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Article: Successful treatment of telomeropathy-related interstitial lung disease with immunosuppression and danazol.

Chambers, Daniel C / Lutzky, Viviana P / Apte, Simon H / Godbolt, David / Feenstra, John / Mackintosh, John

2020 Volume 8, Issue 6, Page(s) e00607

Abstract: We report the case of a 42-year-old female with a history of finger clubbing which improved during pregnancy, a history of unexplained hepatosplenomegaly, and subsequent non-specific interstitial pneumonia with respiratory failure. Given a personal and ... ...

Abstract	We report the case of a 42-year-old female with a history of finger clubbing which improved during pregnancy, a history of unexplained hepatosplenomegaly, and subsequent non-specific interstitial pneumonia with respiratory failure. Given a personal and family history of early greying of the hair, the peripheral blood monocyte telomere length was measured and was confirmed to be <1st centile, explaining the multiorgan presentation. She was treated with prednisolone, mycophenolate mofetil, and the synthetic androgen danazol with a dramatic improvement in respiratory failure and lung function. After 18 months of danazol treatment, the peripheral blood monocyte telomere length had returned to the normal range.
Language	English
Publishing date	2020-06-25
Publishing country	United States
Document type	Case Reports
ZDB-ID	2750180-2
ISSN	2051-3380
ISSN	2051-3380
DOI	10.1002/rcr2.607
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Article ; Online: A Methodological Approach to Identify Natural Compounds with Antifibrotic Activity and the Potential to Treat Pulmonary Fibrosis Using Single-Cell Sequencing and Primary Human Lung Macrophages.

Apte, Simon H / Groves, Penny L / Tan, Maxine E / Lutzky, Viviana P / de Silva, Tharushi / Monteith, Joshua N / Yerkovich, Stephanie T / O'Sullivan, Brendan J / Davis, Rohan A / Chambers, Daniel C

International journal of molecular sciences

2023 Volume 24, Issue 20

Abstract: Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of the interstitial pneumonias. The cause of the disease is unknown, and new therapies that stop or reverse disease progression are desperately needed. Recent advances in next- ... ...

Abstract	Idiopathic pulmonary fibrosis (IPF) is the most common and lethal form of the interstitial pneumonias. The cause of the disease is unknown, and new therapies that stop or reverse disease progression are desperately needed. Recent advances in next-generation sequencing have led to an abundance of freely available, clinically relevant, organ-and-disease-specific, single-cell transcriptomic data, including studies from patients with IPF. We mined data from published IPF data sets and identified gene signatures delineating pro-fibrotic or antifibrotic macrophages and then used the Enrichr platform to identify compounds with the potential to drive the macrophages toward the antifibrotic transcriptotype. We then began testing these compounds in a novel in vitro phenotypic drug screening assay utilising human lung macrophages recovered from whole-lung lavage of patients with silicosis. As predicted by the Enrichr tool, glitazones potently modulated macrophage gene expression towards the antifibrotic phenotype. Next, we assayed a subset of the NatureBank pure compound library and identified the cyclobutane lignan, endiandrin A, which was isolated from the roots of the endemic Australian rainforest plant,
MeSH term(s)	Humans ; Australia ; Idiopathic Pulmonary Fibrosis/drug therapy ; Idiopathic Pulmonary Fibrosis/genetics ; Idiopathic Pulmonary Fibrosis/metabolism ; Lung/metabolism ; Macrophages/metabolism ; Thiazolidinediones/therapeutic use
Chemical Substances	Thiazolidinediones
Language	English
Publishing date	2023-10-12
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms242015104
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Article: CD161 expression defines new human γδ T cell subsets.

Karunathilaka, Amali / Halstrom, Samuel / Price, Patricia / Holt, Michael / Lutzky, Viviana P / Doolan, Denise L / Kupz, Andreas / Bell, Scott C / Thomson, Rachel M / Miles, John J / Ratnatunga, Champa N

Immunity & ageing : I & A

2022 Volume 19, Issue 1, Page(s) 11

Abstract: γδ T cells are a highly versatile immune lineage involved in host defense and homeostasis, but questions remain around their heterogeneity, precise function and role during health and disease. We used ... ...

