Mesenchymal stromal cell-derived extracellular vesicles attenuate lung ischemia-reperfusion injury and enhance reconditioning of donor lungs after circulatory death.

Science.gov (United States)

Stone, Matthew L; Zhao, Yunge; Robert Smith, J; Weiss, Mark L; Kron, Irving L; Laubach, Victor E; Sharma, Ashish K

2017-12-21

Lung ischemia-reperfusion (IR) injury after transplantation as well as acute shortage of suitable donor lungs are two critical issues impacting lung transplant patients. This study investigates the anti-inflammatory and immunomodulatory role of human mesenchymal stromal cells (MSCs) and MSC-derived extracellular vesicles (EVs) to attenuate lung IR injury and improve of ex-vivo lung perfusion (EVLP)-mediated rehabilitation in donation after circulatory death (DCD) lungs. C57BL/6 wild-type (WT) mice underwent sham surgery or lung IR using an in vivo hilar-ligation model with or without MSCs or EVs. In vitro studies used primary iNKT cells and macrophages (MH-S cells) were exposed to hypoxia/reoxygenation with/without co-cultures with MSCs or EVs. Also, separate groups of WT mice underwent euthanasia and 1 h of warm ischemia and stored at 4 °C for 1 h followed by 1 h of normothermic EVLP using Steen solution or Steen solution containing MSCs or EVs. Lungs from MSCs or EV-treated mice had significant attenuation of lung dysfunction and injury (decreased edema, neutrophil infiltration and myeloperoxidase levels) compared to IR alone. A significant decrease in proinflammatory cytokines (IL-17, TNF-α, CXCL1 and HMGB1) and upregulation of keratinocyte growth factor, prostaglandin E2 and IL-10 occurred in the BAL fluid from MSC or EV-treated mice after IR compared to IR alone. Furthermore, MSCs or EVs significantly downregulated iNKT cell-produced IL-17 and macrophage-produced HMGB1 and TNF-α after hypoxia/reoxygenation. Finally, EVLP of DCD lungs with Steen solution including MSCs or EVs provided significantly enhanced protection versus Steen solution alone. Co-cultures of MSCs or EVs with lung endothelial cells prevents neutrophil transendothelial migration after exposure to hypoxia/reoxygenation and TNF-α/HMGB1 cytomix. These results suggest that MSC-derived EVs can attenuate lung inflammation and injury after IR as well as enhance EVLP-mediated reconditioning of

Microarray Meta-Analysis Identifies Acute Lung Injury Biomarkers in Donor Lungs That Predict Development of Primary Graft Failure in Recipients

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Haitsma, Jack J.; Furmli, Suleiman; Masoom, Hussain; Liu, Mingyao; Imai, Yumiko; Slutsky, Arthur S.; Beyene, Joseph; Greenwood, Celia M. T.; dos Santos, Claudia

2012-01-01

Objectives To perform a meta-analysis of gene expression microarray data from animal studies of lung injury, and to identify an injury-specific gene expression signature capable of predicting the development of lung injury in humans. Methods We performed a microarray meta-analysis using 77 microarray chips across six platforms, two species and different animal lung injury models exposed to lung injury with or/and without mechanical ventilation. Individual gene chips were classified and grouped based on the strategy used to induce lung injury. Effect size (change in gene expression) was calculated between non-injurious and injurious conditions comparing two main strategies to pool chips: (1) one-hit and (2) two-hit lung injury models. A random effects model was used to integrate individual effect sizes calculated from each experiment. Classification models were built using the gene expression signatures generated by the meta-analysis to predict the development of lung injury in human lung transplant recipients. Results Two injury-specific lists of differentially expressed genes generated from our meta-analysis of lung injury models were validated using external data sets and prospective data from animal models of ventilator-induced lung injury (VILI). Pathway analysis of gene sets revealed that both new and previously implicated VILI-related pathways are enriched with differentially regulated genes. Classification model based on gene expression signatures identified in animal models of lung injury predicted development of primary graft failure (PGF) in lung transplant recipients with larger than 80% accuracy based upon injury profiles from transplant donors. We also found that better classifier performance can be achieved by using meta-analysis to identify differentially-expressed genes than using single study-based differential analysis. Conclusion Taken together, our data suggests that microarray analysis of gene expression data allows for the detection of �

Lobar lung transplantation from deceased donors: A systematic review.

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Eberlein, Michael; Reed, Robert M; Chahla, Mayy; Bolukbas, Servet; Blevins, Amy; Van Raemdonck, Dirk; Stanzi, Alessia; Inci, Ilhan; Marasco, Silvana; Shigemura, Norihisa; Aigner, Clemens; Deuse, Tobias

2017-02-24

To systematically review reports on deceased-donor-lobar lung transplantation (ddLLTx) and uniformly describe size matching using the donor-to-recipient predicted-total lung-capacity (pTLC) ratio. We set out to systematically review reports on ddLLTx and uniformly describe size matching using the donor-to-recipient pTLC ratio and to summarize reported one-year survival data of ddLLTx and conventional-LTx. We searched in PubMed, CINAHL via EBSCO, Cochrane Database of Systematic Reviews via Wiley (CDSR), Database of Abstracts of Reviews of Effects via Wiley (DARE), Cochrane Central Register of Controlled Trials via Wiley (CENTRAL), Scopus (which includes EMBASE abstracts), and Web of Science for original reports on ddLLTx. Nine observational cohort studies reporting on 301 ddLLTx met our inclusion criteria for systematic review of size matching, and eight for describing one-year-survival. The ddLLTx-group was often characterized by high acuity; however there was heterogeneity in transplant indications and pre-operative characteristics between studies. Data to calculate the pTLC ratio was available for 242 ddLLTx (80%). The mean pTLCratio before lobar resection was 1.25 ± 0.3 and the transplanted pTLCratio after lobar resection was 0.76 ± 0.2. One-year survival in the ddLLTx-group ranged from 50%-100%, compared to 72%-88% in the conventional-LTx group. In the largest study ddLLTx ( n = 138) was associated with a lower one-year-survival compared to conventional-LTx ( n = 539) (65.1% vs 84.1%, P < 0.001). Further investigations of optimal donor-to-recipient size matching parameters for ddLLTx could improve outcomes of this important surgical option.

Expanding the donor lung pool: how many donations after circulatory death organs are we missing?

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Chancellor, William Zachary; Charles, Eric J; Mehaffey, James Hunter; Hawkins, Robert B; Foster, Carrie A; Sharma, Ashish K; Laubach, Victor E; Kron, Irving L; Tribble, Curtis G

2018-03-01

The number of patients with end-stage pulmonary disease awaiting lung transplantation is at an all-time high, while the supply of available organs remains stagnant. Utilizing donation after circulatory death (DCD) donors may help to address the supply-demand mismatch. The objective of this study is to determine the potential donor pool expansion with increased procurement of DCD organs from patients who die at hospitals. The charts of all patients who died at a single, rural, quaternary-care institution between August 2014 and June 2015 were reviewed for lung transplant candidacy. Inclusion criteria were age 65 y (n = 497, 58%). Those without cancer totaled 778 (90.8%) and 512 (59%) did not have lung pathology. This leaves 85 patients qualifying for DCD lung donation (pediatric n = 10, young n = 75, and old n = 0). Potential donors were significantly more likely to have clear chest X-rays (24.3% versus 10.0%, P < 0.0001) and higher mean PaO2/FiO2 (342.1 versus 197.9, P < 0.0001) compared with ineligible patients. A significant number of DCD lungs are available every year from patients who die within hospitals. We estimate the use of suitable DCD lungs could potentially result in a significant increase in the number of lungs available for transplantation. Copyright © 2017 Elsevier Inc. All rights reserved.

Measurement of histamine release from human lung tissue ex vivo by microdialysis technique

DEFF Research Database (Denmark)

Nissen, Dan; Petersen, Lars Jelstrup; Nolte, H

1998-01-01

OBJECTIVE AND DESIGN: Currently no method is available for measurement of mediator release from intact human lung. In this study, a microdialysis technique was used to measure histamine release from mast cells in human lung tissue ex vivo. MATERIAL: Microdialysis fibers of 216 microm were inserted...... responses were observed but data could be reproduced within individual donors. Monocyte chemoattractant protein-1, a potent basophil secretagogue, did not induce histamine release in lung tissue which indicated mast cells to be the histamine source. Substance P did not release histamine in the lung tissue....... CONCLUSIONS: The microdialysis technique allowed measurements of histamine release from mast cells in intact lung ex vivo. The method may prove useful since a number of experiments can be performed in a few hours in intact lung tissue without any dispersion or enzymatic treatment....

Synthetic Secoisolariciresinol Diglucoside (LGM2605 Protects Human Lung in an Ex Vivo Model of Proton Radiation Damage

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Anastasia Velalopoulou

2017-11-01

Full Text Available Radiation therapy for the treatment of thoracic malignancies has improved significantly by directing of the proton beam in higher doses on the targeted tumor while normal tissues around the tumor receive much lower doses. Nevertheless, exposure of normal tissues to protons is known to pose a substantial risk in long-term survivors, as confirmed by our work in space-relevant exposures of murine lungs to proton radiation. Thus, radioprotective strategies are being sought. We established that LGM2605 is a potent protector from radiation-induced lung toxicity and aimed in the current study to extend the initial findings of space-relevant, proton radiation-associated late lung damage in mice by looking at acute changes in human lung. We used an ex vivo model of organ culture where tissue slices of donor living human lung were kept in culture and exposed to proton radiation. We exposed donor human lung precision-cut lung sections (huPCLS, pretreated with LGM2605, to 4 Gy proton radiation and evaluated them 30 min and 24 h later for gene expression changes relevant to inflammation, oxidative stress, and cell cycle arrest, and determined radiation-induced senescence, inflammation, and oxidative tissue damage. We identified an LGM2605-mediated reduction of proton radiation-induced cellular senescence and associated cell cycle changes, an associated proinflammatory phenotype, and associated oxidative tissue damage. This is a first report on the effects of proton radiation and of the radioprotective properties of LGM2605 on human lung.

Donor lung derived myeloid and plasmacytoid dendritic cells differentially regulate T cell proliferation and cytokine production

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Benson Heather L

2012-03-01

Full Text Available Abstract Background Direct allorecognition, i.e., donor lung-derived dendritic cells (DCs stimulating recipient-derived T lymphocytes, is believed to be the key mechanism of lung allograft rejection. Myeloid (cDCs and plasmacytoid (pDCs are believed to have differential effects on T cell activation. However, the roles of each DC type on T cell activation and rejection pathology post lung transplantation are unknown. Methods Using transgenic mice and antibody depletion techniques, either or both cell types were depleted in lungs of donor BALB/c mice (H-2d prior to transplanting into C57BL/6 mice (H-2b, followed by an assessment of rejection pathology, and pDC or cDC-induced proliferation and cytokine production in C57BL/6-derived mediastinal lymph node T cells (CD3+. Results Depleting either DC type had modest effect on rejection pathology and T cell proliferation. In contrast, T cells from mice that received grafts depleted of both DCs did not proliferate and this was associated with significantly reduced acute rejection scores compared to all other groups. cDCs were potent inducers of IFNγ, whereas both cDCs and pDCs induced IL-10. Both cell types had variable effects on IL-17A production. Conclusion Collectively, the data show that direct allorecognition by donor lung pDCs and cDCs have differential effects on T cell proliferation and cytokine production. Depletion of both donor lung cDC and pDC could prevent the severity of acute rejection episodes.

Respiratory Failure due to Possible Donor-Derived Sporothrix schenckii Infection in a Lung Transplant Recipient

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Nathan C. Bahr

2015-01-01

Full Text Available Background. De novo and donor-derived invasive fungal infections (IFIs contribute to morbidity and mortality in solid organ transplant (SOT recipients. Reporting of donor-derived IFIs (DDIFIs to the Organ Procurement Transplant Network has been mandated since 2005. Prior to that time no systematic monitoring of DDIFIs occurred in the United States. Case Presentation. We report a case of primary graft dysfunction in a 49-year-old male lung transplant recipient with diffuse patchy bilateral infiltrates likely related to pulmonary Sporothrix schenckii infection. The organism was isolated from a bronchoalveolar lavage on the second day after transplantation. Clinical and radiographic responses occurred after initiation of amphotericin B lipid formulation. Conclusion. We believe that this was likely a donor-derived infection given the early timing of the Sporothrix isolation after transplant in a bilateral single lung transplant recipient. This is the first case report of sporotrichosis in a lung transplant recipient. Our patient responded well to amphotericin induction therapy followed by maintenance therapy with itraconazole. The implications of donor-derived fungal infections and Sporothrix in transplant recipients are reviewed. Early recognition and management of these fungi are essential in improving outcomes.

Significance of single lung transplantation in the current situation of severe donor shortage in Japan.

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Miyoshi, Ryo; Chen-Yoshikawa, Toyofumi F; Hijiya, Kyoko; Motoyama, Hideki; Aoyama, Akihiro; Menju, Toshi; Sato, Toshihiko; Sonobe, Makoto; Date, Hiroshi

2016-02-01

Although bilateral lung transplantation is the procedure of choice internationally, single lung transplantation is preferred in Japan because of the severe donor shortage except in cases of contraindications to single lung transplantation. This study aimed to evaluate the clinical characteristics of single lung transplant recipients and outcomes of this procedure at one of the largest lung transplant centers in Japan. Between April 2002 and May 2015, 57 cadaveric lung transplantations (33 single and 24 bilateral) were performed in Kyoto University Hospital. The clinical characteristics of the lung transplant recipients and outcomes of these procedures, including overall survival and postoperative complications, were investigated. Overall, the 1-, 3-, and 5-year survival rates were 86, 77, and 72 %, respectively, with a median follow-up period of 1.9 years. There was no significant difference in survival between patients who underwent single lung transplantations and those who underwent bilateral lung transplantations (p = 0.92). The median waiting time was significantly shorter for single lung transplant patients than for bilateral lung transplant patients (p = 0.02). Native lung complications were seen in 14 out of 33 patients (42 %) who underwent single lung transplantation. There was no significant difference in survival between patients with and without postoperative native lung complications. Single lung transplantation has been performed with acceptable outcomes in our institution. In the current situation of severe donor shortage in Japan, single lung transplantation can remain the first choice of treatment except in cases of contraindications to single lung transplantation.

[Short-term outcomes of lung transplant recipients using organs from brain death donors].

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He, W X; Jiang, C; Liu, X G; Huang, W; Chen, C; Jiang, L; Yang, B; Wu, K; Chen, Q K; Yang, Y; Yu, Y M; Jiang, G N

2016-12-01

Objective: To assess short-term outcomes after lung transplantation with organs procured following brain death. Methods: Between April 2015 and July 2016, all 17 recipients after lung transplantation using organs from brain death donors (DBD) at Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine were enrolled in this study. All patients were male, aging (60±7) years, including 11 chronic obstructive pulmonary disease, 5 idiopathic pulmonary fibrosis, 1 silicosis. Seventeen donors were 16 males and 1 female, with 10 traumatic brain injury, 5 cerebrovascular accident and 2 sudden cardiac death. Of 17 recipients receiving DBD lung transplant, 16 were single lung transplant. Data were collected including intubation duration of mechanical ventilation, hospital length of stay, incidence of pulmonary infection bronchus anastomosis complications, primary graft dysfunction (PGD), and acute rejection, bronchiolitis obliterans syndrome (BOS) as well as mortality of 90-day after lung transplantation. Results: Median duration of intubation were 2 (2) days ( M ( Q R )) in recipients after lung transplantation. The incidence of pulmonary infection and bronchus anastomosis complications were 15/17 and 5/17, respectively. Median length of stay in hospital were 56 (19) days. The ratio of readmission 1 month after discharge were 10/17. Mortality of 90-day post-transplant were 2/17. The incidence of PGD and BOS were 1/17 and 2/17, respectively. Conclusion: Recipients with DBD lung transplantation have an acceptable survival during short-term follow-up, but with higher incidences of complications related to infection post-transplantation.

Comparison of lung preservation solutions in human lungs using an ex vivo lung perfusion experimental model

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Israel L. Medeiros

2012-09-01

Full Text Available OBJECTIVE: Experimental studies on lung preservation have always been performed using animal models. We present ex vivo lung perfusion as a new model for the study of lung preservation. Using human lungs instead of animal models may bring the results of experimental studies closer to what could be expected in clinical practice. METHOD: Brain-dead donors whose lungs had been declined by transplantation teams were used. The cases were randomized into two groups. In Group 1, Perfadex®was used for pulmonary preservation, and in Group 2, LPDnac, a solution manufactured in Brazil, was used. An ex vivo lung perfusion system was used, and the lungs were ventilated and perfused after 10 hours of cold ischemia. The extent of ischemic-reperfusion injury was measured using functional and histological parameters. RESULTS: After reperfusion, the mean oxygenation capacity was 405.3 mmHg in Group 1 and 406.0 mmHg in Group 2 (p = 0.98. The mean pulmonary vascular resistance values were 697.6 and 378.3 dyn·s·cm-5, respectively (p =0.035. The mean pulmonary compliance was 46.8 cm H20 in Group 1 and 49.3 ml/cm H20 in Group 2 (p =0.816. The mean wet/dry weight ratios were 2.06 and 2.02, respectively (p=0.87. The mean Lung Injury Scores for the biopsy performed after reperfusion were 4.37 and 4.37 in Groups 1 and 2, respectively (p = 1.0, and the apoptotic cell counts were 118.75/mm² and 137.50/mm², respectively (p=0.71. CONCLUSION: The locally produced preservation solution proved to be as good as Perfadex®. The clinical use of LPDnac may reduce costs in our centers. Therefore, it is important to develop new models to study lung preservation.

Immune and Inflammatory Cell Composition of Human Lung Cancer Stroma.

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G-Andre Banat

Full Text Available Recent studies indicate that the abnormal microenvironment of tumors may play a critical role in carcinogenesis, including lung cancer. We comprehensively assessed the number of stromal cells, especially immune/inflammatory cells, in lung cancer and evaluated their infiltration in cancers of different stages, types and metastatic characteristics potential. Immunohistochemical analysis of lung cancer tissue arrays containing normal and lung cancer sections was performed. This analysis was combined with cyto-/histomorphological assessment and quantification of cells to classify/subclassify tumors accurately and to perform a high throughput analysis of stromal cell composition in different types of lung cancer. In human lung cancer sections we observed a significant elevation/infiltration of total-T lymphocytes (CD3+, cytotoxic-T cells (CD8+, T-helper cells (CD4+, B cells (CD20+, macrophages (CD68+, mast cells (CD117+, mononuclear cells (CD11c+, plasma cells, activated-T cells (MUM1+, B cells, myeloid cells (PD1+ and neutrophilic granulocytes (myeloperoxidase+ compared with healthy donor specimens. We observed all of these immune cell markers in different types of lung cancers including squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma, small cell carcinoma, papillary adenocarcinoma, metastatic adenocarcinoma, and bronchioloalveolar carcinoma. The numbers of all tumor-associated immune cells (except MUM1+ cells in stage III cancer specimens was significantly greater than those in stage I samples. We observed substantial stage-dependent immune cell infiltration in human lung tumors suggesting that the tumor microenvironment plays a critical role during lung carcinogenesis. Strategies for therapeutic interference with lung cancer microenvironment should consider the complexity of its immune cell composition.

Mycobacterium tuberculosis Invasion of the Human Lung: First Contact

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Jeroen Maertzdorf

2018-06-01

Full Text Available Early immune responses to Mycobacterium tuberculosis (Mtb invasion of the human lung play a decisive role in the outcome of infection, leading to either rapid clearance of the pathogen or stable infection. Despite their critical impact on health and disease, these early host–pathogen interactions at the primary site of infection are still poorly understood. In vitro studies cannot fully reflect the complexity of the lung architecture and its impact on host–pathogen interactions, while animal models have their own limitations. In this study, we have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue-resident cell types. As first cell types confronted with pathogens invading the lung, alveolar macrophages, and epithelial cells displayed rapid proinflammatory chemokine and cytokine responses to Mtb infection. Other tissue-resident innate cells like gamma/delta T cells, mucosal associated invariant T cells, and natural killer cells showed partially similar but weaker responses, with a high degree of variability across different donors. Finally, we investigated the responses of tissue-resident innate lymphoid cells to the inflammatory milieu induced by Mtb infection. Our infection model provides a unique approach toward host–pathogen interactions at the natural port of Mtb entry and site of its implantation, i.e., the human lung. Our data provide a first detailed insight into the early responses of different relevant pulmonary cells in the alveolar microenvironment to contact with Mtb. These results can form the basis for the identification of host markers that orchestrate early host defense and provide resistance or susceptibility to stable Mtb infection.

Does Traumatic Donor Cause of Death Influence Outcome after Lung Transplantation? A Single-Centre Analysis.

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Pilarczyk, Kevin; Heckmann, Jens; Carstens, Henning; Lubarski, Jura; Jakob, Heinz; Pizanis, Nikolaus; Kamler, Markus

2017-08-01

Background  Owing to the shortage of donor organs in lung transplantation (LuTX), liberalization of donor selection criteria has been proposed. However, some studies suggested that donor traumatic brain damage might influence posttransplantation allograft function. This article aimed to investigate the association of donor cause of death (DCD) and outcome after LuTX. Methods  A retrospective analysis of 186 consecutive double LuTXs at our institution from January 2000 to December 2008 was performed. DCD was categorized into traumatic brain injury (TBI) and nontraumatic brain injury (NTBI). In addition, NTBI was sub classified as spontaneous intracerebral bleeding (B), hypoxic brain damage (H), and intracerebral neoplasia (N). Results  DCD was classified as TBI in 50 patients (26.9%) and NTBI in 136 patients (73.1%): B in 112 patients (60.2%), H in 21 patients (11.3%), and N in 3 patients (1.6%). Young male donors predominated in group TBI (mean age 36.0 ± 14.5 vs. 42.8 ± 10.7, p  donor ventilation time, or paO 2 /FiO 2 before harvesting. TBI donors received significantly more blood (3.4 ± 3.8 vs. 1.8 ± 1.9, p  = 0.03). A chest trauma was evident only in group T ( n  = 7 [3.7%] vs. 0 [0%], p  donor death did not affect the following indices of graft function: length of postoperative ventilation, paO 2 /FiO 2 ratio up to 48 hours, and lung function up to 36 months. One- and three-year survival was comparable with 84.4 and 70.4% for TBI donors versus 89.4% and 69.2% for NTBI donors. Five-year survival tended to be lower in the TBI group but did not reach statistical significance (43.4 vs. 53.9%). Conclusion  This study indicates that traumatic DCD does not affect outcome after LuTX. These results can be achieved with an ideal donor management combined with an individual case-to-case evaluation by an experienced LuTX surgeon. Georg Thieme Verlag KG Stuttgart · New York.

Ex vivo lung perfusion in clinical lung transplantation--state of the art.

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Andreasson, Anders S I; Dark, John H; Fisher, Andrew J

2014-11-01

Ex vivo lung perfusion (EVLP) has emerged as a new technique for assessing and potentially reconditioning human donor lungs previously unacceptable for clinical transplantation with the potential to dramatically push the limits of organ acceptability. With the recent introduction of portable EVLP, a new era in lung preservation may be upon us with the opportunity to also limit organ ischaemic times and potentially improve the outcome of donor lungs already deemed acceptable for transplantation. It took over half a century for the technique to evolve from basic theory to semi-automated circuits fit for clinical use that are now rapidly being adopted in transplant centres across the globe. With this field in constant evolution and many unanswered questions remaining, our review serves as an update on the state of the art of EVLP in clinical lung transplantation. © The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Transfusion-related acute lung injury (TRALI in two thalassaemia patients caused by the same multiparous blood donor

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George J Kontoghiorghes

2017-10-01

Full Text Available Two separate episodes of transfusion-related acute lung injury (TRALI in thalassaemia patients caused by red blood cell transfusions from the same multiparous blood donor are reported. Both cases had the same symptomatology and occurred 10-60 minutes of transfusion. The patients presented dyspnea, sweating, fatigue, dizziness, fever, and sense of losing consciousness. The chest x-ray showed a pulmonary oedema-like picture with both lungs filled with fluid. The patients were treated in the intensive therapy unit. They were weaned off the ventilator and discharged following hospitalization 7 and 9 days respectively. The TRALI syndrome was diagnosed to be associated with HLA-specific donor antibodies against mismatched HLA-antigens of the transfused patients. Haemovigilance improvements are essential for reducing the morbidity and mortality in transfused patients. Blood from multiparous donors should be tested for the presence of IgG HLA-Class I and –Class II antibodies before being transfused in thalassaemia and other chronically transfused patients.

LungMAP: The Molecular Atlas of Lung Development Program.

Science.gov (United States)

Ardini-Poleske, Maryanne E; Clark, Robert F; Ansong, Charles; Carson, James P; Corley, Richard A; Deutsch, Gail H; Hagood, James S; Kaminski, Naftali; Mariani, Thomas J; Potter, Steven S; Pryhuber, Gloria S; Warburton, David; Whitsett, Jeffrey A; Palmer, Scott M; Ambalavanan, Namasivayam

2017-11-01

The National Heart, Lung, and Blood Institute is funding an effort to create a molecular atlas of the developing lung (LungMAP) to serve as a research resource and public education tool. The lung is a complex organ with lengthy development time driven by interactive gene networks and dynamic cross talk among multiple cell types to control and coordinate lineage specification, cell proliferation, differentiation, migration, morphogenesis, and injury repair. A better understanding of the processes that regulate lung development, particularly alveologenesis, will have a significant impact on survival rates for premature infants born with incomplete lung development and will facilitate lung injury repair and regeneration in adults. A consortium of four research centers, a data coordinating center, and a human tissue repository provides high-quality molecular data of developing human and mouse lungs. LungMAP includes mouse and human data for cross correlation of developmental processes across species. LungMAP is generating foundational data and analysis, creating a web portal for presentation of results and public sharing of data sets, establishing a repository of young human lung tissues obtained through organ donor organizations, and developing a comprehensive lung ontology that incorporates the latest findings of the consortium. The LungMAP website (www.lungmap.net) currently contains more than 6,000 high-resolution lung images and transcriptomic, proteomic, and lipidomic human and mouse data and provides scientific information to stimulate interest in research careers for young audiences. This paper presents a brief description of research conducted by the consortium, database, and portal development and upcoming features that will enhance the LungMAP experience for a community of users. Copyright © 2017 the American Physiological Society.

Maintenance of cAMP in non-heart-beating donor lungs reduces ischemia-reperfusion injury.

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Hoffmann, S C; Bleiweis, M S; Jones, D R; Paik, H C; Ciriaco, P; Egan, T M

2001-06-01

Studies suggest that pulmonary vascular ischemia-reperfusion injury (IRI) can be attenuated by increasing intracellular cAMP concentrations. The purpose of this study was to determine the effect of IRI on capillary permeability, assessed by capillary filtration coeficient (Kfc), in lungs retrieved from non-heart-beating donors (NHBDs) and reperfused with the addition of the beta(2)-adrenergic receptor agonist isoproterenol (iso), and rolipram (roli), a phosphodiesterase (type IV) inhibitor. Using an in situ isolated perfused lung model, lungs were retrieved from NHBD rats at varying intervals after death and either ventilated with O(2) or not ventilated. The lungs were reperfused with Earle's solution with or without a combination of iso (10 microM) and roli (2 microM). Kfc, lung viability, and pulmonary hemodynamics were measured. Lung tissue levels of adenine nucleotides and cAMP were measured by HPLC. Combined iso and roli (iso/roli) reperfusion decreased Kfc significantly (p Kfc in non-iso/roli-reperfused (r = 0.89) and iso/roli-reperfused (r = 0.97) lungs. cAMP levels correlated with Kfc (r = 0.93) in iso/roli-reperfused lungs. Pharmacologic augmentation of tissue TAN and cAMP levels might ameliorate the increased capillary permeability observed in lungs retrieved from NHBDs.

[Lung transplantation: supply and demand in France].

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Stern, M; Souilamas, R; Tixier, D; Mal, H

2008-10-01

For a decade lung transplantation has suffered from a lack of donor organs which aroused a national debate and led to planned action in collaboration with The French National Agency for Transplantation. Analysis of the stages of the process from potential donor to lung transplantation identified lung procurement as the main priority. An increase in the number of potential lung donors and revision of the acceptance criteria led to a doubling of the annual rate of lung transplantation in less than two years. In the near future we may solve the problem of donor family refusals and establish scientifically based criteria for lung acceptance to increase the rate of lung transplantation. Transplantation from non heart-beating donors and the reconditioning of ex vivo non acceptable lungs might supply additional organs to fulfill demand in the long term. The rate of lung transplantation activity in France doubled as the result of a dramatic increase of donor lung proposals. The current improvement in the results of lung transplantation might create new demands and generate future difficulties in the supply of donor lungs. New approaches, such as transplantation from non heart-beating donors and reconditioning ex vivo non acceptable lungs, should be examined in the near future.

Design and validation of a clinical-scale bioreactor for long-term isolated lung culture.

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Charest, Jonathan M; Okamoto, Tatsuya; Kitano, Kentaro; Yasuda, Atsushi; Gilpin, Sarah E; Mathisen, Douglas J; Ott, Harald C

2015-06-01

The primary treatment for end-stage lung disease is lung transplantation. However, donor organ shortage remains a major barrier for many patients. In recent years, techniques for maintaining lungs ex vivo for evaluation and short-term (advance to more complex interventions for lung repair and regeneration, the need for a long-term organ culture system becomes apparent. Herein we describe a novel clinical scale bioreactor capable of maintaining functional porcine and human lungs for at least 72 h in isolated lung culture (ILC). The fully automated, computer controlled, sterile, closed circuit system enables physiologic pulsatile perfusion and negative pressure ventilation, while gas exchange function, and metabolism can be evaluated. Creation of this stable, biomimetic long-term culture environment will enable advanced interventions in both donor lungs and engineered grafts of human scale. Copyright © 2015 Elsevier Ltd. All rights reserved.

Inactivation of high-risk human papillomaviruses by Holder pasteurization: implications for donor human milk banking.

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Donalisio, Manuela; Cagno, Valeria; Vallino, Marta; Moro, Guido E; Arslanoglu, Sertac; Tonetto, Paola; Bertino, Enrico; Lembo, David

2014-01-01

Several studies have recently reported the detection of oncogenic human papillomaviruses (HPV) in human milk of a minority of lactating mothers. These findings raised safety concerns in the context of human donor milk banking given the potential risk of HPV transmission to recipient infants. The aim of this study was to investigate whether the Holder pasteurization, a procedure currently in use in human donor milk banks for milk pasteurization, completely inactivates high-risk and low-risk HPV. HPV pseudoviruses (PsV) were generated, spiked into cell culture medium or donor human milk and subjected to thermal inactivation. HPV PsV infectivity and morphological integrity was analyzed by cell-based assay and by electron microscopy, respectively. The Holder pasteurization completely inactivated the infectivity of high-risk (types 16 and 18) and low-risk (type 6) HPV both in cell culture medium and in human milk causing PsV particle disassembly. The results presented here indicate that the Holder pasteurization is an efficient procedure to inactivate high-risk and low-risk HPV thus preventing the potential risk of their transmission through human donor milk.

Transplantes cardiopulmonar e pulmonar com doador em localidade distante Distant donor procurement for heart-lung and lung transplantation

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Luis Sérgio Fragomeni

1988-12-01

Full Text Available Em situações específicas, os transplantes clínicos cardiopulmonar e pulmonar são, hoje, formas estabelecidas de tratamento para estágio final de doença cardiopulmonar e pulmonar. A obtenção de doadores adequados permanece o maior problema e a remoção de órgãos em localidades distantes é, hoje, uma necessidade. Embora muitos métodos de preservação pulmonar possam ser empregados, para períodos isquémicos de até 5 horas, a hipotermia e o uso de solução cardioplégica com infusão da solução de Collins modificada no tronco pulmonar tem sido método simples e eficiente para preservação do bloco coração-pulmão. Descrevemos, aqui, o método corrente que empregamos, com o qual os transplantes cardiopulmonar e pulmonar combinados foram sucedidos de excelente função cárdio-respiratória.In special situations, clinical heart-lung and lung transplantation are today established methods of therapy for end stage cardiopulmonary and pulmonary disease. Adequate donor availability remains a major problem and distant organ procurement is today a necessity. Although many methods of lung preservation can be used, for periods of up to 5 hours, hypothermic storage with cardioplegic arrest and pulmonary artery flush with modified Collins solution has proven to be a simple and reliable method of heart-lung preservation. We here describe our current method of heart-lung block protection, in which heart-lung and double lung transplantation were performed followed by excelent cardiac and pulmonary function.

Human decellularized bone scaffolds from aged donors show improved osteoinductive capacity compared to young donor bone.

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Christopher A Smith

Full Text Available To improve the safe use of allograft bone, decellularization techniques may be utilized to produce acellular scaffolds. Such scaffolds should retain their innate biological and biomechanical capacity and support mesenchymal stem cell (MSC osteogenic differentiation. However, as allograft bone is derived from a wide age-range, this study aimed to determine whether donor age impacts on the ability an osteoinductive, acellular scaffold produced from human bone to promote the osteogenic differentiation of bone marrow MSCs (BM-MSC. BM-MSCs from young and old donors were seeded on acellular bone cubes from young and old donors undergoing osteoarthritis related hip surgery. All combinations resulted in increased osteogenic gene expression, and alkaline phosphatase (ALP enzyme activity, however BM-MSCs cultured on old donor bone displayed the largest increases. BM-MSCs cultured in old donor bone conditioned media also displayed higher osteogenic gene expression and ALP activity than those exposed to young donor bone conditioned media. ELISA and Luminex analysis of conditioned media demonstrated similar levels of bioactive factors between age groups; however, IGF binding protein 1 (IGFBP1 concentration was significantly higher in young donor samples. Additionally, structural analysis of old donor bone indicated an increased porosity compared to young donor bone. These results demonstrate the ability of a decellularized scaffold produced from young and old donors to support osteogenic differentiation of cells from young and old donors. Significantly, the older donor bone produced greater osteogenic differentiation which may be related to reduced IGFBP1 bioavailability and increased porosity, potentially explaining the excellent clinical results seen with the use of allograft from aged donors.

Perfil do doador de pulmão disponibilizado no estado de São Paulo, Brasil, em 2006 Lung donor profile in the state of São Paulo, Brazil, in 2006

Directory of Open Access Journals (Sweden)

Paulo Manuel Pêgo Fernandes

2008-07-01

Full Text Available OBJETIVO: Analisar a taxa de aproveitamento de pulmões disponibilizados em São Paulo no ano de 2006, bem como caracterizar o perfil dos doadores de pulmão deste período. MÉTODOS: Estudo retrospectivo de 497 prontuários de doadores de pulmão, no período de janeiro a dezembro de 2006. RESULTADOS: Não houve oferta de doação de pulmões para transplante em 149 (30% dos prontuários analisados, sendo excluídos do estudo. A idade média dos 348 doadores eleitos para o estudo foi de 37,4 ± 16,1 anos, e 56,9% deles eram do sexo masculino. As principais causas da morte cerebral dos doadores foram: acidente vascular cerebral (40,5%; trauma cranioencefálico (34,2%; e hemorragia subaracnóidea (10,9%. A grande maioria dos doadores recebia drogas vasoativas (90,5%, sendo que 13,5% haviam apresentado parada cárdio-respiratória. Do ponto de vista infeccioso, o leucograma médio foi de 15.008 ± 6.467 células/mm³, 67,8% recebiam antibioticoterapia e 26,1% apresentavam infecção pulmonar. Quase 40% dos doadores apresentavam alterações radiográficas. Apenas 4,9% dos doadores foram aceitos, representando 28 pulmões (taxa de aproveitamento de órgãos de 4%. Os motivos de recusa foram: alteração gasométrica (30,1%; infecção (23,7%; e distância (10,9%. CONCLUSÕES: A taxa de aproveitamento de pulmões em nosso meio é baixa quando comparada às taxas médias de aproveitamento mundial. Além disso, mais de 50% das recusas deveram-se à gasometria arterial inadequada e infecção pulmonar. Aliar melhor cuidado ao potencial doador à menor rigidez nos critérios de seleção poderia aumentar a utilização dos órgãos doados.OBJECTIVE: To analyze the rate at which lungs available for transplantation in the state of São Paulo in 2006 were utilized and to determine the lung donor profile in the same period. METHODS: A retrospective study of 497 clinical charts of lung tissue donors from January to December of 2006. RESULTS: According to the

Contribution of Human Lung Parenchyma and Leukocyte Influx to Oxidative Stress and Immune System-Mediated Pathology following Nipah Virus Infection.

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Escaffre, Olivier; Saito, Tais B; Juelich, Terry L; Ikegami, Tetsuro; Smith, Jennifer K; Perez, David D; Atkins, Colm; Levine, Corri B; Huante, Matthew B; Nusbaum, Rebecca J; Endsley, Janice J; Freiberg, Alexander N; Rockx, Barry

2017-08-01

strain induced cytopathic lesions in lung grafts similar to those described in patients irrespective of the donor origin or the presence of leukocytes. However, the human immune system interfered with virus spread, responded to infection by leukocyte infiltration in the small airways and alveolar area, induced oxidative stress, and triggered the production of cytokines and chemokines that regulate inflammatory influx by leukocytes in response to infection. Understanding how leukocytes interact with NiV and cause ALI in human lung xenografts is crucial for identifying therapeutic targets. Copyright © 2017 American Society for Microbiology.

The Human Tissue Act 2004 and the child donor.

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Baston, Jenny

2009-05-01

In 2001, the inquiry panel appointed to investigate the removal, retention and disposal of human organs and tissues at the Royal Liverpool Children's Hospital published its report. The panel's recommendations led to a new approach to consent for organ removal and storage under the new Human Tissue Act 2004. For child bone marrow donors, the new consent process requires all donor children or their parent to undergo a separate assessment before the bone marrow donation. They must be assessed by an accredited assessor who will submit a recommendation to the Human Tissue Authority for consideration. The unfortunate circumstances highlighted in the inquiry have led to changes to law, practice and culture that are benefiting other children and families.

Characteristics of the regional human milk bank in Poland - donors, recipients and nutritional value of human milk

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Barbarska, Olga; Zielińska, Monika; Pawlus, Beata; Wesołowska, Aleksandra

In case of shortage of breast milk despite proper lactation care or the poor state of the mother’s health, breast milk from human milk bank is recommended for feeding preterm infants This study retrospectively evaluated the first year of the operation of the Regional Human Milk Bank Data concerning donors was collected in the human milk bank during the cooperation. The clinical characteristics of the recipients was made on the basis of medical documentation from the Holy Family Hospital in Warsaw, Poland. Analysis of nutritional value was performed with the human milk analyzer (MIRIS AB) In the first year of activity, 45 voluntary donors established cooperation, donating from 650 to 32030 ml of human milk. The content of nutrients in milk provided by donors was variable - protein 0.4-1.5 g / 100 ml, fat 1.1-7.4 g / 100 ml, carbohydrates 6.3-7.9 g / 100 ml. The average length of using donated human milk was 4 days and the average volume of milk for one infant was 282 ml The donor profiles have a significant impact on the milk composition form HMB. The nutritional value can be improved by recruitment donors from mothers that gave birth prematurely and by beginning donation at earlier stages of lactation as soon as lactation is stabilized. In case of shortage of mothers own milk the immediate implementation of donors milk as a short-term support can significantly reduce the food intolerance incidence in the group of prematurely born infants

Preferential elevation of Prx I and Trx expression in lung cancer cells following hypoxia and in human lung cancer tissues.

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Kim, H J; Chae, H Z; Kim, Y J; Kim, Y H; Hwangs, T S; Park, E M; Park, Y M

2003-10-01

Transient/chronic microenvironmental hypoxia that exists within a majority of solid tumors has been suggested to have a profound influence on tumor growth and therapeutic outcome. Since the functions of novel antioxidant proteins, peroxiredoxin I (Prx I) and II, have been implicated in regulating cell proliferation, differentiation, and apoptosis, it was of our special interest to probe a possible role of Prx I and II in the context of hypoxic tumor microenvironment. Since both Prx I and II use thioredoxin (Trx) as an electron donor and Trx is a substrate for thioredoxin reductase (TrxR), we investigated the regulation of Trx and TrxR as well as Prx expression following hypoxia. Here we show a dynamic change of glutathione homeostasis in lung cancer A549 cells and an up-regulation of Prx I and Trx following hypoxia. Western blot analysis of 10 human lung cancer and paired normal lung tissues also revealed an elevated expression of Prx I and Trx proteins in lung cancer tissues. Immunohistochemical analysis of the lung cancer tissues confirmed an augmented Prx I and Trx expression in cancer cells with respect to the parenchymal cells in adjacent normal lung tissue. Based on these results, we suggest that the redox changes in lung tumor microenvironment could have acted as a trigger for the up-regulation of Prx I and Trx in lung cancer cells. Although the clinical significance of our finding awaits more rigorous future study, preferential augmentation of the Prx I and Trx in lung cancer cells may well represent an attempt of cancer cells to manipulate a dynamic redox change in tumor microenvironment in a manner that is beneficial for their proliferation and malignant progression.

Effects of pasteurization on adiponectin and insulin concentrations in donor human milk.

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Ley, Sylvia H; Hanley, Anthony J; Stone, Debbie; O'Connor, Deborah L

2011-09-01

Although pasteurization is recommended before distributing donor human milk in North America, limited data are available on its impact on metabolic hormones in milk. We aimed to investigate the effects of pasteurization on adiponectin and insulin concentrations in donor human milk. The study investigates concentrations of components in donor human milk before and after Holder pasteurization. After the guidelines of the Human Milk Bank Association of North America, human milk samples were pooled to produce 17 distinct batches (4 individuals per batch) and pasteurized at 62.5°C for 30 min. Adiponectin, insulin, energy, fat, total protein, and glucose concentrations were measured pre- and postpasteurization. Pasteurization reduced milk adiponectin and insulin by 32.8 and 46.1%, respectively (both p Pasteurization effects on milk hormone concentrations remained significant after adjusting for fat and energy (beta ± SEE: -4.11 ± 1.27, p = 0.003 for adiponectin; -70.0 ± 15.0, p pasteurization reduced adiponectin and insulin concentrations in donor human milk. In view of emerging knowledge on the importance of milk components, continued work to find the optimal pasteurization process that mitigates risks but promotes retention of bioactive components is needed.

Increased Procurement of Thoracic Donor Organs After Thyroid Hormone Therapy.

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Novitzky, Dimitri; Mi, Zhibao; Collins, Joseph F; Cooper, David K C

2015-01-01

Hormonal therapy to the brain-dead organ donor can include thyroid hormone (triiodothyronine [T3] or levothyroxine [T4]), antidiuretic hormone, corticosteroids, or insulin. There has been a controversy on whether thyroid hormone enables more organs to be procured. Data on 63,593 donors of hearts and lungs (2000-2009) were retrospectively reviewed. Documentation on T3/T4 was available in all donors (study 1), and in 40,124 details of all 4 hormones were recorded (study 2). In this cohort, group A (23,022) received T3/T4 and group B (17,102) no T3/T4. Univariate analyses and multiple regressions were performed. Posttransplant graft and recipient survival at 1 and 12 months were compared. In study 1, 30,962 donors received T3/T4, with 36.59% providing a heart and 20.05% providing 1 or both lungs. Of the 32,631 donors who did not receive T3/T4, only 29.62% provided a heart and 14.61% provided lungs, an increase of 6.97% hearts and 5.44% lungs from T3/T4-treated donors (both P donor was associated with either improved posttransplant graft and recipient survival or no difference in survival. T3/T4 therapy results in more transplantable hearts and lungs, with no detriment to posttransplant graft or recipient survival. Copyright © 2015 Elsevier Inc. All rights reserved.

Stochastic rat lung dosimetry for inhaled radon progeny: a surrogate for the human lung for lung cancer risk assessment

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Winkler-Heil, R.; Hofmann, W. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Hussain, M. [University of Salzburg, Division of Physics and Biophysics, Department of Materials Research and Physics, Salzburg (Austria); Higher Education Commission of Pakistan, Islamabad (Pakistan)

2015-05-15

Laboratory rats are frequently used in inhalation studies as a surrogate for human exposures. The objective of the present study was therefore to develop a stochastic dosimetry model for inhaled radon progeny in the rat lung, to predict bronchial dose distributions and to compare them with corresponding dose distributions in the human lung. The most significant difference between human and rat lungs is the branching structure of the bronchial tree, which is relatively symmetric in the human lung, but monopodial in the rat lung. Radon progeny aerosol characteristics used in the present study encompass conditions typical for PNNL and COGEMA rat inhalation studies, as well as uranium miners and human indoor exposure conditions. It is shown here that depending on exposure conditions and modeling assumptions, average bronchial doses in the rat lung ranged from 5.4 to 7.3 mGy WLM{sup -1}. If plotted as a function of airway generation, bronchial dose distributions exhibit a significant maximum in large bronchial airways. If, however, plotted as a function of airway diameter, then bronchial doses are much more uniformly distributed throughout the bronchial tree. Comparisons between human and rat exposures indicate that rat bronchial doses are slightly higher than human bronchial doses by about a factor of 1.3, while lung doses, averaged over the bronchial (BB), bronchiolar (bb) and alveolar-interstitial (AI) regions, are higher by about a factor of about 1.6. This supports the current view that the rat lung is indeed an appropriate surrogate for the human lung in case of radon-induced lung cancers. Furthermore, airway diameter seems to be a more appropriate morphometric parameter than airway generations to relate bronchial doses to bronchial carcinomas. (orig.)

New estimates for human lung dimensions

International Nuclear Information System (INIS)

Kennedy, Christine; Sidavasan, Sivalal; Kramer, Gary

2008-01-01

Full text: The currently used lung dimensions in dosimetry were originally estimated in the 1940s from Army recruits. This study provides new estimates of lung dimensions based on images acquired from a sample from the general population (varying age and sex). Building accurate models, called phantoms, of the human lung requires that the spatial dimensions (length, width, and depth) be quantified, in addition to volume. Errors in dose estimates may result from improperly sized lungs as the counting efficiency of externally mounted detectors (e.g., in a lung counter) is dependent on the position of internally deposited radioactive material (i.e., the size of the lung). This study investigates the spatial dimensions of human lungs. Lung phantoms have previously been made in one of two sizes. The Lawrence Livermore National Laboratory Torso Phantom (LLNL) has deep, short lungs whose dimensions do not comply well with the data published in Report 23 (Reference Man) issued by the International Commission on Radiological Protection (ICRP). The Japanese Atomic Energy Research Institute Torso Phantom(JAERI), has longer, shallower lungs that also deviate from the ICRP values. However, careful examination of the ICRP recommended values shows that they are soft. In fact, they have been dropped from the ICRP's Report 89 which updates Report 23. Literature surveys have revealed a wealth of information on lung volume, but very little data on the spatial dimensions of human lungs. Better lung phantoms need to be constructed to more accurately represent a person so that dose estimates may be quantified more accurately in view of the new, lower, dose limits for occupationally exposed workers and the general public. Retrospective chest images of 60 patients who underwent imaging of the chest- lungs as part of their healthy persons occupational screening for lung disease were chosen. The chosen normal lung images represent the general population). Ages, gender and weight of the

Impact of Donor Arterial Partial Pressure of Oxygen on Outcomes After Lung Transplantation in Adult Cystic Fibrosis Recipients.

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Hayes, Don; Kopp, Benjamin T; Kirkby, Stephen E; Reynolds, Susan D; Mansour, Heidi M; Tobias, Joseph D; Tumin, Dmitry

2016-08-01

Donor PaO2 levels are used for assessing organs for lung transplantation (LTx), but survival implications of PaO2 levels in adult cystic fibrosis (CF) patients receiving LTx are unclear. UNOS registry data spanning 2005-2013 were used to test for associations of donor PaO2 with patient survival and bronchiolitis obliterans syndrome (BOS) in adult (age ≥ 18 years) first-time LTx recipients diagnosed with CF. The analysis included 1587 patients, of whom 1420 had complete data for multivariable Cox models. No statistically significant differences among donor PaO2 categories of ≤200, 201-300, 301-400, or >400 mmHg were found in univariate survival analysis (log-rank test p = 0.290). BOS onset did not significantly differ across donor PaO2 categories (Chi-square p = 0.480). Multivariable Cox models of patient survival supported the lack of difference across donor PaO2 categories. Interaction analysis found a modest difference in survival between the two top categories of donor PaO2 when examining patients with body mass index (BMI) in the lowest decile (≤16.5 kg/m(2)). Donor PaO2 was not associated with survival or BOS onset in adult CF patients undergoing LTx. Notwithstanding statistically significant interactions between donor PaO2 and BMI, there was no evidence of post-LTx survival risk associated with donor PaO2 below conventional thresholds in any subgroup of adults with CF.

The National Heart, Lung, and Blood Institute Recipient Epidemiology and Donor Evaluation Study (REDS-III): A research program striving to improve blood donor and transfusion recipient outcomes

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Kleinman, Steven; Busch, Michael P; Murphy, Edward L; Shan, Hua; Ness, Paul; Glynn, Simone A.

2014-01-01

Background The Recipient Epidemiology and Donor Evaluation Study -III (REDS-III) is a 7-year multicenter transfusion safety research initiative launched in 2011 by the National Heart, Lung, and Blood Institute. Study design The domestic component involves 4 blood centers, 12 hospitals, a data coordinating center, and a central laboratory. The international component consists of distinct programs in Brazil, China, and South Africa which involve US and in-country investigators. Results REDS-III is using two major methods to address key research priorities in blood banking/transfusion medicine. First, there will be numerous analyses of large “core” databases; the international programs have each constructed a donor/donation database while the domestic program has established a detailed research database that links data from blood donors and their donations, the components made from these donations, and data extracts from the electronic medical records of the recipients of these components. Secondly, there are more than 25 focused research protocols involving transfusion recipients, blood donors, or both that are either in progress or scheduled to begin within the next 3 years. Areas of study include transfusion epidemiology and blood utilization; transfusion outcomes; non-infectious transfusion risks; HIV-related safety issues (particularly in the international programs); emerging infectious agents; blood component quality; donor health and safety; and other donor issues. Conclusions It is intended that REDS-III serve as an impetus for more widespread recipient and linked donor-recipient research in the US as well as to help assure a safe and available blood supply in the US and in international locations. PMID:24188564

Lung regeneration by fetal lung tissue implantation in a mouse pulmonary emphysema model.

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Uyama, Koh; Sakiyama, Shoji; Yoshida, Mitsuteru; Kenzaki, Koichiro; Toba, Hiroaki; Kawakami, Yukikiyo; Okumura, Kazumasa; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira

2016-01-01

The mortality and morbidity of chronic obstructive pulmonary disease are high. However, no radical therapy has been developed to date. The purpose of this study was to evaluate whether fetal mouse lung tissue can grow and differentiate in the emphysematous lung. Fetal lung tissue from green fluorescent protein C57BL/6 mice at 16 days' gestation was used as donor material. Twelve-month-old pallid mice were used as recipients. Donor lungs were cut into small pieces and implanted into the recipient left lung by performing thoracotomy under anesthesia. The recipient mice were sacrificed at day 7, 14, and 28 after implantation and used for histological examination. Well-developed spontaneous pulmonary emphysema was seen in 12-month-old pallid mice. Smooth and continuous connection between implanted fetal lung tissue and recipient lung was recognized. Air space expansion and donor tissue differentiation were observed over time. We could clearly distinguish the border zones between injected tissue and native tissue by the green fluorescence of grafts. Fetal mouse lung fragments survived and differentiated in the emphysematous lung of pallid mice. Implantation of fetal lung tissue in pallid mice might lead to further lung regeneration research from the perspective of respiratory and exercise function. J. Med. Invest. 63: 182-186, August, 2016.

Airway complications have a greater impact on the outcomes of living-donor lobar lung transplantation recipients than cadaveric lung transplantation recipients.

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Sugimoto, Seiichiro; Yamane, Masaomi; Otani, Shinji; Kurosaki, Takeshi; Okahara, Shuji; Hikasa, Yukiko; Toyooka, Shinichi; Kobayashi, Motomu; Oto, Takahiro

2018-04-21

Airway complications (ACs) after living-donor lobar lung transplantation (LDLLT) could have different features from those after cadaveric lung transplantation (CLT). We conducted this study to compare the characteristics of ACs after LDLLT vs. those after CLT and investigate their impact on outcomes. We reviewed, retrospectively, data on 163 recipients of lung transplantation, including 83 recipients of LDLLT and 80 recipients of CLT. The incidence of ACs did not differ between LDLLT and CLT. The initial type of AC after LDLLT was limited to stenosis in all eight patients, whereas that after CLT consisted of stenosis in three patients and necrosis in ten patients (p = 0.0034). ACs after LDLLT necessitated significantly earlier initiation of treatment than those after CLT (p = 0.032). The overall survival rate of LDLLT recipients with an AC was significantly lower than that of those without an AC (p = 0.030), whereas the overall survival rate was comparable between CLT recipients with and those without ACs (p = 0.25). ACs after LDLLT, limited to bronchial stenosis, require significantly earlier treatment and have a greater adverse impact on survival than ACs after CLT.

Nonsense and missense mutation of mitochondrial ND6 gene promotes cell migration and invasion in human lung adenocarcinoma

International Nuclear Information System (INIS)

Yuan, Yang; Wang, Weixing; Li, Huizhong; Yu, Yongwei; Tao, Jin; Huang, Shengdong; Zeng, Zhiyong

2015-01-01

Previous study showed that mitochondrial ND6 (mitND6) gene missense mutation resulted in NADH dehydrogenase deficiency and was associated with tumor metastasis in several mouse tumor cell lines. In the present study, we investigated the possible role of mitND6 gene nonsense and missense mutations in the metastasis of human lung adenocarcinoma. The presence of mitND6 gene mutations was screened by DNA sequencing of tumor tissues from 87 primary lung adenocarcinoma patients and the correlation of the mutations with the clinical features was analyzed. In addition, we constructed cytoplasmic hybrid cells with denucleared primary lung adenocarcinoma cell as the mitochondria donor and mitochondria depleted lung adenocarcinoma A549 cell as the nuclear donor. Using these cells, we studied the effects of mitND6 gene nonsense and missense mutations on cell migration and invasion through wounding healing and matrigel-coated transwell assay. The effects of mitND6 gene mutations on NADH dehydrogenase activity and ROS production were analyzed by spectrophotometry and flow cytometry. mitND6 gene nonsense and missense mutations were detected in 11 of 87 lung adenocarcinoma specimens and was correlated with the clinical features including age, pathological grade, tumor stage, lymph node metastasis and survival rate. Moreover, A549 cell containing mitND6 gene nonsense and missense mutation exhibited significantly lower activity of NADH dehydrogenase, higher level of ROS, higher capacity of cell migration and invasion, and higher pAKT and pERK1/ERK2 expression level than cells with the wild type mitND6 gene. In addition, NADH dehydrogenase inhibitor rotenone was found to significantly promote the migration and invasion of A549 cells. Our data suggest that mitND6 gene nonsense and missense mutation might promote cell migration and invasion in lung adenocarcinoma, probably by NADH dehydrogenase deficiency induced over-production of ROS

Sutureless human sclera donor patch graft for Ahmed glaucoma valve.

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Zeppa, Lucio; Romano, Mario R; Capasso, Luigi; Tortori, Achille; Majorana, Mara A; Costagliola, Ciro

2010-01-01

To report the safety and effectiveness of a sutureless human sclera donor patch graft covering the subconjunctival portion of glaucoma drainage implant tube to prevent its erosion throughout the overlying conjunctiva. This was a prospective pilot study. Fifteen eyes of 15 consecutive patients not responsive to medical and to not-implant surgical glaucoma treatment underwent Ahmed glaucoma valve (AGV) implant surgery with sutureless human sclera donor patch graft. The surgical procedure included AVG implant placed 8 mm behind the corneal limbus and fixed to the sclera with two 9-0 black nylon sutures. The tube was passed through the scleral tunnel, parallel to the corneal limbus, and shortened at the desired length. The anterior part of the tube was covered with human donor scleral graft and kept in place with fibrin glue (Tissue Coll) under the conjunctiva. Examinations were scheduled at baseline and then at 1 week and 1, 3, 6, and 12 months after surgery. At 12-month follow-up, the best-corrected visual acuity did not significantly improve from baseline 0.78+/-1.2 logMAR, whereas mean intraocular pressure significantly decreased from preoperative values of 29.8 (SD 8.4) mmHg. In all cases, the scleral patch was found in place at each check during the follow-up period. No conjunctival erosion over the AGV tube nor sign of endophthalmitis was recorded at any time during the follow-up period. AVG implant surgery with sutureless human sclera donor patch graft represents an effective and relatively safe surgical procedure for complicated glaucomas, avoiding conjunctival erosions over the AGV tube.

