scholarly journals Software‐based quantitative analysis of lung parenchyma in patients with systemic sclerosis may provide new generation data for pulmonary fibrosis

2020 ◽  
Author(s):  
Duygu Temiz Karadag ◽  
Ozgur Cakir ◽  
Andac Komac ◽  
Ayten Yazici ◽  
Ayse Cefle
Keyword(s):  
Systemic Sclerosis ◽  
Quantitative Analysis ◽  
Pulmonary Fibrosis ◽  
Lung Parenchyma ◽  
New Generation

Quantitative Microscopic Comparison of the Organization of the Lung in Transgenic Mice Expressing Transforming Growth Factor-α (TGF-α)

1996 ◽  
Vol 54 ◽  
pp. 14-15
Author(s):  
C. G. Plopper ◽  
C. Helton ◽  
A. J. Weir ◽  
J. A. Whitsett ◽  
T. R. Korfhagen
Keyword(s):  
Growth Factor ◽  
Pulmonary Fibrosis ◽  
Transgenic Mice ◽  
Blood Vessels ◽  
Lung Parenchyma ◽  
Lung Maturation ◽  
Alveolar Air ◽  
Parenchymal Tissue ◽  
Air Space ◽  
Conducting Airways

A wide variety of growth factors are thought to be involved in the regulation of pre- and postnatal lung maturation, including factors which bind to the epidermal growth factor receptor. Marked pulmonary fibrosis and enlarged alveolar air spaces have been observed in lungs of transgenic mice expressing human TGF-α under control of the 3.7 KB human SP-C promoter. To test whether TGF-α alters lung morphogenesis and cellular differentiation, we examined morphometrically the lungs of adult (6-10 months) mice derived from line 28, which expresses the highest level of human TGF-α transcripts among transgenic lines. Total volume of lungs (LV) fixed by airway infusion at standard pressure was similar in transgenics and aged-matched non-transgenic mice (Fig. 1). Intrapulmonary bronchi and bronchioles made up a smaller percentage of LV in transgenics than in non-transgenics (Fig. 2). Pulmonary arteries and pulmonary veins were a smaller percentage of LV in transgenic mice than in non-transgenics (Fig. 3). Lung parenchyma (lung tissue free of large vessels and conducting airways) occupied a larger percentage of LV in transgenics than in non-transgenics (Fig. 4). The number of generations of branching in conducting airways was significantly reduced in transgenics as compared to non-transgenic mice. Alveolar air space size, as measured by mean linear intercept, was almost twice as large in transgenic mice as in non-transgenics, especially when different zones within the lung were compared (Fig. 5). Alveolar air space occupied a larger percentage of the lung parenchyma in transgenic mice than in non-transgenic mice (Fig. 6). Collagen abundance was estimated in histological sections as picro-Sirius red positive material by previously-published methods. In intrapulmonary conducting airways, collagen was 4.8% of the wall in transgenics and 4.5% of the wall in non-transgenic mice. Since airways represented a smaller percentage of the lung in transgenics, the volume of interstitial collagen associated with airway wall was significantly less. In intrapulmonary blood vessels, collagen was 8.9% of the wall in transgenics and 0.7% of the wall in non-transgenics. Since blood vessels were a smaller percentage of the lungs in transgenics, the volume of collagen associated with the walls of blood vessels was five times greater. In the lung parenchyma, collagen was 51.5% of the tissue volume in transgenics and 21.2% in non-transgenics. Since parenchyma was a larger percentage of lung volume in transgenics, but the parenchymal tissue was a smaller percent of the volume, the volume of collagen associated with parenchymal tissue was only slightly greater. We conclude that overexpression of TGF-α during lung maturation alters many aspects of lung development, including branching morphogenesis of the airways and vessels and alveolarization in the parenchyma. Further, the increases in visible collagen previously associated with pulmonary fibrosis due to the overexpression of TGF-α are a result of actual increases in amounts of collagen and in a redistribution of collagen within compartments which results from morphogenetic changes. These morphogenetic changes vary by lung compartment. Supported by HL20748, ES06700 and the Cystic Fibrosis Foundation.

