotectin; biomarker; gastrointestinal

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Andréasson, K. (2013). Systemic sclerosis. Novel molecular and epidemiological features of disease. (Doctoral Dissertation). University of Lund. Retrieved from http://lup.lub.lu.se/record/4175733 ; http://portal.research.lu.se/ws/files/3716319/4175734.pdf

Chicago Manual of Style (16^th Edition):

Andréasson, Kristofer. “Systemic sclerosis. Novel molecular and epidemiological features of disease.” 2013. Doctoral Dissertation, University of Lund. Accessed December 09, 2019. http://lup.lub.lu.se/record/4175733 ; http://portal.research.lu.se/ws/files/3716319/4175734.pdf.

MLA Handbook (7^th Edition):

Andréasson, Kristofer. “Systemic sclerosis. Novel molecular and epidemiological features of disease.” 2013. Web. 09 Dec 2019.

Vancouver:

Andréasson K. Systemic sclerosis. Novel molecular and epidemiological features of disease. [Internet] [Doctoral dissertation]. University of Lund; 2013. [cited 2019 Dec 09]. Available from: http://lup.lub.lu.se/record/4175733 ; http://portal.research.lu.se/ws/files/3716319/4175734.pdf.

Council of Science Editors:

Andréasson K. Systemic sclerosis. Novel molecular and epidemiological features of disease. [Doctoral Dissertation]. University of Lund; 2013. Available from: http://lup.lub.lu.se/record/4175733 ; http://portal.research.lu.se/ws/files/3716319/4175734.pdf

22. Bournia, Vasiliki - Kalliopi. Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα.

Degree: 2019, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ)

URL: http://hdl.handle.net/10442/hedi/46131

► Systemic Sclerosis (SSc) is a rare, systemic, autoimmune disorder characterized by vasculopathy, dysregulation of the immune system and fibrosis of skin and internal organs. The… (more)

▼ Systemic Sclerosis (SSc) is a rare, systemic, autoimmune disorder characterized by vasculopathy, dysregulation of the immune system and fibrosis of skin and internal organs. The severity and significant variability of clinical manifestations of SSc and the need for targeted treatment, renders the search for reliable prognostic markers imperative. The present study of prognostic factors in SSc is divided in two sections. In the first section we comparatively assessed the performance of different nailfold video-capillaroscopic (NVC) parameters in identifying SSc among patients with RP. In addition we compared consistency of various clinical correlations of NVC between two different timepoints and evaluated the prognostic capacity of NVC in SSc patients. Patients and Methods: At baseline we clinically and capillaroscopically evaluated 242 consecutive patients referred to our department for NVC (138 with SSc, 12 withvery early diagnosis of SSc, 36 with primary Raynaud phenomenon και 56 with non-SSc related secondary Raynaud phenomenon); 173 were reevaluated after 3.38±1.47years. Sixty-two healthy volunteers served as controls. Capillaroscopy pattern( normal/early/active/late) was qualitatively defined. Capillary loss, dilated, giant or ramified capillaries and micro-hemorrhages were scored semi-quantitatively. Results: Capillary loss score had the highest diagnostic accuracy at discriminating patients with an SSc-spectrum disorder from patients with RP of different etiology and controls, as defined by ROC curve analysis [AUC (95% CI)=0.905 (0.869-0.942)], followed by dilatation score [0.863 (0.818-0.907)] and giant score [0.835(0.787-0.884)]. By contrast, micro-hemorrhages [0.720 (0.662-0.779)] and ramifications scores [0.604 (0.539-0.670)] performed worse. Comparison of clinical correlations of NVC between two sequential time points in 85 SSc patients, showed low levels of consistency over time. Multivariate analysis in 94 SSc patients indicated that active (OR=3.305, p=0.043) and late (OR=6.900, p=0.023) baseline capillaroscopy pattern predicted occurrence of a combined adverse disease outcome [forced vital capacity (FVC) deterioration>10% and/or DLCO deterioration>15%and/or mRSS deterioration>3.5 and/or first occurrence of digital ulcers and/or death) ] at 3 year follow-up. Conclusions: Dilatation score performs best of all semi-quantitative NVC parameters in diagnosing SSc and although clinical correlations of capillaroscopic findings change over time, our study confirms earlier reports that worse capillaroscopy pattern at baseline correlates with higher likelihood for adverse prognosis. In the second section of our study we tried to examine whether plasma levels of CXCL4-L1, the non-allelic variant of CXCL4, a chemokine which has already been implicated in the pathogenesis of SSc and has an established predictive role in this disease, differ between SSc patients and healthy controls. Patients and Methods: CXCL4 plasma levels were measured by ELISA in 94 SSc patients, 5 VEDOSS patients and 74 healthy controls.…

Subjects/Keywords: Συστηματικό σκληρόδερμα; Τριχοειδοσκόπηση; Βιοδείκτες; Systemic sclerosis; Capillaroscopy; Biomarkers

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APA (6^th Edition):

Bournia, V. -. K. (2019). Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα. (Thesis). National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Retrieved from http://hdl.handle.net/10442/hedi/46131

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Bournia, Vasiliki - Kalliopi. “Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα.” 2019. Thesis, National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ). Accessed December 09, 2019. http://hdl.handle.net/10442/hedi/46131.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Bournia, Vasiliki - Kalliopi. “Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα.” 2019. Web. 09 Dec 2019.