Donor Human Milk for the High-Risk Infant: Preparation, Safety, and Usage Options in the United States.

Science.gov (United States)

2017-01-01

The use of donor human milk is increasing for high-risk infants, primarily for infants born weighing Pasteurized donor milk may be considered in situations in which the supply of maternal milk is insufficient. The use of pasteurized donor milk is safe when appropriate measures are used to screen donors and collect, store, and pasteurize the milk and then distribute it through established human milk banks. The use of nonpasteurized donor milk and other forms of direct, Internet-based, or informal human milk sharing does not involve this level of safety and is not recommended. It is important that health care providers counsel families considering milk sharing about the risks of bacterial or viral contamination of nonpasteurized human milk and about the possibilities of exposure to medications, drugs, or herbs in human milk. Currently, the use of pasteurized donor milk is limited by its availability and affordability. The development of public policy to improve and expand access to pasteurized donor milk, including policies that support improved governmental and private financial support for donor milk banks and the use of donor milk, is important. Copyright © 2017 by the American Academy of Pediatrics.

Effect of Holder pasteurization on macronutrients and immunoglobulin profile of pooled donor human milk.

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Adhisivam, B; Vishnu Bhat, B; Rao, Krishna; Kingsley, S M; Plakkal, Nishad; Palanivel, C

2018-03-27

The objective of this study was to study the effect of Holder pasteurization on macronutrients and immunoglobulin profile of pooled donor human milk. This descriptive study was conducted in a Human Milk Bank of a tertiary care teaching institute in south India. Thirty random paired pooled donor human milk samples (before and after pasteurization) were analyzed for macronutrients (protein, fat, carbohydrates) using infrared spectroscopy. Similarly, immunoglobulin profile (IgA and IgG) before and after pasteurization was quantified using ELISA. The mean values of protein, fat, and carbohydrates in pooled donor milk pre-pasteurization were 1.6, 3.6, and 6.1 g/dl compared with post-pasteurization values 1.4, 2.7, and 5.9 g/dl, respectively. Pasteurization reduced protein, fat, and energy content of pooled donor milk by 12.5%, 25%, and 16%, respectively. However, carbohydrates were not significantly reduced. Pasteurization decreased IgA by 30% and IgG by 60%. Holder pasteurization of pooled donor human milk decreases protein, fat, and energy content and also reduces the levels of IgA and IgG.

Best practice guidelines for the operation of a donor human milk bank in an Australian NICU.

Science.gov (United States)

Hartmann, B T; Pang, W W; Keil, A D; Hartmann, P E; Simmer, K

2007-10-01

Until the establishment of the PREM Bank (Perron Rotary Express Milk Bank) donor human milk banking had not occurred in Australia for the past 20 years. In re-establishing donor human milk banking in Australia, the focus of the PREM Bank has been to develop a formal and consistent approach to safety and quality in processing during the operation of the human milk bank. There is currently no existing legislation in Australia that specifically regulates the operation of donor human milk banks. For this reason the PREM Bank has utilised existing and internationally recognised management practices for managing hazards during food production. These tools (specifically HACCP) have been used to guide the development of Standard Operating Procedures and Good Manufacturing Practice for the screening of donors and processing of donor human milk. Donor screening procedures are consistent with those recommended by other human milk banks operating internationally, and also consistent with the requirements for blood and tissue donation in Australia. Controlled documentation and record keep requirements have also been developed that allow complete traceability from individual donation to individual feed dispensed to recipient and maintain a record of all processing and storage conditions. These operational requirements have been developed to reduce any risk associated with feeding pasteurised donor human milk to hospitalised preterm or ill infants to acceptable levels.

Human lung mast cells modulate the functions of airway smooth muscle cells in asthma.

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Alkhouri, H; Hollins, F; Moir, L M; Brightling, C E; Armour, C L; Hughes, J M

2011-09-01

Activated mast cell densities are increased on the airway smooth muscle in asthma where they may modulate muscle functions and thus contribute to airway inflammation, remodelling and airflow obstruction. To determine the effects of human lung mast cells on the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Freshly isolated human lung mast cells were stimulated with IgE/anti-IgE. Culture supernatants were collected after 2 and 24 h and the mast cells lysed. The supernatants/lysates were added to serum-deprived, subconfluent airway smooth muscle cells for up to 48 h. Released chemokines and extracellular matrix were measured by ELISA, proliferation was quantified by [(3) H]-thymidine incorporation and cell counting, and intracellular signalling by phospho-arrays. Mast cell 2-h supernatants reduced CCL11 and increased CXCL8 and fibronectin production from both asthmatic and nonasthmatic muscle cells. Leupeptin reversed these effects. Mast cell 24-h supernatants and lysates reduced CCL11 release from both muscle cell types but increased CXCL8 release by nonasthmatic cells. The 24-h supernatants also reduced asthmatic, but not nonasthmatic, muscle cell DNA synthesis and asthmatic cell numbers over 5 days through inhibiting extracellular signal-regulated kinase (ERK) and phosphatidylinositol (PI3)-kinase pathways. However, prostaglandins, thromboxanes, IL-4 and IL-13 were not involved in reducing the proliferation. Mast cell proteases and newly synthesized products differentially modulated the secretory and proliferative functions of airway smooth muscle cells from donors with and without asthma. Thus, mast cells may modulate their own recruitment and airway smooth muscle functions locally in asthma. © 2011 John Wiley & Sons A/S.

Management to optimize organ procurement in brain dead donors.

Science.gov (United States)

Mascia, L; Mastromauro, I; Viberti, S; Vincenzi, M; Zanello, M

2009-03-01

The demand for donor organs continues to exceed the number of organs available for transplantation. Many reasons may account for this discrepancy, such as the lack of consent, the absence of an experienced coordinator team able to solve logistical problems, the use of strict donor criteria, and suboptimal, unstandardized critical care management of potential organ donors. This has resulted in efforts to improve the medical care delivered to potential organ donors, so as to reduce organ shortages, improve organ procurement, and promote graft survival. The physiological changes that follow brain death entail a high incidence of complications jeopardizing potentially transplantable organs. Adverse events include cardiovascular changes, endocrine and metabolic disturbances, and disruption of internal homeostasis. Brain death also upregulates the release of pro-inflammatory molecules. Recent findings support the hypothesis that a preclinical lung injury characterized by an enhanced inflammatory response is present in potential donors and may predispose recipients to an adverse clinical prognosis following lung transplantation. In clinical practice, hypotension, diabetes insipidus, relative hypothermia, and natremia are more common than disseminated intravascular coagulation, cardiac arrhythmias, pulmonary oedema, acute lung injury, and metabolic acidosis. Strategies for the management of organ donors exist and consist of the normalization of donor physiology. Management has been complicated by the recent use of ''marginal'' donors and donors of advanced age or with ''extended'' criteria. Current guidelines suggest that the priority of critical care management for potential organ donors should be shifted from a ''cerebral protective'' strategy to a multimodal strategy aimed to preserve peripheral organ function.

Determination of an unrelated donor pool size for human leukocyte antigen-matched platelets in Brazil

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Carolina Bonet Bub

2016-02-01

Full Text Available ABSTRACT Background: Successful transfusion of platelet refractory patients is a challenge. Many potential donors are needed to sustain human leukocyte antigen matched-platelet transfusion programs because of the different types of antigens and the constant needs of these patients. For a highly mixed population such as the Brazilian population, the pool size required to provide adequate platelet support is unknown. Methods: A mathematical model was created to estimate the appropriate size of an unrelated donor pool to provide human leukocyte antigen-compatible platelet support for a Brazilian population. A group of 154 hematologic human leukocyte antigen-typed patients was used as the potential patient population and a database of 65,500 human leukocyte antigen-typed bone marrow registered donors was used as the donor population. Platelet compatibility was based on the grading system of Duquesnoy. Results: Using the mathematical model, a pool containing 31,940, 1710 and 321 donors would be necessary to match more than 80% of the patients with at least five completely compatible (no cross-reactive group, partial compatible (one cross-reactive group or less compatible (two cross-reactive group donors, respectively. Conclusion: The phenotypic diversity of the Brazilian population has probably made it more difficulty to find completely compatible donors. However, this heterogeneity seems to have facilitated finding donors when cross-reactive groups are accepted as proposed by the grading system of Duquesnoy. The results of this study may help to establish unrelated human leukocyte antigen-compatible platelet transfusions, a procedure not routinely performed in most Brazilian transfusion services.

A Randomized Trial of the Effects of Nebulized Albuterol on Pulmonary Edema in Brain Dead Organ Donors

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Ware, Lorraine B.; Landeck, Megan; Koyama, Tatsuki; Zhao, Zhiguo; Singer, Jonathan; Kern, Ryan; Neidlinger, Nikole; Nguyen, John; Johnson, Elizabeth; Janz, David R.; Bernard, Gordon R.; Lee, Jae W.; Matthay, Michael A.

2013-01-01

Donor lung utilization rates are persistently low primarily due to donor lung dysfunction. We hypothesized that a treatment that enhances the resolution of pulmonary edema by stimulating the rate of alveolar fluid clearance would improve donor oxygenation and increase donor lung utilization. We conducted a randomized, blinded, placebo-controlled trial of aerosolized albuterol (5 mg q4h) versus saline placebo during active donor management in 506 organ donors. The primary outcome was change in oxygenation (PaO2/FiO2) from enrollment to organ procurement. The albuterol (n=260) and placebo (n=246) groups were well matched for age, gender, ethnicity, smoking, and cause of brain death. The change in PaO2/FiO2 from enrollment to organ procurement did not differ between treatment groups (p=0.54) nor did donor lung utilization (albuterol 29% vs. placebo 32%, p=0.44). Donors in the albuterol vs. placebo group were more likely to have the study drug dose reduced (13% vs. 1%, pdonor management period did not improve donor oxygenation or increase donor lung utilization but did cause tachycardia. High dose aerosolized albuterol should not be used in donors to enhance the resolution of pulmonary edema. PMID:24730050

Seroprevalence of human parvovirus B19 in healthy blood donors.

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Kumar, Satish; Gupta, R M; Sen, Sourav; Sarkar, R S; Philip, J; Kotwal, Atul; Sumathi, S H

2013-07-01

Human parvovirus B19 is an emerging transfusion transmitted infection. Although parvovirus B19 infection is connected with severe complications in some recipients, donor screening is not yet mandatory. To reduce the risk of contamination, plasma-pool screening and exclusion of highly viraemic donations are recommended. In this study the prevalence of parvovirus B19 in healthy blood donors was detected by ELISA. A total of 1633 samples were screened for IgM and IgG antibodies against parvovirus B19 by ELISA. The initial 540 samples were screened for both IgM and IgG class antibodies and remaining 1093 samples were screened for only IgM class antibodies by ELISA. Net prevalence of IgM antibodies to human parvovirus B19 in our study was 7.53% and prevalence of IgG antibodies was 27.96%. Dual positivity (IgG and IgM) was 2.40%. The seroprevalence of human parvovirus B19 among blood donor population in our study is high, and poses an adverse transfusion risk especially in high-risk group of patients who have no detectable antibodies to B19. Studies with large sample size are needed to validate these results.

Comparison of outcomes from smoking and nonsmoking donors: thirteen-year experience.

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Berman, Marius; Goldsmith, Kim; Jenkins, David; Sudarshan, Catherine; Catarino, Pedro; Sukumaran, Nair; Dunning, John; Sharples, Linda D; Tsui, Steven; Parmar, Jasvir

2010-12-01

Lung transplantation remains the best treatment option for a variety of end-stage lung diseases. Pressure on the limited donor pool has led to the use of extended criteria donors. One aspect of this has been the liberalization of the use of smoking donors (SmD). This study is a retrospective review of lung transplants performed between April 1995 and August 2008 at a single institute. We examined the impact of donor smoking on short-term and long-term survival in relationship to recipient and donor demographics such as ischemic time, cytomegalovirus status, rates of rejection and infection, ventilation, and intensive care stay. Endpoints were survival, infection, and rejection. During this 13-year period, 454 lung transplants were performed. Smoking history was available on 424 (93.4%) of these (SmD, n = 184; NSmD, n = 240). Seventy-one patients died within 3 months of transplant leaving 353 alive at 3 months posttransplant. Fatalities within the first 3 months were significantly higher in the SmD group (21% vs 13%, odds ratio 1.9, hazard ratio 3.3, p = 0.04). No significant difference in rejection and infection rates between recipients of lungs from SmD and NSmD at 3 months and at 1 year posttransplantation (p = 0.51 and 0.09) was found. Although recipients of lungs from SmD had higher odds of ventilation for more than 10 hours, the odds were only increased by 20%, which was not statistically significant. Recipients from SmD had significantly longer stays in the intensive care (odds ratio 1.9, p = 0.002). There was little evidence for an effect of SmD on the development of bronchiolitis obliterans. In this large cohort of patients, donor smoking history has an effect on early survival but no effect on long-term survival. The cause of this early mortality is independent of infection and rejection. However, these data suggest that overall outcomes from the use of donor lungs from smokers are acceptable, particularly in the current era with limited donor organs

Human body donation in Thailand: Donors at Khon Kaen University.

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Techataweewan, N; Panthongviriyakul, C; Toomsan, Y; Mothong, W; Kanla, P; Chaichun, A; Amarttayakong, P; Tayles, N

2018-03-01

Culture, society and spirituality contribute to variability in the characteristics of human body donors and donation programmes worldwide. The donors and the body donation programme at Khon Kaen University, northeast Thailand, reflect all these aspects of Thailand, including the status accorded to the donors and the ceremonial acknowledgement of the donors and their families. Data from the programme records and from surveys of samples of currently registering donors and recently received donor bodies are analysed to define the characteristics of both registering and received donors, including motivation, demography, socio-economic status, health, and use of the bodies. The body donation programme at Khon Kaen University currently has a very high rate of registration of body donors, with gender and age differences in the patterns of donation. Registrants include more females than males, a long-standing pattern, and are an average age of 50 years. The bodies of 12% of registrants are received after death and include more males than females. Both sexes are of an average age of 69 years. Males had registered their donation eight years prior to death and females ten years prior. Current registrants identified altruistic motives for their decision to donate, although the coincidence of body donation by a highly revered monk with a surge in donations in 2015 suggests that Buddhism plays a primary role in motivation. The opportunity to make merit for donors and their families, and respect shown to donors and the nature of the ceremonies acknowledging the donors and their families, including the use of the Royal Flame at the cremation ceremony, all contribute to decisions to donate. The characteristics of body donors and the body donation programme at Khon Kaen University are reflective of Thai society and the centrality of Buddhism to Thai culture. Copyright © 2017 Elsevier GmbH. All rights reserved.

Aortic homograft for pulmonary artery augmentation in single lung transplantation.

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Rueda, Pablo; Morales, Jose; Guzman, Enrique; Tellez, Jose L; Niebla, Benito A; Avalos, Alejandro; Patiño, Hilda

2005-06-01

We present a case of unilateral lung transplantation in which a segment of the donor's descending aorta was used as a homograft for pulmonary artery augmentation in the donor lung. This technique can be used when the donor's lung artery has been cut at the base of the hilum during the harvesting procedure.

Effect of primarily cultured human lung cancer-associated fibroblasts on radiosensitivity of lung cancer cells

International Nuclear Information System (INIS)

Ji Xiaoqin; Ji Jiang; Chen Yongbing; Shan Fang; Lu Xueguan

2014-01-01

Objective: To investigate the effect of human lung cancer-associated fibroblasts (CAF) on the radiosensitivity of lung cancer cells when CAF is placed in direct contact co-culture with lung cancer cells. Methods: Human lung CAF was obtained from fresh human lung adenocarcinoma tissue specimens by primary culture and subculture and was then identified by immunofluorescence staining. The CAF was placed in direct contact co-culture with lung cancer A 549 and H 1299 cells, and the effects of CAF on the radiosensitivity of A 549 and H 1299 cells were evaluated by colony-forming assay. Results: The human lung CAF obtained by adherent culture could stably grow and proliferate, and it had specific expression of α-smooth muscle actin, vimentin, and fibroblast activation protein,but without expression of cytokeratin-18. The plating efficiency (PE, %) of A 549 cells at 0 Gy irradiation was (20.0 ± 3.9)% when cultured alone versus (32.3 ± 5.5)% when co-cultured with CAF (t=3.16, P<0.05), and the PE of H 1299 cells at 0 Gy irradiation was (20.6 ± 3.1)% when cultured alone versus (35.2 ± 2.3)% when co-cultured with CAF (t=6.55, P<0.05). The cell survival rate at 2 Gy irradiation (SF 2 ) of A 549 cells was 0.727 ±0.061 when cultured alone versus 0.782 ± 0.089 when co-cultured with CAF (t=0.88, P>0.05), and the SF 2 of H 1299 cells was 0.692 ±0.065 when cultured alone versus 0.782 ± 0.037 when co-cultured with CAF (t=2.08, P>0.05). The protection enhancement ratios of human lung CAF for A 549 cells and H 1299 cells were 1.29 and 1.25, respectively. Conclusions: Human lung CAF reduces the radiosensitivity of lung cancer cells when placed in direct contact co-culture with them, and the radioprotective effect may be attributed to CAF promoting the proliferation of lung cancer cells. (authors)

Thioredoxin priming prolongs lung allograft survival by promoting immune tolerance.

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Hanbo Hu

Full Text Available Tolerance to allograft antigen is the major challenge and final goal of transplant medicine. Our previous study demonstrated that thioredoxin-1 (Trx priming of donor lung significantly protected allogeneic lung graft. To determine whether Trx priming of donor lung inhibits allograft rejection, extends allograft survival and induces immune tolerance, orthotopic left lung transplantation was performed from Lewis to Sprague-Dawley rats without immunosuppression. Donor lungs were primed with Trx at 4°C for 4 hr prior to transplantation. After up to 37 days post-transplantation, allograft lung morphology, recipient T cell and humoral alloantigen-specific immune responses were examined. We found that Trx-primed lungs exhibited much reduced acute rejection and associated lung injuries resulting in loss of graft functional area at 5-37 days post-transplant in contrast to the control groups. CD4+ T cells from the recipients with Trx-primed grafts responded to the stimulation of dendritic cells (DCs of donor origin, in contrast to DCs from the third party, with significantly reduced proliferation. Consistent with above findings, we observed that CD4+Foxp3+ regulatory T cells in spleen cells from the recipients with Trx-primed grafts were significantly increased compared to controls, and CD4+ T cells from the recipients with Trx-primed grafts produced much higher levels of immunosuppressive cytokine, IL-10 when stimulated with allogeneic donor DCs. In addition, humoral immune tolerance was also induced as there was no significant increase levels of serum antibodies against donor antigens in Trx-lung recipients when re-challenged with allogeneic donor antigens. Our results demonstrate that one-time Trx-priming of donor lung grafts prior to transplantation significantly prolongs the survival of the grafts through inducing or promoting cellular and humoral alloantigen-specific immune tolerance, which might be associated with the induction of

99Tcm-N(NOEt2 Uptake Kinetics Difference among KMB17 Human Embryonic Lung Diploid Fibroblast and Different Human Lung Cancer Cells

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Wei JIA

2010-04-01

Full Text Available Background and objective PET/CT imaging is expensive, so searching the tumor imaging agent for SPECT/CT is necessary. 99Tcm-N(NOEt2 [bis (N-ethoxy-N-ethyl dithiocarbamato nitrido99Tcm (V] can be uptaken by lung cancer cells and other cells alike. The aim of this study is to evaluate the distinctive value in lung tumor with 99Tcm-N(NOEt2, the difference in its uptake kinetics in human embryonic lung diploid fibroblasts KMB17 and several kinds of lung cancer cells lines. Methods Firstly, six different cell culture medium which contained YTMLC Gejiu human lung squamous carcinoma cell, SPC-A1 human lung adenocarcinoma cell, AGZY low metastatic human lung adenocarcinoma, 973 high metastatic human lung adenocarcinoma cell, GLC-82 Gejiu human lung adenocarcinoma cell, and KMB17 human embryonic lung diploid fibroblast, respectively with equal cell density of 1×106/mL and the same volume were prepared; secondly, the same radioactive dose of 99Tcm-N(NOEt2 was added into each sample and then 300 μL mixed sample was taken out respectively and cultured in 37 oC culture box; Finally, 5 min, 15 min, 30 min, 45 min, 60 min, 75 min, 90 min after cultivation, centrifuged each cultured sample and determined the intracellular radiocounts of each sample, calculated each cell sample’s uptake rate of 99Tcm-N(NOEt2 at different time. Results Statistical difference was found among six cell samples, and the uptake rate sequence from high to low is 973 and SPC-A1>YTMLC>GLC-82>AGZY>KMB17 respectively; furthermore, 30 min-45 min after culture, the uptake rate reached stability, and the 45 min uptake rate of each sample was higher than its 96.7% uptake peak. Conclusion Based on the results above mentioned, it is supposed that there are discriminative clinical value when using 99Tcm-N(NOEt2 as a tumor targeting imaging agent, and 30 min or so after injection may be the best imaging time in the early imaging stage.

Identification of multiple HPV types on spermatozoa from human sperm donors

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Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob

2011-01-01

Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV...... according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive...

Change in donor profile influenced the percentage of organs transplanted from multiple organ donors.

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Meers, C; Van Raemdonck, D; Van Gelder, F; Van Hees, D; Desschans, B; De Roey, J; Vanhaecke, J; Pirenne, J

2009-03-01

We hypothesized that the change in donor profile over the years influenced the percentage of transplantations. We reviewed medical records for all multiple-organ donors (MODs) within our network. The percentage of transplanted organs was compared between 1991-1992 (A) and 2006-2007 (B). In period A, 156 potential MODs were identified compared with 278 in period B. Fifteen potential donors (10%) in period A and 114 (41%) in period B were rejected because they were medically not suitable (40% vs 75%) or there was no family consent (60% vs 25%). Of the remaining effective MODs (141 in period A and 164 in period B), mean (standard deviation = SD) age was 34 (5) years vs 49 (17) years (P organs transplanted in periods A vs B was kidneys, 97% vs 79%; livers, 64% vs 85%; hearts, 60% vs 26%; lungs, 7% vs 35%; and pancreas, 6% vs 13% (P organs (17%), mainly because of medical contraindications. The MOD profile changed to older age, fewer traumatic brain deaths, and longer ventilation time. We transplanted more livers, lungs, and pancreases but fewer kidneys and hearts.

Zbtb7a induction in alveolar macrophages is implicated in anti-HLA-mediated lung allograft rejection.

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Nayak, Deepak K; Zhou, Fangyu; Xu, Min; Huang, Jing; Tsuji, Moriya; Yu, Jinsheng; Hachem, Ramsey; Gelman, Andrew E; Bremner, Ross M; Smith, Michael A; Mohanakumar, Thalachallour

2017-07-12

Chronic rejection significantly limits long-term success of solid organ transplantation. De novo donor-specific antibodies (DSAs) to mismatched donor human leukocyte antigen after human lung transplantation predispose lung grafts to chronic rejection. We sought to delineate mediators and mechanisms of DSA pathogenesis and to define early inflammatory events that trigger chronic rejection in lung transplant recipients and obliterative airway disease, a correlate of human chronic rejection, in mouse. Induction of transcription factor zinc finger and BTB domain containing protein 7a (Zbtb7a) was an early response critical in the DSA-induced chronic rejection. A cohort of human lung transplant recipients who developed DSA and chronic rejection demonstrated greater Zbtb7a expression long before clinical diagnosis of chronic rejection compared to nonrejecting lung transplant recipients with stable pulmonary function. Expression of DSA-induced Zbtb7a was restricted to alveolar macrophages (AMs), and selective disruption of Zbtb7a in AMs resulted in less bronchiolar occlusion, low immune responses to lung-restricted self-antigens, and high protection from chronic rejection in mice. Additionally, in an allogeneic cell transfer protocol, antigen presentation by AMs was Zbtb7a-dependent where AMs deficient in Zbtb7a failed to induce antibody and T cell responses. Collectively, we demonstrate that AMs play an essential role in antibody-induced pathogenesis of chronic rejection by regulating early inflammation and lung-restricted humoral and cellular autoimmunity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Seroprevalence of human T-cell lymphotropic virus-1/2 in blood donors in northern pakistan: implication for blood donor screening

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Niazi, S.K.

2015-01-01

To determine the seroprevalence of Human T-cell Lymphotropic Virus-1/2 (HTLV-1/2) in blood donors in Northern Pakistan. Study Design: Descriptive study. Place and Duration of Study: Armed Forces Institute of Transfusion, Rawalpindi, from July to August 2013. Methodology:A total of 2100 blood donors were screened for anti-HTLV-1/2 antibodies during the study period, in a pool of six, on a highly sensitive, Chemiluminiscent Microparticle Immunoassay (CMIA) based system. The screening test reactive donors were recalled, counseled and interviewed, and a fresh sample was obtained for confirmatory testing. Confirmation was performed using additional immunoassays including Line Immunoassay (LIA); with additional testing for HTLV-1 pvDNAPCR. Frequency and percentages were determined. Results: Four donors (0.19%) were repeatedly screening test-reactive and were subsequently confirmed to be HTLV-1 infected by line immunoassay and HTLV-1 pvDNAPCR. All four donors were male with mean age of 27 ± 6.27 years. Two (50%) of the positive donors gave history of Multiple Sexual Partners (MSP). Conclusion: HTLV-1 seroprevalence in Northern Pakistan blood donors was determined to be 0.19%. Large scale studies, including the cost effectiveness of screening blood donations for anti-HTLV-1/2 in Pakistan, are recommended. (author)

Donor human milk for preterm infants

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Arslanoglu, Sertac; Corpeleijn, Willemijn; Moro, Guido

2013-01-01

guidelines. Storage and processing of human milk reduces some biological components, which may diminish its health benefits. From a nutritional point of view, DHM, like HM, does not meet the requirements of preterm infants, necessitating a specific fortification regimen to optimize growth. Future research......The Committee on Nutrition of the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition aims to document the existing evidence of the benefits and common concerns deriving from the use of donor human milk (DHM) in preterm infants. The comment also outlines gaps in knowledge...... and gives recommendations for practice and suggestions for future research directions. Protection against necrotizing enterocolitis is the major clinical benefit deriving from the use of DHM when compared with formula. Limited data also suggest unfortified DHM to be associated with improved feeding...

Beware Cold Agglutinins in Organ Donors! Ex Vivo Lung Perfusion From an Uncontrolled Donation After Circulatory-Determination-of-Death Donor With a Cold Agglutinin: A Case Report.

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Venkataraman, A; Blackwell, J W; Funkhouser, W K; Birchard, K R; Beamer, S E; Simmons, W T; Randell, S H; Egan, T M

2017-09-01

We began to recover lungs from uncontrolled donation after circulatory determination of death to assess for transplant suitability by means of ex vivo lung perfusion (EVLP) and computerized tomographic (CT) scan. Our first case had a cold agglutinin with an interesting outcome. A 60-year-old man collapsed at home and was pronounced dead by Emergency Medical Services personnel. Next-of-kin consented to lung retrieval, and the decedent was ventilated and transported. Lungs were flushed with cold Perfadex, removed, and stored cold. The lungs did not flush well. Medical history revealed a recent hemolytic anemia and a known cold agglutinin. Warm nonventilated ischemia time was 51 minutes. O 2 -ventilated ischemia time was 141 minutes. Total cold ischemia time was 6.5 hours. At cannulation for EVLP, established clots were retrieved from both pulmonary arteries. At initiation of EVLP with Steen solution, tiny red aggregates were observed initially. With warming, the aggregates disappeared and the perfusate became red. After 1 hour, EVLP was stopped because of florid pulmonary edema. The lungs were cooled to 20°C; tiny red aggregates formed again in the perfusate. Ex vivo CT scan showed areas of pulmonary edema and a pyramidal right middle lobe opacity. Dissection showed multiple pulmonary emboli-the likely cause of death. However, histology showed agglutinated red blood cells in the microvasculature in pre- and post-EVLP biopsies, which may have contributed to inadequate parenchymal preservation. Organ donors with cold agglutinins may not be suitable owing to the impact of hypothermic preservation. Copyright © 2017 Elsevier Inc. All rights reserved.

Tiny plastic lung mimics human pulmonary function

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Careers Inclusion & Diversity Work-Life Balance Career Resources Apply for a Job Postdocs Students Goals Recycling Green Purchasing Pollution Prevention Reusing Water Resources Environmental Management Releases - 2016 » April » Tiny plastic lung mimics human pulmonary function Tiny plastic lung mimics

Benefits of donor human milk for preterm infants: current evidence.

Science.gov (United States)

Bertino, Enrico; Giuliani, Francesca; Occhi, Luciana; Coscia, Alessandra; Tonetto, Paola; Marchino, Federica; Fabris, Claudio

2009-10-01

It's undoubted that optimum nutrition for term infants is breastfeeding, exclusive for the first six months, then followed by a complementary diet and carried on, if possible, for the first year of life or even more. During the last decades several data confirmed the great advantages of fresh mother's milk use also for feeding very low and extremely low birthweight preterm infants. When mother's milk is unavailable or in short supply, pasteurized donor breast milk is widely used in neonatal intensive care units. Pasteurization partially affects nutritional and immunological properties of breast milk, however it is known that pasteurized milk maintains some biological properties and clinical benefits. The substantial benefits of mother's own milk feeding of preterm infants are supported by strong evidence. However, there is increasing evidence also on specific benefits of donor breast milk. Future research is needed to compare formula vs. nutrient fortified donor breast milk, to compare formula and DM as supplements to maternal milk rather than as sole diet and to compare effects of different methods of heat treatments on donor human milk quality.

Human models of acute lung injury

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Alastair G. Proudfoot

2011-03-01

Full Text Available Acute lung injury (ALI is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome.

Effect of increases in lung volume on clearance of aerosolized solute from human lungs

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Marks, J.D.; Luce, J.M.; Lazar, N.M.; Wu, J.N.; Lipavsky, A.; Murray, J.F.

1985-10-01

To study the effect of increases in lung volume on solute uptake, we measured clearance of /sup 99m/Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosols (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure (12 cmH2O continuous positive airway pressure (CPAP)) or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH2O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH2O; clearance and FRC were determined at CPAP of 12 cmH2O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method.

Effect of increases in lung volume on clearance of aerosolized solute from human lungs

International Nuclear Information System (INIS)

Marks, J.D.; Luce, J.M.; Lazar, N.M.; Wu, J.N.; Lipavsky, A.; Murray, J.F.

1985-01-01

To study the effect of increases in lung volume on solute uptake, we measured clearance of /sup 99m/Tc-diethylenetriaminepentaacetic acid (Tc-DTPA) at different lung volumes in 19 healthy humans. Seven subjects inhaled aerosols (1 micron activity median aerodynamic diam) at ambient pressure; clearance and functional residual capacity (FRC) were measured at ambient pressure (control) and at increased lung volume produced by positive pressure [12 cmH 2 O continuous positive airway pressure (CPAP)] or negative pressure (voluntary breathing). Six different subjects inhaled aerosol at ambient pressure; clearance and FRC were measured at ambient pressure and CPAP of 6, 12, and 18 cmH 2 O pressure. Six additional subjects inhaled aerosol at ambient pressure or at CPAP of 12 cmH 2 O; clearance and FRC were determined at CPAP of 12 cmH 2 O. According to the results, Tc-DTPA clearance from human lungs is accelerated exponentially by increases in lung volume, this effect occurs whether lung volume is increased by positive or negative pressure breathing, and the effect is the same whether lung volume is increased during or after aerosol administration. The effect of lung volume must be recognized when interpreting the results of this method

A human lung xenograft mouse model of Nipah virus infection.

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Gustavo Valbuena

2014-04-01

Full Text Available Nipah virus (NiV is a member of the genus Henipavirus (family Paramyxoviridae that causes severe and often lethal respiratory illness and encephalitis in humans with high mortality rates (up to 92%. NiV can cause Acute Lung Injury (ALI in humans, and human-to-human transmission has been observed in recent outbreaks of NiV. While the exact route of transmission to humans is not known, we have previously shown that NiV can efficiently infect human respiratory epithelial cells. The molecular mechanisms of NiV-associated ALI in the human respiratory tract are unknown. Thus, there is an urgent need for models of henipavirus infection of the human respiratory tract to study the pathogenesis and understand the host responses. Here, we describe a novel human lung xenograft model in mice to study the pathogenesis of NiV. Following transplantation, human fetal lung xenografts rapidly graft and develop mature structures of adult lungs including cartilage, vascular vessels, ciliated pseudostratified columnar epithelium, and primitive "air" spaces filled with mucus and lined by cuboidal to flat epithelium. Following infection, NiV grows to high titers (10(7 TCID50/gram lung tissue as early as 3 days post infection (pi. NiV targets both the endothelium as well as respiratory epithelium in the human lung tissues, and results in syncytia formation. NiV infection in the human lung results in the production of several cytokines and chemokines including IL-6, IP-10, eotaxin, G-CSF and GM-CSF on days 5 and 7 pi. In conclusion, this study demonstrates that NiV can replicate to high titers in a novel in vivo model of the human respiratory tract, resulting in a robust inflammatory response, which is known to be associated with ALI. This model will facilitate progress in the fundamental understanding of henipavirus pathogenesis and virus-host interactions; it will also provide biologically relevant models for other respiratory viruses.

Growth in VLBW infants fed predominantly fortified maternal and donor human milk diets: a retrospective cohort study

Science.gov (United States)

2012-01-01

Background To determine the effect of human milk, maternal and donor, on in-hospital growth of very low birthweight (VLBW) infants. We performed a retrospective cohort study comparing in-hospital growth in VLBW infants by proportion of human milk diet, including subgroup analysis by maternal or donor milk type. Primary outcome was change in weight z-score from birth to hospital discharge. Methods Retrospective cohort study. Results 171 infants with median gestational age 27 weeks (IQR 25.4, 28.9) and median birthweight 899 g (IQR 724, 1064) were included. 97% of infants received human milk, 51% received > 75% of all enteral intake as human milk. 16% of infants were small-for-gestational age (SGA, 75% human milk had a greater negative change in weight z-score from birth to discharge compared to infants receiving human milk fortifier was related to human milk intake (p = 0.04). Among infants receiving > 75% human milk, there was no significant difference in change in weight z-score by milk type (donor −0.84, maternal −0.56, mixed −0.45, p = 0.54). Infants receiving >75% donor milk had higher rates of SGA status at discharge than those fed maternal or mixed milk (56% vs. 35% (maternal), 21% (mixed), p = 0.08). Conclusions VLBW infants can grow appropriately when fed predominantly fortified human milk. However, VLBW infants fed >75% human milk are at greater risk of poor growth than those fed less human milk. This risk may be highest in those fed predominantly donor human milk. PMID:22900590

Ex vivo lung perfusion with adenosine A2A receptor agonist allows prolonged cold preservation of lungs donated after cardiac death.

Science.gov (United States)

Wagner, Cynthia E; Pope, Nicolas H; Charles, Eric J; Huerter, Mary E; Sharma, Ashish K; Salmon, Morgan D; Carter, Benjamin T; Stoler, Mark H; Lau, Christine L; Laubach, Victor E; Kron, Irving L

2016-02-01

Ex vivo lung perfusion has been successful in the assessment of marginal donor lungs, including donation after cardiac death (DCD) donor lungs. Ex vivo lung perfusion also represents a unique platform for targeted drug delivery. We sought to determine whether ischemia-reperfusion injury would be decreased after transplantation of DCD donor lungs subjected to prolonged cold preservation and treated with an adenosine A2A receptor agonist during ex vivo lung perfusion. Porcine DCD donor lungs were preserved at 4°C for 12 hours and underwent ex vivo lung perfusion for 4 hours. Left lungs were then transplanted and reperfused for 4 hours. Three groups (n = 4/group) were randomized according to treatment with the adenosine A2A receptor agonist ATL-1223 or the dimethyl sulfoxide vehicle: Infusion of dimethyl sulfoxide during ex vivo lung perfusion and reperfusion (DMSO), infusion of ATL-1223 during ex vivo lung perfusion and dimethyl sulfoxide during reperfusion (ATL-E), and infusion of ATL-1223 during ex vivo lung perfusion and reperfusion (ATL-E/R). Final Pao2/Fio2 ratios (arterial oxygen partial pressure/fraction of inspired oxygen) were determined from samples obtained from the left superior and inferior pulmonary veins. Final Pao2/Fio2 ratios in the ATL-E/R group (430.1 ± 26.4 mm Hg) were similar to final Pao2/Fio2 ratios in the ATL-E group (413.6 ± 18.8 mm Hg), but both treated groups had significantly higher final Pao2/Fio2 ratios compared with the dimethyl sulfoxide group (84.8 ± 17.7 mm Hg). Low oxygenation gradients during ex vivo lung perfusion did not preclude superior oxygenation capacity during reperfusion. After prolonged cold preservation, treatment of DCD donor lungs with an adenosine A2A receptor agonist during ex vivo lung perfusion enabled Pao2/Fio2 ratios greater than 400 mm Hg after transplantation in a preclinical porcine model. Pulmonary function during ex vivo lung perfusion was not predictive of outcomes after transplantation. Copyright �

Non-heart-beating lung donation : How big is the pool?

NARCIS (Netherlands)

Nijkamp, Danielle M.; van der Bij, Wim; Verschuuren, Erik A. M.; Heemskerk, Martin B. A.; de Buijzer, Erwin; Erasmus, Michiel E.

Lungs from non-heart-beating (NHB) donors are seldom used in The Netherlands despite the good quality of these organs. Based on a retrospective analysis of 162 NHB donor procedures we found that only 5% of the lungs were actually utilized, but that 30% of the lungs were suitable for transplantation.

Utilization of the organ care system as ex-vivo lung perfusion after cold storage transportation.

Science.gov (United States)

Mohite, P N; Maunz, O; Popov, A-F; Zych, B; Patil, N P; Simon, A R

2015-11-01

The Organ Care System (OCS) allows perfusion and ventilation of the donor lungs under physiological conditions. Ongoing trials to compare preservation with OCS Lung with standard cold storage do not include donor lungs with suboptimal gas exchange and donor lungs treated with OCS following cold storage transportation. We present a case of a 48-yr-old man who received such lungs after cold storage transportation treated with ex-vivo lung perfusion utilizing OCS. © The Author(s) 2015.

[Profile of human milk bank donors and relationship with the length of the donation].

Science.gov (United States)

Sierra Colomina, G; García Lara, N; Escuder Vieco, D; Vázquez Román, S; Cabañes Alonso, E; Pallás Alonso, C R

2014-04-01

The promotion of Human Milk Banks is an important social service. The Human Milk Banks depend on donors, and knowing the profile of donors seems quite important. To study the demographics and lifestyles of the donors, the reasons or influences for donating, and to associate these variables with the length of the donation. This is a descriptive, cross-sectional study conducted on 168 mothers who answered the written questionnaire when they agreed to become donors. 98 (58%) responded to the telephone interview. The mean age was 33.1 ± 4.5 years. Of the total 27.9% lived outside Madrid and 21.4% were immigrants, with 23.7% working full time, 65.3% had a university education, and 96.2% had a stable partner. The main reasons for donating were too much milk (77%), and to help others (75%). The main obstacle was transportation to the Human Milk Bank for 20% of the donors, and for 61% the main reason for terminating donation was due to reaching the end of lactation. A longer donation is associated with: having a term newborn, with birth weight over 1500 g, starting donating early and reconciling the donation to the work situation. The most common donor profile was a young woman, with university education and a stable partner. Having a term new born, starting donating early, and the conciliation with work is associated with longer donations. Milk pick-up at home would make donation easier. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Long-term results after lung transplantation using organs from circulatory death donors: a propensity score-matched analysis†.

Science.gov (United States)

Sabashnikov, Anton; Patil, Nikhil P; Popov, Aron-Frederik; Soresi, Simona; Zych, Bartlomiej; Weymann, Alexander; Mohite, Prashant N; García Sáez, Diana; Zeriouh, Mohamed; Wahlers, Thorsten; Choi, Yeong-Hoon; Wippermann, Jens; Wittwer, Thorsten; De Robertis, Fabio; Bahrami, Toufan; Amrani, Mohamed; Simon, André R

2016-01-01

Due to organ shortage in lung transplantation (LTx), donation after circulatory death (DCD) has been implemented in several countries, contributing to an increasing number of organs transplanted. We sought to assess long-term outcomes after LTx with organs procured following circulatory death in comparison with those obtained from donors after brain death (DBD). Between January 2007 and November 2013, 302 LTxs were performed in our institution, whereby 60 (19.9%) organs were retrieved from DCD donors. We performed propensity score matching (DCD:DBD = 1:2) based on preoperative donor and recipient factors that were significantly different in univariate analysis. After propensity matching, there were no statistically significant differences between the groups in terms of demographics and preoperative donor and recipient characteristics. There were no significant differences regarding intraoperative variables and total ischaemic time. Patients from the DCD group had significantly higher incidence of primary graft dysfunction grade 3 at the end of the procedure (P = 0.014), and significantly lower pO2/FiO2 ratio during the first 24 h after the procedure (P = 0.018). There was a trend towards higher incidence of the need for postoperative extracorporeal life support in the DCD group. Other postoperative characteristics were comparable. While the overall cumulative survival was not significantly different, the DCD group had significantly poorer results in terms of bronchiolitis obliterans syndrome (BOS)-free survival in the long-term follow-up. Long-term results after LTx with organs procured following DCD are in general comparable with those obtained after DBD LTx. However, patients transplanted using organs from DCD donors have a predisposition for development of BOS in the longer follow-up. © The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Distinct Properties of Human M-CSF and GM-CSF Monocyte-Derived Macrophages to Simulate Pathological Lung Conditions In Vitro: Application to Systemic and Inflammatory Disorders with Pulmonary Involvement.

Science.gov (United States)

Lescoat, Alain; Ballerie, Alice; Augagneur, Yu; Morzadec, Claudie; Vernhet, Laurent; Fardel, Olivier; Jégo, Patrick; Jouneau, Stéphane; Lecureur, Valérie

2018-03-17

Macrophages play a central role in the pathogenesis of inflammatory and fibrotic lung diseases. However, alveolar macrophages (AM) are poorly available in humans to perform in vitro studies due to a limited access to broncho-alveolar lavage (BAL). In this study, to identify the best alternative in vitro model for human AM, we compared the phenotype of AM obtained from BAL of patients suffering from three lung diseases (lung cancers, sarcoidosis and Systemic Sclerosis (SSc)-associated interstitial lung disease) to human blood monocyte-derived macrophages (MDMs) differentiated with M-CSF or GM-CSF. The expression of eight membrane markers was evaluated by flow cytometry. Globally, AM phenotype was closer to GM-CSF MDMs. However, the expression levels of CD163, CD169, CD204, CD64 and CD36 were significantly higher in SSc-ILD than in lung cancers. Considering the expression of CD204 and CD36, the phenotype of SSc-AM was closer to MDMs, from healthy donors or SSc patients, differentiated by M-CSF rather than GM-CSF. The comparative secretion of IL-6 by SSc-MDMs and SSc-AM is concordant with these phenotypic considerations. Altogether, these results support the M-CSF MDM model as a relevant in vitro alternative to simulate AM in fibrotic disorders such as SSc.

Variation in Pediatric Organ Donor Management Practices Among US Organ Procurement Organizations.

Science.gov (United States)

Ream, Robert S; Armbrecht, Eric S

2018-03-01

Reports of actual pediatric organ donor management practice among US organ procurement organizations are sparse, and the use of standardized management guidelines is unknown. A recent consensus statement from the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations offers guidelines for the management of the pediatric organ donor. To describe the use of guidelines and routine practices in the management of the pediatric organ donor with respect to hemodynamics, lung and ventilator management, fluid and electrolytes, hormonal replacement therapy, the use of blood products, thermoregulation, and prophylactic antibiotics. Cross-sectional observational study using a survey and follow-up telephone interview with respondents from all 58 US organ procurement organizations. All 58 US Organ Procurement Organizations participated. A majority employed written guidelines for the management of pediatric donor hemodynamics, thermoregulation, fluids, and electrolytes. Management of blood products, the lung, and mechanical ventilation were less commonly committed to written guidelines, but common practices were described. All used various forms of hormonal replacement therapy and the majority administered empiric antibiotic therapy. Wide variation was observed in the management of the lung, mechanical ventilation, and glycemic control. Most OPOs used forms of standardized donor management for the pediatric organ donor although variation in the content of that management exists. Barriers to an evidence-based approach to the pediatric donor need to be determined and addressed.

Using optical coherence tomography (OCT) to evaluate the status of human donor kidneys (Conference Presentation)

Science.gov (United States)

Andrews, Peter M.; Konkel, Brandon; Anderson, Erik; Stein, Matthew; Cooper, Matthew; Verbesey, Jennifer E.; Ghasemian, Seyed; Chen, Yu

2016-02-01

The main cause of delayed renal function following the transplant of donor kidneys is ischemic induced acute tubular necrosis (ATN). The ability to determine the degree of ATN suffered by donor kidneys prior to their transplant would enable transplant surgeons to use kidneys that might otherwise be discarded and better predict post-transplant renal function. Currently, there are no reliable tests to determine the extent of ATN of donor kidneys prior to their transplant. In ongoing clinical trials, we have been using optical coherence tomography (OCT) to non-invasively image the superficial proximal tubules of human donor kidneys prior to and following transplant, and correlate these observations with post-transplant renal function. Thus far we have studied over 40 living donor kidneys and 10 cadaver donor kidneys, and demonstrated that this imaging can be performed in a sterile and expeditious fashion in the operating room (OR). Because of many variables associated with a diverse population of donors/recipients and transplant operation parameters, more transplant data must be collected prior to drawing definite conclusions. Nevertheless, our observations have thus far mirrored our previously published laboratory results indicating that damage to the kidney proximal tubules as indicated by tubule swelling is a good measure of post-transplant ATN and delayed graft function. We conclude that OCT is a useful procedure for analyzing human donor kidneys.

Growth in VLBW infants fed predominantly fortified maternal and donor human milk diets: a retrospective cohort study

Directory of Open Access Journals (Sweden)

Colaizy Tarah T

2012-08-01

Full Text Available Abstract Background To determine the effect of human milk, maternal and donor, on in-hospital growth of very low birthweight (VLBW infants. We performed a retrospective cohort study comparing in-hospital growth in VLBW infants by proportion of human milk diet, including subgroup analysis by maternal or donor milk type. Primary outcome was change in weight z-score from birth to hospital discharge. Methods Retrospective cohort study. Results 171 infants with median gestational age 27 weeks (IQR 25.4, 28.9 and median birthweight 899 g (IQR 724, 1064 were included. 97% of infants received human milk, 51% received > 75% of all enteral intake as human milk. 16% of infants were small-for-gestational age (SGA, th percentile at birth, and 34% of infants were SGA at discharge. Infants fed >75% human milk had a greater negative change in weight z-score from birth to discharge compared to infants receiving 75% human milk, there was no significant difference in change in weight z-score by milk type (donor −0.84, maternal −0.56, mixed −0.45, p = 0.54. Infants receiving >75% donor milk had higher rates of SGA status at discharge than those fed maternal or mixed milk (56% vs. 35% (maternal, 21% (mixed, p = 0.08. Conclusions VLBW infants can grow appropriately when fed predominantly fortified human milk. However, VLBW infants fed >75% human milk are at greater risk of poor growth than those fed less human milk. This risk may be highest in those fed predominantly donor human milk.

Analytic Intermodel Consistent Modeling of Volumetric Human Lung Dynamics.

Science.gov (United States)

Ilegbusi, Olusegun; Seyfi, Behnaz; Neylon, John; Santhanam, Anand P

2015-10-01

Human lung undergoes breathing-induced deformation in the form of inhalation and exhalation. Modeling the dynamics is numerically complicated by the lack of information on lung elastic behavior and fluid-structure interactions between air and the tissue. A mathematical method is developed to integrate deformation results from a deformable image registration (DIR) and physics-based modeling approaches in order to represent consistent volumetric lung dynamics. The computational fluid dynamics (CFD) simulation assumes the lung is a poro-elastic medium with spatially distributed elastic property. Simulation is performed on a 3D lung geometry reconstructed from four-dimensional computed tomography (4DCT) dataset of a human subject. The heterogeneous Young's modulus (YM) is estimated from a linear elastic deformation model with the same lung geometry and 4D lung DIR. The deformation obtained from the CFD is then coupled with the displacement obtained from the 4D lung DIR by means of the Tikhonov regularization (TR) algorithm. The numerical results include 4DCT registration, CFD, and optimal displacement data which collectively provide consistent estimate of the volumetric lung dynamics. The fusion method is validated by comparing the optimal displacement with the results obtained from the 4DCT registration.

Expression analysis of asthma candidate genes during human and murine lung development.

Science.gov (United States)

Melén, Erik; Kho, Alvin T; Sharma, Sunita; Gaedigk, Roger; Leeder, J Steven; Mariani, Thomas J; Carey, Vincent J; Weiss, Scott T; Tantisira, Kelan G

2011-06-23

Little is known about the role of most asthma susceptibility genes during human lung development. Genetic determinants for normal lung development are not only important early in life, but also for later lung function. To investigate the role of expression patterns of well-defined asthma susceptibility genes during human and murine lung development. We hypothesized that genes influencing normal airways development would be over-represented by genes associated with asthma. Asthma genes were first identified via comprehensive search of the current literature. Next, we analyzed their expression patterns in the developing human lung during the pseudoglandular (gestational age, 7-16 weeks) and canalicular (17-26 weeks) stages of development, and in the complete developing lung time series of 3 mouse strains: A/J, SW, C57BL6. In total, 96 genes with association to asthma in at least two human populations were identified in the literature. Overall, there was no significant over-representation of the asthma genes among genes differentially expressed during lung development, although trends were seen in the human (Odds ratio, OR 1.22, confidence interval, CI 0.90-1.62) and C57BL6 mouse (OR 1.41, CI 0.92-2.11) data. However, differential expression of some asthma genes was consistent in both developing human and murine lung, e.g. NOD1, EDN1, CCL5, RORA and HLA-G. Among the asthma genes identified in genome wide association studies, ROBO1, RORA, HLA-DQB1, IL2RB and PDE10A were differentially expressed during human lung development. Our data provide insight about the role of asthma susceptibility genes during lung development and suggest common mechanisms underlying lung morphogenesis and pathogenesis of respiratory diseases.

Donor assists acceptor binding and catalysis of human α1,6-fucosyltransferase.

Science.gov (United States)

Kötzler, Miriam P; Blank, Simon; Bantleon, Frank I; Wienke, Martin; Spillner, Edzard; Meyer, Bernd

2013-08-16

α1,6-Core-fucosyltransferase (FUT8) is a vital enzyme in mammalian physiological and pathophysiological processes such as tumorigenesis and progress of, among others, non-small cell lung cancer and colon carcinoma. It was also shown that therapeutic antibodies have a dramatically higher efficacy if the α1,6-fucosyl residue is absent. However, specific and potent inhibitors for FUT8 and related enzymes are lacking. Hence, it is crucial to elucidate the structural basis of acceptor binding and the catalytic mechanism. We present here the first structural model of FUT8 in complex with its acceptor and donor molecules. An unusually large acceptor, i.e., a hexasaccharide from the core of N-glycans, is required as minimal structure. Acceptor substrate binding of FUT8 is being dissected experimentally by STD NMR and SPR and theoretically by molecular dynamics simulations. The acceptor binding site forms an unusually large and shallow binding site. Binding of the acceptor to the enzyme is much faster and stronger if the donor is present. This is due to strong hydrogen bonding between O6 of the proximal N-acetylglucosamine and an oxygen atom of the β-phosphate of GDP-fucose. Therefore, we propose an ordered Bi Bi mechanism for FUT8 where the donor molecule binds first. No specific amino acid is present that could act as base during catalysis. Our results indicate a donor-assisted mechanism, where an oxygen of the β-phosphate deprotonates the acceptor. Knowledge of the mechanism of FUT8 is now being used for rational design of targeted inhibitors to address metastasis and prognosis of carcinomas.

Characterization of human organ donors testing positive for type 1 diabetes-associated autoantibodies

Science.gov (United States)

Wiberg, A; Granstam, A; Ingvast, S; Härkönen, T; Knip, M; Korsgren, O; Skog, O

2015-01-01

In this study we aim to describe the characteristics of non-diabetic organ donors with circulating diabetes-associated autoantibodies collected within the Nordic Network for Islet Transplantation. One thousand and thirty organ donors have been screened in Uppsala for antibodies against glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A). The 32 non-diabetic donors that tested positive for GADA (3·3% of all non-diabetic donors) were studied in more detail, together with 32 matched controls. Mean age among the autoantibody-positive donors was 52·6 (range 21–74), family history of type 1 diabetes (T1D) was unknown, and no donor was genetically predisposed for T1D regarding the human leucocyte antigen (HLA) locus. Subjects were analysed for islet cell antibodies (ICA), insulin autoantibodies (IAA) and zinc transporter 8 antibodies (ZnT8A), and pancreas morphology and clinical data were examined. Eight non-diabetic donors tested positive for two antibodies and one donor tested positive for four antibodies. No insulitis or other signs of a diabetic process were found in any of the donors. While inflammatory cells were present in all donors, subjects with high GADA titres had significantly higher CD45 cell numbers in exocrine tissue than controls. The extent of fibrosis was more pronounced in autoantibody-positive donors, even in subjects with lower GADA titres. Notably, it is possible that events not related directly to T1D (e.g. subclinical pancreatitis) may induce autoantibodies in some cases. PMID:26313035

Ultraviolet-C Irradiation: A Novel Pasteurization Method for Donor Human Milk.

Science.gov (United States)

Christen, Lukas; Lai, Ching Tat; Hartmann, Ben; Hartmann, Peter E; Geddes, Donna T

2013-01-01

Holder pasteurization (milk held at 62.5°C for 30 minutes) is the standard treatment method for donor human milk. Although this method of pasteurization is able to inactivate most bacteria, it also inactivates important bioactive components. Therefore, the objective of this study was to investigate ultraviolet irradiation as an alternative treatment method for donor human milk. Human milk samples were inoculated with five species of bacteria and then UV-C irradiated. Untreated and treated samples were analysed for bacterial content, bile salt stimulated lipase (BSSL) activity, alkaline phosphatase (ALP) activity, and fatty acid profile. All five species of bacteria reacted similarly to UV-C irradiation, with higher dosages being required with increasing concentrations of total solids in the human milk sample. The decimal reduction dosage was 289±17 and 945±164 J/l for total solids of 107 and 146 g/l, respectively. No significant changes in the fatty acid profile, BSSL activity or ALP activity were observed up to the dosage required for a 5-log10 reduction of the five species of bacteria. UV-C irradiation is capable of reducing vegetative bacteria in human milk to the requirements of milk bank guidelines with no loss of BSSL and ALP activity and no change of FA.

Gene Expression Analysis to Assess the Relevance of Rodent Models to Human Lung Injury.

Science.gov (United States)

Sweeney, Timothy E; Lofgren, Shane; Khatri, Purvesh; Rogers, Angela J

2017-08-01

The relevance of animal models to human diseases is an area of intense scientific debate. The degree to which mouse models of lung injury recapitulate human lung injury has never been assessed. Integrating data from both human and animal expression studies allows for increased statistical power and identification of conserved differential gene expression across organisms and conditions. We sought comprehensive integration of gene expression data in experimental acute lung injury (ALI) in rodents compared with humans. We performed two separate gene expression multicohort analyses to determine differential gene expression in experimental animal and human lung injury. We used correlational and pathway analyses combined with external in vitro gene expression data to identify both potential drivers of underlying inflammation and therapeutic drug candidates. We identified 21 animal lung tissue datasets and three human lung injury bronchoalveolar lavage datasets. We show that the metasignatures of animal and human experimental ALI are significantly correlated despite these widely varying experimental conditions. The gene expression changes among mice and rats across diverse injury models (ozone, ventilator-induced lung injury, LPS) are significantly correlated with human models of lung injury (Pearson r = 0.33-0.45, P human lung injury. Predicted therapeutic targets, peptide ligand signatures, and pathway analyses are also all highly overlapping. Gene expression changes are similar in animal and human experimental ALI, and provide several physiologic and therapeutic insights to the disease.

