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Pulmonary fluorescence imaging

Fatemeh Nooshabadi, Hee-Jeong Yang, Yunfeng Cheng, Madeleine S Durkee, Hexin Xie, Jianghong Rao, Jeffrey D Cirillo, Kristen C Maitland
Tuberculosis is a pulmonary disease with an especially high mortality rate in immuno-compromised populations, specifically children and HIV positive individuals. The causative agent, Mycobacterium tuberculosis (Mtb), is a very slow growing and difficult organism to work with, making both diagnosis and development of effective treatments cumbersome. We utilize a fiber-optic fluorescence microendoscope integrated with a whole-body imaging system for in vivo Mtb detection. The system exploits an endogenous enzyme of Mtb (β-lactamase, or BlaC) using a BlaC-specific NIR fluorogenic substrate...
October 18, 2016: Journal of Biophotonics
Simon C Y Chow, Calvin S H Ng
In the modern era when screening and early surveillance of pulmonary nodules is increasing in importance, the management of the pulmonary nodule represents a different challenge to thoracic surgeons. The difficulty lies in the merging of sound surgical and oncological principles with more minimally invasive and appropriate lung sparing surgery. Furthermore, the intra-operative identification and surgical management of small and sometimes multi-focal pulmonary lesions remain challenging. There have been many developments and innovations in the field of video-assisted thoracoscopic surgery (VATS) to cater for the demands from increasing incidence of pulmonary nodules with associated paradigm shift in their surgical management...
July 2016: Journal of Thoracic Disease
Keiichiro Fujii, Ken-Ichiro Ishibashi, Junki Kato, Jushin Kan, Kana Fujii, Yohei Ito, Hisashi Takino, Ayako Masaki, Takayuki Murase, Hiroshi Inagaki
Mucosa-associated lymphoid tissue (MALT) lymphoma mainly consists of three types of tumor B cells, small (centrocyte-like), scattered large transformed, and intraepithelial. However, it is difficult to differentiate tumor B cells from reactive B cells at the cellular level. We examined five cases of API2-MALT1 fusion-positive MALT lymphoma of the lung. A single paraffin section for each case was subjected to sequential retrieval of whole-slide imaging (WSI) data of hematoxylin and eosin (HE) staining, immunofluorescence staining for CD79a, and fluorescence in situ hybridization (FISH) for the MALT1 split...
September 6, 2016: Virchows Archiv: An International Journal of Pathology
Min Li, Suzette Riddle, Hui Zhang, Angelo D'Alessandro, Amanda Flockton, Natalie J Serkova, Kirk C Hansen, Radu Moldvan, B Alexandre McKeon, Maria Frid, Sushil Kumar, Hong Li, Hongbing Liu, Angela Caánovas, Juan F Medrano, Milton G Thomas, Dijana Iloska, Lydie Plecitá-Hlavatá, Petr Ježek, Soni Pullamsetti, Mehdi A Fini, Karim C El Kasmi, QingHong Zhang, Kurt R Stenmark
BACKGROUND: Changes in metabolism have been suggested to contribute to the aberrant phenotype of vascular wall cells, including fibroblasts, in pulmonary hypertension (PH). Here, we test the hypothesis that metabolic reprogramming to aerobic glycolysis is a critical adaptation of fibroblasts in the hypertensive vessel wall that drives proliferative and proinflammatory activation through a mechanism involving increased activity of the NADH-sensitive transcriptional corepressor C-terminal binding protein 1 (CtBP1)...
October 11, 2016: Circulation
Yasunori Tome, Shuya Yano, Naotoshi Sugimoto, Sumiyuki Mii, Fuminari Uehara, Shinji Miwa, Michael Bouvet, Hiroyuki Tsuchiya, Fuminori Kanaya, Robert M Hoffman
BACKGROUND: We report here imaging of the behavior of αv integrin linked to green fluorescent protein (GFP) in human osteosarcoma cells colonizing the lung of nude mice. MATERIALS AND METHODS: 143B osteosarcoma cells expressing αv integrin-GFP were generated by transfection of an αv integrin-GFP fusion-gene vector pCMV-AC- ITGAV-GFP. In order to generate experimental lung metastases, 143B osteosarcoma cells (1×10(6)), stably expressing αv integrin-GFP, were injected intravenously via the tail vein...