Vancouver:

Bournia V-K. Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα. [Internet] [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2019. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/10442/hedi/46131.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Bournia V-K. Προγνωστικοί παράγοντες στο συστηματικό σκληρόδερμα. [Thesis]. National and Kapodistrian University of Athens; Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών (ΕΚΠΑ); 2019. Available from: http://hdl.handle.net/10442/hedi/46131

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Universidad del Rosario

23. Rojas Quintana, Manuel Eduardo. The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study.

Degree: 2019, Universidad del Rosario

URL: http://repository.urosario.edu.co/handle/10336/19850

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BACKGROUND: Resilience is considered the capability to positively respond to adverse events. Since this capacity in considered a “continuum” process, long-term stressors and psychosocial factors… (more)

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BACKGROUND: Resilience is considered the capability to positively respond to adverse events. Since this capacity in considered a “continuum” process, long-term stressors and psychosocial factors are thought to be crucial for resilience development, especially in those patients with chronic inflammatory systemic diseases. However, the role of clinical, biological and socioeconomic characteristics in autoimmune rheumatic diseases (ARDs) is still unknown. OBJECTIVE To evaluate the association between resilience and socioeconomic, biological and clinical factors in four autoimmune rheumatic diseases (ARDs) namely: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Sjögren’s syndrome (SS) and systemic sclerosis (SSc). METHODS: A cross-sectional study in 188 women with SLE (n= 70), RA (n= 51), SS (n= 32), and SSc (n= 35) was done. Resilience was evaluated by the “Brief Resilience Scale”, whereas independent factors including age, age at onset, duration of disease, socioeconomic status, excersice, severity of symptoms and polyautoimmunity (PolyA) were evaluated by surveys and chart reviews. A panel of 15 serum cytokines and 14 autoantibodies were evaluated simultaneously. Bivariate, classification and regression trees (CART), and multiple linear regressions were used to analyze data. RESULTS: CART analysis showed that patients younger than 48 years with SLE, RA, and SSc who had low socioeconomic status showed the lowest resilience scores, whereas those patients between 48 and 66 years exhibited the highest resilience levels despite socioeconomic status. Interestingly, regular physical activity was associated with highest resilience in SSc. In addition, Interleukin-6 (IL-6) was associated low resilience scores (β= -0.581120, p=0.02) and with severity of symptoms (β=1.8395, p=0.04) in SSc. Neither PolyA nor severity of symptoms influenced resilience in the four ARDs studied. Cytokine levels did not significantly differ between groups based on regular physical activity. CONCLUSIONS: Resilience is a continuum trait associated to socioeconomic status and age. In addition, IL-6 and exercise are key factors for resilience in SSc. These results highlight the relevance of biological and socioeconomic factors in the development of resilience in autoimmunity.

Centro de Estudio de Enfermedades Autoinmunes (CREA)

Universidad del Rosario (ABN011)

Colciencias (Grant No 122254531722/Grant No0425-2013)

Advisors/Committee Members: Acosta-Ampudia, Yeny, Molano-González, Nicolas, Anaya, Juan Manuel, Monsalve, Diana M., Pacheco, Yovana, Ramirez-Santana, Carolina, Rodríguez-Jimenez, Monica, Rodríguez, Yhojan, Mantilla, Ruben Dario.

Subjects/Keywords: Resilience; Rheumatoid arthritis; Systemic lupus erythematosus; Systemic sclerosis; Sjögren’s síndrome; 616; Artritis reumatoide; Lupus eritematoso sistémico; Esclerodermia Sistémica; Síndrome de Sjögren

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APA (6^th Edition):

Rojas Quintana, M. E. (2019). The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study. (Thesis). Universidad del Rosario. Retrieved from http://repository.urosario.edu.co/handle/10336/19850

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rojas Quintana, Manuel Eduardo. “The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study.” 2019. Thesis, Universidad del Rosario. Accessed December 09, 2019. http://repository.urosario.edu.co/handle/10336/19850.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rojas Quintana, Manuel Eduardo. “The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study.” 2019. Web. 09 Dec 2019.