High-Temperature Short-Time Pasteurization System for Donor Milk in a Human Milk Bank Setting

Directory of Open Access Journals (Sweden)

Diana Escuder-Vieco

2018-05-01

Full Text Available Donor milk is the best alternative for the feeding of preterm newborns when mother's own milk is unavailable. For safety reasons, it is usually pasteurized by the Holder method (62.5°C for 30 min. Holder pasteurization results in a microbiological safe product but impairs the activity of many biologically active compounds such as immunoglobulins, enzymes, cytokines, growth factors, hormones or oxidative stress markers. High-temperature short-time (HTST pasteurization has been proposed as an alternative for a better preservation of some of the biological components of human milk although, at present, there is no equipment available to perform this treatment under the current conditions of a human milk bank. In this work, the specific needs of a human milk bank setting were considered to design an HTST equipment for the continuous and adaptable (time-temperature combination processing of donor milk. Microbiological quality, activity of indicator enzymes and indices for thermal damage of milk were evaluated before and after HTST treatment of 14 batches of donor milk using different temperature and time combinations and compared to the results obtained after Holder pasteurization. The HTST system has accurate and simple operation, allows the pasteurization of variable amounts of donor milk and reduces processing time and labor force. HTST processing at 72°C for, at least, 10 s efficiently destroyed all vegetative forms of microorganisms present initially in raw donor milk although sporulated Bacillus sp. survived this treatment. Alkaline phosphatase was completely destroyed after HTST processing at 72 and 75°C, but γ-glutamil transpeptidase showed higher thermoresistance. Furosine concentrations in HTST-treated donor milk were lower than after Holder pasteurization and lactulose content for HTST-treated donor milk was below the detection limit of analytical method (10 mg/L. In conclusion, processing of donor milk at 72°C for at least 10 s in

High-Temperature Short-Time Pasteurization System for Donor Milk in a Human Milk Bank Setting.

Science.gov (United States)

Escuder-Vieco, Diana; Espinosa-Martos, Irene; Rodríguez, Juan M; Corzo, Nieves; Montilla, Antonia; Siegfried, Pablo; Pallás-Alonso, Carmen R; Fernández, Leónides

2018-01-01

Donor milk is the best alternative for the feeding of preterm newborns when mother's own milk is unavailable. For safety reasons, it is usually pasteurized by the Holder method (62.5°C for 30 min). Holder pasteurization results in a microbiological safe product but impairs the activity of many biologically active compounds such as immunoglobulins, enzymes, cytokines, growth factors, hormones or oxidative stress markers. High-temperature short-time (HTST) pasteurization has been proposed as an alternative for a better preservation of some of the biological components of human milk although, at present, there is no equipment available to perform this treatment under the current conditions of a human milk bank. In this work, the specific needs of a human milk bank setting were considered to design an HTST equipment for the continuous and adaptable (time-temperature combination) processing of donor milk. Microbiological quality, activity of indicator enzymes and indices for thermal damage of milk were evaluated before and after HTST treatment of 14 batches of donor milk using different temperature and time combinations and compared to the results obtained after Holder pasteurization. The HTST system has accurate and simple operation, allows the pasteurization of variable amounts of donor milk and reduces processing time and labor force. HTST processing at 72°C for, at least, 10 s efficiently destroyed all vegetative forms of microorganisms present initially in raw donor milk although sporulated Bacillus sp. survived this treatment. Alkaline phosphatase was completely destroyed after HTST processing at 72 and 75°C, but γ-glutamil transpeptidase showed higher thermoresistance. Furosine concentrations in HTST-treated donor milk were lower than after Holder pasteurization and lactulose content for HTST-treated donor milk was below the detection limit of analytical method (10 mg/L). In conclusion, processing of donor milk at 72°C for at least 10 s in this HTST system

High-Temperature Short-Time Pasteurization System for Donor Milk in a Human Milk Bank Setting

Science.gov (United States)

Escuder-Vieco, Diana; Espinosa-Martos, Irene; Rodríguez, Juan M.; Corzo, Nieves; Montilla, Antonia; Siegfried, Pablo; Pallás-Alonso, Carmen R.; Fernández, Leónides

2018-01-01

Donor milk is the best alternative for the feeding of preterm newborns when mother's own milk is unavailable. For safety reasons, it is usually pasteurized by the Holder method (62.5°C for 30 min). Holder pasteurization results in a microbiological safe product but impairs the activity of many biologically active compounds such as immunoglobulins, enzymes, cytokines, growth factors, hormones or oxidative stress markers. High-temperature short-time (HTST) pasteurization has been proposed as an alternative for a better preservation of some of the biological components of human milk although, at present, there is no equipment available to perform this treatment under the current conditions of a human milk bank. In this work, the specific needs of a human milk bank setting were considered to design an HTST equipment for the continuous and adaptable (time-temperature combination) processing of donor milk. Microbiological quality, activity of indicator enzymes and indices for thermal damage of milk were evaluated before and after HTST treatment of 14 batches of donor milk using different temperature and time combinations and compared to the results obtained after Holder pasteurization. The HTST system has accurate and simple operation, allows the pasteurization of variable amounts of donor milk and reduces processing time and labor force. HTST processing at 72°C for, at least, 10 s efficiently destroyed all vegetative forms of microorganisms present initially in raw donor milk although sporulated Bacillus sp. survived this treatment. Alkaline phosphatase was completely destroyed after HTST processing at 72 and 75°C, but γ-glutamil transpeptidase showed higher thermoresistance. Furosine concentrations in HTST-treated donor milk were lower than after Holder pasteurization and lactulose content for HTST-treated donor milk was below the detection limit of analytical method (10 mg/L). In conclusion, processing of donor milk at 72°C for at least 10 s in this HTST system

When does the lung die? Kfc, cell viability, and adenine nucleotide changes in the circulation-arrested rat lung.

Science.gov (United States)

Jones, D R; Becker, R M; Hoffmann, S C; Lemasters, J J; Egan, T M

1997-07-01

Lungs harvested from cadaveric circulation-arrested donors may increase the donor pool for lung transplantation. To determine the degree and time course of ischemia-reperfusion injury, we evaluated the effect of O2 ventilation on capillary permeability [capillary filtration coefficient (Kfc)], cell viability, and total adenine nucleotide (TAN) levels in in situ circulation-arrested rat lungs. Kfc increased with increasing postmortem ischemic time (r = 0.88). Lungs ventilated with O2 1 h postmortem had similar Kfc and wet-to-dry ratios as controls. Nonventilated lungs had threefold (P Kfc at 30 and 60 min postmortem compared with controls. Cell viability decreased in all groups except for 30-min postmortem O2-ventilated lungs. TAN levels decreased with increasing ischemic time, particularly in nonventilated lungs. Loss of adenine nucleotides correlated with increasing Kfc values (r = 0.76). This study indicates that lungs retrieved 1 h postmortem may have normal Kfc with preharvest O2 ventilation. The relationship between Kfc and TAN suggests that vascular permeability may be related to lung TAN levels.

The detection, diagnosis and therapy of human lung cancer

International Nuclear Information System (INIS)

1978-01-01

The Cancergram covers clinical aspects of cancers of the lung and tracheo-bronchial tree, i.e., the lower respiratory tract. This includes primary lung cancer in both early and advanced disease status. The topic includes clinically relevant aspects of the prevention, detection, diagnosis, evaluation, and therapy of lung cancer. Certain aspects of metastatic lung disease treatment or therapy which involve aspects of interest to primary lung cancer are included. With certain exceptions, general pre-clinical or animal studies not directly related to the primary human disease are excluded

Age related changes in steroid receptors on cultured lung fibroblasts

International Nuclear Information System (INIS)

Barile, F.A.; Bienkowski, R.S.

1986-01-01

The number of high affinity glucocorticoid receptors (Ro) on human fetal lung fibroblasts decreases as the cells age in vitro, and it has been suggested that these cell systems may be useful models of age-related changes in vivo. They examined the relation between change in Ro with in vitro aging and donor age. Confluent monolayers of lung fibroblasts at various population doubling levels (PDL), were incubated with ( 3 H)-dexamethasone (( 3 H)Dex) either alone or with excess (.01 mM) Dex. Specific binding was calculated as the difference between radioactivity in cells incubated with and without unlabeled Dex; Scatchard plots were used to analyze the data. Ro, measured as fmol ( 3 H)Dex/10 6 cells, for two lines of human fetal cells (HFL-1 and MRC-5) decreased with increasing age in vitro. However, human newborn (CRL-1485) and adult (CCL-201) cells and fetal rabbit cells (FAB-290), showed increases in Ro with continuous passage. For each cell line, the affinity constant (K/sub d/) did not change significantly with passage. They conclude that the direction of changes in steroid receptor levels on cells aging in vitro is influenced by donor age and species. Caution should be used in applying results obtained from model systems to aging organisms

Autoradiographic visualization of muscarinic receptor subtypes in human and guinea pig lung

International Nuclear Information System (INIS)

Mak, J.C.; Barnes, P.J.

1990-01-01

Muscarinic receptor subtypes have been localized in human and guinea pig lung sections by an autoradiographic technique, using [3H](-)quinuclidinyl benzilate [( 3H]QNB) and selective muscarinic antagonists. [3H]QNB was incubated with tissue sections for 90 min at 25 degrees C, and nonspecific binding was determined by incubating adjacent serial sections in the presence of 1 microM atropine. Binding to lung sections had the characterization expected for muscarinic receptors. Autoradiography revealed that muscarinic receptors were widely distributed in human lung, with dense labeling over submucosal glands and airway ganglia, and moderate labeling over nerves in intrapulmonary bronchi and of airway smooth muscle of large and small airways. In addition, alveolar walls were uniformly labeled. In guinea pig lung, labeling of airway smooth muscle was similar, but in contrast to human airways, epithelium was labeled but alveolar walls were not. The muscarinic receptors of human airway smooth muscle from large to small airways were entirely of the M3-subtype, whereas in guinea pig airway smooth muscle, the majority were the M3-subtype with a very small population of the M2-subtype present. In human bronchial submucosal glands, M1- and M3-subtypes appeared to coexist in the proportions of 36 and 64%, respectively. In human alveolar walls the muscarinic receptors were entirely of the M1-subtype, which is absent from the guinea pig lung. No M2-receptors were demonstrated in human lung. The localization of M1-receptors was confirmed by direct labeling with [3H]pirenzepine. With the exception of the alveolar walls in human lung, the localization of muscarinic receptor subtypes on structures in the lung is consistent with known functional studies

Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

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Lingappan, Krithika, E-mail: lingappa@bcm.edu [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I. [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States); Barrios, Roberto [Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, 6565 Fannin Street, Suite M227, Houston, TX 77030 (United States); Moorthy, Bhagavatula [Department of Pediatrics, Section of Neonatology, Texas Children' s Hospital, Baylor College of Medicine, 1102 Bates Avenue, MC: FC530.01, Houston, TX 77030 (United States)

2013-10-15

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

International Nuclear Information System (INIS)

Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

2013-01-01

Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO 2 > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F 2 alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure

Preparation of Tc-99m-macroaggregated albumin from recombinant human albumin for lung perfusion imaging.

Science.gov (United States)

Hunt, A P; Frier, M; Johnson, R A; Berezenko, S; Perkins, A C

2006-01-01

Human serum albumin (HSA) extracted from pooled blood taken from human donors is used in the production of (99m)Tc-labelled macroaggregated albumin (MAA) for lung perfusion imaging. However, concerns for the safety of blood-derived products due to potential contamination by infective agents (e.g. new variant CJD), make alternative production methods necessary. Recombinant DNA technology is a promising method of albumin production avoiding problems associated with human-derived HSA. This paper presents results comparing MAA prepared from recombinant human albumin (rHA, Recombumin) (rMAA) with in-house produced HSA MAA (hMAA) and commercially available MAA (cMAA). (99m)Tc-MAA was prepared using previously published production methods by heating a mixture of albumin and stannous chloride in acetate buffer (pH 5.4) at 70 degrees C for 20 min. Parameters investigated include aggregate size, radiolabelling efficiency, radiochemical and aggregate stability at 4 degrees C and in vitro (in whole human blood) at 37 degrees C and biodistribution studies. Results showed that rMAA could be produced with similar morphology, labelling efficiency and stability to hMAA and cMAA. Our findings confirm that rHA shows significant potential as a direct replacement for HSA in commercially available MAA.

Responses to recipient and donor B cells by genetically donor T cells from human haploidentical chimeras

International Nuclear Information System (INIS)

Schiff, S.; Sampson, H.; Buckley, R.

1986-01-01

Following administration of haploidentical stem cells to infants with severe combined immunodeficiency (SCID), mature T cells of donor karyotype appear later in the recipient without causing graft-versus-host disease. To investigate the effect of the host environment on the responsiveness of these genetically donor T cells, blood B and T lymphocytes from 6 SCID recipients, their parental donors and unrelated controls were purified by double SRBC rosetting. T cells were stimulated by irradiated B cells at a 1:1 ratio in 6 day cultures. Engrafted T cells of donor karyotype gave much smaller responses to irradiated genetically recipient B cells than did fresh donor T cells. Moreover, engrafted T cells of donor karyotype from two of the three SCIDs who are longest post-transplantation responded more vigorously (14,685 and 31,623 cpm) than fresh donor T cells (5141 and 22,709 cpm) to donor B cells. These data indicate that T lymphocytes which have matured from donor stem cells in the recipient microenvironment behave differently from those that have matured in the donor

Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

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Chun-Nun Chao

Full Text Available Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV infection. Therefore, we designed that the JCPyV virus-like particle (VLP packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp or thymidine kinase gene (pSPB-tk under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549 and large cell carcinoma (H460 cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV, a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

Gene Therapy for Human Lung Adenocarcinoma Using a Suicide Gene Driven by a Lung-Specific Promoter Delivered by JC Virus-Like Particles.

Science.gov (United States)

Chao, Chun-Nun; Lin, Mien-Chun; Fang, Chiung-Yao; Chen, Pei-Lain; Chang, Deching; Shen, Cheng-Huang; Wang, Meilin

2016-01-01

Lung adenocarcinoma, the most commonly diagnosed type of lung cancer, has a poor prognosis even with combined surgery, chemotherapy, or molecular targeted therapies. Most patients are diagnosed with an in-operable advanced or metastatic disease, both pointing to the necessity of developing effective therapies for lung adenocarcinoma. Surfactant protein B (SP-B) has been found to be overexpressed in lung adenocarcinoma. In addition, it has also been demonstrated that human lung adenocarcinoma cells are susceptible to the JC polyomavirus (JCPyV) infection. Therefore, we designed that the JCPyV virus-like particle (VLP) packaged with an SP-B promoter-driven thymidine kinase suicide gene (pSPB-tk) for possible gene therapy of human lung adenocarcinoma. Plasmids expressing the GFP (pSPB-gfp) or thymidine kinase gene (pSPB-tk) under the control of the human SP-B promoter were constructed. The promoter's tissue specificity was tested by transfection of pSPB-gfp into A549, CH27, and H460 human lung carcinoma cells and non-lung cells. The JCPyV VLP's gene transfer efficiency and the selective cytotoxicity of pSPB-tk combined with ganciclovir (GCV) were tested in vitro and in a xenograft mouse model. In the current study, we found that SP-B promoter-driven GFP was specifically expressed in human lung adenocarcinoma (A549) and large cell carcinoma (H460) cells. JCPyV VLPs were able to deliver a GFP reporter gene into A549 cells for expression. Selective cytotoxicity was observed in A549 but not non-lung cells that were transfected with pSPB-tk or infected with pSPB-tk-carrying JCPyV VLPs. In mice injected with pSPB-tk-carrying JCPyV VLPs through the tail vein and treated with ganciclovir (GCV), a potent 80% inhibition of growth of human lung adenocarcinoma nodules resulted. The JCPyV VLPs combined with the use of SP-B promoter demonstrates effectiveness as a potential gene therapy against human lung adenocarcinoma.

Risk factors for human immunodeficiency virus among blood donors in Cameroon: evidence for the design of an Africa-specific donor history questionnaire.

Science.gov (United States)

Tagny, Claude T; Nguefack-Tsague, Georges; Fopa, Diderot; Ashu, Celestin; Tante, Estel; Ngo Balogog, Pauline; Donfack, Olivier; Mbanya, Dora; Laperche, Syria; Murphy, Edward

2017-08-01

In sub-Saharan Africa improving the deferral of at-risk blood donors would be a cost-effective approach to reducing transfusion-transmitted human immunodeficiency virus (HIV) infections. We performed a pilot case-control study to identify the risk factors for HIV infection and to develop an adapted donor history questionnaire (DHQ) for sub-Saharan Africa. We recruited 137 HIV-positive donors (cases) and 256 HIV-negative donors (controls) and gathered risk factor data using audio computer-assisted self-interview. Variables with univariate associations were entered into a logistic regression model to assess independent associations. A scoring scheme to distinguish between HIV-positive and HIV-negative donors was developed using receiver operating characteristics curves. We identified 16 risk factors including sex with sex worker, past history or treatment for sexually transmitted infections, and having a partner who used injected or noninjected illegal drugs. Two novel risks were related to local behavior: polygamy (odds ratio [OR], 22.7; 95% confidence interval [CI], 5.9-86.7) and medical or grooming treatment on the street (OR, 1.8; 95% CI, 1.0-3.0). Using the 16 selected items the mean scores (>100) were 82.6 ± 6.7 (range, 53.2-95.1) and 85.1 ± 5.2 for HIV-negative donors versus 77.9 ± 6.8 for HIV-positive ones (p = 0.000). Donors who scored between 80 and 90 were more likely to be HIV negative than those who scored less (OR, 31.4; 95% CI, 3.1-313.9). We identified both typical and novel HIV risk factors among Cameroonian blood donors. An adapted DHQ and score that discriminate HIV-negative donors may be an inexpensive means of reducing transfusion-transmitted HIV through predonation screening. © 2017 AABB.

[Role of donor human milk feeding in preventing nosocomial infection in very low birth weight infants].

Science.gov (United States)

Bi, Hong-Juan; Xu, Jing; Wei, Qiu-Fen

2018-02-01

To investigate the role of donor human milk in the prevention of nosocomial infection in very low birth weight infants. MeETHODS: A total of 105 hospitalized preterm infants with a very low birth weight were enrolled. They were classified into mother's own milk feeding group, donor human milk feeding group, and preterm formula feeding group, with 35 infants in each group. The three groups were compared in terms of incidence rates of nosocomial infection, necrotizing enterocolitis, and feeding intolerance, time to full enteral feeding, and early growth indices. Compared with the preterm formula feeding group, the donor human milk feeding group and the mother's own milk feeding group had significantly lower incidence rates of nosocomial infection and necrotizing enterocolitis and shorter time to full enteral feeding (Pmilk can be used in case of a lack of mother's own milk and may help to reduce nosocomial infection.

Zn-K edge EXAFS study of human nails

Energy Technology Data Exchange (ETDEWEB)

Katsikini, M; Mavromati, E; Pinakidou, F; Paloura, E C [School of Physics, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece); Gioulekas, D, E-mail: katsiki@auth.g [Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki (Greece)

2009-11-15

Extended X-ray absorption fine structure (EXAFS) spectroscopy at the Zn - K edge is applied for the study of the bonding geometry of Zn in human nails. The studied nail clippings belong to healthy donors and donors who suffer from lung diseases. Fitting of the first nearest neighboring shell of Zn reveals that it is bonded with N and S, at distances that take values in the ranges 2.00-2.04 A and 2.23-2.28A, respectively. Zn is four - fold coordinated and the ratio of the number of sulfur and nitrogen atoms (N{sub S}/N{sub N}) in the first coordination shell ranges from 0.52 to 1. The sample that belongs to the donor who suffers from lung fibrosis, a condition that is related to keratinization of the lung tissue, is characterized by the highest number of N{sub S}/N{sub N}. Simulation, using the FEFF8 code, of the Zn - K edge EXAFS spectra with models of tetrahedrally coordinated Zn with 1 (or 2) cysteine and 3 (or 2) histidines is satisfactory.

Comparison of monocyte-derived dendritic cells from colorectal cancer patients, non-small-cell-lung-cancer patients and healthy donors

DEFF Research Database (Denmark)

Kvistborg, P; Bechmann, C M; Pedersen, A W

2009-01-01

Dendritic cells (DCs) are bone marrow-derived professional antigen presenting cells. Due to their role as potent inducers of immune responses, these cells are widely used as adjuvant in experimental clinical settings for cancer immune therapy. We have developed a DC-based vaccine using autologous......-small-cell-lung-cancer (NSCLC). In the present paper we retrospectively compare the maturation profile based on surface marker expression on DCs generated from the three patient cohorts and between cancer patient cohorts and a cohort of healthy donors. Vaccines were generated under cGMP conditions and phenotypic profiles of DC...

An Adoptive Mother Who Became a Human Milk Donor.

Science.gov (United States)

Flores-Antón, Beatriz; García-Lara, Nadia Raquel; Pallás-Alonso, Carmen Rosa

2017-05-01

Inducing lactation in the absence of pregnancy (nonpuerperal lactation) is not always successful and, in many cases, only partial breastfeeding is achieved. Different protocols have been described, but scientific evidence and research are lacking in this area. The authors describe the case of a woman with a history of a miscarriage, for whom the lactation induction process was so effective that she became a milk donor even before she received her adopted child. She had not previously used hormone treatment. She was given domperidone as a galactogogue for 1 month. The pumping protocol began with a double electric breast pump combined with manual pumping 6 months before her child was delivered, and 3 months later, she was accepted as a donor by our milk bank. This highlights the importance of regular stimulation as a milk production mechanism. This is the first case of human milk donation in an adoptive mother described in the literature.

State of the Art in Pediatric Lung Transplantation.

Science.gov (United States)

Lancaster, Timothy S; Eghtesady, Pirooz

2018-04-24

Pediatric lung transplantation is a highly specialized therapy for end stage pulmonary disease in children, performed in only a handful of transplant centers around the world. Advancement in the field has been made on many fronts in recent years, including in public policy and organ allocation strategies, donor selection and management, emerging technologies for donor lung rehabilitation and bridge-to-transplant support of listed candidates, and ongoing refinement of surgical techniques. Despite this progress, children continue to suffer discrepant waitlist mortality and longer waiting times than their adult counterparts, and face special challenges of donor availability and size matching. Here we review the current state of the art in pediatric lung transplantation, reviewing progress made to date and further opportunities to improve care for this unique group of patients. Copyright © 2018 Elsevier Inc. All rights reserved.

Radiation-Induced Differentiation in Human Lung Fibroblast

International Nuclear Information System (INIS)

Park, Sa-Rah; Ahn, Ji-Yeon; Han, Young-Soo; Shim, Jie-Young; Yun, Yeon-Sook; Song, Jie-Young

2007-01-01

One of the most common tumors in many countries is lung cancer and patients with lung cancer may take radiotherapy. Although radiotherapy may have its own advantages, it can also induce serious problems such as acute radiation pneumonitis and pulmonary fibrosis. Pulmonary fibrosis is characterized by excessive production of α-SMA and accumulation of extracellular matrix (ECM) such as collagen and fibronectin. There has been a great amount of research about fibrosis but the exact mechanism causing the reaction is not elucidated especially in radiation-induced fibrosis. Until now it has been known that several factors such as transforming growth factor (TGF-β), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) are related to fibrosis. Among them TGF-β with Smad signaling is known to be the main stream and other signaling molecules such as MAPK, ERK and JNK (3) also participates in the process. In addition to those above factors, it is thought that more diverse and complicate mechanisms may involve in the radiationinduced fibrosis. Therefore, to investigate the underlying mechanisms in radiation induced fibrosis, first of all, we confirmed whether radiation induces trans differentiation in human normal lung fibroblasts. Here, we suggest that not only TGF-β but also radiation can induce trans differentiation in human lung fibroblast WI-38 and IMR-90

Knowledge, attitude, and beliefs of young, college student blood donors about Human immunodeficiency virus

OpenAIRE

Dubey, Anju; Sonker, Atul; Chaudhary, Rajendra K.

2014-01-01

Introduction: Young people, who tend to be healthy, idealistic, and motivated, are an excellent pool of potential voluntary unpaid blood donors. Recruiting and retaining young blood donors improves the long term safety and sufficiency of a country′s blood supply. Knowledge, attitude, and beliefs about Human immunodeficiency virus (HIV) should play an important role in prevention of disease transmission. Materials and Methods: This study was a questionnaire based survey, conducted to explore t...

Norovirus-specific memory T cell responses in adult human donors

Directory of Open Access Journals (Sweden)

Maria Malm

2016-10-01

Full Text Available Norovirus (NoV is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV specific serum antibodies which block the binding of NoV virus-like particles (VLPs to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney, and GI.3, and IFN-g production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539 amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-g in response to the peptides and five subjects produced IFN-g in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151 was identified in two subjects, both having human leukocyte antigen (HLA-A*02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.

Donor age of human platelet lysate affects proliferation and differentiation of mesenchymal stem cells.

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Michael Lohmann

Full Text Available The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS or other serum supplements such as human platelet lysate (HPL. In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1, but it was significantly higher with HPLs from younger donors (45 years. Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal. HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1 or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3 were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation.

Donor Age of Human Platelet Lysate Affects Proliferation and Differentiation of Mesenchymal Stem Cells

Science.gov (United States)

Lohmann, Michael; Walenda, Gudrun; Hemeda, Hatim; Joussen, Sylvia; Drescher, Wolf; Jockenhoevel, Stefan; Hutschenreuter, Gabriele; Zenke, Martin; Wagner, Wolfgang

2012-01-01

The regenerative potential declines upon aging. This might be due to cell-intrinsic changes in stem and progenitor cells or to influences by the microenvironment. Mesenchymal stem cells (MSC) raise high hopes in regenerative medicine. They are usually culture expanded in media with fetal calf serum (FCS) or other serum supplements such as human platelet lysate (HPL). In this study, we have analyzed the impact of HPL-donor age on culture expansion. 31 single donor derived HPLs (25 to 57 years old) were simultaneously compared for culture of MSC. Proliferation of MSC did not reveal a clear association with platelet counts of HPL donors or growth factors concentrations (PDGF-AB, TGF-β1, bFGF, or IGF-1), but it was significantly higher with HPLs from younger donors (45 years). Furthermore, HPLs from older donors increased activity of senescence-associated beta-galactosidase (SA-βgal). HPL-donor age did not affect the fibroblastoid colony-forming unit (CFU-f) frequency, immunophenotype or induction of adipogenic differentiation, whereas osteogenic differentiation was significantly lower with HPLs from older donors. Concentrations of various growth factors (PDGF-AB, TGF-β1, bFGF, IGF-1) or hormones (estradiol, parathormone, leptin, 1,25 vitamin D3) were not associated with HPL-donor age or MSC growth. Taken together, our data support the notion that aging is associated with systemic feedback mechanisms acting on stem and progenitor cells, and this is also relevant for serum supplements in cell culture: HPLs derived from younger donors facilitate enhanced expansion and more pronounced osteogenic differentiation. PMID:22662236

First clinical evaluation of radioimmunoimaging using anti-human lung cancer monoclonal antibodies

International Nuclear Information System (INIS)

Zhou Qian

1991-01-01

Anti-human large cell lung cancer monoclonal antibodies (McAb) 2E3 and 6D1 were produced in the laboratory. Immunohistochemical studies and radiobinding assay showed these antibodies possessed high specificity against lung cancer cells. 28 patients with lung masses were investigated with 131 I-labeled McAb 6D1 and/or 2E3 scintigraphy. 19 of them were histologically proven and 13 were diagnosed primary lung carcinoma. Radioimmunoimaging visualized 10/13 of the primary lung cancers with a detection rate of 77%. Only 1 case of the non-cancer patients and a false localization, giving a true negative rate of 83%. Pathologically the squamous cell lung carcinoma had the highest localization and the small cell lung carcinoma next, but the detection rate was 100% for both. The adenocarcinoma of lung was less sensitive to these McAbs, with a detection rate of only 33% (1 of 3 cases). We conclude that radioimmunoimaging with anti-human large cell lung cancer McAbs is more specific and effective in detecting primary lung cancers and differentiating lung masses than with antibodies against other tumor associated antigens

Diffusion on Networks and Diffusion Weighted NMR of the Human Lung

DEFF Research Database (Denmark)

Buhl, Niels

2011-01-01

of the diffusion propagator to general properties of the underlying graph. Diffusion weighted NMR of the human lung with hyperpolarized noble gases, which over the last decade has been demonstrated to be a very promising way of detecting and quantifying lung diseases like emphysema, represent an obvious...... application of the above mentioned theory, given that the human lung consists of a large network of bifurcating tube like airways. 90-95% of the gas in a human lung resides in the ~30000 pulmonary acini, each of these consists of ~500 airways, which are connected as the edges in a binary tree. We model...... diffusion in the pulmonary acini as diffusion on metric graphs with this structure. The metric graph for each individual pulmonary acinus is embedded in three dimensional space via line segments. By considering an isotropic distribution of acini and a symmetric branching geometry for the line segments...

Lactational Stage of Pasteurized Human Donor Milk Contributes to Nutrient Limitations for Infants

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Christina J. Valentine

2017-03-01

Full Text Available Background. Mother’s own milk is the first choice for feeding preterm infants, but when not available, pasteurized human donor milk (PDM is often used. Infants fed PDM have difficulties maintaining appropriate growth velocities. To assess the most basic elements of nutrition, we tested the hypotheses that fatty acid and amino acid composition of PDM is highly variable and standard pooling practices attenuate variability; however, total nutrients may be limiting without supplementation due to late lactational stage of the milk. Methods. A prospective cross-sectional sampling of milk was obtained from five donor milk banks located in Ohio, Michigan, Colorado, Texas-Ft Worth, and California. Milk samples were collected after Institutional Review Board (#07-0035 approval and informed consent. Fatty acid and amino acid contents were measured in milk from individual donors and donor pools (pooled per Human Milk Banking Association of North America guidelines. Statistical comparisons were performed using Kruskal–Wallis, Spearman’s, or Multivariate Regression analyses with center as the fixed factor and lactational stage as co-variate. Results. Ten of the fourteen fatty acids and seventeen of the nineteen amino acids analyzed differed across Banks in the individual milk samples. Pooling minimized these differences in amino acid and fatty acid contents. Concentrations of lysine and docosahexaenoic acid (DHA were not different across Banks, but concentrations were low compared to recommended levels. Conclusions. Individual donor milk fatty acid and amino acid contents are highly variable. Standardized pooling practice reduces this variability. Lysine and DHA concentrations were consistently low across geographic regions in North America due to lactational stage of the milk, and thus not adequately addressed by pooling. Targeted supplementation is needed to optimize PDM, especially for the preterm or volume restricted infant.

A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death.

Science.gov (United States)

van Suylen, V; Luijk, B; Hoek, R A S; van de Graaf, E A; Verschuuren, E A; Van De Wauwer, C; Bekkers, J A; Meijer, R C A; van der Bij, W; Erasmus, M E

2017-10-01

The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the initial standard use of donation after brain death (DBD) lungs. From the three lung transplant centers in the Netherlands, 130 DCD3 recipients were one-to-one nearest neighbor propensity score matched with 130 DBD recipients. The primary end points were primary graft dysfunction (PGD), posttransplant lung function, freedom from chronic lung allograft dysfunction (CLAD), and overall survival. PGD did not differ between the groups. Posttransplant lung function was comparable after bilateral lung transplantation, but seemed worse after DCD3 single lung transplantation. The incidence of CLAD (p = 0.17) nor the freedom from CLAD (p = 0.36) nor the overall survival (p = 0.40) were significantly different between both groups. The presented multicenter results are derived from a national context where one third of the lung transplantations are performed with DCD3 lungs. We conclude that the long-term outcome after lung transplantation with DCD3 donors is similar to that of DBD donors and that DCD3 donation can substantially enlarge the donor pool. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Donor leucocyte imaging in patients with AIDS: A preliminary report

International Nuclear Information System (INIS)

O'Doherty, M.J.; Kent and Canterbury Hospital; Revell, P.; Page, C.J.; Nunan, T.O.; Lee, S.; Mountford, P.J.

1990-01-01

Four patients with the acquired immunodeficiency syndrome (AIDS) and fever were investigated using donor leucocyte scans. The lung/liver and lung/spleen uptake ratios in these patients were compared with the uptake ratios in donor leucocyte scans in seven neutropenic (non-AIDS) patients and five patients who had autologous leucocyte scans performed over the same time period. All scans used indium oxine In 111 labelled leucocytes except that for one AIDS patient which used technetium hexamethyl-propylene amine oxide Tc99m labelled donor leucocytes. There were no adverse reactions to the donor cell infusions. Two patients had repeat studies 8 weeks apart (from different donors) without ill effect. There were no differences in the 111 In uptake ratios between the three groups. There were three positive studies in the patients with AIDS, and these elucidated the cause of the pyrexia in all three. The negative case is more difficult to confirm, but the clinical course and the absence of focal disease on post-mortem have been taken to support the scan findings. There was no difference in the acceptibility of the technique or the distribution of the labelled leucocytes between the AIDS and non-AIDS patients. Donor leucocyte imaging of patients with AIDS is probably more effective and considerably less hazardous for technical staff than autologous leucocyte methods. This study demonstrates that the technique can be applied successfully to patients with AIDS. (orig.)

Predictive equations for lung volumes from computed tomography for size matching in pulmonary transplantation.

Science.gov (United States)

Konheim, Jeremy A; Kon, Zachary N; Pasrija, Chetan; Luo, Qingyang; Sanchez, Pablo G; Garcia, Jose P; Griffith, Bartley P; Jeudy, Jean

2016-04-01

Size matching for lung transplantation is widely accomplished using height comparisons between donors and recipients. This gross approximation allows for wide variation in lung size and, potentially, size mismatch. Three-dimensional computed tomography (3D-CT) volumetry comparisons could offer more accurate size matching. Although recipient CT scans are universally available, donor CT scans are rarely performed. Therefore, predicted donor lung volumes could be used for comparison to measured recipient lung volumes, but no such predictive equations exist. We aimed to use 3D-CT volumetry measurements from a normal patient population to generate equations for predicted total lung volume (pTLV), predicted right lung volume (pRLV), and predicted left lung volume (pLLV), for size-matching purposes. Chest CT scans of 400 normal patients were retrospectively evaluated. 3D-CT volumetry was performed to measure total lung volume, right lung volume, and left lung volume of each patient, and predictive equations were generated. The fitted model was tested in a separate group of 100 patients. The model was externally validated by comparison of total lung volume with total lung capacity from pulmonary function tests in a subset of those patients. Age, gender, height, and race were independent predictors of lung volume. In the test group, there were strong linear correlations between predicted and actual lung volumes measured by 3D-CT volumetry for pTLV (r = 0.72), pRLV (r = 0.72), and pLLV (r = 0.69). A strong linear correlation was also observed when comparing pTLV and total lung capacity (r = 0.82). We successfully created a predictive model for pTLV, pRLV, and pLLV. These may serve as reference standards and predict donor lung volume for size matching in lung transplantation. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Donor-Derived Regulatory Dendritic Cell Infusion Maintains Donor-Reactive CD4+CTLA4hi T Cells in Non-Human Primate Renal Allograft Recipients Treated with CD28 Co-Stimulation Blockade

OpenAIRE

Mohamed B. Ezzelarab; Lien Lu; William F. Shufesky; Adrian E. Morelli; Adrian E. Morelli; Angus W. Thomson; Angus W. Thomson

2018-01-01

Donor-derived regulatory dendritic cell (DCreg) infusion before transplantation, significantly prolongs renal allograft survival in non-human primates. This is associated with enhanced expression of the immunoregulatory molecules cytotoxic T-lymphocyte-associated antigen (Ag) 4 (CTLA4) and programmed cell death protein 1 (PD1) by host donor-reactive T cells. In rodents and humans, CD28 co-stimulatory pathway blockade with the fusion protein CTLA4:Ig (CTLA4Ig) is associated with reduced differ...

Lung Cancer and Human Papilloma Viruses (HPVs: Examining the Molecular Evidence

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Priya R. Prabhu

2012-01-01

Full Text Available Human papilloma virus (HPV, known to be an etiological agent for genital cancers, has been suggested also to be a possible contributory agent for lung cancer. Alternatively, lung cancer, formerly considered to be solely a smoker's disease, may now be more appropriately categorised into never smoker's and smoker's lung cancer. Through this paper we attempt to bring forth the current knowledge regarding mechanisms of HPV gaining access into the lung tissue, various strategies involved in HPV-associated tumorigenesis in lung tissue.

Human pericytes adopt myofibroblast properties in the microenvironment of the IPF lung.

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Sava, Parid; Ramanathan, Anand; Dobronyi, Amelia; Peng, Xueyan; Sun, Huanxing; Ledesma-Mendoza, Adrian; Herzog, Erica L; Gonzalez, Anjelica L

2017-12-21

Idiopathic pulmonary fibrosis (IPF) is a fatal disease of unknown etiology characterized by a compositionally and mechanically altered extracellular matrix. Poor understanding of the origin of α-smooth muscle actin (α-SMA) expressing myofibroblasts has hindered curative therapies. Though proposed as a source of myofibroblasts in mammalian tissues, identification of microvascular pericytes (PC) as contributors to α-SMA-expressing populations in human IPF and the mechanisms driving this accumulation remain unexplored. Here, we demonstrate enhanced detection of α-SMA+ cells coexpressing the PC marker neural/glial antigen 2 in the human IPF lung. Isolated human PC cultured on decellularized IPF lung matrices adopt expression of α-SMA, demonstrating that these cells undergo phenotypic transition in response to direct contact with the extracellular matrix (ECM) of the fibrotic human lung. Using potentially novel human lung-conjugated hydrogels with tunable mechanical properties, we decoupled PC responses to matrix composition and stiffness to show that α-SMA+ PC accumulate in a mechanosensitive manner independent of matrix composition. PC activated with TGF-β1 remodel the normal lung matrix, increasing tissue stiffness to facilitate the emergence of α-SMA+ PC via MKL-1/MTRFA mechanotranduction. Nintedanib, a tyrosine-kinase inhibitor approved for IPF treatment, restores the elastic modulus of fibrotic lung matrices to reverse the α-SMA+ phenotype. This work furthers our understanding of the role that microvascular PC play in the evolution of IPF, describes the creation of an ex vivo platform that advances the study of fibrosis, and presents a potentially novel mode of action for a commonly used antifibrotic therapy that has great relevance for human disease.

Prevalence of human T-lymphotropic virus type I and type II antibody among blood donors in Eastern Saudi Arabia.

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Ul-Hassan, Zahoor; Al-Bahrani, Ahmad T; Panhotra, Bodh R

2004-10-01

Human T-cell leukemia/lymphoma virus type I and type II (HTLV-I/II) infections can be transfusion associated, leading to tropical paraparesis, myelopathy and other neurological disorders. The aim of this study is to circumvent the risk of transmission through blood transfusion and to describe the prevalence of HTLV-I/II antibody among blood donors of Al-Hasa region and the cost effectiveness of screening blood donors. The study was conducted at the Department of Laboratory and Blood Bank, King Fahad Hospital, Al-Hofuf, Al-Hasa, Kingdom of Saudi Arabia during the period of 1997 to 2003. A total of 47426 blood donors were screened for HTLV-I/II antibody by enzyme-linked immunosorbent assay test, during the 7 years of study period. The positive samples were confirmed by western blot analysis. Overall, HTLV-I antibody positivity (confirmed by western blot) was 3/47426 (0.006%). Out of 3 donors positive for HTLV-I antibody during 1997 to 1998, 2 were expatriates (Indian) and one was native Saudi donor. Human T-cell leukemia/lymphoma virus type I antibody positivity among the native Saudi donors was 1/47426 (0.002%) (2/100000 blood donors). None of the donor were positive for HTLV-II antibody. During the last 5 consecutive years of the study period (1999-2003), none of the donor was positive for HTLV-I/II antibody. Al-Hasa region is non-endemic for HTLV-I/II virus infections. Screening of native Saudi blood donors for these viruses does not appear to be cost effective.

Explant culture of human peripheral lung. I. Metabolism of benzo[alpha]pyrene

DEFF Research Database (Denmark)

Stoner, G.D.; Harris, C.C.; Autrup, Herman

1978-01-01

the predominant alveolar epithelial cell type. Lamellar inclusion bodies were released from the type 2 cells and accumulated in the alveolar spaces. The metabolism of benzo[alpha]pyrene (BP) in human lung explants cultured for up to 7 days was investigated. Human lung explants had measurable aryl hydrocarbon......Human lung explants have been maintained in vitro for a period of 25 days. Autoradiographic studies indicated that the broncholar epithelial cells, type 2 alveolar epithelial cells, and stromal fibroblasts incorporated 3H-thymidine during the culture. After 7 to 10 days, type 2 cells were...... hydroxylase activity and could metabolize BP into forms that were bound to cellular DNA and protein. Peripheral lung had significantly lower aryl hydrocarbon hydroxylase activity than cultured bronchus but both tissues had similar binding levels of BP to DNA. Radioautographic studies indicated that all cell...

Prisoners as Living Donors: A Vulnerabilities Analysis.

Science.gov (United States)

Ross, Lainie Friedman; Thistlethwaite, J Richard

2018-01-01

Although national guidelines exist for evaluating the eligibility of potential living donors and for procuring their informed consent, no special protections or considerations exist for potential living donors who are incarcerated. Human research subject protections in the United States are codified in the Federal Regulations, 45 CFR 46, and special protections are given to prisoners. Living donor transplantation has parallels with human subject research in that both activities are performed with the primary goal of benefiting third parties. In this article, we describe what special considerations should be provided to prisoners as potential living donors using a vulnerabilities approach adapted from the human research subject protection literature.

Human immunodeficiency virus/human parvovirus B19 co-infection in blood donors and AIDS patients in Sichuan, China

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He, Miao; Zhu, Jiang; Yin, Huimin; Ke, Ling; Gao, Lei; Pan, Zhihong; Yang, Xiuhua; Li, Wuping

2012-01-01

Background Human parvovirus B19 (B19) is a common pathogen which causes a variety of diseases. Persistent B19 infection is related to the degree of host immunodeficiency in patients with human immunodeficiency virus (HIV) infection. However, the existence, loading, virus evolution and distribution of B19 in Chinese HIV-positive patients have not been determined. Materials and methods. We investigated 573 HIV-positive blood donors and AIDS patients in Sichuan, China in the last two decades. Bl9-specific serology and quantitative polymerase chain reaction were used to determine the prevalence of B19/HIV co-infection. Viral genome fragments were subjected to phylogeny and haplotype analysis. Results B19 genomic DNA was found in 26 of 573 (4.5%) HIV-positive individuals, a higher prevalence than in blood donors. DNA levels ranged from 5.3×102–1.1×105 copies/mL. The seroprevalence of IgG was significantly lower in HIV-positive samples than in HIV-negative blood donors, indicating deficient production of B19-specific IgG in the former. The B19 isolates were genotype-1 subtype B19-1A which formed a monophyletic group; seven distinct haplotypes were discovered with 60% of the B19/HIV co-infected variants sharing one central haplotype. Discussion. This study on the prevalence, phylogeny and distribution of human parvovirus B19 in Sichuan, China, demonstrates the persistence of B19 in the circulation of both immunocompetent and immunocompromised subjects, with implications for blood safety. PMID:22790259

Transmission of Angiosarcomas From a Common Multiorgan Donor to Four Transplant Recipients

DEFF Research Database (Denmark)

Thoning, J; Liu, Ying; Bistrup, C

2013-01-01

We describe the donor tumor transmission of metastatic angiosarcomas to four transplant recipients through transplantation of deceased-donor organs, i.e. kidneys, lung and liver, from an apparently unaffected common female multiorgan donor. Fluorescent in situ hybridization of angiosarcoma cells...... confirmed that the tumor was of female donor's origin in male kidney recipients. Recent literature associated increased urokinase-plasminogen-activator-receptor (uPAR) and plasma soluble urokinase-plasminogen-activator-receptor (suPAR) levels with metastatic malignancies. Now we found that, compared...... to baseline levels, both deceased-donor kidney recipients showed increased uPAR transcripts in mononuclear cells as well as increased plasma suPAR levels after the diagnosis of metastatic angiosarcomas, i.e. 4 months after donor tumor transmission. These results show an association of uPAR/suPAR in donor...

Profile of Heart Donors from the Human Valve Bank of the Santa Casa de Misericórdia de Curitiba.

Science.gov (United States)

Ferreira, Renata Maria; da Costa, Marise Teresinha Brenner Affonso; Canciglieri Junior, Osiris; Sant'Anna, Ângelo Márcio Oliveira

2016-04-01

Human heart valves are used as replacement valves and have satisfactory functional results compared with conventional prostheses. Characterize the profile of effective heart donors from the human valve bank of the santa casa de misericórdia de curitiba and analyze the association between the profile variables. It consists of a retrospective and quantitative study of electronic medical records from heart donors for heart valves. every heart donation made to the bank between january 2004 and december 2014 was studied. 2,149 donations were analyzed, from donors aged 0 to 71 years old, with an average of 34.9 ± 15.03 years old. most donors were male 65.7% (n=1,411) and 34.3% (n=738) were female. among the most frequent causes of the donors' death are trauma at 53% (n=1,139) and cerebral vascular accident at 34.2% (n=735). there was significant statistical association between the analyzed variables. There has been an improvement in brazil's donation rate, being essential that the tissue banks work together with the state and federal district centers for notification, procurement and distribution of organs in order to increase the number of donors.

Human immunodeficiency virus (HIV) seropositivity and hepatitis B surface antigenemia (HBSAG) among blood donors in Benin city, Edo state, Nigeria.

Science.gov (United States)

Umolu, Patience Idia; Okoror, Lawrence Ehis; Orhue, Philip

2005-03-01

Human Immunodeficiency Virus and Hepatitis B virus are blood borne pathogens that can be transmitted through blood transfusion and could pose a huge problem in areas where mechanisms of ensuring blood safety are suspect. This study became necessary in a population where most of the blood for transfusion is from commercial blood donors. A total of 130 donors comprising 120 commercial donors and 10 voluntary donors were tested for antibodies to human immunodeficiency virus and hepatitis B surface antigen in Benin city using Immunocomb HIV - 1 and 2 Biospot kit and Quimica Clinica Aplicada direct latex agglutination method respectively. Thirteen (10%) samples were HIV seropositive and 7(5.8%) were HBsAg positive. The age bracket 18 - 25years had the highest numbers of donors and also had the highest number of HBsAg positive cases (7.8%) while the age group 29 - 38years had highest number of HIV seropositive cases. High prevalence of HIV antibodies and Hepatitis B surface antigen was found among commercial blood donors. Appropriate and compulsory screening of blood donors using sensitive methods, must be ensured to prevent post transfusion hepatitis and HIV.

Carbonyl Reduction of NNK by Recombinant Human Lung Enzymes. Identification of HSD17β12 as the Reductase important in (R)-NNAL formation in Human Lung.

Science.gov (United States)

Ashmore, Joseph H; Luo, Shaman; Watson, Christy J W; Lazarus, Philip

2018-05-17

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is the most abundant and carcinogenic tobacco-specific nitrosamine in tobacco and tobacco smoke. The major metabolic pathway for NNK is carbonyl reduction to form the (R) and (S) enantiomers of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) which, like NNK, is a potent lung carcinogen. The goal of the present study was to characterize NNAL enantiomer formation in human lung and identify the enzymes responsible for this activity. While (S)-NNAL was the major enantiomer of NNAL formed in incubations with NNK in lung cytosolic fractions, (R)-NNAL comprised ~60 and ~95% of the total NNAL formed in lung whole cell lysates and microsomes, respectively. In studies examining the role of individual recombinant reductase enzymes in lung NNAL enantiomer formation, AKR1C1, AKR1C2, AKR1C3, AKR1C4 and CBR1 all exhibited (S)-NNAL formation activity. To identify the microsomal enzymes responsible for (R)-NNAL formation, 28 microsomal reductase enzymes were screened for expression by real-time PCR in normal human lung. HSD17β6, HSD17β12, KDSR, NSDHL, RDH10, RDH11 and SDR16C5 were all expressed at levels >HSD11β1, the only previously reported microsomal reductase enzyme with NNK-reducing activity, with HSD17β12 the most highly expressed. Of these lung-expressing enzymes, only HSD17β12 exhibited activity against NNK, forming primarily (>95%) (R)-NNAL, a pattern consistent with that observed in lung microsomes. siRNA knockdown of HSD17β12 resulted in significant decreases in (R)-NNAL formation activity in HEK293 cells. These data suggest that both cytosolic and microsomal enzymes are active against NNK and that HSD17β12 is the major active microsomal reductase that contributes to (R)-NNAL formation in human lung.

Human herpesvirus-6A/B binds to spermatozoa acrosome and is the most prevalent herpesvirus in semen from sperm donors

DEFF Research Database (Denmark)

Kaspersen, Maja Døvling; Larsen, Peter B.; Kofod-Olsen, Emil

2012-01-01

An analysis of all known human herpesviruses has not previously been reported on sperm from normal donors. Using an array-based detection method, we determined the cross-sectional frequency of human herpesviruses in semen from 198 Danish sperm donors. Fifty-five of the donors had at least one...... ejaculate that was positive for one or more human herpesvirus. Of these 27.3% (n = 15) had a double herpesvirus infection. If corrected for the presence of multiple ejaculates from some donors, the adjusted frequency of herpesviruses in semen was 27.2% with HSV-1 in 0.4%; HSV-2 in 0.1%; EBV in 6.3%; HCMV...... not necessarily remain positive over time. For the most frequently found herpesvirus, HHV-6A/B, we examined its association with sperm. For HHV-6A/B PCR-positive semen samples, HHV-6A/B could be detected on the sperm by flow cytometry. Conversely, PCR-negative semen samples were negative by flow cytometry. HHV-6B...

Cost and Cost-Effectiveness of Donor Human Milk to Prevent Necrotizing Enterocolitis: Systematic Review.

Science.gov (United States)

Buckle, Abigail; Taylor, Celia

2017-11-01

Necrotizing enterocolitis (NEC) is a costly gastrointestinal disorder that mainly affects preterm and low-birth-weight infants and can lead to considerable morbidity and mortality. Mother's own milk is protective against NEC but is not always available. In such cases, donor human milk has also been shown to be protective (although to a lesser extent) compared with formula milk, but it is more expensive. This systematic review aimed at evaluating the cost of donor milk, the cost of treating NEC, and the cost-effectiveness of exclusive donor milk versus formula milk feeding to reduce the short-term health and treatment costs of NEC. We systematically searched five relevant databases to find studies with verifiable costs or charges of donor milk and/or treatment of NEC and any economic evaluations comparing exclusive donor milk with exclusive formula milk feeding. All search results were double screened. Seven studies with verifiable donor milk costs and 17 with verifiable NEC treatment costs were included. The types of cost or charge included varied considerably across studies, so quantitative synthesis was not attempted. Estimates of the incremental length of stay associated with NEC were ∼18 days for medical NEC and 50 days for surgical NEC. Two studies claimed to report economic evaluations but did not do so in practice. It is likely that donor milk provides short-term cost savings by reducing the incidence of NEC. Future studies should provide more details on cost components included and a full economic evaluation, including long-term outcomes, should be undertaken.

Lung allograft rejection in the rat. I. Accelerated rejection caused by graft lymphocytes

International Nuclear Information System (INIS)

Prop, J.; Nieuwenhuis, P.; Wildevuur, C.R.

1985-01-01

To find out to what extent rejection of lungs differs from that of other organs, functional rejection of lung allografts was studied in five combinations of inbred rat strains. Rejection could be monitored accurately by perfusion scintigraphy, and equally well by chest roentgenography. The rejection of lung grafts was found to proceed remarkably fast, when compared with heart grafts, in combinations with strong RT1-incompatibilities. This accelerated rejection pattern could be converted into rejection at a normal pace by pretreatment of the donor with 10 Gy roentgen irradiation one day before transplantation. Donor pretreatment depleted the lung graft's bronchus-associated lymphoid tissue (BALT) of lymphocytes. When grafts were depleted of all other passenger cells as well--by retransplantation from a cyclosporine-treated intermediate host--they showed an even more reduced immunogenicity, probably because of the loss of donor-type dendritic cells. These results indicate that lymphocytes from the BALT of lung grafts are capable of accelerating the rejection response

Epidermal growth factor receptor in primary human lung cancer

International Nuclear Information System (INIS)

Yu Xueyan; Hu Guoqiang; Tian Keli; Wang Mingyun

1996-01-01

Cell membranes were prepared from 12 human lung cancers for the study of the expression of epidermal growth factor receptors (EGFR). EGFR concentration was estimated by ligand binding studies using 125 I-radiolabeled EGF. The dissociation constants of the high affinity sites were identical, 1.48 nmol and 1.1 nmol in cancer and normal lung tissues, the EGFR contents were higher in lung cancer tissues (range: 2.25 to 19.39 pmol·g -1 membrane protein) than that in normal tissues from the same patients (range: 0.72 to 7.43 pmol·g -1 membrane protein). These results suggest that EGF and its receptor may play a role in the regulatory mechanisms in the control of lung cellular growth and tumor promotion

Evaluation of Fetal Intestinal Cell Growth and Antimicrobial Biofunctionalities of Donor Human Milk After Preparative Processes.

Science.gov (United States)

Kanaprach, Pasinee; Pongsakul, Nutkridta; Apiwattanakul, Nopporn; Muanprasat, Chatchai; Supapannachart, Sarayut; Nuntnarumit, Pracha; Chutipongtanate, Somchai

2018-04-01

Donor human milk is considered the next best nutrition following mother's own milk to prevent neonatal infection and necrotizing enterocolitis in preterm infants who are admitted at neonatal intensive care unit. However, donor milk biofunctionalities after preparative processes have rarely been documented. To evaluate biofunctionalities preserved in donor milk after preparative processes by cell-based assays. Ten pools of donor milk were produced from 40 independent specimens. After preparative processes, including bacterial elimination methods (holder pasteurization and cold-sterilization microfiltration) and storage conditions (-20°C freezing storage and lyophilization) with varied duration of storage (0, 3, and 6, months), donor milk biofunctionalities were examined by fetal intestinal cell growth and antimicrobial assays. At baseline, raw donor milk exhibited 193.1% ± 12.3% of fetal intestinal cell growth and 42.4% ± 11.8% of antimicrobial activities against Escherichia coli. After bacteria eliminating processes, growth promoting activity was better preserved in pasteurized donor milk than microfiltrated donor milk (169.5% ± 14.3% versus 146.0% ± 11.8%, respectively; p pasteurized donor milk was further examined for the effects of storage conditions at 3 and 6 months. Freezing storage, but not lyophilization, could preserve higher growth-promoting activity during 6 months of storage (163.0% ± 9.4% versus 72.8% ± 6.2%, respectively; p < 0.005). Nonetheless, antimicrobial activity was lost at 6 months, regardless of the storage methods. This study revealed that fetal intestinal cell growth and antimicrobial assays could be applied to measure donor milk biofunctionalities and support the utilization of donor milk within 3 months after preparative processes.

KL-6, a human MUC1 mucin, promotes proliferation and survival of lung fibroblasts

International Nuclear Information System (INIS)

Ohshimo, Shinichiro; Yokoyama, Akihito; Hattori, Noboru; Ishikawa, Nobuhisa; Hirasawa, Yutaka; Kohno, Nobuoki

2005-01-01

The serum level of KL-6, a MUC1 mucin, is a clinically useful marker for various interstitial lung diseases. Previous studies demonstrated that KL-6 promotes chemotaxis of human fibroblasts. However, the pathophysiological role of KL-6 remains poorly understood. Here, we further investigate the functional aspects of KL-6 in proliferation and apoptosis of lung fibroblasts. KL-6 accelerated the proliferation and inhibited the apoptosis of all human lung fibroblasts examined. An anti-KL-6 monoclonal antibody counteracted both of these effects induced by KL-6 on human lung fibroblasts. The pro-fibroproliferative and anti-apoptotic effects of KL-6 are greater than and additive to those of the maximum effective concentrations of platelet-derived growth factor, basic fibroblast growth factor, and transforming growth factor-β. These findings indicate that increased levels of KL-6 in the epithelial lining fluid may stimulate fibrotic processes in interstitial lung diseases and raise the possibility of applying an anti-KL-6 antibody to treat interstitial lung diseases

Human umbilical cord derived mesenchymal stem cells promote interleukin-17 production from human peripheral blood mononuclear cells of healthy donors and systemic lupus erythematosus patients.