August 2016: Anticancer Research
Cuifang Kuang, Ye Ma, Renjie Zhou, Guoan Zheng, Yue Fang, Yingke Xu, Xu Liu, Peter T C So
We report a novel superresolution microscopy approach for imaging fluorescence samples. The reported approach, termed virtual k-space modulation optical microscopy (VIKMOM), is able to improve the lateral resolution by a factor of 2, reduce the background level, improve the optical sectioning effect and correct for unknown optical aberrations. In the acquisition process of VIKMOM, we used a scanning confocal microscope setup with a 2D detector array to capture sample information at each scanned x-y position...
July 8, 2016: Physical Review Letters
Sebastian Steven, Kerstin Jurk, Maximilian Kopp, Swenja Kröller-Schön, Yuliya Mikhed, Kathrin Schwierczek, Siyer Roohani, Fatemeh Kashani, Matthias Oelze, Thomas Klein, Sergey Tokalov, Sven Danckwardt, Susanne Strand, Philip Wenzel, Thomas Münzel, Andreas Daiber
BACKGROUND AND PURPOSE: Excessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether dipeptidyl peptidase-4 (DPP-4) inhibition and supplementation with glucagon-like peptide-1 (GLP-1) analogues improves endotoxaemia-associated microvascular thrombosis via immunomodulatory effects. EXPERIMENTAL APPROACH: Endotoxaemia was induced in C57BL/6 J mice by single injection of lipopolysaccharide (LPS) (17...
July 19, 2016: British Journal of Pharmacology
Shota Sasagawa, Yuhei Nishimura, Hirofumi Sawada, Erquan Zhang, Shiko Okabe, Soichiro Murakami, Yoshifumi Ashikawa, Mizuki Yuge, Koki Kawaguchi, Reiko Kawase, Yoshihide Mitani, Kazuo Maruyama, Toshio Tanaka
Pulmonary arterial hypertension (PAH) is a heterogeneous disorder associated with a progressive increase in pulmonary artery resistance and pressure. Although various therapies have been developed, the 5-year survival rate of PAH patients remains low. There is thus an important need to identify novel genes that are commonly dysregulated in PAH of various etiologies and could be used as biomarkers and/or therapeutic targets. In this study, we performed comparative transcriptome analysis of five mammalian PAH datasets downloaded from a public database...
2016: Frontiers in Pharmacology
Arkaprava Dan, Ryan B Huang, Deborah E Leckband
We describe an equibiaxial cell stretcher and hybrid, elastic membrane platform designed for dynamic imaging of cells on substrates with physiological stiffness undergoing cyclic stretch. Studies enabled by this device revealed that both substrate stiffness and cyclic stretch coordinately protect pulmonary endothelial monolayers against thrombin-induced disruption. The fluorescence imaging possible with the designed hybrid membranes further revealed similarities and differences in actin and cell dynamics during monolayer recovery...
June 17, 2016: Annals of Biomedical Engineering
Rebecca Macklin, Haolu Wang, Dorothy Loo, Sally Martin, Andrew Cumming, Na Cai, Rebecca Lane, Natalia Saenz Ponce, Eleni Topkas, Kerry Inder, Nicholas A Saunders, Liliana Endo-Munoz
Osteosarcoma (OS) is the most common pediatric bone tumor and is associated with the emergence of pulmonary metastasis. Unfortunately, the mechanistic basis for metastasis remains unclear. Tumor-derived extracellular vesicles (EVs) have been shown to play critical roles in cell-to-cell communication and metastatic progression in other cancers, but their role in OS has not been explored. We show that EVs secreted by cells derived from a highly metastatic clonal variant of the KHOS cell line can be internalized by a poorly metastatic clonal variant of the same cell line and induce a migratory and invasive phenotype...