Vancouver:

Rojas Quintana ME. The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study. [Internet] [Thesis]. Universidad del Rosario; 2019. [cited 2019 Dec 09]. Available from: http://repository.urosario.edu.co/handle/10336/19850.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rojas Quintana ME. The role of clinical, biological, and socioeconomic factors on the development of resilience in women with autorimmune rheumatic diseases : a cross-sectional study. [Thesis]. Universidad del Rosario; 2019. Available from: http://repository.urosario.edu.co/handle/10336/19850

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Université de Montréal

24. Ghassemi Kakroodi, Parisa. The role of Microsomal prostaglandin synthase-1 (mPGES-1) and Ephrin B2 in Scleroderma .

Degree: 2013, Université de Montréal

URL: http://hdl.handle.net/1866/9946

► La sclérodermie (sclérose systémique, ScS) est une maladie auto-immune du tissu conjonctif caractérisée par l’épaississement de la peau, l’apparition spontanée de lésions cicatricielles, des maladies… (more)

▼ La sclérodermie (sclérose systémique, ScS) est une maladie auto-immune du tissu conjonctif caractérisée par l’épaississement de la peau, l’apparition spontanée de lésions cicatricielles, des maladies des vaisseaux sanguins, divers degrés d’inflammation, en association avec un système immunitaire hyperactif. La pathogénèse exacte de cette maladie est inconnue et aucun traitement approprié n’est disponible. La fibrose est un élément distinctif de la maladie de ScS et est considérée résulter d’une incapacité à mettre fin de façon appropriée à la réponse normale de réparation des plaies. L’analyse histologique du stade initial de la ScS révèle une infiltration périvasculaire de cellules mononucléaires dans le derme, associée à une synthèse accrue de collagène dans les fibroblastes environnants. Ainsi, la compréhension des moyens de contrôler le stade inflammatoire de la ScS pourrait être bénéfique pour contrôler la progression de la maladie peu après son apparition. La mPGES-1 est une enzyme inductible qui agit en aval de la cyclo- oxygénase (COX) pour catalyser spécifiquement la conversion de la prostaglandine (PG) H2 en PGE2. La mPGES-1 joue un rôle clé dans l’inflammation, la douleur et l’arthrite;; toutefois, le rôle de la mPGES-1 dans les mécanismes de fibrose, spécifiquement en rapport avec la ScS humaine, est inconnu. Mon laboratoire a précédemment montré que les souris à mPGES-1 nulle sont résistantes à la fibrose cutanée induite par la bléomycine, à l’inflammation, à l’épaississement cutané, à la production de collagène et à la formation de myofibroblastes. Sur la base de ces résultats, j’ai formulé l’hypothèse que l’inhibition pharmacologique de la mPGES-1 régulera à la baisse la production de médiateurs pro-inflammatoires et pro-fibreux au cours de la maladie de ScS. Afin d’explorer le rôle de la mPGES-1 dans l’inflammation et la fibrose associées à la maladie de ScS, j’ai d’abord examiné l’expression de la mPGES-1 dans la peau normale comparativement à des biopsies de peau extraites de patients atteints de ScS. Mes résultats ont montré que la mPGES-1 est nettement élevée dans la peau de patients atteints de ScS en comparaison avec la peau humaine normale. De plus, les niveaux de PGE2 dérivés de la mPGES-1 étaient également significativement plus élevés dans les fibroblastes cutanés isolés de patients atteints de ScS comparativement aux fibroblastes isolés de témoins sains. J’ai également étudié l’effet de l’inhibition pharmacologique de la mPGES-1 sur l’expression de marqueurs pro- fibreux. Mes études ont montré que l’expression de médiateurs pro-fibreux clés (α-SMA, endothéline-1, collagène de type 1 et facteur de croissance du tissu conjonctif (FCTC)) est élevée dans les fibroblastes cutanés ScS en comparaison avec les fibroblastes cutanés normaux. Un traitement avec un… Advisors/Committee Members: Kapoor, Mohit (advisor).

Subjects/Keywords: Sclérose systémique; Microsomal prostaglandin synthase-1 (mPGES-1); Fibroblaste; Myofibroblaste; Éphrine B2; Éphrine B4; Systemic sclerosis; Systemic sclerosis, Microsomal prostaglandin synthase-1 (mPGES-1); Fibroblasts; Myofibroblasts; Ephrin B2; Ephrin B4

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ghassemi Kakroodi, P. (2013). The role of Microsomal prostaglandin synthase-1 (mPGES-1) and Ephrin B2 in Scleroderma . (Thesis). Université de Montréal. Retrieved from http://hdl.handle.net/1866/9946

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ghassemi Kakroodi, Parisa. “The role of Microsomal prostaglandin synthase-1 (mPGES-1) and Ephrin B2 in Scleroderma .” 2013. Thesis, Université de Montréal. Accessed December 09, 2019. http://hdl.handle.net/1866/9946.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ghassemi Kakroodi, Parisa. “The role of Microsomal prostaglandin synthase-1 (mPGES-1) and Ephrin B2 in Scleroderma .” 2013. Web. 09 Dec 2019.

