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Article ; Online: Channels and Transporters of the Pulmonary Lamellar Body in Health and Disease.

Dietl, Paul / Frick, Manfred

2021 Volume 11, Issue 1

Abstract: The lamellar body (LB) of the alveolar type II (ATII) cell is a lysosome-related organelle (LRO) that contains surfactant, a complex mix of mainly lipids and specific surfactant proteins. The major function of surfactant in the lung is the reduction of ... ...

Abstract	The lamellar body (LB) of the alveolar type II (ATII) cell is a lysosome-related organelle (LRO) that contains surfactant, a complex mix of mainly lipids and specific surfactant proteins. The major function of surfactant in the lung is the reduction of surface tension and stabilization of alveoli during respiration. Its lack or deficiency may cause various forms of respiratory distress syndrome (RDS). Surfactant is also part of the innate immune system in the lung, defending the organism against air-borne pathogens. The limiting (organelle) membrane that encloses the LB contains various transporters that are in part responsible for translocating lipids and other organic material into the LB. On the other hand, this membrane contains ion transporters and channels that maintain a specific internal ion composition including the acidic pH of about 5. Furthermore, P2X
MeSH term(s)	COVID-19/metabolism ; COVID-19/virology ; Humans ; Ion Channels/metabolism ; Lamellar Bodies/metabolism ; Lung/metabolism ; Lung/virology ; Membrane Transport Proteins/metabolism ; Organelles/metabolism ; Organelles/virology ; Pulmonary Alveoli/metabolism ; Pulmonary Alveoli/virology ; Pulmonary Surfactants/metabolism ; SARS-CoV-2/physiology
Chemical Substances	Ion Channels ; Membrane Transport Proteins ; Pulmonary Surfactants
Language	English
Publishing date	2021-12-24
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells11010045
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Article ; Online: Channels and Transporters of the Pulmonary Lamellar Body in Health and Disease

Paul Dietl / Manfred Frick

Cells, Vol 11, Iss 45, p

2022 Volume 45

Abstract	The lamellar body (LB) of the alveolar type II (ATII) cell is a lysosome-related organelle (LRO) that contains surfactant, a complex mix of mainly lipids and specific surfactant proteins. The major function of surfactant in the lung is the reduction of surface tension and stabilization of alveoli during respiration. Its lack or deficiency may cause various forms of respiratory distress syndrome (RDS). Surfactant is also part of the innate immune system in the lung, defending the organism against air-borne pathogens. The limiting (organelle) membrane that encloses the LB contains various transporters that are in part responsible for translocating lipids and other organic material into the LB. On the other hand, this membrane contains ion transporters and channels that maintain a specific internal ion composition including the acidic pH of about 5. Furthermore, P2X 4 receptors, ligand gated ion channels of the danger signal ATP, are expressed in the limiting LB membrane. They play a role in boosting surfactant secretion and fluid clearance. In this review, we discuss the functions of these transporting pathways of the LB, including possible roles in disease and as therapeutic targets, including viral infections such as SARS-CoV-2.
Keywords	lysosome related organelle (LRO) ; surfactant ; alveolus ; exocytosis ; purinergic signaling ; ivermectin ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2022-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
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Article ; Online: PD-L1 Expression and Silva Invasion Pattern in Villoglandular Adenocarcinoma of the Uterine Cervix.

Dietl, Anna K / Beckmann, Matthias W / Stuebs, Frederik A / Gass, Paul / Emons, Julius / Hartmann, Arndt / Erber, Ramona

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists

2024

Abstract: Villoglandular adenocarcinoma (VGA) of the uterine cervix is a rare subtype of endocervical adenocarcinoma in young women. Between 2007 and 2020, all women with endocervical adenocarcinoma were retrospectively reviewed to find patients with VGA. Eight ... ...