AB0987 Quantification of Interstitial Pulmonary Fibrosis in Systemic Sclerosis Using an Open-Source DICOM Software (OSIRIX)

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 1127.1-1127
Author(s):  
M. Carotti ◽  
F. Salaffi ◽  
S. Bosello ◽  
A. Ciapetti ◽  
E. Bichisecchi ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Open Source ◽  
Interstitial Pulmonary Fibrosis

scholarly journals OP0242 EFFECTS OF THE AUTOTAXIN INHIBITOR ZIRITAXESTAT ON SKIN AND LUNG FIBROSIS IN A MURINE GRAFT-VERSUS-HOST DISEASE MODEL OF SYSTEMIC SCLEROSIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 148.1-149
Author(s):  
Y. Zhang ◽  
L. Summa ◽  
B. Heckmann ◽  
J. H. W. Distler
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Graft Versus Host Disease ◽  
Murine Model ◽  
Allogeneic Bone Marrow Transplantation ◽  
Allogeneic Bone ◽  
Host Disease ◽  
Graft Versus Host ◽  
Dermal Thickness ◽  
Disease Modifying

Background:There is an unmet medical need for new drugs to treat systemic sclerosis (SSc). Autotaxin (ATX) is a widely expressed enzyme that regulates diverse cellular processes, including proliferation, differentiation and migration, and has been implicated in the pathogenesis of SSc. Targeting ATX is a promising new strategy for treating SSc. The autotaxin inhibitor ziritaxestat (GLPG1690) is a potential first-in-class disease-modifying drug for SSc that has been shown to improve skin score in the Phase 2a NOVESA (NCT03798366) trial in patients with SSc.Objectives:To investigate the effects of ziritaxestat in a chronic graft-versus-host disease (cGvHD) murine model of SSc.Methods:Effects of ziritaxestat (10 or 30 mg/kg twice daily [bid]) on disease activity were assessed in a cGvHD murine model of SSc (allogeneic bone marrow transplantation [BMT] with B10.D2 donor and BALB/c recipient; syngeneic mice as controls). Ziritaxestat or nintedanib (60 mg/kg once daily [qd]) as active comparator was administered 21 d after BMT and continued for 35 d. Effects of ziritaxestat were assessed by clinical monitoring, histologic assessment of skin and lungs (dermal thickness, Ashcroft scores and collagen-covered area), immunofluorescence staining with Trichrome and Sirius Red for myofibroblasts, and biochemical analysis of collagen content, as measured by hydroxyproline levels.Results:Ziritaxestat 30 mg/kg bid for 35 days significantly reduced the clinical cutaneous score in the murine cGvHD model by 57% (p<0.05) compared with vehicle, and to a similar extent when compared with nintedanib 60 mg/kg (38%; p<0.05). Dermal accumulation of collagen and dermal thickness (Figure) were reduced with ziritaxestat 10 and 30 mg/kg compared with vehicle. At 30 mg/kg, ziritaxestat reversed the increase in the allogeneic model (p<0.001), returning dermal thickness to the levels in non-fibrotic control mice. Ziritaxestat also significantly reduced pulmonary fibrosis in the cGvHD model, with reductions in the fibrotic lung area (ziritaxestat 10 and 30 mg/kg; p<0.001 for both) and Ashcroft scores (ziritaxestat 30 mg/kg; p<0.05). Ziritaxestat was generally well tolerated.Conclusion:Ziritaxestat improved the histological, biochemical and clinical symptom readouts of dermal and pulmonary fibrosis in a murine model, consistent with a broad and rapid disease-modifying effect in SSc.Acknowledgements:This study was funded by Galapagos NV (Mechelen, Belgium). Medical writing/editorial support was provided by Ian Faulkner, PhD (Aspire Scientific, Bollington, UK) funded by Galapagos NV.Disclosure of Interests:Yun Zhang Employee of: 4D Science, Lena Summa Employee of: 4D Science, Bertrand Heckmann Shareholder of: Galapagos, Employee of: Galapagos, Jörg H.W. Distler Shareholder of: 4D Science, Consultant of: Actelion, Active Biotech, Anamar, ARXX, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline, Inventiva, JB Therapeutics, Medac, Pfizer, RuiYi and UCB, Grant/research support from: Anamar, Active Biotech, Array Biopharma, ARXX, aTyr, Bristol Myers Squibb, Bayer Pharma, Boehringer Ingelheim, Celgene, Galapagos, GlaxoSmithKline, Inventiva, Novartis, Sanofi-Aventis, RedX and UCB