Vancouver:

Ghassemi Kakroodi P. The role of Microsomal prostaglandin synthase-1 (mPGES-1) and Ephrin B2 in Scleroderma . [Internet] [Thesis]. Université de Montréal; 2013. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/1866/9946.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ghassemi Kakroodi P. The role of Microsomal prostaglandin synthase-1 (mPGES-1) and Ephrin B2 in Scleroderma . [Thesis]. Université de Montréal; 2013. Available from: http://hdl.handle.net/1866/9946

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

25. Cossu, Marta. Molecular and cellular profiling of systemic sclerosis and its preclinical stages.

Degree: 2017, University Utrecht

URL: http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102

► The development of unrestrained fibrosis in the skin and internal organs is the hallmark of systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is… (more)

▼ The development of unrestrained fibrosis in the skin and internal organs is the hallmark of systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is preceded by vascular and immune modifications. On the basis of SSc-specific autoantibodies and nailfold capillary lesions it is possible to identify individuals with Raynaud’s phenomenon considered at increased risk to develop SSc when compared with the general population. Furthermore, some characteristic SSc features are not fibrotic, they can precede fibrosis and still be sufficient to meet the EUropean League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SSc. In my PhD thesis I aimed to characterize how patients with early SSc and SSc without any sign of fibrosis differ from fibrotic SSc patients (limited and diffuse cutaneous SSc; lcSSc and dcSSc), by that contributing to increase the knowledge about the events which lead to the onset of fibrosis and provide new ground to prevent it. To do so, we first investigated how different factors involved in vascular and immune activation “behave” in the circulation of early SSc individuals, in patients with SSc without fibrotic features, comparing with fibrotic SSc patients. We then investigated in the different groups natural killer (NK) and NKT-like cells, important in infections control, tumor development and immuneregulation. We found that: - the Interferon (IFN) signature described in SSc patients with fibrosis, is already present since the early SSc stage and in the non-fibrotic SSc group to an even higher extent then in fibrotic SSc patients: - markers of vascular damage (angiopoietin-2, CXCL16, E-selectin, ICAM-1) are already elevated in the circulation of early SSc patients and in a gradually increasing fashion in patients with SSc without fibrotic features and to the highest degree in fibrotic SSc patients, mirroring the same deteriorating trend in clinical parameters (inflammation indicators, lung involvement) from early SSc to non-fibrotic SSc and finally to the lcSSc and dcSSc subsets; - CXCL10, CXCL11, TNFR2 and CHI3L1 can clearly distinguish patients with early SSc and even more the ones with SSc without fibrotic features from healthy controls (HC). Furthermore, within each patient group, the patients who faster evolved (early SSc developing full-blown SSc and non-fibrotic SSc developing fibrotic features) were the ones with the highest circulating levels of CXCL10 and TNFR2; - NK and NKT-like cells from early SSc and non-fibrotic SSc patients produce higher levels of pro-inflammatory/pro-fibrotic molecules (TNF-α, IL-6) than HC in response to different activating triggers; - in the circulation of patients with the most extensive skin fibrosis, dcSSc - but not in early SSc nor in patients with SSc without fibrosis -, a reduction of NK cells expressing the activating receptor NKp46 and of NKT-like cells expressing Killer-Immunoglobulin-like (KIR) receptors are observed. These patterns suggest that in dcSSc patients both NK and NKT-like cells could be… Advisors/Committee Members: Radstake, Timothy, Dolstra, H., Vonk, M.C..

Subjects/Keywords: systemic sclerosis; arly systemic sclerosis; NK cells; NKT-like cells

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❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cossu, M. (2017). Molecular and cellular profiling of systemic sclerosis and its preclinical stages. (Doctoral Dissertation). University Utrecht. Retrieved from http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102

Chicago Manual of Style (16^th Edition):

Cossu, Marta. “Molecular and cellular profiling of systemic sclerosis and its preclinical stages.” 2017. Doctoral Dissertation, University Utrecht. Accessed December 09, 2019. http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102.

MLA Handbook (7^th Edition):

Cossu, Marta. “Molecular and cellular profiling of systemic sclerosis and its preclinical stages.” 2017. Web. 09 Dec 2019.

Vancouver:

Cossu M. Molecular and cellular profiling of systemic sclerosis and its preclinical stages. [Internet] [Doctoral dissertation]. University Utrecht; 2017. [cited 2019 Dec 09]. Available from: http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102.

Council of Science Editors:

Cossu M. Molecular and cellular profiling of systemic sclerosis and its preclinical stages. [Doctoral Dissertation]. University Utrecht; 2017. Available from: http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102

26. Cossu, Marta. Molecular and cellular profiling of systemic sclerosis and its preclinical stages.

Degree: 2017, University Utrecht

URL: http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102

► The development of unrestrained fibrosis in the skin and internal organs is the hallmark of systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is… (more)