Science.gov (United States)

Ren, S; Hu, J; Chen, Y; Yuan, T; Hu, H; Li, S

2016-03-01

Inflammation instigated by interleukin (IL)-17-producing cells is central to the development and pathogenesis of several human autoimmune diseases and animal models of autoimmunity. The expansion of IL-17-producing cells from healthy donors is reportedly promoted by mesenchymal stem cells derived from fetal bone marrow. In the present study, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were examined for their effects on lymphocytes from healthy donors and from patients with systemic lupus erythematosus (SLE). Significantly higher levels of IL-17 were produced when CD4(+) T cells from healthy donors were co-cultured with hUC-MSCs than those that were cultured alone. Blocking experiments identified that this effect might be mediated partially through prostaglandin E2 (PGE2 ) and IL-1β, without IL-23 involvement. We then co-cultured hUC-MSCs with human CD4(+) T cells from systemic lupus erythematosus patients. Ex-vivo inductions of IL-17 by hUC-MSCs in stimulated lymphocytes were significantly higher in SLE patients than in healthy donors. This effect was not observed for IL-23. Taken together, our results represent that hUC-MSCs can promote the IL-17 production from CD4(+) T cells in both healthy donor and SLE patients. PGE2 and IL-1β might also be partially involved in the promotive effect of hUC-MSCs. © 2015 British Society for Immunology.

Chronic Exposure to Particulate Nickel Induces Neoplastic Transformation in Human Lung Epithelial Cells

Directory of Open Access Journals (Sweden)

Amie L. Holmes

2013-11-01

Full Text Available Nickel is a well-known human lung carcinogen with the particulate form being the most potent; however, the carcinogenic mechanism remains largely unknown. Few studies have investigated the genotoxicity and carcinogenicity of nickel in its target cell, human bronchial epithelial cells. Thus, the goal of this study was to investigate the effects of particulate nickel in human lung epithelial cells. We found that nickel subsulfide induced concentration- and time-dependent increases in both cytotoxicity and genotoxicity in human lung epithelial cells (BEP2D. Chronic exposure to nickel subsulfide readily induced cellular transformation, inducing 2.55, 2.9 and 2.35 foci per dish after exposure to 1, 2.5 and 5 μg/cm2 nickel subsulfide, respectively. Sixty-one, 100 and 70 percent of the foci isolated from 1, 2.5, and 5 μg/cm2 nickel subsulfide treatments formed colonies in soft agar and the degree of soft agar colony growth increased in a concentration-dependent manner. Thus, chronic exposure to particulate nickel induces genotoxicity and cellular transformation in human lung epithelial cells.

The nutritive and immunoprotective quality of human milk beyond 1 year postpartum: are lactation-duration-based donor exclusions justified?

Science.gov (United States)

Perrin, Maryanne Tigchelaar; Fogleman, April; Allen, Jonathan C

2013-08-01

Donor human milk is critical for the fragile preterm infant who does not have access to his or her mother's milk, improving survival rates and quality of survival and decreasing hospital stay. Despite the opening of donor milk banks around the world, shortages continue as demand for donor milk exceeds supply. One potential means of increasing supply is by reducing exclusion criteria that prohibit mothers from donating milk based on duration of lactation. Minimal research has been done on the composition of human milk during the second year of lactation, with most research focusing on the nutritive compounds and not the immunoprotective compounds. Several immunoprotective compounds, including lysozyme, lactoferrin, secretory immunoglobulin A, and oligosaccharides, are abundant in human milk compared to bovine-based infant formula and are partially or fully retained during Holder pasteurization, making them an important differentiating feature of donor milk. A PubMed search was conducted to review studies in human milk composition during the second year of lactation. Limitations of existing research include sample collection protocols, small study sizes, and use of populations that may have been at risk for nutritional deficiencies. Stable concentrations of several components were reported including protein, lactose, iron, copper, lactoferrin, and secretory immunoglobulin A. Lysozyme concentration increased during extended lactation, while zinc and calcium concentrations declined into the second year. Conflicting findings were reported on fat content, and no information was available regarding oligosaccharide content. More research is needed to create evidence-based guidelines regarding the nutritive and immunoprotective value of donor milk throughout the course of lactation.

Prevalence of human T-cell lymphotropic virus types 1 and 2 in blood donors of the Caruaru Blood Center (Hemope

Directory of Open Access Journals (Sweden)

Waleska Mayara Gomes de Lima

2013-01-01

Full Text Available BACKGROUND: There is difficulty in gathering data on the prevalence of human T-cell lymphotropic virus in blood donors as confirmatory testing is not mandatory in Brazil. This suggests there may be an underreporting of the prevalence. OBJECTIVE: To estimate the prevalence of human T-cell lymphotropic virus types 1 and 2 in donors of a blood bank in Caruaru, Brazil. METHODS: This was an observational, epidemiological, descriptive, longitudinal and retrospective study with information about the serology of donors of the Caruaru Blood Center, Fundação de Hematologia e Hemoterapia de Pernambuco (Hemope from May 2006 to December 2010. The data were analyzed using the Excel 2010 computer program (Microsoft Office(r. RESULTS: Of 61,881 donors, 60 (0.096% individuals were identified as potential carriers of human T-cell lymphotropic virus types 1 and 2. Of these, 28 (0.045% were positive and 32 (0.051% had inconclusive results in the serological screening. Forty-five (0.072% were retested; 17 were positive (0.027% and 3 inconclusive (0.005%. After confirmatory tests, 8 were positive (0.013%. Six (75% of the confirmed cases were women. CONCLUSION: Epidemiological surveys like this are very important in order to create campaigns to attract donors and reduce the costs of laboratory tests.

Early declaration of death by neurologic criteria results in greater organ donor potential.

Science.gov (United States)

Resnick, Shelby; Seamon, Mark J; Holena, Daniel; Pascual, Jose; Reilly, Patrick M; Martin, Niels D

2017-10-01

Aggressive management of patients prior to and after determination of death by neurologic criteria (DNC) is necessary to optimize organ recovery, transplantation, and increase the number of organs transplanted per donor (OTPD). The effects of time management are understudied but potentially pivotal component. The objective of this study was to analyze specific time points (time to DNC, time to procurement) and the time intervals between them to better characterize the optimal timeline of organ donation. Using data over a 5-year time period (2011-2015) from the largest US OPO, all patients with catastrophic brain injury and donated transplantable organs were retrospectively reviewed. Active smokers were excluded. Maximum donor potential was seven organs (heart, lungs [2], kidneys [2], liver, and pancreas). Time from admission to declaration of DNC and donation was calculated. Mean time points stratified by specific organ procurement rates and overall OTPD were compared using unpaired t-test. Of 1719 Declaration of Death by Neurologic Criteria organ donors, 381 were secondary to head trauma. Smokers and organs recovered but not transplanted were excluded leaving 297 patients. Males comprised 78.8%, the mean age was 36.0 (±16.8) years, and 87.6% were treated at a trauma center. Higher donor potential (>4 OTPD) was associated with shorter average times from admission to brain death; 66.6 versus 82.2 hours, P = 0.04. Lung donors were also associated with shorter average times from admission to brain death; 61.6 versus 83.6 hours, P = 0.004. The time interval from DNC to donation varied minimally among groups and did not affect donation rates. A shorter time interval between admission and declaration of DNC was associated with increased OTPD, especially lungs. Further research to identify what role timing plays in the management of the potential organ donor and how that relates to donor management goals is needed. Copyright © 2017 Elsevier Inc. All rights

Experimental studies on lung carcinogenesis and their relationship to future research on radiation-induced lung cancer in humans

International Nuclear Information System (INIS)

Cross, F.T.

1991-03-01

The usefulness of experimental systems for studying human lung carcinogenesis lies in the ease of studying components of a total problem. As an example, the main thrust of attack on possible synergistic interactions between radiation, cigarette smoke, and other irritants must be by means of research on animals. Because animals can be serially sacrificed, a systematic search can be made for progressive lung changes, thereby improving our understanding of carcinogenesis. The mechanisms of radiation-induced carcinogenesis have not yet been delineated, but modern concepts of molecular and cellular biology and of radiation dosimetry are being increasingly applied to both in vivo and in vitro exposure to determine the mechanisms of radiation-induced carcinogenesis, to elucidate human data, and to aid in extrapolating experimental animal data to human exposures. In addition, biologically based mathematical models of carcinogenesis are being developed to describe the nature of the events leading to malignancy; they are also an essential part of a rational approach to quantitative cancer risk assessment. This paper summarizes recent experimental and modeling data on radon-induced lung cancer and includes the confounding effects of cigarette-smoke exposures. The applicability of these data to understanding human exposures is emphasized, and areas of future research on human radiation-induced carcinogenesis are discussed. 7 refs., 2 figs., 3 tabs

4-Methoxyestradiol-induced oxidative injuries in human lung epithelial cells

International Nuclear Information System (INIS)

Cheng Yahsin; Chang, Louis W.; Cheng Lichuan; Tsai, M.-H.; Lin Pinpin

2007-01-01

Epidemiological studies indicated that people exposed to dioxins were prone to the development of lung diseases including lung cancer. Animal studies demonstrated that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) increased liver tumors and promoted lung metaplasia in females. Metabolic changes in 17β-estradiol (E 2 ) resulted from an interaction between TCDD and E 2 could be associated with gender difference. Previously, we reported that methoxylestradiols (MeOE 2 ), especially 4-MeOE 2 , accumulated in human lung cells (BEAS-2B) co-treated with TCDD and E 2 . In the present study, we demonstrate unique accumulation of 4-MeOE 2 , as a result of TCDD/E 2 interaction and revealed its bioactivity in human lung epithelial cell line (H1355). 4-Methoxyestradiol treatment significantly decreased cell growth and increased mitotic index. Elevation of ROS and SOD activity, with a concomitant decrease in the intracellular GSH/GSSG ratio, was also detected in 4-MeOE 2 -treated cells. Quantitative comet assay showed increased oxidative DNA damage in the 4-MeOE 2 -treated H1355 cells, which could be significantly reduced by the anti-oxidant N-acetylcysteine (NAC). However, inhibition of cell growth and increase in mitotic arrest induced by 4-MeOE 2 were unaffected by NAC. We concluded that 4-MeOE 2 accumulation resulting from TCDD and E 2 interaction would contribute to the higher vulnerability on lung pathogenesis in females when exposed to TCDD

Comments on the rat lung as a human surrogate in inhalation studies

International Nuclear Information System (INIS)

Koblinger, L.

1988-01-01

The laboratory rat is often used as a surrogate to estimate the hazard to human health following inhalation exposure to ambient aerosols. Extrapolation of rat deposition data to humans depends, however, on the similarities and differences between the morphometric structures of the two airway systems. The main structural difference between the lungs of the two species, aside from dimensions per se, is their respective airway branching pattern : while the human lung is a rather symmetrically, dichotomously dividing system, the rat network is a more monopodial branching structure. In our stochastic modelling approach to defining suitable morphologies for human and rat lung, we utilise measured morphometric dimensions as the data base upon which a rigorous statistical analysis is performed, instead of forcing them into a formalised, average pathway scheme. This stochastic approach allows us, therefore, to account for structural irregularities, such as asymmetric branching, monopodial structure, and inter and intra-subject variability

Deficient retinoid-driven angiogenesis may contribute to failure of adult human lung regeneration in emphysema.

Science.gov (United States)

Ng-Blichfeldt, John-Poul; Alçada, Joana; Montero, M Angeles; Dean, Charlotte H; Griesenbach, Uta; Griffiths, Mark J; Hind, Matthew

2017-06-01

Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema. The role of RA signalling in alveolar epithelial repair was investigated with a scratch assay using an alveolar cell line (A549) and primary human alveolar type 2 (AT2) cells from resected lung, and the role in angiogenesis using a tube formation assay with human lung microvascular endothelial cells (HLMVEC). Localisation of RA synthetic (RALDH-1) and degrading (cytochrome P450 subfamily 26 A1 (CYP26A1)) enzymes in human lung was determined by immunofluorescence. Regulation of RA pathway components was investigated in emphysematous and control human lung tissue by quantitative real-time PCR and Western analysis. RA stimulated HLMVEC angiogenesis in vitro; this was partially reproduced with a RAR-α agonist. RA induced mRNA expression of vascular endothelial growth factor A (VEGFA) and VEGFR2. RA did not modulate AT2 repair. CYP26A1 protein was identified in human lung microvasculature, whereas RALDH-1 partially co-localised with vimentin-positive fibroblasts. CYP26A1 mRNA and protein were increased in emphysema. RA regulates lung microvascular angiogenesis; the endothelium produces CYP26A1 which is increased in emphysema, possibly leading to reduced RA availability. These data highlight a role for RA in maintenance of the human pulmonary microvascular endothelium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Potent selective nonpeptidic inhibitors of human lung tryptase

OpenAIRE

Burgess, Laurence E.; Newhouse, Bradley J.; Ibrahim, Prabha; Rizzi, James; Kashem, Mohammed A.; Hartman, Ann; Brandhuber, Barbara J.; Wright, Clifford D.; Thomson, David S.; Vigers, Guy P. A.; Koch, Kevin

1999-01-01

Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure–activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting ...

Randomized controlled trial of docosahexaenoic acid supplementation in midwestern U.S. human milk donors.

Science.gov (United States)

Valentine, Christina J; Morrow, Georgia; Pennell, Michael; Morrow, Ardythe L; Hodge, Amanda; Haban-Bartz, Annette; Collins, Kristin; Rogers, Lynette K

2013-02-01

Docosahexaenoic acid (DHA) is a long-chain polyunsaturated fatty acid important for neonatal neurodevelopment and immune homeostasis. Preterm infants fed donor milk from a Midwestern source receive only 20% of the intrauterine accretion of DHA. We tested the hypothesis that DHA supplementation of donor mothers would provide preterm infants with DHA intake equivalent to fetal accretion. After Institutional Review Board approval and informed consent, human milk donors to the Mother's Milk Bank of Ohio were randomized to receive 1 g of DHA (Martek(®) [now DSM Nutritional Lipids, Columbia, MD]) or placebo soy oil. Dietary intake data were collected and analyzed by a registered dietitian. Fatty acids were measured by gas chromatography/flame ionization detection. Statistical analysis used linear mixed models. Twenty-one mothers were randomly assigned to either the DHA group (n=10) or the placebo group (n=11). Donor age was a median of 31 years in both groups with a mean lactational stage of 19 weeks. Dietary intake of DHA at baseline in both groups was a median of 23 mg/day (range, 0-194 mg), significantly (p<0.0001) less than the minimum recommended intake of 200 mg/day. The DHA content of milk increased in the DHA-supplemented group (p<0.05). The women enrolled in this study had low dietary DHA intake. Supplementation with preformed DHA at 1 g/day resulted in increased DHA concentrations in the donor milk with no adverse outcomes. Infants fed donor milk from supplemented women receive dietary DHA levels that closely mimic normal intrauterine accretion during the third trimester.

A Multicenter Study on Long-Term Outcomes After Lung Transplantation Comparing Donation After Circulatory Death and Donation After Brain Death

NARCIS (Netherlands)

van Suylen, Vincent; Luijk, B.; Hoek, R A S; van de Graaf, E. A.; Verschuuren, E A; Van De Wauwer, C; Bekkers, J A; Meijer, R C A; van der Bij, W; Erasmus, M E

2017-01-01

The implementation of donation after circulatory death category 3 (DCD3) was one of the attempts to reduce the gap between supply and demand of donor lungs. In the Netherlands, the total number of potential lung donors was greatly increased by the availability of DCD3 lungs in addition to the

Peer-to-peer milk donors' and recipients' experiences and perceptions of donor milk banks.

Science.gov (United States)

Gribble, Karleen D

2013-07-01

To explore the intersection of peer-to-peer milk sharing and donor milk banks. A descriptive survey design containing closed and open-ended questions was used to examine women's perceptions of peer-to-peer milk sharing and milk banking. Closed-ended questions were analyzed using descriptive statistics and conventional qualitative content analysis was used to analyze open-ended responses. Participants were recruited via the Facebook sites of two online milk-sharing networks (Human Milk 4 Human Babies and Eats on Feet). Ninety-eight milk donors and 41 milk recipients who had donated or received breast milk in an arrangement that was facilitated via the Internet. One half of donor recipients could not donate to a milk bank because there were no banks local to them or they did not qualify as donors. Other respondents did not donate to a milk bank because they viewed the process as difficult, had philosophical objections to milk banking, or had a philosophical attraction to peer sharing. Most donor respondents felt it was important to know the circumstances of their milk recipients. No recipient respondents had obtained milk from a milk bank; it was recognized that they would not qualify for banked milk or that banked milk was cost prohibitive. Peer-to-peer milk donors and recipients may differ from milk bank donors and recipients in significant ways. Cooperation between milk banks and peer sharing networks could benefit both groups. © 2013 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.

Donor-Derived Regulatory Dendritic Cell Infusion Maintains Donor-Reactive CD4+CTLA4hi T Cells in Non-Human Primate Renal Allograft Recipients Treated with CD28 Co-Stimulation Blockade.

Science.gov (United States)

Ezzelarab, Mohamed B; Lu, Lien; Shufesky, William F; Morelli, Adrian E; Thomson, Angus W

2018-01-01

Donor-derived regulatory dendritic cell (DCreg) infusion before transplantation, significantly prolongs renal allograft survival in non-human primates. This is associated with enhanced expression of the immunoregulatory molecules cytotoxic T-lymphocyte-associated antigen (Ag) 4 (CTLA4) and programmed cell death protein 1 (PD1) by host donor-reactive T cells. In rodents and humans, CD28 co-stimulatory pathway blockade with the fusion protein CTLA4:Ig (CTLA4Ig) is associated with reduced differentiation and development of regulatory T cells (Treg). We hypothesized that upregulation of CTLA4 by donor-reactive CD4 + T cells in DCreg-infused recipients treated with CTLA4Ig, might be associated with higher incidences of donor-reactive CD4 + T cells with a Treg phenotype. In normal rhesus monkeys, allo-stimulated CD4 + CTLA4 hi , but not CD4 + CTLA4 med/lo T cells exhibited a regulatory phenotype, irrespective of PD1 expression. CTLA4Ig significantly reduced the incidence of CD4 + CTLA4 hi , but not CD4 + CTLA4 med/lo T cells following allo-stimulation, associated with a significant reduction in the CD4 + CTLA4 hi /CD4 + CTLA4 med/lo T cell ratio. In CTLA4Ig-treated renal allograft recipient monkeys, there was a marked reduction in circulating donor-reactive CD4 + CTLA4 hi T cells. In contrast, in CTLA4Ig-treated monkeys with DCreg infusion, no such reduction was observed. In parallel, the donor-reactive CD4 + CTLA4 hi /CD4 + CTLA4 med/lo T cell ratio was reduced significantly in graft recipients without DCreg infusion, but increased in those given DCreg. These observations suggest that pre-transplant DCreg infusion promotes and maintains donor-reactive CD4 + CTLA4 hi T cells with a regulatory phenotype after transplantation, even in the presence of CD28 co-stimulation blockade.

Quantification of human lung structure and physiology using hyperpolarized 129Xe.

Science.gov (United States)

Chang, Yulin V; Quirk, James D; Ruset, Iulian C; Atkinson, Jeffrey J; Hersman, F William; Woods, Jason C

2014-01-01

To present in vivo, human validation of a previously proposed method to measure key pulmonary parameters related to lung microstructure and physiology. Some parameters, such as blood-air barrier thickness, cannot be measured readily by any other noninvasive modality. Healthy volunteers (n = 12) were studied in 1.5T and 3T whole body human scanners using hyperpolarized xenon. Xenon uptake by lung parenchyma and blood was measured using a chemical shift saturation recovery sequence. Both dissolved-xenon peaks at 197 ppm and 217-218 ppm were fitted against a model of xenon exchange (MOXE) as functions of exchange time. Parameters related to lung function and structure can be obtained by fitting to this model. The following results were obtained from xenon uptake (averaged over all healthy volunteers): surface-area-to-volume ratio = 210 ± 50 cm(-1) ; total septal wall thickness = 9.2 ± 6.5 μm; blood-air barrier thickness = 1.0 ± 0.3 μm; hematocrit = 27 ± 4%; pulmonary capillary blood transit time = 1.3 ± 0.3 s, in good agreement with literature values from invasive experiments. More detailed fitting results are listed in the text. The initial in vivo human results demonstrate that our proposed methods can be used to noninvasively determine lung physiology by simultaneous quantification of a few important pulmonary parameters. This method is highly promising to become a versatile screening method for lung diseases. Copyright © 2013 Wiley Periodicals, Inc.

Mutation and Expression of the DCC Gene in Human Lung Cancer

Directory of Open Access Journals (Sweden)

Takashi Kohno

2000-07-01

Full Text Available Chromosome 18q is frequently deleted in lung cancers, a common region of 18q deletions was mapped to chromosome 18g21. Since the DCC candidate tumor suppressor gene has been mapped in this region, mutation and expression of the DCC gene were examined in 46 lung cancer cell lines, consisting of 14 small cell lung carcinomas (SCLCs and 32 non-small cell lung carcinomas (NSCLCs, to elucidate the pathogenetic significance of DCC alterations in human lung carcinogenesis. A heterozygous missense mutation was detected in a NSCLC cell line, Ma26, while homozygous deletion was not detected in any of the cell lines. The DCC gene was expressed in 11 (24% of the 46 cell lines, the incidence of DCC expression was significantly higher in SCLCs (7/14, 50% than in NSCLCs (4/32, 13% (P = .01, Fisher's exact test. Therefore, genetic alterations of DCC are infrequent; however, the levels of DCC expression vary among lung cancer cells, in particular, between SCLCs and NSCLCs. The present result does not implicate DCC as a specific mutational target of 18q deletions in human lung cancer; however, it suggests that DCC is a potential target of inactivation by genetic defects including intron or promoter mutations and/or epigenetic alterations. The present result also suggests that DCC expression is associated with some properties of SCLCs, such as a neuroendocrine (NE feature.

A 47-Year-Old Man With Fever, Dry Cough, and a Lung Mass After Redo Lung Transplantation.

Science.gov (United States)

Chaddha, Udit; Patil, Pradnya D; Omar, Ashraf; Walia, Rajat; Panchabhai, Tanmay S

2018-06-01

A 47-year-old man who was a redo double lung transplant recipient (cytomegalovirus [CMV] status: donor positive/recipient positive; Epstein-Barr virus status: donor positive/recipient positive) presented to the hospital with 1 week of generalized malaise, low-grade fevers, and dry cough. His redo lung transplantation was necessitated by bronchiolitis obliterans syndrome, and his previous lung transplantation 5 years earlier was for silicosis-related progressive massive fibrosis. He denied any difficulty breathing or chest pain. There was no history of GI or urinary symptoms, and the patient had no anorexia, weight loss, night sweats, sick contacts, or history of travel. He had a history of 1 earlier episode of CMV viremia that was treated with valganciclovir. His immunosuppressive regimen included tacrolimus, mycophenolate mofetil, and prednisone, and his infection prophylaxis included trimethoprim-sulfamethoxazole, itraconazole, and valganciclovir. Results of a chest radiograph 8 weeks earlier were normal. Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

Radiation sensitivity of human lung cancer cell lines

International Nuclear Information System (INIS)

Carmichael, J.; Degraff, W.G.; Gamson, J.; Russo, G.; Mitchell, J.B.; Gazdar, A.F.; Minna, J.D.; Levitt, M.L.

1989-01-01

X-Ray survival curves were determined using a panel of 17 human lung cancer cell lines, with emphasis on non-small cell lung cancer (NSCLC). In contrast to classic small cell lung cancer (SCLC) cell lines, NSCLC cell lines were generally less sensitive to radiation as evidenced by higher radiation survival curve extrapolation numbers, surviving fraction values following a 2Gy dose (SF2) and the mean inactivation dose values (D) values. The spectrum of in vitro radiation responses observed was similar to that expected in clinical practice, although mesothelioma was unexpectedly sensitive in vitro. Differences in radiosensitivity were best distinguished by comparison of SF2 values. Some NSCLC lines were relatively sensitive, and in view of this demonstrable variability in radiation sensitivity, the SF2 value may be useful for in vitro predictive assay testing of clinical specimens. (author)

Donor-recipient human leukocyte antigen matching practices in vascularized composite tissue allotransplantation: a survey of major transplantation centers.

Science.gov (United States)

Ashvetiya, Tamara; Mundinger, Gerhard S; Kukuruga, Debra; Bojovic, Branko; Christy, Michael R; Dorafshar, Amir H; Rodriguez, Eduardo D

2014-07-01

Vascularized composite tissue allotransplant recipients are often highly sensitized to human leukocyte antigens because of multiple prior blood transfusions and other reconstructive operations. The use of peripheral blood obtained from dead donors for crossmatching may be insufficient because of life support measures taken for the donor before donation. No study has been published investigating human leukocyte antigen matching practices in this field. A survey addressing human leukocyte antigen crossmatching methods was generated and sent to 22 vascularized composite tissue allotransplantation centers with active protocols worldwide. Results were compiled by center and compared using two-tailed t tests. Twenty of 22 centers (91 percent) responded to the survey. Peripheral blood was the most commonly reported donor sample for vascularized composite tissue allotransplant crossmatching [78 percent of centers (n=14)], with only 22 percent (n=4) using lymph nodes. However, 56 percent of the 18 centers (n=10) that had performed vascularized composite tissue allotransplantation reported that they harvested lymph nodes for crossmatching. Of responding individuals, 62.5 percent (10 of 16 individuals) felt that lymph nodes were the best donor sample for crossmatching. A slight majority of vascularized composite tissue allotransplant centers that have performed clinical transplants have used lymph nodes for human leukocyte antigen matching, and centers appear to be divided on the utility of lymph node harvest. The use of lymph nodes may offer a number of potential benefits. This study highlights the need for institutional review board-approved crossmatching protocols specific to vascularized composite tissue allotransplantation, and the need for global databases for sharing of vascularized composite tissue allotransplantation experiences.

Viral infection of human lung macrophages increases PDL1 expression via IFNβ.

Directory of Open Access Journals (Sweden)

Karl J Staples

Full Text Available Lung macrophages are an important defence against respiratory viral infection and recent work has demonstrated that influenza-induced macrophage PDL1 expression in the murine lung leads to rapid modulation of CD8+ T cell responses via the PD1 receptor. This PD1/PDL1 pathway may downregulate acute inflammatory responses to prevent tissue damage. The aim of this study was to investigate the mechanisms of PDL1 regulation by human macrophages in response to viral infection. Ex-vivo viral infection models using influenza and RSV were established in human lung explants, isolated lung macrophages and monocyte-derived macrophages (MDM and analysed by flow cytometry and RT-PCR. Incubation of lung explants, lung macrophages and MDM with X31 resulted in mean cellular infection rates of 18%, 18% and 29% respectively. Viral infection significantly increased cell surface expression of PDL1 on explant macrophages, lung macrophages and MDM but not explant epithelial cells. Infected MDM induced IFNγ release from autologous CD8+ T cells, an effect enhanced by PDL1 blockade. We observed increases in PDL1 mRNA and IFNβ mRNA and protein release by MDM in response to influenza infection. Knockdown of IFNβ by siRNA, resulted in a 37.5% reduction in IFNβ gene expression in response to infection, and a significant decrease in PDL1 mRNA. Furthermore, when MDM were incubated with IFNβ, this cytokine caused increased expression of PDL1 mRNA. These data indicate that human macrophage PDL1 expression modulates CD8+ cell IFNγ release in response to virus and that this expression is regulated by autologous IFNβ production.

Low prevalence of antibodies to human T-lymphotropic virus-I/II among blood donors in eastern Saudi Arabia.

Science.gov (United States)

Fawaz, Naglaa A; Tamim, Hala; Almawi, Wassim Y

2005-04-01

The seroprevalence of human T-lymphotropic virus (HTLV)-I/II was assessed in 13,443 consecutive blood donors in eastern Saudi Arabia between 1998 and 2001. Screening by enzyme-linked immunosorbent assay (ELISA) and confirmation by Western blot resulted in 8 (0.060%) positive cases, of which 5 (0.056%) belonged to Saudi and 3 (0.113%) to non-Saudi donors. The majority of the HTLV-positive donations (6/8) were for patients, and none had a history of known risk factor for HTLV-I/II transmission. Although the very low prevalence of HTLV-I/II among Saudi donors does not support routine screening, screening of donors from other nationalities may be initiated, especially those from HTLV-I/II endemic areas.

Blood donations from previously transfused or pregnant donors: a multicenter study to determine the frequency of alloexposure.

Science.gov (United States)

Rios, Jorge A; Schlumpf, Karen S; Kakaiya, Ram M; Triulzi, Darrell J; Roback, John D; Kleinman, Steve H; Murphy, Edward L; Gottschall, Jerome L; Carey, Patricia M

2011-06-01

Transfusion-related acute lung injury (TRALI) mitigation strategies include the deferral of female donors from apheresis platelet (PLT) donations and the distribution of plasma for transfusion from male donors only. We studied the implications of these policies in terms of component loss at six blood centers in the United States. We collected data from allogeneic blood donors making whole blood and blood component donations during calendar years 2006 through 2008. We analyzed the distribution of donations in terms of the sex, transfusion and pregnancy histories, and blood type. A TRALI mitigation policy that would not allow plasma from female whole blood donors to be prepared into transfusable plasma components would result in nearly a 50% reduction in the units of whole blood available for plasma manufacturing and would decrease the number of type AB plasma units that could be made from whole blood donations by the same amount. Deferral of all female apheresis PLT donors, all female apheresis PLT donors with histories of prior pregnancies, or all female apheresis PLT donors with histories of prior pregnancies and positive screening test results for antibodies to human leukocyte antigens (HLAs) will result in a loss of 37.1, 22.5, and 5.4% of all apheresis PLT donations, respectively. A TRALI mitigation policy that only defers female apheresis PLT donors with previous pregnancies and HLAs would result in an approximately 5% decrease in the inventory of apheresis PLTs, but would eliminate a large proportion of components that are associated with TRALI. © 2010 American Association of Blood Banks.

Endostar, a recombined humanized endostatin, enhances the radioresponse for human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts in mice

International Nuclear Information System (INIS)

Wen Qinglian; Meng Maobin; Tu Lingli; Jia Li; Zhou Lin; Xu Yong; Lu You; Yang Bo

2009-01-01

The purpose of this paper is to determine the efficacy of combining radiation therapy with endostar, a recombined humanized endostatin, in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts. Tumor xenografts were established in the hind limb of male athymic nude mice (BALB/c-nu) by subcutaneous transplantation. The tumor-bearing mice were assigned into four treatment groups: sham therapy (control), endostar (20 mg/kg, once daily for 10 days), radiation therapy (6 Gray per day to 30 Gray, once a day for 1 week), and endostar plus radiation therapy (combination). The experiment was repeated and mice were killed at days 3, 6, and 10 after initiation therapy, and the tumor tissues and blood samples were collected to analyze the kinetics of antitumor, antiangiogenesis, and antivascularization responses of different therapies. In human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts, endostar significantly enhanced the effects of tumor growth inhibition, endothelial cell and tumor cell apoptosis induction, and improved tumor cell hypoxia of radiation therapy. Histological analyses demonstrated that endostar plus radiation also induced a significant reduction in microvascular density, microvascular area, and vascular endothelial growth factor and matrix metalloproteinase-2 expression compared with radiation and endostar alone respectively. We concluded that endostar significantly sensitized the function of radiation in antitumor and antiangiogenesis in human nasopharyngeal carcinoma and human lung adenocarcinoma xenografts by increasing the apoptosis of the endothelial cell and tumor cell, improving the hypoxia of the tumor cell, and changing the proangiogenic factors. These data provided a rational basis for clinical practice of this multimodality therapy. (author)

In-vivo counting of 241Am in human lungs and tracheobronchial lymph nodes

International Nuclear Information System (INIS)

Northcutt, A.R.; Binney, S.E.; Palmer, H.E.

1988-01-01

A study was conducted of a human male who had inhaled a mixture of 241 Am and Pu. To distinguish 241 Am deposited in the subject's lungs from translocated activity deposited in the tracheobronchial lymph nodes (TBLN), two intrinsic Ge detectors were collimated with 0.3-cm Pb sheeting. A tissue-equivalent phantom containing either 22.9 kBq (620 nCi) of 241 Am in the lungs or a 81.4 kBq (2200 nCi) 241 Am point source in the TBLN was measured. Calibration curves observed from lateral differential scans on the phantom were compared to data obtained by the same detection system for a human male with a measured lung deposition of 89 Bq (2.4 nCi) of 241 Am. Comparison of the human data to the calibration curves indicated the activity was restricted primarily to the lungs. The calibration curves demonstrate that this method is useful in determining the distribution of inhaled radioactivity between the lungs and TBLN. The measured activity from the male subject generally supported the ICRP Publication 30 model translocation prediction for class Y compounds

Teaching basic lung isolation skills on human anatomy simulator: attainment and retention of lung isolation skills.

Science.gov (United States)

Latif, Rana K; VanHorne, Edgar M; Kandadai, Sunitha Kanchi; Bautista, Alexander F; Neamtu, Aurel; Wadhwa, Anupama; Carter, Mary B; Ziegler, Craig H; Memon, Mohammed Faisal; Akça, Ozan

2016-01-20

Lung isolation skills, such as correct insertion of double lumen endobronchial tube and bronchial blocker, are essential in anesthesia training; however, how to teach novices these skills is underexplored. Our aims were to determine (1) if novices can be trained to a basic proficiency level of lung isolation skills, (2) whether video-didactic and simulation-based trainings are comparable in teaching lung isolation basic skills, and (3) whether novice learners' lung isolation skills decay over time without practice. First, five board certified anesthesiologist with experience of more than 100 successful lung isolations were tested on Human Airway Anatomy Simulator (HAAS) to establish Expert proficiency skill level. Thirty senior medical students, who were naive to bronchoscopy and lung isolation techniques (Novice) were randomized to video-didactic and simulation-based trainings to learn lung isolation skills. Before and after training, Novices' performances were scored for correct placement using pass/fail scoring and a 5-point Global Rating Scale (GRS); and time of insertion was recorded. Fourteen novices were retested 2 months later to assess skill decay. Experts' and novices' double lumen endobronchial tube and bronchial blocker passing rates showed similar success rates after training (P >0.99). There were no differences between the video-didactic and simulation-based methods. Novices' time of insertion decayed within 2 months without practice. Novices could be trained to basic skill proficiency level of lung isolation. Video-didactic and simulation-based methods we utilized were found equally successful in training novices for lung isolation skills. Acquired skills partially decayed without practice.

Genetic Modification of the Lung Directed Toward Treatment of Human Disease.

Science.gov (United States)

Sondhi, Dolan; Stiles, Katie M; De, Bishnu P; Crystal, Ronald G

2017-01-01

Genetic modification therapy is a promising therapeutic strategy for many diseases of the lung intractable to other treatments. Lung gene therapy has been the subject of numerous preclinical animal experiments and human clinical trials, for targets including genetic diseases such as cystic fibrosis and α1-antitrypsin deficiency, complex disorders such as asthma, allergy, and lung cancer, infections such as respiratory syncytial virus (RSV) and Pseudomonas, as well as pulmonary arterial hypertension, transplant rejection, and lung injury. A variety of viral and non-viral vectors have been employed to overcome the many physical barriers to gene transfer imposed by lung anatomy and natural defenses. Beyond the treatment of lung diseases, the lung has the potential to be used as a metabolic factory for generating proteins for delivery to the circulation for treatment of systemic diseases. Although much has been learned through a myriad of experiments about the development of genetic modification of the lung, more work is still needed to improve the delivery vehicles and to overcome challenges such as entry barriers, persistent expression, specific cell targeting, and circumventing host anti-vector responses.

Potent selective nonpeptidic inhibitors of human lung tryptase

Science.gov (United States)

Burgess, Laurence E.; Newhouse, Bradley J.; Ibrahim, Prabha; Rizzi, James; Kashem, Mohammed A.; Hartman, Ann; Brandhuber, Barbara J.; Wright, Clifford D.; Thomson, David S.; Vigers, Guy P. A.; Koch, Kevin

1999-01-01

Human lung tryptase, a homotetrameric serine protease unique to mast cell secretory granules, has been implicated in the pathogenesis of asthma. A hypothesis that tethered symmetrical inhibitors might bridge two adjacent active sites was explored via a rationally designed series of bisbenzamidines. These compounds demonstrated a remarkable distanced-defined structure–activity relationship against human tryptase with one series possessing subnanomolar potencies. Additional evidence supporting the concept of active-site bridging is also presented. PMID:10411878

The cytotoxicity and genotoxicity of soluble and particulate cobalt in human lung fibroblast cells

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Smith, Leah J.; Holmes, Amie L. [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Kandpal, Sanjeev Kumar; Mason, Michael D. [Department of Chemical and Biological Engineering, University of Maine, Orono, ME (United States); Zheng, Tongzhang [Department of Environmental Health Sciences, Yale School of Public Health, New Haven, CT (United States); Wise, John Pierce, E-mail: John.Wise@usm.maine.edu [Wise Laboratory of Environmental and Genetic Toxicology, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Maine Center for Environmental Toxicology and Health, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States); Department of Applied Medical Science, University of Southern Maine, 96 Falmouth St., P.O. Box 9300, Portland, ME 04101-9300 (United States)

2014-08-01

Cobalt exposure is increasing as cobalt demand rises worldwide due to its use in enhancing rechargeable battery efficiency, super-alloys, and magnetic products. Cobalt is considered a possible human carcinogen with the lung being a primary target. However, few studies have considered cobalt-induced toxicity in human lung cells. Therefore, in this study, we sought to determine the cytotoxicity and genotoxicity of particulate and soluble cobalt in human lung cells. Cobalt oxide and cobalt chloride were used as representative particulate and soluble cobalt compounds, respectively. Exposure to both particulate and soluble cobalt induced a concentration-dependent increase in cytotoxicity, genotoxicity, and intracellular cobalt ion levels. Based on intracellular cobalt ion levels, we found that soluble cobalt was more cytotoxic than particulate cobalt while particulate and soluble cobalt induced similar levels of genotoxicity. However, soluble cobalt induced cell cycle arrest indicated by the lack of metaphases at much lower intracellular cobalt concentrations compared to cobalt oxide. Accordingly, we investigated the role of particle internalization in cobalt oxide-induced toxicity and found that particle-cell contact was necessary to induce cytotoxicity and genotoxicity after cobalt exposure. These data indicate that cobalt compounds are cytotoxic and genotoxic to human lung fibroblasts, and solubility plays a key role in cobalt-induced lung toxicity. - Highlights: • Particulate and soluble cobalt are cytotoxic and genotoxic to human lung cells. • Soluble cobalt induces more cytotoxicity compared to particulate cobalt. • Soluble and particulate cobalt induce similar levels of genotoxicity. • Particle-cell contact is required for particulate cobalt-induced toxicity.

Knowledge, attitude, and beliefs of young, college student blood donors about Human immunodeficiency virus.

Science.gov (United States)

Dubey, Anju; Sonker, Atul; Chaudhary, Rajendra K

2014-01-01

Young people, who tend to be healthy, idealistic, and motivated, are an excellent pool of potential voluntary unpaid blood donors. Recruiting and retaining young blood donors improves the long term safety and sufficiency of a country's blood supply. Knowledge, attitude, and beliefs about Human immunodeficiency virus (HIV) should play an important role in prevention of disease transmission. This study was a questionnaire based survey, conducted to explore the levels of knowledge, attitude, and beliefs about HIV in young college student blood donors. The results showed that the proportion of participants with comprehensive knowledge of HIV prevention and transmission was lesser than expected. Increase in education level and male gender was found to be significantly associated with high HIV-related knowledge. The responses on the different aspects of HIV-related attitude were also varied and there is still stigma associated with Acquired Immunodeficiency Syndrome (AIDS) even in the educated groups. There was a spectrum of myths and misperceptions emphasizing the need of education that recognizes the social context of attitude towards HIV. Results from this study may contribute to the development of appropriate educational and training material for this group of donors which in turn, may assist in achieving the elusive goal of safe blood supply in future.

Donor human milk versus mother's own milk in preterm VLBWIs: a case control study.

Science.gov (United States)

Giuliani, F; Prandi, G; Coscia, A; Cresi, F; Di Nicola, P; Raia, M; Sabatino, G; Occhi, L; Bertino, E

2012-01-01

As for term infants, over the past decades there has been increasing evidence of the benefits of human milk in the feeding of Very Low Birth Weight Infants (VLBWI), influencing not only short-term health outcomes but also long-term neurodevelopmental, metabolic outcomes, and growth. Mother's own milk is the first choice for all neonates including preterm infants, when it is unavailable or in short supply, pasteurized donor breast milk offers a safe alternative and is considered the next best choice. The main aim of this case-control retrospective analysis was to evaluate short term advantages of mother's own milk as a sole diet compared to donor milk as a sole diet, in terms of growth, antiinfectious properties, feeding tolerance, NEC and ROP prevention in a population of VLBWI born in a tertiary center. We did not find significant differences in clinical outcome from mother's own milk compared with pasteurized donor milk. Only a slight and statistically not significant difference in growth could be observed, in favour of maternal milk. We conclude that the maximum effort should always be put in supporting and promoting breastfeeding and donor milk used not only as an alternative to mother's milk but also as a breastfeeding promotion and support strategy.

Comparison of seropositivity of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis among Hospital Cornea Retrieval Programme-Donors versus voluntary cornea donors at a large eye bank in Eastern India.

Science.gov (United States)

Basak, Soham; Basak, Samar K; Biswas, Bani

2017-11-01

To compare the serology profile of donors from Hospital Cornea Retrieval Programme-donors (HCRP-D) and voluntary cornea donors (VC-D) from a large eye bank in Eastern India. This is a retrospective analysis of donor details from January 2011 to December 2016. Donor demographics, cause of death, and serology reports were compiled. Postmortem blood was tested for human immunodeficiency virus 1 and 2 (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), and syphilis using government-approved kits as per the National Programme for Control of Blindness Standards of Eye Banking. Donors for whom serology was not possible were excluded. A total of 4300 of 4353 donors were included of which 74.3% were hospital donors and 25.7% were voluntary donors. A total of 93 (2.2%) donors with 94 seropositive reports were noted: 79 (84.9%) from HCRP-D and 14 (15.1%) from VC-D which was statistically significantly higher (P = 0.02). Among seropositive reports, HIV, HBV, HCV, and syphilis accounted for 12 (12.8%), 38 (40.4%), 36 (38.3%), and eight (8.5%), respectively. There was no correlation between the cause of death and seropositivity. A statistically significant decreasing trend in seroprevalence among hospital donors was observed over the years (5.3% in 2011 to 1.4% in 2016; P = 0.004). Two (0.47%) of 421 hospital donors with prior negative serology were found to be seropositive. Seropositive rates are significantly higher among hospital donors in spite of medical prescreening compared to nonscreened voluntary donors. Serology should be repeated even when prior reports are available.

Histogram analysis for age change of human lung with computed tomography

International Nuclear Information System (INIS)

Shirabe, Ichiju

1990-01-01

In order to evaluate physiological changes of normal lung with aging by computed tomography (CT), the peak position (PP) and full width half maximum (FWHM) of CT-histogram were studied in 77 normal human lung. Above 30 years old, PP tended to be seen in the lower attenuation value with advancing ages, with the result that the follow equation was obtained. CT attenuation value of PP=-0.87 x age -815. The peak position shifted to the range of higher CT attenuation in 30's. FWHM did not change with advancing ages. There were no differences of peak value and FWHM among the upper, middle and lower lung field. In this study, physiological changes of lung were evaluated quantitatively. Furthermore, this study was considered to be useful for diagnosis and treatment in lung diseases. (author)

Modeling of the Nitric Oxide Transport in the Human Lungs.

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Karamaoun, Cyril; Van Muylem, Alain; Haut, Benoît

2016-01-01

In the human lungs, nitric oxide (NO) acts as a bronchodilatator, by relaxing the bronchial smooth muscles and is closely linked to the inflammatory status of the lungs, owing to its antimicrobial activity. Furthermore, the molar fraction of NO in the exhaled air has been shown to be higher for asthmatic patients than for healthy patients. Multiple models have been developed in order to characterize the NO dynamics in the lungs, owing to their complex structure. Indeed, direct measurements in the lungs are difficult and, therefore, these models are valuable tools to interpret experimental data. In this work, a new model of the NO transport in the human lungs is proposed. It belongs to the family of the morphological models and is based on the morphometric model of Weibel (1963). When compared to models published previously, its main new features are the layered representation of the wall of the airways and the possibility to simulate the influence of bronchoconstriction (BC) and of the presence of mucus on the NO transport in lungs. The model is based on a geometrical description of the lungs, at rest and during a respiratory cycle, coupled with transport equations, written in the layers composing an airway wall and in the lumen of the airways. First, it is checked that the model is able to reproduce experimental information available in the literature. Second, the model is used to discuss some features of the NO transport in healthy and unhealthy lungs. The simulation results are analyzed, especially when BC has occurred in the lungs. For instance, it is shown that BC can have a significant influence on the NO transport in the tissues composing an airway wall. It is also shown that the relation between BC and the molar fraction of NO in the exhaled air is complex. Indeed, BC might lead to an increase or to a decrease of this molar fraction, depending on the extent of the BC and on the possible presence of mucus. This should be confirmed experimentally and might

[Effect of cisplatin on the expression of Pokemon gene: experiment with different human lung cancer cells].

Science.gov (United States)

Zhao, Zhi-Hong; Wang, Sheng-Fa; Yu, Liang; Wang, Ju; Cong, De-Gang; Chang, Hao; Wang, Xue-Feng; Zhang, Tie-Wa; Zhang, Jian; Fu, Kai; Jiang, Jiu-Yang

2008-04-29

To investigate the correlation between Pokemon gene and cisplatin mechanism. Human lung adenocarcinoma cells of the lines A549 and AGZY83-a, human lung squamous carcinoma cells of the line HE-99, and human giant cell lung cancer cells of the line 95D were cultured and cisplatin was added into the medium. Other lung cancer cells of the above mentioned lines were cultured in the medium without cisplatin and were used as control groups. RT-PCR and Western blotting were used to detect the mRNA and protein expression of Pokemon. Pokemon mRNA and protein were expressed highly in all the 4 cell lines. The Pokemon gene expression did not changed significantly after cisplatin treatment groups. There were not significant differences in the mRNA and protein expression of Pokemon among the 4 experiment groups and the control groups (all P > 0.05). Cisplatin has no effect on the Pokemon gene expression of the human lung cancer cells.

Graft downsizing during ex vivo lung perfusion: case report and technical notes.

Science.gov (United States)

Nosotti, M; Rosso, L; Mendogni, P; Tosi, D; Palleschi, A; Righi, I; Froio, S; Valenza, F; Santambrogio, L

2014-09-01

Among patients with respiratory insufficiency awaiting lung transplantation, small adult patients have a lower opportunity of receiving size-matched pulmonary grafts, because of the shortage of donors, particularly those of small size. Reducing the size of an oversized graft is one of the methods to increase the donor pool; similarly, ex vivo lung perfusion is an emerging technique aimed toward the same purpose. We describe how we combined the 2 techniques (lobar transplantation plus contralateral nonanatomic graft reduction during ex vivo lung perfusion) to overcome graft shortage in a clinical case. For the 1st time, this case report demonstrates that surgical manipulation during ex vivo lung perfusion does not affect the functional improvement in a lung previously judged to be not suitable for transplantation. The 6-month follow-up results are similar to those of standard bilateral lung transplantation. Copyright © 2014 Elsevier Inc. All rights reserved.

Regulated gene expression in cultured type II cells of adult human lung

OpenAIRE

Ballard, Philip L.; Lee, Jae W.; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R.; Fischer, Horst; Illek, Beate; Gonzales, Linda W.; Kolla, Venkatadri; Matthay, Michael A.

2010-01-01

Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at ∼95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days...

Donor-Derived Regulatory Dendritic Cell Infusion Maintains Donor-Reactive CD4+CTLA4hi T Cells in Non-Human Primate Renal Allograft Recipients Treated with CD28 Co-Stimulation Blockade

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Mohamed B. Ezzelarab

2018-02-01

Full Text Available Donor-derived regulatory dendritic cell (DCreg infusion before transplantation, significantly prolongs renal allograft survival in non-human primates. This is associated with enhanced expression of the immunoregulatory molecules cytotoxic T-lymphocyte-associated antigen (Ag 4 (CTLA4 and programmed cell death protein 1 (PD1 by host donor-reactive T cells. In rodents and humans, CD28 co-stimulatory pathway blockade with the fusion protein CTLA4:Ig (CTLA4Ig is associated with reduced differentiation and development of regulatory T cells (Treg. We hypothesized that upregulation of CTLA4 by donor-reactive CD4+ T cells in DCreg-infused recipients treated with CTLA4Ig, might be associated with higher incidences of donor-reactive CD4+ T cells with a Treg phenotype. In normal rhesus monkeys, allo-stimulated CD4+CTLA4hi, but not CD4+CTLA4med/lo T cells exhibited a regulatory phenotype, irrespective of PD1 expression. CTLA4Ig significantly reduced the incidence of CD4+CTLA4hi, but not CD4+CTLA4med/lo T cells following allo-stimulation, associated with a significant reduction in the CD4+CTLA4hi/CD4+CTLA4med/lo T cell ratio. In CTLA4Ig-treated renal allograft recipient monkeys, there was a marked reduction in circulating donor-reactive CD4+CTLA4hi T cells. In contrast, in CTLA4Ig-treated monkeys with DCreg infusion, no such reduction was observed. In parallel, the donor-reactive CD4+CTLA4hi/CD4+CTLA4med/lo T cell ratio was reduced significantly in graft recipients without DCreg infusion, but increased in those given DCreg. These observations suggest that pre-transplant DCreg infusion promotes and maintains donor-reactive CD4+CTLA4hi T cells with a regulatory phenotype after transplantation, even in the presence of CD28 co-stimulation blockade.

Time-resolved autofluorescence imaging of human donor retina tissue from donors with significant extramacular drusen.

Science.gov (United States)

Schweitzer, Dietrich; Gaillard, Elizabeth R; Dillon, James; Mullins, Robert F; Russell, Stephen; Hoffmann, Birgit; Peters, Sven; Hammer, Martin; Biskup, Christoph

2012-06-08

Time and spectrally resolved measurements of autofluorescence have the potential to monitor metabolism at the cellular level. Fluorophores that emit with the same fluorescence intensity can be discriminated from each other by decay time of fluorescence intensity after pulsed excitation. We performed time-resolved autofluorescence measurements on fundus samples from a donor with significant extramacular drusen. Tissue sections from two human donors were prepared and imaged with a laser scanning microscope. The sample was excited with a titanium-sapphire laser, which was tuned to 860 nm, and frequency doubled by a BBO crystal to 430 nm. The repetition rate was 76 MHz and the pulse width was 170 femtoseconds (fs). The time-resolved autofluorescence was recorded simultaneously in 16 spectral channels (445-605 nm) and bi-exponentially fitted. RPE can be discriminated clearly from Bruch's membrane, drusen, and choroidal connective tissue by fluorescence lifetime. In RPE, bright fluorescence of lipofuscin could be detected with a maximum at 510 nm and extending beyond 600 nm. The lifetime was 385 ps. Different types of drusen were found. Most of them did not contain lipofuscin and exhibited a weak fluorescence, with a maximum at 470 nm. The lifetime was 1785 picoseconds (ps). Also, brightly emitting lesions, presumably representing basal laminar deposits, with fluorescence lifetimes longer than those recorded in RPE could be detected. The demonstrated differentiation of fluorescent structures by their fluorescence decay time is important for interpretation of in vivo measurements by the new fluorescence lifetime imaging (FLIM) ophthalmoscopy on healthy subjects as well as on patients.

The safety of donor skin preserved with glycerol - Evaluating the Euro Skin Bank preservation procedures of human donor skin against the prEN 12442 standard

NARCIS (Netherlands)

Geertsma RE; Wassenaar C; LGM

2000-01-01

The procedures for preservation of human donor skin with glycerol, as applied by the Euro Skin Bank (ESB), were evaluated against the prEN 12442 standard: animal tissues and their derivatives used in the manufacture of medical devices. The focus chosen for this review is on risks related to the

Comparison of seropositivity of human immunodeficiency virus, hepatitis B virus, hepatitis C virus, and syphilis among Hospital Cornea Retrieval Programme-Donors versus voluntary cornea donors at a large eye bank in Eastern India

Directory of Open Access Journals (Sweden)

Soham Basak

2017-01-01

Full Text Available Purpose: To compare the serology profile of donors from Hospital Cornea Retrieval Programme-donors (HCRP-D and voluntary cornea donors (VC-D from a large eye bank in Eastern India. Methods: This is a retrospective analysis of donor details from January 2011 to December 2016. Donor demographics, cause of death, and serology reports were compiled. Postmortem blood was tested for human immunodeficiency virus 1 and 2 (HIV, hepatitis B virus (HBV, hepatitis C virus (HCV, and syphilis using government-approved kits as per the National Programme for Control of Blindness Standards of Eye Banking. Donors for whom serology was not possible were excluded. Results: A total of 4300 of 4353 donors were included of which 74.3% were hospital donors and 25.7% were voluntary donors. A total of 93 (2.2% donors with 94 seropositive reports were noted: 79 (84.9% from HCRP-D and 14 (15.1% from VC-D which was statistically significantly higher (P = 0.02. Among seropositive reports, HIV, HBV, HCV, and syphilis accounted for 12 (12.8%, 38 (40.4%, 36 (38.3%, and eight (8.5%, respectively. There was no correlation between the cause of death and seropositivity. A statistically significant decreasing trend in seroprevalence among hospital donors was observed over the years (5.3% in 2011 to 1.4% in 2016; P = 0.004. Two (0.47% of 421 hospital donors with prior negative serology were found to be seropositive. Conclusion: Seropositive rates are significantly higher among hospital donors in spite of medical prescreening compared to nonscreened voluntary donors. Serology should be repeated even when prior reports are available.

Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression.

Science.gov (United States)

Hollander, Zsuzsanna; Chen, Virginia; Sidhu, Keerat; Lin, David; Ng, Raymond T; Balshaw, Robert; Cohen-Freue, Gabriela V; Ignaszewski, Andrew; Imai, Carol; Kaan, Annemarie; Tebbutt, Scott J; Wilson-McManus, Janet E; McMaster, Robert W; Keown, Paul A; McManus, Bruce M

2013-02-01

Acute rejection in cardiac transplant patients remains a contributory factor to limited survival of implanted hearts. Currently, there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplant acute cellular rejection. Such a development would be of great value in personalizing immunosuppressive treatment. Recipient age, donor age, cold ischemic time, warm ischemic time, panel-reactive antibody, gender mismatch, blood type mismatch and human leukocyte antigens (HLA-A, -B and -DR) mismatch between recipients and donors were tested in 53 heart transplant patients for their power to predict post-transplant acute cellular rejection. Donor transplant biopsy and recipient pre-transplant blood were also examined for the presence of genomic biomarkers in 7 rejection and 11 non-rejection patients, using non-targeted data mining techniques. The biomarker based on the 8 clinical variables had an area under the receiver operating characteristic curve (AUC) of 0.53. The pre-transplant recipient blood gene-based panel did not yield better performance, but the donor heart tissue gene-based panel had an AUC = 0.78. A combination of 25 probe sets from the transplant donor biopsy and 18 probe sets from the pre-transplant recipient whole blood had an AUC = 0.90. Biologic pathways implicated include VEGF- and EGFR-signaling, and MAPK. Based on this study, the best predictive biomarker panel contains genes from recipient whole blood and donor myocardial tissue. This panel provides clinically relevant prediction power and, if validated, may personalize immunosuppressive treatment and rejection monitoring. Copyright © 2013 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Follistatin is a novel biomarker for lung adenocarcinoma in humans.