A New Generation of Girls

2019 ◽  
Vol 12 (1) ◽  
pp. 125-127
Author(s):  
Lucy D. Curzon
Keyword(s):  
New York ◽  
Quantitative Analysis ◽  
Qualitative Study ◽  
New York University ◽  
Gendered Spaces ◽  
Transgender Children ◽  
New Generation ◽  
Gender Revolution

BOOK REVIEWAnn Travers. 2018. The Trans Generation: How Trans Kids (and Their Parents) Are Creating a Gender Revolution. New York: New York University Press.Ann Travers’s new book, The Trans Generation: How Trans Kids (and Their Parents) Are Creating a Gender Revolution (hereafter The Trans Generation) is a highly persuasive investigation that sheds much-needed scholarly light on a grossly marginalized, precarious community. Travers interviewed 36 transgender children, and many of their parents, to reveal the challenges they face in everyday use of bathrooms, locker rooms, and other rigidly gendered spaces, as well as in interactions with friends, parents, and siblings, as well as schools, and local and state or provincial governments. Apart from the scope of this study, what is remarkable about The Trans Generation is its accessibility. Instead of presenting a quantitative analysis, which can be alienating to readers outside academia, Travers offers an exhaustive qualitative study parsed in highly thoughtful, eloquent, and open terms—one that prizes the individuality, indeed the knowableness, of each child interviewed. And, although The Trans Generation is not explicitly dedicated to discussions of girlhood, the focus of this journal, it nonetheless offers, I argue, valuable new paradigms or strategies for thinking about girls’ lives and identities.

Quantitative analysis of microchimerism in systemic sclerosis skin tissue

2001 ◽  
Vol 293 (8) ◽  
pp. 387-391 ◽  
Author(s):  
T. Ohtsuka ◽  
Yukari Miyamoto ◽  
Akio Yamakage ◽  
Soji Yamazaki
Keyword(s):  
Systemic Sclerosis ◽  
Quantitative Analysis ◽  
Skin Tissue

Immunogenetic prediction of pulmonary fibrosis in systemic sclerosis

The Lancet ◽  
1991 ◽  
Vol 338 (8775) ◽  
pp. 1152 ◽  
Author(s):  
M Vanoli ◽  
S Della Bella ◽  
C Coppola ◽  
N Eisera ◽  
R Scorza
Keyword(s):  
Systemic Sclerosis ◽  
Pulmonary Fibrosis

scholarly journals Correction: Propylthiouracil prevents cutaneous and pulmonary fibrosis in the reactive oxygen species murine model of systemic sclerosis

2014 ◽  
Vol 16 (2) ◽  
pp. 406
Author(s):  
Gianluca Bagnato ◽  
Alessandra Bitto ◽  
Natasha Irrera ◽  
Gabriele Pizzino ◽  
Donatella Sangari ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Systemic Sclerosis ◽  
Pulmonary Fibrosis ◽  
Murine Model ◽  
Reactive Oxygen ◽  
Oxygen Species
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