▼ The development of unrestrained fibrosis in the skin and internal organs is the hallmark of systemic sclerosis (SSc). Nevertheless, it is known that fibrosis is preceded by vascular and immune modifications. On the basis of SSc-specific autoantibodies and nailfold capillary lesions it is possible to identify individuals with Raynaud’s phenomenon considered at increased risk to develop SSc when compared with the general population. Furthermore, some characteristic SSc features are not fibrotic, they can precede fibrosis and still be sufficient to meet the EUropean League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for SSc. In my PhD thesis I aimed to characterize how patients with early SSc and SSc without any sign of fibrosis differ from fibrotic SSc patients (limited and diffuse cutaneous SSc; lcSSc and dcSSc), by that contributing to increase the knowledge about the events which lead to the onset of fibrosis and provide new ground to prevent it. To do so, we first investigated how different factors involved in vascular and immune activation “behave” in the circulation of early SSc individuals, in patients with SSc without fibrotic features, comparing with fibrotic SSc patients. We then investigated in the different groups natural killer (NK) and NKT-like cells, important in infections control, tumor development and immuneregulation. We found that: - the Interferon (IFN) signature described in SSc patients with fibrosis, is already present since the early SSc stage and in the non-fibrotic SSc group to an even higher extent then in fibrotic SSc patients: - markers of vascular damage (angiopoietin-2, CXCL16, E-selectin, ICAM-1) are already elevated in the circulation of early SSc patients and in a gradually increasing fashion in patients with SSc without fibrotic features and to the highest degree in fibrotic SSc patients, mirroring the same deteriorating trend in clinical parameters (inflammation indicators, lung involvement) from early SSc to non-fibrotic SSc and finally to the lcSSc and dcSSc subsets; - CXCL10, CXCL11, TNFR2 and CHI3L1 can clearly distinguish patients with early SSc and even more the ones with SSc without fibrotic features from healthy controls (HC). Furthermore, within each patient group, the patients who faster evolved (early SSc developing full-blown SSc and non-fibrotic SSc developing fibrotic features) were the ones with the highest circulating levels of CXCL10 and TNFR2; - NK and NKT-like cells from early SSc and non-fibrotic SSc patients produce higher levels of pro-inflammatory/pro-fibrotic molecules (TNF-α, IL-6) than HC in response to different activating triggers; - in the circulation of patients with the most extensive skin fibrosis, dcSSc - but not in early SSc nor in patients with SSc without fibrosis -, a reduction of NK cells expressing the activating receptor NKp46 and of NKT-like cells expressing Killer-Immunoglobulin-like (KIR) receptors are observed. These patterns suggest that in dcSSc patients both NK and NKT-like cells could be… Advisors/Committee Members: Radstake, Timothy, Dolstra, H., Vonk, M.C..

Subjects/Keywords: systemic sclerosis; arly systemic sclerosis; NK cells; NKT-like cells

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Cossu, M. (2017). Molecular and cellular profiling of systemic sclerosis and its preclinical stages. (Doctoral Dissertation). University Utrecht. Retrieved from http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102

Chicago Manual of Style (16^th Edition):

Cossu, Marta. “Molecular and cellular profiling of systemic sclerosis and its preclinical stages.” 2017. Doctoral Dissertation, University Utrecht. Accessed December 09, 2019. http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102.

MLA Handbook (7^th Edition):

Cossu, Marta. “Molecular and cellular profiling of systemic sclerosis and its preclinical stages.” 2017. Web. 09 Dec 2019.

Vancouver:

Cossu M. Molecular and cellular profiling of systemic sclerosis and its preclinical stages. [Internet] [Doctoral dissertation]. University Utrecht; 2017. [cited 2019 Dec 09]. Available from: http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102.

Council of Science Editors:

Cossu M. Molecular and cellular profiling of systemic sclerosis and its preclinical stages. [Doctoral Dissertation]. University Utrecht; 2017. Available from: http://dspace.library.uu.nl/handle/1874/353102 ; URN:NBN:NL:UI:10-1874-353102 ; urn:isbn:978-90-393-68039 ; URN:NBN:NL:UI:10-1874-353102 ; http://dspace.library.uu.nl/handle/1874/353102

27. Rossi, Giulio Antonino. FOXP3, ICOS and ICOSL polymorphisms in an Italian population affected by systemic sclerosis.

Degree: 2017, Università degli Studi di Catania

URL: http://hdl.handle.net/10761/4031

► Associated with substantial morbidity and mortality rates, systemic sclerosis (SSc) is an autoimmune disorder characterized by vasculopathy, inflammation, progressive perivascular and interstitial fibrosis. SSc pathogenesis… (more)