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Fangfang Chen

Full Text Available Follistatin (FST, a single chain glycoprotein, is originally isolated from follicular fluid of ovary. Previous studies have revealed that serum FST served as a biomarker for pregnancy and ovarian mucinous tumor. However, whether FST can serve as a biomarker for diagnosis in lung adenocarcinoma of humans remains unclear.The study population consisted of 80 patients with lung adenocarcinoma, 40 patients with ovarian adenocarcinoma and 80 healthy subjects. Serum FST levels in patients and healthy subjects were measured using ELISA. The results showed that the positive ratio of serum FST levels was 51.3% (41/80, which was comparable to the sensitivity of FST in 40 patients with ovarian adenocarcinoma (60%, 24/40 using the 95th confidence interval for the healthy subject group as the cut-off value. FST expressions in lung adenocarcinoma were examined by immunohistochemical staining, we found that lung adenocarcinoma could produce FST and there was positive correlation between the level of FST expression and the differential degree of lung adenocarcinoma. Furthermore, the results showed that primary cultured lung adenocarcinoma cells could secrete FST, while cells derived from non-tumor lung tissues almost did not produce FST. In addition, the results of CCK8 assay and flow cytometry showed that using anti-FST monoclonal antibody to neutralize endogenous FST significantly augmented activin A-induced lung adenocarcinoma cells apoptosis.These data indicate that lung adenocarcinoma cells can secret FST into serum, which may be beneficial to the survival of adenocarcinoma cells by neutralizing activin A action. Thus, FST can serve as a promising biomarker for diagnosis of lung adenocarcinoma and a useful biotherapy target for lung adenocarcinoma.

Long-term human immune system reconstitution in non-obese diabetic (NOD)-Rag (-)-γ chain (-) (NRG) mice is similar but not identical to the original stem cell donor.

Science.gov (United States)

Harris, D T; Badowski, M; Balamurugan, A; Yang, O O

2013-12-01

The murine immune system is not necessarily identical to it human counterpart, which has led to the construction of humanized mice. The current study analysed whether or not a human immune system contained within the non-obese diabetic (NOD)-Rag1(null) -γ chain(null) (NRG) mouse model was an accurate representation of the original stem cell donor and if multiple mice constructed from the same donor were similar to one another. To that end, lightly irradiated NRG mice were injected intrahepatically on day 1 of life with purified cord blood-derived CD34(+) stem and progenitor cells. Multiple mice were constructed from each cord blood donor. Mice were analysed quarterly for changes in the immune system, and followed for periods up to 12 months post-transplant. Mice from the same donor were compared directly with each other as well as with the original donor. Analyses were performed for immune reconstitution, including flow cytometry, T cell receptor (TCR) and B cell receptor (BCR) spectratyping. It was observed that NRG mice could be 'humanized' long-term using cord blood stem cells, and that animals constructed from the same cord blood donor were nearly identical to one another, but quite different from the original stem cell donor immune system. © 2013 British Society for Immunology.

Isoproterenol reduces ischemia-reperfusion lung injury despite beta-blockade.

Science.gov (United States)

Takashima, Seiki; Schlidt, Scott A; Koukoulis, Giovanna; Sevala, Mayura; Egan, Thomas M

2005-06-01

If lungs could be retrieved from non-heart-beating donors (NHBDs), the shortage of lungs for transplantation could be alleviated. The use of lungs from NHBDs is associated with a mandatory warm ischemic interval, which results in ischemia-reperfusion injury upon reperfusion. In an earlier study, rat lungs retrieved 2-h postmortem from NHBDs had reduced capillary leak measured by filtration coefficient (Kfc) when reperfused with isoproterenol (iso), associated with an increase in lung tissue levels of cyclic AMP (cAMP). The objective was to determine if this decrease in Kfc was because of beta-stimulation, or would persist despite beta-blockade. Donor rats were treated intraperitoneally with beta-blockade (propranolol or pindolol) or carrier, sacrificed, and lungs were retrieved immediately or 2 h postmortem. The lungs were reperfused with or without iso and the beta-blockers in the reperfusate. Outcome measures were Kfc, wet:dry weight ratio (W/D), lung levels of adenine nucleotides and cAMP. Lungs retrieved immediately after death had normal Kfc and W/D. After 2 h of ischemia, Kfc and W/D were markedly elevated in controls (no drug) and lungs reperfused with beta-blockers alone. Isoproterenol-reperfusion decreased Kfc and W/D significantly (P < 0.01) even in the presence of beta-blockade. Lung cAMP levels were increased only with iso in the absence of beta-blockade. The attenuation of ischemia-reperfusion injury because of iso occurs even in the presence of beta-blockade, and may not be a result of beta-stimulated increased cAMP.

Anti-human tissue factor antibody ameliorated intestinal ischemia reperfusion-induced acute lung injury in human tissue factor knock-in mice.

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Xiaolin He

Full Text Available BACKGROUND: Interaction between the coagulation and inflammation systems plays an important role in the development of acute respiratory distress syndrome (ARDS. Anti-coagulation is an attractive option for ARDS treatment, and this has promoted development of new antibodies. However, preclinical trials for these antibodies are often limited by the high cost and availability of non-human primates. In the present study, we developed a novel alternative method to test the role of a humanized anti-tissue factor mAb in acute lung injury with transgenic mice. METHODOLOGY/PRINCIPAL FINDINGS: Human tissue factor knock-in (hTF-KI transgenic mice and a novel humanized anti-human tissue factor mAb (anti-hTF mAb, CNTO859 were developed. The hTF-KI mice showed a normal and functional expression of hTF. The anti-hTF mAb specifically blocked the pro-coagulation activity of brain extracts from the hTF-KI mice and human, but not from wild type mice. An extrapulmonary ARDS model was used by intestinal ischemia-reperfusion. Significant lung tissue damage in hTF-KI mice was observed after 2 h reperfusion. Administration of CNTO859 (5 mg/kg, i.v. attenuated the severity of lung tissue injury, decreased the total cell counts and protein concentration in bronchoalveolar lavage fluid, and reduced Evans blue leakage. In addition, the treatment significantly reduced alveolar fibrin deposition, and decreased tissue factor and plasminogen activator inhibitor-1 activity in the serum. This treatment also down-regulated cytokine expression and reduced cell death in the lung. CONCLUSIONS: This novel anti-hTF antibody showed beneficial effects on intestinal ischemia-reperfusion induced acute lung injury, which merits further investigation for clinical usage. In addition, the use of knock-in transgenic mice to test the efficacy of antibodies against human-specific proteins is a novel strategy for preclinical studies.

Interplay between the lung microbiome and lung cancer.

Science.gov (United States)

Mao, Qixing; Jiang, Feng; Yin, Rong; Wang, Jie; Xia, Wenjie; Dong, Gaochao; Ma, Weidong; Yang, Yao; Xu, Lin; Hu, Jianzhong

2018-02-28

The human microbiome confers benefits or disease susceptibility to the human body through multiple pathways. Disruption of the symbiotic balance of the human microbiome is commonly found in systematic diseases such as diabetes, obesity, and chronic gastric diseases. Emerging evidence has suggested that dysbiosis of the microbiota may also play vital roles in carcinogenesis at multiple levels, e.g., by affecting metabolic, inflammatory, or immune pathways. Although the impact of the gut microbiome on the digestive cancer has been widely explored, few studies have investigated the interplay between the microbiome and lung cancer. Some recent studies have shown that certain microbes and microbiota dysbiosis are correlated with development of lung cancer. In this mini-review, we briefly summarize current research findings describing the relationship between the lung microbiome and lung cancer. We further discuss the potential mechanisms through which the lung microbiome may play a role in lung carcinogenesis and impact lung cancer treatment. A better knowledge of the interplay between the lung microbiome and lung cancer may promote the development of innovative strategies for early prevention and personalized treatment in lung cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Knowledge, attitude, and beliefs of young, college student blood donors about Human immunodeficiency virus

Directory of Open Access Journals (Sweden)

Anju Dubey

2014-01-01

Full Text Available Introduction: Young people, who tend to be healthy, idealistic, and motivated, are an excellent pool of potential voluntary unpaid blood donors. Recruiting and retaining young blood donors improves the long term safety and sufficiency of a country′s blood supply. Knowledge, attitude, and beliefs about Human immunodeficiency virus (HIV should play an important role in prevention of disease transmission. Materials and Methods: This study was a questionnaire based survey, conducted to explore the levels of knowledge, attitude, and beliefs about HIV in young college student blood donors. Results: The results showed that the proportion of participants with comprehensive knowledge of HIV prevention and transmission was lesser than expected. Increase in education level and male gender was found to be significantly associated with high HIV-related knowledge. The responses on the different aspects of HIV-related attitude were also varied and there is still stigma associated with Acquired Immunodeficiency Syndrome (AIDS even in the educated groups. Discussion: There was a spectrum of myths and misperceptions emphasizing the need of education that recognizes the social context of attitude towards HIV. Results from this study may contribute to the development of appropriate educational and training material for this group of donors which in turn, may assist in achieving the elusive goal of safe blood supply in future.

Performance of QuantiFERON TB Gold test in detecting latent tuberculosis infection in brain-dead organ donors in Iran: a brief report.

Science.gov (United States)

Tabarsi, Payam; Yousefzadeh, Amir; Najafizadeh, Katayoun; Droudinia, Atousa; Bayati, Rouzbeh; Marjani, Majid; Shafaghi, Shadi; Farokhzad, Banafsheh; Javanmard, Pedram; Velayati, Ali Akbar

2014-11-01

With regard to the significant morbidity and mortality due to tuberculosis in lung transplant recipients, the identification of brain-dead organ donors with latent tuberculosis by use of the QuantiFERON TB Gold (QFT-G) test may be of help to reduce the risk of TB reactivation and mortality in lung recipients. This study was conducted in the National Research Institute of Tuber-culosis and Lung Diseases (NRITLD) in Iran, from January to March 2013. A total of 38 conse-cutive brain-dead donors, not currently infected with active tuberculosis, were recruited. The medi-cal records of all the study enrollees were reviewed. A whole-blood IFN- release assay (IGRA) in reaction to early secreted antigenic target 6 (ESAT-6), culture filtrate protein 10 (CFP-10), and TB7.7 antigens, was performed and the released Interferon- was measured via enzyme-linked immunosorbent assay (ELISA). The data was analyzed with QFT-G software which was provided by the company. The demographic, characteristics and other variables were entered into SPSS version 11.5. The QFT-G test results of three donors (7.9%) turned out to be positive, negative for 24 donors (63.1%), and indeterminate for 11 cases (28.9%). Our study revealed the potential advantages of QFT-G in lowering the incidence of donor-derived post-transplant tuberculosis among lung recipients. However, a high rate of indeterminate results restricted the performance of QFT-G in this study.

Performance of QuantiFERON TB Gold test in detecting latent tuberculosis infection in brain-dead organ donors in Iran: A brief report

Directory of Open Access Journals (Sweden)

Payam Tabarsi

2014-01-01

Full Text Available With regard to the significant morbidity and mortality due to tuberculosis in lung transplant recipients, the identification of brain-dead organ donors with latent tuberculosis by use of the QuantiFERON TB Gold (QFT-G test may be of help to reduce the risk of TB reactivation and mortality in lung recipients. This study was conducted in the National Research Institute of Tuber-culosis and Lung Diseases (NRITLD in Iran, from January to March 2013. A total of 38 conse-cutive brain-dead donors, not currently infected with active tuberculosis, were recruited. The medi-cal records of all the study enrollees were reviewed. A whole-blood IFN- release assay (IGRA in reaction to early secreted antigenic target 6 (ESAT-6, culture filtrate protein 10 (CFP-10, and TB7.7 antigens, was performed and the released Interferon- was measured via enzyme-linked immunosorbent assay (ELISA. The data was analyzed with QFT-G software which was provided by the company. The demographic, characteristics and other variables were entered into SPSS version 11.5. The QFT-G test results of three donors (7.9% turned out to be positive, negative for 24 donors (63.1%, and indeterminate for 11 cases (28.9%. Our study revealed the potential advantages of QFT-G in lowering the incidence of donor-derived post-transplant tuberculosis among lung recipients. However, a high rate of indeterminate results restricted the performance of QFT-G in this study.

[Effect of freezing on the "creamatocrit" measurement of the lipid content of human donor milk].

Science.gov (United States)

Vázquez-Román, S; Alonso-Díaz, C; García-Lara, N R; Escuder-Vieco, D; Pallás-Alonso, C R

2014-09-01

To determine, by the creamatocrit measurement, the effect on the fat content of raw and pasteurized donor milk of freezing during 3 months at -20 °C. The evolution of the creamatocrit measurement (following Lucas technique) on frozen (-20 °C), raw and pasteurized human milk, was analyzed during 3 months. The fat content of raw milk (n=44) was 3.19 g/dl at the beginning and 2.86 g/dl after 3 months frozen (p=0.02). In pasteurized milk (n=36) fat content at the first determination was 2.59 g/dl and 2.20 g/dl after 1 month frozen (p=0.01). Afterwards there were no significant changes up to 3 months frozen. Variability was observed in the intermediate values. A reduction on the fat content measurement of raw and pasteurized donor human milk after freezing was observed. Freezing does not inactivate the milk lipase but does destroy the fat globule. Creamatocrit measurement may not be the best method to determine the fat content of processed human milk. Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.

Pyrrolidine dithiocarbamate administered during ex-vivo lung perfusion promotes rehabilitation of injured donor rat lungs obtained after prolonged warm ischemia.

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Cyril Francioli

Full Text Available Damaged lung grafts obtained after circulatory death (DCD lungs and warm ischemia may be at high risk of reperfusion injury after transplantation. Such lungs could be pharmacologically reconditioned using ex-vivo lung perfusion (EVLP. Since acute inflammation related to the activation of nuclear factor kappaB (NF-κB is instrumental in lung reperfusion injury, we hypothesized that DCD lungs might be treated during EVLP by pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-κB. Rat lungs exposed to 1h warm ischemia and 2 h cold ischemia were subjected to EVLP during 4h, in absence (CTRL group, N = 6 or in presence of PDTC (2.5g/L, PDTC group, N = 6. Static pulmonary compliance (SPC, peak airway pressure (PAWP, pulmonary vascular resistance (PVR, and oxygenation capacity were determined during EVLP. After EVLP, we measured the weight gain of the heart-lung block (edema, and the concentration of LDH (cell damage, proteins (permeability edema and of the cytokines IL-6, TNF-α and CINC-1 in bronchoalveolar lavage (BAL, and we evaluated NF-κB activation by the degree of phosphorylation and degradation of its inhibitor IκBα in lung tissue. In CTRL, we found significant NF-κB activation, lung edema, and a massive release of LDH, proteins and cytokines. SPC significantly decreased, PAWP and PVR increased, while oxygenation tended to decrease. Treatment with PDTC during EVLP inhibited NF-κB activation, did not influence LDH release, but markedly reduced lung edema and protein concentration in BAL, suppressed TNFα and IL-6 release, and abrogated the changes in SPC, PAWP and PVR, with unchanged oxygenation. In conclusion, suppression of innate immune activation during EVLP using the NF-κB inhibitor PDTC promotes significant improvement of damaged rat DCD lungs. Future studies will determine if such rehabilitated lungs are suitable for in vivo transplantation.

20 CFR 401.200 - Blood donor locator service.

Science.gov (United States)

2010-04-01

... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Blood donor locator service. 401.200 Section... AND INFORMATION Disclosure of Official Records and Information § 401.200 Blood donor locator service... donors whose blood donations show that they are or may be infected with the human immunodeficiency virus...

Neurotrophins expression is decreased in lungs of human infants with congenital diaphragmatic hernia

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O'Hanlon LD

2014-02-01

Full Text Available Lynn D O'Hanlon, Sherry M Mabry, Ikechukwu I EkekezieChildren's Mercy Hospitals/University of Missouri-Kansas City School of Medicine, Department of Pediatrics, Section of Neonatal-Perinatal Medicine, Kansas City, MO, USAObjectives: To evaluate neurotrophin (NT (nerve growth factor [NGF], NT-3, and brain-derived neurotrophic factor [BDNF] expression in autopsy lung tissues of human congenital diaphragmatic hernia (CDH infants versus that of infants that expired with: 1 "normal" lungs (controls; 2 chronic lung disease (CLD; and 3 pulmonary hypertension (PPHN.Hypothesis: NT expression will be significantly altered in CDH lung tissue compared with normal lung tissue and other neonatal lung diseases.Study design: Immunohistochemical studies for NT proteins NGF, BDNF, and NT-3 were applied to human autopsy neonatal lung tissue samples.Subject selection: The samples included a control group of 18 samples ranging from 23-week gestational age to term, a CDH group of 15 samples, a PPHN group of six samples, and a CLD group of 12 samples.Methodology: The tissue samples were studied, and four representative slide fields of alveoli/saccules and four of bronchioles were recorded from each sample. These slide fields were then graded (from 0 to 3 by three blinded observers for intensity of staining.Results: BDNF, NGF, and NT-3 immunostaining intensity scores were significantly decreased in the CDH lung tissue (n=15 compared with normal neonatal lung tissue (n=18 (P<0.001. The other neonatal pulmonary diseases that were studied, CLD and PPHN, were much less likely to be affected and were much more variable in their neurotrophin expression.Conclusion: NT expression is decreased in CDH lungs. The decreased expression of NT in CDH lung tissue may suggest they contribute to the abnormality in this condition.Keywords: nerve growth factor, NGF, brain-derived neurotrophic factor, BDNF, neurotrophin-3, NT-3, chronic lung disease, persistent pulmonary hypertension, lung

In vitro studies of human lung carcinogenesis.

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Harris, C C; Lechner, J F; Yoakum, G H; Amstad, P; Korba, B E; Gabrielson, E; Grafstrom, R; Shamsuddin, A; Trump, B F

1985-01-01

Advances in the methodology to culture normal human lung cells have provided opportunities to investigate fundamental problems in biomedical research, including the mechanism(s) of carcinogenesis. Using the strategy schematically shown in Figure 1, we have initiated studies of the effects of carcinogens on the normal progenitor cells of the human cancers caused by these carcinogens. Extended lifespans and aneuploidy were found after exposure of mesothelial cells to asbestos and bronchial epithelial cells to nickel sulfate. These abnormal cells may be considered to be preneoplastic and at an intermediate position in the multistage process of carcinogenesis. Human bronchial epithelial cells can also be employed to investigate the role of specific oncogenes in carcinogenesis and tumor progression. Using the protoplast fusion method for high frequency gene transfection, vHa-ras oncogene initiates a cascade of events in the normal human bronchial cells leading to their apparent immortality, aneuploidy, and tumorigenicity in athymic nude mice. These results suggest that oncogenes may play an important role in human carcinogenesis.

Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

DEFF Research Database (Denmark)

Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C

2014-01-01

BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This st......BACKGROUND: Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported...

Results from a horizon scan on risks associated with transplantation of human organs, tissues and cells: from donor to patient.

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Herberts, C A; Park, M V D Z; Pot, J W G A; de Vries, C G J C A

2015-03-01

The successful transplantation of human materials such as organs, tissues and cells into patients does not only depend on the benefits, but also on the mitigation of risks. To gain insight into recent publications on risks associated with the process of transferring human materials from donor to recipient we performed a horizon scan by reviewing scientific literature and news websites of 2011 on this subject. We found there is ample information on how extended donor criteria, such as donor age, affect the survival rates of organs or patients. Interestingly, gender mismatch does not appear to be a major risk factor in organ rejection. Data on risks of donor tumor transmission was very scarce; however, risk categories for various tumor types have been suggested. In order to avoid rejection, a lot of research is directed towards engineering tissues from a patient's own tissues and cells. Some but not all of these developments have reached the clinic. Developments in the field of stem cell therapy are rapid. However, many hurdles are yet to be overcome before these cells can be applied on a large scale in the clinic. The processes leading to genetic abnormalities in cells differentiated from stem cells need to be identified in order to avoid transplantation of aberrant cells. New insights have been obtained on storage and preservation of human materials, a critical step for success of their clinical use. Likewise, quality management systems have been shown to improve the quality and safety of human materials used for transplantation.

Donor transplant programme

International Nuclear Information System (INIS)

Abu Bakar Sulaiman

1999-01-01

The transplantation of organs and tissues from one human to another human has become an essential and well established form of therapy for many types of organ and tissue failure. In Malaysia, kidney, cornea and bone marrow transplantation are well established. Recently, liver, bone and heart transplanation have been performed. Unfortunately, because of the lack of cadaveric organ donation, only a limited number of solid organ transplantation have been performed. The cadaveric organ donor rate in Malaysia is low at less than one per million population. The first tissue transplanted in Malaysia was the cornea which was performed in the early 1970s. At that time and even now the majority of corneas came from Sri Lanka. The first kidney transplant was performed in 1975 from a live related donor. The majority of the 629 kidney transplants done at Hospital Kuala Lumpur to date have been from live related donors. Only 35 were from cadaver donors. Similarly, the liver transplantation programme which started in 1995 are from live related donors. A more concerted effort has been made recently to increase the awareness of the public and the health professionals on organ and tissue donation. This national effort to promote organ and tissue donation seems to have gathered momentum in 1997 with the first heart transplant successfully performed at the National Heart Institute. The rate of cadaveric donors has also increased from a previous average of I to 2 per year to 6 per year in the last one year. These developments are most encouraging and may signal the coming of age of our transplantati on programme. The Ministry of Health in conjunction with various institutions, organizations and professional groups, have taken a number of proactive measures to facilitate the development of the cadaveric organ donation programme. Efforts to increase public awareness and to overcome the negative cultural attitude towards organ donation have been intensified. Equally important are efforts

Construction of a T7 Human Lung Cancer cDNA Library

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Wentao YUE

2008-10-01

Full Text Available Background and objective Currently, only a limited numbers of tumor markers for non small lung cancer (NSCLC diagnosis, new biomarker, such as serum autoantibody may improve the early detection of lung cancer. Our objective is construction human lung squamous carcinoma and adenocarcinoma T7 phage display cDNA library from the tissues of NSCLC patients. Methods mRNA was isolated from a pool of total RNA extract from NSCLC tissues obtained from 5 adenocarcinomas and 5 squamous carcinomas, and then mRNA was reverse transcribed into double stranded cDNA. After digestion, the cDNA was inserted into T7Select 10-3 vector. The phage display cDNA library was constructed by package reaction in vitro and plate proliferation. Plaque assay and PCR were used to evaluate the library.Results Two T7 phage display cDNA library were established. Plaque assay show the titer of lung squamas carcinoma library was 1.8×106 pfu, and the adenocarcinoma library was 5×106 pfu. The phage titer of the amplified library were 3.2×1010 pfu/mL and 2.5×1010 pfu/mL. PCR amplification of random plaque show insert ratio were 100% (24/24 in adenocarcinoma library and 95.8% in human lung squamas carcinoma library (23/24. Insert range from 300 bp to 1 500 bp. Conclusion Two phage display cDNA library from NSCLC were constructed.

Receptor tyrosine kinase EphA5 is a functional molecular target in human lung cancer.

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Staquicini, Fernanda I; Qian, Ming D; Salameh, Ahmad; Dobroff, Andrey S; Edwards, Julianna K; Cimino, Daniel F; Moeller, Benjamin J; Kelly, Patrick; Nunez, Maria I; Tang, Ximing; Liu, Diane D; Lee, J Jack; Hong, Waun Ki; Ferrara, Fortunato; Bradbury, Andrew R M; Lobb, Roy R; Edelman, Martin J; Sidman, Richard L; Wistuba, Ignacio I; Arap, Wadih; Pasqualini, Renata

2015-03-20

Lung cancer is often refractory to radiotherapy, but molecular mechanisms of tumor resistance remain poorly defined. Here we show that the receptor tyrosine kinase EphA5 is specifically overexpressed in lung cancer and is involved in regulating cellular responses to genotoxic insult. In the absence of EphA5, lung cancer cells displayed a defective G1/S cell cycle checkpoint, were unable to resolve DNA damage, and became radiosensitive. Upon irradiation, EphA5 was transported into the nucleus where it interacted with activated ATM (ataxia-telangiectasia mutated) at sites of DNA repair. Finally, we demonstrate that a new monoclonal antibody against human EphA5 sensitized lung cancer cells and human lung cancer xenografts to radiotherapy and significantly prolonged survival, thus suggesting the likelihood of translational applications. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Isolation and Characterization of Human Lung Lymphatic Endothelial Cells

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Lorusso, Bruno; Falco, Angela; Madeddu, Denise; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Gervasi, Andrea; Rinaldi, Laura; Lagrasta, Costanza; Maselli, Davide; Gnetti, Letizia; Silini, Enrico M.; Quaini, Eugenio; Ampollini, Luca; Carbognani, Paolo; Quaini, Federico

2015-01-01

Characterization of lymphatic endothelial cells from the respiratory system may be crucial to investigate the role of the lymphatic system in the normal and diseased lung. We describe a simple and inexpensive method to harvest, isolate, and expand lymphatic endothelial cells from the human lung (HL-LECs). Fifty-five samples of healthy lung selected from patients undergoing lobectomy were studied. A two-step purification tool, based on paramagnetic sorting with monoclonal antibodies to CD31 and Podoplanin, was employed to select a pure population of HL-LECs. The purity of HL-LECs was assessed by morphologic criteria, immunocytochemistry, flow cytometry, and functional assays. Interestingly, these cells retain in vitro several receptor tyrosine kinases (RTKs) implicated in cell survival and proliferation. HL-LECs represent a clinically relevant cellular substrate to study lymphatic biology, lymphoangiogenesis, interaction with microbial agents, wound healing, and anticancer therapy. PMID:26137493

Seroepidemiology of human T-cell lymphotropic virus type-I in blood donors of Northeastern Iran, Sabzevar

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Mahtab Maghsudlu

2015-01-01

Full Text Available Background and Objectives: Human T-cell lymphotropic virus type-I (HTLV-I infection is considered as a public health challenge in endemic areas. The virus is associated with severe diseases, such as adult T-cell leukemia/lymphoma, and HTLV-I-associated myelopathy/tropical spastic paraparesis. One of the major routes of the HTLV-I transmission includes blood transfusion. Sabzevar is located in the endemic region of HTLV-I infection. The aim of the present study was to determine the seroprevalence of HTLV-I infection in the blood donors in Sabzevar. Materials and Methods: A total of 35,067 blood donors in Sabzevar from March 2009 to April 2012 who were screened with HTLV-I on the enzyme-linked immunosorbent assay screening test were included in this survey. Reactive samples that confirmed by western blot were considered to be seropositive cases. The required data were obtained from blood donors′ database of blood transfusion service. Results: The overall prevalence of HTLV-1 based on the positive result of western blot test was 0.14%. The seropositive donors aged 17-59 years with a mean age of 38.10 ± 11.82. The prevalence rates of HTLV-I infection in 3 years of study were 0.19%, 0.14%, and 0.09%, respectively. A significant relation between age, sex, educational level, and history of blood donation was observed with seropositivity of HTLV-I. Conclusion: The improvement of donor selection and laboratory screening caused a decline in the prevalence of infection in blood donors. Given the lower prevalence of infection in regular donors with lower age and higher educational level, more efforts should be done to attract blood donors from these populations.

MicroRNA Levels as Prognostic Markers for the Differentiation Potential of Human Mesenchymal Stromal Cell Donors

NARCIS (Netherlands)

Georgi, Nicole; Taipaleenmaeki, H.; Raiss, C.C.; Groen, N.; Portalska, K.K.; van Blitterswijk, Clemens; de Boer, Jan; Post, Janine Nicole; van Wijnen, A.; Karperien, Hermanus Bernardus Johannes

2015-01-01

The ability of human mesenchymal stromal/stem cells (hMSCs) to differentiate into various mesenchymal cell lineages makes them a promising cell source for the use in tissue repair strategies. Because the differentiation potential of hMSCs differs between donors, it is necessary to establish

Human Organotypic Lung Tumor Models: Suitable For Preclinical 18F-FDG PET-Imaging.

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David Fecher

Full Text Available Development of predictable in vitro tumor models is a challenging task due to the enormous complexity of tumors in vivo. The closer the resemblance of these models to human tumor characteristics, the more suitable they are for drug-development and -testing. In the present study, we generated a complex 3D lung tumor test system based on acellular rat lungs. A decellularization protocol was established preserving the architecture, important ECM components and the basement membrane of the lung. Human lung tumor cells cultured on the scaffold formed cluster and exhibited an up-regulation of the carcinoma-associated marker mucin1 as well as a reduced proliferation rate compared to respective 2D culture. Additionally, employing functional imaging with 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET these tumor cell cluster could be detected and tracked over time. This approach allowed monitoring of a targeted tyrosine kinase inhibitor treatment in the in vitro lung tumor model non-destructively. Surprisingly, FDG-PET assessment of single tumor cell cluster on the same scaffold exhibited differences in their response to therapy, indicating heterogeneity in the lung tumor model. In conclusion, our complex lung tumor test system features important characteristics of tumors and its microenvironment and allows monitoring of tumor growth and -metabolism in combination with functional imaging. In longitudinal studies, new therapeutic approaches and their long-term effects can be evaluated to adapt treatment regimes in future.

MMP-10 Is Overexpressed, Proteolytically Active, and a Potential Target for Therapeutic Intervention in Human Lung Carcinomas

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Jason H. Gill

2004-11-01

Full Text Available Matrix metalloproteinase (MMP-mediated degradation of the extracellular matrix is a major factor for tumor development and expansion. This study analysed MMP-10 protein expression and activity in human lung tumors of various grade, stage, and type to address the relationship between MMP-10 and tumor characteristics and to evaluate MMP-10 as a therapeutic target in non small cell lung carcinoma (NSCLC. Unlike the majority of MMPs, MMP-10 was located in the tumor mass as opposed to tumor stroma. MMP-10 protein was observed at low levels in normal human lung tissues and at significantly higher levels in all types of NSCLC. No correlation was observed between MMP-10 protein expression and tumor type, stage, or lymph node invasion. To discriminate between active and inactive forms of MMP-10 in samples of human NSCLC, we have developed an ex vivo fluorescent assay. Measurable MMP-10 activity was detected in 42 of 50 specimens of lung cancer and only 2 of 10 specimens of histologically normal lung tissue. No relationship was observed between MMP-10 activity levels and clinicopathologic characteristics. Our results suggest that MMP-10 is expressed and active at high levels in human NSCLC compared to normal lung tissues, and, as such, is a potential target for the development of novel therapeutics for lung cancer treatment.

SEGEL: A Web Server for Visualization of Smoking Effects on Human Lung Gene Expression.

Science.gov (United States)

Xu, Yan; Hu, Brian; Alnajm, Sammy S; Lu, Yin; Huang, Yangxin; Allen-Gipson, Diane; Cheng, Feng

2015-01-01

Cigarette smoking is a major cause of death worldwide resulting in over six million deaths per year. Cigarette smoke contains complex mixtures of chemicals that are harmful to nearly all organs of the human body, especially the lungs. Cigarette smoking is considered the major risk factor for many lung diseases, particularly chronic obstructive pulmonary diseases (COPD) and lung cancer. However, the underlying molecular mechanisms of smoking-induced lung injury associated with these lung diseases still remain largely unknown. Expression microarray techniques have been widely applied to detect the effects of smoking on gene expression in different human cells in the lungs. These projects have provided a lot of useful information for researchers to understand the potential molecular mechanism(s) of smoke-induced pathogenesis. However, a user-friendly web server that would allow scientists to fast query these data sets and compare the smoking effects on gene expression across different cells had not yet been established. For that reason, we have integrated eight public expression microarray data sets from trachea epithelial cells, large airway epithelial cells, small airway epithelial cells, and alveolar macrophage into an online web server called SEGEL (Smoking Effects on Gene Expression of Lung). Users can query gene expression patterns across these cells from smokers and nonsmokers by gene symbols, and find the effects of smoking on the gene expression of lungs from this web server. Sex difference in response to smoking is also shown. The relationship between the gene expression and cigarette smoking consumption were calculated and are shown in the server. The current version of SEGEL web server contains 42,400 annotated gene probe sets represented on the Affymetrix Human Genome U133 Plus 2.0 platform. SEGEL will be an invaluable resource for researchers interested in the effects of smoking on gene expression in the lungs. The server also provides useful information

Independent organ donor facilities: The future of organ donation?

Science.gov (United States)

Bruzzone, Paolo

2014-01-01

Since 2001 independent Organ Donor Facilities(OFOs) have been proposed within Organ Procurement Organizations (OPOs) with the aim of reducing organ procurement costs 1, cold ischemia time of donor organs and the flight-related risk 2 for donor surgeons, perfusionists and coordinators. An independent OFO has been established in 2001 in St. Louis 3, half away between the 2 Transplant Centers (TCs) (Washington University School of Medicine and St. Louis University) and now includes a two-bed intensive care facility, a complete laboratory, a cardiac catheterization facility, a Computed Tomography (CT) scanner and an operating room. All brain-dead (BD) patients within OPO (Mid-America Transplant Services), after family's informed consent, are transferred, if necessary by an OPO owned and operated airplane, to this facility, where undergo multiorgan harvesting. By doing so the organ acquisition charges (OACs) apparently decreased, as well as delay in recovery, which can affect organ viability and move families to withdraw consent; also risks and tiring of transplant surgeons were reduced. This independent OFO successfully procured in 2001 not only livers, but also pancreas, kidneys, hearts and lungs 4-6. Cold ischemia time was reduced and there was no Primary Non Function (PNF) of harvested organs, but only kidney delayed graft function (DGF). In the past, heart donors were moved to the recipient's hospital. With the development of multiorgan harvesting, usually donor surgeons are sent by the TCs in order to evaluate liver, pancreas, heart and lungs, while the only local surgeons is the "nephrectomist", that in local hospital is not a transplant surgeon. To move a donor, although hemodinamically stable, is always a risk. Finally, the decrease of OAC must balance the extra expenses to create and operate independent OFOs. In all the papers published by the members of this OFO, the control group of the retrospective analysis consisted of less selected BD donors, requiring

Inhibition of fibroblast growth factor receptor 3-dependent lung adenocarcinoma with a human monoclonal antibody

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Yongjun Yin

2016-05-01

Full Text Available Activating mutations in fibroblast growth factor receptor 3 (FGFR3 have been identified in multiple types of human cancer and in congenital birth defects. In human lung cancer, fibroblast growth factor 9 (FGF9, a high-affinity ligand for FGFR3, is overexpressed in 10% of primary resected non-small cell lung cancer (NSCLC specimens. Furthermore, in a mouse model where FGF9 can be induced in lung epithelial cells, epithelial proliferation and ensuing tumorigenesis is dependent on FGFR3. To develop new customized therapies for cancers that are dependent on FGFR3 activation, we have used this mouse model to evaluate a human monoclonal antibody (D11 with specificity for the extracellular ligand-binding domain of FGFR3, that recognizes both human and mouse forms of the receptor. Here, we show that D11 effectively inhibits signaling through FGFR3 in vitro, inhibits the growth of FGFR3-dependent FGF9-induced lung adenocarcinoma in mice, and reduces tumor-associated morbidity. Given the potency of FGF9 in this mouse model and the absolute requirement for signaling through FGFR3, this study validates the D11 antibody as a potentially useful and effective reagent for treating human cancers or other pathologies that are dependent on activation of FGFR3.

Cigarette smoke induces an unfolded protein response in the human lung: a proteomic approach.

Science.gov (United States)

Kelsen, Steven G; Duan, Xunbao; Ji, Rong; Perez, Oscar; Liu, Chunli; Merali, Salim

2008-05-01

Cigarette smoking, which exposes the lung to high concentrations of reactive oxidant species (ROS) is the major risk factor for chronic obstructive pulmonary disease (COPD). Recent studies indicate that ROS interfere with protein folding in the endoplasmic reticulum and elicit a compensatory response termed the "unfolded protein response" (UPR). The importance of the UPR lies in its ability to alter expression of a variety of genes involved in antioxidant defense, inflammation, energy metabolism, protein synthesis, apoptosis, and cell cycle regulation. The present study used comparative proteomic technology to test the hypothesis that chronic cigarette smoking induces a UPR in the human lung. Studies were performed on lung tissue samples obtained from three groups of human subjects: nonsmokers, chronic cigarette smokers, and ex-smokers. Proteomes of lung samples from chronic cigarette smokers demonstrated 26 differentially expressed proteins (20 were up-regulated, 5 were down-regulated, and 1 was detected only in the smoking group) compared with nonsmokers. Several UPR proteins were up-regulated in smokers compared with nonsmokers and ex-smokers, including the chaperones, glucose-regulated protein 78 (GRP78) and calreticulin; a foldase, protein disulfide isomerase (PDI); and enzymes involved in antioxidant defense. In cultured human airway epithelial cells, GRP78 and the UPR-regulated basic leucine zipper, transcription factors, ATF4 and Nrf2, which enhance expression of important anti-oxidant genes, increased rapidly (< 24 h) with cigarette smoke extract. These data indicate that cigarette smoke induces a UPR response in the human lung that is rapid in onset, concentration dependent, and at least partially reversible with smoking cessation. We speculate that activation of a UPR by cigarette smoke may protect the lung from oxidant injury and the development of COPD.

Donor-Specific Anti-HLA Antibodies in Huntington's Disease Recipients of Human Fetal Striatal Grafts.

Science.gov (United States)

Porfirio, Berardino; Paganini, Marco; Mazzanti, Benedetta; Bagnoli, Silvia; Bucciantini, Sandra; Ghelli, Elena; Nacmias, Benedetta; Putignano, Anna Laura; Rombolà, Giovanni; Saccardi, Riccardo; Lombardini, Letizia; Di Lorenzo, Nicola; Vannelli, Gabriella B; Gallina, Pasquale

2015-01-01

Fetal grafting in a human diseased brain was thought to be less immunogenic than other solid organ transplants, hence the minor impact on the efficacy of the transplant. How much prophylactic immune protection is required for neural allotransplantation is also debated. High-sensitive anti-HLA antibody screening in this field has never been reported. Sixteen patients with Huntington's disease underwent human fetal striatal transplantation in the frame of an open-label observational trial, which is being carried out at Florence University. All patients had both brain hemispheres grafted in two separate robotic-stereotactic procedures. The trial started in February 2006 with the first graft to the first patient (R1). R16 was given his second graft on March 2011. All patients received triple immunosuppressive treatment. Pre- and posttransplant sera were analyzed for the presence of anti-HLA antibodies using the multiplexed microsphere-based suspension array Luminex xMAP technology. Median follow-up was 38.5 months (range 13-85). Six patients developed anti-HLA antibodies, which turned out to be donor specific. Alloimmunization occurred in a time window of 0-49 months after the first neurosurgical procedure. The immunogenic determinants were non-self-epitopes from mismatched HLA antigens. These determinants were both public epitopes shared by two or more HLA molecules and private epitopes unique to individual HLA molecules. One patient had non-donor-specific anti-HLA antibodies in her pretransplant serum sample, possibly due to previous sensitization events. Although the clinical significance of donor-specific antibodies is far from being established, particularly in the setting of neuronal transplantation, these findings underline the need of careful pre- and posttransplant immunogenetic evaluation of patients with intracerebral grafts.

Human mesenchymal stem cells suppress donor CD4(+) T cell proliferation and reduce pathology in a humanized mouse model of acute graft-versus-host disease.

Science.gov (United States)

Tobin, L M; Healy, M E; English, K; Mahon, B P

2013-05-01

Acute graft-versus-host disease (aGVHD) is a life-threatening complication following allogeneic haematopoietic stem cell transplantation (HSCT), occurring in up to 30-50% of patients who receive human leucocyte antigen (HLA)-matched sibling transplants. Current therapies for steroid refractory aGVHD are limited, with the prognosis of patients suboptimal. Mesenchymal stem or stromal cells (MSC), a heterogeneous cell population present in many tissues, display potent immunomodulatory abilities. Autologous and allogeneic ex-vivo expanded human MSC have been utilized to treat aGVHD with promising results, but the mechanisms of therapeutic action remain unclear. Here a robust humanized mouse model of aGVHD based on delivery of human peripheral blood mononuclear cells (PBMC) to non-obese diabetic (NOD)-severe combined immunodeficient (SCID) interleukin (IL)-2rγ(null) (NSG) mice was developed that allowed the exploration of the role of MSC in cell therapy. MSC therapy resulted in the reduction of liver and gut pathology and significantly increased survival. Protection was dependent upon the timing of MSC therapy, with conventional MSC proving effective only after delayed administration. In contrast, interferon (IFN)-γ-stimulated MSC were effective when delivered with PBMC. The beneficial effect of MSC therapy in this model was not due to the inhibition of donor PBMC chimerism, as CD45(+) and T cells engrafted successfully in this model. MSC therapy did not induce donor T cell anergy, FoxP3(+) T regulatory cells or cause PBMC apoptosis in this model; however, it was associated with the direct inhibition of donor CD4(+) T cell proliferation and reduction of human tumour necrosis factor-α in serum. © 2012 British Society for Immunology.

RECONSTRUCTION OF HUMAN LUNG MORPHOLOGY MODELS FROM MAGNETIC RESONANCE IMAGES

Science.gov (United States)

Reconstruction of Human Lung Morphology Models from Magnetic Resonance ImagesT. B. Martonen (Experimental Toxicology Division, U.S. EPA, Research Triangle Park, NC 27709) and K. K. Isaacs (School of Public Health, University of North Carolina, Chapel Hill, NC 27514)

Recruitment of feces donors among blood donors

DEFF Research Database (Denmark)

Dahl Jørgensen, Simon Mark; Erikstrup, Christian; Dinh, Khoa Manh

2018-01-01

As the use of fecal microbiota transplantation (FMT) has gained momentum, an increasing need for continuous access to healthy feces donors has developed. Blood donors constitute a healthy subset of the general population and may serve as an appropriate group for recruitment. In this study, we...... investigated the suitability of blood donors as feces donors. In a prospective cohort study, we recruited blood donors onsite at a public Danish blood bank. Following their consent, the blood donors underwent a stepwise screening process: First, blood donors completed an electronic pre-screening questionnaire...... to rule out predisposing risk factors. Second, eligible blood donors had blood and fecal samples examined. Of 155 blood donors asked to participate, 137 (88%) completed the electronic pre-screening questionnaire, 16 declined, and 2 were excluded. Of the 137 donors who completed the questionnaire, 79 (58...

Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

Energy Technology Data Exchange (ETDEWEB)

Palozza, Paola, E-mail: p.palozza@rm.unicatt.it; Simone, Rossella E.; Catalano, Assunta [Institute of General Pathology, School of Medicine, Catholic University, L. Go F. Vito, Rome 1 00168 (Italy); Mele, Maria Cristina [Institute of Biochemistry and Clinical Biochemistry, School of Medicine, Catholic University, L. Go F. Vito, Rome 1 00168 (Italy)

2011-05-11

Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

International Nuclear Information System (INIS)

Palozza, Paola; Simone, Rossella E.; Catalano, Assunta; Mele, Maria Cristina

2011-01-01

Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk

Tomato Lycopene and Lung Cancer Prevention: From Experimental to Human Studies

Directory of Open Access Journals (Sweden)

Assunta Catalano

2011-05-01

Full Text Available Increasing evidence suggests that tomato lycopene may be preventive against the formation and the development of lung cancer. Experimental studies demonstrated that lycopene may inhibit the growth of several cultured lung cancer cells and prevent lung tumorigenesis in animal models through various mechanisms, including a modulation of redox status, cell cycle arrest and/or apoptosis induction, a regulation of growth factor signaling, changes in cell growth-related enzymes, an enhancement of gap junction communication and a prevention of smoke-induced inflammation. In addition, lycopene also inhibited cell invasion, angiogenesis, and metastasis. Several lycopene metabolites have been identified, raising the question as to whether the preventive effects of lycopene on cancer risk is, at least in part, due to its metabolites. Despite these promising reports, it is difficult at the moment to directly relate available experimental data to human pathophysiology. More well controlled clinical intervention trials are needed to further clarify the exact role of lycopene in the prevention of lung cancer cell growth. Such studies should take into consideration subject selection, specific markers of analysis, the levels of carotenoids being tested, metabolism and isomerization of lycopene, interaction with other bioactive food components. This article reviews data on the cancer preventive activities of lycopene, possible mechanisms involved, and the relationship between lycopene consumption and human cancer risk.

N-isopropyl-p-iodoamphetamine receptors in normal and cancerous tissue of the human lung

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Eiko; Mishima, Michiaki; Kawakami, Kenzo; Sakai, Naoki; Sugiura, Naoharu; Kuno, Kenshi [Kyoto Univ. (Japan). Dept. of Clinical Physiology; Taniguchi, Takashi [Kyoto Pharmaceutical Univ. (Japan). Dept. of Neurobiology

1993-04-01

N-Isopropyl-p-iodoamphetamine (IMP) receptors in normal human lung tissue were characterized using a radioligand binding assay with iodine-125 IMP as the ligand. Saturation binding studies revealed the presence of two binding sites with dissociation constant (K[sub d]) values of 53[+-]2 and 4687[+-]124 nM and maximum binding capacity (Bmax) values of 7[+-]1 and 133[+-]27 pmol/mg protein (n=5) respectively. The IC[sub 50] values of various amines were as follows: IMP, 9x10[sup -5] M; propranolol, 5x10[sup -4] M; haloperidol, 6x10[sup -4] M; ketamine, 9x10[sup -3] M; dopamine, 1x10[sup -2] M. The IMP receptors of cancerous tissue obtained from human lung also had two binding sites with K[sub d] values of 54[+-]2 and 5277[+-]652 nM and Bmax values of 7[+-]1 and 103[+-]21 pmol/mg protein (n=3) respectively. There was no significant difference in binding parameters between normal and cancerous lung tissue. These results demonstrate the existence of IMP receptors and suggest that cancer does not affect the nature of IMP receptors in human lung tissue. (orig.).

Alternative Donor Graft Sources for Adults with Hematologic Malignancies: A Donor for All Patients in 2017!

Science.gov (United States)

Kindwall-Keller, Tamila L; Ballen, Karen K

2017-09-01

Hematopoietic stem cell transplant (HSCT) is potentially curative for a wide variety of malignant diseases, including acute and leukemias, lymphoma, and myelodysplasia. Choice of a stem cell donor is dependent on donor availability, donor compatibility and health, recipient disease type, and recipient condition. Current sources of stem cell donation for HSCT are matched sibling donors (MSDs), matched unrelated donors (MUDs), 1-antigen mismatched unrelated donors (MMUDs), haploidentical donors (haplo), and umbilical cord blood (UCB) units. Historically, preferred donors for HSCT have been human leukocyte antigen (HLA)-matched sibling donors; however, only about 30% of U.S. patients will have a MSD available. The majority of patients referred for HSCT will require an alternative donor graft: MUD, MMUD, UCB, or haplo. The likelihood of finding a MUD varies depending on the ethnicity of the recipient. White Caucasians of European descent have the greatest chance of finding a MUD. Chances of finding a MUD are significantly less for African-American or Hispanic recipients due to HLA polymorphisms. Therefore, MMUD, UCB, and haplo donor graft sources expand the donor pool for recipients who do not have a MSD or MUD available. Given the variety of different donor stem cell sources available today, nearly every patient who needs an allogeneic HSCT has a potential donor in 2017. All transplant-eligible patients with hematologic malignancies should be evaluated by a transplant center to determine if HSCT is a viable treatment option for their underlying disease process. The goal of this review is to increase the awareness of oncology practitioners to the availability of alternative donor stem cell transplants for patients with hematologic malignancies. Despite new agents, stem cell transplant remains the only curative therapy for many patients with acute and chronic leukemia, myelodysplasia, and lymphoma. Given the variety of different donor stem cell sources available today

Pulmonary haptoglobin (pHp) is part of the surfactant system in the human lung.

Science.gov (United States)

Abdullah, Mahdi; Goldmann, Torsten

2012-11-20

Since the existence of pHp was demonstrated, it has been shown that this molecule and its receptor CD163 are regulated by different stimuli. Furthermore, a comparably fast secretion of pHp was described as well as the immuno-stimulatory effects. The intention of this study was to elucidate the role of pHp in the human lungs further. Here we show, by means of confocal microscopy and immune-electron-microscopy, a clear co-localization of pHp with surfactant protein-B in lamellar bodies of alveolar epithelial cells type II. These results are underlined by immunohistochemical stainings in differently fixed human lung tissues, which show pHp in vesicular and released form. The images of the released form resemble the intended position of surfactant in the human alveolus. pHp is secreted by Alveolar epithelial cells type II as previously shown. Moreover, pHp is co-localized with Surfactant protein-B. We conclude that the presented data shows that pHp is a native part of the surfactant system in the human lung. http://www.diagnosticpathology.diagnomx.eu/vs/2563584738239912.

Clinical management and outcomes of patients with Hermansky-Pudlak syndrome pulmonary fibrosis evaluated for lung transplantation.

Science.gov (United States)

El-Chemaly, Souheil; O'Brien, Kevin J; Nathan, Steven D; Weinhouse, Gerald L; Goldberg, Hilary J; Connors, Jean M; Cui, Ye; Astor, Todd L; Camp, Philip C; Rosas, Ivan O; Lemma, Merte; Speransky, Vladislav; Merideth, Melissa A; Gahl, William A; Gochuico, Bernadette R

2018-01-01

Pulmonary fibrosis is a progressive, fatal manifestation of Hermansky-Pudlak syndrome (HPS). Some patients with advanced HPS pulmonary fibrosis undergo lung transplantation despite their disease-associated bleeding tendency; others die while awaiting donor organs. The objective of this study is to determine the clinical management and outcomes of a cohort with advanced HPS pulmonary fibrosis who were evaluated for lung transplantation. Six patients with HPS-1 pulmonary fibrosis were evaluated at the National Institutes of Health Clinical Center and one of two regional lung transplant centers. Their median age was 41.5 years pre-transplant. Three of six patients died without receiving a lung transplant. One of these was referred with end-stage pulmonary fibrosis and died before a donor organ became available, and donor organs were not identified for two other patients sensitized from prior blood product transfusions. Three of six patients received bilateral lung transplants; they did not have a history of excessive bleeding. One patient received peri-operative desmopressin, one was transfused with intra-operative platelets, and one received extracorporeal membrane oxygenation and intra-operative prothrombin complex concentrate, platelet transfusion, and desmopressin. One transplant recipient experienced acute rejection that responded to pulsed steroids. No evidence of chronic lung allograft dysfunction or recurrence of HPS pulmonary fibrosis was detected up to 6 years post-transplant in these three lung transplant recipients. In conclusion, lung transplantation and extracorporeal membrane oxygenation are viable options for patients with HPS pulmonary fibrosis. Alloimmunization in HPS patients is an important and potentially preventable barrier to lung transplantation; interventions to limit alloimmunization should be implemented in HPS patients at risk of pulmonary fibrosis to optimize their candidacy for future lung transplants.

Herpes simplex virus-2 transmission following solid organ transplantation: Donor-derived infection and transplantation from prior organ recipients.

Science.gov (United States)

Macesic, Nenad; Abbott, Iain J; Kaye, Matthew; Druce, Julian; Glanville, Allan R; Gow, Paul J; Hughes, Peter D; Korman, Tony M; Mulley, William R; O'Connell, Phillip J; Opdam, Helen; Paraskeva, Miranda; Pitman, Matthew C; Setyapranata, Stella; Rawlinson, William D; Johnson, Paul D R

2017-10-01

Owing to limited availability of donor organs, previous solid organ transplant (SOT) recipients are increasingly considered as potential organ donors. We report donor-derived transmission of herpes simplex virus type-2 (HSV-2) to two clusters of SOT recipients with transmission from the original donor and an HSV-2-infected recipient who subsequently became a donor. We reviewed medical records of the donors and recipients in both clusters. Pre-transplant serology and virological features of HSV-2 were characterized. Genotyping of HSV-2 isolates to determine potential for donor transmission of HSV-2 through transplantation of organs from prior organ recipients was performed. A kidney-pancreas recipient died day 9 post transplant. Following confirmation of brain death, the lungs and recently transplanted kidney were donated to two further recipients. The liver was not retrieved, but biopsy confirmed HSV-2 infection. Testing on the original donor showed negative HSV-2 polymerase chain reaction and HSV immunoglobulin (Ig)M, but positive HSV-2 IgG. The liver recipient from the original donor developed HSV-2 hepatitis and cutaneous infection that responded to treatment with intravenous acyclovir. In the second cluster, lung and kidney recipients both developed HSV-2 viremia that was successfully treated with antiviral therapy. Genotyping of all HSV-2-positive samples showed 100% sequence homology for three recipients. Donor-derived HSV infection affected two clusters of recipients because of transplantation of organs from a prior organ recipient. HSV should be considered as a possible cause of illness in febrile SOT recipients in the immediate post-transplant period and may cause disseminated disease and re-infection in HSV-2-seropositive recipients. Testing of HSV serology and prophylaxis may be considered in SOT recipients not receiving cytomegalovirus prophylaxis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Anti-EGFR therapy radiosensitizes human lung adenocarcinoma xenograft in nude mouse

International Nuclear Information System (INIS)

Wang Hui; Li Tianran; Tian Jiahe; Qu Baolin; Zhu Hui

2008-01-01

Objective: To investigate the effect of Gefitinib on radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. Methods: Human lung adenocarcinoma cell line A549 was used to establish nude mouse xenograft tumor model. The mice were derided into 4 groups: control, irradiation alone, Gefinitib alone and radiation combined with Genifitib. Radiation schedule was 3 fractions of 5 Gy, once daily. Gefitinib was daily administered by gavage at 100 mg/(kg·day -1 ) for 14 days. In the combination group, radiotherapy was performed 2 hours after Gefitinib administration. Tumor diameter was measured every other day. Percentage of tumor growth inhibition, growth delay time and regrowth delay time were evaluated. Results: For A549 xenografts in radiation alone, gefitinib alone and combination therapy groups, the percentage of tumor growth inhibition was 22.7%, 12.4% and 38.2%, respectively (F=25.75, P=0.000). Tumor growth delay time was 6.0, 7.8 and 21.6 days, respectively (F=70.49, P=0.000). Tumor regrowth delay time in combination therapy and irradiation alone groups was 23.4 and 10.2 days. (F=174.24, P= 0.000). Sensitizing enhancement ratio of combination group was 1.5 in growth and 1.7 in regrowth. Conclusions: Anti-EGFR therapy enhances the radiosensitivity of human lung adenocarcinoma xenograft in nude mouse. (authors)

Methylation screening of the TGFBI promoter in human lung and prostate cancer by methylation-specific PCR

International Nuclear Information System (INIS)

Shah, Jinesh N; Shao, Genze; Hei, Tom K; Zhao, Yongliang

2008-01-01

Hypermethylation of the TGFBI promoter has been shown to correlate with decreased expression of this gene in human tumor cell lines. In this study, we optimized a methylation-specific polymerase chain reaction (MSP) method and investigated the methylation status of the TGFBI promoter in human lung and prostate cancer specimens. Methylation-specific primers were designed based on the methylation profiles of the TGFBI promoter in human tumor cell lines, and MSP conditions were optimized for accurate and efficient amplification. Genomic DNA was isolated from lung tumors and prostatectomy tissues of prostate cancer patients, bisulfite-converted, and analyzed by MSP. Among 50 lung cancer samples, 44.0% (22/50) harbored methylated CpG sites in the TGFBI promoter. An analysis correlating gene methylation status with clinicopathological cancer features revealed that dense methylation of the TGFBI promoter was associated with a metastatic phenotype, with 42.9% (6/14) of metastatic lung cancer samples demonstrating dense methylation vs. only 5.6% (2/36) of primary lung cancer samples (p < 0.05). Similar to these lung cancer results, 82.0% (41/50) of prostate cancer samples harbored methylated CpG sites in the TGFBI promoter, and dense methylation of the promoter was present in 38.9% (7/18) of prostate cancer samples with the feature of locoregional invasiveness vs. only 19.4% (6/31) of prostate cancer samples without locoregional invasiveness (p < 0.05). Furthermore, promoter hypermethylation correlated with highly reduced expression of the TGFBI gene in human lung and prostate tumor cell lines. We successfully optimized a MSP method for the precise and efficient screening of TGFBI promoter methylation status. Dense methylation of the TGFBI promoter correlated with the extent of TGFBI gene silencing in tumor cell lines and was related to invasiveness of prostate tumors and metastatic status of lung cancer tumors. Thus, TGFBI promoter methylation can be used as a potential

Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

Energy Technology Data Exchange (ETDEWEB)

Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Oshita, Masatoshi; Ideno, Shoji [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Yunoki, Mikihiro [Osaka Research Laboratory, Benesis Corporation, Yodogawa-ku, Osaka 532-6505 (Japan); Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan); Kuhara, Motoki [Ina Laboratory, Medical and Biological Laboratories Corporation, Ltd., Ina, Nagano 396-0002 (Japan); Yamamoto, Naomasa [Department of Biochemistry, School of Pharmaceutical Sciences, Ohu University, Koriyama, Fukushima 963-8611 (Japan); Okuno, Yoshinobu [Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kanonji, Kagawa 768-0061 (Japan); Ikuta, Kazuyoshi, E-mail: ikuta@biken.osaka-u.ac.jp [Department of Virology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871 (Japan)

2009-09-11

Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.