Abstract	Villoglandular adenocarcinoma (VGA) of the uterine cervix is a rare subtype of endocervical adenocarcinoma in young women. Between 2007 and 2020, all women with endocervical adenocarcinoma were retrospectively reviewed to find patients with VGA. Eight patients in whom pure VGA had been diagnosed were included. The mean age at initial diagnosis was 36.3 years (range 24-46). After surgical treatment, patients were followed up for 59 months (range 16-150). To date, all patients are alive with no evidence of disease. Neither lymph node involvement nor lymphovascular invasion was found. Furthermore, we examined the samples with a focus on morphological invasion pattern (Silva), stromal tumor-infiltrating lymphocytes (sTILs), and immunohistochemical programmed death ligand-1 (PD-L1) expression. PD-L1 expression was observed in 7/8 using the combined positive score (cutoff≥1%), 1/8 of VGAs using the tumor proportion score (cutoff≥1%), and 7/8 using the immune cell (cutoff≥1%). Using combined positive score and immune cell, PD-L1 expression was seen in 7/8 of pattern B and C tumors, with significantly higher expression in tumors with destructive-type patterns (P<0.05, A vs. B+C). Using tumor proportion score, no significant difference in PD-L1 expression was seen between VGAs with different invasion patterns. VGAs demonstrated twice higher sTILs in tumors with destructive-type invasion patterns. Our observations suggest that PD-L1 expression, tumor invasion patterns, and sTILs do not correlate with the excellent prognosis of pure VGA.
Language	English
Publishing date	2024-01-31
Publishing country	United States
Document type	Journal Article
ZDB-ID	604859-6
ISSN	1538-7151 ; 0277-1691
ISSN (online)	1538-7151
ISSN	0277-1691
DOI	10.1097/PGP.0000000000001006
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Article: Core-Shell Imprinted Particles for Adenovirus Binding.

Dietl, Sandra / Walther, Paul / Sobek, Harald / Mizaikoff, Boris

Materials (Basel, Switzerland)

2021 Volume 14, Issue 24

Abstract: Virus-imprinted polymers were synthesized via surface imprinting strategies to produce core-shell imprinted particles selective for human adenovirus type 5. High binding affinity of the target virus towards the resulting imprinted layer was confirmed and ...

Abstract	Virus-imprinted polymers were synthesized via surface imprinting strategies to produce core-shell imprinted particles selective for human adenovirus type 5. High binding affinity of the target virus towards the resulting imprinted layer was confirmed and unspecific binding was reduced in presence of blocking agents, i.e., via bovine serum albumin and skim milk in combination with Tween 20. In addition, the imprinted materials were applied for adenovirus extraction from cell culture supernatants. High levels of virus binding with negligible binding of matrix proteins confirmed the suitability of these materials for binding and extraction of the target virus from complex matrices.
Language	English
Publishing date	2021-12-13
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2487261-1
ISSN	1996-1944
ISSN	1996-1944
DOI	10.3390/ma14247692
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Article ; Online: Aquaporins in the lung.

Wittekindt, Oliver H / Dietl, Paul

Pflugers Archiv : European journal of physiology

2018 Volume 471, Issue 4, Page(s) 519–532

Abstract: The lung is the interface between air and blood where the exchange of oxygen and carbon dioxide occurs. The surface liquid that is directly exposed to the gaseous compartment covers both conducting airways and respiratory zone and forms the air-liquid ... ...

Abstract	The lung is the interface between air and blood where the exchange of oxygen and carbon dioxide occurs. The surface liquid that is directly exposed to the gaseous compartment covers both conducting airways and respiratory zone and forms the air-liquid interface. The barrier that separates this lining fluid of the airways and alveoli from the extracellular compartment is the pulmonary epithelium. The volume of the lining fluid must be kept in a range that guarantees an appropriate gas exchange and other functions, such as mucociliary clearance. It is generally accepted that this is maintained by balancing resorptive and secretory fluid transport across the pulmonary epithelium. Whereas osmosis is considered as the exclusive principle of fluid transport in the airways, filtration may contribute to alveolar fluid accumulation under pathologic conditions. Aquaporins (AQP) facilitate water flux across cell membranes, and as such, they provide a transcellular route for water transport across epithelia. However, their contribution to near-isosmolar fluid conditions in the lung still remains elusive. Herein, we discuss the role of AQPs in the lung with regard to fluid homeostasis across the respiratory epithelium.
MeSH term(s)	Animals ; Aquaporins/metabolism ; Biological Transport/physiology ; Cell Membrane/metabolism ; Humans ; Lung/metabolism ; Pulmonary Alveoli/metabolism ; Respiratory Mucosa/metabolism ; Water/metabolism
Chemical Substances	Aquaporins ; Water (059QF0KO0R)
Language	English
Publishing date	2018-11-05
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-018-2232-y
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Article ; Online: An efficient capture strategy for the purification of human adenovirus type 5 from cell lysates.