▼ Associated with substantial morbidity and mortality rates, systemic sclerosis (SSc) is an autoimmune disorder characterized by vasculopathy, inflammation, progressive perivascular and interstitial fibrosis. SSc pathogenesis is largely unknown, however strong evidences suggest that genetic predisposition may contribute to SSc development. Dysregulation of co-stimulatory and/or co-inhibitory signals, including ICOS signalling, can cause a breakdown of self-tolerance, thus leading to autoimmunity. Furthermore, ICOS has been linked to the function of Tregs. The aim of the present study was to investigate the association between the FOXP3 rs2294020, ICOS rs6726035 and ICOSL rs378299 SNPs and the susceptibility to SSc or to progression from preclinical SSc to definite SSc in a North Italian Caucasian population. Furthermore, we have extended our association analysis of the FOXP3 rs2294020 SNP also in 14 GWAS datasets in order to reveal association between this SNP and susceptibility to other autoimmune diseases in individuals of European ancestry. Autoimmune diseases studied included psoriasis, celiac disease, Crohn s disease, ulcerative colitis, multiple sclerosis, vitiligo, type-1 diabetes, rheumatoid arthritis, and ankylosing spondylitis. Although analysis tests did not show any significant associations between the SNPs under study and SSc, the occurrence of FOXP3 rs2294020 in female patients was associated with an increased risk of progression from early to definite SSc, both in the allelic (HR = 1.43; CI = 1.03-1.99; p=0.03) and in dominant (HR = 1.54; CI = 1.04-2.28; p=0.03) models. The inclusion of presence of ACA, SCL70, and ANA autoantibodies in the model did not significantly change the estimates. Furthermore, the present study shows that rs2204020 may be associated with the susceptibility to autoimmune diseases involving the skin , such as vitiligo and psoriasis (p=0.01 and P=0.038, respectively). In conclusion, this study provides evidence that rs2294020SNP may have a role in SSc evolution, modulating the time of progression from the diagnosis of early SSc to the diagnosis of definite SSc. Moreover, the results of the present study would suggest a potential involvevement of the rs294020 also in other skin-related autoimmune diseases, including vitiligo and psoriasis.

Subjects/Keywords: Area 05 - Scienze biologiche; Systemic sclerosis; single nucleotide polymorphism; GWAS; autoimmune disease

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rossi, G. A. (2017). FOXP3, ICOS and ICOSL polymorphisms in an Italian population affected by systemic sclerosis. (Thesis). Università degli Studi di Catania. Retrieved from http://hdl.handle.net/10761/4031

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Rossi, Giulio Antonino. “FOXP3, ICOS and ICOSL polymorphisms in an Italian population affected by systemic sclerosis.” 2017. Thesis, Università degli Studi di Catania. Accessed December 09, 2019. http://hdl.handle.net/10761/4031.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Rossi, Giulio Antonino. “FOXP3, ICOS and ICOSL polymorphisms in an Italian population affected by systemic sclerosis.” 2017. Web. 09 Dec 2019.

Vancouver:

Rossi GA. FOXP3, ICOS and ICOSL polymorphisms in an Italian population affected by systemic sclerosis. [Internet] [Thesis]. Università degli Studi di Catania; 2017. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/10761/4031.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Rossi GA. FOXP3, ICOS and ICOSL polymorphisms in an Italian population affected by systemic sclerosis. [Thesis]. Università degli Studi di Catania; 2017. Available from: http://hdl.handle.net/10761/4031

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

28. Maria, Alexandre. Evaluation de l'effet thérapeutique des cellules souches mésenchymateuses dans la sclérodermie systémique : Mesenchymal stem cell based therapy in systemic sclerosis.

Degree: Docteur es, Biologie Santé, 2017, Montpellier

URL: http://www.theses.fr/2017MONTT015

►

La sclérodermie systémique (ScS) est une maladie rare et incurable, caractérisée par une fibrose cutanée et la production d’auto-anticorps (maladie auto-immune). Le pronostic vital est… (more)

▼

La sclérodermie systémique (ScS) est une maladie rare et incurable, caractérisée par une fibrose cutanée et la production d’auto-anticorps (maladie auto-immune). Le pronostic vital est engagé dans les formes diffuses et rapidement progressives de la maladie, responsables de fibrose pulmonaire. Par leurs propriétés immunomodulatrices et anti-fibrotiques, les cellules souches mésenchymateuses (CSM) constituent une approche prometteuse pour traiter la ScS. Ce travail a pour objectif d’évaluer le potentiel thérapeutique des CSM dans un modèle préclinique de forme diffuse de la maladie (d-ScS).Patients et Méthodes : Nous avons évalué l’effet de différentes modalités d’injections des CSM par voie intraveineuse dans le modèle murin de ScS-HOCl. Ce modèle, basé sur l’injection d’acide hypochloreux (HOCl), induit un phénotype proche des formes d-ScS. Nous avons notamment comparé un traitement préventif et curatif, des approches syngénique, allogénique et xénogénique, et l’utilisation de CSM d’origine adipocytaire (ASC) à celle de CSM de moelle osseuse (CSM-MO).Résultats : Le modèle ScS-HOCl est caractérisé par l’installation d’un phénotype de d-ScS, avec fibrose cutanée, pulmonaire et production d’anticorps anti-topoisomérase 1. Nous montrons l’effet bénéfique d’une injection préventive ou curative de CSM syngéniques, réduisant la fibrose cutanée et pulmonaire. Cet effet thérapeutique passe par une diminution de la réponse immune réduisant l’inflammation tissulaire et la production d’auto-anticorps, ainsi que par l’induction du remodelage tissulaire via l’activation de métalloprotéases, et l’augmentation des défenses anti-oxydantes. Un bénéfice similaire est obtenu lors d’approches allogénique et xénogénique. Les ASC présentent des capacités immunosuppressives et de remodelage supérieures aux CSM-MO.Discussion et conclusion : Nos travaux démontrent l’effet anti-fibrotique des CSM dans un modèle préclinique pertinent de ScS, mimant les formes diffuses et rapidement progressives de la maladie, pour lesquelles les besoins thérapeutiques sont importants. Le mode d’action pléiotropique des CSM, combinant propriétés anti-inflammatoires, pro-remodelage et anti-oxydantes, est prometteur en vue des applications cliniques à venir dans cette maladie.Mots-clés : sclérodermie systémique, cellules souches mésenchymateuses, HOCl