Broad neutralizing human monoclonal antibodies against influenza virus from vaccinated healthy donors

International Nuclear Information System (INIS)

Kubota-Koketsu, Ritsuko; Mizuta, Hiroyuki; Oshita, Masatoshi; Ideno, Shoji; Yunoki, Mikihiro; Kuhara, Motoki; Yamamoto, Naomasa; Okuno, Yoshinobu; Ikuta, Kazuyoshi

2009-01-01

Human monoclonal antibodies (HuMAbs) prepared from patients with viral infections could provide information on human epitopes important for the development of vaccines as well as potential therapeutic applications. Through the fusion of peripheral blood mononuclear cells from a total of five influenza-vaccinated volunteers, with newly developed murine-human chimera fusion partner cells, named SPYMEG, we obtained 10 hybridoma clones stably producing anti-influenza virus antibodies: one for influenza A H1N1, four for influenza A H3N2 and five for influenza B. Surprisingly, most of the HuMAbs showed broad reactivity within subtype and four (two for H3N2 and two for B) showed broad neutralizing ability. Importantly, epitope mapping revealed that the two broad neutralizing antibodies to H3N2 derived from different donors recognized the same epitope located underneath the receptor-binding site of the hemagglutinin globular region that is highly conserved among H3N2 strains.

Cellular morphometry of the bronchi of human and dog lungs

International Nuclear Information System (INIS)

Robbins, E.S.

1991-09-01

One hundred and forty-seven bronchial samples (generations 3--6) from 66 patients (62 usable; 36 female, 26 male; median age 61) have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. In addition, one hundred and fifty-six mongol dog bronchi (generations 2--6) dissected from different lobes of 26 dog lungs have also been similarly prepared. One hundred and twenty-seven human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 655 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurement of the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 328 micrographs of dog epithelium from 33 bronchial samples have been used to measure the distances of basal and mucous cell nuclei to the epithelial free surface and have been entered into COSAS. Using the COSAS planimetry program, we continue to expand our established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the same 5 epithelial cell types of dog bronchi. Our micrographs of human bronchial epithelium have allowed us to analyze the recent suggestion that the DNA of lymphocytes may be subject to significant damage from Rn progeny while within the lung. Since the last progress report three papers have been submitted for publication. 17 refs., 4 tabs

Prevalence of Human T-lymphotropic virus type 1 and 2 among blood donors in Manaus, Amazonas State, Brazil

Directory of Open Access Journals (Sweden)

Márcia Poinho EncarnaçÃo de Morais

2017-12-01

Full Text Available ABSTRACT Introduction: Human T-lymphotropic virus type 1 and 2 (HTLV-1/2 is endemic in Brazil, but few studies have investigated the seroprevalence of HTLV and its subtypes among blood donors in the capital city Manaus, Amazonas State, Brazil. Aim: To estimate the seroprevalence of HTLV-1/2 and to identify circulating subtypes among blood donors in Manaus. Materials and Methods: Blood donors (2001-2003 were screened for HTLV-1/2 antibodies by ELISA. Positive results were confirmed and subtyped by Western blot assays. Prevalence rates were calculated and compared with demographic data. Results: Among the 87,402 individuals screened, 116 (0.13% were seropositive for HTLV-1/2. A second sample (76/116 was collected and retested by HTLV-1/2 ELISA, of which only 41/76 were positive. Western blot confirmed HTLV infection in 24/41 retested blood donors [HTLV-1 (n=16, HTLV-2 (n=5 and HTLV-untypable (n=3]. Discussion: HTLV-1 and HTLV-2 are prevalent among blood donors in Manaus. However, additional studies are needed to comprehend the epidemiology of HTLV-1/2 in Amazonas not only to understand the pathophysiology of the disease providing adequate medical assistance, but also to reduce or block virus transmission.

Iron concentrations in breast milk and selected maternal factors of human milk bank donors.

Science.gov (United States)

Mello-Neto, Julio; Rondó, Patrícia H C; Morgano, Marcelo A; Oshiiwa, Marie; Santos, Mariana L; Oliveira, Julicristie M

2010-05-01

The aim of this study was to evaluate the relationship between iron concentration in mature breast milk and characteristics of 136 donors of a Brazilian milk bank. Iron, vitamin A, zinc, and copper concentrations were assessed in human milk and maternal blood. Data were collected on maternal anthropometrics, obstetric, socioeconomic, demographic, and lifestyle factors. Iron, zinc, and copper in milk and zinc and copper in blood were detected by spectrophotometry. Vitamin A in milk and blood was determined by high-performance liquid chromatography. Hemoglobin was measured by electronic counting and serum iron and ferritin by colorimetry and chemoluminescence, respectively. Transferrin and ceruloplasmin were determined by nephelometry. According to multivariate linear regression analysis, iron in milk was positively associated with vitamin A in milk and with smoking but negatively associated with timing of breast milk donation (P milk of Brazilian donors may be influenced by nutritional factors and smoking.

Unilateral lung transplantation for pulmonary fibrosis.

Science.gov (United States)

1986-05-01

Improvements in immunosuppression and surgical techniques have made unilateral lung transplantation feasible in selected patients with end-stage interstitial lung disease. We report two cases of successful unilateral lung transplantation for end-stage respiratory failure due to pulmonary fibrosis. The patients, both oxygen-dependent, had progressive disease refractory to all treatment, with an anticipated life expectancy of less than one year on the basis of the rate of progression of the disease. Both patients were discharged six weeks after transplantation and returned to normal life. They are alive and well at 26 months and 14 months after the procedure. Pulmonary-function studies have shown substantial improvement in their lung volumes and diffusing capacities. For both patients, arterial oxygen tension is now normal and there is no arterial oxygen desaturation with exercise. This experience shows that unilateral lung transplantation, for selected patients with end-stage interstitial lung disease, provides a good functional result. Moreover, it avoids the necessity for cardiac transplantation, as required by the combined heart-lung procedure, and permits the use of the donor heart for another recipient.

Salivary agglutinin and lung scavenger receptor cysteine-rich glycoprotein 340 have broad anti-influenza activities and interactions with surfactant protein D that vary according to donor source and sialylation

DEFF Research Database (Denmark)

Hartshorn, Kevan L.; Ligtenberg, Antoon; White, Mitchell R.

2006-01-01

We previously found that scavenger receptor cysteine-rich gp-340 (glycoprotein-340), isolated from lung or saliva, directly inhibits human IAVs (influenza A viruses). We now show that salivary gp-340 has broad antiviral activity against human, equine and porcine IAV strains. Although lung...

Sterols of Pneumocystis carinii hominis organisms isolated from human lungs

DEFF Research Database (Denmark)

Kaneshiro, E S; Amit, Z; Chandra, Jan Suresh

1999-01-01

in conjunction with analyses of chemically synthesized authentic standards. The sterol composition of isolated P. carinii hominis organisms has yet to be reported. If P. carinii from animal models is to be used for identifying potential drug targets and for developing chemotherapeutic approaches to clear human...... infections, it is important to determine whether the 24-alkylsterols of organisms found in rats are also present in organisms in humans. In the present study, sterol analyses of P. carinii hominis organisms isolated from cryopreserved human P. carinii-infected lungs and from bronchoalveolar lavage fluid were...

Regulation of cytochrome P4501A1 expression by hyperoxia in human lung cell lines: Implications for hyperoxic lung injury

International Nuclear Information System (INIS)

Bhakta, Kushal Y.; Jiang, Weiwu; Couroucli, Xanthi I.; Fazili, Inayat S.; Muthiah, Kathirvel; Moorthy, Bhagavatula

2008-01-01

Supplemental oxygen, used to treat pulmonary insufficiency in newborns, contributes to the development of bronchopulmonary dysplasia (BPD). Cytochrome P4501A enzymes are induced by hyperoxia in animal models, but their role in human systems is unknown. Here we investigated the molecular mechanisms of induction of CYP1A1 by hyperoxia in human lung cell lines. Three human lung cell lines were exposed to hyperoxia (95% O2) for 0-72 h, and CYP1A1 activities, apoprotein contents, and mRNA levels were determined. Hyperoxia significantly induced CYP1A1 activity and protein contents (2-4 fold), and mRNA levels (30-40 fold) over control in each cell line. Transfection of a CYP1A1 promoter/luciferase reporter construct, followed by hyperoxia (4-72 h), showed marked (2-6 fold) induction of luciferase expression. EMSA and siRNA experiments strongly suggest that the Ah receptor (AHR) is involved in the hyperoxic induction of CYP1A1. MTT reduction assays showed attenuation of cell injury with the CYP1A1 inducer beta-naphthoflavone (BNF). Our results strongly suggest that hyperoxia transcriptionally activates CYP1A1 expression in human lung cell lines by AHR-dependent mechanisms, and that CYP1A1 induction is associated with decreased toxicity. This novel finding of induction of CYP1A1 in the absence of exogenous AHR ligands could lead to novel interventions in the treatment of BPD

E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells

OpenAIRE

Lee, Hyun-Wook; Park, Sung-Hyun; Weng, Mao-wen; Wang, Hsiang-Tsui; Huang, William C.; Lepor, Herbert; Wu, Xue-Ru; Chen, Lung-Chi; Tang, Moon-shong

2018-01-01

Significance E-cigarette smoke (ECS) delivers nicotine through aerosols without burning tobacco. ECS is promoted as noncarcinogenic. We found that ECS induces DNA damage in mouse lung, bladder, and heart and reduces DNA-repair functions and proteins in lung. Nicotine and its nitrosation product 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone can cause the same effects as ECS and enhance mutations and tumorigenic cell transformation in cultured human lung and bladder cells. These results indica...

Toona Sinensis Extracts Induced Cell Cycle Arrest and Apoptosis in the Human Lung Large Cell Carcinoma

Directory of Open Access Journals (Sweden)

Cheng-Yuan Wang

2010-02-01

Full Text Available Toona sinensis extracts have been shown to exhibit anti-cancer effects in human ovarian cancer cell lines, human promyelocytic leukemia cells and human lung adenocarcinoma. Its safety has also been confirmed in animal studies. However, its anti-cancer properties in human lung large cell carcinoma have not been studied. Here, we used a powder obtained by freeze-drying the super-natant of centrifuged crude extract from Toona sinensis leaves (TSL-1 to treat the human lung carcinoma cell line H661. Cell viability was evaluated by the 3-(4-,5-dimethylthiazol-2-yl-2,5-diphenyl tetrazolium bromide assay. Flow cytometry analysis revealed that TSL-1 blocked H661 cell cycle progression. Western blot analysis showed decreased expression of cell cycle proteins that promote cell cycle progression, including cyclin-dependent kinase 4 and cyclin D1, and increased the expression of proteins that inhibit cell cycle progression, including p27. Furthermore, flow cytometry analysis showed that TSL-1 induced H661 cell apoptosis. Western blot analysis showed that TSL-1 reduced the expression of the anti-apoptotic protein B-cell lymphoma 2, and degraded the DNA repair protein, poly(ADP-ribose polymerase. TSL-1 shows potential as a novel therapeutic agent or for use as an adjuvant for treating human lung large cell carcinoma.

In vivo measurement of actinides in the human lung

International Nuclear Information System (INIS)

Anderson, A.L.; Campbell, G.W.; Griffith, R.V.

1979-01-01

The problems associated with the in vivo detection and measurement of actinides in the human lung are discussed together with various measurement systems currently in use. In particular, the methods and calibration procedures employed at the Lawrence Livermore Laboratory, namely, the use of twin Phoswich detectors and a new, more realistic, tissue-equivalent phantom, are described. Methods for the measurement of chest-wall thickness, fat content, and normal human background counts are also discussed. Detection-efficiency values and minimum detectable activity estimates are given for three common actinides, 238 Pu, 239 Pu, and 241 Am

Utilization of the organ care system for bilateral lung transplantation: preliminary results of a comparative study.

Science.gov (United States)

Zeriouh, Mohamed; Sabashnikov, Anton; Mohite, Prashant N; Zych, Bartlomiej; Patil, Nikhil P; García-Sáez, Diana; Koch, Achim; Weymann, Alexander; Soresi, Simona; Wippermann, Jens; Wahlers, Thorsten; De Robertis, Fabio; Popov, Aron-Frederik; Simon, André R

2016-09-01

Lung transplantation (LTx) remains the gold standard for patients with end-stage lung disease. However, due to donor organ shortage and brain stem death-related lung injury, only a small proportion of lungs are used increasing the mortality rate on the waiting list. A portable normothermic continuous ex vivo perfusion using the organ care system (OCS) represents one of the tools to increase the pool of donor organs and to improve the function of marginal lungs. We sought to assess mid-term outcomes after LTx using OCS and to compare outcomes including overall survival and freedom from bronchiolitis obliterans syndrome (BOS) with those after conventional preservation. Included were 322 consecutive LTx performed at Harefield Hospital between January 2007 and December 2014. Recipients were divided into two groups depending on the organ storage strategy: the majority of patients (n = 308) were transplanted using lungs after cold storage (cold storage group), whereas 14 organs were preserved using OCS (OCS group). The primary end-points were overall survival and freedom from BOS after LTx. The secondary end-points were perioperative clinical characteristics and adverse events. There were no statistically significant differences in terms of most baseline donor and recipient characteristics. The percentage of heavy smokers among donors [8 (2.9%) vs 6 (42.9%), P < 0.001] and the median number of pack-years smoked by donors [14 (7;24) vs 25 (24;30), P = 0.026] were statistically higher in the OCS group. Patients from the OCS group had significantly better postoperative FEV1 at 3 [69 (54;86) vs 93 (87;89), P < 0.001] and 6 [77 (60;90) vs 94 (84;100), P = 0.006] months. There were no statistically significant differences in terms of cumulative survival and freedom from BOS between the two groups. Results after LTx using OCS are acceptable with excellent survival, and superior early outcome in terms of postoperative lung function despite higher risk in the OCS group. Further

Radioimmunological analysis of the levels of the carcinoembryonic antigen and alpha-fetoprotein in the blood of patients with lung cancer

International Nuclear Information System (INIS)

Barbolin, V.I.; Abramov, V.F.; Tkacheva, G.A.

1980-01-01

The level of the carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) are determined in the blood of 41 patients with lung cancer and 70 healthy individuals (donors). It has been found that the CEA content in the blood of patients with lung cancer 2.6-4 times exceeds normal. No variations in the CEA and AFP levels depending upon the age and sex of the donors are revealed. A histological diagnosis of lung cancer has been made in 83.8% of the patients with CEA high concentration in the blood. Determination of the CEA level in the blood may be of diagnostic significance in the clinical picture of lung cancer

Chronic inorganic arsenic exposure in vitro induces a cancer cell phenotype in human peripheral lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Person, Rachel J.; Olive Ngalame, Ntube N.; Makia, Ngome L.; Bell, Matthew W.; Waalkes, Michael P.; Tokar, Erik J., E-mail: tokare@niehs.nih.gov

2015-07-01

Inorganic arsenic is a human lung carcinogen. We studied the ability of chronic inorganic arsenic (2 μM; as sodium arsenite) exposure to induce a cancer phenotype in the immortalized, non-tumorigenic human lung peripheral epithelial cell line, HPL-1D. After 38 weeks of continuous arsenic exposure, secreted matrix metalloproteinase-2 (MMP2) activity increased to over 200% of control, levels linked to arsenic-induced cancer phenotypes in other cell lines. The invasive capacity of these chronic arsenic-treated lung epithelial (CATLE) cells increased to 320% of control and colony formation increased to 280% of control. CATLE cells showed enhanced proliferation in serum-free media indicative of autonomous growth. Compared to control cells, CATLE cells showed reduced protein expression of the tumor suppressor gene PTEN (decreased to 26% of control) and the putative tumor suppressor gene SLC38A3 (14% of control). Morphological evidence of epithelial-to-mesenchymal transition (EMT) occurred in CATLE cells together with appropriate changes in expression of the EMT markers vimentin (VIM; increased to 300% of control) and e-cadherin (CDH1; decreased to 16% of control). EMT is common in carcinogenic transformation of epithelial cells. CATLE cells showed increased KRAS (291%), ERK1/2 (274%), phosphorylated ERK (p-ERK; 152%), and phosphorylated AKT1 (p-AKT1; 170%) protein expression. Increased transcript expression of metallothioneins, MT1A and MT2A and the stress response genes HMOX1 (690%) and HIF1A (247%) occurred in CATLE cells possibly in adaptation to chronic arsenic exposure. Thus, arsenic induced multiple cancer cell characteristics in human peripheral lung epithelial cells. This model may be useful to assess mechanisms of arsenic-induced lung cancer. - Highlights: • Chronic arsenic exposure transforms a human peripheral lung epithelia cell line. • Cells acquire characteristics in common with human lung adenocarcinoma cells. • These transformed cells provide a

Sperm donation: implications of Canada's Assisted Human Reproduction Act 2004 for recipients, donors, health professionals, and institutions.

Science.gov (United States)

Daniels, K; Feyles, V; Nisker, J; Perez-Y-Perez, M; Newton, C; Parker, J A; Tekpetey, F; Haase, J

2006-07-01

On April 22, 2004, the Assisted Human Reproduction Act came into force, prohibiting the purchase of sperm or eggs from donors in Canada. In response to the concerns of medical professionals and some consumers that prohibiting payment would lead to a decline in the number of gamete donors, Health Canada commissioned research on altruistic donor recruitment and recruitment strategies. Twenty-two studies of sperm donors were located and their findings reviewed. The studies spanned 23 years (1980-2003), were undertaken in a range of countries, and were chosen on the merit of their relevance to the development of recruitment strategies within a policy of altruistic sperm donation. Observations were derived from assessing and comparing the purposes, findings, and implications of the 22 studies. Payment for providing sperm was made in all but three studies, although participants in 15 studies indicated clearly that their motivations were primarily altruistic. Observations indicate that men who are more willing to be identified to offspring in the future share demographic characteristics, such as age and parental status, with those who are prepared to donate altruistically. These characteristics appear to be a factor in motivation to donate altruistically. The studies show that there are men who are prepared to donate sperm without financial payment. The findings suggest that a change is required in the culture of sperm donation, specifically the adoption of a new approach to donor recruitment.

21 CFR 640.3 - Suitability of donor.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Suitability of donor. 640.3 Section 640.3 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... determination shall be made on the day of collection from the donor by means of medical history, a test for...

21 CFR 640.63 - Suitability of donor.

Science.gov (United States)

2010-04-01

... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Suitability of donor. 640.63 Section 640.63 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) BIOLOGICS... determination shall be made on the day of collection from the donor by means of a medical history, tests, and...

Waiting narratives of lung transplant candidates.

Science.gov (United States)

Yelle, Maria T; Stevens, Patricia E; Lanuza, Dorothy M

2013-01-01

Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman's concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients' stories and hear what is most meaningful in their lives.

Waiting Narratives of Lung Transplant Candidates

Directory of Open Access Journals (Sweden)

Maria T. Yelle

2013-01-01

Full Text Available Before 2005, time accrued on the lung transplant waiting list counted towards who was next in line for a donor lung. Then in 2005 the lung allocation scoring system was implemented, which meant the higher the illness severity scores, the higher the priority on the transplant list. Little is known of the lung transplant candidates who were listed before 2005 and were caught in the transition when the lung allocation scoring system was implemented. A narrative analysis was conducted to explore the illness narratives of seven lung transplant candidates between 2006 and 2007. Arthur Kleinman’s concept of illness narratives was used as a conceptual framework for this study to give voice to the illness narratives of lung transplant candidates. Results of this study illustrate that lung transplant candidates expressed a need to tell their personal story of waiting and to be heard. Recommendation from this study calls for healthcare providers to create the time to enable illness narratives of the suffering of waiting to be told. Narrative skills of listening to stories of emotional suffering would enhance how healthcare providers could attend to patients’ stories and hear what is most meaningful in their lives.

Donor conversion and procurement failure: the fate of our potential organ donors.

Science.gov (United States)

Branco, Bernardino C; Inaba, Kenji; Lam, Lydia; Salim, Ali; Barmparas, Galinos; Teixeira, Pedro G R; Talving, Peep; Demetriades, Demetrios

2011-02-01

Donor availability remains the primary limiting factor for organ transplantation today. The purpose of this study was to examine the causes of procurement failure amongst potential organ donors. After Institutional Review Board approval, all surgical intensive care unit (SICU) patients admitted to the LAC+USC Medical Center from 01/2006 to 12/2008 who became potential organ donors were identified. Demographics, clinical data, and procurement data were abstracted. In non-donors, the causes of procurement failure were documented. During the 3-year study period, a total of 254 patients were evaluated for organ donation. Mean age was 44.8±18.7 years; 191 (75.2%) were male, 136 (53.5%) were Hispanic, and 148 (58.3%) were trauma patients. Of the 254 patients, 116 (45.7%) were not eligible for donation: 34 had multi-system organ failure, 24 did not progress to brain death and had support withdrawn, 18 had uncontrolled sepsis, 15 had malignancy, 6 had human immunodeficiency virus or hepatitis B or C, and 19 patients had other contraindications to organ donation. Of the remaining 138 eligible patients, 83 (60.2%) did not donate: 56 because the family denied consent, 9 by their own choice. In six, next of kin could not be located, five died because of hemodynamic instability before organ procurement was possible, four had organs that could not be placed, and three had their organs declined by the organ procurement organization. The overall consent rate was 57.5% (n=67). From the 55 donors, 255 organs were procured (yield 4.6 organs/donor). Of all patients screened for organ donation, only a fifth actually donated. Denial of consent was the major potentially preventable cause of procurement failure, whereas hemodynamic instability accounted for only a small percentage of donor losses. With such low conversion rates, the preventable causes of procurement failure warrant further study.

Probability of Finding Marrow Unrelated Donor (MUD) for an Indian patient in a Multi-national Human Leukocyte Antigen (HLA) Registry.

Science.gov (United States)

Tiwari, Aseem K; Bhati-Kushwaha, Himakshi; Kukreja, Pooja; Mishra, Vikash C; Tyagi, Neetu; Sharma, Ashish; Raina, Vimarsh

2015-06-01

With an increase in the number of transplants happening globally, hematopoietic stem cells (HSC) transplantation from matched unrelated donor (MUD) has begun. The increasing trend of MUD transplants across countries has been largely facilitated with the conspicuous growth of volunteer HSC donor noted in the last decade i.e. 8 million HSC donors in 2002 to more than 22 million in 2013 registered in 71 member registries of the Bone Marrow Donor Worldwide (BMDW). Some populations of the world are still very poorly represented in these registries. Since, the chances of successful engraftment and disease free survival are directly proportional to the HLA compatibility between the recipient and the prospective donor, the diversity of the HLA system at the antigenic and allelic level and the heterogeneity of HLA data of the registered donors has a bearing on the probability of finding a volunteer unrelated HSC donor for patients from such populations. In the present study 126 patients were identified suffering from hematological diseases requiring MUD transplant. Their HLA typing was performed and search was done using BMDW database. The search results for these Indian patients in the multinational registry as well as in the Indian Registries were analyzed using mean, range, standard deviation and finally evaluated in terms of probability for finding matched donor (MUD). Total Asian population is only 11 % in the BMDW making it difficult to find a MUD for an Asian patient. The current study supports this, experimentally; revealing that the probability of finding an allele match for an Indian patient in the multinational Human Leukocyte Antigen (HLA) registries is 16 % and a dismal 0.008 % in the Indian registries (donors in Indian registries is just 33,678 as compared to 22.5 million in BMDW). This greatly, emphasizes on enhancing the number of Indian donors in Indian and multi-national registries.

Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor

International Nuclear Information System (INIS)

Patil, Rajreddy; Kumar, B. Mohana; Lee, Won-Jae; Jeon, Ryoung-Hoon; Jang, Si-Jung; Lee, Yeon-Mi; Park, Bong-Wook; Byun, June-Ho; Ahn, Chun-Seob; Kim, Jae-Won; Rho, Gyu-Jin

2014-01-01

Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy. - Highlights: • Isolated and characterized three types of human dental MSCs from a single donor. • MSCs of dental follicle, pulp and papilla had largely similar biological properties. • All MSCs were capable of transdifferentiating into functional hepatocyte-like cells. • 2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs. • Similar proteomic profiles suggest interchangeable applications of dental MSCs

Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor

Energy Technology Data Exchange (ETDEWEB)

Patil, Rajreddy; Kumar, B. Mohana; Lee, Won-Jae; Jeon, Ryoung-Hoon; Jang, Si-Jung; Lee, Yeon-Mi [Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Park, Bong-Wook; Byun, June-Ho [Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju 660-702 (Korea, Republic of); Ahn, Chun-Seob; Kim, Jae-Won [Department of Microbiology, Division of Life Sciences, Research Institute of Life Science, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Rho, Gyu-Jin, E-mail: jinrho@gnu.ac.kr [Department of Theriogenology and Biotechnology, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701 (Korea, Republic of); Research Institute of Life Sciences, Gyeongsang National University, Jinju 660-701 (Korea, Republic of)

2014-01-01

Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy. - Highlights: • Isolated and characterized three types of human dental MSCs from a single donor. • MSCs of dental follicle, pulp and papilla had largely similar biological properties. • All MSCs were capable of transdifferentiating into functional hepatocyte-like cells. • 2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs. • Similar proteomic profiles suggest interchangeable applications of dental MSCs.

Lung transplantation: overall approach regarding its major aspects

Science.gov (United States)

de Camargo, Priscila Cilene León Bueno; Teixeira, Ricardo Henrique de Oliveira Braga; Carraro, Rafael Medeiros; Campos, Silvia Vidal; Afonso, José Eduardo; Costa, André Nathan; Fernandes, Lucas Matos; Abdalla, Luis Gustavo; Samano, Marcos Naoyuki; Pêgo-Fernandes, Paulo Manuel

2015-01-01

ABSTRACT Lung transplantation is a well-established treatment for patients with advanced lung disease. The evaluation of a candidate for transplantation is a complex task and involves a multidisciplinary team that follows the patient beyond the postoperative period. Currently, the mean time on the waiting list for lung transplantation in the state of São Paulo, Brazil, is approximately 18 months. For Brazil as a whole, data from the Brazilian Organ Transplant Association show that, in 2014, there were 67 lung transplants and 204 patients on the waiting list for lung transplantation. Lung transplantation is most often indicated in cases of COPD, cystic fibrosis, interstitial lung disease, non-cystic fibrosis bronchiectasis, and pulmonary hypertension. This comprehensive review aimed to address the major aspects of lung transplantation: indications, contraindications, evaluation of transplant candidates, evaluation of donor candidates, management of transplant recipients, and major complications. To that end, we based our research on the International Society for Heart and Lung Transplantation guidelines and on the protocols used by our Lung Transplant Group in the city of São Paulo, Brazil. PMID:26785965

Intersections of lung progenitor cells, lung disease and lung cancer.

Science.gov (United States)

Kim, Carla F

2017-06-30

The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials. Copyright ©ERS 2017.

Intersections of lung progenitor cells, lung disease and lung cancer

Directory of Open Access Journals (Sweden)

Carla F. Kim

2017-06-01

Full Text Available The use of stem cell biology approaches to study adult lung progenitor cells and lung cancer has brought a variety of new techniques to the field of lung biology and has elucidated new pathways that may be therapeutic targets in lung cancer. Recent results have begun to identify the ways in which different cell populations interact to regulate progenitor activity, and this has implications for the interventions that are possible in cancer and in a variety of lung diseases. Today's better understanding of the mechanisms that regulate lung progenitor cell self-renewal and differentiation, including understanding how multiple epigenetic factors affect lung injury repair, holds the promise for future better treatments for lung cancer and for optimising the response to therapy in lung cancer. Working between platforms in sophisticated organoid culture techniques, genetically engineered mouse models of injury and cancer, and human cell lines and specimens, lung progenitor cell studies can begin with basic biology, progress to translational research and finally lead to the beginnings of clinical trials.

The commitment of human cells to senescence.

Science.gov (United States)

Holliday, Robin

2014-01-01

Fifty years ago, it was demonstrated by Leonard Hayflick that human diploid fibroblasts grown in culture have a finite lifespan. Since that time, innumerable experiments have been published to discover the mechanism(s) that are responsible for this 'Hayflick limit' to continuous growth. Much new information has been gained, but there are certain features of this experimental system which have not been fully understood. One is the fact that different populations of the foetal lung strains WI-38 and MRC-5 have a range in division potential of at least a millionfold. The commitment theory of cellular aging, published more than 30 years ago, is able to explain this, but it has been consistently ignored. The theory predicts that bottlenecks, which are transient reductions in population size, can significantly reduce lifespan, or increase variability of lifespans. Computer simulations specify the effects of bottlenecks on longevity, and these were confirmed in two series of experiments. Commitment to senescence may be the loss of telomerase, which leads to the erosion of telomeres and the inability to grow indefinitely. Many experiments have been done with skin fibroblasts from human donors of different age, and it was originally thought that in vitro lifespan was inversely correlated with donor age. In these experiments, a single skin biopsy produces a population of cells that are grown to senescence. However, there is no reason to believe that skin fibroblasts are less variable in their in vitro lifespan than foetal lung strains, in which case the data points with skin cells are so variable that they may completely obscure any inverse correlation between culture lifespans and donor age.

Evaluation of concentrations of major and trace elements in human lung using INAA and PIXE

International Nuclear Information System (INIS)

Altaf, W.J.; Spyrou, N.M.

1997-01-01

The elemental concentrations of Br, Ca, Ce, Cl, Co, Cr, Cs, F, Fe, Hf, K, Mg, Mn, Na, O, Rb, Sb, Sc, Se, V and Zn in 15 human lung autopsy samples, taken from subjects aged more than fifty years old, were determined by instrumental neutron activation analysis (INAA) using reactor neutrons in conjunction with a high resolution detection system. Two modes of irradiation and counting were applied; namely cyclic neutron activation analysis (CNAA) and conventional neutron activation analysis. Proton induced X-ray emission (PIXE) analysis, using a proton beam emerging from a 2 MV Van de Graaff accelerator, was additionally employed and Ge, Ni, P and Ti were also identified in the lung tissue. Detection of the X-ray spectra was performed using a high resolution Si(Li) semiconductor. The relevance of these results, including a comparison between the concentrations of elements measured in a pig's lung using CNAA and those found in the human lung is discussed. (author)

Comparative microscopic study of human and rat lungs after overexposure to welding fume.

Science.gov (United States)

Antonini, James M; Roberts, Jenny R; Schwegler-Berry, Diane; Mercer, Robert R

2013-11-01

particles were metal complexes with iron, chromium, and nickel being the most common metals present. In conclusion, long-term exposure to specific welding fume can lead to serious chronic lung disease characterized by significant particle deposition and persistence as demonstrated in both a human case study and rat model. Not only were the lung responses similar in the human and rat lungs, as evidenced by inflammatory cell influx and pulmonary disease, but the composition of individual welding particles and agglomerations in situ was comparable.

Ex-vivo perfusion of donor hearts for human heart transplantation (PROCEED II): a prospective, open-label, multicentre, randomised non-inferiority trial.

Science.gov (United States)

Ardehali, Abbas; Esmailian, Fardad; Deng, Mario; Soltesz, Edward; Hsich, Eileen; Naka, Yoshifumi; Mancini, Donna; Camacho, Margarita; Zucker, Mark; Leprince, Pascal; Padera, Robert; Kobashigawa, Jon

2015-06-27

The Organ Care System is the only clinical platform for ex-vivo perfusion of human donor hearts. The system preserves the donor heart in a warm beating state during transport from the donor hospital to the recipient hospital. We aimed to assess the clinical outcomes of the Organ Care System compared with standard cold storage of human donor hearts for transplantation. We did this prospective, open-label, multicentre, randomised non-inferiority trial at ten heart-transplant centres in the USA and Europe. Eligible heart-transplant candidates (aged >18 years) were randomly assigned (1:1) to receive donor hearts preserved with either the Organ Care System or standard cold storage. Participants, investigators, and medical staff were not masked to group assignment. The primary endpoint was 30 day patient and graft survival, with a 10% non-inferiority margin. We did analyses in the intention-to-treat, as-treated, and per-protocol populations. This trial is registered with ClinicalTrials.gov, number NCT00855712. Between June 29, 2010, and Sept 16, 2013, we randomly assigned 130 patients to the Organ Care System group (n=67) or the standard cold storage group (n=63). 30 day patient and graft survival rates were 94% (n=63) in the Organ Care System group and 97% (n=61) in the standard cold storage group (difference 2·8%, one-sided 95% upper confidence bound 8·8; p=0·45). Eight (13%) patients in the Organ Care System group and nine (14%) patients in the standard cold storage group had cardiac-related serious adverse events. Heart transplantation using donor hearts adequately preserved with the Organ Care System or with standard cold storage yield similar short-term clinical outcomes. The metabolic assessment capability of the Organ Care System needs further study. TransMedics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemoprevention of Lung Cancer: Prospects and Disappointments in Human Clinical Trials

Directory of Open Access Journals (Sweden)

William N. Rom

2013-01-01

Full Text Available Decreasing the risk of lung cancer, or preventing its development in high-risk individuals, would have a huge impact on public health. The most effective means to decrease lung cancer incidence is to eliminate exposure to carcinogens. However, with recent advances in the understanding of pulmonary carcinogenesis and the identification of intermediate biomarkers, the prospects for the field of chemoprevention research have improved dramatically. Here we review the most recent research in lung cancer chemoprevention—focusing on those agents that have been investigated in human clinical trials. These agents fall into three major categories. First, oxidative stress plays an important role in pulmonary carcinogenesis; and therefore, antioxidants (including vitamins, selenium, green tea extracts, and isothiocyanates may be particularly effective in preventing the development of lung cancer. Second, inflammation is increasingly accepted as a crucial factor in carcinogenesis, and many investigators have focused on anti-inflammatory agents, such as glucocorticoids, NSAIDs, statins, and PPARγ agonists. Finally, the PI3K/AKT/mTOR pathway is recognized to play a central role in tobacco-induced carcinogenesis, and inhibitors of this pathway, including myoinositol and metformin, are promising agents for lung cancer prevention. Successful chemoprevention will likely require targeting of multiple pathways to carcinogenesis—both to minimize toxicity and maximize efficacy.

Nicotine prevents the apoptosis induced by menadione in human lung cancer cells

International Nuclear Information System (INIS)

Zhang Tao; Lu Heng; Shang Xuan; Tian Yihao; Zheng Congyi; Wang Shiwen; Cheng Hanhua; Zhou Rongjia

2006-01-01

Approximately 50% of long-term cigarette smokers die prematurely from the adverse effects of smoking, including on lung cancer and other illnesses. Nicotine is a main component in tobacco and has been implicated as a potential factor in the pathogenesis of human lung cancer. However, the mechanism of nicotine action in the development of lung cancer remains largely unknown. In the present study, we designed a nicotine-apoptosis system, by pre-treatment of nicotine making lung cancer cell A549 to be in a physiological nicotine environment, and observed that nicotine promoted cell proliferation and prevented the menadione-induced apoptosis, and exerts its role of anti-apoptosis by shift of apoptotic stage induced by menadione from late apoptotic stage to early apoptotic stage, in which NF-κB was up-regulated. Interference analysis of NF-κB in A549 cells showed that knock down of NF-κB resulted in apoptosis promotion and counteracted the protective effect of nicotine. The findings suggest that nicotine has potential effect in lung cancer genesis, especially in patients with undetectable early tumor development and development of specific NF-κB inhibitors would represent a potentially exciting new pharmacotherapy for tobacco-related lung cancer

Intravenous immunoglobulin prevents murine antibody-mediated acute lung injury at the level of neutrophil reactive oxygen species (ROS production.

Directory of Open Access Journals (Sweden)

John W Semple

Full Text Available Transfusion-related acute lung injury (TRALI is a leading cause of transfusion-associated mortality that can occur with any type of transfusion and is thought to be primarily due to donor antibodies activating pulmonary neutrophils in recipients. Recently, a large prospective case controlled clinical study of cardiac surgery patients demonstrated that despite implementation of male donors, a high incidence of TRALI still occurred and suggested a need for additional interventions in susceptible patient populations. To examine if intravenous immunoglobulin (IVIg may be effective, a murine model of antibody-mediated acute lung injury that approximates human TRALI was examined. When BALB/c mice were injected with the anti-major histocompatibility complex class I antibody 34-1-2s, mild shock (reduced rectal temperature and respiratory distress (dyspnea were observed and pre-treatment of the mice with 2 g/kg IVIg completely prevented these symptoms. To determine IVIg's usefulness to affect severe lung damage, SCID mice, previously shown to be hypersensitive to 34-1-2s were used. SCID mice treated with 34-1-2s underwent severe shock, lung damage (increased wet/dry ratios and 40% mortality within 2 hours. Treatment with 2 g/kg IVIg 18 hours before 34-1-2s administration completely protected the mice from all adverse events. Treatment with IVIg after symptoms began also reduced lung damage and mortality. While the prophylactic IVIg administration did not affect 34-1-2s-induced pulmonary neutrophil accumulation, bone marrow-derived neutrophils from the IVIg-treated mice displayed no spontaneous ROS production nor could they be stimulated in vitro with fMLP or 34-1-2s. These results suggest that IVIg prevents murine antibody-mediated acute lung injury at the level of neutrophil ROS production and thus, alleviating tissue damage.

Semen parameters of a semen donor before and after infection with human immunodeficiency virus type 1: Case report

NARCIS (Netherlands)

van Leeuwen, E.; Cornelissen, M.; de Vries, J. W.; Lowe, S. H.; Jurriaans, S.; Repping, S.; van der Veen, F.

2004-01-01

Semen samples from a donor who seroconverted for human immunodeficiency virus type 1 (HIV-1) during the period that he was donating at our clinic were stored before and after infection. Semen analysis was done on all of these samples before cryopreservation. Retrospectively, both qualitative and

Sulfation of chlorotyrosine and nitrotyrosine by human lung endothelial and epithelial cells: Role of the human SULT1A3

International Nuclear Information System (INIS)

Yasuda, Shin; Yasuda, Tomoko; Liu, Ming-Yih; Shetty, Sreerama; Idell, Steven; Boggaram, Vijayakumar; Suiko, Masahito; Sakakibara, Yoichi; Fu Jian; Liu, Ming-Cheh

2011-01-01

During inflammation, potent reactive oxidants formed may cause chlorination and nitration of both free and protein-bound tyrosine. In addition to serving as biomarkers of inflammation-mediated oxidative stress, elevated levels of chlorotyrosine and nitrotyrosine have been linked to the pathogenesis of lung and vascular disorders. The current study was designed to investigate whether the lung cells are equipped with mechanisms for counteracting these tyrosine derivatives. By metabolic labeling, chlorotyrosine O-[ 35 S]sulfate and nitrotyrosine O-[ 35 S]sulfate were found to be generated and released into the labeling media of human lung endothelial and epithelial cells labeled with [ 35 S]sulfate in the presence of added chlorotyrosine and nitrotyrosine. Enzymatic assays using the eleven known human cytosolic sulfotransferases (SULTs) revealed SULT1A3 as the enzyme responsible for catalyzing the sulfation of chlorotyrosine and nitrotyrosine. Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated the expression of SULT1A3 in the lung endothelial and epithelial cells used in this study. Kinetic constants of the sulfation of chlorotyrosine and nitrotyrosine by SULT1A3 were determined. Collectively, these results suggest that sulfation by SULT1A3 in lung endothelial and epithelial cells may play a role in the inactivation and/or disposal of excess chlorotyrosine and nitrotyrosine generated during inflammation.

Prediction of graft-versus-host disease in humans by donor gene-expression profiling.

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Chantal Baron

2007-01-01

Full Text Available BACKGROUND: Graft-versus-host disease (GVHD results from recognition of host antigens by donor T cells following allogeneic hematopoietic cell transplantation (AHCT. Notably, histoincompatibility between donor and recipient is necessary but not sufficient to elicit GVHD. Therefore, we tested the hypothesis that some donors may be "stronger alloresponders" than others, and consequently more likely to elicit GVHD. METHODS AND FINDINGS: To this end, we measured the gene-expression profiles of CD4(+ and CD8(+ T cells from 50 AHCT donors with microarrays. We report that pre-AHCT gene-expression profiling segregates donors whose recipient suffered from GVHD or not. Using quantitative PCR, established statistical tests, and analysis of multiple independent training-test datasets, we found that for chronic GVHD the "dangerous donor" trait (occurrence of GVHD in the recipient is under polygenic control and is shaped by the activity of genes that regulate transforming growth factor-beta signaling and cell proliferation. CONCLUSIONS: These findings strongly suggest that the donor gene-expression profile has a dominant influence on the occurrence of GVHD in the recipient. The ability to discriminate strong and weak alloresponders using gene-expression profiling could pave the way to personalized transplantation medicine.

Regulator of G-protein signaling 5 (RGS5) inhibits cell proliferation and enhances radiosensitivity of human lung cancer cells

International Nuclear Information System (INIS)

Xu Zumin; Wang Jin; Zuo Yufang; Yu Zhonghua; Peng Fang; Hu Xiao; Zhou Qichao; Ma Honglian; Bao Yong; Chen Ming

2014-01-01

Objective: To investigate the effects of regulator and the underlying molecular mechanisms of G-protein signaling 5 (RGS5) on radiation response in human lung cancer cells. Methods: The effects of RGS5 on viability were determined by MTT assay, and apoptosis rate was detected by flow cytometry, in human lung cancer cells. The combined effect of ionizing radiation and RGS5 on tumor cells was detected by colony formation assay. The protein expression was detected by Western blot. Results: RGS5 overexpression remarkably inhibited the survival of human lung cancer cells, and the growth inhibition rate of RGS5 overexpression on A549 and Calu-3 cells were 44.4% (F = 29.18, P < 0.05) and 39.27% (F = 23.04, P < 0.05) at 48 h, and 54.3%(F = 103.45, P < 0.05), 44.7%(F = 108.02, P < 0.05) at 72 h post-irradiation, respectively. RGS5 might exert its inhibitory effects on human lung cancer cells by inducing tumor cell apoptosis, while the apoptotic cells rate in A549 and Calu-3 cells in control group, pTRiEX group and pTRiEX-RGS5 group were (1.3±0.2)%, (3.4±0.6)%, (19.6±2.3)% (F = 86.62, P < 0.05), and (3.2±0.8)%, (3.0±0.9)%, (12.8±1.8)% (F = 28.80, P < 0.05) at 36 h post-irradiation, respectively. Furthermore, RGS5 could sensitize the lung cancer cells to radiation. Conclusions: RGS5 might play an inhibitory role in human lung cancer cell proliferation, which may explain the pathoclinical observation thet high expression of RGSS is a favorable prognostic factor in NSCLC patients. In addition, RGS5 also enhance the anti-tumor effects of radiation in human lung cancer cells. (authors)

Radon, smoking and human papilloma virus as risk factors for lung cancer in an environmental epidemiological study

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G. P. Malinovsky

2017-01-01

Full Text Available The aim of the study: to analyze the risk of lung cancer caused by exposure to indoor radon using an environmental study, taking into account recent data on the possible effect of Human Papillomavirus, based on lung cancer mortality and radon exposure in the Russian regions.Materials and methods: in the analysis, linear dependencies of lung cancer against influencing factors were used. The average radon concentration for the regions of Russia was earlier reconstructed on the basis of the annual reports of the form 4-DOZ. Information on morbidity and mortality from malignant neoplasms in Russia was obtained from annual reports issued by the Р. Hertsen Moscow Oncology Research Institute. As a surrogate of the level of infection with Human Papillomavirus, the incidence of cervix cancer was used. The smoking prevalence was estimated applying data on the incidence of tongue cancer.Results: taking into account smoking and infection with Human Papillomavirus, it is possible to obtain estimates of lung cancer excess relative risk when induced by radon in dwellings consistent with the results of case-control studies.Conclusion: the analysis of regionally aggregated data on deaths from lung cancer in Russia, the average level of indoor radon concentrations and significant risk factors for lung cancer confirms the linear threshold-free concept of radiation-induced carcinogenesis.

21 CFR 1271.80 - What are the general requirements for donor testing?

Science.gov (United States)

2010-04-01

... ADMINISTRATION HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED PRODUCTS Donor Eligibility § 1271.80 What are... mother instead of a specimen from the donor. (b) Timing of specimen collection. You must collect the donor specimen for testing at the time of recovery of cells or tissue from the donor; or up to 7 days...

Recurrence of Intravenous Talc Granulomatosis following Single Lung Transplantation

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Richard C Cook

1998-01-01

Full Text Available Advanced pulmonary disease is an unusual consequence of the intravenous injection of oral medications, usually developing over a period of several years. A number of patients with this condition have undergone lung transplantation for respiratory failure. However, a history of drug abuse is often considered to be a contraindication to transplantation in the context of limited donor resources. A patient with pulmonary talc granulomatosis secondary to intravenous methylphenidate injection who underwent successful lung transplantation and subsequently presented with recurrence of the underlying disease in the transplanted lung 18 months after transplantation is reported.

Compliance with donor age recommendations in oocyte donor recruitment advertisements in the USA.

Science.gov (United States)

Alberta, Hillary B; Berry, Roberta M; Levine, Aaron D

2013-04-01

IVF using donated oocytes offers benefits to many infertile patients, yet the technique also raises a number of ethical concerns, including worries about potential physical and psychological risks to oocyte donors. In the USA, oversight of oocyte donation consists of a combination of federal and state regulations and self-regulatory guidelines promulgated by the American Society for Reproductive Medicine. This study assesses compliance with one of these self-regulatory guidelines - specifically, ASRM's preferred minimum age for donors of 21. To assess compliance, 539 oocyte donor recruitment advertisements from two recruitment channels (Craigslist and college newspapers) were collected and evaluated. Of these, 61% in the Craigslist dataset and 43% in the college newspaper dataset listed minimum ages between 18 and 20, which is inconsistent with ASRM's preferred minimum age recommendation of 21. Advertisements placed by oocyte donor recruitment agencies were more likely than advertisements placed by clinics to specify minimum ages between 18 and 20. These results indicate that ASRM should evaluate and consider revising its donor age guidelines. IVF using donated human eggs can help many patients who have difficulty having children. However, the technique also raises ethical concerns, including concerns about potential physical and psychological harms to egg donors. In the USA, oversight of egg donation relies on a combination of federal and state regulation and professional self-regulation. Governmental regulations address only limited aspects of egg donation, such as the potential spread of infectious diseases and the reporting of success rates, leaving voluntary guidelines developed by an association of medical professionals to address most issues, including ethical concerns raised by the practice. One of these voluntary guidelines recommends that egg donors should be at least 21 years of age. In this article, we analysed 539 egg donor recruitment advertisements

Sero-prevalence of Human Cytomegalovirus among blood donors in Lahore, Pakistan

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Chahat Batool Rizvi

2015-08-01

Full Text Available Background: Transfusion-transmitted cytomegalovirus (TT-CMV infection can cause severe illness and even death among immunocompromised patients; therefore, the spread of CMV through blood products should be prevented. To our knowledge, no study has been carried out in Pakistan to determine the seroprevalence of CMV in general population as well as among blood donors. The goal of this study was to determine CMV seropositivity among blood donors at the blood bank of INMOL Hospital, Lahore, Pakistan. Methods: A sero-epidemiological cross-sectional study was conducted. Sera from 91 blood donors were screened for CMV specific IgG antibodies by enzyme-linked immunosorbent assay (ELISA based kit. Results: The CMV-specific IgG antibodies were detected in 89 blood donors, which gave seroprevalence rate of 97.8%. The statistical analysis of results was done using pearson chi-square test and appeared non-significant with values 0.625 and 0.705 for different age groups and blood groups of donors. Conclusion: Because of high seroprevalence in this study area, an adequate supply of CMV seronegative blood is difficult to maintain. Therefore, we propose that the future strategies for the prevention of post-transfusion CMV infection in recipients should include the transfusion of leukoreduced blood products. Further a prospective study with much greater population can be done to identify major causative risk factors for such highest prevalence rate.

Human umbilical cord-derived mesenchymal stem cells protect from hyperoxic lung injury by ameliorating aberrant elastin remodeling in the lung of O2-exposed newborn rat.

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Hou, Chen; Peng, Danyi; Gao, Li; Tian, Daiyin; Dai, Jihong; Luo, Zhengxiu; Liu, Enmei; Chen, Hong; Zou, Lin; Fu, Zhou

2018-01-08

The incidence and mortality rates of bronchopulmonary dysplasia (BPD) remain very high. Therefore, novel therapies are imminently needed to improve the outcome of this disease. Human umbilical cord-derived mesenchymal stem cells (UC-MSCs) show promising therapeutic effects on oxygen-induced model of BPD. In our experiment, UC-MSCs were intratracheally delivered into the newborn rats exposed to hyperoxia, a well-established BPD model. This study demonstrated that UC-MSCs reduce elastin expression stimulated by 90% O 2 in human lung fibroblasts-a (HLF-a), and inhibit HLF-a transdifferentiation into myofibroblasts. In addition, the therapeutic effects of UC-MSCs in neonatal rats with BPD, UC-MSCs could inhibit lung elastase activity and reduce aberrant elastin expression and deposition in the lung of BPD rats. Overall, this study suggested that UC-MSCs could ameliorate aberrant elastin expression in the lung of hyperoxia-induced BPD model which may be associated with suppressing increased TGFβ1 activation. Copyright © 2017. Published by Elsevier Inc.

Monoclonal Antibody L1Mab-13 Detected Human PD-L1 in Lung Cancers.

Science.gov (United States)

Yamada, Shinji; Itai, Shunsuke; Nakamura, Takuro; Yanaka, Miyuki; Chang, Yao-Wen; Suzuki, Hiroyoshi; Kaneko, Mika K; Kato, Yukinari

2018-04-01

Programmed cell death ligand-1 (PD-L1) is a type I transmembrane glycoprotein expressed on antigen-presenting cells. It is also expressed in several tumor cells such as melanoma and lung cancer cells. A strong correlation has been reported between human PD-L1 (hPD-L1) expression in tumor cells and negative prognosis in cancer patients. Here, a novel anti-hPD-L1 monoclonal antibody (mAb) L 1 Mab-13 (IgG 1 , kappa) was produced using a cell-based immunization and screening (CBIS) method. We investigated hPD-L1 expression in lung cancer using flow cytometry, Western blot, and immunohistochemical analyses. L 1 Mab-13 specifically reacted hPD-L1 of hPD-L1-overexpressed Chinese hamster ovary (CHO)-K1 cells and endogenous hPD-L1 of KMST-6 (human fibroblast) in flow cytometry and Western blot. Furthermore, L 1 Mab-13 reacted with lung cancer cell lines (EBC-1, Lu65, and Lu99) in flow cytometry and stained lung cancer tissues in a membrane-staining pattern in immunohistochemical analysis. These results indicate that a novel anti-hPD-L1 mAb, L 1 Mab-13, is very useful for detecting hPD-L1 of lung cancers in flow cytometry, Western blot, and immunohistochemical analyses.

Successful Kidney and Lung Transplantation From a Deceased Donor With Blunt Abdominal Trauma and Intestinal Perforation

NARCIS (Netherlands)

van Smaalen, Tim C.; Krikke, Christina; Haveman, Jan Willem; van Heurn, L. W. Ernest

2016-01-01

The number of organ donors is limited by many contraindications for donation and poor quality of potential organ donors. Abdominal infection is a generally accepted contraindication for donation of abdominal organs. We present a 43-year-old man with lethal brain injury, blunt abdominal trauma, and

Zero risk tolerance costs lives: loss of transplantable organs due to human immunodeficiency virus nucleic acid testing of potential donors.

Science.gov (United States)

Shafer, Teresa J; Schkade, David; Schkade, Lawrence; Geier, Steven S; Orlowski, Jeffrey P; Klintmalm, Goran

2011-09-01

Patients' deaths due to the organ donor shortage make it imperative that every suitable organ be transplanted. False-positive results of tests for infection with the human immunodeficiency virus (HIV) result in lost organs. A survey of US organ procurement organizations collected the numbers of donors and ruled-out potential donors who had a positive result on an HIV test from January 1,2006, to October 31, 2008. Sixty-two percent of US organ procurement organizations participated. Of the 12397 donor/nondonor cases, 56 (0.45%) had an initial positive result on an HIV antibody or HIV nucleic acid test, and only 8 (14.3%) of those were confirmed positive. Of the false-positive results, 50% were from HIV antibody tests and 50% were from HIV nucleic acid tests. Organs are a scarce, finite, and perishable resource. Use of HIV antibody testing has produced a remarkably safe track record of avoiding HIV transmission, with 22 years of nonoccurrence between transmissions. Because false positives occur with any test, including the HIV Ab test, adding nucleic acid testing to the standard donor testing panel doubles the number of false-positive HIV test results and thus the number of medically suitable donors lost. The required HIV antibody test is 99.99% effective in preventing transmission of the HIV virus. Adding the HIV nucleic acid test to routine organ donor screening could result in as many as 761 to 1551 unnecessary deaths of patients between HIV transmission events because medically suitable organs are wasted.

The influence of gravity on regional lung blood flow in humans: SPECT in the upright and head-down posture.

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Ax, M; Sanchez-Crespo, A; Lindahl, S G E; Mure, M; Petersson, J

2017-06-01

Previous studies in humans have shown that gravity has little influence on the distribution of lung blood flow while changing posture from supine to prone. This study aimed to evaluate the maximal influence of posture by comparison of regional lung blood flow in the upright and head-down posture in 8 healthy volunteers, using a tilt table. Regional lung blood flow was marked by intravenous injection of macroaggregates of human albumin labeled with 99m Tc or 113m In, in the upright and head-down posture, respectively, during tidal breathing. Both radiotracers remain fixed in the lung after administration. The distribution of radioactivity was mapped using quantitative single photon emission computed tomography (SPECT) corrected for attenuation and scatter. All images were obtained supine during tidal breathing. A shift from upright to the head-down posture caused a clear redistribution of blood flow from basal to apical regions. We conclude that posture plays a role for the distribution of lung blood flow in upright humans, and that the influence of posture, and thereby gravity, is much greater in the upright and head-down posture than in horizontal postures. However, the results of the study demonstrate that lung structure is the main determinant of regional blood flow and gravity is a secondary contributor to the distribution of lung blood flow in the upright and head-down positions. NEW & NOTEWORTHY Using a dual-isotope quantitative SPECT method, we demonstrated that although a shift in posture redistributes blood flow in the direction of gravity, the results are also consistent with lung structure being a greater determinant of regional blood flow than gravity. To our knowledge, this is the first study to use modern imaging methods to quantify the shift in regional lung blood flow in humans at a change between the upright and head-down postures. Copyright © 2017 the American Physiological Society.

Pasteurization Procedures for Donor Human Milk Affect Body Growth, Intestinal Structure, and Resistance against Bacterial Infections in Preterm Pigs

DEFF Research Database (Denmark)

Li, Yanqi; Duc Ninh Nguyen; de Waard, Marita

2017-01-01

Background: Holder pasteurization (HP) destroys multiple bioactive factors in donor human milk (DM), and UV-C irradiation (UVC) is potentially a gentler method for pasteurizing DM for preterm infants. Objective: We investigated whether UVC-treated DM improves gut maturation and resistance toward...

Breast Milk and Hair Testing to Detect Illegal Drugs, Nicotine, and Caffeine in Donors to a Human Milk Bank.

Science.gov (United States)

Escuder-Vieco, Diana; Garcia-Algar, Óscar; Joya, Xavier; Marchei, Emilia; Pichini, Simona; Pacifici, Roberta; Pallás-Alonso, Carmen Rosa

2016-08-01

The use of illegal drugs and tobacco is an exclusion criteria for accepting a nursing mother as a milk donor. The detection window for human milk testing is typically a few hours. Hair testing has been considered the gold standard to assess chronic exposure to these toxic substances. The aim of this study was to determine the levels of illegal drugs, nicotine, and caffeine in breast milk and hair samples from donors to assess whether these substances were being used during the donation period and the months leading up to it. Thirty-six samples of hair and breast milk were obtained from 36 donors. The tests performed identified nicotine, caffeine, morphine, cocaine, cannabis, amphetamines, codeine, methadone, and other substances derived therefrom. No illegal drugs were found in any of the samples analyzed. Nicotine and cotinine were found in 33.3% (12/36) of all hair samples. Among these 12 samples, 10 had cotinine concentrations consistent with cutoff values for unexposed nonsmokers, 1 had concentrations consistent with cutoff values for passive smokers, and 1 had concentrations consistent with cutoff values for active smokers. Caffeine was found in 77.7% of the hair samples and in 50% of the donor milk samples. The correlation for caffeine between donor milk and hair samples was r = 0.288, P = .0881. Donors do not use illegal drugs during either the donation period or the months leading up to it. They are occasionally exposed to tobacco smoke and almost all of them consume caffeine. © The Author(s) 2016.

Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

Science.gov (United States)

Sharon, Eilon; Shi, Hao; Kharbanda, Sandhya; Koh, Winston; Martin, Lance R; Khush, Kiran K; Valantine, Hannah; Pritchard, Jonathan K; De Vlaminck, Iwijn

2017-08-01

Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM) of identity-by-descent (IBD) states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD). These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

Influence of lung CT changes in chronic obstructive pulmonary disease (COPD on the human lung microbiome.

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Marion Engel

Full Text Available Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited.Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons.We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group (PC1, Padj = 0.002. Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype.Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system.

Influence of lung CT changes in chronic obstructive pulmonary disease (COPD) on the human lung microbiome.

Science.gov (United States)

Engel, Marion; Endesfelder, David; Schloter-Hai, Brigitte; Kublik, Susanne; Granitsiotis, Michael S; Boschetto, Piera; Stendardo, Mariarita; Barta, Imre; Dome, Balazs; Deleuze, Jean-François; Boland, Anne; Müller-Quernheim, Joachim; Prasse, Antje; Welte, Tobias; Hohlfeld, Jens; Subramanian, Deepak; Parr, David; Gut, Ivo Glynne; Greulich, Timm; Koczulla, Andreas Rembert; Nowinski, Adam; Gorecka, Dorota; Singh, Dave; Gupta, Sumit; Brightling, Christopher E; Hoffmann, Harald; Frankenberger, Marion; Hofer, Thomas P; Burggraf, Dorothe; Heiss-Neumann, Marion; Ziegler-Heitbrock, Loems; Schloter, Michael; Zu Castell, Wolfgang

2017-01-01

Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented. However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited. Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons. We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002). Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects. No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA. Co-occurrence analysis suggests the presence of networks of co-occurring bacteria. Four communities of positively correlated bacteria were revealed. The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype. Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells. This might result in a changed interplay with the host immune system.

The novel human influenza A(H7N9) virus is naturally adapted to efficient growth in human lung tissue.

Science.gov (United States)

Knepper, Jessica; Schierhorn, Kristina L; Becher, Anne; Budt, Matthias; Tönnies, Mario; Bauer, Torsten T; Schneider, Paul; Neudecker, Jens; Rückert, Jens C; Gruber, Achim D; Suttorp, Norbert; Schweiger, Brunhilde; Hippenstiel, Stefan; Hocke, Andreas C; Wolff, Thorsten

2013-10-08

A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumonia and acute respiratory distress syndrome and, apparently, from healthy poultry in March 2013 in Eastern China. We evaluated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture system mimicking infection of the lower respiratory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predominantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or human influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN-β promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory tract disease seen in many patients. Humans are usually not infected by avian influenza A viruses (IAV), but this large group of viruses contributes to the emergence of human pandemic strains. Transmission of virulent avian IAV to humans is therefore an alarming event that requires assessment of the biology as well as pathogenic and pandemic potentials of the viruses in clinically relevant models. Here, we demonstrate that an early virus isolate from the recent A(H7N9) outbreak in Eastern China replicated as efficiently as human-adapted IAV in explanted human lung tissue, whereas avian H7 subtype viruses were unable to

Biological dosimetry of heavy ion induced chromosome lesions in human peripheral blood lymphocytes of different healthy donors

International Nuclear Information System (INIS)

Groesser, T.; Rydberg, B.; Ritter, S.; Hessel, P.; Kraft, G.

2003-01-01

Full text: In the presented work the effect of sparsely ionizing X-rays or densely ionizing carbon ions on human peripheral blood lymphocytes (PBL) from healthy donors regarding the fluctuations in radiosensitivity within the same donor and between different donors was examined. This is not only of special interest for physicians and radiation biologists but also plays an important role in space flights because such fluctuations in the radiation response would reduce the accuracy of the biological dosimetry. In this context, biological changes in the aberration rate of metaphase cells as well as in cell proliferation and the mitotic index were measured. Since chromosome analyses are presently the most powerful biological method to quantify radiation exposure, the study focused on the measurements of chromosome aberrations in first-metaphase cells. The investigations showed that the aberration yield after 400 MeV/u carbon ion exposure (LET = 11 keV/micrometer) was higher than after X-irradiation. The aberration yield in first mitotic cells as well as the proportion of damaged cells was stable over the examined period up to 72h after exposure to X-rays or carbon ions. Furthermore, the results of the presented work revealed pronounced fluctuations in the measured parameters in the same donor as well as between different donors. If the dose effect curves of such parameters were used as calibration curves for radiation dose assessment these fluctuations will decrease their potential of use for dose estimation. This demonstrates that a general calibration curve for dose assessment might not be sufficiently precise and individual calibration curves might improve the accuracy of the biological dosimetry

Use of organs from donors with bloodstream infection, pneumonia, and influenza: Results of a survey of infectious diseases practitioners.

Science.gov (United States)

Mehta, Sanjay R; Logan, Cathy; Kotton, Camille N; Kumar, Deepali; Aslam, Saima

2017-02-01

Potential organ donors may be admitted with an infection to an intensive care unit, or contract a nosocomial infection during their stay, increasing the risk of potential transmission to the recipient. Because of a lack of practice guidelines and large-scale data on this topic, we undertook a survey to assess the willingness of transplant infectious diseases (ID) physicians to accept such organs. We performed a 10-question survey of ID providers from the American Society of Transplantation Infectious Disease Community of Practice to determine the scope of practice regarding acceptance of organs from donors with bloodstream infection, pneumonia, and influenza prior to organ procurement, as well as management of such infections following transplantation. Among 60 respondents to our survey, a majority indicated that organs would be accepted from donors bacteremic with streptococci (76%) or Enterobacteriaceae (73%) without evidence of drug resistance. Acceptance rates varied based on infecting organism, type of organ, and center size. Ten percent of respondents would accept an organ from a donor bacteremic with a carbapenem-resistant organism. Over 90% of respondents would accept an organ other than a lung from a donor with influenza on treatment, compared with 52% that would accept a lung in the same setting. This study is the first to our knowledge to survey transplant ID providers regarding acceptance of organs based on specific infections in the donor. These decisions are often based on limited published data and experience. Better characterization of the outcomes from donors with specific types of infection could lead to liberalization of organ acceptance practices across centers. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Donor Outcomes in Living Donor Liver Transplantation-Analysis of 275 Donors From a Single Centre in India.

Science.gov (United States)

Narasimhan, Gomathy; Safwan, Mohamed; Kota, Venugopal; Reddy, Mettu S; Bharathan, Anand; Dabora, Abderrhaim; Kaliamoorthy, Ilankumaran; Kanagavelu, Rathnavel G; Srinivasan, Vijaya; Rela, Mohamed

2016-06-01

Live donor liver transplantation is the predominant form of liver transplantation in India and in most Asian countries. Donor outcome reports are an important source of information to be shared with prospective donors at the time of informed consent. This is the first donor outcome series from India. Analysis of donor characteristics and morbidity of 275 live donors from a single large volume center is documented. Two hundred seventy-five patients donated from November 2009 to October 2014, 144 were women and 131 were men, 180 donated to adults and 95 donated to children. Right lobe donors were majority at 62.2% followed by left lateral segment 28%. Two thirds of the live donors did not have any morbidity; 114 complications were encountered in 85 patients. The complications were graded as per Clavien 5 tier grading and major morbidity (grade III b, grade IV grade V) was 4.36%. Postoperative biliary complication was seen in 3 donors. This large single-center study is the first donor outcome report from India, and the results are comparable to other published donor series. Documentation and regular audit of donor outcomes is important to help improve the safety of donor hepatectomy and to provide a database for informed consent of prospective donors.

Relative biological effectiveness if alpha radiation for human lung exposure

International Nuclear Information System (INIS)

Yarmoshenko, I.; Kirdin, I.; Zhukovsky, M.

2006-01-01

estimates for cases of indoor radon alpha exposure and exposure to implanted plutonium can be seen. Difference in biological effectiveness of inhaled radon and implanted plutonium may appear due to different distribution of short-lived radon progeny and long lived plutonium within lung tissues. Low RBE value for alpha particle exposures of human lung tissues may be a reason of known inconsistency of dose conversion factors for radon estimates based on dosimetric and epidemiologic approaches. (authors)

Application of a neutral community model to assess structuring of the human lung microbiome.

Science.gov (United States)

Venkataraman, Arvind; Bassis, Christine M; Beck, James M; Young, Vincent B; Curtis, Jeffrey L; Huffnagle, Gary B; Schmidt, Thomas M

2015-01-20

DNA from phylogenetically diverse microbes is routinely recovered from healthy human lungs and used to define the lung microbiome. The proportion of this DNA originating from microbes adapted to the lungs, as opposed to microbes dispersing to the lungs from other body sites and the atmosphere, is not known. We use a neutral model of community ecology to distinguish members of the lung microbiome whose presence is consistent with dispersal from other body sites and those that deviate from the model, suggesting a competitive advantage to these microbes in the lungs. We find that the composition of the healthy lung microbiome is consistent with predictions of the neutral model, reflecting the overriding role of dispersal of microbes from the oral cavity in shaping the microbial community in healthy lungs. In contrast, the microbiome of diseased lungs was readily distinguished as being under active selection. We also assessed the viability of microbes from lung samples by cultivation with a variety of media and incubation conditions. Bacteria recovered by cultivation from healthy lungs represented species that comprised 61% of the 16S rRNA-encoding gene sequences derived from bronchoalveolar lavage samples. Neutral distribution of microbes is a distinguishing feature of the microbiome in healthy lungs, wherein constant dispersal of bacteria from the oral cavity overrides differential growth of bacteria. No bacterial species consistently deviated from the model predictions in healthy lungs, although representatives of many of the dispersed species were readily cultivated. In contrast, bacterial populations in diseased lungs were identified as being under active selection. Quantification of the relative importance of selection and neutral processes such as dispersal in shaping the healthy lung microbiome is a first step toward understanding its impacts on host health. Copyright © 2015 Venkataraman et al.

[Cloning goat producing human lactoferrin with genetically modified donor cells selected by single or dual markers].

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An, Liyou; Yuan, Yuguo; Yu, Baoli; Yang, Tingjia; Cheng, Yong

2012-12-01

We compared the efficiency of cloning goat using human lactoferrin (hLF) with genetically modified donor cells marked by single (Neo(r)) or double (Neo(r)/GFP) markers. Single marker expression vector (pBLC14) or dual markers expression vector (pAPLM) was delivered to goat fetal fibroblasts (GFF), and then the transgenic GFF was used as donor cells to produce transgenic goats. Respectively, 58.8% (20/34) and 86.7% (26/30) resistant cell lines confirmed the transgenic integration by PCR. Moreover, pAPLM cells lines were subcultured with several passages, only 20% (6/30) cell lines was observed fluorescence from each cell during the cell passage. Somatic cell nuclear transfer using the donor cells harbouring pBLC14 or pAPLM construct, resulting in a total of 806 reconstructed embryos, a pregnancy rate at 35 d (53.8%, 39.1%) and 60 d (26.9%, 21.7%), and an offspring birth rate (1.9%, 1.4%) with 5 and 7 newborn cloned goats, respectively. Transgene was confirmed by PCR and southern-blot in all cloned offspring. There were no significant differences at the reconstructed embryo fusion rates, pregnancy rates and the birth rate (P > 0.05) between single and double markers groups. The Neo(r)/GFP double markers could improve the reliability for accurately and efficiently selecting the genetically modified donor cells. No adverse effect was observed on the efficiency of transgenic goat production by SCNT using somatic cells transfected with double (Neo(r)/GFP) markers vector.

Marked longevity of human lung parenchymal elastic fibers deduced from prevalence of D-aspartate and nuclear weapons-related radiocarbon

International Nuclear Information System (INIS)

Shapiro, S.D.; Endicott, S.K.; Province, M.A.; Pierce, J.A.; Campbell, E.J.

1991-01-01

Normal structure and function of the lung parenchyma depend upon elastic fibers. Amorphous elastin is biochemically stable in vitro, and may provide a metabolically stable structural framework for the lung parenchyma. To test the metabolic stability of elastin in the normal human lung parenchyma, we have (a) estimated the time elapsed since the synthesis of the protein through measurement of aspartic acid racemization and (b) modeled the elastin turnover through measurement of the prevalence of nuclear weapons-related 14 C. Elastin purified by a new technique from normal lung parenchyma was hydrolyzed; then the prevalences of D-aspartate and 14 C were measured by gas chromatography and accelerator-mass spectrometry, respectively. D-aspartate increased linearly with age; Kasp (1.76 x 10 - 3 yr - 1 ) was similar to that previously found for extraordinarily stable human tissues, indicating that the age of lung parenchymal elastin corresponded with the age of the subject. Radiocarbon prevalence data also were consistent with extraordinary metabolic stability of elastin; the calculated mean carbon residence time in elastin was 74 yr (95% confidence limits, 40-174 yr). These results indicate that airspace enlargement characteristic of 'aging lung' is not associated with appreciable new synthesis of lung parenchymal elastin. The present study provides the first tissue-specific evaluation of turnover of an extracellular matrix component in humans and underscores the potential importance of elastin for maintenance of normal lung structure. Most importantly, the present work provides a foundation for strategies to directly evaluate extracellular matrix injury and repair in diseases of lung (especially pulmonary emphysema), vascular tissue, and skin

Incidence and distribution of transplantable organs from donors after circulatory determination of death in U.S. intensive care units.

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Halpern, Scott D; Hasz, Richard D; Abt, Peter L

2013-04-01

All U.S. acute care hospitals must maintain protocols for recovering organs from donors after circulatory determination of death (DCDD), but the numbers, types, and whereabouts of available organs are unknown. To assess the maximal potential supply and distribution of DCDD organs in U.S. intensive care units. We conducted a population-based cohort study among a randomly selected sample of 50 acute care hospitals in the highest-volume donor service area in the United States. We identified all potentially eligible donors dying within 90 minutes of the withdrawal of life-sustaining therapy from July 1, 2008 to June 30, 2009. Using prespecified criteria, potential donors were categorized as optimal, suboptimal, or ineligible to donate their lungs, kidneys, pancreas, or liver. If only optimal DCDD organs were used, the deceased donor supplies of these organs could increase by up to 22.7, 8.9, 7.4, and 3.3%, respectively. If optimal and suboptimal DCDD organs were used, the corresponding supply increases could be up to 50.0, 19.7, 18.5, and 10.9%. Three-quarters of DCDD organs could be recovered from the 17.2% of hospitals with the highest annual donor volumes-typically those with trauma centers and more than 20 intensive care unit beds. Universal identification and referral of DCDD could increase the supply of transplantable lungs by up to one-half, and would not increase any other organ supply by more than one-fifth. The marked clustering of DCDD among a small number of identifiable hospitals could guide targeted interventions to improve DCDD identification, referral, and management.

Identification of chondroitin sulfate E proteoglycans and heparin proteoglycans in the secretory granules of human lung mast cells

International Nuclear Information System (INIS)

Stevens, R.L.; Austen, K.F.; Fox, C.C.; Lichtenstein, L.M.

1988-01-01

The predominant subclasses of mast cells in both the rat and the mouse can be distinguished from one another by their preferential synthesis of 35 S-labeled proteoglycans that contain either heparin or oversulfated chondroitin sulfate glycosaminoglycans. Although [ 35 S]heparin proteoglycans have been isolated from human lung mast cells of 40-70% purity and from a skin biopsy specimen of a patient with urticaria pigmentosa, no highly sulfated chondroitin sulfate proteoglycan has been isolated from any enriched or highly purified population of human mast cells. The authors demonstrate that human lung mast cells of 96% purity incorporate [ 35 S]sulfate into separate heparin and chondroitin sulfate proteoglycans in an ∼2:1 ratio. As assessed by HPLC of the chondroitinase ABC digests, the chondroitin [ 35 S]sulfate proteoglycans isolated from these human lung mast cells contain the same unusual chondroitin sulfate E disaccharide that is present in proteoglycans produced by interleukin 3-dependent mucosal-like mouse mast cells. Both the chondroitin [ 35 S]sulfate E proteoglycans and the [ 35 S]heparin proteoglycans were exocytosed from the [ 35 S]sulfate-labeled cells via perturbation of the IgE receptor, indicating that both types of 35 S-labeled proteoglycans reside in the secretory granules of these human lung mast cells

Evaluation of Human Amniotic Membrane as a Wound Dressing for Split-Thickness Skin-Graft Donor Sites

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Denys J. Loeffelbein

2014-01-01

Full Text Available Human amniotic membrane (HAM has been used as a biomaterial in various surgical procedures and exceeds some qualities of common materials. We evaluated HAM as wound dressing for split-thickness skin-graft (STSG donor sites in a swine model (Part A and a clinical trial (Part B. Part A: STSG donor sites in 4 piglets were treated with HAM or a clinically used conventional polyurethane (PU foil (n=8 each. Biopsies were taken on days 5, 7, 10, 20, 40, and 60 and investigated immunohistochemically for alpha-smooth muscle actin (αSMA: wound contraction marker, von Willebrand factor (vWF: angiogenesis, Ki-67 (cell proliferation, and laminin (basement membrane integrity. Part B: STSG donor sites in 45 adult patients (16 female/29 male were treated with HAM covered by PU foam, solely by PU foam, or PU foil/paraffin gauze (n=15 each. Part A revealed no difference in the rate of wound closure between groups. HAM showed improved esthetic results and inhibitory effects on cicatrization. Angioneogenesis was reduced, and basement membrane formation was accelerated in HAM group. Part B: no difference in re-epithelialization/infection rate was found. HAM caused less ichor exudation and less pruritus. HAM has no relevant advantage over conventional dressings but might be a cost-effective alternative.

Lung growth and development.

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Joshi, Suchita; Kotecha, Sailesh

2007-12-01

Human lung growth starts as a primitive lung bud in early embryonic life and undergoes several morphological stages which continue into postnatal life. Each stage of lung growth is a result of complex and tightly regulated events governed by physical, environmental, hormonal and genetic factors. Fetal lung liquid and fetal breathing movements are by far the most important determinants of lung growth. Although timing of the stages of lung growth in animals do not mimic that of human, numerous animal studies, mainly on sheep and rat, have given us a better understanding of the regulators of lung growth. Insight into the genetic basis of lung growth has helped us understand and improve management of complex life threatening congenital abnormalities such as congenital diaphragmatic hernia and pulmonary hypoplasia. Although advances in perinatal medicine have improved survival of preterm infants, premature birth is perhaps still the most important factor for adverse lung growth.

Recombinant human endostatin improves tumor vasculature and alleviates hypoxia in Lewis lung carcinoma

International Nuclear Information System (INIS)

Peng Fang; Wang Jin; Zou Yi; Bao Yong; Huang Wenlin; Chen Guangming; Luo Xianrong; Chen Ming

2011-01-01

Objective: To investigate whether recombinant human endostatin can create a time window of vascular normalization prior to vascular pruning to alleviate hypoxia in Lewis lung carcinoma in mice. Methods: Kinetic changes in morphology of tumor vasculature in response to recombinant human endostatin were detected under a confocal microscope with immunofluorescent staining in Lewis lung carcinomas in mice. The hypoxic cell fraction of different time was assessed with immunohistochemical staining . Effects on tumor growth were monitored as indicated in the growth curve of tumors . Results: Compared with the control group vascularity of the tumors was reduced over time by recombinant human endostatin treatment and significantly regressed for 9 days. During the treatment, pericyte coverage increased at day 3, increased markedly at day 5, and fell again at day 7. The vascular basement membrane was thin and closely associated with endothelial cells after recombinant human endostatin treatment, but appeared thickened, loosely associated with endothelial cells in control tumors. The decrease in hypoxic cell fraction at day 5 after treatment was also found. Tumor growth was not accelerated 5 days after recombinant human endostatin treatment. Conclusions: Recombinant human endostatin can normalize tumor vasculature within day 3 to 7, leading to improved tumor oxygenation. The results provide important experimental basis for combining recombinant human endostatin with radiation therapy in human tumors. (authors)

Pseudomonas aeruginosa vesicles associate with and are internalized by human lung epithelial cells

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Kuehn Meta J

2009-02-01

Full Text Available Abstract Background Pseudomonas aeruginosa is the major pathogen associated with chronic and ultimately fatal lung infections in patients with cystic fibrosis (CF. To investigate how P. aeruginosa-derived vesicles may contribute to lung disease, we explored their ability to associate with human lung cells. Results Purified vesicles associated with lung cells and were internalized in a time- and dose-dependent manner. Vesicles from a CF isolate exhibited a 3- to 4-fold greater association with lung cells than vesicles from the lab strain PAO1. Vesicle internalization was temperature-dependent and was inhibited by hypertonic sucrose and cyclodextrins. Surface-bound vesicles rarely colocalized with clathrin. Internalized vesicles colocalized with the endoplasmic reticulum (ER marker, TRAPα, as well as with ER-localized pools of cholera toxin and transferrin. CF isolates of P. aeruginosa abundantly secrete PaAP (PA2939, an aminopeptidase that associates with the surface of vesicles. Vesicles from a PaAP knockout strain exhibited a 40% decrease in cell association. Likewise, vesicles from PAO1 overexpressing PaAP displayed a significant increase in cell association. Conclusion These data reveal that PaAP promotes the association of vesicles with lung cells. Taken together, these results suggest that P. aeruginosa vesicles can interact with and be internalized by lung epithelial cells and contribute to the inflammatory response during infection.

Multiscale image-based modeling and simulation of gas flow and particle transport in the human lungs

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Tawhai, Merryn H; Hoffman, Eric A

2013-01-01

Improved understanding of structure and function relationships in the human lungs in individuals and sub-populations is fundamentally important to the future of pulmonary medicine. Image-based measures of the lungs can provide sensitive indicators of localized features, however to provide a better prediction of lung response to disease, treatment and environment, it is desirable to integrate quantifiable regional features from imaging with associated value-added high-level modeling. With this objective in mind, recent advances in computational fluid dynamics (CFD) of the bronchial airways - from a single bifurcation symmetric model to a multiscale image-based subject-specific lung model - will be reviewed. The interaction of CFD models with local parenchymal tissue expansion - assessed by image registration - allows new understanding of the interplay between environment, hot spots where inhaled aerosols could accumulate, and inflammation. To bridge ventilation function with image-derived central airway structure in CFD, an airway geometrical modeling method that spans from the model ‘entrance’ to the terminal bronchioles will be introduced. Finally, the effects of turbulent flows and CFD turbulence models on aerosol transport and deposition will be discussed. CFD simulation of airflow and particle transport in the human lung has been pursued by a number of research groups, whose interest has been in studying flow physics and airways resistance, improving drug delivery, or investigating which populations are most susceptible to inhaled pollutants. The three most important factors that need to be considered in airway CFD studies are lung structure, regional lung function, and flow characteristics. Their correct treatment is important because the transport of therapeutic or pollutant particles is dependent on the characteristics of the flow by which they are transported; and the airflow in the lungs is dependent on the geometry of the airways and how ventilation

Hydroxyl Radical Formation from HULIS and Fe(II) Interactions: Fulvic Acid-Fe(II) Complexes in Simulated and Human Lung Fluids

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Gonzalez, D.

2017-12-01

Inhalation of fine particulate matter (PM2.5) has long been associated with adverse health outcomes. However, the causative agents and underlying mechanisms for these health effects have yet to be identified. One hypothesis is that PM2.5 deposited in the alveoli produce an excess of highly reactive radicals, leading to oxidative stress. The OH radical may be the most physiologically damaging, capable of oxidizing of lipids, proteins and DNA. Due to the variability and uncertainty in PM2.5 composition, the components that contribute to OH formation are not well understood. Soluble Fe is a component of PM2.5that produces OH under physiological conditions. Humic-like substances are water soluble organics found in biomass burning and tobacco smoke. Humic-like substances are capable of binding to Fe and enhancing OH formation, but this chemistry is not well understood. In this work, we use soil derived fulvic acid as a surrogate for Humic-like substances and investigate its effect on OH formation from Fe(II) under conditions relevant to the lungs. We use a fluorescent OH trapping probe, chemical kinetics and thermodynamic modeling to investigate OH formation from fulvic acid and Fe(II) dissolved in simulated and human lung fluids. In simulated lung fluid, we find that fulvic acid binds to Fe(II) and enhances the rate of key reactions that form OH. When fulvic acid is added to human lung fluids containing Fe(II), an enhancement of OH formation is observed. In human lung fluid, fulvic acid and metal binding proteins compete for Fe binding. These metal binding proteins are typically not found in simulated lung fluids. Results show that fulvic acid strongly binds Fe(II) and catalyzes key reactions that form OH in both simulated and human lung fluids. These results may help explain the role of Humic-like substances and Fe in oxidative stress and adverse health outcomes. Furthermore, we suggest that future studies employ simulated lung fluids containing metal binding proteins

A Human Antibody That Binds to the Sixth Ig-Like Domain of VCAM-1 Blocks Lung Cancer Cell Migration In Vitro

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Mi Ra Kim

2017-03-01

Full Text Available Vascular cell adhesion molecule-1 (VCAM-1 is closely associated with tumor progression and metastasis. However, the relevance and role of VCAM-1 in lung cancer have not been clearly elucidated. In this study, we found that VCAM-1 was highly overexpressed in lung cancer tissue compared with that of normal lung tissue, and high VCAM-1 expression correlated with poor survival in lung cancer patients. VCAM-1 knockdown reduced migration of A549 human lung cancer cells into Matrigel, and competitive blocking experiments targeting the Ig-like domain 6 of VCAM-1 (VCAM-1-D6 demonstrated that the VCAM-1-D6 domain was critical for VCAM-1 mediated A549 cell migration into Matrigel. Next, we developed a human monoclonal antibody specific to human and mouse VCAM-1-D6 (VCAM-1-D6 huMab, which was isolated from a human synthetic antibody library using phage display technology. Finally, we showed that VCAM-1-D6 huMab had a nanomolar affinity for VCAM-1-D6 and that it potently suppressed the migration of A549 and NCI-H1299 lung cancer cell lines into Matrigel. Taken together, these results suggest that VCAM-1-D6 is a key domain for regulating VCAM-1-mediated lung cancer invasion and that our newly developed VCAM-1-D6 huMab will be a useful tool for inhibiting VCAM-1-expressing lung cancer cell invasion.

Natural innate cytokine response to immunomodulators and adjuvants in human precision-cut lung slices.

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Switalla, S; Lauenstein, L; Prenzler, F; Knothe, S; Förster, C; Fieguth, H-G; Pfennig, O; Schaumann, F; Martin, C; Guzman, C A; Ebensen, T; Müller, M; Hohlfeld, J M; Krug, N; Braun, A; Sewald, K

2010-08-01

Prediction of lung innate immune responses is critical for developing new drugs. Well-established immune modulators like lipopolysaccharides (LPS) can elicit a wide range of immunological effects. They are involved in acute lung diseases such as infections or chronic airway diseases such as COPD. LPS has a strong adjuvant activity, but its pyrogenicity has precluded therapeutic use. The bacterial lipopeptide MALP-2 and its synthetic derivative BPPcysMPEG are better tolerated. We have compared the effects of LPS and BPPcysMPEG on the innate immune response in human precision-cut lung slices. Cytokine responses were quantified by ELISA, Luminex, and Meso Scale Discovery technology. The initial response to LPS and BPPcysMPEG was marked by coordinated and significant release of the mediators IL-1β, MIP-1β, and IL-10 in viable PCLS. Stimulation of lung tissue with BPPcysMPEG, however, induced a differential response. While LPS upregulated IFN-γ, BPPcysMPEG did not. This traces back to their signaling pathways via TLR4 and TLR2/6. The calculated exposure doses selected for LPS covered ranges occurring in clinical studies with human beings. Correlation of obtained data with data from human BAL fluid after segmental provocation with endotoxin showed highly comparable effects, resulting in a coefficient of correlation >0.9. Furthermore, we were interested in modulating the response to LPS. Using dexamethasone as an immunosuppressive drug for anti-inflammatory therapy, we found a significant reduction of GM-CSF, IL-1β, and IFN-γ. The PCLS-model offers the unique opportunity to test the efficacy and toxicity of biological agents intended for use by inhalation in a complex setting in humans. Copyright © 2010 Elsevier Inc. All rights reserved.

Nuclear magnetic resonance relaxation times for human lung cancer and lung tissues

International Nuclear Information System (INIS)

Matsuura, Yoshifumi; Shioya, Sumie; Kurita, Daisaku; Ohta, Takashi; Haida, Munetaka; Ohta, Yasuyo; Suda, Syuichi; Fukuzaki, Minoru.

1994-01-01

We investigated the nuclear magnetic resonance (NMR) relaxation times, T 1 and T 2 , for lung cancer tissue, and other samples of lung tissue obtained from surgical specimens. The samples were nine squamous cell carcinomas, five necrotic squamous cell carcinomas, 15 adenocarcinomas, two benign mesotheliomas, and 13 fibrotic lungs. The relaxation times were measured with a 90 MHz NMR spectrometer and the results were correlated with histological changes. The values of T 1 and T 2 for squamous cell carcinoma and mesothelioma were significantly longer than those of adenocarcinoma and fibrotic lung tissue. There were no significant differences in values of T 1 and T 2 between adenocarcinoma and lung tissue. The values of T 1 and T 2 for benign mesothelioma were similar to those of squamous cell carcinoma, which suggested that increases in T 1 and T 2 are not specific to malignant tissues. (author)

Concentration and distribution of dioxins and related compounds in various human organs

Energy Technology Data Exchange (ETDEWEB)

Iida, T.; Hirakawa, H.; Hori, T.; Tobiishi, K.; Matsueda, T. [Fukuoka Inst. of Health and Environmental Sciences, Dazaifu, Fukuoka (Japan); Todaka, T. [Japan Food Hygiene Association, Tokyo (Japan); Watanabe, S. [Tokyo Univ. of Agriculture, Tokyo (Japan); Yamada, T. [Keio Univ. School of Medicine, Tokyo (Japan)

2004-09-15

Polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs) and non-ortho coplanar polychlorinated biphenyls (Non-Co-PCBs) and mono-ortho coplanar polychlorinated biphenyls (Mono-Co-PCBs) accumulate in the human body due to their highly lipophilic properties. In recent years, there has been some concern about the potential health effects of dioxins and related chemicals for the general population of humans. Although there exists an enormous amount of data on this subject, most of it is from breast milk and blood, due to ease of collection; information concerning concentrations and distribution in various human organs hardly exists. Therefore, new data concerning various human tissues is required to evaluate the pathophysiological significance of dioxins and related compounds in humans. The aim of this study was to investigate the concentration levels and distribution of dioxins and related compounds in various human organ tissues. We previously reported on the concentration levels in the human liver and adipose tissues from 28 donors. In this paper, we determined the concentrations of dioxin-like isomers in 8 organs, including blood, lungs, liver, bile, spleen, pancreas, kidney and mesentery fat from 20 donors.

Accumulation of GC donor splice signals in mammals

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Koonin Eugene V

2008-07-01

Full Text Available Abstract The GT dinucleotide in the first two intron positions is the most conserved element of the U2 donor splice signals. However, in a small fraction of donor sites, GT is replaced by GC. A substantial enrichment of GC in donor sites of alternatively spliced genes has been observed previously in human, nematode and Arabidopsis, suggesting that GC signals are important for regulation of alternative splicing. We used parsimony analysis to reconstruct evolution of donor splice sites and inferred 298 GT > GC conversion events compared to 40 GC > GT conversion events in primate and rodent genomes. Thus, there was substantive accumulation of GC donor splice sites during the evolution of mammals. Accumulation of GC sites might have been driven by selection for alternative splicing. Reviewers This article was reviewed by Jerzy Jurka and Anton Nekrutenko. For the full reviews, please go to the Reviewers' Reports section.

Aluminum is More Cytotoxic than Lunar Dust in Human Skin and Lung Fibroblasts

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Hammond, D.; Shehata, T.; Hammond, D.; Shehata, T.; Wise, J.P.; Martino, J; Wise, J.P.; Wise, J.P.

2009-01-01

NASA plans to build a permanent space station on the moon to explore its surface. The surface of the moon is covered in lunar dust, which consists of fine particles that contain silicon, aluminum and titanium, among others. Because this will be a manned base, the potential toxicity of this dust has to be studied. Also, toxicity standards for potential exposure have to be set. To properly address the potential toxicity of lunar dust we need to understand the toxicity of its individual components, as well as their combined effects. In order to study this we compared NASA simulant JSC-1AVF (volcanic ash particles), that simulates the dust found on the moon, to aluminum, the 3rd most abundant component in lunar dust. We tested the cytotoxicity of both compounds on human lung and skin fibroblasts (WTHBF-6 and BJhTERT cell lines, respectively). Aluminum oxide was more cytotoxic than lunar dust to both cell lines. In human lung fibroblasts 5, 10 and 50 g/sq cm of aluminum oxide induced 85%, 61% and 30% relative survival, respectively. For human skin fibroblasts the same concentrations induced 58%, 41% and 58% relative survival. Lunar dust was also cytotoxic to both cell lines, but its effects were seen at higher concentrations: 50, 100, 200 and 400 g/sq cm of lunar dust induced a 69%, 46%, 35% and 30% relative survival in the skin cells and 53%, 16%, 8% and 2% on the lung cells. Overall, for both compounds, lung cells were more sensitive than skin cells. This work was supported by a NASA EPSCoR grant through the Maine Space Grant Consortium (JPW), the Maine Center for Toxicology and Environmental Health., a Fulbright Grant (JM) and a Delta Kappa Gamma Society International World Fellowship (JM).

Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

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Eilon Sharon

2017-08-01

Full Text Available Quantification of cell-free DNA (cfDNA in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD quantifies donor-derived cfDNA (dd-cfDNA by taking advantage of single-nucleotide polymorphisms (SNPs distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM of identity-by-descent (IBD states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD. These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

HLA Matching at the Eplet Level Protects Against Chronic Lung Allograft Dysfunction.

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Walton, D C; Hiho, S J; Cantwell, L S; Diviney, M B; Wright, S T; Snell, G I; Paraskeva, M A; Westall, G P

2016-09-01

Donor selection in lung transplantation (LTx) is historically based upon clinical urgency, ABO compatibility, and donor size. HLA matching is not routinely considered; however, the presence or later development of anti-HLA antibodies is associated with poorer outcomes, particularly chronic lung allograft dysfunction (CLAD). Using eplet mismatches, we aimed to determine whether donor/recipient HLA incompatibility was a significant predictor of CLAD. One hundred seventy-five LTx undertaken at the Alfred Hospital between 2008 and 2012 met criteria. Post-LTx monitoring was continued for at least 12 months, or until patient death. HLA typing was performed by sequence-based typing and Luminex sequence-specific oligonucleotide. Using HLAMatchmaker, eplet mismatches between each donor/recipient pairing were analyzed and correlated against incidences of CLAD. HLA-DRB1/3/4/5+DQA/B eplet mismatch was a significant predictor of CLAD (hazard ratio [HR] 3.77, 95% confidence interval [CI]: 1.71-8.29 p HLA-DRB1/3/4/5 + DQA/B eplet mismatch was shown to significantly predict RAS (HR 8.3, 95% CI: 2.46-27.97 p HLA-A/B eplet mismatch was shown not to be a significant predictor when analyzed independently but did provide additional stratification of results. This study illustrates the importance of epitope immunogenicity in defining donor-recipient immune compatibility in LTx. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Screening and Establishment of Human Lung Cancer Cell Lines 
with Organ-specific Metastasis Potential

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Qinghua ZHOU

2014-03-01

Full Text Available Background and objective Cancer metastasis is not only the malignant marker and characteristics, but also the main cause of failure to cure and lose their life in the patients with lung cancer. Lung cancer metastasis has organ-specific characteristics. The most common sites of lung cancer metastasis are mediastinal lymph node, brain, bone, liver and adrenal gland. The aim of this study is to screen and establish lung cancer cell model with organ-specific metastasis potential with human high-metastatic large cell lung cancer cell line L9981 established by our laboratory previously, and to provide cell models for studying the mechanisms and signal regulation of organ-specific metastasis of lung cancer. Materials and methods The parent lung cancer cell line, L9981-Luc, was inoculated in the armpit of nude mice. The live animal imaging system, IVIS-200, was used to detect the lung cancer organ-specific metastasis every week. When the organ-specific metastasis were established, the nude mices bearing the lung cancer were sacrificed when they became moribund. Under sterile conditions, the organs (mediastinal lymph nodes, lung, spinal column and brain with lung cancer organ-specific metastasis were removed and the metastasized nodules were dissected free of connective tissue and blood clots, and rinsed twice with medium. The metastasized nodules were finely minced using sterile scalpel blades in medium, and the cells were seeded in tissue culture dishes. Then, the cells with organ-specific metastasis potential were reinoculated into the armpit of nude mice, respectively. This processes were repeated to establish the organ-specific metastatic sublines of L9981-Luc cell line more than 10 times. Finally, the organ-specific metastasis sublines of L9981-Luc were screened and established, which the four cell lines have the characteristics only metastasized to brian, lung, bone and mediastinal lymph node. Results A group of organ-specific metastasis cell

Multiphoton microscopy based cryo-imaging of inflated frozen human lung sections at -60°C in healthy and COPD lungs

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Abraham, Thomas; Kayra, Damian; Zhang, Angela; Suzuki, Masaru; McDonough, John; Elliott, W. M.; Cooper, Joel D.; Hogg, James C.

2013-02-01

Lung is a complex gas exchanger with interfacial area (where the gas exchange takes place) is about the size of a tennis court. Respiratory function is linked to the biomechanical stability of the gas exchange or alveolar regions which directly depends on the spatial distributions of the extracellular matrix fibers such fibrillar collagens and elastin fibers. It is very important to visualize and quantify these fibers at their native and inflated conditions to have correct morphometric information on differences between control and diseased states. This can be only achieved in the ex vivo states by imaging directly frozen lung specimens inflated to total lung capacity. Multiphoton microscopy, which uses ultra-short infrared laser pulses as the excitation source, produces multiphoton excitation fluorescence (MPEF) signals from endogenously fluorescent proteins (e.g. elastin) and induces specific second harmonic generation (SHG) signals from non-centrosymmetric proteins such as fibrillar collagens in fresh human lung tissues [J. Struct. Biol. (2010)171,189-196]. Here we report for the first time 3D image data obtained directly from thick frozen inflated lung specimens (~0.7- 1.0 millimeter thick) visualized at -60°C without prior fixation or staining in healthy and diseased states. Lung specimens donated for transplantation and released for research when no appropriate recipient was identified served as controls, and diseased lung specimens donated for research by patients receiving lung transplantation for very severe COPD (n=4) were prepared as previously described [N. Engl. J. Med. (2011) 201, 1567]. Lung slices evenly spaced between apex and base were examined using multiphoton microscopy while maintained at -60°C using a temperature controlled cold stage with a temperature resolution of 0.1°C. Infrared femto-second laser pulses tuned to 880nm, dry microscopic objectives, and non-de-scanned detectors/spectrophotometer located in the reflection geometry were

Human Milk Processing: A Systematic Review of Innovative Techniques to Ensure the Safety and Quality of Donor Milk.

Science.gov (United States)

Peila, Chiara; Emmerik, Nikki E; Giribaldi, Marzia; Stahl, Bernd; Ruitenberg, Joost E; van Elburg, Ruurd M; Moro, Guido E; Bertino, Enrico; Coscia, Alessandra; Cavallarin, Laura

2017-03-01

Pasteurization, performed at 62.5°C for 30 minutes (holder pasteurization), is currently recommended in all international human milk banks guidelines, but it affects some human milk bioactive and nutritive components. The present systematic review is aimed at critically reviewing evidence on the suitability of human milk processing techniques other than holder pasteurization, both thermal and nonthermal, to ensure microbiological safety, and on the effects of these techniques on biologically active donor milk components. A systematic review of English and non-English articles using Medline, PubMed, Embase, SCOPUS, and CAB Abstracts, with no restriction in publication date was performed. Search terms included: human, breast, donor, or banked milk, breastmilk, breast fed, breastfed, breastfeed; HTST, Flash, High Pressure, UV, ultrasonic or nonthermal; process, pasteuris, pasteuriz. Only primary research articles published in peer-reviewed journals were included, providing or not a comparison with holder pasteurized human milk, provided that the pasteurization technique was clearly described, and not intended for domestic use. Additional studies were identified by searching bibliographies of relevant articles. Twenty-six studies were identified as being relevant. Two examined both High Pressure Processing and High-Temperature-Short-Time pasteurization; 10 only examined High Pressure Processing; 10 only examined High-Temperature-Short-Time; 2 articles examined ultraviolet irradiation; 2 articles examined (thermo-)ultrasonic processing. The results indicate that data about safety for microbiological control are still scarce for most of the novel technologies, and that consensus on processing conditions is necessary for nonthermal technologies, before any conclusions on the qualitative and nutritional advantages of these techniques can be drawn.

Unilateral Dependant Pulmonary Edema During Laparoscopic Donor Nephrectomy: Report of Three Cases

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Manisha Modi

2009-01-01

Full Text Available Unilateral pulmonary edema of the dependant lung was observed in three patients during laparoscopic donor nephrectomy. Patients were treated with 02 supplementation by face mask, fluid restriction and diuretic. All the patients were relieved of symptoms with radiological improvement. The possible causes of this unusual complication following laparoscopic surgery appear to be prolonged lateral decubitus position and high intraoperative fluid infusion.

Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer.

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Linghan Jia

Full Text Available Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

Preliminary study of steep pulse irreversible electroporation technology in human large cell lung cancer cell lines L9981

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Song Zuoqing

2013-01-01

Full Text Available Our aim was to validate the effectiveness of steep pulse irreversible electroporation technology in human large cell lung cancer cells and to screen the optimal treatment of parameters for human large cell lung cancer cells. Three different sets of steep pulse therapy parameters were applied on the lung cancer cell line L9981. The cell line L9981 inhibition rate and proliferation capacity were detected by Vi-Cell vitality analysis and MTT. Steep pulsed irreversible electroporation technology for large cell lung cancer L9981 presents killing effects with various therapy parameters. The optimal treatment parameters are at a voltage amplitude of 2000V/cm, pulse width of 100μs, pulse frequency of 1 Hz, pulse number 10. With this group of parameters, steep pulse could have the best tumor cell-killing effects.

Prevalence of human immunodeficiency virus type 1 p24 antigen in U.S. blood donors--an assessment of the efficacy of testing in donor screening. The HIV-Antigen Study Group.

Science.gov (United States)

Alter, H J; Epstein, J S; Swenson, S G; VanRaden, M J; Ward, J W; Kaslow, R A; Menitove, J E; Klein, H G; Sandler, S G; Sayers, M H

1990-11-08

We performed a multicenter study in 1989 to determine whether screening whole-blood donors for human immunodeficiency virus type 1 (HIV-1) p24 antigen would improve transfusion safety by identifying carriers of the virus who are seronegative for HIV-1 antibody. More than 500,000 donations were tested at 13 U.S. blood centers with test kits from two manufacturers. Units found repeatedly reactive were retested in a central laboratory; if the results were positive, they were confirmed by a neutralization assay. A subgroup of units was also tested for HIV-1 by the polymerase chain reaction. Selected donors confirmed or not confirmed as having p24 antigen were contacted for follow-up interviews to identify risk factors and undergo retesting for HIV-1 markers. Positive tests for p24 antigen were confirmed by neutralization in five donors (0.001 percent of all donations tested), all of whom were also positive for HIV-1 antibody and HIV-1 by polymerase chain reaction. Three of the antigen-positive donors had other markers of infectious disease that would have resulted in the exclusion of their blood; two had risk factors for HIV-1 that should have led to self-exclusion. Of 220 blood units with repeatedly reactive p24 antigen whose presence could not be confirmed by neutralization (0.04 percent of the donations studied), none were positive for HIV-1 antibody, HIV-1 by polymerase chain reaction (120 units tested), or virus culture (76 units tested)--attesting to the specificity of confirmatory neutralization. The finding that no donation studied was positive for p24 antigen and negative for HIV-1 antibody suggests that screening donors for p24 antigen with tests of the current level of sensitivity would not add substantially to the safety of the U.S. blood supply.

Live donor transplantation--the incompetent donor: comparative law.

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Wolfman, Samuel; Shaked, Tali

2008-12-01

Informed consent of the patient to medical treatment is an essential prerequisite for any invasive medical procedure. However in emergency cases, when the patient is unable to sign a consent form due to unconsciousness or to psychotic state, than the primary medical consideration shall take place. In such a case, in order to save life or even prevent a major medical hazard to the patient, doctors are allowed, in certain cases and in accordance with well accepted medical practice, to perform invasive procedures, major surgery or risky pharmacological treatment, without the explicit consent of the patient. All the above refers to the cases when avoidance of such non-consented treatment may harm severely the health and wellbeing of the patient and there is no doubt that such treatment is for the ultimate benefit of the patient. The question, however, shall arise when such a medical procedure is not necessarily for the benefit of the patient, but rather for the benefit of somebody else. Such is the case in the transplantation area and the question of living donor-donee relationship. This paper shall analyze the legal situation in cases of non competent donors whose consent cannot be considered legal consent given in full understanding and out of free will. It will also compare three legal systems, the Israeli, the American and the traditional Jewish law, with regard to the different approaches to this human problem, where the autonomy of the donor may be sacrificed for the purpose of saving life of another person.

Autoradiographic localization of calcitonin gene-related peptide (CGRP) binding sites in human and guinea pig lung

International Nuclear Information System (INIS)

Mak, J.C.; Barnes, P.J.

1988-01-01

125 I-Human calcitonin gene-related peptide (hCGRP) binding sites were localized in human and guinea pig lungs by an autoradiographic method. Scatchard analysis of saturation experiments from slide-mounted sections of guinea pig lung displayed specific 125 I-hCGRP binding sites with a dissociation constant (Kd) of 0.72 +/- 0.05 nM (mean +/- S.E.M., n = 3) and a maximal number of binding sites (Bmax) of 133.4 +/- 5.6 fmol/mg protein. In both human and guinea pig lung, autoradiography revealed that CGRP binding sites were widely distributed, with particularly dense labeling over bronchial and pulmonary blood vessels of all sizes and alveolar walls. Airway smooth muscle and epithelium of large airways was sparsely labeled but no labeling was found over submucosal glands. This localization corresponds well to the reported pattern of CGRP-like immunoreactive innervation. The findings of localization of CGRP binding sites on bronchial and pulmonary blood vessels indicate that CGRP may be important in the regulation of airway and pulmonary blood flow

Sociology and behaviour of West African blood donors: the impact of religion on human immunodeficiency virus infection.

Science.gov (United States)

Allain, J-P; Anokwa, M; Casbard, A; Owusu-Ofori, S; Dennis-Antwi, J

2004-11-01

Ghana is one of the countries of sub-Saharan Africa where the human immunodeficiency virus (HIV) prevalence in blood donors ranges between 1 and 4%. Considering the social importance of religion and the very high level of religious practice observed in Ghana, the hypothesis that these factors may play a role in containing HIV was tested. Consenting HIV-infected candidate blood donors, and two age- and gender-matched seronegative control donors, were asked to complete a questionnaire regarding their religious and sexual behaviour. Multivariable conditional logistic regression was used. Irrespective of their HIV status or religion, 95% of the respondents believed that extra-marital sex was a sin, and 79% of those tempted to have an extra-marital affair considered that their religious beliefs helped them to abstain. In the multivariable models, having a formal role in church activities was associated with reduced odds of HIV [odds ratio (OR) = 0.41; 95% confidence interval (CI): 0.21-0.80]. Worshipping at the same location for more than 20 years was associated with a reduced risk (OR = 0.30; 95% CI: 0.08-1.10). In addition to other factors limiting HIV spread, such as male circumcision, relatively high level of education and an absence of armed conflicts in Ghana, the use of condoms conferred a reduced risk. An active role in religion, and reporting a lengthy duration of worship at the same place was beneficial. Collecting blood at places of worship with a strict behavioural code and from donors practicing in the community of their birth might improve blood safety.

Trends in Transfusion Transmitted Infections Among Replacement Blood Donors in Karachi, Pakistan

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Syed Mohammad Irfan

2013-06-01

Full Text Available OBJECTIVE: To determine the prevalence of Hepatitis-B, Hepatitis-C and Human Immunodeficiency infections in replacement blood donors. METHODS: From January 2004 to December 2011, 108,598 apparently healthy donors donated blood at our Blood Bank. Screening was done by Microparticle Enzyme Immuno Assay (MEIA method on Axsym System (Abbott Diagnostic, USA and in year 2011 by Chemiluminescent Immunoassay (CIA method on Architect i2000 (Abbott Diagnostic, USA. From 2010 onward, HIV reactive donors were advised for confirmatory tests and reported back with the results. RESULTS: Of the 108,598 total donors, 108,393 (99.8% were replacement donors with a mean age of 28.92 (17-55 years. Of this, only 164 (0.15% were females. Among the replacement donors, 4,906 (4.5% were found to be reactive for Hepatitis-B, C and Human Immunodeficiency Virus. All the reactive patients, except one, were males. HbsAg was positive in 2,068 (1.90% and anti-HCV in 2832 (2.61% donors, while 111 (0.10% were positive for Human Immunodeficiency Virus. Co-infectivity was observed in 103 (0.09% cases. The prevalence appeared to be higher in younger age group (17-30 yrs. Only 16.6% cases should be patients returned with results of the confirmatory tests for HIV and were found positive. CONCLUSION: Hepatitis-B and C sero-prevalence in our series of replacement donors appears high compared to most studies from neighboring countries and relatively low in comparison to earlier studies from Pakistan. Prevalence of HIV, however, appears low and turn out of HIV positive cases for confirmatory tests is low.

Thioredoxin reductase 1 knockdown enhances selenazolidine cytotoxicity in human lung cancer cells via mitochondrial dysfunction

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Poerschke, Robyn L.; Moos, Philip J.

2010-01-01

Thioredoxin reductase (TR1) is a selenoprotein that is involved in cellular redox status control and deoxyribonucleotide biosynthesis. Many cancers, including lung, overexpress TR1, making it a potential cancer therapy target. Previous work has shown that TR1 knockdown enhances the sensitivity of cancer cells to anticancer treatments, as well as certain selenocompounds. However, it is unknown if TR1 knockdown produces similar effect on the sensitivity of human lung cancer cells. To further elucidate the role of TR1 in the mechanism of selenocompounds in lung cancer, a lentiviral microRNA delivery system to knockdown TR1 expression in A549 human lung adenocarcinoma cells was utilized. Cell viability was assessed after 48 hr treatment with the selenocysteine prodrug selenazolidines 2-butylselenazolidine-4(R)-carboxylic acid (BSCA) and 2-cyclohexylselenazolidine-4-(R)-carboxylic acid (ChSCA), selenocystine (SECY), methylseleninic acid (MSA), 1,4-phenylenebis(methylene)selenocyanate (p-XSC), and selenomethionine (SEM). TR1 knockdown increased the cytotoxicity of BSCA, ChSCA, and SECY but did not sensitize cells to MSA, SEM, or p-XSC. GSH and TR1 depletion together decreased cell viability, while no change was observed with GSH depletion alone. Reactive oxygen species generation was induced only in TR1 knockdown cells treated with the selenazolidines or SECY. These three compounds also decreased total intracellular glutathione levels and oxidized thioredoxin, but in a TR1 independent manner. TR1 knockdown increased selenazolidine and SECY-induced mitochondrial membrane depolarization, as well as DNA strand breaks and AIF translocation from the mitochondria. These results indicate the ability of TR1 to modulate the cytotoxic effects of BSCA, ChSCA and SECY in human lung cancer cells through mitochondrial dysfunction. PMID:20920480

Aging effects on airflow dynamics and lung function in human bronchioles.

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Kim, JongWon; Heise, Rebecca L; Reynolds, Angela M; Pidaparti, Ramana M

2017-01-01

The mortality rate for patients requiring mechanical ventilation is about 35% and this rate increases to about 53% for the elderly. In general, with increasing age, the dynamic lung function and respiratory mechanics are compromised, and several experiments are being conducted to estimate these changes and understand the underlying mechanisms to better treat elderly patients. Human tracheobronchial (G1 ~ G9), bronchioles (G10 ~ G22) and alveolar sacs (G23) geometric models were developed based on reported anatomical dimensions for a 50 and an 80-year-old subject. The aged model was developed by altering the geometry and material properties of the model developed for the 50-year-old. Computational simulations using coupled fluid-solid analysis were performed for geometric models of bronchioles and alveolar sacs under mechanical ventilation to estimate the airflow and lung function characteristics. The airway mechanical characteristics decreased with aging, specifically a 38% pressure drop was observed for the 80-year-old as compared to the 50-year-old. The shear stress on airway walls increased with aging and the highest shear stress was observed in the 80-year-old during inhalation. A 50% increase in peak strain was observed for the 80-year-old as compared to the 50-year-old during exhalation. The simulation results indicate that there is a 41% increase in lung compliance and a 35%-50% change in airway mechanical characteristics for the 80-year-old in comparison to the 50-year-old. Overall, the airway mechanical characteristics as well as lung function are compromised due to aging. Our study demonstrates and quantifies the effects of aging on the airflow dynamics and lung capacity. These changes in the aging lung are important considerations for mechanical ventilation parameters in elderly patients. Realistic geometry and material properties need to be included in the computational models in future studies.

Modification by antioxidant supplementation of changes in human lung function associated with air pollutant exposure: A systematic review

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Chow Katherine S

2011-07-01

Full Text Available Abstract Background Outdoor air pollution, given its demonstrated negative effects on the respiratory system, is a growing public health concern worldwide, particularly in urban cities. Human exposure to pollutants such as ozone, nitrogen oxides, combustion-related particulate matter and oxides of sulfur is responsible for significant cardiopulmonary morbidity and mortality in both adults and children. Several antioxidants have shown an ability to partially attenuate the negative physiological and functional impacts of air pollutants. This study systematically presents current data on the potential benefits of antioxidant supplementation on lung function outcomes associated with air pollutant exposures in intact humans. Methods Electronic databases (MEDLINE, EMBASE, BIOSIS Previews, Web of Sciences, Environmental Sciences & Pollution Management and TOXNET were systematically searched for all studies published up to April 2009. Search terms relating to the concepts of respiratory tract diseases, respiratory function tests, air pollution, and antioxidants were used. Data was systematically abstracted from original articles that satisfied selection criteria for inclusion. For inclusion, the studies needed to have evaluated human subjects, given supplemental antioxidants, under conditions of known levels of air pollutants with measured lung function before and after antioxidant administration and/or air pollution exposure. Selected studies were summarized and conclusions presented. Results Eight studies investigated the role of antioxidant supplementation on measured lung function outcomes after subject exposure to air pollutants under controlled conditions; 5 of these studies concluded that pollutant-induced airway hyper-responsiveness and diminution in lung function measurements were attenuated by antioxidant supplementation. The remaining five studies took place under ambient (uncontrolled exposures and unanimously concluded that antioxidant

A Comparison of Nutritional Antioxidant Content in Breast Milk, Donor Milk, and Infant Formulas.

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Hanson, Corrine; Lyden, Elizabeth; Furtado, Jeremy; Van Ormer, Matthew; Anderson-Berry, Ann

2016-10-28

Human milk is the optimal food for human infants, including infants born prematurely. In the event that a mother of a hospitalized infant cannot provide breast milk, donor milk is considered an acceptable alternative. It is known that the macronutrient composition of donor milk is different than human milk, with variable fat content and protein content. However, much less is known about the micronutrient content of donor milk, including nutritional antioxidants. Samples of breast milk from 12 mothers of infants hospitalized in the Newborn Intensive Care Unit until were collected and analyzed for concentrations of nutritional antioxidants, including α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, and α-tocopherol. Additionally, a homogenized sample of donor milk available from a commercial milk bank and samples of infant formulas were also analyzed. Concentrations of nutritional antioxidants were measured using high-performance liquid chromatography. Compared to breast milk collected from mothers of hospitalized infants, commercially available donor milk had 18%-53% of the nutritional antioxidant content of maternal breast milk. As donor milk is becoming a common nutritional intervention for the high risk preterm infant, the nutritional antioxidant status of donor milk-fed premature infants and outcomes related to oxidative stress may merit further investigation.