June 2, 2016: Oncotarget
Naoya Kawakita, Hiromitsu Takizawa, Kazuya Kondo, Shoji Sakiyama, Akira Tangoku
Indocyanine green can selectively accumulate in primary hepatocellular carcinoma (HCC) and extrahepatic metastases. We report a patient who underwent resection of pulmonary metastasis of HCC using a thoracoscopic near-infrared imaging system and fluorescent navigation surgery. A 66-year-old man with suspicion of pulmonary metastasis of HCC was referred to our hospital. Indocyanine green was injected intravenously at a dose of 0.5 mg/kg body weight, 20 h before thoracoscopic surgery. An endoscopic indocyanine green near-infrared fluorescence imaging system showed clear blue fluorescence, indicating pulmonary metastasis of HCC in a lingular segment...
May 17, 2016: Annals of Thoracic and Cardiovascular Surgery
Anand Shah, Shichina Kannambath, Susanne Herbst, Andrew Rogers, Simona Soresi, Martin Carby, Anna Reed, Serge Mostowy, Matthew C Fisher, Sunil Shaunak, Darius P Armstrong-James
RATIONALE: Pulmonary aspergillosis is a lethal mould infection in the immunocompromised host. Understanding initial control of infection, and how this is altered in the immunocompromised host, is a key goal for understanding the pathogenesis of pulmonary aspergillosis. OBJECTIVES: To characterise the outcome of human macrophage infection with Aspergillus fumigatus, and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. METHODS: We defined the outcome of human macrophage infection with Aspergillus fumigatus, and the impact of calcineurin inhibitors, through a combination of single cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies...
May 10, 2016: American Journal of Respiratory and Critical Care Medicine
Christopher Kuehl, Ti Zhang, Lisa M Kaminskas, Christopher J H Porter, Neal M Davies, Laird Forrest, Cory Berkland
Hyaluronic acid (HA) has emerged as a versatile polymer for drug delivery. Multiple commercial products utilize HA, it can be obtained in a variety of molecular weights, and it offers chemical handles for cross-linkers, drugs, or imaging agents. Previous studies have investigated multiple administration routes, but the absorption, biodistribution, and pharmacokinetics of HA after delivery to the lung is relatively unknown. Here, pharmacokinetic parameters were investigated by delivering different molecular weights of HA (between 7 and 741 kDa) to the lungs of mice...
May 24, 2016: Molecular Pharmaceutics
Susanne R Youngren-Ortiz, Nishant S Gandhi, Laura España-Serrano, Mahavir B Chougule
This article reviews the pulmonary route of administration, aerosol delivery devices, characterization of pulmonary drug delivery systems, and discusses the rationale for inhaled delivery of siRNA. Diseases with known protein malfunctions may be mitigated through the use of siRNA therapeutics. The inhalation route of administration provides local delivery of siRNA therapeutics for the treatment of various pulmonary diseases, however barriers to pulmonary delivery and intracellular delivery of siRNA exists. siRNA loaded nanocarriers can be used to overcome the barriers associated with the pulmonary route, such as anatomical barriers, mucociliary clearance, and alveolar macrophage clearance...
February 28, 2016: Kona: Powder Science and Technology in Japan
Francesca Polverino, Maria Laucho-Contreras, Joselyn Rojas Quintero, Miguel Divo, Victor Pinto-Plata, Lynette Sholl, Juan P de-Torres, Bartolome R Celli, Caroline A Owen
BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) is characterized by an excessive activation of the adaptive immune system and, in particular, uncontrolled expansion of the B-cell pool. One of the key promoters of B cell expansion is A PRoliferation-Inducing Ligand (APRIL). APRIL has been strongly linked to non small cell lung cancer (NSCLC) onset and progression previously. However, little is known about the expression of APRIL in the lungs of COPD patients. METHODS: Using immuno-fluorescence staining, the expression of APRIL was assessed in sections of lungs from 4 subjects with primary diagnosis of COPD (FEV1 33 ± 20 % predicted), 4 subjects with primary diagnosis of NSCLC, 4 subjects diagnosed with both COPD and NSCLC, smokers without COPD or NSCLC and 3 healthy never-smokers...