Systemic sclerosis (SSc) is a rare intractable disease characterized by skin fibrosis and autoimmunity. Diffuse and rapidly progressive SSc (d-SSc) is associated with life-threatening involvements such as lung fibrosis, where there still is an unmet medical need. Displaying immunomodulatory and antifibrotic properties, mesenchymal stem cells (MSC) are an attractive cure for SSc. In this study, we aim at evaluating the therapeutic potential of MSC in a preclinical model of d-ScS.Patients and Methods: We evaluated the effects of MSC infusion in the murine model of ScS-HOCl, based on repeated injections of hypochlorite (HOCl). We compared several approaches using MSC in a preventive and curative approach, in…

Advisors/Committee Members: Guilpain, Philippe (thesis director).

Subjects/Keywords: Sclérodermie systémique; Cellules souches mésenchymateuses; HOCl; Systemic sclerosis; Mesenchymal stem cell; HOCl

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Maria, A. (2017). Evaluation de l'effet thérapeutique des cellules souches mésenchymateuses dans la sclérodermie systémique : Mesenchymal stem cell based therapy in systemic sclerosis. (Doctoral Dissertation). Montpellier. Retrieved from http://www.theses.fr/2017MONTT015

Chicago Manual of Style (16^th Edition):

Maria, Alexandre. “Evaluation de l'effet thérapeutique des cellules souches mésenchymateuses dans la sclérodermie systémique : Mesenchymal stem cell based therapy in systemic sclerosis.” 2017. Doctoral Dissertation, Montpellier. Accessed December 09, 2019. http://www.theses.fr/2017MONTT015.

MLA Handbook (7^th Edition):

Maria, Alexandre. “Evaluation de l'effet thérapeutique des cellules souches mésenchymateuses dans la sclérodermie systémique : Mesenchymal stem cell based therapy in systemic sclerosis.” 2017. Web. 09 Dec 2019.

Vancouver:

Maria A. Evaluation de l'effet thérapeutique des cellules souches mésenchymateuses dans la sclérodermie systémique : Mesenchymal stem cell based therapy in systemic sclerosis. [Internet] [Doctoral dissertation]. Montpellier; 2017. [cited 2019 Dec 09]. Available from: http://www.theses.fr/2017MONTT015.

Council of Science Editors:

Maria A. Evaluation de l'effet thérapeutique des cellules souches mésenchymateuses dans la sclérodermie systémique : Mesenchymal stem cell based therapy in systemic sclerosis. [Doctoral Dissertation]. Montpellier; 2017. Available from: http://www.theses.fr/2017MONTT015

University of Cincinnati

29. Khurma, Vandana. Coronary Artherosclerosis in Systemic Sclerosis: A Cross-Sectional Pilot Study of Cases and Controls.

Degree: MS, Medicine : Epidemiology (Environmental Health), 2007, University of Cincinnati

URL: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1179353380

► Objectives: 1) Determine the prevalence of subclinical coronary atherosclerosis (CA) in patients with systemic sclerosis (SSc) 2) evaluate serum proinflammatory HDL (piHDL) and transforming growth… (more)

Subjects/Keywords: Health Sciences, Immunology; systemic sclerosis; atherosclerosis; proinflammatory HDL; transforming growth factor-beta

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Khurma, V. (2007). Coronary Artherosclerosis in Systemic Sclerosis: A Cross-Sectional Pilot Study of Cases and Controls. (Masters Thesis). University of Cincinnati. Retrieved from http://rave.ohiolink.edu/etdc/view?acc_num=ucin1179353380

Chicago Manual of Style (16^th Edition):

Khurma, Vandana. “Coronary Artherosclerosis in Systemic Sclerosis: A Cross-Sectional Pilot Study of Cases and Controls.” 2007. Masters Thesis, University of Cincinnati. Accessed December 09, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1179353380.

MLA Handbook (7^th Edition):

Khurma, Vandana. “Coronary Artherosclerosis in Systemic Sclerosis: A Cross-Sectional Pilot Study of Cases and Controls.” 2007. Web. 09 Dec 2019.