Abstract	γδ T cells are a highly versatile immune lineage involved in host defense and homeostasis, but questions remain around their heterogeneity, precise function and role during health and disease. We used multi
Language	English
Publishing date	2022-02-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2168941-6
ISSN	1742-4933
ISSN	1742-4933
DOI	10.1186/s12979-022-00269-w
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Article ; Online: Characterizing and correcting immune dysfunction in non-tuberculous mycobacterial disease.

Ratnatunga, Champa N / Tungatt, Katie / Proietti, Carla / Halstrom, Sam / Holt, Michael R / Lutzky, Viviana P / Price, Patricia / Doolan, Denise L / Bell, Scott C / Field, Matt A / Kupz, Andreas / Thomson, Rachel M / Miles, John J

Frontiers in immunology

2022 Volume 13, Page(s) 1047781

Abstract: Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, and economic costs. Improvements in NTM-PD management are urgently needed, which ... ...

Abstract	Non-tuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic, progressive, and growing worldwide health burden associated with mounting morbidity, mortality, and economic costs. Improvements in NTM-PD management are urgently needed, which requires a better understanding of fundamental immunopathology. Here, we examine temporal dynamics of the immune compartment during NTM-PD caused by
MeSH term(s)	Humans ; Nontuberculous Mycobacteria ; Mycobacterium avium Complex ; Mycobacterium avium-intracellulare Infection/drug therapy ; Lung Diseases/microbiology ; Immune System Diseases
Language	English
Publishing date	2022-11-10
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1047781
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Article ; Online: Alveolar crystal burden in stone workers with artificial stone silicosis.

Apte, Simon H / Tan, Maxine E / Lutzky, Viviana P / De Silva, Tharushi A / Fiene, Andreas / Hundloe, Justin / Deller, David / Sullivan, Clair / Bell, Peter T / Chambers, Daniel C

Respirology (Carlton, Vic.)

2022 Volume 27, Issue 6, Page(s) 437–446

Abstract: Background and objective: An epidemic of silicosis has emerged due to a failure to control risks associated with exposure to high-silica content respirable dust generated while working with artificial stone products. Methods for quantification of ... ...

Abstract	Background and objective: An epidemic of silicosis has emerged due to a failure to control risks associated with exposure to high-silica content respirable dust generated while working with artificial stone products. Methods for quantification of alveolar crystal burden are needed to advance our understanding of the pathobiology of silica-related lung injury as well as assisting in the diagnosis, clinical management and prognostication of affected workers. The objective of this study was to develop and validate novel methods to quantify alveolar crystal burden in bronchoalveolar lavage (BAL) fluid from patients with artificial stone silicosis. Methods: New methods to quantify and analyse alveolar crystal in BAL from patients with artificial stone silicosis were developed. Crystals were isolated and counted by microscopy and alveolar crystal burden was calculated using a standard curve generated by titration of respirable α-Quartz. The utility of the assay was then assessed in 23 patients with artificial stone silicosis. Results: Alveolar crystal burden was greater in patients with silicosis (0.44 picograms [pg]/cell [0.08-3.49]) compared to patients with other respiratory diagnoses (0.057 pg/cell [0.01-0.34]; p < 0.001). Alveolar crystal burden was positively correlated with years of silica exposure (ρ = 0.49, p = 0.02) and with decline in diffusing capacity of the lungs for carbon monoxide (ρ = -0.50, p = 0.02). Conclusion: Alveolar crystal burden quantification differentiates patients with silicosis from patients with other respiratory disorders. Furthermore, crystal burden is correlated with the rate of decline in lung function in patients with artificial stone silicosis.
MeSH term(s)	Dust/analysis ; Humans ; Lung ; Occupational Exposure/adverse effects ; Silicon Dioxide/adverse effects ; Silicosis/epidemiology
Chemical Substances	Dust ; Silicon Dioxide (7631-86-9)
Language	English
Publishing date	2022-02-17
Publishing country	Australia
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1435849-9
ISSN	1440-1843 ; 1323-7799
ISSN (online)	1440-1843
ISSN	1323-7799
DOI	10.1111/resp.14229
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Article ; Online: Synthetic hookworm-derived peptides are potent modulators of primary human immune cell function that protect against experimental colitis in vivo.

