Inhibition of Cyclin G-Associated Kinase (GAK) Impairs Growth of Alveolar Type 2 Cells in a 3-Dimensional Culture System

2019 ◽  
Author(s):  
C.A. Bates ◽  
B. Zhao ◽  
A. Schlobohm ◽  
C. Asquith ◽  
W. Zuercher ◽  
...  
Keyword(s):  
Culture System ◽  
Alveolar Type ◽  
3 Dimensional ◽  
Cyclin G

scholarly journals The Promise of Lung Organoids for Growth and Investigation of Pneumocystis Species

2021 ◽  
Vol 2 ◽  
Author(s):  
Nikeya Tisdale-Macioce ◽  
Jenna Green ◽  
Anne-Karina T. Perl ◽  
Alan Ashbaugh ◽  
Nathan P. Wiederhold ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Culture System ◽  
Ex Vivo ◽  
Alveolar Type ◽  
Proof Of Concept ◽  
3 Dimensional ◽  
Alveolar Epithelial

Pneumocystis species (spp.) are host-obligate fungal parasites that colonize and propagate almost exclusively in the alveolar lumen within the lungs of mammals where they can cause a lethal pneumonia. The emergence of this pneumonia in non-HIV infected persons caused by Pneumocystis jirovecii (PjP), illustrates the continued importance of and the need to understand its associated pathologies and to develop new therapies and preventative strategies. In the proposed life cycle, Pneumocystis spp. attach to alveolar type 1 epithelial cells (AEC1) and prevent gas exchange. This process among other mechanisms of Pneumocystis spp. pathogenesis is challenging to observe in real time due to the absence of a continuous ex vivo or in vitro culture system. The study presented here provides a proof-of-concept for the development of murine lung organoids that mimic the lung alveolar sacs expressing alveolar epithelial type 1 cells (AEC1) and alveolar type 2 epithelial cells (AEC2). Use of these 3-dimensional organoids should facilitate studies of a multitude of unanswered questions and serve as an improved means to screen new anti- PjP agents.

Resection of 2 Intradural Extramedullary Cervical Spine Tumors in a Patient With Neurofibromatosis Type 2: 3-Dimensional Operative Video

2018 ◽  
Vol 16 (2) ◽  
pp. 274-274
Author(s):  
Simone E Dekker ◽  
Chad A Glenn ◽  
Thomas A Ostergard ◽  
Osmond C Wu ◽  
Fernando Alonso ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Cervical Spine ◽  
Treatment Options ◽  
Tumor Resection ◽  
Neurofibromatosis Type ◽  
Cord Compression ◽  
Neurofibromatosis Type 2 ◽  
3 Dimensional ◽  
Intradural Extramedullary

Abstract This 3-dimensional operative video illustrates resection of 2 cervical spine schwannomas in a 19-yr-old female with neurofibromatosis type 2. The patient presented with lower extremity hyperreflexity and hypertonicity. Magnetic resonance imaging (MRI) demonstrated 2 contrast-enhancing intradural extramedullary cervical spine lesions causing spinal cord compression at C4 and C5. The patient underwent a posterior cervical laminoplasty with a midline dural opening for tumor resection. Curvilinear spine cord compression is demonstrated in the operative video. After meticulous dissection, the tumors were resected without complication. The dural closure was performed in watertight fashion followed by laminoplasty using osteoplastic titanium miniplates and screws. Postoperative MRI demonstrated gross total resection with excellent decompression of the spinal cord. The postoperative course was uneventful. The natural history of this disease, treatment options, and potential complications are discussed.

Comparison of the Osteogenic Potential of Mineral Trioxide Aggregate and Endosequence Root Repair Material in a 3-dimensional Culture System

2016 ◽  
Vol 42 (5) ◽  
pp. 760-765 ◽  
Author(s):  
Hisham S. Rifaey ◽  
Max Villa ◽  
Qiang Zhu ◽  
Yu-Hsiung Wang ◽  
Kamran Safavi ◽  
...  
Keyword(s):  
Culture System ◽  
Mineral Trioxide Aggregate ◽  
Osteogenic Potential ◽  
Repair Material ◽  
3 Dimensional ◽  
Root Repair

scholarly journals Loss of Nrf2 promotes alveolar type 2 cell loss in irradiated, fibrotic lung