Vancouver:

Khurma V. Coronary Artherosclerosis in Systemic Sclerosis: A Cross-Sectional Pilot Study of Cases and Controls. [Internet] [Masters thesis]. University of Cincinnati; 2007. [cited 2019 Dec 09]. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1179353380.

Council of Science Editors:

Khurma V. Coronary Artherosclerosis in Systemic Sclerosis: A Cross-Sectional Pilot Study of Cases and Controls. [Masters Thesis]. University of Cincinnati; 2007. Available from: http://rave.ohiolink.edu/etdc/view?acc_num=ucin1179353380

Université de Montréal

30. Chokr, Nidaa. Assessing the Activity of Agonistic Autoantibodies in Systemic Sclerosis and their Effects on Cultured Vascular Smooth Muscle Cells .

Degree: 2012, Université de Montréal

URL: http://hdl.handle.net/1866/8319

► La sclérose systémique (ScS) est une maladie auto-immune dévastatrice d'étiologie inconnue. Le dysfonctionnement immunitaire, la fibrose et la vasculopathie sont les trois principales caractéristiques de… (more)

▼ La sclérose systémique (ScS) est une maladie auto-immune dévastatrice d'étiologie inconnue. Le dysfonctionnement immunitaire, la fibrose et la vasculopathie sont les trois principales caractéristiques de cette maladie. Une récente étude a révélé un nouveau lien entre l'auto-immunité et la fibrose, par la présence d'auto-anticorps stimulant le récepteur du facteur de croissance dérivé des plaquettes (PDGFR) des fibroblastes. Ces auto-anticorps sont capables de stimuler les espèces réactives de l'oxygène et d’activer la kinase régulée par un signal extracellulaire (ERK1/2). L’hypothèse que nous formulons est que les cellules musculaires lisses vasculaires (VSMCs) exprimant conjointement les PDGFR, répondront elles aussi aux autoanticorps anti-PDGF-R. Le travail présenté ici vise à valider la présence d'auto-anticorps PDGFR dans les sérums de patients ScS, et à caractériser ensuite la réponse de VSMCs exposées à de l'immunoglobuline G (IgG) de ces sérums, en mesurant l’activation des cascades de signalisation spécifiques, ainsi que l'induction des gènes impliqués dans la réponse fibrotique. Nos résultats démontrent la présence d'une fraction IgG stimulant une réponse phénotypique dans les cultures de VSMCs. Notamment, d’importantes régulations positive et négative des gènes pro-fibrotiques tgfb1 et tgfb2 respectivement, ont été observées dans les VSMCs exposées à des fractions de ScS-IgG. Les fractions de IgG positives pour l'activation de ERK étaient présentes dans la plupart, mais pas dans tous les échantillons de SSc (68%, 19/28), et moins présentes dans les contrôles 27% (11/3). Bien que, les fractions de SSc-IgG ont pu considérablement immunoprécipiter le PDGFR, l'utilisation d'un inhibiteur spécifique des récepteurs au PDGF (AG1296), n'a pas inhibé l'activation de ERK médiée par les fractions de SSc-IgG. Globalement, nos résultats indiquent la présence d'autoanticorps stimulants avec activité pro-fibrotique dans les sérums des patients ScS. Des travaux sont en cours pour identifier l'entité moléculaire responsable de la réponse d’IgG observée dans les cultures de VSMCs. Advisors/Committee Members: Servant, Marc (advisor), Baron, Murray (advisor).

Subjects/Keywords: Sclérose systémique; CMLV; PDGFR; auto-anticorps; Systemic Sclerosis; vascular smooth muscle cells; PDGFR; autoantibodies

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Chokr, N. (2012). Assessing the Activity of Agonistic Autoantibodies in Systemic Sclerosis and their Effects on Cultured Vascular Smooth Muscle Cells . (Thesis). Université de Montréal. Retrieved from http://hdl.handle.net/1866/8319

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Chokr, Nidaa. “Assessing the Activity of Agonistic Autoantibodies in Systemic Sclerosis and their Effects on Cultured Vascular Smooth Muscle Cells .” 2012. Thesis, Université de Montréal. Accessed December 09, 2019. http://hdl.handle.net/1866/8319.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Chokr, Nidaa. “Assessing the Activity of Agonistic Autoantibodies in Systemic Sclerosis and their Effects on Cultured Vascular Smooth Muscle Cells .” 2012. Web. 09 Dec 2019.

Vancouver:

Chokr N. Assessing the Activity of Agonistic Autoantibodies in Systemic Sclerosis and their Effects on Cultured Vascular Smooth Muscle Cells . [Internet] [Thesis]. Université de Montréal; 2012. [cited 2019 Dec 09]. Available from: http://hdl.handle.net/1866/8319.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chokr N. Assessing the Activity of Agonistic Autoantibodies in Systemic Sclerosis and their Effects on Cultured Vascular Smooth Muscle Cells . [Thesis]. Université de Montréal; 2012. Available from: http://hdl.handle.net/1866/8319

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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Open Access Theses and Dissertations