Smallwood, Taylor B / Navarro, Severine / Cristofori-Armstrong, Ben / Watkins, Thomas S / Tungatt, Katie / Ryan, Rachael Y M / Haigh, Oscar L / Lutzky, Viviana P / Mulvenna, Jason P / Rosengren, K Johan / Loukas, Alex / Miles, John J / Clark, Richard J

The Journal of biological chemistry

2021 Volume 297, Issue 1, Page(s) 100834

Abstract: The prevalence of autoimmune diseases is on the rise globally. Currently, autoimmunity presents in over 100 different forms and affects around 9% of the world's population. Current treatments available for autoimmune diseases are inadequate, expensive, ... ...

Abstract	The prevalence of autoimmune diseases is on the rise globally. Currently, autoimmunity presents in over 100 different forms and affects around 9% of the world's population. Current treatments available for autoimmune diseases are inadequate, expensive, and tend to focus on symptom management rather than cure. Clinical trials have shown that live helminthic therapy can decrease chronic inflammation associated with inflammatory bowel disease and other gastrointestinal autoimmune inflammatory conditions. As an alternative and better controlled approach to live infection, we have identified and characterized two peptides, Acan1 and Nak1, from the excretory/secretory component of parasitic hookworms for their therapeutic activity on experimental colitis. We synthesized Acan1 and Nak1 peptides from the Ancylostoma caninum and Necator americanus hookworms and assessed their structures and protective properties in human cell-based assays and in a mouse model of acute colitis. Acan1 and Nak1 displayed anticolitic properties via significantly reducing weight loss and colon atrophy, edema, ulceration, and necrosis in 2,4,6-trinitrobenzene sulfonic acid-exposed mice. These hookworm peptides prevented mucosal loss of goblet cells and preserved intestinal architecture. Acan1 upregulated genes responsible for the repair and restitution of ulcerated epithelium, whereas Nak1 downregulated genes responsible for epithelial cell migration and apoptotic cell signaling within the colon. These peptides were nontoxic and displayed key immunomodulatory functions in human peripheral blood mononuclear cells by suppressing CD4
MeSH term(s)	Amino Acid Sequence ; Ancylostoma ; Ancylostomatoidea/chemistry ; Animals ; Cell Proliferation/drug effects ; Colitis/drug therapy ; Colitis/prevention & control ; Cytokines/metabolism ; Disease Models, Animal ; Gene Expression Regulation/drug effects ; Humans ; Inflammation Mediators/metabolism ; Intestines/pathology ; Kv1.3 Potassium Channel/antagonists & inhibitors ; Kv1.3 Potassium Channel/metabolism ; Leukocytes/drug effects ; Leukocytes/immunology ; Magnetic Resonance Spectroscopy ; Male ; Mice, Inbred C57BL ; Necator americanus ; Peptides/chemistry ; Peptides/metabolism ; Peptides/pharmacology ; Peptides/therapeutic use ; Principal Component Analysis ; Protein Domains ; Protein Folding ; T-Lymphocytes/cytology ; Trinitrobenzenesulfonic Acid ; Xenopus laevis ; Mice
Chemical Substances	Cytokines ; Inflammation Mediators ; Kv1.3 Potassium Channel ; Peptides ; Trinitrobenzenesulfonic Acid (8T3HQG2ZC4)
Language	English
Publishing date	2021-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.100834
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Article: Sequencing of Historical Isolates, K-mer Mining and High Serological Cross-Reactivity with Ross River Virus Argue against the Presence of Getah Virus in Australia.

Rawle, Daniel J / Nguyen, Wilson / Dumenil, Troy / Parry, Rhys / Warrilow, David / Tang, Bing / Le, Thuy T / Slonchak, Andrii / Khromykh, Alexander A / Lutzky, Viviana P / Yan, Kexin / Suhrbier, Andreas

Pathogens (Basel, Switzerland)

2020 Volume 9, Issue 10

Abstract: Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original ... ...

Abstract	Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original isolates (N544 and N554), illustrated that these viruses were virtually identical to the 1955 GETV
Language	English
Publishing date	2020-10-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens9100848
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Article ; Online: Venom of the Red-Bellied Black Snake

Ryan, Rachael Y M / Lutzky, Viviana P / Herzig, Volker / Smallwood, Taylor B / Potriquet, Jeremy / Wong, Yide / Masci, Paul / Lavin, Martin F / King, Glenn F / Lopez, J Alejandro / Ikonomopoulou, Maria P / Miles, John J

Toxins

2020 Volume 12, Issue 11

Abstract: Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of ... ...