2017 ◽  
Vol 112 ◽  
pp. 578-586 ◽  
Author(s):  
Geri Traver ◽  
Stacey Mont ◽  
David Gius ◽  
William E. Lawson ◽  
George X. Ding ◽  
...  
Keyword(s):  
Cell Loss ◽  
Alveolar Type

scholarly journals Hypercapnia limits β-catenin mediated alveolar type 2 cell progenitor function by altering Wnt production from adjacent fibroblasts

2022 ◽  
Author(s):  
Laura A Dada ◽  
Lynn C Welch ◽  
Natalia D Magnani ◽  
Ziyou Ren ◽  
Patricia L Brazee ◽  
...  
Keyword(s):  
Alveolar Type ◽  
Mechanically Ventilated ◽  
Persistent Symptoms ◽  
Low Tidal Volume ◽  
Lung Repair ◽  
Ventilator Induced Lung Injury ◽  
Lung Flooding ◽  
Volume Ventilation

Persistent symptoms and radiographic abnormalities suggestive of failed lung repair are among the most common symptoms in patients with COVID-19 after hospital discharge. In mechanically ventilated patients with ARDS secondary to SARS-CoV-2 pneumonia, low tidal volume ventilation to reduce ventilator-induced lung injury necessarily elevate blood CO2 levels, often leading to hypercapnia. The role of hypercapnia on lung repair after injury is not completely understood. Here, we show that hypercapnia limits β-catenin signaling in alveolar type 2 (AT2) cells, leading to reduced proliferative capacity. Hypercapnia alters expression of major Wnts in PDGFRα-fibroblasts from those maintaining AT2 progenitor activity and towards those that antagonize β-catenin signaling and limit progenitor function. Activation of β-catenin signaling in AT2 cells, rescues the effects of hypercapnia on proliferation. Inhibition of AT2 proliferation in hypercapnic patients may contribute to impaired lung repair after injury, preventing sealing of the epithelial barrier, increasing lung flooding, ventilator dependency and mortality.

Abstract TP436: Dysfunctional Cerebral Neovascularization And Remodeling Patterns In Obese And Lean Models Of Type 2 Diabetes

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Roshini Prakash ◽  
Maribeth Johnson ◽  
Susan C Fagan ◽  
Adviye Ergul
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Structural Characteristics ◽  
Structural Parameters ◽  
Volume Density ◽  
3 Dimensional ◽  
Gk Rats ◽  
Dimensional Reconstruction ◽  
Branch Density

We previously reported intense pial cerebral collateralization and arteriogenesis in a mild and lean model of type 2 diabetes, Goto-Kakizaki (GK) rats. Further 3-dimensional fluroscein (FITC) imaging studies revealed regional differences in increased cerebral neovascularization which was associated with poor vessel wall maturity. Building upon these findings, the goals of this study were a) to compare and contrast this pathological neovascularization pattern in db/db mice and GK models of diabetes, and b) determine the effect of glycemic control on erratic cerebral neovascularization. Total vascular volume, density and surface area as well as structural parameters including microvessel/macrovessel ratio, non-FITC perfusing vessel abundance, penetrating arteriole (PA) branching density and diameter, and tortuosity were measured by 3 dimensional reconstruction of FITC stained vasculature using Z-stacked images obtained with confocal microscopy. Lean GK rats exhibited an increase in both micro and macrovessel density, non-perfusing vessel abundance, branch density, diameter and tortuosity. Glycemic control with metformin prevented these changes. Obese db/db mice, on the other hand, showed an increase in only microvascular density but this was not associated with an increase in non-FITC perfusing vessels. PA branch density was higher than controls but branch diameter was reduced. Diabetes also promoted astrogliosis. These results suggests that type 2 diabetes leads to cerebral neovascularization and remodeling but structural characteristics of newly formed vessels differ between lean and obese models that have mild or severe hyperglycemia, respectively. The prevention of dysfunctional cerebral neovascularization by early glucose control suggests that hyperglycemia is a mediator of this response. N=4-8 * p≤ 0.05, ** p≤ 0.005 *** 0.0005

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