Dietl, Sandra / Kiefer, Franziska / Binder, Stefanie / Walther, Paul / Sobek, Harald / Mizaikoff, Boris

Journal of biotechnology

2022

Abstract: An efficient capture step for human adenovirus type 5 from cell lysate was developed as an initial virus purification step from cell debris supernatant. Organosilane-based polymer particles were synthesized and experimental monomer screening allowed the ... ...

Abstract	An efficient capture step for human adenovirus type 5 from cell lysate was developed as an initial virus purification step from cell debris supernatant. Organosilane-based polymer particles were synthesized and experimental monomer screening allowed the selection of appropriate functionalities for the development of particles for virus binding. After elution, virus recoveries of 83% were obtained with significant reduction of matrix proteins and residual host cell DNA. Therefore, the implemented capture strategy for adenovirus via polymer particles provides a scalable and reproducible approach to reduce time and cost during virus purification processes.
Language	English
Publishing date	2022-12-06
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	843647-2
ISSN	1873-4863 ; 0168-1656 ; 1389-0352
ISSN (online)	1873-4863
ISSN	0168-1656 ; 1389-0352
DOI	10.1016/j.jbiotec.2022.11.015
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Article ; Online: Impact of the Corona Pandemic on Cervical Cancer Screening Assessment.

Stuebs, Frederik A / Behrens, Annika S / Seibold, Anja / Adler, Werner / Geppert, Carol / Hartmann, Arndt / Knöll, Antje / Koch, Martin C / Mehlhorn, Grit / Beckmann, Matthias W / Theuser, Anna-Katharin / Schulmeyer, Carla E / Gass, Paul / Dietl, Anna K

In vivo (Athens, Greece)

2024 Volume 38, Issue 2, Page(s) 734–740

Abstract: Background/aim: The global impact of the COVID-19 pandemic resulted in disruptions to healthcare systems throughout the world. The numbers of cytology examinations, human papillomavirus (HPV) tests, and women referred for colposcopy decreased in many ... ...