A Comparison of Nutritional Antioxidant Content in Breast Milk, Donor Milk, and Infant Formulas

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Corrine Hanson

2016-10-01

Full Text Available Human milk is the optimal food for human infants, including infants born prematurely. In the event that a mother of a hospitalized infant cannot provide breast milk, donor milk is considered an acceptable alternative. It is known that the macronutrient composition of donor milk is different than human milk, with variable fat content and protein content. However, much less is known about the micronutrient content of donor milk, including nutritional antioxidants. Samples of breast milk from 12 mothers of infants hospitalized in the Newborn Intensive Care Unit until were collected and analyzed for concentrations of nutritional antioxidants, including α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein + zeaxanthin, retinol, and α-tocopherol. Additionally, a homogenized sample of donor milk available from a commercial milk bank and samples of infant formulas were also analyzed. Concentrations of nutritional antioxidants were measured using high-performance liquid chromatography. Compared to breast milk collected from mothers of hospitalized infants, commercially available donor milk had 18%–53% of the nutritional antioxidant content of maternal breast milk. As donor milk is becoming a common nutritional intervention for the high risk preterm infant, the nutritional antioxidant status of donor milk–fed premature infants and outcomes related to oxidative stress may merit further investigation.

A 3D Human Lung Tissue Model for Functional Studies on Mycobacterium tuberculosis Infection.

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Braian, Clara; Svensson, Mattias; Brighenti, Susanna; Lerm, Maria; Parasa, Venkata R

2015-10-05

Tuberculosis (TB) still holds a major threat to the health of people worldwide, and there is a need for cost-efficient but reliable models to help us understand the disease mechanisms and advance the discoveries of new treatment options. In vitro cell cultures of monolayers or co-cultures lack the three-dimensional (3D) environment and tissue responses. Herein, we describe an innovative in vitro model of a human lung tissue, which holds promise to be an effective tool for studying the complex events that occur during infection with Mycobacterium tuberculosis (M. tuberculosis). The 3D tissue model consists of tissue-specific epithelial cells and fibroblasts, which are cultured in a matrix of collagen on top of a porous membrane. Upon air exposure, the epithelial cells stratify and secrete mucus at the apical side. By introducing human primary macrophages infected with M. tuberculosis to the tissue model, we have shown that immune cells migrate into the infected-tissue and form early stages of TB granuloma. These structures recapitulate the distinct feature of human TB, the granuloma, which is fundamentally different or not commonly observed in widely used experimental animal models. This organotypic culture method enables the 3D visualization and robust quantitative analysis that provides pivotal information on spatial and temporal features of host cell-pathogen interactions. Taken together, the lung tissue model provides a physiologically relevant tissue micro-environment for studies on TB. Thus, the lung tissue model has potential implications for both basic mechanistic and applied studies. Importantly, the model allows addition or manipulation of individual cell types, which thereby widens its use for modelling a variety of infectious diseases that affect the lungs.

Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling.

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Ito, Yoko; Correll, Kelly; Schiel, John A; Finigan, Jay H; Prekeris, Rytis; Mason, Robert J

2014-07-01

There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS. Lung fibroblasts (FBs) migrate and proliferate early after lung injury and likely are an important source of growth factors for epithelial repair. However, how lung FBs affect epithelial wound healing in the human adult lung has not been investigated in detail. Hepatocyte growth factor (HGF) is known to be released mainly from FBs and to stimulate both migration and proliferation of primary rat ATII cells. HGF is also increased in lung tissue, bronchoalveolar lavage fluid, and serum in patients with ALI/ARDS. Therefore, we hypothesized that HGF secreted by FBs would enhance wound closure in alveolar epithelial cells (AECs). Wound closure was measured using a scratch wound-healing assay in primary human AEC monolayers and in a coculture system with FBs. We found that wound closure was accelerated by FBs mainly through HGF/c-Met signaling. HGF also restored impaired wound healing in AECs from the elderly subjects and after exposure to cyclic stretch. We conclude that HGF is the critical factor released from FBs to close wounds in human AEC monolayers and suggest that HGF is a potential strategy for hastening alveolar repair in patients with ALI/ARDS. Copyright © 2014 the American Physiological Society.

Production of decellularized porcine lung scaffolds for use in tissue engineering†

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Balestrini, Jenna L.; Gard, Ashley L.; Liu, Angela; Leiby, Katherine L.; Schwan, Jonas; Kunkemoeller, Britta; Calle, Elizabeth A.; Sivarapatna, Amogh; Lin, Tylee; Dimitrievska, Sashka; Cambpella, Stuart G.; Niklason, Laura E.

2015-01-01

There is a growing body of work dedicated to producing acellular lung scaffolds for use in regenerative medicine by decellularizing donor lungs of various species. These scaffolds typically undergo substantial matrix damage due to the harsh conditions required to remove cellular material (e.g., high pH, strong detergents), lengthy processing times, or pre-existing tissue contamination from microbial colonization. In this work, a new decellularization technique is described that maintains the global tissue architecture, key matrix components, mechanical composition and cell-seeding potential of lung tissue while effectively removing resident cellular material. Acellular lung scaffolds were produced from native porcine lungs using a combination of Triton X-100 and sodium deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of matrix decellularization by measuring residual PMID:26426090

Dengue antibodies in blood donors.

Science.gov (United States)

Ribas-Silva, Rejane Cristina; Eid, Andressa Ahmad

2012-01-01

Dengue is an urban arbovirus whose etiologic agent is a virus of the genus Flavorius with four distinct antigen serotypes (DENV-1, DENV-2, DENV-3 and DENV-4) that is transmitted to humans through the bite of the mosquito Aedes aegypti. The Campo Mourão region in Brazil is endemic for dengue fever. OBTECTIVE: The aim of this study was to evaluate the presence of IgG and IgM antibodies specific to the four serotypes of dengue in donors of the blood donor service in the city of Campo Mourão. Epidemiological records were evaluated and 4 mL of peripheral blood from 213 blood donors were collected in tubes without anticoagulant. Serum was then obtained and immunochromatographic tests were undertaken (Imuno-Rápido Dengue IgM/IgG(TM)). Individuals involved in the study answered a social and epidemiological questionnaire on data which included age, gender and diagnosis of dengue. Only three (1.4%) of the 213 blood tests were positive for IgG anti-dengue antibodies. No donors with IgM antibody, which identifies acute infection, were identified. The results of the current analysis show that the introduction of quantitative or molecular serological methods to determine the presence of anti-dengue antibodies or the detection of the dengue virus in blood donors in endemic regions should be established so that the quality of blood transfusions is guaranteed.

Generation of human induced pluripotent stem cells from urinary cells of a healthy donor using a non-integration system

OpenAIRE

Uhm, Kyung-Ok; Jo, Eun Hee; Go, Gue Youn; Kim, So-Jung; Choi, Hye Young; Im, Young Sam; Ha, Hye-Yeong; Jung, Ji-Won; Koo, Soo Kyung

2017-01-01

Urinary cells can be an ideal source for generating hiPSCs and progenitors, as they are easily accessible, non-invasive, and universally available. We generated human induced pluripotent stem cells (hiPSCs) from the urinary cells of a healthy donor using a Sendai virus-based gene delivery method. The generated hiPSC line, KSCBi001-A, has a normal karyotype (46,XY). The pluripotency and capacity of multilineage differentiation were characterized by comparison with those of a human embryonic st...

Human Lung Cancer Risks from Radon – Part II – Influence from Combined Adaptive Response and Bystander Effects – A Microdose Analysis

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Leonard, Bobby E.; Thompson, Richard E.; Beecher, Georgia C.

2010-01-01

In the prior Part I, the potential influence of the low level alpha radiation induced bystander effect (BE) on human lung cancer risks was examined. Recent analysis of adaptive response (AR) research results with a Microdose Model has shown that single low LET radiation induced charged particles traversals through the cell nucleus activates AR. We have here conducted an analysis based on what is presently known about adaptive response and the bystander effect (BE) and what new research is needed that can assist in the further evaluation human cancer risks from radon. We find that, at the UNSCEAR (2000) worldwide average human exposures from natural background and man-made radiations, the human lung receives about a 25% adaptive response protection against the radon alpha bystander damage. At the UNSCEAR (2000) minimum range of background exposure levels, the lung receives minimal AR protection but at higher background levels, in the high UNSCEAR (2000) range, the lung receives essentially 100% protection from both the radon alpha damage and also the endogenic, spontaneously occurring, potentially carcinogenic, lung cellular damage. PMID:22461760

Cellular morphometry of the bronchi of human and dog lungs

International Nuclear Information System (INIS)

Robbins, E.S.

1991-03-01

One hundred and thirty-one bronchial samples from 62 patients have been dissected by generation from fixed surgical lung specimens obtained after the removal of pathological lesions. Complete patient records including occupational and smoking histories, as well as possible exposure to radon, are obtained. In addition, one hundred and sixty-two mongol dog bronchi dissected from different lobes of 23 dog lungs have also been similarly prepared. Ninety-four human samples have been completely processed for electron microscopy and have yielded 994 electron micrographs of which 532 have been entered into the Computerized Stereological Analysis System (COSAS) and been used for the measurement of the distances of basal and mucous cell nuclei to the epithelial free surface. Similarly 240 micrographs of dog epithelium from 31 bronchial samples have been entered into COSAS. We have, using the COSAS planimetry program, established data bases which describe the volume density and nuclear numbers per electron micrograph for 5 cell types of the human bronchial epithelial lining of men and women, as well as smokers, non-smokers and ex-smokers and similar parameters for the epithelial cell types of dog bronchi. The data are being used to develop weighting factors for dosimetry and radon risk analysis. 26 refs., 7 figs., 4 tabs

DEPOSITION DISTRICUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE.

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DEPOSITION DISTRIBUTION AMONG THE PARALLEL PATHWAYS IN THE HUMAN LUNG CONDUCTING AIRWAY STRUCTURE. Chong S. Kim*, USEPA National Health and Environmental Effects Research Lab. RTP, NC 27711; Z. Zhang and C. Kleinstreuer, Department of Mechanical and Aerospace Engineering, North C...

Lung density

DEFF Research Database (Denmark)

Garnett, E S; Webber, C E; Coates, G

1977-01-01

The density of a defined volume of the human lung can be measured in vivo by a new noninvasive technique. A beam of gamma-rays is directed at the lung and, by measuring the scattered gamma-rays, lung density is calculated. The density in the lower lobe of the right lung in normal man during quiet...... breathing in the sitting position ranged from 0.25 to 0.37 g.cm-3. Subnormal values were found in patients with emphsema. In patients with pulmonary congestion and edema, lung density values ranged from 0.33 to 0.93 g.cm-3. The lung density measurement correlated well with the findings in chest radiographs...... but the lung density values were more sensitive indices. This was particularly evident in serial observations of individual patients....

SENIEUR status of the originating cell donor negates certain 'anti-immunosenescence' effects of ebselen and N-acetyl cysteine in human T cell clone cultures.

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Marthandan, Shiva; Freeburn, Robin; Steinbrecht, Susanne; Pawelec, Graham; Barnett, Yvonne

2014-01-01

Damage to T cells of the immune system by reactive oxygen species may result in altered cell function or cell death and thereby potentially impact upon the efficacy of a subsequent immune response. Here, we assess the impact of the antioxidants Ebselen and N-acetyl cysteine on a range of biological markers in human T cells derived from a SENIEUR status donor. In addition, the impact of these antioxidants on different MAP kinase pathways in T cells from donors of different ages was also examined. T cell clones were derived from healthy 26, 45 and SENIEUR status 80 year old people and the impact of titrated concentrations of Ebselen or N-acetyl cysteine on their proliferation and in vitro lifespan, GSH:GSSG ratio as well as levels of oxidative DNA damage and on MAP kinase signaling pathways was examined. In this investigation neither Ebselen nor N-acetyl cysteine supplementation had any impact on the biological endpoints examined in the T cells derived from the SENIEUR status 80 year old donor. This is in contrast to the anti-immunosenescent effects of these antioxidants on T cells from donors of 26 or 45 years of age. The analysis of MAP kinases showed that pro-apoptotic pathways become activated in T cells with increasing in vitro age and that Ebselen or N-acetyl cysteine could decrease activation (phosphorylation) in T cells from 26 or 45 year old donors, but not from the SENIEUR status 80 year old donor. The results of this investigation demonstrate that the biological phenotype of SENIEUR status derived human T cells negates the anti-immunosenescence effects of Ebselen and also N-acetyl cysteine. The results highlight the importance of pre-antioxidant intervention evaluation to determine risk-benefit.

Twenty-Year Evolution of Hepatitis B Virus and Human Immunodeficiency Virus Prevalence and Incidence in Voluntary Blood Donors in Côte d'Ivoire.

Science.gov (United States)

Seri, Benjamin; Minga, Albert; Gabillard, Delphine; Dembele, Bamori; Konate, Seidou; Le Carrou, Jérôme; Dohoun, Lambert; Abo, Yao; Karcher, Sophie; Coffie, Patrick; N'Dri-Yoman, Thérèse; Attia, Alain; Eholié, Serge P; Danel, Christine; Lacombe, Karine; Anglaret, Xavier; Boyd, Anders

2018-04-01

Hepatitis B virus (HBV) and human immunodeficiency virus (HIV) share common risk factors. The parallel description of their frequency over time may help capture their similarities and differences. Using data from the National Transfusion Center of Abidjan, we estimated the following over a 20-year period: (1) the prevalence of HIV and hepatitis B surface antigen (HBsAg) positivity at first contact; and (2) the incidence of HIV and HBsAg seroconversion in negative first-time blood donors. Between 1992 and 2012, 422319 donors (men [M] = 74%) provided 1063825 blood donations. For first-time donors, HIV prevalence decreased from 7.1% (M = 5.9%, women [W] =11.0%) in 1992-1994 to 1.1% (M = 0.8%, W = 2.0%) in 2010-2012. Prevalence of HBsAg positivity remained stable at 10.8% (M = 11.7%, W = 7.3%) in 1992-1994 to 11.1% (M = 12.5%, W = 7.1%) in 2010-2012. Among regular donors (N = 129256), the incidence of becoming HIV or HBsAg positive, respectively, decreased from 4.9 per 100 (M = 4.5, W = 8.6) and 7.3 per 100 person-years (M = 7.8, W = 2.3) in 1992-1994 to 0.07 (M = 0.06, W = 0.11) and 0.2 per 100 person-years (M = 0.2, W = 0.2) in 2010-2012. Human immunodeficiency virus prevalence and incidence decreased dramatically over time, whereas HBV prevalence remained stable. Incidence of HBsAg seroconversion, although decreasing, still reached unexpected levels, suggesting that the risk of HBV infection in adults may be higher than expected. Hepatitis B surface antigen-negative blood-donors should be offered HBV vaccination.

Are drowned donors marginal donors? A single pediatric center experience.

Science.gov (United States)

Kumm, Kayla R; Galván, N Thao N; Koohmaraie, Sarah; Rana, Abbas; Kueht, Michael; Baugh, Katherine; Hao, Liu; Yoeli, Dor; Cotton, Ronald; O'Mahony, Christine A; Goss, John A

2017-09-01

Drowning, a common cause of death in the pediatric population, is a potentially large donor pool for OLT. Anecdotally, transplant centers have deemed these organs high risk over concerns for infection and graft dysfunction. We theorized drowned donor liver allografts do not portend worse outcomes and therefore should not be excluded from the donation pool. We reviewed our single-center experience of pediatric OLTs between 1988 and 2015 and identified 33 drowned donor recipients. These OLTs were matched 1:2 to head trauma donor OLTs from our center. A chart review assessed postoperative peak AST and ALT, incidence of HAT, graft and recipient survival. Recipient survival at one year between patients with drowned donor vs head trauma donor allografts was not statistically significant (94% vs 97%, P=.63). HAT incidence was 6.1% in the drowned donor group vs 7.6% in the control group (P=.78). Mean postoperative peak AST and ALT was 683 U/L and 450 U/L for drowned donors vs 1119 U/L and 828 U/L in the matched cohort. These results suggest drowned donor liver allografts do not portend worse outcomes in comparison with those procured from head trauma donors. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human airway organoid engineering as a step toward lung regeneration and disease modeling.

Science.gov (United States)

Tan, Qi; Choi, Kyoung Moo; Sicard, Delphine; Tschumperlin, Daniel J

2017-01-01

Organoids represent both a potentially powerful tool for the study cell-cell interactions within tissue-like environments, and a platform for tissue regenerative approaches. The development of lung tissue-like organoids from human adult-derived cells has not previously been reported. Here we combined human adult primary bronchial epithelial cells, lung fibroblasts, and lung microvascular endothelial cells in supportive 3D culture conditions to generate airway organoids. We demonstrate that randomly-seeded mixed cell populations undergo rapid condensation and self-organization into discrete epithelial and endothelial structures that are mechanically robust and stable during long term culture. After condensation airway organoids generate invasive multicellular tubular structures that recapitulate limited aspects of branching morphogenesis, and require actomyosin-mediated force generation and YAP/TAZ activation. Despite the proximal source of primary epithelium used in the airway organoids, discrete areas of both proximal and distal epithelial markers were observed over time in culture, demonstrating remarkable epithelial plasticity within the context of organoid cultures. Airway organoids also exhibited complex multicellular responses to a prototypical fibrogenic stimulus (TGF-β1) in culture, and limited capacity to undergo continued maturation and engraftment after ectopic implantation under the murine kidney capsule. These results demonstrate that the airway organoid system developed here represents a novel tool for the study of disease-relevant cell-cell interactions, and establishes this platform as a first step toward cell-based therapy for chronic lung diseases based on de novo engineering of implantable airway tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

Imaging evaluation of potential donors in living-donor liver transplantation

International Nuclear Information System (INIS)

Low, G.; Wiebe, E.; Walji, A.H.; Bigam, D.L.

2008-01-01

Liver transplants, originally obtained from deceased donors, can now be harvested from living donors as well. This technique, called living-donor liver transplantation (LDLT), provides an effective alternative means of liver transplantation and is a method of expanding the donor pool in light of the demand and supply imbalance for organ transplants. Imaging plays an important role in LDLT programmes by providing robust evaluation of potential donors to ensure that only anatomically suitable donors with no significant co-existing pathology are selected and that crucial information that allows detailed preoperative planning is available. Imaging evaluation helps to improve the outcome of LDLT for both donors and recipients, by improving the chances of graft survival and reducing the postoperative complication rate. In this review, we describe the history of LDLT and discuss in detail the application of imaging in donor assessment with emphasis on use of modern computed tomography (CT) and magnetic resonance imaging (MRI) techniques

Methyl donor deficient diets cause distinct alterations in lipid metabolism but are poorly representative of human NAFLD [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Marcus J. Lyall

2017-08-01

Full Text Available Background: Non-alcoholic fatty liver disease (NAFLD is a global health issue. Dietary methyl donor restriction is used to induce a NAFLD/non-alcoholic steatohepatitis (NASH phenotype in rodents, however the extent to which this model reflects human NAFLD remains incompletely understood. To address this, we undertook hepatic transcriptional profiling of methyl donor restricted rodents and compared these to published human NAFLD datasets.              Methods: Adult C57BL/6J mice were maintained on control, choline deficient (CDD or methionine/choline deficient (MCDD diets for four weeks; the effects on methyl donor and lipid biology were investigated by bioinformatic analysis of hepatic gene expression profiles followed by a cross-species comparison with human expression data of all stages of NAFLD. Results: Compared to controls, expression of the very low density lipoprotein (VLDL packaging carboxylesterases (Ces1d, Ces1f, Ces3b and the NAFLD risk allele Pnpla3 were suppressed in MCDD; with Pnpla3 and the liver predominant Ces isoform, Ces3b, also suppressed in CDD. With respect to 1-carbon metabolism, down-regulation of Chka, Chkb, Pcty1a, Gnmt and Ahcy with concurrent upregulation of Mat2a suggests a drive to maintain S-adenosylmethionine levels. There was minimal similarity between global gene expression patterns in either dietary intervention and any stage of human NAFLD, however some common transcriptomic changes in inflammatory, fibrotic and proliferative mediators were identified in MCDD, NASH and HCC. Conclusions: This study suggests suppression of VLDL assembly machinery may contribute to hepatic lipid accumulation in these models, but that CDD and MCDD rodent diets are minimally representative of human NAFLD at the transcriptional level.

Abnormal extraosseous activity in both lungs and stomach in pre-transplant 99mTc-MDP bone scan disappearing after renal transplant

International Nuclear Information System (INIS)

Sonavane, Sunita Tarsarya; Marwah, Atul; Jaiswar, Rajnath; Shah, Hardik

2013-01-01

A chronic kidney disease male patient presenting with bone pains, fever, weakness, and clinically ascites was subjected to four technetium-99m-methylene diphosphonate ( 99m Tc-MDP) bone scans, two before renal transplant and two after renal transplants. Pretransplant bone scan revealed metabolic bone disease with focal insufficiency fractures. Marked extraosseous activity in both lungs and stomach was also visualized. On regular hemodialysis (HD) after 4 months, repeat pretransplant bone scan showed persistent uptake in lungs and stomach, representing altered calcium metabolism with microcalcifications. He underwent human leukocyte antigen (HLA) matched live donor renal transplantation, started on immune-suppression and steroids. Posttransplant bone scan at 20 days revealed no definite interval change, but bone scan performed approximately 17 months posttransplant showed resolving metabolic bone disease and the tracer uptake in the lungs and stomach was no more visualized. Patient clinically followed-up until the date (February 2013) is asymptomatic with serum creatinine of 1.5 mg/dl, no bone scan done. (author)

Inhibition of human lung cancer cell proliferation and survival by wine

Science.gov (United States)

2014-01-01

Background Compounds of plant origin and food components have attracted scientific attention for use as agents for cancer prevention and treatment. Wine contains polyphenols that were shown to have anti-cancer and other health benefits. The survival pathways of Akt and extracellular signal-regulated kinase (Erk), and the tumor suppressor p53 are key modulators of cancer cell growth and survival. In this study, we examined the effects of wine on proliferation and survival of human Non-small cell lung cancer (NSCLC) cells and its effects on signaling events. Methods Human NSCLC adenocarcinoma A549 and H1299 cells were used. Cell proliferation was assessed by thymidine incorporation. Clonogenic assays were used to assess cell survival. Immunoblotting was used to examine total and phosphorylated levels of Akt, Erk and p53. Results In A549 cells red wine inhibited cell proliferation and reduced clonogenic survival at doses as low as 0.02%. Red wine significantly reduced basal and EGF-stimulated Akt and Erk phosphorylation while it increased the levels of total and phosphorylated p53 (Ser15). Control experiments indicated that the anti-proliferative effects of wine were not mediated by the associated contents of ethanol or the polyphenol resveratrol and were independent of glucose transport into cancer cells. White wine also inhibited clonogenic survival, albeit at a higher doses (0.5-2%), and reduced Akt phosphorylation. The effects of both red and white wine on Akt phosphorylation were also verified in H1299 cells. Conclusions Red wine inhibits proliferation of lung cancer cells and blocks clonogenic survival at low concentrations. This is associated with inhibition of basal and EGF-stimulated Akt and Erk signals and enhancement of total and phosphorylated levels of p53. White wine mediates similar effects albeit at higher concentrations. Our data suggest that wine may have considerable anti-tumour and chemoprevention properties in lung cancer and deserves further

Gamete donation: parents' experiences of searching for their child's donor siblings and donor.

Science.gov (United States)

Freeman, T; Jadva, V; Kramer, W; Golombok, S

2009-03-01

This study investigates the new phenomenon of parents of donor offspring searching for and contacting their child's 'donor siblings' (i.e. donor offspring conceived by the same donor) and donor. Online questionnaires were completed by 791 parents (39% lone-mother, 35% lesbian-couple, 21% heterosexual-couple, 5% non-specified) recruited via the Donor Sibling Registry; a US-based international registry that facilitates contact between donor conception families who share the same donor. Data were collected on parents' reasons for searching for their child's donor siblings and/or donor, the outcome of these searches and parents' and their child's experiences of any resulting contact. Parents' principal motivation for searching for their child's donor siblings was curiosity and for their donor, enhancing their child's sense of identity. Some parents had discovered large numbers of donor siblings (maximum = 55). Most parents reported positive experiences of contacting and meeting their child's donor siblings and donor. This study highlights that having access to information about a child's donor origins is important for some parents and has potentially positive consequences. These findings have wider implications because the removal of donor anonymity in the UK and elsewhere means that increasing numbers of donor offspring are likely to seek contact with their donor relations in the future.

Avian and human influenza A virus receptors in trachea and lung of animals.

Science.gov (United States)

Thongratsakul, Sukanya; Suzuki, Yasuo; Hiramatsu, Hiroaki; Sakpuaram, Thavajchai; Sirinarumitr, Theerapol; Poolkhet, Chaithep; Moonjit, Pattra; Yodsheewan, Rungrueang; Songserm, Thaweesak

2010-12-01

Influenza A viruses are capable of crossing the specific barrier between human beings and animals resulting in interspecies transmission. The important factor of potential infectivity of influenza A viruses is the suitability of the receptor binding site of the host and viruses. The affinities of avian and human influenza virus to bind with the receptors and the distributions of receptors in animals are different. This study aims to investigate the anatomical distribution of avian and human influenza virus receptors using the double staining lectin histochemistry method. Double staining of lectin histochemistry was performed to identify both SA alpha2,3 Gal and SA alpha2,6 Gal receptors in trachea and lung tissue of dogs, cats, tigers, ferret, pigs, ducks and chickens. We have demonstrated that avian and human influenza virus receptors were abundantly present in trachea, bronchus and bronchiole, but in alveoli of dogs, cats and tigers showed SA alpha2,6 Gal only. Furthermore, endothelial cells in lung tissues showed presence of SA alpha2,3 Gal. The positive sites of both receptors in respiratory tract, especially in the trachea, suggest that all mammalian species studied can be infected with avian influenza virus. These findings suggested that dogs and cats in close contact with humans should be of greater concern as an intermediate host for avian influenza A in which there is the potential for viral adaptation and reassortment.

Effects of calcium, inorganic phosphate, and pH on isometric force in single skinned cardiomyocytes from donor and failing human hearts

NARCIS (Netherlands)

van der Velden, J.; Klein, L. J.; Zaremba, R.; Boontje, N. M.; Huybregts, M. A.; Stooker, W.; Eijsman, L.; de Jong, J. W.; Visser, C. A.; Visser, F. C.; Stienen, G. J.

2001-01-01

During ischemia, the intracellular calcium and inorganic phosphate (P(i)) concentrations rise and pH falls. We investigated the effects of these changes on force development in donor and failing human hearts to determine if altered contractile protein composition during heart failure changes the

MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

International Nuclear Information System (INIS)

Li, Xiaoou; Liu, Lian; Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan; Wen, Fuqiang

2014-01-01

Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis

MicroRNA-26a modulates transforming growth factor beta-1-induced proliferation in human fetal lung fibroblasts

Energy Technology Data Exchange (ETDEWEB)

Li, Xiaoou [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Liu, Lian [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Shen, Yongchun; Wang, Tao; Chen, Lei; Xu, Dan [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Wen, Fuqiang, E-mail: wenfuqiang.scu@gmail.com [Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China); Department of Respiratory Medicine, West China Hospital, West China School of Medicine, Sichuan University, Chengdu, Sichuan (China)

2014-11-28

Highlights: • Endogenous miR-26a inhibits TGF-beta 1 induced proliferation of lung fibroblasts. • miR-26a induces G1 arrest through directly targeting 3′-UTR of CCND2. • TGF indispensable receptor, TGF-beta R I, is regulated by miR-26a. • miR-26a acts through inhibiting TGF-beta 2 feedback loop to reduce TGF-beta 1. • Collagen type I and connective tissue growth factor are suppressed by miR-26a. - Abstract: MicroRNA-26a is a newly discovered microRNA that has a strong anti-tumorigenic capacity and is capable of suppressing cell proliferation and activating tumor-specific apoptosis. However, whether miR-26a can inhibit the over-growth of lung fibroblasts remains unclear. The relationship between miR-26a and lung fibrosis was explored in the current study. We first investigated the effect of miR-26a on the proliferative activity of human lung fibroblasts with or without TGF-beta1 treatment. We found that the inhibition of endogenous miR-26a promoted proliferation and restoration of mature miR-26a inhibited the proliferation of human lung fibroblasts. We also examined that miR-26a can block the G1/S phase transition via directly targeting 3′-UTR of CCND2, degrading mRNA and decreasing protein expression of Cyclin D2. Furthermore, we showed that miR-26a mediated a TGF-beta 2-TGF-beta 1 feedback loop and inhibited TGF-beta R I activation. In addition, the overexpression of miR-26a also significantly suppressed the TGF-beta 1-interacting-CTGF–collagen fibrotic pathway. In summary, our studies indicated an essential role of miR-26a in the anti-fibrotic mechanism in TGF-beta1-induced proliferation in human lung fibroblasts, by directly targeting Cyclin D2, regulating TGF-beta R I as well as TGF-beta 2, and suggested the therapeutic potential of miR-26a in ameliorating lung fibrosis.

Cost-effective master cell bank validation of multiple clinical-grade human pluripotent stem cell lines from a single donor.

Science.gov (United States)

Devito, Liani; Petrova, Anastasia; Miere, Cristian; Codognotto, Stefano; Blakely, Nicola; Lovatt, Archie; Ogilvie, Caroline; Khalaf, Yacoub; Ilic, Dusko

2014-10-01

Standardization guidelines for human pluripotent stem cells are still very broadly defined, despite ongoing clinical trials in the U.S., U.K., and Japan. The requirements for validation of human embryonic (hESCs) and induced pluripotent stem cells (iPSCs) in general follow the regulations for other clinically compliant biologics already in place but without addressing key differences between cell types or final products. In order to realize the full potential of stem cell therapy, validation criteria, methodology, and, most importantly, strategy, should address the shortfalls and efficiency of current approaches; without this, hESC- and, especially, iPSC-based therapy will not be able to compete with other technologies in a cost-efficient way. We addressed the protocols for testing cell lines for human viral pathogens and propose a novel strategy that would significantly reduce costs. It is highly unlikely that the multiple cell lines derived in parallel from a tissue sample taken from one donor would have different profiles of endogenous viral pathogens; we therefore argue that samples from the Master Cell Banks of sibling lines could be safely pooled for validation. We illustrate this approach with tiered validation of two sibling clinical-grade hESC lines, KCL033 and KCL034 (stage 1, sterility; stage 2, specific human pathogens; and stage 3, nonspecific human pathogens). The results of all tests were negative. This cost-effective strategy could also be applied for validation of Master Cell Banks of multiple clinical-grade iPSC lines derived from a single donor. ©AlphaMed Press.

Adverse effects to transfusion with red donor blood cells are frequent

DEFF Research Database (Denmark)

Pommergaard, Hans-Christian; Nørgaard, Astrid; Burcharth, Jakob

2014-01-01

Adverse effects to transfusion with red donor blood cells are potentially life-threatening. Due to screening, transmission of infectious diseases has decreased; however, the risk is still present. Various immune reactions are common including simple allergic reactions as well as devastating...... conditions such as transfusion-related acute lung injury and circulatory overload in patients with heart disease. Knowledge of the clinical signs of transfusion-related complications is important for clinicians in order to provide the best possible treatment....

The accumulation of nickel in human lungs.

OpenAIRE

Edelman, D A; Roggli, V L

1989-01-01

Using data from published studies, lung concentrations of nickel were compare for persons with and without occupational exposure to nickel. As expected, the concentrations were much higher for persons with occupational exposure. To estimate the effects of nickel-containing tobacco smoke and nickel in the ambient air on the amount of nickel accumulated in lungs over time, a model was derived that took into account various variables related to the deposition of nickel in lungs. The model predic...

Production of decellularized porcine lung scaffolds for use in tissue engineering.

Science.gov (United States)

Balestrini, Jenna L; Gard, Ashley L; Liu, Angela; Leiby, Katherine L; Schwan, Jonas; Kunkemoeller, Britta; Calle, Elizabeth A; Sivarapatna, Amogh; Lin, Tylee; Dimitrievska, Sashka; Cambpell, Stuart G; Niklason, Laura E

2015-12-01

There is a growing body of work dedicated to producing acellular lung scaffolds for use in regenerative medicine by decellularizing donor lungs of various species. These scaffolds typically undergo substantial matrix damage due to the harsh conditions required to remove cellular material (e.g., high pH, strong detergents), lengthy processing times, or pre-existing tissue contamination from microbial colonization. In this work, a new decellularization technique is described that maintains the global tissue architecture, key matrix components, mechanical composition and cell-seeding potential of lung tissue while effectively removing resident cellular material. Acellular lung scaffolds were produced from native porcine lungs using a combination of Triton X-100 and sodium deoxycholate (SDC) at low concentrations in 24 hours. We assessed the effect of matrix decellularization by measuring residual DNA, biochemical composition, mechanical characteristics, tissue architecture, and recellularization capacity.

The Role of Serotonin Transporter in Human Lung Development and in Neonatal Lung Disorders

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E. C. C. Castro

2017-01-01

Full Text Available Introduction. Failure of the vascular pulmonary remodeling at birth often manifests as pulmonary hypertension (PHT and is associated with a variety of neonatal lung disorders including a uniformly fatal developmental disorder known as alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV. Serum serotonin regulation has been linked to pulmonary vascular function and disease, and serotonin transporter (SERT is thought to be one of the key regulators in these processes. We sought to find evidence of a role that SERT plays in the neonatal respiratory adaptation process and in the pathomechanism of ACD/MPV. Methods. We used histology and immunohistochemistry to determine the timetable of SERT protein expression in normal human fetal and postnatal lungs and in cases of newborn and childhood PHT of varied etiology. In addition, we tested for a SERT gene promoter defect in ACD/MPV patients. Results. We found that SERT protein expression begins at 30 weeks of gestation, increases to term, and stays high postnatally. ACD/MPV patients had diminished SERT expression without SERT promoter alteration. Conclusion. We concluded that SERT/serotonin pathway is crucial in the process of pulmonary vascular remodeling/adaptation at birth and plays a key role in the pathobiology of ACD/MPV.

CRISPR-Mediated Integration of Large Gene Cassettes Using AAV Donor Vectors

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Rasmus O. Bak

2017-07-01

Full Text Available The CRISPR/Cas9 system has recently been shown to facilitate high levels of precise genome editing using adeno-associated viral (AAV vectors to serve as donor template DNA during homologous recombination (HR. However, the maximum AAV packaging capacity of ∼4.5 kb limits the donor size. Here, we overcome this constraint by showing that two co-transduced AAV vectors can serve as donors during consecutive HR events for the integration of large transgenes. Importantly, the method involves a single-step procedure applicable to primary cells with relevance to therapeutic genome editing. We use the methodology in primary human T cells and CD34+ hematopoietic stem and progenitor cells to site-specifically integrate an expression cassette that, as a single donor vector, would otherwise amount to a total of 6.5 kb. This approach now provides an efficient way to integrate large transgene cassettes into the genomes of primary human cells using HR-mediated genome editing with AAV vectors.

Molecular profile and cellular characterization of human bone marrow mesenchymal stem cells: donor influence on chondrogenesis.

Science.gov (United States)

Cicione, Claudia; Díaz-Prado, Silvia; Muiños-López, Emma; Hermida-Gómez, Tamara; Blanco, Francisco J

2010-01-01

The use of autologous or allogenic stem cells has recently been suggested as an alternative therapeutic approach for treatment of cartilage defects. Bone marrow mesenchymal stem cells (BM-MSCs) are well-characterized multipotent cells that can differentiate into different cell types. Understanding the potential of these cells and the molecular mechanisms underlying their differentiation should lead to innovative protocols for clinical applications. The aim of this study was to evaluate the usefulness of surface antigen selection of BM-MSCs and to understand the mechanisms underlying their differentiation. MSCs were isolated from BM stroma and expanded. CD105+ subpopulation was isolated using a magnetic separator. We compared culture-expanded selected cells with non-selected cells. We analyzed the phenotypic profiles, the expression of the stem cell marker genes Nanog, Oct3/4, and Sox2 and the multi-lineage differentiation potential (adipogenic, osteogenic, and chondrogenic). The multi-lineage differentiation was confirmed using histochemistry, immunohistochemistry and/or real-time polymerase chain reaction (qPCR) techniques. The selected and non-selected cells displayed similar phenotypes and multi-lineage differentiation potentials. Analyzing each cell source individually, we could divide the six donors into two groups: one with a high percentage of CD29 (β1-integrin) expression (HL); one with a low percentage of CD29 (LL). These two groups had different chondrogenic capacities and different expression levels of the stem cell marker genes. This study showed that phenotypic profiles of donors were related to the chondrogenic potential of human BM-MSCs. The chondrogenic potential of donors was related to CD29 expression levels. The high expression of CD29 antigen seemed necessary for chondrogenic differentiation. Further investigation into the mechanisms responsible for these differences in BM-MSCs chondrogenesis is therefore warranted. Understanding the mechanisms

Assessment of regional ventilation and deformation using 4D-CT imaging for healthy human lungs during tidal breathing.

Science.gov (United States)

Jahani, Nariman; Choi, Sanghun; Choi, Jiwoong; Iyer, Krishna; Hoffman, Eric A; Lin, Ching-Long

2015-11-15

This study aims to assess regional ventilation, nonlinearity, and hysteresis of human lungs during dynamic breathing via image registration of four-dimensional computed tomography (4D-CT) scans. Six healthy adult humans were studied by spiral multidetector-row CT during controlled tidal breathing as well as during total lung capacity and functional residual capacity breath holds. Static images were utilized to contrast static vs. dynamic (deep vs. tidal) breathing. A rolling-seal piston system was employed to maintain consistent tidal breathing during 4D-CT spiral image acquisition, providing required between-breath consistency for physiologically meaningful reconstructed respiratory motion. Registration-derived variables including local air volume and anisotropic deformation index (ADI, an indicator of preferential deformation in response to local force) were employed to assess regional ventilation and lung deformation. Lobar distributions of air volume change during tidal breathing were correlated with those of deep breathing (R(2) ≈ 0.84). Small discrepancies between tidal and deep breathing were shown to be likely due to different distributions of air volume change in the left and the right lungs. We also demonstrated an asymmetric characteristic of flow rate between inhalation and exhalation. With ADI, we were able to quantify nonlinearity and hysteresis of lung deformation that can only be captured in dynamic images. Nonlinearity quantified by ADI is greater during inhalation, and it is stronger in the lower lobes (P < 0.05). Lung hysteresis estimated by the difference of ADI between inhalation and exhalation is more significant in the right lungs than that in the left lungs. Copyright © 2015 the American Physiological Society.

A Short Period of Ventilation without Perfusion Seems to Reduce Atelectasis without Harming the Lungs during Ex Vivo Lung Perfusion

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Sandra Lindstedt

2013-01-01

Full Text Available To evaluate the lung function of donors after circulatory deaths (DCDs, ex vivo lung perfusion (EVLP has been shown to be a valuable method. We present modified EVLP where lung atelectasis is removed, while the lung perfusion is temporarily shut down. Twelve pigs were randomized into two groups: modified EVLP and conventional EVLP. When the lungs had reached 37°C in the EVLP circuit, lung perfusion was temporarily shut down in the modified EVLP group, and positive end-expiratory pressure (PEEP was increased to 10 cm H2O for 10 minutes. In the conventional EVLP group, PEEP was increased to 10 cm H2O for 10 minutes with unchanged lung perfusion. In the modified EVLP group, the arterial oxygen partial pressure (PaO2 was 18.5 ± 7.0 kPa before and 64.5 ± 6.0 kPa after the maneuver (P<0.001. In the conventional EVLP group, the PaO2 was 16.8 ± 3.1 kPa and 46.8 ± 2.7 kPa after the maneuver (P<0.01; P<0.01. In the modified EVLP group, the pulmonary graft weight was unchanged, while in the conventional EVLP group, the pulmonary graft weight was significantly increased. Modified EVLP with normoventilation of the lungs without ongoing lung perfusion for 10 minutes may eliminate atelectasis almost completely without harming the lungs.

Associations of health status with subsequent blood donor behavior-An alternative perspective on the Healthy Donor Effect from Donor InSight

NARCIS (Netherlands)

van den Hurk, Katja; Zalpuri, Saurabh; Prinsze, Femmeke J.; Merz, Eva-Maria; de Kort, Wim L. A. M.

2017-01-01

In donor health research, the 'Healthy Donor Effect' (HDE) often biases study results and hampers their interpretation. This refers to the fact that donors are a selected 'healthier' subset of a population due to both donor selection procedures and self-selection. Donors with long versus short donor

Preventing Mitochondrial Diseases: Embryo-Sparing Donor-Independent Options.

Science.gov (United States)

Adashi, Eli Y; Cohen, I Glenn

2018-05-01

Mutant mitochondrial DNA gives rise to a broad range of incurable inborn maladies. Prevention may now be possible by replacing the mutation-carrying mitochondria of zygotes or oocytes at risk with donated unaffected counterparts. However, mitochondrial replacement therapy is being held back by theological, ethical, and safety concerns over the loss of human zygotes and the involvement of a donor. These concerns make it plain that the identification, validation, and regulatory adjudication of novel embryo-sparing donor-independent technologies remains a pressing imperative. This Opinion highlights three emerging embryo-sparing donor-independent options that stand to markedly allay theological, ethical, and safety concerns raised by mitochondrial replacement therapy. Copyright © 2018 Elsevier Ltd. All rights reserved.

One window-period donation in two years of individual donor-nucleic acid test screening for hepatitis B, hepatitis C and human immunodeficiency virus

Directory of Open Access Journals (Sweden)

Jose Eduardo Levi

2013-06-01

Full Text Available Objective: To describe general data on nucleic acid/serology testing and report the first hepatitis B-nucleic acid testing yield case of an immunized donor in Brazil. Methods: A total of 24,441 donations collected in 2010 and 2011 were submitted to individual nucleic acid testing for hepatitis B, hepatitis C and human immunodeficiency virus using the TaqMan® MPX kit (Roche on the Cobas s201 platform, in addition to routine screening for serological markers. Nucleic acid testing-reactive donations were further evaluated by real-time polymerase chain reaction using Cobas AmpliPrep/Cobas TaqMan hepatitis B virus, hepatitis C virus and human immunodeficiency virus tests. Results: Thirty-two donations were reactive by nucleic acid testing, 31 were also serologically reactive and one first-time donor was identified as having hepatitis B in the window period. Follow-up samples showed increasing titers of anti-HBs rising from 19 UI/mL in the index donation to 109 IU/mL seven months later attributable to his vaccination history. Curiously, this donor was never reactive for HbsAg nor for anti-HBc. In the yield donation, he was concomitantly reactive for syphilis (enzyme immunoassay and fluorescent treponemal antibody-absorption; venereal disease research laboratory non-reactive. Overall, six donors (0.02% were characterized as occult hepatitis B. A total of 35% of the confirmed (recombinant immunoblot assay positive hepatitis C donations were nucleic acid testing non-reactive and no human immunodeficiency virus "elite controller" was identified. Conclusion: The yield rate (1:24,441; 95% confidence interval: 1:9,537 - 1:89,717 contrasts to the North American rate (1:410,540 donations and strongly advocates the adoption of nucleic acid testing for hepatitis B in Brazil despite the increasing rate of anti-HBs reactive subjects due to the successful immunization program.

Factors affecting the serological testing of cadaveric donor cornea.

Science.gov (United States)

Raj, Anuradha; Mittal, Garima; Bahadur, Harsh

2018-01-01

The purpose of this study was to evaluate the serological profile of the eye donors and to study the influence of various factors on serological test results. A cross-sectional, observational study was conducted, and data of 509 donors were reviewed from the records of eye bank from December 2012 to June 2017. Various details of donors analyzed included the age, sex of the donor, cause of death, source of tissue, time since blood collection after death, macroscopic appearance of blood sample, and details of discarded tissues. Serological examination of blood was performed for human immunodeficiency virus (HIV), hepatitis B virus, hepatitis C virus (HCV), venereal disease research laboratory (VDRL), and serology reports reactive or nonreactive were analyzed. Among the 509 donors, 295 (58%) were male, and 420 (82.50%) belonged to age group ≥60 years. Most donors (354, 69.5%) died due to cardiac arrest. Macroscopically, sera were normal in the majority of 488 (95.9%) cases. Among 509 donors, 475 (93.3%) were nonreactive, 12 (2.4%) donors were found to be reactive to hepatitis B surface antigen (HBsAg), and 1 (0.2%) was reactive to HCV, but no donor serology was reactive to HIV or VDRL. Twenty-one (4.12%) donors' sera were not fit for serological testing. Among all donors, 475 (93.32%) donors were accepted and 34 (6.67%) were rejected or discarded on the basis of serological testing. Cause of death and macroscopic aspect of sera influenced the serological results in a highly significant manner (P = 0.00). Acceptance or rejection of the donor was significantly influenced by the serological results of the donor (P = 0.00). The seroprevalence among eye donor for HBsAg and HCV was 12 (2.4%) and 1 (0.2%), respectively. Factors such as cause of death and macroscopic aspect of sera influence the serological results. Time since blood collection or sampling will not show any impact on viral serological results if postmortem sampling will be done in donor cornea.

The Stem Cell Club: a model for unrelated stem cell donor recruitment.

Science.gov (United States)

Fingrut, Warren; Parmar, Simran; Cuperfain, Ari; Rikhraj, Kiran; Charman, Erin; Ptak, Emilie; Kahlon, Manjot; Graham, Alice; Luong, Susan; Wang, Yongjun George; Yu, Janice; Arora, Neha; Suppiah, Roopa; Li, Edward W; Lee, Anna; Welsh, Christopher; Benzaquen, Menachem; Thatcher, Alicia; Baharmand, Iman; Ladd, Aedan; Petraszko, Tanya; Allan, David; Messner, Hans

2017-12-01

Patients with blood, immune, or metabolic diseases may require a stem cell transplant as part of their treatment. However, 70% of patients do not have a suitable human leukocyte antigen match in their family, and need an unrelated donor. Individuals can register as potential donors at stem cell drives, where they provide consent and a tissue sample for human leukocyte antigen typing. The ideal donors are young, male, and from a diversity of ethnic backgrounds. However, in Canada, non-Caucasian males ages 17 to 35 years represent only 8.8% of listed donors. The Stem Cell Club is a non-profit organization founded in 2011 in Canada that aims to augment recruitment of the most needed donors. The initiative published a recruitment toolkit online (www.stemcellclub.ca). Currently, there are 12 chapters at universities across Canada. To date, the Stem Cell Club has recruited 6585 potential registrants, representing 1.63% of donors on Canada's donor-database. Of the recruited registrants, 58.3% were male; 60.3% of males self-reported as non-Caucasian, and 78.5% were ages 17 to 25 years. From 2015 to 2016, the initiative recruited 13.7% of all ethnically diverse males ages 17 to 35 years listed in Canada's donor database. Data from this initiative demonstrate sustainability and performance on key indicators of stem cell drive quality. The Stem Cell Club has developed a capacity to recruit 2600 donors annually, with the majority being males with a high degree of ethnic diversity. The initiative enhances the quality of Canada's unrelated donor-database, improving the chances that patients in need of an unrelated donor will find a match for transplant. The Stem Cell Club is a model relevant to recruitment organizations around the world. © 2017 AABB.

Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells

International Nuclear Information System (INIS)

Perkins, Timothy N.; Dentener, Mieke A.; Stassen, Frank R.; Rohde, Gernot G.; Mossman, Brooke T.; Wouters, Emiel F.M.; Reynaert, Niki L.

2016-01-01

Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. - Highlights: • Pathway analysis reveals silica-induced WNT-signaling in lung epithelial cells. • Silica-induced canonical WNT-signaling is mediated by autocrine/paracrine signals. • Crystalline silica decreases non-canonical WNT

Alteration of canonical and non-canonical WNT-signaling by crystalline silica in human lung epithelial cells

Energy Technology Data Exchange (ETDEWEB)

Perkins, Timothy N.; Dentener, Mieke A. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Stassen, Frank R. [Department of Medical Microbiology, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Rohde, Gernot G. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Mossman, Brooke T. [Department of Pathology, University of Vermont College of Medicine, Burlington, VT (United States); Wouters, Emiel F.M. [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands); Reynaert, Niki L., E-mail: n.reynaert@maastrichtuniversity.nl [Department of Respiratory Medicine, Maastricht University Medical Centre +, Maastricht University Maastricht (Netherlands)

2016-06-15

Growth and development of the mature lung is a complex process orchestrated by a number of intricate developmental signaling pathways. Wingless-type MMTV-integration site (WNT) signaling plays critical roles in controlling branching morphogenesis cell differentiation, and formation of the conducting and respiratory airways. In addition, WNT pathways are often re-activated in mature lungs during repair and regeneration. WNT- signaling has been elucidated as a crucial contributor to the development of idiopathic pulmonary fibrosis as well as other hyper-proliferative lung diseases. Silicosis, a detrimental occupational lung disease caused by excessive inhalation of crystalline silica dust, is hallmarked by repeated cycles of damaging inflammation, epithelial hyperplasia, and formation of dense, hyalinized nodules of whorled collagen. However, mechanisms of epithelial cell hyperplasia and matrix deposition are not well understood, as most research efforts have focused on the pronounced inflammatory response. Microarray data from our previous studies has revealed a number of WNT-signaling and WNT-target genes altered by crystalline silica in human lung epithelial cells. In the present study, we utilize pathway analysis to designate connections between genes altered by silica in WNT-signaling networks. Furthermore, we confirm microarray findings by QRT-PCR and demonstrate both activation of canonical (β-catenin) and down-regulation of non-canonical (WNT5A) signaling in immortalized (BEAS-2B) and primary (PBEC) human bronchial epithelial cells. These findings suggest that WNT-signaling and cross-talk with other pathways (e.g. Notch), may contribute to proliferative, fibrogenic and inflammatory responses to silica in lung epithelial cells. - Highlights: • Pathway analysis reveals silica-induced WNT-signaling in lung epithelial cells. • Silica-induced canonical WNT-signaling is mediated by autocrine/paracrine signals. • Crystalline silica decreases non-canonical WNT

Global gene expression profiling in human lung cells exposed to cobalt

Energy Technology Data Exchange (ETDEWEB)

Malard, V.; Berenguer, F.; Prat, O.; Ruat, S.; Steinmetz, G.; Quemeneur, E. [CEA VALRHO, Serv Biochim and Toxicol Nucl, DSV, iBEB, F-30207 Bagnols Sur Ceze (France)

2007-06-06

It has been estimated that more than 1 million workers in the United States are exposed to cobalt. Occupational exposure to {sup 59}Co occurs mainly via inhalation and leads to various lung diseases. Cobalt is classified by the IARC as a possible human carcinogen (group 2B). Although there is evidence for in vivo and in vitro toxicity, the mechanisms of cobalt-induced lung toxicity are not fully known. The purpose of this work was to identify potential signatures of acute cobalt exposure using a toxico-genomic approach. Data analysis focused on some cellular processes and protein targets that are thought to be relevant for carcinogenesis, transport and bio-marker research. Results: A time course transcriptome analysis was performed on A549 human pulmonary cells, leading to the identification of 85 genes which are repressed or induced in response to soluble 59 Co. A group of 29 of these genes, representing the main biological functions, was assessed by quantitative RT-PCR. The expression profiles of six of them were then tested by quantitative RT-PCR in a time-dependent manner and three modulations were confirmed by Western blotting. The 85 modulated genes include potential cobalt carriers (FBXL2, ZNT1, SLC12A5), tumor suppressors or transcription factors (MAZ, DLG1, MYC, AXL) and genes linked to the stress response (UBC, HSPCB, BN1P3L). We also identified nine genes coding for secreted proteins as candidates for bio-marker research. Of those, T1MP2 was found to be down-regulated and this modulation was confirmed, in a dose-dependent manner, at protein level in the supernatant of exposed cells. Conclusion: Most of these genes have never been described as related to cobalt stress and provide original hypotheses for further study of the effects of this metal ion on human lung epithelial cells. A putative bio-marker of cobalt toxicity was identified. (authors)

Unconfirmed reactive screening tests and their impact on donor management

International Nuclear Information System (INIS)

Rahman, M.; Khan, S.A.

2008-01-01

To determine the percentage of false positive testing for transfusion transmitted infections (TTIs) using immunochromatographic test (ICT) as first line of screening tests and its effect on loss of volunteer blood donors. Over a period of three months, samples from blood bags of donors undergoing phlebotomy at teaching hospital blood banks in Lahore were screened for human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) by immunochromatographic tests. Those found positive on initial screening were re-tested by ELISA method at the screening laboratory of the Institute of Haematology and Blood Transfusion Service, Punjab. Lahore. Out of a total of 62090 voluntary blood donors, 469 donors were found to be initially reactive for either HIV, HBV or HCV. Amongst these 96 (0.15%) blood donors were found to have tested falsely positive for HIV, HBV or HCV as compared to testing by ELISA. False positive testing rate of 0.15% or 96 out of a total of 62090 donors is rather small in terms of loss of voluntary donors and appropriate utilization of available resources. Although immunochromatographic testing is not the gold standard, however it serves an important purpose of initial donor screening. (author)

[Establishment of human multidrug-resistant lung carcinoma cell line (D6/MVP)].

Science.gov (United States)

Ma, Sheng-lin; Feng, Jian-guo; Gu, Lin-hui; Ling, Yu-tian

2003-03-01

To establish human multidrug-resistant lung carcinoma cell line (D6/MVP) with its characteristics studied. Intermittent administration of high-dose MMC, VDS and DDP (MVP) was used to induce human lung carcinoma cell line (D6) to a multidrug-resistant variety (D6/MVP). MTT assay was used to study the multidrug resistance of D6/MVP to multianticarcinogen. Flow cytometry was used to study the cell cycle distribution and the expression of P-gp, multidrug resistance-associated protein (MRP) and GSH/GST. 1. D6/MVP was resistant to many anti-tumor agents, with the IC(50) 13.3 times higher and the drug resistance 2 - 6 times higher than D6, 2. The multiplication time of D6/MVP was prolonged and the cell number of S-phase decreased while that of G1- and G(2)-phase increased and 3. The expression of P-gp and MRP was enhanced significantly (96.2% vs 51.7%), but the expression of GSH/GST kept stable. D6/MVP is a multidrug-resistant cell line possessing the basic characteristics of drug-resistance.

Role of Alternative Donor Allogeneic Transplants in the Therapy of Acute Myeloid Leukemia.

Science.gov (United States)

Elmariah, Hany; Pratz, Keith W

2017-07-01

Adult acute myeloid leukemia (AML) is often associated with a poor prognosis, with allogeneic transplantation representing the greatest chance of cure for eligible patients. Historically, the preferred donor source is a human leukocyte antigen-matched blood relative, although only approximately 30% of patients have access to such a donor. Alternative donor sources, including matched unrelated donors, umbilical cord blood, and haploidentical related donors, are available for almost every patient and are increasingly being used for patients without a matched related donor. Survival outcomes with these alternative donor sources now approximate those of matched related donor transplants. Given the safety and success of alternative donor transplants, comparative trials are needed to reassess the optimal donor source for patients with AML. This review summarizes the available data on these alternative donor transplants. Further investigation is needed to contemporize donor selection algorithms, but, in the current era, donor availability should no longer preclude a patient's eligibility for an allogeneic blood or marrow transplant. Copyright © 2017 by the National Comprehensive Cancer Network.

Evaluation of lung immunity in chimpanzees

International Nuclear Information System (INIS)

Bice, D.E.; Harris, D.L.; Muggenburg, B.A.; Bowen, J.A.

1980-01-01

The effects of inhaled pollutants on the immune defenses in the lung can be studied in several animal species. To assure that the data obtained can be extrapolated to man, it is essential that the development of lung immunity is similar in the experimental animal selected and in humans. Because of the similarity of immune responses in chimpanzees and in humans, the development of immunity in the chimpanzee after lung immunization was evaluated. The results from the chimpanzees were qualitatively the same as those from previous studies in which single lung lobes of dogs were immunized. It was concluded that immunotoxicology data obtained in dogs can be used to estimate the effects of inhaled pollutants on the immune defense mechanism in the human lung