2016: Multidisciplinary Respiratory Medicine
Lorena Mendive-Tapia, Can Zhao, Ahsan R Akram, Sara Preciado, Fernando Albericio, Martin Lee, Alan Serrels, Nicola Kielland, Nick D Read, Rodolfo Lavilla, Marc Vendrell
Fluorescent antimicrobial peptides are promising structures for in situ, real-time imaging of fungal infection. Here we report a fluorogenic probe to image Aspergillus fumigatus directly in human pulmonary tissue. We have developed a fluorogenic Trp-BODIPY amino acid with a spacer-free C-C linkage between Trp and a BODIPY fluorogen, which shows remarkable fluorescence enhancement in hydrophobic microenvironments. The incorporation of our fluorogenic amino acid in short antimicrobial peptides does not impair their selectivity for fungal cells, and enables rapid and direct fungal imaging without any washing steps...
2016: Nature Communications
Ying Kong, Dong Yang, Suat L G Cirillo, Shaoji Li, Ali Akin, Kevin P Francis, Taylor Maloney, Jeffrey D Cirillo
The slow growth of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), hinders development of new diagnostics, therapeutics and vaccines. Using non-invasive real-time imaging technologies to monitor the disease process in live animals would facilitate TB research in all areas. We developed fluorescent protein (FP) expressing Mycobacterium bovis BCG strains for in vivo imaging, which can be used to track bacterial location, and to quantify bacterial load in live animals. We selected an optimal FP for in vivo imaging, by first cloning six FPs: tdTomato, mCherry, mPlum, mKate, Katushka and mKeima, into mycobacteria under either a mycobacterial Hsp60 or L5 promoter, and compared their fluorescent signals in vitro and in vivo...
2016: PloS One
Fa-Ping Wang, Ying-Qi Fan, Su-Yun Li, Hui Mao
Airway inflammation is a central component of the manifestation of asthma but is relatively inaccessible to study. Current imaging techniques such as X-ray CT, MRI, and PET, have advanced noninvasive research on pulmonary diseases. However, these techniques mainly facilitate the anatomical or structural assessment of the diseased lung and/or typically use radioactive agents. In vivo fluorescence imaging is a novel method for noninvasive, real-time, and specific monitoring of lung airway inflammation, which is particularly important to gain a further understanding asthma...
April 2016: Molecular and Cellular Probes
Fatemeh Nooshabadi, Hee-Jeong Yang, Joel N Bixler, Ying Kong, Jeffrey D Cirillo, Kristen C Maitland
Whole-animal fluorescence imaging with recombinant or fluorescently-tagged pathogens or cells enables real-time analysis of disease progression and treatment response in live animals. Tissue absorption limits penetration of fluorescence excitation light, particularly in the visible wavelength range, resulting in reduced sensitivity to deep targets. Here, we demonstrate the use of an optical fiber bundle to deliver light into the mouse lung to excite fluorescent bacteria, circumventing tissue absorption of excitation light in whole-animal imaging...
2016: PloS One
Hen Prizant, Manisha Taya, Irina Lerman, Allison Light, Aritro Sen, Soumya Mitra, Thomas H Foster, Stephen R Hammes
Lymphangioleiomyomatosis (LAM) is a rare disease in women. Patients with LAM develop metastatic smooth-muscle cell adenomas within the lungs, resulting in reduced pulmonary function. LAM cells contain mutations in tuberous sclerosis genes (TSC1 or TSC2), leading to up-regulation of mTORC1 activity and elevated proliferation. The origin of LAM cells remains unknown; however, inactivation of Tsc2 gene in the mouse uterus resulted in myometrial tumors exhibiting LAM features, and approximately 50% of animals developed metastatic myometrial lung tumors...
April 2016: Endocrine-related Cancer
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