Abstract	Background/aim: The global impact of the COVID-19 pandemic resulted in disruptions to healthcare systems throughout the world. The numbers of cytology examinations, human papillomavirus (HPV) tests, and women referred for colposcopy decreased in many countries. There have been no reports on cervical cancer screening in Germany. This study aimed to describe changes in the numbers of colposcopies, cytology examinations, HPV tests, and histological results during the pandemic compared to the pre-pandemic years in order to evaluate the impact of the COVID-19 pandemic on cervical cancer screening. Patients and methods: The numbers of colposcopies, cytology examinations, HPV tests, and histologic results were analyzed retrospectively for the period January 2018 to December 2022. The 2 years period before the pandemic (2018 and 2019) were compared with the 3 years period of the pandemic (2020-2022). Results: In total, 6,518 colposcopies were performed in 5,579 women. The numbers of colposcopies, cytology examinations, and high-risk HPV (hrHPV) tests increased during the pandemic years. The number of biopsies per year taken was stable (range=450-554). The relative numbers of cervical intraepithelial neoplasia (CIN) III/HSIL findings were stable, while the numbers of cervical cancers identified increased slightly from 15 (6.6%) in 2018 to 22 (7.4%) in 2022. Conclusion: Increases in numbers of women examined and colposcopies were observed in the years 2021 and 2022 during the pandemic, in comparison to the preceding years. These also led to increases in the figures for cytology, hrHPV, histology, and operations. The onset of the pandemic occurred in the same year as a newly organized screening program started in Germany. The increases might therefore be due to the newly organized screening system.
MeSH term(s)	Female ; Humans ; Uterine Cervical Neoplasms/diagnosis ; Uterine Cervical Neoplasms/epidemiology ; Uterine Cervical Neoplasms/pathology ; Pandemics ; Papillomavirus Infections/complications ; Papillomavirus Infections/diagnosis ; Papillomavirus Infections/epidemiology ; Early Detection of Cancer/methods ; Retrospective Studies ; Uterine Cervical Dysplasia/diagnosis ; COVID-19/epidemiology ; Papillomaviridae
Language	English
Publishing date	2024-02-27
Publishing country	Greece
Document type	Journal Article
ZDB-ID	807031-3
ISSN	1791-7549 ; 0258-851X
ISSN (online)	1791-7549
ISSN	0258-851X
DOI	10.21873/invivo.13495
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Article: Standardized Procedures for Patients with Dysplasia and Other Diseases of the Cervix, Vulva, and Vagina at a Certified Dysplasia Unit Prior to the Introduction of the Organized Cervical Cancer Screening Program.

Schulmeyer, Carla E / Koch, Martin C / Dietl, Anna K / Stuebs, Frederik A / Behrens, Annika / Renner, Simone K / Mehlhorn, Grit / Geppert, Carol C / Hartmann, Arndt / Beckmann, Matthias W / Gass, Paul

Geburtshilfe und Frauenheilkunde

2023 Volume 83, Issue 8, Page(s) 1031–1042

Abstract: ... ...

Abstract	Introduction
Language	English
Publishing date	2023-08-15
Publishing country	Germany
Document type	Journal Article
ZDB-ID	80111-2
ISSN	1438-8804 ; 0016-5751 ; 1615-3359
ISSN (online)	1438-8804
ISSN	0016-5751 ; 1615-3359
DOI	10.1055/a-1934-1686
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Article ; Online: Management of Cervical Intraepithelial Neoplasia in Pregnant Women.

Stuebs, Frederik A / Koch, Martin C / Dietl, Anna K / Schulmeyer, Carla E / Behrens, Annika S / Seibold, Anja / Adler, Werner / Geppert, Carol / Hartman, Arndt / Knoll, Antje / Beckmann, Matthias W / Gass, Paul / Mehlhorn, Grit

Anticancer research

2023 Volume 43, Issue 7, Page(s) 3153–3158

Abstract: Background/aim: The aims of the present study were to evaluate the accuracy of colposcopic findings, investigate the way in which untreated cervical intraepithelial neoplasia (CIN) 2/3 develops during pregnancy, and identify factors associated with ... ...

Abstract	Background/aim: The aims of the present study were to evaluate the accuracy of colposcopic findings, investigate the way in which untreated cervical intraepithelial neoplasia (CIN) 2/3 develops during pregnancy, and identify factors associated with regression, persistence, or progression rates. Patients and methods: In a tertiary gynecology and obstetrics department, 655 pregnant women were seen for colposcopy. The most common reason for referral was abnormal cytology findings. The follow-up findings were analyzed retrospectively on the basis of colposcopic findings and cytological and histological tests. Results: The rate of accuracy for major colposcopic findings was 89.2%. Among the colposcopic findings considered "suspicious for invasion" were invasive carcinoma in 42.9% and CIN 3 in 57.1%. The persistence of CIN 3 postpartum was 80% and the rate of progression 4.1%. The rate of regression for CIN 3 was 21.9%. For CIN 2, the rate of persistence was 37.5%, with a regression rate of 31.3%. The rate of regression was higher after vaginal delivery in comparison with caesarean section. Conclusion: The accuracy rate of colposcopy is comparatively high, at 89.2%. This might be because pregnant women are seen by more experienced examiners in our dysplasia unit. The rate of progression is comparable with that in other studies. Vaginal delivery increases the regression rate. The newborns' birth weight or birth week did not affect the rates of regression or persistence.
MeSH term(s)	Infant, Newborn ; Female ; Pregnancy ; Humans ; Uterine Cervical Neoplasms/pathology ; Pregnant Women ; Retrospective Studies ; Cesarean Section ; Uterine Cervical Dysplasia/pathology ; Colposcopy ; Vaginal Smears
Language	English
Publishing date	2023-06-20
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
DOI	10.21873/anticanres.16488
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Article ; Online: TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei.