Abstract	Venoms act with remarkable specificity upon a broad diversity of physiological targets. Venoms are composed of proteins, peptides, and small molecules, providing the foundation for the development of novel therapeutics. This study assessed the effect of venom from the red-bellied black snake (
MeSH term(s)	Animals ; Antigen-Presenting Cells/drug effects ; Antigen-Presenting Cells/immunology ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; Cytokines/immunology ; Elapid Venoms/pharmacology ; Elapidae ; Humans ; Immunosuppressive Agents/pharmacology ; Lipopolysaccharides/pharmacology
Chemical Substances	Cytokines ; Elapid Venoms ; Immunosuppressive Agents ; Lipopolysaccharides
Language	English
Publishing date	2020-10-26
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518395-3
ISSN	2072-6651 ; 2072-6651
ISSN (online)	2072-6651
ISSN	2072-6651
DOI	10.3390/toxins12110674
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Article ; Online: The Rise of Non-Tuberculosis Mycobacterial Lung Disease.

Ratnatunga, Champa N / Lutzky, Viviana P / Kupz, Andreas / Doolan, Denise L / Reid, David W / Field, Matthew / Bell, Scott C / Thomson, Rachel M / Miles, John J

Frontiers in immunology

2020 Volume 11, Page(s) 303

Abstract: The incidence and number of deaths from non-tuberculous mycobacterial (NTM) disease have been steadily increasing globally. These lesser known "cousins" ... ...

Abstract	The incidence and number of deaths from non-tuberculous mycobacterial (NTM) disease have been steadily increasing globally. These lesser known "cousins" of
MeSH term(s)	Age Distribution ; Climate Change ; Cost of Illness ; Global Health ; Host-Pathogen Interactions ; Humans ; Mycobacterium Infections, Nontuberculous/economics ; Mycobacterium Infections, Nontuberculous/epidemiology ; Mycobacterium Infections, Nontuberculous/immunology ; Mycobacterium Infections, Nontuberculous/microbiology ; Opportunistic Infections/economics ; Opportunistic Infections/epidemiology ; Opportunistic Infections/immunology ; Opportunistic Infections/microbiology ; Pneumonia, Bacterial/economics ; Pneumonia, Bacterial/epidemiology ; Pneumonia, Bacterial/immunology ; Pneumonia, Bacterial/microbiology ; Research ; Risk ; Sex Distribution ; Tropical Climate ; Water Microbiology
Language	English
Publishing date	2020-03-03
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.00303
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Article ; Online: Sequencing of Historical Isolates, K-mer Mining and High Serological Cross-Reactivity with Ross River Virus Argue against the Presence of Getah Virus in Australia

Daniel J. Rawle / Wilson Nguyen / Troy Dumenil / Rhys Parry / David Warrilow / Bing Tang / Thuy T. Le / Andrii Slonchak / Alexander A. Khromykh / Viviana P. Lutzky / Kexin Yan / Andreas Suhrbier

Pathogens, Vol 9, Iss 848, p

2020 Volume 848

Abstract	Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original isolates (N544 and N554), illustrated that these viruses were virtually identical to the 1955 GETV MM2021 isolate from Malaysia. K-mer mining of the >40,000 terabases of sequence data in the Sequence Read Archive followed by BLASTn confirmation identified multiple GETV sequences in biosamples from Asia (often as contaminants), but not in biosamples from Australia. In contrast, sequence reads aligning to the Australian Ross River virus (RRV) were readily identified in Australian biosamples. To explore the serological relationship between GETV and other alphaviruses, an adult wild-type mouse model of GETV was established. High levels of cross-reactivity and cross-protection were evident for convalescent sera from mice infected with GETV or RRV, highlighting the difficulties associated with the interpretation of early serosurveys reporting GETV antibodies in Australian cattle and pigs. The evidence that GETV circulates in Australia is thus not compelling.
Keywords	Getah virus ; Ross River virus ; Sequence Read Archive ; serology ; mouse model ; virus contamination ; Medicine ; R
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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