Schilpp, Carolin / Lochbaum, Robin / Braubach, Peter / Jonigk, Danny / Frick, Manfred / Dietl, Paul / Wittekindt, Oliver H

Pflugers Archiv : European journal of physiology

2021 Volume 473, Issue 2, Page(s) 287–311

Abstract: TGF-β1 is a major mediator of airway tissue remodelling during atopic asthma and affects tight junctions (TJs) of airway epithelia. However, its impact on TJs of ciliated epithelia is sparsely investigated. Herein we elaborated effects of TGF-β1 on TJs ... ...

Abstract	TGF-β1 is a major mediator of airway tissue remodelling during atopic asthma and affects tight junctions (TJs) of airway epithelia. However, its impact on TJs of ciliated epithelia is sparsely investigated. Herein we elaborated effects of TGF-β1 on TJs of primary human bronchial epithelial cells. We demonstrate that TGF-β1 activates TGF-β1 receptors TGFBR1 and TGFBR2 resulting in ALK5-mediated phosphorylation of SMAD2. We observed that TGFBR1 and -R2 localize specifically on motile cilia. TGF-β1 activated accumulation of phosphorylated SMAD2 (pSMAD2-C) at centrioles of motile cilia and at cell nuclei. This triggered an increase in paracellular permeability via cellular redistribution of claudin 3 (CLDN3) from TJs into cell nuclei followed by disruption of epithelial integrity and formation of epithelial lesions. Only ciliated cells express TGF-β1 receptors; however, nuclear accumulations of pSMAD2-C and CLDN3 redistribution were observed with similar time course in ciliated and non-ciliated cells. In summary, we demonstrate a role of motile cilia in TGF-β1 sensing and showed that TGF-β1 disturbs TJ permeability of conductive airway epithelia by redistributing CLDN3 from TJs into cell nuclei. We conclude that the observed effects contribute to loss of epithelial integrity during atopic asthma.
MeSH term(s)	Bronchi/drug effects ; Bronchi/metabolism ; Cells, Cultured ; Cilia/drug effects ; Cilia/metabolism ; Claudin-3/genetics ; Claudin-3/metabolism ; Electric Impedance ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Humans ; Permeability ; Phosphorylation ; Protein Transport ; Receptor, Transforming Growth Factor-beta Type I/agonists ; Receptor, Transforming Growth Factor-beta Type I/metabolism ; Receptor, Transforming Growth Factor-beta Type II/agonists ; Receptor, Transforming Growth Factor-beta Type II/metabolism ; Signal Transduction ; Smad2 Protein/metabolism ; Tight Junctions/drug effects ; Tight Junctions/genetics ; Tight Junctions/metabolism ; Transforming Growth Factor beta1/pharmacology
Chemical Substances	CLDN3 protein, human ; Claudin-3 ; SMAD2 protein, human ; Smad2 Protein ; Transforming Growth Factor beta1 ; Receptor, Transforming Growth Factor-beta Type I (EC 2.7.11.30) ; Receptor, Transforming Growth Factor-beta Type II (EC 2.7.11.30) ; TGFBR1 protein, human (EC 2.7.11.30) ; TGFBR2 protein, human (EC 2.7.11.30)
Language	English
Publishing date	2021-01-02
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	6380-0
ISSN	1432-2013 ; 0031-6768
ISSN (online)	1432-2013
ISSN	0031-6768
DOI	10.1007/s00424-020-02501-2
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